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Prostate Carcinoma (prostate + carcinoma)
Kinds of Prostate Carcinoma Terms modified by Prostate Carcinoma Selected AbstractsCross-sectional and longitudinal comparisons of health-related quality of life between patients with prostate carcinoma and matched controls,,§CANCER, Issue 9 2004M.P.H., Richard M. Hoffman M.D. Abstract BACKGROUND Prostate carcinoma and treatments affect health-related quality of life (HRQOL). The authors prospectively compared prostate and general HRQOL between prostate carcinoma cases and an age-matched and ethnicity-matched control group. METHODS The case cohort consisted of 293 men with localized prostate carcinoma who were selected randomly from the population-based New Mexico Tumor Registry, and the control cohort consisted of 618 men who were selected randomly from administrative databases and matched for age and ethnicity. Subjects completed a baseline survey of demographics, socioeconomic status, comorbidity, and prostate and general HRQOL. Also, 210 cases (71.7%) and 421 controls (67.8%) completed a follow-up survey 5 years later. Multinomial logistic regression models compared baseline characteristics as well as 5-year general HRQOL outcomes measured by selected domains of the Medical Outcomes Study SF-36. The authors used a mixed-model repeated-measures analysis of variance and multinomial regression analyses to compare longitudinal changes in urinary, bowel, and sexual function between groups. RESULTS At baseline, patients with prostate carcinoma had better urinary control and sexual function than controls. Over 5 years, sexual function declined significantly among controls, although urinary function remained stable. However, patients with cancer subsequently reported significant declines in both domains and were left with much worse function and more bother than controls. Bowel function and general HRQOL were similar for both groups at follow-up. CONCLUSIONS Prostate carcinoma treatment led to significant 5-year declines in urinary and sexual function that far exceeded age-related changes in controls. Patients with cancer had significantly worse function and more bother than controls for these disease-specific domains of HRQOL. Bowel function and general HRQOL were not affected by cancer status. Cancer 2004. Published 2004 American Cancer Society. [source] Prostate carcinoma with testicular or penile metastasesCANCER, Issue 10 2002Clinical, immunohistochemical features, pathologic Abstract BACKGROUND Despite the proximity, prostate carcinoma seldom metastasizes to the penis or testis. METHODS In the current study, the authors retrospectively examined the clinical history of 12 patients with prostate carcinoma and testicular or penile metastases. Pathologic review and immunohistochemical staining were performed on tumors from eight of these patients. RESULTS Patients with prostate carcinoma and testicular or penile metastasis responded to androgen ablative therapy (median duration, 33 months). They were predisposed to developing persistent or recurrent urinary symptoms and visceral metastases. Six of 9 evaluable patients had elevated serum carcinoembryonic antigen levels (> 6 ng/mL), whereas 2 of 10 patients had low or undetectable serum prostate specific antigen levels (< 4 ng/mL). In seven of the eight patients for whom specimens were available, the tumors were found to contain histologic features that were compatible with a diagnosis of ductal or endometrioid adenocarcinoma of the prostate. CONCLUSIONS Patients with prostate carcinoma and testicular or penile metastases have unique clinical and pathologic characteristics. Many of these patients' tumors are compatible with a subtype of prostate carcinoma known as ductal adenocarcinoma. Further studies need to be performed to elucidate the biologic basis of the various histologic subtypes of prostate carcinoma. Cancer 2002;94:2610,7. © 2002 American Cancer Society. DOI 10.1002/cncr.10546 [source] Fine needle aspiration of metastatic prostate carcinoma simulating a primary adrenal cortical neoplasm: A case report and review of the literatureDIAGNOSTIC CYTOPATHOLOGY, Issue 2 2010Andrea P. Subhawong M.D. Abstract Adrenal metastases usually occur in prostate cancer patients with widespread bone and visceral disease. Autopsy studies have shown that adrenal metastases may be found in up to 23% of these patients. However, the finding of an isolated adrenal metastasis without the involvement of other organs in a patient with prostate cancer is exceedingly rare. Thus, it may cause a diagnostic dilemma on FNA cytology. We report a patient with a history of prostate cancer, status post radiation, and hormonal therapy 4 years before, who presented with a new, single adrenal mass on abdominal imaging studies. The ultrasound-guided FNA cytology of the adrenal mass revealed cytomorphological features that were suggestive of a primary adrenal cortical neoplasm, but overlapped with those of a prostate metastasis. To our knowledge, FNA findings of metastatic prostate cancer simulating an adrenal cortical neoplasm have not been previously reported in the English literature. The purpose of our study is to discuss the differential diagnosis of these entities. The accurate diagnosis is important because of different prognosis and treatment implications for the various diseases. Diagn. Cytopathol. 