Androgen Independent Prostate Cancer
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Marked improvement of cytotoxic effects induced by docetaxel on highly metastatic and androgen-independent prostate cancer cells by downregulating macrophage inhibitory cytokine-1
& S K Batra (Source: British Journal of Cancer AOP)
Source: British Journal of Cancer AOP - February 28, 2013 Category: Cancer & Oncology Authors: M MimeaultS L JohanssonS K Batra Source Type: research
A comparison of the effects of Angiotensin IV on androgen-dependent and androgen-independent prostate cancer cell lines
Conclusions:
These findings suggested that Angiotensin IV can modulate tumour cell proliferation in the early stage of androgen-dependent prostate cancer. The effect might be promoted by the change of the angiotensin receptor level. (Source: Journal of the Renin-Angiotensin-Aldosterone System : JRAAS)
Source: Journal of the Renin-Angiotensin-Aldosterone System : JRAAS - February 15, 2013 Category: Biomedical Science Authors: Dominska, K., Piastowska-Ciesielska, A. W., Pluciennik, E., Lachowicz-Ochedalska, A., Ochedalski, T. Tags: Articles Source Type: research
Protein kinase A (PKA) pathway is functionally linked to androgen receptor (AR) in the progression of prostate cancer.
CONCLUSION: Our study revealed a novel mechanism to precisely define the functional and clinical interrelationship between the cAMP/PKA pathway and AR signaling in the development of androgen-independent growth of CaPs and metastasis progression.
PMID: 23410945 [PubMed - as supplied by publisher] (Source: Urologic Oncology)
Source: Urologic Oncology - February 11, 2013 Category: Urology & Nephrology Authors: Sarwar M, Sandberg S, Abrahamsson PA, Persson JL Tags: Urol Oncol Source Type: research
The Vav3 oncogene enhances the malignant potential of prostate cancer cells under chronic hypoxia.
CONCLUSIONS: Our results demonstrate that Vav3 plays a crucial role in prostate cancer growth and malignant behavior, thus revealing a novel potential therapeutic target.
PMID: 23403204 [PubMed - as supplied by publisher] (Source: Urologic Oncology)
Source: Urologic Oncology - February 8, 2013 Category: Urology & Nephrology Authors: Hirai K, Nomura T, Yamasaki M, Inoue T, Narimatsu T, Chisato Nakada PD, Yoshiyuki Tsukamoto PD, Matsuura K, Sato F, Moriyama M, Mimata H Tags: Urol Oncol Source Type: research
Transcription Factor KLLN Inhibits Tumor Growth by AR Suppression, Induces Apoptosis by TP53/TP73 Stimulation in Prostate Carcinomas, and Correlates With Cellular Differentiation.
Conclusions:Our observations suggest that KLLN is a transcription factor directly regulating AR, TP53, and TP73 expression, with a role in prostate carcinogenesis. Loss of KLLN associates with high Gleason scores, suggesting that KLLN might be used as a potential prognostic marker for risk management and as a novel therapy target for advanced prostate carcinomas.
PMID: 23386643 [PubMed - as supplied by publisher] (Source: The Journal of Clinical Endocrinology and Metabolism)
Source: The Journal of Clinical Endocrinology and Metabolism - February 5, 2013 Category: Endocrinology Authors: Wang Y, Radhakrishnan D, He X, Peehl DM, Eng C Tags: J Clin Endocrinol Metab Source Type: research
MAGE-A11 Links Androgen Receptor Dimers [Gene Regulation]
In this report, we provide evidence how increased expression of MAGE-A11 during prostate cancer progression enhances AR signaling and prostate cancer growth. MAGE-A11 protein levels were highest in castration-recurrent prostate cancer. The cyclic AMP-induced increase in androgen-dependent and androgen-independent AR transcriptional activity correlated with an increase in MAGE-A11 and was inhibited by silencing MAGE-A11 expression. MAGE-A11 mediated synergistic AR transcriptional activity in LAPC-4 prostate cancer cells. The ability of MAGE-A11 to rescue transcriptional activity of complementary inactive AR mutants and prom...
Source: Journal of Biological Chemistry - January 18, 2013 Category: Chemistry Authors: Minges, J. T., Su, S., Grossman, G., Blackwelder, A. J., Pop, E. A., Mohler, J. L., Wilson, E. M. Tags: Molecular Bases of Disease Source Type: research
Truncated AR Splice Variants and Enzalutamide Resistance
In this study, we show that cells with AR gene rearrangements expressing both full-length and AR-Vs are androgen independent and enzalutamide resistant. However, selective knock-down of AR-V expression inhibited androgen-independent growth and restored responsiveness to androgens and antiandrogens. In heterogeneous cell populations, AR gene rearrangements marked individual AR-V–dependent cells that were resistant to enzalutamide. Gene expression profiling following knock-down of full-length AR or AR-Vs showed that AR-Vs drive resistance to AR-targeted therapy by functioning as constitutive and independent effectors of th...
