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Regulation of prostaglandin metabolism by calcitriol attenuates growth stimulation in prostate cancer cells.
Cancer Res. 2005 Sep 1;65(17):7917-25
Authors: Moreno J, Krishnan AV, Swami S, Nonn L, Peehl DM, Feldman D
Calcitriol exhibits antiproliferative and pro-differentiation effects in prostate cancer. Our goal is to further define the mechanisms underlying these actions. We studied established human prostate cancer cell lines and primary prostatic epithelial cells and showed that calcitriol regulated the expression of genes involved in the metabolism of prostaglandins (PGs), known stimulators of prostate cell growth. Calcitriol significantly repressed the mRNA and protein expression of prostaglandin endoperoxide synthase/cyclooxygenase-2 (COX-2), the key PG synthesis enzyme. Calcitriol also up-regulated the expression of 15-hydroxyprostaglandin dehydrogenase, the enzyme initiating PG catabolism. This dual action was associated with decreased prostaglandin E2 secretion into the conditioned media of prostate cancer cells exposed to calcitriol. Calcitriol also repressed the mRNA expression of the PG receptors EP2 and FP, providing a potential additional mechanism of suppression of the biological activity of PGs. Calcitriol treatment attenuated PG-mediated functional responses, including the stimulation of prostate cancer cell growth. The combination of calcitriol with nonsteroidal anti-inflammatory drugs (NSAIDs) synergistically acted to achieve significant prostate cancer cell growth inhibition at approximately 2 to 10 times lower concentrations of the drugs than when used alone. In conclusion, the regulation of PG metabolism and biological actions constitutes a novel pathway of calcitriol action that may contribute to its antiproliferative effects in prostate cells. We propose that a combination of calcitriol and nonselective NSAIDs might be a useful chemopreventive and/or therapeutic strategy in men with prostate cancer, as it would allow the use of lower concentrations of both drugs, thereby reducing their toxic side effects.
PMID: 16140963 [PubMed - indexed for MEDLINE]
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Some sociodemographic and diagnostic characteristics of military patients treated in the Department of Medical Oncology, G lhane Military Medical Academy.
Mil Med. 2006 May;171(5):420-4
Authors: Acikel CH, Kir T, Komurcu S, Kilic S, Ozett A, Rzayev M, Arpaci F, Ozturk B, Ogur R, Ataergin S, Kuzhan O, Hasde M
Today, chronic diseases have increased importance. Cancer, for which 10 million new cases are diagnosed around the world each year, is in the lead of such diseases. This study included military personnel with cancer who applied to the Department of Medical Oncology, G lhane Military Medical Academy, in the period between 1998 and 2003, and it aims to describe some sociodemographic and diagnostic characteristics of the patients. The total number of cases was 938, which included both active duty and retired military personnel with diagnoses of cancer who were given medical care between 1998 and 2003 in the Department of Medical Oncology. For the study group, the five most common diagnoses were lung cancer, colorectal cancer, testicular cancer, non-Hodgkin's lymphoma, and Hodgkin's disease. Although the first three diagnoses among officers were lung cancer, testicular cancer, and Hodgkin's disease, those among retired officers were colorectal cancer, lung cancer, and prostate cancer. Among noncommissioned officers, the first three diagnoses were colorectal cancer, testicular cancer, and Hodgkin's disease for active duty patients and lung cancer, colorectal cancer, and gastric cancer for retired patients. In the group of privates, testicular cancer, Hodgkin's disease, and non-Hodgkin's lymphoma were the first three diagnoses. When we consider the characteristics of cancers, such as high costs of treatment, loss of manpower, and high mortality rates, prevention of cancers and early diagnosis are very important. Because the frequent types of cancers differed for groups according to age and occupation, those characteristics should be considered when cancer screening programs are being developed for the Armed Forces.
PMID: 16761893 [PubMed - in process]
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Expression of BAG-1 protein correlates with aggressive behavior of prostate cancers.
