MedWorm: Hormone Refractory Prostate Cancer

Radical Radiotherapy for Localised Hormone Refractory Prostate Cancer

Clinical Oncology — Thu, 09 Feb 2012 08:13:42 +0100

Introduction: Since PR07 and the Scandinavian Prostate Cancer Group showed survival benefit from adding radical radiotherapy (RT) to androgen deprivation therapy, prostate RT is routinely offered to fit patients with locally advanced prostate cancer [1,2]. Previously these patients were treated with hormones alone and followed up. Adding prostate RT when they become hormone refractory (and still have radiologically localised cancer) is controversial, but there is some evidence that patients with locally advanced hormone refractory prostate cancer (HRPC) may benefit [3]. The natural history of non-metastatic HRPC is unknown and treatment options are limited. Metastatic HRPC is associated with poor prognosis; widely quoted survival being 12–18 months, which with PSA lead time may be an und...

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Bayer Initiates Expanded Access Program For Investigational Compound Radium-223 Chloride

Pharmaceutical Online News — Thu, 02 Feb 2012 11:00:00 +0100

Bayer HealthCare, LLC today announced that the U.S. Food and Drug Administration agreed that Bayer can proceed with its expanded access program to provide the investigational drug radium-223 chloride to patients diagnosed with castration-resistant prostate cancer (CRPC)/hormone-refractory prostate cancer (HRPC) with symptomatic bone metastases. (Source: Pharmaceutical Online News)

NICE FAD does not recommend cabazitaxel for the second line treatment of prostate cancer

NeLM - News — Thu, 12 Jan 2012 05:00:00 +0100

Source: NICE Area: News NICE has issued a Final Appraisal Determination (FAD) on the use of cabazitaxel for the second line treatment of hormone refractory, metastatic prostate cancer. The FAD does not recommend cabazitaxel in combination with prednisone or prednisolone for the treatment of hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing regimen. In a related press release, the Chief Executive of NICE said, "We need to be sure that new treatments provide sufficient benefits to patients to justify the significant resources the NHS would need to make available. Although cabazitaxel has been shown to be effective in extending life, it is also associated with a number of side effects. The committee was concerned about the natu...

Indication Of Considerable Added Benefit From Abiraterone In Certain Prostate Cancer Patients

Health News from Medical News Today — Tue, 10 Jan 2012 08:00:00 +0100

Advantages for men with metastatic hormone-refractory prostate cancer who are no longer eligible for docetaxel therapy Abiraterone (trade name: Zytiga®) has been approved since September 2011 for men with metastatic prostate cancer that is no longer responsive to hormone therapy and progresses further during or after therapy with the cytostatic drug docetaxel... (Source: Health News from Medical News Today)

[How should hormone therapy for castration-resistant prostate cancer be continued?].

Der Urologe. Ausg. A — Sun, 01 Jan 2012 05:00:00 +0100

Authors: Spahn M, Krebs M Abstract After an average of 18-36 months under androgen suppression therapy by surgical castration, LHRH, and steroidal or non-steroidal antiandrogens, almost all patients with metastatic prostate cancer show PSA progression as a sign of androgen-independent but still androgen-sensitive tumor growth. Our understanding and the treatment of such castration-resistant prostate cancer has changed markedly. The introduction of new drugs like abiraterone and MDV3100 has shown that prostate cancer progression even in the"hormone-refractory" stage is driven by androgen receptor signaling. Based on this information the question of whether androgen deprivation therapy in castration-resistant prostate cancer should be continued or not is still of relevance. This revi...

Improvement in urinary retention due to recurrent anastomotic prostate cancer treated with various therapies by intra-arterial infusion of cisplatin and ifosfamide

Journal of Infection and Chemotherapy — Tue, 27 Dec 2011 16:51:16 +0100

We report a patient who improved following intra-arterial infusion of cisplatin (CDDP) and ifosfamide (IFM) to treat urinary retention caused by locally recurring HRPC. After chemotherapy, cancer volume was remarkably reduced and symptoms improved. Content Type Journal ArticleCategory Case ReportPages 1-3DOI 10.1007/s10156-011-0352-9Authors Keiichiro Uemura, Department of Urology, Kurume University School of Medicine, Asahimach 67, Kurume, Fukuoka, JapanKiyoaki Nishihara, Department of Urology, Kurume University School of Medicine, Asahimach 67, Kurume, Fukuoka, JapanTokumasa Hayashi, Department of Urology, Kurume University School of Medicine, Asahimach 67, Kurume, Fukuoka, JapanKatsuro Tomiyasu, Department of Urology, Kurume University School of Medicine, Asahimach 67, Kurume, F...

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Inhibition of IGF-1 Signaling by Genistein: Modulation of E-Cadherin Expression and Downregulation of β-Catenin Signaling in Hormone Refractory PC-3 Prostate Cancer Cells.

Nutrition and Cancer — Fri, 18 Nov 2011 05:00:00 +0100

Authors: Lee J, Ju J, Park S, Hong SJ, Yoon S Abstract Elevated levels of insulin-like growth factor-1 (IGF-1) are associated with an increased risk of several different cancers, including prostate cancer. Inhibition of IGF-1 and the downstream signaling pathways mediated by the activation of the IGF-1 receptor (IGF-1R) may be involved in inhibiting prostate carcinogenesis. We investigated whether genistein downregulated the IGF-1/IGF-1R signaling pathway and inhibited cell growth in hormone refractory PC-3 prostate cancer cells. Genistein treatment caused a significant inhibition of IGF-1-stimulated cell growth. Flow cytometry analysis revealed that genistein significantly decreased the number of IGF-1-stimulated cells in the G0/G1 phase of the cell cycle. In IGF-1-treated cells, ...

SMC does not recommend cabazitaxel (Jevtana®) for the treatment of prostate cancer

NeLM - Drug Specific Reviews — Tue, 08 Nov 2011 05:00:00 +0100

Source: Scottish Medicines Consortium (SMC) Area: Evidence > Drug Specific Reviews The Scottish Medicines Consortium (SMC) does not recommend cabazitaxel (Jevtana®) for use within NHS Scotland for the treatment of patients with hormone refractory metastatic prostate cancer who have previously been treated with a docetaxel-containing regimen. The Drug Advice notes that the use of cabazitaxel in combination with prednisone/prednisolone was associated with a 2.4 month survival gain compared to an alternative chemotherapy regimen, in an open-label Phase III study in patients with metastatic hormone-refractory prostate cancer. The SMC however concluded that the company's justification of the treatment's cost in relation to its health benefits was not sufficient to gain it...

Targeting JunD: A potential strategy to counteract hormone-refractory prostate cancer.

Cell Cycle — Mon, 31 Oct 2011 04:00:00 +0100

Authors: Sarkar D, Wang XY, Fisher PB Abstract Comment on: Zerbini LF, et al. Cell Cycle 2011; 10:2583-91. PMID: 22030692 [PubMed - as supplied by publisher] (Source: Cell Cycle)

Protopine, a novel microtubule-stabilizing agent, causes mitotic arrest and apoptotic cell death in human hormone-refractory prostate cancer cell lines

Cancer Letters — Fri, 28 Oct 2011 04:00:00 +0100

In conclusion, the data suggest that protopine is a novel microtubule stabilizer with anticancer activity in HRPC cells through apoptotic pathway by modulating Cdk1 activity and Bcl-2 family of proteins. (Source: Cancer Letters)

Living with Bodily Changes in Hormone-Refractory Prostate Cancer

Seminars in Oncology Nursing — Thu, 27 Oct 2011 02:33:50 +0100

Conclusion: Alleviation of bodily problems and providing care for men with HRPC is of utmost importance. It is important to talk about their situation and everyday life before asking about expected changes and problems related to the disease and its treatments.Implications for Nursing Practice: A preliminary framework is suggested for understanding the experience of HRPC from a nursing perspective. These results support an existing body of knowledge emphasizing the paramount importance of symptom alleviation, but indicate another motivation, that of freeing time, when time is so limited. The importance of dialogue between patients and health care providers is highlighted. (Source: Seminars in Oncology Nursing)

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Phase I study of BIBF 1120 with docetaxel and prednisone in metastatic chemo-naive hormone-refractory prostate cancer patients

British Journal of Cancer AOP — Tue, 25 Oct 2011 04:00:00 +0100

Authors: G Bousquet, J Alexandre, C Le Tourneau, F Goldwasser, S Faivre, H de Mont-Serrat, R Kaiser, J L Misset & E Raymond (Source: British Journal of Cancer AOP)

Paclitaxel Induces Apoptosis Through Activation of Nuclear Protein Kinase C-δ and Subsequent Activation of Golgi Associated Cdk1 in Human Hormone Refractory Prostate Cancer

The Journal of Urology — Fri, 21 Oct 2011 04:00:00 +0100

Conclusions: Data suggest that paclitaxel induces nuclear translocation and activation of PKC-δ, which in turn causes Golgi-Cdk1 activation, leading to Golgi associated DR5 up-regulation, and caspase-8 and 3 activation. Golgi mediated signaling cascades facilitate mitochondria involved apoptotic pathways and at least partly explain the anticancer activity of paclitaxel action. (Source: The Journal of Urology)

Tumor-targeted gene therapy using Adv-AFP-HRPC/IAA prodrug system suppresses growth of hepatoma xenografted in mice

Cancer Gene Therapy — Fri, 30 Sep 2011 04:00:00 +0100

Tumor-targeted gene therapy using Adv-AFP-HRPC/IAA prodrug system suppresses growth of hepatoma xenografted in mice Cancer Gene Therapy advance online publication, September 30, 2011. doi:10.1038/cgt.2011.65 Authors: M Dai, J Liu, D-E Chen, Y Rao, Z-J Tang, W-Z Ho & C-Y Dong (Source: Cancer Gene Therapy)

NICE issues ACD on the use of cabazitaxel for prostate cancer

NeLM - News — Fri, 30 Sep 2011 04:00:00 +0100

Source: NICE Area: News Draft guidance (appraisal consultation document - ACD) from the National Institute of Health and Clinical Excellence (NICE) does not recommend cabazitaxel in combination with prednisone or prednisolone for the treatment of hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing regimen. An analysis carried out by the Evidence Review Group (ERG) produced an incremental cost-effectiveness ratio (ICER) of £89,500 per QALY gained for cabazitaxel compared with mitoxantrone. The Appraisal Committee concluded that this ICER would be an appropriate starting point for its decision making. The Committee further noted that there remains considerable uncertainty in the robustness of this ICER because the utility values that were...

Alpharadin (radium-223 Chloride) Improves Prostate Cancer Patient Survival Considerably

Health News from Medical News Today — Sat, 24 Sep 2011 19:00:00 +0100

Alpharadin (radium-223 chloride) was found to improve overall survival by patients with CRPC (castration-resistant prostate cancer) and symptomatic bone metastases - survival rates improved by 44%, presenters explained at the Presidential Session at the 2011 European Multidisciplinary Cancer Congress in Stockholm, Sweden. The presenters described how the Phase 3 ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial met its primary endpoint - significantly improving overall survival. Castration-resistant prostate cancer (CRPC) is also known as HRPC (hormone-refractory prostate cancer)... (Source: Health News from Medical News Today)

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New drugs for prostate cancer

BJU International — Tue, 20 Sep 2011 04:00:00 +0100

CONCLUSION• Treatments emerging from these areas of scientific endeavour are progressing into clinical trials and are both good cause for hope in patients, and excellent examples of mechanism based drug discovery. (Source: BJU International)

Chemotherapy-Based Treatment for Castration-Resistant Prostate Cancer [Review Articles]

Journal of Clinical Oncology — Fri, 16 Sep 2011 04:00:00 +0100

Most men with metastatic prostate cancer respond to various types of androgen ablation but progress to castration-resistant disease. The TAX 327 and Southwest Oncology Group (SWOG) 99-16 clinical trials established docetaxel-based chemotherapy as preferred first-line treatment for most men with symptomatic metastatic castration-resistant prostate cancer (mCRPC). However, only about half receive benefit from docetaxel, and those who respond initially progress and eventually die of (or with) mCRPC. Both cellular mechanisms and the tumor microenvironment are implicated in the development of resistance to docetaxel. New agents are being evaluated for men with mCRPC, either as first-line treatment in combination with docetaxel, or in men progressing during or after treatment with docetaxel. Thu...

Functionalized radioactive gold nanoparticles in tumor therapy

Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology — Thu, 01 Sep 2011 04:00:00 +0100

AbstractThe development of new treatment modalities that offer clinicians the ability to reduce sizes of tumor prior to surgical resection or to achieve complete ablation without surgery would be a significant medical breakthrough in the overall care and treatment of prostate cancer patients. The goal of our investigation is aimed at validating the hypothesis that Gum Arabic‐functionalized radioactive gold nanoparticles (GA‐198AuNP) have high affinity toward tumor vasculature. We hypothesized further that intratumoral delivery of the GA‐198AuNP agent within prostate tumor will allow optimal therapeutic payload that will significantly or completely ablate tumor without side effects, in patients with hormone refractory prostate cancer. In order to evaluate the therapeutic efficacy of t...