2010. © 2009 Wiley-Liss, Inc. [source] ,-Methylacyl-CoA racemase (AMACR) in fine-needle aspiration specimens of prostate lesionsDIAGNOSTIC CYTOPATHOLOGY, Issue 11 2009Gordana Kai, M.D. Abstract The elevated expression of P504S gene and its product ,-methylacyl-CoA racemase (AMACR) can serve as a molecular marker for prostate cancer. The goal of this study is to investigate P504S/AMACR expression in fine-needle aspiration smears and correlate it with cytological diagnosis. Immunocytochemistry was performed in 35 patients with morphological diagnosis of prostate carcinoma (n = 16), atypia (n = 15), and benign hyperplasia (n = 4). Among 16 malignant cases there were two low-grade, eight intermediate, and six high-grade prostate carcinomas. Cytoplasmic positivity is analyzed qualitatively as predominantly diffuse or focal and quantitatively as <5%, 5,50%, and >50% of cells. Benign cases showed no P504S/AMACR expression. Positive staining was recorded in 75% of malignant cases, but in the majority of them it was weak and focal or diffuse and in a small amount of cells. The most intensive staining was seen in low-grade carcinomas and some atypical cases. This observation indicates a correlation between P504S/AMACR expression and differentiation of cells. P504S/AMACR staining might be of great value in cytodiagnosis of prostate lesions as well as an example of the characterization of cells at the molecular level using fresh tissue obtained by fine-needle aspiration. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc. [source] High levels of serum prostate-specific antigen due to PSA producing follicular non-Hodgkin's lymphomaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2007Jan Jelrik Oosterheert Abstract Objective:, Both carcinoma of the prostate and non-Hodgkin's lymphoma are common in elderly patients. Measurement of serum prostate-specific antigen (PSA) is a frequently used tool to diagnose and monitor prostate carcinoma and is generally specific for diseases of the prostate. Case:, We describe a 68-yr-old patient with voiding difficulties and high PSA levels, but without inflammatory or malignant changes upon multiple transrectal ultrasound guided prostate biopsies. Digital rectal examination was normal. Laboratory showed a strongly elevated PSA level (62 ,g/L, Immulight 2000®; DPC, USA). A CT-scan showed a retroperitoneal process with mass in the right pelvis and infiltration of the bladder wall, suggestive for metastatic prostate carcinoma. Surgical excision of an axillary lymph node set the diagnosis at a stage IV follicular lymphoma, Berard grade I to II in which the majority of neoplastic cells expressed PSA. After lymphoma-specific treatment, there was a positron emission tomography (PET) confirmed complete remission with normal PSA levels (6 ,g/L), which still persists. Conclusion:, Although rare, high PSA levels can be due to the presence of non-Hodgkin's lymphoma. Such a diagnosis should be considered when patients present with lymphadenopathy other than regional prostatic lymphadenopathy. [source] Camellia sinensis treatment for metastatic prostate carcinomaFOCUS ON ALTERNATIVE AND COMPLEMENTARY THERAPIES AN EVIDENCE-BASED APPROACH, Issue 3 2003Article first published online: 14 JUN 2010 [source] Expression of microRNA-221 is progressively reduced in aggressive prostate cancer and metastasis and predicts clinical recurrenceINTERNATIONAL JOURNAL OF CANCER, Issue 2 2010Martin Spahn Abstract Emerging evidence shows that microRNAs (miR) are involved in the pathogenesis of a variety of cancers, including prostate carcinoma (PCa). Little information is available regarding miR expression levels in lymph node metastasis of prostate cancer or the potential of miRs as prognostic markers in this disease. Therefore, we analyzed the global expression of miRs in benign, hyperplastic prostate tissue (BPH), primary PCa of a high risk group of PCa patients, and corresponding metastatic tissues by microarray analysis. Consistent with the proposal that some miRs are oncomirs, we found aberrant expression of several miRs, including the downregulation of miR-221, in PCa metastasis. Downregulation of miR-221 was negatively correlated with the expression of the proto-oncogen c-kit in primary carcinoma. In a large study cohort, the prostate-specific oncomir miR-221 was progressively downregulated in aggressive forms of PCa. Downregulation of miR-221 was associated with clinicopathological parameters, including the Gleason score and the clinical recurrence during follow up. Kaplan,Meier estimates and Cox proportional hazard models showed that miR-221 downregulation was linked to tumor progression and recurrence in a high risk prostate cancer cohort. Our results showed that progressive miR-221 downregulation hallmarks metastasis and presents a novel prognostic marker in high risk PCa. This suggests that miR-221 has potential as a diagnostic marker and therapeutic target in PCa. [source] Expression of estrogen receptor alpha increases leptin-induced STAT3 activity in breast cancer cellsINTERNATIONAL JOURNAL OF CANCER, Issue 1 2010Nadine A. Binai Abstract Adipositas correlates with an enhanced risk of developing malignant diseases such as breast cancer, endometrial tumor or prostate carcinoma, but the molecular basis for this is not well understood. Potential mechanisms include increased bioavailability of adipocytokines (e.g. leptin) and steroid hormones. Here, we investigated cross-talk between ER, (estrogen receptor alpha) and leptin-induced activation of signal transducer and activator of transcription 3 (STAT3), a transactivator of important oncogenes. Upon leptin binding to its receptor Ob-RL (obesity receptor), STAT3 tyrosine phosphorylation and transactivation activity were enhanced by simultaneously expressing ER,. Downregulation of ER, using small interfering RNA abolished leptin-induced STAT3 phosphorylation. Interestingly, leptin-mediated STAT3 activation was unaffected by co-stimulation with the ER, ligands estradiol (E2) or estrogen antagonists ICI182,780 and tamoxifen, implying that enhancement of leptin-mediated STAT3 activity is independent of ER, ligands. We also detected ER, binding to STAT3 and JAK2 (Janus kinase 2), resulting in enhanced JAK2 activity upstream of STAT3 in response to leptin that might lead to an increased ER,-dependent cell viability. Altogether, our results indicate that leptin-induced STAT3 activation acts as a key event in ER,-dependent development of malignant diseases. [source] Relevance of a new rat model of osteoblastic metastases from prostate carcinoma for preclinical studies using zoledronic acidINTERNATIONAL JOURNAL OF CANCER, Issue 4 2008François Lamoureux Abstract Animal models that mimic osteoblastic metastases associated with prostate carcinoma