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Sample records for androgen-independent prostate cancer

  1. Development of the VCaP Androgen Independent Model of Prostate Cancer

    OpenAIRE

    Loberg, Robert D; St. John, Lauren N; Day, LaShon L.; Neeley, Chris K; Kenneth J. Pienta

    2006-01-01

    Prostate epithelial cell growth is dependent on the presence of androgens and the transition of prostate cancer to an androgen independent phenotype results in a highly aggressive, currently incurable cancer. We have developed a new preclinical model of androgen independent prostate cancer derived from the VCaP prostate cancer epithelial cell line. VCaP cells were subcutaneously implanted and serially passaged in castrated male SCID mice. Androgen independence was confirmed by WST-1 (a tetraz...

  2. LEF1 in androgen-independent prostate cancer: regulation of androgen receptor expression, prostate cancer growth and invasion

    OpenAIRE

    Li, Yirong; Wang, Longgui; Zhang, Miao; Melamed, Jonathan; Liu, Xiaomei; Reiter, Robert; Wei, Jianjun; Peng, Yi; Zou, Xuanyi; Pellicer, Angel; Garabedian, Michael J.; Ferrari, Anna; Lee, Peng

    2009-01-01

    A major obstacle in treating prostate cancer is the development of androgen-independent disease. In this study, we examined LEF1 expression in androgen-independent cancer as well as its regulation of androgen receptor (AR) expression, prostate cancer growth and invasion in androgen-independent prostate cancer cells. Affymetrix microarray analysis of LNCaP and LNCaP-AI (androgen-independent variant LNCaP) cells revealed 100-fold increases in LEF1 expression in LNCaP-AI cells. We showed that LE...

  3. Expression of a hyperactive androgen receptor leads to androgen-independent growth of prostate cancer cells.

    Science.gov (United States)

    Hsieh, Chen-Lin; Cai, Changmeng; Giwa, Ahmed; Bivins, Aaronica; Chen, Shao-Yong; Sabry, Dina; Govardhan, Kumara; Shemshedini, Lirim

    2008-07-01

    Cellular changes that affect the androgen receptor (AR) can cause prostate cancer to transition from androgen dependent to androgen independent, which is usually lethal. One common change in prostate tumors is overexpression of the AR, which has been shown to lead to androgen-independent growth of prostate cancer cells. This led us to hypothesize that expression of a hyperactive AR would be sufficient for androgen-independent growth of prostate cancer cells. To test this hypothesis, stable lune cancer prostate (LNCaP) cell lines were generated, which express a virion phosphoprotein (VP)16-AR hybrid protein that contains full-length AR fused to the strong viral transcriptional activation domain VP16. This fusion protein elicited as much as a 20-fold stronger transcriptional activity than the natural AR. Stable expression of VP16-AR in LNCaP cells yielded androgen-independent cell proliferation, while under the same growth conditions the parental LNCaP cells exhibited only androgen-dependent growth. These results show that expression of a hyperactive AR is sufficient for androgen-independent growth of prostate cancer cells. To study the molecular basis of this enhanced growth, we measured the expression of soluble guanylyl cyclase-alpha1 (sGCalpha1), a subunit of the sGC, an androgen-regulated gene that has been shown to be involved in prostate cancer cell growth. Interestingly, the expression of sGCalpha1 is androgen independent in VP16-AR-expressing cells, in contrast to its androgen-induced expression in control LNCaP cells. RNA(I)-dependent inhibition of sGCalpha1 expression resulted in significantly reduced proliferation of VP16-AR cells, implicating an important role for sGCalpha1 in the androgen-independent growth of these cells. PMID:18469090

  4. Oncogenic herpesvirus HHV-8 promotes androgen-independent prostate cancer growth.

    Science.gov (United States)

    Mygatt, Justin G; Singhal, Adit; Sukumar, Gauthaman; Dalgard, Clifton L; Kaleeba, Johnan A R

    2013-09-15

    Mechanisms underlying progression to androgen-independent prostate cancer following radical ablation therapy remain poorly defined. Although intraprostatic infections have been highlighted as potential cofactors, pathogen influences on pathways that support tumor regrowth are not known. To explore this provocative concept, we derived androgen-sensitive and -insensitive prostate epithelial cells persistently infected with human herpesvirus 8 (HHV-8), an oncogenic herpesvirus that has been detected in normal prostate epithelium, prostate adenocarcinoma, and biologic fluids of patients with prostate cancer, to explore its effects on transition to hormone-refractory disease. Strikingly, we found that HHV-8 infection of androgen-sensitive prostate cancer cells conferred the capacity for androgen-independent growth. This effect was associated with altered expression and transcriptional activity of the androgen receptor (AR). However, HHV-8 infection bypassed AR signaling by promoting enhancer of zeste homolog 2 (EZH2)-mediated epigenetic silencing of tumor-suppressor genes, including MSMB and DAB2IP that are often inactivated in advanced disease. Furthermore, we found that HHV-8 triggered epithelial-to-mesenchymal transition. Although HHV-8 has not been linked etiologically to prostate cancer, virologic outcomes revealed by our study provide mechanistic insight into how intraprostatic infections could constitute risk for progression to androgen-independent metastatic disease where EZH2 has been implicated. Taken together, our findings prompt further evaluations of the relationship between HHV-8 infections and risk of advanced prostate cancer. PMID:24005834

  5. Carmustine enhances the anticancer activity of selenite in androgen-independent prostate cancer cells

    International Nuclear Information System (INIS)

    Apoptosis is one of the major mechanisms targeted in the development of therapies against various cancers, including prostate cancer. Resistance to chemotherapy poses a significant problem for the effective treatment of androgen-independent (hormone-refractory) prostate cancer. Although high concentrations of sodium selenite exert strong anticarcinogenic effects in several cell culture systems and animal models, the therapeutic potential of selenite in patients with advanced or metastatic prostate cancer is extremely limited by the genotoxicity of high-dose selenite. We examined the ability of nontoxic concentrations of selenite to promote apoptosis and inhibit proliferation in carmustine-sensitized androgen-independent human prostate cancer cells. Androgen-dependent LNCaP cells exhibited a significant decrease in cell viability when exposed to nontoxic concentrations of selenite, whereas androgen-independent PC-3 and DU145 cells showed a significant decrease in cell viability only at higher concentrations. Treatment of PC-3 cells with a combination of nontoxic selenite and carmustine resulted in greater increases in cytotoxicity, reactive oxygen species generation, growth inhibition, apoptosis, and DNA double-strand breaks, with concomitant decreases in DNA synthesis, glutathione, glutathione reductase, and antiapoptotic proteins. Combination treatment with carmustine and selenite triggered caspase-dependent apoptosis in PC-3 cells, which was not apparent when these cells were treated with selenite or carmustine alone. Genotoxicity in normal prostate epithelial cells was completely absent in the combination treatment of carmustine and selenite. In addition, carmustine decreased the induction of DNA double strand breaks by high-dose selenite in normal prostate epithelial cells. This is the first study to demonstrate that a nontoxic dose of selenite, in combination with carmustine, significantly induces apoptosis and growth inhibition in androgen-independent

  6. Glutathione S-transferase Pi mediates proliferation of androgen-independent prostate cancer cells

    OpenAIRE

    Hokaiwado, Naomi; Takeshita, Fumitaka; Naiki-Ito, Aya; Asamoto, Makoto; Ochiya, Takahiro; Shirai, Tomoyuki

    2008-01-01

    Prostate cancers generally acquire an androgen-independent growth capacity with progression, resulting in resistance to antiandrogen therapy. Therefore, identification of the genes regulated through this process may be important for understanding the mechanisms of prostate carcinogenesis. We here utilized androgen-dependent/independent transplantable tumors, newly established with the ‘transgenic rat adenocarcinoma in prostate’ (TRAP) model, to analyze their gene expression using microarrays....

  7. Growth inhibiting effects of terazosin on androgen-independent prostate cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    许克新; 王向红; 凌明达; 王云川

    2003-01-01

    Objective To study the effects of an α1-adrenoceptor antagonist, terazosin on the androgen-independent prostate cancer cell lines PC-3 and DU145.Methods Two androgen independent cell lines, PC-3 and DU145, were used to determine cell viability, colony-forming ability, as well as cell cycle distribution, after exposure to terazosin. Western blot analysis was used to determine the expression of p21WAF1 and p27KIP1.Results This study shows that terazosin inhibits not only prostate cancer cell growth but also its colony forming ability, both of which are main targets of clinical treatment. In addition, terazosin is shown to inhibit cell growth through G1 phase cell cycle arrest and the up-regulation of p27KIP1.Conclusion This study provides evidence that the α1-adrenoceptor antagonist terazosin may have therapeutic potential in the treatment of advanced hormone refractory prostate cancer.

  8. Phosphoproteome analysis demonstrates the potential role of THRAP3 phosphorylation in androgen-independent prostate cancer cell growth.

    Science.gov (United States)

    Ino, Yoko; Arakawa, Noriaki; Ishiguro, Hitoshi; Uemura, Hiroji; Kubota, Yoshinobu; Hirano, Hisashi; Toda, Tosifusa

    2016-04-01

    Elucidating the androgen-independent growth mechanism is critical for developing effective treatment strategies to combat androgen-independent prostate cancer. We performed a comparative phosphoproteome analysis using a prostate cancer cell line, LNCaP, and an LNCaP-derived androgen-independent cell line, LNCaP-AI, to identify phosphoproteins involved in this mechanism. We performed quantitative comparisons of the phosphopeptide levels in tryptic digests of protein extracts from these cell lines using MS. We found that the levels of 69 phosphopeptides in 66 proteins significantly differed between LNCaP and LNCaP-AI. In particular, we focused on thyroid hormone receptor associated protein 3 (THRAP3), which is a known transcriptional coactivator of the androgen receptor. The phosphorylation level of THRAP3 was significantly lower at S248 and S253 in LNCaP-AI cells. Furthermore, pull-down assays showed that 32 proteins uniquely bound to the nonphosphorylatable mutant form of THRAP3, whereas 31 other proteins uniquely bound to the phosphorylation-mimic form. Many of the differentially interacting proteins were identified as being involved with RNA splicing and processing. These results suggest that the phosphorylation state of THRAP3 at S248 and S253 might be involved in the mechanism of androgen-independent prostate cancer cell growth by changing the interaction partners.

  9. Hedgehog/Gli supports androgen signaling in androgen deprived and androgen independent prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Shtutman Michael

    2010-04-01

    Full Text Available Abstract Background Castration resistant prostate cancer (CRPC develops as a consequence of hormone therapies used to deplete androgens in advanced prostate cancer patients. CRPC cells are able to grow in a low androgen environment and this is associated with anomalous activity of their endogenous androgen receptor (AR despite the low systemic androgen levels in the patients. Therefore, the reactivated tumor cell androgen signaling pathway is thought to provide a target for control of CRPC. Previously, we reported that Hedgehog (Hh signaling was conditionally activated by androgen deprivation in androgen sensitive prostate cancer cells and here we studied the potential for cross-talk between Hh and androgen signaling activities in androgen deprived and androgen independent (AI prostate cancer cells. Results Treatment of a variety of androgen-deprived or AI prostate cancer cells with the Hh inhibitor, cyclopamine, resulted in dose-dependent modulation of the expression of genes that are regulated by androgen. The effect of cyclopamine on endogenous androgen-regulated gene expression in androgen deprived and AI prostate cancer cells was consistent with the suppressive effects of cyclopamine on the expression of a reporter gene (luciferase from two different androgen-dependent promoters. Similarly, reduction of smoothened (Smo expression with siRNA co-suppressed expression of androgen-inducible KLK2 and KLK3 in androgen deprived cells without affecting the expression of androgen receptor (AR mRNA or protein. Cyclopamine also prevented the outgrowth of AI cells from androgen growth-dependent parental LNCaP cells and suppressed the growth of an overt AI-LNCaP variant whereas supplemental androgen (R1881 restored growth to the AI cells in the presence of cyclopamine. Conversely, overexpression of Gli1 or Gli2 in LNCaP cells enhanced AR-specific gene expression in the absence of androgen. Overexpressed Gli1/Gli2 also enabled parental LNCaP cells to

  10. Up-regulation of Bcl-2 is required for the progression of prostate cancer cells from an androgen-dependent to an androgen-independent growth stage

    Institute of Scientific and Technical Information of China (English)

    Yuting Lin; Junichi Fukuchi; Richard A Hiipakka; John M Kokontis; Jialing Xiang

    2007-01-01

    Bcl-2 is an anti-apoptotic oncoprotein and its protein levels are inversely correlated with prognosis in many cancers.However, the role of Bcl-2 in the progression of prostate cancer is not clear. Here we report that Bcl-2 is required for the progression of LNCaP prostate cancer cells from an androgen-dependent to an androgen-independent growth stage. The mRNA and protein levels of Bcl-2 are significantly increased in androgen-independent prostate cancer cells, shRNA-mediated gene silencing of Bcl-2 in androgen-independent prostate cancer cells promotes UV-induced apoptosis and suppresses the growth of prostate tumors in vivo. Growing androgen-dependent cells under androgen-deprivation conditions results in formation of androgen-independent colonies; and the transition from androgen-dependent to androgen-independent growth is blocked by ectopic expression of the Bcl-2 antagonist Bax or Bcl-2 shRNA. Thus, our results demonstrate that Bcl-2 is not only critical for the survival of androgen-independent prostate cancer cells, but is also required for the progression of prostate cancer cells from an androgen-dependent to an androgen-independent growth stage.

  11. Effect of miR-296 on the Apoptosis of Androgen-independent Prostate Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    Pei CHENG; Run-sheng LI; Biao-yang LIN; Wei-qun WANG; Yu-hua LI; Yan GUO; Wei LI

    2009-01-01

    Objective To investigate the miR-296's function in prostate carcinoma(PCa) cells. Methods In order to profile the miRNA expression in LNCaP cells, the cultured cells were stimulated with androgen after 48-h starvation, miRNA microarray analysis and Q-RT-PCR assay were performed. To characterize the effects of miR296 on PCa cells, CL-1 and PC-3 cells were transfected with miR-296 and antisense-miR-296, cell growth and apoptosis were then analyzed. Results The miR-296-5p expression was up-regulated by 2.22 folds in the CL-1 cells, which do not express significantly androgen receptor, than in LNCaP cells. Knockdown of miR-296-Sp induced apoptosis of CL-1 cells, but not LNCaP cells. However, knockdown of miR-296-Sp inhibited the growth rate of LNCaP cells cultured in absence of androgen. Conclusion MiR-296-5p could be irnportant for development of prostate cancer from androgen dependence to androgen independence.

  12. Histological changes caused by meclofenamic acid in androgen independent prostate cancer tumors: evaluation in a mouse model

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    Iván Delgado-Enciso

    2015-10-01

    Full Text Available ABSTRACT Meclofenamic acid is a nonsteroidal anti-inflammatory drug that has shown therapeutic potential for different types of cancers, including androgen-independent prostate neoplasms. The antitumor effect of diverse nonsteroidal anti-inflammatory drugs has been shown to be accompanied by histological and molecular changes that are responsible for this beneficial effect. The objective of the present work was to analyze the histological changes caused by meclofenamic acid in androgen-independent prostate cancer. Tumors were created in a nude mouse model using PC3 cancerous human cells. Meclofenamic acid (10 mg/kg/day; experimental group, n=5 or saline solution (control group, n=5 was administered intraperitoneally for twenty days. Histological analysis was then carried out on the tumors, describing changes in the cellular architecture, fibrosis, and quantification of cellular proliferation and tumor vasculature. Meclofenamic acid causes histological changes that indicate less tumor aggression (less hypercellularity, fewer atypical mitoses, and fewer nuclear polymorphisms, an increase in fibrosis, and reduced cellular proliferation and tumor vascularity. Further studies are needed to evaluate the molecular changes that cause the beneficial and therapeutic effects of meclofenamic acid in androgen-independent prostate cancer.

  13. The role of mesenchymal stem cells in promoting the transformation of androgen-dependent human prostate cancer cells into androgen-independent manner

    OpenAIRE

    Jiwen Cheng; Keqin Yang; Qingyun Zhang; Yang Yu; Qinggui Meng; Ning Mo; Yang Zhou; Xianlin Yi; Chengzhong Ma; Aming Lei; Yan Liu

    2016-01-01

    Mesenchymal stem cells (MSCs) play an important role in the development of human prostate cancer (PCa). However, the role of MSCs in the transformation of androgen-dependent human PCa cells into androgen-independent manner has been poorly understood. In this study, we investigated the underlying mechanism of MSCs in promoting PCa cells from androgen-dependent into androgen-independent manner. Firstly, we demonstrated that MSCs could affect the transformation of androgen-dependent human PCa ce...

  14. Androgen-independent proliferation of LNCaP prostate cancer cells infected by xenotropic murine leukemia virus-related virus

    International Nuclear Information System (INIS)

    Highlights: • XMRV infection induces androgen-independent growth in LNCaP cells. • XMRV infection reduces expression of androgen receptor. • XMRV promotes appearance of androgen blocker-resistant prostate cancer cells. - Abstract: Xenotropic murine leukemia virus-related virus (XMRV) is a novel gammaretrovirus that was originally isolated from human prostate cancer. It is now believed that XMRV is not the etiologic agent of prostate cancer. An analysis of murine leukemia virus (MLV) infection in various human cell lines revealed that prostate cancer cell lines are preferentially infected by XMRV, and this suggested that XMRV infection may confer some sort of growth advantage to prostate cancer cell lines. To examine this hypothesis, androgen-dependent LNCaP cells were infected with XMRV and tested for changes in certain cell growth properties. We found that XMRV-infected LNCaP cells can proliferate in the absence of the androgen dihydrotestosterone. Moreover, androgen receptor expression is significantly reduced in XMRV-infected LNCaP cells. Such alterations were not observed in uninfected and amphotropic MLV-infected LNCaP cells. This finding explains why prostate cancer cell lines are preferentially infected with XMRV

  15. Androgen-independent proliferation of LNCaP prostate cancer cells infected by xenotropic murine leukemia virus-related virus

    Energy Technology Data Exchange (ETDEWEB)

    Kakoki, Katsura [Division of Cytokine Signaling, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523 (Japan); Department of AIDS Research, Institute of Tropical Medicine, G-COE, Nagasaki University, Nagasaki 852-8523 (Japan); Department of Urology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523 (Japan); Kamiyama, Haruka [Division of Cytokine Signaling, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523 (Japan); Department of AIDS Research, Institute of Tropical Medicine, G-COE, Nagasaki University, Nagasaki 852-8523 (Japan); Izumida, Mai; Yashima, Yuka; Hayashi, Hideki [Division of Cytokine Signaling, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523 (Japan); Yamamoto, Naoki [Department of AIDS Research, Institute of Tropical Medicine, G-COE, Nagasaki University, Nagasaki 852-8523 (Japan); Department of Microbiology, National University of Singapore (Singapore); Matsuyama, Toshifumi [Division of Cytokine Signaling, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523 (Japan); Igawa, Tsukasa; Sakai, Hideki [Department of Urology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523 (Japan); Kubo, Yoshinao, E-mail: yoshinao@nagasaki-u.ac.jp [Division of Cytokine Signaling, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523 (Japan); Department of AIDS Research, Institute of Tropical Medicine, G-COE, Nagasaki University, Nagasaki 852-8523 (Japan)

    2014-04-25

    Highlights: • XMRV infection induces androgen-independent growth in LNCaP cells. • XMRV infection reduces expression of androgen receptor. • XMRV promotes appearance of androgen blocker-resistant prostate cancer cells. - Abstract: Xenotropic murine leukemia virus-related virus (XMRV) is a novel gammaretrovirus that was originally isolated from human prostate cancer. It is now believed that XMRV is not the etiologic agent of prostate cancer. An analysis of murine leukemia virus (MLV) infection in various human cell lines revealed that prostate cancer cell lines are preferentially infected by XMRV, and this suggested that XMRV infection may confer some sort of growth advantage to prostate cancer cell lines. To examine this hypothesis, androgen-dependent LNCaP cells were infected with XMRV and tested for changes in certain cell growth properties. We found that XMRV-infected LNCaP cells can proliferate in the absence of the androgen dihydrotestosterone. Moreover, androgen receptor expression is significantly reduced in XMRV-infected LNCaP cells. Such alterations were not observed in uninfected and amphotropic MLV-infected LNCaP cells. This finding explains why prostate cancer cell lines are preferentially infected with XMRV.

  16. Hedgehog/Gli supports androgen signaling in androgen deprived and androgen independent prostate cancer cells

    OpenAIRE

    Shtutman Michael; Tanner Matthew J; Carkner Richard D; Baghel Prateek S; Levina Elina; Feuerstein Michael A; Chen Mengqian; Vacherot Francis; Terry Stéphane; de la Taille Alexandre; Buttyan Ralph

    2010-01-01

    Abstract Background Castration resistant prostate cancer (CRPC) develops as a consequence of hormone therapies used to deplete androgens in advanced prostate cancer patients. CRPC cells are able to grow in a low androgen environment and this is associated with anomalous activity of their endogenous androgen receptor (AR) despite the low systemic androgen levels in the patients. Therefore, the reactivated tumor cell androgen signaling pathway is thought to provide a target for control of CRPC....

  17. Inhibition of Androgen-Independent Prostate Cancer by Estrogenic Compounds Is Associated with Increased Expression of Immune-Related Genes

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    Ilsa M. Coleman

    2006-10-01

    Full Text Available The clinical utility of estrogens for treating prostate cancer (CaP was established in the 1940s by Huggins. The classic model of the anti-CaP activity of estrogens postulates an indirect mechanism involving the suppression of androgen production. However, clinical, preclinical studies have shown that estrogens exert growth-inhibitory effects on CaP under low-androgen conditions, suggesting additional modes whereby estrogens affect CaP cells and/or the microenvironment. Here we have investigated the activity of 17β estradiol (E2 against androgen-independent CaP, identified molecular alterations in tumors exposed to E2. E2 treatment inhibited the growth of all four androgen-independent CaP xenografts studied (LuCaP 35V, LuCaP 23.1AI, LuCaP 49, LuCaP 58 in castrated male mice. The molecular basis of growth suppression was studied by cDNA microarray analysis, which indicated that multiple pathways are altered by E2 treatment. Of particular interest are changes in transcripts encoding proteins that mediate immune responses, regulate androgen receptor signaling. In conclusion, our data show that estrogens have powerful inhibitory effects on CaP in vivo in androgendepleted environments, suggest novel mechanisms of estrogen-mediated antitumor activity. These results indicate that incorporating estrogens into CaP treatment protocols could enhance therapeutic efficacy even in cases of advanced disease.

  18. The PPARγ ligand ciglitazone regulates androgen receptor activation differently in androgen-dependent versus androgen-independent human prostate cancer cells

    International Nuclear Information System (INIS)

    The androgen receptor (AR) regulates growth and progression of androgen-dependent as well as androgen-independent prostate cancer cells. Peroxisome proliferator-activated receptor gamma (PPARγ) agonists have been reported to reduce AR activation in androgen-dependent LNCaP prostate cancer cells. To determine whether PPARγ ligands are equally effective at inhibiting AR activity in androgen-independent prostate cancer, we examined the effect of the PPARγ ligands ciglitazone and rosiglitazone on C4-2 cells, an androgen- independent derivative of the LNCaP cell line. Luciferase-based reporter assays and Western blot analysis demonstrated that PPARγ ligand reduced dihydrotestosterone (DHT)-induced increases in AR activity in LNCaP cells. However, in C4-2 cells, these compounds increased DHT-induced AR driven luciferase activity. In addition, ciglitazone did not significantly alter DHT-mediated increases in prostate specific antigen (PSA) protein or mRNA levels within C4-2 cells. siRNA-based experiments demonstrated that the ciglitazone-induced regulation of AR activity observed in C4-2 cells was dependent on the presence of PPARγ. Furthermore, overexpression of the AR corepressor cyclin D1 inhibited the ability of ciglitazone to induce AR luciferase activity in C4-2 cells. Thus, our data suggest that both PPARγ and cyclin D1 levels influence the ability of ciglitazone to differentially regulate AR signaling in androgen-independent C4-2 prostate cancer cells.

  19. p38MAPK activation is involved in androgen-independent proliferation of human prostate cancer cells by regulating IL-6 secretion

    International Nuclear Information System (INIS)

    Increased levels of serum interleukin-6 (IL-6) are frequently observed in patients with advanced, hormone-refractory prostate cancer. However, the precise mechanism of IL-6 regulation is still largely unknown. Since prostate cancer gradually progresses to an androgen-independent state despite the stress caused by various therapeutic agents, we hypothesized the stress-activated protein kinases (SAPKs) involvement in androgen-independent growth or IL-6 secretion of prostate cancer cells. Using PC-3 and DU145 human prostate cancer cells, we analyzed the role of SAPKs in IL-6 mediated cell growth and found that the p38MAPK and JNK are involved in androgen-independent cancer cell growth. Furthermore, IL-6 secretion by PC-3 and DU145 cells was significantly suppressed by SAPKs inhibitor, especially by p38MAPK inhibitor SB203580, but not by JNK inhibitor SP600125 nor by MEK inhibitor, PD98059. These results raised the possibility that the IL-6 mediated androgen-independent proliferation of PC-3 and DU145 cells is regulated at least partly via SAPKs signaling pathway especially through p38MAPK activation

  20. Increased expression of heparin binding EGF (HB-EGF), amphiregulin, TGF alpha and epiregulin in androgen-independent prostate cancer cell lines.

    DEFF Research Database (Denmark)

    Tørring, Niels; Sørensen, Boe Sandahl; Nexø, Ebba

    2000-01-01

    BACKGROUND: The proliferation of androgen-independent prostate cancer cell lines has previously been shown to be influenced by an autocrine loop of the epidermal growth factor (EGF) system. This observation has alerted us to study the expression of ligands and receptors from the EGF-system in pro...

  1. Primary Research on Chinese Medicine Treatment of Androgen-Independent Prostate Cancer

    Institute of Scientific and Technical Information of China (English)

    张蜀武; 周仕轶; 邵继春; 曲晓伟

    2009-01-01

    Prostate cancer(PC) is a common malignant tumor in the male seniors,and its incidence has been ascending in China in recent years. Over 80%of the patients are diagnosed as being in the late stage and lose the opportunity of radical operation because of its early stage metastasis. Endocrinotherapy is regarded

  2. Detection of bony metastases of androgen-independent prostate cancer by PET-FDG

    Energy Technology Data Exchange (ETDEWEB)

    Yeh, Samuel D. J.; Imbriaco, Massimo; Larson, Steven M.; Garza, Dahlia; Zhang Jiaju; Kalaigian, Hovanes; Finn, Ronald D.; Reddy, David; Horowitz, Steven M.; Goldsmith, Stanley J.; Scher, Howard I

    1996-08-01

    Fourteen F-18 fluorodeoxyglucose (FDG) studies were carried out in 13 patients known to have bony metastases from carcinoma of the prostate. One patient was newly diagnosed. The remaining patients had various types of therapy and were considered hormonally resistant. The average age was 67. All patients had extensive bony metastases shown on the conventional Tc99m-MDP bone scans. Only about 18% of bony lesions apparent on the conventional bone scans showed corresponding increase of FDG uptake. Anatomical correlation was performed by using co-registered images of SPECT and PET in the same area. The positive FDG uptake was not related to the duration of illness, level of PSA, previous therapy, and magnitude of disease involvement. It appears that only a small percentage of bony metastases is associated with increased glycolysis. It is possible that other metabolic processes are more important than glycolysis for providing prostate cancer with a source of energy and nutrients.

  3. The PPAR{gamma} ligand ciglitazone regulates androgen receptor activation differently in androgen-dependent versus androgen-independent human prostate cancer cells

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    Moss, Patrice E.; Lyles, Besstina E.; Stewart, LaMonica V., E-mail: lstewart@mmc.edu

    2010-12-10

    The androgen receptor (AR) regulates growth and progression of androgen-dependent as well as androgen-independent prostate cancer cells. Peroxisome proliferator-activated receptor gamma (PPAR{gamma}) agonists have been reported to reduce AR activation in androgen-dependent LNCaP prostate cancer cells. To determine whether PPAR{gamma} ligands are equally effective at inhibiting AR activity in androgen-independent prostate cancer, we examined the effect of the PPAR{gamma} ligands ciglitazone and rosiglitazone on C4-2 cells, an androgen- independent derivative of the LNCaP cell line. Luciferase-based reporter assays and Western blot analysis demonstrated that PPAR{gamma} ligand reduced dihydrotestosterone (DHT)-induced increases in AR activity in LNCaP cells. However, in C4-2 cells, these compounds increased DHT-induced AR driven luciferase activity. In addition, ciglitazone did not significantly alter DHT-mediated increases in prostate specific antigen (PSA) protein or mRNA levels within C4-2 cells. siRNA-based experiments demonstrated that the ciglitazone-induced regulation of AR activity observed in C4-2 cells was dependent on the presence of PPAR{gamma}. Furthermore, overexpression of the AR corepressor cyclin D1 inhibited the ability of ciglitazone to induce AR luciferase activity in C4-2 cells. Thus, our data suggest that both PPAR{gamma} and cyclin D1 levels influence the ability of ciglitazone to differentially regulate AR signaling in androgen-independent C4-2 prostate cancer cells.

  4. Clinical evaluation of internal iliac artery anticancer drug infusion for the treatment of androgen-independent prostate cancer

    International Nuclear Information System (INIS)

    Objective: To evaluate the clinical efficacy of bilateral internal iliac artery chemotherapy infusion for the treatment of androgen-independent prostate cancer (ALPC). Methods: Thirty eight eases of confirmed AIPC were randomly divided into treatment group and control group. The patients in treatment group (23 cases) were treated with androgen deprivation therapy and regular internal iliac artery chemotherapy, while patients in control group (15 cases) were only received androgen deprivation therapy. The therapeutic efficacies of the two groups were compared and analyzed after completion of the treatment. Results: The clinical symptoms and maximum urine flow rates of' treatment group were improved rapidly 6 months later. After 2 years follow-up, the total efficacies of treatment group and control group were 65.2% and 26.7% respectively, showing a significant statistical difference (P<0.05). Conclusions: The treatment of AlPC with bilateral internal iliac artery chemotherapy is effective, providing melioration the quality of life and alleviation of the symptoms. (authors)

  5. Natural proteasome inhibitor celastrol suppresses androgen-independent prostate cancer progression by modulating apoptotic proteins and NF-kappaB.

    Directory of Open Access Journals (Sweden)

    Yao Dai

    Full Text Available Celastrol is a natural proteasome inhibitor that exhibits promising anti-tumor effects in human malignancies, especially the androgen-independent prostate cancer (AIPC with constitutive NF-κB activation. Celastrol induces apoptosis by means of proteasome inhibition and suppresses prostate tumor growth. However, the detailed mechanism of action remains elusive. In the current study, we aim to test the hypothesis that celastrol suppresses AIPC progression via inhibiting the constitutive NF-κB activity as well as modulating the Bcl-2 family proteins.We examined the efficacy of celastrol both in vitro and in vivo, and evaluated the role of NF-κB in celastrol-mediated AIPC regression. We found that celastrol inhibited cell proliferation in all three AIPC cell lines (PC-3, DU145 and CL1, with IC₅₀ in the range of 1-2 µM. Celastrol also suppressed cell migration and invasion. Celastrol significantly induced apoptosis as evidenced by increased sub-G1 population, caspase activation and PARP cleavage. Moreover, celastrol promoted cleavage of the anti-apoptotic protein Mcl-1 and activated the pro-apoptotic protein Noxa. In addition, celastrol rapidly blocked cytosolic IκBα degradation and nuclear translocation of RelA. Likewise, celastrol inhibited the expression of multiple NF-κB target genes that are involved in proliferation, invasion and anti-apoptosis. Celastrol suppressed AIPC tumor progression by inhibiting proliferation, increasing apoptosis and decreasing angiogenesis, in PC-3 xenograft model in nude mouse. Furthermore, increased cellular IκBα and inhibited expression of various NF-κB target genes were observed in tumor tissues.Our data suggest that, via targeting the proteasome, celastrol suppresses proliferation, invasion and angiogenesis by inducing the apoptotic machinery and attenuating constitutive NF-κB activity in AIPC both in vitro and in vivo. Celastrol as an active ingredient of traditional herbal medicine could thus be

  6. Contragestazol (DL111-IT) inhibits proliferation of human androgen-independent prostate cancer cell line PC3 in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    Qiao-Jun He; Bo Yang; Yi-Jia Lou; Rui-Ying Fang

    2005-01-01

    Aim: To evaluate the antiproliferative activity of contragestazol (DL 1 11-IT) on the human prostate cancer cell line PC3 in vitro and in vivo and to elucidate its potential molecular mechanisms. Methods: The cell killing ability of DL111-IT was measured by the 3-(4,5-dimethylthia-zol,2-yl)-2,5-diphenyltetrazolium bromide (MTT) reagent assay method and the tumor xenograft model. The cell cycle was analyzed by flow cytometry and protein expression,including retinoblastoma (pRb), cyclin-dependent kinase 4 (CDK4) and cyclin D1, was detected by Western blotting.Results: DL111-IT exhibited high efficiency on cell growth inhibition of the human androgen-independent prostate cancer cell line PC3. The drug concentration that yielded 50 % cell inhibition (IC50 value) was 9.9 mg/mL. In the PC3tumor xenograft study, DL111-IT (1.25 mg/kg-20.0 mg/kg) given once a day for 10 days significantly inhibited tumor growth, with the inhibition rate ranging from 21% to 50 %. Flow cytometric analysis indicated that DL111-IT could cause G1 arrest in the PC3 cell line, but not apoptosis. DL111-IT enhanced pRb expression and down-regulated CDK4and cyclin D1 expression, suggesting that cell cycle regulation might contribute to the anticancer property of DL111-IT. Conclusion: DL111-Itinhibits the proliferation of human androgen-independent prostate cancer cell line PC3 in vitro and in vivo by a cell cycle regulation pathway.

  7. PROGRESSION TO ANDROGEN-INDEPENDENT LNCAP HUMAN PROSTATE TUMORS: CELLULAR AND MOLECULAR ALTERATIONS

    OpenAIRE

    Zhou, Jin-Rong; Yu, Lunyin; Zerbini, Luiz F.; Libermann, Towia A.; Blackburn, George L.

    2004-01-01

    Lethal phenotypes of human prostate cancer are characterized by progression to androgen-independence and metastasis. For want of a clinically relevant animal model, mechanisms behind this progression remain unclear. Our study used an in vivo model of androgen-sensitive LNCaP human prostate cancer cell xenografts in male SCID mice to study the cellular and molecular biology of tumor progression. Primary tumors were established orthotopically, and the mice were then surgically castrated to with...

  8. Cardiac glycosides induce resistance to tubulin-dependent anticancer drugs in androgen-independent human prostate cancer.

    Science.gov (United States)

    Huang, Dong-Ming; Guh, Jih-Hwa; Huang, Yao-Ting; Chueh, Shih-Chieh; Wang, Hui-Po; Teng, Che-Ming

    2002-01-01

    Due to high prevalence and mortality and the lack of effective therapies, prostate cancer is one of the most crucial health problems in men. Drug resistance aggravates the situation, not only in human prostate cancer but also in other cancers. In this study, we report for the first time that cardiac glycosides (e.g. ouabain and digitoxin) induced resistance of human prostate cancer cells (PC-3) in vitro to tubulin-binding anticancer drugs, such as paclitaxel, colchicine, vincristine and vinblastine. Cardiac glycosides exhibited amazing ability to reverse the G2/M arrest of the cell cycle and cell apoptosis induced by tubulin-binding agents. However, neither ionomycin (a Ca(2+) ionophore) nor veratridine (a Na(+) ionophore) mimicked the preventive action of cardiac glycosides, indicating that elevation of the intracellular Ca(2+) concentration and Na(+) accumulation were not involved in the cardiac glycoside action. Furthermore, cardiac glycosides showed little influence on the effects induced by actinomycin D, anisomycin and doxorubicin, suggesting selectivity for microtubule-targeted anticancer drugs. Using in situ immunofluorescent detection of mitotic spindles, our data showed that cardiac glycosides diminished paclitaxel-induced accumulation of microtubule spindles; however, in a non-cell assay system, cardiac glycosides had little influence on colchicine- and paclitaxel-induced microtubule dynamics. Using an isotope-labeled assay method, we found that ouabain modestly but significantly inhibited the transport of [(14)C]paclitaxel from the cytosol into the nucleus. It is suggested that cardiac glycosides inhibit the G2/M arrest induced by tubulin-binding anticancer drugs via an indirect blockade on microtubule function. The decline in transport of these drugs into the nucleus may partly explain the action of cardiac glycosides. PMID:12218360

  9. Pomegranate Juice Metabolites, Ellagic Acid and Urolithin A, Synergistically Inhibit Androgen-Independent Prostate Cancer Cell Growth via Distinct Effects on Cell Cycle Control and Apoptosis

    Directory of Open Access Journals (Sweden)

    Roberto Vicinanza

    2013-01-01

    Full Text Available Ellagitannins (ETs from pomegranate juice (PJ are bioactive polyphenols with chemopreventive potential against prostate cancer (PCa. ETs are not absorbed intact but are partially hydrolyzed in the gut to ellagic acid (EA. Colonic microflora can convert EA to urolithin A (UA, and EA and UA enter the circulation after PJ consumption. Here, we studied the effects of EA and UA on cell proliferation, cell cycle, and apoptosis in DU-145 and PC-3 androgen-independent PCa cells and whether combinations of EA and UA affected cell proliferation. EA demonstrated greater dose-dependent antiproliferative effects in both cell lines compared to UA. EA induced cell cycle arrest in S phase associated with decreased cyclin B1 and cyclin D1 levels. UA induced a G2/M arrest and increased cyclin B1 and cdc2 phosphorylation at tyrosine-15, suggesting inactivation of the cyclin B1/cdc2 kinase complex. EA induced apoptosis in both cell lines, while UA had a less pronounced proapoptotic effect only in DU-145. Cotreatment with low concentrations of EA and UA dramatically decreased cell proliferation, exhibiting synergism in PC-3 cells evaluated by isobolographic analysis and combination index. These data provide information on pomegranate metabolites for the prevention of PCa recurrence, supporting the role of gut flora-derived metabolites for cancer prevention.

  10. Withaferin A Induces Cell Death Selectively in Androgen-Independent Prostate Cancer Cells but Not in Normal Fibroblast Cells.

    Directory of Open Access Journals (Sweden)

    Yukihiro Nishikawa

    Full Text Available Withaferin A (WA, a major bioactive component of the Indian herb Withania somnifera, induces cell death (apoptosis/necrosis in multiple types of tumor cells, but the molecular mechanism underlying this cytotoxicity remains elusive. We report here that 2 μM WA induced cell death selectively in androgen-insensitive PC-3 and DU-145 prostate adenocarcinoma cells, whereas its toxicity was less severe in androgen-sensitive LNCaP prostate adenocarcinoma cells and normal human fibroblasts (TIG-1 and KD. WA also killed PC-3 cells in spheroid-forming medium. DNA microarray analysis revealed that WA significantly increased mRNA levels of c-Fos and 11 heat-shock proteins (HSPs in PC-3 and DU-145, but not in LNCaP and TIG-1. Western analysis revealed increased expression of c-Fos and reduced expression of the anti-apoptotic protein c-FLIP(L. Expression of HSPs such as HSPA6 and Hsp70 was conspicuously elevated; however, because siRNA-mediated depletion of HSF-1, an HSP-inducing transcription factor, reduced PC-3 cell viability, it is likely that these heat-shock genes were involved in protecting against cell death. Moreover, WA induced generation of reactive oxygen species (ROS in PC-3 and DU-145, but not in normal fibroblasts. Immunocytochemistry and immuno-electron microscopy revealed that WA disrupted the vimentin cytoskeleton, possibly inducing the ROS generation, c-Fos expression and c-FLIP(L suppression. These observations suggest that multiple events followed by disruption of the vimentin cytoskeleton play pivotal roles in WA-mediated cell death.

  11. Expression changes of androgen receptor RNA in androgen-independence prostatic cancer%前列腺癌雄激素依赖转化后雄激素受体基因表达变化的研究

    Institute of Scientific and Technical Information of China (English)

    潘寿华; 阎家峻; 郑专

    2011-01-01

    Background and purpose: The mechanism for transforming androgen-dependent prostatic cancer cells into androgen-independent prostatic cancer cells is uncertain. Androgen receptor RNA plays a vital role in transforming androgen-dependent prostatic cancer into androgen-independent prostatic cancer. This study investigated the transcription of androgen receptor (AR) RNA in order to determine the role of AR-RNA in the transformation.Methods: Thirty three patients with prostate cancer were treated using androgen deprivation and all of the patients had long time follow-up. Of these patients, 18 were transformed into the androgen-independent prostatic cancer. The transcription of AR RNA was detected using RT-PCR at androgen-dependent and androgen-independent conditions in 18 patients, and before or after androgen deprivation in 15 patients. Results: The transcription of androgen receptor RNA at androgen-dependent and androgen-independent conditions in 18 patients were [(28.4±3.4) Ct vs (36.7±1.8) Ct, t=14.43, P<0.001]. Before and after androgen deprivation in 15 patients were [(29.5±3.1) Ct vs (29.1±3.2) Ct,t=0.409, P>0.05]. Conclusion: The elevation of transcription in androgen receptor RNA is most likely related to the mechanism used for the transformation of androgen-dependent prostatic cancer into androgen-independent prostatic cancer.%背景与目的:前列腺癌雄激素依赖性转化的机制目前尚不完全清楚,多数认为雄激素受体(androgen receptor,AR)基因的变化可能起重要作用,本研究主要探讨AR基因表达变化在前列腺癌雄激素依赖转化过程中的作用.方法:通过对33例晚期前列腺癌患者进行雄激素阻断治疗并长时间的随访,期间有18例患者发生了雄激素依赖转化,15例患者未发生雄激素依赖转化.采用RT-PCR法测定18例患者雄激素依赖转化前后及15例患者雄激素阻断治疗前后癌细胞内AR基因的表达情况.结果:18例患者雄激素依赖转化前

  12. Proteasomal degradation of sphingosine kinase 1 and inhibition of dihydroceramide desaturase by the sphingosine kinase inhibitors, SKi or ABC294640, induces growth arrest in androgen-independent LNCaP-AI prostate cancer cells.

    Science.gov (United States)

    McNaughton, Melissa; Pitman, Melissa; Pitson, Stuart M; Pyne, Nigel J; Pyne, Susan

    2016-03-29

    Sphingosine kinases (two isoforms termed SK1 and SK2) catalyse the formation of the bioactive lipid sphingosine 1-phosphate. We demonstrate here that the SK2 inhibitor, ABC294640 (3-(4-chlorophenyl)-adamantane-1-carboxylic acid (pyridin-4-ylmethyl)amide) or the SK1/SK2 inhibitor, SKi (2-(p-hydroxyanilino)-4-(p-chlorophenyl)thiazole)) induce the proteasomal degradation of SK1a (Mr = 42 kDa) and inhibit DNA synthesis in androgen-independent LNCaP-AI prostate cancer cells. These effects are recapitulated by the dihydroceramide desaturase (Des1) inhibitor, fenretinide. Moreover, SKi or ABC294640 reduce Des1 activity in Jurkat cells and ABC294640 induces the proteasomal degradation of Des1 (Mr = 38 kDa) in LNCaP-AI prostate cancer cells. Furthermore, SKi or ABC294640 or fenretinide increase the expression of the senescence markers, p53 and p21 in LNCaP-AI prostate cancer cells. The siRNA knockdown of SK1 or SK2 failed to increase p53 and p21 expression, but the former did reduce DNA synthesis in LNCaP-AI prostate cancer cells. Moreover, N-acetylcysteine (reactive oxygen species scavenger) blocked the SK inhibitor-induced increase in p21 and p53 expression but had no effect on the proteasomal degradation of SK1a. In addition, siRNA knockdown of Des1 increased p53 expression while a combination of Des1/SK1 siRNA increased the expression of p21. Therefore, Des1 and SK1 participate in regulating LNCaP-AI prostate cancer cell growth and this involves p53/p21-dependent and -independent pathways. Therefore, we propose targeting androgen-independent prostate cancer cells with compounds that affect Des1/SK1 to modulate both de novo and sphingolipid rheostat pathways in order to induce growth arrest.

  13. Proteasomal degradation of sphingosine kinase 1 and inhibition of dihydroceramide desaturase by the sphingosine kinase inhibitors, SKi or ABC294640, induces growth arrest in androgen-independent LNCaP-AI prostate cancer cells

    Science.gov (United States)

    McNaughton, Melissa; Pitman, Melissa; Pitson, Stuart M.; Pyne, Nigel J.; Pyne, Susan

    2016-01-01

    Sphingosine kinases (two isoforms termed SK1 and SK2) catalyse the formation of the bioactive lipid sphingosine 1-phosphate. We demonstrate here that the SK2 inhibitor, ABC294640 (3-(4-chlorophenyl)-adamantane-1-carboxylic acid (pyridin-4-ylmethyl)amide) or the SK1/SK2 inhibitor, SKi (2-(p-hydroxyanilino)-4-(p-chlorophenyl)thiazole)) induce the proteasomal degradation of SK1a (Mr = 42 kDa) and inhibit DNA synthesis in androgen-independent LNCaP-AI prostate cancer cells. These effects are recapitulated by the dihydroceramide desaturase (Des1) inhibitor, fenretinide. Moreover, SKi or ABC294640 reduce Des1 activity in Jurkat cells and ABC294640 induces the proteasomal degradation of Des1 (Mr = 38 kDa) in LNCaP-AI prostate cancer cells. Furthermore, SKi or ABC294640 or fenretinide increase the expression of the senescence markers, p53 and p21 in LNCaP-AI prostate cancer cells. The siRNA knockdown of SK1 or SK2 failed to increase p53 and p21 expression, but the former did reduce DNA synthesis in LNCaP-AI prostate cancer cells. Moreover, N-acetylcysteine (reactive oxygen species scavenger) blocked the SK inhibitor-induced increase in p21 and p53 expression but had no effect on the proteasomal degradation of SK1a. In addition, siRNA knockdown of Des1 increased p53 expression while a combination of Des1/SK1 siRNA increased the expression of p21. Therefore, Des1 and SK1 participate in regulating LNCaP-AI prostate cancer cell growth and this involves p53/p21-dependent and -independent pathways. Therefore, we propose targeting androgen-independent prostate cancer cells with compounds that affect Des1/SK1 to modulate both de novo and sphingolipid rheostat pathways in order to induce growth arrest. PMID:26934645

  14. Androgen and taxol cause cell type-specific alterations of centrosome and DNA organization in androgen-responsive LNCaP and androgen-independent DU145 prostate cancer cells

    Science.gov (United States)

    Schatten, H.; Ripple, M.; Balczon, R.; Weindruch, R.; Chakrabarti, A.; Taylor, M.; Hueser, C. N.

    2000-01-01

    We investigated the effects of androgen and taxol on the androgen-responsive LNCaP and androgen-independent DU145 prostate cancer cell lines. Cells were treated for 48 and 72 h with 0.05-1 nM of the synthetic androgen R1881 and with 100 nM taxol. Treatment of LNCaP cells with 0.05 nM R1881 led to increased cell proliferation, whereas treatment with 1 nM R1881 resulted in inhibited cell division, DNA cycle arrest, and altered centrosome organization. After treatment with 1 nM R1881, chromatin became clustered, nuclear envelopes convoluted, and mitochondria accumulated around the nucleus. Immunofluorescence microscopy with antibodies to centrosomes showed altered centrosome structure. Although centrosomes were closely associated with the nucleus in untreated cells, they dispersed into the cytoplasm after treatment with 1 nM R1881. Microtubules were only faintly detected in 1 nM R1881-treated LNCaP cells. The effects of taxol included microtubule bundling and altered mitochondria morphology, but not DNA organization. As expected, the androgen-independent prostate cancer cell line DU145 was not affected by R1881. Treatment with taxol resulted in bundling of microtubules in both cell lines. Additional taxol effects were seen in DU145 cells with micronucleation of DNA, an indication of apoptosis. Simultaneous treatment with R1881 and taxol had no additional effects on LNCaP or DU145 cells. These results suggest that LNCaP and DU145 prostate cancer cells show differences not only in androgen responsiveness but in sensitivity to taxol as well. Copyright 2000 Wiley-Liss, Inc.

  15. MiR-221 promotes the development of androgen independence in prostate cancer cells via downregulation of HECTD2 and RAB1A

    OpenAIRE

    Sun, T; Wang, X; He, HH; Sweeney, CJ; Liu, SX; Brown, M.; Balk, S.; Lee, G-SM; Kantoff, PW

    2013-01-01

    Hormone-sensitive prostate cancer typically progresses to castration resistant prostate cancer (CRPC) after the androgen deprivation therapy. We investigated the impact of microRNAs (miRs) in the transition of prostate cancer to CRPC. MiR-221/-222 was highly expressed in bone metastatic CRPC tumor specimens. We previously demonstrated that transient overexpression of miR-221/-222 in LNCaP promoted the development of the CRPC phenotype. In current study, we show that stably overexpressing miR-...

  16. The relationship between cb1-b gene and androgen independent prostate cancer during the immunotherapy%Cb1-b基因与免疫治疗激素非依赖性前列腺癌

    Institute of Scientific and Technical Information of China (English)

    李学峰; 史振铎

    2010-01-01

    前列腺肿瘤主要的治疗手段包括手术、放化疗、内分泌治疗等.大多数晚期前列腺癌往往转变为激素非依赖性,对于激素非依赖性前列腺癌(Androgen Independent Prostate Cancer,AIPC)目前缺乏有效的治疗手段.研究发现Cb1-b(Casitas B cell lymphoma-b)基因在调节抗肿瘤免疫方面发挥着重要作用.通过沉默T细胞Cb1-b基因的表达从而增强机体的抗肿瘤免疫有望在AIPC治疗上实现重大突破.

  17. Overexpression of lysine-specific demethylase 1 promotes androgen-independent transition of human prostate cancer LNCaP cells through activation of the AR signaling pathway and suppression of the p53 signaling pathway.

    Science.gov (United States)

    Li, Xuechao; Li, Tao; Chen, Dehong; Zhang, Peng; Song, Yarong; Zhu, Hongxue; Xiao, Yajun; Xing, Yifei

    2016-01-01

    Lysine-specific demethylase 1 (LSD1) is the first defined histone demethylase, and was found to be closely correlated with the development and progression of various types of cancers, including prostate cancer (PCa). Previous research suggests that LSD1 is closely related with cell proliferation, angiogenesis, migration and invasion in PCa. However, it remains to be elucidated whether LSD1 is correlated with androgen-independent (AI) transition of PCa under androgen-ablated conditions. The present study aimed to investigate the correlation of LSD1 expression with AI transition of human androgen-dependent PCa LNCaP cells. Our data showed that LSD1 was overexpressed in human PCa specimens and in AI PCa LNCaP-AI cells, which were established through a three-month continuous culture of LNCaP cells in androgen-deprived medium. Under androgen-deprived conditions, LNCaP-AI cells grew perfectly with less apoptosis and G0/G1 cell cycle arrest. Overexpression of LSD1 protected the LNCaP cells from androgen deprivation-induced apoptosis and G0/G1 arrest, while knockdown of LSD1 drove LNCaP-AI cells into a higher rate of apoptosis and G0/G1 arrest. Furthermore, LSD1 was found to regulate the androgen receptor (AR) and p53 signaling pathways via demethylation, subsequently influencing apoptosis and cell cycle progression. These findings revealed that overexpression of LSD1 promoted AI transition of PCa LNCaP cells under androgen-ablated conditions via activation of the AR signaling pathway and suppression of the p53 signaling pathway. PMID:26534764

  18. Abrogation of heat-shock protein (HSP)70 expression induced cell growth inhibition and apoptosis in human androgen-independent prostate cancer cell line PC-3m

    Institute of Scientific and Technical Information of China (English)

    Zhi-GangZhao; Qing-ZhengMa; Chun-XiaoXu

    2004-01-01

    Aim: To investigate the effect of abrogating heat shock protein (HSP) 70 expression by antisense HSP70 oligonucleotides treatment on human androgen-independent prostate cancer cell line PC-3m growth. Methods: PC3m cells were treated with 0-16μmol/L antisense HSP70 oligomers for 0-100 hr. Cell growth inhibition was analyzed using a trypan blue dye exclusion test. Apoptotic cells were detected and confirmed by flow cytometric analysis and DNA fragmentation analysis. The protein expression of HSP70 and bcl-2 affected by antisense HSP70 oligomers were determined using Western blot. Results: Antisense HSP70 oligomer induced apoptosis and then inhibited proliferation of PC-3m cells in a dose- and time-dependent manner. Ladder-like patterns of DNA fragments were observed in PC-3m cells treated with 10μmol/L antisense HSP70 oligomer for 48 hr or 8μtmol/L for 72 hr on agarose gel electrophoresis. Antisense HSP70 oligomer pretreatment enhanced the subsequent induction of apoptosis by heat shock in PC-3m cells. In addition, undetectable HSP70 expression was observed at a concentration of 10μtmol/L antisense HSP70 oligomer treatment for 48 hr or 8μtmol/L for 72 hr in Western blot, which was paralleled by decreased expression levels of anti-apoptotic protein bcl-2. Conclusion: HSP70 antisense oligomer treatment abro-gates the expression of HSP70, which may disrupt HSP70-bcl-2-interactions and further down-regulate bcl-2 expression,in turn inducing apoptosis and inhibiting cell growth in PC-3m cells. (Asian JAndro12004 Dec;6:319-324)

  19. New Prostate Cancer Treatment Target

    Science.gov (United States)

    Researchers have identified a potential alternative approach to blocking a key molecular driver of an advanced form of prostate cancer, called androgen-independent or castration-resistant prostate cancer.

  20. A partner monoclonal antibody to Moab 730 kills 100% of DU145 and PC3 androgen-independent cancer cells

    Indian Academy of Sciences (India)

    Hemant Kumar Vyas; Rahul Pal; Nirmal K Lohiya; G P Talwar

    2009-12-01

    A number of therapeutic options are available for patients with prostate carcinoma till the time that the tumour is hormone dependent. However, no fully effective therapy is available for the treatment of androgen-independent prostate carcinomas. Antibodies directed at epitopes unique to or overexpressed on the cancer cells could be of therapeutic utility. A monoclonal antibody (Moab) 2C4 has been generated, which binds with cells of two androgenindependent prostate cancers, DU145 and PC3, and does not bind to peripheral blood leukocytes (PBLs) of healthy donors. This antibody, along with the previously developed Moab 730, kills 100% of both DU145 and PC3 cells in the presence of complement and does not have a deleterious effect on PBLs of healthy males. The anti-tumour action of the two antibodies prevents the establishment of DU145 cell tumour in nude mice in vivo. Moab 2C4 in combination with 730 has potential for use as therapy for androgen-independent cancers.

  1. 多西他赛联合沙利度胺治疗激素非依赖性晚期前列腺癌的临床观察%Clinical research on treatment of advanced androgen independent prostate cancer with Docetaxel and Thalidomide

    Institute of Scientific and Technical Information of China (English)

    Jing Tian; Donghai Teng; Xiangdong Shu; Hong Lu; Hui Chen; Peng Guo

    2009-01-01

    Objective:To evaluate the clinical effects and adverse reactions of Docetaxel and Thalidomide in treating ad-vanced androgen independent prostate cancer (AIPC). Methods:12 cases of advanced AIPC were given a combined treat-ment of Docataxel and Thalidomide, with Docetaxel 75 mg/m2 on day 1 and Thalidomide 100 mg per day as initial dose and 300 mg as terminal dose by an increase of 50 mg every week. Results:The post-treatment values of prostate specific antigen (PSA) were normal (< 4 ng/L) in 10 patients, less than 50% of pretreatment value in one patient, and no significant change in one patient. The median survival time was 14 months and period of the median symptoms reduction was 16.3 months. Com-mon adverse reactions were tolerable, including nausea, vomiting, leukopenia, anemia and thrombocytopenia. Conclusion:The regimen of Docetaxel combined with Thalidomide was effective and tolerable in the treatment of advanced AIPC.

  2. Neuroendocrine differentiation in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Jiaoti Huang

    2008-01-01

    @@ The treatment of choice for advanced/metastatic prostate cancer(PC) is hormonal therapy. Although patients respond initially to this therapy, the tumor will recur and enter the androgen-independent state, which is the major obstacle in therapy.

  3. 基因沉默白介素8对激素非依赖前列腺癌干细胞的生物特性的影响%Effect of Interleukin-8 Silencing on Androgen-independent Prostate Cancer Stem Cells

    Institute of Scientific and Technical Information of China (English)

    孙梦奎; 张纪恒; 崔韵; 金杰

    2016-01-01

    Objective To explore the effect of IL-8 silencing via small interfering RNA on androgen-independent pros-tate cancer stem cells and drug sensitive.Methods DU145 cells transfected with different concentration of IL-8 siRNA were col-lected .The percentage of ALDH+cells were detected by flow cytometry.The sphere formation rate and cloning efficiency were de-termined by sphere formation assay and clonogenic assay.The viability of cells was detected by CCK-8 assay.The phosphorylation of Akt was evaluated by Western blot.Results The percentage of ALDH+cells were declined under different concentration of IL-8 siRNA in DU145 cells.Sphere formation rate and cloning efficiency of prostate cancer stem cells were decreased by siRNA. The viability of IL-8 silencing DU145 cells was significantly suppressed compared with control groups and the Akt phosphorylation was activated.Conclusion IL-8 siRNA can eliminate androgen-independent prostate cancer stem cells and suppresses the self-renew and clonogenic capacity of prostate cancer stem cells.IL-8 silencing sensitizes prostate cancer stem cells to docetaxel and inactivates the Akt pathway.%目的:探讨小干扰RNA沉默激素非依赖前列腺癌DU145细胞白介素8基因对肿瘤干细胞生物学特性及耐药性的影响。方法用不同剂量的小干扰RNA沉默激素非依赖前列腺癌DU145细胞IL-8基因,应用流式仪检测AL-DH阳性细胞比例的变化。采用悬浮细胞成球和克隆形成实验分别观察肿瘤干细胞自我更新和体外成瘤能力的变化。Annexin V-PE/7-AAD细胞凋亡双染试剂盒检测细胞凋亡率的变化,Western-blot法分析Akt蛋白的变化。结果 DU145细胞IL-8基因的沉默能降低肿瘤干细胞的比例,显著降低肿瘤干细胞悬浮细胞成球率和克隆形成率。多西他赛能显著抑制IL-8基因沉默DU145细胞的活性。 Western-blot显示Akt的磷酸化被显著抑制。结论 IL-8基因的沉默能显著抑制激素非依赖前列

  4. Prolonged androgen deprivation leads to downregulation of androgen receptor and prostate-specific membrane antigen in prostate cancer cells

    OpenAIRE

    Liu, Tiancheng; Wu, Lisa Y.; Fulton, Melody D.; JOHNSON, JACQUELINE M.; Berkman, Clifford E.

    2012-01-01

    Emergence of androgen-independent cancer cells during androgen deprivation therapy presents a significant challenge to successful treatment outcomes in prostate cancer. Elucidating the role of androgen deprivation in the transition from an androgen-dependent to an androgen-independent state may enable the development of more effective therapeutic strategies against prostate cancer. Herein, we describe an in vitro model for assessing the effects of continuous androgen-deprivation on prostate c...

