MedWorm: Hormone Refractory Prostate Cancer

Flavokawain B, a kava chalcone, induces apoptosis via up-regulation of death-receptor 5 and Bim expression in androgen receptor negative, hormonal refractory prostate cancer cell lines and reduces tumor growth

International Journal of Cancer — Tue, 16 Mar 2010 00:00:00 +0100

Limited success has been achieved in extending the survival of patients with metastatic and hormone-refractory prostate cancer (HRPC). There is a strong need for novel agents in the treatment and prevention of HRPC. We have shown that flavokawain B (FKB), a kava chalcone, is about 4- to 12-fold more effective in reducing the cell viabilities of androgen receptor (AR)-negative, HRPC cell lines DU145 and PC-3 than AR-positive, hormone-sensitive prostate cancer cell lines LAPC4 and LNCaP, with minimal effect on normal prostatic epithelial and stromal cells. FKB induces apoptosis with an associated increased expression of proapoptotic proteins: death receptor-5, Bim and Puma and a decreased expression of inhibitors of apoptosis protein: XIAP and survivin. Among them, Bim expression was signifi...

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Investigational drug may boost survival for certain prostate cancer patients

Modern Medicine — Mon, 15 Mar 2010 00:00:00 +0100

Cabazitaxel, an investigational compound under development by Sanofi-aventis, plus prednisone/prednisolone, is associated with overall survival and progression-free survival in patients with metastatic (advanced) hormone-refractory prostate cancer whose disease advanced after treatment with docetaxel-based chemotherapy. (Source: Modern Medicine)

Investigational drug may boost survival for certain prostate cancer patients

Drug Topics - Pharmacy News — Mon, 15 Mar 2010 00:00:00 +0100

Investigational drug may boost survival for certain prostate cancer patients

Drug Topics - Clinical News — Mon, 15 Mar 2010 00:00:00 +0100

Investigational drug may boost survival for certain prostate cancer patients

Drug Topics - Top News — Mon, 15 Mar 2010 00:00:00 +0100

Genentech Provides Update On Phase III Study Of Avastin In Men With Late Stage Prostate Cancer

Health News from Medical News Today — Sun, 14 Mar 2010 07:00:00 +0100

Genentech, Inc., a wholly owned member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today the topline results of a Phase III trial led by the U.S. Cancer and Leukemia Group B (CALGB) and sponsored by the National Cancer Institute (NCI) investigating the use of Avastin® (bevacizumab) in combination with docetaxel chemotherapy and prednisone in men with late stage prostate cancer (hormone-refractory / HRPC). The study, known as CALGB 90401, did not meet its primary objective of extending overall survival compared to chemotherapy and prednisone alone... (Source: Health News from Medical News Today)

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Roche provides update on phase III study of Avastin in men with late stage prostate cancer

Roche Media News — Fri, 12 Mar 2010 06:00:00 +0100

Roche announced today the topline results of a phase III trial led by the US Cancer and Leukemia Group B (CALGB) and sponsored by the National Cancer Institute investigating the use of Avastin (bevacizumab) in combination with docetaxel chemotherapy and prednisone in men with late stage prostate cancer (hormone-refractory / HRPC). The study, known as CALGB 90401, did not meet its primary objective of extending overall survival compared to chemotherapy and prednisone alone. A preliminary assessment of safety performed by CALGB has shown adverse events that have been previously observed in pivotal trials with Avastin. (Source: Roche Media News)

Roche provides update on phase III study of Avastin in men with late stage prostate cancer

Roche Investor Update — Fri, 12 Mar 2010 06:00:00 +0100

CCR9 mediates PI3K/AKT-dependent antiapoptotic signals in prostate cancer cells and inhibition of CCR9-CCL25 interaction enhances the cytotoxic effects of etoposide

International Journal of Cancer — Fri, 12 Mar 2010 00:00:00 +0100

In this study, we show that CC chemokine receptor-9 (CCR9) and its natural ligand CCL25 interaction upregulates antiapoptotic proteins (i.e., PI3K, AKT, ERK1/2 and GSK-3[beta]) and downregulate activation of caspase-3 in PCa cells. Significant downregulation of these CCR9-mediated antiapoptotic proteins in the presence of a PI3K inhibitor (wortmannin), further suggests that the antiapoptotic action of CCR9 is primarily regulated through PI3K. Furthermore, the cytotoxic effect of etoposide was significantly inhibited in the presence of CCL25, and this inhibitory effect of CCL25 was abrogated when CCR9-CCL25 interaction was blocked using anti-CCR9 monoclonal antibodies. In conformation to these in vitro studies, significant reduction in tumor burden was found in mice receiving CCL25 neutrali...

Identifying Patient-Relevant Outcomes In Metastatic Prostate Cancer

Health News from Medical News Today — Thu, 11 Mar 2010 12:00:00 +0100

The objective of this study was to develop a framework of patient-relevant outcome issues in men being treated for metastatic, hormone-refractory prostate cancer in order to enhance and support the clarity of measurement in this population... (Source: Health News from Medical News Today)

Combination chemotherapy with weekly paclitaxel or docetaxel, carboplatin, and estramustine for hormone-refractory prostate cancer

Journal of Infection and Chemotherapy — Thu, 11 Mar 2010 02:42:08 +0100

In conclusion, weekly DTX-based chemotherapy was no less effective and less toxic than triweekly DTX-based chemotherapy for HRPC patients and therefore can be useful as the first-line chemotherapy regimen for HRPC patients, especially the elderly or those with a poor performance status. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10156-010-0047-7Authors Tomihiko Yasufuku, Kobe University Graduate School of Medicine Division of Urology, Department of Surgery 7-5-1 Kusunoki-cho, Chuo-ku Kobe 650-0017 JapanKatsumi Shigemura, Kobe University Graduate School of Medicine Division of Urology, Department of Surgery 7-5-1 Kusunoki-cho, Chuo-ku Kobe 650-0017 JapanOsamu Matsumoto, Miki City Hospital Department of Urology Miki JapanSoichi Arakawa, Kobe University Gradua...

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Constructing a Conceptual Framework of Patient-Reported Outcomes for Metastatic Hormone-Refractory Prostate Cancer

Value in Health — Thu, 11 Mar 2010 00:00:00 +0100

Conclusion: Findings were used to propose a conceptual framework of PROs for metastatic HRPC. Such frameworks can be used to help specify targets for assessment in clinical studies such as treatment trials. (Source: Value in Health)

Association of circulating tumor cells with tumor-related methylated DNA in patients with hormone-refractory prostate cancer

International Journal of Urology — Thu, 11 Mar 2010 00:00:00 +0100

Conclusions: Hormone refractory prostate cancer patients with circulating tumor cells and/or tumor-related methylated DNA show a significantly poorer outcome than those without these blood markers. (Source: International Journal of Urology)

Poniard Pharmaceuticals Presents Positive Survival Data From A Phase 2 Clinical Study Of Picoplatin In Metastatic Prostate Cancer

Health News from Medical News Today — Sat, 06 Mar 2010 09:00:00 +0100

Poniard Pharmaceuticals, Inc. (Nasdaq: PARD), a biopharmaceutical company focused on innovative oncology therapies, announced the presentation of positive final data, including survival data, from the Company's Phase 2 clinical trial of picoplatin as a first-line therapy in men with metastatic castration-resistant (hormone-refractory) prostate cancer (CRPC). The results were presented in a General Poster Session at the 2010 American Society of Clinical Oncology's Genitourinary Cancers Symposium in San Francisco, CA... (Source: Health News from Medical News Today)

Poniard Pharmaceuticals Presents Positive Survival Data From A Phase 2 Clinical Study Of Picoplatin In Metastatic Prostate Cancer

Pharma Industry News From Medical News Today — Sat, 06 Mar 2010 09:00:00 +0100

Poniard Pharmaceuticals, Inc. (Nasdaq: PARD), a biopharmaceutical company focused on innovative oncology therapies, announced the presentation of positive final data, including survival data, from the Company's Phase 2 clinical trial of picoplatin as a first-line therapy in men with metastatic castration-resistant (hormone-refractory) prostate cancer (CRPC)... (Source: Pharma Industry News From Medical News Today)

Horizon Scanning: Cabazitaxel found to improve survival in prostate cancer patients in Phase III study

NeLM - News — Fri, 05 Mar 2010 00:00:00 +0100

Source: PharmaTimes Area: News According to PharmaTimes, Phase III data relating to cabazitaxel have been presented by the company developing it (Sanofi-Aventis). The drug is under development for prostate cancer and the study found cabazitaxel improved overall and progression-free survival in patients with metastatic hormone-refractory prostate cancer whose disease progressed following chemotherapy with docetaxel. The study, (called TROPIC study), involved 755 men with advanced prostate cancer who received either a combination of cabazitaxel and prednisone or mitoxantrone and prednisone. The results found an overall median survival of 15.1 months in the cabazitaxel arm compared to 12.7 months in the mitoxantrone arm. Patients in the cabazitaxel arm also experienced an increase...

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Dendreon Presents Updated IMPACT Results Confirming PROVENGE Improves Overall Survival In Patients With Metastatic Castrate-Resistant Prostate Cancer

Pharma Industry News From Medical News Today — Thu, 04 Mar 2010 13:00:00 +0100

Dendreon Presents Updated IMPACT Results Confirming PROVENGE Improves Overall Survival In Patients With Metastatic Castrate-Resistant Prostate Cancer

Health News from Medical News Today — Thu, 04 Mar 2010 13:00:00 +0100

Dendreon Corporation (Nasdaq: DNDN) announced updated results from its pivotal Phase 3 IMPACT (IMmunotherapy for Prostate AdenoCarcinoma Treatment) study demonstrating that PROVENGE® (sipuleucel-T) extends overall survival in men with metastatic, castrate-resistant (hormone-refractory) prostate cancer (CRPC). The data will be presented at the American Society of Clinical Oncology 2010 Genitourinary Cancers Symposium (ASCO-GU) in San Francisco on Friday, March 5 at 1:45 pm PT. A sensitivity analysis performed with longer-term follow-up (36... (Source: Health News from Medical News Today)

Cabazitaxel Increased Survival for Patients with Advanced Hormone-Refractory Prostate Cancer

Drugs.com - Clinical Trials — Thu, 04 Mar 2010 12:54:30 +0100

- Results observed in patients treated with cabazitaxel plus prednisone whose disease progressed despite prior docetaxel-based chemotherapy - - Data from large international Phase 3 study to be presented at the 2010 Genitourinary Cancers Symposium... (Source: Drugs.com - Clinical Trials)

Cabazitaxel Increased Survival For Patients With Advanced Hormone-Refractory Prostate Cancer

Health News from Medical News Today — Thu, 04 Mar 2010 12:00:00 +0100

Sanofi-aventis (EURONEXT: SAN and NYSE: SNY) announced results from a Phase 3 trial which demonstrated cabazitaxel, an investigational compound, plus prednisone/prednisolone significantly improved overall survival and progression-free survival in patients with metastatic (advanced) hormone-refractory prostate cancer whose disease progressed following treatment with docetaxel-based chemotherapy. The TROPIC trial compared the combination of cabazitaxel plus prednisone/prednisolone to the active agent mitoxantrone plus prednisone/prednisolone... (Source: Health News from Medical News Today)

Cabazitaxel Increased Survival For Patients With Advanced Hormone-Refractory Prostate Cancer

Pharma Industry News From Medical News Today — Thu, 04 Mar 2010 12:00:00 +0100

Sanofi-aventis (EURONEXT: SAN and NYSE: SNY) announced results from a Phase 3 trial which demonstrated cabazitaxel, an investigational compound, plus prednisone/prednisolone significantly improved overall survival and progression-free survival in patients with metastatic (advanced) hormone-refractory prostate cancer whose disease progressed following treatment with docetaxel-based chemotherapy... (Source: Pharma Industry News From Medical News Today)

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Ursolic acid induces PC-3 cell apoptosis via activation of JNK and inhibition of Akt pathways in vitro

Molecular Carcinogenesis — Tue, 09 Feb 2010 00:00:00 +0100

Ursolic acid (UA), a pentacyclic triterpenoid compound, has been demonstrated to have an antiproliferative effect in various tumors. We investigated the cell killing effects of UA in the human hormone refractory prostate cancer cell line, PC-3 cells. Also, the molecular mechanisms underlying its antigrowth effect were explored. We found that UA treatment in vitro can effectively inhibit PC-3 cell viability in a dose-dependent manner by inducing apoptosis, demonstrated by annexin V-FITC/propidium iodide staining. Both extrinsic and intrinsic apoptotic pathways appear to be triggered by UA treatment, because inhibiting activation of both caspase-8 and -9 could prevent UA-induced apoptosis in PC-3 cells. The c-Jun N-terminal kinase (JNK) was found to be activated, followed by Bcl-2 phosphoryl...

