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February 27, 2006

Androgen Deprivation Therapy Does Not Keep Localized Prostate Cancer From Spreading, New Study Says 


Androgen Deprivation Therapy Does Not Keep Localized Prostate Cancer From Spreading, New Study Says 
Science Daily - Feb 27 4:09 PM
Oregon Health & Science University Cancer Institute researchers wanted to know if depriving men of testosterone actually keeps cancer from spreading beyond the prostate. What they found is that men who have localized prostate cancer with certain high-risk features and receive this treatment -- known as androgen deprivation therapy -- remain at risk of dying from prostate cancer.Save to My Web

Posted by blogposter at 08:31 PM |

Prostate Cancer Screening - Intra-operative prostate examination: predictive value and effect on margin status.


Intra-operative prostate examination: predictive value and effect on margin status.
Related Articles Intra-operative prostate examination: predictive value and effect on margin status. BJU Int. 2005 Nov;96(7):1005-8 Authors: Rapp DE, Orvieto MA, Lucioni A, Gong EM, Shalhav AL, Brendler CB OBJECTIVE: To evaluate the ability of intra-operative prostate examination (IOPE) to predict extraprostatic extension (EPE) and its effect on margin status in the region of the neurovascular bundle (NVB) when combined with wide excision. PATIENTS AND METHODS: We retrospectively reviewed 403 patients with clinical stage T1c prostate adenocarcinoma undergoing radical retropubic prostatectomy (RRP). All patients had IOPE during RRP, and those with palpable abnormalities in the region of the NVB underwent wide excision. Pathological outcomes were analysed. RESULTS: Of 403 patients, 49 (12%) had a palpable abnormality in the region of the NVB. After wide excision, 18 (37%) of these 49 patients were found to have EPE at the site of the palpable abnormality; with wide excision of the NVB, only one of these 18 patients (6%) had a corresponding positive surgical margin (PSM). In 354 patients with a normal IOPE and who underwent bilateral NVB preservation, 30 were found to have EPE in the region of the NVB. The PSM rate in this subset was 23% (seven of 30). The positive predictive value of IOPE for detecting EPE was 37%. CONCLUSION: IOPE detects abnormalities in 12% of patients with preoperative stage T1c prostate cancer. Although the predictive value of this test is limited, IOPE may decrease PSMs in a subset of patients with EPE in the region of the NVB. The present study reaffirms the value of IOPE for assessing the risk of extraprostatic disease, and for guiding surgical management. PMID: 16225517 [PubMed - indexed for MEDLINE]

Posted by blogposter at 08:31 PM |

Maspin alters the carcinoma proteome.


Maspin alters the carcinoma proteome.
Related Articles Maspin alters the carcinoma proteome. FASEB J. 2005 Jul;19(9):1123-4 Authors: Chen EI, Florens L, Axelrod FT, Monosov E, Barbas CF, Yates JR, Felding-Habermann B, Smith JW Maspin, a member of the serine protease inhibitor (serpin) family, is a tumor suppressor in breast and prostate cancer. To address molecular mechanisms underlying maspin's activity, we restored its expression in invasive carcinoma cells and analyzed the resulting changes by shotgun proteomics. Using a mass spectrometry-based multidimensional proteomic method, we observed changes to the expression of approximately 27% of the detectable proteome. In particular, we noted changes to the expression of proteins that regulate cytoskeletal architecture, cell death, and protein turnover. In each case, changes in protein expression were accompanied by measurable changes in tumor cell phenotype. Thus, maspin-expressing cells exhibit a more prominent actin cytoskeleton, a reduced invasive capacity, an increased rate of spontaneous apoptosis, and an altered proteasome function. These observations reveal for the first time the far reaching effects of maspin on multiple protein networks and a new hypothesis of maspin function based on the regulation of proteasome function. PMID: 15857880 [PubMed - indexed for MEDLINE]

Posted by blogposter at 08:30 PM |

Inhibition of DNA methyltransferase activity prevents tumorigenesis in a mouse model of prostate cancer.


Inhibition of DNA methyltransferase activity prevents tumorigenesis in a mouse model of prostate cancer.
Related Articles Inhibition of DNA methyltransferase activity prevents tumorigenesis in a mouse model of prostate cancer. Cancer Res. 2006 Jan 1;66(1):385-92 Authors: McCabe MT, Low JA, Daignault S, Imperiale MJ, Wojno KJ, Day ML Transcriptional silencing of tumor suppressor genes by DNA methylation plays an important role in tumorigenesis. These aberrant epigenetic modifications may be mediated in part by elevated DNA methyltransferase levels. DNA methyltransferase 1 (DNMT1), in particular, is overexpressed in many tumor types. Recently, we showed that Dnmt1 is transcriptionally regulated by E2F transcription factors and that retinoblastoma protein (pRb) inactivation induces Dnmt1. Based on these observations, we investigated regulation of Dnmt1 by polyomavirus oncogenes, which potently inhibit the pRb pocket protein family. Infection of primary human prostate epithelial cells with BK polyomavirus dramatically induced Dnmt1 transcription following large T antigen (TAg) translation and E2F activation. For in vivo study of Dnmt1 regulation, we used the transgenic adenocarcinoma of the mouse prostate (TRAMP) model, which expresses the SV40 polyomavirus early region, including TAg, under control of a prostate-specific promoter. Analysis of TRAMP prostate lesions revealed greatly elevated Dnmt1 mRNA and protein levels beginning in prostatic intraepithelial neoplasia and continuing through advanced prostate cancer and metastasis. Interestingly, when TRAMP mice were treated in a chemopreventive manner with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza), 0 of 14 mice developed prostate cancer at 24 weeks of age, whereas 7 of 13 (54%) control-treated mice developed poorly differentiated prostate cancer. Treatment with 5-aza also prevented the development of lymph node metastases and dramatically extended survival compared with control-treated mice. Taken together, these data suggest that Dnmt1 is rapidly activated by pRb pathway inactivation, and that DNA methyltransferase activity is required for malignant transformation and tumorigenesis. PMID: 16397253 [PubMed - indexed for MEDLINE]

Posted by blogposter at 08:30 PM |

Technology Insight: vaccine therapy for prostate cancer.


Technology Insight: vaccine therapy for prostate cancer.
Related Articles Technology Insight: vaccine therapy for prostate cancer. Nat Clin Pract Urol. 2005 Jan;2(1):44-51 Authors: Vieweg J, Dannull J The lack of effective therapies for advanced prostate cancer mandates continued development of alternative treatment strategies. Insights into the regulation of immune responses and the malignant process have facilitated the emergence of new immune-based strategies, currently under investigation in clinical trials. Like other forms of targeted therapy, cancer vaccines hold the promise of achieving cancer control without inducing overt toxicity. Many prostate cancer vaccines at different phases of development have been tested in clinical trials. Vaccination strategies under consideration include: immunization with defined antigenic preparations such as synthetic peptides, proteins or plasmid DNA; antigen-loaded dendritic cells; manipulated tumor cells; or with viral vectors engineered to express immunogenic genes. Although the underlying mechanisms of immunization may vary, all strategies share the common goal of eliciting immune responses against prostate tumor-associated antigens or of enhancing an otherwise weak antitumor response in the cancer patient. Unlocking the therapeutic potential of cancer vaccines will require a thorough understanding of cellular and molecular mechanisms that modulate the immune response. In this review, we provide an overview of vaccine-based strategies for prostate cancer therapy, discuss their mechanisms of action, and provide relevant clinical trial data. PMID: 16474576 [PubMed - in process]

Posted by blogposter at 08:30 PM |

[Results of a series of transrectal ultrasound guided biopsy of the prostate in 6000 patients. Part II: PSA derived parameters]


[Results of a series of transrectal ultrasound guided biopsy of the prostate in 6000 patients. Part II: PSA derived parameters]
Related Articles [Results of a series of transrectal ultrasound guided biopsy of the prostate in 6000 patients. Part II: PSA derived parameters] Arch Esp Urol. 2005 Sep;58(7):623-34 Authors: Rodr guez-Patr n Rodr guez R, Mayayo Dehesa T, Burgos Revilla FJ, Alonso Gonz lez M, Lennie Zucharino A, Garc a Gonz lez R OBJECTIVES: We review the results of 6000 patients with the clinical suspect of prostate cancer who underwent one or more prostate, biopsies, analyzing the role of PSA derived parameters in the probability of having prostate cancer in the TRUS biopsy. METHODS: We selected 6000 patients who under- went TRUS biopsy between 1994 and 2002. 861 of them underwent more than one is biopsy, adding up to a total of 7127 biopsies. For the study of PSA derived indexes we established ranges based on the 10th percentile for the first biopsy for all patients and also for those with PSA between 4 and 10 ng/ml. Several predictive models were determined by logistic regression of the variables related with presence/no presence of cancer. RESULTS: For first biopsies the ranges of PSAD established showed a diagnostic effectiveness below 8% with PSA densities lower than 0.11 ng/ml/cc. The free/total PSA ratio is less discriminant in the ranges obtained with a 13.7% incidence of prostate cancer for values above 0.24. In the case of second biopsies the group of patients with PSAD below 0.12 had only a 5.3% incidence, and only one patient with F/T PSA ratio higher than 0.24 had a prostate cancer (2.9%). All studied parameters but F/T PSA ratio showed statistical significance in the multivariant analysis. CONCLUSIONS: Although the establishment of a cut point for PSAD diminishes sensitivity, prostate biopsy habits should be modified assuming the loss of tumors in patients with low PSAD and increasing the number of biopsies in patients with total PSA values below 4 ng/ml with higher densities. PMID: 16294784 [PubMed - indexed for MEDLINE]

Posted by blogposter at 08:30 PM |

A comparison of three-field and four-field techniques in different clinical target volumes in prostate cancer irradiation using dose volume histograms: a prospective three-dimensional analysis.


A comparison of three-field and four-field techniques in different clinical target volumes in prostate cancer irradiation using dose volume histograms: a prospective three-dimensional analysis.
Related Articles A comparison of three-field and four-field techniques in different clinical target volumes in prostate cancer irradiation using dose volume histograms: a prospective three-dimensional analysis. Br J Radiol. 2006 Feb;79(938):148-57 Authors: Hille A, T ws N, Hess CF The purpose of the current study was to quantitatively assess differences between irradiation techniques on normal tissue exposure in different clinical target volumes (CTVs) in irradiation of prostate cancer. 14 patients with prostate cancer undergoing external beam radiotherapy were investigated. The prostate and prostate + proximal/entire seminal vesicles were delineated as CTVs. A three-field and two different four-field plans were generated and compared concerning rectum, bladder and femoral head dose-volume histograms (DVHs). The exposure of the rectum exposed to 40-60 Gy was significantly lower for all CTVs with the three-field technique compared with both four-field techniques. The exposure of the rectum to 70 Gy was significantly lower for all CTVs with the weighted four-field technique compared with the unweighted four-field and three-field techniques. The weighted four-field technique was worst in bladder dose sparing for the three CTVs. Comparing the three-field and the unweighted four-field technique for irradiation of the prostate and prostate + entire seminal vesicles, no technique provided a clear advantage or disadvantage in bladder dose sparing. For irradiation of the prostate + proximal seminal vesicles the unweighted four-field technique provided the best bladder dose sparing. Concerning the exposure of the femoral heads, the three-field technique was significantly worse for the three CTVs compared with both four-field techniques. No difference was found between the unweighted and the weighted four-field techniques. In conclusion, none of the studied techniques consistently proved superior in different CTVs in prostate cancer irradiation with respect to sparing all organs at risk. The absolute differences between the three techniques were small and the clinical relevance of these findings is uncertain. PMID: 16489196 [PubMed - in process]

Posted by blogposter at 08:29 PM |

Nuclear imaging of Met-expressing human and canine cancer xenografts with radiolabeled monoclonal antibodies (MetSeek).


Nuclear imaging of Met-expressing human and canine cancer xenografts with radiolabeled monoclonal antibodies (MetSeek).
Related Articles Nuclear imaging of Met-expressing human and canine cancer xenografts with radiolabeled monoclonal antibodies (MetSeek). Clin Cancer Res. 2005 Oct 1;11(19 Pt 2):7064s-7069s Authors: Hay RV, Cao B, Skinner RS, Su Y, Zhao P, Gustafson MF, Qian CN, Teh BT, Knudsen BS, Resau JH, Shen S, Waters DJ, Gross MD, Vande Woude GF PURPOSE: Met, an oncogene product and receptor tyrosine kinase, is a keystone molecule for malignant progression in solid human tumors. We are developing Met-directed imaging and therapeutic agents, including anti-Met monoclonal antibodies (MetSeek). In this study, we compared two antibodies, Met5 and Met3, for nuclear imaging of human and canine Met-expressing tumor xenografts in nude mice. EXPERIMENTAL DESIGN: Xenografts representing cancers of three different human tissue origins and metastatic canine prostate cancer were raised s.c. in host athymic nude mice. Animals were injected i.v. with I-125-Met5 or I-125-Met3, posterior total body gamma camera images were acquired for several days postinjection, and quantitative region-of-interest activity analysis was done. RESULTS: PC-3, SK-LMS-1/HGF, and CNE-2 xenografts imaged with I-125-Met5 were compared with PC-3, SK-LMS-1/HGF, and DU145 xenografts imaged with I-125-Met3. Nuclear imaging contrast was qualitatively similar for I-125-Met5 and I-125-Met3 in PC-3 and SK-LMS-1/HGF host mice. However, by region-of-interest analysis, the set of human tumors imaged with I-125-Met3 exhibited a pattern of rapid initial tumor uptake followed by a continuous decline in activity, whereas the set of human tumors imaged with I-125-Met5 showed slow initial uptake, peak tumor-associated activity at 1 day postinjection, and persistence of activity in xenografts for at least 5 days. GN4 canine prostate cancer xenografts were readily imaged with I-125-Met5. CONCLUSIONS: We conclude that radioiodinated Met3 and Met5 offer qualitatively similar nuclear images in xenograft-bearing mice, but quantitative considerations indicate that Met5 might be more useful for radioimmunotherapy. Moreover, canine prostate cancer seems to be a suitable model for second-stage preclinical evaluation of Met5. PMID: 16203803 [PubMed - indexed for MEDLINE]

Posted by blogposter at 08:29 PM |

In vitro and in vivo prodrug therapy of prostate cancer using anti-gamma-Sm-scFv/hCPA fusion protein.


In vitro and in vivo prodrug therapy of prostate cancer using anti-gamma-Sm-scFv/hCPA fusion protein.
Related Articles In vitro and in vivo prodrug therapy of prostate cancer using anti-gamma-Sm-scFv/hCPA fusion protein. Prostate. 2006 Feb 20; Authors: Hao XK, Liu JY, Yue QH, Wu GJ, Bai YJ, Yin Y BACKGROUND: Raising selectivity to tumor cells is a major challenge for most chemotherapy drugs. One of approaches to realizing this goal is antibody-directed enzyme prodrug therapy (ADEPT). This study was done to investigate the curative effect of a new ADEPT system for the treatment of prostate cancer. METHODS: Methotrexate (MTX) prodrugs were synthesized and anti-seminoprotein (SM) single-chain antibody/human carboxypeptidase-A fusion protein (scFv/hCPA) was prepared. Therapeutic effects of this ADEPT system were evaluated. RESULTS: The synthesis of prodrugs was successful and the prodrugs were confirmed no cytotoxicity, but hydrolysis with tumor-targeted scFv/hCPA fusion protein gave 1,000-fold higher cytotoxicity than MTX-alpha-Phe only. Cell cycle assays showed that tumor cells were arrested in the S phase after ADEPT treatment; furthermore, tumors were inhibited significantly in scFv/hCPA and MTX-alpha-Phe treated mice. CONCLUSIONS: Our results suggest that targeted activation cytotoxicity against established prostate cancer by scFv/hCPA mediated ADEPT is tumor-specific and has no systemic toxicity in vitro and in vivo. Prostate (c) 2006 Wiley-Liss, Inc. PMID: 16491483 [PubMed - as supplied by publisher]

Posted by blogposter at 08:29 PM |

Can docetaxel plus estramustine prolong survival of men with metastatic hormone-refractory prostate cancer?


Can docetaxel plus estramustine prolong survival of men with metastatic hormone-refractory prostate cancer?
Related Articles Can docetaxel plus estramustine prolong survival of men with metastatic hormone-refractory prostate cancer? Nat Clin Pract Oncol. 2005 Feb;2(2):70-1 Authors: Sleijfer S, Stoter G PMID: 16264874 [PubMed - indexed for MEDLINE]

Posted by blogposter at 08:29 PM |

February 20, 2006

In King's death, a lesson in ovarian cancer's deadliness 


In King's death, a lesson in ovarian cancer's deadliness 
The Daily Reflector - Feb 15 11:09 PM
Before she died last month, Coretta Scott King turned to a Mexican alternative-medicine clinic for treatment never begun of her stage III ovarian cancer. Whatever her reasons, with that move, the widow of slain civil rights icon Martin Luther King Jr. spotlighted a grim truth, say cancer experts: With even the best mainstream medical care, the odds for fighting advanced cases of the disease Save to My Web

Posted by blogposter at 01:39 PM |

Prostate Cancer Screening - Urinary estrogen metabolites, prostate specific antigen, and body mass index among African-American men in South Carolina.


Urinary estrogen metabolites, prostate specific antigen, and body mass index among African-American men in South Carolina.
Related Articles Urinary estrogen metabolites, prostate specific antigen, and body mass index among African-American men in South Carolina. Cancer Detect Prev. 2005;29(6):494-500 Authors: Teas J, Cunningham JE, Fowke JH, Nitcheva D, Kanwat CP, Boulware RJ, Sepkovic DW, Hurley TG, Hebert JR INTRODUCTION: Estrogen metabolites have been linked to risk of breast cancer, and we were interested in whether they are associated with prostate specific antigen (PSA) and other factors associated with prostate cancer. African-American (AA) men in South Carolina have among the highest prostate cancer rates in the world, and thus provide an ideal population in which to investigate this hypothesis. METHODS: We recruited AA men attending prostate cancer screenings in and around Columbia, South Carolina. Because very few men had elevated PSAs, we restricted our study to the 77 men whose PSA was below the cutpoint used by the screening program to indicate need for diagnostic workup. These men provided spot urine samples and answered demographic and lifestyle questions including self-reported body weight, height, exercise, tobacco use, medications, cancer history and age. Levels of urinary 2-hydroxyestrone (2-OHE1) and 16alpha-hydroxyestrone (16alpha-OHE1), and their ratio (2/16) and blood PSA levels were determined. RESULTS: After adjusting for a statistically significant interaction between age and BMI, we found a reduction of 14.2% in 2-OHE1 for each 1.0 ng/ml increase in PSA (p=0.05). For obese AA men only (BMI> or =30 kg/m2), 2-OHE1 increased by 36% for each decade of age (p=0.009). CONCLUSIONS: Estrogen metabolites may be related to PSA level in AA men. Older men with BMIs greater than 30 kg/m2 had an unexpected increase in 2-OHE1, suggesting a dysregulation of this estrogen metabolism pathway. Further studies of estrogen metabolites may provide insights into prostate cancer risk factors. PMID: 16289388 [PubMed - in process]

Posted by blogposter at 01:39 PM |

Prostate Cancer Prevention Through Pomegranate Fruit.


Prostate Cancer Prevention Through Pomegranate Fruit.
Related Articles Prostate Cancer Prevention Through Pomegranate Fruit. Cell Cycle. 2006 Feb 15;5(4) Authors: Malik A, Mukhtar H Prostate cancer (CaP) is the second leading cause of cancer-related deaths among U.S. males with a similar trend in many Western countries. CaP is an ideal candidate disease for chemoprevention because it is typically diagnosed in men over 50 years of age, and thus even a modest delay in disease progression achieved through pharmacological or nutritional intervention could significantly impact the quality of life of these patients. In this regard we and others have proposed the use of dietary antioxidants as candidate CaP chemopreventive agents. The fruit pomegranate derived from the tree Punica granatum has been shown to possess strong antioxidant and anti-inflammatory properties. In a recent study, we showed that pomegranate fruit extract (PFE), through modulations in the cyclin kinase inhibitor-cyclin-dependent kinase machinery, resulted in inhibition of cell growth followed by apoptosis of highly aggressive human prostate carcinoma PC3 cells. These events were associated with alterations in the levels of Bax and Bcl-2 shifting the Bax:Bcl-2 ratio in favor of apoptosis. Further, we showed that oral administration of a human acceptable dose of PFE to athymic nude mice implanted with CWR22Rnu1 cells resulted in significant inhibition of tumor growth with concomitant reduction in secretion of prostate-specific antigen (PSA) in the serum. The outcome of this study could have a direct practical implication and translational relevance to CaP patients, because it suggests that pomegranate consumption may retard CaP progression, which may prolong the survival and quality of life of the patients. PMID: 16479165 [PubMed - as supplied by publisher]

Posted by blogposter at 01:39 PM |

Under pressure: stromal fibroblasts change their ways.


Under pressure: stromal fibroblasts change their ways.
Under pressure: stromal fibroblasts change their ways. Cell. 2005 Dec 16;123(6):985-7 Authors: Bierie B, Moses HL In this issue of Cell, Hill et al. (2005) demonstrate in a mouse model of prostate cancer that the tumor cells can initiate and promote expansion of stromal fibroblasts that lack the tumor-suppressor protein p53 through a paracrine mechanism. This results in selection of highly proliferative fibroblasts associated with the carcinoma that further promote tumor progression. PMID: 16360028 [PubMed - indexed for MEDLINE]

Posted by blogposter at 01:39 PM |

Technology Insight: vaccine therapy for prostate cancer.


