Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report our experience in evaluating PSA-follow-up of patients treated with radical prostatectomy. Also PSA is the most sensitive available screening test for relapse after radical prostatectomy, it is not 100% specific for cancer relapse while this serum marker is not specific for prostate cancer. In our opinion, patients with biochemical relapse (PSA > 0.5 ng/l) should undergo an early restaging including biopsy of the anastomosis. In 57% of our patients with PSA > 1.0 ng/l two months after surgery we found clinical recurrence 27 months later on.
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PMID:[The value of PSA follow-up in recurrent prostate carcinoma after radical prostatovesiculectomy]. 753 47

Clinical effects of estramustine phosphate (EMT) on hormone refractory prostate cancer were studied. Prostate cancer relapsed in 70 of the 259 patients with stage C and D diseases who had initially responded to endocrine therapy. After cancer relapse, endocrine therapy was changed to oral administration of EMT in 21 patients, while initial endocrine therapy was continued in 14 and additional radiation therapy was given in 35. A partial response or no change was observed in 11 of the 21 patients (52%) given EMT therapy, the mean duration of the response being 14.2 months. The 21 patients given EMT therapy survived significantly longer than the 14 patients with continued on endocrine therapy, and those responding to EMT therapy tended to have a better survival than those unresponsive. Side effects of EMT included loss of appetite in 2 patients and edema of the lower limb in 1, but they were not severe enough to require discontinuation of the drug. EMT may be a useful drug for patients with advanced prostate cancer with relapse after endocrine therapy.
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PMID:[Effect of estramustine phosphate on hormone refractory prostate cancer]. 912 65

Cancer relapse after surgery is a common occurrence, most frequently resulting from the outgrowth of minimal residual disease in the form of metastases. We examined the effectiveness of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) blockade as an adjunctive immunotherapy to reduce metastatic relapse after primary prostate tumor resection. For these studies, we developed a murine model in which overt metastatic outgrowth of TRAMP-C2 (C2) prostate cancer ensues after complete primary tumor resection. Metastatic relapse in this model occurs reliably and principally within the draining lymph nodes in close proximity to the primary tumor, arising from established metastases present at the time of surgery. Using this model, we demonstrate that adjunctive CTLA-4 blockade administered immediately after primary tumor resection reduces metastatic relapse from 97.4 to 44%. Consistent with this, lymph nodes obtained 2 weeks after treatment reveal marked destruction or complete elimination of C2 metastases in 60% of mice receiving adjunctive anti-CTLA-4 whereas 100% of control antibody-treated mice demonstrate progressive C2 lymph node replacement. Our study demonstrates the potential of adjunctive CTLA-4 blockade immunotherapy to reduce cancer relapse emanating from minimal residual metastatic disease and may have broader implications for improving the capability of immunotherapy by combining such forms of therapy with other cytoreductive measures including surgery.
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PMID:Elimination of residual metastatic prostate cancer after surgery and adjunctive cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) blockade immunotherapy. 1061 40

Interaction between extracellular matrices and cancer cell receptors frequently alters signal transduction pathways, leading to malignant transformation and metastasis. Hyaluronan (HA) is a tumor promoter and enhancer in transformation of androgen-independent (AI) prostate cancer (CaP); however, the signal transduction pathway involved in this mechanism remains unclear. We report here that HA-mediated CD168, a receptor for HA-mediated motility, and its downstream signal molecules, including ROK1, Gab-1, PI3K*p110alpha and eIF4E3, accelerate the progression of AI rather than androgen-dependent CaP and enhance AI cell invasion and metastasis in human bone marrow endothelial layers. MicroRNA-based small hairpin RNA-mediated suppression of ROK1 can reverse the malignant role of CD168 signaling in human AI CaP PC3 and DU145 cells. This differential activation of ROK-PI3K signaling in AI CaP cells may provide clues to shed light on some mechanisms of cancer relapse after androgen ablation. These findings reveal a novel signal transduction mechanism for matrix-mediated cancer transformation and metastasis in hormone-refractory CaP.
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PMID:Hyaluronan stimulates transformation of androgen-independent prostate cancer. 1686 94