Clinical Trial Update and Novel Therapeutic Approaches for Metastatic Prostate Cancer.

Current Medicinal Chemistry — Wed, 24 Aug 2011 23:00:00 +0100

Authors: Larsson R, Mongan NP, Johansson M, Shcherbina L, Abrahamsson PA, Gudas LJ, Sterner O, Persson JL Abstract Recurrent prostate cancer (PCa) remains a major clinical challenge. Invasive and metastatic PCa lesions often exhibit a partial and time-limited response to therapy before the cancer progresses and the patient succumbs to the disease. Despite recent advances in early diagnosis and treatment, approximately one-third of treated patients will relapse and become resistant to currently available treatments. In this review we evaluate current treatment practices and recent advances in therapy for localized prostate malignancy and advanced, metastatic prostate cancer. Some of the promising new drugs for PCa treatment include MDV3100, an androgen receptor (AR) antagonist that ...

FDA Grants Fast Track Designation For Alpharadin For Castration Resistant Prostate Cancer In Patients With Bone Metastases

Health News from Medical News Today — Tue, 23 Aug 2011 20:00:00 +0100

Investigational drug Alpharadin (radium-223 chloride) for the treatment of castration-resistant prostate cancer in patients whose cancer has spread to the bone (bone metastasis) has been granted Fast Track designation by the FDA (Food and Drug Administration), Bayer Health Care announced today. Alpharadin is exclusively licenced to Bayer from Algeta ASA. Castration-resistant prostate cancer (CRPC) used to be known as hormone-refractory prostate cancer (HRPC)... (Source: Health News from Medical News Today)

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FDA Grants Fast Track Designation To Bayer's Investigational Compound Radium-223 Chloride for the Treatment Of Castration-Resistant Prostate Cancer That Has Spread To The Bone

Pharmaceutical Online News — Tue, 23 Aug 2011 12:27:34 +0100

Bayer HealthCare Pharmaceuticals, Inc. today announced that its investigational compound radium-223 chloride, which is exclusively licensed from Algeta ASA, has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment of castration-resistant (hormone-refractory) prostate cancer in patients with bone metastases. (Source: Pharmaceutical Online News)

Combination of docetaxel and vandetanib in docetaxel-sensitive or resistant PC3 cell line.

Urologic Oncology — Sun, 24 Jul 2011 23:00:00 +0100

CONCLUSIONS: Our data suggest that combined treatment with vandetanib and docetaxel alters the balance of proapoptotic and prosurvival proteins, ultimately leading to potentiation of docetaxel-induced apoptosis in human prostate cancer cells in vitro, irrespective of cells being sensitive or resistant to docetaxel. PMID: 21795074 [PubMed - as supplied by publisher] (Source: Urologic Oncology)

A novel histone deacetylase inhibitor, CG200745, potentiates anticancer effect of docetaxel in prostate cancer via decreasing Mcl-1 and Bcl-XL

Investigational New Drugs — Tue, 19 Jul 2011 23:38:55 +0100

Summary We synthesized a novel hydroxamate-based pan-histone deacetylase inhibitor (HDACI), CG200745 {(E)-2-(Naphthalen-1-yloxymethyl)-oct-2-enedioic acid 1-[(3-dimethylamino-propyl)-amide] 8-hydroxyamide]}. Like other inhibitors, for example vorinostat and belinostat, CG200745 has the hydroxamic acid moiety to bind zinc at the bottom of catalytic pocket. Firstly, we analyzed its inhibitory activity against histone deacetylase (HDAC) in hormone-dependent LNCaP cells and hormone-independent DU145 and PC3 cells. CG200745 inhibited deacetylation of histone H3 and tubulin as much as vorinostat and belinostat did. CG200745 also inhibited growth of prostate cancer cells, increased sub-G1 population, and activated caspase-9, -3 and −8 in LNCaP, DU145 and PC3 cells. These result...

Hepatic resection for metastatic breast cancer: A systematic review

European Journal of Cancer — Mon, 11 Jul 2011 04:00:00 +0100

Conclusion: Hepatectomy is rarely performed for BCLM but the studies described in this review indicate consistent results with superior 5-year survival for selected patients with isolated liver metastases and in those with well controlled minimal extrahepatic disease. To evaluate its efficacy and control for selection bias, a randomised trial of standard chemotherapy with or without hepatectomy for BCLM is warranted. (Source: European Journal of Cancer)

Regulation of Bombesin-Stimulated Cyclooxygenase-2 Expression in Prostate Cancer Cells

BMC Molecular Biology - Latest articles — Sun, 10 Jul 2011 23:00:00 +0100

Conclusions: Our study establishes a mechanistic link between GRPR activation and enhanced COX-2 expression in prostate cancer cell lines, and suggests that inhibiting GRPR may, in the future, provide an effective therapeutic alternative to non-steroidal anti-inflammatory drugs for inhibiting COX-2 in patients with recurrent prostate cancer. (Source: BMC Molecular Biology - Latest articles)

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Sanofi-aventis announces launch of cabazitaxel (Jevtana) for metastatic prostate cancer

NeLM - News — Mon, 04 Jul 2011 23:00:00 +0100

Source: Sanofi-aventis Area: News Sanofi-aventis has announced the launch of cabazitaxel (Jevtana) for use in combination with prednisone or prednisolone for the treatment of patients with hormone refractory metastatic prostate cancer previously treated with a docetaxel-containing regimen. The recommended dose of cabazitaxel is 25mg/m2 administered as a 1 hour intravenous infusion every 3 weeks in combination with oral prednisone or prednisolone 10 mg administered daily throughout treatment. The cost of a 60mg/1.5mL vial is £3696 (excluding VAT). Please see link to the SPC below for full prescribing information. (Source: NeLM - News)

Quantitative Analysis of the Enzymes Associated with 5-Fluorouracil Metabolism in Prostate Cancer Biopsies

Springer protocols feed by Biotechnology — Thu, 30 Jun 2011 23:00:00 +0100

In this study, we investigated the expression of these enzymes in normal prostate gland (NP), hormone-sensitive prostate cancer (HSPC), and hormone-refractory prostate cancer (HRPC). The prostatic tissue specimens were obtained from patients who had undergone prostate needle biopsies without any treatments or with PSA failure after initial androgen deprivation. The tissue samples derived from formalin-fixed, paraffin-embedded (FFPE) sections were prepared by laser-capture microdissection, and from them RNA was extracted. The levels of OPRT and DPD mRNA expression were examined by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). The level of OPRT mRNA expression in the HSPC or the HRPC specimens was significantly higher than that in the NP specimens. There was a signif...

Immunotherapy of prostate cancer: should we be targeting stem cells and EMT?

Cancer Immunology, Immunotherapy — Tue, 21 Jun 2011 18:01:04 +0100

Abstract Cancer stem cells have been implicated in a number of solid malignancies including prostate cancer. In the case of localised prostate cancer, patients are often treated with surgery (radical prostatectomy) and/or radiotherapy. However, disease recurrence is an issue in about 30% of patients, who will then go on to receive hormone ablation therapy. Hormone ablation therapy is often palliative in a vast proportion of individuals, and for hormone-refractory patients, there are several immunotherapies targeting a number of prostate tumour antigens which are currently in development. However, clinical responses in this setting are inconsistent, and it is believed that the failure to achieve full and permanent tumour eradication is due to a small, resistant population o...

Correlation Analysis of JAK-STAT Pathway Components on Prognosis of Patients with Prostate Cancer.

Pathology Oncology Research — Fri, 17 Jun 2011 23:00:00 +0100

Authors: Liu X, He Z, Li CH, Huang G, Ding C, Liu H Janus kinases (JAK)/signal transducers and activator of transcription (STAT) pathway is activated constitutively in prostate cancer (PCa). Despite previous reports implying a role of this pathway in the development of clinical hormone-refractory PCa, the correlation of pathway members with the clinicopathologic features and prognosis of patients with PCa has not been elucidated. To address this problem, pJAK-1(Tyr1022/1023) and pSTAT-3(Tyr705) were evaluated by immunostaining in needle biopsies of the prostate from 202 PCa patients treated by definitive therapy (105 cases) or hormonal therapy (97 cases). The correlation of two protein expression with the clinicopathologic features and the prognosis of PCa were subsequently assessed. T...

Re: Expression of Estrogen Related Proteins in Hormone Refractory Prostate Cancer: Association With Tumor Progression: O. Celhay, M. Yacoub, J. Irani, B. Dore, O. Cussenot and G. Fromont J Urol 2010; 184: 2172–2178

The Journal of Urology — Thu, 16 Jun 2011 23:00:00 +0100

The authors investigated the expression of proteins related to androgen and estrogen metabolism in paired prostate cancer samples before androgen deprivation therapy (ADT) and after hormonal relapse. They concluded that aromatase and BCAR1 decreased time to biochemical recurrence after androgen deprivation, while high estrogen receptor-α expression by stromal cells achieved delayed recurrence and survival advantage after relapse. I read this article with great interest, as it addressed an important yet unclear issue of the role of estrogen signaling in the transition from hormone sensitive to hormone refractory tumors. However, I believe the conclusions are premature. (Source: The Journal of Urology)

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Outcome after surgery for metastatic spinal cord compression in 54 patients with prostate cancer.

Acta Orthopaedica — Thu, 09 Jun 2011 23:00:00 +0100

Authors: Crnalic S, Hildingsson C, Wikström P, Bergh A, Löfvenberg R, Widmark A Background and purpose The criteria for selecting patients who may benefit from surgery of spinal cord compression in metastatic prostate cancer are poorly defined. We therefore studied patients operated for metastatic spinal cord compression in order to evaluate outcome of surgery and to find predictors of survival. Patients and methods We reviewed the records of 54 consecutive patients with metastatic prostate cancer who were operated for spinal cord compression at Umeå University Hospital. The indication for surgery was neurological deficit due to spinal cord compression. 41 patients had hormone-refractory cancer and 13 patients had previously untreated, hormone-naïve prostate cancer. 29 patients wer...

Ethanolic Extract of Propolis Augments TRAIL-Induced Apoptotic Death in Prostate Cancer Cells

Clinical and Developmental Immunology — Tue, 07 Jun 2011 13:59:59 +0100

We examined the cytotoxic and apoptotic effects of EEP and phenolic compounds isolated from propolis in combination with TRAIL on two prostate cancer cell lines, hormone-sensitivity LNCaP and hormone-refractory DU145. The cytotoxicity was evaluated by MTT and LDH assays. The apoptosis was determined using flow cytometry with annexin V-FITC/propidium iodide. The prostate cancer cell lines were proved to be resistant to TRAIL-induced apoptosis. Our study demonstrated that EEP and its components significantly sensitize to TRAIL-induced death in prostate cancer cells. The percentage of the apoptotic cells after cotreatment with 50 μg mL−1 EEP and 100 ng mL−1 TRAIL increased to 74.9 ± 0.7% for LNCaP and 57.4 ± 0.7% for DU145 ce...

Targeted Cancer Therapy Kills Prostate Tumor Cells

Health News from Medical News Today — Mon, 06 Jun 2011 08:00:00 +0100

A new targeted therapy for prostate cancer halts tumor growth in animals with advanced prostate cancer that is resistant to hormone therapy, a new study finds. The results will be presented Saturday at The Endocrine Society's 93rd Annual Meeting in Boston. "This targeted therapy may provide a treatment breakthrough that will extend the lives of men with advanced, hormone-refractory prostate cancer," said lead investigator Shuk-mei Ho, PhD, chairwoman of the Department of Environmental Health at the University of Cincinnati... (Source: Health News from Medical News Today)

Effect of D: -allose on prostate cancer cell lines: phospholipid profiling by nanoflow liquid chromatography-tandem mass spectrometry.

Analytical and Bioanalytical Chemistry — Thu, 02 Jun 2011 23:00:00 +0100

Authors: Jeong RU, Lim S, Kim MO, Moon MH D: -Allose, a rare, naturally occurring monosaccharide, is known to exert anti-proliferative effects on cancer cells. The effects of D: -allose on the cellular membranes of hormone-refractory prostate cancer cell line (DU145), hormone-sensitive prostate cancer cell line (LNCaP), and normal prostate epithelial cells (PrEC) were studied at the molecular level by phospholipid (PL) profiling using a shotgun lipidomic method. The molecular structures of 85 PL species including 23 phosphatidylcholines, 12 phosphatidylethanolamines (PEs), 11 phosphatidylserines (PSs), 16 phosphatidylinositols, 9 phosphatidic acids (PAs), and 14 phosphatidylglycerols (PGs) were identified by data-dependent collision-induced dissociation of nanoflow liquid chromatograph...

Molecular Validation of PACE4 as a Target in Prostate Cancer.

Translational Oncology — Tue, 31 May 2011 23:00:00 +0100

Authors: D'Anjou F, Routhier S, Perreault JP, Latil A, Bonnel D, Fournier I, Salzet M, Day R Prostate cancer remains the single most prevalent cancer in men. Standard therapies are still limited and include androgen ablation that initially causes tumor regression. However, tumor cells eventually relapse and develop into a hormone-refractory prostate cancer. One of the current challenges in this disease is to define new therapeutic targets, which have been virtually unchanged in the past 30 years. Recent studies have suggested that the family of enzymes known as the proprotein convertases (PCs) is involved in various types of cancers and their progression. The present study examined PC expression in prostate cancer and validates one PC, namely PACE4, as a target. The evidence includes t...