Source: Cancer Research - January 16, 2013 Category: Cancer & Oncology Authors: Li, Y., Chan, S. C., Brand, L. J., Hwang, T. H., Silverstein, K. A. T., Dehm, S. M. Tags: Priority Reports Source Type: research
Integration of the Transcriptome and Glycome for Identification of Glycan Cell Signatures
by Sandra V. Bennun, Kevin J. Yarema, Michael J. Betenbaugh, Frederick J. Krambeck
Abnormalities in glycan biosynthesis have been conclusively linked to many diseases but the complexity of glycosylation has hindered the analysis of glycan data in order to identify glycoforms contributing to disease. To overcome this limitation, we developed a quantitative N-glycosylation model that interprets and integrates mass spectral and transcriptomic data by incorporating key glycosylation enzyme activities. Using the cancer progression model of androgen-dependent to androgen-independent Lymph Node Carcinoma of the Prostate (LNC...
Source: PLoS Computational Biology - January 10, 2013 Category: Biology Authors: Sandra V. Bennun et al. Source Type: research
Inhibition of Constitutive Aryl Hydrocarbon Receptor (AhR) Signaling Attenuates Androgen Independent Signaling and Growth in (C4-2) Prostate Cancer Cells.
Abstract
The aryl hydrocarbon receptor is a member of the basic-helix-loop-helix family of transcription factors. AhR mediates the biochemical and toxic effects of a number of polyaromatic hydrocarbons such as 2,3,7,8,-tetrachloro-dibenzo-p-dioxin (TCDD). AhR is widely known for regulating the transcription of drug metabolizing enzymes involved in the xenobiotic metabolism of carcinogens and therapeutic agents, such as cytochrome P450-1B1 (CYP1B1). Additionally, AhR has also been reported to interact with multiple signaling pathways during prostate development. Here we investigate the effect of sustained AhR signal...
Source: Biochemical Pharmacology - December 21, 2012 Category: Drugs & Pharmacology Authors: Tran C, Richmond O, Aaron L, Powell JB Tags: Biochem Pharmacol Source Type: research
Neural protein gamma-synuclein interacting with androgen receptor promotes human prostate cancer progression
Conclusions:
Our data suggest that SNCG may serve as a biomarker for predicting human prostate cancer progression and metastasis. It also may become as a novel target for biomedical therapy in advanced prostate cancer. (Source: BMC Cancer)
Source: BMC Cancer - December 11, 2012 Category: Cancer & Oncology Authors: Junyi ChenLi JiaoChuanliang XuYongwei YuZhensheng ZhangZheng ChangZhen DengYinghao Sun Source Type: research
Sensitivity and mechanisms of taxol-resistant prostate adenocarcinoma cells to Vernonia amygdalina extract.
This study shows that TAX-resistant PC-3 cells are sensitive to VA, perhaps explained by differential regulatory patterns of MAPK, c-Myc, AKT, and Pgp activities/expressions.
PMID: 23238229 [PubMed - as supplied by publisher] (Source: Experimental and Toxicologic Pathology)
Source: Experimental and Toxicologic Pathology - December 10, 2012 Category: Pathology Authors: Cameron KS, Howard CB, Izevbigie EB, Hill BJ, Tchounwou PB Tags: Exp Toxicol Pathol Source Type: research
Persistent androgen receptor-mediated transcription in castration-resistant prostate cancer under androgen-deprived conditions
The androgen receptor (AR) is a ligand-inducible transcription factor that mediates androgen action in target tissues. Upon ligand binding, the AR binds to thousands of genomic loci and activates a cell-type specific gene program. Prostate cancer growth and progression depend on androgen-induced AR signaling. Treatment of advanced prostate cancer through medical or surgical castration leads to initial response and durable remission, but resistance inevitably develops. In castration-resistant prostate cancer (CRPC), AR activity remains critical for tumor growth despite androgen deprivation. Although previous studies have fo...
Source: Nucleic Acids Research - November 24, 2012 Category: Research Authors: Decker, K. F., Zheng, D., He, Y., Bowman, T., Edwards, J. R., Jia, L. Tags: Gene Regulation, Chromatin and Epigenetics Source Type: research
Role of proprotein convertases in prostate cancer progression.
In this study, we investigated the functional redundancy of PCs in prostate cancer in the commonly used androgen-sensitive LNCaP and the androgen-independent DU145 human cell lines. Using a lentiviral-based shRNA delivery system, we examined in vitro and in vivo cell proliferation characteristics of knockdown cell lines for the endogenous PCs furin, PACE4, and PC7 in both cell lines. Of the three PCs, only PACE4 was essential to maintain a high-proliferative status, as determined in vitro using XTT proliferation assays and in vivo using tumor xenografts in nude mice. Furin knockdowns in both cell lines had no effects on ce...
Source: Neoplasia - November 1, 2012 Category: Cancer & Oncology Authors: Couture F, D'Anjou F, Desjardins R, Boudreau F, Day R Tags: Neoplasia Source Type: research
In vitro cytotoxicity, pharmacokinetics, tissue distribution, and metabolism of small-molecule protein kinase D inhibitors, kb-NB142-70 and kb-NB165-09, in mice bearing human cancer xenografts
Conclusions kb-NB142-70 and kb-NB165-09 were rapidly metabolized, and concentrations in tumor were lower than those required for in vitro
cytotoxicity. Replacement of the phenolic hydroxyl group with a methoxy group increased the plasma half-life of kb-NB165-09
2.3-fold over that of kb-NB142-70. Rapid metabolism in mice suggests that next-generation compounds will require further structural
modifications to increase potency and/or metabolic stability.