EMEA Gives Official Scientific Advice On Clinical Phase IIb Efficacy Study Of Inecalcitol In Hormone-refractory Prostate Cancer

Health News from Medical News Today — Thu, 04 Feb 2010 09:00:00 +0100

Hybrigenics, a bio-pharmaceutical company with a focus on research and development of new cancer treatments and specialized in protein interactions, announced that it has received the official scientific advice from the European Medicines Agency (EMEA) on Hybrigenics' clinical development plan for inecalcitol in hormone-refractory prostate cancer patients... (Source: Health News from Medical News Today)

EMEA Gives Official Scientific Advice On Clinical Phase IIb Efficacy Study Of Inecalcitol In Hormone-refractory Prostate Cancer

Prostate News From Medical News Today — Thu, 04 Feb 2010 09:00:00 +0100

Far-infrared rays control prostate cancer cells in vitro and in vivo

Central European Journal of Biology — Mon, 01 Feb 2010 06:47:50 +0100

Abstract We introduce a new effective method to control hormone-refractory prostate cancer cells using an activated rubber/resin form (RB), far-infrared ray (FIR) emitter, with or without sodium butyrate treatment (NaB). The growth of three human prostate cancer cell lines (Du145, PC-3 and LNCaP) was suppressed in vitro and vivo by FIR, and the cells were eradicated with FIR + 3 mM NaB. G1 arrest and apoptotic pathway proteins were induced by FIR with elevated expressions of apoptosis-related transcripts in cDNA microarray. RB reflects and radiates in the wavelengths of about 4 to 25 µm in the FIR that work to suppress the growth of human prostate cancer cells. Accordingly, this technique may be used as a new therapeutic treatment in hormone-refractory prostate cancer. ...

Rapamycin enhances the susceptibility of both androgen-dependent and -independent prostate carcinoma cells to docetaxel.

Chinese Medical Journal — Mon, 01 Feb 2010 00:00:00 +0100

CONCLUSIONS: RPM could significantly increase the susceptibility of both androgen-dependent and -independent PC cells to DOC; the synergy of RPM and DOC was demonstrated. RPM enhanced the DOC-induced upregulation of caspase activity, resulting in an increasing number of cells in sub-G1 phases. The synergy of the combined treatment might be observed in both androgen-dependent and -independent PC cell lines. PMID: 20193259 [PubMed - in process] (Source: Chinese Medical Journal)

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Targeted therapeutic approaches for hormone-refractory prostate cancer

Cancer Treatment Reviews — Wed, 27 Jan 2010 00:00:00 +0100

Summary: Prostate cancer is one of the leading causes of cancer related death in men, and remains incurable in the metastatic setting. Despite the initial response to androgen deprivation, the disease gradually progresses to a hormone-refractory state due to cumulative genetic alterations in tumour cells or the microenvironment. Docetaxel represents the first chemotherapeutic agent with a small survival benefit for metastatic hormone-refractory prostate cancer (HRPC). In an attempt to improve survival benefit, several novel drugs targeting specific pathways involved in cell signaling, proliferation, angiogenesis, apoptosis and immune modulation are currently under investigation either as single agents or in combination with cytotoxic drugs. Clinical trials evaluate the inhibition of prosta...

Possible benefits of curcumin regimen in combination with taxane chemotherapy for hormone-refractory prostate cancer treatment.

Nutrition and Cancer — Tue, 26 Jan 2010 12:54:04 +0100

Authors: Cabrespine-Faugeras A, Bayet-Robert M, Bay JO, Chollet P, Barthomeuf C Complementary and alternative therapies for neoplastic diseases treatment and prevention receive increasing attention from the medical community. Prostate cancer (PC) is the most frequently diagnosed malignancy and the second major cause of male death in industrialized countries. The chemopreventive properties and clinical safety of curcumin, a polyphenolic derivative, have already been established. However, curcumin regimen value in addition to conventional hormone refractory (HR) PC treatment remains largely unknown. This review article summarizes mechanisms by which curcumin may decrease HRPC aggressive proliferation and potentiate activity of taxane therapy. Our analysis suggests that curcumin alone has...

Evaluation of the safety, pharmacokinetics and treatment effects of an ανβ3 integrin inhibitor on bone turnover and disease activity in men with hormone-refractory prostate cancer and bone metastases

Asia-Pacific Journal of Clinical Oncology — Tue, 26 Jan 2010 00:00:00 +0100

Conclusion: MK-0429 was generally well tolerated, with the most common side-effect being nausea. There was some evidence of an early reduction of bone turnover, indicating a potential for clinical use in the treatment of MBD although serum PSA was unexpectedly increased during the study. (Source: Asia-Pacific Journal of Clinical Oncology)

Possible Benefits of Curcumin Regimen in Combination With Taxane Chemotherapy for Hormone-Refractory Prostate Cancer Treatment

Nutrition and Cancer — Sat, 23 Jan 2010 13:46:47 +0100

(Source: Nutrition and Cancer)

A phase II study of fenretinide in patients with hormone refractory prostate cancer: a trial of the Cancer Therapeutics Research Group

Cancer Chemotherapy and Pharmacology — Fri, 15 Jan 2010 17:58:52 +0100

Conclusion High-dose fenretinide had limited anti-tumour activity in patients with advanced hormone refractory prostate cancer: further evaluation in this setting is not warranted. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00280-009-1228-xAuthors M. M. Moore, Sydney Cancer Centre Hospital Rd Concord NSW 2139 AustraliaM. Stockler, University of Sydney Sydney Cancer Centre and NHMRC Clinical Trials Centre Missenden Rd Camperdown NSW 2050 AustraliaR. Lim, National University Hospital Department of Hematology-Oncology 5 Lower Kent Ridge Road Singapore 119074 Republic of SingaporeT. S. K. Mok, Prince of Wales Hospital Department of Clinical Oncology, Chinese University of Hong Kong Shatin Hong KongM. Millward, Sir Charles Gairdner Hospital Hospital A...

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Malignant pericardial tamponade in a patient with hormone-refractory prostate cancer

International Journal of Clinical Oncology — Tue, 12 Jan 2010 06:44:52 +0100

Abstract An 82-year-old man who was receiving treatment for prostate cancer and cholangiocellular carcinoma was admitted to our hospital because of chest discomfort and dyspnea. At the time of admission, 16 months after the start of hormone therapy, the prostate-specific antigen level was 454.08 ng/ml. Chest radiography revealed cardiomegaly, and ultrasonography demonstrated significant pericardial effusion. Pericardiocentesis yielded a hemorrhagic exudate, and a routine cytological study revealed malignant cells. It was difficult to determine whether these cells had originated from the prostate cancer or the cholangiocellular carcinoma. However, immunohistochemical analysis of a cell-block section of the pericardial effusion allowed a diagnosis of pericardial met...

Polyamine reduced diet (PRD) nutrition therapy in hormone refractory prostate cancer patients.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie — Sat, 09 Jan 2010 00:00:00 +0100

CONCLUSIONS: Polyamine-reduced diet is well observed and tolerated. It seems to improve and/or maintain quality of life for HRPC patients. Early PRD initiation in HRPC is promising and may impact favorably cancer specific survival. These results open a rationale for PRD in HRPC management and warrant further investigation. PMID: 20106631 [PubMed - as supplied by publisher] (Source: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie)

Molecular characterization of the G[gamma]-globin-Tag transgenic mouse model of hormone refractory prostate cancer: Comparison to human prostate cancer

The Prostate — Fri, 08 Jan 2010 00:00:00 +0100

Prostate cancer (PrCa) has a high incidence in Western countries and at present, there is no cure for hormone refractory prostate cancer. Transgenic mouse models have proven useful for understanding mechanisms of prostate carcinogenesis. The characterization of genetically modified mouse PrCa models using high-throughput genomic analyses provides important information to guide appropriate experiment applications for such model.We have analyzed the transcriptome of the hormone refractory and highly metastatic Fetal Globin-SV40/T-antigen (G[gamma]-globin-Tag) transgenic mouse model for PrCa compared to normal mouse prostate tissue. Gene expression patterns found in G[gamma]-globin-Tag mouse prostate tumors were compared with publicly available human localized and metastatic prostate tumors (...

Prolonged treatment with bicalutamide induces androgen receptor overexpression and androgen hypersensitivity

The Prostate — Thu, 07 Jan 2010 00:00:00 +0100

Various hormone refractory prostate cancer cell models have been established with androgen depletion and have helped to clarify the mechanism for the transition into androgen-depletion independent status. However, the mechanism of bicalutamide resistance remains unclear because few cell models have been generated.We generated a bicalutamide-resistant subline, LNCaP-BC2, from LNCaP after prolonged treatment with bicalutamide. Androgen and/or bicalutamide responsiveness for proliferation and prostate-specific antigen (PSA) secretion were examined in vitro and in vivo. Testosterone and dihydrotestosterone (DHT) levels in xenografted tumors were analyzed by liquid chromatography-tandem mass spectrometry. Androgen receptor (AR) gene mutation and amplification and AR and pAR210 expression were d...

The role of microRNA-128a in regulating TGFbeta signaling in letrozole-resistant breast cancer cells

Breast Cancer Research and Treatment — Wed, 06 Jan 2010 18:07:00 +0100

Abstract Resistance to endocrine therapy agents has presented a clinical obstacle in the treatment of hormone-dependent breast cancer. Our laboratory has initiated a study of microRNA regulation of signaling pathways that may result in breast cancer progression on aromatase inhibitors (AI). Microarray analysis of hormone refractory cell lines identified 115 differentially regulated microRNAs, of which 49 microRNAs were believed to be hormone-responsive. A group of microRNAs were inversely expressed in the AI-resistant lines versus LTEDaro and tamoxifen-resistant. We focused our work on hsa-miR-128a which was hormone-responsive and selectively up-regulated in the letrozole-resistant cell lines. Human miR-128a was predicted to target the TGFβ signaling pathway and indeed se...

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Docetaxel in Combination with Prednisolone for Hormone Refractory Prostate Cancer

Japanese Journal of Clinical Oncology — Thu, 31 Dec 2009 11:15:28 +0100

Conclusions The combination of docetaxel 75 mg/m2 every 3 weeks and prednisolone 10 mg daily was effective and well tolerated in Japanese patients with HRPC. The results of this study suggest that a decision concerning discontinuation of this treatment should be carefully considered because a transient PSA rise was observed. Although interstitial pneumonia was rare, the potential risk of its development should be taken into consideration. (Source: Japanese Journal of Clinical Oncology)

KN-93 inhibits androgen receptor activity and induces cell death irrespective of p53 and Akt status in prostate cancer.

Cancer Biology and Therapy — Thu, 24 Dec 2009 01:48:13 +0100

In this study, we found that the CaMKII inhibitor KN-93 has a broader effect on apoptosis than just inhibition of CaMKII: first, KN-93 inhibits AR activity and induces cell death in PCa cells after androgen deprivation when many other drugs fail to kill prostate cancer cells; second, KN-93 inhibits expression of the anti-apoptotic protein Mcl-1 and induces expression of the pro-apoptotic protein PUMA; third, KN-93-mediated cell death is p53-independent; and fourth, KN-93 induces the generation of ROS. The ROS induction allows KN-93 to circumvent the activation of Akt, which occurs in prostate cancer cells under androgen deprivation, since Akt could not inhibit ROS-mediated apoptosis. KN-93 also synergistically induces cell death in combination with low doses of doxorubicin and converts the...

Chromosome 8p Deletions and 8q Gains are Associated with Tumor Progression and Poor Prognosis in Prostate Cancer.