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TRP channels in prostate cancer: the good, the bad and the ugly?

Asian Journal of Andrology — Sun, 29 May 2011 23:00:00 +0100

Authors: Gkika D, Prevarskaya N During the last decade, transient receptor potential (TRP) channels emerge as key proteins in central mechanisms of the carcinogenesis such as cell proliferation, apoptosis and migration. Initial studies showed that expression profile of some TRP channels, notably TRP melastatin 8 (TRPM8), TRP vanilloid 6 (TRPV6),TRP canonical (TRPC6) and TRPV2, is changing during the development and the progression of prostate cancer towards the hormone-refractory stages. The link between the change in expression levels and the functional role of these channels in prostate cancer is step by step being elucidated. These recent advances are here described and discussed.Asian Journal of Andrology advance online publication, 30 May 2011; doi:10.1038/aja.2011.18. PMID: 2...

Synergy between Heregulin and Troglitazone [Signal Transduction]

Journal of Biological Chemistry — Thu, 26 May 2011 23:00:00 +0100

Here, we demonstrate that troglitazone (Rezulin), a peroxisome proliferator-activated receptor agonist, acted in synergy with heregulin to induce massive cell death in breast cancer cells. Although the combination of heregulin and troglitazone (HRG/TGZ) induced both apoptosis and necrosis, the main mode of cell death was caspase-independent and occurred via necrosis. This combination increased generation of superoxide in mitochondria, which in turn destabilized mitochondria potential. Pretreatment with N-acetyl-l-cysteine and catalase expression ameliorated cell death induced by the combination treatment, indicating a role of oxidative stress in mediating HRG/TGZ-induced cell death. Notably, pretreatment with pyruvate significantly prevented the cell death, suggesting a potential mechanist...

Natura-Alpha Targets Forkhead Box M1 and Inhibits Androgen-Dependent and -Independent Prostate Cancer Growth and Invasion.

Clinical Cancer Research — Sun, 22 May 2011 23:00:00 +0100

CONCLUSIONS: Natura-alpha could serve as a novel and effective therapeutic agent for treatment of both hormone sensitive and hormone refractory prostate cancer with minimal side effects. PMID: 21606178 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Randomized Trial of the Effect of the Low Molecular Weight Heparin Nadroparin on Survival in Patients With Cancer [Clinical Trials]

Journal of Clinical Oncology — Tue, 17 May 2011 23:00:00 +0100

Conclusion This study did not show a survival benefit of nadroparin in patients with advanced prostate, lung, or pancreatic cancer. Given the ongoing studies in this area and the previous data, the role of low molecular weight heparins in cancer survival remains undefined. (Source: Journal of Clinical Oncology)

Suppression of growth and invasive behavior of human prostate cancer cells by ProstaCaidTM: Mechanism of activity.

International Journal of Oncology — Sat, 14 May 2011 07:51:46 +0100

In conclusion, the dietary supplement PC is a promising natural complex with the potency to inhibit invasive human prostate cancer. PMID: 21468543 [PubMed - in process] (Source: International Journal of Oncology)

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PEDF inhibits IL8 production in prostate cancer cells through PEDF receptor/phospholipase A2 and regulation of NFκB and PPARγ

Cytokine — Wed, 11 May 2011 23:00:00 +0100

Authors: Hirsch J, Johnson CL, Nelius T, Kennedy R, Riese WD, Filleur S Interleukin-8 (IL8/CXCL8) has been described as a key effector in prostate cancer progression and resistance to standard chemotherapeutic drugs. In the present study, we investigated the effect of the natural, angio-inhibitory and anti-tumoral Pigment Epithelium-Derived Factor (PEDF) on the expression of IL8 cytokine by prostate cancer cells. Using a cytokine antibody array and ELISA, in addition to IL8 quantitative RT PCR, we showed that PEDF inhibits the production of IL8 in human hormone-refractory prostate cancer cells, and delays the growth of these cells in vitro. IL8 reduction was mimicked in cancer cells treated with PPARγ agonist and NFκB-specific inhibitors. Accordingly, PPARγ expression increased in r...

Benzyldihydroxyoctenone, a novel nonsteroidal antiandrogen, shows differential apoptotic induction in prostate cancer cells in response to their androgen responsiveness.

Journal of Microbiology and Biotechnology — Sat, 30 Apr 2011 23:00:00 +0100

Authors: Suh H, Oh HL, Lee CH The molecular mechanisms of apoptotic induction by benzyldihydroxyoctenone (BDH), a nonsteroidal antiandrogen, isolated from the culture broth of Streptomyces sp., have been previously published in prostate cancer LNCaP cells. Apoptotic induction of BDH-treated LNCaP cells was associated with downregulation of Bcl-xL that caused, in turn, cytochrome c release from mitochondria, and activation of procaspases and specific proteolytic cleavage of poly(ADP-ribose) polymerase (PARP). The purpose of the present study was to investigate the patterns of apoptotic induction by BDH in non-prostate, ovarian cancer PA-1 (androgen-independent and -insensitive) cells and prostate cancer cells with different androgen responsiveness, such as C4-2 (androgen-independent and...

Molecular chemotherapy and Chemotherapy: A new front against late stage hormone refractory prostate cancer.

Clinical Cancer Research — Thu, 28 Apr 2011 23:00:00 +0100

CONCLUSIONS: PNP-GDEPT and docetaxel are a potent combination against CRPC in immunocompetent and in immunodeficient settings; the outcomes have translational potential for improved treatment and management of CRPC patients. PMID: 21531822 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

The significance of Her2 on androgen receptor protein stability in the transition of androgen requirement in prostate cancer cells

AJP: Endocrinology and Metabolism — Mon, 25 Apr 2011 23:00:00 +0100

Androgen ablation therapy is the most common strategy for suppressing prostate cancer progression; however, tumor cells eventually escape androgen dependence and progress to an androgen-independent phase. The androgen receptor (AR) plays a pivotal role in this transition. To address this transition mystery in prostate cancer, we established an androgen-independent prostate cancer cell line (LNCaPdcc), by long-term screening of LNCaP cells in androgen-deprived conditions, to investigate changes of molecular mechanisms before and after androgen withdrawal. We found that LNCaPdcc cells displayed a neuroendocrine morphology, less aggressive growth, and lower expression levels of cell cycle-related factors, although the cell cycle distribution was similar to parental LNCaP cells. Notably, highe...

Active sonic hedgehog signaling between androgen independent human prostate cancer cells and normal/benign but not cancer‐associated prostate stromal cells

The Prostate — Sun, 24 Apr 2011 23:00:00 +0100

CONCLUSIONSBased on co‐culture and chimeric tumor models, active Shh‐mediated signaling was demonstrated between AI prostate cancer and NPF in a paracrine‐ and tumor progression‐dependent manner. Our study suggests that drugs like cyclopamine that interfere with Shh signaling could be beneficial in preventing AI progression in prostate cancer cells. Prostate © 2011 Wiley‐Liss, Inc. (Source: The Prostate)

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Phase 3 Trial Finds No Benefit From Atrasentan Added To Chemo For Advanced Prostate Cancer

Health News from Medical News Today — Fri, 22 Apr 2011 07:00:00 +0100

A Data and Safety Monitoring Committee (DSMC) has determined that patients in a phase III clinical trial given atrasentan in addition to a standard chemotherapy regimen for advanced prostate cancer did not have longer survival or longer progression-free survival than patients on the same chemotherapy regimen who got a placebo rather than atrasentan. Almost 1,000 patients who had advanced, hormone-refractory prostate cancer were given up to 36 weeks of chemotherapy with docetaxel and prednisone... (Source: Health News from Medical News Today)

Phase III trial finds no benefit from atrasentan added to chemo for advanced prostate cancer

ScienceDaily Headlines — Thu, 21 Apr 2011 16:23:23 +0100

The SWOG trial S0421 closed early based on interim finding that atrasentan added to docetaxel and prednisone did not confer additional survival benefit to patients with advanced hormone-refractory prostate cancer. (Source: ScienceDaily Headlines)

Phase 3 trial finds no benefit from atrasentan added to chemo for advanced prostate cancer

EurekAlert! - Medicine and Health — Thu, 21 Apr 2011 04:00:00 +0100

(University of Michigan Health System) The NCI-supported SWOG trial S0421 closed early based on interim finding that atrasentan added to docetaxel and prednisone did not confer additional survival benefit to patients with advanced hormone-refractory prostate cancer. (Source: EurekAlert! - Medicine and Health)

Study finds the LMWH nadroparin does not improve survival in patients with prostate, lung or pancreatic cancer

NeLM - News — Mon, 18 Apr 2011 23:00:00 +0100

Source: Journal of Clinical Oncology Area: News The authors note that there are data to suggest that LMWH improve survival when added to chemotherapy in patients with cancer without venous thromboembolism (VTE); there are however unresolved issues, including study design limitations, inclusion of heterogeneous group of patients with cancer, and the application of regimens including different types, doses and durations of LMWH. The purpose of this study was to specifically assess the effects of the LWMH nadroparin on survival in three cancer types: hormone-refractory prostate cancer, non-small-cell lung cancer and locally advanced pancreatic cancer. Patients were randomised to open-label treatment with nadroparin (2 weeks at therapeutic dose, and 4 weeks at half ther...

Methylseleninic acid down regulates hypoxia inducible factor‐1α in invasive prostate cancer

International Journal of Cancer — Thu, 14 Apr 2011 23:00:00 +0100

AbstractAlternative strategies are needed to control growth of advanced and hormone refractory prostate cancer. In this regard, we investigated the efficacy of methylseleninic acid (MSeA), a penultimate precursor to the highly reactive selenium metabolite, methylselenol, to inhibit growth of invasive and hormone refractory rat (PAIII) and human (PC‐3, PC‐3M) prostate cancer cells. Our results demonstrate that MSeA inhibits PAIII cell growth in vitro as well as reduces weights of tumors generated by PAIII cells treated ex vivo. A significant reduction in the number of metastatic lung foci by MSeA treatment was also noted in Lobund Wistar rats. The PAIII cells along with PC‐3, DU145 and PC‐3M cells undergo apoptosis following MSeA treatments in both normoxia and hypoxia. Treatment of...

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Methylseleninic acid downregulates hypoxia‐inducible factor‐1α in invasive prostate cancer

International Journal of Cancer — Thu, 14 Apr 2011 23:00:00 +0100

AbstractAlternative strategies are needed to control growth of advanced and hormone refractory prostate cancer. In this regard, we investigated the efficacy of methylseleninic acid (MSeA), a penultimate precursor to the highly reactive selenium metabolite, methylselenol, to inhibit growth of invasive and hormone refractory rat (PAIII) and human (PC‐3 and PC‐3M) prostate cancer cells. Our results demonstrate that MSeA inhibits PAIII cell growth in vitro as well as reduces weights of tumors generated by PAIII cells treated ex vivo. A significant reduction in the number of metastatic lung foci by MSeA treatment was also noted in Lobund‐Wistar rats. The PAIII cells along with PC‐3, DU145 and PC‐3M cells undergo apoptosis after MSeA treatments in both normoxia and hypoxia. Treatment o...

Medicare to Cover Prostate Cancer Immunotherapy

MedPage Today Urology — Fri, 01 Apr 2011 03:13:11 +0100

(MedPage Today) -- Medicare plans to pay for sipuleucel-T (Provenge), the autologous immunotherapy for prostate cancer, following a determination that it is genuinely effective in metastatic hormone-refractory disease, according to the Centers for Medicare and Medicaid Services. (Source: MedPage Today Urology)

Advanced Prostate Cancer Drug Provenge $93,000 Per Patient Likely To Be Covered By Medicare

Health News from Medical News Today — Thu, 31 Mar 2011 16:00:00 +0100

Medicare has indicated that it proposes to cover the $93,000 cost per patient for a four month course of advanced prostate cancer vaccine Provenge (Sipuleucel-T). Provenge is a therapeutic cancer vaccine designed to prolong the life of patients with advanced to late stage prostate cancer, metastatic, asymptomatic, hormone-refractory prostate cancer. Provenge makes it possible for the patient's immune system to identify and target prostate cancer cells. According to the Centers for Medicare and Medicaid, Provenge was described as a "reasonable and necessary" medication... (Source: Health News from Medical News Today)

Cabazitaxel Provides Multiple Benefits In Men With Advanced Prostate Cancer

Health News from Medical News Today — Fri, 25 Mar 2011 20:00:00 +0100

The tubulin-binding taxane cabazitaxel in combination with prednisone significantly extends overall survival in men with hormone-refractory prostate cancer previously treated with a docetaxel-containing regimen and also improves disease control, researchers said at the 26th Anniversary European Association of Urology (EAU) Congress... (Source: Health News from Medical News Today)

Poly(2-hydroxyethyl methacrylate) for enzyme immobilization - impact on activity and stability of Horseradish Peroxidase.