Content Type Journal ArticleCategory Original ArticlePages 1-14DOI 10.1007/s00280-012-2010-zAuthors
Jianxia Guo, Molecular Therapeutics and Drug Disc...
Source: Cancer Chemotherapy and Pharmacology - October 29, 2012 Category: Cancer & Oncology Tags: Cancer Chemotherapy and Pharmacology Source Type: research
Myeloid cell leukemia-1 is a key molecular target for mithramycin A-induced apoptosis in androgen-independent prostate cancer cells and a tumor xenograft animal model
Abstract: Mithramycin A (Mith) is a natural polyketide that has been used in multiple areas of research including apoptosis of various cancer cells. Here, we examined the critical role of Mith in apoptosis and its molecular mechanism in DU145 and PC3 prostate cancer cells and tumor xenografts. Mith decreased cell growth and induced apoptosis in DU145 and PC-3 cells. Myeloid cell leukemia-1 (Mcl-1) was over-expressed in both cell lines compared to RWPE1 cells. Mith inhibited Mcl-1 protein expression in both cells, but only altered Mcl-1 mRNA levels in PC-3 cells. We also found that Mith reduced Mcl-1 protein levels through ...
Source: Cancer Letters - October 11, 2012 Category: Cancer & Oncology Authors: Eun-Sun Choi, Ji-Youn Jung, Jin-Seok Lee, Jong-Hwan Park, Nam-Pyo Cho, Sung-Dae Cho Tags: Research Articles Source Type: research
PROS1 Is Elevated in Aggressive Prostate Cancer [Molecular Bases of Disease]
Androgen deprivation constitutes the principal therapy for advanced and metastatic prostate cancers. However, this therapeutic intervention usually results in the transition to a more aggressive androgen-independent prostate cancer. The elucidation of molecular alterations during the progression to androgen independence is an integral step toward discovering more effective targeted therapies. With respect to identifying crucial mediators of this transition, we compared the proteomes of androgen-independent (PC3, DU145, PPC1, LNCaP-SF, and 22Rv1) and androgen-dependent (LNCaP and VCaP) and/or normal prostate epithelial (RWP...
Source: Journal of Biological Chemistry - October 5, 2012 Category: Chemistry Authors: Saraon, P., Musrap, N., Cretu, D., Karagiannis, G. S., Batruch, I., Smith, C., Drabovich, A. P., Trudel, D., van der Kwast, T., Morrissey, C., Jarvi, K. A., Diamandis, E. P. Tags: Genomics and Proteomics Source Type: research
Xenotransplanted Human Prostate Carcinoma (DU145) Cells Develop into Carcinomas and Cribriform Carcinomas: Ultrastructural Aspects.
Abstract
Androgen-independent, human prostate carcinoma cells (DU145) develop into solid, carcinomatous xenotransplants on the diaphragm of nu/nu mice. Tumors encompass at least two poorly differentiated cell types: a rapidly dividing, eosinophilic cell comprises the main cell population and a few, but large basophilic cells able to invade the peritoneal stroma, the muscular tissue, lymph vessels. Poor cell contacts, intracytoplasmic lumina, and signet cells are noted. Lysosomal activities are reflected by entoses and programmed cell deaths forming cribriform carcinomas. In large tumors, degraded cells may align wi...
Source: Ultrastructural Pathology - October 1, 2012 Category: Pathology Authors: Gilloteaux J, Jamison JM, Neal DR, Summers JL, Taper HS Tags: Ultrastruct Pathol Source Type: research
Krüppel-like factor 8 is a novel androgen receptor co-activator in human prostate cancer.
Conclusion:The results demonstrate that KLF8 is a novel AR transcriptional co-activator that is overexpressed in PCa and may play a role in progression of hormone-refractory PCa.
PMID: 23023312 [PubMed - as supplied by publisher] (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - October 1, 2012 Category: Drugs & Pharmacology Authors: He HJ, Gu XF, Xu WH, Yang DJ, Wang XM, Su Y Tags: Acta Pharmacol Sin Source Type: research
MiRNA Targets of Prostate Cancer
Prostate cancer (PC) is the most prevalent strain of cancer in men, but it is often slow-acting or undetected. Common diagnostic tools for PC include prostate biopsy and consequent analysis by the Gleason scoring of the tissue samples, as well as tests for the presence and levels of prostate-specific antigens. Common treatments for androgen-dependent PC include prostatectomy or irradiation, which can be invasive and significantly lower the patient’s quality of life. Alternative treatments exist, such as androgen ablation therapy, which, though effective, causes relapse into androgen-independent PC, which is far more ...
