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      Gamma-glutamyltransferase activity in exosomes as a potential marker for prostate cancer.

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          Abstract

          Exosomes or extracellular vesicles have the potential as a diagnostic marker for various diseases including cancer. In order to identify novel exosomal markers for prostate cancer (PC), we performed proteomic analysis of exosomes isolated from PC cell lines and examined the usefulness of the marker in patients.

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          Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study.

          Dominik R. Berthold, Gregory R. Pond, Freidele Soban … (2008)
          The TAX 327 study compared docetaxel administered every 3 weeks (D3), weekly docetaxel (D1), and mitoxantrone (M), each with prednisone (P), in 1,006 men with metastatic hormone-resistant prostate cancer (HRPC). The original analysis, undertaken in August 2003 when 557 deaths had occurred, showed significantly better survival and response rates for pain, prostate-specific antigen (PSA), and quality of life for D3P when compared with MP. Here, we report an updated analysis of survival. Investigators were asked to provide the date of death or last follow-up for all participants who were alive in August 2003. By March 2007, data on 310 additional deaths were obtained (total = 867 deaths). The survival benefit of D3P compared with MP has persisted with extended follow-up (P = .004). Median survival time was 19.2 months (95% CI, 17.5 to 21.3 months) in the D3P arm, 17.8 months (95% CI, 16.2 to 19.2 months) in the D1P arm, and 16.3 months (95% CI, 14.3 to 17.9 months) in the MP arm. More patients survived >/= 3 years in the D3P and D1P arms (18.6% and 16.6%, respectively) compared with the MP arm (13.5%). Similar trends in survival between treatment arms were seen for men greater than and less than 65 years of age, for those with and without pain at baseline, and for those with baseline PSA greater than and less than the median value of 115 ng/mL. The present analysis confirms that survival of men with metastatic HRPC is significantly longer after treatment with D3P than with MP. Consistent results are observed across subgroups of patients.
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            Androgen-independent cancer progression and bone metastasis in the LNCaP model of human prostate cancer.

            G. N. Thalmann, P Anezinis, S Chang … (1994)
            Our laboratory has previously reported on the derivation of LNCaP cell sublines from LNCaP tumors maintained in castrated and intact athymic male mice. These LNCaP sublines differ from the parental line in tumorigenicity and androgen dependence. This paper demonstrates that one of these sublines acquired metastatic potential. When inoculated either s.c. or orthotopically, the C4-2 subline metastasized to the lymph node and bone with an incidence of 11-50%. Interestingly, the incidence of osseous metastasis was higher in castrated than in intact male hosts. We evaluated the chromosomal, immunohistochemical, and biochemical characteristics of the LNCaP sublines derived from C4-2 tumors that metastasized to the lymph node and bone. Cytogenetic analysis showed that all sublines were human and shared common marker chromosomes with the parental LNCaP cells. This experimental human prostate cancer model may permit, for the first time, the study of the molecular mechanisms underlying human prostate cancer metastasis.
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              Gamma glutamyl transferase and metabolic syndrome, cardiovascular disease, and mortality risk: the Framingham Heart Study.

              B D’Agostino, R Vasan, Sheng-Jun Wang … (2006)
              To determine whether serum gamma-glutamyl transferase (GGT) predicts cardiovascular disease (CVD) morbidity and mortality, accounting for temporal changes in known CVD risk factors and C-reactive protein (CRP). In 3451 Framingham Study participants (mean age 44 years, 52% women) we examined the relations of GGT with CVD risk factors, and prospectively determined the risk of new-onset metabolic syndrome, incident CVD, and death. GGT was positively associated with body mass index, blood pressure, LDL cholesterol, triglycerides, and blood glucose in cross-sectional analysis (P<0.005). On follow-up (mean 19 years), 968 participants developed metabolic syndrome, 535 developed incident CVD, and 362 died. The risk of metabolic syndrome increased with higher GGT (multivariable-adjusted hazard ratio [HR] per SD increment log-GGT, 1.26 [95%CI; 1.18 to 1.35]). Adjusting for established CVD risk factors (as time-dependent covariates updated quadriennially) and baseline CRP, a 1-SD increase in log-GGT conferred a 13% increase in CVD risk (P=0.007) and 26% increased risk of death (P<0.001). Individuals in the highest GGT quartile experienced a 67% increase in CVD incidence (multivariable-adjusted HR 1.67, 95%CI; 1.25 to 2.22). An increase in serum GGT predicts onset of metabolic syndrome, incident CVD, and death suggesting that GGT is a marker of metabolic and cardiovascular risk.
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                Author and article information

                Journal
                Journal ID (iso-abbrev): BMC Cancer
                Title: BMC cancer
                Publisher: Springer Nature
                ISSN (Electronic): 1471-2407
                ISSN (Print): 1471-2407
                Publication date (Electronic): May 05 2017
                Volume: 17
                Issue: 1
                Affiliations
                [1 ] Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan.
                [2 ] Department of Pathology, Tokyo Metropolitan Geriatric Hospital, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan.
                [3 ] Department of Urology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, Gifu, 501-1193, Japan.
                [4 ] Department of Urology, Tokyo Metropolitan Geriatric Hospital, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan.
                [5 ] Department of Clinical Laboratory, Tokyo Metropolitan Geriatric Hospital, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan.
                [6 ] Department of Urology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, Gifu, 501-1193, Japan. mizutech@gifu-u.ac.jp.
                [7 ] Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan. mito@tmig.or.jp.
                Article
                Publisher Item ID: 10.1186/s12885-017-3301-x
                DOI: 10.1186/s12885-017-3301-x
                PMC ID: 5420129
                PubMed ID: 28476099
                SO-VID: a3562aa6-4f4f-4a6c-a110-d0f06749ce83
                History

                Keywords: Benign prostatic hyperplasia,Diagnostic marker,Exosome,Prostate cancer,γ-glutamyl transpeptidase,γ-glutamyltransferase 1
                Data availability:
                Keywords: Benign prostatic hyperplasia, Diagnostic marker, Exosome, Prostate cancer, γ-glutamyl transpeptidase, γ-glutamyltransferase 1

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