are required to improve the therapeutic options in humans. A new model was then developed and characterized in immunocompetent rats. The bisphosphonate zoledronic acid (ZOL) was tested to validate this model as a therapeutic application. Rat AT6-1 prostate tumor cells were characterized in vitro at the transcriptional (bone and epithelial markers) and functional (induction of mineralized nodules) levels. The bone lesions induced after their direct injection into the femur bone marrow were characterized by radiography, microscanner and histology analyses. ZOL effects were studied in vivo on bone lesion development and in vitro on AT6-1 cell proliferation, apoptosis and cell cycle analysis. Apart from epithelial markers, AT6-1 cells express an osteoblast phenotype as they express osteoblastic markers and are able to induce mineralized nodule formation in vitro. A disorganization of the trabecular bone at the growth zone level was observed in vivo after intraosseous AT6-1 cell injection as well as cortical erosion. The tumor itself is associated with bone formation as revealed by SEM analysis and polarized light microscopy. ZOL prevents the development of such osteoblastic lesions, related to a direct inhibitory effect on tumor cell proliferation independent of caspase 3 activation, but associated with cell cycle arrest. A new rat model of osteoblastic bone metastases was validated in immunocompetent rats and used to show the relevance of using ZOL in such lesions, as this compound shows bifunctional effects on both bone remodelling and tumor cell proliferation. © 2007 Wiley-Liss, Inc. [source] Diverse roles of 2-arachidonoylglycerol in invasion of prostate carcinoma cells: Location, hydrolysis and 12-lipoxygenase metabolismINTERNATIONAL JOURNAL OF CANCER, Issue 5 2007Michael P. Endsley Abstract Endogenous 2-arachidonoylglycerol (2-AG) is antiinvasive in androgen-independent prostate carcinoma (PC-3) cells. Invasion of PC-3 cells is also inhibited by exogenously added noladin ether, a non-hydrolyzable analog of 2-AG. In contrast, exogenous 2-AG has the opposite effect. Cell invasion significantly increased with high concentrations of exogenous 2-AG. In PC-3 cells, arachidonic acid (AA) and 12-hydroxyeicosatetraenoic acid (12-HETE) concentrations increased along with exogenously added 2-AG, and 12-HETE concentrations increased with exogenously added AA. Invasion of PC-3 cells also increased with exogenously added AA and 12(S)-HETE but not 12(R)-HETE. The exogenous 2-AG-induced invasion of PC-3 cells was inhibited by 3-octylthio-1,1,1-trifluoropropan-2-one (OTFP, an inhibitor of 2-AG hydrolysis) and baicalein (a 12-LO inhibitor). Western blot and RT-PCR analyses indicated expression of 12-HETE producing lipoxygenases (LOs), platelet-type 12-LO (P-12-LO) and leukocyte-type 12-LO (L-12-LO), in PC-3 cells. These results suggest that exogenous 2-AG induced, rather inhibited, cell invasion because of its rapid hydrolysis to free AA, and further metabolism by 12-LO of AA to 12(S)-HETE, a promoter of PC cell invasion. The results also suggest that PC-3 cells and human prostate stromal (WPMY-1) cells released free AA, 2-AG, and 12-HETE. In the microenvironment of the PC cells, this may contribute to the cell invasion. The 2-AG hydrolysis and concentration of 2-AG in microenvironment are critical for PC cell's fate. Therefore, inhibitors of 2-AG hydrolysis could potentially serve as therapeutic agents for the treatment of prostate cancer. © 2007 Wiley-Liss, Inc. [source] Original Article: Prospective comparative study of single dose versus 3-day administration of antimicrobial prophylaxis in minimum incision endoscopic radical prostatectomyINTERNATIONAL JOURNAL OF UROLOGY, Issue 4 2008Mizuaki Sakura Objective: From the critical stand point against the overuse of antimicrobial agents, appropriate reduction of antimicrobial prophylaxis (AMP) should be considered. We have prospectively reduced AMP and evaluated the occurrence of surgical site infection (SSI) following radical retropubic prostatectomy (RRP) by minimum incision endoscopic surgery (MIES). Methods: A total of 101 consecutive patients who underwent MIES-RRP for prostate carcinoma were classified into two groups according to AMP dose. The 3-day group of 52 patients received tazobactam sodium/piperacillin sodium (TAZ/PIPC) 2.5 g intravenously before the operation and continued twice daily until postoperative day 2, and the single dose group of 49 patients received TAZ/PIPC 2.5 g intravenously only once before the operation. Additional antimicrobial agents were given only when SSI occurred. The occurrence of SSI and remote infection (RI) were analyzed. Results: There was no significant difference in the rate of SSI occurrence between the 3-day group (3.8%) and single dose group (6.1%) (P = 0.6). RI did not increase in the single dose group. Conclusion: Antimicrobial prophylaxis dose was successfully reduced without increasing SSI or RI. A single dose of AMP is feasible to prevent SSI and RI and would be a standard regimen in MIES-RRP. Active surveillance of postoperative infection is mandatory to promptly administer antimicrobial treatment as the need arises. [source] Apoptosis in prostate cancer: Bax correlation with stageINTERNATIONAL JOURNAL OF UROLOGY, Issue 4 2005ZAHRA AMIRGHOFRAN Abstract Background:, Dysregulation of apoptosis may contribute to the process of prostate tumorigenesis by reducing the rate of cell death. Bcl-2 and bax are important molecules involved in the regulation of apoptosis. The aim of the present study is to examine apoptosis and related regulatory molecular markers in a group of Iranian patients with prostate cancer. Methods:, Paraffin-embedded tissues from 50 patients of prostate carcinoma were examined for the expression of bcl-2 antiapoptotic and bax proapoptotic markers and also proliferation marker, Ki-67, by immunohistochemistry. Detection of apoptotic cells was performed using TUNEL method. Correlation between apoptotic index, proliferation index and bcl-2 and bax expression with stage, pathological grade and Gleason score was