Clinical Cancer Research — Tue, 22 Dec 2009 00:00:00 +0100

Conclusions: 8p deletions and 8q gains are relatively rare in early stage prostate cancer but often develop during tumor progression. The prognostic effect does not seem to be strong enough to warrant clinical application. Clin Cancer Res; 16(1); 56-64. PMID: 20028754 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Algeta Announces First US Patient Randomized In ALSYMPCA Phase III Study At Tulane Cancer Center, New Orleans

Health News from Medical News Today — Sat, 12 Dec 2009 09:00:00 +0100

Algeta ASA (OSE: ALGETA), the cancer therapeutics company, announces that the first clinical center in the US, the Tulane Cancer Center, New Orleans, has started randomizing patients in the phase III clinical study of Alpharadin in men with castration-resistant (also known as hormone-refractory) prostate cancer (CRPC) that has metastasized to the skeleton... (Source: Health News from Medical News Today)

Algeta Announces First US Patient Randomized In ALSYMPCA Phase III Study At Tulane Cancer Center, New Orleans

Endocrinology News From Medical News Today — Sat, 12 Dec 2009 09:00:00 +0100

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Algeta Announces First US Patient Randomized In ALSYMPCA Phase III Study At Tulane Cancer Center, New Orleans

Endocrinology News From Medical News Today — Sat, 12 Dec 2009 09:00:00 +0100

Syndecan-1 expression in prostate cancer and its value as biomarker for disease progression

BJU International — Fri, 11 Dec 2009 00:00:00 +0100

To evaluate the association between syndecan-1 (CD138) expression and prostate cancer. We evaluated syndecan-1 expression using a recently constructed tissue microarray of prostatic samples taken from 243 patients, corresponding to 1400 cores, with 69.8%, 5.6%, 17.6% and 7% of the cores representing localized prostate cancer, high-grade prostatic intraepithelial neoplasia, benign prostate tissue and hormone refractory/metastatic disease, respectively. Metastatic cases had the highest frequency and membranous staining intensity for syndecan-1 overexpression, followed by hormone refractory and localized disease (83.3% vs 34.8% and 25.7%, respectively). There was no significant difference in the frequency of membranous syndecan-1 expression between localized prostate cancer and benign glands ...

Oral Chemotherapy in Hormone-Refractory Prostate Carcinoma Patients Unwilling to Be Admitted to Hospital

Urologia Internationalis : Last 20 articles — Mon, 07 Dec 2009 23:00:00 +0100

Urol Int 2009;83:452-457 (DOI:10.1159/000251187) (Source: Urologia Internationalis : Last 20 articles)

Predictive Implications Of Bone Turnover Markers After Treatment In Hormone-Refractory Prostate Cancer Patients With Painful Osseous Metastases

Health News from Medical News Today — Sat, 05 Dec 2009 09:00:00 +0100

UroToday.com - Bone is a very common site of prostate cancer metastases, and in most patients the only site of disease progression. At the skeletal site of metastatic invasion, the bone metabolism is deregulated as a result of the presence of tumour cells in the bone microenvironment... (Source: Health News from Medical News Today)

Predictive Implications Of Bone Turnover Markers After Treatment In Hormone-Refractory Prostate Cancer Patients With Painful Osseous Metastases

Bones / Orthopaedics News From Medical News Today — Sat, 05 Dec 2009 09:00:00 +0100

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Predictive Implications Of Bone Turnover Markers After Treatment In Hormone-Refractory Prostate Cancer Patients With Painful Osseous Metastases

Bones / Orthopaedics News From Medical News Today — Sat, 05 Dec 2009 09:00:00 +0100

Predictive value of the clinically and scintigraphically important bone lesions in hormone-refractory prostate cancer (HRPC)

Clinical and Translational Oncology — Thu, 03 Dec 2009 18:25:06 +0100

Content Type Journal ArticleCategory CorrespondenceDOI 10.1007/s12094-009-0443-6Authors Athanasios Zafeirakis, 401 Army Hospital of Athens Department of Nuclear Medicine Mesogeion & Kanellopoulou, 1 GR-11525 Athens GreeceGeorgios S. Limouris, Aretaieion University Hospital Department of Nuclear Medicine Athens Greece Journal Clinical and Translational OncologyOnline ISSN 1699-3055Print ISSN 1699-048X Journal Volume Volume 11 Journal Issue Volume 11, Number 11 / November, 2009 (Source: Clinical and Translational Oncology)

Differential phosphoprotein levels and pathway analysis identify the transition mechanism of LNCaP cells into androgen-independent cells

The Prostate — Fri, 20 Nov 2009 00:00:00 +0100

Androgen withdrawal can prolong life in men with advanced prostate cancer, but these remissions are temporary because the surviving cells progress as hormone-refractory cancer. The mechanisms that are involved in the transition of androgen-dependent prostate cancer into androgen-independent prostate cancer (AIPC) are not fully understood.To identify globally differentially expressed phosphoproteins in the androgen-independent prostate, to elucidate the molecular mechanisms that underlie the formation of AIPC and to identify new molecular targets that can be used to develop treatments for the disease.An androgen-independent LNCaP cell line, LNCaP-AI, was established using androgen ablation. Differentially expressed phosphoproteins in LNCaP cells and LNCaP-AI cells were enriched by immunopre...

Androgen receptor functioned as a suppressor in the prostate cancer cell line PC3 in vitro and in vivo.

Chinese Medical Journal — Fri, 20 Nov 2009 00:00:00 +0100

CONCLUSION: The AR might function as a tumor suppressor in PC3 cells both in vitro and in vivo. PMID: 19951614 [PubMed - in process] (Source: Chinese Medical Journal)

Phase I Clinical Trial of an Adenovirus/Prostate-Specific Antigen Vaccine for Prostate Cancer: Safety and Immunologic Results.

Clinical Cancer Research — Tue, 17 Nov 2009 00:00:00 +0100

CONCLUSIONS: The adenovirus/PSA vaccine was proven safe with no serious vaccine-related adverse events. The majority of vaccinated patients produced anti-PSA T-cell responses and over half survived longer than predicted by nomogram. Although the latter data are only derived from a small number of patients in this phase I trial, they are encouraging enough to pursue further studies. (Clin Cancer Res 2009;15(23):1-6). PMID: 19920098 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

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Synthesis and antitumor properties of selenocoxib-1 against rat prostate adenocarcinoma cells

International Journal of Cancer — Mon, 16 Nov 2009 00:00:00 +0100

This study demonstrates that Selenocoxib-1 is more effective against prostate cancer than Celecoxib. (Source: International Journal of Cancer)

Establishment and characterization of an androgen receptor-dependent, androgen-independent human prostate cancer cell line, LNCaP-CS10

The Prostate — Tue, 10 Nov 2009 00:00:00 +0100

Hormone refractoriness is a lethal event for advanced prostate cancer patients, but the mechanisms of the disease are not well elucidated, especially for the so-called "outlaw" pathways of androgen receptor (AR)-dependent, androgen-independent hormone-refractory prostate cancer.Androgen-dependent prostate cancer LNCaP cells were treated with bicalutamide under an androgen-depleted condition to obtain refractory cells. In the obtained cell line, LNCaP-CS10, we analyzed the effects of androgen and bicalutamide on cell growth and prostate-specific antigen (PSA) production. In addition, AR gene mutation, AR expression levels, and AR subcellular localizations were analyzed.In LNCaP-CS10, cell growth and PSA production were found under an androgen-depleted condition and were induced by both R188...

Investigative clinical study on prostate cancer: on the role of the pretreatment total PSA to free testosterone ratio in selecting different biology groups of prostate cancer patients

International Urology and Nephrology — Mon, 09 Nov 2009 19:01:39 +0100

Conclusions The PSA to FT ratio is the growing rate parameter expressing different biology patterns and assessing different groups of prostate cancer patients. In our opinion, the results of the present study might have wide applications in understanding, assessing and planning prostate cancer studies including basic science, screening, assessing risk of the disease, predicting disease stage as well natural history after a planned treatment involving biochemical recurrence, progression, hormone refractory prostate cancer and disease-specific survival. Content Type Journal ArticleCategory Urology - Original PaperDOI 10.1007/s11255-009-9669-zAuthors Antonio B. Porcaro, Azienda Ospedaliera, Universitaria di Verona, Ospedale Civile Maggiore Department of Urology Verona ...

Clusterin (CLU) and prostate cancer.

Advances in Cancer Research — Wed, 04 Nov 2009 02:42:03 +0100

Authors: Rizzi F, Bettuzzi S The role of clusterin (CLU) in prostate tumorigenesis is probably the most highly controversial, with evidence that CLU expression is increased or decreased in different cancer models. For example, some studies showed that CLU expression is increased in advanced stages of prostate cancer and that suppression of CLU expression sensitizes prostate cancer cells to chemotherapeutic drugs killing. In contrast with the hypothesis that CLU is a positive modulator of prostate cancer, we and others have observed that CLU is downregulated during human prostate cancer progression. Accordingly, a meta-analysis of available microarray data shows that CLU mRNA is significantly downregulated in prostate cancer tissue compared to normal prostate in 14 out of 15 independent...

Vadimezan

Prous Science - Molecule of the Month — Fri, 30 Oct 2009 15:46:28 +0100

Tumor cells rely on the existence of a specialized vasculature for the oxygen and nutrients that they require in order to grow and survive. Targeting the tumor vasculature as a technique for inhibiting tumor growth was first attempted with angiogenesis inhibitors, a class of drugs that compromise the formation of new blood vessels. More recently a new class of drugs called vascular disrupting agents (VDAs) has been reported. Rather than preventing the formation of new blood vessels, VDAs target endothelial cells and pericytes in the already-established vascular network supporting the tumor. VDAs are designed to induce massive downstream tumor cell death in a tumor-specific manner, i.e. by shutting down the supporting vasculature. Two subtypes of VDAs have been described: ligand-directed VD...

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Critical Role Of The Bone Microenvironment In Cancer Metastases - Treating Bone Metastases In Prostate Cancer Patients

Health News from Medical News Today — Mon, 26 Oct 2009 10:00:00 +0100

UroToday.com - Most men with advanced, hormone refractory prostate cancer have metastases which occur preferentially in the skeleton (1). Why is this bad? Bone metastases are incurable and cause skeletal-related events (SREs) that contribute substantial morbidity: fractures, nerve compression, and severe bone pain. (Source: Health News from Medical News Today)

TNF-blockade in patients with advanced hormone refractory prostate cancer

Investigational New Drugs — Wed, 21 Oct 2009 12:15:40 +0100

Content Type Journal ArticleCategory SHORT REPORTDOI 10.1007/s10637-009-9346-1Authors Luis A. Diaz, The Ludwig Center for Cancer Genetics & Therapeutics at Johns Hopkins Baltimore MD 21231 USAWells Messersmith, University of Colorado Cancer Center Division of Medical Oncology Aurora CO 80045 USALori Sokoll, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Department of Oncology Baltimore MD 21231 USAVicki Sinibaldi, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Department of Oncology Baltimore MD 21231 USASandy Moore, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Department of Oncology Baltimore MD 21231 USAMichael Carducci, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Department of Oncology Baltimore MD 21231 USAMario Eisenberger, Johns Hopkins Si...

A Novel Experimental Heme Oxygenase-1-Targeted Therapy for Hormone-Refractory Prostate Cancer

Cancer Research — Thu, 15 Oct 2009 04:07:38 +0100

Heme oxygenase-1 (HO-1), a member of the heat shock protein family, plays a key role as a sensor and regulator of oxidative stress. Herein, we identify HO-1 as a biomarker and potential therapeutic target for advanced prostate cancer (PCA). Immunohistochemical analysis of prostate tissue using a progression tissue microarray from patients with localized PCA and across several stages of disease progression revealed a significant elevation of HO-1 expression in cancer epithelial cells, but not in surrounding stromal cells, from hormone-refractory PCA (HRPCA) compared with hormone-responsive PCA and benign tissue. Silencing the ho-1 gene in HRPCA cells decreased the HO-1 activity, oxidative stress, and activation of the mitogen-activated protein kinase–extracellular signal-regulated kin...

Weekly administration of docetaxel and epirubicin as first-line treatment for hormone-refractory prostate carcinoma.