Source: Springer protocols feed by Genetics/Genomics - September 26, 2012 Category: Genetics & Stem Cells Source Type: news
Receptor-based Discovery of a Novel AR Antagonist [Gene Regulation]
Hormonal therapies, mainly combinations of anti-androgens and androgen deprivation, have been the mainstay treatment for advanced prostate cancer because the androgen-androgen receptor (AR) system plays a pivotal role in the development and progression of prostate cancers. However, the emergence of androgen resistance, largely due to inefficient anti-hormone action, limits the therapeutic usefulness of these therapies. Here, we report that 6-(3,4-dihydro-1H-isoquinolin-2-yl)-N-(6-methylpyridin-2-yl)nicotinamide (DIMN) acts as a novel anti-androgenic compound that may be effective in the treatment of both androgen-dependent...
Source: Journal of Biological Chemistry - August 31, 2012 Category: Chemistry Authors: Song, C.-H., Yang, S. H., Park, E., Cho, S. H., Gong, E.-Y., Khadka, D. B., Cho, W.-J., Lee, K. Tags: Gene Regulation Source Type: research
Potential Establishment of Lung Metastatic Xenograft Model of Androgen Receptor-positive and Androgen-independent Prostate Cancer (C4-2B)
Conclusion:
We have shown the potential establishment of a mouse lung metastatic xenograft model of androgen receptor-positive and androgen-independent C4-2B PCa tumor. However, the present model requires improvement to be a more reproducible, accurate and complete experimental model. Additional study is necessary to verify the relationship between metastasis and CTCs. (Source: Urology)
Source: Urology - August 22, 2012 Category: Urology & Nephrology Authors: Fukashi Yamamichi, Takayuki Matsuoka, Katsumi Shigemura, Masato Kawabata, Toshiro Shirakawa, Masato Fujisawa Tags: Basic and Translational Science Source Type: research
Poly[3-(3, 4-dihydroxyphenyl) glyceric acid] from Comfrey exerts anti-cancer efficacy against human prostate cancer via targeting androgen receptor, cell cycle arrest and apoptosis
The major obstacles in human prostate cancer (PCA) treatment are the development of resistance to androgen ablation therapy leading to hormone-refractory state and the toxicity associated with chemotherapeutic drugs. Thus, the identification of additional non-toxic agents that are effective against both androgen-dependent and androgen-independent PCA is needed. In the present study, we investigated the efficacy of a novel phytochemical poly[3-(3, 4-dihydroxyphenyl)glyceric acid] (p-DGA) from Caucasian species of comfrey (Symphytum caucasicum) and its synthetic derivative syn-2, 3-dihydroxy-3-(3, 4-dihydroxyphenyl) propioni...
Source: Carcinogenesis - August 13, 2012 Category: Cancer & Oncology Authors: Sangeeta, S., Gagan, D., Kumaraguruparan, R., Komal, R., Vakhtang, B., Maia, M., Lali, G., Lela, A., Karen, M., Kyriakos, P., Chapla, A., Rajesh, A. Tags: Original Manuscript Source Type: research
An integrated approach to identify normal tissue expression of targets for antibody drug conjugates: case study of TENB2
Conclusions and implications: Our findings provide the anatomical location and biological interpretation of target‐mediated clearance of anti‐TENB2 antibodies and corresponding drug conjugates. Further investigations may be beneficial in addressing the relative contributions to ADC disposition from antigen expression in both normal and pathological tissues.
© 2012 Genentech, Inc. British Journal of Pharmacology © 2012 The British Pharmacological Society (Source: British Journal of Pharmacology)
Source: British Journal of Pharmacology - August 13, 2012 Category: Drugs & Pharmacology Authors: C. Andrew Boswell, Eduardo E. Mundo, Ron Firestein, Crystal Zhang, Weiguang Mao, Herman Gill, Cynthia Young, Nina Ljumanovic, Shannon Stainton, Sheila Ulufatu, Aimee Fourie, Katherine R. Kozak, Reina Fuji, Paul Polakis, Leslie A. Khawli, Kedan Lin Source Type: research
Androgen-independent prostate cancer cells circumvent EGFR inhibition by overexpression of alternative HER receptors and ligands.
Androgen-independent prostate cancer cells circumvent EGFR inhibition by overexpression of alternative HER receptors and ligands.
Int J Oncol. 2012 Sep;41(3):1128-38
Authors: Carrión-Salip D, Panosa C, Menendez JA, Puig T, Oliveras G, Pandiella A, De Llorens R, Massaguer A
Abstract
The deregulation of the epidermal growth factor receptor (EGFR) pathway plays a major role in the pathogenesis of prostate cancer (PCa). However, therapies targeting EGFR have demonstrated limited effectiveness in PCa. A potential mechanism to overcome EGFR blockade in cancer cells is the autocrine activa...
Source: International Journal of Oncology - August 6, 2012 Category: Cancer & Oncology Authors: Carrión-Salip D, Panosa C, Menendez JA, Puig T, Oliveras G, Pandiella A, De Llorens R, Massaguer A Tags: Int J Oncol Source Type: research
Immunohistochemical analysis of gastrin-releasing peptide receptor (GRPR) and possible regulation by estrogen receptor βcx in human prostate carcinoma.