Biomacromolecules — Fri, 25 Mar 2011 00:00:00 +0100

Authors: Lane SM, Kuang Z, Yom J, Arifuzzaman S, Genzer J, Farmer B, Naik R, Vaia RA Based on their versatile structure and chemistry, as well as tunable mechanical properties, polymer brushes are well-suited as supports for enzyme immobilization. A robust surface design though is hindered by an inadequate understanding of the impact on activity from the coupling motif and enzyme distribution within the brush. Herein, horseradish peroxidase C (HRP C, 44 kDa), chosen as a model enzyme, was immobilized covalently through its lysine residues on a N-hydroxysuccinimidyl carbonate-activated poly(2-hydroxyethyl methacrylate) (PHEMA) brush grafted chemically onto a flat impenetrable surface. Up to a monolayer coverage of HRP C is achieved, where most of the HRP C resides at or near the brush-a...

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JEVTANA(R) (Cabazitaxel) Approved By European Commission For Treatment Of Advanced Second-Line Prostate Cancer

Health News from Medical News Today — Mon, 21 Mar 2011 09:00:00 +0100

Sanofi-aventis (EURONEXT: SAN and NYSE: SNY) announced it has received marketing authorization from the European Commission for JEVTANA® (cabazitaxel) in combination with prednisone/prednisolone for the treatment of patients with metastatic hormone-refractory prostate cancer (mHRPC) previously treated with a docetaxel-containing regimen.1 JEVTANA is the first approved agent to significantly extend overall survival in mHRPC patients whose disease has progressed during or after treatment containing docetaxel (15.1 months median overall survival vs 12.7 months in the mitoxantrone arm; HR=0... (Source: Health News from Medical News Today)

Horizon scanning: Aflibercept fails in meet primary endpoint in phase III (VITAL) trial of NSCLC

NeLM - News — Fri, 11 Mar 2011 00:00:00 +0100

Source: PharmaTimes Area: News The investigational agent aflibercept (also known as VEGF Trap) developed by Sanofi Aventis and partner Regeneron has failed to meet the primary endpoint of a phase III (VITAL) trial evaluating its use for the second-line treatment of non small cell lung cancer (NSCLC) in 913 patients. The addition of aflibercept to docetaxel did not meet the primary endpoint of improvement in overall survival compared with docetaxel plus placebo. The companies said they will conduct a detailed analysis of the efficacy and safety results of VITAL and present full results at an upcoming medical meeting. The drug has suffered earlier setbacks: in September 2009, the firms stopped a late-stage trial in metastatic pancreatic cancer and it was withdrawn in ovarian canc...

Trapping prostate cancer cells to keep them from spreading provides hope

EurekAlert! - Biology — Thu, 10 Mar 2011 05:00:00 +0100

(Cell Transplantation Center of Excellence for Aging and Brain Repair) When prostate cancer stem cells (CSCs) were enclosed in self-assembling nanomaterials made of peptides (SAP), the SAPs stopped cancer stem cell colony formation and also stopped the division of cancer cells in vitro. The cancer cells grew and multiplied after they were "liberated" from the SAP nanomaterials. Trapping CSCs in SAPs loaded with chemotherapy agents may allow increased effectiveness for localized treatment for hormone refractory prostate cancer. (Source: EurekAlert! - Biology)

ADAM12 induces estrogen-independence in breast cancer cells

Breast Cancer Research and Treatment — Wed, 09 Mar 2011 07:00:22 +0100

Abstract Antiestrogen therapy has been used successfully to prolong disease-free and overall survival of ER positive breast cancer patients. However, 50% of patients with ER+ tumors fail to respond to such therapy or eventually acquire resistance to endocrine therapy, resulting in tumor progression and mortality. It is imperative, therefore, to understand the mechanisms that lead to hormone refractory breast cancer in order to develop therapeutics that can modulate the resistance to antiestrogen therapy. The protease, ADAM12, can be detected in the urine of breast cancer patients and its levels correlate with disease status, stage, and cancer risk. Within the context of this study, the authors have investigated the role of the two distinct isoforms of ADAM12 in breast...

Macrophages induce neuroendocrine differentiation of prostate cancer cells via BMP6‐IL6 Loop

The Prostate — Thu, 03 Mar 2011 00:00:00 +0100

CONCLUSIONSTherefore, we propose that BMP‐6 secreted by prostate cancer cells induces IL‐6 expression in macrophages; IL‐6, in turn, stimulates the NED of prostate cancer cells. Prostate © 2011 Wiley‐Liss, Inc. (Source: The Prostate)

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[News] Where next for research and development in oncology?

The Lancet Oncology — Tue, 01 Mar 2011 00:00:00 +0100

Pfizer are closing their main European research and development (R&D) headquarters and making cuts to their US sites. They are slicing US$2 billion from their 2012 R&D budget, and have their $330 million settlements due for Prempro's risks of breast cancer. MannKind are cutting 41% of their workforce. Patents for Novartis' Femara (letrozole) and Zometa (zoledronic acid) expire in 2012. Combined with several oncological drugs recently failing in phase 3 trials—Bristol-Myers Squibb and Lilly's necitumumab in non-squamous NSCLC (INSPIRE trial) and AstraZeneca's ZD4054 for metastatic hormone-refractory prostate cancer (study 15 of ENTHUSE)—storms are gathering for future pharmaceutical drug development. (Source: The Lancet Oncology)

The supportive care needs of men with advanced prostate cancer.

Oncology Nursing Forum — Tue, 01 Mar 2011 00:00:00 +0100

Conclusions: A priority health need for men with advanced prostate cancer is to improve or maintain functional abilities. In addition, men require support to meet their stage-specific information needs and to address concerns about the diagnosis and ambivalent feelings about past treatment decisions.Interpretation: Nurses could play an important role in addressing men's information needs and providing emotional support. The complex care needs of men with advanced prostate cancer provide opportunity for the development of advanced practice nurse roles that would use the clinical and nonclinical aspects of the role. PMID: 21356656 [PubMed - in process] (Source: Oncology Nursing Forum)

Mathematical analysis of the heart rate performance curve during incremental exercise testing.

Acta Physiologica Hungarica — Tue, 01 Mar 2011 00:00:00 +0100

In this study we performed laboratory treadmill protocols of increasing load. Heart rate was continuously recorded and blood lactate concentration was measured for determination of lactate threshold by means of LTD-max and LT4.0 methods.Our results indicate that the shape of heart rate performance curve (HRPC) during incremental testing depends on the applied exercise protocol (change of initial speed and the step of running speed increase, with the constant stage duration). Depending on the applied protocol, the HRPC can be described by linear, polynomial (S-shaped), and exponential mathematical expression.We presented mathematical procedure for estimation of heart rate threshold points at the level of LTD-max and LT4.0, by means of exponential curve and its relative deflection from the i...

The significance of Her2 on androgen receptor protein stability in the transition of androgen requirement in prostate cancer cells.

American Journal of Physiology. Endocrinology and Metabolism — Tue, 01 Mar 2011 00:00:00 +0100

Authors: Hsu FN, Yang MS, Lin E, Tseng CF, Lin H Androgen ablation therapy is the most common strategy to suppress prostate cancer progression; however, tumor cells eventually escape androgen dependence and progress to an androgen-independent phase. The androgen receptor (AR) plays a pivotal role in this transition. To address this transition mystery in prostate cancer, we established an androgen-independent prostate cancer cell line (LNCaPdcc), by long-term screening of LNCaP cells in androgen-deprived conditions, to investigate changes of molecular mechanisms before and after androgen withdrawal. We found that LNCaPdcc cells displayed a neuroendocrine morphology, less aggressive growth, and lower expression levels of cell cycle-related factors, although the cell cycle distribution wa...

535 prediction of hormone-refractory prostate cancer on the basis of the pretreatment androgen content in prostate needle biopsy specimen

European Urology Supplements — Tue, 01 Mar 2011 00:00:00 +0100

(Source: European Urology Supplements)

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1094 clinical benefits of epoetin beta in patients with advanced stage hormone refractory prostate cancer

European Urology Supplements — Tue, 01 Mar 2011 00:00:00 +0100

(Source: European Urology Supplements)

HY251, a novel decahydrocyclopenta[a]indene analog, from Aralia continentalis induces apoptosis via down-regulation of AR expression in human prostate cancer LNCaP cells.

Bioorganic and Medicinal Chemistry Letters — Fri, 25 Feb 2011 14:30:22 +0100

Authors: Oh HL, Lee CH In the course of screening for a novel anticancer drug candidate, we previously isolated HY251 with the molecular structure of 3-propyl-2-vinyl-1,2,3,3a,3b,6,7,7a,8,8a-decahydrocyclopenta[a]indene-3,3a,7a,8a-tetraol from the roots of Aralia continentalis. The current study was designed to evaluate the detailed mechanisms of apoptotic induction of HY251 in androgen-sensitive prostate cancer LNCaP cells. TUNEL assay and Western blot analysis revealed an appreciable apoptotic induction in LNCaP cells treated with 95μM of HY251 for 24h. This apoptotic induction is also associated with cytochrome c release from mitochondria which, in turn, resulted in the activation of caspase-9 and -3, and the cleavage of poly(ADP-ribose) polymerase (PARP). Moreover, we found that H...

Survivin Is Associated With Cell Proliferation and Has a Role in 1a,25-Dihydroxyvitamin D3 Induced Cell Growth Inhibition in Prostate Cancer

The Journal of Urology — Mon, 21 Feb 2011 00:00:00 +0100

Conclusions: Findings suggest that survivin has a significant association with prostate cancer cell proliferation and an essential role in 1a,25-dihydroxyvitamin D3 induced prostate cancer cell growth inhibition. It seems that the eliminating survivin in 1a,25-dihydroxyvitamin D3 therapy for hormone refractory prostate cancer is a potential therapeutic option. (Source: The Journal of Urology)

Activity of Different Anthracycline Formulations in Hormone‐Refractory Prostate Cancer Cell Lines: Role of Golgi Apparatus

Journal of Cellular Physiology — Tue, 01 Feb 2011 00:00:00 +0100

AbstractThe efficacy of therapy for hormone‐refractory prostate cancer (HRPC) is still unsatisfactory and new agents and therapeutic modalities are needed. The aims of the present work were to examine the in vitro activity and mechanisms of action of doxorubicin (DX), pegylated liposomal DX (PLDX) and non‐pegylated liposomal DX (NPLDX) in DU145 and taxane‐resistant DU145‐R HRPC cell lines. Drug activity and incorporation, apoptosis, and expression of cell death‐related markers were evaluated by SRB test, cytofluorimetric assays and western blot, respectively. Among the different DX formulations, NPLDX showed the highest cytotoxic activity in both cell lines, with more than 50% of apoptotic cells at only 1/10 of the plasma peak concentration after 72 hours' exposure. Anthracycline...

Retrospective Analysis of an Oral Combination of Dexamethasone, Uracil plus Tegafur and Cyclophosphamide for Hormone-refractory Prostate Cancer

Japanese Journal of Clinical Oncology — Thu, 27 Jan 2011 00:00:00 +0100

Conclusions The combination of dexamethasone, uracil plus tegafur and cyclophosphamide is an effective and well tolerated regimen for hormone-refractory prostate cancer. To evaluate the survival benefits, further randomized studies are required. (Source: Japanese Journal of Clinical Oncology)

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European CHMP adopts positive opinion on marketing application for cabazitaxel (Jevtana)

NeLM - News — Fri, 21 Jan 2011 00:00:00 +0100

Source: European Medicines Agency (EMA) Area: News The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending the granting of a marketing authorisation for cabazitaxel (Jevtana) for the treatment of patients with hormone refractory metastatic prostate cancer previously treated with a docetaxel-containing regimen. (Source: NeLM - News)

AN N-terminal Smac peptide sensitizes human prostate carcinoma cells to methyl jasmonate-induced apoptosis

Cancer Letters — Tue, 18 Jan 2011 00:00:00 +0100

Abstract: Although the anti-cancer agent methyl jasmonate (MJ) has been shown to selectively target malignant cells while sparing normal ones, hormone-refractory prostate cancer cells are relatively resistant to MJ than other cancer cells. In the present study, we investigated the effect of cell permeable seven-residue peptide of Smac (SmacN7), an antagonist of the inhibitor of apoptosis proteins (IAPs), on MJ-induced apoptosis. SmacN7 significantly enhanced the growth inhibition effect of MJ in human prostate cancer cells, but not in proximal tubular epithelial cells. Moreover, SmacN7 sensitizes MJ-induced apoptosis through both caspase-9-dependent and -independent pathways. Thus, blockade of the over-expressed IAPs in cancer cells could yield a potential therapeutic benefit in jasmonates...