determined. Results:, Apoptosis was detected in 12% of prostate cancers. No correlation was observed between apoptosis and differentiation status of carcinoma. Bcl-2 expression was detected in 21 of samples. A significant correlation between bcl-2 expression and Ki-67 staining index (r = 0.349, P = 0.012) was observed. High bax protein expression was shown in our study. We found a significant correlation between bax expression and stage of carcinoma (r = 0.388, P = 0.031), but not with the apoptosis index, suggesting the presence of a non-functional bax protein or the role of other proapoptotic molecules. Conclusion:, The patients in the present study showed a different pattern of apoptosis positivity compared to other reports. Bax expression may be a useful marker for prognosis of prostate cancer. [source] Histologic upgrading of prostate cancer occurs frequently over a short period of time: Single hospital experiences of radical prostatectomyINTERNATIONAL JOURNAL OF UROLOGY, Issue 8 2001Hideki Mukouyama Abstract A total of 163 patients with localized prostate cancer underwent retropubic radical prostatectomy and pelvic lymphadenectomy at a single hospital from 1989 to 1998. We reviewed the patients in terms of their prognostic factors and survival. The patients without advanced diseases were diagnosed as having prostate carcinoma, using either biopsies or transurethral resection of the prostate. The carcinomas were categorized into localized prostate carcinomas (stage A, B or C) as a result of digital rectal examinations, computed tomography scans and bone scans. The patients were informed of the risk of surgery and, if they agreed to sign the consent form, underwent radical prostatectomy under general and epidural anesthesia usually 2 months after a positive biopsy. The surgical specimens were sent for pathology and were graded according to classifications of well-, moderately and poorly differentiated adenocarcinoma. The patients were usually discharged from the hospital 2,3 weeks postoperatively and had regular follow-up treatment. The mean age (± SD) was 68.75 (± 5.59) years and the mean follow-up period was 47.2 months. There was a significant difference (34.4%) in pathologic grades between biopsy and surgical specimen. In a quarter of the patients (approximately 26.4%) upgrading of the surgical report occurred despite neoadjuvant therapy. Three-year, 5-year and 7-year actuarial survival rates were 91.8%, 79.9% and 71.9%, respectively. Patients with organ-confined prostate cancer underwent radical prostatectomy and survived a fairly good period of time. Histologic upgrading was frequently observed within a short period of time (2 months). [source] Epigenetics of prostate cancer: beyond DNA methylationJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 1 2006W. A. Schulz Abstract Epigenetic mechanisms permit the stable inheritance of cellular properties without changes in DNA sequence or amount. In prostate carcinoma, epigenetic mechanisms are essential for development and progression, complementing, amplifying and diversifying genetic alterations. DNA hypermethylation affects at least 30 individual genes, while repetitive sequences including retrotransposons and selected genes become hypomethylated. Hypermethylation of several genes occurs in a coordinate manner early in carcinogenesis and can be exploited for cancer detection, whereas hypomethylation and further hypermethylation events are associated with progression. DNA methylation alterations interact with changes in chromatin proteins. Prominent alterations at this level include altered patterns of histone modification, increased expression of the EZH2 polycomb histone methyltransferase, and changes in transcriptional corepressors and coactivators. These changes may make prostate carcinoma particularly susceptible to drugs targeting chromatin and DNA modifications. They relate to crucial alterations in a network of transcription factors comprising ETS family proteins, the androgen receptor, NKX3.1, KLF, and HOXB13 homeobox proteins. This network controls differentiation and proliferation of prostate epithelial cells integrating signals from hormones, growth factors and cell adhesion proteins that are likewise distorted in prostate cancer. As a consequence, prostate carcinoma cells appear to be locked into an aberrant state, characterized by continued proliferation of largely differentiated cells. Accordingly, stem cell characteristics of prostate cancer cells appear to be secondarily acquired. The aberrant differentiation state of prostate carcinoma cells also results in distorted mutual interactions between epithelial and stromal cells in the tumor that promote tumor growth, invasion, and metastasis. [source] Umbilical metastasis from prostate carcinoma (Sister Mary Joseph's nodule): a case report and review of literatureJOURNAL OF CUTANEOUS PATHOLOGY, Issue 7 2007Bahram Sina Sister Mary Joseph's nodule is referred to as metastatic lesion of the umbilicus. Most of the tumors are adenocarcinomas originating from gastroenteric and genital tracts. Only rarely were metastases from other locations reported. We describe here an unusual case of a Sister Mary Joseph's nodule that was metastasized from prostate carcinoma 3 years after radiation therapy. The lesion was the first sign of metastatic disease, and the diagnosis was made on skin biopsy. The patient died of extensive metastases of prostate carcinoma 4 months later. We report this case to extend the list of differential diagnosis for Sister Mary Joseph's nodule in male patients and emphasize the importance of Sister Mary Joseph's nodule as an ominous diagnostic sign. [source] Peroxisome proliferator-activated receptor gamma in human prostate carcinomaPATHOLOGY INTERNATIONAL, Issue 5 2009Yasuhiro Nakamura Peroxisome proliferator-activated receptor (PPAR) is a member of the nuclear hormone receptor superfamily of transcription factors. Peroxisome proliferator-activated receptor gamma (PPAR,) plays an important role in the regulation of lipid homeostasis, adipogenesis, insulin resistance, and