Abstract
Gastrin-releasing peptide (GRP) belongs to the family of bombesin-like peptides. GRP was demonstrated to stimulate the proliferation and invasiveness of androgen-independent prostate carcinoma. GRP mediates its action through the membrane-bound receptor, GRP receptor (GRPR), which is characterized by a high-affinity binding for both GRP and bombesin. In human prostate cancer tissue, GRPR mRNA was reported to be detectable in more than 90% but its immunolocalizaition has not been reported. Therefore, in this study we immunolocalized GRPR in 51 human prostate cancer cases and correlated the findings with sev...
Source: Neoplasma - August 6, 2012 Category: Cancer & Oncology Authors: Nagasaki S, Nakamura Y, Maekawa T, Akahira J, Miki Y, Suzuki T, Ishidoya S, Arai Y, Sasano H Tags: Neoplasma Source Type: research
Quercetin increased the antiproliferative activity of green tea polyphenol (-)-epigallocatechin gallate in prostate cancer cells.
Abstract
We previously demonstrated that 50% of (-)-epigallocatechin gallate (EGCG) was present in methylated form (4″-MeEGCG) in human prostate tissue, which is less bioactive. We therefore investigated whether quercetin, a natural inhibitor of catechol-O-methyl transferase (COMT), will inhibit EGCG methylation leading to enhanced antiproliferative activity of EGCG in prostate cancer cells. Incubation with both quercetin and EGCG for 2 h increased the cellular concentrations of EGCG by 4- to 8-fold and 6- to 10-fold in androgen-independent PC-3 cells and androgen-dependent LNCaP cells, respectively. Concurrently...
Source: Nutrition and Cancer - August 6, 2012 Category: Cancer & Oncology Authors: Wang P, Heber D, Henning SM Tags: Nutr Cancer Source Type: research
Diet-induced hyperinsulinemia accelerates growth of androgen-independent PC-3 cells in vitro.
Abstract
We investigated the effect of insulin and diet-induced hyperinsulinemia on the growth of the PC-3 cells in vitro and discerned the growth promoting effect of insulin in the androgen-independent cells. Sprague-Dawley rats were kept on a high-fat diet for 4 wk for the induction of insulin resistance and hyperinsulinemia. Insulin alone or serum of the rats kept on either normal-pellet diet or high-fat diet was used to stimulate the serum-starved PC-3 cells growth in culture. S961, a high-affinity insulin-receptor antagonist, was used to confirm the insulin-mediated effects. Significant impairment in the gluco...
Source: Nutrition and Cancer - August 6, 2012 Category: Cancer & Oncology Authors: Vikram A, Jena G Tags: Nutr Cancer Source Type: research
Inhibition kinetics and regulation of sphingosine kinase 1 expression in prostate cancer cells: Functional differences between sphingosine kinase 1a and 1b.
Abstract
Sphingosine kinase 1 catalyses the formation of the bioactive lipid, sphingosine 1-phosphate and is a target for anti-cancer agents. We demonstrate here that 2-(p-hydroxyanilino)-4-(p-chlorophenyl)thiazole (SKi, also referred to as SKI-II), FTY720 (Fingolimod), and (S)-FTY720 vinylphosphonate inhibit sphingosine kinase 1 activity with distinct kinetics, indicating that these compounds exhibit different binding modalities with sphingosine kinase 1. Thus, SKi is a mixed inhibitor of sphingosine and ATP binding, whereas FTY720 is competitive with sphingosine and uncompetitive with ATP, and (S)-FTY720 vinylpho...
Source: The International Journal of Biochemistry and Cell Biology - August 4, 2012 Category: Biochemistry Authors: Lim KG, Tonelli F, Berdyshev E, Gorshkova I, Leclercq T, Pitson SM, Bittman R, Pyne S, Pyne NJ Tags: Int J Biochem Cell Biol Source Type: research
Protein kinase A-mediated phosphorylation of RhoA on serine 188 triggers the rapid induction of a neuroendocrine-like phenotype in prostate cancer epithelial cells.
Abstract
Whilst androgen ablation therapy is used to treat locally advanced or metastatic forms of prostate cancer, side-effects can include the emergence of an androgen-independent neuroendocrine cell population which is associated with poor prognosis. Here we have examined how cyclic AMP elevation regulates early events in the neuroendocrine differentiation process. We demonstrate that selective activation of protein kinase A is necessary and sufficient for cyclic AMP (cAMP) elevation to rapidly promote a neuroendocrine phenotype in LNCaP cells independent of de novo protein synthesis. Furthermore, the effects of...
Source: Cellular Signalling - August 1, 2012 Category: Cytology Authors: Jones SE, Palmer TM Tags: Cell Signal Source Type: research
Effect of HUVEC apoptosis inducing proteinase from Vipera lebetina venom (VLAIP) on viability of cancer cells and on platelet aggregation.
Abstract
Three cancer cell lines, the human androgen independent prostate cancer PC-3, androgen dependent LNCaP prostate cancer and human chronic myeloid leukaemia cell line K-562, were treated with Sephadex G-100 sf fractions of Vipera lebetina venom and with HUVEC apoptosis inducing heterodimeric metalloproteinase (VLAIP) from the same venom. The venom was separated into nine fractions using size-exclusion chromatography on Sephadex G-100 sf. The effect of V. lebetina venom gel filtration fractions on the viability of studied cancer cells was different: high molecular mass fractions were the most effective on PC-...