  5. Genipin blocks Uncoupling protein 2 in the inhibition effect of energy production and growth on androgen independent prostate cancer cells%京尼平阻断线粒体解耦联蛋白2对激素非依赖性前列腺癌细胞产能及生长的抑制作用

    Institute of Scientific and Technical Information of China (English)

    杨清滔; 谷江; 张永春; 朱致晖; 杨永安; 王楠; 祝庆亮; 姚茂良

    2014-01-01

    目的 从能量生成角度研究京尼平(Genipin)对激素非依赖性前列腺癌(AIPC)的抑制作用是否与线粒体解耦联蛋白2(UCP2)被阻断有关,并探讨其临床意义.方法 以低、中、高(40、80、120 μmol/L)剂量Genipin干预PC-3细胞培养基48 h,噻唑蓝(MTT)和流式细胞仪检测细胞增殖及凋亡,实时荧光定量聚合酶链反应(Real-time PCR)、Western blot检测UCP2表达,荧光探针检测细胞内Ca2含量,分光光度计检测线粒体膜电势(△ψm)、膜通透性转换孔(mPTP)变化及三磷酸腺苷(ATP)含量.结果 Genipin能显著抑制PC-3细胞增殖,其中对照组及低、中、高剂量组细胞凋亡率分别为(7.60±1.48)%、(9.38±1.01)%、(20.77±1.14)%、(23.48±1.99)%,Genipin可降低UCP2表达,此时细胞内Ca2含量明显增加,且mPTP开放程度增加及△ψm减小,ATP生成明显减少,其中对照组及低、中、高剂量组ATP含量分别为(0.120 ±0.015)、(0.110 ±0.013)、(0.080 ±0.007)、(0.050 ±0.008) mmol/L,以上改变均与Genipin浓度呈正相关,且各组间比较差异均有统计学意义(P<0.05).结论 Genipin能明显抑制AIPC细胞的增殖,该抑制作用可能与其阻断UCP2,导致线粒体功能异常,ATP生成减少有关.%Objective To investigate whether uncoupling protein 2 (UCP2) blocked was participated in genipin inhibiting proliferation of androgen independent prostate cancer cells from the perspective of energy,and to explore its clinical significance.Methods PC-3 cells were cultured in vitro,three concentrations of genipin solutions were added to the culture medium.The differences in proliferation,apoptosis,expressions of UCP2,levels of Ca2+,mitochondrion membrane potential (△ψm),membrane permeability transition pore (mPTP) and adenosine triphosphate (ATP) between before and after treated with various concentrations of genipin were measured by methyl thiazolyl tetrazolium (MTT) assay,flow cytometry assay,Real-time polymerase chain reaction

  6. Activated Cdc42-associated kinase Ack1 promotes prostate cancer progression via androgen receptor tyrosine phosphorylation

    OpenAIRE

    Mahajan, Nupam P.; Liu, Yuanbo; Majumder, Samarpan; Warren, Maria R.; Parker, Carol E.; Mohler, James L.; Earp, H. Shelton; Whang, Young E.

    2007-01-01

    Activation of the androgen receptor (AR) may play a role in androgen-independent progression of prostate cancer. Multiple mechanisms of AR activation, including stimulation by tyrosine kinases, have been postulated. We and others have recently shown involvement of activated Cdc42-associated tyrosine kinase Ack1 in advanced human prostate cancer. Here we provide the molecular basis for interplay between Ack1 and AR in prostate cancer cells. Activated Ack1 promoted androgen-independent growth o...

  7. Inhibitory effect of oridonin on androgen independent prostate cancer xenografts in nude mice%冬凌草甲素对雄激素非依赖性前列腺癌裸鼠移植瘤的抑制作用

    Institute of Scientific and Technical Information of China (English)

    徐凯; 郭剑明; 刘宇军; 徐志兵; 王国民

    2012-01-01

    Objective To research the inhibition effect of oridonin on androgen independent prostate cancer (AlPCa) xenografts in nude mice and its mechanism. Methods DU145 cells were injected subcutaneously to 20 male BALB/c-nude mice and those mice were randomly divided into oridonin group and control group. From day 2 after the injection, the mice were fed with 0.9% saline solution in the control group and odidonin (15 mg·Kg-1·D-1) in the oridonin group every day. The average size of xenografts was measured every week from week 2 to week 7. At the end of week 7, all mice were executed and the tumors were removed. The Mrna expression of G1/S regulatory factor p 16, cell proliferation related factor interleukin (IL-6 and immune escape related factor indoleamine 2, 3-dioxygenase (IDO) were analyzed by reverse transcriptase polymerase chain reaction. Results The growth of xenografts in the oridonin group was significantly inhibited, and the tumors were significantly smaller than those in the control group from the end of week 3 to week 7 (all P<0.001). Compared with control group, the growth inhibiting rate of the tumors in the oridonin group was 58.12% at the end of week 7. After 7 weeks, the average level of p16 Mrna in the control group was lower than that in the oridonin group (0.46 vs. 0.95); the average level of IL-6 Mrna in the control group was high than that in the oridonin group (0.33 vs. 0.02); the average level of IDO Mrna in the control group was 0.08, but it could not be measured in the oridonin group because there were no obvious electrophoretic bands. Conclusion Oridonin can obviously inhibit the growth of DU145 cells, indicating that oridonin has the antitumor activity to AlPCa. It may be achieved by downregulating cell cycle, immune escape and IL-6 level.%目的 探讨冬凌草甲素对雄激素非依赖性前列腺癌(AIPCa)裸鼠移植瘤的抑制作用及其机制.方法 雄性裸小鼠20只,皮下接种DU145细胞,随机分成用药组和

  8. Mitochondrial DNA determines androgen dependence in prostate cancer cell lines

    OpenAIRE

    Higuchi, M; Kudo, T; Suzuki, S.; Evans, TT; Sasaki, R.; Wada, Y; Shirakawa, T.; Sawyer, JR; Gotoh, A

    2006-01-01

    Prostate cancer progresses from an androgen-dependent to androgen-independent stage after androgen ablation therapy. Mitochondrial DNA plays a role in cell death and metastatic competence. Further, heteroplasmic large-deletion mitochondrial DNA is verycommon in prostate cancer. To investigate the role of mitochondrial DNA in androgen dependence of prostate cancers, we tested the changes of normal and deleted mitochondrial DNA in accordance with the progression of prostate cancer. We demonstra...

  9. Pomegranate Polyphenols Downregulate Expression of Androgen Synthesizing Genes in Human Prostate Cancer Cells Overexpressing the Androgen Receptor

    OpenAIRE

    Hong, Mee Young; Seeram, Navindra P.; Heber, David

    2008-01-01

    Prostate cancer is dependent on circulating testosterone in its early stages and is treatable with radiation and surgery. However, recurrent prostate tumors advance to an androgen-independent state where they progress in the absence of circulating testosterone leading to metastasis and death. During the development of androgen independence, prostate cancer cells are known to increase intracellular testosterone synthesis which maintains cancer cell growth in the absence of significant amounts ...

  10. Androgen-independent effects of Serenoa repens extract (Prostasan®) on prostatic epithelial cell proliferation and inflammation

    DEFF Research Database (Denmark)

    Iglesias-Gato, Diego; Carsten, Tober; Vesterlund, Mattias;

    2012-01-01

    Extracts from Serenoa repens are widely used for the treatment of benign prostatic hyperplasia (BPH) and traditionally for prostatitis. In the present study we evaluated the biological effects of Serenoa repens extract (Prostasan®) on prostate cells beyond its known antiandrogenic actions. Prosta...

  11. Prostate cancer and metastasis initiating stem cells

    Institute of Scientific and Technical Information of China (English)

    Kathleen Kelly; Juan Juan Yin

    2008-01-01

    Androgen refractory prostate cancer metastasis is a major clinical challenge.Mechanism-based approaches to treating prostate cancer metastasis require an understanding of the developmental origin of the metastasis-initiating cell.Properties of prostate cancer metastases such as plasticity with respect to differentiated phenotype and androgen independence are consistent with the transformation of a prostate epithelial progenitor or stem cell leading to metastasis.This review focuses upon current evidence and concepts addressing the identification and properties of normal prostate stem or progenitor cells and their transformed counterparts.

  12. Pharmacoeconomics of Available Treatment Options for Metastatic Prostate Cancer

    OpenAIRE

    Zeliadt, Steven B.; Penson, David F.

    2007-01-01

    The resources devoted to managing metastatic prostate cancer are enormous, yet little attention has been given to directly measuring the economic consequences of treatment alternatives. The purpose of this article was to evaluate the pharmacoeconomics of available treatments for metastatic prostate cancer, including hormone-sensitive disease, androgen-independent prostate cancer and locally advanced/progressive disease. We identified 58 articles addressing economic issues related to metastati...

  13. Stages of Prostate Cancer

    Science.gov (United States)

    ... Renal Cell) Cancer Leukemia Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ... Cancer Treatment Prostate Cancer Prevention Genetics of Prostate Cancer Prostate Cancer Screening Research Prostate Cancer Treatment (PDQ®)–Patient ...

  14. Neuroendocrine differentiation in prostate cancer%前列腺癌的神经内分泌分化

    Institute of Scientific and Technical Information of China (English)

    Jingwen Wang; Yang Yao

    2008-01-01

    Hormonal therapy is an important treatment for advanced/metastatic prostate cancer. But it can induce neuroen-docrine (NE) differentiation in prostate cancer cells. These NE cells will secrete manifold neural peptide or hormones which can lead to androgen-independent growth of non-NE tumor cells. When this happens, hormonal therapy becomes useless and indicates bad prognosis. In this paper, the mechanism of neuroendocrine differentiation and its relationship with androgen-independent were reviewed.

  15. Prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, G.P.; Kuss, R., Khoury, S.; Chatelain, C.; Denis, L.

    1987-01-01

    This book contains over 70 selections. Some of the titles are: Place of the Computed Tomography in the Staging of Prostatic Cancer; Magnetic Resonance Imaging (MRI) in Staging of the Prostatic Cancer; Magnetic Resonance Imaging of the Prostate; Long-Term Results in Radiotherapy of Prostatic Cancer; Interstitial Irradiation Using I-125 Seeds; and Treatment of Cancer of the Prostate by Use of Physiotherapy: Long-Term Results.

  16. A Mathematical Model of Intermittent Androgen Suppression for Prostate Cancer

    Science.gov (United States)

    Ideta, Aiko Miyamura; Tanaka, Gouhei; Takeuchi, Takumi; Aihara, Kazuyuki

    2008-12-01

    For several decades, androgen suppression has been the principal modality for treatment of advanced prostate cancer. Although the androgen deprivation is initially effective, most patients experience a relapse within several years due to the proliferation of so-called androgen-independent tumor cells. Bruchovsky et al. suggested in animal models that intermittent androgen suppression (IAS) can prolong the time to relapse when compared with continuous androgen suppression (CAS). Therefore, IAS has been expected to enhance clinical efficacy in conjunction with reduction in adverse effects and improvement in quality of life of patients during off-treatment periods. This paper presents a mathematical model that describes the growth of a prostate tumor under IAS therapy based on monitoring of the serum prostate-specific antigen (PSA). By treating the cancer tumor as a mixed assembly of androgen-dependent and androgen-independent cells, we investigate the difference between CAS and IAS with respect to factors affecting an androgen-independent relapse. Numerical and bifurcation analyses show how the tumor growth and the relapse time are influenced by the net growth rate of the androgen-independent cells, a protocol of the IAS therapy, and the mutation rate from androgen-dependent cells to androgen-independent ones.

  17. Prostate Cancer

    Science.gov (United States)

    ... man's bladder that produces fluid for semen. Prostate cancer is common among older men. It is rare ... younger than 40. Risk factors for developing prostate cancer include being over 65 years of age, family ...

  18. Prostate-specific antigen-activated thapsigargin prodrug as targeted therapy for prostate cancer

    DEFF Research Database (Denmark)

    Denmeade, Samuel R; Jakobsen, Carsten M; Janssen, Samuel;

    2003-01-01

    Standard anti-proliferative chemotherapy is relatively ineffective against slowly proliferating androgen-independent prostate cancer cells within metastatic sites. In contrast, the lipophilic cytotoxin thapsigargin, which causes apoptosis by disrupting intracellular free Ca2+ levels, is effective...... against both proliferative and quiescent (i.e., G0-arrested) cells. However, thapsigargin's mechanism of action indicates that it is unlikely to be selective for cancer cells or prostate cells....

  19. Learning about Prostate Cancer

    Science.gov (United States)

    ... of Information on Prostate Cancer What is prostate cancer? Prostate cancer is the most common cancer in American ... of page Additional Resources of Information on Prostate Cancer Prostate Cancer [nlm.nih.gov] From Medline Plus Medical ...

  20. Novel role of microRNAs in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    YU Jun-jie; XIA Shu-jie

    2013-01-01

    Objective To discuss the novel biomarkers of microRNAs in prostate cancer.Data sources The literatures about microRNAs and prostate cancer cited in this review were obtained mainly from Pubmed published in English from 2004 to 2012.Study selection Original articles regarding the novel role of microRNAs in prostate cancer were selected.Results MicroRNAs play an important role in prostate cancer such as cell differentiation,proliferation,apoptosis,and invasion.Especially microRNAs correlate with prostate cancer cell epithelial-mesenchymal transition (EMT),cancer stem cells (CSCs),drug sensitivity,cancer microenvironment,energy metabolism,androgen independence transformation,and diagnosis prediction.Conclusions MicroRNAs are involved in various aspects of prostate cancer biology.The role of microRNA in the initiation and development of prostate cancer deserves further study.

  1. Prostate Cancer

    OpenAIRE

    Eggener, Scott

    2011-01-01

    Prostate cancer continues to be a significant public health issue worldwide, particularly in countries where men have life expectancies long enough to clinically manifest the disease. In many countries, it remains one of the leading causes of cancer-related morbidity and mortality.Although significant progress has been made over the past few decades, many elements regarding the diagnosis and management of patients with prostate cancer remain enigmatic. In this Prostate Cancer special issue, o...

  2. Progress against Prostate Cancer

    Science.gov (United States)

    ... this page please turn Javascript on. Feature: Prostate Cancer Progress Against Prostate Cancer Past Issues / Winter 2010 Table of Contents ... Read More "Prostate Cancer" Articles Progress Against Prostate Cancer / Prostate Cancer Research Trial Helps John Spencer Treat His ...

  3. Cryotherapy for prostate cancer

    Science.gov (United States)

    Cryosurgery-prostate cancer; Cryoablation-prostate cancer ... Prostate Cancer. American Cancer Society. www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-treating-cryosurgery. Accessed August 31, 2015. Horwich ...

  4. Prostate cancer

    International Nuclear Information System (INIS)

    This work is about diagnosis, treatment and monitoring of prostate cancer. The techniques used are: transrectal ultrasound, laparascopy, bone scan, chest x-ray, radiography, chemoterapy and radiotherapy

  5. What is Prostate Cancer?

    Science.gov (United States)

    ... Research Get Involved Find Local ACS Learn About Cancer » Prostate Cancer » Detailed Guide » What is prostate cancer? Share ... how cancers start and spread, see What Is Cancer? Prostate cancer begins when cells in the prostate gland ...

  6. Chemotherapy of prostate cancer: present and future.

    Science.gov (United States)

    Trump, Donald; Lau, Yiu-Keung

    2003-06-01

    The role of chemotherapy in prostate cancer continues to evolve. In men with symptomatic androgen-independent prostate cancer, significant reduction in pain and analgesic requirements are achievable with mitoxantrone and glucocorticoid combinations compared with glucocorticoids alone. However, survival rates are not improved. Taxane-based combinations with estramustine phosphate or other new agents show promise. Prostate-specific antigen response rates with these combinations appear to be 1.5 to 2 times more frequent than with mitoxantrone-based combinations. Randomized trials of taxane versus mitoxantrone-based therapies are underway. New agents and applications of current agents in adjuvant settings should be explored if survival in men with prostate cancer is to be improved. PMID:12756087

  7. Chemotherapy of prostate cancer: present and future.

    Science.gov (United States)

    Trump, Donald; Lau, Yiu-Keung

    2003-06-01

    The role of chemotherapy in prostate cancer continues to evolve. In men with symptomatic androgen-independent prostate cancer, significant reduction in pain and analgesic requirements are achievable with mitoxantrone and glucocorticoid combinations compared with glucocorticoids alone. However, survival rates are not improved. Taxane-based combinations with estramustine phosphate or other new agents show promise. Prostate-specific antigen response rates with these combinations appear to be 1.5 to 2 times more frequent than with mitoxantrone-based combinations. Randomized trials of taxane versus mitoxantrone-based therapies are underway. New agents and applications of current agents in adjuvant settings should be explored if survival in men with prostate cancer is to be improved.

  8. Prostate Cancer (Radiation Therapy)

    Science.gov (United States)

    ... Physician Resources Professions Site Index A-Z Prostate Cancer Treatment Prostate cancer overview? What are my treatment options? What ... any new developments in treating my disease? Prostate cancer overview Prostate cancer is the most common form of cancer ...

  9. Genomic rearrangements of PTEN in prostate cancer

    Directory of Open Access Journals (Sweden)

    Sopheap ePhin

    2013-09-01

    Full Text Available The phosphatase and tensin homolog gene on chromosome 10q23.3 (PTEN is a negative regulator of the PIK3/Akt survival pathway and is the most frequently deleted tumor suppressor gene in prostate cancer. Monoallelic loss of PTEN is present in up to 60% of localized prostate cancers and complete loss of PTEN in prostate cancer is linked to metastasis and androgen independent progression. Studies on the genomic status of PTEN in prostate cancer initially used a two-color fluorescence in-situ hybridization (FISH assay for PTEN copy number detection in formalin fixed paraffin embedded tissue preparations. More recently, a four-color FISH assay containing two additional control probes flanking the PTEN locus with a lower false-positive rate was reported. Combined with the detection of other critical genomic biomarkers for prostate cancer such as ERG, AR, and MYC, the evaluation of PTEN genomic status has proven to be invaluable for patient stratification and management. Although less frequent than allelic deletions, point mutations in the gene and epigenetic silencing are also known to contribute to loss of PTEN function, and ultimately to prostate cancer initiation. Overall, it is clear that PTEN is a powerful biomarker for prostate cancer. Used as a companion diagnostic for emerging therapeutic drugs, FISH analysis of PTEN is promisingly moving human prostate cancer closer to more effective cancer management and therapies.

  10. Prostate cancer

    DEFF Research Database (Denmark)

    Chabanova, Elizaveta; Balslev, Ingegerd; Logager, Vibeke;

    2011-01-01

    To investigate diagnostic accuracy of detection of prostate cancer by magnetic resonance: to evaluate the performance of T2WI, DCEMRI and CSI and to correlate the results with biopsy and radical prostatectomy histopathological data....

  11. Prostate cancer

    DEFF Research Database (Denmark)

    Chabanova, Elizaveta; Balslev, Ingegerd; Logager, Vibeke;

    2011-01-01

    To investigate diagnostic accuracy of detection of prostate cancer by magnetic resonance: to evaluate the performance of T2WI, DCEMRI and CSI and to correlate the results with biopsy and radical prostatectomy histopathological data.......To investigate diagnostic accuracy of detection of prostate cancer by magnetic resonance: to evaluate the performance of T2WI, DCEMRI and CSI and to correlate the results with biopsy and radical prostatectomy histopathological data....

  12. Development of New Treatments for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    DiPaola, R. S.; Abate-Shen, C.; Hait, W. N.

    2005-02-01

    The Dean and Betty Gallo Prostate Cancer Center (GPCC) was established with the goal of eradicating prostate cancer and improving the lives of men at risk for the disease through research, treatment, education and prevention. GPCC was founded in the memory of Dean Gallo, a beloved New Jersey Congressman who died tragically of prostate cancer diagnosed at an advanced stage. GPCC unites a team of outstanding researchers and clinicians who are committed to high-quality basic research, translation of innovative research to the clinic, exceptional patient care, and improving public education and awareness of prostate cancer. GPCC is a center of excellence of The Cancer Institute of New Jersey, which is the only NCI-designated comprehensive cancer center in the state. GPCC efforts are now integrated well as part of our Prostate Program at CINJ, in which Dr. Robert DiPaola and Dr. Cory Abate-Shen are co-leaders. The Prostate Program unites 19 investigators from 10 academic departments who have broad and complementary expertise in prostate cancer research. The overall goal and unifying theme is to elucidate basic mechanisms of prostate growth and oncogenesis, with the ultimate goal of promoting new and effective strategies for the eradication of prostate cancer. Members' wide range of research interests collectively optimize the chances of providing new insights into normal prostate biology and unraveling the molecular pathophysiology of prostate cancer. Cell culture and powerful animal models developed by program members recapitulate the various stages of prostate cancer progression, including prostatic intraepithelial neoplasia, adenocarcinoma, androgen-independence, invasion and metastases. These models promise to further strengthen an already robust program of investigator-initiated therapeutic clinical trials, including studies adopted by national cooperative groups. Efforts to translate laboratory results into clinical studies of early detection and

  13. [Prostate cancer and chemotherapy].

    Science.gov (United States)

    Gravis, Gwenaelle; Salem, Naji; Bladou, Franck; Viens, Patrice

    2007-07-01

    Androgen deprivation in patients with metastatic prostate cancer produces palliation of symptoms, PSA decrease and tumoral regression in most patients. After a brief period of disease regression lasting 18 to 24 months nearly all pts will progress to androgen independence disease (HRPC) with progressive clinical deterioration and ultimately death. Chemotherapy with mitoxantrone has been shown to palliate symptoms but did not extend survival. Two large randomized trials showed a survival benefit for pts with HRPC treated with docetaxel with a reduction risk of death by 21-24%, and significant improvement in palliation of symptoms and quality of life. New agents targeting angiogenesis, apoptosis, signal transduction pathway, used alone or in combination with docetaxel currently are under trial in an attempt to provide much needed improvements in outcome. Questions remains in suspend when and who need to be treated, earlier, in high risk as in adjuvant setting? Current data have demonstrated that neoadjuvant or adjuvant chemotherapy is relatively safe and feasible. Further investigation through prospective randomize trials is critical to define the precise role of this modality in high risk populations. PMID:17845990

  14. Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Scott Eggener

    2011-01-01

    Full Text Available Prostate cancer continues to be a significant public health issue worldwide, particularly in countries where men have life expectancies long enough to clinically manifest the disease. In many countries, it remains one of the leading causes of cancer-related morbidity and mortality.

  15. Prostate cancer - treatment

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000403.htm Prostate cancer - treatment To use the sharing features on this ... a combination of drugs is recommended. References National Cancer Institute. Prostate cancer treatment (PDQ): Stages of prostate cancer. Updated ...

  16. Cancer of the Prostate

    Science.gov (United States)

    ... will die of this disease. Who Gets This Cancer? Prostate cancer occurs only in men, and it is ... Percent of New Cases by Age Group: Prostate Cancer Prostate cancer is most frequently diagnosed among men aged ...

  17. Prostate cancer - resources

    Science.gov (United States)

    Resources - prostate cancer ... The following organizations are good resources for information on prostate cancer : American Cancer Society -- www.cancer.org/cancer/prostatecancer/index National Cancer Institute -- www.cancer.gov/cancertopics/ ...

  18. What Is Prostate Cancer?

    Medline Plus

    Full Text Available ... no such thing as one type of prostate cancer. Prostate cancer is really a spectrum of diseases where on ... very benevolent in its behavior. Men will develop prostate cancer and live the rest of their lives -- 20, ...

  19. Prostate Cancer Foundation

    Science.gov (United States)

    ... P 2 rovocative Questions PCCTC Scientific Retreat Coffey-Holden Research News Faces of Prostate Cancer [4] Survivors ... Foundation News The Prostate Cancer Foundation’s 2016 Coffey-Holden Prostate Cancer Academy Meeting accelerates advances in the ...

  20. Experimental Evidence of Persistent Androgen-Receptor-Dependency in Castration-Resistant Prostate Cancer

    OpenAIRE

    Osamu Ogawa; Tomomi Kamba; Takahiro Inoue; Takashi Kobayashi

    2013-01-01

    In the majority of castration-resistant prostate cancer (CRPC), prostate-specific antigen (PSA), product of a gene that is almost exclusively regulated by the androgen receptor (AR), still acts as a serum marker reflecting disease burden, indicating that AR signaling is activated even under castrate level of serum androgen. Accumulated evidence shows that transcriptional ability of AR is activated both in ligand-dependent and -independent manners in CRPC cells. Some androgen-independent subli...

  1. Localized Prostate Cancer

    Science.gov (United States)

    ... a decision aid for men with clinically localized prostate cancer (available at http://effectivehealthcare.ahrq.gov/prostate_da) ... A Decision Aid for Men With Clinically Localized Prostate Cancer Page 1 of 24 Introduction Men with clinically ...

  2. Stroma-epithelium crosstalk in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Yi-Nong Niu; Shu-Jie Xia

    2009-01-01

    The critical role played by stroma-epithelium crosstalk in carcinogenesis and progression of prostate cancer has been increasingly recognized.These interactions are mediated by a variety of paracrine factors secreted by cancer cells and/or stromal cells.In human prostate cancer,reactive stroma is characterized by an increase in myofibroblasts and a corresponding amplification of extracellular matrix production and angiogenesis.Permanent genetic mutations have been reported in stromal cells as well as in turnout cells.Transforming growth factor-β,vascular endothelial growth factor,platelet-derived growth factor and fibroblast growth factor signalling pathways are involved in the process of angiogenesis,whereas hepatocyte growth factor,insulin-like growth factor-1,epidermal growth factor,CXC12 and Interleukin-6 play active roles in the progression,androgen-independent conversion and distal metastasis of prostate cancer.Some soluble factors have reciprocal interactions with androgens and the androgen receptor (AR),and can even activate AR in the absence of the androgen ligand.In this article,we review the complex interactions between cancer cells and the surrounding microenvironment,and discuss the potential therapeutic targets in the stromal compartment of prostate cancer.

  3. Can Prostate Cancer Be Found Early?

    Science.gov (United States)

    ... Research Get Involved Find Local ACS Learn About Cancer » Prostate Cancer » Detailed Guide » Can prostate cancer be found ... and symptoms of prostate cancer Tests for prostate cancer Prostate cancer stages Survival rates for prostate cancer Previous ...

  4. Prostate cancer screenings

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000846.htm Prostate cancer screenings To use the sharing features on this ... Intern Med . 2011;155(11):762-71. National Cancer Institute. Prostate Cancer Screening -- for health professionals. Revised April 2, ...

  5. 6 Common Cancers - Prostate Cancer

    Science.gov (United States)

    ... PSA tests. Read More "6 Common Cancers" Articles Lung Cancer / Breast Cancer / Prostate Cancer / Colorectal Cancer / Skin Cancer / Gynecologic Cancers Spring 2007 Issue: Volume 2 Number 2 Page 10 MedlinePlus | Subscribe | Magazine Information | Contact Us | Viewers & ...

  6. Differential CARM1 expression in prostate and colorectal cancers

    Directory of Open Access Journals (Sweden)

    Nguyen Nguyen

    2010-05-01

    Full Text Available Abstract Background Coactivator-associated arginine methyltransferase 1 (CARM1 functions as a transcriptional coactivator of androgen receptor (AR-mediated signaling. Correspondingly, overexpression of CARM1 has been associated with the development of prostate cancer (PCa and its progression to androgen-independent PCa. In our preliminary study, however, the promoting effects of CARM1, with regard to androgen-stimulated AR target gene expression were minimal. These results suggested that the AR target gene expression associated with CARM1 may result primarily from non-hormone dependent activity. The goal of this study was to confirm the pattern of expression of CARM1 in human tumors and determine the mechanism of action in CARM1 overexpressed tumors. Methods Tissue microarray was used to determine the pattern of expression of CARM1 in human cancers by immunohistochemistry. CARM1 expression was also evaluated in prostate and colorectal surgical specimens and the clinical records of all cases were reviewed. In addition, a reporter transcription assay using the prostate-specific antigen (PSA promoter was used to identify the signaling pathways involved in non-hormone-mediated signal activation associated with CARM1. Results The tissue microarray showed that CARM1 was particularly overexpressed in the colorectal cancers while CARM1 expression was not prevalent in the prostate and breast cancers. Further studies using surgical specimens demonstrated that CARM1 was highly overexpressed in 75% of colorectal cancers (49 out of 65 but not in the androgen-independent PCa. In addition, CARM1's coactivating effect on the entire PSA promoter was very limited in both androgen-dependent and androgen-independent PCa cells. These results suggest that there are other factors associated with CARM1 expression in PSA regulation. Indeed, CARM1 significantly regulated both p53 and NF-κB target gene transcription. Conclusions The results of this study suggest that, in

  7. Arsenic trioxide enhances the radiation sensitivity of androgen-dependent and -independent human prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Hui-Wen Chiu

    Full Text Available Prostate cancer is the most common malignancy in men. In the present study, LNCaP (androgen-sensitive human prostate cancer cells and PC-3 cells (androgen-independent human prostate cancer cells were used to investigate the anti-cancer effects of ionizing radiation (IR combined with arsenic trioxide (ATO and to determine the underlying mechanisms in vitro and in vivo. We found that IR combined with ATO increases the therapeutic efficacy compared to individual treatments in LNCaP and PC-3 human prostate cancer cells. In addition, combined treatment showed enhanced reactive oxygen species (ROS generation compared to treatment with ATO or IR alone in PC-3 cells. Combined treatment induced autophagy and apoptosis in LNCaP cells, and mainly induced autophagy in PC-3 cells. The cell death that was induced by the combined treatment was primarily the result of inhibition of the Akt/mTOR signaling pathways. Furthermore, we found that the combined treatment of cells pre-treated with 3-MA resulted in a significant change in AO-positive cells and cytotoxicity. In an in vivo study, the combination treatment had anti-tumor growth effects. These novel findings suggest that combined treatment is a potential therapeutic strategy not only for androgen-dependent prostate cancer but also for androgen-independent prostate cancer.

  8. Prostate cancer staging

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000397.htm Prostate cancer staging To use the sharing features on this ... trials you may be able to join How Prostate Cancer Staging is Done Initial staging is based on ...

  9. Prostate cancer in Denmark

    DEFF Research Database (Denmark)

    Brasso, K; Friis, S; Kjaer, S K;

    1998-01-01

    To review the trends in prostate cancer (PC) incidence and mortality rates in Denmark during a 50-year period.......To review the trends in prostate cancer (PC) incidence and mortality rates in Denmark during a 50-year period....

  10. Prostate Cancer Prevention

    Science.gov (United States)

    ... prostate cancer increases as men get older. Family history of prostate cancer A man whose father, brother, ... some foods, such as green vegetables, beans and orange juice. Folic acid is a man-made form ...

  11. Analysis of the molecular networks in androgen dependent and independent prostate cancer revealed fragile and robust subsystems.

    Directory of Open Access Journals (Sweden)

    Ryan Tasseff

    Full Text Available Androgen ablation therapy is currently the primary treatment for metastatic prostate cancer. Unfortunately, in nearly all cases, androgen ablation fails to permanently arrest cancer progression. As androgens like testosterone are withdrawn, prostate cancer cells lose their androgen sensitivity and begin to proliferate without hormone growth factors. In this study, we constructed and analyzed a mathematical model of the integration between hormone growth factor signaling, androgen receptor activation, and the expression of cyclin D and Prostate-Specific Antigen in human LNCaP prostate adenocarcinoma cells. The objective of the study was to investigate which signaling systems were important in the loss of androgen dependence. The model was formulated as a set of ordinary differential equations which described 212 species and 384 interactions, including both the mRNA and protein levels for key species. An ensemble approach was chosen to constrain model parameters and to estimate the impact of parametric uncertainty on model predictions. Model parameters were identified using 14 steady-state and dynamic LNCaP data sets taken from literature sources. Alterations in the rate of Prostatic Acid Phosphatase expression was sufficient to capture varying levels of androgen dependence. Analysis of the model provided insight into the importance of network components as a function of androgen dependence. The importance of androgen receptor availability and the MAPK/Akt signaling axes was independent of androgen status. Interestingly, androgen receptor availability was important even in androgen-independent LNCaP cells. Translation became progressively more important in androgen-independent LNCaP cells. Further analysis suggested a positive synergy between the MAPK and Akt signaling axes and the translation of key proliferative markers like cyclin D in androgen-independent cells. Taken together, the results support the targeting of both the Akt and MAPK

  12. Loss of mir-146a function in hormone-refractory prostate cancer

    OpenAIRE

    Lin, Shi-Lung; Chiang, Angela; Chang, Donald; Ying, Shao-Yao

    2008-01-01

    The pattern of microRNA (miRNA) expression is associated with the degree of tumor cell differentiation in human prostate cancer. MiRNAs bind complementarily to either oncogenes or tumor suppressor genes, which are consequently silenced, resulting in alterations of tumorigenecity. We have detected eight down-regulated and three up-regulated known miRNAs in androgen-independent human prostate cancer cells compared to those in androgen-dependent cells, using miRNA microarray analyses. These iden...

  13. Prostate cancer stem cells

    OpenAIRE

    Tu, Shi-Ming; Lin, Sue-Hwa

    2011-01-01

    Stem cells have long been implicated in prostate glandular formation. The prostate undergoes regression after androgen deprivation and regeneration after testosterone replacement. Regenerative studies suggest that these cells are found in the proximal ducts and basal layer of the prostate. Many characteristics of prostate cancer indicate that it originates from stem cells. For example, the putative AR− status of prostate stem cells renders them inherently insensitive to androgen blockade ther...

  14. Cryotherapy for prostate cancer

    Science.gov (United States)

    Cryotherapy uses very cold temperatures to freeze and kill prostate cancer cells. The goal of cryosurgery is ... Possible short-term side effects of cryotherapy for prostate ... of the penis or scrotum Problems controlling your bladder (more ...

  15. Detecting Prostate Cancer

    Medline Plus

    Full Text Available ... like to do is just do a rectal examination and feel that prostate. Narrator: The other necessary ... they do have an abnormality in their rectal examination does not mean that they have prostate cancer. ...

  16. Hormone therapy for prostate cancer

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000908.htm Hormone therapy for prostate cancer To use the sharing ... helps slow the growth of prostate cancer. Male Hormones and Prostate Cancer Androgens are male sex hormones. ...

  17. Prostate Cancer Screening

    Science.gov (United States)

    ... man's bladder that produces fluid for semen. Cancer screening is looking for cancer before you have any ... be easier to treat. There is no standard screening test for prostate cancer. Researchers are studying different ...

  18. Targeting Btk/Etk of prostate cancer cells by a novel dual inhibitor

    Science.gov (United States)

    Guo, W; Liu, R; Bhardwaj, G; Yang, J C; Changou, C; Ma, A-H; Mazloom, A; Chintapalli, S; Xiao, K; Xiao, W; Kumaresan, P; Sanchez, E; Yeh, C-T; Evans, C P; Patterson, R; Lam, K S; Kung, H-J

    2014-01-01

    Btk and Etk/BMX are Tec-family non-receptor tyrosine kinases. Btk has previously been reported to be expressed primarily in B cells and has an important role in immune responses and B-cell malignancies. Etk has been shown previously to provide a strong survival and metastasis signal in human prostate cancer cells, and to confer androgen independence and drug resistance. While the role of Etk in prostate carcinogenesis is well established, the functions of Btk in prostate cancer have never been investigated, likely due to the perception that Btk is a hematopoietic, but not epithelial, kinase. Herein, we found that Btk is overexpressed in prostate cancer tissues and prostate cancer cells. The level of Btk in prostate cancer tissues correlates with cancer grades. Knockdown of Btk expression selectively inhibits the growth of prostate cancer cells, but not that of the normal prostate epithelial cells, which express very little Btk. Dual inhibition of Btk and Etk has an additive inhibitory effect on prostate cancer cell growth. To explore Btk and Etk as targets for prostate cancer, we developed a small molecule dual inhibitor of Btk and Etk, CTN06. Treatment of PC3 and other prostate cancer cells, but not immortalized prostate epithelial cells with CTN06 resulted in effective cell killing, accompanied by the attenuation of Btk/Etk signals. The killing effect of CTN06 is more potent than that of commonly used inhibitors against Src, Raf/VEGFR and EGFR. CTN06 induces apoptosis as well as autophagy in human prostate cancer cells, and is a chemo-sensitizer for docetaxel (DTX), a standard of care for metastatic prostate cancer patients. CTN06 also impeded the migration of human prostate cancer cells based on a ‘wound healing' assay. The anti-cancer effect of CTN06 was further validated in vivo in a PC3 xenograft mouse model. PMID:25188519

  19. Hydrogen Sulfide Signaling Axis as a Target for Prostate Cancer Therapeutics

    Directory of Open Access Journals (Sweden)

    Mingzhe Liu

    2016-01-01

    Full Text Available Hydrogen sulfide (H2S was originally considered toxic at elevated levels; however just in the past decade H2S has been proposed to be an important gasotransmitter with various physiological and pathophysiological roles in the body. H2S can be generated endogenously from L-cysteine by multiple enzymes, including cystathionine gamma-lyase, cystathionine beta-synthase, and 3-mercaptopyruvate sulfurtransferase in combination with cysteine aminotransferase. Prostate cancer is a major health concern and no effective treatment for prostate cancers is available. H2S has been shown to inhibit cell survival of androgen-independent, androgen-dependent, and antiandrogen-resistant prostate cancer cells through different mechanisms. Various H2S-releasing compounds, including sulfide salts, diallyl disulfide, diallyl trisulfide, sulforaphane, and other polysulfides, also have been shown to inhibit prostate cancer growth and metastasis. The expression of H2S-producing enzyme was reduced in both human prostate cancer tissues and prostate cancer cells. Androgen receptor (AR signaling is indispensable for the development of castration resistant prostate cancer, and H2S was shown to inhibit AR transactivation and contributes to antiandrogen-resistant status. In this review, we summarized the current knowledge of H2S signaling in prostate cancer and described the molecular alterations, which may bring this gasotransmitter into the clinic in the near future for developing novel pharmacological and therapeutic interventions for prostate cancer.

  20. Hydrogen Sulfide Signaling Axis as a Target for Prostate Cancer Therapeutics

    Science.gov (United States)

    Liu, Mingzhe; Wu, Lingyun; Montaut, Sabine; Yang, Guangdong

    2016-01-01

    Hydrogen sulfide (H2S) was originally considered toxic at elevated levels; however just in the past decade H2S has been proposed to be an important gasotransmitter with various physiological and pathophysiological roles in the body. H2S can be generated endogenously from L-cysteine by multiple enzymes, including cystathionine gamma-lyase, cystathionine beta-synthase, and 3-mercaptopyruvate sulfurtransferase in combination with cysteine aminotransferase. Prostate cancer is a major health concern and no effective treatment for prostate cancers is available. H2S has been shown to inhibit cell survival of androgen-independent, androgen-dependent, and antiandrogen-resistant prostate cancer cells through different mechanisms. Various H2S-releasing compounds, including sulfide salts, diallyl disulfide, diallyl trisulfide, sulforaphane, and other polysulfides, also have been shown to inhibit prostate cancer growth and metastasis. The expression of H2S-producing enzyme was reduced in both human prostate cancer tissues and prostate cancer cells. Androgen receptor (AR) signaling is indispensable for the development of castration resistant prostate cancer, and H2S was shown to inhibit AR transactivation and contributes to antiandrogen-resistant status. In this review, we summarized the current knowledge of H2S signaling in prostate cancer and described the molecular alterations, which may bring this gasotransmitter into the clinic in the near future for developing novel pharmacological and therapeutic interventions for prostate cancer. PMID:27019751

  1. A clinical data validated mathematical model of prostate cancer growth under intermittent androgen suppression therapy

    Science.gov (United States)

    Portz, Travis; Kuang, Yang; Nagy, John D.

    2012-03-01

    Prostate cancer is commonly treated by a form of hormone therapy called androgen suppression. This form of treatment, while successful at reducing the cancer cell population, adversely affects quality of life and typically leads to a recurrence of the cancer in an androgen-independent form. Intermittent androgen suppression aims to alleviate some of these adverse affects by cycling the patient on and off treatment. Clinical studies have suggested that intermittent therapy is capable of maintaining androgen dependence over multiple treatment cycles while increasing quality of life during off-treatment periods. This paper presents a mathematical model of prostate cancer to study the dynamics of androgen suppression therapy and the production of prostate-specific antigen (PSA), a clinical marker for prostate cancer. Preliminary models were based on the assumption of an androgen-independent (AI) cell population with constant net growth rate. These models gave poor accuracy when fitting clinical data during simulation. The final model presented hypothesizes an AI population with increased sensitivity to low levels of androgen. It also hypothesizes that PSA production is heavily dependent on androgen. The high level of accuracy in fitting clinical data with this model appears to confirm these hypotheses, which are also consistent with biological evidence.

  2. What Is Prostate Cancer?

    Medline Plus

    Full Text Available ... the more likely he is to develop the disease. Physician: Come on back, first room. Narrator: Most ... cancer. Prostate cancer is really a spectrum of diseases where on one end of the spectrum there ...

  3. Detecting Prostate Cancer

    Medline Plus

    Full Text Available ... abnormal and raises the index of suspicion that cancer may be present. Narrator: While the use of ... examination does not mean that they have prostate cancer. It means that we're concerned about it ...

  4. Prostate Cancer and Sexual Function

    OpenAIRE

    Hyun, Jae Saog

    2012-01-01

    Prostate cancer is now ranked fifth in incidence among cancers in Korean adult males. This is attributable to the more Westernized dietary style which increases the morbidity of prostate cancer and the development of cancer diagnostic technologies, such as prostate-specific antigen and advanced medical systems, increasing the rate of prostate cancer diagnosis. Prostate cancer effects include not only erectile dysfunction caused by the disease itself, but also by psychiatric disorders caused b...

  5. Prostate Cancer Research Trial Helps John Spencer Treat His Cancer

    Science.gov (United States)

    ... this page please turn Javascript on. Feature: Prostate Cancer Prostate Cancer Research Trial Helps John Spencer Treat His ... Read More "Prostate Cancer" Articles Progress Against Prostate Cancer / Prostate Cancer Research Trial Helps John Spencer Treat His ...

  6. Prostate Cancer Screening (Beyond the Basics)

    Science.gov (United States)

    ... best in your individual situation. WHAT IS PROSTATE CANCER? — Prostate cancer is a cancer of the prostate, a ... most of them do not die from their cancer. Prostate cancer often grows so slowly that many men ...

  7. GLI1, a crucial mediator of sonic hedgehog signaling in prostate cancer, functions as a negative modulator for androgen receptor

    International Nuclear Information System (INIS)

    Research highlights: → GLI1, which play a central role in sonic hedgehog signaling in prostate cancer, can act as a co-repressor to substantially block androgen receptor-mediated transactivation. → GLI1 directly interacts with AR. → SHH-GLI pathway might be one of determinants governing the transition of prostate cancer from an androgen-dependent to an androgen-independent state. -- Abstract: Sonic hedgehog (SHH) signaling, acting in a combinatorial manner with androgen signaling, is essential for prostate patterning and development. Recently, elevated activation of SHH signaling has been shown to play important roles in proliferation, progression and metastasis of prostate cancer. In this report, we demonstrate for the first time, that GLI1, which has been shown to play a central role in SHH signaling in prostate cancer, can act as a co-repressor to substantially block androgen receptor (AR)-mediated transactivation, at least in part, by directly interacting with AR. Our observations suggest that the SHH-GLI pathway might be one of determinants governing the transition of prostate cancer from an androgen-dependent to an androgen-independent state by compensating, or even superseding androgen signaling.

  8. GLI1, a crucial mediator of sonic hedgehog signaling in prostate cancer, functions as a negative modulator for androgen receptor

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Guangchun; Goto, Yutaka; Sakamoto, Ryuichi; Tanaka, Kimitaka; Matsubara, Eri [Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582 (Japan); Nakamura, Masafumi [Department of Cancer Therapy and Research, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582 (Japan); Zheng, Hong [School of Pharmacy, Second Military Medical University, Shanghai 200433 (China); Lu, Jian [Department of Pathophysiology, Second Military Medical University, Shanghai 200433 (China); Takayanagi, Ryoichi [Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582 (Japan); Nomura, Masatoshi, E-mail: nomura@med.kyushu-u.ac.jp [Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582 (Japan)

    2011-01-21

    Research highlights: {yields} GLI1, which play a central role in sonic hedgehog signaling in prostate cancer, can act as a co-repressor to substantially block androgen receptor-mediated transactivation. {yields} GLI1 directly interacts with AR. {yields} SHH-GLI pathway might be one of determinants governing the transition of prostate cancer from an androgen-dependent to an androgen-independent state. -- Abstract: Sonic hedgehog (SHH) signaling, acting in a combinatorial manner with androgen signaling, is essential for prostate patterning and development. Recently, elevated activation of SHH signaling has been shown to play important roles in proliferation, progression and metastasis of prostate cancer. In this report, we demonstrate for the first time, that GLI1, which has been shown to play a central role in SHH signaling in prostate cancer, can act as a co-repressor to substantially block androgen receptor (AR)-mediated transactivation, at least in part, by directly interacting with AR. Our observations suggest that the SHH-GLI pathway might be one of determinants governing the transition of prostate cancer from an androgen-dependent to an androgen-independent state by compensating, or even superseding androgen signaling.

  9. Prostate cancer; Cancer de la prostate

    Energy Technology Data Exchange (ETDEWEB)

    Vieillot, S.; Fenoglietto, P.; Ailleres, N.; Hay, M.H.; Dubois, J.B.; Azria, D. [Departement de cancerologie radiotherapie, Universite Montpellier I, CRLC Val d' Aurelle, 34 - Montpellier (France)

    2010-07-01

    Radiation therapy is now widely accepted as an efficacious treatment of localized prostate cancer. The technical developments of recent years have enabled the evolution of a three-dimensional conformal radiotherapy, offering a better adaptation of the dose distribution, and leading therefore to preserve organs at risk. In addition, the required dose delivered to the target volume permit physician to increase the total dose if necessary. This requires a thorough knowledge of the radio-anatomy of the prostate, the natural history of the disease but also the ballistics and dosimetry. The objectives of this work were to detail epidemiology and radio-anatomy of the prostate cancer. In addition, conformal radiation modalities are illustrated by a case report. (authors)

  10. Casodex treatment induces hypoxia-related gene expression in the LNCaP prostate cancer progression model

    Directory of Open Access Journals (Sweden)

    Gopalakrishnan Velliyur K

    2005-03-01

    Full Text Available Abstract Background The changes in gene expression profile as prostate cancer progresses from an androgen-dependent disease to an androgen-independent disease are still largely unknown. Methods We examined the gene expression profile in the LNCaP prostate cancer progression model during chronic treatment with Casodex using cDNA microarrays consisting of 2305 randomly chosen genes. Results Our studies revealed a representative collection of genes whose expression was differentially regulated in LNCaP cells upon treatment with Casodex. A set of 15 genes were shown to be highly expressed in Casodex-treated LNCaP cells compared to the reference sample. This set of highly expressed genes represents a signature collection unique to prostate cancer since their expression was significantly greater than that of the collective pool of ten cancer cell lines of the reference sample. The highly expressed signature collection included the hypoxia-related genes membrane metallo-endopeptidase (MME, cyclin G2, and Bcl2/adenovirus E1B 19 kDa (BNIP3. Given the roles of these genes in angiogenesis, cell cycle regulation, and apoptosis, we further analyzed their expression and concluded that these genes may be involved in the molecular changes that lead to androgen-independence in prostate cancer. Conclusion Our data indicate that one of the mechanisms of Casodex action in prostate cancer cells is induction of hypoxic gene expression.

  11. XAF1 expression and regulatory effects of somatostatin on XAF1 in prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Li Chunde

    2010-12-01

    Full Text Available Abstract Background Somatostatin prevents cell proliferation by inducing apoptosis. Downregulation of the XAF1 transcript may occur during the development of prostate cancer. It is interesting to evaluate the potential regulatory effects of somatostatin on XAF1 expression during the development of prostate cancer cells. Methods XAF1 mRNA and protein expression in human prostate epithelial cells RWPE-1, androgen dependent prostate cancer LNCaP, and androgen independent DU145 and PC3 cells were evaluated using RT-PCR and Western blot. The regulation of XAF1 mRNA and protein expression by somatostatin and its analogue Octreotide was evaluated. Results Substantial levels of XAF1 mRNA and proteins were detected in RWPE-1 cells, whereas prostate cancer cells LNCaP, DU145 and PC3 exhibited lower XAF1 expression. Somatostatin and Octreotide up-regulated XAF1 mRNA and protein expression in all prostate cancer cell lines. Conclusions XAF1 down-regulation may contribute to the prostate cancer development. The enhanced XAF1 expression by somatostatin indicates a promising strategy for prostate cancer therapy.

  12. What Tests Can Detect Prostate Cancer?

    Science.gov (United States)

    ... saved articles window. My Saved Articles » My ACS » Prostate Cancer Prevention and Early Detection + - Text Size Download Printable Version [ ... coverage for prostate cancer screening Additional resources for prostate cancer prevention and early detection References: Prostate cancer prevention and ...

  13. Detecting Prostate Cancer

    Medline Plus

    Full Text Available ... rectal examination does not mean that they have prostate cancer. It means that we're concerned about it and they should go on to have other tests, such as a trans-rectal ultrasound ... made of the prostate gland. Usually these are accompanied by a biopsy -- ...

  14. Detecting Prostate Cancer

    Science.gov (United States)

    ... rectal examination does not mean that they have prostate cancer. It means that we're concerned about it and they should go on to have other tests, such as a trans-rectal ultrasound ... made of the prostate gland. Usually these are accompanied by a biopsy -- ...

  15. Epigenetics in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Costantine Albany

    2011-01-01

    Full Text Available Prostate cancer (PC is the most commonly diagnosed nonskin malignancy and the second most common cause of cancer death among men in the United States. Epigenetics is the study of heritable changes in gene expression caused by mechanisms other than changes in the underlying DNA sequences. Two common epigenetic mechanisms, DNA methylation and histone modification, have demonstrated critical roles in prostate cancer growth and metastasis. DNA hypermethylation of cytosine-guanine (CpG rich sequence islands within gene promoter regions is widespread during neoplastic transformation of prostate cells, suggesting that treatment-induced restoration of a “normal” epigenome could be clinically beneficial. Histone modification leads to altered tumor gene function by changing chromosome structure and the level of gene transcription. The reversibility of epigenetic aberrations and restoration of tumor suppression gene function have made them attractive targets for prostate cancer treatment with modulators that demethylate DNA and inhibit histone deacetylases.

  16. Screening for Prostate Cancer

    Science.gov (United States)

    ... absolute reduction in mortal- ity. Preliminary results from PIVOT (Prostate Cancer In- tervention Versus Observation Trial), in ... early PSA screening era, prelim- inary findings from PIVOT show that, after 12 years, in- tention to ...

  17. Detecting Prostate Cancer

    Medline Plus

    Full Text Available ... have by having their blood sampled and what we look for is a particular glyco-protein that's ... that they have prostate cancer. It means that we're concerned about it and they should go ...

  18. Prostate Cancer Foundation

    Science.gov (United States)

    ... Financials Our Leadership Leadership Team A Legacy of Leadership Featured ... Medicine Revolution Welcome to the world of precision medicine—where doctors can target each prostate cancer with new, more effective drugs. And this is just the beginning. Learn ...

  19. Akt- and CREB-Mediated Prostate Cancer Cell Proliferation Inhibition by Nexrutine, a Phellodendron amurense Extract

    Directory of Open Access Journals (Sweden)

    Gretchen E. Garcia

    2006-06-01

    Full Text Available Evidence from epidemiological studies suggests that plant-based diets can reduce the risk of prostate cancer. However, very little information is available concerning the use of botanicals in preventing prostate cancer. As a first step toward developing botanicals as prostate cancer preventives, we examined the effect of Nexrutine on human prostate cancer cells. Nexrutine is a herbal extract developed from Phellodendron amurense. Phellodendron extracts have been used traditionally in Chinese medicine for hundreds of years as an antidiarrheal, astringent, and anti-inflammatory agent. The present study investigated its potential antitumor effect on human prostate cancer cells. Our results suggest that it inhibits tumor cell proliferation through apoptosis induction and inhibition of cell survival signaling. The results of the present study indicate that Nexrutine treatment 1 inhibits the proliferation of both androgenresponsive and androgen-independent human prostate cancer cells through induction of apoptosis; 2 reduces levels of pAkt, phosphorylated cAMP response-binding protein (pCREB, and CREB DNA-binding activity; and 3 induces apoptosis in prostate cancer cells stably overexpressing Bcl-2. Further Akt kinase activity was reduced in cells treated with Nexrutine, and ectopic expression of myristoylated Akt protected from Nexrutine induced inhibition of proliferation, implicating a role for Akt signaling.

  20. Staging of prostate cancer.

    Science.gov (United States)

    Cheng, Liang; Montironi, Rodolfo; Bostwick, David G; Lopez-Beltran, Antonio; Berney, Daniel M

    2012-01-01

    Prostatic carcinoma (PCa) is a significant cause of cancer morbidity and mortality worldwide. Accurate staging is critical for prognosis assessment and treatment planning for PCa. Despite the large volume of clinical activity and research, the challenge to define the most appropriate and clinically relevant staging system remains. The pathologically complex and uncertain clinical course of prostate cancer further complicates the design of staging classification and a substaging system suitable for individualized care. This review will focus on recent progress and controversial issues related to prostate cancer staging. The 2010 revision of the American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) tumour, node and metastasis (TNM) system is the most widely used staging system at this time. Despite general acceptance of the system as a whole, there is controversy and uncertainty about its application, particularly for T2 subclassification. The three-tiered T2 classification system for organ-confined prostate cancer is superfluous, considering the biology and anatomy of PCa. A tumour size-based substaging system may be considered in the future TNM subclassification of pT2 cancer. Lymph node status is one of the most important prognostic factors for prostate cancer. Nevertheless, clinical outcomes in patients with positive lymph nodes are variable. Identification of patients at the greatest risk of systemic progression helps in the selection of appropriate therapy. The data suggest that the inherent aggressiveness of metastatic prostate cancer is closely linked to the tumour volume of lymph node metastasis. We recommend that a future TNM staging system should consider subclassification of node-positive cancer on the basis of nodal cancer volume, using the diameter of the largest nodal metastasis and/or the number of positive nodes.

  1. Genetic epidemiology of prostate cancer

    OpenAIRE

    Wiklund, Fredrik

    2004-01-01

    Prostate cancer is a major health burden throughout the world, yet the etiology of prostate cancer is poorly understood. Evidence has accumulated supporting the existence of a hereditary form of this disease. Improved understanding of the genetic mechanisms underlying the development and progression of prostate cancer would be a major advance for improved prevention, detection and treatment strategies. This thesis evaluates different aspects of the genetic epidemiology of prostate cancer. In ...

  2. Prostate cancer: emerging pharmacotherapeutic modalities

    OpenAIRE

    Pratap Shankar; Anoop Kumar Verma; Rakesh Kumar Dixit; Amod Kumar Sachan

    2013-01-01

    Prostate cancer is the most common cancer in the world due to factors like old age, family history, ethnicity, diet and some elements exposure, with lot of controversies regarding prevention of prostate cancer. Though the exact pathogenesis is not clear, epidemiological evidence supports a relationship between prostate cancer and hormone levels. In this review article we are focusing on the advances in different pharmacotherapeutic modalities i.e. Chemoprevention, Prostate-Specific Antigen, H...

  3. American Cancer Society Recommendations for Prostate Cancer Early Detection

    Science.gov (United States)

    ... saved articles window. My Saved Articles » My ACS » Prostate Cancer Prevention and Early Detection + - Text Size Download Printable Version [ ... coverage for prostate cancer screening Additional resources for prostate cancer prevention and early detection References: Prostate cancer prevention and ...

  4. Androgen receptor signaling is required for androgen-sensitive human prostate cancer cell proliferation and survival

    Directory of Open Access Journals (Sweden)

    Day Wanda V

    2005-04-01

    Full Text Available Abstract Background Androgens and androgen receptors (AR regulate normal prostate development and growth. They also are involved in pathological development of prostatic diseases, including benign prostatic hyperplasia (BPH and prostate cancer (PCa. Antiandrogen therapy for PCa, in conjunction with chemical or surgical castration, offers initial positive responses and leads to massive prostate cell death. However, cancer cells later appear as androgen-independent PCa. To investigate the role of AR in prostate cell proliferation and survival, we introduced a vector-based small interfering RNA (siRNA. This siRNA targeted 5'-untranslated region of AR mRNA for extended suppression of AR expression in androgen-sensitive human prostate LNCaP cells. Results The siRNA design successfully suppressed endogenous AR expression, as revealed by western blotting and immunofluorescence staining in LNCaP cells. LNCaP cells did not proliferate in the absence of AR and underwent apoptosis, based on elevated phospho-Histone H2B expression and higher number of apoptotic body as compared to control cells. Conclusion We demonstrated that AR is vital for prostate cell proliferation and survival in this androgen-sensitive prostate cell line. These results further strengthen the hypothesis that AR can be a therapeutic target for treating androgen-sensitive stages of PCa. Unlike antiandorgens, however, siRNA targeting AR provides a direct inactivation of AR function through the suppression of AR protein expression.

  5. JNK and PTEN cooperatively control the development of invasive adenocarcinoma of the prostate

    OpenAIRE

    Hübner, Anette; Mulholland, David J; Standen, Claire L.; Karasarides, Maria; Cavanagh-Kyros, Julie; Barrett, Tamera; Chi, Hongbo; Dale L Greiner; Tournier, Cathy; Sawyers, Charles L.; Richard A Flavell; Wu, Hong; Davis, Roger J

    2012-01-01

    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 (Δ...

  6. Osteoporosis and prostate cancer

    DEFF Research Database (Denmark)

    Poulsen, Mads Hvid; Nielsen, Morten Frost Munk; Abrahamsen, Bo;

    2014-01-01

    Abstract Objective. The aim of this study was to analyse the prevalence of osteoporosis and risk factors of osteoporotic fractures before androgen deprivation in Danish men. Treatment and prognosis of prostate cancer necessitate management of long-term consequences of androgen deprivation therapy...... (ADT), including accelerated bone loss resulting in osteoporosis. Osteoporotic fractures are associated with excess morbidity and mortality. Material and methods. Patients with prostate cancer awaiting initiation of ADT were consecutively included. Half of the patients had localized disease and were...... level was 30.5 g/l (1-5714 g/l). The average Gleason score was 7.8 (range 5-10, SD 1.1). Fifty patients had localized prostate cancer and the other 55 patients had disseminated disease. The prevalence of osteoporosis was 10% and the prevalence of osteopenia was 58% before ADT. There was no significant...

  7. ETS rearrangements in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Mark A Rubin

    2012-01-01

    Prostate cancer is a clinically and molecularly heterogeneous disease.Understanding the biologic underpinning of prostate cancer is necessary to best determine how biology is associated with the risk of disease progression and how this understanding might provide insight into the development of novel therapeutic approaches.The focus of this review is on the recently identified common ETS and non-ETS gene rearrangements in prostate cancer.Although multiple molecular alterations have been detected in prostate cancer,a basic understanding of gene fusion prostate cancer should help explain the clinical and biologic diversity,providing a rationale for a molecular subclassification of the disease.