development of various organs. Agonists of PPAR, have been also reported to inhibit proliferation of prostate carcinoma cells as in other human malignancies, and these synthetic ligands have been used in differentiation-mediated therapy of various human carcinomas associated with high levels of PPAR,. The significance of PPAR, expression, however, was unknown in human prostate carcinoma tissues. The purpose of the present study was therefore to examine the immunolocalization of PPAR, in human prostate cancer tissues (40 cases) and correlate the findings with clinicopathological features of the patients in order to evaluate its possible biological significance. Twenty-nine patients were positive for PPAR, immunoreactivity (73%) and a significant inverse correlation was detected between PPAR, immunoreactivity, pT stage (P = 0.036), and serum concentration of prostate-specific antigen (P = 0.0004). In conclusion, PPAR, immunoreactivity is considered to be a new clinicopathological parameter of human prostate cancer. [source] Controversies in the treatment of high-risk prostate cancer,what is the optimal combination of hormonal therapy and radiotherapy: a review of literature,THE PROSTATE, Issue 7 2010Abrahim Al-Mamgani Abstract BACKGROUND In high-risk prostate carcinoma, there is controversy whether these patients should be treated with escalated-dose (,74 Gy) or conventional-dose radiotherapy (<74 Gy) combined with hormonal therapy. Furthermore, the issue of the optimal duration and timing of hormonal therapy are not well crystallized. PATIENTS AND METHODS A search for evidence from randomized- and large non-randomized studies in order to address these issues, was therefore initiated. For this purpose, MedLine, EMbase, and PubMed and the data base of the Dutch randomized dose-escalation trial, were consulted. RESULTS AND CONCLUSIONS From this search it was concluded that the benefit of hormonal therapy in combination with conventional-dose radiotherapy (<74 Gy) in high-risk prostate cancer is evident (Level 2 evidence); Levels 2 and 3 evidence were provided by several studies supporting the use of escalated-dose radiotherapy in high-risk prostate cancer. For the combination of hormonal therapy with escalated-dose radiotherapy in these patients, there is Level 2 evidence for moderately escalated dose (74 Gy) and high escalated dose (,78 Gy). The optimal duration and timing of hormonal therapy are not well defined. More randomized-controlled trials and meta-analyses are therefore needed to clearly determine the independent role of dose-escalation in high-risk patients treated with hormonal therapy and the optimal duration and timing of hormonal therapy. Prostate 70: 701,709, 2010. © 2009 Wiley-Liss, Inc. [source] Association of CASP8 D302H polymorphism with reduced risk of aggressive prostate carcinomaTHE PROSTATE, Issue 6 2010Jessica Lubahn Abstract BACKGROUND Because of the dramatically different clinical course of aggressive and indolent prostate carcinoma (PCa), markers that distinguish between these phenotypes are of critical importance. Apoptosis is an important protective mechanism for unrestrained cellular growth and metastasis. Therefore, dysfunction in this pathway is a key step in cancer progression. As such, genetic variants in apoptosis genes are potential markers of aggressive PCa. Recent work in breast carcinoma has implicated the histidine variant of CASP8 D302H (rs1045485) as a protective risk allele. METHODS We tested the hypothesis that the H variant was protective for aggressive PCa in a pooled analysis of 796 aggressive cases and 2,060 controls. RESULTS The H allele was associated with a reduced risk of aggressive PCa (ORper allele,= 0.67, 95% CI: 0.54,0.83, Ptrend,=,0.0003). The results were similar for European-Americans (ORper allele,=,0.68; 95% CI: 0.54,0.86) and African-Americans (ORper allele,=,0.61; 95% CI: 0.34,1.10). We further determined from the full series of 1,160 cases and 1,166 controls in the Prostate, Lung, Colorectal, Ovarian (PLCO) population that the protective effect of the H allele tended to be limited to high-grade and advanced PCa (all cases ORper allele,=,0.94; 95% CI: 0.79,1.11; localized, low-grade disease ORper allele,=,0.98; 95% CI: 0.79,1.23; and aggressive disease ORper allele,=,0.73; 95% CI: 0.50,1.07). CONCLUSION These results suggest that histidine variant of CASP8 D302H is a protective allele for aggressive PCa with potential utility for identification of patients at differential risk for this clinically significant phenotype. Prostate 70: 646,653, 2010. © 2009 Wiley-Liss, Inc. [source] Novel multi-peptide vaccination in Hla-A2+ hormone sensitive patients with biochemical relapse of prostate cancerTHE PROSTATE, Issue 9 2009Susan Feyerabend Abstract BACKGROUND A phase I/II trial was conducted to assess feasibility and tolerability of tumor associated antigen peptide vaccination in hormone sensitive prostate carcinoma (PC) patients with biochemical recurrence after primary surgical treatment. METHODS Nineteen HLA-A2 positive patients with rising PSA without detectable metastatic disease or local recurrence received 11 HLA-A*0201-restricted and two HLA class II synthetic peptides derived from PC tumor antigens subcutaneously for 18 months or until PSA progression. The vaccine was emulgated in montanide ISA51 and combined with imiquimod, GM-CSF, mucin-1-mRNA/protamine complex, local hyperthermia or no adjuvant. PSA was assessed, geometric mean doubling times (DT) calculated and clinical performance monitored. RESULTS PSA DT of 4 out of 19 patients (21%) increased from 4.9 to 25.8 months during vaccination. Out of these, two patients (11%) exhibited PSA stability for 28 and 31 months which were still continuing at data cut-off. One patient showed no change of PSA DT during vaccination but decline after the therapy. Three patients had an interim PSA decline or DT increase followed by DT decrease compared to baseline PSA DT. Three of the responding patients received imiquimod and one the mucin-1-mRNA/protamine complex as adjuvant; both are Toll-like