Prostate. 2006 Jun 1;66(8):801-10
Authors: Krajewska M, Turner BC, Shabaik A, Krajewski S, Reed JC
BACKGROUND: Differences in tumor behavior, ranging from indolent to aggressive, create a need for novel prognostic biomarkers. BAG-1 is a co-chaperone that regulates the activity of Hsp70, Bcl-2, Raf-1, growth factor, and steroid receptors (e.g., the Androgen Receptor). METHODS: Using immunohistochemical method, we explored BAG-1 expression in prostate cancers and its association with clinicopathological parameters. RESULTS: BAG-1 immunostaining was elevated in prostate cancer compared to normal prostatic epithelium. Higher nuclear BAG-1 in hormone-refractory (n = 34) compared to localized untreated tumors (n = 58) (P < 0.0001) suggested that upregulation of the nuclear isoform may contribute to disease progression. In 64 early-stage patients (T2N0M0) treated with external-beam irradiation, cytosolic BAG-1 correlated with higher pretreatment levels of serum Prostate specific antigen (P = 0.04) and shorter time to disease progression (P = 0.00004). CONCLUSIONS: Increased cytosolic and nuclear BAG-1 expression may denote more aggressive variants of prostate cancer.
PMID: 16482527 [PubMed - indexed for MEDLINE]
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Vaccination of hormone-refractory prostate cancer patients with peptide cocktail-loaded dendritic cells: results of a phase I clinical trial.
Prostate. 2006 Jun 1;66(8):811-21
Authors: Fuessel S, Meye A, Schmitz M, Zastrow S, Linn C, Richter K, L bel B, Hakenberg OW, Hoelig K, Rieber EP, Wirth MP
BACKGROUND: Immunotherapies might represent promising alternatives for the treatment of patients with hormone-refractory prostate cancer (HRPC). In a Phase I clinical trial, we evaluated a vaccination with dendritic cells (DCs) loaded with a cocktail consisting of HLA-A*0201-restricted peptides derived from five different prostate cancer-associated antigens [prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA), survivin, prostein, transient receptor potential p8 (trp-p8)]. METHODS: Eight HRPC patients received a total of four vaccinations every other week. Clinical and immunological responses were monitored by the determination of the serum PSA levels and by enzyme linked immunospot (ELISPOT) analyses, respectively. RESULTS: Apart from local skin reactions no side effects were noted. One patient displayed a partial response (PR; PSA decrease >50%) and three other patients showed stable PSA values or decelerated PSA increases. In ELISPOT analyses, three of four PSA responders also showed antigen-specific CD8+ T-cell activation against prostein, survivin, and PSMA. CONCLUSIONS: The described protocol represents a safe and feasible concept for the induction of clinical and immunological responses. The application of a peptide cocktail-derived from different antigens as a novel treatment modality is supposed to allow for the genetic and biologic heterogeneity of PCa.
PMID: 16482569 [PubMed - indexed for MEDLINE]
28 new PubMed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
prostate cancer Radiation therapy
These PubMed results were generated on 2006/06/13
PubMed, a service of the National Library of Medicine, includes over 15 million citations for biomedical articles back to the 1950's. These citations are from MEDLINE and additional life science journals. PubMed includes links to many sites providing full text articles and other related resources.
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[Cancer immunotherapy--current status]
Ther Umsch. 2006 Apr;63(4):262-6
Authors: Kundig TM, Renner Ch, Knuth A
Cancer immunotherapy includes passive and active strategies. Passive immunotherapy such as the use of therapeutic monoclonal antibodies, and in a broader sense also of other immunological effector molecules, such as interferon-alpha is clinically established. The efficacy of passive immunotherapy attests to the fact that the immune system can successfully fight cancer. The logical next step is therefore to develop strategies for active immunotherapy, i.e. "vaccines against cancer". This review focuses on the current status of active immunotherapy with respect to clinical application. Although active immunotherapy is still in the experimental stage, the data are highly encouraging and it is expected that vaccination will soon become part of cancer management.
PMID: 16689457 [PubMed - indexed for MEDLINE]
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Response to second-line chemotherapy in patients with hormone refractory prostate cancer receiving two sequences of mitoxantrone and taxanes.