Technology Insight: vaccine therapy for prostate cancer.
Related Articles Technology Insight: vaccine therapy for prostate cancer. Nat Clin Pract Urol. 2005 Jan;2(1):44-51 Authors: Vieweg J, Dannull J The lack of effective therapies for advanced prostate cancer mandates continued development of alternative treatment strategies. Insights into the regulation of immune responses and the malignant process have facilitated the emergence of new immune-based strategies, currently under investigation in clinical trials. Like other forms of targeted therapy, cancer vaccines hold the promise of achieving cancer control without inducing overt toxicity. Many prostate cancer vaccines at different phases of development have been tested in clinical trials. Vaccination strategies under consideration include: immunization with defined antigenic preparations such as synthetic peptides, proteins or plasmid DNA; antigen-loaded dendritic cells; manipulated tumor cells; or with viral vectors engineered to express immunogenic genes. Although the underlying mechanisms of immunization may vary, all strategies share the common goal of eliciting immune responses against prostate tumor-associated antigens or of enhancing an otherwise weak antitumor response in the cancer patient. Unlocking the therapeutic potential of cancer vaccines will require a thorough understanding of cellular and molecular mechanisms that modulate the immune response. In this review, we provide an overview of vaccine-based strategies for prostate cancer therapy, discuss their mechanisms of action, and provide relevant clinical trial data. PMID: 16474576 [PubMed - in process]

Posted by blogposter at 01:38 PM |

[Advancement of treatment for prostate cancer.]


[Advancement of treatment for prostate cancer.]
Related Articles [Advancement of treatment for prostate cancer.] Gan To Kagaku Ryoho. 2006 Feb;33(2):178-82 Authors: Hara I The number of prostate cancer patients is rapidly increasing in Japan,as aging people are more common and the lifestyle is more westernized. Another reason is that prostate specific antigen(PSA) is prevalent and PSA test can detect organ-confined prostate cancer in the early stage. In the past, endocrine therapy was the main treatment modality since many prostate cancer patients were diagnosed in the advanced stage. However, endocrine therapy is not suitable for young patients with organ-confined prostate cancer. Surgery and radiation therapy are becoming standard therapy for these patients. Although retropubic radical prostatectomy is widely performed,urinary incontinence and sexual dysfunction are still problems. Other approaches such as laparoscopic rostatectomy, portless endoscopic prostatectomy and perineal prostatectomy are also performed. Radiation therapy is commonly used for organ-confined prostate cancer in Europe and the U.S.A. The advancement in computer technology has made it possible to accumulate enough radiation dose to target without damaging the surrounding organs(3 D conformal, intensity-modulated radiotherapy). Heavy ion particle radiotherapy is also attempted in some institutes.Moreover, brachytherapy can be another choice in radiation therapy. In Japan, only high-dose brachytherapy with (192)Ir has been performed. In July 2003,permanent seed brachytherapy with (121)I was legally approved in Japan, and more organ-confined prostate cancer patients are expected to undergo this treatment. There are several treatment modalities for organ-confined prostate cancer patients these days. Therefore, not only tumor grade and stage, but also patients'lifestyle and thought should be considered in determining treatment. PMID: 16484852 [PubMed - in process]

Posted by blogposter at 01:38 PM |

[Advancement of treatment for prostate cancer.]


[Advancement of treatment for prostate cancer.]
Related Articles [Advancement of treatment for prostate cancer.] Gan To Kagaku Ryoho. 2006 Feb;33(2):178-82 Authors: Hara I The number of prostate cancer patients is rapidly increasing in Japan,as aging people are more common and the lifestyle is more westernized. Another reason is that prostate specific antigen(PSA) is prevalent and PSA test can detect organ-confined prostate cancer in the early stage. In the past, endocrine therapy was the main treatment modality since many prostate cancer patients were diagnosed in the advanced stage. However, endocrine therapy is not suitable for young patients with organ-confined prostate cancer. Surgery and radiation therapy are becoming standard therapy for these patients. Although retropubic radical prostatectomy is widely performed,urinary incontinence and sexual dysfunction are still problems. Other approaches such as laparoscopic rostatectomy, portless endoscopic prostatectomy and perineal prostatectomy are also performed. Radiation therapy is commonly used for organ-confined prostate cancer in Europe and the U.S.A. The advancement in computer technology has made it possible to accumulate enough radiation dose to target without damaging the surrounding organs(3 D conformal, intensity-modulated radiotherapy). Heavy ion particle radiotherapy is also attempted in some institutes.Moreover, brachytherapy can be another choice in radiation therapy. In Japan, only high-dose brachytherapy with (192)Ir has been performed. In July 2003,permanent seed brachytherapy with (121)I was legally approved in Japan, and more organ-confined prostate cancer patients are expected to undergo this treatment. There are several treatment modalities for organ-confined prostate cancer patients these days. Therefore, not only tumor grade and stage, but also patients'lifestyle and thought should be considered in determining treatment. PMID: 16484852 [PubMed - in process]

Posted by blogposter at 01:38 PM |

Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers.


Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers.
Related Articles Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers. Br J Cancer. 2006 Jan 16;94(1):128-35 Authors: Went P, Vasei M, Bubendorf L, Terracciano L, Tornillo L, Riede U, Kononen J, Simon R, Sauter G, Baeuerle PA Epithelial cell adhesion molecule (Ep-CAM; CD326) is used as a target by many immunotherapeutic approaches, but little data are available about Ep-CAM expression in major human malignancies with respect to level, frequency, tumour stage, grade, histologic tumour type and impact on survival. We analysed by immunohistochemical staining tissue microarrays with 4046 primary human carcinoma samples from colon, stomach, prostate and lung cancers for both frequency and intensity of Ep-CAM expression under highly standardised conditions. A total of 3360 samples were analysable. High-level Ep-CAM expression was observed in 97.7% (n=1186) of colon, 90.7% of gastric (n=473), and 87.2% of prostate cancers (n=414), and in 63.9% of lung cancers (n=1287). No detectable Ep-CAM staining was found with only 0.4% of colon, 2.5% of gastric, 1.9% of prostate cancers, and 13.5% of lung cancers. The only significant correlation of Ep-CAM expression with tumour grading was observed in colon cancer where high-level Ep-CAM expression on grade 3 tumours was down to 92.1% (P<0.0001). Adenosquamous and squamous carcinomas of the lung had a lower percentage of high-level Ep-CAM expression compared to adenocarcinomas with 35.4 and 53.6%, respectively, and with 45.5 and 17.3% of tumours being Ep-CAM negative. With the exception of moderately differentiated colon carcinoma, where patients not expressing Ep-CAM on their tumours showed an inferior survival (P=0.0014), correlation of Ep-CAM expression with survival did not reach statistical significance for any of the other cancer indications and subgroups. In conclusion, the data strongly support the notion that Ep-CAM is a prime target for immunotherapies in major human malignancies. This is because the most common human cancers show (i) a low frequency of Ep-CAM-negative tumours, (ii) a high frequency of Ep-CAM expression on cells of a given tumour, and (iii) for most cancers, an insignificant influence of tumour staging, grading and histology on Ep-CAM expression. PMID: 16404366 [PubMed - indexed for MEDLINE]

Posted by blogposter at 01:38 PM |

Targeting of cytotoxic luteinizing hormone-releasing hormone analogs to breast, ovarian, endometrial, and prostate cancers.


Targeting of cytotoxic luteinizing hormone-releasing hormone analogs to breast, ovarian, endometrial, and prostate cancers.
Related Articles Targeting of cytotoxic luteinizing hormone-releasing hormone analogs to breast, ovarian, endometrial, and prostate cancers. Biol Reprod. 2005 Nov;73(5):851-9 Authors: Nagy A, Schally AV Targeted chemotherapy is a modern approach aimed at increasing the efficacy of systemic chemotherapy and reducing its side effects. The peptide receptors expressed primarily on cancerous cells can serve as targets for a selective destruction of malignant tumors. Binding sites for LHRH (now known in genome and microarray databases as GNRH1), were found on 52% of human breast cancers, about 80% of human ovarian and endometrial cancers, and 86% of human prostatic carcinoma specimens. Because LHRH receptors are not expressed on most normal tissues, they represent a specific target for cancer chemotherapy with antineoplastic agents linked to an LHRH vector molecule. To test the efficacy of targeted chemotherapy based on LHRH analogs, we recently developed a cytotoxic analog of LHRH, designated AN-152, which consists of [D-Lys6]LHRH covalently linked to one of the most widely used chemotherapeutic agents, doxorubicin (DOX). In addition, we designed and synthesized a highly active derivative of DOX, 2-pyrrolino-DOX (AN-201), which is 500-1000 times more potent than DOX in vitro. AN-201 is active against tumors resistant to DOX, and noncardiotoxic. As in the case of DOX, AN-201 was coupled to carrier peptide [D-Lys6]LHRH to form a superactive targeted cytotoxic LHRH analog, AN-207. Both AN-152 and AN-207 can effectively inhibit the growth of LHRH receptor-positive human breast, ovarian, endometrial, and prostate cancers xenografted into nude mice. DOX-containing cytotoxic LHRH analog AN-152 is scheduled for clinical phase I/IIa trials in patients with advanced ovarian and breast cancers in 2005. PMID: 16033997 [PubMed - indexed for MEDLINE]

Posted by blogposter at 01:37 PM |

Development and evaluation of a prostate sexual rehabilitation clinic: a pilot project.


Development and evaluation of a prostate sexual rehabilitation clinic: a pilot project.
Related Articles Development and evaluation of a prostate sexual rehabilitation clinic: a pilot project. BJU Int. 2005 Dec;96(9):1360-4 Authors: Davison BJ, Elliott S, Ekland M, Griffin S, Wiens K OBJECTIVE: To evaluate a sexual rehabilitation service for men with prostate cancer and to use these results to inform the development of future care. PATIENTS AND METHODS: The study participants included 155 men with prostate cancer referred to a sexual rehabilitation clinic by their urologists or radiation oncologists, of whom the partners of 58 were in attendance. Questionnaires to measure sexual function and positive feelings towards the partner were completed before the clinic visit; and for satisfaction with the clinic service immediately after the appointment; and for sexual function, positive feelings towards the partner, and satisfaction with treatments at 4 months afterward. RESULTS: Ninety patients completed the 4-month evaluation, of whom 35 were couples. Enhancement of erection and understanding sexual changes related to treatment were the two main concerns of patients. Phosphodiesterase-5 inhibitors and intracavernosal injections were the treatments of choice. Compared with partners, patients had significantly greater positive feelings towards their partners at both measurement times and were more satisfied with their prescribed treatment. The total scores on sexual function were significantly higher at 4 months. CONCLUSIONS: These results support the need to include partners as a necessary part of these men's sexual rehabilitation. A structured follow-up is necessary to monitor the success of treatment and to document the quality of erection. PMID: 16287458 [PubMed - indexed for MEDLINE]

Posted by blogposter at 01:37 PM |

Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers.


Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers.
Related Articles Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers. Br J Cancer. 2006 Jan 16;94(1):128-35 Authors: Went P, Vasei M, Bubendorf L, Terracciano L, Tornillo L, Riede U, Kononen J, Simon R, Sauter G, Baeuerle PA Epithelial cell adhesion molecule (Ep-CAM; CD326) is used as a target by many immunotherapeutic approaches, but little data are available about Ep-CAM expression in major human malignancies with respect to level, frequency, tumour stage, grade, histologic tumour type and impact on survival. We analysed by immunohistochemical staining tissue microarrays with 4046 primary human carcinoma samples from colon, stomach, prostate and lung cancers for both frequency and intensity of Ep-CAM expression under highly standardised conditions. A total of 3360 samples were analysable. High-level Ep-CAM expression was observed in 97.7% (n=1186) of colon, 90.7% of gastric (n=473), and 87.2% of prostate cancers (n=414), and in 63.9% of lung cancers (n=1287). No detectable Ep-CAM staining was found with only 0.4% of colon, 2.5% of gastric, 1.9% of prostate cancers, and 13.5% of lung cancers. The only significant correlation of Ep-CAM expression with tumour grading was observed in colon cancer where high-level Ep-CAM expression on grade 3 tumours was down to 92.1% (P<0.0001). Adenosquamous and squamous carcinomas of the lung had a lower percentage of high-level Ep-CAM expression compared to adenocarcinomas with 35.4 and 53.6%, respectively, and with 45.5 and 17.3% of tumours being Ep-CAM negative. With the exception of moderately differentiated colon carcinoma, where patients not expressing Ep-CAM on their tumours showed an inferior survival (P=0.0014), correlation of Ep-CAM expression with survival did not reach statistical significance for any of the other cancer indications and subgroups. In conclusion, the data strongly support the notion that Ep-CAM is a prime target for immunotherapies in major human malignancies. This is because the most common human cancers show (i) a low frequency of Ep-CAM-negative tumours, (ii) a high frequency of Ep-CAM expression on cells of a given tumour, and (iii) for most cancers, an insignificant influence of tumour staging, grading and histology on Ep-CAM expression. PMID: 16404366 [PubMed - indexed for MEDLINE]

Posted by blogposter at 01:37 PM |

February 15, 2006

Ovarian Cancer's Deadliness


Ovarian Cancer's Deadliness
Washington Post - Before she died last month, Coretta Scott King turned to a Mexican alternative medicine clinic for treatment -- never begun -- of her stage III ovarian cancer. Whatever her reasons, with that move, the widow of slain civil rights icon Martin Luther

Posted by blogposter at 01:44 PM |

Prostate Cancer Screening - Clinical and physical determinants for toxicity of 125-I seed prostate brachytherapy.


Clinical and physical determinants for toxicity of 125-I seed prostate brachytherapy.
Related Articles Clinical and physical determinants for toxicity of 125-I seed prostate brachytherapy. J Urol. 2005 Nov;174(5):1969-70 Authors: Albertsen PC PMID: 16217368 [PubMed - indexed for MEDLINE]

Posted by blogposter at 01:44 PM |

Do the Benefits of Finasteride Outweigh the Risks in the Prostate Cancer Prevention Trial?


Do the Benefits of Finasteride Outweigh the Risks in the Prostate Cancer Prevention Trial?
Related Articles Do the Benefits of Finasteride Outweigh the Risks in the Prostate Cancer Prevention Trial? J Urol. 2006 Mar;175(3):934-938 Authors: Grover S, Lowensteyn I, Hajek D, Trachtenberg J, Coupal L, Marchand S PURPOSE: The Prostate Cancer Prevention Trial demonstrated that finasteride could reduce the incidence of prostate cancer by 25%. However, its use was also associated with an increased risk of high grade cancer resulting in uncertainty surrounding the net benefits of therapy. MATERIALS AND METHODS: We used the Montreal Prostate Cancer Model, a validated Markov model of prostate cancer progression, to compare the forecasted survival in treated and untreated men. The conditions of the model were varied to reflect different assumptions about whether the cancer grade difference observed in the PCPT was real or a treatment associated artifact, and whether cancers detected on end of study biopsies were clinically significant. RESULTS: For a hypothetical cohort of 1,000, 62-year-old men treated with finasteride, an increased survival of 140 life-years (0.14 years per individual) is forecasted if all diagnosed cancers are considered. If tumor grade differences are held to be artifactual, the forecasted benefits increase to 200 life-years. However, if the tumor grade difference is real and only clinically detected cancers are considered, estimated increased survival is only 20 life-years (0.02 years per individual). CONCLUSIONS: The primary prevention of prostate cancer with finasteride looks promising. However, at the present time it should only be considered with caution until we have answered critical questions surrounding the difference in cancer grade observed in the PCPT and the clinical significance of cancers detected on protocol directed end of study biopsies. PMID: 16469585 [PubMed - as supplied by publisher]

Posted by blogposter at 01:43 PM |

Stable suppression of tumorigenicity by Pin1-targeted RNA interference in prostate cancer.


Stable suppression of tumorigenicity by Pin1-targeted RNA interference in prostate cancer.
Related Articles Stable suppression of tumorigenicity by Pin1-targeted RNA interference in prostate cancer. Clin Cancer Res. 2005 Oct 15;11(20):7523-31 Authors: Ryo A, Uemura H, Ishiguro H, Saitoh T, Yamaguchi A, Perrem K, Kubota Y, Lu KP, Aoki I PURPOSE: The peptidyl-prolyl isomrase Pin1 plays a catalytic role in oncogenesis in solid cancers, including prostate cancer. In the present study, we sought to determine the potential of Pin1-targeted gene silencing in inhibiting cellular growth and tumorigenicity in prostate cancer. EXPERIMENTAL DESIGN: A retrovirus-mediated RNA interference targeting Pin1 was expressed in PC3 and LNCaP cells, and cell growth and several transformed properties were investigated. RESULTS: The stable expression of Pin1-specific small interfering RNA constructs in PC3 and LNCaP cells significantly reduced cellular proliferation, colony formation, migration, and invasion but strongly enhanced the apoptotic response induced by serum depletion or treatment with anticancer agents. Furthermore, Pin1 depletion significantly suppressed tumorigenic potential in athymic mice, resulting in the inhibition of both tumor growth and angiogeneisis. CONCLUSIONS: These results strongly suggest that Pin1 plays an important role not only in tumorigenesis but also in the maintenance of the transformed phenotype in prostate cancer cells. Hence, Pin1 may serve as a promising therapeutic target, particularly for recurrent prostate tumors. PMID: 16243827 [PubMed - indexed for MEDLINE]

Posted by blogposter at 01:43 PM |

Technology Insight: vaccine therapy for prostate cancer.


Technology Insight: vaccine therapy for prostate cancer.
Related Articles Technology Insight: vaccine therapy for prostate cancer. Nat Clin Pract Urol. 2005 Jan;2(1):44-51 Authors: Vieweg J, Dannull J The lack of effective therapies for advanced prostate cancer mandates continued development of alternative treatment strategies. Insights into the regulation of immune responses and the malignant process have facilitated the emergence of new immune-based strategies, currently under investigation in clinical trials. Like other forms of targeted therapy, cancer vaccines hold the promise of achieving cancer control without inducing overt toxicity. Many prostate cancer vaccines at different phases of development have been tested in clinical trials. Vaccination strategies under consideration include: immunization with defined antigenic preparations such as synthetic peptides, proteins or plasmid DNA; antigen-loaded dendritic cells; manipulated tumor cells; or with viral vectors engineered to express immunogenic genes. Although the underlying mechanisms of immunization may vary, all strategies share the common goal of eliciting immune responses against prostate tumor-associated antigens or of enhancing an otherwise weak antitumor response in the cancer patient. Unlocking the therapeutic potential of cancer vaccines will require a thorough understanding of cellular and molecular mechanisms that modulate the immune response. In this review, we provide an overview of vaccine-based strategies for prostate cancer therapy, discuss their mechanisms of action, and provide relevant clinical trial data. PMID: 16474576 [PubMed - in process]

Posted by blogposter at 01:43 PM |

Robotic extraperitoneal radical prostatectomy: an alternative approach.


Robotic extraperitoneal radical prostatectomy: an alternative approach.
Related Articles Robotic extraperitoneal radical prostatectomy: an alternative approach. J Urol. 2006 Mar;175(3):945-51 Authors: Joseph JV, Rosenbaum R, Madeb R, Erturk E, Patel HR PURPOSE: Laparoscopic radical prostatectomy with or without a robot has been increasingly performed worldwide, primarily using a transperitoneal approach. We report our experience with daVinci(R) robot assisted extraperitoneal laparoscopic radical prostatectomy. MATERIALS AND METHODS: A total of 325 patients underwent robot assisted extraperitoneal laparoscopic radical prostatectomy for clinically localized prostate cancer at our center during a 2-year period. Perioperative data, and oncological and functional results were prospectively recorded. RESULTS: Perioperative demographics included mean age, PSA and Gleason score, which were 60 years (range 42 to 76), 6.6 ng/ml (range 0.6 to 26) and 6 (range 5 to 9), respectively. Preoperative clinical stage was 81%, 16% and 3% for T1c, T2a and T2b, respectively. Average total operative time was 130 minutes (range 80 to 480). Intraoperative data included a mean blood loss of 196 cc with no open conversions. Bilateral, unilateral and nonnerve sparing prostatectomy was performed in 70%, 24% and 6% of patients, respectively. Of the patients 96% were discharged home within 8 to 23 hours of surgery. Pathological stage was pT2a, pT2b, pT3a and pT3b in 18%, 63%, 14% and 5% of all radical prostatectomy specimens, respectively, with an overall positive surgical margin rate of 13%. Two of 92 patients had positive nodal disease after lymph node dissection. Continence and erectile function were measured. CONCLUSIONS: The extraperitoneal approach offers the advantages of improved dexterity and visualization of the robot, while avoiding the abdominal cavity and potential associated morbidity. As surgeons gain more experience with this new technology, the extraperitoneal approach simulating the standard open retropubic technique is likely to gain popularity. PMID: 16469589 [PubMed - in process]

Posted by blogposter at 01:43 PM |

Rising prostate-specific antigen after primary prostate cancer therapy.


Rising prostate-specific antigen after primary prostate cancer therapy.
Related Articles Rising prostate-specific antigen after primary prostate cancer therapy. Nat Clin Pract Urol. 2005 Apr;2(4):174-82 Authors: Ward JF, Moul JW An estimated 20-40% of men experience a biochemical recurrence within 10 years of definitive prostate cancer treatment. No single prostate-specific antigen (PSA) value is invariably associated with clinical metastasis or cancer-specific survival; PSA kinetics might prove to be a more important predictor of eventual progression-free survival and cancer-specific survival than absolute PSA level alone. With only one-third of patients progressing from biochemical recurrence to clinical disease, therapeutic morbidity should not outpace risk of disease progression. Salvage radiation therapy following radical prostatectomy has widely variable long-term biochemical control rates (from 18 to 64% depending on the follow-up period). Early hormonal therapy delivered as castration or complete androgen blockade might delay clinical metastasis in patients with high-risk pathologic disease; however, the adverse effects and morbidity of long-term therapy must not be underestimated. Non-steroidal antiandrogens as monotherapy for early biochemical recurrence, particularly for younger men who wish to preserve their libido and sexual potency, have received considerable attention, but there are conflicting data on long-term outcomes. Because of their favorable adverse-effect profiles, non-traditional therapies that exert localized hormonal or cellular effects are receiving considerable attention for treatment of early, PSA-only recurrence. Data from animal models provide a rationale for the use of these therapies, but there is a lack of evidence to support prolongation of progression-free survival or cancer-specific survival. PMID: 16474760 [PubMed - in process]

Posted by blogposter at 01:42 PM |

Chemosensitization of hormone-refractory prostate cancer cells by curcumin to TRAIL-induced apoptosis.