receptor-7 agonists. Eleven (58%) patients had progressive PSA values. The vaccine was well tolerated, and no grade III or IV toxicity occurred. CONCLUSION Multi-peptide vaccination stabilized or slowed down PSA progress in four of 19 cases. The vaccination approach is promising with moderate adverse events. Long-term stability delayed androgen deprivation up to 31 months. TLR-7 co-activation seems to be beneficial. Prostate 69: 917,927, 2009. © 2009 Wiley-Liss, Inc. [source] Neuroendocrine transdifferentiation induced by VPA is mediated by PPAR, activation and confers resistance to antiblastic therapy in prostate carcinomaTHE PROSTATE, Issue 6 2008Adriano Angelucci Abstract BACKGROUND Prostate cancer (PCa) is the most commonly diagnosed cancer in men in the Western Countries. When prostatectomy fails to eradicate the primary tumor, PCa is generally refractory to all therapeutic approaches. Valproic acid (VPA) is a promising anticancer agent recently assigned to the class of histone deacetylase (HDAC) inhibitors. However molecular mechanisms underlying VPA action in PCa cells are largely unknown and further experimental validation to prove its potential application in clinic practice is needed. RESULTS In our study we show that VPA is a potent inducer of neuro-endocrine transdifferentiation (NET) in androgen receptor null PCa cells, both in vitro and in vivo. NET was an early event detectable through the expression of neuro-endocrine (NE) markers within 72 hr after VPA treatment and it was associated to a reduction in the overall cell proliferation. When we interrupted VPA treatment we observed the recovery in residual cells of the basal proliferation rate both in vitro and in a xenograft model. The NET process was related to Bcl-2 over-expression in non-NE PCa cells and to the activation of PPAR, in NE cells. The use of specific PPAR, antagonist was able to reduce significantly the expression of NE markers induced by VPA. CONCLUSIONS Our data indicate that the use of VPA as monotherapy in PCa has to be considered with extreme caution, since it may induce an unfavorable NET. In order to counteract the VPA-induced NET, the inhibition of PPAR, may represent a suitable adjuvant treatment strategy and awaits further experimental validation. Prostate 68: 588,598, 2008. © 2008 Wiley-Liss, Inc. [source] Overexpression of cyclooxygenase-2 in human prostate carcinoma and prostatic intraepithelial neoplasia-association with increased expression of polo-like kinase-1THE PROSTATE, Issue 4 2007Carsten Denkert Abstract BACKGROUND Cyclooxygenases (COX) as well as Polo-like kinases (PLK) are involved in proliferation and cell cycle regulation and have been suggested for preventive and therapeutic approaches in prostate carcinoma. METHODS In this study, we studied expression and prognostic impact of COX-2 in invasive prostate carcinoma, prostatic intraepithelial neoplasia (PIN), atrophic glands, and normal prostatic glands, and investigated the association between COX-2 and PLK-1. RESULTS We observed a positivity for COX-2 in 72.1% of PIN and in 44.7% of prostate carcinomas with an overexpression of COX-2 in prostate cancer and PIN compared to benign prostatic tissue (P,<,0.0005). Furthermore, we observed a strong correlation between expression of PLK-1 and COX-2 (P,<,0.0005). CONCLUSIONS To our knowledge, this is the first report of a correlation between COX-2 and PLK-1 in a malignant tumor. COX-2 and PLK-1 may be interesting targets for new molecular therapies in prostate cancer. Prostate 67: 361,369, 2007. © 2007 Wiley-Liss, Inc. [source] FGF17 is an autocrine prostatic epithelial growth factor and is upregulated in benign prostatic hyperplasiaTHE PROSTATE, Issue 1 2004Nathaniel Polnaszek Abstract BACKGROUND Fibroblast growth factors (FGFs) are known to play an important role in the growth of prostatic epithelial cells. Benign prostatic hyperplasia (BPH) is characterized by increased epithelial and stromal proliferation within the transition zone of the prostate. FGF2, FGF7, and FGF9 are expressed in BPH tissue but expression of FGF17 has not been previously characterized in human prostate tissue. METHODS Expression of FGF17 in human prostate tissue and primary cultures of prostatic epithelial and stromal cells was determined by reverse-transcriptase polymerase chain reaction (RT-PCR). Growth response to FGF17 was assessed by addition of recombinant FGF17 to immortalized normal and neoplastic epithelial cell lines and primary cultures of prostatic stromal cells in the presence of insulin. Quantitative analysis of expression of FGF17 relative to keratin 18 and/or ,-actin in normal and hyperplastic prostate and prostate carcinoma was carried out by real-time quantitative RT-PCR. RESULTS FGF17 is expressed by prostatic epithelial cells and can act as an autocrine growth factor for immortalized and neoplastic prostatic epithelial cells. It can also promote stromal proliferation, although only at higher concentrations. Expression of FGF17 per epithelial cell was increased 2-fold in BPH. CONCLUSIONS FGF17 is expressed by normal, hyperplastic, and neoplastic prostatic epithelial cells and can promote epithelial proliferation in an autocrine manner. FGF17 expression is increased 2-fold in BPH and may contribute to the increased epithelial proliferation seen in this disease. © 2004 Wiley-Liss, Inc. [source] Expression of androgen receptor coactivators in normal and cancer prostate tissues and cultured cell linesTHE PROSTATE, Issue 3 2003C. Mestayer Abstract BACKGROUND In prostate cancer cell lines, androgen receptor (AR) coactivators modulate the transcriptional activity of AR. However, very little is known about their expression in normal prostate tissue and during progression to cancer. METHODS AR and coactivators ARA54, ARA55, ARA70, and SRC1 RNA were analyzed by RT-PCR in normal and tumoral tissues of the same prostate, in prostate cell lines, and after hormonal treatments of prostate epithelial cells. RESULTS AR-coactivators were expressed in normal and tumoral tissues and in cultured prostate cells; only ARA55 expression