  8. Chemotherapy in Prostate Cancer.

    Science.gov (United States)

    Hurwitz, Michael

    2015-10-01

    For approximately a decade, chemotherapy has been shown to prolong life in patients with metastatic castration-resistant prostate cancer (mCRPC). Since that time, however, only two agents have proven to prolong life (docetaxel and cabazitaxel). However, in the last year, the addition of chemotherapy to primary hormonal therapy became a standard of care for high-volume castration-sensitive metastatic disease. Here I will review current prostate cancer chemotherapies, mechanisms of resistance to those therapies, and ongoing clinical studies of chemotherapy combinations and novel chemotherapeutics. PMID:26216506

  9. [Chemotherapy for prostate cancer].

    Science.gov (United States)

    Rauchenwald, Michael; De Santis, Maria; Fink, Eleonore; Höltl, Wolfgang; Kramer, Gero; Marei, Isabella-Carolina; Neumann, Hans-Jörg; Reissigl, Andreas; Schmeller, Nikolaus; Stackl, Walter; Hobisch, Alfred; Krainer, Michael

    2008-01-01

    For many years the benefit of chemotherapy in patients with prostate cancer was thought to be limited to palliation of late-stage disease, and thus this treatment option only became involved in patient care towards the end of the disease process, if at all. However, two landmark phase-III trials with docetaxel-based therapy (TAX 327 and Southwest Oncology Group, SWOG, 9916) have shown a survival benefit for patients with hormone refractory prostate cancer (HRPC) thus prompting a change in patterns of care. With raising interest for chemotherapeutic options and clinical trials for new drugs and new indications (neoadjuvant therapy, adjuvant therapy, increasing PSA levels after local treatment, and hormone sensitive cancer) under way our goal was to review within the context of a multidisciplinary team the available evidence and explore the standard for the medical treatment of prostate cancer outside of clinical trials. We are carefully evaluating the current treatment recommendations based on the available evidence and highlight potential future treatment options but also discuss important clinical topics (treatment until progression versus the advantage of chemo holidays, definition of particular patient subgroups and potential second line options) for which there are no clear cut answers to date. The role and importance of radiotherapy, biphosphonate treatment and the medical management of pain and side effects is also discussed. The multitude of treatment options for patients with advanced prostate cancer clearly asks for a close collaboration between urologists, medical oncologists and radiation therapists. PMID:18726672

  10. Vitamin E and Prostate Cancer

    Science.gov (United States)

    Vitamin E, its metabolites or its analogs, might help prevent prostate cancer initiation or progression. Prostate cancer is the most common non-skin malignancy and the second leading cause of cancer deaths among men in the United States, exceeded only by lung cancer. About 218,890 new cases of prost...

  11. Prevention strategies in prostate cancer

    OpenAIRE

    Trottier, Greg; Lawrentschuk, N.; Fleshner, N.E.

    2010-01-01

    Prostate cancer (pca) prevention has been an exciting and controversial topic since the results of the Prostate Cancer Prevention Trial (pcpt) were published. With the recently published results of the reduce (Reduction by Dutasteride of Prostate Cancer Events) trial, interest in this topic is at a peak. Primary pca prevention will be unlikely to affect mortality significantly, but the reduction in overtreatment and the effect on quality of life from the avoidance of a cancer diagnosis are im...

  12. Survival in prostate cancer prevention trial detailed

    Science.gov (United States)

    In the NCI-sponsored Prostate Cancer Prevention Trial, initial findings from a decade ago showed that the drug finasteride significantly reduced the risk of prostate cancer, but among those who did develop prostate cancer, paradoxically, the drug was asso

  13. Quantitative mathematical modeling of PSA dynamics of prostate cancer patients treated with intermittent androgen suppression

    Institute of Scientific and Technical Information of China (English)

    Yoshito Hirata; Koichiro Akakura; Celestia S.Higano; Nicholas Bruchovsky; Kazuyuki Aihara

    2012-01-01

    If a mathematical model is to be used in the diagnosis,treatment,or prognosis of a disease,it must describe the inherent quantitative dynamics of the state.An ideal candidate disease is prostate cancer owing to the fact that it is characterized by an excellent biomarker,prostate-specific antigen (PSA),and also by a predictable response to treatment in the form of androgen suppression therapy.Despite a high initial response rate,the cancer will often relapse to a state of androgen independence which no longer responds to manipulations of the hormonal environment.In this paper,we present relevant background information and a quantitative mathematical model that potentially can be used in the optimal management of patients to cope with biochemical relapse as indicated by a rising PSA.

  14. Molecular markers for prostate cancer.

    NARCIS (Netherlands)

    Reynolds, M.A.; Kastury, K.; Groskopf, J.; Schalken, J.A.; Rittenhouse, H.G.

    2007-01-01

    Serum PSA testing has been used for over 20 years as an aid in the diagnosis and management of prostate cancer. Although highly sensitive, it suffers from a lack of specificity, showing elevated serum levels in a variety of other conditions including prostatitis, benign prostate hyperplasia, and non

  15. Prostate cancer is not breast cancer

    Directory of Open Access Journals (Sweden)

    Ajit Venniyoor

    2016-01-01

    Full Text Available Cancers of the prostate and breast are hormone dependent cancers. There is a tendency to equate them and apply same algorithms for treatment. It is pointed out that metastatic prostate cancer with bone-only disease is a potentially fatal condition with a much poorer prognosis than metastatic breast cancer and needs a more aggressive approach.

  16. Biomarkers in Prostate Cancer Epidemiology

    Directory of Open Access Journals (Sweden)

    Mudit Verma

    2011-09-01

    Full Text Available Understanding the etiology of a disease such as prostate cancer may help in identifying populations at high risk, timely intervention of the disease, and proper treatment. Biomarkers, along with exposure history and clinical data, are useful tools to achieve these goals. Individual risk and population incidence of prostate cancer result from the intervention of genetic susceptibility and exposure. Biochemical, epigenetic, genetic, and imaging biomarkers are used to identify people at high risk for developing prostate cancer. In cancer epidemiology, epigenetic biomarkers offer advantages over other types of biomarkers because they are expressed against a person’s genetic background and environmental exposure, and because abnormal events occur early in cancer development, which includes several epigenetic alterations in cancer cells. This article describes different biomarkers that have potential use in studying the epidemiology of prostate cancer. We also discuss the characteristics of an ideal biomarker for prostate cancer, and technologies utilized for biomarker assays. Among epigenetic biomarkers, most reports indicate GSTP1 hypermethylation as the diagnostic marker for prostate cancer; however, NKX2-5, CLSTN1, SPOCK2, SLC16A12, DPYS, and NSE1 also have been reported to be regulated by methylation mechanisms in prostate cancer. Current challenges in utilization of biomarkers in prostate cancer diagnosis and epidemiologic studies and potential solutions also are discussed.

  17. Cabazitaxel Plus Prednisone With Octreotide For Castration-Resistant Prostate Cancer (CRPC) Previously Treated With Docetaxel

    Science.gov (United States)

    2014-11-21

    Diarrhea; Hormone-resistant Prostate Cancer; Recurrent Prostate Cancer; Stage I Prostate Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer; Stage III Prostate Cancer; Stage IV Prostate Cancer

  18. The Early Prostate Cancer program: bicalutamide in nonmetastatic prostate cancer

    DEFF Research Database (Denmark)

    Iversen, Peter; Roder, Martin Andreas; Røder, Martin Andreas

    2008-01-01

    The Early Prostate Cancer program is investigating the addition of bicalutamide 150 mg to standard care for localized or locally advanced, nonmetastatic prostate cancer. The third program analysis, at 7.4 years' median follow-up, has shown that bicalutamide 150 mg does not benefit patients...

  19. HUMAN PROSTATE CANCER RISK FACTORS

    Science.gov (United States)

    Prostate cancer has the highest prevalence of any non-skin cancer in the human body, with similar likelihood of neoplastic foci found within the prostates of men around the world regardless of diet, occupation, lifestyle, or other factors. Essentially all men with circulating an...

  20. Androgen Control in Prostate Cancer.

    Science.gov (United States)

    Pelekanou, Vasiliki; Castanas, Elias

    2016-10-01

    Research on prostate cancer has extensively advanced in the past decade, through an improved understanding for its genetic basis and risk-stratification. Molecular classification of prostate cancer into distinct subtypes and the recognition of new histologic entities promise the development of tailored-made management strategies of patients. Nowadays, various alternatives are available for clinical management of localized disease ranging from observation alone through radical prostatectomy. In patients with castration-resistant prostate cancer, the approval of new drugs for the management of metastatic disease has offered promising results improving the survival of these patients. In this context, androgen receptors (AR) remain at the epicenter of prostate cancer research holding a prominent role in the biology and therapeutic regimens of prostate cancer. As many of castration-resistant tumors retain hormone-responsiveness, AR is a clinical relevant, druggable target. However, AR paradoxically remains neglected as a prostate cancer biomarker. The great advancements in prostate cancer preclinical and clinical research, imply further improvement in clinical and translational data, for patient selection and treatment optimization. For a precision medicine-guided clinical management of prostate cancer, AR evaluation has to be implemented in companion and complementary diagnostics, as discussed here. J. Cell. Biochem. 117: 2224-2234, 2016. © 2016 Wiley Periodicals, Inc. PMID:27104784

  1. Multidrug Resistance in Prostate Cancer

    NARCIS (Netherlands)

    J.P. van Brussel

    2005-01-01

    textabstractAdvanced hormone refractory prostate cancer constitutes a therapeutic challenge, because all available treatment strategies have failed to substantially increase cancer specific survival. Among these strategies, a multitude of chemotherapeutic approaches did not offer a superior life

  2. Neural protein gamma-synuclein interacting with androgen receptor promotes human prostate cancer progression

    International Nuclear Information System (INIS)

    Gamma-synuclein (SNCG) has previously been demonstrated to be significantly correlated with metastatic malignancies; however, in-depth investigation of SNCG in prostate cancer is still lacking. In the present study, we evaluated the role of SNCG in prostate cancer progression and explored the underlying mechanisms. First, alteration of SNCG expression in LNCaP cell line to test the ability of SNCG on cellular properties in vitro and vivo whenever exposing with androgen or not. Subsequently, the Dual-luciferase reporter assays were performed to evaluate whether the role of SNCG in LNCaP is through AR signaling. Last, the association between SNCG and prostate cancer progression was assessed immunohistochemically using a series of human prostate tissues. Silencing SNCG by siRNA in LNCaP cells contributes to the inhibition of cellular proliferation, the induction of cell-cycle arrest at the G1 phase, the suppression of cellular migration and invasion in vitro, as well as the decrease of tumor growth in vivo with the notable exception of castrated mice. Subsequently, mechanistic studies indicated that SNCG is a novel androgen receptor (AR) coactivator. It interacts with AR and promotes prostate cancer cellular growth and proliferation by activating AR transcription in an androgen-dependent manner. Finally, immunohistochemical analysis revealed that SNCG was almost undetectable in benign or androgen-independent tissues prostate lesions. The high expression of SNCG is correlated with peripheral and lymph node invasion. 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

  3. Novel pharmacologic targeting of tight junctions and focal adhesions in prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Patrick J Hensley

    Full Text Available Cancer cell resistance to anoikis driven by aberrant signaling sustained by the tumor microenvironment confers high invasive potential and therapeutic resistance. We recently generated a novel lead quinazoline-based Doxazosin® derivative, DZ-50, which impairs tumor growth and metastasis via anoikis. Genome-wide analysis in the human prostate cancer cell line DU-145 identified primary downregulated targets of DZ-50, including genes involved in focal adhesion integrity (fibronectin, integrin-α6 and talin, tight junction formation (claudin-11 as well as insulin growth factor binding protein 3 (IGFBP-3 and the angiogenesis modulator thrombospondin 1 (TSP-1. Confocal microscopy demonstrated structural disruption of both focal adhesions and tight junctions by the downregulation of these gene targets, resulting in decreased cell survival, migration and adhesion to extracellular matrix (ECM components in two androgen-independent human prostate cancer cell lines, PC-3 and DU-145. Stabilization of cell-ECM interactions by overexpression of talin-1 and/or exposing cells to a fibronectin-rich environment mitigated the effect of DZ-50. Loss of expression of the intracellular focal adhesion signaling effectors talin-1 and integrin linked kinase (ILK sensitized human prostate cancer to anoikis. Our findings suggest that DZ-50 exerts its antitumor effect by targeting the key functional intercellular interactions, focal adhesions and tight junctions, supporting the therapeutic significance of this agent for the treatment of advanced prostate cancer.

  4. Role of the tumor-associated trypsin inhibitor SPINK1 in cancer development%Role of the tumor-associated trypsin inhibitor SPINK1in cancer development

    Institute of Scientific and Technical Information of China (English)

    Ulf-H(a)kan Stenman

    2011-01-01

    @@ In most industrialized countries, prostate cancer is the most common non-skin cancer of men.When detected early, most cases are curable, but for tumors that have metastasized, there is no curative therapy.Pharmaceutical androgen ablation or castration induces remission in most patients with metastatic disease, but if the patient lives long enough, the tumor becomes androgen-independent.In some patients, chemotherapy induces remission, which mostly is of short duration.Therefore, new treatment modalities are needed for androgen-independent prostate cancer.

  5. Role of Proprotein Convertases in Prostate Cancer Progression

    Directory of Open Access Journals (Sweden)

    Frédéric Couture

    2012-11-01

    Full Text Available Better understanding of the distinct and redundant functions of the proprotein convertase (PC enzyme family within pathophysiological states has a great importance for potential therapeutic strategies. 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 cell proliferation or tumor xenograft growth. Paradoxically, PC7 knockdowns reduced in vitro cellular proliferation but had no effect in vivo. Because PCs act within secretion pathways, we showed that conditioned media derived from PACE4 knockdown cells had very poor cell growth-stimulating effects in vitro. Immunohistochemistry of PACE4 knockdown tumors revealed reduced Ki67 and higher p27KIP levels (proliferation and cell cycle arrest markers, respectively. Interestingly, we determined that the epidermal growth factor receptor signaling pathway was activated in PC7 knockdown tumors only, providing some explanations of the paradoxical effects of PC7 silencing in prostate cancer cell lines. We conclude that PACE4 has a distinct role in maintaining proliferation and tumor progression in prostate cancer and this positions PACE4 as a relevant therapeutic target for this disease.

  6. Proliferative response of human prostate cancer cell to hormone inhibited by androgen receptor antisense RNA

    Institute of Scientific and Technical Information of China (English)

    江军; 王洛夫; 方玉华; 靳风烁; 靳文生

    2004-01-01

    Background The failure of endocrine treatment for advanced prostate cancer might be related to aberrant activation of androgen receptor (AR). Prostate cancer cell line LNCaP contains AR that can be activated by androgen, estrogen and progesterone. This study was set to investigate the effects of antisense AR RNA on growth of LNCaP cultured in medium containing varied concentrations of R1881, 17β-estradiol, and progesterone, respectively. Methods LNCaP cells transfected with antisense AR RNA retroviral vector pL-AR-SN were designated as LNCaPas-AR. LNCaP cells containing empty vector pLXSN served as LNCaPNeo. LNCaP and LNCaPNeo were taken as controls. In vitro cell growth assay, proliferative cells of LNCaP and tranfected LNCaPs were counted by typan staining when they cultured with synthetic androgen R1881, 17β-estradiol, and progesterone, respectively. Results Growth of LNCaPas-AR was inhibited significantly (P<0.05) compared with that of LNCaP and LNCaPNeo at 1 nmol/L R1881, 10 nmol/L 17β-estradiol, and 1 nmol/L progesterone, respectively. No difference was seen between LNCaP and LNCaPNeo(P>0.05). Microscopic observation showed that LNCaP and LNCaPNeo cells grew well, but only few LNCaPas-AR cells were alive. Conclusions Our observations indicate that antisense AR RNA retroviral vector pL-AR-SN could change androgen-independent characteristics of LNCaP cells, which might shed some novel insights into the treatment of androgen-independent prostate cancer.

  7. Survivin gene silencing sensitizes prostate cancer cells to selenium growth inhibition

    International Nuclear Information System (INIS)

    Prostate cancer is a leading cause of cancer-related death in men worldwide. Survivin is a member of the inhibitor of apoptosis (IAP) protein family that is expressed in the majority of human tumors including prostate cancer, but is barely detectable in terminally differentiated normal cells. Downregulation of survivin could sensitize prostate cancer cells to chemotherapeutic agents in vitro and in vivo. Selenium is an essential trace element. Several studies have shown that selenium compounds inhibit the growth of prostate cancer cells. The objective of this study is to investigate whether survivin gene silencing in conjunction with selenium treatment could enhance the therapeutic efficacy for prostate cancer and to elucidate the underlying mechanisms. Expression of survivin was analyzed in a collection of normal and malignant prostatic tissues by immunohistochemical staining. In vitro studies were conducted in PC-3M, C4-2B, and 22Rv1 prostate cancer cells. The effect of selenium on survivin expression was analyzed by Western blotting and semi-quantitative RT-PCR. Survivin gene knockdown was carried out by transfecting cells with a short hairpin RNA (shRNA) designed against survivin. Cell proliferation was quantitated by the 3-(4,5-Dimethylthiazol-2-yl)- 2,5-Diphenyltetrazolium Bromide (MTT) assay and apoptosis by propidium iodide staining followed by flow cytometry analysis. Finally, in vivo tumor growth assay was performed by establishing PC-3M xenograft in nude mice and monitoring tumor growth following transfection and treatment. We found that survivin was undetectable in normal prostatic tissues but was highly expressed in prostate cancers. Survivin knockdown or selenium treatment inhibited the growth of prostate cancer cells, but the selenium effect was modest. In contrast to what have been observed in other cell lines, selenium treatment had little or no effect on survivin expression in several androgen-independent prostate cancer cell lines. Survivin

  8. Prostate cancer stem cell biology

    OpenAIRE

    Yu, Chunyan; Yao, Zhi; Jiang, Yuan; Keller, Evan T.

    2012-01-01

    The cancer stem cell (CSC) model provides insights into pathophysiology of cancers and their therapeutic response. The CSC model has been both controversial, yet provides a foundation to explore cancer biology. In this review, we provide an overview of CSC concepts, biology and potential therapeutic avenues. We then focus on prostate CSC including (1) their purported origin as either basal-derived or luminal-derived cells; (2) markers used for prostate CSC identification; (3) alterations of s...

  9. Human Prostate Cancer Hallmarks Map.

    Science.gov (United States)

    Datta, Dipamoy; Aftabuddin, Md; Gupta, Dinesh Kumar; Raha, Sanghamitra; Sen, Prosenjit

    2016-01-01

    Human prostate cancer is a complex heterogeneous disease that mainly affects elder male population of the western world with a high rate of mortality. Acquisitions of diverse sets of hallmark capabilities along with an aberrant functioning of androgen receptor signaling are the central driving forces behind prostatic tumorigenesis and its transition into metastatic castration resistant disease. These hallmark capabilities arise due to an intense orchestration of several crucial factors, including deregulation of vital cell physiological processes, inactivation of tumor suppressive activity and disruption of prostate gland specific cellular homeostasis. The molecular complexity and redundancy of oncoproteins signaling in prostate cancer demands for concurrent inhibition of multiple hallmark associated pathways. By an extensive manual curation of the published biomedical literature, we have developed Human Prostate Cancer Hallmarks Map (HPCHM), an onco-functional atlas of human prostate cancer associated signaling and events. It explores molecular architecture of prostate cancer signaling at various levels, namely key protein components, molecular connectivity map, oncogenic signaling pathway map, pathway based functional connectivity map etc. Here, we briefly represent the systems level understanding of the molecular mechanisms associated with prostate tumorigenesis by considering each and individual molecular and cell biological events of this disease process.

  10. Human Prostate Cancer Hallmarks Map.

    Science.gov (United States)

    Datta, Dipamoy; Aftabuddin, Md; Gupta, Dinesh Kumar; Raha, Sanghamitra; Sen, Prosenjit

    2016-01-01

    Human prostate cancer is a complex heterogeneous disease that mainly affects elder male population of the western world with a high rate of mortality. Acquisitions of diverse sets of hallmark capabilities along with an aberrant functioning of androgen receptor signaling are the central driving forces behind prostatic tumorigenesis and its transition into metastatic castration resistant disease. These hallmark capabilities arise due to an intense orchestration of several crucial factors, including deregulation of vital cell physiological processes, inactivation of tumor suppressive activity and disruption of prostate gland specific cellular homeostasis. The molecular complexity and redundancy of oncoproteins signaling in prostate cancer demands for concurrent inhibition of multiple hallmark associated pathways. By an extensive manual curation of the published biomedical literature, we have developed Human Prostate Cancer Hallmarks Map (HPCHM), an onco-functional atlas of human prostate cancer associated signaling and events. It explores molecular architecture of prostate cancer signaling at various levels, namely key protein components, molecular connectivity map, oncogenic signaling pathway map, pathway based functional connectivity map etc. Here, we briefly represent the systems level understanding of the molecular mechanisms associated with prostate tumorigenesis by considering each and individual molecular and cell biological events of this disease process. PMID:27476486

  11. Chemotherapeutic prevention studies of prostate cancer

    DEFF Research Database (Denmark)

    Djavan, Bob; Zlotta, Alexandre; Schulman, Claude;

    2004-01-01

    Despite advances in the detection and management of prostate cancer, this disease remains a major cause of morbidity and mortality in men. Increasing attention has focused on the role of chemoprevention for prostate cancer, ie the administration of agents that inhibit 1 or more steps in the natural...... history of prostate carcinogenesis. We review prostate cancer chemoprevention studies in Europe....

  12. Prevention and early detection of prostate cancer

    NARCIS (Netherlands)

    Cuzick, J.; Thorat, M.A.; Andriole, G.; Brawley, O.W.; Brown, P.H.; Culig, Z.; Eeles, R.A.; Ford, L.G.; Hamdy, F.C.; Holmberg, L.; Ilic, D.; Key, T.J.; Vecchia, C. La; Lilja, H.; Marberger, M.; Meyskens, F.L.; Minasian, L.M.; Parker, C.; Parnes, H.L.; Perner, S.; Rittenhouse, H.; Schalken, J.A.; Schmid, H.P.; Schmitz-Drager, B.J.; Schroder, F.H.; Stenzl, A.; Tombal, B.; Wilt, T.J.; Wolk, A.

    2014-01-01

    Prostate cancer is a common malignancy in men and the worldwide burden of this disease is rising. Lifestyle modifications such as smoking cessation, exercise, and weight control offer opportunities to reduce the risk of developing prostate cancer. Early detection of prostate cancer by prostate-speci

  13. Sphingosine kinase-1 is central to androgen-regulated prostate cancer growth and survival.

    Directory of Open Access Journals (Sweden)

    Audrey Dayon

    Full Text Available BACKGROUND: Sphingosine kinase-1 (SphK1 is an oncogenic lipid kinase notably involved in response to anticancer therapies in prostate cancer. Androgens regulate prostate cancer cell proliferation, and androgen deprivation therapy is the standard of care in the management of patients with advanced disease. Here, we explored the role of SphK1 in the regulation of androgen-dependent prostate cancer cell growth and survival. METHODOLOGY/PRINCIPAL FINDINGS: Short-term androgen removal induced a rapid and transient SphK1 inhibition associated with a reduced cell growth in vitro and in vivo, an event that was not observed in the hormono-insensitive PC-3 cells. Supporting the critical role of SphK1 inhibition in the rapid effect of androgen depletion, its overexpression could impair the cell growth decrease. Similarly, the addition of dihydrotestosterone (DHT to androgen-deprived LNCaP cells re-established cell proliferation, through an androgen receptor/PI3K/Akt dependent stimulation of SphK1, and inhibition of SphK1 could markedly impede the effects of DHT. Conversely, long-term removal of androgen support in LNCaP and C4-2B cells resulted in a progressive increase in SphK1 expression and activity throughout the progression to androgen-independence state, which was characterized by the acquisition of a neuroendocrine (NE-like cell phenotype. Importantly, inhibition of the PI3K/Akt pathway--by negatively impacting SphK1 activity--could prevent NE differentiation in both cell models, an event that could be mimicked by SphK1 inhibitors. Fascinatingly, the reversability of the NE phenotype by exposure to normal medium was linked with a pronounced inhibition of SphK1 activity. CONCLUSIONS/SIGNIFICANCE: We report the first evidence that androgen deprivation induces a differential effect on SphK1 activity in hormone-sensitive prostate cancer cell models. These results also suggest that SphK1 activation upon chronic androgen deprivation may serve as a

  14. New horizons in prostate cancer imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ravizzini, Gregory; Turkbey, Baris; Kurdziel, Karen [Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States); Choyke, Peter L. [Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States)], E-mail: pchoyke@nih.gov

    2009-05-15

    Prostate cancer is the most common non-cutaneous malignancy among American men. Imaging has recently become more important in detection of prostate cancer since screening techniques such as digital rectal examination (DRE), prostate specific and transrectal ultrasound guided biopsy have considerable limitations in diagnosis and localization of prostate cancer. In this manuscript, we reviewed conventional, functional and targeted imaging modalities used in diagnosis and local staging of prostate cancer with exquisite images.

  15. Prostate Cancer Genetics: A Review

    Science.gov (United States)

    Wallis, Christopher J.D.

    2015-01-01

    Over the past decades, research has focussed on identifying the genetic underpinnings of prostate cancer. It has been recognized that a number of forms of genetic changes coupled with epigenetic and gene expression changes can increase the prediction to develop prostate cancer. This review outlines the role of somatic copy number alterations (SCNAs), structural rearrangements, point mutations, and single nucleotide polymorphisms (SNPs) as well as miRNAs. Identifying relevant genetic changes offers the ability to develop novel biomarkers to allow early and accurate detection of prostate cancer as well as provide risk stratification of patients following their diagnosis. The concept of personalized or individualized medicine has gained significant attention. Therefore, a better understanding of the genetic and metabolic pathways underlying prostate cancer development offers the opportunity to explore new therapeutic interventions with the possibility of offering patient-specific targeted therapy.

  16. Contemporary Management of Prostate Cancer.

    Science.gov (United States)

    Cotter, Katherine; Konety, Badrinath; Ordonez, Maria A

    2016-01-01

    Prostate cancer represents a spectrum ranging from low-grade, localized tumors to devastating metastatic disease. We discuss the general options for treatment and recent developments in the field. PMID:26949522

  17. The Expression of MTUS1/ATIP and Its Major Isoforms, ATIP1 and ATIP3, in Human Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Louis, Simon N.S., E-mail: simonnsl@unimelb.edu.au; Chow, Laurie T.C.; Varghayee, Naghmeh; Rezmann, Linda A.; Frauman, Albert G.; Louis, William J. [Clinical Pharmacology and Therapeutics Unit, Department of Medicine, University of Melbourne, Austin Health, Heidelberg 3084, Victoria (Australia)

    2011-10-11

    Angiotensin II (Ang II), the main effector of the renin angiotensin system, acts upon two distinct transmembrane receptors, the Ang II type 1 and the type 2 (AT{sub 2}-) receptor, to induce promotion and inhibition of ERK2 phosphorylation. The AT{sub 2}-receptor, through an interaction with its putative signaling partner MTUS1/ATIP (AT{sub 2}-receptor interacting protein), inhibits the mitogenic effects of EGF in prostate cancer cell lines representing both early and late stage disease. This is the first report on the expression of ATIP in normal and malignant human prostatic biopsies. The expression of ATIP and its major isoforms, ATIP1 and ATIP3, in normal prostatic cells and three prostate cancer cell lines was examined using QPCR and immunohistochemistry. Human biopsies containing benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN) and well, moderately and poorly differentiated prostate cancer were also examined. Overall, ATIP1 and ATIP3 mRNA expression was increased in malignant compared to normal tissues and cell lines. ATIP immunostaining was low or absent in both the basal and columnar epithelial cell layers surrounding BPH acini; however, it was observed in high concentration in neoplastic epithelial cells of HGPIN and was clearly evident in cytoplasms of malignant cells in all prostate cancer grades. ATIP immunostaining was also identified in the cytoplasms of LNCaP and PC3 prostate cancer cells. As the AT{sub 2}-receptor/ATIP inhibitory signaling pathway exists in malignant cells in all grades of prostate cancer, enhancement of this pathway may be a therapeutic target even after the development of androgen-independence.

  18. Biomarkers in Prostate Cancer Epidemiology

    OpenAIRE

    Mudit Verma; Mukesh Verma; Payal Patel

    2011-01-01

    Understanding the etiology of a disease such as prostate cancer may help in identifying populations at high risk, timely intervention of the disease, and proper treatment. Biomarkers, along with exposure history and clinical data, are useful tools to achieve these goals. Individual risk and population incidence of prostate cancer result from the intervention of genetic susceptibility and exposure. Biochemical, epigenetic, genetic, and imaging biomarkers are used to identify people at high ris...

  19. A novel finding: Anti-androgen flutamide kills androgen-independent PC-3 cells: A radiolabelled methyl-choline incorporation into tumour cells

    International Nuclear Information System (INIS)

    Full text: [Methyl-11C]-choline was introduced to image many types of cancers especially the prostate cancer. Al-Saeedi et al. reported that the incorporation of [Methyl-3H]-choline into breast tumour (MCF-7) cells correlated strongly with proliferation as determined by [Methyl-14C]- thymidine uptake. Also, Al-Saeedi, et al. showed that the chemotherapy using MCF-7 cells treated with 5-Fluorouracil (5-FU) induced modulation in [Methyl-3H]-choline incorporation and certain mechanisms for this modulation were reported. In this study, the androgen-dependent prostate tumour (LNCaP) cells were treated with the well known pure anti-androgen drug, flutamide, for three days. The cells were then incubated with [Methyl-3H]-choline for 10 mint to detect the effect of flutamide on both cell proliferation and choline incorporation. At the same time, a preliminary work was established using androgen-independent PC-3 cells treated with flutamide as controls in this study. PC-3 cells were treated with a range of doses of flutamide inhibiting growth by 20[Methyl-3H]-Choline Incorporation into MCF-7 Cells: Correlation with Proliferation: choline kinase and phospholipase D assay. [Methyl-3H]-Choline Incorporation into MCF-7 Cells: Correlation with Proliferation: choline kinase and phospholipase D assay. - 70%. Treated and control cells were incubated with [Methyl-3H]-choline for 10 min, then in non-radioactive medium to simulate the rapid blood clearance of [Methyl-11C]-choline tracer in control and treated PC-3 cells, and then extracted with organic and aqueous solvents to determine its effect on the intracellular distribution of this tracer. Interesting results showed that flutamide killed the androgen-independent prostate cancer cells, PC-3 and mechanisms responsible for flutamide-induced modulation on [Methyl-3H]- choline incorporation were reported. The PC-3 cells' proliferation was inhibited by flutamide. In addition, treatment of PC-3 cells with flutamide for 3 days resulted

  20. Inhibitory effects of antagonists of growth hormone-releasing hormone on growth and invasiveness of PC3 human prostate cancer.

    Science.gov (United States)

    Muñoz-Moreno, Laura; Arenas, M Isabel; Schally, Andrew V; Fernández-Martínez, Ana B; Zarka, Elías; González-Santander, Marta; Carmena, María J; Vacas, Eva; Prieto, Juan C; Bajo, Ana M

    2013-02-15

    New approaches are needed to the therapy of advanced prostate cancer. This study determined the effect of growth hormone-releasing hormone (GHRH) antagonists, JMR-132 and JV-1-38 on growth of PC3 tumors as well as on angiogenesis and metastasis through the evaluation of various factors that contribute largely to the progression of prostate cancer. Human PC3 androgen-independent prostate cancer cells were injected subcutaneously into nude mice. The treatment with JMR-132 (10 μg/day) or JV-1-38 (20 μg/day) lasted 41 days. We also evaluated the effects of JMR-132 and JV-1-38 on proliferation, cell adhesion and migration in PC-3 cells in vitro. Several techniques (Western blot, reverse transcription polymerase chain reaction, immunohistochemistry, ELISA and zymography) were used to evaluate the expression levels of GHRH receptors and its splice variants, GHRH, vascular endothelial growth factor (VEGF), hypoxia inducible factor (HIF)-1α, metalloproteinases (MMPs) -2 and -9, β-catenin and E-cadherin. GHRH antagonists suppressed the proliferation of PC-3 cells in vitro and significantly inhibited growth of PC3 tumors. After treatment with these analogues, we found an increase in expression of GHRH receptor accompanied by a decrease of GHRH levels, a reduction in both VEGF and HIF-1α expression and in active forms of MMP-2 and MMP-9, a significant increase in levels of membrane-associated β-catenin and a significant decline in E-cadherin. These results support that the blockade of GHRH receptors can modulate elements involved in angiogenesis and metastasis. Consequently, GHRH antagonists could be considered as suitable candidates for therapeutic trials in the management of androgen-independent prostate cancer.

  1. Detecting Prostate Cancer

    Medline Plus

    Full Text Available ... such as a trans-rectal ultrasound and a biopsy. Physician: Now, just relax -- the best thing to ... prostate gland. Usually these are accompanied by a biopsy -- a sampling of the prostate tissue with a ...

  2. To Die or to Survive, a Fatal Question for the Destiny of Prostate Cancer Cells after Androgen Deprivation Therapy

    International Nuclear Information System (INIS)

    Prostate cancer is the most frequently diagnosed non-skin cancer in adult males in North America and is the second leading cause of cancer-related mortality. For locally advanced or metastatic disease, androgen deprivation, through medical or surgical castration, is the primary treatment to induce prostate cancer cell death and extend patient survival. However, the vast majority of cancers progress to a castration-resistant/androgen-independent state where the cell death processes are no longer active. This review describes the main cell death processes, apoptosis, autophagy, necrosis and necroptosis, which may be activated in prostate cancers after androgen deprivation therapy as well as the molecular mechanisms through which the cancers progress to become castration resistant. In particular, the central role of persistent androgen receptor (AR)-mediated signaling and AR crosstalk with other critical cell signaling pathways, including (i) the PI3K/Akt pathway, (ii) receptor tyrosine kinases, (iii) the p38 MAPK pathway, and (iv) the Wnt/β-catenin pathway, as well as reactivation of AR by de novo synthesized androgen are discussed in this context. Understanding the molecular changes that subvert normal cell death mechanisms and thereby compromise the survival of prostate cancer patients continues to be a major challenge

  3. What Do Prostate Cancer Patients Die Of?

    OpenAIRE

    Riihimäki, Matias; Thomsen, Hauke; Brandt, Andreas; Sundquist, Jan; Hemminki, Kari

    2011-01-01

    The cause of death in prostate cancer patients is examined using the Swedish Family-Cancer Database. Prostate cancer patients were found to have a higher risk for dying from various causes other than prostate cancer, including external causes and heart failure.

  4. Dietary Antioxidants and Prostate Cancer: A Review

    OpenAIRE

    Vance, Terrence M.; Su, Joseph; Fontham, Elizabeth T. H.; Koo, Sung I; Chun, Ock K.

    2013-01-01

    Prostate cancer is the most common non-cutaneous cancer in men in the United States. Several studies have examined the relationship between prostate cancer and antioxidants; however, the results of these studies are inconsistent. This article provides a systematic review of studies on prostate cancer and antioxidant intake from diet and supplements. Tea and coffee appear to offer protection against advanced prostate cancer. Different forms of vitamin E appear to exert different effects on pro...

  5. Deprivation of arginine by recombinant human arginase in prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Hsueh Eddy C

    2012-04-01

    Full Text Available Abstract Background Recombinant human arginase (rhArg has been developed for arginine deprivation therapy in cancer, and is currently under clinical investigation. During pre-clinical evaluation, rhArg has exhibited significant anti-proliferative activity in cancer cells deficient in the expression of ornithine carbamoyl transferase (OCT. Interestingly, a variety of cancer cells such as melanoma and prostate cancer deficient in argininosuccinate synthetase (ASS are sensitive to arginine deprivation by arginine deiminase. In this study, we investigated levels of gene expression of OCT and ASS, and the effects of rhArg in human prostate cancer cells: LNCaP (androgen-dependent, PC-3 and DU-145 (both androgen-independent. Results Quantitative real-time PCR showed minimal to absent gene expression of OCT, but ample expression of ASS expression in all 3 cell lines. Cell viability assay after 72-h exposure of rhArg showed all 3 lines had half maximal inhibitory concentration less than or equal to 0.02 U/ml. Addition of ornithine to cell culture media failed to rescue these cells from rhArg-mediated cytotoxicity. Decreased phosphorylation of 4E-BP1, a downstream effector of mammalian target of rapamycin (mTOR, was noted in DU-145 and PC-3 after exposure to rhArg. Moreover, there was no significant apoptosis induction after arginine deprivation by rhArg in all 3 prostate cancer cell lines. 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.

  6. The Danish Prostate Cancer Database

    Directory of Open Access Journals (Sweden)

    Nguyen-Nielsen M

    2016-10-01

    Full Text Available Mary Nguyen-Nielsen,1,2 Søren Høyer,3 Søren Friis,4 Steinbjørn Hansen,5 Klaus Brasso,6 Erik Breth Jakobsen,7 Mette Moe,8 Heidi Larsson,9 Mette Søgaard,9 Anne Nakano,9,10 Michael Borre1 1Department of Urology, Aarhus University Hospital, Aarhus, 2Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, 3Department of Pathology, Aarhus University Hospital, Aarhus, 4Danish Cancer Society Research Centre, Danish Cancer Society, Copenhagen, 5Department of Oncology, Odense University Hospital, Odense, 6Copenhagen Prostate Cancer Center and Department of Urology, Rigshospitalet, University of Copenhagen, Copenhagen, 7Department of Urology, Næstved Hospital, Næstved, 8Department of Oncology, Aalborg University Hospital, Aalborg, 9Department of Clinical Epidemiology, Aarhus University Hospital, 10Competence Centre for Health Quality and Informatics (KCKS-Vest, Aarhus, Denmark Aim of database: The Danish Prostate Cancer Database (DAPROCAdata is a nationwide clinical cancer database that has prospectively collected data on patients with incident prostate cancer in Denmark since February 2010. The overall aim of the DAPROCAdata is to improve the quality of prostate cancer care in Denmark by systematically collecting key clinical variables for the purposes of health care monitoring, quality improvement, and research. Study population: All Danish patients with histologically verified prostate cancer are included in the DAPROCAdata. Main variables: The DAPROCAdata registers clinical data and selected characteristics for patients with prostate cancer at diagnosis. Data are collected from the linkage of nationwide health registries and supplemented with online registration of key clinical variables by treating physicians at urological and oncological departments. Main variables include Gleason scores, cancer staging, prostate-specific antigen values, and therapeutic measures (active surveillance, surgery, radiotherapy, endocrine

  7. Prostate cancer, prostate cancer death, and death from other causes, among men with metabolic aberrations.

    OpenAIRE

    Häggström, Christel; Stocks, Tanja; Nagel, Gabriele; Manjer, Jonas; Bjørge, Tone; Hallmans, Göran; Engeland, Anders; Ulmer, Hanno; Lindkvist, Björn; Selmer, Randi; Concin, Hans; Tretli, Steinar; Jonsson, Håkan; Stattin, Pär

    2014-01-01

    Few previous studies of metabolic aberrations and prostate cancer risk have taken into account the fact that men with metabolic aberrations have an increased risk of death from causes other than prostate cancer. The aim of this study was to calculate, in a real-life scenario, the risk of prostate cancer diagnosis, prostate cancer death, and death from other causes.

  8. Perceived causes of prostate cancer among prostate cancer survivors in the Netherlands

    NARCIS (Netherlands)

    Kok, D.E.G.; Cremers, R.G.H.M.; Aben, K.K.H.; Oort, van I.M.; Kampman, E.; Kiemeney, L.A.L.M.

    2013-01-01

    Introduction The aim of this study was to evaluate self-reported causes of prostate cancer among prostate cancer survivors in the Netherlands to obtain insight into the common beliefs and perceptions of risk factors for prostate cancer. Materials and methods A total of 956 prostate cancer survivors,

  9. 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

    Directory of Open Access Journals (Sweden)

    Ho-Jeong Lee

    2012-04-01

    Full Text Available Antivascular therapy has emerged as a rational strategy to improve the treatment of androgen-independent prostate cancer owing to the necessity of establishing a vascular network for the growth and progression of the primary and metastatic tumor. We determined whether recombinant human apolipoprotein(a kringle V, rhLK8, produces therapeutic efficacy in an orthotopic human prostate cancer animal model. Fifty thousand androgen-independent human prostate cancer cells (PC-3MM2 were injected into the prostate of nude mice. After 3 days, these mice were randomized to receive the vehicle solution (intraperitoneally [i.p.], daily, paclitaxel (8 mg/kg i.p., weekly, rhLK8 (50 mg/kg i.p., daily, or a combination of paclitaxel and rhLK8 for 4 weeks. Treatment with paclitaxel or rhLK8 alone did not show significant therapeutic effects on tumor incidence or on tumor size compared with the control group. The combination of rhLK8 and paclitaxel significantly reduced tumor size and incidence of lymph node metastasis. Significant reduction in microvessel density and cellular proliferation and induction of apoptosis of tumor cells, and tumor-associated endothelial cells, were also achieved. Similarly, PC-3MM2 tumors growing in the tibia showed significant suppression of tumor growth and lymph node metastasis by the combination treatment with rhLK8 and paclitaxel. The integrity of the bone was significantly preserved, and apoptosis of tumor cells and tumor-associated endothelial cells was increased. 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.

  10. 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.

    Science.gov (United States)

    Lee, Ho-Jeong; Yu, Hyun-Kyung; Papadopoulos, John N; Kim, Seung Wook; He, Junqin; Park, Yong-Keun; Yoon, Yeup; Kim, Jang-Seong; Kim, Sun Jin

    2012-04-01

    Antivascular therapy has emerged as a rational strategy to improve the treatment of androgen-independent prostate cancer owing to the necessity of establishing a vascular network for the growth and progression of the primary and metastatic tumor. We determined whether recombinant human apolipoprotein(a) kringle V, rhLK8, produces therapeutic efficacy in an orthotopic human prostate cancer animal model. Fifty thousand androgen-independent human prostate cancer cells (PC-3MM2) were injected into the prostate of nude mice. After 3 days, these mice were randomized to receive the vehicle solution (intraperitoneally [i.p.], daily), paclitaxel (8 mg/kg i.p., weekly), rhLK8 (50 mg/kg i.p., daily), or a combination of paclitaxel and rhLK8 for 4 weeks. Treatment with paclitaxel or rhLK8 alone did not show significant therapeutic effects on tumor incidence or on tumor size compared with the control group. The combination of rhLK8 and paclitaxel significantly reduced tumor size and incidence of lymph node metastasis. Significant reduction in microvessel density and cellular proliferation and induction of apoptosis of tumor cells, and tumor-associated endothelial cells, were also achieved. Similarly, PC-3MM2 tumors growing in the tibia showed significant suppression of tumor growth and lymph node metastasis by the combination treatment with rhLK8 and paclitaxel. The integrity of the bone was significantly preserved, and apoptosis of tumor cells and tumor-associated endothelial cells was increased. 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.

  11. beta-TrCP inhibition reduces prostate cancer cell growth via upregulation of the aryl hydrocarbon receptor.

    Directory of Open Access Journals (Sweden)

    Udi Gluschnaider

    Full Text Available BACKGROUND: Prostate cancer is a common and heterogeneous disease, where androgen receptor (AR signaling plays a pivotal role in development and progression. The initial treatment for advanced prostate cancer is suppression of androgen signaling. Later on, essentially all patients develop an androgen independent stage which does not respond to anti hormonal treatment. Thus, alternative strategies targeting novel molecular mechanisms are required. beta-TrCP is an E3 ligase that targets various substrates essential for many aspects of tumorigenesis. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that beta-TrCP depletion suppresses prostate cancer and identify a relevant growth control mechanism. shRNA targeted against beta-TrCP reduced prostate cancer cell growth and cooperated with androgen ablation in vitro and in vivo. We found that beta-TrCP inhibition leads to upregulation of the aryl hydrocarbon receptor (AhR mediating the therapeutic effect. This phenomenon could be ligand independent, as the AhR ligand 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD did not alter prostate cancer cell growth. We detected high AhR expression and activation in basal cells and atrophic epithelial cells of human cancer bearing prostates. AhR expression and activation is also significantly higher in tumor cells compared to benign glandular epithelium. CONCLUSIONS/SIGNIFICANCE: Together these observations suggest that AhR activation may be a cancer counteracting mechanism in the prostate. We maintain that combining beta-TrCP inhibition with androgen ablation could benefit advanced prostate cancer patients.

  12. Small molecule screening reveals a transcription-independent pro-survival function of androgen receptor in castration-resistant prostate cancer.

    Science.gov (United States)

    Narizhneva, Natalia V; Tararova, Natalia D; Ryabokon, Petro; Shyshynova, Inna; Prokvolit, Anatoly; Komarov, Pavel G; Purmal, Andrei A; Gudkov, Andrei V; Gurova, Katerina V

    2009-12-15

    In prostate cancer (PCa) patients, initial responsiveness to androgen deprivation therapy is frequently followed by relapse due to development of treatment-resistant androgen-independent PCa. This is typically associated with acquisition of mutations in AR that allow activity as a transcription factor in the absence of ligand, indicating that androgen-independent PCa remains dependent on AR function. Our strategy to effectively target AR in androgen-independent PCa involved using a cell-based readout to isolate small molecules that inhibit AR transactivation function through mechanisms other than modulation of ligand binding. A number of the identified inhibitors were toxic to AR-expressing PCa cells regardless of their androgen dependence. Among these, some only suppressed PCa cell growth (ARTIS), while others induced cell death (ARTIK). ARTIK, but not ARTIS, compounds caused disappearance of AR protein from treated cells. siRNA against AR behaved like ARTIK compounds, while a dominant negative AR mutant that prevents AR-mediated transactivation but does not eliminate the protein showed only a growth suppressive effect. These observations reveal a transcription-independent function of AR that is essential for PCa cell viability and, therefore, is an ideal target for anti-PCa treatment. Indeed, several of the identified AR inhibitors demonstrated in vivo efficacy in mouse models of PCa and are candidates for pharmacologic optimization.

  13. Road to Recovery from Prostate Cancer

    Medline Plus

    Full Text Available ... about robotic prostatectomies for the treatment of prostate cancer. During the program, we would like to go ... potency post- surgery. So in 2008, while prostate cancer remains a very controversial subject, it is obviously ...

  14. African American Men and Prostate Cancer

    Medline Plus

    Full Text Available ... Americans have one of the highest incidences of prostate cancer in the world, and in this country ... is -- an epidemic. Winston Dyer: My introduction to prostate cancer started with the death of my 46- ...

  15. African American Men and Prostate Cancer

    Medline Plus

    Full Text Available ... Americans have one of the highest incidences of prostate cancer in the world, and in this country the ... is -- an epidemic. Winston Dyer: My introduction to prostate cancer started with the death of my 46-year- ...

  16. African American Men and Prostate Cancer

    Medline Plus

    Full Text Available ... have one of the highest incidences of prostate cancer in the world, and in this country the ... an epidemic. Winston Dyer: My introduction to prostate cancer started with the death of my 46-year- ...

  17. Active surveillance for prostate cancer.

    Science.gov (United States)

    Romero-Otero, Javier; García-Gómez, Borja; Duarte-Ojeda, José M; Rodríguez-Antolín, Alfredo; Vilaseca, Antoni; Carlsson, Sigrid V; Touijer, Karim A

    2016-03-01

    It is worth distinguishing between the two strategies of expectant management for prostate cancer. Watchful waiting entails administering non-curative androgen deprivation therapy to patients on development of symptomatic progression, whereas active surveillance entails delivering curative treatment on signs of disease progression. The objectives of the two management strategies and the patients enrolled in either are different: (i) to review the role of active surveillance as a management strategy for patients with low-risk prostate cancer; and (ii) review the benefits and pitfalls of active surveillance. We carried out a systematic review of active surveillance for prostate cancer in the literature using the National Center for Biotechnology Information's electronic database, PubMed. We carried out a search in English using the terms: active surveillance, prostate cancer, watchful waiting and conservative management. Selected studies were required to have a comprehensive description of the demographic and disease characteristics of the patients at the time of diagnosis, inclusion criteria for surveillance, and a protocol for the patients' follow up. Review articles were included, but not multiple papers from the same datasets. Active surveillance appears to reduce overtreatment in patients with low-risk prostate cancer without compromising cancer-specific survival at 10 years. Therefore, active surveillance is an option for select patients who want to avoid the side-effects inherent to the different types of immediate treatment. However, inclusion criteria for active surveillance and the most appropriate method of monitoring patients on active surveillance have not yet been standardized. PMID:26621054

  18. Prevention strategies for prostate cancer.

    Science.gov (United States)

    Schmitz-Dräger, B J; Lümmen, G; Bismarck, E; Fischer, C

    2012-12-01

    Through the last decade consideration of the role of vitamins and minerals in primary prevention of genitourinary tumors has dramatically changed. Despite all efforts efficacy of a specific compound has not been proven, so far. In consequence, recommendations for a use of vitamins or other supplements with the intention of prostate cancer prevention should be avoided today. In contrast, there is some evidence that life style modification might be helpful: recent investigations suggest that smoking may be involved in prostate cancer carcinogenesis. In addition, there is evidence that moderate food consumption, reduction of dairy products and an Asian or Mediterranean diet might not only prevent prostate cancer but also harbors additional beneficial effects on general health. This move from single compounds to more complex diets can be considered as a change of paradigm in prostate cancer prevention and could be the starting point of future epidemiological research. Disappointing findings with regards to nutritional cancer prevention contrast with a solid evidence concerning the efficacy of chemoprevention using 5a-reductase inhibitors: Long-term use of Finasteride and Dutasteride significantly reduces prostate cancer detection. Further candidate drugs are under investigation. However, translation of these findings into urological practice remains a matter of controversial discussion. PMID:23288209

  19. The diverse and contrasting effects of using human prostate cancer cell lines to study androgen receptor roles in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Sheng-Qiang Yu; Kuo-Pao Lai; Shu-Jie Xia; Hong-Chiang Chang; Chawnshang Chang; Shuyuan Yeh

    2009-01-01

    The androgen receptor (AR) plays an important role in the development and progression of prostate cancer (PCa).Androgen deprivation therapy is initially effective in blocking tumor growth,but it eventually leads to the hormonerefractory state.The detailed mechanisms of the conversion from androgen dependence to androgen independence remain unclear.Several PCa cell lines were established to study the role of AR in PCa,but the results were often inconsistent or contrasting in different cell lines,or in the same cell line grown under different conditions.The cellular and molecular alteration of epithelial cells and their microenvironments are complicated,and it is difficult to use a single cell line to address this important issue and also to study the pathophysiological effects of AR.In this paper,we summarize the different effects of AR on multiple cell lines and show the disadvantages of using a single human PCa cell line to study AR effects on PCa.We also discuss the advantages of widely used epithelium-stroma co-culture systems,xenograft mouse models,and genetically engineered PCa mouse models.The combination of in vitro cell line studies and in vivo mouse models might lead to more credible results and better strategies for the study of AR roles in PCa.

  20. The link between benign prostatic hyperplasia and prostate cancer

    DEFF Research Database (Denmark)

    Ørsted, David Dynnes; Bojesen, Stig E

    2013-01-01

    therapy. Furthermore, risk factors such as prostate inflammation and metabolic disruption have key roles in the development of both diseases. Despite these commonalities, BPH and prostate cancer exhibit important differences in terms of histology and localization. Although large-scale epidemiological......Benign prostatic hyperplasia (BPH) and prostate cancer are among the most common diseases of the prostate gland and represent significant burdens for patients and health-care systems in many countries. The two diseases share traits such as hormone-dependent growth and response to antiandrogen...... studies have shown that men with BPH have an increased risk of prostate cancer and prostate-cancer-related mortality, it remains unclear whether this association reflects a causal link, shared risk factors or pathophysiological mechanisms, or detection bias upon statistical analysis. Establishing BPH...

  1. Serum Oxidized Protein and Prostate Cancer Risk within the Prostate Cancer Prevention Trial

    OpenAIRE

    Hoque, Ashraful; Ambrosone, Christine B; Till, Cathee; Goodman, Phyllis J.; Tangen, Cathy; Kristal, Alan; Lucia, Scott; Wang, Qiao; Kappil, Maya; Thompson, Ian; Hsing, Ann W.; Parnes, Howard; Lippman, Scott M.; Santella, Regina M.

    2010-01-01

    To evaluate the role of oxidative stress in prostate cancer risk, we analyzed serum levels of protein carbonyl groups in 1808 prostate cancer cases and 1805 controls, nested in the Prostate Cancer Prevention Trial, a randomized, placebo-control trial that found finasteride decreased prostate cancer risk. There were no significant differences in protein carbonyl levels in baseline samples between those later diagnosed with prostate cancer and those without at the end of study biopsy. Adjusted ...

  2. Finasteride Concentrations and Prostate Cancer Risk: Results from the Prostate Cancer Prevention Trial

    OpenAIRE

    Chau, Cindy H.; Price, Douglas K.; Cathee Till; Goodman, Phyllis J.; Xiaohong Chen; Leach, Robin J; Johnson-Pais, Teresa L.; Hsing, Ann W.; Ashraful Hoque; Tangen, Catherine M.; Lisa Chu; Parnes, Howard L.; Schenk, Jeannette M.; Reichardt, Juergen K. V.; Thompson, Ian M

    2015-01-01

    Objective In the Prostate Cancer Prevention Trial (PCPT), finasteride reduced the risk of prostate cancer by 25%, even though high-grade prostate cancer was more common in the finasteride group. However, it remains to be determined whether finasteride concentrations may affect prostate cancer risk. In this study, we examined the association between serum finasteride concentrations and the risk of prostate cancer in the treatment arm of the PCPT and determined factors involved in modifying dru...

  3. Anti-cancer agents based on 6-trifluoromethoxybenzimidazole derivatives and method of making

    Science.gov (United States)

    Gakh, Andrei A; Vovk, Mykhaylo V; Mel& #x27; nychenko, Nina V; Sukach, Volodymyr A

    2012-10-23

    The present disclosure relates to novel compounds having the structural Formulas (1a,1b), stereoisomers, tautomers, racemics, prodrugs, metabolites thereof, or pharmaceutically acceptable salt and/or solvate thereof as chemotherapy agents for treating of cancer, particularly androgen-independent prostate cancer. The disclosure also relates to methods for preparing said compounds, and to pharmaceutical compositions comprising said compounds.

  4. Association of Symptomatic Benign Prostatic Hyperplasia and Prostate Cancer: Results from the Prostate Cancer Prevention Trial

    OpenAIRE

    Schenk, Jeannette M.; Kristal, Alan R.; Arnold, Kathryn B.; Tangen, Catherine M.; Neuhouser, Marian L; Lin, Daniel W; White, Emily; Thompson, Ian M

    2011-01-01

    This study examined the association between symptomatic benign prostatic hyperplasia (BPH) and prostate cancer risk in 5,068 placebo-arm participants enrolled in the Prostate Cancer Prevention Trial (1993–2003). These data include 1,225 men whose cancer was detected during the 7-year trial—556 detected for cause (following abnormal prostate-specific antigen or digital rectal examination) and 669 detected not for cause (without indication), as well as 3,843 men who had biopsy-proven absence of...

  5. The liver X receptor agonist T0901317 acts as androgen receptor antagonist in human prostate cancer cells

    International Nuclear Information System (INIS)

    T0901317 is a potent non-steroidal synthetic liver X receptor (LXR) agonist. T0901317 blocked androgenic stimulation of the proliferation of androgen-dependent LNCaP 104-S cells and androgenic suppression of the proliferation of androgen-independent LNCaP 104-R2 cells, inhibited the transcriptional activation of an androgen-dependent reporter gene by androgen, and suppressed gene and protein expression of prostate specific antigen (PSA), a target gene of androgen receptor (AR) without affecting gene and protein expression of AR. T0901317 also inhibited binding of a radiolabeled androgen to AR, but inhibition was much weaker compared to the effect of the antiandrogens, bicalutamide and hydroxyflutamide. The LXR agonist T0901317, therefore, acts as an antiandrogen in human prostate cancer cells

  6. Prostate Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing prostate cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  7. Potassium channels in prostate and colonic cancer

    OpenAIRE

    Ousingsawat, Jiraporn

    2007-01-01

    Large conductance Ca2+-activated K+ channels in human prostate cancer The KCNMA1 gene encoding the alpha-subunit of BK channels is amplified and BK channel expression is enhanced in late-stage, metastatic and hormone-refractory human prostate cancer tissues, whereas benign prostate tissues show only a weak expression of BK channels. PC-3 hormone-insensitive prostate cancer cells, but not hormone-sensitive prostate cancer cells (LNCaP) and benign prostate hyperplasia cells (BPH-1), show an ...

  8. Low Risk Prostate Cancer and Active Surveillance

    NARCIS (Netherlands)

    M. Bul (Meelan)

    2013-01-01

    textabstractThe first part of this thesis comprises an introduction to prostate cancer and screening (chapter 1). The European Randomized study of Screening for Prostate Cancer (ERSPC) has shown an effect of screening on prostate cancer mortality in favor of the screening population, however, contro

  9. Prevention and early detection of prostate cancer

    NARCIS (Netherlands)

    J. Cuzick (Jack); M.A. Thorat (Mangesh A); G. Andriole (Gerald); O.W. Brawley (Otis W); P.H. Brown (Powel H); Z. Culig (Zoran); R. Eeles (Rosalind); L.G. Ford (Leslie G); F. Hamdy (Freddie); L. Holmberg (Lars); D. Ilic (Dragan); T.J. Key (Timothy J); C.L. Vecchia (Carlo La); H. Lilja (Hans); M. Marberger (Michael); F.L. Meyskens (Frank L); L.M. Minasian (Lori M); C. Parker (C.); H.L. Parnes (Howard L); S. Perner (Sven); H. Rittenhouse (Harry); J.A. Schalken (J.); H.-P. Schmid (Hans-Peter); B.J. Schmitz-Dräger (Bernd J); F.H. Schröder (Fritz); A. Stenzl (Arnulf); B. Tombal (Bertrand); T.J. Wilt (Timothy J.); K. Wolk (Kerstin)

    2014-01-01

    textabstractProstate cancer is a common malignancy in men and the worldwide burden of this disease is rising. Lifestyle modifications such as smoking cessation, exercise, and weight control offer opportunities to reduce the risk of developing prostate cancer. Early detection of prostate cancer by pr

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

    Directory of Open Access Journals (Sweden)

    Dan Smith

    2010-06-01

    Full Text Available PURPOSE: Recent work has demonstrated the return of hormone sensitivity after palliative chemotherapy in androgen independent prostate cancer. We wished to establish whether a similar phenomenon existed in patients with no exposure to chemotherapy. MATERIALS AND METHODS: A review of “hormone resistant” patients who had received salvage brachytherapy for localized prostate cancer after previous external beam radiotherapy was undertaken. Three patients with subsequent biochemical relapse responded to the rechallenge with hormonal treatment. RESULTS: The series of patients presented here demonstrates this phenomenon occurs after salvage brachytherapy with no exposure to chemotherapy. Recovery of sensitivity is demonstrated both to androgen deprivation and to androgen receptor antagonism. The recovery of hormone sensitivity was surprisingly durable, ranging from eight months to over twenty-one months. CONCLUSIONS: Hormone sensitivity may be recovered after salvage brachytherapy. Potential mechanisms underlying these observations are discussed and the likely central role of the activity of the androgen receptor highlighted. The relevance of these findings to the management of advanced prostate cancer is considered including thoughts on the practice of intermittent anti-androgen therapy.