CaM Kinase Kinase {beta}-Mediated Activation of the Growth Regulatory Kinase AMPK Is Required for Androgen-Dependent Migration of Prostate Cancer Cells

Cancer Research — Thu, 13 Jan 2011 00:00:00 +0100

While patients with advanced prostate cancer initially respond favorably to androgen ablation therapy, most experience a relapse of the disease within 1–2 years. Although hormone-refractory disease is unresponsive to androgen-deprivation, androgen receptor (AR)-regulated signaling pathways remain active and are necessary for cancer progression. Thus, both AR itself and the processes downstream of the receptor remain viable targets for therapeutic intervention. Microarray analysis of multiple clinical cohorts showed that the serine/threonine kinase Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ) is both highly expressed in the prostate and further elevated in prostate cancers. Using cellular models of prostate cancer, we have determined that androgens (a) directly...

Loss of EGFR induced autophagy sensitizes hormone refractory prostate cancer cells to adriamycin

The Prostate — Wed, 12 Jan 2011 00:00:00 +0100

CONCLUSIONTaken together, these data suggest that decreasing the expression level of EGFR protein, rather than inhibiting its tyrosine kinase activity, may enhance the efficiency of EGFR targeted therapy for prostate cancer. Prostate in 2011 Wiley‐Liss, Inc. (Source: The Prostate)

Enhanced Radiosensitivity of Androgen-Resistant Prostate Cancer: AZD1152-Mediated Aurora Kinase B Inhibition.

Radiation Research — Tue, 11 Jan 2011 00:00:00 +0100

This study identifies the optimal AZD1152 treatment conditions to maximize the radiosensitization of PC3 and DU145 cells. These results suggest a major role for DNA damage and impairment of DNA repair mechanisms in AZD1152-induced radiosensitization of prostate cancer cells. PMID: 21222513 [PubMed - as supplied by publisher] (Source: Radiation Research)

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WJ9708012 exerts anticancer activity through PKC-α related crosstalk of mitochondrial and endoplasmic reticulum stresses in human hormone-refractory prostate cancer cells.

Acta Pharmacologica Sinica — Mon, 06 Dec 2010 00:00:00 +0100

Conclusion:WJ9708012 induces an increase of cytosolic Ca(2+) concentration and activation of PKC-α. Subsequently, a crosstalk between ER stress and mitochondrial insult is induced, leading to the inhibition of mTOR pathways and arrest of the cell-cycle at G(1) phase. The apoptosis is ultimately induced by a severe damage of mitochondrial function. PMID: 21132000 [PubMed - as supplied by publisher] (Source: Acta Pharmacologica Sinica)

How multidisciplinary teams (MDTs) work in practice in the management of advanced prostate cancer: A survey of oncologists and urologists in the UK

British Journal of Medical and Surgical Urology — Thu, 25 Nov 2010 00:00:00 +0100

Conclusion: Within an environment where treatment options for advanced prostate cancer continue to evolve, it is important that management approaches are considered by the multidisciplinary team with a focus on the patient's individual needs and circumstances. (Source: British Journal of Medical and Surgical Urology)

Glucocorticoid receptor signaling and prostate cancer

Cancer Letters — Mon, 15 Nov 2010 00:00:00 +0100

Abstract: Glucocorticoids (GCs) are provided to hormone-refractory prostate cancer (HRPC) patients partly due to the inhibitory effects on adrenal androgen production acting as a pituitary suppressant. Nowadays, the combination of chemotherapy and dexamethasone is a standard treatment for HRPC patients while increasing evidence suggests that a lot of local tissue factors like growth factors, angiogenic/lymphogenic factors, apoptosis-related factors, cytokines related to the transition of prostate cancer from androgen dependence to hormone-refractory status, are among the targets of GR signaling. However, although glucocorticoids have been recognized to be one of a limited number of treatment options for HRPC, the molecular basis of GC-induced effects in prostate cancer remains poorly defin...

FTY720 (Fingolimod) Sensitizes Prostate Cancer Cells to Radiotherapy by Inhibition of Sphingosine Kinase-1

Cancer Research — Sun, 31 Oct 2010 00:00:00 +0100

Radiotherapy is widely used as a radical treatment for prostate cancer, but curative treatments are elusive for poorly differentiated tumors where survival is just 15% at 15 years. Dose escalation improves local response rates but is limited by tolerance in normal tissues. A sphingosine analogue, FTY720 (fingolimod), a drug currently in phase III studies for treatment of multiple sclerosis, has been found to be a potent apoptosis inducer in prostate cancer cells. Using in vitro and in vivo approaches, we analyzed the impact of FTY720 on sphingolipid metabolism in hormone-refractory metastatic prostate cancer cells and evaluated its potential as a radiosensitizer on cell lines and prostate tumor xenografts. In prostate cancer cell lines, FTY720 acted as a sphingosine kinase 1 (SphK1) inhibi...

Definition of Hormone Refractory Prostate Cancer

About.com Prostate Cancer — Sat, 30 Oct 2010 00:00:00 +0100

What is hormone refractory prostate cancer? (Source: About.com Prostate Cancer)

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Histone Deacetylase Inhibitor Potentiates Anticancer Effect of Docetaxel via Modulation of Bcl-2 Family Proteins and Tubulin in Hormone Refractory Prostate Cancer Cells

The Journal of Urology — Thu, 28 Oct 2010 00:00:00 +0100

Conclusions: These preclinical results indicate that the sequential combination of docetaxel and histone deacetylase inhibitors led to a synergistic increase in the death of hormone refractory prostate cancer cells via intrinsic and extrinsic apoptotic pathways by modulating Bcl-2 family proteins and tubulin in vitro and in vivo. Results suggest that this combination may be a new therapeutic modality in patients with hormone refractory prostate cancer. (Source: The Journal of Urology)

Docetaxel-Prednisolone Combination Therapy for Japanese Patients with Hormone-refractory Prostate Cancer: a Single Institution Experience

Japanese Journal of Clinical Oncology — Mon, 25 Oct 2010 23:00:00 +0100

Conclusion Docetaxel plus prednisolone treatment is effective in Japanese HRPC patients. The main toxicity is neutropenia, which can be safely controlled by outpatient treatment with granulocyte-colony stimulating factor. However, the Japanese patients in our study developed ARDS more frequently than other patients in previous studies did. (Source: Japanese Journal of Clinical Oncology)

Growth factor stimulation induces a distinct ER{alpha} cistrome underlying breast cancer endocrine resistance [Research Papers]

Genes and Development — Fri, 01 Oct 2010 14:02:14 +0100

Estrogen receptor (ER) expression in breast cancer is predictive of response to endocrine therapy; however, resistance is common in ER-positive tumors that overexpress the growth factor receptor ERBB2. Even in the absence of estrogen, ER can be activated by growth factors, including the epidermal growth factor (EGF). EGF induces a transcriptional program distinct from estrogen; however, the mechanism of the stimulus-specific response is unknown. Here we show that the EGF-induced ER genomic targets, its cistromes, are distinct from those induced by estrogen in a process dependent on the transcription factor AP-1. The EGF-induced ER cistrome specifically regulates genes found overexpressed in ERBB2-positive human breast cancers. This provides a potential molecular explanation for the endocri...

Drug for late-stage prostate cancer

NHS News Feed — Fri, 01 Oct 2010 10:17:00 +0100

Conclusion This phase 3 clinical trial has demonstrated that cabazitaxel extends progression-free survival by an average of 1.4 months and overall survival by an average of 2.3 months in a subgroup of men with advanced castration-resistant prostate cancer which has progressed after treatment with docetaxel. Cabazitaxel has been approved for use in this group of patients by the American Food and Drug Administration this year and is currently being considered by the European Medicines Agency and other UK regulatory bodies. Links To The Headlines Drug extends lives of advanced prostate cancer patients. The Daily Telegraph, October 1 2010 Prostate cancer drug could provide two precious extra months of life to men in advanced stages of the disease. Daily Mail, October 1 2010 Links To Scienc...

[Comment] Cabazitaxel in prostate cancer: stretching a string

LANCET — Thu, 30 Sep 2010 23:00:00 +0100

Improvements in the survival of patients who are at the fatal edge of the prostate-cancer kaleidoscope have been difficult to come by. Trial accrual and practice-changing results for hormone-refractory, castration-resistant, or androgen-independent prostate cancer, each a fatal malady, have lagged 20 years behind those for breast cancer. In 1996, the National Cancer Institute of Canada investigators reported that, compared to prednisone alone, mitoxantrone with prednisone improved quality of life and symptoms for a median of 6 months, but had a negligible effect on survival. These data were summarised in a subsequent Cancer and Leukemia Group B (CALGB) trial. In 2004, the Southwest Oncology Group (SWOG)-S9916 trial of docetaxel-based chemotherapy compared to mitoxantrone, and the TAX 327 t...

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Preclinical Characterization of Mitochondria-Targeted Small Molecule Hsp90 Inhibitors, Gamitrinibs, in Advanced Prostate Cancer.

Clinical Cancer Research — Thu, 30 Sep 2010 23:00:00 +0100

CONCLUSIONS: Gamitrinibs have preclinical activity and favorable safety in models of drug-resistant and bone metastatic prostate cancer in vivo. Clin Cancer Res; 16(19); 4779-88. Â©2010 AACR. PMID: 20876793 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Three Weekly Docetaxel plus Predinsolone for Patients with Hormone-Refractory Metastatic Prostate Cancer: Preliminary Result

Journal of Men's Health — Thu, 30 Sep 2010 23:00:00 +0100

Purpose. The aim of this phase II clinical study was to evaluate three -weekly docetaxel plus prednisolone as first-line chemotherapy for treatment of hormone-refractory metastatic prostate cancer (HRMPC). (Source: Journal of Men's Health)

Benefit of New Taxane Affirmed in Prostate CA (CME/CE)

MedPage Today Hematology/Oncology — Thu, 30 Sep 2010 22:30:00 +0100

(MedPage Today) -- The recently approved chemotherapy agent cabazitaxel (Jevtana) improves overall survival in metastatic, hormone-refractory prostate cancer resistant to docetaxel (Taxotere), researchers affirmed. (Source: MedPage Today Hematology/Oncology)

Early response assessment in prostate carcinoma by 18F-fluorothymidine following anticancer therapy with docetaxel using preclinical tumour models

European Journal of Nuclear Medicine and Molecular Imaging — Wed, 29 Sep 2010 05:43:55 +0100

Conclusion These results indicate that FLT is a promising tracer for monitoring the early effects of anticancer therapy with DTX in patients with HRPC. Content Type Journal ArticleDOI 10.1007/s00259-010-1613-zAuthors Nobuyuki Oyama, Department of Urology, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Fukui, 9101193 JapanYoko Hasegawa, Department of Urology, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Fukui, 9101193 JapanYasushi Kiyono, Biomedical Imaging Research Center, University of Fukui, Fukui, JapanMasato Kobayashi, Biomedical Imaging Research Center, University of Fukui, Fukui, JapanYasuhisa Fujibayashi, Biomedical Imaging Research Center, University of Fukui, Fukui, JapanDatta E. Ponde, Mallinckro...

NICE work programme referrals - September 2010

NeLM - News — Thu, 23 Sep 2010 23:00:00 +0100

Source: Department of Health (DH) Area: News The Department of Health has issued a press release confirming topics for referral to the National Institute for Health and Clinical Excellence (NICE) work programme. The technology appraisal topics have each been subject to consultation on the remit and scope. Ministers have agreed that the following topics should be finally referred: Single Technology appraisals (STA) To appraise the clinical and cost effectiveness of: . Cabazitaxel within its licensed indication for the treatment of hormone refractory metastatic prostate cancer previously treated with docetaxel chemotherapy regimens. . Retigabine within its licensed indication for the adjunctive treatment of adults with partial onset seizures in e...

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Hybrigenics Unveils Positive Final Results Of Inecalcitol Phase IIa Clinical Study In Hormone-Refractory Prostate Cancer

Health News from Medical News Today — Tue, 21 Sep 2010 07:00:00 +0100

Hybrigenics (ALHYG), a bio-pharmaceutical company listed on Alternext (NYSE-Euronext) in Paris, with a focus on research and development of new cancer treatments, today announces the positive outcomes of clinical tolerance Phase IIa study of daily oral inecalcitol in combination with gold standard Taxotere(R) chemotherapy in hormone-refractory prostate cancer patients. The maximal tolerated dose of inecalcitol is 4 milligrams (mg) per day and the response rate to combination treatment reached 85 per cent based on Prostate-Specific Antigen (PSA) decline within 3 months... (Source: Health News from Medical News Today)

Expression of Estrogen Related Proteins in Hormone Refractory Prostate Cancer: Association With Tumor Progression

The Journal of Urology — Thu, 16 Sep 2010 23:00:00 +0100

Purpose: Despite increasing evidence that estrogen signaling has a key role in prostate cancer development and progression, few studies have focused on the estrogen pathway in the transition from hormone sensitive to hormone refractory tumors. We investigated the expression of proteins related to androgen and estrogen metabolism in paired prostate cancer samples collected before androgen deprivation therapy and after hormonal relapse.Materials and Methods: The study included 55 patients treated for prostate cancer only with androgen deprivation therapy and in whom tissue was available before treatment induction and after recurrence. Immunohistochemistry was performed using tissue microarray with antibodies directed against androgen receptor, phosphorylated androgen receptor, estrogen recep...