Chemosensitization of hormone-refractory prostate cancer cells by curcumin to TRAIL-induced apoptosis.
Related Articles Chemosensitization of hormone-refractory prostate cancer cells by curcumin to TRAIL-induced apoptosis. J Exp Ther Oncol. 2005;5(2):81-91 Authors: Deeb DD, Jiang H, Gao X, Divine G, Dulchavsky SA, Gautam SC Failure to undergo apoptosis has been implicated in the resistance of tumor cells to anticancer therapies. Promotion of apoptosis in tumor cells could potentially increase the efficacy of conventional treatment regimens and improve prognosis. Prostate cancer cells are generally resistant to induction of apoptosis by anticancer agents and death ligands. We investigated the sensitization of prostate cancer cell lines by curcumin (diferuloyl-methane) to TNF-related apoptosis inducing ligand (TRAIL)-induced apoptosis. Prostate cancer cells treated with curcumin or TRAIL or curcumin and TRAIL together were assessed for induction of apoptosis and pathway of apoptosis was determined from the activation of procaspases and release of cytochrome c from mitochondria. Curcumin sensitized LNCaP, DU145 and PC3 tumor cell lines to TRAIL. Combined curcumin and TRAIL treatment produced the most loss of viable cells by inducing apoptosis as revealed by accumulation of hypodiploid cells in sub-G1 phase, enhanced annexin V binding, DNA fragmentation, cleavage of procaspases-3, -8, and 9, truncation of proapoptotic Bid, and release of cytochrome c from mitochondria. Tumor cells expressed constitutively active NF-kappaB and sensitization to TRAIL involved inhibition of NF-kappaB by curcumin. These findings suggest that combined curcumin/TRAIL chemo-immunotherapy may be a beneficial adjunct to the standard therapeutic regimens for prostate cancer. PMID: 16471035 [PubMed - in process]

Posted by blogposter at 01:42 PM |

Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors.


Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors.
Related Articles Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors. J Clin Oncol. 2005 Dec 1;23(34):8580-7 Authors: Bamias A, Kastritis E, Bamia C, Moulopoulos LA, Melakopoulos I, Bozas G, Koutsoukou V, Gika D, Anagnostopoulos A, Papadimitriou C, Terpos E, Dimopoulos MA PURPOSE: Osteonecrosis of the jaw (ONJ) has been associated recently with the use of pamidronate and zoledronic acid. We studied the incidence, characteristics, and risk factors for the development of ONJ among patients treated with bisphosphonates for bone metastases. PATIENTS AND METHODS: ONJ was assessed prospectively since July 2003. The first bisphosphonate treatment among patients with ONJ was administered in 1997. Two hundred fifty-two patients who received bisphosphonates since January 1997 were included in this analysis. RESULTS: Seventeen patients (6.7%) developed ONJ: 11 of 111 (9.9%) with multiple myeloma, two of 70 (2.9%) with breast cancer, three of 46 (6.5%) with prostate cancer, and one of 25 (4%) with other neoplasms (P = .289). The median number of treatment cycles and time of exposure to bisphosphonates were 35 infusions and 39.3 months for patients with ONJ compared with 15 infusions (P < .001) and 19 months (P = .001), respectively, for patients with no ONJ. The incidence of ONJ increased with time to exposure from 1.5% among patients treated for 4 to 12 months to 7.7% for treatment of 37 to 48 months. The cumulative hazard was significantly higher with zoledronic acid compared with pamidronate alone or pamidronate and zoledronic acid sequentially (P < .001). All but two patients with ONJ had a history of dental procedures within the last year or use of dentures. CONCLUSION: The use of bisphosphonates seems to be associated with the development of ONJ. Length of exposure seems to be the most important risk factor for this complication. The type of bisphosphonate may play a role and previous dental procedures may be a precipitating factor. PMID: 16314620 [PubMed - indexed for MEDLINE]

Posted by blogposter at 01:42 PM |

Intra-operative prostate examination: predictive value and effect on margin status.


Intra-operative prostate examination: predictive value and effect on margin status.
Related Articles Intra-operative prostate examination: predictive value and effect on margin status. BJU Int. 2005 Nov;96(7):1005-8 Authors: Rapp DE, Orvieto MA, Lucioni A, Gong EM, Shalhav AL, Brendler CB OBJECTIVE: To evaluate the ability of intra-operative prostate examination (IOPE) to predict extraprostatic extension (EPE) and its effect on margin status in the region of the neurovascular bundle (NVB) when combined with wide excision. PATIENTS AND METHODS: We retrospectively reviewed 403 patients with clinical stage T1c prostate adenocarcinoma undergoing radical retropubic prostatectomy (RRP). All patients had IOPE during RRP, and those with palpable abnormalities in the region of the NVB underwent wide excision. Pathological outcomes were analysed. RESULTS: Of 403 patients, 49 (12%) had a palpable abnormality in the region of the NVB. After wide excision, 18 (37%) of these 49 patients were found to have EPE at the site of the palpable abnormality; with wide excision of the NVB, only one of these 18 patients (6%) had a corresponding positive surgical margin (PSM). In 354 patients with a normal IOPE and who underwent bilateral NVB preservation, 30 were found to have EPE in the region of the NVB. The PSM rate in this subset was 23% (seven of 30). The positive predictive value of IOPE for detecting EPE was 37%. CONCLUSION: IOPE detects abnormalities in 12% of patients with preoperative stage T1c prostate cancer. Although the predictive value of this test is limited, IOPE may decrease PSMs in a subset of patients with EPE in the region of the NVB. The present study reaffirms the value of IOPE for assessing the risk of extraprostatic disease, and for guiding surgical management. PMID: 16225517 [PubMed - indexed for MEDLINE]

Posted by blogposter at 01:42 PM |

Advanced refractory prostate cancer: new treatment trial.


Advanced refractory prostate cancer: new treatment trial.
Related Articles Advanced refractory prostate cancer: new treatment trial. Nat Clin Pract Urol. 2004 Dec;1(2):64-5 Authors: PMID: 16474510 [PubMed - in process]

Posted by blogposter at 01:41 PM |

February 14, 2006

Prostate Cancer Screening - Correlation between LUTS (AUA-SS) and erectile dysfunction (SHIM) in an age-matched racially diverse male population: data from the prostate cancer awareness week (PCAW).


Correlation between LUTS (AUA-SS) and erectile dysfunction (SHIM) in an age-matched racially diverse male population: data from the prostate cancer awareness week (PCAW).
Related Articles Correlation between LUTS (AUA-SS) and erectile dysfunction (SHIM) in an age-matched racially diverse male population: data from the prostate cancer awareness week (PCAW). J Urol. 2005 Nov;174(5):1940 Authors: Seftel A PMID: 16217355 [PubMed - indexed for MEDLINE]

Posted by blogposter at 09:10 PM |

HER-2/neu peptide vaccine for the prevention of prostate cancer recurrence.


HER-2/neu peptide vaccine for the prevention of prostate cancer recurrence.
Related Articles HER-2/neu peptide vaccine for the prevention of prostate cancer recurrence. Nat Clin Pract Urol. 2006 Jan;3(1):6 Authors: Sole K PMID: 16474473 [PubMed - in process]

Posted by blogposter at 09:10 PM |

[Expression of Trp-p8 in prostate and its significant]


[Expression of Trp-p8 in prostate and its significant]
Related Articles [Expression of Trp-p8 in prostate and its significant] Zhonghua Yi Xue Za Zhi. 2005 Jun 15;85(22):1571-3 Authors: Wang HP, Yang XR, Wang XH, Ma SL PMID: 16179122 [PubMed - indexed for MEDLINE]

Posted by blogposter at 09:10 PM |

Technology Insight: vaccine therapy for prostate cancer.


Technology Insight: vaccine therapy for prostate cancer.
Related Articles Technology Insight: vaccine therapy for prostate cancer. Nat Clin Pract Urol. 2005 Jan;2(1):44-51 Authors: Vieweg J, Dannull J The lack of effective therapies for advanced prostate cancer mandates continued development of alternative treatment strategies. Insights into the regulation of immune responses and the malignant process have facilitated the emergence of new immune-based strategies, currently under investigation in clinical trials. Like other forms of targeted therapy, cancer vaccines hold the promise of achieving cancer control without inducing overt toxicity. Many prostate cancer vaccines at different phases of development have been tested in clinical trials. Vaccination strategies under consideration include: immunization with defined antigenic preparations such as synthetic peptides, proteins or plasmid DNA; antigen-loaded dendritic cells; manipulated tumor cells; or with viral vectors engineered to express immunogenic genes. Although the underlying mechanisms of immunization may vary, all strategies share the common goal of eliciting immune responses against prostate tumor-associated antigens or of enhancing an otherwise weak antitumor response in the cancer patient. Unlocking the therapeutic potential of cancer vaccines will require a thorough understanding of cellular and molecular mechanisms that modulate the immune response. In this review, we provide an overview of vaccine-based strategies for prostate cancer therapy, discuss their mechanisms of action, and provide relevant clinical trial data. PMID: 16474576 [PubMed - in process]

Posted by blogposter at 09:10 PM |

Salvage surgery in prostate cancer: assessment of rectal wall invasion.


Salvage surgery in prostate cancer: assessment of rectal wall invasion.
Related Articles Salvage surgery in prostate cancer: assessment of rectal wall invasion. Nat Clin Pract Urol. 2005 Jan 16;2(1):5 Authors: PMID: 16474556 [PubMed - as supplied by publisher]

Posted by blogposter at 09:09 PM |

Is pretreatment PSA velocity associated with prostate-cancer-specific mortality rate after radiotherapy?


Is pretreatment PSA velocity associated with prostate-cancer-specific mortality rate after radiotherapy?
Related Articles Is pretreatment PSA velocity associated with prostate-cancer-specific mortality rate after radiotherapy? Nat Clin Pract Urol. 2006 Jan;3(1):12-3 Authors: Pollack A PMID: 16474485 [PubMed - in process]

Posted by blogposter at 09:09 PM |

Chemosensitization of hormone-refractory prostate cancer cells by curcumin to TRAIL-induced apoptosis.


Chemosensitization of hormone-refractory prostate cancer cells by curcumin to TRAIL-induced apoptosis.
Related Articles Chemosensitization of hormone-refractory prostate cancer cells by curcumin to TRAIL-induced apoptosis. J Exp Ther Oncol. 2005;5(2):81-91 Authors: Deeb DD, Jiang H, Gao X, Divine G, Dulchavsky SA, Gautam SC Failure to undergo apoptosis has been implicated in the resistance of tumor cells to anticancer therapies. Promotion of apoptosis in tumor cells could potentially increase the efficacy of conventional treatment regimens and improve prognosis. Prostate cancer cells are generally resistant to induction of apoptosis by anticancer agents and death ligands. We investigated the sensitization of prostate cancer cell lines by curcumin (diferuloyl-methane) to TNF-related apoptosis inducing ligand (TRAIL)-induced apoptosis. Prostate cancer cells treated with curcumin or TRAIL or curcumin and TRAIL together were assessed for induction of apoptosis and pathway of apoptosis was determined from the activation of procaspases and release of cytochrome c from mitochondria. Curcumin sensitized LNCaP, DU145 and PC3 tumor cell lines to TRAIL. Combined curcumin and TRAIL treatment produced the most loss of viable cells by inducing apoptosis as revealed by accumulation of hypodiploid cells in sub-G1 phase, enhanced annexin V binding, DNA fragmentation, cleavage of procaspases-3, -8, and 9, truncation of proapoptotic Bid, and release of cytochrome c from mitochondria. Tumor cells expressed constitutively active NF-kappaB and sensitization to TRAIL involved inhibition of NF-kappaB by curcumin. These findings suggest that combined curcumin/TRAIL chemo-immunotherapy may be a beneficial adjunct to the standard therapeutic regimens for prostate cancer. PMID: 16471035 [PubMed - in process]

Posted by blogposter at 09:09 PM |

Promising chemotherapy regimen for hormone-refractory prostate cancer.


Promising chemotherapy regimen for hormone-refractory prostate cancer.
Related Articles Promising chemotherapy regimen for hormone-refractory prostate cancer. Nat Clin Pract Urol. 2006 Jan;3(1):8-9 Authors: Osborne T PMID: 16474476 [PubMed - in process]

Posted by blogposter at 09:09 PM |

Clinical staging of prostate cancer: a computer-simulated study of transperineal prostate biopsy.


Clinical staging of prostate cancer: a computer-simulated study of transperineal prostate biopsy.
Related Articles Clinical staging of prostate cancer: a computer-simulated study of transperineal prostate biopsy. BJU Int. 2005 Nov;96(7):999-1004 Authors: Crawford ED, Wilson SS, Torkko KC, Hirano D, Stewart JS, Brammell C, Wilson RS, Kawata N, Sullivan H, Lucia MS, Werahera PN OBJECTIVE: To identify the precise location of prostate cancer within the gland and thus possibly permit more aggressive therapy of the lesion, while potentially sparing the noncancerous gland from ablative therapy. MATERIALS AND METHODS: Three-dimensional "solid" computer models were reconstructed for 86 autopsy specimens and 20 stage T1c radical prostatectomy specimens. Transperineal biopsies were simulated for grid sizes of 5-mm (method A) and 10-mm (method B) with an 18 G, 23-mm long biopsy needle. One or two biopsies per grid point were obtained for a total of 12-108 biopsies, depending on the size of the prostate. Clinically threatening cancers were defined as having volumes of > or = 0.5 mL or Gleason sum > or = 7. RESULTS: Method A detected significantly more carcinomas than method B in both the autopsy and prostatectomy specimens (autopsy, 72 vs 51; prostatectomy, 50 vs 32, both P < 0.001). Method A also detected more clinically threatening cancers found at autopsy (38/40 vs 31/40, P = 0.008). Among autopsy patients with negative sextant biopsies whose disease was localized to one side, method A detected 72% and method B detected 29-43% (P < 0.001). CONCLUSIONS: The results of this computer simulation show that 5- and 10-mm grid biopsies detect three-quarters and a third, respectively, at autopsy, of patients with the disease localized to one side of the prostate, which may be useful when planning highly selective ablative treatments in the future. PMID: 16225516 [PubMed - indexed for MEDLINE]

Posted by blogposter at 09:09 PM |

An educational workshop on the early detection of prostate cancer--a before-after evaluation.


An educational workshop on the early detection of prostate cancer--a before-after evaluation.
Related Articles An educational workshop on the early detection of prostate cancer--a before-after evaluation. Aust Fam Physician. 2005 Oct;34(10):889-91 Authors: Steginga SK, Pinnock C, Baade PD, Jackson C, Green A, Preston J, Heathcote P, McAvoy B PMID: 16217583 [PubMed - indexed for MEDLINE]

Posted by blogposter at 09:08 PM |

Ovarian Cancer's Deadliness


Ovarian Cancer's Deadliness
Washington Post - Before she died last month, Coretta Scott King turned to a Mexican alternative medicine clinic for treatment -- never begun -- of her stage III ovarian cancer. Whatever her reasons, with that move, the widow of slain civil rights icon Martin Luther

Posted by blogposter at 02:50 PM |

Prostate Cancer Screening - Cancer chemotherapy by deoxynucleotide depletion and E2F-1 elevation.


Cancer chemotherapy by deoxynucleotide depletion and E2F-1 elevation.
Related Articles Cancer chemotherapy by deoxynucleotide depletion and E2F-1 elevation. Cancer Res. 2005 Sep 1;65(17):7809-14 Authors: Wang A, Li CJ, Reddy PV, Pardee AB We propose that the lethality of commonly used anticancer drugs, e.g., methotrexate and cis-platinum are due, at least in part, to an increase of the E2F-1-mediated apoptotic cascade. The drugs directly or indirectly decrease deoxynucleoside triphosphates. The E2F family acts to provide control of S phase by transcribing genes required for deoxynucleoside triphosphate and DNA synthesis. Thus, a mechanism for control of E2F-1 is essential, a signal safeguarding against aberrant or uncontrolled cell proliferation. We have proposed a feedback control by NTPs that down-regulates E2F-1. Here, we provide evidence in support of this hypothesis. PMID: 16140949 [PubMed - indexed for MEDLINE]

Posted by blogposter at 02:49 PM |

Do the Benefits of Finasteride Outweigh the Risks in the Prostate Cancer Prevention Trial?


Do the Benefits of Finasteride Outweigh the Risks in the Prostate Cancer Prevention Trial?
Related Articles Do the Benefits of Finasteride Outweigh the Risks in the Prostate Cancer Prevention Trial? J Urol. 2006 Mar;175(3):934-938 Authors: Grover S, Lowensteyn I, Hajek D, Trachtenberg J, Coupal L, Marchand S PURPOSE: The Prostate Cancer Prevention Trial demonstrated that finasteride could reduce the incidence of prostate cancer by 25%. However, its use was also associated with an increased risk of high grade cancer resulting in uncertainty surrounding the net benefits of therapy. MATERIALS AND METHODS: We used the Montreal Prostate Cancer Model, a validated Markov model of prostate cancer progression, to compare the forecasted survival in treated and untreated men. The conditions of the model were varied to reflect different assumptions about whether the cancer grade difference observed in the PCPT was real or a treatment associated artifact, and whether cancers detected on end of study biopsies were clinically significant. RESULTS: For a hypothetical cohort of 1,000, 62-year-old men treated with finasteride, an increased survival of 140 life-years (0.14 years per individual) is forecasted if all diagnosed cancers are considered. If tumor grade differences are held to be artifactual, the forecasted benefits increase to 200 life-years. However, if the tumor grade difference is real and only clinically detected cancers are considered, estimated increased survival is only 20 life-years (0.02 years per individual). CONCLUSIONS: The primary prevention of prostate cancer with finasteride looks promising. However, at the present time it should only be considered with caution until we have answered critical questions surrounding the difference in cancer grade observed in the PCPT and the clinical significance of cancers detected on protocol directed end of study biopsies. PMID: 16469585 [PubMed - as supplied by publisher]

Posted by blogposter at 02:49 PM |

[Expression of Trp-p8 in prostate and its significant]


[Expression of Trp-p8 in prostate and its significant]
Related Articles [Expression of Trp-p8 in prostate and its significant] Zhonghua Yi Xue Za Zhi. 2005 Jun 15;85(22):1571-3 Authors: Wang HP, Yang XR, Wang XH, Ma SL PMID: 16179122 [PubMed - indexed for MEDLINE]

Posted by blogposter at 02:49 PM |

Technology Insight: vaccine therapy for prostate cancer.


Technology Insight: vaccine therapy for prostate cancer.
Related Articles Technology Insight: vaccine therapy for prostate cancer. Nat Clin Pract Urol. 2005 Jan;2(1):44-51 Authors: Vieweg J, Dannull J The lack of effective therapies for advanced prostate cancer mandates continued development of alternative treatment strategies. Insights into the regulation of immune responses and the malignant process have facilitated the emergence of new immune-based strategies, currently under investigation in clinical trials. Like other forms of targeted therapy, cancer vaccines hold the promise of achieving cancer control without inducing overt toxicity. Many prostate cancer vaccines at different phases of development have been tested in clinical trials. Vaccination strategies under consideration include: immunization with defined antigenic preparations such as synthetic peptides, proteins or plasmid DNA; antigen-loaded dendritic cells; manipulated tumor cells; or with viral vectors engineered to express immunogenic genes. Although the underlying mechanisms of immunization may vary, all strategies share the common goal of eliciting immune responses against prostate tumor-associated antigens or of enhancing an otherwise weak antitumor response in the cancer patient. Unlocking the therapeutic potential of cancer vaccines will require a thorough understanding of cellular and molecular mechanisms that modulate the immune response. In this review, we provide an overview of vaccine-based strategies for prostate cancer therapy, discuss their mechanisms of action, and provide relevant clinical trial data. PMID: 16474576 [PubMed - in process]

Posted by blogposter at 02:48 PM |

Predictors of prostate cancer tissue acquisition by an undirected core bone marrow biopsy in metastatic castration-resistant prostate cancer--a Cancer and Leukemia Group B study.


Predictors of prostate cancer tissue acquisition by an undirected core bone marrow biopsy in metastatic castration-resistant prostate cancer--a Cancer and Leukemia Group B study.
Related Articles Predictors of prostate cancer tissue acquisition by an undirected core bone marrow biopsy in metastatic castration-resistant prostate cancer--a Cancer and Leukemia Group B study. Clin Cancer Res. 2005 Nov 15;11(22):8109-13 Authors: Ross RW, Halabi S, Ou SS, Rajeshkumar BR, Woda BA, Vogelzang NJ, Small EJ, Taplin ME, Kantoff PW, PURPOSE: Analyzing metastatic prostate cancer tissue is of considerable importance in evaluating new targeted agents, yet acquiring such tissue presents a challenge due to the predominance of bone metastases. We assessed factors predicting a successful tumor harvest from bone marrow biopsies (BMBx) in castration-resistant metastatic prostate cancer patients. MATERIAL AND METHODS: Data from Cancer and Leukemia Group B study 9663 were reviewed. Bone marrow biopsies were obtained from 184 patients who underwent an office-based, unguided bone marrow biopsy of the posterior iliac crest. RESULTS: Forty-seven of the 184 patients (25.5%) had a positive bone marrow biopsy. When considered in a multivariate logistic regression analysis, lower hemoglobin levels, higher alkaline phosphatase, and higher lactate dehydrogenase levels were associated with a higher likelihood of a positive BMBx. The median survival time was 11 months (95% confidence interval, 8.0-14) among patients with a positive BMBx compared with 23 months (95% confidence interval, 19-27) with a negative BMBx. The median time to progression and time to prostate-specific antigen progression-free survival were also significantly decreased among positive BMBx patients. No patients with a positive BMBx survived beyond 3 years, whereas 11 of the 137 patients with a negative BMBx survived beyond 5 years. DISCUSSION: Using common laboratory values, a specific patient cohort can be defined from whom the yield of a nonguided BMBx would be high enough to justify this approach. For studies that require broader entry criteria, a more directed approach with image guidance is recommended. PMID: 16299243 [PubMed - indexed for MEDLINE]

Posted by blogposter at 02:48 PM |

Locally advanced prostate cancer treated with radiotherapy and androgen deprivation.