  11. Gene therapy for prostate cancer.

    LENUS (Irish Health Repository)

    Tangney, Mark

    2012-01-31

    Cancer remains a leading cause of morbidity and mortality. Despite advances in understanding, detection, and treatment, it accounts for almost one-fourth of all deaths per year in Western countries. Prostate cancer is currently the most commonly diagnosed noncutaneous cancer in men in Europe and the United States, accounting for 15% of all cancers in men. As life expectancy of individuals increases, it is expected that there will also be an increase in the incidence and mortality of prostate cancer. Prostate cancer may be inoperable at initial presentation, unresponsive to chemotherapy and radiotherapy, or recur following appropriate treatment. At the time of presentation, patients may already have metastases in their tissues. Preventing tumor recurrence requires systemic therapy; however, current modalities are limited by toxicity or lack of efficacy. For patients with such metastatic cancers, the development of alternative therapies is essential. Gene therapy is a realistic prospect for the treatment of prostate and other cancers, and involves the delivery of genetic information to the patient to facilitate the production of therapeutic proteins. Therapeutics can act directly (eg, by inducing tumor cells to produce cytotoxic agents) or indirectly by upregulating the immune system to efficiently target tumor cells or by destroying the tumor\\'s vasculature. However, technological difficulties must be addressed before an efficient and safe gene medicine is achieved (primarily by developing a means of delivering genes to the target cells or tissue safely and efficiently). A wealth of research has been carried out over the past 20 years, involving various strategies for the treatment of prostate cancer at preclinical and clinical trial levels. The therapeutic efficacy observed with many of these approaches in patients indicates that these treatment modalities will serve as an important component of urological malignancy treatment in the clinic, either in isolation or

  12. Diagnosis and treatment for prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Zuoxing Niu; Guohua Ren; Shuping Song

    2008-01-01

    The morbility of prostate cancer has risen in China in recent years, it is important to diagnose and treat prostate cancer standardly and systemically.This review analyzed the status and advances of PSA examination, digital rectal examination, prostate biopsy in prostate cancer, and it gave a detailed description of radical prostatectomy, radiotherapy, chemotherapy, hormonal therapy, etc.The advances of targeted therapy and tumor vaccine is also discussed.

  13. Cancer stem cells in prostate cancer

    OpenAIRE

    Moltzahn, Felix; Thalmann, George N

    2013-01-01

    Prostate cancer (P-Ca) remains a leading cause of cancer-related death in men. Lately, increasing evidence for a hierarchically organized cancer stem cell (CSC) model emerged for different tumors entities, including P-Ca. CSCs are defined by several characteristics including self-renewal, pluripotency and tumorigenicity and are thought to be responsible for tumor recurrence, metastasis and cancer related death. In this review we discuss the recent research in the field of CSCs, its limitation...

  14. Modulators of estrogen receptor inhibit proliferation and migration of prostate cancer cells.

    Science.gov (United States)

    Piccolella, Margherita; Crippa, Valeria; Messi, Elio; Tetel, Marc J; Poletti, Angelo

    2014-01-01

    In the initial stages, human prostate cancer (PC) is an androgen-sensitive disease, which can be pharmacologically controlled by androgen blockade. This therapy often induces selection of androgen-independent PC cells with increased invasiveness. We recently demonstrated, both in cells and mice, that a testosterone metabolite locally synthetized in prostate, the 5α-androstane-3β, 17β-diol (3β-Adiol), inhibits PC cell proliferation, migration and invasion, acting as an anti-proliferative/anti-metastatic agent. 3β-Adiol is unable to bind androgen receptor (AR), but exerts its protection against PC by specifically interacting with estrogen receptor beta (ERβ). Because of its potential retro-conversion to androgenic steroids, 3β-Adiol cannot be used "in vivo", thus, the aims of this study were to investigate the capability of four ligands of ERβ (raloxifen, tamoxifen, genistein and curcumin) to counteract PC progression by mimicking the 3β-Adiol activity. Our results demonstrated that raloxifen, tamoxifen, genistein and curcumin decreased DU145 and PC3 cell proliferation in a dose-dependent manner; in addition, all four compounds significantly decreased the detachment of cells seeded on laminin or fibronectin. Moreover, raloxifen, tamoxifen, genistein and curcumin-treated DU145 and PC3 cells showed a significant decrease in cell migration. Notably, all these effects were reversed by the anti-estrogen, ICI 182,780, suggesting that their actions are mediated by the estrogenic pathway, via the ERβ, the only isoform present in these PCs. In conclusion, these data demonstrate that by selectively activating the ERβ, raloxifen, tamoxifen, genistein and curcumin inhibit human PC cells proliferation and migration favoring cell adesion. These synthetic and natural modulators of ER action may exert a potent protective activity against the progression of PC even in its androgen-independent status. PMID:24184124

  15. Prostate cancer immunotherapy: beyond immunity to curability.

    Science.gov (United States)

    Simons, Jonathan W

    2014-11-01

    Metastatic prostate cancer is the second leading cause of death from cancer in the United States. It is the first prevalent cancer in which overall survival in advanced disease is modestly, but objectively, improved with outpatient delivered dendritic cell-based immunotherapy. More prostate cancer patients have enrolled through Facebook and trusted-site Internet searches in clinical trials for prostate cancer vaccine-based immunotherapy than in immunotherapy trials for lung, breast, colon, pancreas, ovarian, and bladder cancer combined in the past 7 years. Exceptional responses to anti-CTLA-4 treatment have been documented in clinics, and prostate cancer neoantigen characterization and T-cell clonotyping are in their research ascendancy. The prostate is an accessory organ; it is not required for fertility, erectile function, or urinary continence. The true evolutionary advantage of having a prostate for male mammalian physiology is a topic of speculation in seminar rooms and on bar stools, but it remains unknown. Hundreds of prostate lineage-unique proteins (PLUP) exist among the >37,000 normal human prostate lineage-unique open reading frames that can be targeted for immunologic ablation of PLUP(+) prostate cancer cells by prostate-specific autoimmunity. This bioengineered graft-versus-prostate disease is a powerful strategy that can eliminate deaths from prostate cancer. Immunologic tolerance to prostate cancer can be overcome at every clinical stage of presentation. This Cancer Immunology at the Crossroads article aims to present advances in the past two decades of basic, translational, and clinical research in prostate cancer, including bioengineering B-cell and T-cell responses, and ongoing prostate cancer immunotherapy trials. PMID:25367978

  16. Inflammatory Genetic Markers of Prostate Cancer Risk

    Energy Technology Data Exchange (ETDEWEB)

    Tindall, Elizabeth A.; Hayes, Vanessa M. [Cancer Genetics Group, Children’s Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, University of New South Wales, PO Box 81, Randwick, NSW 2031 (Australia); University of New South Wales, Kensington Campus, Sydney, NSW 2052 (Australia); Petersen, Desiree C., E-mail: dpetersen@ccia.unsw.edu.au [Cancer Genetics Group, Children’s Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, University of New South Wales, PO Box 81, Randwick, NSW 2031 (Australia)

    2010-06-08

    Prostate cancer is the most common cancer in Western society males, with incidence rates predicted to rise with global aging. Etiology of prostate cancer is however poorly understood, while current diagnostic tools can be invasive (digital rectal exam or biopsy) and/or lack specificity for the disease (prostate-specific antigen (PSA) testing). Substantial histological, epidemiological and molecular genetic evidence indicates that inflammation is important in prostate cancer pathogenesis. In this review, we summarize the current status of inflammatory genetic markers influencing susceptibility to prostate cancer. The focus will be on inflammatory cytokines regulating T-helper cell and chemokine homeostasis, together with the Toll-like receptors as key players in the host innate immune system. Although association studies indicating a genetic basis for prostate cancer are presently limited mainly due to lack of replication, larger and more ethnically and clinically defined study populations may help elucidate the true contribution of inflammatory gene variants to prostate cancer risk.

  17. Inflammatory Genetic Markers of Prostate Cancer Risk

    International Nuclear Information System (INIS)

    Prostate cancer is the most common cancer in Western society males, with incidence rates predicted to rise with global aging. Etiology of prostate cancer is however poorly understood, while current diagnostic tools can be invasive (digital rectal exam or biopsy) and/or lack specificity for the disease (prostate-specific antigen (PSA) testing). Substantial histological, epidemiological and molecular genetic evidence indicates that inflammation is important in prostate cancer pathogenesis. In this review, we summarize the current status of inflammatory genetic markers influencing susceptibility to prostate cancer. The focus will be on inflammatory cytokines regulating T-helper cell and chemokine homeostasis, together with the Toll-like receptors as key players in the host innate immune system. Although association studies indicating a genetic basis for prostate cancer are presently limited mainly due to lack of replication, larger and more ethnically and clinically defined study populations may help elucidate the true contribution of inflammatory gene variants to prostate cancer risk

  18. Vitamin D, Sunlight and Prostate Cancer Risk

    OpenAIRE

    Krishna Vanaja Donkena; Young, Charles Y. F.

    2011-01-01

    Prostate cancer is the second common cancer in men worldwide. The prevention of prostate cancer remains a challenge to researchers and clinicians. Here, we review the relationship of vitamin D and sunlight to prostate cancer risk. Ultraviolet radiation of the sunlight is the main stimulator for vitamin D production in humans. Vitamin D's antiprostate cancer activities may be involved in the actions through the pathways mediated by vitamin D metabolites, vitamin D metabolizing enzymes, vitamin...

  19. Progress in Gene Therapy for Prostate Cancer

    OpenAIRE

    KamranAliAhmed; BrianJamesDavis; TorrenceMWilson; GregoryAWiseman; MarkJFederspiel; JohnCMorris

    2012-01-01

    Gene therapy has held promise to correct various disease processes. Prostate cancer represents the second leading cause of cancer death in American men. A number of clinical trials involving gene therapy for the treatment of prostate cancer have been reported. The ability to efficiently transduce tumors with effective levels of therapeutic genes has been identified as a fundamental barrier to effective cancer gene therapy. The approach utilizing gene therapy in prostate cancer patients at our...

  20. Detecting Prostate Cancer

    Medline Plus

    Full Text Available ... have other tests, such as a trans-rectal ultrasound and a biopsy. Physician: Now, just relax -- the ... exam or PSA test indicates an abnormality, an ultrasound image is made of the prostate gland. Usually ...

  1. Detecting Prostate Cancer

    Medline Plus

    Full Text Available ... stands for Prostate Specific Antigen. It is a test that men have by having their blood sampled ... be present. Narrator: While the use of the test remains controversial, a normal PSA level is considered ...

  2. Detecting Prostate Cancer

    Medline Plus

    Full Text Available ... M.D.: PSA stands for Prostate Specific Antigen. It is a test that men have by having ... detection is the digital rectal exam. Barry Trevithick: It doesn't make sense to be afraid of ...

  3. What Is Prostate Cancer?

    Medline Plus

    Full Text Available ... visit to their urologist. John Bertini, M.D.: It's a wide variety of reasons why they might ... have a prostate. Most men don't pronounce it correctly and wouldn't know where it's located ...

  4. Improving Screening Strategies for Prostate Cancer

    NARCIS (Netherlands)

    T. Wolters (Tineke)

    2010-01-01

    textabstractTh is thesis describes research on screening for prostate cancer. To improve understanding of the thesis, some background information will be provided in this introduction. First, a short description of the prostate and of prostate cancer will be given in Chapter 1, followed by more deta

  5. The Clinical Genetics of Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Kommu Sashi

    2004-07-01

    Full Text Available Abstract Prostate cancer is the most common cancer in men and the second highest cause of cancer-related mortality in the U.K. A genetic component in predisposition to prostate cancer has been recognized for decades. One of the strongest epidemiological risk factors for prostate cancer is a positive family history. The hunt for the genes that predispose to prostate cancer in families has been the focus of many research groups worldwide for the past 10 years. Both epidemiological and twin studies support a role for genetic predisposition to prostate cancer. Familial cancer loci have been found, but the genes that cause familial prostate cancer remain largely elusive. Unravelling the genetics of prostate cancer is challenging and is likely to involve the analysis of numerous predisposition genes. Current evidence supports the hypothesis that excess familial risk of prostate cancer could be due to the inheritance of multiple moderate-risk genetic variants. Although research on hereditary prostate cancer has improved our knowledge of the genetic aetiology of the disease, a lot of questions still remain unanswered. This article explores the current evidence that there is a genetic component to the aetiology of prostate cancer and attempts to put into context the diverse findings that have been shown to be possibly associated with the development of hereditary prostate cancer. Linkage searches over the last decade are summarised. It explores issues as to why understanding the genetics of prostate cancer has been so difficult and why despite this, it is still a major focus of research. Finally, current and future management strategies of men with Hereditary Prostate Cancer (HPC are discussed.

  6. Screening spectroscopy of prostate cancer

    Science.gov (United States)

    Yermolenko, S. B.; Voloshynskyy, D. I.; Fedoruk, O. S.

    2015-11-01

    The aim of the study was to establish objective parameters of the field of laser and incoherent radiation of different spectral ranges (UV, visible, IR) as a non-invasive optical method of interaction with different samples of biological tissues and fluids of patients to determine the state of prostate cancer and choosing the best personal treatment. The objects of study were selected venous blood plasma of patient with prostate cancer, histological sections of rat prostate gland in the postoperative period. As diagnostic methods have been used ultraviolet spectrometry samples of blood plasma in the liquid state, infrared spectroscopy middle range (2,5-25 microns) dry residue of plasma by spectral diagnostic technique of thin histological sections of biological tissues.

  7. WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics

    Institute of Scientific and Technical Information of China (English)

    Isabelle Bisson; David M Prowse

    2009-01-01

    Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their abil-ity to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heteroge-neous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treat-ment with WNT inhibitors reduced both prostasphere size and self-renewal, In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear β-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer cells express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are con-sistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector β-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen re-ceptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit am-plifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the self-renewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell charac-teristics and improve the therapeutic outcome.

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

    Institute of Scientific and Technical Information of China (English)

    YU Sheng-qiang; HAN Bang-min; SHAO Yi; WU Ji-tao; ZHAO Fu-jun; LIU Hai-tao; SUN Xiao-wen; TANG Yue-qing; XIA Shu-jie

    2009-01-01

    Background Prostate cancer is one of the most common urogenital tumors in the world with an increasing incidence in China. Androgen deprivation therapy is the major therapeutic option for advanced prostate cancer. However, the role of androgen receptor (AR) in hormone-refractory prostate cancer still remains unclear. This work aimed to investigate the role of AR in an androgen independent prostate cancer cell line by in vitro and in vivo studies.Methods The role of AR in the proliferation and invasion/metastasis ability of PC3-AR9 (a PC3 stable clone expressing human AR driven by natural human AR promoter) were examined with MTT assay, soft agar assay, chamber invasion assay, wound healing assay, and also with orthotopic xenograft mouse model.Results Restoring androgen receptor in PC3 cells resulted in decreased proliferation and invasion/metastasis ability in MTT, soft agar, chamber invasion and wound healing assay. In the mouse orthotopic xenograft model, PC3-AR9 resulted in smaller primary tumors and metastasis tumors, with a lower proliferation rate and higher apoptosis rate.Conclusion The AR might function as a tumor suppressor in PC3 cells both in vitro and in vivo.

  9. Road to Recovery from Prostate Cancer

    Medline Plus

    Full Text Available ... of Urology and the Director of the Deane Prostate Health and Research Center at the Mount Sinai ... more about robotic prostatectomies for the treatment of prostate cancer. During the program, we would like to ...

  10. Prostate Cancer, Prostate Cancer Death, and Death from Other Causes, Among Men with Metabolic Aberrations

    OpenAIRE

    Häggström, Christel; Stocks, Tanja; Nagel, Gabriele; Manjer, Jonas; Bjørge, Tone; Hallmans, Göran; Engeland, Anders; Ulmer, Hanno; Lindkvist, Bjorn; Selmer, Randi; Concin, Hans; Tretli, Steinar; Jonsson, Håkan; Stattin, Pär

    2014-01-01

    Background: Few previous studies of metabolic aberrations and prostate cancer risk have taken into account the fact that men with metabolic aberrations have an increased risk of death from causes other than prostate cancer. The aim of this study was to calculate, in a real-life scenario, the risk of prostate cancer diagnosis, prostate cancer death, and death from other causes. Methods: In the Metabolic Syndrome and Cancer Project, prospective data on body mass index, blood pressure, glucose, ...

  11. Effects of Prostate Cancer Screening and Treatment

    NARCIS (Netherlands)

    E.M. Wever (Elisabeth)

    2012-01-01

    textabstractProstate cancer is the second most frequently diagnosed cancer of men worldwide. The number of new cases worldwide was estimated at 899,000 and accounted for 13.6% of all cancers in men in 2008. With an estimated 258,000 deaths in 2008, prostate cancer is the sixth leading cause of death

  12. Pancreatic Metastasis from Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Julian Jacob

    2010-01-01

    Full Text Available The pancreas is an unusual location for metastases from other primary cancers. Rarely, pancreatic metastases from kidney or colorectal cancers have been reported. However, a variety of other cancers may also spread to the pancreas. We report an exceptional case of pancreatic metastasis from prostate cancer. Differences in management between primary and secondary pancreatic tumors make recognition of metastases to the pancreas an objective of first importance. Knowledge of unusual locations for metastatic spread will reduce diagnostic delay and lead to a timely delivery of an appropriate treatment.

  13. Immunotherapy and Immune Evasion in Prostate Cancer

    OpenAIRE

    Archana Thakur; Ulka Vaishampayan; Lum, Lawrence G.

    2013-01-01

    Metastatic prostate cancer remains to this day a terminal disease. Prostatectomy and radiotherapy are effective for organ-confined diseases, but treatment for locally advanced and metastatic cancer remains challenging. Although advanced prostate cancers treated with androgen deprivation therapy achieves debulking of disease, responses are transient with subsequent development of castration-resistant and metastatic disease. Since prostate cancer is typically a slowly progressing disease, use o...

  14. Prostate Cancer and Bone: The Elective Affinities

    OpenAIRE

    Nadia Rucci; Adriano Angelucci

    2014-01-01

    The onset of metastases dramatically changes the prognosis of prostate cancer patients, determining increased morbidity and a drastic fall in survival expectancy. Bone is a common site of metastases in few types of cancer, and it represents the most frequent metastatic site in prostate cancer. Of note, the prevalence of tumor relapse to the bone appears to be increasing over the years, likely due to a longer overall survival of prostate cancer patients. Bone tropism represents an intriguing c...

  15. Multidisciplinary Functional MR Imaging for Prostate Cancer

    OpenAIRE

    Kim, Jeong Kon; Jang, Yun-Jin; Cho, Gyunggoo

    2009-01-01

    Various functional magnetic resonance (MR) imaging techniques are used for evaluating prostate cancer including diffusion-weighted imaging, dynamic contrast-enhanced MR imaging, and MR spectroscopy. These techniques provide unique information that is helpful to differentiate prostate cancer from non-cancerous tissue and have been proven to improve the diagnostic performance of MRI not only for cancer detection, but also for staging, post-treatment monitoring, and guiding prostate biopsies. Ho...

  16. Prostate and Urologic Cancer | Division of Cancer Prevention

    Science.gov (United States)

    Conducts and supports research on the prevention and early detection of prostate and bladder cancer. | Conducts and supports research on the prevention and early detection of prostate, bladder, and skin cancers.

  17. Retinoic Acid Induces Apoptosis of Prostate Cancer DU145 Cells through Cdk5 Overactivation

    Directory of Open Access Journals (Sweden)

    Mei-Chih Chen

    2012-01-01

    Full Text Available Retinoic acid (RA has been believed to be an anticancer drug for a long history. However, the molecular mechanisms of RA actions on cancer cells remain diverse. In this study, the dose-dependent inhibition of RA on DU145 cell proliferation was identified. Interestingly, RA treatment triggered p35 cleavage (p25 formation and Cdk5 overactivation, and all could be blocked by Calpain inhibitor, Calpeptin (CP. Subsequently, RA-triggered DU145 apoptosis detected by sub-G1 phase accumulation and Annexin V staining could also be blocked by CP treatment. Furthermore, RA-triggered caspase 3 activation and following Cdk5 over-activation were destroyed by treatments of both CP and Cdk5 knockdown. In conclusion, we report a new mechanism in which RA could cause apoptosis of androgen-independent prostate cancer cells through p35 cleavage and Cdk5 over-activation. This finding may contribute to constructing a clearer image of RA function and bring RA as a valuable chemoprevention agent for prostate cancer patients.

  18. Detecting Prostate Cancer

    Medline Plus

    Full Text Available Roger Babaian, M.D.: PSA stands for Prostate Specific Antigen. It is a test that men have by having their blood sampled and ... testing may be required. Physician: OK, what I'd like to do is just do a rectal ...

  19. Immunotherapy and Immune Evasion in Prostate Cancer

    International Nuclear Information System (INIS)

    Metastatic prostate cancer remains to this day a terminal disease. Prostatectomy and radiotherapy are effective for organ-confined diseases, but treatment for locally advanced and metastatic cancer remains challenging. Although advanced prostate cancers treated with androgen deprivation therapy achieves debulking of disease, responses are transient with subsequent development of castration-resistant and metastatic disease. Since prostate cancer is typically a slowly progressing disease, use of immune-based therapies offers an advantage to target advanced tumors and to induce antitumor immunity. This review will discuss the clinical merits of various vaccines and immunotherapies in castrate resistant prostate cancer and challenges to this evolving field of immune-based therapies

  20. Immunotherapy and Immune Evasion in Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Thakur, Archana, E-mail: thakur@karmanos.org; Vaishampayan, Ulka [Department of Oncology, Wayne State University, Detroit, MI 48201 (United States); Lum, Lawrence G., E-mail: thakur@karmanos.org [Department of Oncology, Wayne State University, Detroit, MI 48201 (United States); Department of Medicine, Wayne State University, Detroit, MI 48201 (United States); Department of Immunology and Microbiology, Wayne State University, Detroit, MI 48201 (United States)

    2013-05-24

    Metastatic prostate cancer remains to this day a terminal disease. Prostatectomy and radiotherapy are effective for organ-confined diseases, but treatment for locally advanced and metastatic cancer remains challenging. Although advanced prostate cancers treated with androgen deprivation therapy achieves debulking of disease, responses are transient with subsequent development of castration-resistant and metastatic disease. Since prostate cancer is typically a slowly progressing disease, use of immune-based therapies offers an advantage to target advanced tumors and to induce antitumor immunity. This review will discuss the clinical merits of various vaccines and immunotherapies in castrate resistant prostate cancer and challenges to this evolving field of immune-based therapies.

  1. Role of androgen receptor in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    HiroyoshiSuzuki; HaruoIto

    1999-01-01

    The growth of prostate cancer is sensitive to androgen, and hormonal therapy has been used for treatment of ad-vanced cancer. About 80 % of prostate cancers initially respond to hormonal therapy, howcrver, more than half of the re-sponders gradtmlly become resistant to this therapy. Changes in tumors from an androgen-responsive to an androgen-unre-sponsive state have been widely discussed. Since androgen action is mediated by androgen receptor (AR), abnonnalitiesof AR is believed to play an important role of the loss of androgen responsiveness in prostate cancer. "Ilais article focusedon the role of AR in the progression of prostate cancer.

  2. TRICHOMONOSIS AND SUBSEQUENT RISK OF PROSTATE CANCER IN THE PROSTATE CANCER PREVENTION TRIAL

    OpenAIRE

    Sutcliffe, Siobhan; Alderete, John F.; Till, Cathee; Goodman, Phyllis J.; Hsing, Ann W.; Zenilman, Jonathan M; De Marzo, Angelo M.; Platz, Elizabeth A.

    2009-01-01

    We previously observed a positive association between a history of trichomonosis, a sexually transmitted infection caused by the protozoan, Trichomonas vaginalis, and prostate cancer risk in the Health Professionals Follow-up Study. To determine the reproducibility of this finding, we conducted a second, prospective investigation of trichomonosis and prostate cancer in the Prostate Cancer Prevention Trial. Participants were men ≥55 years of age with no evidence of prostate cancer at enrollmen...

  3. Serum Phospholipid Fatty Acids and Prostate Cancer Risk: Results From the Prostate Cancer Prevention Trial

    OpenAIRE

    Brasky, Theodore M.; Till, Cathee; White, Emily; Neuhouser, Marian L; Song, Xiaoling; Goodman, Phyllis; Thompson, Ian M; King, Irena B.; Albanes, Demetrius; Kristal, Alan R.

    2011-01-01

    Inflammation may be involved in prostate cancer development and progression. This study examined the associations between inflammation-related phospholipid fatty acids and the 7-year-period prevalence of prostate cancer in a nested case-control analysis of participants, aged 55–84 years, in the Prostate Cancer Prevention Trial during 1994–2003. Cases (n = 1,658) were frequency matched to controls (n = 1,803) on age, treatment, and prostate cancer family history. Phospholipid fatty acids were ...

  4. Anti-cancer effects of novel flavonoid vicenin-2 as a single agent and in synergistic combination with docetaxel in prostate cancer.

    Science.gov (United States)

    Nagaprashantha, Lokesh Dalasanur; Vatsyayan, Rit; Singhal, Jyotsana; Fast, Spence; Roby, Rhonda; Awasthi, Sanjay; Singhal, Sharad S

    2011-11-01

    The present study was conducted to determine the efficacy of novel flavonoid vicenin-2 (VCN-2), an active constituent of the medicinal herb Ocimum Sanctum Linn or Tulsi, as a single agent and in combination with docetaxel (DTL) in carcinoma of prostate (CaP). VCN-2 effectively induced anti-proliferative, anti-angiogenic and pro-apoptotic effect in CaP cells (PC-3, DU-145 and LNCaP) irrespective of their androgen responsiveness or p53 status. VCN-2 inhibited EGFR/Akt/mTOR/p70S6K pathway along with decreasing c-Myc, cyclin D1, cyclin B1, CDK4, PCNA and hTERT in vitro. VCN-2 reached a level of 2.6±0.3μmol/l in serum after oral administration in mice which reflected that VCN-2 is orally absorbed. The i.v. administration of docetaxel (DTL), current drug of choice in androgen-independent CaP, is associated with dose-limiting toxicities like febrile neutropenia which has lead to characterization of alternate routes of administration and potential combinatorial regimens. In this regard, VCN-2 in combination with DTL synergistically inhibited the growth of prostate tumors in vivo with a greater decrease in the levels of AR, pIGF1R, pAkt, PCNA, cyclin D1, Ki67, CD31, and increase in E-cadherin. VCN-2 has been investigated for radioprotection and anti-inflammatory properties. This is the first study on the anti-cancer effects of VCN-2. In conclusion, our investigations collectively provide strong evidence that VCN-2 is effective against CaP progression along with indicating that VCN-2 and DTL co-administration is more effective than either of the single agents in androgen-independent prostate cancer.

  5. Role of transurethral resection of the prostate in the management of prostate cancer

    OpenAIRE

    Szollosi Attila; Martha Orsolya; Denes Lorand; Vida Arpad Oliver; Maier Adrian; Pavai Zoltan

    2016-01-01

    Introduction: Prostate cancer is the second most diagnosed cancer in men, after lung cancer. The gold standard procedure in prostate cancer (PCa) diagnosis is the ultrasound guided prostate biopsy. Transurethral resection of the prostate (TURP) used in solving the bladder outlet obstruction, can have a role in detection of PCa. The aim of this retrospective study is to examine the role of transurethral resection of the prostate in the diagnosis and therapy of prostate cancer.

  6. A precisely substituted benzopyran targets androgen refractory prostate cancer cells through selective modulation of estrogen receptors.

    Science.gov (United States)

    Kumar, Rajeev; Verma, Vikas; Sharma, Vikas; Jain, Ashish; Singh, Vishal; Sarswat, Amit; Maikhuri, Jagdamba P; Sharma, Vishnu L; Gupta, Gopal

    2015-03-15

    Dietary consumption of phytoestrogens like genistein has been linked with lower incidence of prostate cancer. The estradiol-like benzopyran core of genistein confers estrogen receptor-β (ER-β) selectivity that imparts weak anti-proliferative activity against prostate cancer cells. DL-2-[4-(2-piperidinoethoxy)phenyl]-3-phenyl-2H-1-benzopyran (BP), a SERM designed with benzopyran core, targeted androgen independent prostate cancer (PC-3) cells 14-times more potently than genistein, ~25% more efficiently than tamoxifen and 6.5-times more actively than ICI-182780, without forfeiting significant specificity in comparison to genistein. BP increased apoptosis (annexin-V and TUNEL labeling), arrested cell cycle, and significantly increased caspase-3 activity along with mRNA expressions of estrogen receptor (ER)-β and FasL (qPCR) in PC-3 cells. In classical ERE-luc reporter assay BP behaved as a potent ER-α antagonist and ER-β agonist. Accordingly, it decreased expression of ER-α target PS2 (P<0.01) and increased expression of ER-β target TNF-α (P<0.05) genes in PC-3. ER-β deficient PC-3 (siRNA-transfected) was resistant to apoptotic and anti-proliferative actions of SERMs, including stimulation of FasL expression by BP. BP significantly inhibited phosphorylation of Akt and ERK-1/2, JNK and p38 in PC-3 (immunoblotting), and thus adopted a multi-pathway mechanism to exert a more potent anti-proliferative activity against prostate cancer cells than natural and synthetic SERMs. Its precise ER-subtype specific activity presents a unique lead structure for further optimization.

  7. Prostate Cancer Screening : The effect on prostate cancer mortality and incidence

    NARCIS (Netherlands)

    P.J. van Leeuwen (Pim)

    2012-01-01

    textabstractAt first glance, deciding whether to get the PSA screening test for prostate cancer seems to be pretty straightforward and attractive. It’s a simple blood test that can pick up the prostate cancer long before your symptoms appear. After all, your prostate cancer is earlier treated result

  8. Saposin C promotes survival and prevents apoptosis via PI3K/Akt-dependent pathway in prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Lee Tae-Jin

    2004-11-01

    Full Text Available Abstract Background In addition to androgens, growth factors are also implicated in the development and neoplastic growth of the prostate gland. Prosaposin is a potent neurotrophic molecule. Homozygous inactivation of prosaposin in mice has led to the development of a number of abnormalities in the male reproductive system, including atrophy of the prostate gland and inactivation of mitogen-activated protein kinase (MAPK and Akt in prostate epithelial cells. We have recently reported that prosaposin is expressed at a higher level by androgen-independent (AI prostate cancer cells as compared to androgen-sensitive prostate cancer cells or normal prostate epithelial and stromal cells. In addition, we have demonstrated that a synthetic peptide (prosaptide TX14A, derived from the trophic sequence of the saposin C domain of prosaposin, stimulated cell proliferation, migration and invasion and activated the MAPK signaling pathway in prostate cancer cells. The biological significances of saposin C and prosaposin in prostate cancer are not known. Results Here, we report that saposin C, in a cell type-specific and dose-dependent manner, acts as a survival factor, activates the Akt-signaling pathway, down-modulates caspase-3, -7, and -9 expression and/or activity, and decreases the cleaved nuclear substrate of caspase-3 in prostate cancer cells under serum-starvation stress. In addition, prosaptide TX14A, saposin C, or prosaposin decreased the growth-inhibitory effect, caspase-3/7 activity, and apoptotic cell death induced by etoposide. We also discovered that saposin C activates the p42/44 MAP kinase pathway in a pertussis toxin-sensitive and phosphatidylinositol 3-kinase (PI3K /Akt-dependent manner in prostate cancer cells. Our data also show that the anti-apoptotic activity of saposin C is at least partially mediated via PI3K/Akt signaling pathway. Conclusion We postulate that as a mitogenic, survival, and anti-apoptotic factor for prostate cancer cells

  9. CRITICAL REVIEW OF PROSTATE CANCER PREDICTIVE TOOLS

    OpenAIRE

    Shahrokh F. Shariat; Michael W Kattan; Vickers, Andrew J; Karakiewicz, Pierre I; Scardino, Peter T.

    2009-01-01

    Prostate cancer is a very complex disease, and the decision-making process requires the clinician to balance clinical benefits, life expectancy, comorbidities, and potential treatment related side effects. Accurate prediction of clinical outcomes may help in the difficult process of making decisions related to prostate cancer. In this review, we discuss attributes of predictive tools and systematically review those available for prostate cancer. Types of tools include probability formulas, lo...

  10. Antisense approaches in prostate cancer.

    Science.gov (United States)

    Chi, Kim N; Gleave, Martin E

    2004-06-01

    Patients with hormone refractory prostate cancer have limited treatment options and new therapies are urgently needed. Advances in the understanding of the molecular mechanisms implicated in prostate cancer progression have identified many potential therapeutic gene targets that are involved in apoptosis, growth factors, cell signalling and the androgen receptor (AR). Antisense oligonucleotides are short sequences of synthetic modified DNA that are designed to be complimentary to a selected gene's mRNA and thereby specifically inhibit expression of that gene. The antisense approach continues to hold promise as a therapeutic modality to target genes involved in cancer progression, especially those in which the gene products are not amenable to small molecule inhibition or antibodies. The current status and future direction of a number of antisense oligonucleotides targeting several genes, including BCL-2, BCL-XL, clusterin, the inhibitors of apoptosis (IAP) family, MDM2, protein kinase C-alpha, c-raf, insulin-like growth factor binding proteins and the AR, that have potential clinical use in prostate cancer are reviewed. PMID:15174974

  11. Aging Men and Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Thompson B

    2015-01-01

    Full Text Available Prostate cancer (PCa is one of the most commonly diagnosed cancers in men worldwide and its incidence increases with age, mainly affecting elderly men aged 60 and above. Factors known to be associated with the development and progression of PCa are age, family history, and race/ethnicity, with age being the most important factor. The reasons for the increased incidence and mortality due to prostate cancer in elderly men are not entirely clear. Continued exposure to environmental and dietary factors may lead to accumulation of genetic and epigenetic changes over the life-span, leading to altered expression and/or activity of tumor promoter and tumor suppressor genes. Changing levels of endogenous hormones (like androgens and metabolism in elderly men may also play a role in the development of prostate cancers which may be further influenced by testosterone replacement therapy. For many decades now preventative strategies and treatments such as radiation therapy or hormone therapy, and others have been administered to manage PCa; however current studies and evidence suggest that PCa is undertreated in elderly men, despite evidence of efficacy of these treatments, which leads to higher prevalence of mortality in this age group. Studies involving basic research, preventative and management strategies are still underway to understand the mechanisms of PCa development in elderly men and treatment of this disease in ageing male population.

  12. FGF Signaling in Prostate Cancer Progression

    Institute of Scientific and Technical Information of China (English)

    Nora M. NAVONE

    2009-01-01

    @@ Objective: prostate cancer is the second leading cause of cancer death in men in the United States. Localized prostate cancer can be cured by andro-gen ablation, but when the disease escapes the confines of the gland, the prospects for cure decrease drastically and the disease becomes "castrate resistant.

  13. Vitamin D, Sunlight and Prostate Cancer Risk

    Directory of Open Access Journals (Sweden)

    Krishna Vanaja Donkena

    2011-01-01

    Full Text Available Prostate cancer is the second common cancer in men worldwide. The prevention of prostate cancer remains a challenge to researchers and clinicians. Here, we review the relationship of vitamin D and sunlight to prostate cancer risk. Ultraviolet radiation of the sunlight is the main stimulator for vitamin D production in humans. Vitamin D's antiprostate cancer activities may be involved in the actions through the pathways mediated by vitamin D metabolites, vitamin D metabolizing enzymes, vitamin D receptor (VDR, and VDR-regulated genes. Although laboratory studies including the use of animal models have shown that vitamin D has antiprostate cancer properties, whether it can effectively prevent the development and/or progression of prostate cancer in humans remains to be inconclusive and an intensively studied subject. This review will provide up-to-date information regarding the recent outcomes of laboratory and epidemiology studies on the effects of vitamin D on prostate cancer prevention.

  14. Predictive value of prostate-specific antigen for prostate cancer

    DEFF Research Database (Denmark)

    Shepherd, Leah; Borges, Alvaro Humberto; Ravn, Lene;

    2014-01-01

    INTRODUCTION: Although prostate cancer (PCa) incidence is lower in HIV+ men than in HIV- men, the usefulness of prostate-specific antigen (PSA) screening in this population is not well defined and may have higher false negative rates than in HIV- men. We aimed to describe the kinetics and predict...

  15. Syndecan-1 responsive microRNA-126 and 149 regulate cell proliferation in prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, Tomomi; Shimada, Keiji [Department of Pathology, Nara Medical University School of Medicine, Nara (Japan); Tatsumi, Yoshihiro [Department of Pathology, Nara Medical University School of Medicine, Nara (Japan); Department of Urology, Nara Medical University School of Medicine, Nara (Japan); Fujimoto, Kiyohide [Department of Urology, Nara Medical University School of Medicine, Nara (Japan); Konishi, Noboru, E-mail: nkonishi@naramed-u.ac.jp [Department of Pathology, Nara Medical University School of Medicine, Nara (Japan)

    2015-01-02

    Highlights: • Syndecan-1 is highly expressed in androgen independent prostate cancer cells, PC3. • Syndecan-1 regulates the expression of miR-126 and -149 in prostate cancer cells. • MiR-126 and 149 control cell growth via p21 induction and senescence mechanism. • MiR-126 and 149 promote cell proliferation by suppressing SOX2, NANOG, and Oct4. - Abstract: MicroRNAs (miRNAs) are short (19–24 nt), low molecular weight RNAs that play important roles in the regulation of target genes associated with cell proliferation, differentiation, and development, by binding to the 3′-untranslated region of the target mRNAs. In this study, we examined the expression of miRNA-126 (miR-126) and miR-149 in prostate cancer, and investigated the molecular mechanisms by which they affect syndecan-1 in prostate cancer. Functional analysis of miR-126 and miR-149 was conducted in the prostate cancer cell lines, PC3, Du145, and LNCaP. The expression levels of SOX2, NANOG, Oct4, miR-126 and miR-149 were evaluated by quantitative RT-PCR. After silencing syndecan-1, miR-126, and/or miR-149 in the PC3 cells, cell proliferation, senescence, and p21 induction were assessed using the MTS assay, senescence-associated β-galactosidase (SA-β-Gal) assay, and immunocytochemistry, respectively. Compared to the Du145 and LNCaP cells, PC3 cells exhibited higher expression of syndecan-1. When syndecan-1 was silenced, the PC3 cells showed reduced expression of miR-126 and miR-149 most effectively. Suppression of miR-126 and/or miR-149 significantly inhibited cell growth via p21 induction and subsequently, induced senescence. The mRNA expression levels of SOX2, NANOG, and Oct4 were significantly increased in response to the silencing of miR-126 and/or miR-149. Our results suggest that miR-126 and miR-149 are associated with the expression of syndecan-1 in prostate cancer cells. These miRNAs promote cell proliferation by suppressing SOX2, NANOG, and Oct4. The regulation of these factors by mi

  16. Macrophage inhibitory cytokine-1 (MIC-1/GDF15 slows cancer development but increases metastases in TRAMP prostate cancer prone mice.

    Directory of Open Access Journals (Sweden)

    Yasmin Husaini

    Full Text Available Macrophage inhibitory cytokine-1 (MIC-1/GDF15, a divergent member of the TGF-β superfamily, is over-expressed by many common cancers including those of the prostate (PCa and its expression is linked to cancer outcome. We have evaluated the effect of MIC-1/GDF15 overexpression on PCa development and spread in the TRAMP transgenic model of spontaneous prostate cancer. TRAMP mice were crossed with MIC-1/GDF15 overexpressing mice (MIC-1(fms to produce syngeneic TRAMP(fmsmic-1 mice. Survival rate, prostate tumor size, histopathological grades and extent of distant organ metastases were compared. Metastasis of TC1-T5, an androgen independent TRAMP cell line that lacks MIC-1/GDF15 expression, was compared by injecting intravenously into MIC-1(fms and syngeneic C57BL/6 mice. Whilst TRAMP(fmsmic-1 survived on average 7.4 weeks longer, had significantly smaller genitourinary (GU tumors and lower PCa histopathological grades than TRAMP mice, more of these mice developed distant organ metastases. Additionally, a higher number of TC1-T5 lung tumor colonies were observed in MIC-1(fms mice than syngeneic WT C57BL/6 mice. Our studies strongly suggest that MIC-1/GDF15 has complex actions on tumor behavior: it limits local tumor growth but may with advancing disease, promote metastases. As MIC-1/GDF15 is induced by all cancer treatments and metastasis is the major cause of cancer treatment failure and cancer deaths, these results, if applicable to humans, may have a direct impact on patient care.

  17. Smoking and prostate cancer survival and recurrence

    Institute of Scientific and Technical Information of China (English)

    Roberto L Muller; Daniel M Moreira

    2011-01-01

    Smooking is associated with several major benign and malignant diseases,representing one of the most important modifiable risk factors.Among urothelial neoplasms,smoking is pivotal in tumor carcinogenesis,but its role in prostate cancer is still controversial.Many authors have failed to demonstrate an association between smoking and prostate cancer.1-3 However,large epidemiological studies have shown that smoking is associated with higher risk of developing and dying of prostate cancer.4 Thus,large sample sizes and long follow-ups are important when studying prostate cancer given that its natural history can be quite long.

  18. [Medical treatment of prostate cancer].

    Science.gov (United States)

    Lobel, B; Cipolla, B; Labrador, J

    1994-03-01

    Hormone dependence of prostate cancer is well known. In 80% of cases with metastases, hormone suppression leads to the reduction of tumour volume and related disorders. However the treatment is generally palliative because malignant process recurs after about around 16 months. Mean survival is less than 3 years in these forms. Lack of response come always together with a poor prognosis, and there is 90% mortality at 2 years. Advanced prostatic cancer should not be treated with hormones if the patient has few symptoms and his quality of life is satisfactory. Symptomatic forms require hormone manipulation. Orchidectomy or LH-RH are recommended. Total androgen ablation (combined treatment) leads rapidly to more relief of symptoms, but its drawbacks and especially high cost indicate that its use should be weighed individually. Estramustine is not a first-lune treatment. Presently, there is no criteria to predict response to treatment. PMID:8066398

  19. Toll-like Receptors and Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Shu eZhao

    2014-07-01

    Full Text Available Prostate cancer is the second leading cause of cancer-related death in men after lung cancer. Immune responses clearly play a critical role in the tumorigenesis and in the efficacy of radiation therapy and chemotherapy in prostate cancer; however, the underlying molecular mechanisms are still poorly understood. Toll-like receptors (TLRs are a well-known family of pattern recognition receptors that play a key role in host immune system. Recent studies demonstrate that there are links between TLRs and cancer; however, the function and biological importance of TLRs in prostate cancer seems complex. To elucidate the role of TLRs and innate immunity in prostate cancer might provide us with a better understanding of the molecular mechanisms of this disease. Moreover, utilizing the agonists or antagonists of TLRs might represent a promising new strategy against prostate cancer. In this review, we summarize recent advances on the studies of association between TLR signaling and prostate cancer, TLR polymorphisms and prostate cancer risk, and provide some insights about TLRs as potential targets for prostate cancer immunotherapy.

  20. Cancer of the prostate - role of PSA

    International Nuclear Information System (INIS)

    Since 1979 when prostate specific antigen (PSA), found in the cytoplasm of benign and malignant prostatic cells, was first purified, it has attained world wide popularity in prostate cancer detection. It is also a sensitive test for skeletal meta states from carcinoma of the prostate. Prostate cancer has become the number one cancer in men and constitutes 11% of all cancers. Approximately 50% of men over 50 years have symptoms referable to the lower urinary tract. 50% or more of patients at Ibadan present an advanced stage of the disease and are therefore not curable. Thus, lacking the skill to manage advanced manifestations, early detection and screening programs are the best means to reduce mortality due to prostate cancer

  1. The genomic landscape of prostate cancer

    Directory of Open Access Journals (Sweden)

    Sylvan eBaca

    2012-05-01

    Full Text Available Prostate cancer is a common malignancy in men, with a markedly variable clinical course. Somatic alterations in DNA drive the growth of prostate cancers and may underlie the behavior of aggressive versus indolent tumors. The accelerating application of genomic technologies over the last two decades has identified mutations that drive prostate cancer formation, progression, and therapeutic resistance. Here, we discuss exemplary somatic mutations in prostate cancer, and highlight mutated cellular pathways with biological and possible therapeutic importance. Examples include mutated genes involved in androgen signaling, cell cycle regulation, signal transduction and development. Some genetic alterations may also predict the clinical course of disease or response to therapy, although the molecular heterogeneity of prostate tumors poses challenges to genomic biomarker identification. The widespread application of massively parallel sequencing technology to the analysis of prostate cancer genomes should continue to advance both discovery-oriented and diagnostic avenues.

  2. Diet, Supplement Use, and Prostate Cancer Risk: Results From the Prostate Cancer Prevention Trial

    OpenAIRE

    Kristal, Alan R.; Arnold, Kathryn B.; Neuhouser, Marian L; Goodman, Phyllis; Platz, Elizabeth A.; Albanes, Demetrius; Thompson, Ian M

    2010-01-01

    The authors examined nutritional risk factors for prostate cancer among 9,559 participants in the Prostate Cancer Prevention Trial (United States and Canada, 1994–2003). The presence or absence of cancer was determined by prostate biopsy, which was recommended during the trial because of an elevated prostate-specific antigen level or an abnormal digital rectal examination and was offered to all men at the trial's end. Nutrient intake was assessed using a food frequency questionnaire and a str...

  3. Epidemiology of prostate cancer in India

    OpenAIRE

    Shalu Jain; Sunita Saxena; Anup Kumar

    2014-01-01

    Data from national cancer registries shows that incidence of certain cancers are on rise in India. The cancers which are showing significant increase in incidence rates include prostate, mouth and kidney among male population, corpus uteri, breast and thyroid among female population and lung cancer in both male and female populations. In the present review article we have focused on epidemiology of prostate cancer in Indian subcontinent in terms of incidence, survival, and mortality etc. The ...

  4. Prostate Cancer Stem Cells: Research Advances

    OpenAIRE

    Dagmara Jaworska; Wojciech Król; Ewelina Szliszka

    2015-01-01

    Cancer stem cells have been defined as cells within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Experimental evidence showed that these highly tumorigenic cells might be responsible for initiation and progression of cancer into invasive and metastatic disease. Eradicating prostate cancer stem cells, the root of the problem, has been considered as a promising target in prostate cancer treatment to improve th...

  5. Shared care in prostate cancer

    DEFF Research Database (Denmark)

    Lund, Anette Svarre; Lund, Lars; Jønler, Morten;

    2016-01-01

    OBJECTIVE: The aim of this study was to investigate 3 year follow-up in patients with stable prostate cancer (PCa) managed in a shared care program by general practitioners (GPs) in collaboration with urological departments. PCa patients who have undergone curative treatment or endocrine therapy...... require long-term follow-up. Until recently, follow-up has primarily been managed by urologists at hospital-based outpatient clinics. However, new organizational strategies are needed to meet the needs of the growing number of elderly, comorbid cancer patients. These new organizational strategies target...

  6. Prognostic factors in prostate cancer.

    Science.gov (United States)

    Braeckman, Johan; Michielsen, Dirk

    2007-01-01

    In the nineteenth century the main goal of medicine was predictive: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted to cure the disease. Since the twentieth century, the word prognosis has also been used in nonmedical contexts, for example in corporate finance or elections. The most accurate form of prognosis is achieved statistically. Based on different prognostic factors it should be possible to tell patients how they are expected to do after prostate cancer has been diagnosed and how different treatments may change this outcome. A prognosis is a prediction. The word prognosis comes from the Greek word (see text) and means foreknowing. In the nineteenth century this was the main goal of medicine: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted towards seeking a cure. Prognostic factors in (prostate) cancer are defined as "variables that can account for some of the heterogeneity associated with the expected course and outcome of a disease". Bailey defined prognosis as "a reasoned forecast concerning the course, pattern, progression, duration, and end of the disease. Prognostic factors are not only essential to understand the natural history and the course of the disease, but also to predict possible different outcomes of different treatments or perhaps no treatment at all. This is extremely important in a disease like prostate cancer where there is clear evidence that a substantial number of cases discovered by prostate-specific antigen (PSA) testing are unlikely ever to become clinically significant, not to mention mortal. Furthermore, prognostic factors are of paramount importance for correct interpretation of clinical trials and for the construction of future trials. Finally, according to WHO national screening committee criteria for implementing a national screening programme, widely accepted prognostic factors must be defined before

  7. Prostate Cancer Imaging with Novel PET Tracers.

    Science.gov (United States)

    Lindenberg, Liza; Choyke, Peter; Dahut, William

    2016-03-01

    Molecular imaging of prostate cancer is in a dynamic phase of development. Currently approved techniques are limited and researchers have been working on novel agents to improve accuracy in targeting and detecting prostate tumors. In addition, the complexity of various prostate cancer states also contributes to the challenges in evaluating suitable radiotracer candidates. We have highlighted nuclear medicine tracers that focus on mechanisms involved in bone metastasis, prostate cancer cell membrane synthesis, amino acid analogs, androgen analogs, and the prostate specific membrane antigen. Encouraging results with many of these innovative radiotracer compounds will not only advance diagnostic capabilities for prostate cancer but open opportunities for theranostic applications to treat this worldwide malignancy. PMID:26874530

  8. Vietnam military service history and prostate cancer

    Directory of Open Access Journals (Sweden)

    Fritschi Lin

    2006-03-01

    Full Text Available Abstract Background Three decades after US and Australian forces withdrew from Vietnam, there has been much public interest in the health consequences of service in Vietnam. One controversial question is whether the risk of prostate cancer amongst Vietnam veterans is increased. This paper examines relationships between military history, family history and risk of prostate cancer in a population-based case control study. Methods Cases were selected from the Cancer Registry of Western Australia as incident cases of histologically-confirmed prostate cancer, and controls were age-matched and selected from the Western Australian electoral roll. Study participants were asked to report any military service history and details about that service. Results Between January 2001 and September 2002, 606 cases and 471 controls aged between 40–75 years were recruited. An increased prostate cancer risk was observed in men reporting they were deployed in Vietnam although this was not statistically significant (OR = 2.12; 95% CI 0.88–5.06. An increased risk was also observed in men reporting prostate cancer in fathers (OR = 1.90; 95% CI 1.20–3.00 or brothers (OR = 2.05; 95% CI 1.20–3.50 diagnosed with prostate cancer. Conclusion These findings support a positive association between prostate cancer and military service history in the Vietnam war and a first degree relative family history of prostate cancer.

  9. Overview of Dietary Supplements in Prostate Cancer.

    Science.gov (United States)

    Yacoubian, Aline; Dargham, Rana Abu; Khauli, Raja B; Bachir, Bassel G

    2016-11-01

    Prostate cancer is a key health concern for men with its etiology still under investigation. Recently, the role of dietary supplements has been noted to have a major inhibitory effect on prostate cancer and numerous studies have been conducted in this regard. This review provides a summary on numerous recent studies conducted in this field. Some of the studies reviewed revealed a protective role for supplements, and others showed no correlation while some even had an adverse effect. The mechanism of how these supplements act on the prostate is still not clear. Further studies are warranted especially for supplements that have been shown to have a potential inhibitory role in prostate cancer.

  10. Molecular Profiling of Prostate Cancer Patients

    OpenAIRE

    Nna, Emmanuel Okechukwu

    2009-01-01

    In the UK, more than 30 000 men are diagnosed annually with prostate cancer (PCa) and about 10 000 men die from it each year. Although several molecular markers have been associated with prostate cancer development and/ or progression, only few of them are used in diagnostic pathology. The current standard tests include serum PSA test, digital rectal examination and histology of prostate biopsy. Recently the PCA-3 molecular test was approved in the European Union, and it is now...

  11. Prostate Cancer Genomics: Toward a New Understanding

    OpenAIRE

    John S Witte

    2008-01-01

    Recent genetics and genomics studies of prostate cancer help clarify the genetic basis of this common but complex disease. Genome-wide studies have detected numerous variants associated with disease as well as common gene fusions and expression ‘signatures’ in prostate tumors. Based on these results, some advocate gene-based individualized screening for prostate cancer, although such testing may only be worthwhile to distinguish disease aggressiveness. Lessons learned here provide strategies ...

  12. Prostate carcinomas; Cancer de la prostate

    Energy Technology Data Exchange (ETDEWEB)

    Toledano, A.; Chauveinc, L.; Flam, T.; Thiounn, N.; Solignac, S.; Timbert, M.; Rosenwald, J.C.; Cosset, J.M.; Ammor, A.; Bonnetain, F.; Brenier, J.P.; Maingon, P.; Peignaux, K.; Truc, G.; Bosset, M.; Crevoisier, R. de; Tucker, S.; Dong, L.; Cheung, R.; Kuban, D.; Azria, D.; Llacer Moscardo, C.; Ailleres, N.; Allaw, A.; Serre, A.; Fenoglietto, P.; Hay, M.H.; Thezenas, S.; Dubois, J.B.; Pommier, P.; Perol, D.; Lagrange, J.L.; Richaud, P.; Brune, D.; Le Prise, E.; Azria, D.; Beckendorf, V.; Chabaud, S.; Carrie, C.; Bosset, M.; Bosset, J.F.; Maingon, P.; Ammor, A.; Crehangen, G.; Truc, G.; Peignaux, K.; Bonnetain, F.; Keros, L.; Bernier, V.; Aletti, P.; Wolf, D.; Marchesia, V.; Noel, A.; Artignan, X.; Fourneret, P.; Bacconier, M.; Shestaeva, O.; Pasquier, D.; Descotes, J.L.; Balosso, J.; Bolla, M.; Burette, R.; Corbusier, A.; Germeau, F.; Crevoisier, R. de; Dong, L.; Bonnen, M.; Cheung, R.; Tucker, S.; Kuban, D.; Crevoisier, R. de; Melancon, A.; Kuban, D.; Cheung, R.; Dong, L.; Peignaux, K.; Brenier, J.P.; Truc, G.; Bosset, M.; Ammor, A.; Barillot, I.; Maingon, P.; Molines, J.C.; Berland, E.; Cornulier, J. de; Coulet-Parpillon, A.; Cohard, C.; Picone, M.; Fourneret, P.; Artignan, X.; Daanen, V.; Gastaldo, J.; Bolla, M.; Collomb, D.; Dusserre, A.; Descotes, J.L.; Troccaz, J.; Giraud, J.Y.; Quero, L.; Hennequin, C.; Ravery, V.; Desgrandschamps, F.; Maylin, C.; Boccon-Gibod, L.; Salem, N.; Bladou, F.; Gravis, G.; Tallet, A.; Simonian, M.; Serment, G.; Salem, N.; Bladou, F.; Gravis, G.; Simonian, M.; Rosello, R.; Serment, G

    2005-11-15

    Some short communications on the prostate carcinoma are given here. The impact of pelvic irradiation, conformation with intensity modulation, association of radiotherapy and chemotherapy reduction of side effects, imaging, doses escalation are such subjects studied and reported. (N.C.)

  13. Skip Regulates TGF-β1-Induced Extracellular Matrix Degrading Proteases Expression in Human PC-3 Prostate Cancer Cells

    Directory of Open Access Journals (Sweden)

    Victor Villar

    2013-01-01

    Full Text Available Purpose. To determine whether Ski-interacting protein (SKIP regulates TGF-β1-stimulated expression of urokinase-type plasminogen activator (uPA, matrix metalloproteinase-9 (MMP-9, and uPA Inhibitor (PAI-1 in the androgen-independent human prostate cancer cell model. Materials and Methods. PC-3 prostate cancer cell line was used. The role of SKIP was evaluated using synthetic small interference RNA (siRNA compounds. The expression of uPA, MMP-9, and PAI-1 was evaluated by zymography assays, RT-PCR, and promoter transactivation analysis. Results. In PC-3 cells TGF-β1 treatment stimulated uPA, PAI-1, and MMP-9 expressions. The knockdown of SKIP in PC-3 cells enhanced the basal level of uPA, and TGF-β1 treatment inhibited uPA production. Both PAI-1 and MMP-9 production levels were increased in response to TGF-β1. The ectopic expression of SKIP inhibited both TGF-β1-induced uPA and MMP-9 promoter transactivation, while PAI-1 promoter response to the factor was unaffected. Conclusions. SKIP regulates the expression of uPA, PAI-1, and MMP-9 stimulated by TGF-β1 in PC-3 cells. Thus, SKIP is implicated in the regulation of extracellular matrix degradation and can therefore be suggested as a novel therapeutic target in prostate cancer treatment.

  14. Primary Care of the Prostate Cancer Survivor.

    Science.gov (United States)

    Noonan, Erika M; Farrell, Timothy W

    2016-05-01

    This summary of the American Cancer Society Prostate Cancer Survivorship Care Guidelines targets primary care physicians who coordinate care of prostate cancer survivors with subspecialists. Prostate cancer survivors should undergo prostate-specific antigen screening every six to 12 months and digital rectal examination annually. Surveillance of patients who choose watchful waiting for their prostate cancer should be conducted by a subspecialist. Any hematuria or rectal bleeding must be thoroughly evaluated. Prostate cancer survivors should be screened regularly for urinary incontinence and sexual dysfunction. Patients with predominant urge incontinence symptoms, which can occur after surgical and radiation treatments, may benefit from an anticholinergic agent. If there is difficulty with bladder emptying, a trial of an alpha blocker may be considered. A phosphodiesterase type 5 inhibitor can effectively treat sexual dysfunction following treatment for prostate cancer. Osteoporosis screening should occur before initiation of androgen deprivation therapy, and patients treated with androgen deprivation therapy should be monitored for anemia, metabolic syndrome, and vasomotor symptoms. Healthy lifestyle choices should be encouraged, including weight management, regular physical activity, proper nutrition, and smoking cessation. Primary care physicians should be vigilant for psychosocial distress, including depression, among prostate cancer survivors, as well as the potential impact of this distress on patients' family members and partners. PMID:27175954

  15. Genetically engineered mouse models of prostate cancer

    NARCIS (Netherlands)

    Nawijn, Martijn C.; Bergman, Andreas M.; van der Poel, Henk G.

    2008-01-01

    Objectives: Mouse models of prostate cancer are used to test the contribution of individual genes to the transformation process, evaluate the collaboration between multiple genetic lesions observed in a single tumour, and perform preclinical intervention studies in prostate cancer research. Methods:

  16. Multimodality Magnetic Resonance Imaging of Prostate Cancer

    NARCIS (Netherlands)

    M.R. Engelbrecht; P. Puech; P. Colin; O. Akin; L. Lemaître; A. Villers

    2010-01-01

    The purpose of this article is to review both routine T2-weighted and new MRI techniques in the imaging of prostate cancer (PCa) for focal therapy. T2-weighted imaging, knowledge of MRI prostate zonal anatomy, cancer morphology, and intraprostatic tumor spread remain essential for clinical PCa imagi

  17. Road to Recovery from Prostate Cancer

    Medline Plus

    Full Text Available ... 2008, while prostate cancer remains a very controversial subject, it is obviously a very important disease. It’s ... another question, which is a little off the subject concerning bladder cancer, so I’m actually going ...