Oncology Research — Fri, 09 Oct 2009 00:44:03 +0100

Authors: Neri B, Molinara E, Pantaleo P, Rangan S, Crisci A, Della Melina A, Raugei A, Villari D, Nicitat G Androgen-independent prostate carcinoma (AICP) is one of the tumors that continue to respond poorly to chemotherapy. Recently, protocols based on the use of docetaxel have significantly improved survival for patients in this disease. In other types of neoplastic disease, combined therapy with taxanes and anthracycline derivatives has been shown to produce additive effects in terms of growth inhibition, and superior tolerability when associated with weekly administration schedules. These findings prompted us to examine the tolerability and efficacy of weekly treatment of AICP with docetaxel (DOX) plus epirubicin (EPI). We enrolled 35 chemotherapy-naive men with AICP (mean age 72 y...

A Novel Experimental Heme Oxygenase-1-Targeted Therapy for Hormone-Refractory Prostate Cancer.

Cell Research — Mon, 05 Oct 2009 23:00:00 +0100

Authors: Alaoui-Jamali MA, Bismar TA, Gupta A, Szarek WA, Su J, Song W, Xu Y, Xu B, Liu G, Vlahakis JZ, Roman G, Jiao J, Schipper HM Heme oxygenase-1 (HO-1), a member of the heat shock protein family, plays a key role as a sensor and regulator of oxidative stress. Herein, we identify HO-1 as a biomarker and potential therapeutic target for advanced prostate cancer (PCA). Immunohistochemical analysis of prostate tissue using a progression tissue microarray from patients with localized PCA and across several stages of disease progression revealed a significant elevation of HO-1 expression in cancer epithelial cells, but not in surrounding stromal cells, from hormone-refractory PCA (HRPCA) compared with hormone-responsive PCA and benign tissue. Silencing the ho-1 gene in HRPCA cells decre...

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Oncoforum Urology: Prostate Cancer 2008 at a Glance

European Urology Supplements — Sun, 04 Oct 2009 23:00:00 +0100

Conclusions: Many interesting new data on PCa were presented at the 2008 oncological and urological congresses. Some may have an impact on clinical practice, whereas other data raise new questions that will have to be answered by further research.Take Home Message: This paper discusses interesting new data on prostate cancer (PCa) presented at 2008 urological and oncological congresses. These data cover diagnosis and staging, localised PCa, locally advanced PCa and hormone-refractory PCa and may have an impact on current or future clinical practice. (Source: European Urology Supplements)

Identification of Candidate Biomarkers of Therapeutic Response to Docetaxel by Proteomic Profiling

Cancer Research — Thu, 01 Oct 2009 18:26:05 +0100

This study aimed to identify novel therapeutic targets and predictive biomarkers of Docetaxel resistance in HRPC. We used iTRAQ-mass spectrometry analysis to identify proteins associated with the development of Docetaxel resistance using Docetaxel-sensitive PC3 cells and Docetaxel-resistant PC3-Rx cells developed by Docetaxel dose escalation. Functional validation experiments were performed using recombinant protein treatment and siRNA knockdown experiments. Serum/plasma levels of the targets in patient samples were measured by ELISA. The IC50 for Docetaxel in the PC3-Rx cells was 13-fold greater than the parent PC-3 cell line (P = 0.004). Protein profiling identified MIC-1 and AGR2 as respectively up-regulated and down-regulated in Docetaxel-resistant cells. PC-3 cells treated with recomb...

A rapid PSA half-life following docetaxel chemotherapy is associated with improved survival in hormone refractory prostate cancer.

Canadian Urological Association Journal — Wed, 30 Sep 2009 23:00:00 +0100

CONCLUSION: A more rapid rate of PSA decline (PSAHL <70 days) measured after 4 cycles of chemotherapy was associated with a longer OS. This result was independent of other known markers of survival and allowed for a greater survival differentiation than PSA response. PMID: 19829727 [PubMed - as supplied by publisher] (Source: Canadian Urological Association Journal)

The biology of hormone refractory breast and prostate cancer: An NCI workshop report.

Cancer Biology and Therapy — Tue, 29 Sep 2009 19:18:15 +0100

Authors: Mohla S, Stearns V, Sathyamoorthy N, Rosenfeld MG, Nelson P The molecular regulation of growth and progression of hormone refractory breast and prostate cancers remains challenging. The Division of Cancer Biology, NCI organized a small "think tank" style workshop and invited scientists in relevant areas to assess the state of science on the biology of hormone refractory tumors and to identify potential research opportunities to enhance a better understanding of the molecular regulation of these tumors. The meeting, held on May 27-29, 2008 in Bethesda, MD, was co-chaired by Drs. Michael Geoffrey Rosenfeld and Michael Press. While expression of estrogen or progesterone receptors (ER/PR) is required for benefit from endocrine manipulations, many women with breast cancer will not ...

Docetaxel-ST1481 sequence exerts a potent cytotoxic activity on hormone-resistant prostate cancer cells by reducing drug resistance-related gene expression

The Prostate — Mon, 28 Sep 2009 23:00:00 +0100

The efficacy of current therapy for hormone-refractory prostate cancer 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 different antitumor drug combinations in hormone-resistant prostate cancer (HRPC) cell lines.The activity of docetaxel (Doc), cisplatin (Cis), oxaliplatin (Oxa), SN-38 and ST1481, singly or in combination, was assessed in different HRPC cell lines (PC3, parental DU145 and taxane-resistant DU145-R) by SRB test. Apoptosis was evaluated by TUNEL and ANN-V assays. Extrusion pump activity was studied by Hoechst 33342 assay, while gene expression related to drug efflux mechanisms and DNA damage repair was analyzed by RT-PCR.Doc induced a high cytocidal eff...

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aPKC{lambda}/{iota} promotes growth of prostate cancer cells in an autocrine manner through transcriptional activation of interleukin-6 [Medical_Sciences]

Proceedings of the National Academy of Sciences — Mon, 21 Sep 2009 23:00:00 +0100

Understanding the mechanism by which hormone refractory prostate cancer (HRPC) develops remains a major issue. Alterations in HRPC include androgen... (Source: Proceedings of the National Academy of Sciences)

Uptake of resveratrol and role of resveratrol-targeting protein, quinone reductase 2, in normally cultured human prostate cells.

Asian Journal of Andrology — Sun, 20 Sep 2009 23:00:00 +0100

Authors: Hsieh TC Resveratrol is a dietary polyphenol espoused to have chemopreventive activity against a variety of human cancer types. We first reported that resveratrol significantly decreases the proliferation of both androgen-dependent and hormone-refractory prostate cancer cells. However, the effects of resveratrol in normal prostate epithelial and stromal cells, particularly with regard to its uptake, subcellular distribution and intracellular targets, have not been investigated. To advance the knowledge on accessibility and cellular disposition of resveratrol in prostate cells, [(3)H] resveratrol, fractionation of cell extracts into subcellular compartments, western blot analysis, resveratrol affinity column chromatography and flow cytometry were used to study the uptake and in...

Reports From Duke University Describe Recent Advances In Prostate Cancer

Cancercompass News: Prostate Cancer — Thu, 17 Sep 2009 05:00:00 +0100

"The impact of ligand binding on nuclear receptor (NR) structure and the ability of target cells to distinguish between different receptor-ligand complexes are key determinants of the pharmacological activity of NR ligands. However, until relatively recently, these mechanistic insights have not been used in a prospective manner to develop screens for NR modulators with specific therapeutic activities," investigators in the United States report. "Driven by the need for unique androgen receptor (AR) antagonists that retain activity in hormone-refractory prostate cancer, we developed and applied a conformation-based screen to identify AR antagonists that were mechanistically distinct from existing drugs of this class. Two molecules were ide... (Source: Cancercompass News: Prostate Cancer)

Ets-1 and hypoxia inducible factor-1[alpha] inhibition by angiotensin II type-1 receptor blockade in hormone-refractory prostate cancer

The Prostate — Wed, 16 Sep 2009 23:00:00 +0100

This study suggests that AT1R blockade may have a significant impact on HRPC through the inhibition of HIF-1[alpha] and Ets-1 and the resulting suppression of angiogenesis. Our results provide the molecular basis of the clinical benefit of ARB as an angiogenic inhibitor in HRPC. Prostate © 2009 Wiley-Liss, Inc. (Source: The Prostate)

The Neuroendocrine-Derived Peptide Parathyroid Hormone-Related Protein Promotes Prostate Cancer Cell Growth by Stabilizing the Androgen Receptor

Cancer Research — Sun, 13 Sep 2009 23:00:00 +0100

In this study, we show that neuroendocrine-derived parathyroid hormone–related protein (PTHrP)–mediated signaling through the epidermal growth factor receptor (EGFR) and Src pathways contributes to the phenotype of advanced prostate cancer by reducing AR protein turnover. PTHrP-induced accumulation of AR depended on the activity of Src and EGFR and consequent phosphorylation of the AR on Tyr534. PTHrP-induced tyrosine phosphorylation of AR resulted in reduced AR ubiquitination and interaction with the ubiquitin ligase COOH terminus of Hsp70-interacting protein. These events result in increased accumulation of AR and thus enhanced growth of prostate cancer cells at low levels of androgen. [Cancer Res 2009;69(18):7402–11] (Source: Cancer Research)

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Global levels of histone modifications predict prostate cancer recurrence

The Prostate — Mon, 07 Sep 2009 23:00:00 +0100

Epigenetic alterations such as DNA methylation and histone modifications play important roles in carcinogenesis. It was reported that global histone modification patterns are predictors of cancer recurrence in various tumor entities. Our study was performed to evaluate histone lysine (HxKy) and histone acetyl (HxAc) modifications in prostate tissue.A tissue microarray with 113 prostate cancer (PCA), 23 non-malignant prostate tissues was stained with antibodies against H3K4 mono-(H3K4me1), di-(H3K4me2), tri-(H3K4me3) methylation, H3K9me1, H3K9me2, H3K9me3, H3 and H4 pan-acetylation (H3Ac, H4Ac). We also analyzed H3K4 methylation in patients with advanced PCA (hormone-refractory PCA - HRPC, n = 34; hormone-dependent PCA, n = 30). Sections were scored according the staining intensity and the ...

Bayer And Algeta Enter Global Agreement For Development And Commercialization Of Treatment For Bone Metastases In Cancer Patients

Pharmaceutical Online News — Thu, 03 Sep 2009 09:01:00 +0100

Bayer Schering Pharma AG, Germany has entered into a global agreement with Algeta ASA, Oslo, Norway for the development and commercialization of Alpharadin, a novel alpha-emitting radiopharmaceutical, based on radium-223. Alpharadin is currently being evaluated in a global Phase III trial for the treatment of bone metastases in symptomatic hormone-refractory prostate cancer (HRPC) patients. (Source: Pharmaceutical Online News)

Docetaxel-induced prostate cancer cell death involves concomitant activation of caspase and lysosomal pathways and is attenuated by LEDGF/p75

Molecular Cancer — Thu, 27 Aug 2009 23:00:00 +0100

Conclusions: These results underscore the ability of docetaxel to induce concomitantly caspase-dependent and independent death pathways in prostate cancer cells. The results also point to LEDGF/p75 as a potential contributor to cellular resistance to docetaxel-induced lysosomal destabilization and cell death, and an attractive candidate for molecular targeting in HRPC. (Source: Molecular Cancer)

The Neuroendocrine-Derived Peptide Parathyroid Hormone-Related Protein Promotes Prostate Cancer Cell Growth by Stabilizing the Androgen Receptor.

Cell Research — Mon, 24 Aug 2009 23:00:00 +0100

In this study, we show that neuroendocrine-derived parathyroid hormone-related protein (PTHrP)-mediated signaling through the epidermal growth factor receptor (EGFR) and Src pathways contributes to the phenotype of advanced prostate cancer by reducing AR protein turnover. PTHrP-induced accumulation of AR depended on the activity of Src and EGFR and consequent phosphorylation of the AR on Tyr(534). PTHrP-induced tyrosine phosphorylation of AR resulted in reduced AR ubiquitination and interaction with the ubiquitin ligase COOH terminus of Hsp70-interacting protein. These events result in increased accumulation of AR and thus enhanced growth of prostate cancer cells at low levels of androgen. [Cancer Res 2009;69(18):OF1-10]. PMID: 19706771 [PubMed - as supplied by publisher] (Source: Cell...