Urology. 2006 Jun;67(6):1235-40
Authors: Oh WK, Manola J, Babcic V, Harnam N, Kantoff PW
OBJECTIVES: Clinical trials have demonstrated a survival benefit with docetaxel chemotherapy, but limited data exist regarding the activity of second-line chemotherapy. METHODS: We retrospectively identified all patients at one institution who received at least two chemotherapy regimens for hormone-refractory prostate cancer, one mitoxantrone-based and the other taxane-based, either including docetaxel or paclitaxel. Patients were evaluated using criteria modified from the Prostate-Specific Antigen Working Group. RESULTS: A total of 68 patients were analyzed; 33 patients received mitoxantrone followed by taxane-based treatment, and 35 received taxane-based chemotherapy followed by mitoxantrone. The median patient age was 66 and 58 years and the median prostate-specific antigen at the start of treatment was 23 and 24 ng/mL in the mitoxantrone-first and taxane-first group, respectively. The response rates to taxane-based chemotherapy were greater whether it was used first or second (P <0.0001). Progression-free survival (PFS) was longer with taxanes than with mitoxantrone, whether used first or second (P <0.05). However, the corresponding total PFS from start of the first regimen to progression during the second regimen was similar at 39.9 and 38.7 weeks (P = 0.67). Overall survival was also not significantly different (15.2 and 17.1 months, P = 0.97). Neither age nor the interval from diagnosis to chemotherapy influenced the differences in PFS. CONCLUSIONS: Taxane-based chemotherapy is active before or after mitoxantrone. Although PFS was longer with taxane-based chemotherapy, the total PFS and overall survival were equivalent for both sequences in this retrospective analysis, suggesting that taxane-based chemotherapy retains activity, even if delayed. Although responses were seen with mitoxantrone after taxanes, the median PFS was short, and new agents are needed after taxane-based chemotherapy.
PMID: 16765185 [PubMed - in process]
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A tumour stem cell hypothesis for the origins of prostate cancer.
BJU Int. 2005 Dec;96(9):1219-23
Authors: Maitland NJ, Collins A
Cancer stem cells undoubtedly exist in many tumour types, including the prostate. This hypothesis can explain both the heterogeneity of prostate tumours and their variable responses to several conventional therapies. In the longer term, therapies directed against tumour stem cells should offer a real possibility of long-term cure, rather than current palliative therapy. Identifying specific tumour stem-cell markers will enhance this process, but the scarcity of these cells within the mass of more differentiated amplifying progeny that comprise >99.9% of most cancers makes this a severe technical challenge. In addition, many tumour stem-cell markers are probably shared with normal stem cells, both in prostate and in stem cells from other tissues, but tumour-specific patterns of gene expression, probably designed to allow the tumour stem cell to survive outside its protective 'niche' in normal tissues, will be the best initial targets for new therapeutic agents.
PMID: 16287434 [PubMed - indexed for MEDLINE]
215 new PubMed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These PubMed results were generated on 2006/06/13
PubMed, a service of the National Library of Medicine, includes over 15 million citations for biomedical articles back to the 1950's. These citations are from MEDLINE and additional life science journals. PubMed includes links to many sites providing full text articles and other related resources.
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Phase II trial of tesmilifene plus mitoxantrone and prednisone for hormone refractory prostate cancer: high subjective and objective response in patients with symptomatic metastases.
J Urol. 2005 Nov;174(5):1808-13; discussion 1813
Authors: Raghavan D, Brandes LJ, Klapp K, Snyder T, Styles E, Tsao-Wei D, Lieskovsky G, Quinn DI, Ramsey EW
PURPOSE: Symptomatic, hormone refractory prostate cancer (HRCAP) is a major cause of morbidity with a median survival of less than 12 months and a 2-year survival of only up to 10% in most series. Mitoxantrone has been approved by the Food and Drug Administration for HRCAP. Preliminary data suggest that DPPE (N,N-diethyl-2-[4-(phenylmethyl) phenoxy]-ethanamine) or tesmilifene modulates cytotoxics to enhance the anticancer effect. In this phase II trial we assessed whether there is sufficient evidence of enhanced efficacy of DPPE and mitoxantrone to lead to a phase III clinical trial. MATERIALS AND METHODS: A total of 29 patients with a median age of 73 years, of whom 10% were older than 80 years, with progressive HRCAP received 5.3 mg/kg DPPE intravenously every 3 weeks, 12 mg/m mitoxantrone intravenously every weeks and 5 mg prednisone orally twice daily. All patients had pain at presentation, while 97% had bone metastases, 10% had liver metastases and 17% had lung metastases. Median prostate specific antigen (PSA) was 210 ng/ml (IQR 77 to 430). RESULTS: Of the patients 75% had some pain improvement, 66% had decreased analgesia, 59% had a PSA decrease of 50% or greater and 45% had a PSA decrease of 75% or greater. Actual (not actuarial) 2-year survival was 21%. CONCLUSIONS: Despite major limitations of historical comparison the PSA decrease and decreased symptoms with DPPE-mitoxantrone-prednisone compare favorably to those of mitoxantrone-prednisone and docetaxel-estramustine in the literature. The 2-year survival rate of 21% mandates further assessment. This will be tested in a phase III Southwest Oncology Group trial.
PMID: 16217292 [PubMed - indexed for MEDLINE]
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The role of genistein and synthetic derivatives of isoflavone in cancer prevention and therapy.