  18. Redefining Hormone Sensitive Disease in Advanced Prostate Cancer

    OpenAIRE

    Xiaoyu Hou; Flaig, Thomas W.

    2012-01-01

    Prostate cancer is the most common cancer among men in the United States. For decades, the cornerstone of medical treatment for advanced prostate cancer has been hormonal therapy, intended to lower testosterone levels, known as Androgen Deprivation Therapy (ADT). The development of hormone-resistant prostate cancer (now termed castration-resistant prostate cancer:CRPC) remains the key roadblock in successful long-term management of prostate cancer. New advancements in medical therapy for pros...

  19. ARP2, a novel pro-apoptotic protein expressed in epithelial prostate cancer LNCaP cells and epithelial ovary CHO transformed cells.

    Directory of Open Access Journals (Sweden)

    Jaime Mas-Oliva

    Full Text Available Neoplastic epithelial cells generate the most aggressive types of cancers such as those located in the lung, breast, colon, prostate and ovary. During advanced stages of prostate cancer, epithelial cells are associated to the appearance of androgen-independent tumors, an apoptotic-resistant phenotype that ultimately overgrows and promotes metastatic events. We have previously identified and electrophysiologically characterized a novel Ca(2+-permeable channel activated during apoptosis in the androgen-independent prostate epithelial cancer cell line, LNCaP. In addition, we reported for the first time the cloning and characterization of this channel-like molecule named apoptosis regulated protein 2 (ARP2 associated to a lethal influx of Ca(2+ in Xenopus oocytes. In the present study, LNCaP cells and Chinese hamster ovary cells (CHO cell line transfected with arp2-cDNA are induced to undergo apoptosis showing an important impact on cell viability and activation of caspases 3 and 7 when compared to serum deprived grown cells and ionomycin treated cells. The subcellular localization of ARP2 in CHO cells undergoing apoptosis was studied using confocal microscopy. While apoptosis progresses, ARP2 initially localized in the peri-nuclear region of cells migrates with time towards the plasma membrane region. Based on the present results and those of our previous studies, the fact that ARP2 constitutes a novel cation channel is supported. Therefore, ARP2 becomes a valuable target to modulate the influx and concentration of calcium in the cytoplasm of epithelial cancer cells showing an apoptotic-resistant phenotype during the onset of an apoptotic event.

  20. Molecular imaging of prostate cancer with PET.

    Science.gov (United States)

    Jadvar, Hossein

    2013-10-01

    Molecular imaging is paving the way for precision and personalized medicine. In view of the significant biologic and clinical heterogeneity of prostate cancer, molecular imaging is expected to play an important role in the evaluation of this prevalent disease. The natural history of prostate cancer spans from an indolent localized process to biochemical relapse after radical treatment with curative intent to a lethal castrate-resistant metastatic disease. The ongoing unraveling of the complex tumor biology of prostate cancer uniquely positions molecular imaging with PET to contribute significantly to every clinical phase of prostate cancer evaluation. The purpose of this article was to provide a concise review of the current state of affairs and potential future developments in the diagnostic utility of PET in prostate cancer.

  1. Chemoresistance in prostate cancer cells is regulated by miRNAs and Hedgehog pathway.

    Directory of Open Access Journals (Sweden)

    Saurabh Singh

    Full Text Available Many prostate cancers relapse due to the generation of chemoresistance rendering first-line treatment drugs like paclitaxel (PTX ineffective. The present study aims to determine the role of miRNAs and Hedgehog (Hh pathway in chemoresistant prostate cancer and to evaluate the combination therapy using Hh inhibitor cyclopamine (CYA. Studies were conducted on PTX resistant DU145-TXR and PC3-TXR cell lines and clinical prostate tissues. Drug sensitivity and apoptosis assays showed significantly improved cytotoxicity with combination of PTX and CYA. To distinguish the presence of cancer stem cell like side populations (SP, Hoechst 33342 flow cytometry method was used. PTX resistant DU145 and PC3 cells, as well as human prostate cancer tissue possess a distinct SP fraction. Nearly 75% of the SP cells are in the G0/G1 phase compared to 62% for non-SP cells and have higher expression of stem cell markers as well. SP cell fraction was increased following PTX monotherapy and treatment with CYA or CYA plus PTX effectively reduced their numbers suggesting the effectiveness of combination therapy. SP fraction cells were allowed to differentiate and reanalyzed by Hoechst staining and gene expression analysis. Post differentiation, SP cells constitute 15.8% of total viable cells which decreases to 0.6% on treatment with CYA. The expression levels of P-gp efflux protein were also significantly decreased on treatment with PTX and CYA combination. MicroRNA profiling of DU145-TXR and PC3-TXR cells and prostate cancer tissue from the patients showed decreased expression of tumor suppressor miRNAs such as miR34a and miR200c. Treatment with PTX and CYA combination restored the expression of miR200c and 34a, confirming their role in modulating chemoresistance. We have shown that supplementing mitotic stabilizer drugs such as PTX with Hh-inhibitor CYA can reverse PTX chemoresistance and eliminate SP fraction in androgen independent, metastatic prostate cancer cell

  2. Algorithms, nomograms and the detection of indolent prostate cancer

    NARCIS (Netherlands)

    M.J. Roobol-Bouts (Monique)

    2008-01-01

    textabstractPurpose: Prostate cancer is the most commonly diagnosed cancer in men. However, only about 12% of the men diagnosed with prostate cancer will die of their disease. Result: The serum PSA test can detect prostate cancers early, but using a PSA based cut-off indication for prostate biopsy r

  3. Hypoxia in the androgen-dependent Shionogi model for prostate cancer at three stages.

    Science.gov (United States)

    Skov, Kirsten; Adomat, Hans; Bowden, Mary; Dragowska, Wieslawa; Gleave, Martin; Koch, Cameron J; Woo, Janet; Yapp, Donald T T

    2004-11-01

    The objective of this study was to investigate a possible relationship between androgen status and hypoxia in the Shionogi murine prostate tumor model, which is widely used to study the effects of androgen withdrawal on hormone resistance and radiation response. Binding of the nitroimidazole hypoxia marker EF5 was assessed using the Cy3-tagged monoclonal antibody ELK3-51. Three hours after injection of EF5 (30 mg/kg), tumors from the following three stages were excised: androgen-dependent, regressed tumors 7 days after castration, and androgen-independent. Half of each tumor was disaggregated for analysis by flow cytometry and the remainder was flash frozen. Statistically significant differences (P 0.1). The results from this preliminary study indicate that hypoxia may play an important role with respect to the timing of irradiation in prostate cancer treatments and possibly may be a useful prognostic tool. In addition, hypoxia may also be relevant to progression in this disease after androgen ablation. PMID:15624309

  4. Molecular Characterization of TMPRSS2-ERG Gene Fusion in the NCI-H660 Prostate Cancer Cell Line: A New Perspective for an Old Model

    Directory of Open Access Journals (Sweden)

    Kirsten D. Mertz

    2007-03-01

    Full Text Available Recent studies have established that a significant fraction of prostate cancers harbor a signature gene fusion between the 5' region of androgen-regulated TMPRSS2 and an ETS family transcription factor, most commonly ERG. Studies on the molecular mechanisms and functional consequences of this important chromosomal rearrangement are currently limited to the VCaP cell line derived from a vertebral bone metastasis of a hormone-refractory prostate tumor. Here we report on the NCI-H660 cell line, derived from a metastasic site of an extrapulmonary small cell carcinoma arising from the prostate. NCI-H660 harbors TMPRSS2-ERG fusion with a homozygous intronic deletion between TMPRSS2 and ERG. We demonstrate this by real-time quantitative polymerase chain reaction, a two-stage dual-color interphase fluorescence in situ hybridization (FISH assay testing for TMPRSS2 and ERG break-aparts, and single-nucleotide polymorphism oligonucleotide arrays. The deletion is consistent with the common intronic deletion found on chromosome 21q22.2-3 in human prostate cancer samples. We demonstrate the physical juxtaposition of TMPRSS2 and ERG on the DNA level by fiber FISH. The androgen receptor-negative NCI-H660 cell line expresses ERG in an androgen-independent fashion. This in vitro model system has the potential to provide important pathobiologic insights into TMPRSS2-ERG fusion prostate cancer.

  5. Prostate cancer in Denmark. Incidence, morbidity and mortality

    DEFF Research Database (Denmark)

    Brasso, K; Iversen, Peter

    1999-01-01

    Prostate cancer incidence and mortality rates in Denmark are reviewed for a 50-year period from 1943 to 1992. The prostate cancer incidence rate nearly tripled and prostate cancer mortality rate increased during this period. Until recently in Denmark the routine management of prostate cancer has...... been by deferred hormonal therapy. Morbidity and mortality associated with prostate cancer are analysed in a group of 1459 patients aged 55-74 years, who were diagnosed as having clinically localized prostate cancer in the 5-year period 1983 to 1987. In this group of patients prostate cancer...... is demonstrated to cause significant morbidity. Furthermore, the patients suffered significant excess mortality and loss of life expectancy....

  6. Vitamins and Prostate Cancer Risk

    Directory of Open Access Journals (Sweden)

    Charles Y.F. Young

    2010-03-01

    Full Text Available Prostate cancer (PC is the second most common cancer in men worldwide. Its prevention and treatment remain a challenge to clinicians. Here we review the relationship of vitamins to PC risk. Many vitamins and related chemicals, including vitamin A, retinoids, several B vitamins, vitamin C, vitamin D and vitamin E have shown their anti-cancer activities as anti-oxidants, activators of transcription factors or factors influencing epigenetic events. Although laboratory tests including the use of animal models showed these vitamins may have anti-PC properties, whether they can effectively prevent the development and/or progression of PC in humans remains to be intensively studied subjects. This review will provide up-to-date information regarding the recent outcomes of laboratory, epidemiology and/or clinical trials on the effects of vitamins on PC prevention and/or treatment.

  7. Combination of genistein with ionizing radiation on andro-gen-independent prostate cancer cells

    Institute of Scientific and Technical Information of China (English)

    Sen-XiangYan; YasuoEjima; RyoheiSasaki; Shu-SenZheng; YusukeDemizu; ToshinoriSoejima; KazuroSugimura

    2004-01-01

    Aim: To study the effect of the combined use of genistein and ionizing radiation (IR) on prostate DUI45 cancer cells. Methods: DU145, an androgen-independent human prostate cancer cell line, was used in the experiment.Clonogenic assay was used to compare the survival of DU145 cells after treatments with genistein alone and in combination with graded IR. Apoptosis was assayed by DNA ladder and TUNEL stain. Cell cycle alterations were observed by flow cytometry and related protein expressions by immunoblotting. Results: Clonogenic assay demonstrated that genistein, even at low to medium concentrations, enhanced the radiosensitivity of DU 145 cells. Twenty four hours after treatment with IR and/or genistein, apoptosis was mainly seen with genistein at high concentrations and was minimally related to IR. At 72 h, apoptosis also occurred in treatment with lower concentration of genistein,especially when combined with IR. While both IR and genistein led to G2/M cell cycle arrest, combination of them further increased the DUI45 cells at G2/M phase. This G2/M arrest was largely maintained at 72 h, accompanied by increasing apoptosis and hyperdiploid cell population. Cell-cycle related protein analysis disclosed biphasic changes in cyclin B 1 and less dramatically cdc-2, but stably elevated p21cip1 levels with increasing genistein concentrations.Conclusion: Genistein enhanced the radiosensitivity of DUI45 prostate cancer cells. The mechanisms might be involved in the increased apoptosis, prolonged cell cycle arrest and impaired damage repair. (Asian J Androl 2004 Dec; 6: 285-290)

  8. Multiparametric MRI in Prostate Cancer

    OpenAIRE

    Tarık Esen; Barıs Turkbey; Anup Patel; Jurgen Futterer

    2014-01-01

    Editorial Multiparametric MRI in Prostate Cancer TarJk Esen,1 BarJs Turkbey,2 Anup Patel,3 and Jurgen Futterer4 1 Department of Urology, School of Medicine, Koc University, 34450 Istanbul, Turkey 2Molecular Imaging Program, NCI, NIH, Bethesda, MD 20892, USA 3Royal London Hospital, Barts Health NHS Trust, London E1 1BB,UK 4Department of Radiology, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands Correspondence should be addressed to Tarık Esen;...

  9. ETS fusion genes in prostate cancer.

    Science.gov (United States)

    Gasi Tandefelt, Delila; Boormans, Joost; Hermans, Karin; Trapman, Jan

    2014-06-01

    Prostate cancer is very common in elderly men in developed countries. Unravelling the molecular and biological processes that contribute to tumor development and progressive growth, including its heterogeneity, is a challenging task. The fusion of the genes ERG and TMPRSS2 is the most frequent genomic alteration in prostate cancer. ERG is an oncogene that encodes a member of the family of ETS transcription factors. At lower frequency, other members of this gene family are also rearranged and overexpressed in prostate cancer. TMPRSS2 is an androgen-regulated gene that is preferentially expressed in the prostate. Most of the less frequent ETS fusion partners are also androgen-regulated and prostate-specific. During the last few years, novel concepts of the process of gene fusion have emerged, and initial experimental results explaining the function of the ETS genes ERG and ETV1 in prostate cancer have been published. In this review, we focus on the most relevant ETS gene fusions and summarize the current knowledge of the role of ETS transcription factors in prostate cancer. Finally, we discuss the clinical relevance of TMRPSS2-ERG and other ETS gene fusions in prostate cancer.

  10. Activation of the hedgehog pathway in advanced prostate cancer

    OpenAIRE

    McCormick Frank; Chen Kai; He Nonggao; Chi Sumin; Zhang Xiaoli; Li Chengxin; Sheng Tao; Gatalica Zoran; Xie Jingwu

    2004-01-01

    Abstract Background The hedgehog pathway plays a critical role in the development of prostate. However, the role of the hedgehog pathway in prostate cancer is not clear. Prostate cancer is the second most prevalent cause of cancer death in American men. Therefore, identification of novel therapeutic targets for prostate cancer has significant clinical implications. Results Here we report that activation of the hedgehog pathway occurs frequently in advanced human prostate cancer. We find that ...

  11. Is prostate cancer screening responsible for the negative results of prostate cancer treatment trials?

    Science.gov (United States)

    Prasad, Vinay

    2016-08-01

    Clinical guidelines continue to move away from routine prostate specific antigen screening (PSA), once a widespread medical practice. A curious difference exists between early prostate cancer and early breast cancer. While randomized trials of therapy in early breast cancer continue to show overall survival benefit, this is not the case in prostate cancer, where prostatectomy was no better than observation in a recent trial, and where early androgen deprivation is no better than late androgen deprivation. Here, I make the case that prostate cancer screening contributes so greatly to over diagnosis that even treatment trials yield null results due to contamination with non-life threatening disease. PMID:27372859

  12. Comparison of telomerase activity in prostate cancer, prostatic intraepithelial neoplasia and benign prostatic hyperplasia

    Directory of Open Access Journals (Sweden)

    Soleiman Mahjoub

    2006-11-01

    Full Text Available BACKGROUND: Telomerase is a reverse transcriptase enzyme that synthesizes telomeric DNA on chromosome ends. The enzyme is important for the immortalization of cancer cells because it maintains the telomeres. METHODS: Telomerase activity (TA was measured by fluorescence-based telomeric repeat amplification protocol (FTRAP assay in prostate carcinoma and benign prostatic hyperplasia (BPH. RESULTS: TA was present in 91.4% of 70 prostate cancers, 68.8% of 16 prostatic intraepithelial neoplasia (PIN, 43.3% of 30 BPH*, 21.4% of 14 atrophy and 20% of 15 normal samples adjacent to tumor. There was not any significant correlation between TA, histopathological tumor stage or gleason score. In contrast to high TA in the BPH* tissue from the cancer-bearing gland, only 6.3% of 32 BPH specimens from patients only diagnosed with BPH were telomerase activity-positive. CONCLUSIONS: These results indicate that TA is present in most prostate cancers. The high rate of TA in tissue adjacent to tumor may be attributed either to early molecular alteration of cancer that was histologically unapparent, or to the presence of occult cancer cells. Our findings suggest that the re-expression of telomerase activity could be one step in the transformation of BPH to PIN. KEY WORDS: Telomerase activity, prostate cancer, prostatic intraepithelial neoplasia, benign prostatic hyperplasia.

  13. Targeting prostate cancer stem cells for cancer therapy

    OpenAIRE

    Wang, Guocan; Wang, Zhiwei; Sarkar, Fazlul H; Wei, Wenyi

    2012-01-01

    Prostate cancer (PCa) is the most common malignant neoplasm in men and the second most frequent cause of cancer death for males in the United States. Recently, emerging evidence suggests that prostate cancer stem cells (CSCs) may play a critical role in the development and progression of PCa. Therefore, targeting prostate CSCs for the prevention of tumor progression and treatment of PCa could become a novel strategy for better treatment of patients diagnosed with PCa. In this review article, ...

  14. Serum Retinol and Risk of Prostate Cancer

    OpenAIRE

    Mondul, Alison M.; Watters, Joanne L; Männistö, Satu; Weinstein, Stephanie J.; Snyder, Kirk; Virtamo, Jarmo; Albanes, Demetrius

    2011-01-01

    Greater exposure to retinol (vitamin A) may prevent prostate cancer, although under some conditions it could promote cell growth and de-differentiation. The authors prospectively examined prostate cancer risk and serum retinol levels, measured by using high-performance liquid chromatography, at baseline (n = 29,104) and after 3 years (n = 22,843) in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. Cox proportional hazards models were used to estimate the relative risk of to...

  15. [Treatment strategies for advanced prostate cancer].

    Science.gov (United States)

    Küronya, Zsófia; Bíró, Krisztina; Géczi, Lajos; Németh, Hajnalka

    2015-09-01

    There has been dramatic improvement in the diagnosis and treatment of prostate cancer recently. The treatment of localized disease became more successful with the application of new, sophisticated techniques available for urologic surgeons and radiotherapists. Nevertheless a significant proportion of patients relapses after the initial local treatment or is diagnosed with metastatic disease at the beginning. In the past five years, six new drugs became registered for the treatment of metastatic, castration-resistant prostate cancer, such as sipuleucel-T, cabazitaxel, abiraterone, enzalutamide, the α-emitting radionuclide alpharadin and the receptor activator of nuclear factor kappa-B (RANK) ligand inhibitor denosumab. The availability of these new treatment options raises numerous questions. In this review we present the standard of care of metastatic prostate cancer by disease stage (hormone naive/ hormone sensitive metastatic prostate cancer, non-metastatic castration-resistant prostate cancer, oligometastatic/multimetastatic castration-resistant prostate cancer) and the emerging treatment modalities presently assessed in clinical trials. We would also like to give advice on debatable aspects of the management of metastatic prostate cancer. PMID:26339912

  16. New serum biomarkers for prostate cancer diagnosis

    OpenAIRE

    Chadha, Kailash C.; Austin Miller; Nair, Bindukumar B.; Schwartz, Stanley A.; Trump, Donald L.; Willie Underwood

    2014-01-01

    Background: Prostate-specific antigen (PSA) is currently used as a biomarker for diagnosis and management of prostate cancer (CaP). However, PSA typically lacks the sensitivity and specificity desired of a diagnostic marker. Objective: The goal of this study was to identify an additional biomarker or a panel of biomarkers that is more sensitive and specific than PSA in differentiating benign versus malignant prostate disease and/or localized CaP versus metastatic CaP. Methods: Concurrent meas...

  17. Enrichment of prostate cancer stem cells from primary prostate cancer cultures of biopsy samples

    OpenAIRE

    Wang, Shunqi; Huang, Shengsong; Zhao, Xin; Zhang, Qimin; Wu, Min; Sun, Feng; Han, Gang; Wu, Denglong

    2013-01-01

    This study was to enrich prostate cancer stem cells (PrCSC) from primary prostate cancer cultures (PPrCC). Primary prostate cancer cells were amplified in keratinocyte serum-free medium with epidermal growth factor (EGF) and bovine pituitary extract (BPE), supplemented with leukemia inhibitory factor (LIF), stem cell factor (SCF) and cholera toxin. After amplification, cells were transferred into ultra-low attachment dishes with serum-free DMEM/F12 medium, supplemented with EGF, basic fibrobl...

  18. Evolving Recommendations on Prostate Cancer Screening.

    Science.gov (United States)

    Brawley, Otis W; Thompson, Ian M; Grönberg, Henrik

    2016-01-01

    Results of a number of studies demonstrate that the serum prostate-specific antigen (PSA) in and of itself is an inadequate screening test. Today, one of the most pressing questions in prostate cancer medicine is how can screening be honed to identify those who have life-threatening disease and need aggressive treatment. A number of efforts are underway. One such effort is the assessment of men in the landmark Prostate Cancer Prevention Trial that has led to a prostate cancer risk calculator (PCPTRC), which is available online. PCPTRC version 2.0 predicts the probability of the diagnosis of no cancer, low-grade cancer, or high-grade cancer when variables such as PSA, age, race, family history, and physical findings are input. Modern biomarker development promises to provide tests with fewer false positives and improved ability to find high-grade cancers. Stockholm III (STHLM3) is a prospective, population-based, paired, screen-positive, prostate cancer diagnostic study assessing a combination of plasma protein biomarkers along with age, family history, previous biopsy, and prostate examination for prediction of prostate cancer. Multiparametric MRI incorporates anatomic and functional imaging to better characterize and predict future behavior of tumors within the prostate. After diagnosis of cancer, several genomic tests promise to better distinguish the cancers that need treatment versus those that need observation. Although the new technologies are promising, there is an urgent need for evaluation of these new tests in high-quality, large population-based studies. Until these technologies are proven, most professional organizations have evolved to a recommendation of informed or shared decision making in which there is a discussion between the doctor and patient. PMID:27249774

  19. CH5137291, an androgen receptor nuclear translocation-inhibiting compound, inhibits the growth of castration-resistant prostate cancer cells.

    Science.gov (United States)

    Ishikura, Nobuyuki; Kawata, Hiromitsu; Nishimoto, Ayako; Nakamura, Ryo; Tsunenari, Toshiaki; Watanabe, Miho; Tachibana, Kazutaka; Shiraishi, Takuya; Yoshino, Hitoshi; Honma, Akie; Emura, Takashi; Ohta, Masateru; Nakagawa, Toshito; Houjo, Takao; Corey, Eva; Vessella, Robert L; Aoki, Yuko; Sato, Haruhiko

    2015-04-01

    Resistance of prostate cancer to castration is currently an unavoidable problem. The major mechanisms underlying such resistance are androgen receptor (AR) overexpression, androgen-independent activation of AR, and AR mutation. To address this problem, we developed an AR pure antagonist, CH5137291, with AR nuclear translocation-inhibiting activity, and compared its activity and characteristics with that of bicalutamide. Cell lines corresponding to the mechanisms of castration resistance were used: LNCaP-BC2 having AR overexpression and LNCaP-CS10 having androgen-independent AR activation. VCaP and LNCaP were used as hormone-sensitive prostate cancer cells. In vitro functional assay clearly showed that CH5137291 inhibited the nuclear translocation of wild-type ARs as well as W741C- and T877A-mutant ARs. In addition, it acted as a pure antagonist on the transcriptional activity of these types of ARs. In contrast, bicalutamide did not inhibit the nuclear translocation of these ARs, and showed a partial/full agonistic effect on the transcriptional activity. CH5137291 inhibited cell growth more strongly than bicalutamide in VCaP and LNCaP cells as well as in LNCaP-BC2 and LNCaP-CS10 cells in vitro. In xenograft models, CH5137291 strongly inhibited the tumor growth of LNCaP, LNCaP-BC2, and LNCaP-CS10, whereas bicalutamide showed a weaker effect in LNCaP and almost no effect in LNCaP-BC2 and LNCaP-CS10 xenografts. Levels of prostate-specific antigen (PSA) in plasma correlated well with the antitumor effect of both agents. CH5137291 inhibited the growth of LNCaP tumors that had become resistant to bicalutamide treatment. A docking model suggested that CH5137291 intensively collided with the M895 residue of helix 12, and therefore strongly inhibited the folding of helix 12, a cause of AR agonist activity, in wild-type and W741C-mutant ARs. In cynomolgus monkeys, the serum concentration of CH5137291 increased dose-dependently and PSA level decreased 80% at 100 mg/kg. CH

  20. Novel diagnostic biomarkers for prostate cancer

    Directory of Open Access Journals (Sweden)

    Chikezie O. Madu, Yi Lu

    2010-01-01

    Full Text Available Prostate cancer is the most frequently diagnosed malignancy in American men, and a more aggressive form of the disease is particularly prevalent among African Americans. The therapeutic success rate for prostate cancer can be tremendously improved if the disease is diagnosed early. Thus, a successful therapy for this disease depends heavily on the clinical indicators (biomarkers for early detection of the presence and progression of the disease, as well as the prediction after the clinical intervention. However, the current clinical biomarkers for prostate cancer are not ideal as there remains a lack of reliable biomarkers that can specifically distinguish between those patients who should be treated adequately to stop the aggressive form of the disease and those who should avoid overtreatment of the indolent form.A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. A biomarker reveals further information to presently existing clinical and pathological analysis. It facilitates screening and detecting the cancer, monitoring the progression of the disease, and predicting the prognosis and survival after clinical intervention. A biomarker can also be used to evaluate the process of drug development, and, optimally, to improve the efficacy and safety of cancer treatment by enabling physicians to tailor treatment for individual patients. The form of the prostate cancer biomarkers can vary from metabolites and chemical products present in body fluid to genes and proteins in the prostate tissues.Current advances in molecular techniques have provided new tools facilitating the discovery of new biomarkers for prostate cancer. These emerging biomarkers will be beneficial and critical in developing new and clinically reliable indicators that will have a high specificity for the diagnosis and prognosis of

  1. Novel diagnostic biomarkers for prostate cancer.

    Science.gov (United States)

    Madu, Chikezie O; Lu, Yi

    2010-10-06

    Prostate cancer is the most frequently diagnosed malignancy in American men, and a more aggressive form of the disease is particularly prevalent among African Americans. The therapeutic success rate for prostate cancer can be tremendously improved if the disease is diagnosed early. Thus, a successful therapy for this disease depends heavily on the clinical indicators (biomarkers) for early detection of the presence and progression of the disease, as well as the prediction after the clinical intervention. However, the current clinical biomarkers for prostate cancer are not ideal as there remains a lack of reliable biomarkers that can specifically distinguish between those patients who should be treated adequately to stop the aggressive form of the disease and those who should avoid overtreatment of the indolent form.A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. A biomarker reveals further information to presently existing clinical and pathological analysis. It facilitates screening and detecting the cancer, monitoring the progression of the disease, and predicting the prognosis and survival after clinical intervention. A biomarker can also be used to evaluate the process of drug development, and, optimally, to improve the efficacy and safety of cancer treatment by enabling physicians to tailor treatment for individual patients. The form of the prostate cancer biomarkers can vary from metabolites and chemical products present in body fluid to genes and proteins in the prostate tissues.Current advances in molecular techniques have provided new tools facilitating the discovery of new biomarkers for prostate cancer. These emerging biomarkers will be beneficial and critical in developing new and clinically reliable indicators that will have a high specificity for the diagnosis and prognosis of prostate cancer. The

  2. Obesity, body composition, and prostate cancer

    Directory of Open Access Journals (Sweden)

    Fowke Jay H

    2012-01-01

    Full Text Available Abstract Background Established risk factors for prostate cancer have not translated to effective prevention or adjuvant care strategies. Several epidemiologic studies suggest greater body adiposity may be a modifiable risk factor for high-grade (Gleason 7, Gleason 8-10 prostate cancer and prostate cancer mortality. However, BMI only approximates body adiposity, and may be confounded by centralized fat deposition or lean body mass in older men. Our objective was to use bioelectric impedance analysis (BIA to measure body composition and determine the association between prostate cancer and total body fat mass (FM fat-free mass (FFM, and percent body fat (%BF, and which body composition measure mediated the association between BMI or waist circumference (WC with prostate cancer. Methods The study used a multi-centered recruitment protocol targeting men scheduled for prostate biopsy. Men without prostate cancer at biopsy served as controls (n = 1057. Prostate cancer cases were classified as having Gleason 6 (n = 402, Gleason 7 (n = 272, or Gleason 8-10 (n = 135 cancer. BIA and body size measures were ascertained by trained staff prior to diagnosis, and clinical and comorbidity status were determined by chart review. Analyses utilized multivariable linear and logistic regression. Results Body size and composition measures were not significantly associated with low-grade (Gleason 6 prostate cancer. In contrast, BMI, WC, FM, and FFM were associated with an increased risk of Gleason 7 and Gleason 8-10 prostate cancer. Furthermore, BMI and WC were no longer associated with Gleason 8-10 (ORBMI = 1.039 (1.000, 1.081, ORWC = 1.016 (0.999, 1.033, continuous scales with control for total body FFM (ORBMI = 0.998 (0.946, 1.052, ORWC = 0.995 (0.974, 1.017. Furthermore, increasing FFM remained significantly associated with Gleason 7 (ORFFM = 1.030 (1.008, 1.052 and Gleason 8-10 (ORFFM = 1.044 (1.014, 1.074 after controlling for FM. Conclusions Our results

  3. Lymph node staging in prostate cancer.

    Science.gov (United States)

    Sankineni, Sandeep; Brown, Anna M; Fascelli, Michele; Law, Yan Mee; Pinto, Peter A; Choyke, Peter L; Turkbey, Baris

    2015-05-01

    Nodal staging is important in prostate cancer treatment. While surgical lymph node dissection is the classic method of determining whether lymph nodes harbor malignancy, this is a very invasive technique. Current noninvasive approaches to identifying malignant lymph nodes are limited. Conventional imaging methods rely on size and morphology of lymph nodes and have notoriously low sensitivity for detecting malignant nodes. New imaging techniques such as targeted positron emission tomography (PET) imaging and magnetic resonance lymphography (MRL) with iron oxide particles are promising for nodal staging of prostate cancer. In this review, the strengths and limitations of imaging techniques for lymph node staging of prostate cancer are discussed.

  4. Statin Use in Prostate Cancer: An Update

    Science.gov (United States)

    Babcook, Melissa A.; Joshi, Aditya; Montellano, Jeniece A.; Shankar, Eswar; Gupta, Sanjay

    2016-01-01

    3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, known as statins, are commonly prescribed for the treatment of hypercholesterolemia and cardiovascular disease. A systematic review was conducted using the keywords “statin and prostate cancer” within the title search engines including PubMed, Web of Science, and the Cochrane Library for relevant research work published between 2004 and December 2015. Although still premature, accumulating clinical evidence suggests that statin use may be beneficial in the prevention and/or treatment of prostate cancer. These human studies consist of meta-analyses of secondary endpoints obtained from randomized, controlled cardiovascular disease clinical trials of statins, patient database, observational studies, and a few, small case–control studies, directly addressing statin use on prostate cancer pathology and recurrence. This review summarizes and discusses the recent clinical literature on statins and prostate cancer with a recommendation to move forward with randomized, placebo-controlled clinical trials, investigating the use of statins. Additional preclinical testing of statins on prostate cancer cell lines and in vivo models is needed to elucidate pathways and determine its efficacy for prevention and/or treatment of prostate cancer, more specifically, the difference in the effectiveness of lipophilic versus hydrophilic statins in prostate cancer. PMID:27441003

  5. Focal therapy for prostate cancer: The current status

    OpenAIRE

    Marshall, Susan; Taneja, Samir

    2015-01-01

    Purpose In an era of increasing prostate cancer incidence and earlier detection, the assessment of clinical significance of prostate cancer is critical. Minimally invasive therapies are increasingly being investigated in localized prostate cancer. Methods and results In this review, we discuss the current status of magnetic resonance imaging targeted fusion prostate biopsy and focal therapy for prostate cancer, its rationale, and techniques. Conclusion Focal therapy offers a promising outlook...

  6. A precisely substituted benzopyran targets androgen refractory prostate cancer cells through selective modulation of estrogen receptors

    International Nuclear Information System (INIS)

    Dietary consumption of phytoestrogens like genistein has been linked with lower incidence of prostate cancer. The estradiol-like benzopyran core of genistein confers estrogen receptor-β (ER-β) selectivity that imparts weak anti-proliferative activity against prostate cancer cells. DL-2-[4-(2-piperidinoethoxy)phenyl]-3-phenyl-2H-1-benzopyran (BP), a SERM designed with benzopyran core, targeted androgen independent prostate cancer (PC-3) cells 14-times more potently than genistein, ~ 25% more efficiently than tamoxifen and 6.5-times more actively than ICI-182780, without forfeiting significant specificity in comparison to genistein. BP increased apoptosis (annexin-V and TUNEL labeling), arrested cell cycle, and significantly increased caspase-3 activity along with mRNA expressions of estrogen receptor (ER)-β and FasL (qPCR) in PC-3 cells. In classical ERE-luc reporter assay BP behaved as a potent ER-α antagonist and ER-β agonist. Accordingly, it decreased expression of ER-α target PS2 (P < 0.01) and increased expression of ER-β target TNF-α (P < 0.05) genes in PC-3. ER-β deficient PC-3 (siRNA-transfected) was resistant to apoptotic and anti-proliferative actions of SERMs, including stimulation of FasL expression by BP. BP significantly inhibited phosphorylation of Akt and ERK-1/2, JNK and p38 in PC-3 (immunoblotting), and thus adopted a multi-pathway mechanism to exert a more potent anti-proliferative activity against prostate cancer cells than natural and synthetic SERMs. Its precise ER-subtype specific activity presents a unique lead structure for further optimization. - Highlights: • BP with benzopyran core of genistein was identified for ER-β selective action. • BP was 14-times more potent than genistien in targeting prostate cancer cells. • It behaved as a potent ER-β agonist and ER-α antagonist in gene reporter assays. • BP's anti-proliferative action was inhibited significantly in ER-β deficient cells. • BP — a unique lead

  7. A precisely substituted benzopyran targets androgen refractory prostate cancer cells through selective modulation of estrogen receptors

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Rajeev; Verma, Vikas; Sharma, Vikas; Jain, Ashish; Singh, Vishal [Division of Endocrinology, CSIR—Central Drug Research Institute, Lucknow 226 031 (India); Sarswat, Amit [Division of Medicinal & Process Chemistry, CSIR—Central Drug Research Institute, Lucknow 226 031 (India); Maikhuri, Jagdamba P. [Division of Endocrinology, CSIR—Central Drug Research Institute, Lucknow 226 031 (India); Sharma, Vishnu L. [Division of Medicinal & Process Chemistry, CSIR—Central Drug Research Institute, Lucknow 226 031 (India); Gupta, Gopal, E-mail: g_gupta@cdri.res.in [Division of Endocrinology, CSIR—Central Drug Research Institute, Lucknow 226 031 (India)

    2015-03-15

    Dietary consumption of phytoestrogens like genistein has been linked with lower incidence of prostate cancer. The estradiol-like benzopyran core of genistein confers estrogen receptor-β (ER-β) selectivity that imparts weak anti-proliferative activity against prostate cancer cells. DL-2-[4-(2-piperidinoethoxy)phenyl]-3-phenyl-2H-1-benzopyran (BP), a SERM designed with benzopyran core, targeted androgen independent prostate cancer (PC-3) cells 14-times more potently than genistein, ~ 25% more efficiently than tamoxifen and 6.5-times more actively than ICI-182780, without forfeiting significant specificity in comparison to genistein. BP increased apoptosis (annexin-V and TUNEL labeling), arrested cell cycle, and significantly increased caspase-3 activity along with mRNA expressions of estrogen receptor (ER)-β and FasL (qPCR) in PC-3 cells. In classical ERE-luc reporter assay BP behaved as a potent ER-α antagonist and ER-β agonist. Accordingly, it decreased expression of ER-α target PS2 (P < 0.01) and increased expression of ER-β target TNF-α (P < 0.05) genes in PC-3. ER-β deficient PC-3 (siRNA-transfected) was resistant to apoptotic and anti-proliferative actions of SERMs, including stimulation of FasL expression by BP. BP significantly inhibited phosphorylation of Akt and ERK-1/2, JNK and p38 in PC-3 (immunoblotting), and thus adopted a multi-pathway mechanism to exert a more potent anti-proliferative activity against prostate cancer cells than natural and synthetic SERMs. Its precise ER-subtype specific activity presents a unique lead structure for further optimization. - Highlights: • BP with benzopyran core of genistein was identified for ER-β selective action. • BP was 14-times more potent than genistien in targeting prostate cancer cells. • It behaved as a potent ER-β agonist and ER-α antagonist in gene reporter assays. • BP's anti-proliferative action was inhibited significantly in ER-β deficient cells. • BP — a unique lead

  8. Physical activity and prostate gene expression in men with low-risk prostate cancer

    OpenAIRE

    Magbanua, MJM; Richman, EL; Sosa, EV; Jones, LW; Simko, J; Shinohara, K.; Haqq, CM; Carroll, PR; Chan, JM

    2014-01-01

    Purpose: Vigorous physical activity after diagnosis of localized prostate cancer may reduce the risk of disease progression and prostate cancer-specific mortality. The molecular mechanisms by which physical activity may exert protective effects in the prostate remain unknown. Methods: We examined the associations between self-reported physical activity and gene expression patterns in morphologically normal prostate tissue of 71 men with low-risk prostate cancer on active surveillance. Differe...

  9. d -Limonene sensitizes docetaxel-induced cytotoxicity in human prostate cancer cells: Generation of reactive oxygen species and induction of apoptosis

    Directory of Open Access Journals (Sweden)

    Rabi Thangaiyan

    2009-01-01

    Full Text Available Background: Clinical trials have shown that docetaxel combined with other novel agents can improve the survival of androgen-independent prostate cancer patients. d -Limonene, a non-nutrient dietary component, has been found to inhibit various cancer cell growths without toxicity. We sought to characterize whether a non-toxic dose of d -limonene may enhance tumor response to docetaxel in an in vitro model of metastatic prostate cancer. Materials and Methods: Human prostate carcinoma DU-145 and normal prostate epithelial PZ-HPV-7 cells were treated with various concentrations of d -limonene, docetaxel or a combination of both, and cell viability was determined by MTT assay. Intracellular reactive oxygen species (ROS, reduced glutathione (GSH and caspase activity were measured. Apoptosis and apoptosis-related proteins were studied by enzyme-linked immunosorbent assay and Western blotting, respectively. Results: d -Limonene and docetaxel in combination significantly enhanced the cytotoxicity to DU-145 cells than PZ-HPV-7 cells. Exposure of DU-145 cells to a combined d -limonene and docetaxel resulted in higher ROS generation, depletion of GSH, accompanied by increased caspase activity than docetaxel alone. It also triggered a series of effects involving cytochrome c , cleavages of caspase-9, 3 and poly (ADP-ribose polymerase, and a shift in Bad:Bcl-xL ratio in favor of apoptosis. Apoptotic effect was significantly blocked on pretreatment with N -acetylcystein, indicating that antitumor effect is initiated by ROS generation, and caspase cascades contribute to the cell death. Conclusion: Our results show, for the first time, that d -limonene enhanced the antitumor effect of docetaxel against prostate cancer cells without being toxic to normal prostate epithelial cells. The combined beneficial effect could be through the modulation of proteins involved in mitochondrial pathway of apoptosis. d -Limonene could be used as a potent non-toxic agent to

  10. MR imaging of prostate cancer

    International Nuclear Information System (INIS)

    Accurate diagnosis and staging of prostate cancer (PC) is developing into an important health care issue in light of the high incidence of PC and the improvements in stage-adapted therapy. The purpose of this paper is to provide an overview on the current role of MR imaging and MR spectroscopy in the diagnosis and staging of PC.Material and methods Pertinent literature was searched and evaluated to collect information on current clinical indications, study techniques, diagnostic value, and limitations of magnetic resonance imaging and spectroscopy. Major indications for MR imaging of patients with supected PC are to define tumor location before biopsy when clinical or TRUS findings are inconclusive, and to provide accurate staging of histologically proven PC to ascertain effective therapy. Current MR imaging techniques for the evaluation of PC include multiplanar high-resolution T2-weighted FSE and T1-weighted SE sequences using combined endorectal and phased-array coils. Using these techniques, the reported accuracy of MR imaging for the diagnosis of extracapsular tumor extension ranges between 82 and 88% with sensitivities between 80 and 95%, and specificities between 82 and 93%. Typical MR findings of PC in different stages of disease, as well as diagnostic problems, such as chronic prostatitis, biopsy-related hemorrhage and therapy-related changes of prostatic tissue are discussed. In addition, the current perspectives and limitations of MR spectroscopy in PC are summarized. Current MR imaging techniques provide important diagnostic information in the pretherapeutic workup of PC including a high staging accuracy, and is superior to TRUS. (orig.)

  11. Image guided prostate cancer treatments

    Energy Technology Data Exchange (ETDEWEB)

    Bard, Robert L. [Bard Cancer Center, Biofoundation for Angiogenesis Research and Development, New York, NY (United States); Fuetterer, Jurgen J. [Radboud Univ. Nijmegen, Medical Centre (Netherlands). Dept. of Radiology; Sperling, Dan (ed.) [Sperling Prostate Center, Alpha 3TMRI, New York, NY (United States)

    2014-07-01

    Systematic overview of the application of ultrasound and MRI in the diagnosis and treatment of diseases of the lower urinary tract. Detailed information on image-guided therapies, including focused ultrasound, photodynamic therapy, and microwave and laser ablation. Numerous high-quality illustrations based on high-end equipment. Represents the state of the art in Non Invasive Imaging and Minimally Invasive Ablation Treatment (MIAT). Image-Guided Prostate Cancer Treatments is a comprehensive reference and practical guide on the technology and application of ultrasound and MRI in the male pelvis, with special attention to the prostate. The book is organized into three main sections, the first of which is devoted to general aspects of imaging and image-guided treatments. The second section provides a systematic overview of the application of ultrasound and MRI to the diagnosis and treatment of diseases of the lower urinary tract. Performance of the ultrasound and MRI studies is explained, and the normal and abnormal pathological anatomy is reviewed. Correlation with the ultrasound in the same plane is provided to assist in understanding the MRI sequences. Biopsy and interventional procedures, ultrasound-MRI fusion techniques, and image-guided therapies, including focused ultrasound, photodynamic therapy, microwave and laser ablation, are all fully covered. The third section focuses on securing treatment effectiveness and the use of follow-up imaging to ensure therapeutic success and detect tumor recurrence at an early stage, which is vital given that prompt focal treatment of recurrence is very successful. Here, particular attention is paid to the role of Doppler ultrasound and DCE-MRI technologies. This book, containing a wealth of high-quality illustrations based on high-end equipment, will acquaint beginners with the basics of prostate ultrasound and MRI, while more advanced practitioners will learn new skills, means of avoiding pitfalls, and ways of effectively

  12. Vaccine Therapy and Pembrolizumab in Treating Patients With Hormone-Resistant, Metastatic Prostate Cancer

    Science.gov (United States)

    2016-06-22

    Hormone-Resistant Prostate Cancer; Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Neoplasm in the Soft Tissues; Metastatic Prostate Carcinoma; Prostate Adenocarcinoma; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer

  13. Correlations between meteorological parameters and prostate cancer

    Directory of Open Access Journals (Sweden)

    Mandal Rakesh

    2010-04-01

    Full Text Available Abstract Background There exists a north-south pattern to the distribution of prostate cancer in the U.S., with the north having higher rates than the south. The current hypothesis for the spatial pattern of this disease is low vitamin D levels in individuals living at northerly latitudes; however, this explanation only partially explains the spatial distribution in the incidence of this cancer. Using a U.S. county-level ecological study design, we provide evidence that other meteorological parameters further explain the variation in prostate cancer across the U.S. Results In general, the colder the temperature and the drier the climate in a county, the higher the incidence of prostate cancer, even after controlling for shortwave radiation, age, race, snowfall, premature mortality from heart disease, unemployment rate, and pesticide use. Further, in counties with high average annual snowfall (>75 cm/yr the amount of land used to grow crops (a proxy for pesticide use was positively correlated with the incidence of prostate cancer. Conclusion The trends found in this USA study suggest prostate cancer may be partially correlated with meteorological factors. The patterns observed were consistent with what we would expect given the effects of climate on the deposition, absorption, and degradation of persistent organic pollutants including pesticides. Some of these pollutants are known endocrine disruptors and have been associated with prostate cancer.

  14. Prostate Cancer Stem Cells: Research Advances.

    Science.gov (United States)

    Jaworska, Dagmara; Król, Wojciech; Szliszka, Ewelina

    2015-01-01

    Cancer stem cells have been defined as cells within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Experimental evidence showed that these highly tumorigenic cells might be responsible for initiation and progression of cancer into invasive and metastatic disease. Eradicating prostate cancer stem cells, the root of the problem, has been considered as a promising target in prostate cancer treatment to improve the prognosis for patients with advanced stages of the disease.

  15. Prostate Cancer Stem Cells: Research Advances

    Directory of Open Access Journals (Sweden)

    Dagmara Jaworska

    2015-11-01

    Full Text Available Cancer stem cells have been defined as cells within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Experimental evidence showed that these highly tumorigenic cells might be responsible for initiation and progression of cancer into invasive and metastatic disease. Eradicating prostate cancer stem cells, the root of the problem, has been considered as a promising target in prostate cancer treatment to improve the prognosis for patients with advanced stages of the disease.

  16. Road to Recovery from Prostate Cancer

    Medline Plus

    Full Text Available ... too enamored with the gimmick of using the robot or having limited bleeding and we’ve had ... the Department of Urology, I felt that the robot surgery for the treatment of prostate cancer is ...

  17. Road to Recovery from Prostate Cancer

    Medline Plus

    Full Text Available ... remember the rule of ones. This is the number one treatment option for prostate cancer in 2008. ... over the past few years and the estimated number in 2008, it’s going to be a little ...

  18. Abiraterone Improves Survival in Metastatic Prostate Cancer

    Science.gov (United States)

    A multinational phase III trial found that the drug abiraterone acetate prolonged the median survival of patients with metastatic castration-resistant prostate cancer by 4 months compared with patients who received a placebo.

  19. Road to Recovery from Prostate Cancer

    Medline Plus

    Full Text Available ... over two housekeeping items. First, please keep in mind that this live webcast will be archived on ... prostate cancer, we must keep the trifecta in mind. Certainly, there are many naysayers of using minimally ...

  20. African American Men and Prostate Cancer

    Medline Plus

    Full Text Available ... the African-American that we treat this as what it is -- an epidemic. Winston Dyer: My introduction ... being ignorant to prostate cancer -- and not knowing what it was -- that was my first, first, first- ...

  1. Road to Recovery from Prostate Cancer

    Medline Plus

    Full Text Available ... to get the da Vinci S or the latest model of the robot, and would that comes the ... If you have a Gleason 8 or high risk prostate cancer, certainly that’s important to know whether ...

  2. Genomic Predictors of Outcome in Prostate Cancer

    NARCIS (Netherlands)

    Bostrom, P.J.; Bjartell, A.S.; Catto, J.W.; Eggener, S.E.; Lilja, H.; Loeb, S.; Schalken, J.A.; Schlomm, T.; Cooperberg, M.R.

    2015-01-01

    CONTEXT: Given the highly variable behavior and clinical course of prostate cancer (PCa) and the multiple available treatment options, a personalized approach to oncologic risk stratification is important. Novel genetic approaches offer additional information to improve clinical decision making. OBJ

  3. Radium-223 for Advanced Prostate Cancer

    Science.gov (United States)

    A summary of results from a phase III trial that compared radium-223 dichloride plus the best standard of care versus a placebo plus the best standard of care in men with metastatic, castration-resistant prostate cancer.

  4. The bicalutamide Early Prostate Cancer Program. Demography

    DEFF Research Database (Denmark)

    See, W A.; McLeod, D; Iversen, P;

    2001-01-01

    BACKGROUND: The optimal treatment for early prostate cancer has yet to be established. A well-tolerated hormonal therapy such as bicalutamide could be a useful treatment option in this setting, either as adjuvant or immediate therapy. A major collaborative clinical trials program was set up to...... investigate bicalutamide as a treatment option for local prostate cancer (localized or locally advanced disease). METHODS: The bicalutamide Early Prostate Cancer program comprises three randomized, double-blind, placebo-controlled trials of similar design that are being conducted in distinct geographical...... areas (North America; Australia, Europe, Israel, South Africa and Mexico; and Scandinavia). Men with T1b-4N0-1M0 (TNM 1997) prostate cancer have been randomized on a 1:1 basis to receive bicalutamide 150 mg daily or placebo. Recruitment to the program closed in July 1998, and follow-up is ongoing. Study...

  5. Road to Recovery from Prostate Cancer

    Medline Plus

    Full Text Available ... the web for anyone to reference in the future. Secondly, we welcome you to email any questions ... for the treatment of prostate cancer is the future. When we wanted to build a program at ...

  6. Immunohistochemical Analysis of Omi/HtrA2 Expression in Prostate Cancer and Benign Prostatic Hyperplasia

    Institute of Scientific and Technical Information of China (English)

    HU Xiaoyong; CHEN Xiaochun; PING Hao; CHEN Zhaohui; ZENG Fuqing; LU Gongcheng

    2005-01-01

    To study the expression and significance of the serine protease Omi/HtrA2 in prostate cancer and benign prostatic hyperplasia. The expression of Omi/HtrA2 was assayed by means of immunohistochemical technique in 41 prostate cancer (Cap), 20 benign prostatic hyperplasia (BPH) and 10 normal prostate (NP) specimens. Omi/HtrA2 expression was positive in 30 (73.17%) prostate cancer specimens, and the positive rate of Omi/HtrA2 was lower in well differentiated than in poorly and moderately differentiated groups (P<0.05). By contrast, the cells in normal prostate and benign prostatic hyperplasia groups showed no or weak expression of Omi/HtrA2.Prostate cancer cells in vivo may need Omi/HtrA2 expression for apoptosis, and that Omi/HtrA2expression might be involved in prostate cancer development.

  7. Finasteride concentrations and prostate cancer risk: results from the Prostate Cancer Prevention Trial.

    Directory of Open Access Journals (Sweden)

    Cindy H Chau

    Full Text Available In the Prostate Cancer Prevention Trial (PCPT, finasteride reduced the risk of prostate cancer by 25%, even though high-grade prostate cancer was more common in the finasteride group. However, it remains to be determined whether finasteride concentrations may affect prostate cancer risk. In this study, we examined the association between serum finasteride concentrations and the risk of prostate cancer in the treatment arm of the PCPT and determined factors involved in modifying drug concentrations.Data for this nested case-control study are from the PCPT. Cases were drawn from men with biopsy-proven prostate cancer and matched controls. Finasteride concentrations were measured using a liquid chromatography-mass spectrometry validated assay. The association of serum finasteride concentrations with prostate cancer risk was determined by logistic regression. We also examine whether polymorphisms in the enzyme target and metabolism genes of finasteride are related to drug concentrations using linear regression.Among men with detectable finasteride concentrations, there was no association between finasteride concentrations and prostate cancer risk, low-grade or high-grade, when finasteride concentration was analyzed as a continuous variable or categorized by cutoff points. Since there was no concentration-dependent effect on prostate cancer, any exposure to finasteride intake may reduce prostate cancer risk. Of the twenty-seven SNPs assessed in the enzyme target and metabolism pathway, five SNPs in two genes, CYP3A4 (rs2242480; rs4646437; rs4986910, and CYP3A5 (rs15524; rs776746 were significantly associated with modifying finasteride concentrations. These results suggest that finasteride exposure may reduce prostate cancer risk and finasteride concentrations are affected by genetic variations in genes responsible for altering its metabolism pathway.ClinicalTrials.gov NCT00288106.

  8. Prostate Cancer: Current Treatment and Prevention Strategies

    OpenAIRE

    Chen, Fang-zhi; Zhao, Xiao-kun

    2013-01-01

    Abstract Prostate cancer is one of the life threatening disorders of male. Although, over the last two decades, a high rate of overdiagnosis, and overtreatment has lowered the incidence rate of prostate cancer, the treatment or prevention strategies are not enough to control the high rate of disease related mortality. Current medical treatment approaches include surgery, radiation therapy, chemotherapy, hormonal therapy, cryosurgery and other methods. These approaches are more or less effecti...

  9. Prostate cancer: a review of active surveillance

    OpenAIRE

    Lund L; Svolgaard N; Poulsen MH

    2014-01-01

    Lars Lund,1,2 Niels Svolgaard,1 Mads Hvid Poulsen1 1Department of Urology, Odense University Hospital, 2Clinical Institute, Southern University of Southern Denmark, Odense, Denmark Abstract: The objective of this paper is to review the current recommendations for active surveillance in prostate cancer from the present prospective studies. Worldwide, there are increasing numbers of men with prostate cancer. It is now accepted as standard care that a number of men with favorable-risk disease c...

  10. Prostate cancer research in China

    Institute of Scientific and Technical Information of China (English)

    Shan-Cheng Ren; Rui Chen; Ying-Hao Sun

    2013-01-01

    Prostate cancer (PCa) research in China has been on a rocketing trend in recent years.The first genome-wide association study (GWAS)in China identified two new PCa risk associated single nucleotide polymorphisms (SNPs).Next generation sequencing is beginning to be used,yielding novel findings:gene fusions,long non-coding RNAs and other variations.Mechanisms of PCa progression have been illustrated while various diagnosis biomarkers have been investigated extensively.Personalized therapy based on genetic factors,nano-medicine and traditional Chinese medicine has been the focus of experimental therapeutic research for PCa.This review intends to shed light upon the recent progress in PCa research in China and points out the possible breakthroughs in the future.

  11. Epidemiology, etiology, diagnosis and treatment of prostate cancer.

    Science.gov (United States)

    Daniyal, Muhammad; Siddiqui, Zamir Ali; Akram, Muhammad; Asif, H M; Sultana, Sabira; Khan, Asmatullah

    2014-01-01

    Prostate cancer is more common in men over the age of 65 years. There are 15% cases with positive family history of prostate cancer Worldwide. Prostate cancer is the second leading cause of death among the U.S. men. Prostate cancer incidence is strongly related to age with the highest rates in older man. Globally millions of people are suffering from this disease. This study aims to provide awareness about prostate cancer as well as an updated knowledge about the epidemiology, etiology, diagnosis and treatment of prostate cancer.

  12. The politics of prostate cancer screening.

    Science.gov (United States)

    Kaffenberger, Samuel D; Penson, David F

    2014-05-01

    The controversial recent recommendation by the United States Preventive Services Task Force (USPSTF) against prostate-specific antigen (PSA) screening for early-stage prostate cancer has caused much debate. Whereas USPSTF recommendations against routine screening mammography in younger women resulted in fierce public outcry and eventual alteration in the language of the recommendation, the same public and political response has not been seen with PSA screening for prostate cancer. It is of paramount importance to ensure improved efficiency and transparency of the USPSTF recommendation process, and resolution of concerns with the current USPSTF recommendation against PSA screening for all ages. PMID:24725487

  13. Focal Therapy in the Management of Prostate Cancer: An Emerging Approach for Localized Prostate Cancer

    OpenAIRE

    Takeo Nomura; Hiromitsu Mimata

    2012-01-01

    A widespread screening with prostate-specific antigen (PSA) has led increased diagnosis of localized prostate cancer along with a reduction in the proportion of advanced-stage disease at diagnosis. Over the past decade, interest in focal therapy as a less morbid option for the treatment of localized low-risk prostate cancer has recently been renewed due to downward stage migration. Focal therapy stands midway between active surveillance and radical treatments, combining minimal morbidity with...

  14. The Role of Estrogen Receptor β in Prostate Cancer

    OpenAIRE

    Christoforou, Paraskevi; Christopoulos, Panagiotis F; Koutsilieris, Michael

    2014-01-01

    Although androgen receptor (AR) signaling is the main molecular tool regulating growth and function of the prostate gland, estrogen receptor β (ERβ) is involved in the differentiation of prostatic epithelial cells and numerous antiproliferative actions on prostate cancer cells. However, ERβ splice variants have been associated with prostate cancer initiation and progression mechanisms. ERβ is promising as an anticancer therapy and in the prevention of prostate cancer. Herein, we review the re...

  15. Dietary Zinc and Prostate Cancer in the TRAMP Mouse Model

    OpenAIRE

    Prasad, Ananda S; Mukhtar, Hasan; Beck, Frances W.J.; Adhami, Vaqar M.; Siddiqui, Imtiaz A.; Din, Maria; Hafeez, Bilal B.; KUCUK, Omer

    2010-01-01

    Circumstantial evidence indicates that zinc may have an important role in the prostate. Total zinc levels in the prostate are 10 times higher than in other soft tissues. Zinc concentrations in prostate epithethial cancer cells are decreased significantly. Zinc supplementation for prevention and treatment of prostate cancer in humans has yielded controversial results. No studies have been reported in animal models to show the effect of zinc supplementation on prevention of prostate cancer, thu...

  16. The role of Estrogen Receptor Beta in Prostate Cancer.

    OpenAIRE

    Christoforou, Paraskevi; Christopoulos, Panagiotis F; Koutsilieris, Michael

    2014-01-01

    Although androgen receptor (AR) signaling is the main molecular tool regulating growth and function of prostate gland, estrogen receptor beta (ERβ) is involved contributive in the differentiation of prostatic epithelial cells and numerous antiproliferative actions on prostate cancer cells. However, ERβ splice variants have been associated with prostate cancer initiation and progression mechanisms. Nowadays, ERß is a promising target as an anticancer therapy and prevention for prostate cancer....

  17. Behavioral stress accelerates prostate cancer development in mice

    OpenAIRE

    Hassan, Sazzad; Karpova, Yelena; Baiz, Daniele; Yancey, Dana; Pullikuth, Ashok; Flores, Anabel; Register, Thomas; Cline, J. Mark; D’Agostino, Ralph; Danial, Nika; Datta, Sandeep Robert; Kulik, George

    2013-01-01

    Prostate cancer patients have increased levels of stress and anxiety. Conversely, men who take beta blockers, which interfere with signaling from the stress hormones adrenaline and noradrenaline, have a lower incidence of prostate cancer; however, the mechanisms underlying stress–prostate cancer interactions are unknown. Here, we report that stress promotes prostate carcinogenesis in mice in an adrenaline-dependent manner. Behavioral stress inhibited apoptosis and delayed prostate tumor invol...

  18. 75 FR 54453 - National Prostate Cancer Awareness Month, 2010

    Science.gov (United States)

    2010-09-07

    ... the last decade, prostate cancer is still the second leading cause of cancer deaths among men in the... it. The exact causes of prostate cancer are not known, but awareness can help men make more informed... Documents#0;#0; ] Proclamation 8552 of August 31, 2010 National Prostate Cancer Awareness Month, 2010 By...

  19. Genetics of Prostate Cancer (PDQ®)—Health Professional Version

    Science.gov (United States)

    Expert-reviewed information summary about the genetics of prostate cancer, including information about specific genes and family cancer syndromes. The summary also contains information about screening for prostate cancer and research aimed at prevention of this disease. Psychosocial issues associated with genetic testing and counseling of individuals who may have hereditary prostate cancer syndrome are also discussed.