Pathological Effects of Prostate Cancer Correlate With Neuroendocrine Differentiation and PTEN Expression After Bicalutamide Monotherapy

The Journal of Urology — Thu, 13 Aug 2009 23:00:00 +0100

Conclusions: PTEN inactivation and neuroendocrine differentiation were related to refractoriness to bicalutamide therapy. These results support the hypothesis that neuroendocrine differentiation is caused by activation of the serine threonine kinase Akt pathway, which results from PTEN inactivation. (Source: The Journal of Urology)

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Discovery of BMS-641988, a Novel and Potent Inhibitor of Androgen Receptor Signaling for the Treatment of Prostate Cancer

Cancer Research — Tue, 11 Aug 2009 23:00:00 +0100

Despite an excellent initial response to first-line hormonal treatment, most patients with metastatic prostate cancer will succumb to a hormone-refractory form of the disease. Because these tumors are still dependent on a functional androgen receptor (AR), there is a need to find novel and more potent antiandrogens. While searching for small molecules that bind to the AR and inhibit its transcriptional activity, BMS-641988 was discovered. This novel antiandrogen showed an increased (>1 log) potency compared with the standard antiandrogen, bicalutamide, in both binding affinity to the AR and inhibition of AR-mediated transactivation in cell-based reporter assays. In mature rats, BMS-641988 strongly inhibited androgen-dependent growth of the ventral prostate and seminal vesicles. In the C...

Predictive implications of bone turnover markers after palliative treatment with 186Re-HEDP in hormone-refractory prostate cancer patients with painful osseous metastases

European Journal of Nuclear Medicine and Molecular Imaging — Fri, 07 Aug 2009 11:08:36 +0100

Conclusion NTx, a potent collagenous marker of bone resorption, along with the novel NTx/PINP ratio provide useful cut-off values for identifying a group of patients suffering from painful osseous metastases from hormone-refractory prostatic carcinoma who do not respond to palliative treatment with 186Re-HEDP. This information could help avoid an inefficient and expensive radionuclide treatment. Also, in the cohort of patients who will eventually undergo such treatment, the medium-term posttreatment changes in NTx offer valuable predictive information regarding long-term palliative response. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00259-009-1243-5Authors Athanasios Zafeirakis, 401 Army Hospital of Athens Department of Nuclear Medicine Mesog...

Discovery of BMS-641988, a Novel and Potent Inhibitor of Androgen Receptor Signaling for the Treatment of Prostate Cancer.

Cell Research — Mon, 03 Aug 2009 23:00:00 +0100

Authors: Attar RM, Jure-Kunkel M, Balog A, Cvijic ME, Dell-John J, Rizzo CA, Schweizer L, Spires TE, Platero JS, Obermeier M, Shan W, Salvati ME, Foster WR, Dinchuk J, Chen SJ, Vite G, Kramer R, Gottardis MM Despite an excellent initial response to first-line hormonal treatment, most patients with metastatic prostate cancer will succumb to a hormone-refractory form of the disease. Because these tumors are still dependent on a functional androgen receptor (AR), there is a need to find novel and more potent antiandrogens. While searching for small molecules that bind to the AR and inhibit its transcriptional activity, BMS-641988 was discovered. This novel antiandrogen showed an increased (>1 log) potency compared with the standard antiandrogen, bicalutamide, in both binding affinity t...

A case of indirect cauda equina syndrome from metastatic prostate cancer.

Canadian Urological Association Journal — Fri, 31 Jul 2009 23:00:00 +0100

We report the case of a patient with metastatic hormone refractory prostate cancer in whom "indirect" cauda equina syndrome developed concurrent with multilevel spinal cord compression (SCC). Three months after his first positive bone scan, a 65-year-old otherwise healthy man presented with severe back pain, bilateral lower extremity paresthesias, leg weakness and urinary retention. Magnetic resonance imaging (MRI) showed a dural-based mass causing SCC at the T9, T10 and T11 vertebrae, with a normal cauda equina. He received corticosteroids and palliative external beam radiotherapy, resulting in good pain control and gradual improvement in his neurological symptoms. He did well for 8 months, at which time his residual bilateral leg weakness abruptly worsened and he experienced numbness, pa...

A novel androgen-dependent prostate cancer xenograft model derived from skin metastasis of a Japanese patient

The Prostate — Wed, 29 Jul 2009 23:00:00 +0100

The incidence of, and mortality from, prostate cancer (PCa) has increased in Asian countries over the past decades, partly due to a change in dietary habits. Recent reports have revealed differences in the molecular basis of PCa among people of differing racial or ethnic backgrounds. PCa xenograft models established from Asian patients would be useful for understanding the basis of PCa in Asian populations; we therefore established and characterized a novel PCa xenograft model, JDCaP, from a metastatic skin lesion of a Japanese hormone-refractory prostate cancer (HRPC) patient.Skin metastatic tissue derived from poorly differentiated prostatic adenocarcinoma in a 61-year-old Japanese male was transplanted to nude mice and JDCaP was established by serial passage. Expression of androgen rece...

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Surveyed Oncologists Expect To Prescribe Provenge To About Half Of Their Prostate Cancer Patients If The Vaccine Is Approved

Health News from Medical News Today — Wed, 29 Jul 2009 09:00:00 +0100

Decision Resources, one of the world's leading research and advisory firms for pharmaceutical and healthcare issues, finds that, if Dendreon's Provenge receives regulatory approval, surveyed oncologists expect to prescribe Provenge to 54 percent of patients with asymptomatic hormone refractory metastatic prostate cancer. (Source: Health News from Medical News Today)

Driven By Launch Of Emerging Therapies, Overall Prostate Cancer Drug Market Will Increase By $2B Through 2018

Pharmaceutical Online News — Mon, 27 Jul 2009 06:20:00 +0100

Decision Resources, one of the world's leading research and advisory firms for pharmaceutical and healthcare issues, finds that $2 billion growth in the prostate cancer drug market though 2018 will be driven principally by the launch of emerging therapies in the metastatic hormone-refractory population, most notably Dendreon's Provenge. (Source: Pharmaceutical Online News)

Clinical and Pharmacodynamic Evaluation of Metronomic Cyclophosphamide, Celecoxib, and Dexamethasone in Advanced Hormone-refractory Prostate Cancer.

Clinical Cancer Research — Mon, 20 Jul 2009 23:00:00 +0100

CONCLUSION: Metronomic CTX plus CXB and DEX showed favorable toxicity and activity profile in patients. VE-C gene expression and VEGF levels represent potentially useful pharmacodynamic markers for the clinical response. PMID: 19622584 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Failing to achieve a nadir prostate-specific antigen after combined androgen blockade: Predictive factors

International Journal of Urology — Mon, 13 Jul 2009 23:00:00 +0100

Objectives: To determine the optimal cut-off of a nadir prostate-specific antigen (PSA) for prediction of progression within 24 months after combined androgen blockade (CAB) and to analyze predictive factors of failing to achieve the nadir PSA.Methods: We retrospectively reviewed the medical records of 343 patients with prostate cancer treated with CAB from 2000 to 2005. We determined the nadir PSA level that predicts progression to hormone refractory prostate cancer (HRPC) at 24 months after CAB. Predictive factors for failing to achieve a determined nadir PSA were analyzed.Results: Mean age was 74.0 years. Mean follow up was 42.1 month. Seventy-seven patients experienced progression to HRPC. A nadir PSA of 1.0 ng/mL predicts progression to HRPC at 24 months. Predictive factors for fail...

Treatment of Painful Bone Metastases in Hormone-Refractory Prostate Cancer with Zoledronic Acid and Samarium-153-Ethylenediaminetetramethylphosphonic Acid Combined

Journal of Palliative Medicine — Mon, 13 Jul 2009 16:43:27 +0100

Journal of Palliative Medicine Jul 2009, Vol. 12, No. 7: 649-651. (Source: Journal of Palliative Medicine)

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Evaluation of docetaxel plus estramustine in the treatment of patients with hormone-refractory prostate cancer

International Journal of Urology — Tue, 07 Jul 2009 23:00:00 +0100

Conclusions: Docetaxel plus estramustine chemotherapy represents an active and well tolerated treatment for Japanese HRPC patients. (Source: International Journal of Urology)

Hormone Therapy for Prostate Cancer: Exploring Current Controversies

European Urology Supplements — Tue, 07 Jul 2009 23:00:00 +0100

Conclusions: Neoadjuvant or adjuvant hormone therapy with radical treatment may improve survival in carefully selected patients with PCa. Intermittent hormone therapy seems to reduce adverse events and improve QoL without a negative effect on survival. The availability of different formulations of a luteinising hormone-releasing hormone agonist offers patients an individualised treatment approach.Take Home Message: Hormone therapy is beneficial in carefully selected prostate cancer patients; however, patients’ preferences should be taken into consideration in the treatment decision-making process. (Source: European Urology Supplements)

Celastrol Potentiates Radiotherapy by Impairment of DNA Damage Processing in Human Prostate Cancer

International Journal of Radiation Oncology * Biology * Physics — Thu, 25 Jun 2009 08:18:12 +0100

Conclusion: Celastrol sensitized PC-3 cells to radiation both in vitro and in vivo by impairing DNA damage processing and augmenting apoptosis. Celastrol might represent a promising new adjuvant regimen for the treatment of hormone-refractory prostate cancer. (Source: International Journal of Radiation Oncology * Biology * Physics)

Effects of cIAP-1, cIAP-2 and XIAP triple knockdown on prostate cancer cell susceptibility to apoptosis, cell survival and proliferation

Molecular Cancer — Mon, 22 Jun 2009 23:00:00 +0100

Conclusion: Simultaneous knock down of the IAPs not only sensitised the PC-3 to TRAIL but also inhibited their proliferation rates and clonogenic survival. The inability to alter sensitivity to other triggers of apoptosis suggests that this effect is specific for death receptor pathways and knock down might facilitate immune-surveillance mechanisms to counter cancer progression and, in combination with therapeutic approaches using TRAIL, could represent an important treatment strategy. (Source: Molecular Cancer)

Phosphorylation of Bcl-2 and activation of caspase-3 via the c-Jun N-terminal kinase pathway in ursolic acid-induced DU145 cells apoptosis.

Biochimie — Thu, 18 Jun 2009 23:00:00 +0100

Authors: Zhang YX, Kong CZ, Wang HQ, Wang LH, Xu CL, Sun YH There is currently no successful therapy for androgen-independent prostate cancer. Ursolic acid (UA), a pentacyclic triterpenoid compound, has been shown to have an anti-proliferative effect on various tumors. We investigated the effect of UA on cell viability in the human hormone-refractory prostate cancer cell line DU-145, as well as the molecular mechanisms underlying its growth inhibiting effect. We demonstrated that UA induces apoptosis and the activation of caspase-3 in DU145 cells. UA also causes the activation of c-Jun N-terminal kinase (JNK), but has no effect on extracellular signal-regulated protein kinases (ERK1/2) and p38 MAP kinases (p38). UA-induced JNK activation could result in Bcl-2 phosphorylation (Ser70) an...

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18F-choline PET/CT imaging of RECIST measurable lesions in hormone refractory prostate cancer

Annals of Nuclear Medicine — Tue, 16 Jun 2009 05:52:19 +0100

Conclusion Lesions detected with 18F-choline PET/CT are frequently measurable by RECIST at baseline. Therefore, it may be feasible to include comparisons to RECIST in evaluations of 18F-choline as a therapeutic response marker for hormone refractory prostate cancer. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s12149-009-0273-1Authors Sandi A. Kwee, Hamamatsu/Queen’s PET Imaging Center 1301 Punchbowl St. Honolulu HI 96813 USAMarc N. Coel, Hamamatsu/Queen’s PET Imaging Center 1301 Punchbowl St. Honolulu HI 96813 USABevan H. Ly, University of Hawaii Department of Medicine, John A. Burns School of Medicine Honolulu USAJohn Lim, Hamamatsu/Queen’s PET Imaging Center 1301 Punchbowl St. Honolulu HI 96813 USA Journal Annals of Nuclear MedicineO...