Source: Toxicon - July 31, 2012 Category: Toxicology Authors: Samel M, Trummal K, Siigur E, Siigur J Tags: Toxicon Source Type: research
NGF/γ-IFN Inhibits Androgen-Independent Prostate Cancer and Reverses Androgen Receptor Function Through Downregulation of FGFR2 and Decrease in Cancer Stem Cells
Stem Cells and Development , Vol. 0, No. 0. (Source: Stem Cells and Development)
Source: Stem Cells and Development - July 30, 2012 Category: Stem Cells Tags: article Source Type: research
Role of JNK and PTEN in prostate cancer [Cell Biology]
The c-Jun NH2-terminal kinase (JNK) signal transduction pathway is implicated in cancer, but the role of JNK in tumorigenesis is poorly understood. Here, we demonstrate that the JNK signaling pathway reduces the development of invasive adenocarcinoma in the phosphatase and tensin homolog (Pten) conditional deletion model of prostate cancer. Mice with JNK deficiency in the prostate epithelium (ΔJnk ΔPten mice) develop androgen-independent metastatic prostate cancer more rapidly than control (ΔPten) mice. Similarly, prevention of JNK activation in the prostate epithelium (ΔMkk4 ΔMkk7 ΔPten mice) causes rapid developmen...
Source: Proceedings of the National Academy of Sciences - July 24, 2012 Category: Science Authors: Hubner, A., Mulholland, D. J., Standen, C. L., Karasarides, M., Cavanagh–Kyros, J., Barrett, T., Chi, H., Greiner, D. L., Tournier, C., Sawyers, C. L., Flavell, R. A., Wu, H., Davis, R. J. Tags: Biological Sciences Source Type: research
Perspectives on mTOR Inhibitors for Castration-Refractory Prostate Cancer.
This article discusses many of the mechanisms involved, specifically in the context of prostate cancer. In addition, we present an overview of preliminary data on the activity of mTOR inhibitors and on the key steps to evaluate which of these compounds are most suitable for the treatment of prostate cancer. Particular emphasis is also placed on the development of novel perspectives to improve the poor prognosis of patients with CRPC.
PMID: 22831278 [PubMed - as supplied by publisher] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - July 24, 2012 Category: Cancer & Oncology Authors: Burgio SL, Fabbri F, Seymour IJ, Zoli W, Amadori D, De Giorgi U Tags: Curr Cancer Drug Targets Source Type: research
Mifepristone Inhibits GRβ Coupled Prostate Cancer Cell Proliferation
Conclusions:
Results suggest that patients with a primary tumor that expresses GRβ and ARA70β may benefit from mifepristone. (Source: The Journal of Urology)
Source: The Journal of Urology - July 23, 2012 Category: Urology & Nephrology Authors: Martin Ligr, Yirong Li, Susan K. Logan, Samir Taneja, Jonathan Melamed, Hebert Lepor, Michael J. Garabedian, Peng Lee Tags: Investigative Urology Source Type: research
The Significance of Ral in Human Cancer
RalA and RalB are small GTPases that support malignant development and progression in experimental models of bladder, prostate, and squamous cancer. However, demonstration of their clinical relevance in human tumors remains lacking. Here, we developed tools to evaluate Ral protein expression, activation, and transcriptional output and evaluated their association with clinicopathologic parameters in common human tumor types. To evaluate the relevance of Ral activation and transcriptional output, we correlated RalA and RalB activation with the mutational status of key human bladder cancer genes. We also identified and evalua...
Source: Cancer Research - July 15, 2012 Category: Cancer & Oncology Authors: Smith, S. C., Baras, A. S., Owens, C. R., Dancik, G., Theodorescu, D. Tags: Integrated Systems and Technologies Source Type: research
Effect of diallyl disulfide on insulin-like growth factor signaling molecules involved in cell survival and proliferation of human prostate cancer cells in vitro and in silico approach through docking analysis
Conclusion: The present investigation showed downregulation of Akt and a concomitant increase in apoptosis in DADS treated prostate cancer cells. Since inhibition of this Akt pathway by DADS leads to inhibition in cancer cell progression, it is highly suggested that DADS has the potential use as a therapy for prostate cancer. (Source: Phytomedicine)
Source: Phytomedicine - June 27, 2012 Category: Drugs & Pharmacology Authors: R. Arunkumar, G. Sharmila, P. Elumalai, K. Senthilkumar, S. Banudevi, D.N. Gunadharini, C.S. Benson, P. Daisy, J. Arunakaran Tags: Oncology and Hematology Source Type: research
Neuropeptide-inducible upregulation of proteasome activity precedes nuclear factor kappa B activation in androgen-independent prostate cancer cells
Conclusions:
Our results support evidence for a direct mechanistic connection between the NPs and NFkappaB/proteasome signaling pathways, with a distinct NP-induced profile in the more aggressive AI cancer state. (Source: Cancer Cell International)
Source: Cancer Cell International - June 20, 2012 Category: Cancer & Oncology Authors: Anna PatrikidouPanagiotis VlachostergiosIoannis VoutsadakisEleana HatzidakiRosalia ValeriChariklia DestouniEffie ApostolouChristos Papandreou Source Type: research
Transcriptional Activation by Truncated AR Variants [Gene Regulation]
Synthesis of truncated androgen receptor (AR) splice variants has emerged as an important mechanism of prostate cancer (PCa) resistance to AR-targeted therapy and progression to a lethal castration-resistant phenotype. However, the precise role of these factors at this stage of the disease is not clear due to loss of multiple COOH-terminal AR protein domains, including the canonical nuclear localization signal (NLS) in the AR hinge region. Despite loss of this NLS, we show that diverse truncated AR variant species have a basal level of nuclear localization sufficient for ligand-independent transcriptional activity. Whereas...
