« June 2006 | Main | September 2006 »
| 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]
| Related Articles |
GU radiation oncologists consensus on bone loss from androgen deprivation.
Can J Urol. 2006 Feb;13(1):2962-6
Authors: Duncan GG, Corbett T, Lukka H, Warde P, Pickles T
The majority of GU radiation oncologists in Canada attended a consensus meeting in November 2004. The topic of osteoporosis in men receiving androgen deprivation therapy (ADT) for prostate cancer was identified as a key theme. A chaired session with keynote speakers and review of the evidence took place followed by open debate. Participants were provided with background information. Osteoporosis was defined as a T-score < or = -2.5, but the importance of risk factors and clinical findings is noted. Dual DEXA is the current standard for assessment of bone density and relates well to fracture risk. The lifetime risk of fracture is 13% for men over the age of 50 years even without the influence of ADT. Lifestyle, dietary and supplementation advice are provided both to prevent and to manage osteoporosis. The role for prophylactic bisphosphonate therapy in men on ADT without osteoporosis has not been established. Follow-up DEXA scans are required to monitor density, risk and response to interventions. Fracture incidence and BMD should be considered in the trial design of studies involving prolonged ADT. Osteoporosis is a treatable condition and the oncologist should employ ADT with this knowledge. A follow-up e-mail survey was carried out regarding the consensus statement. Responses were received from 49 of the 69 attendees (71%), and overall there was an 89% agreement with the consensus statement. This is now adopted as national practice guidelines for radiation oncologists employed prolonged ADT in prostate cancer patients.
PMID: 16515750 [PubMed - indexed for MEDLINE]
| Related Articles |
Molecular biology in prostate cancer.
Clin Transl Oncol. 2006 Mar;8(3):148-52
Authors: Cansino Alcaide JR, Mart nez-Pi eiro L
Genes involved in cancer generation are usually tumor suppressors and oncogenes. Progressive genetic alterations in these genes are involved in the mechanisms of tumorigenesis. In prostate cancer, additionally several chromosomal loci that should harbor mutated genes have been proposed. Some genes have been found altered in prostate cancer, such as PTEN, TP53, AR, RNASEL (HPC1), ELAC2 (HPC2), CDKN2A and MSR1 and those can be natural targets for new strategies of treatment. Besides, gene therapy has been suggested to be suitable for prostate cancer treatment. This approach includes ex vivo corrective therapy, suicide, and antisense therapy.
PMID: 16648113 [PubMed - indexed for MEDLINE]
| Related Articles |
Sipuleucel-T: APC 8015, APC-8015, prostate cancer vaccine--Dendreon.
Drugs R D. 2006;7(3):197-201
Authors:
Sipuleucel-T [APC 8015, Provenge] is an autologous, dendritic cell-based vaccine under development with Dendreon Corporation for the treatment of androgen-independent and androgen-dependent prostate cancer. It was generated using the company's active immunotherapy platform to stimulate a patient's own immune system to specifically target and destroy cancer cells, while leaving healthy cells unharmed. This approach could provide patients with a meaningful survival benefit and an improved tolerability profile over existing anticancer therapies. Sipuleucel-T selectively targets the prostate-specific antigen (PSA) known as prostatic acid phosphatase (PAP) that is expressed in approximately 95% of prostate cancers. It is produced by ex vivo exposure of dendritic cell precursors to PA 2024, a recombinant fusion protein composed of the PAP target fused to granulocyte-macrophage colony-stimulating factor (GM-CSF) and incorporated into Dendreon's proprietary Antigen Delivery Cassette. Patients are typically administered three intravenous (IV)-infusions of the vaccine over a 1-month period as a complete course of therapy. It is undergoing late-stage clinical evaluation among patients with early and advanced prostate cancer. In November 2003, Kirin Brewery returned to Dendreon the full rights to Sipuleucel-T for Asia. In exchange, Dendreon licensed patent rights relating to the use of certain HLA-DR antibodies to Kirin for $US20 million. This amended agreement enables Dendreon to complete ongoing discussions for a worldwide marketing and sales partnership for Sipuleucel-T. Similarly, Kirin is able to develop its HLA-DR monoclonal antibodies free of potential infringement claims arising from Dendreon's patent rights to HLA-DR. The licensing agreement relates to patent rights owned by Dendreon relating to monoclonal antibodies against the HLA-DR antigen. In addition, Dendreon retains rights to develop and commercialise its two existing HLA-DR monoclonal antibodies, DN 1921 and DN 1924, as well as other HLA-DR antibodies