FOCUS On FOCIS: Combined Chemo-Immunotherapy For The Treatment Of Hormone-Refractory Metastatic Prostate Cancer

Health News from Medical News Today — Mon, 15 Jun 2009 07:00:00 +0100

UroToday.com - The long-term goal of the Tumor Immunology and Immunotherapy group at The Institute of Immunology, Charles University, 2nd Medical School is the development of dendritic cell-based cancer vaccine. (Source: Health News from Medical News Today)

Editorial Comment

The Journal of Urology — Sun, 14 Jun 2009 23:00:00 +0100

In this preliminary study the authors report that denosumab, a human antibody against RANKL, normalized the increased uNTx levels more frequently than continuous BP administration in patients with prostate cancer with bone metastases previously treated with BP. They also indicate that the incidence of SRE was reduced in the denosumab group compared to the control group despite the fact that the numbers were too small to be statistically significant. Although this report is informative, the characteristics of the enrolled patients were not well illustrated. Prostate specific antigen levels which reflect the severity of the disease were not collected. The state of prostate cancer in terms of androgen or hormone sensitivity should be considered in the study because endocrine therapies are ini...

Continuous and intermittent dosing of lonafarnib potentiates the therapeutic efficacy of docetaxel on preclinical human prostate cancer models

International Journal of Cancer — Sun, 14 Jun 2009 23:00:00 +0100

In conclusion, coadministration of continuous and intermittent lonafarnib enhanced the antitumor activity of docetaxel in a panel of prostate cancer models. An intermittent dosing schedule of lonafarnib coadministered with docetaxel may allow enhanced efficacy to that of continuous dosing by improving the tolerability of higher doses of lonafarnib. © 2009 UICC (Source: International Journal of Cancer)

ADAMTS1, a putative anti-angiogenic factor, is decreased in human prostate cancer

BJU International — Thu, 11 Jun 2009 23:00:00 +0100

To investigate the expression of 'ADAM metallopeptidase with thrombospondin type I motif, 1' (ADAMTS1) in human prostate cancer, and to study its relationship to microvessel density (MVD) and metastasis. ADAMTS1 has been described as an anti-angiogenic and antitumour factor, but its function in prostate cancer is unknown. ADAMTS1 expression was evaluated by immunohistochemistry in specimens obtained by transurethral resection of the prostate from patients with hormone-naïve and hormone-refractory prostate tumours, including adjacent benign tissue. A semiquantitative scoring system was used for evaluating the staining. MVD was quantified by counting the number of CD34-positive blood vessels. ADAMTS1 was strongly expressed in the luminal epithelial cells in benign prostate glands, whereas e...

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Radiotherapy for patients with localized hormone-refractory prostate cancer: results of the Patterns of Care Study in Japan

BJU International — Thu, 11 Jun 2009 23:00:00 +0100

To evaluate the clinical results of radiotherapy (RT) for patients with regionally localized hormone-refractory prostate carcinoma (HRPC). As part of a Patterns of Care Study in Japan, a nationwide survey was conducted of RT for patients with prostate adenocarcinoma. We reviewed the detailed information of 140 patients with regionally localized HRPC who received RT between 1996 and 1998, and between 1999 and 2001, in 117 randomly selected institutes in Japan. The median (range) age of the patients was 74 (51[ndash]94) years, and their tumours were defined as well (14), moderately (51) or poorly (54) differentiated, or of unknown differentiation (21). The median (range) interval between hormonal therapy (HT) and RT was 32.5 (1.1[ndash]168.4) months. Ninety-five patients had T3-4 tumours and...

Growth kinetics and transplantation of human retinal progenitor cells.

Experimental Eye Research — Thu, 11 Jun 2009 23:00:00 +0100

In conclusion, we have determined the growth kinetics of hRPCs and have shown that cells from donor tissue of 16-18 weeks G.A. exhibit the best proliferative dynamics under the specified conditions, and that hRPCs can also be differentiated along the photoreceptor lineage. Further, we have also demonstrated that following transplantation, some of these cells integrate within the host retina and differentiate to express rhodopsin, thereby supporting the potential utility of hRPC transplantation in the setting of retinal degenerative disorders. PMID: 19524569 [PubMed - as supplied by publisher] (Source: Experimental Eye Research)

Good localized hormone-refractory prostate cancer control with EBRT

MedWire News - Prostate Cancer — Tue, 09 Jun 2009 00:00:00 +0100

For clinically localized hormone-refractory prostate cancer, external beam radiotherapy has a good local control rates, with nadir prostate-specific antigen levels predicting outcomes, say Japanese scientists. (Source: MedWire News - Prostate Cancer)

[Patients with metastatic hormone-refractory prostate cancer : Second-line chemotherapy with mitoxantrone plus prednisone.]

Der Urologe. Ausg. A — Thu, 04 Jun 2009 23:00:00 +0100

CONCLUSIONS: Presently, we see the indication for MP as being second-line chemotherapy in docetaxel-refractory patients with mHRPC who cannot be included in phase II/III studies. Even with only a moderate rate of partial PSA remission, every second patient had an improvement in tumor-related pain. Progression-free survival was prolonged, and the side effects of MP were comparatively low. PMID: 19513599 [PubMed - as supplied by publisher] (Source: Der Urologe. Ausg. A)

Mre11 inhibition by oncolytic adenovirus associates with autophagy and underlies synergy with ionizing radiation

International Journal of Cancer — Mon, 01 Jun 2009 23:00:00 +0100

New treatment approaches are needed for hormone refractory prostate cancer. Oncolytic adenoviruses are promising anti-cancer agents, and their efficacy can be improved by combining with conventional therapies such as ionizing radiation. The aim of this study was to determine the timing of oncolytic adenovirus treatment with regard to radiation and study the mechanisms of synergy in combination treatment. Prostate cancer cells were infected with oncolytic adenoviruses, irradiated and synergy mechanisms were assessed. In vivo models of combination treatment were tested. Radiation and oncolytic viruses were synergistic when viral infection was scheduled 24 hr after irradiation. Combination of oncolytic adenovirus with radiotherapy significantly increased antitumor efficacy in vivo compared to...

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Percutaneous Tumor Ablation: Microencapsulated Echo-guided Interstitial Chemotherapy Combined with Cryosurgery Increases Necrosis in Prostate Cancer.

Technology in Cancer Research and Treatment — Sun, 31 May 2009 23:00:00 +0100

This study aimed at confirming the increased growth inhibition (GI) of human prostate tumors produced by a intentionally palliative combination treatment of cryochemotherapy, i.e., partial cryoablation (CA) followed by intratumor partial chemotherapy with injection of microencapsulated 5-fluorouracil (MCC/5FU) at the ice ball (IB) periphery. We report the local effectiveness of cryochemotherapy compared to chemotherapy only with using multiple injections of MCC/5FU spaced out to maximize cumulative effect of sustained release of 5-fluorouracil (5FU) during a 21-day period. Prostate bioluminescent tumor cells - DU145 Luc+ - were implanted sub-cutaneously and bilaterally in each flank of nude mice. Tumors were treated with: (i) cryoablation alone (CA), causing necrosis in approximately 45% o...

Poniard Pharmaceuticals Announces Positive Efficacy And Safety Data From Phase 2 Clinical Trial Of Picoplatin In Men With Metastatic Prostate Cancer

Health News from Medical News Today — Fri, 29 May 2009 08:00:00 +0100

Poniard Pharmaceuticals, Inc. (Nasdaq: PARD), a biopharmaceutical company focused on innovative oncology therapies, today announced updated efficacy and safety data from its Phase 2 clinical trial of picoplatin in patients with metastatic castration-resistant (hormone-refractory) prostate cancer (CRPC). (Source: Health News from Medical News Today)

Palliative prostate radiotherapy for symptomatic advanced prostate cancer

Radiotherapy and Oncology — Mon, 25 May 2009 00:00:00 +0100

Conclusion: Palliative radiotherapy to the prostate gland for local symptoms appears to be an effective means of palliation with minimal toxic side effects. Prospective studies are now required to assess its benefits in more detail. (Source: Radiotherapy and Oncology)

Phase II study of paclitaxel and vinorelbine (Pacl-Vin) in hormone-refractory metastatic prostate cancer: double tubulin targeting

Internal Medicine Journal — Thu, 21 May 2009 00:00:00 +0100

Conclusion: In a poor prognostic cohort of patients paclitaxel and vinorelbine is a tolerable regimen, with a 20% PSA and objective response rate. The majority of patients achieved PSA stability. Furthermore, quality of life parameters, such as pain, were improved. However, the low level of activity of this regimen precludes its further testing. (Source: Internal Medicine Journal)

Palliative prostate radiotherapy for symptomatic advanced prostate cancer.

Wed, 20 May 2009 23:00:00 +0100

CONCLUSION: Palliative radiotherapy to the prostate gland for local symptoms appears to be an effective means of palliation with minimal toxic side effects. Prospective studies are now required to assess its benefits in more detail. PMID: 19464745 [PubMed - as supplied by publisher] (Source: Radiotherapy and Oncology : journal of the European Society for Therapeutic Radiology and Oncology)

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Merrion Pharmaceuticals plc Announces Preliminary Results On Phase II Orazol(tm) Study

Medical News (via PRIMEZONE) — Fri, 15 May 2009 07:00:00 +0100

DUBLIN, Ireland, May 15, 2009 (GLOBE NEWSWIRE) -- Dr. John Fox, of Merrion Pharmaceuticals ("Merrion" or the "Company"), will address the 7th International Cancer Conference in Dublin today, and will speak about the very positive preliminary results from a multi centre Phase II study on Merrion's Orazol(tm) drug (formerly known as MER 101). The study, conducted in hormone refractory prostate cancer patients with proven bone metastases, enrolled patients at sites in the U.S. and Europe. (Source: Medical News (via PRIMEZONE))

Treatment-Dependent Androgen Receptor Mutations in Prostate Cancer Exploit Multiple Mechanisms to Evade Therapy

Cancer Research — Fri, 15 May 2009 04:00:00 +0100

Mutations in the androgen receptor (AR) that enable activation by antiandrogens occur in hormone-refractory prostate cancer, suggesting that mutant ARs are selected by treatment. To validate this hypothesis, we compared AR variants in metastases obtained by rapid autopsy of patients treated with flutamide or bicalutamide, or by excision of lymph node metastases from hormone-naïve patients. AR mutations occurred at low levels in all specimens, reflecting genetic heterogeneity of prostate cancer. Base changes recurring in multiple samples or multiple times per sample were considered putative selected mutations. Of 26 recurring missense mutations, most in the NH2-terminal domain (NTD) occurred in multiple tumors, whereas those in the ligand binding domain (LBD) were case specific. Hormon...

3,3'-Diindolylmethane Enhances Taxotere-Induced Apoptosis in Hormone-Refractory Prostate Cancer Cells through Survivin Down-regulation

Cancer Research — Fri, 15 May 2009 04:00:00 +0100

Survivin, a member of inhibitor of apoptosis family, is associated with both prostate cancer progression and drug resistance. Therefore, we hypothesized that survivin may play a potentially important role in hormone-refractory prostate cancer (HRPC) and bone metastatic disease; thus, targeting of survivin signaling could enhance therapeutic efficacy in prostate cancer. 3,3'-Diindolylmethane (DIM) has been known to have cancer chemoprevention activity. However, no information is available regarding the down-regulation of survivin by DIM, which could result in the chemosensitization of HRPC cells to Taxotere-induced killing. We investigated the effect of DIM alone or in combination with Taxotere using LNCaP and C4-2B prostate cancer cells. We observed that DIM enhanced Taxotere-induced apopt...

Tranilast inhibits hormone refractory prostate cancer cell proliferation and suppresses transforming growth factor [beta]1-associated osteoblastic changes

The Prostate — Mon, 11 May 2009 04:00:00 +0100

Tranilast is a therapeutic agent used in treatment of allergic diseases, although it has been reported to show anti-tumor effects on some cancer cells. To elucidate the effects of tranilast on prostate cancer, we investigated the mechanisms of its anti-tumor effect on prostate cancer.The anti-tumor effects and related mechanisms of tranilast were investigated both in vitro on prostate cancer cell lines and bone-derived stromal cells, and in vivo on severe combined immunodeficient (SCID) mice. We verified its clinical effect in patients with advanced hormone refractory prostate cancer (HRPC).Tranilast inhibited the proliferation of LNCaP, LNCaP-SF, and PC-3 cells in a dose-dependent manner and growth of the tumor formed by inoculation of LNCaP-SF in the dorsal subcutis and in the tibia of c...