Consensus has not been reached on the exact definition of biochemical relapse after prostatectomy; individual institution definitions of relapse after prostatectomy range from consecutively rising prostate-specific antigen (PSA) values of > 0.2 to > 0.6 ng/mL. PSA measurements after radiation are even less predictable. PSA level is a sensitive marker of occult prostate-cancer relapse and provides early notification of recurrence, but a PSA relapse does not equal a clinical relapse or death from prostate cancer. Data are reviewed from retrospective, single-institution trials that have clarified features of PSA relapse after both prostatectomy and radiation, such as the PSA doubling time and the time to the first PSA elevation, which are associated with clinical progression. Various options for treatment of biochemical relapse are also reviewed; these include hormone therapy, combined chemohormonal therapy, alternative medicine and dietary tactics, new agents, and future strategies, such as vaccination. Currently, there is no standard treatment for biochemical failure with proven benefit in terms of quality of life, time to metastases, or survival. Current options include observation for patients with long PSA doubling times or comorbid medical issues and standard or nontraditional hormone therapy or a clinical trial for men who desire early therapy or who have rapid PSA doubling times (< 10-12 months). Trials combining the early use of chemotherapy with hormone therapy are promising. Patients should be encouraged to enroll in clinical trials to help establish standards of care.
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PMID:Biochemical (Prostate-Specific Antigen) Relapse: An Oncologist's Perspective. 1698 48

Consensus has not been reached on the exact definition of biochemical relapse after prostatectomy; individual institution definitions of relapse after prostatectomy range from consecutively rising prostate-specific antigen (PSA) values of > 0.2 to > 0.6 ng/mL. PSA measurements after radiation are even less predictable. PSA level is a sensitive marker of occult prostate-cancer relapse and provides early notification of recurrence, but a PSA relapse does not equal a clinical relapse or death from prostate cancer. Data are reviewed from retrospective, single-institution trials that have clarified features of PSA relapse after both prostatectomy and radiation, such as the PSA doubling time and the time to the first PSA elevation, which are associated with clinical progression. Various options for treatment of biochemical relapse are also reviewed; these include hormone therapy, combined chemohormonal therapy, alternative medicine and dietary tactics, new agents, and future strategies, such as vaccination. Currently, there is no standard treatment for biochemical failure with proven benefit in terms of quality of life, time to metastases, or survival. Current options include observation for patients with long PSA doubling times or comorbid medical issues and standard or nontraditional hormone therapy or a clinical trial for men who desire early therapy or who have rapid PSA doubling times (< 10-12 months). Trials combining the early use of chemotherapy with hormone therapy are promising. Patients should be encouraged to enroll in clinical trials to help establish standards of care.
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PMID:Biochemical (Prostate-Specific Antigen) Relapse: An Oncologist's Perspective. 1698 44

Conventional therapies for prostate cancer, especially in its androgen-independent form, may result in the survival of small populations of resistant cells with tumor-initiating potential. These "cancer stem cells" are believed to be responsible for cancer relapse, and therapeutic strategies targeting these cells are of great importance. Telomerase is a ribonucleoprotein enzyme responsible for telomere elongation and is activated in the majority of malignancies, including prostate cancer, but is absent in most normal cells. Putative tumor-initiating cells have significant levels of telomerase, indicating that they are an excellent target for telomerase inhibition therapy. In this review, we present some evidence for the hypothesis that conventional therapies (standard chemotherapy and/or radiation therapy) in combination with telomerase inhibitors may result in effective and more durable responses.
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PMID:Prostate tumor-initiating cells: a new target for telomerase inhibition therapy? 1926 26