was decreased in tumoral relative to normal tissue of all seven prostates analyzed. It was not expressed in LNCaP and DU145 cancer cells and low in PNT2 immortalized cells in which all coactivator's expression were down regulated by DHT and up regulated by E2. In addition, coactivator's expression was increased in hyperplastic relative to normal prostate fibroblasts. CONCLUSIONS ARA55 is both an AR coactivator and a focal adhesion protein (Hic-5). Its role in the progression of prostate carcinoma may therefore involve these two different functions. Its decrease in cancer tissue suggests that it plays a different role than that expected, namely, facilitate cell proliferation and therefore mobility and metastasis. Prostate 56: 192,200, 2003. © 2003 Wiley-Liss, Inc. [source] PEAZ-1: A new human prostate neoplastic epithelial cell lineTHE PROSTATE, Issue 2 2001Monika Schmelz Abstract BACKGROUND The generation of prostatic cell lines provides in vitro models for experimental studies of the pathogenesis of prostate carcinoma. Therefore, we established and characterized a new human prostate epithelial cell line, PEAZ-1 (prostate epithelial Arizona-1). METHODS The PEAZ-1 cells were grown from a primary human prostate carcinoma specimen obtained from radical prostatectomy. The isolated cells were characterized by immunobiochemistry, immunohistochemistry, and tumorigenicity studies. RESULTS PEAZ-1 cells are near diploid, tumorigenic, and androgen independent for cell growth. PEAZ-1 cells express N-cadherin, ,- and ,-catenins, and p120 at cell,cell contacts, cytoplasmic laminin 5, vinculin, paxillin, and phosphotyrosine at focal adhesions, vimentin, and cytokeratins 8 and 18. They do not express plakoglobin, E-cadherin, and PSA, and do not form desmosomes and hemidesomomes. PEAZ-1 respond to ocadaic acid, a pro-apoptotic agent, by expression of p53. CONCLUSIONS PEAZ-1 cells is a human prostate cancer cell line that has a number of mesenchymal characteristics. Prostate 48:79,92, 2001. © 2001 Wiley-Liss, Inc. [source] Mutational analysis of caspase genes in prostate carcinomasAPMIS, Issue 4 2010MIN SUNG KIM Kim MS, Park SW, Kim YR, Lee JY, Lim HW, Song SY, Yoo NJ, Lee SH. Mutational analysis of caspase genes in prostate carcinomas. APMIS 2010; 118: 308,12. Evasion of apoptosis is one of the hallmarks of cancer. Of the components of apoptosis machinery, caspases are the main executioners of apoptosis that initiate and propagate the apoptosis, and finally degrade target molecules. Caspase-encoding genes have been reported to harbor inactivating mutations in many human cancers. However, mutational status of caspase genes in prostate carcinomas has not been identified. The aim of this study was to explore whether caspase genes are somatically mutated in prostate carcinomas. For this, we analyzed entire coding regions of 11 human caspase-encoding genes (CASP1,10 and 14) in 45 prostate carcinoma tissues by a single-strand conformation polymorphism (SSCP) assay. In this study, however, we detected no somatic mutation of CASP genes in the prostate carcinomas by the SSCP. This is the first report on systematic evaluation of caspase-encoding gene mutations in human prostate carcinomas, and our data indicate that CASP genes may not be mutated in prostate carcinomas. The data suggest that apoptosis evasion in prostate carcinoma may be dependent on other mechanisms besides genetic alteration of caspase-encoding genes. [source] Platinum and Palladium-triazole Complexes as Highly Potential Antitumor AgentsARCHIV DER PHARMAZIE, Issue 4 2010Najim A. Al-Masoudi Abstract The palladium complexes [(dppe)Pd(L)2PdCl2], [(dppe)Pd(L)2PtCl2], [(dppp)Pd(L)2PdCl2], [(dppm) Pd(L)2NiCl2], and [(dppm)Pd(L)2SnCl4] 15,19 were prepared. The antiproliferative activity of the newly synthesized complexes as well as their previously prepared analogues 3,14 and 20,26 were screened against a large panel of human cancer cell lines derived from haematological CD4+ human T-cells containing an integrated HTLV-1 genome (MT-4). The complex 12a, b exhibited remarkable antiproliferative activity against MT-4, CD4+ human acute T-lymphoblastic leukemia (CCRF-CEM), human splenic B-lymphoblastoid cells (WIL-2NS), human acute B-lymphoblastic leukemia (CCRF-SB), skin melanoma (SK-MEL-28), and prostate carcinoma (DU145) cell lines (CC50 = 0.5 ,M, 0.4 ± 0.05 ,M, 0.6 ± 0.05 ,M, 0.4 ± 0.1 ,M, and 0.8 ± 0.2 ,M, respectively), meanwhile, 9a, b, 14a, b, and 23 showed significant activity against the CCRF-SB cell lines (CC50 = 0.6 ± 0.06 ,M, 0.7 ± 0.05 ,M, 0.6 ± 0.05 ,M, and 0.8 ± 0.15 ,M, respectively). Further, 19 exhibited activity against the CCRF-CEM cell line (CC50 = 0.4 ± 0.05 ,M). [source] Abarelix and other gonadotrophin-releasing hormone antagonists in prostate cancerBJU INTERNATIONAL, Issue 11 2009Roger S. Kirby Hormonal therapy is the main recommended treatment for locally advanced and metastatic prostate cancer. Luteinizing hormone-releasing hormone (LHRH) agonists, such as buserelin, goserelin, leuprorelin and triptorelin, stimulate the pituitary's gonadotrophin-releasing hormone (GnRH) receptor, ultimately leading to its de-sensitization and subsequent reduction of LH and testosterone levels. However, this reduction is accompanied by a well described increase or ,surge' in LH and testosterone levels, necessitating the concomitant administration of an antiandrogen to combat the potential effects of transient acceleration in cancer activity. Two pure GnRH antagonists have been developed, abarelix and degarelix, that are devoid of any agonist effect on the GnRH receptor and consequently do not result in testosterone flare. Abarelix was the first GnRH antagonist to be developed and was approved by the USA Food and Drug Administration in 2004 for the initiation of hormonal castration in advanced or metastasizing hormone-dependent prostate carcinoma, when rapid androgen suppression is necessary. Clinical data on both abarelix and degarelix show that they can produce rapid and sustained decreases in testosterone to castrate levels without the need for co-administration of an antiandrogen, and with a very low complication rate in the short term. [source] 65 Multi-resistant Escherichia coli septicaemia following transrectal ultrasound guided prostate biopsy , an emerging riskBJU INTERNATIONAL, Issue 2006A.