Mini Rev Med Chem. 2006 Apr;6(4):401-7
Authors: Sarkar FH, Adsule S, Padhye S, Kulkarni S, Li Y
Genistein, one of the predominant soy isoflavones, has been shown to compete with 17beta-estradiol for estrogen receptor binding because of its structural similarity, resulting in agonistic or antagonistic activity. It causes inhibition of cell growth in breast and prostate cancers in vivo and in vitro. From gene expression profiles, genistein has been found to regulate the genes that are critical for the control of cell proliferation, cell cycle, apoptosis, oncogenesis, transcription regulation, and cell signal transduction pathways. It has been reported that genistein induces apoptosis and inhibits activation of NF-kappaB and Akt signaling pathways, both of which are known to maintain a balance between cell survival and apoptosis. Recently, we found that genistein sensitized cancer cells to apoptosis induced by chemotherapeutic agents including docetaxel, gemcitabine and cisplatin through inactivation of NF-kappaB in multiple cancer cell lines. To enhance the anti-cancer activity of genistein, we have synthesized structurally-modified derivatives of isoflavone based on the structural requirements for optimal anti-cancer effect. We found that these synthetic derivatives of isoflavone exerted higher anti-cancer activity with lower IC50. These derivatives of isoflavone also induced more apoptosis compared to genistein. These results suggest that genistein and synthetic structurally-modified derivatives of isoflavone may be promising agents for cancer chemoprevention and therapy either alone or in combination with existing chemotherapeutic agents.
PMID: 16613577 [PubMed - indexed for MEDLINE]
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Phase II study evaluating oral triamcinolone in patients with androgen-independent prostate cancer.
Urology. 2006 May;67(5):1001-6
Authors: Srinivas S, Krishnan AV, Colocci N, Feldman D
OBJECTIVES: To assess the effect of triamcinolone administration on the serum prostate-specific antigen (PSA) response and the time to progression in patients with androgen-independent prostate cancer (AIPC). METHODS: Patients with AIPC were prospectively treated with oral triamcinolone 4 mg twice daily, and their serum PSA and cortisol levels were measured monthly. Patients with greater than 25% increases in serum PSA from baseline were considered to have progressive disease and were removed from the study. Those patients who had a decrease in serum PSA levels or stable disease continued in the study until disease progression. Bone scans were obtained every 12 weeks and at progression. RESULTS: Twenty-four patients with AIPC were treated from November 2002 to June 2004. A partial response with a more than 50% decrease in serum PSA level was seen in 29%. Another 21% achieved stable disease. No statistically significant difference was found in the time to progression in the partial responders and patients with stable disease. The median time to progression in both groups was 7.5 months. Treatment was well tolerated without any grade 3 or 4 toxicity. CONCLUSIONS: Oral triamcinolone was well tolerated by patients with AIPC, with 50% of the patients exhibiting a good response to therapy in terms of serum PSA level and time to progression.
PMID: 16698360 [PubMed - indexed for MEDLINE]
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Humoral and cellular immune responses against the breast cancer antigen NY-BR-1: definition of two HLA-A2 restricted peptide epitopes.
Cancer Immun. 2005;5:11
Authors: J ger D, Karbach J, Pauligk C, Seil I, Frei C, Chen YT, Old LJ, Knuth A, J ger E
Cancer immunotherapy depends on the identification of tumor-specific target antigens that are predominantly expressed in cancer cells and not in normal tissues. Here, we report the cloning and the expression analysis of the differentiation antigen NY-BR-1 that we have identified in a previous SEREX (serological analysis of recombinant cDNA expression libraries) screening. The cloning of the full length NY-BR-1 sequence led to the prediction of an open reading frame of 4.2 kb, encoding a protein of 158.9 kDa. NY-BR-1 mRNA expression analysis revealed tissue-specific expression in normal testis and breast tissues, as well as in 70% of breast tumors. We now show that NY-BR-1 is also sporadically expressed in normal prostate and in 32% of prostate tumors. Furthermore, we were able to identify two HLA-A2 restricted NY-BR-1 epitopes (p158-167 and p960-968) that are recognized by CD8+ T cell clones (NW1100-CTL-7 and NW1100-CTL-43, respectively), as determined by ELISPOT analysis and tetramer staining. Cotransfection assays of COS-7 cells also demonstrated that these two peptides are naturally processed and presented on HLA-A2 molecules. The identification of these two naturally processed NY-BR-1-specific CD8+ T cell epitopes opens the perspective for active immunotherapy of HLA-A2 positive patients with NY-BR-1 expressing tumors.