not being developed by Kirin. Previously, in May 1999, Dendreon and Kirin established a collaboration for the development of dendritic cell-based immunotherapeutics for cancer, including Sipuleucel-T. Under the agreement, Kirin would provide financial support for Dendreon's research on dendritic cells focused on developing immunotherapies for cancers most prevalent in Asia. Dendreon would retain US rights to products arising from the collaboration while Kirin would hold the rights to such immuno-therapeutics in Asia and Oceania. In August 2005, Dendreon signed an agreement to lease a commercial manufacturing facility in Hanover, New Jersey, USA. The company intends to develop the facility to meet anticipated clinical and commercial demands of Sipuleucel-T as well as other active immunotherapy product candidates. Dendreon and Diosynth Biotechnology (Akzo Nobel) have an agreement for the commercial production of the PA 2024 antigen component of Sipuleucel-T. In November 2003, Dendreon announced that Diosynth successfully manufactured PA 2024 on a commercial scale. In October 2001, Dendreon announced that Gambro Healthcare Inc. would provide a network of centres for cell collection to support commercial production and clinical development of various Dendreon vaccines, including Sipuleucel-T. Dendreon has outsourced its cell processing operations in Mountain View, California, USA to Progenitor Cell Therapy under an amended agreement signed in August 2002. This agreement is an expansion of an existing agreement, under which Progenitor provided Dendreon with cell-processing services through its facility in Hackensack, New Jersey, USA. The pivotal, two-stage, phase III trial (D9902 study) has been initiated at clinical sites in the US. The first stage of the trial (D9902A study) is a double-blind, placebo-controlled phase III trial designed to evaluate Sipuleucel-T in men with asymptomatic, metastatic, androgen-independent prostate cancer. The trial was originally designed to be the companion study to a previously completed phase III trial, called D9901. However, the D9902A study with 98 patients recruited was halted in December 2002, when analysis of the D9901 study revealed no statistically significant benefit in time to disease progression in the overall group, although a benefit was seen in a subgroup of patients with Gleason scores of < or =7. In April 2002, the US FDA requested clarification regarding cellular composition of Sipuleucel-T and the suspension of additional patient enrollment for the D9902 study; the request was related solely to manufacturing issues without patient safety being an issue. Trial enrollment resumed in October 2002 following FDA authorisation. Dendreon amended the protocol for the D9902 study and is only recruiting patients with asymptomatic, metastatic, androgen-independent prostate cancer, regardless of their Gleason Score (D9902B study). The ongoing pivotal phase III trial underwent a Special Protocol Assessment (SPA) with the FDA in August 2003 and is enrolling approximately 500 patients. The primary endpoint is overall survival with time to objective disease progression being a secondary endpoint. Final 3-year survival analysis of the D9902A study has been completed and presented. Previously, Dendreon completed an earlier phase III trial (D9901 study) that assessed Sipuleucel-T among 127 patients with late-stage, metastatic, hormone-independent prostate cancer in the US. All subjects had undergone surgical resection of the prostate, but had rising levels of PSA. Final 3-year survival data have been reported. Dendreon also conducted a phase II trial, known as D9905, that investigated Sipuleucel-T monotherapy among patients with early-stage prostate cancer. Study findings have been reported. In September 2003, the FDA designated Sipuleucel-T as a fast-track development programme for the treatment of asymptomatic, metastatic, androgen-independent prostate cancer. Subsequently, the FDA granted fast-track status to the vaccine in November 2005. Dendreon announced in September 1999 that a phase I trial of Sipuleucel-T in patients with prostate cancer had commenced in Japan. This study was being conducted at a dendritic cell processing centre that was formed as part of Dendreon's collaboration with Kirin. In addition, the US NCI is conducting a phase II trial (P-16) of Sipuleucel-T in combination with bevacizumab among patients with hormone-dependent prostate cancer. Trial results have been announced. In April 2001, Dendreon was awarded a US patent (No. 6,210,662) covering the composition of Sipuleucel-T. Dendreon acquired an exclusive worldwide licence to dendritic cell therapy for cancers and other diseases from the Immune Response Corporation; Immune Response originally received the exclusive patent rights to the technology from the University of Brussels in Belgium.
