Epicatechins Purified from Green Tea (Camellia sinensis) Differentially Suppress Growth of Gender-Dependent Human Cancer Cell Lines.

The anticancer potential of catechins derived from green tea is not well understood, in part because catechin-related growth suppression and/or apoptosis appears to vary with the type and stage of malignancy as well as with the type of catechin. This in vitro study examined the biological effects of epicatechin (EC), epigallocatechin (EGC), EC 3-gallate (ECG) and EGC 3-gallate (EGCG) in cell lines from human gender-specific cancers. Cell lines developed from organ-confined (HH870) and metastatic (DU145) prostate cancer, and from moderately (HH450) and poorly differentiated (HH639) epithelial ovarian cancer were grown with or without EC, EGC, ECG or EGCG. When untreated cells reached confluency, viability and doubling time were measured for treated and untreated cells. Whereas EC treatment reduced proliferation of HH639 cells by 50%, EGCG suppressed proliferation of all cell lines by 50%. ECG was even more potent: it inhibited DU145, HH870, HH450 and HH639 cells at concentrations of 24, 27, 29 and 30 microM, whereas EGCG inhibited DU145, HH870, HH450 and HH639 cells at concentrations 89, 45, 62 and 42 microM. When compared with EGCG, ECG more effectively suppresses the growth of prostate cancer and epithelial ovarian cancer cell lines derived from tumors of patients with different stages of disease.

Long-term outcome for men with androgen independent prostate cancer treated with ketoconazole and hydrocortisone.

PURPOSE: The combination of high dose ketoconazole and hydrocortisone (HDK) is active against androgen independent prostate cancer (AIPC). Median response times with HDK tend to be brief but a significant minority of AIPC patients benefit with extended responses. Well characterized response and survival information, especially in the cohort of patients who experience these longer, more durable, responses has not been previously reported. Characterization of this subgroup is of particular interest since men with long-term responses derive the greatest benefit from HDK therapy. MATERIALS AND METHODS: The medical records of 78 patients with AIPC treated with HDK between March 1991 and February 1999 were retrospectively reviewed. Baseline clinical and laboratory factors predictive of prolonged response and survival were identified. RESULTS: The median baseline prostate specific antigen (PSA) before the initiation of HDK was 25.1. The number of patients with zero, 1 to 3, and more than 3 lesions on bone scan were 25, 35 and 18, respectively. Median and mean time to PSA progression was 6.7 and 14.5 months. Median and mean survival time was 38.0 and 42.4 months, respectively. Response time and survival were highly correlated (r = 0.799). A total of 34 (44%) men had a greater than 75% decrease in PSA. The median survival times in men with more vs less than a 75% decrease were 60 vs 24 months, respectively. In a Cox proportional hazard regression, prolonged survival was predicted by percent PSA decrease, extent of disease on bone scan and baseline PSA. CONCLUSIONS: Ketoconazole can induce prolonged responses, occasionally lasting for years. Long responses are more likely to occur in men initiating HDK earlier in the course of disease before the cancer burden becomes excessive.

Endogenous immune response to gangliosides in patients with confined prostate cancer.