  20. The evolving biology and treatment of prostate cancer

    OpenAIRE

    Taichman, Russel S.; Loberg, Robert D; Mehra, Rohit; Kenneth J Pienta

    2007-01-01

    Since the effectiveness of androgen deprivation for treatment of advanced prostate cancer was first demonstrated, prevention strategies and medical therapies for prostate cancer have been based on understanding the biologic underpinnings of the disease. Prostate cancer treatment is one of the best examples of a systematic therapeutic approach to target not only the cancer cells themselves, but the microenvironment in which they are proliferating. As the population ages and prostate cancer pre...

  1. Risk of prostate cancer among cancer survivors in the Netherlands

    NARCIS (Netherlands)

    Kok, D.E.; Schans, S.A. van de; Liu, L.; Kampman, E.; Coebergh, J.W.W.; Kiemeney, L.A.L.M.; Soerjomataram, I.; Aben, K.K.H.

    2013-01-01

    BACKGROUND: In parallel with increasing numbers of cancer patients and improving cancer survival, the occurrence of second primary cancers becomes a relevant issue. The aim of our study was to evaluate risk of prostate cancer as second primary cancer in a population-based setting. METHODS: Data from

  2. Risk of prostate cancer among cancer survivors in the Netherlands

    NARCIS (Netherlands)

    Kok, D.E.G.; Schans, van de S.A.; Liu, L.; Kampman, E.; Coebergh, J.W.; Kiemeney, L.A.; Soerjomataram, I.; Aben, K.K.

    2013-01-01

    In parallel with increasing numbers of cancer patients and improving cancer survival, the occurrence of second primary cancers becomes a relevant issue. The aim of our study was to evaluate risk of prostate cancer as second primary cancer in a population-based setting. Methods Data from the Netherla

  3. Prostate-specific antigen in the early detection of prostate cancer

    OpenAIRE

    Thompson, Ian M; Ankerst, Donna P.

    2007-01-01

    Throughout Canada, the United States and much of Europe, prostate-specific antigen (PSA) screening for prostate cancer has proliferated over the past 2 decades, leading to dramatic increases in detection rates of prostate cancer. Although it has unquestionably led to increased detection of cancer and a migration to lower-stage and -volume tumours, it is still unknown whether PSA screening significantly reduces mortality from prostate cancer. Often thought to be dichotomous (i.e., either norma...

  4. The role of inflammatory mediators in the development of prostatic hyperplasia and prostate cancer

    OpenAIRE

    Elkahwaji JE

    2012-01-01

    Johny E Elkahwaji1–31Section of Urologic Surgery, 2Section of Medical Oncology and Hematology, 3Genitourinary Oncology Research Laboratory, University of Nebraska Medical Center, Omaha, NE, USAAbstract: Benign prostatic hyperplasia and prostate cancer remain the most prevalent urologic health concerns affecting elderly men in their lifetime. Only 20% of benign prostatic hyperplasia and prostate cancer cases coexist in the same zone of the prostate and require a long time for initiat...

  5. Prostate-specific antigen: does the current evidence support its use in prostate cancer screening?

    LENUS (Irish Health Repository)

    Duffy, Michael J

    2012-02-01

    Although widely used, the value of prostate-specific antigen (PSA) in screening asymptomatic men for prostate cancer is controversial. Reasons for the controversy relate to PSA being less than an ideal marker in detecting early prostate cancer, the possibility that screening for prostate cancer may result in the overdetection and thus overtreatment of indolent disease and the lack of clarity as to the definitive or best treatment for men diagnosed with localized prostate cancer. Although the results from some randomized prospective trials suggest that screening with PSA reduces mortality from prostate cancer, the overall benefit was modest. It is thus currently unclear as to whether the modest benefit of reduced mortality outweighs the harms of overdetection and overtreatment. Thus, prior to undergoing screening for prostate cancer, men should be informed of the risks and benefits of early detection. Newly emerging markers that may complement PSA in the early detection of prostate cancer include specific isoforms of PSA and PCA3.

  6. Prostate cancer in men of African origin.

    Science.gov (United States)

    McGinley, Kathleen F; Tay, Kae Jack; Moul, Judd W

    2016-02-01

    Men of African origin are disproportionately affected by prostate cancer: prostate cancer incidence is highest among men of African origin in the USA, prostate cancer mortality is highest among men of African origin in the Caribbean, and tumour stage and grade at diagnosis are highest among men in sub-Saharan Africa. Socioeconomic, educational, cultural, and genetic factors, as well as variations in care delivery and treatment selection, contribute to this cancer disparity. Emerging data on single-nucleotide-polymorphism patterns, epigenetic changes, and variations in fusion-gene products among men of African origin add to the understanding of genetic differences underlying this disease. On the diagnosis of prostate cancer, when all treatment options are available, men of African origin are more likely to choose radiation therapy or to receive no definitive treatment than white men. Among men of African origin undergoing surgery, increased rates of biochemical recurrence have been identified. Understanding differences in the cancer-survivorship experience and quality-of-life outcomes among men of African origin are critical to appropriately counsel patients and improve cultural sensitivity. Efforts to curtail prostate cancer screening will likely affect men of African origin disproportionately and widen the racial disparity of disease.

  7. Differential effects of genistein on prostate cancer cells depend on mutational status of the androgen receptor.

    Directory of Open Access Journals (Sweden)

    Abeer M Mahmoud

    Full Text Available Blocking the androgen receptor (AR activity is the main goal of therapies for advanced prostate cancer (PCa. However, relapse with a more aggressive, hormone refractory PCa arises, which harbors restored AR activity. One mechanism of such reactivation occurs through acquisition of AR mutations that enable its activation by various steroidal and non-steroidal structures. Thus, natural and chemical compounds that contribute to inappropriate (androgen-independent activation of the AR become an area of intensive research. Here, we demonstrate that genistein, a soy phytoestrogen binds to both the wild and the Thr877Ala (T877A mutant types of AR competitively with androgen, nevertheless, it exerts a pleiotropic effect on PCa cell proliferation and AR activity depending on the mutational status of the AR. Genistein inhibited, in a dose-dependent way, cell proliferation and AR nuclear localization and expression in LAPC-4 cells that have wild AR. However, in LNCaP cells that express the T877A mutant AR, genistein induced a biphasic effect where physiological doses (0.5-5 µmol/L stimulated cell growth and increased AR expression and transcriptional activity, and higher doses induced inhibitory effects. Similar biphasic results were achieved in PC-3 cells transfected with AR mutants; T877A, W741C and H874Y. These findings suggest that genistein, at physiological concentrations, potentially act as an agonist and activate the mutant AR that can be present in advanced PCa after androgen ablation therapy.

  8. Differential effects of genistein on prostate cancer cells depend on mutational status of the androgen receptor.

    Science.gov (United States)

    Mahmoud, Abeer M; Zhu, Tian; Parray, Aijaz; Siddique, Hifzur R; Yang, Wancai; Saleem, Mohammad; Bosland, Maarten C

    2013-01-01

    Blocking the androgen receptor (AR) activity is the main goal of therapies for advanced prostate cancer (PCa). However, relapse with a more aggressive, hormone refractory PCa arises, which harbors restored AR activity. One mechanism of such reactivation occurs through acquisition of AR mutations that enable its activation by various steroidal and non-steroidal structures. Thus, natural and chemical compounds that contribute to inappropriate (androgen-independent) activation of the AR become an area of intensive research. Here, we demonstrate that genistein, a soy phytoestrogen binds to both the wild and the Thr877Ala (T877A) mutant types of AR competitively with androgen, nevertheless, it exerts a pleiotropic effect on PCa cell proliferation and AR activity depending on the mutational status of the AR. Genistein inhibited, in a dose-dependent way, cell proliferation and AR nuclear localization and expression in LAPC-4 cells that have wild AR. However, in LNCaP cells that express the T877A mutant AR, genistein induced a biphasic effect where physiological doses (0.5-5 µmol/L) stimulated cell growth and increased AR expression and transcriptional activity, and higher doses induced inhibitory effects. Similar biphasic results were achieved in PC-3 cells transfected with AR mutants; T877A, W741C and H874Y. These findings suggest that genistein, at physiological concentrations, potentially act as an agonist and activate the mutant AR that can be present in advanced PCa after androgen ablation therapy.

  9. Multiparametric MR imaging in diagnosis of chronic prostatitis and its differentiation from prostate cancer

    Directory of Open Access Journals (Sweden)

    Vivek Kumar Sah

    2015-03-01

    Full Text Available Chronic prostatitis is a heterogeneous condition with high prevalence rate. Chronic prostatitis has overlap in clinical presentation with other prostate disorders and is one of the causes of high serum prostate specific antigen (PSA level. Chronic prostatitis, unlike acute prostatitis, is difficult to diagnose reliably and accurately on the clinical grounds alone. Not only this, it is also challenging to differentiate chronic prostatitis from prostate cancer with imaging modalities like TRUS and conventional MR Imaging, as the findings can mimic those of prostate cancer. Even biopsy doesn't play promising role in the diagnosis of chronic prostatitis as it has limited sensitivity and specificity. As a result of this, chronic prostatitis may be misdiagnosed as a malignant condition and end up in aggressive surgical management resulting in increased morbidity. This warrants the need of reliable diagnostic tool which has ability not only to diagnose it reliably but also to differentiate it from the prostate cancer. Recently, it is suggested that multiparametric MR Imaging of the prostate could improve the diagnostic accuracy of the prostate cancer. This review is based on the critically published literature and aims to provide an overview of multiparamateric MRI techniques in the diagnosis of chronic prostatitis and its differentiation from prostate cancer.

  10. Cholesterol Metabolism and Prostate Cancer Lethality.

    Science.gov (United States)

    Stopsack, Konrad H; Gerke, Travis A; Sinnott, Jennifer A; Penney, Kathryn L; Tyekucheva, Svitlana; Sesso, Howard D; Andersson, Swen-Olof; Andrén, Ove; Cerhan, James R; Giovannucci, Edward L; Mucci, Lorelei A; Rider, Jennifer R

    2016-08-15

    Cholesterol metabolism has been implicated in prostate cancer pathogenesis. Here, we assessed the association of intratumoral mRNA expression of cholesterol synthesis enzymes, transporters, and regulators in tumor specimen at diagnosis and lethal prostate cancer, defined as mortality or metastases from prostate cancer in contrast to nonlethal disease without evidence of metastases after at least 8 years of follow-up. We analyzed the prospective prostate cancer cohorts within the Health Professionals Follow-up Study (n = 249) and the Physicians' Health Study (n = 153) as well as expectantly managed patients in the Swedish Watchful Waiting Study (n = 338). The expression of squalene monooxygenase (SQLE) was associated with lethal cancer in all three cohorts. Men with high SQLE expression (>1 standard deviation above the mean) were 8.3 times (95% confidence interval, 3.5 to 19.7) more likely to have lethal cancer despite therapy compared with men with the mean level of SQLE expression. Absolute SQLE expression was associated with lethal cancer independently from Gleason grade and stage, as was a SQLE expression ratio in tumor versus surrounding benign prostate tissue. Higher SQLE expression was tightly associated with increased histologic markers of angiogenesis. Collectively, this study establishes the prognostic value of intratumoral cholesterol synthesis as measured via SQLE, its second rate-limiting enzyme. SQLE expression at cancer diagnosis is prognostic for lethal prostate cancer both after curative-intent prostatectomy and in a watchful waiting setting, possibly by facilitating micrometastatic disease. Cancer Res; 76(16); 4785-90. ©2016 AACR.

  11. By inhibiting snail signaling and miR-23a-3p, osthole suppresses the EMT-mediated metastatic ability in prostate cancer.

    Science.gov (United States)

    Wen, Yu-Ching; Lee, Wei-Jiunn; Tan, Peng; Yang, Shun-Fa; Hsiao, Michael; Lee, Liang-Ming; Chien, Ming-Hsien

    2015-08-28

    Here we showed that Osthole, 7-methoxy-8-(3-methyl-2-butenyl) coumarin, a bioactive coumarin derivative extracted from medicinal plants, inhibited migration, invasion, epithelial to mesenchymal transition (EMT) in androgen-independent prostate cancer (AIPC) cells in vitro and metastasis of AIPC in vivo. In patients, high Snail levels were correlated with a higher histological Gleason sum and poor survival rates. Osthole inhibited the TGF-β/Akt/MAPK pathways, reduced Snail-DNA-binding activity and induced E-cadherin. We found that osthole decreased miR-23a-3p. Ectopic miR-23a-3p suppressed E-cadherin 3' untranslated region reporter activity and E-cadherin expression, and relieved the motility suppression caused by osthole treatment. PMID:26110567

  12. Breast and Prostate Cancer Cohort Consortium (BPC3)

    Science.gov (United States)

    Breast and Prostate Cancer Cohort Consortium collaborates with three genomic facilities, epidemiologists, population geneticists, and biostatisticians from multiple institutions to study hormone-related gene variants and environmental factors in breast and prostate cancers.

  13. Prostate cancer epigenetics and its clinical implications

    Directory of Open Access Journals (Sweden)

    Srinivasan Yegnasubramanian

    2016-01-01

    Full Text Available Normal cells have a level of epigenetic programming that is superimposed on the genetic code to establish and maintain their cell identity and phenotypes. This epigenetic programming can be thought as the architecture, a sort of cityscape, that is built upon the underlying genetic landscape. The epigenetic programming is encoded by a complex set of chemical marks on DNA, on histone proteins in nucleosomes, and by numerous context-specific DNA, RNA, protein interactions that all regulate the structure, organization, and function of the genome in a given cell. It is becoming increasingly evident that abnormalities in both the genetic landscape and epigenetic cityscape can cooperate to drive carcinogenesis and disease progression. Large-scale cancer genome sequencing studies have revealed that mutations in genes encoding the enzymatic machinery for shaping the epigenetic cityscape are among the most common mutations observed in human cancers, including prostate cancer. Interestingly, although the constellation of genetic mutations in a given cancer can be quite heterogeneous from person to person, there are numerous epigenetic alterations that appear to be highly recurrent, and nearly universal in a given cancer type, including in prostate cancer. The highly recurrent nature of these alterations can be exploited for development of biomarkers for cancer detection and risk stratification and as targets for therapeutic intervention. Here, we explore the basic principles of epigenetic processes in normal cells and prostate cancer cells and discuss the potential clinical implications with regards to prostate cancer biomarker development and therapy.

  14. Prostate cancer epigenetics and its clinical implications.

    Science.gov (United States)

    Yegnasubramanian, Srinivasan

    2016-01-01

    Normal cells have a level of epigenetic programming that is superimposed on the genetic code to establish and maintain their cell identity and phenotypes. This epigenetic programming can be thought as the architecture, a sort of cityscape, that is built upon the underlying genetic landscape. The epigenetic programming is encoded by a complex set of chemical marks on DNA, on histone proteins in nucleosomes, and by numerous context-specific DNA, RNA, protein interactions that all regulate the structure, organization, and function of the genome in a given cell. It is becoming increasingly evident that abnormalities in both the genetic landscape and epigenetic cityscape can cooperate to drive carcinogenesis and disease progression. Large-scale cancer genome sequencing studies have revealed that mutations in genes encoding the enzymatic machinery for shaping the epigenetic cityscape are among the most common mutations observed in human cancers, including prostate cancer. Interestingly, although the constellation of genetic mutations in a given cancer can be quite heterogeneous from person to person, there are numerous epigenetic alterations that appear to be highly recurrent, and nearly universal in a given cancer type, including in prostate cancer. The highly recurrent nature of these alterations can be exploited for development of biomarkers for cancer detection and risk stratification and as targets for therapeutic intervention. Here, we explore the basic principles of epigenetic processes in normal cells and prostate cancer cells and discuss the potential clinical implications with regards to prostate cancer biomarker development and therapy. PMID:27212125

  15. Neuroendocrine differentiation in prostate cancer – a review

    Directory of Open Access Journals (Sweden)

    R. Popescu

    2015-12-01

    Full Text Available Objectives: This review aims to provide practicing clinicians with the most recent knowledge of the biological nature of prostate cancer especially the information regarding neuroendocrine differentiation. Methods: Review of the literature using PubMed search and scientific journal publications. Results: Much progress has been made towards an understanding of the development and progression of prostate cancer. The prostate is a male accessory sex gland which produces a fraction of seminal fluid. The normal human prostate is composed of a stromal compartment (which contains: nerves, fibroblast, smooth muscle cells, macrophages surrounding glandular acins – epithelial cells. Neuroendocrine cells are one of the epithelial populations in the normal prostate and are believed to provide trophic signals trough the secretion of neuropeptides that diffuse and influence surrounding epithelial cells. Prostate cancer is the most frequently diagnosed malignancy in men. In prostate cancer, neuroendocrine cells can stimulate growth of surrounding prostate adenocarcinoma cells (proliferation of neighboring cancer cells in a paracrine manner by secretion of neuroendocrine products. Neuroendocrine prostate cancer is an aggressive variant of prostate cancer that commonly arises in later stages of castration resistant prostate cancer. The detection of neuroendocrine prostate cancer has clinical implications. These patients are often treated with platinum chemotherapy rather than with androgen receptor targeted therapies. Conclusion: This review shows the need to improve our knowledge regarding diagnostic and treatment methods of the Prostate Cancer, especially cancer cells with neuroendocrine phenotype.

  16. Methods to Predict and Lower the Risk of Prostate Cancer

    OpenAIRE

    Barbara Ercole; Dipen J Parekh

    2011-01-01

    Chemoprevention for prostate cancer (PCa) continues to generate interest from both physicians and the patient population. The goal of chemoprevention is to stop the malignant transformation of prostate cells into cancer. Multiple studies on different substances ranging from supplements to medical therapy have been undertaken. Thus far, only the studies on 5α-reductase inhibitors (the Prostate Cancer Prevention Trial [PCPT] and Reduction by Dutasteride of Prostate Cancer Events [REDUCE] trial)...

  17. Developing a nanoparticle test for prostate cancer scoring

    OpenAIRE

    Huo Qun; Litherland Sally A; Sullivan Shannon; Hallquist Hillari; Decker David A; Rivera-Ramirez Inoel

    2012-01-01

    Abstract Background Over-diagnosis and treatment of prostate cancer has been a major problem in prostate cancer care and management. Currently the most relevant prognostic factor to predict a patient's risk of death due to prostate cancer is the Gleason score of the biopsied tissue samples. However, pathological analysis is subjective, and the Gleason score is only a qualitative estimate of the cancer malignancy. Molecular biomarkers and diagnostic tests that can accurately predict prostate t...

  18. A good molecular target for prostate cancer chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Sidney R Grimes

    2011-01-01

    @@ An exciting new basic medical research study shows that inhibition of the activity of the kinesin spindle protein Eg5 effectively blocks cell division and induces cell death in prostate cancer cells.1 The potent anticancer drug S-(methoxytrityl)-L-cysteine(S(MeO)TLC)spe-cifically blocks activity of Eg5 in prostate cancer cells, arrests cell division, induces cell death during mitosis and inhibits prostate cancer cells in a mouse model of prostate cancer.

  19. Development of PROSTVAC immunotherapy in prostate cancer.

    Science.gov (United States)

    Singh, Parminder; Pal, Sumanta K; Alex, Anitha; Agarwal, Neeraj

    2015-01-01

    PROSTVAC immunotherapy is a heterologous prime-boost regimen of two different recombinant pox-virus vectors; vaccinia as the primary immunotherapy, followed by boosters employing fowlpox, to provoke immune responses against prostate-specific antigen. Both vectors contain transgenes for prostate-specific antigen and a triad of T-cell costimulatory molecules (TRICOM). In a placebo-controlled Phase II trial of men with minimally symptomatic, chemotherapy-naive metastatic castration-resistant prostate cancer, PROSTVAC was well tolerated and associated with a 44% reduction in death. With a novel mechanism of action, and excellent tolerability, PROSTVAC has the potential to dramatically alter the treatment landscape of prostate cancer, not only as a monotherapy, but also in combination with other novel agents, such as immune check point inhibitors and novel androgen receptor blockers. A Phase III trial recently completed accrual. PMID:26235179

  20. Highlights from the prostate cancer genome report

    Institute of Scientific and Technical Information of China (English)

    Shyh-Han Tan; Gyorgy Petrovics; Shiv Srivastava

    2011-01-01

    @@ Prostate cancer (Cap) is the second most frequently diagnosed cancer of men worldwide (899 000 new cases,13.6% of the total),with nearly 75% of the registered cases occurring in developed countries (644000 cases).1 Blood prostate-specific antigen test has revolutionized the early detection of Cap and organ-confined Cap is effectively managed by state-of-the-art treatments including radical prostatectomy or radiation therapy.2 In the past decade,tremendous progress has also been made in our understanding of the biology and common genomicalterations in Cap 3.4 New molecular marker assays have promise in improving CaP diagnosis.Despite these advances,major challenges remain with our ability to distinguish indolent cancers from the more aggressive cancers detected early due to widely used prostate-specific antigen test.Furthermore,development of molecular stratification of CaP for targeted and more effective therapies is critically needed.

  1. Prostatic and dietary omega-3 fatty acids and prostate cancer progression during active surveillance.

    Science.gov (United States)

    Moreel, Xavier; Allaire, Janie; Léger, Caroline; Caron, André; Labonté, Marie-Ève; Lamarche, Benoît; Julien, Pierre; Desmeules, Patrice; Têtu, Bernard; Fradet, Vincent

    2014-07-01

    The association between omega-3 (ω-3) fatty acids and prostate cancer has been widely studied. However, little is known about the impact of prostate tissue fatty acid content on prostate cancer progression. We hypothesized that compared with the estimated dietary ω-3 fatty acids intake and the ω-3 fatty acids levels measured in red blood cells (RBC), the prostate tissue ω-3 fatty acid content is more strongly related to prostate cancer progression. We present the initial observations from baseline data of a phase II clinical trial conducted in a cohort of 48 untreated men affected with low-risk prostate cancer, managed under active surveillance. These men underwent a first repeat biopsy session within 6 months after the initial diagnosis of low-risk prostate cancer, at which time 29% of the men had progressed from a Gleason score of 6 to a Gleason score of 7. At the first repeat biopsy session, fatty acid levels were assessed with a food-frequency questionnaire, and determined in the RBC and in the prostate tissue biopsy. We found that eicosapentaenoic acid (EPA) was associated with a reduced risk of prostate cancer progression when measured directly in the prostate tissue. Thus, this initial interim study analysis suggests that prostate tissue ω-3 fatty acids, especially EPA, may be protective against prostate cancer progression in men with low-risk prostate cancer.

  2. Met-Independent Hepatocyte Growth Factor-mediated regulation of cell adhesion in human prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Davis Rodney

    2006-07-01

    Full Text Available Abstract Background Prostate cancer cells communicate reciprocally with the stromal cells surrounding them, inside the prostate, and after metastasis, within the bone. Each tissue secretes factors for interpretation by the other. One stromally-derived factor, Hepatocyte Growth Factor (HGF, was found twenty years ago to regulate invasion and growth of carcinoma cells. Working with the LNCaP prostate cancer progression model, we found that these cells could respond to HGF stimulation, even in the absence of Met, the only known HGF receptor. The new HGF binding partner we find on the cell surface may help to clarify conflicts in the past literature about Met expression and HGF response in cancer cells. Methods We searched for Met or any HGF binding partner on the cells of the PC3 and LNCaP prostate cancer cell models, using HGF immobilized on agarose beads. By using mass spectrometry analyses and sequencing we have identified nucleolin protein as a novel HGF binding partner. Antibodies against nucleolin (or HGF were able to ameliorate the stimulatory effects of HGF on met-negative prostate cancer cells. Western blots, RT-PCR, and immunohistochemistry were used to assess nucleolin levels during prostate cancer progression in both LNCaP and PC3 models. Results We have identified HGF as a major signaling component of prostate stromal-conditioned media (SCM and have implicated the protein nucleolin in HGF signal reception by the LNCaP model prostate cancer cells. Antibodies that silence either HGF (in SCM or nucleolin (on the cell surfaces eliminate the adhesion-stimulatory effects of the SCM. Likewise, addition of purified HGF to control media mimics the action of SCM. C4-2, an LNCaP lineage-derived, androgen-independent human prostate cancer cell line, responds to HGF in a concentration-dependent manner by increasing its adhesion and reducing its migration on laminin substratum. These HGF effects are not due to shifts in the expression levels of

  3. COPING STRATEGIES IN PATIENTS WITH PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    J. R. Gardanova

    2015-01-01

    Full Text Available Diagnostics of psycho-emotional disorders of patients with malignant diseases of the prostate is not doubt, because timely correction contributes to the shortening of rehabilitation period and restoration of the quality of life of patients after treatment. Detection and diagnosis of prostate cancer for many patients is stressful and causes changes in the affective sphere, and manifests itself in increased levels of anxiety and depression in men. To cope with stress is possible due to the used coping strategies.Purpose. Studying the coping mechanisms in prostate cancer patients.Materials and methods. 56 men treated in FGBU "LRTS" Russian Ministry of Health. The average age was 65.7 ± 6.1 years. The average duration of the disease prostate cancer is 3 ± 2 months. All men were subjected to the standard algorithm for the evaluation of hormonal status, the PSA, taking a history, inspection and physical examination, magnetic resonance imaging and scintigraphy of bones of a skeleton. All the patients underwent laparoscopic radical prostatectomy. Psychological testing with the use of the method of "Coping test" the scale of reactive and personal anxiety for the differentiated evaluation of anxiety. Results. The most common for prostate cancer revealed constructive coping strategies are "planning solve", "selfcontrol" and "search of social support". According to the scale Spielberg–Hanin a high level of situational anxiety was revealed.Conclusion. According to the results of the research, patients with prostate cancer are likely to use constructive coping strategies, that leads to stabilization of psycho-emotional state of men and promotes more effective adaptation in the terms of stress, that is caused by treatment of prostate cancer.

  4. From Prostate to Bone: Key Players in Prostate Cancer Bone Metastasis

    OpenAIRE

    Thobe, Megan N.; Rinker-Schaeffer, Carrie W.; Clark, Robert J; Bainer, Russell O.; Prasad, Sandip M.

    2011-01-01

    Bone is the most common site for metastasis in human prostate cancer patients. Skeletal metastases are a significant cause of morbidity and mortality and overall greatly affect the quality of life of prostate cancer patients. Despite advances in our understanding of the biology of primary prostate tumors, our knowledge of how and why secondary tumors derived from prostate cancer cells preferentially localize bone remains limited. The physiochemical properties of bone, and signaling molecules ...

  5. TUMOR MARKERS IN BONE MARROW IN PATIENTS WITH PROSTATIC CANCER

    OpenAIRE

    Iwai, Akio; Ozono, Seiichiro; Tanaka, Yozo; Nagayoshi, Junichi; Hirayama, Akihide; Kumon, Toshihiko; Joko, Masanori; Hirata, Naoya; Yoshikawa, Motoyoshi; Tabata, Shoichi; Uemura, Hirotsugu; Moriya, Akira; Kaneko, Yoshiteru; Okamoto, Shinji; Hirao, Yoshihiko

    1991-01-01

    We compared prostatic specific acid phosphatase (PAP), prostatic specificantigen (PA) and γ-seminoprotein (γ-SM) levels between bone marrow and serum for the purpose of assessing of the usefulness of these tumor markers in early detection ofbone metastasis in cases with prostatic cancer. Thirty-three patients were entered into this study. Of the patients, 20 had prostatic cancer including 11 with bone metastasis, and 13 patients had benign prostatic hypertrophy (BPH) served as controls. It se...

  6. Advanced research on separating prostate cancer stem cells

    International Nuclear Information System (INIS)

    Prostate cancer is a common malignant tumor in male urinary system,and may easily develop into the hormone refractory prostate cancer which can hardly be cured. Recent studies had found that the prostate cancer stem cells may be the source of the prostate cancer's occurrence,development, metastasis and recurrence. The therapy targeting the prostate cancer stem cells may be the effective way to cure prostate cancer. But these cells is too low to be detected. The difficulty lies in the low separation efficiency of prostate cancer stem cell, so the effectively separating prostate cancer stem cells occupied the main position for the more in-depth research of prostate cancer stem cells. This paper reviews the research progress and existing problems on the several main separating methods of prostate cancer stem cells, includes the fluorescence activated cells sorting and magnetic activated cells sorting based on prostate cancer stem cell surface markers, the side-population sorting and serum-free medium sphere forming sorting based on prostate cancer stem cell's biology. (authors)

  7. The Role of FSH in Prostate Cancer: A Case Report

    OpenAIRE

    Salvatore Catarinicchia; E David Crawford

    2016-01-01

    Castrate Resistant Prostate Cancer (CRPC) is a difficult entity to treat in the spectrum of prostate cancer disease. Recently, Follicle Stimulating Hormone (FSH) has been shown to play an important part in the natural history of prostate cancer disease progression (Crawford et al., 2014). Here, we discuss a now deceased 94 year-old patient who illustrates the importance of this.

  8. 77 FR 55099 - National Prostate Cancer Awareness Month, 2012

    Science.gov (United States)

    2012-09-06

    ... preventing, detecting, and treating this terrible illness. While the causes of prostate cancer are still... Documents#0;#0; ] Proclamation 8855 of August 31, 2012 National Prostate Cancer Awareness Month, 2012 By the President of the United States of America A Proclamation Prostate cancer is among the most common...

  9. Interleukin 7 and Patient Selection in Immunotherapy for Prostate Cancer

    NARCIS (Netherlands)

    C. Schroten-Loef (Caroline)

    2013-01-01

    textabstractProstate cancer is a disease of elderly males. An increase in prostate cancer is expected in the coming years due to a growing population of men aged over 60 years of age from 475 million in 2009 to 1.6 billion in the year 2050 worldwide. Moreover, if screening for prostate cancer is tak

  10. Population based screening for prostate cancer : tumor characteristics

    NARCIS (Netherlands)

    I.W. van der Cruijsen (Ingrid W)

    2008-01-01

    markdownabstract__Abstract__ The European Randomized study of Screening for Prostate Cancer is a multi-centre randomized controlled trial to examine whether screening for prostate cancer has an effect on prostate cancer mortality. The total study cohort consists of 268.000 men in eight different Eu

  11. Organoid cultures derived from patients with advanced prostate cancer

    NARCIS (Netherlands)

    Gao, Dong; Vela, Ian; Sboner, Andrea; Iaquinta, Phillip J; Karthaus, Wouter R; Gopalan, Anuradha; Dowling, Catherine; Wanjala, Jackline N; Undvall, Eva A; Arora, Vivek K; Wongvipat, John; Kossai, Myriam; Ramazanoglu, Sinan; Barboza, Luendreo P; Di, Wei; Cao, Zhen; Zhang, Qi Fan; Sirota, Inna; Ran, Leili; MacDonald, Theresa Y; Beltran, Himisha; Mosquera, Juan-Miguel; Touijer, Karim A; Scardino, Peter T; Laudone, Vincent P; Curtis, Kristen R; Rathkopf, Dana E; Morris, Michael J; Danila, Daniel C; Slovin, Susan F; Solomon, Stephen B; Eastham, James A; Chi, Ping; Carver, Brett; Rubin, Mark A; Scher, Howard I; Clevers, Hans; Sawyers, Charles L; Chen, Yu

    2014-01-01

    The lack of in vitro prostate cancer models that recapitulate the diversity of human prostate cancer has hampered progress in understanding disease pathogenesis and therapy response. Using a 3D organoid system, we report success in long-term culture of prostate cancer from biopsy specimens and circu

  12. COPING STRATEGIES IN PATIENTS WITH PROSTATE CANCER

    OpenAIRE

    J. R. Gardanova; I. I. Abdullin; D. N. Chernov; Chernov, A. V.; Y. I. Kekteeva

    2015-01-01

    Diagnostics of psycho-emotional disorders of patients with malignant diseases of the prostate is not doubt, because timely correction contributes to the shortening of rehabilitation period and restoration of the quality of life of patients after treatment. Detection and diagnosis of prostate cancer for many patients is stressful and causes changes in the affective sphere, and manifests itself in increased levels of anxiety and depression in men. To cope with stress is possible due to the used...

  13. Measurement of quality of life in men with prostate cancer.

    Science.gov (United States)

    Albaugh, Jeffrey; Hacker, Eileen Danaher

    2008-02-01

    Prostate cancer continues to be one of the most common cancers diagnosed in men. In light of the excellent survival rates for prostate cancer, quality of life is a primary concern during and following prostate cancer treatment. Quality of life is defined and determined in multiple ways. This article explores quality of life in men with prostate cancer. Quality-of-life dimensions, measurement tools, and implications of quality of life with prostate cancer on clinical practice for oncology nurses will be presented. PMID:18258577

  14. Management of locally advanced prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Heather Payne

    2009-01-01

    The management of all stages of prostate cancer is an increasingly complex process and involves a variety of available treatments and many disciplines.Despite prostate-specific antigen (PSA) testing,the presentation of prostate cancer at a locally advanced stage is common in the UK,accounting for one-third of all new cases.There is no universally accepted definition of locally advanced prostate cancer;the term is loosely used to encompass a spectrum of disease profiles that show high-risk features.Men with high-risk prostate cancer generally have a significant risk of disease progression and cancer-related death if left untreated.High-risk patients,including those with locally advanced disease,present two specific challenges.There is a need for local control as well as a need to treat any microscopic metastases likely to be present but undetectable until disease progression.The optimal treatment approach will therefore often necessitate multiple modalities.The exact combinations,timing and intensity of treatment continue to be strongly debated.Management decisions should be made after all treatments have been discussed by a multidisciplinary team (including urologists,oncologists,radiologists,pathologists and nurse specialists) and after the balance of benefits and side effects of each therapy modality has been considered by the patient with regard to his own individual circumstances.This article reviews the current therapy options.

  15. Treatment of locally advanced prostatic cancer

    Directory of Open Access Journals (Sweden)

    Marušić Goran

    2010-01-01

    Full Text Available Introduction. A locally advanced prostate cancer is defined as a malignant process spreading beyond the prostate capsule or in seminal vesicles but without distant metastasis or regional lymph nodes invasion. Clinical classification, prediction and treatment of prostate cancer. An exact staging of clinical T3 stadium is usually difficult because of the frequent over and under staging. The risk prognostic stratification is performed through nomograms and ANN (artificial neural networks. The options for treatment are: radical prostatectomy, external radiotherapy and interstitial implantation of radioisotopes, hormonal therapy by androgen blockade. Radical prostatectomy is considered in patients with T3 stage but extensive dissection of lymph nodes, dissection of neurovascular bundle (on tumor side, total removal of seminal vesicle and sometimes resection of bladder neck are obligatory. Postoperative radiotherapy is performed in patients with invasion of seminal vesicles and capsular penetration or with prostate specific antigen value over 0.1 ng/ml, one month after the surgical treatment. Definitive radiotherapy could be used as the best treatment option considering clinical stage, Gleason score, age, starting prostate specific antigen (PSA value, concomitant diseases, life expectancy, quality of life, through multidisciplinary approach (combined with androgen deprivation. Hormonal therapy in intended for patients who are not eligible for surgical treatment or radiotherapy. Conclusion. Management of locally advanced prostate cancer is still controversial and studies for better diagnosis and new treatment modalities are ongoing.

  16. Combined androgen blockade in the treatment of advanced prostate cancer--an overview. The Scandinavian Prostatic Cancer Group

    DEFF Research Database (Denmark)

    Iversen, P

    1997-01-01

    The value of combined androgen blockade in the treatment of patients with advanced prostate cancer is still controversial. In this review by the Scandinavian Prostatic Cancer Group, the literature addressing the concept and its clinical use is critically reviewed.......The value of combined androgen blockade in the treatment of patients with advanced prostate cancer is still controversial. In this review by the Scandinavian Prostatic Cancer Group, the literature addressing the concept and its clinical use is critically reviewed....

  17. Serum estrogen levels and prostate cancer risk in the prostate cancer prevention trial: a nested case–control study

    OpenAIRE

    Yao, Song; Till, Cathee; Kristal, Alan R.; Goodman, Phyllis J.; Hsing, Ann W.; Tangen, Catherine M.; Platz, Elizabeth A.; Stanczyk, Frank Z.; Reichardt, Juergen K. V.; Tang, Li; Neuhouser, Marian L; Santella, Regina M.; William D Figg; Price, Douglas K.; Parnes, Howard L.

    2011-01-01

    Objective Finasteride reduces prostate cancer risk by blocking the conversion of testosterone to dihydrotestosterone. However, whether finasteride affects estrogens levels or change in estrogens affects prostate cancer risk is unknown. Methods These questions were investigated in a case–control study nested within the prostate cancer prevention trial (PCPT) with 1,798 biopsy-proven prostate cancer cases and 1,798 matched controls. Results Among men on placebo, no relationship of serum estroge...

  18. Diffusion tensor imaging of the prostate cancer

    International Nuclear Information System (INIS)

    Objective: To explore the diagnostic value of DTI for prostate cancer. Methods: From October 2009 to December 2010,44 patients suspected of prostate cancer received MRI and DTI. The data of MRI and DTI were analyzed retrospectively. By histopathology, prostate cancer was proved in 16 patients,and benign prostatic hyperplasia (BPH) was proved in 28 patients. Differences in ADC and FA values between prostate cancer and BPH were compared by independent samples t test. Diagnostic accuracy of FA value and ADC value for prostate cancer was analyzed by using ROC curve, and the diagnostic threshold of FA value and ADC value for prostate cancer was determined. Results: The mean FA value of the tumor regions and BPH were 0.308±0.084 and 0.203 ±0.029, respectively. The mean ADC value of the tumor regions and BPH were (0.883±0.192) × 10-3 mm2/s and ( 1.408 ±0.130) × 10-3 mm2/s, respectively. There were statistically significant differences in ADC and FA values between tumor regions and BPH (t values were 4.833 and 10.779 respectively, P<0.01). The ADC value area under curve of ROC was 0.996 (95% CI was 0.984 to 1.007); the FA value area under curve of ROC was 0.904 (95% CI was 0.812 to 0.996); Combined the FA and ADC value area under curve of ROC is 0.996 (95% CI was 0.984 to 1.007); Using the ADC value of 0.725 × 10-3 mm2/s as the ROC cut off point, the diagnostic sensitivity and specificity were 100.0% and 96.0%, respectively; Using the FA value of 0.311 as the ROC cut off point,the diagnostic sensitivity and specificity was 100.0% and 68.7%, respectively. Conclusion: DTI imaging can provide valuable information for prostate cancer diagnosis and differential diagnosis, and improve the diagnosis ability of prostate cancer. (authors)

  19. SOST Inhibits Prostate Cancer Invasion.

    Directory of Open Access Journals (Sweden)

    Bryan D Hudson

    Full Text Available Inhibitors of Wnt signaling have been shown to be involved in prostate cancer (PC metastasis; however the role of Sclerostin (Sost has not yet been explored. Here we show that elevated Wnt signaling derived from Sost deficient osteoblasts promotes PC invasion, while rhSOST has an inhibitory effect. In contrast, rhDKK1 promotes PC elongation and filopodia formation, morphological changes characteristic of an invasive phenotype. Furthermore, rhDKK1 was found to activate canonical Wnt signaling in PC3 cells, suggesting that SOST and DKK1 have opposing roles on Wnt signaling in this context. Gene expression analysis of PC3 cells co-cultured with OBs exhibiting varying amounts of Wnt signaling identified CRIM1 as one of the transcripts upregulated under highly invasive conditions. We found CRIM1 overexpression to also promote cell-invasion. These findings suggest that bone-derived Wnt signaling may enhance PC tropism by promoting CRIM1 expression and facilitating cancer cell invasion and adhesion to bone. We concluded that SOST and DKK1 have opposing effects on PC3 cell invasion and that bone-derived Wnt signaling positively contributes to the invasive phenotypes of PC3 cells by activating CRIM1 expression and facilitating PC-OB physical interaction. As such, we investigated the effects of high concentrations of SOST in vivo. We found that PC3-cells overexpressing SOST injected via the tail vein in NSG mice did not readily metastasize, and those injected intrafemorally had significantly reduced osteolysis, suggesting that targeting the molecular bone environment may influence bone metastatic prognosis in clinical settings.

  20. Population Based Screening for Prostate Cancer: prognostic findings of two subsequent screening rounds

    OpenAIRE

    Postma, Renske

    2006-01-01

    textabstractProstate cancer is nowadays the most common non-cutaneous cancer in men in the Western world. Since the introduction of Prostate Specific Antigen (PSA) testing in the last decade, prostate cancer incidence increased dramatically. In addition, the population is aging, and prostate cancer incidence increases with higher age. The dilemma of prostate cancer is that more men die with prostate cancer than from prostate cancer, as reflected by the observation that in 70% of men who are 8...

  1. ROLE OF LYCOPENE IN PREVENTING PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    Made Tami Budirejeki

    2013-11-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 Prostate cancer is the most common male cancer in the United States in 2003. Prostate cancer is the second cause of death after lung cancer. The possibility of a man suffering from prostate cancer is about 3 %. Increasing age is the main risk factor for this disease. Eighty percent of prostate cancer patients aged over 65 years. Prostate cancer occurs due to accumulation of DNA damage. There are various mechanisms that cause DNA damage, one of them is due to oxidative stress. Imbalance levels of free radicals and antioxidant in tissues causes oxidative stress. Antioxidants are substance that has ability to neutralize free radicals. One of the powerful antioxidant is lycopene. It is belived have ability to prevent prostate cancer. Various studies and reviews have been conducted to determine the role of lycopene in the prevention of prostate cancer. Although most studies have found an association between the consumption of foods that contain lycopene with a reduced risk of prostate cancer, but few studies have found no such relationship. /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

  2. Imaging of recurrent prostate cancer

    NARCIS (Netherlands)

    Futterer, J.J.

    2012-01-01

    Approximately 30\\% of patients who underwent radical prostatectomy or radiation therapy will develop biochemical recurrent disease. Biochemical recurrent disease is defined as an increase in the serum value of prostate-specific antigen (PSA) after reaching the nadir. Prostate recurrence can present

  3. Prostate radiation in non-metastatic castrate refractory prostate cancer provides an interesting insight into biology of prostate cancer

    Directory of Open Access Journals (Sweden)

    Pascoe Abigail C

    2012-03-01

    Full Text Available Abstract Background The natural history of non-metastatic castrate refractory prostate cancer is unknown and treatment options are limited. We present a retrospective review of 13 patients with locally advanced or high risk prostate cancer, initially treated with hormone monotherapy and then treated with prostate radiation after becoming castration refractory. Findings Median PSA response following prostate radiation was 67.4%. Median time to biochemical progression following radiotherapy was 15 months and to detection of metastatic disease was 18.5 months. Median survival from castration resistance (to date of death or November 2011 was 60 months, with median survival from RT 42 months. Conclusion Prostate radiation appears to be beneficial even in patients with potential micrometastatic disease, which supports the hypothesis that the primary tumour is important in the progression of prostate cancer. These results are an interesting addition to the literature on the biology of prostate cancer especially as this data is unlikely to be available in the future due to combined prostate radiation and androgen deprivation therapy now being the standard of care.

  4. Unfoldomics of prostate cancer: on the abundance and roles of intrinsically disordered proteins in prostate cancer

    Science.gov (United States)

    Landau, Kevin S; Na, Insung; Schenck, Ryan O; Uversky, Vladimir N

    2016-01-01

    Prostatic diseases such as prostate cancer and benign prostatic hyperplasia are highly prevalent among men. The number of studies focused on the abundance and roles of intrinsically disordered proteins in prostate cancer is rather limited. The goal of this study is to analyze the prevalence and degree of disorder in proteins that were previously associated with the prostate cancer pathogenesis and to compare these proteins to the entire human proteome. The analysis of these datasets provides means for drawing conclusions on the roles of disordered proteins in this common male disease. We also hope that the results of our analysis can potentially lead to future experimental studies of these proteins to find novel pathways associated with this disease. PMID:27453073

  5. Unfoldomics of prostate cancer: on the abundance and roles of intrinsically disordered proteins in prostate cancer.

    Science.gov (United States)

    Landau, Kevin S; Na, Insung; Schenck, Ryan O; Uversky, Vladimir N

    2016-01-01

    Prostatic diseases such as prostate cancer and benign prostatic hyperplasia are highly prevalent among men. The number of studies focused on the abundance and roles of intrinsically disordered proteins in prostate cancer is rather limited. The goal of this study is to analyze the prevalence and degree of disorder in proteins that were previously associated with the prostate cancer pathogenesis and to compare these proteins to the entire human proteome. The analysis of these datasets provides means for drawing conclusions on the roles of disordered proteins in this common male disease. We also hope that the results of our analysis can potentially lead to future experimental studies of these proteins to find novel pathways associated with this disease.

  6. From Prostate to Bone: Key Players in Prostate Cancer Bone Metastasis

    International Nuclear Information System (INIS)

    Bone is the most common site for metastasis in human prostate cancer patients. Skeletal metastases are a significant cause of morbidity and mortality and overall greatly affect the quality of life of prostate cancer patients. Despite advances in our understanding of the biology of primary prostate tumors, our knowledge of how and why secondary tumors derived from prostate cancer cells preferentially localize bone remains limited. The physiochemical properties of bone, and signaling molecules including specific chemokines and their receptors, are distinct in nature and function, yet play intricate and significant roles in prostate cancer bone metastasis. Examining the impact of these facets of bone metastasis in vivo remains a significant challenge, as animal models that mimic the natural history and malignant progression clinical prostate cancer are rare. The goals of this article are to discuss (1) characteristics of bone that most likely render it a favorable environment for prostate tumor cell growth, (2) chemokine signaling that is critical in the recruitment and migration of prostate cancer cells to the bone, and (3) current animal models utilized in studying prostate cancer bone metastasis. Further research is necessary to elucidate the mechanisms underlying the extravasation of disseminated prostate cancer cells into the bone and to provide a better understanding of the basis of cancer cell survival within the bone microenvironment. The development of animal models that recapitulate more closely the human clinical scenario of prostate cancer will greatly benefit the generation of better therapies

  7. Circulating Tumor Cells in Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Brian [Institute of Urology, University of Southern California, 1441 Eastlake Avenue, Suite 7416, Los Angeles, CA 90033 (United States); Rochefort, Holly [Department of Surgery, University of Southern California, 1520 San Pablo Street, HCT 4300, Los Angeles, CA 90033 (United States); Goldkorn, Amir, E-mail: agoldkor@usc.edu [Department of Internal Medicine and Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, 1441 Eastlake Avenue, Suite 3440, Los Angeles, CA 90033 (United States)

    2013-12-04

    Circulating tumor cells (CTCs) can provide a non-invasive, repeatable snapshot of an individual patient’s tumor. In prostate cancer, CTC enumeration has been extensively studied and validated as a prognostic tool and has received FDA clearance for use in monitoring advanced disease. More recently, CTC analysis has been shifting from enumeration to more sophisticated molecular characterization of captured cells, which serve as a “liquid biopsy” of the tumor, reflecting molecular changes in an individual’s malignancy over time. Here we will review the main CTC studies in advanced and localized prostate cancer, highlighting the important gains as well as the challenges posed by various approaches, and their implications for advancing prostate cancer management.

  8. Circulating Tumor Cells in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Brian Hu

    2013-12-01

    Full Text Available Circulating tumor cells (CTCs can provide a non-invasive, repeatable snapshot of an individual patient’s tumor. In prostate cancer, CTC enumeration has been extensively studied and validated as a prognostic tool and has received FDA clearance for use in monitoring advanced disease. More recently, CTC analysis has been shifting from enumeration to more sophisticated molecular characterization of captured cells, which serve as a “liquid biopsy” of the tumor, reflecting molecular changes in an individual’s malignancy over time. Here we will review the main CTC studies in advanced and localized prostate cancer, highlighting the important gains as well as the challenges posed by various approaches, and their implications for advancing prostate cancer management.

  9. [THE EVOLUTION OF MARKERS OF PROSTATE CANCER].

    Science.gov (United States)

    Peshkov, M N; Generozov, E V; Kostryukova, E S

    2016-03-01

    The implementation of biochemical laboratory tests in oncology practice increased exponentially during last decades and continues to be in progress nowadays. The application of modern molecular genetic technologies permits using diagnostic systems with greater diagnostic sensitivity and specificity. The new tests are actively implemented permitting to diagnose physical presence of tumor systemic manifestations of malignant neoplasm (cachexia, pyrexia), paraneoplastic syndromes and also to detect tumor markers. The oncomarker permits to differentiate malignant from benign tumor on the basis of quantitative differences in content of corresponding antigene-tumor marker in blood serum independently of localization of tumor nidus. The prostate cancer is a medical social problem of male population. On initial stages, this disease can take its course asymptomatically or with symptomatic conditioned by such concomitant and more prevalent pathologies as chronic prostatitis and prostate benign hyperplasia. The early diagnostic ofprostate cancer permits implementing timely radical treatment frequently contributing to total recovery of patients. The article presents detailed description of evolutionary conception of markers using in diagnostic, staging and prognostication of course of prostate cancer. The acid phosphatase was applied for the first time in early diagnostic of staging of prostate cancer in 1974. Nowadays, in century of "OMX"-technologies, in common clinical practice detection of RNA in urine of patient is used for staging diagnostic and prognostication of progression of process of tissue neotransformation. PMID:27506103

  10. Prostate cancer: a review of active surveillance

    Directory of Open Access Journals (Sweden)

    Lund L

    2014-08-01

    Full Text Available Lars Lund,1,2 Niels Svolgaard,1 Mads Hvid Poulsen1 1Department of Urology, Odense University Hospital, 2Clinical Institute, Southern University of Southern Denmark, Odense, Denmark Abstract: The objective of this paper is to review the current recommendations for active surveillance in prostate cancer from the present prospective studies. Worldwide, there are increasing numbers of men with prostate cancer. It is now accepted as standard care that a number of men with favorable-risk disease can be followed with active surveillance. In 1995, the first prospective studies were initiated to assess the feasibility of active surveillance, in which the decision to intervene was determined by prostate-specific antigen and/or histological progression. The strategy was to provide therapy individualized to the biological behavior of the cancer. Clinical trials assessing active surveillance have usually included patients younger than 70 years of age, although the guidelines have changed over time for Gleason score and prostate-specific antigen, eg, doubling time, thereby changing the indication for active treatment. The present review focuses on patient selection, prospective studies reported in the literature, and future directions. Keywords: active surveillance, prostate cancer, prospective studies, review

  11. Prostate cancer radiotherapy 2002: the way forward.

    Science.gov (United States)

    Lukka, Himu; Pickles, Tom; Morton, Gerard; Catton, Charles; Souhami, Luis; Warde, Padraig

    2005-02-01

    In November 2000, the GU Radiation Oncologists of Canada had their first meeting, "Controversies in prostate cancer radiotherapy: consensus development". The success of this meeting prompted a second meeting, held in December 2002 to discuss "The Way Forward" in prostate radiotherapy. Radiation oncologists from across Canada were brought together and integrated with key opinion leaders in prostate cancer treatment from throughout North America. The group debated current controversies including: intensity modulated radiotherapy (IMRT), external beam hypofractionation, high dose-rate brachytherapy, and hormone therapy in the management of prostate cancer. The meeting also sought to identify and prioritize clinical trial opportunities and to highlight steps required to achieve these research goals. In summary, advances involving IMRT have enabled the use of higher radiation doses without increasing morbidity. With renewed interest in hypofractionated radiation schedules, the value of hypofractionation using IMRT was discussed and initial results from ongoing clinical trials were presented. The emerging role for high dose-rate brachytherapy in higher risk patients was also discussed. Based on existing preliminary evidence the group expressed enthusiasm for further investigation of the role for brachytherapy in intermediate to high-risk patients. Despite significant advances in radiotherapy, hormone therapy continues to play an important role in prostate cancer treatment for patients with intermediate and high-risk disease. Although evidence supports the effectiveness of hormone therapy, the optimal timing, and duration of hormonal treatment are unclear. Results from ongoing clinical trials will provide insight into these questions and will assist in the design of future clinical trials.

  12. 5-Alpha reductase inhibitor use and prostate cancer survival in the Finnish Prostate Cancer Screening Trial.

    Science.gov (United States)

    Murtola, Teemu J; Karppa, Elina K; Taari, Kimmo; Talala, Kirsi; Tammela, Teuvo L J; Auvinen, Anssi

    2016-06-15

    Randomized clinical trials have shown that use of 5α-reductase inhibitors (5-ARIs) lowers overall prostate cancer (PCa) risk compared to placebo, while the proportion of Gleason 8-10 tumors is elevated. It is unknown whether this affects PCa-specific survival. We studied disease-specific survival by 5-ARI usage in a cohort of 6,537 prostate cancer cases diagnosed in the Finnish Prostate Cancer Screening Trial and linked to the national prescription database for information on medication use. Cox proportional hazards regression was used to estimate hazard ratios and 95% confidence intervals for prostate cancer-specific deaths. For comparison, survival among alpha-blocker users was also evaluated. During the median follow-up of 7.5 years after diagnosis a total of 2,478 men died; 617 due to prostate cancer and 1,861 due to other causes. The risk of prostate cancer death did not differ between 5-ARI users and nonusers (multivariable adjusted HR 0.94, 95% CI 0.72-1.24 and HR 0.98, 95% CI 0.69-1.41 for usage before and after the diagnosis, respectively). Alpha-blocker usage both before and after diagnosis was associated with increased risk of prostate cancer death (HR 1.29, 95% CI 1.08-1.54 and HR 1.56, 95% CI 1.30-1.86, respectively). The risk increase vanished in long-term alpha-blocker usage. Use of 5-ARIs does not appear to affect prostate cancer mortality when used in management of benign prostatic hyperplasia. Increased risk associated with alpha-blocker usage should prompt further exploration on the prognostic role of lower urinary tract symptoms.

  13. Preselection of A- and B- modified d-homo lactone and d-seco androstane derivatives as potent compounds with antiproliferative activity against breast and prostate cancer cells - QSAR approach and molecular docking analysis.

    Science.gov (United States)

    Kovačević, Strahinja Z; Podunavac-Kuzmanović, Sanja O; Jevrić, Lidija R; Vukić, Vladimir R; Savić, Marina P; Djurendić, Evgenija A

    2016-10-10

    The problem with trial-and-error approach in organic synthesis of targeted anticancer compounds can be successfully avoided by computational modeling of molecules, docking studies and chemometric tools. It has been proven that A- and B- modified d-homo lactone and d-seco androstane derivatives are compounds with significant antiproliferative activity against estrogen-independent breast adenocarcinoma (ER-, MDA-MB-231) and androgen-independent prostate cancer cells (AR-, PC-3). This paper presents the quantitative structure-activity relationship (QSAR) models based on artificial neural networks (ANNs) which are able to predict whether d-homo lactone and/or d-seco androstane-based compounds will express antiproliferative activity against breast cancer cells (MDA-MB-231) or not. Also, the present paper describes the molecular docking study of 3β-acetoxy-5α,6α-epoxy- (3) and 6α,7α-epoxy-1,4-dien-3-one (24) d-homo lactone androstane derivatives, as well as 4-en-3-one (15) d-seco androstane derivative, which are compounds with strong or moderate antiproliferative activity against prostate cancer cells (PC-3), and compares them with commercially available medicament for prostate cancer - abiraterone. The obtained promising results can be used as guidelines in further syntheses of novel d-homo lactone and d-seco androstane derivatives with antiproliferative activity against breast and prostate cancer cells.

  14. N-Myc Drives Neuroendocrine Prostate Cancer Initiated from Human Prostate Epithelial Cells

    OpenAIRE

    Lee, JK; Phillips, JW; Smith, BA; Park, JW; Stoyanova, T; McCaffrey, EF; Baertsch, R.; Sokolov, A.; Meyerowitz, JG; Mathis, C.; Cheng, D; Stuart, JM; Shokat, KM; Gustafson, WC; Huang, J.

    2016-01-01

    MYCN amplification and overexpression are common in neuroendocrine prostate cancer (NEPC). However, the impact of aberrant N-Myc expression in prostate tumorigenesis and the cellular origin of NEPC have not been established. We define N-Myc and activated AKT1 as oncogenic components sufficient to transform human prostate epithelial cells to prostate adenocarcinoma and NEPC with phenotypic and molecular features of aggressive, late-stage human disease. We directly show that prostate adenocarci...

  15. Glucocorticoids and prostate cancer treatment:friend or foe?

    Institute of Scientific and Technical Information of China (English)

    Bruce Montgomery; Heather H Cheng; James Drechsler; Elahe A Mostaghel

    2014-01-01

    Glucocorticoids have been used in the treatment of prostate cancer to slow disease progression, improve pain control and offset side effects of chemo-and hormonal therapy. However, they may also have the potential to drive prostate cancer growth via mutated androgen receptors or glucocorticoid receptors (GRs). In this review we examine historical and contemporary use of glucocorticoids in the treatment of prostate cancer, review potential mechanisms by which they may inhibit or drive prostate cancer growth, and describe potential means of deifning their contribution to the biology of prostate cancer.

  16. CXCL5 Promotes Prostate Cancer Progression

    Directory of Open Access Journals (Sweden)

    Lesa A Begley

    2008-03-01

    Full Text Available CXCL5 is a proangiogenic CXC-type chemokine that is an inflammatory mediator and a powerful attractant for granulocytic immune cells. Unlike many other chemokines, CXCL5 is secreted by both immune (neutrophil, monocyte, and macrophage and nonimmune (epithelial, endothelial, and fibroblastic cell types. The current study was intended to determine which of these cell types express CXCL5 in normal and malignant human prostatic tissues, whether expression levels correlated with malignancy and whether CXCL5 stimulated biologic effects consistent with a benign or malignant prostate epithelial phenotype. The results of these studies show that CXCL5 protein expression levels are concordant with prostate tumor progression, are highly associated with inflammatory infiltrate, and are frequently detected in the lumens of both benign and malignant prostate glands. Exogenous administration of CXCL5 stimulates cellular proliferation and gene transcription in both nontransformed and transformed prostate epithelial cells and induces highly aggressive prostate cancer cells to invade through synthetic basement membrane in vitro. These findings suggest that the inflammatory mediator, CXCL5, may play multiple roles in the etiology of both benign and malignant proliferative diseases in the prostate.

  17. Management of patients with advanced prostate cancer

    DEFF Research Database (Denmark)

    Gillessen, S; Omlin, A; Attard, G;

    2015-01-01

    -resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion......, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary Material, available at Annals of Oncology online. Detailed...

  18. Inuit are protected against prostate cancer

    DEFF Research Database (Denmark)

    Dewailly, Eric; Mulvad, Gert; Pedersen, Henning Sloth;

    2003-01-01

    Incidence and mortality rates for prostate cancer are reported to be low among Inuit, but this finding must be additionally supported given the difficulty of obtaining a precise medical diagnosis in the Arctic. We conducted an autopsy study in 1990–1994 among 61 deceased males representative of all...... deaths occurring in Greenland and found only one invasive prostate cancer. Histological data were available for 27 autopsies and revealed no latent carcinoma. Our results suggest that in situ carcinoma is rare among Inuit and that their traditional diet, which is rich in omega-3 polyunsaturated fatty...