Locally advanced prostate cancer treated with radiotherapy and androgen deprivation.
Related Articles Locally advanced prostate cancer treated with radiotherapy and androgen deprivation. Nat Clin Pract Urol. 2005 Jun;2(6):304-8 Authors: Kirby R Background A 60-year-old man, with a 2-year history of lower-urinary-tract symptoms (frequency and reduced flow) and perineal discomfort, presented with a serum PSA level of 42 ng/ml.Investigations Digital rectal examination, transrectal ultrasound, prostate biopsy (8 cores), prostate and pelvic MRI, renal ultrasound and bone scan.Diagnosis cT3b, N0, M0 prostate cancer (Gleason score 7 [4 + 3]).Management Hormonal down-staging with bicalutamide 150 mg/day for 3 months, then conformal radiotherapy (70 Gy over 7 weeks) with adjuvant bicalutamide 150 mg/day, to be continued until disease progression. Breast radiotherapy administered over a 5-day period at a dose of 15 Gy to reduce nonsteroidal antiandrogen-associated gynecomastia and breast pain. PMID: 16474813 [PubMed - in process]

Posted by blogposter at 02:48 PM |

Chemosensitization of hormone-refractory prostate cancer cells by curcumin to TRAIL-induced apoptosis.


Chemosensitization of hormone-refractory prostate cancer cells by curcumin to TRAIL-induced apoptosis.
Related Articles Chemosensitization of hormone-refractory prostate cancer cells by curcumin to TRAIL-induced apoptosis. J Exp Ther Oncol. 2005;5(2):81-91 Authors: Deeb DD, Jiang H, Gao X, Divine G, Dulchavsky SA, Gautam SC Failure to undergo apoptosis has been implicated in the resistance of tumor cells to anticancer therapies. Promotion of apoptosis in tumor cells could potentially increase the efficacy of conventional treatment regimens and improve prognosis. Prostate cancer cells are generally resistant to induction of apoptosis by anticancer agents and death ligands. We investigated the sensitization of prostate cancer cell lines by curcumin (diferuloyl-methane) to TNF-related apoptosis inducing ligand (TRAIL)-induced apoptosis. Prostate cancer cells treated with curcumin or TRAIL or curcumin and TRAIL together were assessed for induction of apoptosis and pathway of apoptosis was determined from the activation of procaspases and release of cytochrome c from mitochondria. Curcumin sensitized LNCaP, DU145 and PC3 tumor cell lines to TRAIL. Combined curcumin and TRAIL treatment produced the most loss of viable cells by inducing apoptosis as revealed by accumulation of hypodiploid cells in sub-G1 phase, enhanced annexin V binding, DNA fragmentation, cleavage of procaspases-3, -8, and 9, truncation of proapoptotic Bid, and release of cytochrome c from mitochondria. Tumor cells expressed constitutively active NF-kappaB and sensitization to TRAIL involved inhibition of NF-kappaB by curcumin. These findings suggest that combined curcumin/TRAIL chemo-immunotherapy may be a beneficial adjunct to the standard therapeutic regimens for prostate cancer. PMID: 16471035 [PubMed - in process]

Posted by blogposter at 02:48 PM |

[Prognostic factors for PSA relapse of prostate cancer after endocrine therapy]


[Prognostic factors for PSA relapse of prostate cancer after endocrine therapy]
Related Articles [Prognostic factors for PSA relapse of prostate cancer after endocrine therapy] Nippon Hinyokika Gakkai Zasshi. 2005 Nov;96(7):685-90 Authors: Nakata S, Nakano K, Takahashi H, Shimizu K, Kawashima K PURPOSE: Advanced prostate cancer responds well to endocrine therapy initially, but soon becomes refractory and has a poor prognosis. We analyzed the prognostic factors of prostate cancer responding well initially to endocrine therapy with lowering of serum prostate specific antigen (PSA) level but later showing PSA relapse. MATERIALS AND METHODS: In prostate cancer patients newly diagnosed from January 1992 to December 2004 at our institution, there were 93 patients in that the PSA level of 10 ng/ml or more before therapy initially dropped below 10 ng/ml by endocrine therapy, but showed PSA relapse thereafter. We investigated the relationship between clinical stage, pathological differentiation, initial PSA, duration between initiation of therapy and PSA nadir, the value of PSA nadir, duration between initiation of therapy and PSA relapse, PSA doubling time (PSA-DT) at relapse, PSA response three months after initiation of second line therapy and prognosis after PSA relapse. RESULTS: In Kaplan-Meier method, between all or some categories investigated showed significant difference in prognosis after PSA relapse. In multivariate analysis, the factors that significantly affected prognosis after PSA relapse were clinical stage, pathological differentiation, PSA nadir value, duration between initiation of therapy and PSA relapse and PSA response three months after initiation of second line therapy. CONCLUSION: We investigated the prognostic factors refractory to endocrine therapy. These results are useful in planning the therapy, and in explaining the status or future prospective of the disease to patients and families. PMID: 16363654 [PubMed - indexed for MEDLINE]

Posted by blogposter at 02:48 PM |

Intermittent androgen ablation in patients with biochemical failure after pelvic radiotherapy for localized prostate cancer.


Intermittent androgen ablation in patients with biochemical failure after pelvic radiotherapy for localized prostate cancer.
Related Articles Intermittent androgen ablation in patients with biochemical failure after pelvic radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys. 2006 Mar 1;64(3):842-8 Authors: Cury FL, Souhami L, Rajan R, Tanguay S, Gagnon B, Duclos M, Shenouda G, Faria SL, David M, Freeman CR Purpose: To assess the efficacy of intermittent androgen ablation (IAA) in patients with biochemical failure after radiotherapy for prostate cancer. Methods and Materials: Thirty-nine patients received a luteinizing hormone-releasing hormone analog every 2 months for a total of 4 doses. IAA was then discontinued if serum prostate-specific antigen (PSA) fell to a normal level with a castrate level of testosterone. Therapy was restarted when the serum PSA level reached >/=10 ng/mL and was discontinued if hormone resistance or unacceptable toxicity occurred. Results: Median PSA was 9.1 ng/mL at the time of first IAA. The median time between the first and the second cycles was 20.1 months, decreasing to 15.5 months between the third and fourth cycles. Two patients discontinued the treatment because of severe hot flushes. Four patients developed hormone resistance. With a median follow-up of 56.4 months, 5-year survival is 92.3%. Three patients died of unrelated causes. The incidence of distant metastasis is 6.8%. Conclusions: The use of IAA seems to be a safe and effective treatment for patients with biochemical failure post radiotherapy and no evidence of metastatic disease. The use of IAA limits hormone-related side effects and health care costs without an apparent increase in the risk for the development of metastatic disease. PMID: 16289909 [PubMed - in process]

Posted by blogposter at 02:47 PM |

Management of clinically localized prostate cancer by radical prostatectomy followed by watchful waiting.


Management of clinically localized prostate cancer by radical prostatectomy followed by watchful waiting.
Related Articles Management of clinically localized prostate cancer by radical prostatectomy followed by watchful waiting. Nat Clin Pract Urol. 2005 Jun;2(6):298-303 Authors: Kirby R Background A 65-year-old married man requested a PSA screening test and was found to have an elevated PSA level of 5.26 ng/ml.Investigations Digital rectal examination, sextant biopsy, bone scan, and MRI to confirm diagnosis and stage the disease. Subsequent histopathologic examination of the excised prostate.Diagnosis Preoperative stage cT2b prostate cancer (Gleason score 7 [3 + 4]). Postoperative stage pT3b, N0, M0 prostate cancer (Gleason score 9 [4 + 5]), with extensive cancer within the left side of the prostate gland, involving several of the surgical margins and extending to the proximal portion of the left seminal vesicle.Management Open radical retropubic prostatectomy, then watchful waiting with further treatment deferred until disease progression. Postoperative erectile dysfunction treated with sildenafil plus prostaglandin E(1) combination therapy. PMID: 16474812 [PubMed - in process]

Posted by blogposter at 02:47 PM |

February 13, 2006

Start-up hopes to challenge Google 


Start-up hopes to challenge Google 
San Jose Mercury News - Feb 09 8:01 AM
Anand Rajaraman and Venky Harinarayan, who knew Google's co-founders while the four studied at Stanford University together, are launching an ambitious new search engine company, Kosmix.Save to My Web

Posted by blogposter at 08:11 PM |

Prostate Cancer Screening - A prospective study of physical activity and incident and fatal prostate cancer Giovannucci EL, Liu Y, Leitzmann MF, Stampfer MJ, Willett WC, Department of Nutrition, Harvard School of Public Health, Boston, MA.


A prospective study of physical activity and incident and fatal prostate cancer Giovannucci EL, Liu Y, Leitzmann MF, Stampfer MJ, Willett WC, Department of Nutrition, Harvard School of Public Health, Boston, MA.
Related Articles A prospective study of physical activity and incident and fatal prostate cancer Giovannucci EL, Liu Y, Leitzmann MF, Stampfer MJ, Willett WC, Department of Nutrition, Harvard School of Public Health, Boston, MA. Urol Oncol. 2005 Nov-Dec;23(6):463-4 Authors: Smith JA BACKGROUND: Whether physical activity has benefits against prostate cancer incidence or progression is unclear. Therefore, we assessed physical activity in relation to prostate cancer incidence, mortality, and Gleason histologic grade. METHODS: We used data from the Health Professionals Follow-up Study, a prospective cohort study, to determine the number of cases of incident, advanced (seminal vesicle invasion, metastasis, or fatal), fatal, and high-grade prostate cancer in a cohort of 47,620 US male health professionals, followed up from February 1, 1986, to January 31, 2000. RESULTS: During 14 years of follow-up, we documented 2892 new cases of prostate cancer, including 482 advanced cases (280 of which were fatal). For total prostate cancer, no association was observed for total, vigorous, and nonvigorous physical activity. In men 65 years or older, we observed a lower risk in the highest category of vigorous activity for advanced (multivariable relative risk, 0.33; 95% confidence interval, 0.17-0.62, for more than 29 vs 0 metabolic equivalent hours) and for fatal (relative risk, 0.26; 95% confidence interval, 0.11-0.66) prostate cancer. No associations were observed in younger men. Differential screening by prostate-specific antigen or a reduction in physical activity due to undiagnosed prostate cancer did not appear to account for the results. Among cases, men with high levels of physical activity were less likely to be diagnosed with poorly differentiated cancers (Gleason grade >/=7). CONCLUSION: Although the mechanisms are not yet understood, these findings suggest that regular vigorous activity could slow the progression of prostate cancer and might be recommended to reduce mortality from prostate cancer, particularly given the many other documented benefits of exercise. PMID: 16301135 [PubMed - in process]

Posted by blogposter at 08:11 PM |

Radiation therapy for prostate cancer and erectile (dys)function: the role of imaging.


Radiation therapy for prostate cancer and erectile (dys)function: the role of imaging.
Related Articles Radiation therapy for prostate cancer and erectile (dys)function: the role of imaging. Acta Oncol. 2005;44(7):673-8 Authors: Incrocci L Incidence of erectile dysfunction (ED) after radiotherapy reported in the literature varies from 7 to 72% after external-beam radiotherapy to 5-51% after brachytherapy. Most of these studies are retrospective, the definition of ED is variable and sexual functioning is frequently assessed by asking only one question. Already in the 1980's it was suggested that post-radiation ED was attributable to vascular damage. The most reliable method to assess vasculogenic ED is the use of the Doppler ultrasound. More recently, many studies have assessed the relationship between radiation dose and volume of the penile bulb and post-radiation ED, though the outcome is controversial. The penile structures and the neurovascular bundles are best seen on magnetic resonance imaging (MRI). Therefore the use of a computer tomography scan/MRI image fusion can result in reducing the planning target volume and consequently the radiation dose to the penile bulb and bodies. If radiation induces vascular damage that causes ED, any means of reducing the dose to the pelvic vascular structures would likely decrease ED, therefore new radiation techniques such as the intensity modulated radiation therapy or the implant of fiducial markers can help decrease the margins and therefore ED. PMID: 16227156 [PubMed - indexed for MEDLINE]

Posted by blogposter at 08:11 PM |

E-cadherin gene 3'-UTR C/T polymorphism is associated with prostate cancer.


E-cadherin gene 3'-UTR C/T polymorphism is associated with prostate cancer.
Related Articles E-cadherin gene 3'-UTR C/T polymorphism is associated with prostate cancer. Urol Int. 2005;75(4):350-3 Authors: Wu HC, Lai MT, Wu CI, Chen HY, Wan L, Tsai FJ, Chen WC INTRODUCTION: E-cadherin (CDH-1) is a cell-cell adhesive molecule which maintains cell integrity and communication between the intracellular and extracellular world. CDH-1 may therefore be related to carcinogenesis. A polymorphism located at the 3'-UTR of the CDH-1 gene is associated with stone disease; however, its relationship to prostate cancer has not been reported. We aimed to study whether there is an association between the 3'-UTR polymorphism and prostate cancer. MATERIALS AND METHODS: We collected 96 patients with prostate cancer and 114 normal controls for this study. The polymorphism of the CDH-1 gene was studied by polymerase chain reaction-based restriction analysis. RESULTS: There was a significant difference in genotype distribution of the CDH-1 gene polymorphism between cancer patients and normal controls (p < 0.001). The distribution of the CDH-1 gene CC genotype in prostate cancer patients (51.0%) was higher than in the controls (10.5%). The odds ratio for the CDH-1 'C' allele was 2.896 (95% CI = 1.908-4.396). There was no significant difference according to age, pathological grading, clinical staging, and responsiveness to hormonal therapy among patients. Only 3 patients (3.1%) had a history of urolithiasis. CONCLUSIONS: The CDH-1 gene 3'-UTR C/T polymorphism is associated with prostate cancer. The 'CC' homozygote indicates a relatively higher risk for developing prostate cancer than other genotypes. PMID: 16327305 [PubMed - indexed for MEDLINE]

Posted by blogposter at 08:10 PM |

Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA.


Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA.
Related Articles Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA. J Med Primatol. 2006 Feb;35(1):12-7 Authors: Marshall DJ, Rudnick KA, Lu J, Snyder LA BACKGROUND: Prostate-specific antigen (PSA) is an invaluable tumor marker for the detection of early prostate cancer, and can be a target for active immunotherapy of prostate cancer. We wanted to assess the usefulness of the cynomolgus monkey (Macaca fascicularis) as a relevant animal model to evaluate PSA-specific therapies. METHODS: RNA was isolated from the prostate of cynomolgus monkeys, and PSA gene products were amplified by reverse transcriptase-polymerase chain reaction using primers from conserved regions of human and rhesus monkey (Macaca mulatta) PSA genes. These amplified products were then sequenced. RESULTS: The cynomolgus PSA amino acid sequence is 89.7% identical to the human PSA gene, and 99.2% identical to the rhesus PSA amino acid sequence. Like the human and rhesus PSA genes, an open-reading frame of 261 amino acids was identified for the cynomolgus gene. Expression of the cynomolgus PSA gene appears to be restricted to the prostate, as it is in humans. CONCLUSIONS: The high identity between human and cynomolgus PSA sequences suggests that the cynomolgus monkey should be studied further for its potential as a large animal model to evaluate PSA-specific therapies. PMID: 16430490 [PubMed - in process]

Posted by blogposter at 08:10 PM |

Value of prostate volume measurement using transabdominal ultrasonography for the improvement of prostate-speci fi c antigen-based cancer detection.


Value of prostate volume measurement using transabdominal ultrasonography for the improvement of prostate-speci fi c antigen-based cancer detection.
Related Articles Value of prostate volume measurement using transabdominal ultrasonography for the improvement of prostate-speci fi c antigen-based cancer detection. Int J Urol. 2005 Oct;12(10):881-5 Authors: Kobayashi T, Kawahara T, Nishizawa K, Ogura K, Mitsumori K, Ide Y PURPOSE: To examine value of prostate-speci fi c antigen (PSA) adjusted by prostate volume measured using transabdominal ultrasonography in prostate cancer detection among men with elevated PSA. METHODS: 238 men aged 79 years or younger with serum PSA levels of 2.0-20.0 ng/mL and normal digital rectal examination fi ndings were studied in terms of total and free PSA, prostate volumes with transrectal (TRUS) and transabdominal (TAUS) ultrasonography and transition zone volumes with TRUS prior to transrectal 10-core biopsy. In addition to sole PSA values and the free-to-total PSA ratio, volume-adjusted PSA values, PSA densities determined by TRUS (PSAD(TRUS)), and TAUS (PSAD(TAUS)), and PSA transition zone densities (PSATzD) were compared using receiver operating characteristic (ROC) analysis. RESULTS: Prostate cancer was diagnosed in 58 (24.4%) of the 238 men who underwent prostate biopsies. Of the areas under ROC curves (AUC) of studied parameters, PSATzD (AUC 0.751) was the best and signi fi cantly superior to PSAD(TAUS) (AUC 0.664, P = 0.007). However, PSAD(TAUS) exceeded PSA (AUC 0.559, P = 0.004) and showed potential capability of a one-fourth reduction in unnecessary biopsies without spoiling sensitivity (90%). Cancer detection rate was only 4.2% in the 48 patients whose prostate volume in TAUS was > 50 mL and PSAD(TAUS) was < 0.075. CONCLUSIONS: Since PSAD(TRUS) and PSATzD were signi fi cantly superior to PSAD(TAUS), TRUS is feasible as the standard fashion to determine prostate volume in the diagnosis of prostate cancers. However, TAUS is also worthwhile as it can improve the prostate cancer detection using sole PSA, and primary use of TAUS has the potential to reduce the substantial number of unnecessary biopsy safely. PMID: 16323981 [PubMed - indexed for MEDLINE]

Posted by blogposter at 08:10 PM |

Advances in radiotherapy for prostate cancer.


Advances in radiotherapy for prostate cancer.
Related Articles Advances in radiotherapy for prostate cancer. Br J Radiol. 2005;78 Spec No 2:S112-6 Authors: Ash D PMID: 16306633 [PubMed - indexed for MEDLINE]

Posted by blogposter at 08:10 PM |

Current drug therapy for prostate cancer: an overview.


Current drug therapy for prostate cancer: an overview.
Related Articles Current drug therapy for prostate cancer: an overview. Curr Med Chem Anticancer Agents. 2005 Nov;5(6):603-12 Authors: Stewart AB, Lwaleed BA, Douglas DA, Birch BR Prostate cancer is the most common cancer amongst men in the USA and the second most common malignant cause of male death worldwide after lung cancer. The life time risk of having microscopic evidence of prostate cancer for a 50 year old man is 42%. Prostate cancer is thus becoming an increasingly significant global health problem in terms of mortality, morbidity, as well as economically. This review, discusses current medical therapeutic options for prostate cancer including traditional treatments using luteinising hormone releasing analogues (LHRH), anti-androgens and estrogen treatments, and the use of novel drugs directed against molecular targets considered important in oncogenesis and metastasis. Prostate cancer chemoprevention using 5alpha-reductase inhibitors and the role of gene therapy are also considered. PMID: 16305482 [PubMed - indexed for MEDLINE]

Posted by blogposter at 08:09 PM |

Changes in tissue prostatic acidic phosphatase during endocrine treatment of patients with prostatic carcinoma.


Changes in tissue prostatic acidic phosphatase during endocrine treatment of patients with prostatic carcinoma.
Related Articles Changes in tissue prostatic acidic phosphatase during endocrine treatment of patients with prostatic carcinoma. Scand J Urol Nephrol. 2005;39(5):393-8 Authors: Grande M, Carlström K, Lundh-Rozell B, Stege R, Pousette A OBJECTIVE: We have previously developed methods for the quantification of different macromolecules in aspiration biopsy material and described the changes in prostate-specific antigen (T-PSA) during cancer treatment. We have now studied the changes in tissue prostatic acidic phosphatase (T-PAP) in 58 endocrine-treated patients with prostatic carcinoma and compared these data with cancer development data and tissue PSA (T-PSA) levels. MATERIAL AND METHODS: PAP and PSA were quantified in aspiration biopsies taken before treatment and after 6 and 12 months of treatment. Patients were followed until death or for >98 months. RESULTS: Pretreatment T-PSA was more strongly associated with survival than T-PAP. Both T-PSA and T-PAP decreased in responders during treatment. In non-responders, T-PSA and T-PAP increased after 12 months in 17/18 and 7/13 patients, respectively. Estrogen-treated responders had significantly higher T-PSA, but not T-PAP, treatment values than those treated with orchidectomy or gonadotropin-releasing hormone. CONCLUSIONS: The inferiority of serum PAP compared to PSA for monitoring cancer treatment may reflect its less pronounced changes at the tissue level, indicating different in vivo regulation of the two markers. Estrogen stimulation of PSA synthesis in vivo may underlie the higher PSA levels observed during estrogen treatment. PMID: 16257841 [PubMed - indexed for MEDLINE]

Posted by blogposter at 08:09 PM |

Multidisciplinary treatment of synchronous primary rectal and prostate cancers.


Multidisciplinary treatment of synchronous primary rectal and prostate cancers.
Related Articles Multidisciplinary treatment of synchronous primary rectal and prostate cancers. Nat Clin Pract Oncol. 2005 May;2(5):271-4; quiz 1 p following 274 Authors: Colonias A, Farinash L, Miller L, Jones S, Medich DS, Greenberg L, Miller R, Parda DS BACKGROUND: A 58-year-old Caucasian man with a history of irritable bowel syndrome and occasional rectal bleeding presented with a 4-week history of progressive, bright red blood per rectum. A digital rectal examination revealed a 3 cm distal, midrectal mass. Laboratory tests showed an elevated serum prostate-specific antigen of 32 ng/ml but other physical and medical examinations were unremarkable. INVESTIGATIONS: Digital rectal examination, colonoscopy, rectal mass biopsy, endorectal ultrasound, transrectal ultrasound-guided prostate biopsy, CT scan and MRI. DIAGNOSIS: Clinical stage III (T3N1M0), moderately differentiated adenocarcinoma of the rectum and clinical stage II (T1cN0M0) adenocarcinoma of the prostate. MANAGEMENT: Intensity-modulated radiation therapy, chemoradiation, chemotherapy, hormone therapy and surgery. PMID: 16264963 [PubMed - indexed for MEDLINE]

Posted by blogposter at 08:09 PM |

The significance of tumor heterogeneity for prediction of DNA ploidy of prostate cancer.