Source: Journal of Biological Chemistry - June 1, 2012 Category: Chemistry Authors: Chan, S. C., Li, Y., Dehm, S. M. Tags: Molecular Bases of Disease Source Type: research
Contrasted effects of the multitarget TKi vandetanib on docetaxel-sensitive and docetaxel-resistant prostate cancer cell lines.
CONCLUSION: Present results suggest that vandetanib should not be associated with docetaxel in treatment-naive or docetaxel-resistant prostate cancer (CaP). The use of high-dose vandetanib alone may warrant further investigation in patients with docetaxel-resistant AIPC overexpressing VEGFR/EGFR pathways.
PMID: 22608542 [PubMed - as supplied by publisher] (Source: Urologic Oncology)
Source: Urologic Oncology - May 17, 2012 Category: Urology & Nephrology Authors: Guérin O, Etienne-Grimaldi MC, Monteverde M, Sudaka A, Brunstein MC, Formento P, Lattanzio L, Maffi M, Tonissi F, Ortholan C, Pagès G, Fischel JL, Lo Nigro C, Merlano M, Milano G Tags: Urol Oncol Source Type: research
α-Santalol, a derivative of sandalwood oil, induces apoptosis in human prostate cancer cells by causing caspase-3 activation
In conclusion, the present study reveals the apoptotic effects of α-santalol in inhibiting the growth of human prostate cancer cells. (Source: Phytomedicine)
Source: Phytomedicine - May 9, 2012 Category: Drugs & Pharmacology Authors: Ajay Bommareddy, Brittny Rule, Adam L. VanWert, Sreevidya Santha, Chandradhar Dwivedi Tags: Oncology and Hematology Source Type: research
Expression and function of nuclear receptor co-activator 4: evidence of a potential role independent of co-activator activity.
Abstract
Nuclear receptor coactivator 4 (NcoA4), also known as androgen receptor-associated protein 70 (ARA70), was initially discovered as a component of Ret-Fused Gene expressed in a subset of papillary thyroid carcinomas. Subsequent studies have established NcoA4 as a coactivator for a variety of nuclear receptors, including peroxisome proliferator activated receptors α and γ, and receptors for steroid hormones, vitamins D and A, thyroid hormone, and aryl hydrocarbons. While human NcoA4 has both LXXLL and FXXLF motifs that mediate p160 coactivator nuclear receptor interactions, this ubiquitously expressed prot...
Source: Cellular and Molecular Life Sciences : CMLS - May 5, 2012 Category: Cytology Authors: Kollara A, Brown TJ Tags: Cell Mol Life Sci Source Type: research
Deprivation of arginine by recombinant human arginase in prostate cancer cells
Conclusion:
rhArg causes significant cytotoxicity in LNCaP, DU-145 and PC-3 prostate cancer cells which all demonstrate decreased OCT expression. Inhibition of mTOR manifested by hypophosphorylation of 4E-BP1 suggests autophagy is involved as alternative cell death mechanism. rhArg demonstrates a promising novel agent for prostate cancer treatment. (Source: Journal of Hematology and Oncology)
Source: Journal of Hematology and Oncology - April 30, 2012 Category: Hematology Authors: Eddy HsuehStephanie KnebelWai-Hung LoYun-Chung LeungPaul Ning-Man ChengChung-Tsen Hsueh Source Type: research
Chemopreventive Effects of Rubus coreanus Miquel on Prostate Cancer.
Abstract
The growing incidence of prostate cancer and the traditional use of Rubus coreanus Miquel (RCM) for prostate health led us to compare RCM extracts and to test their efficacy in inhibiting the growth of prostate cancer cells differing in androgen dependency. Ethanol extracts of unripe RCM (EUR) were more effective in reducing cell viability than water extracts or ripe RCM. EUR-induced growth inhibition, as indicated by significant reductions in numbers of proliferating cells and decreases in the protein levels of proliferating cell nuclear antigen (PCNA), cyclin D1 and CDK4, was greater in the androgen-depe...