  19. Prostate cancer in Denmark. Incidence, morbidity and mortality

    DEFF Research Database (Denmark)

    Brasso, K; Iversen, Peter

    1999-01-01

    been by deferred hormonal therapy. Morbidity and mortality associated with prostate cancer are analysed in a group of 1459 patients aged 55-74 years, who were diagnosed as having clinically localized prostate cancer in the 5-year period 1983 to 1987. In this group of patients prostate cancer...... is demonstrated to cause significant morbidity. Furthermore, the patients suffered significant excess mortality and loss of life expectancy.......Prostate cancer incidence and mortality rates in Denmark are reviewed for a 50-year period from 1943 to 1992. The prostate cancer incidence rate nearly tripled and prostate cancer mortality rate increased during this period. Until recently in Denmark the routine management of prostate cancer has...

  20. Gene delivery for the treatment of prostate cancer

    OpenAIRE

    Fitzgerald, Kathleen A.

    2016-01-01

    Prostate cancer is one of the most common cancers diagnosed in men. Whilst treatments for early-stage disease are largely effective, current therapies for metastatic prostate cancer, particularly for bone metastasis, offer only a few months increased lifespan at best. Hence new treatments are urgently required. Small interfering RNA (siRNA) has been investigated for the treatment of prostate cancer where it can ‘silence’ specific cancer-related genes. However the clinical application of siRNA...

  1. Pigmentation-related phenotypes and risk of prostate cancer

    OpenAIRE

    Weinstein, S J; Virtamo, J; Albanes, D

    2013-01-01

    Background: Solar ultraviolet radiation exposure has been inversely related to prostate cancer incidence and mortality, possibly mediated through vitamin D status. Pigmentation-related traits influence endogenous vitamin D synthesis and may alter risk of prostate cancer. Methods: We examined prostate cancer in relation to hair and eye colour, and skin phototype in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. Incident cancer was diagnosed in 1982 out of 20 863 men. Multi...

  2. MMP inhibition in prostate cancer.

    Science.gov (United States)

    Lokeshwar, B L

    1999-06-30

    Matrix metalloproteinases (MMPs) play a significant role during the development and metastasis of prostate cancer (CaP). CaP cells secrete high levels of MMPs and low levels of endogenous MMP inhibitors (TIMPs), thus creating an excess balance of MMPs. Established CaP cell lines that express high levels of MMPs frequently metastasize to the bone and the lungs. Drugs such as Taxol and alendronate that reduce cell motility and calcium metabolism reduce bony metastasis of xenografted CaP tumors. We tested several synthetic, nontoxic inhibitors of MMPs that can be administered orally, including doxycycline (DC) and chemically modified tetracyclines (CMTs) on CaP cells in vitro and on a rat CaP model in vivo. Among several anti-MMP agents tested, CMT-3 (6-deoxy, 6-demethyl,4-de-dimethylamino tetracycline) showed highest activity against CaP cell invasion and cell proliferation. Micromolar concentration of CMT-3 and DC inhibited both the secretion and activity of MMPs by CaP cells. When tested for in vivo efficacy in the Dunning rat CaP model by daily oral gavage, CMT-3 and DC both reduced the lung metastases (> 50%). CMT-3, but not DC, inhibited tumor incidence (55 +/- 9%) and also reduced the tumor growth rate (27 +/- 9.3%). More significantly, the drugs showed minimum systemic toxicity. Ongoing studies indicate that CMT-3 may inhibit the skeletal metastases of CaP cells and delay the onset of paraplegia due to lumbar metastases. These preclinical studies provide the basis for clinical trials of CMT-3 for the treatment of metastatic disease. PMID:10415736

  3. Reduction in the risk of prostate cancer: future directions after the Prostate Cancer Prevention Trial.

    Science.gov (United States)

    Crawford, E David; Andriole, Gerald L; Marberger, Michael; Rittmaster, Roger S

    2010-03-01

    The landmark Prostate Cancer Prevention Trial (PCPT) generated interest in the potential health benefits and cost of reducing prostate cancer risk--specifically, the potential role of 5alpha-reductase inhibitors. However, the PCPT raised several unanswered questions, including the cause and significance of the increased incidence of high-grade tumors associated with finasteride. In the present study, we review the PCPT findings and unanswered questions, next steps in this field, and ongoing prostate cancer prevention trials addressing these unanswered questions. Particular emphasis is placed on the design of the second large-scale trial of a 5alpha-reductase inhibitor, the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial. PMID:20035983

  4. Multiparametric magnetic resonance imaging predicts the presence of prostate cancer in patients with negative prostate biopsy

    OpenAIRE

    Lista, F; Castillo, Ernesto; Gimbernat, H.; Rodríguez-Barbero, José M.; Panizo, J.; Angulo Cuesta, Javier

    2015-01-01

    The objective of this study is to assess the ability of multiparametric prostate magnetic resonance imaging (mpMRI) to detect prostate cancer in patients with prior negative transrectal prostate biopsy (TPB). mpMRI (TSE-T2-w, DWI and DCE sequences) was performed on 1.5 T (Magnetom Avanto; Siemens Healthcare Solutions) in 150 patients suspicious of prostate cancer and with negative TPB. European Society of Urogenital Radiology (ESUR) criteria were used. PSA measurement (total and free), digita...

  5. Effect of endocrine treatment on voiding and prostate size in men with prostate cancer

    DEFF Research Database (Denmark)

    Klarskov, Louise L; Klarskov, Peter; Mommsen, Søren;

    2012-01-01

    The aim of this study was to assess and quantify changes in voiding parameters and prostate size in men with prostate cancer from before the start of endocrine treatment and during long-term follow-up.......The aim of this study was to assess and quantify changes in voiding parameters and prostate size in men with prostate cancer from before the start of endocrine treatment and during long-term follow-up....

  6. External beam radiation therapy for prostate cancer

    International Nuclear Information System (INIS)

    Purpose/Objectives: The intent of this course is to review the issues involved in the management of non-metastatic adenocarcinoma of the prostate. -- The value of pre-treatment prognostic factors including stage, grade and PSA value will be presented, and their value in determining therapeutic strategies will be discussed. -- Controversies involving the simulation process and treatment design will be presented. The value of CT scanning, Beams-Eye View, 3-D planning, intravesicle, intraurethral and rectal contrast will be presented. The significance of prostate and patient movement and strategies for dealing with them will be presented. -- The management of low stage, low to intermediate grade prostate cancer will be discussed. The dose, volume and timing of irradiation will be discussed as will the role of neo-adjuvant hormonal therapy, neutron irradiation and brachytherapy. The current status of radical prostatectomy and cryotherapy will be summarized. Treatment of locally advanced, poorly differentiated prostate cancer will be presented including a discussion of neo-adjuvant and adjuvant hormones, dose-escalation and neutron irradiation. -- Strategies for post-radiation failures will be presented including data on cryotherapy, salvage prostatectomy and hormonal therapy (immediate, delayed and/or intermittent). New areas for investigation will be reviewed. -- The management of patients post prostatectomy will be reviewed. Data on adjuvant radiation and therapeutic radiation for biochemical or clinically relapsed patients will be presented. This course hopes to present a realistic and pragmatic overview for treating patients with non-metastatic prostatic cancer

  7. Treatment Option Overview (Prostate Cancer)

    Science.gov (United States)

    ... This procedure is done to treat benign prostatic hypertrophy and it is sometimes done to relieve symptoms ... or part of the small intestine through weak muscles into the groin ). Inguinal hernia may occur more ...

  8. [Prostate cancer external beam radiotherapy].

    Science.gov (United States)

    de Crevoisier, R; Pommier, P; Latorzeff, I; Chapet, O; Chauvet, B; Hennequin, C

    2016-09-01

    The prostate external beam radiotherapy techniques are described, when irradiating the prostate or after prostatectomy, with and without pelvic lymph nodes. The following parts are presented: indications of radiotherapy, total dose and fractionation, planning CT image acquisition, volume of interest delineation (target volumes and organs at risk) and margins, Intensity modulated radiotherapy planning and corresponding dose-volume constraints, and finally Image guided radiotherapy. PMID:27516051

  9. The role of inflammatory mediators in the development of prostatic hyperplasia and prostate cancer

    Directory of Open Access Journals (Sweden)

    Elkahwaji JE

    2012-12-01

    Full Text Available Johny E Elkahwaji1–31Section of Urologic Surgery, 2Section of Medical Oncology and Hematology, 3Genitourinary Oncology Research Laboratory, University of Nebraska Medical Center, Omaha, NE, USAAbstract: Benign prostatic hyperplasia and prostate cancer remain the most prevalent urologic health concerns affecting elderly men in their lifetime. Only 20% of benign prostatic hyperplasia and prostate cancer cases coexist in the same zone of the prostate and require a long time for initiation and progression. While the pathogenesis of both diseases is not fully understood, benign prostatic hyperplasia and prostate cancer are thought to have a multifactorial etiology, their incidence and prevalence are indeed affected by age and hormones, and they are associated with chronic prostatic inflammation. At least 20% of all human malignancies arise in a tissue microenvironment dominated by chronic or recurrent inflammation. In prostate malignancy, chronic inflammation is an extremely common histopathologic finding; its origin remains a subject of debate and may in fact be multifactorial. Emerging insights suggest that prostate epithelium damage potentially inflicted by multiple environmental factors such as infectious agents, dietary carcinogens, and hormones triggers procarcinogenic inflammatory processes and promotes cell transformation and disease development. Also, the coincidence of chronic inflammation and tumorigenesis in the peripheral zone has recently been linked by studies identifying so-called proliferative inflammatory atrophy as a possible precursor of prostatic intraepithelial neoplasia and prostate cancer. This paper will discuss the available evidence suggesting that chronic inflammation may be involved in the development and progression of chronic prostatic disease, although a direct causal role for chronic inflammation or infection in prostatic carcinogenesis has yet to be established in humans. Further basic and clinical research in the

  10. Prostate cancer screening with PSA: new data, old debate

    Directory of Open Access Journals (Sweden)

    Stefania Sciallero

    2011-12-01

    Full Text Available Two prostate cancer screening randomised controlled trials from Europe (European Randomised Study of Screening for Prostate Cancer—ERSPC and U.S. (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Program— PLCO have been published earlier this year...

  11. PSA Screening Has Led to Overtreatment of Many Prostate Cancers

    Science.gov (United States)

    Screening for prostate cancer with the prostate-specific antigen (PSA) test has led to overtreatment of many prostate cancers, including aggressive treatments in older men considered to be at low risk for progression of the disease according to a study published in the July 26, 2010 Archives of Internal Medicine.

  12. What's wrong with chemoprevention of prostate cancer?

    Science.gov (United States)

    Justman, Stewart

    2011-12-01

    When prostate-specific antigen (PSA) testing was introduced, proponents expected it to cut prostate-cancer mortality and did not expect it to unleash an epidemic of unnecessary treatments. Now that evidence of a mortality benefit remains unclear while evidence of overtreatment in undeniable, there is understandable interest in reducing the human costs of the PSA system. Two related drugs, finasteride and dutasteride, both proven to reduce the incidence of prostate cancer and the "risk of diagnosis," are being promoted accordingly. However, if not for the flaws of the PSA system the use of these drugs for purposes of prevention would lose its rationale. Not only are the drugs in this sense dependent on a faulty system, but their own mortality benefits are as speculative as PSA's-in addition to which, they introduce new risks. PMID:22146025

  13. Prostate-specific extracellular vesicles as a novel biomarker in human prostate cancer.

    Science.gov (United States)

    Park, Yong Hyun; Shin, Hyun Woo; Jung, Ae Ryang; Kwon, Oh Sung; Choi, Yeong-Jin; Park, Jaesung; Lee, Ji Youl

    2016-01-01

    Extracellular vesicles (EVs) may play an important role in cancer development and progression. We aimed to investigate the prognostic potential of prostate-specific EVs in prostate cancer (PCa) patients. Plasma and prostate tissue were collected from patients who underwent surgery for PCa (n = 82) or benign prostatic hyperplasia (BPH, n = 28). To analyze the quantity of EVs in prostate, we performed transmission electron microscopy (TEM), immuno-TEM with CD63 and prostate-specific membrane antigen (PSMA), and immunofluorescence staining. After EV isolation from plasma, CD63 and PSMA concentration was measured using ELISA kits. PSMA-positive areas in prostate differed in patients with BPH, and low-, intermediate-, and high-risk PCa (2.4, 8.2, 17.5, 26.5%, p prostate volume (50.2 vs. 33.4 cc, p prostate-specific EVs (p = 0.085). PMID:27503267

  14. Interleukin 7 and Patient Selection in Immunotherapy for Prostate Cancer

    OpenAIRE

    Schroten-Loef, Caroline

    2013-01-01

    textabstractProstate cancer is a disease of elderly males. An increase in prostate cancer is expected in the coming years due to a growing population of men aged over 60 years of age from 475 million in 2009 to 1.6 billion in the year 2050 worldwide. Moreover, if screening for prostate cancer is taken into account, even more men will be diagnosed with this disease.[1-3] In the early disease stages, prostate cancer is a slow-growing and symptom-free malignancy. Men suffering from prostate canc...

  15. Sexual activity and the risk of prostate cancer: Review article

    Directory of Open Access Journals (Sweden)

    Ahmed Fouad Kotb

    2015-09-01

    Full Text Available Introduction: Sexual activity can affect prostate cancer pathogenesis in a variety of ways; including the proposed high androgen status, risk of sexually transmitted infections and the potential effect of retained carcinogens within the prostatic cells. Methods: PubMed review of all publications concerning sexual activity and the risk of prostate cancer was done by two researchers. Results: Few publications could be detected and data were classified as a prostate cancer risk in association with either heterosexual or homosexual activities. Conclusion: Frequent ejaculation seems to be protective from the development of prostate cancer. Multiple sexual partners may be protective from prostate cancer, excluding the risk of sexually transmitted infections. Homosexual men are at a greater risk for the diagnosis of prostate cancer.

  16. Prostate cancer postoperative nomogram scores and obesity.

    Directory of Open Access Journals (Sweden)

    Jacqueline M Major

    Full Text Available PURPOSE: Nomograms are tools used in clinical practice to predict cancer outcomes and to help make decisions regarding management of disease. Since its conception, utility of the prostate cancer nomogram has more than tripled. Limited information is available on the relation between the nomograms' predicted probabilities and obesity. The purpose of this study was to examine whether the predictions from a validated postoperative prostate cancer nomogram were associated with obesity. METHODS: We carried out a cross-sectional analysis of 1220 patients who underwent radical prostatectomy (RP in southern California from 2000 to 2008. Progression-free probabilities (PFPs were ascertained from the 10-year Kattan postoperative nomogram. Multivariable logistic regression models estimated odds ratios (ORs and 95% confidence intervals (CIs. RESULTS: In the present study, aggressive prostate cancer (Gleason ≥7, but not advanced stage, was associated with obesity (p = 0.01. After adjusting for age, black race, family history of prostate cancer and current smoking, an inverse association was observed for 10-year progression-free predictions (OR = 0.50; 95% CI = 0.28-0.90 and positive associations were observed for preoperative PSA levels (OR = 1.23; 95% CI = 1.01-1.50 and Gleason >7 (OR = 1.45; 95% CI = 1.11-1.90. CONCLUSION: Obese RP patients were more likely to have lower PFP values than non-obese patients, suggesting a higher risk of experiencing prostate cancer progression. Identifying men with potentially higher risks due to obesity may improve disease prognosis and treatment decision-making.

  17. Are we ready for prostate cancer?

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ The incidence of prostate cancer(PCa)in Western developed countries is higher than in Asia where it is presently increasing rapidly.1 Data from Shanghai and Macau2 suggest that the incidence of PCa in the Chinese population has also shown an increasing trend over the last twenty years.

  18. Radiotherapy for prostate cancer and sexual health

    NARCIS (Netherlands)

    L. Incrocci (Luca)

    2015-01-01

    textabstractSexual dysfunction is very common after treatment of prostate cancer. Radiation therapy together with radical prostatectomy is the most effective treatment for localized disease. Percentages of erectile dysfunction (ED) reported in prospective studies after external-beam radiotherapy (RT

  19. Screening for prostatic cancer. Investigational models

    DEFF Research Database (Denmark)

    Iversen, P; Torp-Pedersen, S T

    1991-01-01

    Prostatic cancer has a long natural history and a significant preclinical period, during which the disease is detectable. Thus, this common malignancy in males fulfills some of the most important criteria for initiating screening programs. However, the still enigmatic epidemiology also includes...

  20. Risk-based prostate cancer screening

    NARCIS (Netherlands)

    X.D. Zhu (Xiaoye); P.C. Albertsen (Peter); G.L. Andriole (Gerald); M.J. Roobol-Bouts (Monique); F.H. Schröder (Fritz); A.J. Vickers (Andrew)

    2012-01-01

    textabstractContext: Widespread mass screening of prostate cancer (PCa) is not recommended because the balance between benefits and harms is still not well established. The achieved mortality reduction comes with considerable harm such as unnecessary biopsies, overdiagnoses, and overtreatment. There

  1. Management of synchronous rectal and prostate cancer.

    LENUS (Irish Health Repository)

    Kavanagh, D O

    2012-11-01

    Although well described, there is limited published data related to management on the coexistence of prostate and rectal cancer. The aim of this study was to describe a single institution\\'s experience with this and propose a treatment algorithm based on the best available evidence.

  2. [Primary prevention of urologic tumors: prostate cancer].

    Science.gov (United States)

    Schmitz-Dräger, B J; Lümmen, G; Bismarck, E; Fischer, C

    2011-10-01

    Assessment of the role of vitamins and micronutrients in the primary prevention of prostate cancer has changed dramatically in the past 10 years. Efforts to confirm the efficacy of a single substance have not yet succeeded. Therefore, such recommendations should at present no longer be given. Consideration could even be given to discussing whether additional large-scale interventional studies are expedient in this regard. There is still solid evidence that a well-balanced moderate diet, reduced consumption of milk products, and an Asian or Mediterranean diet are not only beneficial for general good health but can also prevent the development of prostate cancer. This should be the focus of further epidemiological studies. Thus, one can certainly speak of a paradigm shift in the prevention of prostate cancer. In contrast, available data on chemoprevention with 5α-reductase inhibitors is unequivocal: intake of finasteride as well as dutasteride correlates with significantly decreased evidence for prostate cancer. Converting this result into urologic practice remains the topic of extensive controversy. PMID:21927877

  3. African American Men and Prostate Cancer

    Medline Plus

    Full Text Available Curtis Pettaway, M.D.: We know that black Americans have one of the highest incidences of prostate cancer in the world, and in ... not go to the doctor's. Curtis Pettaway, M.D.: Those are the individuals where the message really ...

  4. New genetic variants associated with prostate cancer

    Science.gov (United States)

    Researchers have newly identified 23 common genetic variants -- one-letter changes in DNA known as single-nucleotide polymorphisms or SNPs -- that are associated with risk of prostate cancer. These results come from an analysis of more than 10 million SNP

  5. African American Men and Prostate Cancer

    Medline Plus

    Full Text Available Curtis Pettaway, M.D.: We know that black Americans have one of the highest incidences of prostate cancer in the world, and in this country ... have even suggested that our testosterone runs higher. We really don't know. But I would strongly ...

  6. Enzalutamide in metastatic prostate cancer before chemotherapy

    DEFF Research Database (Denmark)

    Beer, Tomasz M; Armstrong, Andrew J; Rathkopf, Dana E;

    2014-01-01

    BACKGROUND: Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer in whom the disease has progressed after chemotherapy. New treatment options are needed for patients with metastatic prostate cancer who have not rece......BACKGROUND: Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer in whom the disease has progressed after chemotherapy. New treatment options are needed for patients with metastatic prostate cancer who have...... not received chemotherapy, in whom the disease has progressed despite androgen-deprivation therapy. METHODS: In this double-blind, phase 3 study, we randomly assigned 1717 patients to receive either enzalutamide (at a dose of 160 mg) or placebo once daily. The coprimary end points were radiographic progression...... at the data-cutoff date (29% reduction in the risk of death; hazard ratio, 0.71; 95% CI, 0.60 to 0.84; Pchemotherapy (hazard ratio, 0.35), the time until the first...

  7. Road to Recovery from Prostate Cancer

    Medline Plus

    Full Text Available ... in learning more about robotic prostatectomies for the treatment of prostate cancer. During the program, we would ... ask us, “Why is a prostatectomy the best treatment for me?” So, certainly we know it’s the ...

  8. The impact of obesity on prostate cancer.

    NARCIS (Netherlands)

    Roermund, J.G. van; Witjes, J.A.

    2007-01-01

    Increasing prevalence of obesity in many parts of the world emphasizes the importance of learning more about the relationship between obesity and prostate cancer (PC). The present paper reviews the impact of obesity on PC using knowledge obtained from the available literature. Search of published li

  9. Childhood height, adult height, and the risk of prostate cancer

    DEFF Research Database (Denmark)

    Bjerregaard, Lise Geisler; Aarestrup, Julie; Gamborg, Michael;

    2016-01-01

    PURPOSE: We previously showed that childhood height is positively associated with prostate cancer risk. It is, however, unknown whether childhood height exerts its effects independently of or through adult height. We investigated whether and to what extent childhood height has a direct effect...... on the risk of prostate cancer apart from adult height. METHODS: We included 5,871 men with height measured at ages 7 and 13 years in the Copenhagen School Health Records Register who also had adult (50-65 years) height measured in the Danish Diet, Cancer and Health study. Prostate cancer status was obtained...... through linkage to the Danish Cancer Registry. Direct and total effects of childhood height on prostate cancer risk were estimated from Cox regressions. RESULTS: From 1996 to 2012, 429 prostate cancers occurred. Child and adult heights were positively and significantly associated with prostate cancer risk...

  10. Accumulation of [{sup 11}C]acetate in normal prostate and benign prostatic hyperplasia: comparison with prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Takashi; Tsukamoto, Eriko; Takei, Toshiki; Shiga, Tohru; Nakada, Kunihiro; Tamaki, Nagara [Department of Nuclear Medicine, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 6, Kita-ku, Sapporo 060-8638 (Japan); Kuge, Yuji; Katoh, Chietsugu [Department of Tracer Kinetics, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Shinohara, Nobuo [Department of Nuclear Medicine, Hokkaido University Graduate School of Medicine, Sapporo (Japan)

    2002-11-01

    Carbon-11 acetate positron emission tomography (PET) has been reported to be of clinical value for the diagnosis of prostate cancer. However, no detailed analysis has yet been carried out on the physiological accumulation of [{sup 11}C]acetate in the prostate. The purpose of this study was to elucidate the physiological accumulation of [{sup 11}C]acetate in the prostate using dynamic PET. The study included 30 subjects without prostate cancer [21 with normal prostate and nine with benign prostatic hyperplasia (BPH)] and six patients with prostate cancer. A dynamic PET study was performed for 20 min after intravenous administration of 555 MBq of [{sup 11}C]acetate. The standardised uptake value (SUV) at 16-20 min post tracer administration and the early-to-late-activity ratio of the SUV (E/L ratio), which was determined by dividing the SUV{sub 6-10} {sub min} by the SUV {sub 16-20min}, were calculated to evaluate the accumulation of [ {sup 11}C]acetate. The prostate was clearly visualised and distinguished from adjacent organs in PET images in most of the cases. The SUV of the prostate (2.6 {+-}0.8) was significantly higher than that of the rectum (1.7 {+-}0.4) or bone marrow (1.3 {+-}0.3) (P <0.0001 in each case). The SUV of the normal prostate of subjects aged <50 years (3.4 {+-}0.7) was significantly higher than both the SUV for the normal prostate of subjects aged {>=}50 years (2.3 {+-}0.7) and that of subjects with BPH (2.1 {+-}0.6) (P <0.01 in each case). The primary prostate cancer in six cases was visualised by [ {sup 11}C]acetate PET. However, the difference in the SUV between subjects aged {>=}50 with normal prostate or with BPH and the patients with prostate cancer (1.9 {+-}0.6) was not statistically significant. There was also no significant difference in the E/L ratio between subjects aged {>=}50 with normal prostate (0.98 {+-}0.04) or BPH (0.96 {+-}0.08) and patients with prostate cancer (1.02 {+-}0.12). In conclusion, a normal prostate exhibits age

  11. Dynamic contrast enhanced MRI in prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Alonzi, Roberto [Marie Curie Research Wing, Mount Vernon Cancer Centre, Rickmansworth Road, Northwood, Middlesex, HA6 2RN (United Kingdom)], E-mail: robertoalonzi@btinternet.com; Padhani, Anwar R. [Paul Strickland Scanner Centre, Mount Vernon Cancer Centre, Rickmansworth Road, Northwood, Middlesex, HA6 2RN (United Kingdom); Synarc Inc. 575 Market Street, San Francisco, CA 94105 (United States)], E-mail: anwar.padhani@paulstrickland-scannercentre.org.uk; Allen, Clare [Department of Imaging, University College Hospital, London, 235 Euston Road, NW1 2BU (United Kingdom)], E-mail: clare.allen@uclh.nhs.uk

    2007-09-15

    Angiogenesis is an integral part of benign prostatic hyperplasia (BPH), is associated with prostatic intraepithelial neoplasia (PIN) and is key to the growth and for metastasis of prostate cancer. Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) using small molecular weight gadolinium chelates enables non-invasive imaging characterization of tissue vascularity. Depending on the technique used, data reflecting tissue perfusion, microvessel permeability surface area product, and extracellular leakage space can be obtained. Two dynamic MRI techniques (T{sub 2}*-weighted or susceptibility based and T{sub 1}-weighted or relaxivity enhanced methods) for prostate gland evaluations are discussed in this review with reference to biological basis of observations, data acquisition and analysis methods, technical limitations and validation. Established clinical roles of T{sub 1}-weighted imaging evaluations will be discussed including lesion detection and localisation, for tumour staging and for the detection of suspected tumour recurrence. Limitations include inadequate lesion characterisation particularly differentiating prostatitis from cancer, and in distinguishing between BPH and central gland tumours.

  12. Liposomal nanomedicines in the treatment of prostate cancer

    NARCIS (Netherlands)

    Kroon, Jan; Metselaar, Josbert M; Storm, G; van der Pluijm, Gabri

    2014-01-01

    Prostate cancer is the most common cancer type and the second leading cause of death from cancer in males. In most cases, no curative treatment options are available for metastatic castration-resistant prostate cancer as these tumors are highly resistant to chemotherapy. Targeted drug delivery, usin

  13. 78 FR 54745 - National Prostate Cancer Awareness Month, 2013

    Science.gov (United States)

    2013-09-06

    ... Documents#0;#0; ] Proclamation 9010 of August 30, 2013 National Prostate Cancer Awareness Month, 2013 By the President of the United States of America A Proclamation Among American men, prostate cancer is both the second most commonly diagnosed cancer and the second-leading cause of cancer deaths. Although...

  14. Risk of prostate, ovarian, and endometrial cancer among relatives of women with breast cancer.

    OpenAIRE

    Tulinius, H.; Egilsson, V.; Olafsdóttir, G. H.; Sigvaldason, H

    1992-01-01

    OBJECTIVE--To investigate the risk of prostate, ovarian, and endometrial cancer among relatives of patients with breast cancer. DESIGN--Cohort study of 947 pedigrees in which the proband had breast cancer, linked with the Icelandic cancer registry. SETTING--Iceland. SUBJECTS--The 947 pedigrees included 29,725 people, of whom 1539 had breast cancer, 467 had prostate cancer, 135 ovarian cancer, and 105 endometrial cancer. MAIN OUTCOME MEASURES--Risk of prostate, ovarian, and endometrial cancer ...

  15. Survival of patients with prostate cancer

    OpenAIRE

    Fabienne Camilo da Silveira Pirajá; Rafael Bandeira Lages; Uylma Assunção Costa; João Batista Mendes Teles; Viriato Campelo

    2013-01-01

    Objective: To analyze the survival after five years among patients treated of prostate cancer at Hospital São Marcos. Methods: A descriptive population-based epidemiological study performed in Teresina-PI, evaluating a hospital cohort consisting of 71 patients of Hospital São Marcos, enrolled in Hospital Cancer Registry (HCR) from 2000 to 2001, under ICD10 - C61. The variables considered in the evaluation of survival were: age group, tumor staging and skin color. The Kaplan-Meier method ...

  16. IGFBP-3 is a Metastasis Suppression Gene in Prostate Cancer

    OpenAIRE

    Mehta, Hemal H.; Gao, Qinglei; Galet, Colette; Paharkova, Vladislava; Wan, Junxiang; Said, Jonathan; Sohn, Joanne J.; Lawson, Gregory; Cohen, Pinchas; Cobb, Laura J.; Lee, Kuk-Wha

    2011-01-01

    The insulin-like growth factor binding protein IGFBP-3 is a pro-apoptotic and anti-angiogenic protein in prostate cancer (CaP). Epidemiological studies suggest that low IGFBP-3 is associated with greater risk of aggressive, metastatic prostate cancers, but in vivo functional data are lacking. Here we show that mice that are genetically deficient in IGFBP-3 exhibit weaker growth of primary prostate tumors growth but higher incidence of metastatic disease. Prostates in IGFBP-3 knockout mice (IG...

  17. ADT for prostate cancer: true love or heartbreak?

    OpenAIRE

    Efstathiou, Jason A.; Shipley, William U; Zietman, Anthony L.; Smith, Matthew R.

    2010-01-01

    The addition of hormonal therapy to radiation therapy improves survival in men with unfavorable risk prostate cancer. Yet, men with prostate cancer have higher rates of non-cancer death than the general population and most will die from causes other than their index malignancy. Co-morbid cardiovascular disease is strongly associated with cause of death and this raises the possibility that prostate cancer or its treatment increases cardiovascular disease risk and possibly mortality.

  18. Detection of infectious organisms in archival prostate cancer tissues

    OpenAIRE

    Yow, Melissa A; Tabrizi, Sepehr N.; Severi, Gianluca; Bolton, Damien M; Pedersen, John; Longano, Anthony; Suzanne M Garland; Southey, Melissa C.; Graham G Giles

    2014-01-01

    Background Seroepidemiological studies have reported associations between exposure to sexually transmitted organisms and prostate cancer risk. This study sought DNA evidence of candidate organisms in archival prostate cancer tissues with the aim of assessing if a subset of these cancers show any association with common genital infections. Methods 221 archival paraffin-embedded tissue blocks representing 128 histopathologically confirmed prostate cancers comprising 52 “aggressive” (Gleason sco...

  19. The Nrf1 and Nrf2 Balance in Oxidative Stress Regulation and Androgen Signaling in Prostate Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Schultz, Michelle A. [Department of Pharmacology, Tulane University Medical Center, 1430 Tulane Avenue, New Orleans, LA 70112 (United States); Abdel-Mageed, Asim B. [Department of Urology, Tulane University Medical Center, 1430 Tulane Avenue, New Orleans, LA 70112 (United States); Mondal, Debasis, E-mail: dmondal@tulane.edu [Department of Pharmacology, Tulane University Medical Center, 1430 Tulane Avenue, New Orleans, LA 70112 (United States)

    2010-06-21

    Reactive oxygen species (ROS) signaling has recently sparked a surge of interest as being the molecular underpinning for cancer cell survival, but the precise mechanisms involved have not been completely elucidated. This review covers the possible roles of two ROS-induced transcription factors, Nrf1 and Nrf2, and the antioxidant proteins peroxiredoxin-1 (Prx-1) and Thioredoxin-1 (Txn-1) in modulating AR expression and signaling in aggressive prostate cancer (PCa) cells. In androgen independent (AI) C4-2B cells, in comparison to the parental androgen dependent (AD) LNCaP cells, we present evidence of high Nrf1 and Prx-1 expression and low Nrf2 expression in these aggressive PCa cells. Furthermore, in DHT treated C4-2B cells, increased expression of the p65 (active) isoform of Nrf1 correlated with enhanced AR transactivation. Our findings implicate a crucial balance of Nrf1 and Nrf2 signaling in regulating AR activity in AI-PCa cells. Here we will discuss how understanding the mechanisms by which oxidative stress may affect AR signaling may aid in developing novel therapies for AI-PCa.

  20. Redefining Hormone Sensitive Disease in Advanced Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Xiaoyu Hou

    2012-01-01

    Full Text Available Prostate cancer is the most common cancer among men in the United States. For decades, the cornerstone of medical treatment for advanced prostate cancer has been hormonal therapy, intended to lower testosterone levels, known as Androgen Deprivation Therapy (ADT. The development of hormone-resistant prostate cancer (now termed castration-resistant prostate cancer:CRPC remains the key roadblock in successful long-term management of prostate cancer. New advancements in medical therapy for prostate cancer have added to the hormonal therapy armamentarium. These new therapeutic agents not only provide a survival benefit but also show potential for reversing hormonal resistance in metastatic CRPC, and thus redefining hormonally sensitive disease.

  1. Survival after radical prostatectomy for clinically localised prostate cancer

    DEFF Research Database (Denmark)

    Røder, Martin Andreas; Brasso, Klaus; Christensen, Ib Jarle;

    2014-01-01

    OBJECTIVES: To describe survival and cause of death in a nationwide cohort of Danish patients with prostate cancer undergoing radical prostatectomy (RP). To describe risk factors associated with prostate cancer mortality. PATIENTS AND METHODS: Observational study of 6489 men with localised prostate...... cancer treated with RP at six different hospitals in Denmark between 1995 and 2011. Survival was described using Kaplan-Meier estimates. Causes of death were obtained from the national registry and cross-checked with patient files. Cumulative incidence of death, any cause and prostate cancer...... cancer and 219 (66.8%) from other causes. Six patients (0.09%) died ≤30 days of RP. In multivariate analysis, cT-category was a predictor of prostate cancer death (P prostate cancer...

  2. The novel prostate cancer antigen 3 (PCA3 biomarker

    Directory of Open Access Journals (Sweden)

    Andreas Bourdoumis

    2010-12-01

    Full Text Available PCA3 is a prostate specific, nonprotein coding RNA that is significantly over expressed in prostate cancer, without any correlation to prostatic volume and/or other prostatic diseases (e.g. prostatitis. It can now easily be measured in urine with a novel transcription-mediated amplification based test. Quantification of PCA3 mRNA levels can predict the outcome of prostatic biopsies with a higher specificity rate in comparison to PSA. Several studies have demonstrated that PCA3 can be used as a prognostic marker of prostate cancer, especially in conjunction with other predictive markers. Novel PCA3-based nomograms have already been introduced into clinical practice. PCA3 test may be of valuable help in several PSA quandary situations such as negative prostatic biopsies, concomitant prostatic diseases, and active surveillance. Results from relevant clinical studies, comparative with PSA, are warranted in order to confirm the perspective of PCA3 to substitute PSA.

  3. Gossypol induces apoptosis by activating p53 in prostate cancer cells and prostate tumor-initiating cells

    OpenAIRE

    Volate, Suresh R.; Kawasaki, Brian T.; Hurt, Elaine M.; Milner, John A.; Kim, Young S.; White, Jeffrey; Farrar, William L.

    2010-01-01

    Prostate cancer (PCa) continues to represent a burgeoning medical problem in the United States. Recent studies suggest that gossypol, a bioactive phytochemical produced by cotton plants, is a promising agent against prostate cancer. The current studies were undertaken to examine the chemotherapeutic efficacy of gossypol on human prostate cancer cell lines and prostate tumor-initiating cells (pTICs). Gossypol reduced viability of three prostate cancer cell lines (LAPC4, PC3, and DU145) with an...

  4. Matrine inhibits the proliferation, invasion and migration of castration-resistant prostate cancer cells through regulation of the NF-κB signaling pathway.

    Science.gov (United States)

    Li, Qi; Lai, Yiming; Wang, Chengbin; Xu, Guibin; He, Zheng; Shang, Xiaohong; Sun, Yi; Zhang, Fan; Liu, Leyuan; Huang, Hai

    2016-01-01

    Matrine is a naturally occurring alkaloid extracted from the Chinese herb Sophora flavescens. It has been demonstrated to exhibit antiproliferative properties, promote apoptosis and inhibit cell invasion in a number of cancer cell lines. It has also been shown to improve the efficacy of chemotherapy when it is combined with other chemotherapy drugs. However, the therapeutic efficacy of matrine for prostate cancer remains poorly understood. In the present study, we showed that matrine inhibited the proliferation, migration and invasion of both DU145 and PC-3 cells in a dose- and time-dependent manner. It also reduced the cell population at S phase and increased the cell population at sub-G1 phase. The increases in both the apoptotic cell population and cell population at S and sub-G1 phases consistently indicated a pro-apoptotic effect of matrine. Decreases in levels of P65, p-P65, IKKα/β, p-IKKα/β, IKBα and p-IKBα as detected by immunoblot analysis in the matrine-treated DU145 and PC-3 cells suggested an involvement of the NF-κB signaling pathway. Therefore, it is a novel promising addition to the current arsenal of chemotherapy drugs for the treatment of androgen-independent prostate cancer.

  5. Matrine inhibits the proliferation, invasion and migration of castration-resistant prostate cancer cells through regulation of the NF-κB signaling pathway.

    Science.gov (United States)

    Li, Qi; Lai, Yiming; Wang, Chengbin; Xu, Guibin; He, Zheng; Shang, Xiaohong; Sun, Yi; Zhang, Fan; Liu, Leyuan; Huang, Hai

    2016-01-01

    Matrine is a naturally occurring alkaloid extracted from the Chinese herb Sophora flavescens. It has been demonstrated to exhibit antiproliferative properties, promote apoptosis and inhibit cell invasion in a number of cancer cell lines. It has also been shown to improve the efficacy of chemotherapy when it is combined with other chemotherapy drugs. However, the therapeutic efficacy of matrine for prostate cancer remains poorly understood. In the present study, we showed that matrine inhibited the proliferation, migration and invasion of both DU145 and PC-3 cells in a dose- and time-dependent manner. It also reduced the cell population at S phase and increased the cell population at sub-G1 phase. The increases in both the apoptotic cell population and cell population at S and sub-G1 phases consistently indicated a pro-apoptotic effect of matrine. Decreases in levels of P65, p-P65, IKKα/β, p-IKKα/β, IKBα and p-IKBα as detected by immunoblot analysis in the matrine-treated DU145 and PC-3 cells suggested an involvement of the NF-κB signaling pathway. Therefore, it is a novel promising addition to the current arsenal of chemotherapy drugs for the treatment of androgen-independent prostate cancer. PMID:26497618

  6. HUMAN PAPILLOMAVIRUS TYPES 16, 18 AND 31 SEROSTATUS AND PROSTATE CANCER RISK IN THE PROSTATE CANCER PREVENTION TRIAL

    OpenAIRE

    Sutcliffe, Siobhan; Viscidi, Raphael P.; Till, Cathee; Goodman, Phyllis J.; Hoque, Ashraful M.; Hsing, Ann W.; Thompson, Ian M; Zenilman, Jonathan M; De Marzo, Angelo M.; Platz, Elizabeth A.

    2010-01-01

    Since human papillomavirus (HPV) infection was first identified as a risk factor for cervical cancer, several seroepidemiologic and tissue-based studies have investigated HPV in relation to prostate cancer, another common genitourinary malignancy, with mixed results. To further inform this potential association, we conducted a large, prospective investigation of HPV types 16, 18, and 31 in relation to risk of prostate cancer in the Prostate Cancer Prevention Trial (PCPT). Cases were a sample ...

  7. Does length of prostate biopsy cores have an impact on diagnosis of prostate cancer?

    Science.gov (United States)

    Ergün, Müslüm; İslamoğlu, Ekrem; Yalçınkaya, Soner; Tokgöz, Hüsnü; Savaş, Murat

    2016-01-01

    Objective To investigate whether core length is a significant biopsy parameter in the detection of prostate cancer. Material and methods We retrospectively analyzed pathology reports of the specimens of 188 patients diagnosed with prostate cancer who had undergone initial transrectal ultrasound (TRUS) guided prostate biopsy, and compared biopsy core lengths of the patients with, and without prostate cancer. The biopsy specimens of prostate cancer patients were divided into 3 groups according to core length, and the data obtained were compared (Group 1; total core length 20 mm). Biopsy core lengths of the patients diagnosed as prostate cancer, and benign prostatic hyperplasia were compared, and a certain cut-off value for core length with optimal diagnostic sensitivity and specificity for prostate cancer was calculated. Results Mean age, PSA and total length of cores were 65.08±7.41 years, 9.82±6.34 ng/mL and 11.2±0.2 mm, respectively. Assessment of biopsy core lengths showed that cores with cancer (n=993, median length 12.5 mm) were significantly longer than benign cores (n=1185, median length=11.3 mm) (pcancer (odds ratio: 1.08). Conclusion Biopsy core length is one of the most important parameter that determines the quality of biopsy and detection of prostate cancer. A median sample length of 12 mm is ideal lower limit for cancer detection, and biopsy procedures which yield shorter biopsy cores should be repeated. PMID:27635285

  8. Pomegranate and Its Components as Alternative Treatment for Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Lei Wang

    2014-08-01

    Full Text Available Prostate cancer is the second leading cause of cancer deaths in men in the United States. There is a major need for less toxic but yet effective therapies to treat prostate cancer. Pomegranate fruit from the tree Punica granatum has been used for centuries for medicinal purposes and is described as “nature’s power fruit”. Recent research has shown that pomegranate juice (PJ and/or pomegranate extracts (PE significantly inhibit the growth of prostate cancer cells in culture. In preclinical murine models, PJ and/or PE inhibit growth and angiogenesis of prostate tumors. More recently, we have shown that three components of PJ, luteolin, ellagic acid and punicic acid together, have similar inhibitory effects on prostate cancer growth, angiogenesis and metastasis. Results from clinical trials are also promising. PJ and/or PE significantly prolonged the prostate specific antigen (PSA doubling time in patients with prostate cancer. In this review we discuss data on the effects of PJ and PE on prostate cancer. We also discuss the effects of specific components of the pomegranate fruit and how they have been used to study the mechanisms involved in prostate cancer progression and their potential to be used in deterring prostate cancer metastasis.

  9. Algorithms, nomograms and the detection of indolent prostate cancer

    OpenAIRE

    Roobol-Bouts, Monique

    2008-01-01

    textabstractPurpose: Prostate cancer is the most commonly diagnosed cancer in men. However, only about 12% of the men diagnosed with prostate cancer will die of their disease. Result: The serum PSA test can detect prostate cancers early, but using a PSA based cut-off indication for prostate biopsy results in unnecessary testing in app. 75-80% of the men and perhaps even more important the serum PSA test cannot tell how aggressive the cancer is. To decrease unnecessary testing different test r...

  10. Methods to Predict and Lower the Risk of Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Barbara Ercole

    2011-01-01

    Full Text Available Chemoprevention for prostate cancer (PCa continues to generate interest from both physicians and the patient population. The goal of chemoprevention is to stop the malignant transformation of prostate cells into cancer. Multiple studies on different substances ranging from supplements to medical therapy have been undertaken. Thus far, only the studies on 5α-reductase inhibitors (the Prostate Cancer Prevention Trial [PCPT] and Reduction by Dutasteride of Prostate Cancer Events [REDUCE] trial have demonstrated a reduction in the risk of PCa, while results from the Selenium and Vitamin E Cancer Prevention Trial (SELECT concluded no decreased risk for PCa with selenium or vitamin E.

  11. Incidental prostate cancer in radical cystoprostatectomy specimens

    Institute of Scientific and Technical Information of China (English)

    Xiao-Dong Jin; Zhao-Dian Chen; Bo Wang; Song-Liang Cai; Xiao-Lin Yao; Bai-Ye Jin

    2008-01-01

    Aim: To investigate the rates of prostate cancer (Pca) in radical cystoprostatectomy (RCP) specimens for bladder cancer in mainland China. To determine the follow-up outcome of patients with two concurrent cancers and identify whether prostate-specific antigen (PSA) is a useful tool for the detection of Pca prior to surgery. Methods: From January 2002 to January 2007, 264 male patients with bladder cancer underwent RCP at our center. All patients underwent digital rectal examination (DRE) and B ultrasound. Serum PSA levels were tested in 168 patients. None of the patients had any evidence of Pca before RCP. Entire prostates were embedded and sectioned at 5 mm intervals. Results: Incidental Pca was observed in 37 of 264 (14.0%) RCP specimens. Of these, 12 (32.4%) were clinically significant according to an accepted definition. The PSA levels were not significantly different between patients with Pca and those without Pca, nor between patients with significant Pca and those with insignificant Pca. Thirty-four patients with incidental Pca were followed up. During a mean follow-up period of 26 months, two patients with PSA > 4 ng/mL underwent castration. None of the patients died of Pca. Conclusion: The incidence of Pca in RCP specimens in mainland China is lower than that in most developed countries. PSA cannot identify asymptomatic Pca prior to RCP. In line with published reports, incidental Pca does not impact the prognosis of bladder cancer patients undergoing RCP.

  12. Prostate Cancer Segmentation Using Multispectral Random Walks

    Science.gov (United States)

    Artan, Yusuf; Haider, Masoom A.; Yetik, Imam Samil

    Several studies have shown the advantages of multispectral magnetic resonance imaging (MRI) as a noninvasive imaging technique for prostate cancer localization. However, a large proportion of these studies are with human readers. There is a significant inter and intra-observer variability for human readers, and it is substantially difficult for humans to analyze the large dataset of multispectral MRI. To solve these problems a few studies were proposed for fully automated cancer localization in the past. However, fully automated methods are highly sensitive to parameter selection and often may not produce desirable segmentation results. In this paper, we present a semi-supervised segmentation algorithm by extending a graph based semi-supervised random walker algorithm to perform prostate cancer segmentation with multispectral MRI. Unlike classical random walker which can be applied only to dataset of single type of MRI, we develop a new method that can be applied to multispectral images. We prove the effectiveness of the proposed method by presenting the qualitative and quantitative results of multispectral MRI datasets acquired from 10 biopsy-confirmed cancer patients. Our results demonstrate that the multispectral MRI noticeably increases the sensitivity and jakkard measures of prostate cancer localization compared to single MR images; 0.71 sensitivity and 0.56 jakkard for multispectral images compared to 0.51 sensitivity and 0.44 jakkard for single MR image based segmentation.

  13. Prostate cancer: a serious disease suitable for prevention.

    Science.gov (United States)

    Fitzpatrick, John M; Schulman, Claude; Zlotta, Alexandre R; Schröder, Fritz H

    2009-04-01

    Prostate cancer is among the most common causes of death from cancer in men, and accounts for 10% of all new male cancers worldwide. The diagnosis and treatment of prostate cancer place a substantial physical and emotional burden on patients and their families, and have considerable financial implications for healthcare providers and society. Given that the risk of prostate cancer continues to increase with age, the burden of the disease is likely to increase in line with population life-expectancy. Reducing the risk of prostate cancer has gained increasing coverage in recent years, with proof of principle shown in the Prostate Cancer Prevention Trial with the type 2 5alpha-reductase (5AR) inhibitor, finasteride. The long latency period, high disease prevalence, and significant associated morbidity and mortality make prostate cancer a suitable target for a risk-reduction approach. Several agents are under investigation for reducing the risk of prostate cancer, including selenium/vitamin E and selective oestrogen receptors modulators (e.g. toremifene). In addition, the Reduction by Dutasteride of Prostate Cancer Events trial, involving >8000 men, is evaluating the effect of the dual 5AR inhibitor, dutasteride, on the risk of developing prostate cancer. A successful risk-reduction strategy might decrease the incidence of the disease, as well as the anxiety, cost and morbidity associated with its diagnosis and treatment. PMID:19302133

  14. Multidrug resistance protein 1 localization in lipid raft domains and prostasomes in prostate cancer cell lines

    Directory of Open Access Journals (Sweden)

    Gomà A

    2014-12-01

    Full Text Available Alba Gomà,1,* Roser Mir,1–3,* Fina Martínez-Soler,1,4 Avelina Tortosa,4 August Vidal,5,6 Enric Condom,5,6 Ricardo Pérez–Tomás,6 Pepita Giménez-Bonafé1 1Departament de Ciències Fisiològiques II, Faculty of Medicine, Campus of Health Sciences of Bellvitge, Universitat de Barcelona, IDIBELL, Barcelona, Spain; 2División de Investigación Básica, Instituto Nacional de Cancerología, México DF, Mexico; 3Instituto de Física, Universidad Nacional Autónoma de México (UNAM, México DF, Mexico; 4Department of Basic Nursing, School of Nursing of the Health Campus of Bellvitge, Universitat de Barcelona, 5Department of Pathology, Hospital Universitari de Bellvitge, 6Department of Pathology and Experimental Therapeutics, Universitat de Barcelona, IDIBELL, Barcelona, Spain*These authors contributed equally to this work Background: One of the problems in prostate cancer (CaP treatment is the appearance of the multidrug resistance phenotype, in which ATP-binding cassette transporters such as multidrug resistance protein 1 (MRP1 play a role. Different localizations of the transporter have been reported, some of them related to the chemoresistant phenotype.Aim: This study aimed to compare the localization of MRP1 in three prostate cell lines (normal, androgen-sensitive, and androgen-independent in order to understand its possible role in CaP chemoresistance.Methods: MRP1 and caveolae protein markers were detected using confocal microscopy, performing colocalization techniques. Lipid raft isolation made it possible to detect these proteins by Western blot analysis. Caveolae and prostasomes were identified by electron microscopy.Results: We show that MRP1 is found in lipid raft fractions of tumor cells and that the number of caveolae increases with malignancy acquisition. MRP1 is found not only in the plasma membrane associated with lipid rafts but also in cytoplasmic accumulations colocalizing with the prostasome markers Caveolin-1 and CD59

  15. Superficial Urothelial Cancer in the Prostatic Urethra

    Directory of Open Access Journals (Sweden)

    Ziya Kirkali

    2006-01-01

    Full Text Available Transitional cell carcinoma (TCC is a multifocal disease of the urinary tract that can also involve the prostatic urethra (PU. The exact incidence of superficial involvement of the PU in patients with bladder TCC is not well known. Bladder TCC may involve the prostate in 12—40% of the patients and the degree of involvement can include urethral mucosa, ducts, acini, and stroma of the gland, which has been shown to affect the outcome. Risk factors for superficial urothelial cancer in the PU are high-grade, multifocal bladder TCC and presence of carcinoma in situ (CIS in the bladder. While visible tumors are easy to detect and resect, controversy still exists regarding the optimal technique to identify prostatic involvement by TCC. Prostatic urethral sampling by a transurethral resection biopsy or a cold-cup biopsy, particularly in the high-risk group of bladder cancer patients, has been recommended for detecting prostatic urethral involvement. Management of superficial prostatic involvement by TCC is also unclear. Currently, there is increasing recognition of the value of conservative treatment options with intravesical agents when there is superficial involvement of the PU. Particularly, intravesical bacillus Calmette-Guèrin (BCG seems to be an effective treatment alternative in the management of superficial involvement of the PU by TCC. Close follow-up by cystoscopy and PU biopsy at 3-month intervals, particularly in intermediate and high-risk patients who respond to intravesical therapy and in whom cystectomy is appropriate, is recommended in order to detect persistent tumor, recurrences, or progression.

  16. New serum biomarkers for prostate cancer diagnosis

    Directory of Open Access Journals (Sweden)

    Kailash C Chadha

    2014-01-01

    Full Text Available Background: Prostate-specific antigen (PSA is currently used as a biomarker for diagnosis and management of prostate cancer (CaP. However, PSA typically lacks the sensitivity and specificity desired of a diagnostic marker. Objective: The goal of this study was to identify an additional biomarker or a panel of biomarkers that is more sensitive and specific than PSA in differentiating benign versus malignant prostate disease and/or localized CaP versus metastatic CaP. Methods: Concurrent measurements of circulating interleukin-8 (IL-8, Tumor necrosis factor-α (TNF-α and soluble tumor necrosis factor-α receptors 1 (sTNFR1 were obtained from four groups of men: (1 Controls (2 with elevated prostate-specific antigen with a negative prostate biopsy (elPSA_negBx (3 with clinically localized CaP and (4 with castration resistant prostate cancer. Results: TNF-α Area under the receiver operating characteristic curve (AUC = 0.93 and sTNFR1 (AUC = 0.97 were strong predictors of elPSA_negBx (vs. CaP. The best predictor of elPSA_negBx vs CaP was sTNFR1 and IL-8 combined (AUC = 0.997. The strongest single predictors of localized versus metastatic CaP were TNF-α (AUC = 0.992 and PSA (AUC = 0.963 levels. Conclusions: The specificity and sensitivity of a PSA-based CaP diagnosis can be significantly enhanced by concurrent serum measurements of IL-8, TNF-α and sTNFR1. In view of the concerns about the ability of PSA to distinguish clinically relevant CaP from indolent disease, assessment of these biomarkers in the larger cohort is warranted.

  17. New serum biomarkers for prostate cancer diagnosis

    Science.gov (United States)

    Chadha, Kailash C.; Miller, Austin; Nair, Bindukumar B.; Schwartz, Stanley A.; Trump, Donald L.; Underwood, Willie

    2014-01-01

    Background Prostate-specific antigen (PSA) is currently used as a biomarker for diagnosis and management of prostate cancer (CaP). However, PSA typically lacks the sensitivity and specificity desired of a diagnostic marker. Objective The goal of this study was to identify an additional biomarker or a panel of biomarkers that is more sensitive and specific than PSA in differentiating benign versus malignant prostate disease and/or localized CaP versus metastatic CaP. Methods Concurrent measurements of circulating interleukin-8 (IL-8), Tumor necrosis factor-α (TNF-α) and soluble tumor necrosis factor-α receptors 1 (sTNFR1) were obtained from four groups of men: (1) Controls (2) with elevated prostate-specific antigen with a negative prostate biopsy (elPSA_negBx) (3) with clinically localized CaP and (4) with castration resistant prostate cancer. Results TNF-α Area under the receiver operating characteristic curve (AUC = 0.93) and sTNFR1 (AUC = 0.97) were strong predictors of elPSA_negBx (vs. CaP). The best predictor of elPSA_negBx vs CaP was sTNFR1 and IL-8 combined (AUC = 0.997). The strongest single predictors of localized versus metastatic CaP were TNF-α (AUC = 0.992) and PSA (AUC = 0.963) levels. Conclusions The specificity and sensitivity of a PSA-based CaP diagnosis can be significantly enhanced by concurrent serum measurements of IL-8, TNF-α and sTNFR1. In view of the concerns about the ability of PSA to distinguish clinically relevant CaP from indolent disease, assessment of these biomarkers in the larger cohort is warranted. PMID:25593898

  18. Oncolytic targeting of androgen-sensitive prostate tumor by the respiratory syncytial virus (RSV: consequences of deficient interferon-dependent antiviral defense

    Directory of Open Access Journals (Sweden)

    Hubbard Gene B

    2011-01-01

    Full Text Available Abstract Background Oncolytic virotherapy for cancer treatment utilizes viruses for selective infection and death of cancer cells without any adverse effect on normal cells. We previously reported that the human respiratory syncytial virus (RSV is a novel oncolytic virus against androgen-independent PC-3 human prostate cancer cells. The present study extends the result to androgen-dependent prostate cancer, and explores the underlying mechanism that triggers RSV-induced oncolysis of prostate cancer cells. Methods The oncolytic effect of RSV on androgen-sensitive LNCaP human prostate cancer cells and on androgen-independent RM1 murine prostate cancer cells was studied in vitro in culture and in vivo in a xenograft or allograft tumor model. In vitro, cell viability, infectivity and apoptosis were monitored by MTT assay, viral plaque assay and annexin V staining, respectively. In vivo studies involved virus administration to prostate tumors grown in immune compromised nude mice and in syngeneic immune competent C57BL/6J mice. Anti-tumorogenic oncolytic activity was monitored by measuring tumor volume, imaging bioluminescent tumors in live animals and performing histopathological analysis and TUNEL assay with tumors Results We show that RSV imposes a potent oncolytic effect on LNCaP prostate cancer cells. RSV infectivity was markedly higher in LNCaP cells compared to the non-tumorigenic RWPE-1 human prostate cells. The enhanced viral burden led to LNCaP cell apoptosis and growth inhibition of LNCaP xenograft tumors in nude mice. A functional host immune response did not interfere with RSV-induced oncolysis, since growth of xenograft tumors in syngeneic C57BL/6J mice from murine RM1 cells was inhibited upon RSV administration. LNCaP cells failed to activate the type-I interferon (IFNα/β-induced transcription factor STAT-1, which is required for antiviral gene expression, although these cells could produce IFN in response to RSV infection. The

  19. Oncolytic targeting of androgen-sensitive prostate tumor by the respiratory syncytial virus (RSV): consequences of deficient interferon-dependent antiviral defense

    International Nuclear Information System (INIS)

    Oncolytic virotherapy for cancer treatment utilizes viruses for selective infection and death of cancer cells without any adverse effect on normal cells. We previously reported that the human respiratory syncytial virus (RSV) is a novel oncolytic virus against androgen-independent PC-3 human prostate cancer cells. The present study extends the result to androgen-dependent prostate cancer, and explores the underlying mechanism that triggers RSV-induced oncolysis of prostate cancer cells. The oncolytic effect of RSV on androgen-sensitive LNCaP human prostate cancer cells and on androgen-independent RM1 murine prostate cancer cells was studied in vitro in culture and in vivo in a xenograft or allograft tumor model. In vitro, cell viability, infectivity and apoptosis were monitored by MTT assay, viral plaque assay and annexin V staining, respectively. In vivo studies involved virus administration to prostate tumors grown in immune compromised nude mice and in syngeneic immune competent C57BL/6J mice. Anti-tumorogenic oncolytic activity was monitored by measuring tumor volume, imaging bioluminescent tumors in live animals and performing histopathological analysis and TUNEL assay with tumors We show that RSV imposes a potent oncolytic effect on LNCaP prostate cancer cells. RSV infectivity was markedly higher in LNCaP cells compared to the non-tumorigenic RWPE-1 human prostate cells. The enhanced viral burden led to LNCaP cell apoptosis and growth inhibition of LNCaP xenograft tumors in nude mice. A functional host immune response did not interfere with RSV-induced oncolysis, since growth of xenograft tumors in syngeneic C57BL/6J mice from murine RM1 cells was inhibited upon RSV administration. LNCaP cells failed to activate the type-I interferon (IFNα/β)-induced transcription factor STAT-1, which is required for antiviral gene expression, although these cells could produce IFN in response to RSV infection. The essential role of IFN in restricting infection was further

  20. EVALUATION OF FREE-TO-TOTAL PROSTATE SPECIFIC ANTIGEN RATIO IN THE DIAGNOSIS OF PROSTATE CANCER

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    @@ It's reported that free to total prostate specific antigen ration (f/tPSA) can provide more benefit than the single use of prostate specific antigen (PSA) in the diagnosis of prostate cancer (PCa). We measured serum PSA and fPSA levels in 62 cases of benign prostatic hyperplasia (BPH) and 40 cases of PCa using radioimmunoassay, with patients' age range 59y~ 89y.

  1. A monoterpene, unique component of thyme honeys, induces apoptosis in prostate cancer cells via inhibition of NF-κB activity and IL-6 secretion.