Cabazitaxel

Nature Reviews Drug Discovery — Thu, 02 Sep 2010 05:50:44 +0100

Authors: Matthew D. Galsky, Argyris Dritselis, Peter Kirkpatrick & William K. Oh In June 2010, the taxane anticancer drug cabazitaxel (Jevtana; Sanofi–Aventis), in combination with prednisone, was approved by the US Food and Drug Administration (FDA) for the treatment of patients with hormone-refractory metastatic prostate cancer who had been previously treated with a regimen containing the taxane docetaxel. (Source: Nature Reviews Drug Discovery)

Efficacy of Dendritic Cells Matured Early with OK-432 (Picibanil(R)), Prostaglandin E(2), and Interferon-alpha as a Vaccine for a Hormone Refractory Prostate Cancer Cell Line.

J Korean Med Sci — Tue, 31 Aug 2010 23:00:00 +0100

Authors: Yoo C, Do HA, Jeong IG, Park H, Hwang JJ, Hong JH, Cho JS, Choo MS, Ahn H, Kim CS Dendritic cells (DCs) are potent antigen-presenting cells. OK432 (Picibanil(R)) was introduced as a potent stimulator of DC maturation in combination with prostaglandin-E(2) and interferon-alpha. We compared the efficacy of a DC-prostate cancer vaccine using early-mature DCs stimulated with OK432, PGE2 and INF-alpha (OPA) with that of vaccines using other methods. On days 3 or 7 of DC culture, TNF-alpha (T), TNF-alpha and LPS (TL) or OPA were employed as maturation stimulators. DU145 cells subjected to heat stress were hybridized with mature DCs using polyethyleneglycol. T cells were sensitized by the hybrids, and their proliferative and cytokine secretion activities and cytotoxicity were measure...

Influence of caspases 8 and 9 gene promoter polymorphism on prostate cancer susceptibility and early development of hormone refractory prostate cancer

BJU International — Sat, 28 Aug 2010 08:09:51 +0100

(Source: BJU International)

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Recovery of hormone sensitivity after salvage brachytherapy for hormone refractory localized prostate cancer

International Braz J Urol — Sun, 22 Aug 2010 08:06:55 +0100

CONCLUSIONS: Hormone sensitivity may be recovered after salvage brachytherapy. Potential mechanisms underlying these observations are discussed and the likely central role of the activity of the androgen receptor highlighted. The relevance of these findings to the management of advanced prostate cancer is considered including thoughts on the practice of intermittent anti-androgen therapy. (Source: International Braz J Urol)

Androgen receptor signaling and mutations in prostate cancer.

Asian Journal of Andrology — Sun, 15 Aug 2010 23:00:00 +0100

Authors: Koochekpour S Normal and neoplastic growth of the prostate gland are dependent on androgen receptor (AR) expression and function. Androgenic activation of the AR, in association with its coregulatory factors, is the classical pathway that leads to transcriptional activity of AR target genes. Alternatively, cytoplasmic signaling crosstalk of AR by growth factors, neurotrophic peptides, cytokines or nonandrogenic hormones may have important roles in prostate carcinogenesis and in metastatic or androgen-independent (AI) progression of the disease. In addition, cross-modulation by various nuclear transcription factors acting through basal transcriptional machinery could positively or negatively affect the AR or AR target genes expression and activity. Androgen ablation leads to an...

Immunohistochemical Expression of Hsp60 Correlates With Tumor Progression and Hormone Resistance in Prostate Cancer

Urology — Wed, 11 Aug 2010 23:00:00 +0100

Conclusions: Hsp60 protein is overexpressed in poorly differentiated prostate cancers. Hsp60 expression is strongly associated with prognostic clinical parameters, such as Gleason score, initial serum PSA levels, and lymph node metastasis and with the onset of hormone-refractory disease and reduced cancer-specific survival. Identification of such markers could be of relevance in the clinical management of prostate cancer. (Source: Urology)

Survivin gene silencing sensitizes prostate cancer cells to selenium growth inhibition

BMC Cancer — Mon, 09 Aug 2010 23:00:00 +0100

Conclusions: Selenium could inhibit the growth of hormone-refractory prostate cancer cells both in vitro and in vivo, but the effects were modest. The growth inhibition was not mediated by downregulating survivin expression. Survivin silencing greatly enhanced the growth inhibitory effects of selenium. (Source: BMC Cancer)

FDA Approval For TroVax® Phase II Study In Prostate Cancer

Health News from Medical News Today — Fri, 06 Aug 2010 15:00:00 +0100

Oxford BioMedica plc announces that it has received approval from the US Food and Drug Administration (FDA) and Recombinant DNA Advisory Committee (RAC) to initiate a clinical Phase II study in the United States to assess the activity of TroVax® (MVA-5T4) in patients with progressive hormone refractory prostate cancer (HRPC). The randomised, open-label Phase II study will enroll 80 patients with metastatic HRPC in five centres across the US and will assess the activity of TroVax® plus chemotherapy drug Docetaxel (Taxotere®), versus Docetaxel alone... (Source: Health News from Medical News Today)

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Fisetin induces autophagic cell death through suppression of mTOR signaling pathway in prostate cancer cells

Carcinogenesis — Wed, 04 Aug 2010 12:50:39 +0100

The mammalian target of rapamycin (mTOR) kinase is an important component of PTEN/PI3K/Akt signaling pathway, which is frequently deregulated in prostate cancer (CaP). Recent studies suggest that targeting PTEN/PI3K/Akt and mTOR signaling pathway could be an effective strategy for the treatment of hormone refractory CaP. Here, we show that the treatment of androgen-independent and PTEN-negative human CaP PC3 cells with fisetin, a dietary flavonoid, resulted in inhibition of mTOR kinase signaling pathway. Treatment of cells with fisetin inhibited mTOR activity and downregulated Raptor, Rictor, PRAS40 and GβL that resulted in loss of mTOR complexes (mTORC)1/2 formation. Fisetin also activated the mTOR repressor TSC2 through inhibition of Akt and activation of AMPK. Fisetin-mediated inhi...

Prostate cancer chemopreventive activity of phenethyl isothiocyanate through epigenetic regulation (Review).

International Journal of Oncology — Sat, 31 Jul 2010 21:06:51 +0100

Authors: Wang LG, Chiao JW Prostate cancer is one of the most commonly diagnosed cancers in men. The number of affected men is expected to rapidly increase as the population of males over the age of 50 grows worldwide. For patients who are not cured by local treatment and experience metastatic disease, neither androgen ablation nor chemotherapy can abrogate progression and death from androgen-independent/hormone-refractory disease. Therefore, finding strategies for the prevention of prostate cancer initiation and disease progression is a medical challenge. Consumption of cruciferous vegetables has been reported to be associated with reduced incidence of prostate cancer cases. The isothiocyanates, including phenethyl isothiocyanate (PEITC), from cruciferous vegetables have been demonstr...

Human Prostatic Acid Phosphatase, an Authentic Tyrosine Phosphatase, Dephosphorylates ErbB-2 and Regulates Prostate Cancer Cell Growth [Signal Transduction]

Journal of Biological Chemistry — Fri, 23 Jul 2010 13:37:12 +0100

In this report, our data show that the phosphorylation level of ErbB-2 primarily at Tyr1221/2 correlates with the growth rate of both LNCaP and MDA PCa2b human PCa cells. Further, cPAcP reciprocally co-immunoprecipitated with ErbB-2 in a non-permissive growth condition. Expression of wild type cPAcP, but not inactive mutant, by cDNA in cPAcP-null LNCaP C-81 cells results in decreased tyrosine phosphorylation of ErbB-2 including Tyr1221/2. Concurrently, Tyr317 phosphorylation of p52Shc, proliferating cell nuclear antigen expression, and cell growth are decreased in these cells. Conversely, decreased cPAcP expression by short hairpin RNA in LNCaP C-33 cells was associated with elevated phosphorylation of ErbB-2 initially at Tyr1221/2. Its downstream p52Shc, ERK1/2, Akt, Src, STAT-3, and STAT...

HIF1alfa isoforms in benign and malignant prostate tissue and their correlation to neuroendocrine differentiation

BMC Cancer — Tue, 20 Jul 2010 23:00:00 +0100

Conclusion: Our results indicate that the cytoplasmic stablization of HIF1alfa in NE-differentiated cells in benign and malignant prostate tissue is due to presence of an HIF1alfa isoform, HIF1alfa1.2. Co-localization of this isoform with HIF1beta indicated that the HIF1alfa1.2 isoform might sequester HIF1beta in the cytoplasm. (Source: BMC Cancer)

Hormone refractory carcinoma prostate with peritoneal metastases and malignant ascites without skeletal involvement: A case report and review of literature

Indian Journal of Urology — Tue, 13 Jul 2010 07:07:18 +0100

We report a case of hormone refractory adenocarcinoma prostate presenting with only peritoneal metastases and massive malignant ascites. Palliation with docetaxel based cytotoxic chemotherapy resulted in clinical improvement of refractory ascites decreasing respiratory embarrassment and thereby improving the quality of life. (Source: Indian Journal of Urology)

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FDA approves chemotherapy agent for advanced prostate Ca

Modern Medicine — Sat, 10 Jul 2010 05:55:39 +0100

FDA has approved cabazitaxel (Jevtana), a chemotherapeutic agent used in combination with prednisone for treatment of advanced, hormone-refractory prostate cancer following docetaxel (Taxotere)-based treatment. (Source: Modern Medicine)

Sodium Selenite Radiosensitizes Hormone-Refractory Prostate Cancer Xenograft Tumors but Not Intestinal Crypt Cells In Vivo

International Journal of Radiation Oncology * Biology * Physics — Wed, 07 Jul 2010 23:00:00 +0100

Conclusions: Sodium selenite significantly enhances the effect of radiation on well-established hormone-independent prostate tumors and does not sensitize the intestinal epithelial cells to radiation. These results suggest that SSE may increase the therapeutic index of XRT for the treatment of prostate cancer. (Source: International Journal of Radiation Oncology * Biology * Physics)

Liposomal imatinib-mitoxantrone combination: Formulation development and therapeutic evaluation in an animal model of prostate cancer

The Prostate — Tue, 06 Jul 2010 23:00:00 +0100

Mitoxantrone plus prednisone is a palliative treatment for hormone-refractory prostate cancer (HRPC) but without survival benefit. Imatinib has shown activity against HRPC but only in the preclinical setting. Our previous in vitro cytotoxicity screening study established that their free combination act additively to inhibit proliferation of PC-3 cells. We aim to develop a liposomal imatinib-mitoxantrone (LIM) formulation with improved in vivo therapeutic activity.Imatinib and mitoxantrone were simultaneously co-loaded into DSPC/Chol liposomes by means of a (NH4)2SO4-generated proton gradient method. The optimized formulation was characterized in terms of mean size diameter, loading parameters and drug retention in human serum. In vivo antitumor activity of developed LIM formulation was eva...

1,4-Phenylenebis(Methylene)Selenocyanate, but Not Selenomethionine, Inhibits Androgen Receptor and Akt Signaling in Human Prostate Cancer Cells.

Cell Research — Mon, 05 Jul 2010 23:00:00 +0100

Authors: Facompre ND, El-Bayoumy K, Sun YW, Pinto JT, Sinha R The lack of treatment for worried-well patients with high-grade prostatic intraepithelial neoplasia combined with issues of recurrence and hormone resistance in prostate cancer survivors remains a major public health obstacle. The long latency of prostate cancer development provides an opportunity to intervene with agents of known mechanisms at various stages of disease progression. A number of signaling cascades have been shown to play important roles in prostate cancer development and progression, including the androgen receptor (AR) and phosphatidylinositol 3-kinase/Akt signaling pathways. Crosstalk between these two pathways is also thought to contribute to progression and hormone-refractory prostate disease. Our initial...

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Recombinant peroxidase production in species of lepidoptera frequently found in argentina.

New Biotechnology — Sun, 04 Jul 2010 23:00:00 +0100

In this study, a screening of different lepidopteran species frequently found in Argentina to produce this protein was carried out. Two recombinant viruses were constructed: AcMNPV HRPC polyhedrin-minus (occ-), an intrahemocelical infective virus; and AcMNPV HRPC polyhedrin-plus (occ+), to achieve an oral infective baculovirus. Each lepidopteran species was infected either with AcMNPV HRPC occ- or AcMNPV HRPC occ+ and the harvesting time post-infection (dpi) were optimized. All species were susceptible to AcMNPV HRPC occ- infection, giving Spodoptera frugiperda the best yield: 41mug per larva. Rachiplusia nu was highly susceptible to oral infection, reaching 22mug per larva at 4 dpi. HRPC was purified by IMAC from S. frugiperda extracts with a yield of 86% and a purification factor of 29. ...