Source: Bioscience, Biotechnology, and Biochemistry - April 7, 2012 Category: Biochemistry Authors: Kim Y, Kim J, Lee SM, Lee HA, Park S, Kim Y, Kim JH Tags: Biosci Biotechnol Biochem Source Type: research
Chemoaffinity capture of pre‐targeted prostate cancer cells with magnetic beads
CONCLUSIONSThis methodology for the detection, isolation, and culture of PCTCs from peripheral blood can serve as an effective tool for the detection of metastatic prostate cancer, treatment monitoring, and the development of personalized therapy based on the responsiveness of PCTCs to chemotherapeutic strategies. Prostate © 2012 Wiley Periodicals, Inc. (Source: The Prostate)
Source: The Prostate - April 5, 2012 Category: Urology & Nephrology Authors: Lisa Y. WuTiancheng LiuMark R. HopkinsWilliam C. DavisClifford E. Berkman Tags: Review Article Source Type: research
FDA grants priority review of aflibercept (Zaltrap) for metastatic colorectal cancer
Source: PharmaTimes
Area: News
The FDA has granted priority review of the Biologics License Application for aflibercept (Zaltrap) in combination with an irinotecan-fluoropyrimidine-based regimen in patients with metastatic colorectal cancer (mCRC) previously treated with an oxaliplatin-containing regimen. The filing was based on the phase III VELOUR study which compared aflibercept in combination with the FOLFIRI regimen versus FOLFIRI plus placebo, which met its primary endpoint of improving overall survival in the second-line treatment of mCRC. However the phase III VENICE trial evaluating the addition of aflibercept to...
Source: NeLM - News - April 5, 2012 Category: Drugs & Pharmacology Source Type: news
Chemoaffinity capture of pre‐targeted prostate cancer cells with magnetic beads
CONCLUSIONSThis methodology for the detection, isolation, and culture of PCTCs from peripheral blood can serve as an effective tool for the detection of metastatic prostate cancer, treatment monitoring, and the development of personalized therapy based on the responsiveness of PCTCs to chemotherapeutic strategies. Prostate © 2012 Wiley Periodicals, Inc. (Source: The Prostate)
Source: The Prostate - April 4, 2012 Category: Urology & Nephrology Authors: Lisa Y. Wu, Tiancheng Liu, Mark R. Hopkins, William C. Davis, Clifford E. Berkman Tags: Review Article Source Type: research
Targeted Antivascular Therapy with the Apolipoprotein(a) Kringle V, rhLK8, Inhibits the Growth and Metastasis of Human Prostate Cancer in an Orthotopic Nude Mouse Model.
In conclusion, these results suggest that targeting the tumor microenvironment with the antivascular effect of rhLK8 combined with conventional cytotoxic chemotherapy could be a new and effective approach in the treatment of androgen-independent prostate cancer and their metastases.
PMID: 22577348 [PubMed - in process] (Source: Neoplasia)
Source: Neoplasia - April 1, 2012 Category: Cancer & Oncology Authors: Lee HJ, Yu HK, Papadopoulos JN, Kim SW, He J, Park YK, Yoon Y, Kim JS, Kim SJ Tags: Neoplasia Source Type: research
Aggressive Prostate Cancer Tumors Controlled By Botanical Formula
A study by researchers at Indiana University, Methodist Research Institute that is published in The International Journal of Oncology reveals that a non-toxic, botanical orally administered formula controls aggressive human prostate tumors in mice. The peer-reviewed pre-clinical in vivo study demonstrated that the prostate formula substantially suppresses tumor growth in aggressive, hormone-refractory (androgen-independent) human prostate cancer cells without any toxic side effects, even when administered at high doses... (Source: Health News from Medical News Today)
Source: Health News from Medical News Today - March 29, 2012 Category: Consumer Health News Tags: Prostate / Prostate Cancer Source Type: news
Prostate Cancer And Androgen Suppression
Androgen suppression - the inhibition of testosterone and other male hormones - is a routine therapy for prostate cancer. Unfortunately, it can dramatically reduce the quality of patients' sex lives and, more importantly, lead to cancer recurrence in a more deadly androgen-independent form. A new paper combining mathematical modeling with clinical data validates a different approach: cycling patients on and off treatment. Such intermittent androgen suppression alleviates most unwanted side effects and postpones the development of resistance to treatment... (Source: Health News from Medical News Today)
Source: Health News from Medical News Today - March 28, 2012 Category: Consumer Health News Tags: Prostate / Prostate Cancer Source Type: news
Carnosic acid modulates Akt/IKK/NF-κB signaling by PP2A and induces intrinsic and extrinsic pathway mediated apoptosis in human prostate carcinoma PC-3 cells
This study investigates the efficacy of carnosic acid (CA), a polyphenolic diterpene, isolated from the plant rosemary (Rosemarinus officinalis), on androgen-independent human prostate cancer PC-3 cells. CA induced anti-proliferative effects in PC-3 cells in a concentration-
and time-dependent manner, which was due to apoptotic induction as evident from flow-cytometry, DNA laddering and TUNEL assay.
Apoptosis was associated with the activation of caspase-8, -9, -3 and -7, increase in Bax:Bcl-2 ratio, release of cytochrome-c
and decrease in expression of inhibitor of apoptosis (IAP) family of proteins. Apoptosis was atte...
Source: Apoptosis - March 28, 2012 Category: Molecular Biology Tags: Apoptosis Source Type: research