    Science.gov (United States)

    Kassi, Eva; Chinou, Ioanna; Spilioti, Eliana; Tsiapara, Anna; Graikou, Konstantia; Karabournioti, Sofia; Manoussakis, Menelaos; Moutsatsou, Paraskevi

    2014-09-25

    We have previously demonstrated that Greek thyme honey inhibits significantly the cell viability of human prostate cancer cells. Herein, 15 thyme honey samples from several regions of Greece were submitted to phytochemical analysis for the isolation, identification and determination (through modern spectral means) of the unique thyme honey monoterpene, the compound trihydroxy ketone E-4-(1,2,4-trihydroxy-2,6,6-trimethylcyclohexyl)-but-3-en-2-one. We investigated the anti-growth and apoptotic effects of the trihydroxy ketone on PC-3 human androgen independent prostate cancer cells using MTT assay and Annexin V-FITC respectively. The molecular pathways involved to such effects were further examined by evaluating its ability to inhibit (a) the NF-κB phosphorylation (S536), (b) JNK and Akt phosphorylation (Thr183/Tyr185 and S473 respectively) and (c) IL-6 production, using ELISA method. The anti-microbial effects of the trihydroxy ketone against a panel of nine pathogenic bacteria and three fungi were also assessed. The trihydroxy ketone exerted significant apoptotic activity in PC-3 prostate cancer cells at 100 μM, while it inhibited NF-κB phosphorylation and IL-6 secretion at a concentration range 10(-6)-10(-4)M. Akt and JNK signaling were not found to participate in this process. The trihydroxy ketone exerted significant anti-microbial profile against many human pathogenic bacteria and fungi (MIC values ranged from 0.04 to 0.57 mg/ml). Conclusively, the Greek thyme honey-derived monoterpene exerted significant apoptotic activity in PC-3 cells, mediated, at least in part, through reduction of NF-κB activity and IL-6 secretion and may play a key role in the anti-growth effect of thyme honey on prostate cancer cells. PMID:24932974

  2. Does amount or type of alcohol influence the risk of prostate cancer?

    DEFF Research Database (Denmark)

    Albertsen, Katrine; Grønbaek, Morten; Strandberg-Larsen, Katrine

    2002-01-01

    Prostate cancer is one of the most common cancers among men, and it is unknown whether alcohol is associated with the development of prostate cancer.......Prostate cancer is one of the most common cancers among men, and it is unknown whether alcohol is associated with the development of prostate cancer....

  3. Efficacy of c-Met inhibitor for advanced prostate cancer

    Directory of Open Access Journals (Sweden)

    Christensen James G

    2010-10-01

    Full Text Available Abstract Background Aberrant expression of HGF/SF and its receptor, c-Met, often correlates with advanced prostate cancer. Our previous study showed that expression of c-Met in prostate cancer cells was increased after attenuation of androgen receptor (AR signalling. This suggested that current androgen ablation therapy for prostate cancer activates c-Met expression and may contribute to development of more aggressive, castration resistant prostate cancer (CRPC. Therefore, we directly assessed the efficacy of c-Met inhibition during androgen ablation on the growth and progression of prostate cancer. Methods We tested two c-Met small molecule inhibitors, PHA-665752 and PF-2341066, for anti-proliferative activity by MTS assay and cell proliferation assay on human prostate cancer cell lines with different levels of androgen sensitivity. We also used renal subcapsular and castrated orthotopic xenograft mouse models to assess the effect of the inhibitors on prostate tumor formation and progression. Results We demonstrated a dose-dependent inhibitory effect of PHA-665752 and PF-2341066 on the proliferation of human prostate cancer cells and the phosphorylation of c-Met. The effect on cell proliferation was stronger in androgen insensitive cells. The c-Met inhibitor, PF-2341066, significantly reduced growth of prostate tumor cells in the renal subcapsular mouse model and the castrated orthotopic mouse model. The effect on cell proliferation was greater following castration. Conclusions The c-Met inhibitors demonstrated anti-proliferative efficacy when combined with androgen ablation therapy for advanced prostate cancer.

  4. Laser Illumination Modality of Photoacoustic Imaging Technique for Prostate Cancer

    Science.gov (United States)

    Peng, Dong-qing; Peng, Yuan-yuan; Guo, Jian; Li, Hui

    2016-02-01

    Photoacoustic imaging (PAI) has recently emerged as a promising imaging technique for prostate cancer. But there was still a lot of challenge in the PAI for prostate cancer detection, such as laser illumination modality. Knowledge of absorbed light distribution in prostate tissue was essential since the distribution characteristic of absorbed light energy would influence the imaging depth and range of PAI. In order to make a comparison of different laser illumination modality of photoacoustic imaging technique for prostate cancer, optical model of human prostate was established and combined with Monte Carlo simulation method to calculate the light absorption distribution in the prostate tissue. Characteristic of light absorption distribution of transurethral and trans-rectal illumination case, and of tumor at different location was compared with each other.The relevant conclusions would be significant for optimizing the light illumination in a PAI system for prostate cancer detection.

  5. Absence of XMRV and closely related viruses in primary prostate cancer tissues used to derive the XMRV-infected cell line 22Rv1.

    Directory of Open Access Journals (Sweden)

    Jaydip Das Gupta

    Full Text Available The 22Rv1 cell line is widely used for prostate cancer research and other studies throughout the world. These cells were established from a human prostate tumor, CWR22, that was serially passaged in nude mice and selected for androgen independence. The 22Rv1 cells are known to produce high titers of xenotropic murine leukemia virus-related virus (XMRV. Recent studies suggested that XMRV was inadvertently created in the 1990's when two murine leukemia virus (MLV genomes (pre-XMRV1 and pre-XMRV-2 recombined during passaging of the CWR22 tumor in mice. The conclusion that XMRV originated from mice and not the patient was based partly on the failure to detect XMRV in early CWR22 xenografts. While that deduction is certainly justified, we examined the possibility that a closely related virus could have been present in primary tumor tissue. Here we report that we have located the original prostate tumor tissue excised from patient CWR22 and have assayed the corresponding DNA by PCR and the tissue sections by fluorescence in situ hybridization for the presence of XMRV or a similar virus. The primary tumor tissues lacked mouse DNA as determined by PCR for intracisternal A type particle DNA, thus avoiding one of the limitations of studying xenografts. We show that neither XMRV nor a closely related virus was present in primary prostate tissue of patient CWR22. Our findings confirm and reinforce the conclusion that XMRV is a recombinant laboratory-generated mouse virus that is highly adapted for human prostate cancer cells.

  6. Focal Therapy in the Management of Prostate Cancer: An Emerging Approach for Localized Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Takeo Nomura

    2012-01-01

    Full Text Available A widespread screening with prostate-specific antigen (PSA has led increased diagnosis of localized prostate cancer along with a reduction in the proportion of advanced-stage disease at diagnosis. Over the past decade, interest in focal therapy as a less morbid option for the treatment of localized low-risk prostate cancer has recently been renewed due to downward stage migration. Focal therapy stands midway between active surveillance and radical treatments, combining minimal morbidity with cancer control. Several techniques of focal therapy have potential for isolated ablation of a tumor focus with sparing of uninvolved surround tissue demonstrating excellent short-term cancer control and a favorable patient’s quality of life. However, to date, tissue ablation has mostly used for near-whole prostate gland ablation without taking advantage of accompanying the technological capabilities. The available ablative technologies include cryotherapy, high-intensity focused ultrasound (HIFU, and vascular-targeted photodynamic therapy (VTP. Despite the interest in focal therapy, this technology has not yet been a well-established procedure nor provided sufficient data, because of the lack of randomized trial comparing the efficacy and morbidity of the standard treatment options. In this paper we briefly summarize the recent data regarding focal therapy for prostate cancer and these new therapeutic modalities.

  7. Prostate cancer:diagnosis and staging

    Institute of Scientific and Technical Information of China (English)

    Nigel Borley; Mark R.Feneley

    2009-01-01

    Prostate cancer represents an increasing health burden.The past 20 years,with the introduction of prostate-specific antigen (PSA),has seen prostate cancer move increasingly from a condition that presented with locally advanced disease or metastases to one that is found upon screening.More is also known about the pathology of pre-malignant lesions.Diagnosis relies on trans-rectal ultrasound (TRUS) to obtain biopsies from throughout the prostate,but TRUS is not useful for staging.Imaging for staging,such as magnetic resonance imaging or computed tomography,still has a low accuracy compared with pathological specimens.Current techniques are also inaccurate in identifying lymph node and bony metastases.Nomograms have been developed from the PSA,Gleason score and clinical grading to help quantify the risk of extra-capsular extension in radical prostatectomy specimens.Improved clinical staging modalities are required for more reliable prediction of pathological stage and for monitoring of response to treatments.

  8. DNA Methylation and the HOXC6 Paradox in Prostate Cancer

    OpenAIRE

    Schulz, Wolfgang A; Masanori Yamanaka; Anna Vinarskaja; Marc Ingenwerth

    2011-01-01

    Overexpression of the classical homeobox transcription factor HOXC6 is frequent in prostate cancers and correlates with adverse clinical parameters. Since surprisingly many HOXC6 target genes are downregulated in prostate cancer, it has been posited that oncogenic effects of HOXC6 in prostate cancer may be unmasked by concurrent epigenetic downregulation of target genes exerting tumor suppressive effects. To test this hypothesis, we have studied the expression of three HOXC6 target genes, CNT...

  9. The Integrated Proactive Surveillance System for Prostate Cancer

    OpenAIRE

    Wang, Haibin; Yatawara, Mahendra; Huang, Shao-Chi; Dudley, Kevin; Szekely, Christine; Holden, Stuart; Piantadosi, Steven

    2012-01-01

    In this paper, we present the design and implementation of the integrated proactive surveillance system for prostate cancer (PASS-PC). The integrated PASS-PC is a multi-institutional web-based system aimed at collecting a variety of data on prostate cancer patients in a standardized and efficient way. The integrated PASS-PC was commissioned by the Prostate Cancer Foundation (PCF) and built through the joint of efforts by a group of experts in medical oncology, genetics, pathology, nutrition, ...

  10. Dietary Polyphenols in Prevention and Treatment of Prostate Cancer

    OpenAIRE

    Rahul K. Lall; Syed, Deeba N.; Adhami, Vaqar M.; Mohammad Imran Khan; Hasan Mukhtar

    2015-01-01

    Prostate cancer is the most prevalent disease affecting males in many Western countries, with an estimated 29,480 deaths in 2014 in the US alone. Incidence rates for prostate cancer deaths have been decreasing since the early 1990s in men of all races/ethnicities, though they remain about 60% higher in African Americans than in any other group. The relationship between dietary polyphenols and the prevention of prostate cancer has been examined previously. Although results are sometimes incons...

  11. CD4+ lymphocytes modulate prostate cancer progression in mice

    OpenAIRE

    Poutahidis, Theofilos; Rao, Varada P.; Olipitz, Werner; Taylor, Christie L.; Jackson, Erin A.; Levkovich, Tatiana; Lee, Chung Wei; Fox, James G.; Ge, Zhongming; Erdman, Susan E

    2009-01-01

    Chronic inflammation contributes to the development of prostate cancer in humans. Here, we show that male ApcMin/+ mice also develop prostate carcinoma with increasing age, mimicking that seen in humans in their 5th or 6th decade of life. Proinflammatory cytokines were significantly linked with cancer and increasing age in our mouse model; however, prostate and bowel tissues lacked evidence of inflammatory cell infiltrates other than mast cells. Lymphocytes protected against cancer, and prote...

  12. Perspectives on the Role of Isoflavones in Prostate Cancer

    OpenAIRE

    Ahmad, Aamir; Biersack, Bernhard; Li, Yiwei; Bao, Bin; Kong, Dejuan; Ali, Shadan; Banerjee, Sanjeev; Sarkar, Fazlul H

    2013-01-01

    Isoflavones have been investigated in detail for their role in the prevention and therapy of prostate cancer. This is primarily because of the overwhelming data connecting high dietary isoflavone intake with reduced risk of developing prostate cancer. A number of investigations have evaluated the mechanism(s) of anticancer action of isoflavones such as genistein, daidzein, biochanin A, equol, etc., in various prostate cancer models, both in vitro and in vivo. Genistein quickly jumped to the f...

  13. Oxidative Stress and DNA Methylation in Prostate Cancer

    OpenAIRE

    Krishna Vanaja Donkena; Young, Charles Y. F.; Tindall, Donald J.

    2010-01-01

    The protective effects of fruits, vegetables, and other foods on prostate cancer may be due to their antioxidant properties. An imbalance in the oxidative stress/antioxidant status is observed in prostate cancer patients. Genome oxidative damage in prostate cancer patients is associated with higher lipid peroxidation and lower antioxidant levels. Oxygen radicals are associated with different steps of carcinogenesis, including structural DNA damage, epigenetic changes, and protein and lipid al...

  14. Canadian Nurses’ Perspectives on Prostate Cancer Support Groups

    OpenAIRE

    Yu Ko, Wellam F.; Oliffe, John L.; Han, Christina S.; Garrett, Bernie; Henwood, Tim; Tuckett, Anthony G.; Sohrevardi, Armin

    2016-01-01

    Background: Prostate cancer support groups (PCSGs) are community-based organizations that offer information and psychosocial support to men who experience prostate cancer and their families. Nurses are well positioned to refer men to a range of psychosocial resources to help them adjust to prostate cancer; however, little is known about nurses’ perspectives on PCSGs. Objective: The aim of this study was to describe nurses’ views about PCSGs as a means to making recommendations for advancing t...

  15. Androgen receptor: structure, role in prostate cancer and drug discovery

    OpenAIRE

    Tan, MH Eileen; Li, Jun; Xu, H. Eric; Melcher, Karsten; Yong, Eu-Leong

    2014-01-01

    Androgens and androgen receptors (AR) play a pivotal role in expression of the male phenotype. Several diseases, such as androgen insensitivity syndrome (AIS) and prostate cancer, are associated with alterations in AR functions. Indeed, androgen blockade by drugs that prevent the production of androgens and/or block the action of the AR inhibits prostate cancer growth. However, resistance to these drugs often occurs after 2–3 years as the patients develop castration-resistant prostate cancer ...

  16. Identification of Biomarkers for Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2014-12-01

    Full Text Available BACKGROUND: Prostate cancer (PCa was the second most common type of cancer and the fifth leading cause of cancer-related death in men. The great challenge for physicians is being able to accurately predict PCa prognosis and treatment response in order to reduce PCa-speciic mortality while avoiding overtreatment by identifying of when to intervene, and in which patients. CONTENT: Currently, PCa prognosis and treatment decision of PCa involved digital rectal examination, Prostate-Speciic Antigens (PSA, and subsequent biopsies for histopathological staging, known as Gleason score. However, each procedure has its shortcomings. Efforts to find a better clinically meaningful and non-invasive biomarkers still developed involving proteins, circulating tumor cells, nucleic acids, and the ‘omics' approaches. SUMMARY: Biomarkers for PCa will most likely be an assay employing multiple biomarkers in combination using protein and gene microarrays, containing markers that are differentially expressed in PCa. KEYWORDS: prostate cancer, PSA, biomarkers, nomograms, miRNA, proteomic, genomic, metabolomic.

  17. Diagnosis of prostate cancer via nanotechnological approach

    Directory of Open Access Journals (Sweden)

    Kang BJ

    2015-10-01

    Full Text Available Benedict J Kang,1,2,* Minhong Jeun,1,2,* Gun Hyuk Jang,1,2 Sang Hoon Song,3 In Gab Jeong,3 Choung-Soo Kim,3 Peter C Searson,4 Kwan Hyi Lee1,2 1KIST Biomedical Research Institute, 2Department of Biomedical Engineering, Korea University of Science and Technology (UST, 3Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 4Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA *These authors contributed equally to this work Abstract: Prostate cancer is one of the leading causes of cancer-related deaths among the Caucasian adult males in Europe and the USA. Currently available diagnostic strategies for patients with prostate cancer are invasive and unpleasant and have poor accuracy. Many patients have been overly or underly treated resulting in a controversy regarding the reliability of current conventional diagnostic approaches. This review discusses the state-of-the-art research in the development of novel noninvasive prostate cancer diagnostics using nanotechnology coupled with suggested diagnostic strategies for their clinical implication.Keywords: bioassay, nanomaterial, nanodevice, PSA, non-PSA biomarker, bodily fluid

  18. Prostate Cancer Severity Associations with Neighborhood Deprivation

    Directory of Open Access Journals (Sweden)

    Charnita M. Zeigler-Johnson

    2011-01-01

    Full Text Available Background. The goal of this paper was to examine neighborhood deprivation and prostate cancer severity. Methods. We studied African American and Caucasian prostate cancer cases from the Pennsylvania State Cancer Registry. Census tract-level variables and deprivation scores were examined in relation to diagnosis stage, grade, and tumor aggressiveness. Results. We observed associations of low SES with high Gleason score among African Americans residing in neighborhoods with low educational attainment (OR = 1.34, 95% CI = 1.13–1.60, high poverty (OR = 1.39, 95% CI = 1.15–1.67, low car ownership (OR = 1.46, 95% CI = 1.20–1.78, and higher percentage of residents on public assistance (OR = 1.32, 95% = 1.08–1.62. The highest quartile of neighborhood deprivation was also associated with high Gleason score. For both Caucasians and African Americans, the highest quartile of neighborhood deprivation was associated with high Gleason score at diagnosis (OR = 1.34, 95% CI = 1.19–1.52; OR = 1.71, 95% CI = 1.21–2.40, resp.. Conclusion. Using a neighborhood deprivation index, we observed associations between high-grade prostate cancer and neighborhood deprivation in Caucasians and African-Americans.

  19. 76 FR 55551 - National Prostate Cancer Awareness Month, 2011

    Science.gov (United States)

    2011-09-07

    ... Documents#0;#0; ] Proclamation 8706 of September 1, 2011 National Prostate Cancer Awareness Month, 2011 By the President of the United States of America A Proclamation Prostate cancer is the second leading cause of cancer- related deaths among men in the United States. The weight of this illness is felt...

  20. Prostate Cancer Treatments: Different Choices for Different Men

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_160953.html Prostate Cancer Treatments: Different Choices for Different Men Survival rates are ... in fact, found that survival from localized prostate cancer was approximately 99 percent, irrespective of the treatment assigned. However, the cancer spread in 33 of ...

  1. Preventing and Treating Prostate Cancer Spread to Bone

    Science.gov (United States)

    ... options Preventing and treating prostate cancer spread to bones If prostate cancer spreads to other parts of the body, it ... a vein and settle in areas of damaged bones (like those containing cancer spread). Once there, they give off radiation that ...

  2. Can Western Based Online Prostate Cancer Risk Calculators Be Used to Predict Prostate Cancer after Prostate Biopsy for the Korean Population?

    OpenAIRE

    Lee, Dong Hoon; Jung, Ha Bum; Park, Jae Won; Kim, Kyu Hyun; Kim, Jongchan; Lee, Seung Hwan; Chung, Byung Ha

    2013-01-01

    Purpose To access the predictive value of the European Randomized Screening of Prostate Cancer Risk Calculator (ERSPC-RC) and the Prostate Cancer Prevention Trial Risk Calculator (PCPT-RC) in the Korean population. Materials and Methods We retrospectively analyzed the data of 517 men who underwent transrectal ultrasound guided prostate biopsy between January 2008 and November 2010. Simple and multiple logistic regression analysis were performed to compare the result of prostate biopsy. Area u...

  3. Isolation of Cancer Stem Cells From Human Prostate Cancer Samples

    Science.gov (United States)

    Vidal, Samuel J.; Quinn, S. Aidan; de la Iglesia-Vicente, Janis; Bonal, Dennis M.; Rodriguez-Bravo, Veronica; Firpo-Betancourt, Adolfo; Cordon-Cardo, Carlos; Domingo-Domenech, Josep

    2014-01-01

    The cancer stem cell (CSC) model has been considerably revisited over the last two decades. During this time CSCs have been identified and directly isolated from human tissues and serially propagated in immunodeficient mice, typically through antibody labeling of subpopulations of cells and fractionation by flow cytometry. However, the unique clinical features of prostate cancer have considerably limited the study of prostate CSCs from fresh human tumor samples. We recently reported the isolation of prostate CSCs directly from human tissues by virtue of their HLA class I (HLAI)-negative phenotype. Prostate cancer cells are harvested from surgical specimens and mechanically dissociated. A cell suspension is generated and labeled with fluorescently conjugated HLAI and stromal antibodies. Subpopulations of HLAI-negative cells are finally isolated using a flow cytometer. The principal limitation of this protocol is the frequently microscopic and multifocal nature of primary cancer in prostatectomy specimens. Nonetheless, isolated live prostate CSCs are suitable for molecular characterization and functional validation by transplantation in immunodeficient mice. PMID:24686446

  4. Current state of prostate cancer treatment in Jamaica.

    Science.gov (United States)

    Morrison, Belinda F; Aiken, William D; Mayhew, Richard

    2014-01-01

    Prostate cancer is the commonest cancer in Jamaica as well as the leading cause of cancer-related deaths. One report suggested that Jamaica has the highest incidence rate of prostate cancer in the world, with an age-standardised rate of 304/100,000 per year. The Caribbean region is reported to have the highest mortality rate of prostate cancer worldwide. Prostate cancer accounts for a large portion of the clinical practice for health-care practitioners in Jamaica. The Jamaica Urological Society is a professional body comprising 19 urologists in Jamaica who provide most of the care for men with prostate cancer in collaboration with medical oncologists, radiation oncologists, and a palliative care physician. The health-care system is structured in two tiers in Jamaica: public and private. The urologist-to-patient ratio is high, and this limits adequate urological care. Screening for prostate cancer is not a national policy in Jamaica. However, the Jamaica Urological Society and the Jamaica Cancer Society work synergistically to promote screening as well as to provide patient education for prostate cancer. Adequate treatment for localised prostate cancer is available in Jamaica in the forms of active surveillance, nerve-sparing radical retropubic prostatectomy, external beam radiation, and brachytherapy. However, there is a geographic maldistribution of centres that provide prostate cancer treatment, which leads to treatment delays. Also, there is difficulty in affording some treatment options in the private health-care sectors. Androgen deprivation therapy is available for treatment of locally advanced and metastatic prostate cancer and is subsidised through a programme called the National Health Fund. Second-line hormonal agents and chemotherapeutic agents are available but are costly to most of the population. The infrastructure for treatment of prostate cancer in Jamaica is good, but it requires additional technological advances as well as additional specialist

  5. Organoid culture systems for prostate epithelial and cancer tissue

    NARCIS (Netherlands)

    Drost, Jarno; Karthaus, Wouter R; Gao, Dong; Driehuis, Else; Sawyers, Charles L; Chen, Yu; Clevers, Hans

    2016-01-01

    This protocol describes a strategy for the generation of 3D prostate organoid cultures from healthy mouse and human prostate cells (either bulk or FACS-sorted single luminal and basal cells), metastatic prostate cancer lesions and circulating tumor cells. Organoids derived from healthy material cont

  6. Magnetic resonance spectroscopy-guided transperineal prostate biopsy and brachytherapy for recurrent prostate cancer.

    Science.gov (United States)

    Barnes, Agnieszka Szot; Haker, Steven J; Mulkern, Robert V; So, Minna; D'Amico, Anthony V; Tempany, Clare M

    2005-12-01

    Brachytherapy targeted to the peripheral zone with magnetic resonance imaging (MRI) guidance is a prostate cancer treatment option with potentially fewer complications than other treatments. Follow-up MRI when failure is suspected is, however, difficult because of radiation-induced changes. Furthermore, MR spectroscopy (MRS) is compromised by susceptibility artifacts from radioactive seeds in the peripheral zone. We report a case in which combined MRI/MRS was useful for the detection of prostate cancer in the transitional zone in patients previously treated with MR-guided brachytherapy. We propose that MRI/MRS can help detect recurrent prostate cancer, guide prostate biopsy, and help manage salvage treatment decisions. PMID:16360468

  7. Prostatic MR imaging. Accuracy in differentiating cancer from other prostatic disorders

    Energy Technology Data Exchange (ETDEWEB)

    Ikonen, S.; Kivisaari, L.; Tervahartiala, P. [Helsinki Univ. Central Hospital (Finland). Dept of Radiology; Vehmas, T. [Finnish Inst. of Occupational Health, Helsinki (Finland); Taari, K.; Rannikko, S. [Helsinki Univ. Central Hospital (Finland). Dept of Urology

    2001-03-01

    Purpose: We assessed the accuracy of MR imaging in differentiating between cancer and other prostatic disorders, and evaluated the diagnostic criteria for various prostatic diseases. Material and Methods: A total of 74 endorectal coil MR studies were performed on 72 patients. Twenty patients had prostatic cancer, 20 benign prostatic hyperplasia (BPH), 4 acute bacterial prostatitis, 5 chronic bacterial prostatitis (2 also belonging to the previous category), 19 chronic non-bacterial prostatitis/chronic pelvic pain syndrome, and 6 were symptomless voluntary controls. All studies were interpreted by two experienced radiologists in random order. Radiologists were blinded to all clinical data including the age of the patients. Based on MR findings, both radiologists filled in a form covering diagnostic criteria and diagnosis. Results: Accuracy in diagnosing prostate cancer was 74%. Sensitivity was 50% and specificity 83%, and positive and negative predictive values were 53 and 82%, respectively. Bacterial prostatitis showed some features similar to carcinoma. Abundant BPH rendered cancer detection more difficult. No diagnostic criterion was clearly better than the others. Interobserver agreement on the MR diagnosis ranged from moderate to good. Conclusion: Without knowledge of accurate clinical data, MR seems to be too insensitive in detecting prostate cancer to be used as a primary diagnostic tool.

  8. Europa Uomo: the European Prostate Cancer Coalition.

    Science.gov (United States)

    Hudson, Tom; Denis, Louis J

    2007-01-01

    Europa Uomo is a patient-led, non-governmental association (NGO), launched formally in Milan in 2004 with a legal base in Antwerp. As a coalition of prostate cancer patient groups with representation in 18 European countries, the NGO focusses on awareness, early detection, optimal treatment, multi-professional care and, above all, quality of life and patient advocacy. In the majority of European countries prostate cancer is the most commonly diagnosed cancer affecting men beyond middle age. The incidence and substantial mortality rises with age, peaking in the seventh decade. Standards of diagnosis and treatment vary across Europe and attitudes differ. Information about the early detection and awareness of prostate cancer available to the public leaves much to be desired. Since 2002, involved individuals, patient support groups, patients, family members, physicians, urologists, oncologists and nurses joined in the formation of an independent, international, non-profit association of patient-led prostate cancer support groups from European countries known as Europa Uomo, the European Prostate Cancer Coalition. This Coalition was legally established as an NGO in June 2004 in Milan with the headquarters and secretariat in Antwerp, Belgium. Its membership represents 18 countries by the national or regional groups listed in Table 16.1 with their respective contact persons. The coalition is led by a steering committee under the control of the annual general assembly. The steering committee members and their co-ordinates are listed in Table 16.2. Scientific advice is given by a scientific committee chaired by Prof. H. Van Poppel as the liaison officer with the European Association of Urology (EAU). The support for EAU guidelines appears on the Web site and will be linked to all members in their own language (www.cancerworld.org/europauomo). The goals and activities of Europa Uomo have been condensed in a series of slides at the request of the Eurocan+Plus collaboration to

  9. [Chemoprevention of prostate cancer - a plea].

    Science.gov (United States)

    Schmitz-Dräger, B J; Bismarck, E; Schöffski, O; Fischer, C

    2012-05-01

    The high disease prevalence, the presentation in older age, a frequently slowly progressing course of disease, and high costs make the diagnosis of and therapy for prostate cancer a special challenge for urologists. Effective prevention of the disease may help to improve some of the problems mentioned above. Two randomised, controlled studies have proved that effective chemoprevention of prostate cancer is viable using 5α-reductase inhibitors (finasteride, dutasteride). Furthermore, there is increasing evidence that other compounds, e. g., selective oestrogen receptor modulators (SERMs), NSAIDs and statins might also be effective. This review investigates potential risks and benefits of chemoprevention including a consideration of health economical aspects. The authors conclude that the options of chemoprevention should be investigated in an open and unbiased way. PMID:22639024

  10. Integrated Proteomic and Glycoproteomic Analyses of Prostate Cancer Cells Reveal Glycoprotein Alteration in Protein Abundance and Glycosylation.

    Science.gov (United States)

    Shah, Punit; Wang, Xiangchun; Yang, Weiming; Toghi Eshghi, Shadi; Sun, Shisheng; Hoti, Naseruddin; Chen, Lijun; Yang, Shuang; Pasay, Jered; Rubin, Abby; Zhang, Hui

    2015-10-01

    Prostate cancer is the most common cancer among men in the U.S. and worldwide, and androgen-deprivation therapy remains the principal treatment for patients. Although a majority of patients initially respond to androgen-deprivation therapy, most will eventually develop castration resistance. An increased understanding of the mechanisms that underline the pathogenesis of castration resistance is therefore needed to develop novel therapeutics. LNCaP and PC3 prostate cancer cell lines are models for androgen-dependence and androgen-independence, respectively. Herein, we report the comparative analysis of these two prostate cancer cell lines using integrated global proteomics and glycoproteomics. Global proteome profiling of the cell lines using isobaric tags for relative and absolute quantitation (iTRAQ) labeling and two- dimensional (2D) liquid chromatography-tandem MS (LC-MS/MS) led to the quantification of 8063 proteins. To analyze the glycoproteins, glycosite-containing peptides were isolated from the same iTRAQ-labeled peptides from the cell lines using solid phase extraction followed by LC-MS/MS analysis. Among the 1810 unique N-linked glycosite-containing peptides from 653 identified N-glycoproteins, 176 glycoproteins were observed to be different between the two cell lines. A majority of the altered glycoproteins were also observed with changes in their global protein expression levels. However, alterations in 21 differentially expressed glycoproteins showed no change at the protein abundance level, indicating that the glycosylation site occupancy was different between the two cell lines. To determine the glycosylation heterogeneity at specific glycosylation sites, we further identified and quantified 1145 N-linked glycopeptides with attached glycans in the same iTRAQ-labeled samples. These intact glycopeptides contained 67 glycan compositions and showed increased fucosylation in PC3 cells in several of the examined glycosylation sites. The increase in

  11. Ureteral Metastasis Secondary to Prostate Cancer: A Case Report.

    Science.gov (United States)

    Morales, I; Bassa, C; Pavlovic, A; Morales, C

    2016-03-01

    Prostate cancer is very frequent, but secondary ureteral metastasis are extremely rare. We present a 55 year old man with a 2 month history of right flank pain and lower urinary tract symptoms. Prostatic specific antigen of 11.3 ng/mL. Computed tomography showed right hydroureteronephrosis, a developing urinoma and right iliac adenopathies. He underwent right ureteronephrectomy, iliac lymphadenectomy and prostate biopsy. Pathology revealed prostatic carcinoma infiltrating the ureteral muscularis propria, without mucosal involvement. There are 46 reported cases of prostate cancer with ureteral metastases. Ureteral metastasis are a rare cause of renal colic and need of a high index of suspicion. PMID:26793587

  12. Ureteral Metastasis Secondary to Prostate Cancer: A Case Report

    Science.gov (United States)

    Morales, I.; Bassa, C.; Pavlovic, A.; Morales, C.

    2015-01-01

    Prostate cancer is very frequent, but secondary ureteral metastasis are extremely rare. We present a 55 year old man with a 2 month history of right flank pain and lower urinary tract symptoms. Prostatic specific antigen of 11.3 ng/mL. Computed tomography showed right hydroureteronephrosis, a developing urinoma and right iliac adenopathies. He underwent right ureteronephrectomy, iliac lymphadenectomy and prostate biopsy. Pathology revealed prostatic carcinoma infiltrating the ureteral muscularis propria, without mucosal involvement. There are 46 reported cases of prostate cancer with ureteral metastases. Ureteral metastasis are a rare cause of renal colic and need of a high index of suspicion. PMID:26793587

  13. Ureteral Metastasis Secondary to Prostate Cancer: A Case Report

    Directory of Open Access Journals (Sweden)

    I. Morales

    2016-03-01

    Full Text Available Prostate cancer is very frequent, but secondary ureteral metastasis are extremely rare. We present a 55 year old man with a 2 month history of right flank pain and lower urinary tract symptoms. Prostatic specific antigen of 11.3 ng/mL. Computed tomography showed right hydroureteronephrosis, a developing urinoma and right iliac adenopathies. He underwent right ureteronephrectomy, iliac lymphadenectomy and prostate biopsy. Pathology revealed prostatic carcinoma infiltrating the ureteral muscularis propria, without mucosal involvement. There are 46 reported cases of prostate cancer with ureteral metastases. Ureteral metastasis are a rare cause of renal colic and need of a high index of suspicion.

  14. Total antioxidant intake and prostate cancer in the Cancer of the Prostate in Sweden (CAPS) study. A case control study

    OpenAIRE

    Russnes, Kjell M; Möller, Elisabeth; Wilson, Kathryn M.; Carlsen,Monica; Blomhoff, Rune; Smeland, Sigbjørn; Adami, Hans-Olov; Grönberg, Henrik; Mucci, Lorelei A.; Bälter, Katarina

    2016-01-01

    Background The total intake of dietary antioxidants may reduce prostate cancer risk but available data are sparse and the possible role of supplements unclear. We investigated the potential association between total and dietary antioxidant intake and prostate cancer in a Swedish population. Methods We used FFQ data from 1499 cases and 1112 controls in the population based case–control study Cancer of the Prostate in Sweden (CAPS). The ferric reducing antioxidant potential (FRAP) assay was use...

  15. General Information about Prostate Cancer

    Science.gov (United States)

    ... Español 1-800-4-CANCER Live Chat Publications Dictionary Menu Contact Dictionary Search About Cancer Causes and Prevention Risk Factors ... Contacts Other Funding Find NCI funding for small business innovation, technology transfer, and contracts Training Cancer Training ...

  16. Molecular mechanisms of metastasis in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Noel W.Clarke; Claire A.Hart; Mick D.Brown

    2009-01-01

    Prostate cancer (PCa) preferentially metastasizes to the bone marrow stroma of the axial skeleton.This activity is the principal cause of PCa morbidity and mortality.The exact mechanism of PCa metastasis is currently unknown,although considerable progress has been made in determining the key players in this process.In this review,we present the current understanding of the molecular processes driving PCa metastasis to the bone.

  17. Sulforaphane increases the efficacy of anti-androgens by rapidly decreasing androgen receptor levels in prostate cancer cells.

    Science.gov (United States)

    Khurana, Namrata; Talwar, Sudha; Chandra, Partha K; Sharma, Pankaj; Abdel-Mageed, Asim B; Mondal, Debasis; Sikka, Suresh C

    2016-10-01

    Prostate cancer (PCa) cells utilize androgen for their growth. Hence, androgen deprivation therapy (ADT) using anti-androgens, e.g. bicalutamide (BIC) and enzalutamide (ENZ), is a mainstay of treatment. However, the outgrowth of castration resistant PCa (CRPC) cells remains a significant problem. These CRPC cells express androgen receptor (AR) and utilize the intratumoral androgen towards their continued growth and invasion. Sulforaphane (SFN), a naturally occurring isothiocyanate found in cruciferous vegetables, can decrease AR protein levels. In the present study, we tested the combined efficacy of anti-androgens and SFN in suppressing PCa cell growth, motility and clonogenic ability. Both androgen-dependent (LNCaP) and androgen-independent (C4-2B) cells were used to monitor the effects of BIC and ENZ, alone and in combination with SFN. Co-exposure to SFN significantly (pcell migration. In addition, long-term exposures (14 days) to much lower concentrations of these agents, SFN (0.2 µM), BIC (1 µM) and/or ENZ (0.4 µM) significantly (pcells. PMID:27499349

  18. The Effect of Interleukin-6 on the Proliferation of Prostate Cancer Cells in Vitro and the Modulation of This Procedure

    Institute of Scientific and Technical Information of China (English)

    XING Yifei; XIAO Yajun; ZHANG Qijun; LU Gongcheng

    2001-01-01

    The role of interleukin-6 (IL-6) in the growth of an androgen-independent prostate cancer cell line (PC-3m) was defined and the effect of dexamethasone, which was previously shown to modulate IL-6/IL-6 receptor (IL-6R) on this procedure was investigated. By using a pretty sensitive and specific enzyme immunoassay (ELISA), it was found that PC-3m produced certain IL-6, but there was no difference in IL-6 secretion between the group with or without dexamethasone treatment. It was also found that PC-3m cells could not be stimulated to grow by exogenous IL-6 (P>0.05), while it could be inhibited to grow by anti-IL-6 monoclonal antibody and dexamethasone with a dose-dependent fashion. Our observation indicated that IL-6 acted as an autocrine growth factor for PC-3m, and dexamethasone could inhibit cell proliferation by a mechanism independent of its effect on IL-6 mRNA expression.

  19. Discovery Radiomics for Multi-Parametric MRI Prostate Cancer Detection

    CERN Document Server

    Chung, Audrey G; Kumar, Devinder; Khalvati, Farzad; Haider, Masoom A; Wong, Alexander

    2015-01-01

    Prostate cancer is the most diagnosed form of cancer in Canadian men, and is the third leading cause of cancer death. Despite these statistics, prognosis is relatively good with a sufficiently early diagnosis, making fast and reliable prostate cancer detection crucial. As imaging-based prostate cancer screening, such as magnetic resonance imaging (MRI), requires an experienced medical professional to extensively review the data and perform a diagnosis, radiomics-driven methods help streamline the process and has the potential to significantly improve diagnostic accuracy and efficiency, and thus improving patient survival rates. These radiomics-driven methods currently rely on hand-crafted sets of quantitative imaging-based features, which are selected manually and can limit their ability to fully characterize unique prostate cancer tumour phenotype. In this study, we propose a novel \\textit{discovery radiomics} framework for generating custom radiomic sequences tailored for prostate cancer detection. Discover...

  20. Novel approaches for the molecular classification of prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Robert H. Getzenberg

    2010-01-01

    @@ Among the urologic cancers, prostate cancer is by far the most common, and it appears to have the potential to affect almost all men throughout the world as they age. A number of studies have shown that many men with prostate cancer will not die from their disease, but rather with the disease but from other causes. These men have a form of prostate cancer that is de-scribed as "very low risk" and has often been called indolent. There are however a group of men that have a form of prostate cancer that is much more aggressive and life threatening. Unlike other cancer types, we have few tools to provide for the molecular classification of prostate cancer.

  1. Controversies in proton therapy for prostate cancer.

    Science.gov (United States)

    Bryant, Curtis; Henderson, Randal H; Hoppe, Bradford S; Mendenhall, William M; Nichols, R Charles; Su, Zhong; Li, Zuofeng; Mendenhall, Nancy P

    2016-08-01

    Proton therapy (PT) for prostate cancer has been a subject of controversy over the past two decades. Because of its dosimetric advantages when compared to conventional radiation, PT has the potential to improve the therapeutic ratio in the management of prostate cancer by decreasing toxicity and improving disease control. Nevertheless, its higher costs and the current lack of level I evidence documenting improved clinical outcomes have led some to question its cost-effectiveness. A number of new PT centers have been built over the past decade, leading many stakeholders, including patients, physicians, and insurers, to demand comparative effectiveness data to support its current use. In this review, we summarize the results of recently published studies that support the safety and efficacy of PT in the treatment of prostate cancer. We also review the available cost-effectiveness data for PT and discuss the future of PT, including the current randomized trial comparing PT to intensity-modulated radiation therapy and the need for additional research that may help to establish the relative benefit of PT when compared to photon-based radiation therapy. PMID:27558255

  2. Upfront Chemotherapy for Metastatic Prostate Cancer.

    Science.gov (United States)

    Lam, Elaine T; Flaig, Thomas W

    2015-12-01

    Traditionally, androgen deprivation therapy (ADT) has been the standard initial treatment for metastatic hormone-sensitive prostate cancer (mHSPC), with chemotherapy utilized in the castration-resistant setting. Data reported from three recent clinical trials shed new light on the role of upfront docetaxel in advanced or mHSPC. Two of these studies-CHAARTED and STAMPEDE-showed significant improvement in overall survival, while the third study, GETUG-AFU 15, showed no statistical difference. The CHAARTED study showed a 13.6-month survival improvement and the STAMPEDE study showed a 10-month survival improvement with ADT plus docetaxel, compared with ADT alone, in the hormone-sensitive setting. These numbers are remarkable when compared with the 2.9-month survival benefit from docetaxel in the metastatic castration-resistant setting, which has been the standard setting for the use of docetaxel in advanced prostate cancer. In this review, we describe the historical data for chemotherapy in the perioperative and metastatic prostate cancer settings, and the recent trials that are changing the paradigm in support of docetaxel in the upfront setting. PMID:26676900

  3. [Metastatic hormone-sensitive prostate cancer].

    Science.gov (United States)

    Gravis, Gwenaelle; Salem, Naji; Walz, Jochen

    2015-01-01

    The prostate cancer in its hormone-sensitive metastatic presentation is infrequent, it is either an initial presentation of the disease or an evolution after local treatment, without castration of the biological relapse. The surgical or biological castration remains the cornerstone of the treatment. The deadline of castration initiation and its modalities of administration, intermittent or continuous rest debated but consensual on the initiation is the appearance of the symptomatic disease. The chemotherapy by docetaxel in association with the castration increases significantly the survival of the patients having a high tumoral volume. The efficacy on the whole metastatic population requires additional analyses. Clinical prognostic factors as the bone localizations (axial or appendicular), the visceral involvement (liver, lung) are determining for the survival of these patients. Biological prognostic factors are in evaluation. Except the clodronate acid, which showed a survival improvement in the hormone-sensitive metastatic prostate cancer (HSMPC), the other treatments targeting the bone (zoledronic acid, rank-ligand inhibitor) demonstrated a benefit only in castrate resistant metastatic prostate cancer (MCRPC). The management of local disease lets suggest a benefit to at least symptomatic disease, but it requires to be estimated prospectively in clinical trials. The new hormonal treatments targeting the androgen receptor in CPMRC are in evaluation in CPMHS. The objective is to increase the survival and the quality of life of the CPMHS and to delay the evolution towards the castration resistant metastatic disease. PMID:25609491

  4. The diagnostic value of transrectal ultrasonographic features in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Xiaoli Zou; Guang Yang; Hui Wang

    2012-01-01

    Objective: The aim of the study was to detect the valuable ultrasonographic features in diagnosing prostate cancer.Methods: The patients who underwent transrectal ultrasound in the period from May 2005 to October 2009 at the 1st Affiliated Hospital of Dalian Medical University, China, were included, with needle biopsy diagnosis for patients with the prostate cancer and prostatic hyperplasia.Seventy-four cases of prostate cancer were diagnosed as adenocarcinoma, compared with 51 cases diagnosed as prostatic hyperplasia.Retrospective analysis of patients with transrectal ultrasound were done, comparing the difference between the two groups in the echo level (hypoechogenic), outlines (ill-defined margin), posterior acoustic attenuation, periphery halo, microcalcification incidence, the blood supply level, peak systolic velocity (Vs) and resistance index (RI).Results: The ratios of hypoechogenic lesions in the prostate cancer group and prostatic hyperplasia group were 56.76% and 35.90%, respectively (P 0.05).Vs of the two groups were (44.00 ± 15.30) cm/s and (17.32 ± 4.65) cm/s, respectively (P < 0.05).RI of the two groups were 0.76 ± 0.10, and 0.51 ± 0.03 respectively (P < 0.05).The significant correlation was designated in the blood supply level between the prostate cancer group and prostatic hyperplasia group (r = -0.388, P < 0.01).Higher revascularization grade was seen in the prostate cancer group compared to benign prostatic hyperplasia group.Conclusion: (1) The significant roles for diagnosing prostate cancer are hypoechogenic, irregular outlines, spiculation, microcalcification, high revascularization grade, posterior acoustic attenuation, high Vs and high RI.(2) It could not help in diagnosing prostate cancer with ultrasonographic periphery halo or not.

  5. Targeted prostate biopsy and MR-guided therapy for prostate cancer.

    Science.gov (United States)

    Woodrum, David A; Kawashima, Akira; Gorny, Krzysztof R; Mynderse, Lance A

    2016-05-01

    Prostate cancer is the most commonly diagnosed noncutaneous cancer and second-leading cause of death in men. Many patients with clinically organ-confined prostate cancer undergo definitive treatment of the whole gland including radical prostatectomy, radiation therapy, and cryosurgery. Active surveillance is a growing alternative option for patients with documented low-volume, low-grade prostate cancer. With recent advances in software and hardware of MRI, multiparametric MRI of the prostate has been shown to improve the accuracy in detecting and characterizing clinically significant prostate cancer. Targeted biopsy is increasingly utilized to improve the yield of MR-detected, clinically significant prostate cancer and to decrease in detection of indolent prostate cancer. MR-guided targeted biopsy techniques include cognitive MR fusion TRUS biopsy, in-bore transrectal targeted biopsy using robotic transrectal device, and in-bore direct MR-guided transperineal biopsy with a software-based transperineal grid template. In addition, advances in MR compatible thermal ablation technology allow accurate focal or regional delivery of optimal thermal energy to the biopsy-proved, MRI-detected tumor, utilizing cryoablation, laser ablation, high-intensity focused ultrasound ablation under MR guidance and real-time or near simultaneous monitoring of the ablation zone. Herein we present a contemporary review of MR-guided targeted biopsy techniques of MR-detected lesions as well as MR-guided focal or regional thermal ablative therapies for localized naïve and recurrent cancerous foci of the prostate. PMID:26907717

  6. Survival of patients with prostate cancer

    OpenAIRE

    Fabienne Camilo da Silveira Pirajá; Rafael Bandeira Lages; Uylma Assunção Costa; João Batista Mendes Teles; Viriato Campelo

    2013-01-01

    Objective: To analyze the survival after five years among patients treated of prostate cancer at Hospital São Marcos. Methods: A descriptive population-based epidemiological study performed in Teresina-PI, evaluating a hospital cohort consisting of 71 patients of Hospital São Marcos, enrolled in Hospital Cancer Registry (HCR) from 2000 to 2001, under ICD10 -C61. The variables considered in the evaluation of survival were: age group, tumor staging and skin color. The Kaplan-Meier method was us...

  7. Molecular diagnosis of prostate cancer: Topical issues

    Directory of Open Access Journals (Sweden)

    E. N. Knyazev

    2014-01-01

    Full Text Available Prostate cancer (PC is the second most common cancer and the fifth highest malignancy mortality rate in men worldwide. Although PC is detectable in 15-20% of men during life, its death risk is only about 3%. This means that not all PC cases require the same management tactics. The given review analyzes the current investigations searching for molecular biological markers to predict the course of PC and to choose its treatment policy, including that in the development of resistance to androgen-deprivation therapy.

  8. Molecular diagnosis of prostate cancer: Topical issues

    OpenAIRE

    E. N. Knyazev; K. A. Fomicheva; K. M. Nyushko; Kaprin, A. D.; B. Ya. Alekseev; M. Yu. Shkurnikov

    2014-01-01

    Prostate cancer (PC) is the second most common cancer and the fifth highest malignancy mortality rate in men worldwide. Although PC is detectable in 15-20% of men during life, its death risk is only about 3%. This means that not all PC cases require the same management tactics. The given review analyzes the current investigations searching for molecular biological markers to predict the course of PC and to choose its treatment policy, including that in the development of resistance to androge...

  9. Molecular diagnosis of prostate cancer: Topical issues

    Directory of Open Access Journals (Sweden)

    E. N. Knyazev

    2014-12-01

    Full Text Available Prostate cancer (PC is the second most common cancer and the fifth highest malignancy mortality rate in men worldwide. Although PC is detectable in 15-20% of men during life, its death risk is only about 3%. This means that not all PC cases require the same management tactics. The given review analyzes the current investigations searching for molecular biological markers to predict the course of PC and to choose its treatment policy, including that in the development of resistance to androgen-deprivation therapy.

  10. New testosterone derivatives as semi-synthetic anticancer agents against prostate cancer: synthesis and preliminary biological evaluation.

    Science.gov (United States)

    Morin, Nathalie; Bruneau, Julie; Fortin, Sebastien; Brasseur, Kevin; Leblanc, Valerie; Asselin, Eric; Berube, Gervais

    2015-01-01

    Prostate cancer (PC) is a major health issue in the world. Treatments of localized PC are quite efficient and usually involve surgery, radiotherapy and/or hormonal therapy. Metastatic PC is however rarely curable to this day. Treatments of metastatic PC involve radiotherapy, chemotherapy and hormonal treatment such as orchiectomy, antiandrogens and luteinizing hormone-releasing hormone agonists. The suppression of tumor growth by hormonal treatment is efficient but overtime resistance still occurs and the disease progresses. Thus, more urgently than ever there is a need for discovery of new treatment options for castration-resistant PC (CRPC). Hence, we designed and tested a series of amide derivatives located at position 7α of testosterone as prospective "natural" or "semisynthetic" anticancer agents against CRPC with the goal of discovering therapeutic alternatives for the disease. This manuscript describes an efficient path towards the target molecules that are made in only 6 or 7 chemical steps from testosterone in good overall yields. This strategy can be used to make several compounds of interest that present higher biological activity than the classic antiandrogen; cyproterone acetate (3). The best testosterone-7α-amide was the N-2-pyridylethylamide (25) which was as active as the antiandrogen cyproterone acetate (3) on androgen-dependent LNCaP cells and 2.7 times more active on androgen-independent PC3 prostate cancer cells. The results obtained show the synthetic feasibility and the potential for future development of this unique class of semi-synthetic anticancer agents that offer the premise of new treatment modalities for patients afflicted with CRPC. PMID:25675439

  11. miRNA Expression Analyses in Prostate Cancer Clinical Tissues.

    Science.gov (United States)

    Bucay, Nathan; Shahryari, Varahram; Majid, Shahana; Yamamura, Soichiro; Mitsui, Yozo; Tabatabai, Z Laura; Greene, Kirsten; Deng, Guoren; Dahiya, Rajvir; Tanaka, Yuichiro; Saini, Sharanjot

    2015-01-01

    A critical challenge in prostate cancer (PCa) clinical management is posed by the inadequacy of currently used biomarkers for disease screening, diagnosis, prognosis and treatment. In recent years, microRNAs (miRNAs) have emerged as promising alternate biomarkers for prostate cancer diagnosis and prognosis. However, the development of miRNAs as effective biomarkers for prostate cancer heavily relies on their accurate detection in clinical tissues. miRNA analyses in prostate cancer clinical specimens is often challenging owing to tumor heterogeneity, sampling errors, stromal contamination etc. The goal of this article is to describe a simplified workflow for miRNA analyses in archived FFPE or fresh frozen prostate cancer clinical specimens using a combination of quantitative real-time PCR (RT-PCR) and in situ hybridization (ISH). Within this workflow, we optimize the existing methodologies for miRNA extraction from FFPE and frozen prostate tissues and expression analyses by Taqman-probe based miRNA RT-PCR. In addition, we describe an optimized method for ISH analyses formiRNA detection in prostate tissues using locked nucleic acid (LNA)- based probes. Our optimized miRNA ISH protocol can be applied to prostate cancer tissue slides or prostate cancer tissue microarrays (TMA). PMID:26382040

  12. miRNA Expression Analyses in Prostate Cancer Clinical Tissues.

    Science.gov (United States)

    Bucay, Nathan; Shahryari, Varahram; Majid, Shahana; Yamamura, Soichiro; Mitsui, Yozo; Tabatabai, Z Laura; Greene, Kirsten; Deng, Guoren; Dahiya, Rajvir; Tanaka, Yuichiro; Saini, Sharanjot

    2015-09-08

    A critical challenge in prostate cancer (PCa) clinical management is posed by the inadequacy of currently used biomarkers for disease screening, diagnosis, prognosis and treatment. In recent years, microRNAs (miRNAs) have emerged as promising alternate biomarkers for prostate cancer diagnosis and prognosis. However, the development of miRNAs as effective biomarkers for prostate cancer heavily relies on their accurate detection in clinical tissues. miRNA analyses in prostate cancer clinical specimens is often challenging owing to tumor heterogeneity, sampling errors, stromal contamination etc. The goal of this article is to describe a simplified workflow for miRNA analyses in archived FFPE or fresh frozen prostate cancer clinical specimens using a combination of quantitative real-time PCR (RT-PCR) and in situ hybridization (ISH). Within this workflow, we optimize the existing methodologies for miRNA extraction from FFPE and frozen prostate tissues and expression analyses by Taqman-probe based miRNA RT-PCR. In addition, we describe an optimized method for ISH analyses formiRNA detection in prostate tissues using locked nucleic acid (LNA)- based probes. Our optimized miRNA ISH protocol can be applied to prostate cancer tissue slides or prostate cancer tissue microarrays (TMA).

  13. Genomic and epigenomic alterations in prostate cancer

    Directory of Open Access Journals (Sweden)

    Anna Maria eAschelter

    2012-11-01

    Full Text Available Prostate cancer (PC is the second most frequently diagnosed cancer and the second leading cause of cancer deaths in man. The treatment of localized PC includes surgery or radiation therapy. In case of relapse after a definitive treatment or in patients with locally advanced or metastatic disease, the standard treatment includes the androgen-deprivation therapy (ADT. By reducing the levels of Testosterone and dihydrotestosterone (DHT under the castration threshold, the ADT acts on the androgen receptor (AR, even if indirectly. The effects of the ADT are usually temporary and nearly all patients, initially sensitive to the androgen ablation therapy, have a disease progression after a 18-24 months medium term. This is probably due to the selection of the cancer cell clones and to their acquisition of critical somatic genome and epigenomic changes. This review aims to provide an overview about the genetic and epigenetic alterations having a crucial role in the carcinogenesis and in the disease progression toward the castration resistant prostate cancer (CRPC. We focused on the role of the androgen receptor, on its signaling cascade and on the clinical implications that the knowledge of these aspects would have on hormonal therapy, on its failure and its toxicity.

  14. LOW RISK PROSTATE CANCER: ACTIVE TREATMENT OR ACTIVE SURVEILLANCE?

    Science.gov (United States)

    Tomašković, Igor

    2015-09-01

    The widely used screening for prostate cancer with prostate specific antigen has resulted in identification of potentially lethal prostate cancers at a much more curable stage and has been associated with significant falls in prostate cancer mortality. In spite of the fact that prostate cancer is one of the deadliest malignancies in men, the advent of sensitive diagnostic testing has also resulted in detection of low risk cancers due to the high incidence of latent prostate cancer in aging men and prolonged natural history of the disease. This, in turn, has entailed the problem of cancer overdiagnosis and subsequent overtreatment. Approximately 6 times as many men will be diagnosed with the disease as will die from it. Active surveillance appeared as a response to the clearly documented risks of overdiagnosis and overtreatment of low risk prostate cancer for localized prostate cancer. It entails initial expectant management rather than immediate therapy, with 'curative-intent' treatment deferred until there is evidence that the patient is at an increased risk of disease progression. This approach attempts to balance the risks and side effects of overtreatment against the possibility of disease progression and lost opportunity for cure. A systematic literature review brings current knowledge on the subject.

  15. Magnetic resonance imaging for prostate cancer clinical application

    Institute of Scientific and Technical Information of China (English)

    Bing Li; Yong Du; Hanfeng Yang; Yayong Huang; Jun Meng; Dongmei Xiao

    2013-01-01

    As prostate cancer is a biologically heterogeneous disease for which a variety of treatment options are available,the major objective of prostate cancer imaging is to achieve more precise disease characterization.In clinical practice,magnetic resonance imaging (MRI) is one of the imaging tools for the evaluation of prostate cancer,the fusion of MRI or dynamic contrast-enhanced MRI (DCE-MRI) with magnetic resonance spectroscopic imaging (MRSI) is improving the evaluation of cancer location,size,and extent,while providing an indication of tumor aggressiveness.This review summarizes the role of MRI in the application of prostate cancer and describes molecular MRI techniques (including MRSI and DCE-MRI)for aiding prostate cancer management.

  16. PET/CT Imaging and Radioimmunotherapy of Prostate Cancer

    DEFF Research Database (Denmark)

    Bouchelouche, Kirsten; Tagawa, Scott T; Goldsmith, Stanley J;

    2011-01-01

    of more effective treatment modalities that could improve outcome. Prostate cancer represents an attractive target for radioimmunotherapy (RIT) for several reasons, including pattern of metastatic spread (lymph nodes and bone marrow, sites with good access to circulating antibodies) and small volume...... antitumor activity and is well tolerated. Clinical trials are underway to further improve upon treatment efficacy and patient selection. This review focuses on the recent advances of clinical PET/CT imaging and RIT of prostate cancer.......Prostate cancer is a common cancer in men and continues to be a major health problem. Imaging plays an important role in the clinical management of patients with prostate cancer. An important goal for prostate cancer imaging is more accurate disease characterization through the synthesis...

  17. Steps in Prostate Cancer Progression that lead to Bone Metastasis

    OpenAIRE

    Jin, Jung-Kang; Dayyani, Farshid; Gallick, Gary E.

    2011-01-01

    Prostate cancer is a complex disease in which metastasis to the bone is the main cause of death. Initial stages of metastasis are generally similar to those for most solid tumors; however, the mechanisms that underlie the homing of prostate tumor cells to the bone remain incompletely understood. Prostate cancer bone metastasis is also a microenvironment-driven disease, involving bi-directional interactions between the tumor and the bone microenvironment. In this review, we discuss the current...

  18. Overcoming docetaxel resistance in prostate cancer: a perspective review

    OpenAIRE

    Hwang, Clara

    2012-01-01

    The treatment of metastatic castrate-resistant prostate cancer has been historically challenging, with few therapeutic successes. Docetaxel was the first cytotoxic therapy associated with a survival benefit in castrate-resistant prostate cancer. Toxicity is typical of other cytotoxic agents, with myelosuppression being the dose-limiting toxicity and neurotoxicity also a notable side effect for some patients. Unfortunately, a significant proportion of men with castrate-resistant prostate cance...

  19. A Perspective of Immunotherapy for Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Ida Silvestri

    2016-07-01

    Full Text Available In cancer patients, the immune system is often altered with an excess of inhibitory factors, such as immunosuppressive cytokines, produced by regulatory T cells (Treg or myeloid-derived suppressor cells (MDSC. The manipulation of the immune system has emerged as one of new promising therapies for cancer treatment, and also represents an attractive strategy to control prostate cancer (PCa. Therapeutic cancer vaccines and immune checkpoint inhibitors have been the most investigated in clinical trials. Many trials are ongoing to define the effects of immune therapy with established treatments: androgen deprivation therapy (ADT and chemotherapy (CT or radiotherapy (RT. This article discusses some of these approaches in the context of future treatments for PCa.

  20. A Perspective of Immunotherapy for Prostate Cancer.

    Science.gov (United States)

    Silvestri, Ida; Cattarino, Susanna; Giantulli, Sabrina; Nazzari, Cristina; Collalti, Giulia; Sciarra, Alessandro

    2016-01-01

    In cancer patients, the immune system is often altered with an excess of inhibitory factors, such as immunosuppressive cytokines, produced by regulatory T cells (Treg) or myeloid-derived suppressor cells (MDSC). The manipulation of the immune system has emerged as one of new promising therapies for cancer treatment, and also represents an attractive strategy to control prostate cancer (PCa). Therapeutic cancer vaccines and immune checkpoint inhibitors have been the most investigated in clinical trials. Many trials are ongoing to define the effects of immune therapy with established treatments: androgen deprivation therapy (ADT) and chemotherapy (CT) or radiotherapy (RT). This article discusses some of these approaches in the context of future treatments for PCa. PMID:27399780