Dendreon Statement On CMS National Coverage Analysis

Health News from Medical News Today — Sat, 03 Jul 2010 08:00:00 +0100

Dendreon Corporation (Nasdaq: DNDN) announced that the Centers for Medicare and Medicaid Services (CMS) initiated a National Coverage Analysis (NCA) of PROVENGE® (sipuleucel-T), an autologous cellular immunotherapy for the treatment of asymptomatic or minimally symptomatic metastatic, castrate-resistant (hormone-refractory) prostate cancer (CRPC). PROVENGE is the first in a new therapeutic class known as autologous cellular immunotherapies. In CMS's announcement of the NCA, CMS is requesting public comments on the effects of PROVENGE on health outcomes in patients with prostate cancer... (Source: Health News from Medical News Today)

Jevtana® (cabazitaxel) Injection Approved By U.S. FDA After Priority Review

Health News from Medical News Today — Thu, 24 Jun 2010 10:00:00 +0100

Sanofi-aventis (EURONEXT: SAN and NYSE: SNY) announced that the U.S. Food and Drug Administration (FDA) has granted marketing authorization for Jevtana® (cabazitaxel) Injection in combination with prednisone for the treatment of patients with metastatic hormone-refractory prostate cancer (mHRPC) previously treated with a docetaxel-containing treatment regimen... (Source: Health News from Medical News Today)

FDA Approves New Treatment For Advanced Prostate Cancer

Health News from Medical News Today — Wed, 23 Jun 2010 09:00:00 +0100

The U.S. Food and Drug Administration approved Jevtana (cabazitaxel), a chemotherapy drug used in combination with the steroid prednisone to treat men with prostate cancer. Jevtana is the first treatment for advanced, hormone-refractory, prostate cancer that has worsened during or after treatment with docetaxel, a commonly used drug for advanced prostate cancer. In prostate cancer, the male sex hormone testosterone can cause prostate tumors to grow. Drugs, surgery, or other hormones are used to reduce testosterone production or to block it... (Source: Health News from Medical News Today)

New Dendreon Competition Is Not Really Competition (DNDN, SNY)

BioHealth Investor — Fri, 18 Jun 2010 18:11:46 +0100

Dendreon Corp. (NASDAQ: DNDN) is holding up rather well considering that competition from its prostate cancer drug market may be higher than before. The FDA has approved a competing product called Jevtana (cabazitaxel) from Sanofi-Aventis (NYSE: SNY). Jevtana is a chemotherapy drug used in combination with the steroid prednisone to treat men with prostate cancer. The release from the FDA noted that Jevtana is the first treatment for advanced, hormone-refractory, prostate cancer that has worsened during or after treatment with docetaxel, a commonly used drug for advanced prostate cancer. The approval came after a priority drug review and before the September 30, 2010 deadline. Jevtana’s safety and effectiveness was established in a 755-patient study and all had previously received doc...

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Cabazitaxel: New Chemo Approved for Advanced Prostate Cancer

Medscape Today Headlines — Fri, 18 Jun 2010 12:55:49 +0100

The new drug is approved for second-line use in advanced hormone-refractory prostate cancer, after progression on docetaxel. Medscape Medical News (Source: Medscape Today Headlines)

FDA Okays First Drug for Hormone-Refractory Prostate Cancer

MedPage Today Public Health — Fri, 18 Jun 2010 03:13:15 +0100

WASHINGTON (MedPage Today) -- The FDA has approved the chemotherapy agent cabazitaxel (Jevtana) to be used in conjunction with the steroid prednisone for treatment of hormone-refractory prostate cancer. (Source: MedPage Today Public Health)

FDA approves cabazitaxel (Jevtana®) for advanced prostate cancer

NeLM - News — Thu, 17 Jun 2010 23:00:00 +0100

Source: FDA, Reuters Health Area: News The US FDA has approved the microtubule inhibitor cabazitaxel (Jevtana®) for use in combination with prednisone for the treatment of men with metastatic hormone-refractory prostate cancer previously treated with a docetaxel-containing treatment regimen. The safety and efficacy of cabazitaxel was established in a trial (n=755) which found that it was associated with a median overall survival of 15.1 months, compared to 12.7 months in men who received mitoxantrone (both were given in combination with prednisone). The FDA conducted a fast-track review of cabazitaxel and the approval has come months ahead of the Agency's deadline. It is currently under review in Europe. A Reuters report notes that this is the first drug...

FDA Approves New Treatment for Advanced Prostate Cancer

Food and Drug Administration — Thu, 17 Jun 2010 18:17:00 +0100

The U.S. Food and Drug Administration today approved Jevtana (cabazitaxel), a chemotherapy drug used in combination with the steroid prednisone to treat men with prostate cancer. Jevtana is the first treatment for advanced, hormone-refractory, prostate cancer that has worsened during or after treatment with docetaxel, a commonly used drug for advanced prostate cancer. (Source: Food and Drug Administration)

Loss of PDEF, a prostate-derived Ets factor is associated with aggressive phenotype of prostate cancer: Regulation of MMP 9 by PDEF

Molecular Cancer — Mon, 14 Jun 2010 23:00:00 +0100

Conclusions: These studies demonstrate for the first time negative regulation of MMP9 expression by PDEF, and that PDEF expression was lost in aggressive prostate cancer and was inversely associated with MMP9 expression in clinical samples of prostate cancer. Based on these exciting results, we propose that loss of PDEF along with increased MMP9 expression should serve as novel markers for early detection of aggressive prostate cancer. (Source: Molecular Cancer)

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Syndax Pharmaceuticals' Entinostat Shows Clinical Promise In Patients With Advanced Hormone Refractory Breast Cancer

Cancercompass News: Breast Cancer — Sat, 12 Jun 2010 00:00:00 +0100

Syndax Pharmaceuticals, Inc., a clinical-stage epigenetics oncology company, reported final results from the Phase 2, open-label ENCORE 303 trial in post-menopausal women with advanced, estrogen receptor (ER) positive breast cancer who were progressing on aromatase inhibitor (AI) therapy. Safety and efficacy results from the trial will be presented in a poster at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago, IL tomorrow, Saturday, June 5, 2010. (Source: Cancercompass News: Breast Cancer)

MiR-148a Attenuates Paclitaxel Resistance of Hormone-refractory, Drug-resistant Prostate Cancer PC3 Cells by Regulating MSK1 Expression [Rna]

Journal of Biological Chemistry — Fri, 11 Jun 2010 13:38:29 +0100

In this report, we showed that miR-148a expression levels were lower in PC3 and DU145 hormone-refractory prostate cancer cells in comparison to PrEC normal human prostate epithelial cells and LNCaP hormone-sensitive prostate cancer cells. Transfection with miR-148a precursor inhibited cell growth, and cell migration and invasion, and increased the sensitivity to anti-cancer drug paclitaxel in PC3 cells. Computer-aided algorithms predicted mitogen- and stress-activated protein kinase, MSK1, as a potential target of miR-148a. Indeed, miR-148a overexpression decreased expression of MSK1. Using luciferase reporter assays, we identified MSK1 as a direct target of miR-148a. Suppression of MSK1 expression by siRNA, however, showed little or no effects on malignant phenotypes of PC3 cells. In PC3P...

The chemopreventive retinoid 4HPR impairs prostate cancer cell migration and invasion by interfering with FAK/AKT/GSK3beta pathway and beta-catenin stability

Molecular Cancer — Wed, 09 Jun 2010 23:00:00 +0100

Conclusion: These data point to 4HPR as a negative regulator of AKT phosphorylation, effectively targeting the beta-catenin pathway and inducing a relatively benign phenotype in prostate cancer cells, limiting neoangiogenesis and cell invasion. (Source: Molecular Cancer)

Periostin is up-regulated in high grade and high stage prostate cancer

BMC Cancer — Tue, 08 Jun 2010 23:00:00 +0100

Background: Expression of periostin is an indicator of epithelial-mesenchymal transition in cancer but a detailed analysis of periostin expression in prostate cancer has not been conducted so far. Methods: Here, we evaluated periostin expression in prostate cancer cells and peritumoural stroma immunohistochemically in two independent prostate cancer cohorts, including a training cohort (n=93) and a test cohort (n=325). Metastatic prostate cancers (n=20), hormone refractory prostate cancers (n=19) and benign prostatic tissues (n=38) were also analyzed. Results: In total, strong epithelial periostin expression was detectable in 142 of 418 (34.0%) of prostate carcinomas and in 11 of 38 benign prostate glands (28.9%). Increased periostin expression in carcinoma cells was significantly associat...

Ductal Variant of Adenocarcinoma Prostate Responding to Docetaxel — a Case Report

Clinical Oncology — Tue, 08 Jun 2010 23:00:00 +0100

Sir — Ductal carcinoma is an unusual variant of adenocarcinoma of the prostate with poorly understood natural history. Equally, treatment is not well defined. Docetaxel and prednisolone is standard first-line treatment in men with hormone refractory metastatic prostate cancer . A search of published studies failed to find any reports of metastatic ductal cancer treated successfully with docetaxel . We therefore report a case of a 62-year-old man with metastatic ductal prostate cancer who responded to this regimen. (Source: Clinical Oncology)

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Conference report: Phase III study of denosumab versus zoledronic acid in bone metastases from hormone-refractory prostate cancer

NeLM - News — Mon, 07 Jun 2010 23:00:00 +0100

Source: BioSpace Area: News BioSpace has reported on results from a Phase III study comparing denosumab and zoledronic acid (Zometa®) in the treatment of patients with hormone-refractory prostate cancer and bone metastases. The international, double-blind study randomised 1,901 patients to treatment with denosumab (120mg subcutaneously every four weeks) or zoledronic acid (4mg IV every four weeks). The primary endpoint was to evaluate if denosumab is non-inferior to zoledronic acid with respect to the first on-study skeletal related event (SRE); superiority of denosumab with respect to this was evaluated as a secondary endpoint. Denosumab was found to be superior to zoledronic acid in delaying the time to first on-study SRE (hazard ratio [HR] 0.82,...

Denosumab Demonstrated Superiority Over Zometa(R) in Delay of Complications Due to Bone Metastases in Advanced Prostate Cancer

Amgen News Service — Fri, 04 Jun 2010 23:00:00 +0100

The Third Of Three Pivotal Head-To-Head Trials Submitted To FDA For Treatment Of Patients With Bone Metastases THOUSAND OAKS, Calif., June 5, 2010 /PRNewswire via COMTEX/ --Amgen (Nasdaq: AMGN) today announced detailed results from a Phase 3, head-to-head trial which compared the efficacy and safety of denosumab versus Zometa(R) (zoledronic acid) in 1,901 patients with hormone-refractory prostate cancer and bone metastases. The study met its primary and secondary endpoints and demonstrated denosumab’s superiority over Zometa in delaying or preventing skeletal related events (SREs). These statistically significant results will be presented in an oral session on June 6, 2010 at the American Society of Clinical Oncology (ASCO) 2010 Annual Meeting in Chicago (Late Breaking Abstract Number #L...

Sorafenib induces apoptosis and autophagy in prostate cancer cells in vitro.

International Journal of Oncology — Fri, 04 Jun 2010 19:58:12 +0100

Authors: UllÃ©n A, Farnebo M, Thyrell L, Mahmoudi S, Kharaziha P, Lennartsson L, GrandÃ©r D, Panaretakis T, Nilsson S The multiple tyrosine kinase inhibitor sorafenib has recently demonstrated clinical effects in patients with androgen-independent prostate cancer. These observations provided the rational for investigating the anti-tumoral properties of this compound on prostate cancer cell lines at the molecular level. Two hormone refractory (PC3 and DU145) and one hormone responsive cell line (22Rv1) were used. By use of a panel of cell biology techniques such as immunoblotting, flow cytometry and immunocytochemistry, effects on the MAPK pathway and induction of apoptosis and autophagy were evaluated. We demonstrate that sorafenib reduced cell viability in a dose-dependent manner,...

Sipuleucel-T Demonstrates Well-Tolerated Safety Profile Across Randomized, Placebo-Controlled Trials

Health News from Medical News Today — Tue, 01 Jun 2010 11:00:00 +0100

Sipuleucel-T (Provenge), an immunotherapy for men with asymptomatic or minimally symptomatic metastatic, castrate resistant (hormone refractory) prostate cancer, showed a favorable safety profile for androgen dependent prostate cancer (ADPC) and metastatic castrate-resistant prostate cancer (mCRPC), according to new data being presented at the 105th Annual Scientific Meeting of the American Urological Association (AUA). These safety data from integrated analyses was presented to the media during a special press conference on Monday, May 31, 2010... (Source: Health News from Medical News Today)

MiR-34a attenuates paclitaxel-resistance of hormone-refractory prostate cancer PC3 cells through direct and indirect mechanisms

The Prostate — Mon, 31 May 2010 23:00:00 +0100

Patients with hormone-refractory prostate cancer are treated with taxane drugs, but eventually become drug resistant. We aimed to elucidate the molecular mechanisms underlying paclitaxel resistance of hormone-refractory prostate cancer with a special focus on the roles of miR-34a and SIRT1.Paclitaxel-resistant cells (PC3PR) were generated from hormone-refractory PC3 cells. The expression levels of mRNA and miRNA were determined by reverse transcriptase PCR and those of protein were by Western blot analysis. Transfection of miRNA precursor or siRNA was performed using the liposome-mediated method.MiR-34a over-expression and SIRT1 knockdown attenuated paclitaxel resistance of PC3PR cells. MiR-34a expression was reduced in PC3PR cells compared with PC3 cells, while the expression levels of Hu...