The significance of tumor heterogeneity for prediction of DNA ploidy of prostate cancer.
Related Articles The significance of tumor heterogeneity for prediction of DNA ploidy of prostate cancer. Scand J Urol Nephrol. 2005;39(5):387-92 Authors: H ggarth L, Auer G, Busch C, Norberg M, H ggman M, Egevad L OBJECTIVE: In a previous study, we mapped the ploidy heterogeneity of prostate cancer using flow cytometry in 676 tumor samples from 50 radical prostatectomy specimens. Ploidy heterogeneity was common (42% of tumors) and was found in all non-diploid tumors. The volume of non-diploid tumor was estimated and found to predict extra-prostatic extension and seminal vesicle invasion. The aim of this study was to evaluate the impact of tumor heterogeneity on preoperative ploidy assessment. MATERIAL AND METHODS: In 50 men at least six core biopsies were taken before prostatectomy. Sections from biopsies with cancer were Feulgen-stained for image cytometry. After exclusion of biopsies with insufficient material, 123 histograms from 48 men (mean 2.6; range 1-7) remained for analysis. RESULTS: In 32 men, biopsies were diploid. In 16 men, at least one biopsy was non-diploid (14 tetraploid, two aneuploid) and 10 of them also had diploid biopsies. In 34 men (71%), the prostatectomy specimens were correctly predicted as being either diploid (48%) or non-diploid (23%). The sensitivity and specificity of biopsies for predicting non-diploid cancer were 55% and 82%, respectively, and the positive and negative predictive values were 69% and 72%, respectively. The ploidy status of tumors with and without ploidy heterogeneity was correctly predicted in 55% and 82% of cases, respectively (p=0.04). Biopsies underestimated ploidy in 9/20 tumors (45%) with heterogeneous ploidy status. Underestimation mainly occurred when one or two cores were analyzed. CONCLUSIONS: Preoperative prediction of the ploidy status of prostate cancer is hampered by tumor heterogeneity. Analysis of multiple biopsies is important for correct preoperative ploidy estimation. PMID: 16257840 [PubMed - indexed for MEDLINE]

Posted by blogposter at 08:08 PM |

Winning the Battle 


Winning the Battle 
RedNova - Feb 13 2:31 AM
By Held, Shari CANCER IS THE SECOND-leading cause of death in the U.S., following close on the heels of heart disease. Despite that, cancer centers around Indiana are winning the important battles, if not the war. "Over one million people in the U.S.Save to My Web

Posted by blogposter at 01:34 PM |

Prostate Cancer Screening - Serum levels of phytanic acid are associated with prostate cancer risk.


Serum levels of phytanic acid are associated with prostate cancer risk.
Related Articles Serum levels of phytanic acid are associated with prostate cancer risk. J Urol. 2005 Nov;174(5):1824 Authors: Walsh PC PMID: 16217297 [PubMed - indexed for MEDLINE]

Posted by blogposter at 01:33 PM |

Radiation therapy for prostate cancer and erectile (dys)function: the role of imaging.


Radiation therapy for prostate cancer and erectile (dys)function: the role of imaging.
Related Articles Radiation therapy for prostate cancer and erectile (dys)function: the role of imaging. Acta Oncol. 2005;44(7):673-8 Authors: Incrocci L Incidence of erectile dysfunction (ED) after radiotherapy reported in the literature varies from 7 to 72% after external-beam radiotherapy to 5-51% after brachytherapy. Most of these studies are retrospective, the definition of ED is variable and sexual functioning is frequently assessed by asking only one question. Already in the 1980's it was suggested that post-radiation ED was attributable to vascular damage. The most reliable method to assess vasculogenic ED is the use of the Doppler ultrasound. More recently, many studies have assessed the relationship between radiation dose and volume of the penile bulb and post-radiation ED, though the outcome is controversial. The penile structures and the neurovascular bundles are best seen on magnetic resonance imaging (MRI). Therefore the use of a computer tomography scan/MRI image fusion can result in reducing the planning target volume and consequently the radiation dose to the penile bulb and bodies. If radiation induces vascular damage that causes ED, any means of reducing the dose to the pelvic vascular structures would likely decrease ED, therefore new radiation techniques such as the intensity modulated radiation therapy or the implant of fiducial markers can help decrease the margins and therefore ED. PMID: 16227156 [PubMed - indexed for MEDLINE]

Posted by blogposter at 01:33 PM |

A novel cancer testis antigen that is frequently expressed in pancreatic, lung, and endometrial cancers.


A novel cancer testis antigen that is frequently expressed in pancreatic, lung, and endometrial cancers.
Related Articles A novel cancer testis antigen that is frequently expressed in pancreatic, lung, and endometrial cancers. Clin Cancer Res. 2006 Jan 1;12(1):191-7 Authors: Okada T, Akada M, Fujita T, Iwata T, Goto Y, Kido K, Okada T, Matsuzaki Y, Kobayashi K, Matsuno S, Sunamura M, Kawakami Y PURPOSE: To isolate cancer testis antigens that are expressed in pancreatic cancers and may be useful in clinical applications. EXPERIMENTAL DESIGN: To efficiently isolate cancer testis antigens, a testis cDNA library was immunoscreened (SEREX) with serum from a patient with pancreatic ductal adenocarcinoma. The expression of isolated antigens in various cancer cell lines and tissues was evaluated by reverse transcription-PCR and Northern blot analyses. The immunogenicity of the antigen in cancer patients was evaluated by detection of the IgG antibody in sera from patients with various cancers. RESULTS: Of the three clones isolated through screening of a total of 2 x 10(6) cDNA library clones, one clone (KU-CT-1) was found to be expressed in various cancers but only in testis among normal tissues, indicating that it was a novel cancer testis antigen. The KU-CT-1 gene is located on chromosome 10p12 and produces two splice variants, which encode proteins of 397 and 872 amino acids, respectively. KU-CT-1 was expressed in pancreatic cancer tissues (3 of 9, 33%), lung cancer tissues (9 of 24, 38%), and endometrial cancer tissues (7 of 11, 64%). Specific serum IgG antibodies were detected in 3 of 20 pancreatic cancer patients, 2 of 12 endometrial cancer patients, 1 of 18 colon cancer patients, and 1 of 10 prostate cancer patients but not detected in 30 healthy individuals. CONCLUSIONS: KU-CT-1 is a new cancer testis antigen that is expressed in pancreatic, lung, and endometrial cancers and may be useful for diagnosis and immunotherapy for patients with various cancers. PMID: 16397042 [PubMed - indexed for MEDLINE]

Posted by blogposter at 01:33 PM |

Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA.


Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA.
Related Articles Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA. J Med Primatol. 2006 Feb;35(1):12-7 Authors: Marshall DJ, Rudnick KA, Lu J, Snyder LA BACKGROUND: Prostate-specific antigen (PSA) is an invaluable tumor marker for the detection of early prostate cancer, and can be a target for active immunotherapy of prostate cancer. We wanted to assess the usefulness of the cynomolgus monkey (Macaca fascicularis) as a relevant animal model to evaluate PSA-specific therapies. METHODS: RNA was isolated from the prostate of cynomolgus monkeys, and PSA gene products were amplified by reverse transcriptase-polymerase chain reaction using primers from conserved regions of human and rhesus monkey (Macaca mulatta) PSA genes. These amplified products were then sequenced. RESULTS: The cynomolgus PSA amino acid sequence is 89.7% identical to the human PSA gene, and 99.2% identical to the rhesus PSA amino acid sequence. Like the human and rhesus PSA genes, an open-reading frame of 261 amino acids was identified for the cynomolgus gene. Expression of the cynomolgus PSA gene appears to be restricted to the prostate, as it is in humans. CONCLUSIONS: The high identity between human and cynomolgus PSA sequences suggests that the cynomolgus monkey should be studied further for its potential as a large animal model to evaluate PSA-specific therapies. PMID: 16430490 [PubMed - in process]

Posted by blogposter at 01:33 PM |

Value of prostate volume measurement using transabdominal ultrasonography for the improvement of prostate-speci fi c antigen-based cancer detection.


Value of prostate volume measurement using transabdominal ultrasonography for the improvement of prostate-speci fi c antigen-based cancer detection.
Related Articles Value of prostate volume measurement using transabdominal ultrasonography for the improvement of prostate-speci fi c antigen-based cancer detection. Int J Urol. 2005 Oct;12(10):881-5 Authors: Kobayashi T, Kawahara T, Nishizawa K, Ogura K, Mitsumori K, Ide Y PURPOSE: To examine value of prostate-speci fi c antigen (PSA) adjusted by prostate volume measured using transabdominal ultrasonography in prostate cancer detection among men with elevated PSA. METHODS: 238 men aged 79 years or younger with serum PSA levels of 2.0-20.0 ng/mL and normal digital rectal examination fi ndings were studied in terms of total and free PSA, prostate volumes with transrectal (TRUS) and transabdominal (TAUS) ultrasonography and transition zone volumes with TRUS prior to transrectal 10-core biopsy. In addition to sole PSA values and the free-to-total PSA ratio, volume-adjusted PSA values, PSA densities determined by TRUS (PSAD(TRUS)), and TAUS (PSAD(TAUS)), and PSA transition zone densities (PSATzD) were compared using receiver operating characteristic (ROC) analysis. RESULTS: Prostate cancer was diagnosed in 58 (24.4%) of the 238 men who underwent prostate biopsies. Of the areas under ROC curves (AUC) of studied parameters, PSATzD (AUC 0.751) was the best and signi fi cantly superior to PSAD(TAUS) (AUC 0.664, P = 0.007). However, PSAD(TAUS) exceeded PSA (AUC 0.559, P = 0.004) and showed potential capability of a one-fourth reduction in unnecessary biopsies without spoiling sensitivity (90%). Cancer detection rate was only 4.2% in the 48 patients whose prostate volume in TAUS was > 50 mL and PSAD(TAUS) was < 0.075. CONCLUSIONS: Since PSAD(TRUS) and PSATzD were signi fi cantly superior to PSAD(TAUS), TRUS is feasible as the standard fashion to determine prostate volume in the diagnosis of prostate cancers. However, TAUS is also worthwhile as it can improve the prostate cancer detection using sole PSA, and primary use of TAUS has the potential to reduce the substantial number of unnecessary biopsy safely. PMID: 16323981 [PubMed - indexed for MEDLINE]

Posted by blogposter at 01:32 PM |

Advances in radiotherapy for prostate cancer.


Advances in radiotherapy for prostate cancer.
Related Articles Advances in radiotherapy for prostate cancer. Br J Radiol. 2005;78 Spec No 2:S112-6 Authors: Ash D PMID: 16306633 [PubMed - indexed for MEDLINE]

Posted by blogposter at 01:32 PM |

Current drug therapy for prostate cancer: an overview.


Current drug therapy for prostate cancer: an overview.
Related Articles Current drug therapy for prostate cancer: an overview. Curr Med Chem Anticancer Agents. 2005 Nov;5(6):603-12 Authors: Stewart AB, Lwaleed BA, Douglas DA, Birch BR Prostate cancer is the most common cancer amongst men in the USA and the second most common malignant cause of male death worldwide after lung cancer. The life time risk of having microscopic evidence of prostate cancer for a 50 year old man is 42%. Prostate cancer is thus becoming an increasingly significant global health problem in terms of mortality, morbidity, as well as economically. This review, discusses current medical therapeutic options for prostate cancer including traditional treatments using luteinising hormone releasing analogues (LHRH), anti-androgens and estrogen treatments, and the use of novel drugs directed against molecular targets considered important in oncogenesis and metastasis. Prostate cancer chemoprevention using 5alpha-reductase inhibitors and the role of gene therapy are also considered. PMID: 16305482 [PubMed - indexed for MEDLINE]

Posted by blogposter at 01:32 PM |

February 12, 2006

Annual cancer deaths fall for first time in 70 years


Annual cancer deaths fall for first time in 70 years
Detroit News - A popular herbal pill used by millions of men doesn't reduce the frequent urge to go to the bathroom or other annoying symptoms of an enlarged prostate, a new study concludes. The yearlong research found the plant extract, saw palmetto, was no more

Posted by blogposter at 04:11 PM |

Prostate Cancer Screening - Salvage radiotherapy for biochemical recurrence after radical prostatectomy.


Salvage radiotherapy for biochemical recurrence after radical prostatectomy.
Related Articles Salvage radiotherapy for biochemical recurrence after radical prostatectomy. BJU Int. 2005 Nov;96(7):1009-13 Authors: Terai A, Matsui Y, Yoshimura K, Arai Y, Dodo Y OBJECTIVE: To evaluate the clinical outcome of salvage radiotherapy (RT) for biochemical recurrence after radical prostatectomy (RP) at our institution. PATIENTS AND METHODS: Between March 1999 and January 2004, 37 patients had salvage RT for prostate-specific antigen (PSA) failure after RP, including eight who had had neoadjuvant hormone therapy. After surgery, PSA was measured with ultrasensitive immunoassays. In all patients RT was delivered to the prostatic bed at a total dose of 60 Gy with a four-field box technique. RESULTS: The median (range) PSA level before salvage RT was 0.146 (0.06-3.216) ng/mL and RT was started at a PSA level of <0.5 ng/mL in 34 of the 37 patients (92%). With a median follow-up of 31.9 (0-69.8), months, 11 patients (30%) had disease progression after RT and the 3- and 5-year progression-free probability was 74% and 54%, respectively. Univariate analysis showed that clinical and pathological tumour stages and PSA level before RT (>0.15 vs < or = 0.15 ng/mL) were significant predictors of disease progression. There were no late adverse events related to RT. CONCLUSION: Salvage RT for biochemical failure after RP at a low PSA level, using ultrasensitive immunoassays for monitoring, is a reasonably effective treatment. A relatively low radiation dose (60 Gy) seems to be effective. PMID: 16225518 [PubMed - indexed for MEDLINE]

Posted by blogposter at 04:10 PM |

Radiation therapy for prostate cancer and erectile (dys)function: the role of imaging.


Radiation therapy for prostate cancer and erectile (dys)function: the role of imaging.
Related Articles Radiation therapy for prostate cancer and erectile (dys)function: the role of imaging. Acta Oncol. 2005;44(7):673-8 Authors: Incrocci L Incidence of erectile dysfunction (ED) after radiotherapy reported in the literature varies from 7 to 72% after external-beam radiotherapy to 5-51% after brachytherapy. Most of these studies are retrospective, the definition of ED is variable and sexual functioning is frequently assessed by asking only one question. Already in the 1980's it was suggested that post-radiation ED was attributable to vascular damage. The most reliable method to assess vasculogenic ED is the use of the Doppler ultrasound. More recently, many studies have assessed the relationship between radiation dose and volume of the penile bulb and post-radiation ED, though the outcome is controversial. The penile structures and the neurovascular bundles are best seen on magnetic resonance imaging (MRI). Therefore the use of a computer tomography scan/MRI image fusion can result in reducing the planning target volume and consequently the radiation dose to the penile bulb and bodies. If radiation induces vascular damage that causes ED, any means of reducing the dose to the pelvic vascular structures would likely decrease ED, therefore new radiation techniques such as the intensity modulated radiation therapy or the implant of fiducial markers can help decrease the margins and therefore ED. PMID: 16227156 [PubMed - indexed for MEDLINE]

Posted by blogposter at 04:10 PM |

Tightly-regulated suicide gene expression kills PSA-expressing prostate tumor cells.


Tightly-regulated suicide gene expression kills PSA-expressing prostate tumor cells.
Related Articles Tightly-regulated suicide gene expression kills PSA-expressing prostate tumor cells. Gene Ther. 2005 Nov;12(21):1573-80 Authors: Peng W, Chen J, Huang YH, Sawicki JA We have previously shown that a dual system for controlling gene expression that relies both on transcriptional regulation and DNA recombination mediated by the site-directed recombinase, Flp, effectively controls the expression of a gene encoding diphtheria toxin (DT-A). In this study, we investigated the use of a chimeric modified enhancer/promoter sequence of the human prostate-specific antigen (PSA) gene to regulate DT-A expression in human prostate cancer cells in culture, in xenografts derived from these cells, and in autochthonous tumors in TRAMP mice. Following adenoviral delivery of DNA encoding PSA promoter-driven Flp recombinase and DT-A, we demonstrate that this transcriptional/DNA recombination control strategy effectively activates DT-A expression in a manner that correlates with the amount of PSA and androgen in cells. Significantly, the size of xenografts was reduced by 50%, and tumor cells in TRAMP mice died following intratumoral injection of DT-A viruses. Direct injection of virally-delivered DT-A into normal mouse prostates resulted in a dramatic reduction in the size of the gland. Our results suggest that the PSA promoter-driven Flp recombinase regulatory system will allow for targeted death of PSA-expressing cells. When combined with newly developed strategies for targeted gene delivery, this approach holds promise as an effective systemically-administered therapy for metastatic prostate cancer. PMID: 16034457 [PubMed - indexed for MEDLINE]

Posted by blogposter at 04:10 PM |

Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA.


Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA.
Related Articles Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA. J Med Primatol. 2006 Feb;35(1):12-7 Authors: Marshall DJ, Rudnick KA, Lu J, Snyder LA BACKGROUND: Prostate-specific antigen (PSA) is an invaluable tumor marker for the detection of early prostate cancer, and can be a target for active immunotherapy of prostate cancer. We wanted to assess the usefulness of the cynomolgus monkey (Macaca fascicularis) as a relevant animal model to evaluate PSA-specific therapies. METHODS: RNA was isolated from the prostate of cynomolgus monkeys, and PSA gene products were amplified by reverse transcriptase-polymerase chain reaction using primers from conserved regions of human and rhesus monkey (Macaca mulatta) PSA genes. These amplified products were then sequenced. RESULTS: The cynomolgus PSA amino acid sequence is 89.7% identical to the human PSA gene, and 99.2% identical to the rhesus PSA amino acid sequence. Like the human and rhesus PSA genes, an open-reading frame of 261 amino acids was identified for the cynomolgus gene. Expression of the cynomolgus PSA gene appears to be restricted to the prostate, as it is in humans. CONCLUSIONS: The high identity between human and cynomolgus PSA sequences suggests that the cynomolgus monkey should be studied further for its potential as a large animal model to evaluate PSA-specific therapies. PMID: 16430490 [PubMed - in process]

Posted by blogposter at 04:09 PM |

E-cadherin gene 3'-UTR C/T polymorphism is associated with prostate cancer.


E-cadherin gene 3'-UTR C/T polymorphism is associated with prostate cancer.
Related Articles E-cadherin gene 3'-UTR C/T polymorphism is associated with prostate cancer. Urol Int. 2005;75(4):350-3 Authors: Wu HC, Lai MT, Wu CI, Chen HY, Wan L, Tsai FJ, Chen WC INTRODUCTION: E-cadherin (CDH-1) is a cell-cell adhesive molecule which maintains cell integrity and communication between the intracellular and extracellular world. CDH-1 may therefore be related to carcinogenesis. A polymorphism located at the 3'-UTR of the CDH-1 gene is associated with stone disease; however, its relationship to prostate cancer has not been reported. We aimed to study whether there is an association between the 3'-UTR polymorphism and prostate cancer. MATERIALS AND METHODS: We collected 96 patients with prostate cancer and 114 normal controls for this study. The polymorphism of the CDH-1 gene was studied by polymerase chain reaction-based restriction analysis. RESULTS: There was a significant difference in genotype distribution of the CDH-1 gene polymorphism between cancer patients and normal controls (p < 0.001). The distribution of the CDH-1 gene CC genotype in prostate cancer patients (51.0%) was higher than in the controls (10.5%). The odds ratio for the CDH-1 'C' allele was 2.896 (95% CI = 1.908-4.396). There was no significant difference according to age, pathological grading, clinical staging, and responsiveness to hormonal therapy among patients. Only 3 patients (3.1%) had a history of urolithiasis. CONCLUSIONS: The CDH-1 gene 3'-UTR C/T polymorphism is associated with prostate cancer. The 'CC' homozygote indicates a relatively higher risk for developing prostate cancer than other genotypes. PMID: 16327305 [PubMed - indexed for MEDLINE]

Posted by blogposter at 04:09 PM |

Large deformation three-dimensional image registration in image-guided radiation therapy.


Large deformation three-dimensional image registration in image-guided radiation therapy.
Related Articles Large deformation three-dimensional image registration in image-guided radiation therapy. Phys Med Biol. 2005 Dec 21;50(24):5869-92 Authors: Foskey M, Davis B, Goyal L, Chang S, Chaney E, Strehl N, Tomei S, Rosenman J, Joshi S In this paper, we present and validate a framework, based on deformable image registration, for automatic processing of serial three-dimensional CT images used in image-guided radiation therapy. A major assumption in deformable image registration has been that, if two images are being registered, every point of one image corresponds appropriately to some point in the other. For intra-treatment images of the prostate, however, this assumption is violated by the variable presence of bowel gas. The framework presented here explicitly extends previous deformable image registration algorithms to accommodate such regions in the image for which no correspondence exists. We show how to use our registration technique as a tool for organ segmentation, and present a statistical analysis of this segmentation method, validating it by comparison with multiple human raters. We also show how the deformable registration technique can be used to determine the dosimetric effect of a given plan in the presence of non-rigid tissue motion. In addition to dose accumulation, we describe a method for estimating the biological effects of tissue motion using a linear-quadratic model. This work is described in the context of a prostate treatment protocol, but it is of general applicability. PMID: 16333161 [PubMed - indexed for MEDLINE]

Posted by blogposter at 04:09 PM |

Current drug therapy for prostate cancer: an overview.


Current drug therapy for prostate cancer: an overview.
Related Articles Current drug therapy for prostate cancer: an overview. Curr Med Chem Anticancer Agents. 2005 Nov;5(6):603-12 Authors: Stewart AB, Lwaleed BA, Douglas DA, Birch BR Prostate cancer is the most common cancer amongst men in the USA and the second most common malignant cause of male death worldwide after lung cancer. The life time risk of having microscopic evidence of prostate cancer for a 50 year old man is 42%. Prostate cancer is thus becoming an increasingly significant global health problem in terms of mortality, morbidity, as well as economically. This review, discusses current medical therapeutic options for prostate cancer including traditional treatments using luteinising hormone releasing analogues (LHRH), anti-androgens and estrogen treatments, and the use of novel drugs directed against molecular targets considered important in oncogenesis and metastasis. Prostate cancer chemoprevention using 5alpha-reductase inhibitors and the role of gene therapy are also considered. PMID: 16305482 [PubMed - indexed for MEDLINE]

Posted by blogposter at 04:09 PM |

Molecular modelling of the androgen receptor axis: rational basis for androgen receptor intervention in androgen-independent prostate cancer.