Prostate cancer is the most common malignancy of the urogenital tract. Although controversial, prostate-specific antigen (PSA) testing is widely used for screening and follow-up of prostate cancer, but because of its limited specificity and sensitivity, PSA is not an ideal test. We currently lack the necessary tools to differentiate between latent disease with little likelihood of clinical manifestation and aggressive tumours that are likely to metastasize and lead to potentially lethal disease. DNA methylation is an important epigenetic mechanism of gene regulation and plays essential roles in tumour initiation and progression. Currently, aberrant promoter hypermethylation has been investigated in specific genes from the following groups: tumour-suppressor genes, proto-oncogenes, genes involved in cell adhesion, and genes involved in cell-cycle regulation. Glutathione S-transferase P1 (GSTP1) has been shown to be a biomarker for prostate cancer. Other genes, e.g. CD44, PTGS2, E-cadherin, CDH13, and cyclin D2 have been found to be prognostic markers for prostate cancer. In cell samples derived from the urine, the presence of the hypermethylation of either GSTP1 or RASS1a has been shown to be both sensitive and specific for detecting prostate cancer. Several studies have found that analysis of hypermethylation using a panel of tumour-suppressor genes yielded better results for detecting prostate cancer than the analysis of single-gene methylation. Hence, these different panels (e.g. GSTP1, APC, PTGS2, T1G1 and EDNRB) are of interest for detecting prostate cancer. Also, the methylation profile of multiple regulatory genes might be altered at the time of cancer relapse. Thus, preliminary results on the use of the methylation status of specific genes as potential tumour biomarkers for the early diagnosis and the risk stratification of patients with prostate cancer are promising.
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PMID:Methylated genes as potential biomarkers in prostate cancer. 2006 51

Escape of prostate cancer (PCa) cells from ionizing radiation-induced (IR-induced) killing leads to disease progression and cancer relapse. The influence of sphingolipids, such as ceramide and its metabolite sphingosine 1-phosphate, on signal transduction pathways under cell stress is important to survival adaptation responses. In this study, we demonstrate that ceramide-deacylating enzyme acid ceramidase (AC) was preferentially upregulated in irradiated PCa cells. Radiation-induced AC gene transactivation by activator protein 1 (AP-1) binding on the proximal promoter was sensitive to inhibition of de novo ceramide biosynthesis, as demonstrated by promoter reporter and ChIP-qPCR analyses. Our data indicate that a protective feedback mechanism mitigates the apoptotic effect of IR-induced ceramide generation. We found that deregulation of c-Jun induced marked radiosensitization in vivo and in vitro, which was rescued by ectopic AC overexpression. AC overexpression in PCa clonogens that survived a fractionated 80-Gy IR course was associated with increased radioresistance and proliferation, suggesting a role for AC in radiotherapy failure and relapse. Immunohistochemical analysis of human PCa tissues revealed higher levels of AC after radiotherapy failure than those in therapy-naive PCa, prostatic intraepithelial neoplasia, or benign tissues. Addition of an AC inhibitor to an animal model of xenograft irradiation produced radiosensitization and prevention of relapse. These data indicate that AC is a potentially tractable target for adjuvant radiotherapy.
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PMID:Radiation-induced acid ceramidase confers prostate cancer resistance and tumor relapse. 2409 26

Tumor Protein 53-Induced Nuclear Protein 1 (TP53INP1) plays an important role during cell stress response in synergy with the potent "genome-keeper" p53. In human, the gene encoding TP53INP1 is expressed at very high level in some pathological situations, such as inflammation and prostate cancer (PC). TP53INP1 overexpression in PC seems to be a worse prognostic factor, particularly predictive of biological cancer relapse, making TP53INP1 a relevant specific target for molecular therapy of Castration Resistant (CR) PC. In that context, detection of TP53INP1 in patient biological fluids is a promising diagnostic avenue. We report here successful development of a new Enzyme-Linked Immunosorbent Assay (ELISA) detecting TP53INP1, taking advantage of molecular tools (monoclonal antibodies (mAbs) and recombinant proteins) generated in the laboratory during the course of basic functional investigations devoted to TP53INP1. The ELISA principle is based on a sandwich immunoenzymatic system, TP53INP1 protein being trapped by a first specific mAb coated on microplate then recognized by a second specific mAb. This new assay allows specific detection of TP53INP1 in serum of several PC patients. This breakthrough paves the way towards investigation of a large cohort of patients and assessment of clinical applications of TP53INP1 dosage.
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PMID:Development of an ELISA detecting Tumor Protein 53-Induced Nuclear Protein 1 in serum of prostate cancer patients. 2460 May 58


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