PMID: 16752945 [PubMed - indexed for MEDLINE]
 | Related Articles |
Distorted rectal tissue on prostate needle biopsy: a mimicker of prostate cancer.
Am J Surg Pathol. 2006 Jul;30(7):866-70
Authors: Schowinsky JT, Epstein JI
Rectal tissue is often seen in needle biopsies of the prostate gland. On rare occasion distorted rectal glands can mimic prostatic adenocarcinoma, an issue not previously addressed in the peer-reviewed literature. We evaluated 16 prostate needle biopsies received in consultation where the submitting pathologist questioned whether a focus of rectal tissue was prostate cancer. In addition to the distorted architecture, features mimicking prostate cancer included: (1) blue-tinged intraluminal mucinous secretions in 10 cases (63%), (2) prominent nucleoli in 6 cases (37%), (3) mitotic activity in 6 cases (37%), (4) extracellular mucin in 5 cases (31%), and (5) adenomatous changes of the rectal tissue in 1 case (6%). Immunohistochemical results further mimicked prostate cancer with negative stains for the basal cell markers high-molecular weight cytokeratin (n=6) and p63 (n=4), and positive stains for racemase in 4 of 5 biopsies. Diagnostic clues to recognizing that these foci were distorted rectal fragments were the presence of (1) lamina propria in 12 cases (75%), (2) rectal tissue located on a detached fragment of tissue in 10 biopsies (63%), (3) associated inflammation in 10 cases (63%), (4) goblet cells in 7 cases (44%), and (5) muscularis propria in 6 cases (37%). In 2 cases, there was negative staining for prostate specific antigen (PSA) and in 1 case negative staining for cytokeratin 7 and positivity for cytokeratin 20. Rectal glands are associated with many of the classical features of prostate cancer, and immunohistochemistry may be misleading. Recognition of these features mimicking prostate cancer and awareness of other findings that are diagnostic of rectal tissue on biopsy can prevent a misdiagnosis of atypical prostate glands or prostate cancer.
PMID: 16819329 [PubMed - indexed for MEDLINE]
40 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 2006/08/21
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 |
Combination immunotherapy with prostatic acid phosphatase pulsed antigen-presenting cells (provenge) plus bevacizumab in patients with serologic progression of prostate cancer after definitive local therapy.
Cancer. 2006 Jul 1;107(1):67-74
Authors: Rini BI, Weinberg V, Fong L, Conry S, Hershberg RM, Small EJ
BACKGROUND: APC8015 (sipuleucel-T) is a cellular prostate cancer vaccine containing autologous antigen-presenting cells (APC) loaded with PA2024, a recombinant prostatic acid phosphatase/granulocyte-macrophage-colony-stimulating factor fusion protein, as the immunogen. Bevacizumab is a recombinant antibody against vascular endothelial growth factor, a proangiogenic protein with inhibitory effects on APC. A clinical trial was conducted to determine the prostate-specific antigen (PSA) and immunomodulatory effects of this combination immunotherapy. METHODS: Patients with androgen-dependent prostate cancer who had received prior definitive therapy with nonmetastatic, recurrent disease as manifested by a rising PSA of between 0.4 ng/mL and 6.0 ng/mL were enrolled. APC8015 was given intravenously(i.v.) on Weeks 0, 2, and 4. Bevacizumab was given at a dose of 10 mg/kg i.v. on Weeks 0, 2, 4, and every 2 weeks thereafter until toxicity or disease progression. PSA changes were recorded and the PSA doubling time (PSADT) was calculated. Immune response versus PA2024 was measured at baseline and after treatment by T-cell proliferation and interferon-gamma enzyme-linked immunospot (ELISPOT) assays. RESULTS: Twenty-two patients were treated. One patient achieved a > or =50% decrease in PSA. Nine patients exhibited some decrease in PSA from baseline, ranging from 6% to 72%, with the PSA of 3 patients decreasing at least 25%. The median pretreatment PSADT for the 20 evaluable patients was 6.9 months and the median posttreatment PSADT was 12.7 months (P = .01). All patients demonstrated induction of an immune response against PA2024. CONCLUSIONS: The combination of APC8015 and bevacizumab induces an immune response and modulates PSA in patients with biochemically recurrent prostate cancer.