Our study investigated whether endogenous IgM antibodies to gangliosides occur in patients with early stages of prostate cancer (CaP) patients, after defining ganglioside profiles of CaP cell lines. Immune and resorcinol staining detected the presence of gangliosides GM3, GM2, GD3, GD2 and GD1a but not GM1a, GD1b or GT1b in the extracts of normal prostatic epithelial cells (PrEC) and neoplastic androgen-insensitive (PC-3, DU145) and -sensitive (LNCaP-FGC and LNCaP-FGC-10) CaP cells. Using a sensitive ELISA, developed and validated in our laboratory, the titers of IgM against 8 gangliosides from sera of patients with benign prostatic hyperplasia (BPH) (n = 11), organ-confined (T1/T2, n = 36) and unconfined (T3/T4, n = 27) CaP and age-matched healthy men (n = 11) were determined double-blinded. Using ANOVA and Fisher's least significant difference (LSD) methods, the log-titers among different groups were compared. CaP patients differed from healthy and BPH patients in increased titers against GD1a and decreased titers against GD3. Titers of antibodies to other gangliosides exhibited no difference between CaP patients and others. The specific augmentation of anti-GD1a IgM in patients with organ-confined CaP (stage T1/T2) but not in patients with unconfined CaP (stage T3/T4) or BPH or in healthy controls is striking. This finding together with identification of GD1a as a major ganglioside in CaP cell lines and with the accruing studies on the immunosuppressive nature of GD1a indicates that augmentation of anti-GD1a IgM in confined CaP may signify an early endogenous immune response to eliminate a "danger signal" from tumor microenvironment and circulation.

Gangliosides of organ-confined versus metastatic androgen-receptor-negative prostate cancer.

Prior development of a unique androgen-receptor (AR)-negative cell line (HH870) from organ-confined (T2b) human prostate cancer (CaP) enabled comparison of the gangliosides associated with normal and neoplastic prostate epithelial cells, organ-confined versus metastatic (DU 145, PC-3), and AR-negative versus AR-positive CaP cell lines. Resorcinol-HCl and specific monoclonal antibodies were used to characterize gangliosides on 2D-chromatograms, and to visualize them on the cell surface with confocal-fluorescence microscopy. AR-negative cells expressed GM1b, GM2, GD2, GD1a, and GM3. GM1a, GD1b, and GT1b were undetectable. GM1b and GD1a were more prominent in AR-negative than in AR-positive cells. PC-3 and HH870 cells were unique in the expression of O-acetylGD2 (O-AcGD2) and two alpha2,3-sialidase-resistant, alkali-susceptible GMR17-reactive gangliosides. Expression of GD1a, GM1b, doublets of GD3, GD2, and O-AcGD2, and the presence of an additional alkali-labile-14.G2a-reactive ganglioside, two alkali-susceptible, and three alkali-resistant GMR17-reactive gangliosides makes HH870 a potential component of a polyvalent-vaccine for active-specific immunotherapy of CaP.

An open-label study of abarelix in men with symptomatic prostate cancer at risk of treatment with LHRH agonists.

OBJECTIVES: To evaluate the ability of abarelix, a gonadotropin-releasing hormone antagonist, to provide an alternative treatment to bilateral orchiectomy in men with advanced prostate cancer symptoms and to evaluate its safety, clinical and biochemical efficacy, and effects on prostate-specific antigen and serum hormone levels. METHODS: For 168 days, 81 patients from 17 centers received monthly intramuscular injections of open-label abarelix 100 mg (at least one dose). Patients were evaluated for the avoidance of bilateral orchiectomy, efficacy, disease response, percentage of change in prostate-specific antigen level, change in the intensity of pain, neurologic compromise, and other efficacy variables. Safety was evaluated through reports of adverse events and abnormal laboratory values. RESULTS: No patients required bilateral orchiectomy, but 2 patients were withdrawn from the study because of treatment-related events and were considered as failures to avoid orchiectomy. Treatment produced an 88% (38 of 43) objective response rate on day 85. Sixty-five (90%) of 72 patients experienced improvement in the pain score and/or analgesic use, urinary obstruction, urinary catheter removal, hydronephrosis, and/or azotemia. No patient with impending neurologic compromise at study entry developed spinal cord compression. The median reduction from the baseline prostate-specific antigen value was 75% on day 15 and greater than 95% from day 57 onward. Abarelix was well tolerated, and adverse events were the sequelae of advanced prostate cancer, comorbid medical disorders, or medical castration. CONCLUSIONS: These results suggest that abarelix provides a safe and effective medical alternative to surgical castration in symptomatic patients with advanced prostate cancer without the risk of the clinical flare associated with luteinizing hormone-releasing hormone agonists.