Molecular modelling of the androgen receptor axis: rational basis for androgen receptor intervention in androgen-independent prostate cancer.
Related Articles Molecular modelling of the androgen receptor axis: rational basis for androgen receptor intervention in androgen-independent prostate cancer. BJU Int. 2005 Dec;96 Suppl 2:2-9 Authors: Fletterick RJ Androgen depletion in combination with antiandrogenic agents is initially highly effective for treating prostate cancer, and is the recommended treatment for more advanced or higher-grade tumours. However, many tumours eventually become insensitive to androgens, even though the androgen receptor (AR) continues to be expressed. Computational chemistry combined with structural analysis of nuclear receptors and determination of binding affinities of natural and designed coregulators (coactivators and corepressors) provides the theoretical framework for the rational design of novel therapeutic agents directed at the AR. Adding alternative groups to various sites throughout the receptor can alter the conformation of the molecule and its functional binding with coactivators or corepressors. Possible molecules can be identified thoroughly and systematically using intelligent high-throughput screening and FASTrack chemistry (three-dimensional crystallography). Applying these techniques should eventually result in therapeutic agents for androgen-independent prostate cancer that can block binding of AR coactivators while simultaneously increasing binding of AR corepressors. PMID: 16359432 [PubMed - indexed for MEDLINE]

Posted by blogposter at 04:09 PM |

Re: luteinizing hormone-releasing hormone agonist effects on skeletal muscle: how hormonal therapy in prostate cancer affects muscular strength.


Re: luteinizing hormone-releasing hormone agonist effects on skeletal muscle: how hormonal therapy in prostate cancer affects muscular strength.
Related Articles Re: luteinizing hormone-releasing hormone agonist effects on skeletal muscle: how hormonal therapy in prostate cancer affects muscular strength. J Urol. 2005 Nov;174(5):2068-9 Authors: Marcora S, Oliver S, Callow N, Lemmey A, Stuart N PMID: 16217402 [PubMed - indexed for MEDLINE]

Posted by blogposter at 04:08 PM |

Targeting apoptosis in prostate cancer: focus on caspases and inhibitors of apoptosis proteins.


Targeting apoptosis in prostate cancer: focus on caspases and inhibitors of apoptosis proteins.
Related Articles Targeting apoptosis in prostate cancer: focus on caspases and inhibitors of apoptosis proteins. BJU Int. 2005 Dec;96 Suppl 2:30-4 Authors: Watson RW, Fitzpatrick JM Androgens are critical to the growth and differentiation of prostate epithelial cells. Removal of androgen normally results in apoptosis, but androgen-independent tumours have developed mechanisms that allow cells to survive the loss of androgen. The caspases are central mediators of cell death. An important area for research involves manipulating caspases by novel mechanisms to induce apoptosis. However, such mechanisms as diethylmaleate priming are limited by an inability to selectively target tumour cells. Inhibitors of apoptosis proteins (IAPs) are recently identified anti-apoptotic caspase regulators. Each IAP homologue has a different mechanism of action. Because more than one member of the IAP family may be overexpressed in prostate cancer, successful treatment strategies will be defined by the ability to block all of the IAP expressed. Anti-sense oligonucleotide strategies have been shown to decrease IAP expression and increase prostate cancer cell susceptibility to apoptotic induction, although not by mitochondrial-mediated pathways. Fully understanding the basic apoptotic pathway and its regulation in prostate cancer will lead to more targets for manipulation, which can be translated into novel therapies. This article focuses on the role of the caspases and IAP in developing a rational approach to using apoptosis as a therapeutic target. PMID: 16359436 [PubMed - indexed for MEDLINE]

Posted by blogposter at 04:08 PM |

February 09, 2006

Annual cancer deaths fall for first time in 70 years


Annual cancer deaths fall for first time in 70 years
DetNews.com, MI - 20 hours agoA popular herbal pill used by millions ... Prostate: The prostate cancer death rate has been ... campaigns, radiation and chemotherapy cancer treatments remained harsh ...

Posted by blogposter at 10:31 PM |

Prostate Cancer Screening - Incidence and management of gynecomastia in men treated for prostate cancer.


Incidence and management of gynecomastia in men treated for prostate cancer.
Related Articles Incidence and management of gynecomastia in men treated for prostate cancer. J Urol. 2005 Nov;174(5):1737-42 Authors: Dobs A, Darkes MJ PURPOSE: Gynecomastia is a potentially treatment limiting adverse event in men receiving hormone therapy for prostate cancer. MATERIALS AND METHODS: In large, randomized, placebo controlled studies approximately 50% or more of patients with prostate cancer experienced gynecomastia due to multiple mechanisms. Although its severity was mostly reported as mild to moderate, gynecomastia was cited as the reason for most premature withdrawals from therapy. In patients with advanced forms of prostate cancer bilateral orchiectomy was associated with the lowest incidence of gynecomastia, followed by nonsteroidal antiandrogen therapy, diethylstilbestrol and estrogen in rank order. RESULTS: It is important that gynecomastia is well managed in patients with prostate cancer who want to proceed with hormone therapy. Patients should be assessed for the likely etiology of gynecomastia and preventive therapy or treatment for established gynecomastia should be instituted. Prophylactic radiotherapy has been shown to decrease the incidence of hormone induced gynecomastia by more than 50%. An alternative course of action, which may be more convenient for the patient, is the prophylactic use of tamoxifen. Tamoxifen may also mitigate or resolve gynecomastia during its early or proliferative phase. In severe long-standing gynecomastia surgery is warranted since medical therapies are less likely to succeed. Aromatase inhibitors and 4-hydroxytamoxifen are investigational. CONCLUSIONS: Gynecomastia is a significant problem in men undergoing hormonal therapy for prostate cancer. It requires prompt recognition, evaluation and management. PMID: 16217274 [PubMed - indexed for MEDLINE]

Posted by blogposter at 10:31 PM |

[Prostate cancer prevention]


[Prostate cancer prevention]
Related Articles [Prostate cancer prevention] Rev Med Suisse. 2006 Jan 11;2(48):163-5 Authors: Wisard M, Leisinger HJ The prevention of prostate cancer is conceivable. Finasteride, even though it diminishes the risk of cancer in the male adult, cannot be used as a prophylaxis in chemoprevention so far as we do not know if they produce more aggressive cancers. On the other hand, weight control, through a varied and balanced diet, rich in lycopene, soja beans, omega 3 acid, selenium, vit E, physical and sexual activity and no smoking are without risks, efficient and commendable. PMID: 16463803 [PubMed - in process]

Posted by blogposter at 10:30 PM |

Optimizing prostate cancer treatment by combining local radiation therapy with systemic vaccination.


Optimizing prostate cancer treatment by combining local radiation therapy with systemic vaccination.
Related Articles Optimizing prostate cancer treatment by combining local radiation therapy with systemic vaccination. Clin Cancer Res. 2005 Oct 1;11(19 Pt 1):6757-62 Authors: Kaufman HL, Divgi CR PMID: 16203760 [PubMed - indexed for MEDLINE]

Posted by blogposter at 10:30 PM |

Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA.


Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA.
Related Articles Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA. J Med Primatol. 2006 Feb;35(1):12-7 Authors: Marshall DJ, Rudnick KA, Lu J, Snyder LA Background Prostate-specific antigen (PSA) is an invaluable tumor marker for the detection of early prostate cancer, and can be a target for active immunotherapy of prostate cancer. We wanted to assess the usefulness of the cynomolgus monkey (Macaca fascicularis) as a relevant animal model to evaluate PSA-specific therapies. Methods RNA was isolated from the prostate of cynomolgus monkeys, and PSA gene products were amplified by reverse transcriptase-polymerase chain reaction using primers from conserved regions of human and rhesus monkey (Macaca mulatta) PSA genes. These amplified products were then sequenced. Results The cynomolgus PSA amino acid sequence is 89.7% identical to the human PSA gene, and 99.2% identical to the rhesus PSA amino acid sequence. Like the human and rhesus PSA genes, an open-reading frame of 261 amino acids was identified for the cynomolgus gene. Expression of the cynomolgus PSA gene appears to be restricted to the prostate, as it is in humans. Conclusions The high identity between human and cynomolgus PSA sequences suggests that the cynomolgus monkey should be studied further for its potential as a large animal model to evaluate PSA-specific therapies. PMID: 16430490 [PubMed - in process]

Posted by blogposter at 10:30 PM |

Molecular alterations in primary prostate cancer after androgen ablation therapy.


Molecular alterations in primary prostate cancer after androgen ablation therapy.
Related Articles Molecular alterations in primary prostate cancer after androgen ablation therapy. Clin Cancer Res. 2005 Oct 1;11(19 Pt 1):6823-34 Authors: Best CJ, Gillespie JW, Yi Y, Chandramouli GV, Perlmutter MA, Gathright Y, Erickson HS, Georgevich L, Tangrea MA, Duray PH, González S, Velasco A, Linehan WM, Matusik RJ, Price DK, Figg WD, Emmert-Buck MR, Chuaqui RF PURPOSE: After an initial response to androgen ablation, most prostate tumors recur, ultimately progressing to highly aggressive androgen-independent cancer. The molecular mechanisms underlying progression are not well known in part due to the rarity of androgen-independent samples from primary and metastatic sites. EXPERIMENTAL DESIGN: We compared the gene expression profiles of 10 androgen-independent primary prostate tumor biopsies with 10 primary, untreated androgen-dependent tumors. Samples were laser capture microdissected, the RNA was amplified, and gene expression was assessed using Affymetrix Human Genome U133A GeneChip. Differential expression was examined with principal component analysis, hierarchical clustering, and Student's t testing. Analysis of gene ontology was done with Expression Analysis Systematic Explorer and gene expression data were integrated with genomic alterations with Differential Gene Locus Mapping. RESULTS: Unsupervised principal component analysis showed that the androgen-dependent and androgen-independent tumors segregated from one another. After filtering the data, 239 differentially expressed genes were identified. Two main gene ontologies were found discordant between androgen-independent and androgen-dependent tumors: macromolecule biosynthesis was down-regulated and cell adhesion was up-regulated in androgen-independent tumors. Other differentially expressed genes were related to interleukin-6 signaling as well as angiogenesis, cell adhesion, apoptosis, oxidative stress, and hormone response. The Differential Gene Locus Mapping analysis identified nine regions of potential chromosomal deletion in the androgen-independent tumors, including 1p36, 3p21, 6p21, 8p21, 11p15, 11q12, 12q23, 16q12, and 16q21. CONCLUSIONS: Taken together, these data identify several unique characteristics of androgen-independent prostate cancer that may hold potential for the development of targeted therapeutic intervention. PMID: 16203770 [PubMed - indexed for MEDLINE]

Posted by blogposter at 10:30 PM |

Radiation sensitivity of human carcinoma cells transfected with small interfering RNA targeted against cyclooxygenase-2.


Radiation sensitivity of human carcinoma cells transfected with small interfering RNA targeted against cyclooxygenase-2.
Related Articles Radiation sensitivity of human carcinoma cells transfected with small interfering RNA targeted against cyclooxygenase-2. Clin Cancer Res. 2005 Oct 1;11(19 Pt 1):6980-6 Authors: Palayoor ST, Arayankalayil MJ, Shoaibi A, Coleman CN PURPOSE: Cyclooxygenase-2 (COX-2) is considered a potential target for cancer therapy, because COX-2 levels are elevated in the majority of human tumors compared with the normal tissues. COX-2 inhibitors inhibit tumor growth and enhance radiation response in vitro as well as in vivo. However, the precise role of COX-2 in radiation response is not clear. The purpose of the present study was to investigate the in vitro radiosensitivity of tumor cells as a function of COX-2 expression. EXPERIMENTAL DESIGN AND RESULTS: PC3 and HeLa cells express COX-2 protein constitutively. We silenced the COX-2 gene in these cells using small interfering RNA (siRNA). Transfection of PC3 cells with 100 nmol/L siRNA targeted against COX-2 resulted in reduction of COX-2 protein by 75% and inhibition of arachidonic acid-induced prostaglandin E2 synthesis by approximately 50% compared with the vehicle control. In HeLa cells, 100 nmol/L COX-2 siRNA inhibited COX-2 protein expression by 80%. Cell cycle analysis showed that transfection with COX-2 siRNA did not alter the cell cycle distribution. Radiosensitivity was determined by clonogenic cell survival assay. There was no significant difference in the radiosensitivity of cells in which COX-2 was silenced compared with the cells transfected vehicle or with negative control siRNAs (enhancement ratio = 1.1). CONCLUSIONS: These data indicate that the in vitro radiosensitivity of tumor cells is minimally dependent on the cellular COX-2 status. Given that a number of potential mechanisms are attributed to COX-2 inhibitors for radiosensitization, specific intervention of COX-2 by RNA interference could help elucidate the precise role of COX-2 in cancer therapy and to optimize strategies for COX-2 inhibition. PMID: 16203791 [PubMed - indexed for MEDLINE]

Posted by blogposter at 10:30 PM |

Current drug therapy for prostate cancer: an overview.


Current drug therapy for prostate cancer: an overview.
Related Articles Current drug therapy for prostate cancer: an overview. Curr Med Chem Anticancer Agents. 2005 Nov;5(6):603-12 Authors: Stewart AB, Lwaleed BA, Douglas DA, Birch BR Prostate cancer is the most common cancer amongst men in the USA and the second most common malignant cause of male death worldwide after lung cancer. The life time risk of having microscopic evidence of prostate cancer for a 50 year old man is 42%. Prostate cancer is thus becoming an increasingly significant global health problem in terms of mortality, morbidity, as well as economically. This review, discusses current medical therapeutic options for prostate cancer including traditional treatments using luteinising hormone releasing analogues (LHRH), anti-androgens and estrogen treatments, and the use of novel drugs directed against molecular targets considered important in oncogenesis and metastasis. Prostate cancer chemoprevention using 5alpha-reductase inhibitors and the role of gene therapy are also considered. PMID: 16305482 [PubMed - indexed for MEDLINE]

Posted by blogposter at 10:29 PM |

Docetaxel in hormone-refractory metastatic prostate cancer.


Docetaxel in hormone-refractory metastatic prostate cancer.
Related Articles Docetaxel in hormone-refractory metastatic prostate cancer. Drugs. 2005;65(16):2287-94; discussion 2295-7 Authors: McKeage K, Keam SJ The taxoid analogue docetaxel is a potent inhibitor of microtubular depolymerisation and, in hormone-refractory metastatic prostate cancer, it also counters the effects of the anti-apoptotic protein Bcl-2. Overall survival was significantly increased in patients with hormone-refractory metastatic prostate cancer receiving intravenous docetaxel every 3 weeks plus oral prednisone or estramustine, compared with patients receiving intravenous mitoxantrone every 3 weeks plus prednisone in two large phase III trials (TAX 327 and SWOG [Southwest Oncology Group] 9916). In the TAX 327 study, patients receiving docetaxel 75 mg/m(2) every 3 weeks plus prednisone had a median overall survival duration of 18.9 months; in the SWOG 9916 study, median overall survival duration was 17.5 months with docetaxel 60 mg/m(2) every 3 weeks plus estramustine 280 mg three times daily on days 1-5. The median overall survival duration for the control arm of mitoxantrone 12 mg/m(2) every 3 weeks plus prednisone was 16-17 months. Compared with mitoxantrone plus prednisone, docetaxel plus prednisone improved prostate specific antigen response rate, pain and health-related quality of life, and docetaxel plus estramustine increased progression-free survival. Adverse events were more common with docetaxel- than mitoxantrone-based treatment regimens, but most events associated with docetaxel were mild-to-moderate in severity. PMID: 16266195 [PubMed - indexed for MEDLINE]

Posted by blogposter at 10:29 PM |

Acute renal failure secondary to imatinib mesylate treatment in prostate cancer.


Acute renal failure secondary to imatinib mesylate treatment in prostate cancer.
Related Articles Acute renal failure secondary to imatinib mesylate treatment in prostate cancer. Ann Pharmacother. 2005 Dec;39(12):2136-8 Authors: Foringer JR, Verani RR, Tjia VM, Finkel KW, Samuels JA, Guntupalli JS OBJECTIVE: To report a case of acute renal failure associated with the administration of imatinib mesylate. CASE SUMMARY: A 64-year-old man diagnosed with prostate cancer was enrolled in a Phase I trial of imatinib mesylate plus taxotere on a protocol that required a run-in period of imatinib mesylate alone. During therapy with imatinib mesylate, the patient developed acute renal failure, requiring hemodialysis. A renal biopsy revealed tubular vacuolization. Renal failure resolved with cessation of imatinib mesylate. DISCUSSION: Imatinib mesylate is a protein tyrosine kinase inhibitor that inhibits the BCR-ABL tyrosine kinase, the receptor tyrosine kinases for platelet-derived growth factor, and stem cell factor c-kit. Prostate cancer has been identified as a target for therapy with imatinib mesylate. This patient had no other confounding factors for the cause of the renal failure. An objective causality assessment determined that imatinib mesylate was the probable cause of the acute renal failure. The presence of a primary glomerular disease was excluded by biopsy. CONCLUSIONS: Imatinib mesylate-induced acute renal failure has now been linked to toxic effects on renal tubular cells in 3 cases. Renal function should be closely monitored during imatinib mesylate therapy. PMID: 16288076 [PubMed - in process]

Posted by blogposter at 10:29 PM |

Evaluation of human fetal bone implants in SCID mice as a model of prostate cancer bone metastasis.


Evaluation of human fetal bone implants in SCID mice as a model of prostate cancer bone metastasis.
Related Articles Evaluation of human fetal bone implants in SCID mice as a model of prostate cancer bone metastasis. Oncol Rep. 2006 Mar;15(3):519-24 Authors: Singh AS, Macpherson GR, Price DK, Schimel D, Figg WD The metastasis of prostate cancer cells to the bone marrow constitutes the major source of morbidity and mortality in prostate cancer. Studying this process has been hampered by the lack of preclinical models to evaluate novel therapeutics and to study the biology of the disease. One proposed model utilizes human fetal bone implants to serve as the target for prostate cancer cells injected via the tail vein. We employed this model to test the ability of zoledronic acid to prophylax and to treat bone metastases. To improve the rate of bone metastasis, we used two bone implants instead of one to evaluate the cell lines PC3 and PC3M, a more metastatic subline. For this purpose we generated the novel cell line PC3EGFPLuc, which can be used for luminescence and/or fluorescence imaging in vivo. We did not observe bone implant metastases in 52 mice, with 90 bone implants following tail vein injection of 1x10(6) PC3 or PC3M cells. Soft tissue lesions in the buttocks and hind limbs as well as cellular growth in the hindlimbs were observed via bioluminescence imaging. This evidence together with literature findings suggests that this model produces artifactual 'bone metastasis' lesions. PMID: 16465406 [PubMed - in process]

Posted by blogposter at 10:29 PM |

February 08, 2006

Is Cancer becoming an epidemic?


Is Cancer becoming an epidemic?
ProgressiveU.org, CA - Feb 2, 2006... into the cancer "theory" and its treatments, from toxic chemotherapy to alternative herbal remedies. ... My dad (59)had prostate cancer, a family friend (42 ...

Posted by blogposter at 05:28 PM |

Prostate Cancer Screening - The need to reduce patient discomfort during transrectal ultrasonography-guided prostate biopsy: what do we know?


The need to reduce patient discomfort during transrectal ultrasonography-guided prostate biopsy: what do we know?
Related Articles The need to reduce patient discomfort during transrectal ultrasonography-guided prostate biopsy: what do we know? BJU Int. 2005 Nov;96(7):977-83 Authors: De Sio M, D'Armiento M, Di Lorenzo G, Damiano R, Perdon S, De Placido S, Autorino R PMID: 16225512 [PubMed - indexed for MEDLINE]

Posted by blogposter at 05:27 PM |

Leuprolide acetate given by a subcutaneous extended-release injection: less of a pain?


Leuprolide acetate given by a subcutaneous extended-release injection: less of a pain?
Related Articles Leuprolide acetate given by a subcutaneous extended-release injection: less of a pain? Expert Rev Anticancer Ther. 2005 Aug;5(4):605-11 Authors: Cox MC, Scripture CD, Figg WD Androgen deprivation therapy is a mainstay for the treatment of advanced prostate cancer. Hormonal therapy commonly consists of injection of gonadotropin hormone-releasing hormone agonists. Based on the need for improved convenience of administration, a novel formulation of leuprolide acetate (Eligard; Atrix Laboratories Inc. & Sanofi Aventis) which incorporates a mixture of selected polymers and solvents to achieve sustained drug delivery after subcutaneous injection, was developed. The US Food and Drug Administration has approved 1-, 3-, 4- and 6-month formulations of leuprolide acetate. In clinical trials, leuprolide acetate achieves sustained suppression of serum testosterone to castration levels (< or =50 ng/dl). The adverse-event profile is consistent with the effects of testosterone suppression. This novel delivery system in addition to the availability of a 6-month formulation of leuprolide acetate, offers patients the option of a convenient twice-yearly injection schedule. PMID: 16111462 [PubMed - indexed for MEDLINE]

Posted by blogposter at 05:27 PM |

Human Kruppel-like factor 5 is a target of the E3 ubiquitin ligase WWP1 for proteolysis in epithelial cells.