PMID: 16736512 [PubMed - indexed for MEDLINE]
 | Related Articles |
Combined therapy of Sr-89 and zoledronic acid in patients with painful bone metastases.
Bone. 2006 Jul;39(1):35-41
Authors: Storto G, Klain M, Paone G, Liuzzi R, Molino L, Marinelli A, Soricelli A, Pace L, Salvatore M
PURPOSE: We evaluated the pain response and daily discomfort in patients with painful bone metastases treated by merging 89Sr-chloride and zoledronic acid. The results were compared with those of patients who received 89Sr-chloride or zoledronic acid separately. METHODS: 25 patients (12 women; mean age 65+/-13 years) chronically treated with zoledronic acid underwent bone pain palliation with 150 MBq of 89Sr-chloride at least 6 months later that bisphoshonate therapy started (group A). 13 patients (6 women; mean age 70+/-12 years) received 89Sr-chloride alone (group B) and 11 patients (5 women; mean age 69+/-12 years) were chronically treated and continued to receive only zoledronic acid therapy (group C), both constituted the control groups. Patients kept a daily pain diary assessing both their discomfort and the pain of specific sites by using a visual analog scale (VAS), rating from 0 (no d iscomfort-no pain) to 10 (worst discomfort-pain). These diaries were reviewed weekly for 2 months and three different physicians rated the pain response on a scale of -2 (considerable deterioration) to +2 (considerable improvement). RESULTS: Baseline characteristics were similar in the three groups. The reduction of total discomfort and of bone pain in the group A was significantly greater as compared to group B (P<0.01) and group C (P<0.01). During the monitored period, a significant improvement of clinical conditions was observed in the group A, varying the rate from -1 to 1 as compared to both groups B and C in which the rate changed from -1 to 0. CONCLUSION: Our findings indicate that combined therapy of 89Sr-chloride and zoledronic acid in patients with painful bone metastases is more effective in treating pain and improving clinical conditions than 89Sr-chloride or zoledronic acid used separately.
PMID: 16434248 [PubMed - indexed for MEDLINE]
| 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]
128 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 2006/08/21
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 |
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]
75 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 2006/08/09
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.
158 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 2006/08/09
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 |
New molecular targets in advanced prostate cancer.
Expert Rev Anticancer Ther. 2006 Jul;6(7):993-1002
Authors: Dawson NA
Classically, advanced prostate cancer has been treated with hormonal therapy and, most recently, chemotherapy. This treatment clearly demonstrated a survival benefit, but never a cure. With the ever-expanding understanding of the pathophysiology of prostate cancer, there has been a recent explosion in the potential molecular targets and novel therapeutic approaches to both advanced and potentially localized prostate cancer. This review will focus on what the author perceives to be the most promising of these new strategies. The endothelin pathway has been identified as pivotal in the viscous cycle of tumorigenesis in bone, leading to the development of endothelial receptor antagonists. Vaccine therapy using autologous granulocyte-macrophage colony-stimulating factor-producing prostate cancer cells has been effective in producing both immune and clinical responses. Randomized clinical trials of the immunotherapy cell product APC8015 (Provenge) have demonstrated improved survival in the hormone-refractory setting. The development of antisense oligonucleotides to segments of mRNA critical to the progression to androgen-independent disease has emerged as one further tool in the expanding armamentarium of potential therapies being tested. Clearly, headway is being made in improving outcomes in this most prevalent health problem.