Phase II Trial of Radiation Dose Escalation With Conformal External Beam Radiotherapy and High-Dose-Rate Brachytherapy Combined With Long-Term Androgen Suppression in Unfavorable Prostate Cancer: Feasibility Report

International Journal of Radiation Oncology * Biology * Physics — Mon, 11 May 2009 00:00:00 +0100

Conclusions: Intermediate-term results show that dose escalation with HDR brachytherapy combined with long-term AST is feasible and has a toxicity profile similar to that reported by previous HDR brachytherapy studies. (Source: International Journal of Radiation Oncology * Biology * Physics)

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Rare sugar d-allose induces programmed cell death in hormone refractory prostate cancer cells

Apoptosis — Wed, 06 May 2009 06:01:22 +0100

Content Type Journal ArticleCategory ErratumDOI 10.1007/s10495-009-0336-8Authors Nibedita Naha, Gyeongsang National University Division of Life Science, Applied Life Science (Brain Korea 21 and EB-NCRC) Jinju 660701 South KoreaHae Young Lee, Gyeongsang National University Division of Life Science, Applied Life Science (Brain Korea 21 and EB-NCRC) Jinju 660701 South KoreaMi Ja Jo, Gyeongsang National University Division of Life Science, Applied Life Science (Brain Korea 21 and EB-NCRC) Jinju 660701 South KoreaBong Chul Chung, Korea Institute of Science and Technology Bioanalysis and Biotransformation Research Centre Cheongryang Seoul South KoreaSung Hoon Kim, Kyunghee University Cancer Preventive Material Development Research Centre (CPMDRC) and Institute College of Oriental Medicine Se...

Skeletal complications worsen HRPC prognosis

MedWire News - Oncology — Tue, 05 May 2009 00:00:00 +0100

Patients with hormone-refractory prostate cancer have a high prevalence and mortality rate of skeletal complications, with the prognosis substantially worse in those with bone pain at diagnosis, say Japanese scientists. (Source: MedWire News - Oncology)

Skeletal complications worsen HRPC prognosis

MedWire News - Prostate Cancer — Tue, 05 May 2009 00:00:00 +0100

A Randomized, Double-Blind, Placebo-Controlled Phase II Study of Vandetanib Plus Docetaxel/Prednisolone in Patients with Hormone-Refractory Prostate Cancer

Cancer Biotherapy and Radiopharmaceuticals — Sat, 02 May 2009 20:38:18 +0100

Cancer Biotherapy & Radiopharmaceuticals Apr 2009, Vol. 24, No. 2: 175-180. (Source: Cancer Biotherapy and Radiopharmaceuticals)

[Toxicity and efficacy of intermittent docetaxel chemotherapy for hormone refractory prostate cancer]

Aktuelle Urologie — Thu, 30 Apr 2009 23:00:00 +0100

CONCLUSION: Intermittent docetaxel therapy is well tolerated and shows high response rates in the sec-ond and third sequences of treatment in select-ed HRPC patients who presented with low docetaxel toxicity, good clinical condition and responded to prior docetaxel-based treatment. PMID: 19370533 [PubMed - in process] (Source: Aktuelle Urologie)

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Chemotherapy for Prostate Cancer in Senior Adults: Are We Treating the Elderly or the Frail?

European Urology — Wed, 29 Apr 2009 05:58:00 +0100

Chemotherapy was considered ineffective in hormone-refractory prostate cancer (HRPC) until a paradigm shift was established in 2004. Two randomised phase 3 trials were published (the TAX327 trial and the Southwest Oncology Group [SWOG] trial) showing a statistically significant survival benefit with docetaxel in combination with estramustine1 or prednisone when compared to the standard mitoxantrone prednisone (MP). Since then, docetaxel chemotherapy has become the standard first-line treatment for HRPC. However, because patients randomised in phase 3 clinical trials are highly selected, they may not represent a real-life population. Consequently, the benefit observed in both trials is only applicable to patients fulfilling specific eligibility criteria. (Source: European Urology)

GnRH receptor expression in human prostate cancer cells is affected by hormones and growth factors

Endocrine — Tue, 28 Apr 2009 12:57:56 +0100

In this study, we investigated GnRH-R expression in androgen-sensitive (LNCaP) and -insensitive (PC-3) PCa cells treated for 4 and 6 days with a GnRH agonist (Leuprorelin acetate, LA, 10−11 or 10−6 M), Dihydrotestosterone (DHT, 10−9 M), Cyproterone acetate (CA, 10−7 M), and Epidermal growth factor (EGF, 10 ng/ml), either alone or combined. The RT-PCR analysis showed no variation in GnRH-R mRNA levels of both treated LNCaP and PC-3 cells. On the contrary, immunoblotting indicated that in LNCaP and PC-3 cells, LA upregulated membrane GnRH-R expression (up to 92%). In androgen-sensitive cells, DHT induced a GnRH-R increase (up to 119%) always comparable to that occurring in the presence of CA. GnRH-R upregulation by LA/DHT or CA/DHT association was simila...

Liposomal gemcitabine (GemLip) - efficient drug against hormone-refractory Du145 and PC-3 prostate cancer xenografts

The Prostate — Mon, 27 Apr 2009 04:00:00 +0100

Gemcitabine (Gemc) is an efficient chemotherapeutic drug in various cancer types (e.g., pancreas) but has only limited effects on hormone-refractory prostate cancer (HRPCa). Since HRPCa cells are highly sensitive to even low doses of Gemc in vitro, the lack of clinical effects might be due to rapid degradation of Gemc by deaminases combined with impaired accumulation in tumor tissue and PCa cells. Liposomal formulation (GemLip) is expected to protect the entrapped cytotoxic substance from enzymatic degradation and furthermore augment its accumulation within tumor tissues due to an enhanced permeability of the tumor vessels.Anti-tumoral and anti-metastatic activity of GemLip and Gemc were investigated in two luciferase-expressing, human hormone-refractory PC-3 and Du145 HRPCa xenograft mode...

Intermittent docetaxel therapy with estramustine for hormone-refractory prostate cancer in Japanese patients

International Journal of Clinical Oncology — Fri, 24 Apr 2009 07:03:53 +0100

Conclusion Intermittent DCT/EM therapy was well tolerated, and has the potential to prolong survival, with a high QOL, in patients with HRPC. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10147-008-0814-yAuthors Norihito Soga, Mie University Graduate School of Medicine Division of Nephro-Urologic Surgery and Andrology, Department of Reparative and Regenerative Medicine, Institute of Medical Life Science 2-174 Edobashi Tsu, Mie 514-8507 JapanManabu Kato, Mie University Graduate School of Medicine Division of Nephro-Urologic Surgery and Andrology, Department of Reparative and Regenerative Medicine, Institute of Medical Life Science 2-174 Edobashi Tsu, Mie 514-8507 JapanKouhei Nishikawa, Mie University Graduate School of Medicine Division of Nephro-Uro...

Safety and Efficacy of the Specific Endothelin-A Receptor Antagonist ZD4054 in Patients with Hormone-Resistant Prostate Cancer and Bone Metastases Who Were Pain Free or Mildly Symptomatic: A Double-Blind, Placebo-Controlled, Randomised, Phase 2 Trial

European Urology — Tue, 21 Apr 2009 23:58:24 +0100

Conclusions: The primary end point of time to progression was not achieved in this study, but an improvement was seen in overall survival in both active treatment arms. ZD4054 was well tolerated.Trial registration: Clinicaltrials.gov NCT00090363.Take Home Message: Specific endothelin-A receptor antagonist ZD4054 was associated with a promising improvement in overall survival compared with placebo and was generally well tolerated in patients with pain-free or mildly symptomatic metastatic hormone-resistant prostate cancer. Phase 3 trials are underway. (Source: European Urology)

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Survival outcomes in men receiving androgen-deprivation therapy as primary or salvage treatment for localized or advanced prostate cancer: 20-year single-centre experience

BJU International — Tue, 21 Apr 2009 04:00:00 +0100

To evaluate the overall survival (OS) and disease-specific survival (DSS) in men receiving primary androgen-deprivation therapy (PADT) or salvage medical ADT (SADT) for prostate cancer. After Institutional Review Board approval, we retrospectively reviewed patients receiving ADT for prostate cancer between July 1987 and June 2007. Variables included age at diagnosis and ADT induction, race, PSA level before ADT, ADT schedule (continuous/intermittent), clinical/pathological stage, hormone-refractory prostate cancer (HRCP) status, PADT or SADT, and deaths. In all, 548 men were analysed. The mean age at diagnosis and ADT induction were 70.1 and 72.3 years, respectively, and 321 (58.6%) were African-American. The median PSA level before ADT was 16.3 ng/mL. ADT was administered continuously in ...

Promising Interim Results From Hybrigenics' Inecalcitol Phase II In Combination With Taxotere(R) For Hormone-Refractory Prostate Cancer

Health News from Medical News Today — Sun, 19 Apr 2009 08:00:00 +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 and specialised in protein interactions, today announces preliminary results from its phase II clinical trial of inecalcitol in patients wi (Source: Health News from Medical News Today)

Modern chemotherapy strategies for management of ‘Hormone Resistant Prostate Cancer’ (HRPC)—When should the urologist refer?

British Journal of Medical and Surgical Urology — Sat, 18 Apr 2009 16:04:06 +0100

This article addresses many of these practical issues. (Source: British Journal of Medical and Surgical Urology)

Editorial

British Journal of Medical and Surgical Urology — Sat, 18 Apr 2009 16:04:03 +0100

As the debate continues about the NICE guidelines on prostate cancer, it is good to see a well-written and well-researched review of the current status of chemotherapy in advanced disease (Persad and Bahl). For most of my professional lifetime, hormone refractory prostate cancer has been an area of therapeutic nihilism and this manuscript tries to put recent advances in context. It brings to the fore the importance of effective MDT working in streamlining and enhancing patient care. (Source: British Journal of Medical and Surgical Urology)

A Potential New Target For Treatment Of Hormone Refractory Prostate Cancer

Cancercompass News: Prostate Cancer — Sat, 18 Apr 2009 05:00:00 +0100

A new study identifies a protein that modifies the androgen receptor (AR) and influences its ability to regulate target genes linked with the progression of prostate cancer. The research, published by Cell Press in the April 7th issue of the journal Cancer Cell, may also drive creation of new strategies for the treatment of advanced prostate cancer that no longer responds to traditional anti-hormone therapies. The AR is an important mediator for the development and progression of prostate cancer, including the progression to the aggressive and often lethal androgen-independent form of the disease. "Androgen ablation therapy is the most common treatment for advanced prostate cancer," offers senior study author, Dr. Yun Qiu from the Univer... (Source: Cancercompass News: Prostate Cancer)

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Promising interim results from Hybrigenics' Inecalcitol Phase II in Combination with Taxotere(R) for Hormone-Refractory Prostate Cancer

Drugs.com - Clinical Trials — Fri, 17 Apr 2009 19:59:46 +0100

Hybrigenics will present interim results at the 2009 Meeting of the American Society of Clinical Oncology in Orlando, Florida on May 31st Paris, France, April 17th 2009 - Hybrigenics (ALHYG), a bio-pharmaceutical company listed on Alternext... (Source: Drugs.com - Clinical Trials)

Vitamin D Analog Safe in Prostate Cancer

MedPage Today Hematology/Oncology — Fri, 17 Apr 2009 18:17:02 +0100

TORONTO (MedPage Today) -- A vitamin D analog was well tolerated in combination with docetaxel (Taxotere) in men with hormone-refractory prostate cancer, the drug's developer said. (Source: MedPage Today Hematology/Oncology)

Clinical outcome of patients with docetaxel-resistant hormone-refractory prostate cancer treated with second-line cyclophosphamide-based metronomic chemotherapy

Medical Oncology — Tue, 14 Apr 2009 06:13:58 +0100

In this study, we evaluate the efficacy of cyclophosphamide (CP)-based metronomic chemotherapy in this patient population. Patients with metastatic HRPC with disease progression under docetaxel-based chemotherapy were eligible. The primary endpoint was prostate-specific antigen (PSA) response. Secondary endpoints were survival and toxicity. Low-dose CP (50 mg/d) and dexamethasone (1 mg/d) were administered orally in a metronomic manner. Treatment was continued until disease progression or intolerable side effects occurred. Seventeen patients were enrolled in this study. The median follow-up was 12 weeks (range: 4–60). Median age was 68 years (range: 42–85). Median PSA at study entry was 134 ng/ml (range: 46.0–6554). Nine patients had a PSA response (med...