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HOXB13 promotes androgen independent growth of LNCaP prostate cancer cells by the activation of E2F signaling

Molecular Cancer — Wed, 26 May 2010 23:00:00 +0100

Conclusions: Taken together, the results of this study demonstrated the presence of a novel pathway that helps understand androgen-independent survival of prostate cancer cells. These findings suggest that upregulation of HOXB13 is associated with an additive growth advantage of prostate cancer cells in the absence of or low androgen concentrations, by the regulation of p21-mediated E2F signaling. (Source: Molecular Cancer)

The disintegrin contortrostatin in combination with docetaxel is a potent inhibitor of prostate cancer in vitro and in vivo

The Prostate — Wed, 26 May 2010 23:00:00 +0100

There are few available treatments for hormone refractory prostate cancer. Through the inhibition of integrins, contortrostatin (CN) effects tumor cell growth directly as well as through the inhibition of angiogenesis. The effect of CN in combination with docetaxel on prostate cancer cell lines in vitro and in vivo is evaluated in the present study.FACS analysis of integrin expression, assessment of CN and docetaxel exposure on viability of plated cancer cells, and scratch test migration analysis were performed on PC-3 prostate cancer cells. CN and docetaxel inhibition of both PC-3 and CWR-22 prostate cancer cell lines were evaluated in a mouse xenograft bone model. Angiogenic activity in tumors were assessed using IHC with antibodies to CD31.Cell culture experiments indicate that the comb...

Role of Androgen Receptor in Prostate Cancer Cell Cycle Regulation: Interaction with Cell Cycle Regulatory Proteins and Enzymes of DNA Synthesis.

Current Protein and Peptide Science — Sun, 23 May 2010 23:00:00 +0100

Authors: Sivanandam A, Murthy S, Kim SH, Barrack ER, Veer Reddy GP The androgen receptor (AR) plays a critical role in proliferation and viability of prostate cancer cells. Therefore, suppressing AR activity by androgen deprivation or anti-androgen treatment has been the frontline therapy for over six decades. However, these treatment strategies are not curative and patients succumb to castration-resistant disease. Although AR is evidently critical for proliferation of prostate cancer cells, very little is known about its mechanism of action in this process. Over the years, the role of AR in prostate cancer cell proliferation and viability has been studied by focusing primarily on its role as a transcription factor. However, recent observations indicate that besides its role as a trans...

Synthesis and initial tumor affinity testing of iodine-123 labelled EGFR-affine agents as potential imaging probes for hormone-refractory prostate cancer.

European Journal of Medicinal Chemistry — Sat, 22 May 2010 23:00:00 +0100

CONCLUSION: These data suggest that (123)I-mAb425 and (123)I-PD153035 are promising candidates as imaging probes for EGFR-positive prostate cancer and warrant further in vivo validations to ascertain their potential as imaging agents for clinical used. PMID: 20538380 [PubMed - as supplied by publisher] (Source: European Journal of Medicinal Chemistry)

Advanced Prostate Cancer Patients Finally Have Another Option

Health News from Medical News Today — Sat, 22 May 2010 09:00:00 +0100

Today is an exciting day for men with advanced prostate cancer and the millions of families and loved ones who are profoundly affected. Today a new prostate cancer treatment option, Provenge, was approved by the Food and Drug Administration (FDA). Men's Health Network (MHN) is excited to see this innovative treatment option made available for patients with asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone refractory) prostate cancer. Provenge harnesses the individual's own immune system to fight cancer through a process called active cellular immunotherapy... (Source: Health News from Medical News Today)

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Tumor cytoreduction results in better response to androgen ablation-a preliminary report of palliative transurethral resection of the prostate in metastatic hormone sensitive prostate cancer.

Urologic Oncology — Tue, 04 May 2010 23:00:00 +0100

CONCLUSIONS: TURP resulted in a better and more prolonged response to hormone therapy in mHSPC, with a trend towards positive influence in disease specific survival and overall survival. To date, our preliminary report is the first study regarding long-term survival of cytoreductive surgery in mHSPC, and further investigations are warranted. PMID: 20451424 [PubMed - as supplied by publisher] (Source: Urologic Oncology)

FDA Approves PROVENGE(R) For The Treatment Of Men With Advanced Prostate Cancer

Health News from Medical News Today — Sat, 01 May 2010 08:00:00 +0100

Dendreon Corporation (Nasdaq: DNDN) announced that the U.S. Food and Drug Administration (FDA) has approved PROVENGE® (sipuleucel-T), an autologous cellular immunotherapy for the treatment of asymptomatic or minimally symptomatic metastatic, castrate-resistant (hormone-refractory) prostate cancer (CRPC). PROVENGE is designed to induce an immune response against prostatic acid phosphatase (PAP), an antigen expressed in most prostate cancers, and is the first in a new therapeutic class known as autologous cellular immunotherapies... (Source: Health News from Medical News Today)

Horizon scanning: FDA approves prostate cancer immunotherapy - sipuleucel-T (Provenge®) in the United States

NeLM - News — Thu, 29 Apr 2010 23:00:00 +0100

Source: PharmaTimes Area: News PharmaTimes reports that the United States Food and Drug Administration (FDA) has approved the prostate cancer "vaccine" sipuleucel-T (Provenge®) for use in men with advanced prostate cancer. Unlike traditional vaccines, which are used to prevent disease, Provenge will be used to treat it. The company's website states that the FDA has approved the agent for "the treatment of asymptomatic or minimally symptomatic metastatic, castrate-resistant (hormone-refractory) prostate cancer (CRPC). The approval is based on a study, involving 512 patients, which found an increase in overall survival of 4.1 months for patients receiving Provenge (25.8 months) compared to 21.7 months for those who did not receive the treatment. No further study data are provided in the Ph...

FDA Approves PROVENGE For The Treatment Of Men With Advanced Prostate Cancer

Pharmaceutical Online News — Thu, 29 Apr 2010 10:21:00 +0100

Dendreon Corporation (Nasdaq: DNDN) today announced that the U.S. Food and Drug Administration (FDA) has approved PROVENGE® (sipuleucel-T), an autologous cellular immunotherapy for the treatment of asymptomatic or minimally symptomatic metastatic, castrate-resistant (hormone-refractory) prostate cancer (CRPC). (Source: Pharmaceutical Online News)

Safety and efficacy of docetaxel, estramustine phosphate and hydrocortisone in hormone-refractory prostate cancer patients

International Journal of Urology — Mon, 26 Apr 2010 23:00:00 +0100

Conclusions: Combination chemotherapy with DTX, EMP and hydrocortisone provides survival benefits for patients with HRPC with an acceptable toxicity profile. We need to further evaluate who might benefit most from this regimen. (Source: International Journal of Urology)

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[Comment] Revisiting the ultimate target of treatment for prostate cancer

LANCET — Thu, 22 Apr 2010 23:00:00 +0100

Targeted treatment has become the mantra of medical oncologists. With some exceptions (MS4A1 [CD20] in non-Hodgkin lymphoma, ERBB2 [HER2] in breast cancer, and the fusion protein BCR-ABL in chronic myeloid leukaemia), a drug's mechanism of action or its appropriate target in a tumour can be uncertain. One of the original targeted treatments was for prostate cancer. For almost 70 years, men with this metastatic disease have been treated with medical or surgical procedures targeted against testosterone. Initially, patients who progressed after testosterone-lowering treatment were believed to be hormone-refractory and, therefore, unlikely to respond to additional hormonal strategies. However, clinical evidence indicated that some individuals who were hormone-refractory could still respond to ...

KLK5 gene expression is severely upregulated in androgen-independent prostate cancer cells after treatment with the chemotherapeutic agents docetaxel and mitoxantrone

Biological Chemistry — Fri, 16 Apr 2010 15:21:29 +0100

Biological Chemistry 391 (4): 467-474 Abstract Kallikrein-related peptidases (KLKs), including KLK5, have been proposed as promising biomarkers for prostate cancer diagnosis and prognosis. In the present study, we report that distinct augmentations (up to 6.4-fold) of KLK5 mRNA expressional levels, calculated via quantitative real-time PCR, occur after treatment of DU145 cells with appropriate concentrations, determined by the MTT method, of docetaxel and mitoxantrone. Our data reveal the endogenous need of prostate cancer cells for modified KLK5 expression to cope with the administration of chemotherapeutic drugs. Furthermore, it is proposed that the expression profile of KLK5 could serve as a putative biomarker for monitoring the treatment response in hormone refractory prostate cancer p...

Health-related quality of life in pain-free or mildly symptomatic patients with metastatic hormone-resistant prostate cancer following treatment with the specific endothelin A receptor antagonist zibotentan (ZD4054)

Journal of Cancer Research and Clinical Oncology — Tue, 13 Apr 2010 18:15:01 +0100

Conclusions High-baseline HRQoL scores were maintained throughout treatment with zibotentan. The FACT-P instrument was selected to further assess the impact of zibotentan on HRQoL in the Phase III clinical trial program. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00432-010-0864-1Authors Nancy Dawson, Georgetown University Lombardi Comprehensive Cancer Center Washington DC USAHeather Payne, University College Hospital London UKClare Battersby, AstraZeneca Pharmaceuticals Alderley Park Macclesfield, Cheshire SK10 4TF UKMaria Taboada, AstraZeneca Pharmaceuticals Alderley Park Macclesfield, Cheshire SK10 4TF UKNick James, University of Birmingham School of Cancer Sciences Birmingham UK Journal Journal of Cancer Research and Clinical OncologyOn...

CytRx To Initiate A Phase 2 Clinical Trial With Bafetinib In Advanced Prostate Cancer

Health News from Medical News Today — Fri, 09 Apr 2010 08:00:00 +0100

CytRx Corporation (NASDAQ:CYTR), a biopharmaceutical company specializing in oncology, today announced plans to initiate a Phase 2 proof-of-concept clinical trial in the second half of 2010 to evaluate the effectiveness and safety of its oncology drug candidate bafetinib (formerly known as INNO-406) in patients with an advanced form of prostate cancer known as metastatic hormone-refractory prostate cancer. CytRx Chief Medical Officer Daniel Levitt, MD, Ph.D., stated, "We see an opportunity for bafetinib in the treatment of this advanced-stage cancer due to its ability to inhibit Lyn kinase... (Source: Health News from Medical News Today)

Schedule treatment design and quantitative in vitro evaluation of chemotherapeutic combinations for metastatic prostate cancer therapy

Cancer Chemotherapy and Pharmacology — Thu, 08 Apr 2010 17:59:38 +0100

Conclusions Ciprofloxacin and imatinib significantly improve growth inhibition activity of standard antineoplastic drugs in a schedule-dependent manner and, therefore, may have an important role as adjuvant therapeutic agents in a clinical setting. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00280-010-1315-zAuthors Ana Catarina Pinto, University of Coimbra Laboratory of Pharmaceutical Technology, Faculty of Pharmacy Coimbra PortugalSusana Ângelo, University of Coimbra Department of Biochemistry, Faculty of Science and Technology Coimbra PortugalJoão Nuno Moreira, University of Coimbra Laboratory of Pharmaceutical Technology, Faculty of Pharmacy Coimbra PortugalSérgio Simões, University of Coimbra Laboratory of Pharmaceutical Technology, Facu...

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In vivo Evidence of Î³-Tocotrienol as a Chemosensitizer in the Treatment of Hormone-Refractory Prostate Cancer

Pharmacology — Tue, 06 Apr 2010 23:00:00 +0100

Pharmacology 2010;85:248â258 (DOI:10.1159/000278205) (Source: Pharmacology)

Ozarelix, a fourth generation GnRH antagonist, induces apoptosis in hormone refractory androgen receptor negative prostate cancer cells modulating expression and activity of death receptors

The Prostate — Sun, 04 Apr 2010 23:00:00 +0100

This study explored the in vitro effects on DU145 and PC3 cell lines, two models of androgen-independent prostate cancer, of a fourth generation GnRH antagonist (Ozarelix).Ozarelix was added to cultures and toxicity, cell cycle modifications, cell viability and caspase activity were investigated.Ozarelix showed antiproliferative effects and produced an accumulation of cells in G2/M cell cycle phase. Apoptosis was related with caspase-8-dependent caspase 3 activation with down-regulation of c-FLIP (L) and a sensitization to TRAIL-induced apoptosis linked also to increased expression and activity of death receptors DR4/5 and Fas.TRAIL-resistant cancer cells can be sensitized to TRAIL by Ozarelix. This effect may be achieved by the activation of apoptotic pathway improving the therapeutic eff...

904 initial results from phase i/ii trial with dendritic cells loaded with an allogeneic prostate cancer-lysate in hormone-refractory prostate cancer patients

European Urology Supplements — Mon, 29 Mar 2010 15:06:23 +0100

(Source: European Urology Supplements)

898 docetaxel: rechallenge at psa relapse after docetaxel chemotherapy at hormone refractory prostate cancer

European Urology Supplements — Mon, 29 Mar 2010 15:06:19 +0100

(Source: European Urology Supplements)