Human Kruppel-like factor 5 is a target of the E3 ubiquitin ligase WWP1 for proteolysis in epithelial cells.
Related Articles Human Kruppel-like factor 5 is a target of the E3 ubiquitin ligase WWP1 for proteolysis in epithelial cells. J Biol Chem. 2005 Dec 16;280(50):41553-61 Authors: Chen C, Sun X, Guo P, Dong XY, Sethi P, Cheng X, Zhou J, Ling J, Simons JW, Lingrel JB, Dong JT The transcription factor KLF5 plays an important role in human carcinogenesis. In epithelial cells, the KLF5 protein is tightly regulated by the ubiquitin-proteasome pathway. To better understand the mechanisms for the regulation of KLF5 protein, we identified and characterized an E3 ubiquitin ligase for KLF5, i.e. WWP1. We found that WWP1 formed a protein complex with KLF5 in vivo and in vitro. Furthermore, WWP1 mediated the ubiquitination and degradation of KLF5, and the catalytic cysteine residue of WWP1 is essential for its function. A PY motif in a transactivation domain of KLF5 is necessary for its interaction with WWP1. Finally, WWP1 was amplified and overexpressed in some cancer cell lines from the prostate and breast, which negatively regulated the function of KLF5 in gene regulation. These findings not only established WWP1 as an E3 ubiquitin ligase for KLF5, they also further implicated the KLF5 pathway in human carcinogenesis. PMID: 16223724 [PubMed - indexed for MEDLINE]

Posted by blogposter at 05:27 PM |

Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA.


Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA.
Related Articles Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA. J Med Primatol. 2006 Feb;35(1):12-7 Authors: Marshall DJ, Rudnick KA, Lu J, Snyder LA Background Prostate-specific antigen (PSA) is an invaluable tumor marker for the detection of early prostate cancer, and can be a target for active immunotherapy of prostate cancer. We wanted to assess the usefulness of the cynomolgus monkey (Macaca fascicularis) as a relevant animal model to evaluate PSA-specific therapies. Methods RNA was isolated from the prostate of cynomolgus monkeys, and PSA gene products were amplified by reverse transcriptase-polymerase chain reaction using primers from conserved regions of human and rhesus monkey (Macaca mulatta) PSA genes. These amplified products were then sequenced. Results The cynomolgus PSA amino acid sequence is 89.7% identical to the human PSA gene, and 99.2% identical to the rhesus PSA amino acid sequence. Like the human and rhesus PSA genes, an open-reading frame of 261 amino acids was identified for the cynomolgus gene. Expression of the cynomolgus PSA gene appears to be restricted to the prostate, as it is in humans. Conclusions The high identity between human and cynomolgus PSA sequences suggests that the cynomolgus monkey should be studied further for its potential as a large animal model to evaluate PSA-specific therapies. PMID: 16430490 [PubMed - in process]

Posted by blogposter at 05:27 PM |

Ablation of stage T1/T2 prostate cancer with permanent interstitial temperature self-regulating rods.


Ablation of stage T1/T2 prostate cancer with permanent interstitial temperature self-regulating rods.
Related Articles Ablation of stage T1/T2 prostate cancer with permanent interstitial temperature self-regulating rods. J Endourol. 2005 Sep;19(7):865-7 Authors: Tucker RD, Huidobro C, Larson T PURPOSE: To determine if stage T(1)/T(2) prostate cancer can be treated safely and effectively with interstitial thermal ablation. PATIENTS AND METHODS: Twenty patients with biopsy-confirmed prostate cancer were enrolled in the protocol. The average age was 71.0 years, and the pretreatment prostate specific antigen (PSA) concentration ranged from 2.5 to 10.7 ng/mL and the Gleason sum from 3 to 7. An array of small biocompatible magnetic alloy rods was placed in the patients percutaneously in a procedure analogous to the placement of brachytherapy seeds. Rods were placed end-to-end and no further than 1 cm apart; rods extended to the capsule and were placed at the capsule in the rectal grove. The rods are temperature self-regulating and heat to 70 degrees C when placed in an alternating magnetic field. Each patient was treated in a coil system that supplies a uniform magnetic field throughout the patient's pelvis for a single 60-minute session. Urethral cooling and rectal temperature monitoring was performed. Serial PSA was followed, and biopsy was performed 1 year post-treatment. RESULTS: Immediately after treatment, most PSA values increased dramatically but then fell to <1.0 ng/mL within 8 weeks. After 1 year, five patients had positive biopsies; these patients had significantly lower rodimplant densities. Eight patients reported erectile dysfunction, but none reported incontinence. Other complications were minor. CONCLUSION: The data suggest that this technique is well tolerated and safe and may be useful in certain patients with T(1)/T(2) prostate cancer. PMID: 16190846 [PubMed - indexed for MEDLINE]

Posted by blogposter at 05:26 PM |

Influence of number of CAG repeats on local control in the RTOG 86-10 protocol.


Influence of number of CAG repeats on local control in the RTOG 86-10 protocol.
Related Articles Influence of number of CAG repeats on local control in the RTOG 86-10 protocol. Am J Clin Oncol. 2006 Feb;29(1):14-20 Authors: Abdel-Wahab M, Berkey BA, Krishan A, O'Brien T, Hammond E, Roach M, Lawton C, Pilepich M, Markoe A, Pollack A OBJECTIVES: The number of CAG repeats on the androgen receptor (AR) gene is inversely proportional to transcriptional activity. The purpose of this study was to determine if short-term androgen deprivation therapy (RT + HT) can improve outcome in patients with tumors with short CAG repeats (<19). MATERIALS AND METHODS: Prostate cancer patients were randomized to receive either radiotherapy (RT) alone or (RT + HT) in the RTOG 86-10 study. CAG repeats were measured in 94 tumor specimens (21%; test cohort) of the 456 (parent cohort) analyzable cases. AR flow cytometry measurements were done on 13 patients. The effect on local failure (LF), distant metastases (DM), prostate cancer survival (PSS), and overall survival (OS) was studied. RESULTS: Pretreatment characteristics and assigned treatment arm were not significantly different between the parent and test groups except for a significantly higher risk of death (P = 0.049) in the test group. The median CAG repeat was 19. There were no significant differences in stage, or Gleason score between high (19 or greater) and low CAG (<19) patients within each treatment group. Number of CAG repeats alone did not significantly influence LF, DM, PSS, and OS. However, when the CAG repeat outcome was studied in conjunction with androgen deprivation therapy, patients with CAG <19 who received H + RT had improved local control as compared with patients who received RT alone (P = 0.026, 5-year rates 4.6% versus 36.4%) and improved local control over patients with CAG > or =19 that received H + RT (P = 0.028). CONCLUSIONS: Patients with short CAG repeats show a local control benefit with short-term androgen deprivation therapy, but no improvement in survival. PMID: 16462497 [PubMed - in process]

Posted by blogposter at 05:26 PM |

Current drug therapy for prostate cancer: an overview.


Current drug therapy for prostate cancer: an overview.
Related Articles Current drug therapy for prostate cancer: an overview. Curr Med Chem Anticancer Agents. 2005 Nov;5(6):603-12 Authors: Stewart AB, Lwaleed BA, Douglas DA, Birch BR Prostate cancer is the most common cancer amongst men in the USA and the second most common malignant cause of male death worldwide after lung cancer. The life time risk of having microscopic evidence of prostate cancer for a 50 year old man is 42%. Prostate cancer is thus becoming an increasingly significant global health problem in terms of mortality, morbidity, as well as economically. This review, discusses current medical therapeutic options for prostate cancer including traditional treatments using luteinising hormone releasing analogues (LHRH), anti-androgens and estrogen treatments, and the use of novel drugs directed against molecular targets considered important in oncogenesis and metastasis. Prostate cancer chemoprevention using 5alpha-reductase inhibitors and the role of gene therapy are also considered. PMID: 16305482 [PubMed - indexed for MEDLINE]

Posted by blogposter at 05:26 PM |

Dramatic synergistic anticancer effect of clinically achievable doses of lovastatin and troglitazone.


Dramatic synergistic anticancer effect of clinically achievable doses of lovastatin and troglitazone.
Related Articles Dramatic synergistic anticancer effect of clinically achievable doses of lovastatin and troglitazone. Int J Cancer. 2006 Mar 1;118(3):773-9 Authors: Yao CJ, Lai GM, Chan CF, Cheng AL, Yang YY, Chuang SE Lovastatin (an HMG-CoA reductase inhibitor) and troglitazone (a PPAR-gamma agonist) have been intensively studied prospectively for their application in cancer treatment. However, clinical trials of lovastatin or troglitazone in cancer treatment resulted in only limited responses. To improve their efficacy, lovastatin and troglitazone have, respectively, been tried to combine with other anticancer agents with varied outcomes. In our study, we found a dramatic synergism between lovastatin and troglitazone in anticancer at clinically achievable concentrations. This synergism was found in far majority of cell lines tested including DBTRG 05 MG (glioblastoma) and CL1-0 (lung). This amazing synergism was accompanied by synergistic modulation of E2F-1 and p27(Kip1), which were reported to mediate the anticancer activities of lovastatin and troglitazone, respectively, and other cell cycle regulating proteins such as CDK2, cyclin A and RB phosphorylation status. With this dramatic combination effect of lovastatin and troglitazone, a promising regimen of cancer therapy may be materialized in the future. PMID: 16094629 [PubMed - indexed for MEDLINE]

Posted by blogposter at 05:26 PM |

Long-term clinical outcomes of 420 consecutive prostate cancer patients in a single institute.


Long-term clinical outcomes of 420 consecutive prostate cancer patients in a single institute.
Related Articles Long-term clinical outcomes of 420 consecutive prostate cancer patients in a single institute. Acta Med Okayama. 2005 Oct;59(5):195-9 Authors: Edamura K, Saika T, Senoh T, Koizumi F, Manabe D, Ebara S, Kaku H, Yokoyama T, Abarzua F, Nagai A, Nasu Y, Tsushima T, Kumon H This study was undertaken to reveal the trends of prostate cancer and the outcome of treatment modalities for each disease stage in patients in a single institute over a 10-year period. From January 1994 through December 2003, 420 consecutive patients with previously untreated and histologically confirmed prostate cancer were analyzed for annual distributions of disease stages and treatment modalities and for long-term clinical progression-free survival, prostate cancer-specific survival, and prostate-specific antigen (PSA) failure-free survival rates for each stage and treatment modality. Annual trends showed that the number of patients, especially those with clinically localized cancer, increased dramatically. The 5-year disease-specific survival rates for patients with clinically localized disease were 100 percent for all treatment modalities, including hormonal therapy alone. Patients with PSA levels less than 10 ng/ml showed an 81 percent 5-year PSA failure-free survival rate with radical prostatectomy. Stage C patients treated by surgery or radiation-based therapy with concomitant hormonal therapy obtained 93 percent and 100 percent cause-specific survival rates, respectively, and those treated by hormonal therapy alone showed a 79 percent rate. The number of patients with localized prostate cancer was increasing in this decade. While long-term hormonal therapy alone was highly efficient in controlling localized prostate cancer, radical therapies in conjunction with neo-adjuvant hormonal therapy produced better survival rates in cases of locally advanced disease. PMID: 16286958 [PubMed - in process]

Posted by blogposter at 05:26 PM |

Laparoscopic surgery for melanoma metastases to the adrenal gland.


Laparoscopic surgery for melanoma metastases to the adrenal gland.
Related Articles Laparoscopic surgery for melanoma metastases to the adrenal gland. Expert Rev Anticancer Ther. 2004 Oct;4(5):837-41 Authors: Sturgeon C, Leong SP, Duh QY The probability of developing cutaneous melanoma is now predicted to be one in 55 for males and one in 88 for females. Although melanoma is relatively uncommon compared with other malignancies such as breast (one in seven) or prostate cancer (one in six), the incidence is growing at an alarming rate. The development of novel strategies for the management of advanced disease will become even more urgent and require continued and controlled investigations over the next 10 years. Surgery is effective for the palliation of isolated resectable metastases. However, most patients with Stage IV melanoma have widespread disease and are not cured by metastasectomy. For the few individuals with isolated adrenal metastases from melanoma, complete resection appears to confer a survival advantage. New data are emerging about the efficacy and outcome of laparoscopic adrenalectomy for malignant lesions. However, the natural history of laparoscopic surgery for these lesions is still unknown. The indications for and limitations of laparoscopic adrenalectomy for metastatic melanoma are discussed. PMID: 15485317 [PubMed - indexed for MEDLINE]

Posted by blogposter at 05:25 PM |

February 07, 2006

Controlling Your Impulses After Parkinson's Treatment


Controlling Your Impulses After Parkinson's Treatment
ABC News - Select a Health Topic ADD & ADHD Allergy Alternative Medicine Alzheimer's Disease Arthritis Asthma Body Aches and Pains Breast Cancer Cancer Awareness Cardio Health Children's Health Colon Cancer Contraception COPD/Emphysema Dental Health Diabetes

Posted by blogposter at 05:13 PM |

Prostate Cancer Screening - Urinary estrogen metabolites, prostate specific antigen, and body mass index among African-American men in South Carolina.


Urinary estrogen metabolites, prostate specific antigen, and body mass index among African-American men in South Carolina.
Related Articles Urinary estrogen metabolites, prostate specific antigen, and body mass index among African-American men in South Carolina. Cancer Detect Prev. 2005;29(6):494-500 Authors: Teas J, Cunningham JE, Fowke JH, Nitcheva D, Kanwat CP, Boulware RJ, Sepkovic DW, Hurley TG, Hebert JR INTRODUCTION: Estrogen metabolites have been linked to risk of breast cancer, and we were interested in whether they are associated with prostate specific antigen (PSA) and other factors associated with prostate cancer. African-American (AA) men in South Carolina have among the highest prostate cancer rates in the world, and thus provide an ideal population in which to investigate this hypothesis. METHODS: We recruited AA men attending prostate cancer screenings in and around Columbia, South Carolina. Because very few men had elevated PSAs, we restricted our study to the 77 men whose PSA was below the cutpoint used by the screening program to indicate need for diagnostic workup. These men provided spot urine samples and answered demographic and lifestyle questions including self-reported body weight, height, exercise, tobacco use, medications, cancer history and age. Levels of urinary 2-hydroxyestrone (2-OHE1) and 16alpha-hydroxyestrone (16alpha-OHE1), and their ratio (2/16) and blood PSA levels were determined. RESULTS: After adjusting for a statistically significant interaction between age and BMI, we found a reduction of 14.2% in 2-OHE1 for each 1.0 ng/ml increase in PSA (p=0.05). For obese AA men only (BMI> or =30 kg/m2), 2-OHE1 increased by 36% for each decade of age (p=0.009). CONCLUSIONS: Estrogen metabolites may be related to PSA level in AA men. Older men with BMIs greater than 30 kg/m2 had an unexpected increase in 2-OHE1, suggesting a dysregulation of this estrogen metabolism pathway. Further studies of estrogen metabolites may provide insights into prostate cancer risk factors. PMID: 16289388 [PubMed - in process]

Posted by blogposter at 05:13 PM |

A cancer DNA phenotype in healthy prostates, conserved in tumors and adjacent normal cells, implies a relationship to carcinogenesis.


A cancer DNA phenotype in healthy prostates, conserved in tumors and adjacent normal cells, implies a relationship to carcinogenesis.
Related Articles A cancer DNA phenotype in healthy prostates, conserved in tumors and adjacent normal cells, implies a relationship to carcinogenesis. Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):19093-6 Authors: Malins DC, Gilman NK, Green VM, Wheeler TM, Barker EA, Anderson KM A cancer DNA phenotype, identical to the DNA structure of tumors, has been identified in the prostate glands of certain healthy men over 55 years of age. We now show that the same DNA signature exists in normal tissues adjacent to tumors. This finding implies that the phenotype is maintained in normal prostate cells from its inception through tumor development. The presence of the phenotype in tumors, adjacent normal cells, and in the normal prostate cells of certain older men suggests that it is a potentially critical factor in tumor development and may serve as an early biomarker for cancer risk assessment. Intervention to inhibit the development of the phenotype in healthy men, or to eliminate it once formed, may suppress or even prevent tumor formation. PMID: 16361440 [PubMed - indexed for MEDLINE]

Posted by blogposter at 05:12 PM |

A cancer DNA phenotype in healthy prostates, conserved in tumors and adjacent normal cells, implies a relationship to carcinogenesis.


A cancer DNA phenotype in healthy prostates, conserved in tumors and adjacent normal cells, implies a relationship to carcinogenesis.
Related Articles A cancer DNA phenotype in healthy prostates, conserved in tumors and adjacent normal cells, implies a relationship to carcinogenesis. Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):19093-6 Authors: Malins DC, Gilman NK, Green VM, Wheeler TM, Barker EA, Anderson KM A cancer DNA phenotype, identical to the DNA structure of tumors, has been identified in the prostate glands of certain healthy men over 55 years of age. We now show that the same DNA signature exists in normal tissues adjacent to tumors. This finding implies that the phenotype is maintained in normal prostate cells from its inception through tumor development. The presence of the phenotype in tumors, adjacent normal cells, and in the normal prostate cells of certain older men suggests that it is a potentially critical factor in tumor development and may serve as an early biomarker for cancer risk assessment. Intervention to inhibit the development of the phenotype in healthy men, or to eliminate it once formed, may suppress or even prevent tumor formation. PMID: 16361440 [PubMed - indexed for MEDLINE]

Posted by blogposter at 05:12 PM |

Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA.


Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA.
Related Articles Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA. J Med Primatol. 2006 Feb;35(1):12-7 Authors: Marshall DJ, Rudnick KA, Lu J, Snyder LA Background Prostate-specific antigen (PSA) is an invaluable tumor marker for the detection of early prostate cancer, and can be a target for active immunotherapy of prostate cancer. We wanted to assess the usefulness of the cynomolgus monkey (Macaca fascicularis) as a relevant animal model to evaluate PSA-specific therapies. Methods RNA was isolated from the prostate of cynomolgus monkeys, and PSA gene products were amplified by reverse transcriptase-polymerase chain reaction using primers from conserved regions of human and rhesus monkey (Macaca mulatta) PSA genes. These amplified products were then sequenced. Results The cynomolgus PSA amino acid sequence is 89.7% identical to the human PSA gene, and 99.2% identical to the rhesus PSA amino acid sequence. Like the human and rhesus PSA genes, an open-reading frame of 261 amino acids was identified for the cynomolgus gene. Expression of the cynomolgus PSA gene appears to be restricted to the prostate, as it is in humans. Conclusions The high identity between human and cynomolgus PSA sequences suggests that the cynomolgus monkey should be studied further for its potential as a large animal model to evaluate PSA-specific therapies. PMID: 16430490 [PubMed - in process]

Posted by blogposter at 05:12 PM |

Transrectal ultrasound guided biopsy for detecting early prostate cancer: An Indian experience.


Transrectal ultrasound guided biopsy for detecting early prostate cancer: An Indian experience.
Related Articles Transrectal ultrasound guided biopsy for detecting early prostate cancer: An Indian experience. Indian J Cancer. 2005 Jul-Sep;42(3):151-4 Authors: Gupta NP, Ansari MS, Dass SC BACKGROUND: With the advent of prostate specific antigen the number of patients undergoing prostate biopsy has dramatically increased. The sextant biopsy technique has been conventionally used for the diagnosis of prostate cancer. Recently, concern has arisen that the original sextant method may not include an adequate sample of the prostate, hence it may result in high false negative rates. We conducted a prospective study to determine whether the 5-region prostate biopsy technique significantly increases the chance of prostate cancer detection as compared to the sextant biopsy technique. AIMS: To evaluate the efficacy of TRUS guided sextant and 5-region biopsy techniques in detecting carcinoma prostate in patients with PSA between 4 and 10 ng/ml and normal digital rectal examination. METHODS AND MATERIAL: Between December 2001 and August 2003 one forty-two men, aged 49-82 years, who presented with LUTS, normal digital rectal examination (DRE) and PSA between 4 and 10 ng/ml underwent TRUS guided sextant prostate biopsy. Serum PSA was reassessed after 3 months in patients whose biopsies were negative for cancer. If PSA was still raised, the patients underwent extensive 5-region biopsy. RESULTS: Mean patient age was 64 years and median PSA was 6.9 ng/ml. TRUS guided sextant biopsy revealed adenocarcinoma prostate in 34 men (24%). Median Gleason score was 7. Seven men (4.9%) had cellular atypia and 3(2.1%) had prostatic intraepithelial neoplasia (high grade). On repeat PSA estimation after 3 months, 48 patients showed stagnant or rising trend for which they underwent TRUS guided 13-core biopsy. Five (10.4%) patients were detected to have adenocarcinoma on repeat biopsy. Biopsy negative patients are on regular follow up with yearly PSA estimation. Complications included transient mild haematuria in14 patients (9.82%) and haematospermia in 4 (2.8%). Urinary retention developed in one patient and required an indwelling catheter for 4 days. CONCLUSION: Transrectal ultrasound guided sextant biopsy has shown a false negative rate of approximately 11%. A repeat 5- region (13-core) biopsy strategy can decrease the false negative rate of conventional sextant biopsy in patients with previously negative biopsies but persistently high PSA levels, high grade PIN or cellular atypia. PMID: 16276016 [PubMed - indexed for MEDLINE]

Posted by blogposter at 05:12 PM |

Integral radiation dose to normal structures with conformal external beam radiation.


Integral radiation dose to normal structures with conformal external beam radiation.
Related Articles Integral radiation dose to normal structures with conformal external beam radiation. Int J Radiat Oncol Biol Phys. 2006 Mar 1;64(3):962-7 Authors: Aoyama H, Westerly DC, Mackie TR, Olivera GH, Bentzen SM, Patel RR, Jaradat H, Tome WA, Ritter MA, Mehta MP Background: This study was designed to evaluate the integral dose (ID) received by normal tissue from intensity-modulated radiotherapy (IMRT) for prostate cancer. Methods and Materials: Twenty-five radiation treatment plans including IMRT using a conventional linac with both 6 MV (6MV-IMRT) and 20 MV (20MV-IMRT), as well as three-dimensional conformal radiotherapy (3DCRT) using 6 MV (6MV-3DCRT) and 20 MV (20MV-3DCRT) and IMRT using tomotherapy (6MV) (Tomo-IMRT), were created for 5 patients with localized prostate cancer. The ID (mean dose x tissue volume) received by normal tissue (NTID) was calculated from dose-volume histograms. Results: The 6MV-IMRT resulted in 5.0% lower NTID than 6MV-3DCRT; 20 MV beam plans resulted in 7.7%-11.2% lower NTID than 6MV-3DCRT. Tomo-IMRT NTID was comparable to 6MV-IMRT. Compared with 6MV-3DCRT, 6MV-IMRT reduced IDs to the rectal wall and penile bulb by 6.1% and 2.7%, respectively. Tomo-IMRT further reduced these IDs by 11.9% and 16.5%, respectively. The 20 MV did not reduce IDs to those structures. Conclusions: The difference in NTID between 3DCRT and IMRT is small. The 20 MV plans somewhat reduced NTID compared with 6 MV plans. The advantage of tomotherapy over conventional IMRT and 3DCRT for localized prostate cancer was demonstrated in regard to dose sparing of rectal wall and penile bulb while slightly decreasing NTID as compared with 6MV-3DCRT. PMID: 16458781 [PubMed - in process]

Posted by blogposter at 05:12 PM |

Current drug therapy for prostate cancer: an overview.