Amplitude-modulated electromagnetic fields for the treatment of cancer: Discovery of tumor-specific frequencies and assessment of a novel therapeutic approach

Journal of Experimental and Clinical Cancer Research — Tue, 14 Apr 2009 04:00:00 +0100

CONCLUSION: Cancer-related frequencies appear to be tumor-specific and treatment with tumor-specific frequencies is feasible, well tolerated and may have biological efficacy in patients with advanced cancer. Trial registration: clinicaltrials.gov identifier NCT00805337 (Source: Journal of Experimental and Clinical Cancer Research)

New Way to Treat Hormone Refractory Prostate Cancer

Medical Headlines From Ivanhoe.com — Mon, 13 Apr 2009 05:00:00 +0100

There may be a new way to treat advanced forms of prostate cancer. Scientists from the University of Maryland School of Medicine have found a protein that modifies the androgen receptor (AR) and influences how it regulates target genes linked with the progression of prostate cancer. (Source: Medical Headlines From Ivanhoe.com)

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Drug Shows Activity In Men With Advanced Prostate Cancer

Cancercompass News: Prostate Cancer — Sat, 11 Apr 2009 05:00:00 +0100

NEW YORK -- A new multi-center study shows that an experimental drug lowers prostate specific antigen (PSA) levels - a marker for tumor growth - in men with advanced prostate cancer for whom traditional treatment options have failed. The study, led by researchers at Memorial Sloan-Kettering Cancer Center (MSKCC), is published today in Science Express, the online version of the journal Science. Most men with metastatic prostate cancer eventually build up resistance to the drugs that lower or block male hormones and develop a more aggressive form of the illness called castration-resistant prostate cancer (CRPC), or hormone-refractory disease. According to the study's findings, investigators studied two novel compounds, RD162 and MDV3100, a... (Source: Cancercompass News: Prostate Cancer)

Potential New Target For Treatment Of Hormone Refractory Prostate Cancer

Prostate News From Medical News Today — Fri, 10 Apr 2009 08:00:00 +0100

Tumor specific cytotoxicity and telomerase down-regulation in prostate cancer by autologous dendritic cells loaded with whole tumor cell antigens.

Urologic Oncology — Thu, 09 Apr 2009 23:00:00 +0100

CONCLUSIONS: Cytotoxic immune response to prostate cancer-associated antigens can be elicited in vitro in patients with HRPC using an allogeneic tumor cell-based strategy. DC-based active immunotherapy appears as an effective treatment method in the pre-clinical setting and further phase I/II trials are warranted. PMID: 19362861 [PubMed - as supplied by publisher] (Source: Urologic Oncology)

New drug shows promise in treating drug-resistant prostate cancer

UCLA Newsroom: Health Sciences — Thu, 09 Apr 2009 07:00:00 +0100

This study will assess MDV3100's effect on cancer survival and will take several years. While the preliminary results are promising, Sawyers said his laboratory will continue to seek further improvements in drug therapy for prostate cancer. "There were some men in the initial trial in which the drug didn't work at all, and we want to find out why," he said. "It may be because the drug is not potent enough to overcome resistance due to androgen receptor over-expression. Or it may be that the cancers in these men are not driven by the androgen receptor anymore. Also, there were men who initially received benefit from the drug but then relapsed, and their PSA levels came back up. We want to understand the mechanism of that relapse and to try to develop drugs that prevent tha...

A potential new target for treatment of hormone refractory prostate cancer

EurekAlert! - Cancer — Mon, 06 Apr 2009 04:00:00 +0100

(Cell Press) A new study identifies a protein that modifies the androgen receptor and influences its ability to regulate target genes linked with the progression of prostate cancer. The research, published by Cell Press in the April 7 issue of the journal Cancer Cell, may also drive creation of new strategies for the treatment of advanced prostate cancer that no longer responds to traditional anti-hormone therapies. (Source: EurekAlert! - Cancer)

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Suppression of mutant androgen receptors by flutamide

International Journal of Urology — Mon, 06 Apr 2009 04:00:00 +0100

Conclusions: Flutamide, with its suppressive effects on mutant androgen receptors, may be an alternative to conventional antiandrogens for hormone refractory prostate cancer. (Source: International Journal of Urology)

Replication-Competent Ad11p Vector (RCAd11p) Efficiently Transduces and Replicates in Hormone-Refractory Metastatic Prostate Cancer Cells

Human Gene Therapy — Thu, 02 Apr 2009 00:35:09 +0100

Human Gene Therapy Apr 2009, Vol. 20, No. 4: 361-373. (Source: Human Gene Therapy)

188Re-HEDP combined with capecitabine in hormone-refractory prostate cancer patients with bone metastases: a phase I safety and toxicity study

European Journal of Nuclear Medicine and Molecular Imaging — Wed, 25 Mar 2009 06:58:11 +0100

Conclusion Capecitabine may be safely used in combination with 188Re-HEDP in a dose of 2,500 mg/m2 per day and 37 MBq/kg, respectively. Efficacy will be further studied in a phase II study using these dosages. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00259-009-1119-8Authors Marnix G. E. H. Lam, University Medical Center Utrecht Department of Nuclear Medicine Utrecht The NetherlandsTjitske B. Bosma, University Medical Center Utrecht Department of Nuclear Medicine Utrecht The NetherlandsPeter P. van Rijk, University Medical Center Utrecht Department of Nuclear Medicine Utrecht The NetherlandsBernard A. Zonnenberg, UMC Utrecht Department of Internal Medicine Utrecht The Netherlands Journal European Journal of Nuclear Medicine and M...

PTEN genomic deletion is associated with p-Akt and AR signalling in poorer outcome, hormone refractory prostate cancer

The Journal of Pathology — Fri, 20 Mar 2009 00:00:00 +0100

PTEN haploinsufficiency is common in hormone-sensitive prostate cancer, though the incidence of genomic deletion and its downstream effects have not been elucidated in clinical samples of hormone refractory prostate cancer (HRPC). Progression to androgen independence is pivotal in prostate cancer and mediated largely by the androgen receptor (AR). Since this process is distinct from metastatic progression, we examined alterations of the PTEN gene in locally advanced recurrent, non-metastatic human HRPC tissues. Retrospective analyses of PTEN deletion status were correlated with activated downstream phospho-Akt (p-Akt) pathway proteins and with the androgen receptor. The prevalence of PTEN genomic deletions in transurethral resection samples of 59 HRPC patients with known clinical outcome w...

Health-Related Quality of Life in Patients with Hormone Refractory Prostate Cancer Receiving Gefitinib

Urologia Internationalis : Last 20 articles — Thu, 19 Mar 2009 15:02:38 +0100

Urol Int 2009;82:196-202 (DOI:10.1159/000200800) (Source: Urologia Internationalis : Last 20 articles)

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Characterization of circulating tumor cells by fluorescence in situ hybridization

Cytometry Part A — Wed, 18 Mar 2009 04:00:00 +0100

Tumor cells in blood of patients with metastatic carcinomas have been associated with poor survival prospects. Further characterization of these cells may provide further insights into the metastatic process. Circulating Tumor Cells (CTC) were enumerated in 7.5 mL of blood with the CellSearchTM system. After enumeration of Cytokeratin+, CD45-, nucleated cells, the cells are fixed in the cartridge while maintaining their original position. Cartridges were hybridized with FISH probes against the centromeric regions of chromosome 1, 7, 8, and 17. Next fluorescence images of the FISH probes of the previous identified CTC were acquired. Leukocytes surrounding the CTC were used as internal controls. The number of copies of chromosome 1, 7, 8, and 17 could be determined in 118 CTC containing bloo...

This Month in Adult Urology

The Journal of Urology — Wed, 18 Mar 2009 00:22:06 +0100

Neoadjuvant chemotherapy using taxane for tumors such as breast cancer generally results in a P0 status in up to 15% of patients. Because docetaxel has proven efficacy in patients with hormone refractory prostate cancer, a new nanoparticle colloidal formulation of nab-paclitaxel, which achieves higher concentrations in tumors than docetaxel, was evaluated in this phase II trial reported by Shepard et al (page 1672) from Cleveland, Ohio. Patients with locally advanced prostate cancer (stage T2b, T2c or T3) received 2 cycles of 150 mg/m2 nab-paclitaxel weekly for 3 weeks during each 4-week cycle followed by radical prostatectomy with bilateral lymphadenectomy. Although prostate specific antigen was undetectable in 94%, no patient achieved a complete pathological response (P0). Further studie...

Overcoming drug resistance in hormone- and drug-refractory prostate cancer cell line, PC-3 by docetaxel and gossypol combination.

Molecular Biology Reports — Sat, 14 Mar 2009 04:00:00 +0100

Authors: Cengiz E, Karaca B, Kucukzeybek Y, Gorumlu G, Gul MK, Erten C, Atmaca H, Uzunoglu S, Karabulut B, Sanli UA, Uslu R Drug resistance is a significant challenge of daily oncology practice. Docetaxel and gossypol both have antitumoral activity in hormone-refractory prostate cancer (HRPC). Our results revealed that docetaxel and gossypol were synergistically cytotoxic and apoptotic in PC-3 cells in a dose- and time-dependent manner. We further investigated the expression profiles of genes involved in drug resistance and metabolism with a Human Cancer Drug Resistance and Metabolism PCR Array((R)) (SuperArray). Six of the 84 genes that are known to regulate drug resistance, metabolism, cell cycle, DNA repair and oncogenesis were downregulated >/=3-fold change by the combination tr...

CTCs predict lower survival in hormone-refractory prostate cancer

MedWire News - Oncology — Tue, 10 Mar 2009 00:00:00 +0100

Patients with hormone-refractory prostate cancer who have circulating tumor cells have significantly reduced survival compared with other patients, Japanese study findings indicate. (Source: MedWire News - Oncology)

CTCs predict lower survival in hormone-refractory prostate cancer

MedWire News - Prostate Cancer — Tue, 10 Mar 2009 00:00:00 +0100

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Purine-rich element binding protein (PUR) [alpha] induces endoplasmic reticulum stress response, and cell differentiation pathways in prostate cancer cells

The Prostate — Sun, 08 Mar 2009 05:00:00 +0100

Following androgen ablation treatment for advanced prostate cancer, almost all men relapse after a period of initial response to therapy, which eventually is life threatening. We have previously found that purine-rich element binding protein, PUR[alpha], was significantly repressed in androgen-independent prostate cancer cell lines in comparison to an androgen-dependent line. Moreover, over-expressing PUR[alpha] in androgen-independent prostate cancer cells attenuated their cell proliferation. The aim of the studies described here was to uncover some of the mechanisms by which over-expression of PUR[alpha] attenuates cell proliferation.A set of common genes induced by over-expressing PUR[alpha] both in PC3 and LNCaP cells was analyzed by DNA microarray. The results were then validated util...

ASCO GU: Abiraterone Shows Activity in Hormone-Refractory Prostate Cancer

MedPage Today Meeting Coverage — Wed, 04 Mar 2009 18:19:18 +0100

ORLANDO (MedPage Today) -- A majority of patients with hormone-refractory prostate cancer had at least a 50% decrease in PSA levels when treated with the enzyme inhibitor abiraterone, according to data from a small clinical trial. (Source: MedPage Today Meeting Coverage)

Phase II trial of estramustine phosphate and oral etoposide in patients with hormone-refractory prostate cancer

Annals of Oncology — Wed, 25 Feb 2009 05:00:00 +0100

Conclusions: Estramustine plus etoposide is active and has a manageable safety profile in patients with HRPC. In asymptomatic patients with nonaggressive disease this combination could be useful to delay the start of more demanding treatments. (Source: Annals of Oncology)

No benefit with lycopene for hormone refractory prostate cancer

MedWire News - Oncology — Tue, 24 Feb 2009 00:00:00 +0100

Lycopene supplements for the treatment of advanced hormone refractory prostate cancer offer no clinically relevant benefit, German study findings indicate. (Source: MedWire News - Oncology)