PMID: 16335914 [PubMed - indexed for MEDLINE]
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Failure of gonadotropin-releasing hormone agonists with and without sterile abscess formation at depot sites: insight into mechanisms?
Urology. 2006 May;67(5):1084.e15-7
Authors: Daskivich TJ, Oh WK
We describe a patient with advanced prostate cancer who failed to achieve testosterone suppression with depot leuprolide after developing sterile abscesses at the injection sites. When the patient was switched to depot goserelin, he did not have any evidence of inflammation at the injection sites, but testosterone suppression again failed. This case suggests variable mechanisms for failure of gonadotropin-releasing hormone agonist therapy and highlights the necessity of prospective testosterone monitoring in patients who have developed sterile abscesses, even if switched to another gonadotropin-releasing hormone agonist.
PMID: 16698377 [PubMed - indexed for MEDLINE]
31 new PubMed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
prostate cancer Radiation therapy
These PubMed results were generated on 2006/06/05
PubMed, a service of the National Library of Medicine, includes over 15 million citations for biomedical articles back to the 1950's. These citations are from MEDLINE and additional life science journals. PubMed includes links to many sites providing full text articles and other related resources.
 | Related Articles |
Preventive and therapeutic vaccination with PAP-3, a novel human prostate cancer peptide, inhibits carcinoma development in HLA transgenic mice.
Cancer Immunol Immunother. 2006 Jun 1;
Authors: Machlenkin A, Azriel-Rosenfeld R, Volovitz I, Vadai E, Lev A, Paz A, Goldberger O, Reiter Y, Tzehoval E, Benhar I, Eisenbach L
Conventional treatment of recurrent and metastasized prostate cancer (CaP) remains inadequate; this fact mandates development of alternative therapeutic modalities, such as specific active or passive immunotherapy. Previously, we reported the identification of a novel highly immunogenic HLA-A*0201-restricted Prostatic Acid Phosphatase-derived peptide (PAP-3) by a two-step in vivo screening in an HLA-transgenic (HHD) mouse system. In the present study we aimed at elucidating the efficiency of PAP-3-based vaccine upon active antitumor immunization. To this end we established preventive and therapeutic carcinoma models in HHD mice. The 3LL murine Lewis lung carcinoma clone D122 transduced to express HLA-A*0201 and PAP served as a platform for these models. The HLA-A*0201-PAP-3 complex specific recombinant single chain scFV-PAP-3 antibodies were generated and used to confirm an endogenous PAP processing resulting in PAP-3 presentation by HLA-A*0201. PAP-3 based vaccines significantly decreased tumor incidence in a preventive immunization setting. Therapeutic vaccination of HHD mice with PAP-3 led to rejection of early established tumors and to increase of mouse survival. These results strongly support a therapeutic relevance of the identified CTL epitope upon active antitumor immunization. The newly established carcinoma model presented herein might be a useful tool for cancer vaccine design and optimization.
PMID: 16738849 [PubMed - as supplied by publisher]
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Casodex treatment induces hypoxia-related gene expression in the LNCaP prostate cancer progression model.
BMC Urol. 2005;5:5
Authors: Rothermund CA, Gopalakrishnan VK, Eudy JD, Vishwanatha JK
BACKGROUND: The changes in gene expression profile as prostate cancer progresses from an androgen-dependent disease to an androgen-independent disease are still largely unknown. METHODS: We examined the gene expression profile in the LNCaP prostate cancer progression model during chronic treatment with Casodex using cDNA microarrays consisting of 2305 randomly chosen genes. RESULTS: Our studies revealed a representative collection of genes whose expression was differentially regulated in LNCaP cells upon treatment with Casodex. A set of 15 genes were shown to be highly expressed in Casodex-treated LNCaP cells compared to the reference sample. This set of highly expressed genes represents a signature collection unique to prostate cancer since their expression was significantly greater than that of the collective pool of ten cancer cell lines of the reference sample. The highly expressed signature collection included the hypoxia-related genes membrane metallo-endopeptidase (MME), cyclin G2, and Bcl2/adenovirus E1B 19 kDa (BNIP3). Given the roles of these genes in angiogenesis, cell cycle regulation, and apoptosis, we further analyzed their expression and concluded that these genes may be involved in the molecular changes that lead to androgen-independence in prostate cancer. CONCLUSION: Our data indicate that one of the mechanisms of Casodex action in prostate cancer cells is induction of hypoxic gene expression.
PMID: 15790403 [PubMed - indexed for MEDLINE]