PMID: 16831072 [PubMed - indexed for MEDLINE]
260 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 2006/08/09
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.
178 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 2006/08/09
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 |
Nitroreductase-based therapy of prostate cancer, enhanced by raising expression of heat shock protein 70, acts through increased anti-tumour immunity.
Cancer Immunol Immunother. 2006 Mar;55(3):347-54
Authors: Lipinski KS, Pelech S, Mountain A, Irvine AS, Kraaij R, Bangma CH, Mills KH, Todryk SM
Gene-directed enzyme-prodrug therapy (GDEPT) using nitroreductase (NTR), with efficient adenoviral delivery, and CB1954 (CB), is an effective means of directly killing tumours. However, an immune-mediated bystander effect remains an important product of GDEPT since it is often critical to the elimination of untransduced tumour cells both locally and at distal metastatic sites through generation of tumour-specific immunity without the need for tumour antigen identification or the generation of a personalised vaccine. The mode of induced tumour cell death is thought to contribute to the immunisation process, together with the induction and release of stress proteins. Here, RM-9 murine prostate tumour cells were efficiently killed by adenovirally delivered NTR/CB treatment both in vitro and in vivo, and bystander effects were observed. Cells appeared to die by pathways that suggest necrosis more than that of classical apoptosis. NTR/CB-induced expression of a range of stress proteins was determined by proteomic analysis, revealing chiefly heat shock protein (HSP)25 and HSP70 upregulation, whilst immune responses in vivo were weak. In an attempt to enhance the anti-tumour effect, an adenoviral vector was constructed that co-expressed NTR and HSP70, the latter being a known immune stimulator and chaperone of antigen. This combination elicited significantly enhanced protection over NTR alone for both the treated tumour and a subsequent re-challenge. Protection was CD4+ and CD8+ T cell-dependent and was associated with tumour-specific CTL, IFNgamma and IL-5 responses. The use of such a cytotoxic and immunomodulatory gene combination in cancer therapy warrants further pursuit.
PMID: 16075195 [PubMed - indexed for MEDLINE]
179 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 2006/08/09
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 |
Inactivation of Id-1 in prostate cancer cells: A potential therapeutic target in inducing chemosensitization to taxol through activation of JNK pathway.
Int J Cancer. 2006 Apr 15;118(8):2072-81
Authors: Zhang X, Ling MT, Wang X, Wong YC
Resistance to anticancer drugs is the major problem in the treatment of many advanced cancers, including androgen-independent prostate cancer. Recently, increased expression of Id-1, a basic helix-loop-helix protein, is reported in several types of advanced cancer. It is suggested that high expression of Id-1 may provide an advantage for cancer cell survival and inactivation of Id-1 may be able to increase cancer cells' susceptibility to apoptosis. To test this hypothesis, in this study, by using RNA interfering technology, we inactivated the Id-1 gene in 2 androgen-independent prostate cancer cell lines, DU145 and PC3, and investigated whether downregulation of Id-1 could lead to increased sensitivity to a commonly used anticancer drug, taxol. By using colony forming assay and MTT assay, we found that inactivation of Id-1 resulted in both decreased colony forming ability and cell viability in prostate cancer cells, after taxol treatment. In addition, the si-Id-1-induced sensitization to taxol was associated with activation of apoptosis pathway, which is demonstrated by increased apoptotic index, DNA laddering, sub-G1 phase of the cell cycle, as well as cleaved-PARP and Caspase 3. Furthermore, c-Jun N-terminal kinase (JNK), one of the common pathways responsible for taxol-induced apoptosis, was also activated in the si-Id-1 transfected cells. Inhibition of JNK activity by a specific inhibitor, SP600125, blocked the si-Id-1-induced sensitivity to taxol. These results indicate that increased Id-1 expression in prostate cancer cells may play a protective role against apoptosis, and downregulation of Id-1 may be a potential target to increase sensitivity of taxol-induced apoptosis in prostate cancer cells.
PMID: 16287090 [PubMed - indexed for MEDLINE]
634 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 2006/08/09
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.