-J. DAVIDSON Introduction:, Transrectal ultrasound (TRUS) guided biopsy of the prostate is the standard procedure for diagnosing prostate carcinoma. Complications range from discomfort and bleeding to asymptomatic bacteruria and sepsis. Rarely, sepsis is fatal. E. coli is the most common pathogen causing infection and although no international standard for the use of prophylactic antibiotics exists their use has decreased the incidence of infection to around 2%. Worldwide the incidence of multi-resistant E. coli (MREC) is increasing, and we report two cases of septicaemia secondary to MREC infection postprostate biopsy. Methods:, We performed a review of case records involving postprostate biopsy MREC infection. A comprehensive literature review of TRUS guided biopsy of the prostate was also performed. Results:, All patients in our series had MREC cultured following TRUS guided biopsy of the prostate. All received the same prophylactic antibiotic regime (norfloxacin and gentamicin). They required admission to hospital for intravenous antibiotics and in two cases inotropic support, eventually making full recoveries. All had a history of recent travel to a developing country whilst two had self-limiting diarrhoea and this is the first report in the English literature of MREC following prostate biopsy. Other risk factors for acquiring multi-resistant urinary tract infections have been identified including age and previous quinolone therapy. Conclusion:, Antibiotic prophylaxis for biopsy of the prostate, being predominantly quinolones, will continue to aid in reducing morbidity. However, with the prevalence of MREC increasing current regimens will not cover such organisms potentially leading to sepsis. In our cases travel to developing countries appeared to be a risk factor for being colonised with MREC. We believe through careful history risk factors for multi-resistant urinary tract infection including travel may alert doctors to the potential risk of MREC at the time of biopsy leading to the addition of a broader spectrum antibiotic such as intravenous meropenem. [source] Predictors of androgen independence in metastatic prostate cancerBJU INTERNATIONAL, Issue 9 2004H.G. Sim OBJECTIVE To assess the factors that influence the onset of androgen independence (AI, which heralds a dismal outcome) in patients with metastatic prostate carcinoma. PATIENTS AND METHODS The records of 361 consecutive patients with prostate carcinoma diagnosed and treated in the authors' institution from 1 January 1996 to 31 December 1999 were reviewed retrospectively; 92 with metastatic prostate carcinoma were assessed (median age 71.0 years, range 42,93). Patients were included if they developed metastatic disease from prostate cancer at the time of diagnosis. The nadir for prostate specific antigen (PSA) level was defined as the date of the lowest PSA level after hormonal therapy, and AI was defined as the date of the third consecutive PSA increase above the nadir value by any threshold. RESULTS The median Gleason sum was 8 and the modal Gleason score 4 + 5. The median (range) pretreatment PSA level was 274.0 (1.3,2179) ng/mL. Of the 92 men, 57 (62%) attained a nadir PSA, including 23 with a nadir of <,2 ng/mL; 32 (35%) progressed to AI within 2 years and 27% reached a nadir PSA but did not develop AI. The mean (sd) time from diagnosis to the nadir PSA was 13.7 (11.8) months, while the mean time from diagnosis to progression to AI was 30.3 (15.6) months. Univariate analysis showed that a nadir PSA level after treatment of ,,1 ng/mL (P = 0.0128) was an early predictor of progression to AI; a nadir PSA level of ,,2 ng/mL (P = 0.0216) was a predictor of poor overall survival. CONCLUSION Failure to attain a nadir PSA of <,1 ng/mL after treatment predicts progression to AI and a nadir PSA of >,2 ng/mL predicts poorer overall survival. The development of skeletal events predicts the onset of AI but occurs late in the disease and is unsuitable as an early prognostic marker. [source] Long-term outcome of antiandrogen monotherapy in advanced prostate carcinoma: 12-year results of a phase II studyBJU INTERNATIONAL, Issue 6 2003V. Serretta OBJECTIVE To present the long-term outcome of patients with locally advanced or metastatic prostate carcinoma treated by first-line antiandrogen monotherapy. PATIENTS AND METHODS From 1983 to 1990, 41 patients with advanced prostate carcinoma were treated with flutamide monotherapy until progression or the appearance of toxicity. Twenty-five patients (61%) had T3-T4N0M0 and 16 (39%) T2,4N0,3M1 prostate carcinoma. Consensus criteria were adopted to evaluate the response. Plasma testosterone and sexual function were recorded for the first 3 years. RESULTS Flutamide was administered for up to 147 months; seven patients (17%) interrupted the treatment because of toxicity. There was an objective response in 17 (41%) patients; 20 (49%) had stable disease while four (10%) progressed. There were objective responses, lasting up to 150 months, in 82% of those with M0 and in 18% with M1 disease (P = 0.05). The median time to progression in patients with an objective response and stable disease was 45 and 16 months, respectively (P < 0.001). Thirty-one patients (76%) died from prostate cancer and 10 (24%) from unrelated diseases. The median survival was 67 and 36 months in patients with an objective response and stable disease, respectively (P < 0.001). There was an improvement in performance status in 85% and reduction in bone pain in 83% of the patients; sexual activity was maintained in 63%. CONCLUSION Monotherapy with flutamide is well tolerated. Objective responses are more frequent in patients with locally advanced disease. Patients with an objective response within 6 months have a prolonged progression-free and overall survival. [source] | |||||||||||||||||||||||||||||||