Current drug therapy for prostate cancer: an overview.
Related Articles Current drug therapy for prostate cancer: an overview. Curr Med Chem Anticancer Agents. 2005 Nov;5(6):603-12 Authors: Stewart AB, Lwaleed BA, Douglas DA, Birch BR Prostate cancer is the most common cancer amongst men in the USA and the second most common malignant cause of male death worldwide after lung cancer. The life time risk of having microscopic evidence of prostate cancer for a 50 year old man is 42%. Prostate cancer is thus becoming an increasingly significant global health problem in terms of mortality, morbidity, as well as economically. This review, discusses current medical therapeutic options for prostate cancer including traditional treatments using luteinising hormone releasing analogues (LHRH), anti-androgens and estrogen treatments, and the use of novel drugs directed against molecular targets considered important in oncogenesis and metastasis. Prostate cancer chemoprevention using 5alpha-reductase inhibitors and the role of gene therapy are also considered. PMID: 16305482 [PubMed - indexed for MEDLINE]

Posted by blogposter at 05:12 PM |

Hormone refractory prostate cancer: Management and advances.


Hormone refractory prostate cancer: Management and advances.
Related Articles Hormone refractory prostate cancer: Management and advances. Cancer Treat Rev. 2006 Feb 1; Authors: Sonpavde G, Hutson TE, Berry WR Effective therapeutic options have not existed for prostate cancer progressing after androgen deprivation therapy until very recently. Secondary hormonal manipulations offer marginal benefits. Docetaxel based chemotherapy has been demonstrated to extend survival and change the natural history of the disease in two large randomized trials. These studies have provided the impetus to combine docetaxel with novel biologic agents to further consolidate the gains in long-term outcome. With the arrival of exciting agents including vaccines, monoclonal antibodies, bone-targeted drugs, antisense oligonucleotides, anti-angiogenic drugs and small molecule receptor tyrosine kinase inhibitors, the future treatment of prostate cancer appears promising. PMID: 16458434 [PubMed - as supplied by publisher]

Posted by blogposter at 05:11 PM |

Correlation between LUTS (AUA-SS) and erectile dysfunction (SHIM) in an age-matched racially diverse male population: data from the prostate cancer awareness week (PCAW).


Correlation between LUTS (AUA-SS) and erectile dysfunction (SHIM) in an age-matched racially diverse male population: data from the prostate cancer awareness week (PCAW).
Related Articles Correlation between LUTS (AUA-SS) and erectile dysfunction (SHIM) in an age-matched racially diverse male population: data from the prostate cancer awareness week (PCAW). J Urol. 2005 Nov;174(5):1940 Authors: Seftel A PMID: 16217355 [PubMed - indexed for MEDLINE]

Posted by blogposter at 05:11 PM |

Cancer map patterns are they random or not?


Cancer map patterns are they random or not?
Related Articles Cancer map patterns are they random or not? Am J Prev Med. 2006 Feb;30(Suppl 2):S37-49 Authors: Kulldorff M, Song C, Gregorio D, Samociuk H, Dechello L BACKGROUND: Maps depicting the geographic variation in cancer incidence, mortality or treatment can be useful tools for developing cancer control and prevention programs, as well as for generating etiologic hypotheses. An important question with every cancer map is whether the geographic pattern seen is due to random fluctuations, as by pure chance there are always some areas with more cases than expected, or whether the map reflects true underlying geographic variation in screening, treatment practices, or etiologic risk factors. METHODS: Nine different tests for spatial randomness are evaluated in very practical settings by applying them to cancer maps for different types of data at different scales of spatial resolution: breast, prostate, and thyroid cancer incidence; breast cancer treatment and prostate cancer stage in Connecticut; and nasopharynx and prostate cancer mortality in the U.S. RESULTS: Tango's MEET, Oden's Ipop, and the spatial scan statistic performed well across all the data sets. Besag-Newell's R, Cuzick-Edwards k-NN, and Turnbull's CEPP often perform well, but the results are highly dependent on the parameter chosen. Moran's I performs poorly for most data sets, whereas Swartz Entropy Test and Whittemore's Test perform well for some data sets but not for other. CONCLUSIONS: When publishing cancer maps we recommend evaluating the spatial patterns observed using Tango's MEET, a global clustering test, and the spatial scan statistic, a cluster detection test. PMID: 16458789 [PubMed - in process]

Posted by blogposter at 05:11 PM |

February 05, 2006

Prostate Cancer Screening - Calcitonin increases invasiveness of prostate cancer cells: role for cyclic AMP-dependent protein kinase A in calcitonin action.


Calcitonin increases invasiveness of prostate cancer cells: role for cyclic AMP-dependent protein kinase A in calcitonin action.
Related Articles Calcitonin increases invasiveness of prostate cancer cells: role for cyclic AMP-dependent protein kinase A in calcitonin action. Int J Cancer. 2005 Nov 20;117(4):551-60 Authors: Sabbisetti VS, Chirugupati S, Thomas S, Vaidya KS, Reardon D, Chiriva-Internati M, Iczkowski KA, Shah GV Calcitonin (CT) is synthesized and secreted in prostate epithelium, and its secretion from malignant prostates is several-fold higher than from benign prostates. CT receptor (CTR) is expressed in malignant prostate epithelium, and its activation stimulates growth of prostate cancer (PC) cells via activation of adenylyl cyclase and calcium/phospholipid pathways. To identify the role of "CT System" in prostate cancer, we tested the expression of CT and CTR mRNAs in invading tumor cells of prostate cancer specimens. The effect of CT on in vitro invasion of PC cell lines and on activation of gelatinases was also examined. The cells of primary tumors and those invading stroma co-expressed CT/CTR mRNAs. Exogenously added CT increased in vitro invasion of PC cell lines and caused a rapid, several-fold but transient increase in protein kinase A activity. In contrast, anti-CT serum caused a dose-dependent inhibition of in vitro invasion of PC-3M cells. CT also increased the concentration and activities of MMP-2 and MMP-9. Rp.cAMP, a competitive inhibitor of cAMP-dependent protein kinase A, myristoylated protein kinase A inhibitory peptide (PKI) as well as the expression of dominant negative form of PKA all attenuated basal in vitro invasion of PC-3M cells, and CT could not increase in vitro invasiveness in their presence. These results suggest that overexpression of "CT System" in invasive PC tumors significantly contributes to increased invasiveness of prostate cancer cells. The action of CT may be mediated by protein kinase A signaling, which subsequently leads to increased cell invasion and secretion of gelatinases. PMID: 15929083 [PubMed - indexed for MEDLINE]

Posted by blogposter at 11:42 AM |

Red wine may influence prostate cancer risk.


Red wine may influence prostate cancer risk.
Related Articles Red wine may influence prostate cancer risk. Mayo Clin Health Lett. 2005 Dec;23(12):4 Authors: PMID: 16440466 [PubMed - indexed for MEDLINE]

Posted by blogposter at 11:42 AM |

Prostate-cancer-associated I260M variant of DNA polymerase beta is a sequence-specific mutator.


Prostate-cancer-associated I260M variant of DNA polymerase beta is a sequence-specific mutator.
Related Articles Prostate-cancer-associated I260M variant of DNA polymerase beta is a sequence-specific mutator. Biochemistry. 2005 Dec 6;44(48):15664-73 Authors: Dalal S, Hile S, Eckert KA, Sun KW, Starcevic D, Sweasy JB Studies show that 30% of 189 tumors sequenced to date express variants of the polymerase beta (pol beta) protein that are not present in normal tissue. This raises the possibility that variants of pol beta might be linked to the etiology of cancer. Here, we characterize the I260M prostate-cancer-associated variant of pol beta. Ile260 is a key residue of the hydrophobic hinge that is important for the closing of the polymerase. In this study, we demonstrate that the I260M variant is a sequence context-dependent mutator polymerase. Specifically, I260M is a mutator for misalignment-mediated errors in dipyrimidine sequences. I260M is also a low-fidelity polymerase with regard to the induction of transversions within specific sequence contexts. Our results suggest that the hinge influences the geometry of the DNA within the polymerase active site that is important for accurate DNA synthesis. Importantly, characterization of the I260M variant shows that it has a functional phenotype that could be linked to the etiology or malignant progression of human cancer. PMID: 16313169 [PubMed - indexed for MEDLINE]

Posted by blogposter at 11:41 AM |

Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA.


Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA.
Related Articles Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA. J Med Primatol. 2006 Feb;35(1):12-7 Authors: Marshall DJ, Rudnick KA, Lu J, Snyder LA Background Prostate-specific antigen (PSA) is an invaluable tumor marker for the detection of early prostate cancer, and can be a target for active immunotherapy of prostate cancer. We wanted to assess the usefulness of the cynomolgus monkey (Macaca fascicularis) as a relevant animal model to evaluate PSA-specific therapies. Methods RNA was isolated from the prostate of cynomolgus monkeys, and PSA gene products were amplified by reverse transcriptase-polymerase chain reaction using primers from conserved regions of human and rhesus monkey (Macaca mulatta) PSA genes. These amplified products were then sequenced. Results The cynomolgus PSA amino acid sequence is 89.7% identical to the human PSA gene, and 99.2% identical to the rhesus PSA amino acid sequence. Like the human and rhesus PSA genes, an open-reading frame of 261 amino acids was identified for the cynomolgus gene. Expression of the cynomolgus PSA gene appears to be restricted to the prostate, as it is in humans. Conclusions The high identity between human and cynomolgus PSA sequences suggests that the cynomolgus monkey should be studied further for its potential as a large animal model to evaluate PSA-specific therapies. PMID: 16430490 [PubMed - in process]

Posted by blogposter at 11:41 AM |

Complications following combined transrectal ultrasound-guided prostate needle biopsies and transurethral resection of the prostate.


Complications following combined transrectal ultrasound-guided prostate needle biopsies and transurethral resection of the prostate.
Related Articles Complications following combined transrectal ultrasound-guided prostate needle biopsies and transurethral resection of the prostate. Arch Androl. 2006 Mar-Apr;52(2):123-7 Authors: Shen BY, Chang PL, Lee SH, Chen CL, Tsui KH In order to evaluate safety and morbidity aspects of additional systematic prostate biopsies, we have conducted a retrospective review of patients who had undergone transurethral resection of the prostate (TUR-P) combined with additional systemic prostate needle biopsies at the Chang Gung Memorial Hospital. To this end, the records of 80 men presenting consecutively at our institution between February 2001 and January 2004 inclusively were examined. These 80 individuals included patients experiencing obstructive voiding symptoms and those featuring suspicious screening parameters, all of whom were to undergo transurethral resection of the prostate for symptomatic benign prostatic hyperplasia (BPH), all procedures being performed by a single surgeon. A total of 20 (25%) specimens were found to be positive for prostate cancer. Cancer was detected in the transrectal prostate biopsy specimen of 16 of 57 men (28%) who had not undergone a previous prostate biopsy, and for four of 23 (17%) who had undergone at least one previous (benign) biopsy. Mild complications associated with transurethral prostrate resection, such as hematuria and hemospermia, were reported frequently, featuring rates of 10% and 2.5%, respectively; more severe complications being noted far less frequently. Fever, usually of a low grade, was observed post-operatively for six (7.5%) patients, but a prompt return to normal temperature following antibiotic treatment for one day was revealed. Four (5%) patients remained admitted to the hospital for a prolonged period following surgery. A review of the literature concerning transrectal biopsies and TUR-P has shown that surgery-associated complication rates are slightly lower than was the case for our study. Additional systematic prostate biopsies for patients undergoing TUR-P would appear to be a relatively safe treatment procedure. Identification of risk factors for post-surgery complications might further improve the safety of the screening procedure. PMID: 16443589 [PubMed - in process]

Posted by blogposter at 11:41 AM |

[Evaluation of Setup Error and Adequate Setup Margins in Patients with Prostate Cancer Treated by IMRT and Fixed in the Prone Position Using a Set of Immobilization Devices.]


[Evaluation of Setup Error and Adequate Setup Margins in Patients with Prostate Cancer Treated by IMRT and Fixed in the Prone Position Using a Set of Immobilization Devices.]
Related Articles [Evaluation of Setup Error and Adequate Setup Margins in Patients with Prostate Cancer Treated by IMRT and Fixed in the Prone Position Using a Set of Immobilization Devices.] Nippon Hoshasen Gijutsu Gakkai Zasshi. 2006 Jan 20;62(1):130-5 Authors: Takakura T, Nakata M, Yano S, Okada T, Fujimoto T, Matsubara K, Mizowaki T, Takayama K, Norihisa Y Purpose: Positional reproducibility in patients with prostate cancer fixed in the prone position with a set of immobilization devices for external-beam intensity-modulated radiation therapy (IMRT) was evaluated. In addition, the adequacy of our positional error reduction strategy and current planning target volume (PTV) margins was also evaluated. Results: Systematic error was corrected by the positional correction that we executed at the first stage of irradiation. The setup margin that we had calculated was 1.1 mm in the L-R direction, 1.3 mm in the A-P direction, and 2.7 mm in the C-C direction. Conclusion: We determined that the effectiveness of the method of correcting the error margin and the setup accuracy of the fixed method were well maintained. PMID: 16456514 [PubMed - in process]

Posted by blogposter at 11:41 AM |

Current drug therapy for prostate cancer: an overview.


Current drug therapy for prostate cancer: an overview.
Related Articles Current drug therapy for prostate cancer: an overview. Curr Med Chem Anticancer Agents. 2005 Nov;5(6):603-12 Authors: Stewart AB, Lwaleed BA, Douglas DA, Birch BR Prostate cancer is the most common cancer amongst men in the USA and the second most common malignant cause of male death worldwide after lung cancer. The life time risk of having microscopic evidence of prostate cancer for a 50 year old man is 42%. Prostate cancer is thus becoming an increasingly significant global health problem in terms of mortality, morbidity, as well as economically. This review, discusses current medical therapeutic options for prostate cancer including traditional treatments using luteinising hormone releasing analogues (LHRH), anti-androgens and estrogen treatments, and the use of novel drugs directed against molecular targets considered important in oncogenesis and metastasis. Prostate cancer chemoprevention using 5alpha-reductase inhibitors and the role of gene therapy are also considered. PMID: 16305482 [PubMed - indexed for MEDLINE]

Posted by blogposter at 11:41 AM |

Antiproliferative activity of angiotensin II receptor blocker through cross-talk between stromal and epithelial prostate cancer cells.


Antiproliferative activity of angiotensin II receptor blocker through cross-talk between stromal and epithelial prostate cancer cells.
Related Articles Antiproliferative activity of angiotensin II receptor blocker through cross-talk between stromal and epithelial prostate cancer cells. Mol Cancer Ther. 2005 Nov;4(11):1699-709 Authors: Uemura H, Ishiguro H, Nagashima Y, Sasaki T, Nakaigawa N, Hasumi H, Kato S, Kubota Y We showed previously that angiotensin II activated the proliferation of prostate cancer cells and that angiotensin II receptor blockers (ARB) could inhibit it. Here, we investigated whether angiotensin II exerts mitogenic effects on the cross-talk between stromal and cancer cells and whether an ARB can inhibit tumor growth through actions on stromal cells. Cell proliferation and interleukin-6 secretion of prostate stromal PrSC cells stimulated with angiotensin II, tumor necrosis factor-alpha, or epidermal growth factor were examined in the absence and presence of ARB. We examined the effect of ARB on mitogen-activated protein kinase (MAPK) phosphorylation of PrSC and PC-3 cells treated with conditioned medium of PrSC cells and determined the effect of ARB on tumor growth induced by paracrine factors from PrSC cells. Angiotensin II activated the cell proliferation and interleukin-6 secretion of PrSC cells, and ARB inhibited it. Angiotensin II, tumor necrosis factor-alpha, or epidermal growth factor induced MAPK phosphorylation in PrSC cells, and this phosphorylation was inhibited by ARB. Conditioned medium of PrSC cells with angiotensin II activated MAPK phosphorylation in PC-3 cells, and ARB-treated conditioned medium of PrSC cells inhibited it. The tumor growth and angiogenesis of a mixture of PC-3 with PrSC were inhibited by ARB administration, whereas those of PC-3 xenografts were not inhibited. ARB exerted an antiproliferative effect on prostate cancer through paracrine factors from stromal cells. Because prostate stromal cells are thought to be involved in the initiation and development of prostate cancer, the present data suggest the possibility that ARBs are a novel therapeutic class of agents for prostate cancer. PMID: 16275991 [PubMed - indexed for MEDLINE]

Posted by blogposter at 11:40 AM |

Positive Inter-Regulation between beta-Catenin/T Cell Factor-4 Signaling and Endothelin-1 Signaling Potentiates Proliferation and Survival of Prostate Cancer Cells.


Positive Inter-Regulation between beta-Catenin/T Cell Factor-4 Signaling and Endothelin-1 Signaling Potentiates Proliferation and Survival of Prostate Cancer Cells.
Related Articles Positive Inter-Regulation between beta-Catenin/T Cell Factor-4 Signaling and Endothelin-1 Signaling Potentiates Proliferation and Survival of Prostate Cancer Cells. Mol Pharmacol. 2006 Feb;69(2):520-31 Authors: Sun P, Xiong H, Kim TH, Ren B, Zhang Z Both malignant and normal prostate epithelial cells produce endothelin-1 (ET-1), a critical factor in prostate cancer (CaP) progression. beta-Catenin (beta-cat), a key component of the Wnt signaling pathway, is also implicated in CaP progression via beta-cat/T cell factor (Tcf) signaling. We recently demonstrated that beta-cat/Tcf-4 regulates transcription of ET-1 in colon cancer cells. In the present study, we found that Tcf-4 specifically bound to and activated the ET-1 promoter in vivo in human CaP cells and mouse prostate tissue. Expression of ET-1 in DU145 CaP cells was down-regulated by knocking down endogenous beta-cat or Tcf-4. Ectopic activation of beta-cat/Tcf-4 signaling significantly elevated expression of ET-1 in LNCaP cells. In addition, genetic ablation of beta-cat significantly inhibited transcription of ET-1 in primary prostate epithelial cells. Meanwhile, exogenous ET-1 enhanced beta-cat/Tcf signaling and ET-1 expression in DU145 cells, which was blocked by both selective phosphatidylinositol 3-kinase (PI3K) inhibitor 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002) and endothelin-A receptor antagonist cyclo(l-Leu-d-Trp-d-Asp-l-Pro-d-Val) (BQ123). Furthermore, knockdown of either beta-cat or Tcf-4 substantially reduced cell proliferation and potentiated paclitaxel-induced apoptosis in DU145 cells, which largely were rescued by treatment with exogenous ET-1. Together, our results suggest that beta-cat/Tcf-4 signaling transcriptionally activates ET-1 in CaP cells; meanwhile, ET-1 enhances beta-cat/Tcf-4 signaling and in turn further increases ET-1 expression in a PI3K-dependent manner. The positive inter-regulation between beta-cat/Tcf-4 signaling and ET-1 signaling potentiates proliferation and survival of CaP cells, thereby representing a novel mechanism that contributes to CaP progression. PMID: 16291872 [PubMed - in process]

Posted by blogposter at 11:40 AM |

[Nutrition and pharmacological treatment for prevention of prostate cancer]


[Nutrition and pharmacological treatment for prevention of prostate cancer]
Related Articles [Nutrition and pharmacological treatment for prevention of prostate cancer] Harefuah. 2006 Jan;145(1):47-51, 76-7 Authors: Segev Y, Nativ O Prostate cancer is the most common neoplasm and the second cause of cancer death. It is an excellent target for primary chemopreventive strategies for the following reasons: it is highly prevalent and has a long latency period, there are identifiable risk factors and a precursor lesion and it produces a biochemical marker (serum PSA) which can serve as an intermediate end point in chemoprevention studies. The goal of primary prevention strategies is to prevent development of clinical life-threatening neoplasms in asymptomatic patients with no evidence of clinical disease. Identification of populations at risk for developing cancer is the cornerstone of chemoprevention. Well-established risk factors for prostate cancer include African-American race, older age and family history. Data on diet and obesity are less clearly defined. Since high grade prostatic intraepithelial neoplasia (PIN) is an early predictor of prostate cancer, preventive strategies focusing on men with high grade PIN are being explored. It was demonstrated that finasteride could significantly reduce prostate cancer in asymptomatic men with normal PSA and no abnormalities on rectal examination. Elevated prostaglandin levels, and upregulation of cyclooxygenase-2 (COX-2) are found in prostate cancer cell lines. There is some epidemiologic evidence that regular use of NSAIDs, which inhibit COX-2, may be associated with a lower risk of prostate cancer. In the field of nutrition, data from prospective large-scale studies demonstrated that increased consumption of lycopene-rich tomato-based foods referred to a reduction in the risk for prostate cancer. Vitamin E was also found to reduce prostate cancer risk. Prospective data showed that vitamin D has an inhibitory effect on prostate cancer development while increased calcium consumption, independent from dietary intake, might increase the risk. Dietary fat intake, particularly from animal sources, may also increase the risk for prostate cancer. Whether this effect is strictly due to the already identified compounds or to other compounds, remains to be explored. Further study will hopefully help to establish a core set of nutritional and dietary factors that can positively or negatively affect prostate cancer development, as well as a set of pharmacologic agents that can reduce the risk of prostate cancer development and/or progression in selected patients. PMID: 16450727 [PubMed - in process]

Posted by blogposter at 11:40 AM |