Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study evaluated three human prostate xenograft tumors (CWR22, CWR22R, and CWR91) as models for drug activity evaluation. The chemosensitivity and the expression of several proteins (i.e., p-glycoprotein or Pgp, prostate specific antigen or PSA, p53, and Bcl-2) in xenograft tumors were compared with those in patient tumors obtained through radical prostatectomy (n = 26). CWR22 is androgen-dependent, CWR22R is the androgen-independent subline of CWR22, and CWR91 is a separately derived androgen-independent tumor. The results of immunohistochemical and/or Western blot analysis indicate that the expression of PSA, Pgp, p53, and Bcl-2 in the three CWR xenograft tumors are representative of their expression in 100, 85, 90, and 60%, respectively, of patient tumors. The responses of histocultures of xenograft tumors to doxorubicin and paclitaxel, including inhibition of DNA precursor incorporation and cell death induction, were qualitatively similar to the responses of patient tumors. For example, in all three xenograft and patient tumors, doxorubicin produced complete antiproliferation and cytotoxicity (ie., cell kill) whereas paclitaxel produced incomplete effects. A comparison of the concentration-effect relationships in xenograft and patient tumors (population median values) indicates that the chemosensitivity observed in patient tumors is represented by the chemosensitivity of one or more of the three xenograft tumors, as follows: (a) the three xenograft tumors and patient tumors responded equally to doxorubicin-induced antiproliferation; (b) CWR22R, CWR91 and patient tumors responded equally to doxorubicin-induced cytotoxicity, whereas CWR22 was 2-3-fold less sensitive; (c) CWR22 and CWR22R tumors were less sensitive to paclitaxel-induced antiproliferation compared with patient tumors, whereas CWR91 was several-fold more sensitive; and (d) CWR22, CWR22R and patient tumors responded equally to paclitaxel-induced cytotoxicity, whereas CWR91 was 2-3-fold more sensitive. The results of this study indicate that the three xenograft tumors, which show chemosensitivity comparable with the results of > or =50% patient tumors and encompass the majority of the heterogeneous patient prostate tumors in the expression of Pgp, PSA, p53 and Bcl-2 proteins, are useful models for drug activity evaluation.
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PMID:Androgen-dependent and -independent human prostate xenograft tumors as models for drug activity evaluation. 966 91

Neoadjuvant hormone therapy (NHT) prior to radical prostatectomy (RP) results in residual foci of atrophic glands, which can be difficult to identify with hematoxylin-eosin staining, raising the possibility that the low positive-margin rates are an artifact of pathologic understaging. The purpose of this study was to evaluate changes in prostate specific antigen (PSA) and prostatic acid phosphatase (PAP), as well as proliferation marker Ki-67 and Bcl-2 oncoprotein, by immunostaining after 8 months of NHT. Twenty-nine men with clinically confined prostate cancer who received 8 months of NHT and had both pretreatment biopsy and RP specimens obtained at Vancouver Hospital constituted the treatment group. The control group consisted of 23 RP specimens from patients not receiving NHT. Sections were stained with antibodies against PSA, PAP, proliferation marker Ki-67, and the antiapoptosis protein Bcl-2. The PSA and PAP immunostaining were graded for percentage of positive tumor cells and intensity of staining, while Ki-67 and Bcl-2 staining was graded according to the percentage of positive tumor cells. Absent or low percentage-positive PSA and PAP staining was observed in 40% to 50% of the NHT-treated RP specimens but none of the needle biopsy or untreated control RP specimens. Low-intensity PSA and PAP staining was detected only in RP specimens after NHT treatment, and then in only 20% of cases. Low or absent Ki-67 staining was noted in 78% of the NHT- treated RP specimens, compared with only 13% of the matched pre-NHT needle biopsies and 26% of untreated RP specimens. The percentage of specimens with high (>5%) Ki-67 staining decreased from 37% in the pre-NHT needle biopsies to 8% in the NHT-treated RP specimens. Bcl-2 staining increased after treatment with NHT, with 20% of the needle biopsies having high (>5%) Bcl-2 staining compared with 53% of the NHT-treated RP specimens. The frequency of low Bcl-2 staining (<1%) decreased from 53% in the pre-NHT needle biopsies to 27% in the NHT-treated RP specimens. Although PAP and PSA staining decreased after NHT, both markers remain sufficiently positive to be used as epithelial markers to help detect residual foci of prostate cancer that are difficult to identify on H&E-stained slides after NHT. Increased Bcl-2 after NHT, even in early-stage disease, is consistent with its role in the prevention of apoptosis and progression to androgen independence. Low levels of Ki-67 staining indicates a low probability of proliferation and outgrowth of androgen-independent clones after 8 months of NHT.
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PMID:Immunohistochemical Analysis of Radical Prostatectomy Specimens After 8 Months of Neoadjuvant Hormonal Therapy. 1085 34

Population studies have suggested that lycopene, which is mostly found in tomato and tomato products, may reduce the risk of prostate cancer. We previously found that tomato sauce consumption prior to prostatectomy for prostate cancer decreased serum prostate specific antigen, decreased oxidative DNA damage, and increased lycopene concentrations in prostate tissue (Chen et al., 2001). Here, we extended those investigations to determine whether apoptotic cell death and associated Bcl-2 and Bax proteins were modulated by tomato sauce intervention. Thirty-two patients diagnosed by biopsy with prostate carcinoma were given tomato sauce pasta entrees (30 mg lycopene/day) for 3 wk before prostatectomy. Thirty-four patients with prostate cancer who did not consume tomato sauce and underwent prostatectomy served as controls. When tumor areas with the most apoptotic cells were compared in the biopsy (before) and resected prostate tissue (after), tomato sauce consumption increased apoptotic cells in benign prostate hyperplasia (BPH) from 0.66 +/- 0.10% to 1.38 +/- 0.31% (P = 0.013) and in carcinomas from 0.84 +/- 0.13% to 2.76 +/- 0.58% (P = 0.0003). When comparable morphological areas were counted, apoptotic cell death in carcinomas increased significantly with treatment, from 0.84 +/- 0.13% to 1.17 +/- 0.19% (P = 0.028), and apoptotic cell death in BPH showed a tendency toward an increase from 0.66 +/- 0.10% to 1.20 +/- 0.32% (P = 0.20). When the values of apoptotic cells in BPH and carcinomas of patients who consume tomato sauce were compared with corresponding control lesions of the patients who did not consume tomato sauce in resected prostate tissue, the differences of values were not significant [BPH 1.38 +/- 0.31% vs. 1.14 +/- 0.32% (P = 0.97); carcinomas 2.76 +/- 0.58% vs. 1.91 +/- 0.32% (P = 0.24)]. Tomato sauce consumption did not affect Bcl-2 expression but decreased Bax expression in carcinomas. These data provide the first in vivo evidence that tomato sauce consumption may suppress the progression of the disease in a subset of patients with prostate cancer by increasing apoptotic cell death. However, because of the relatively small number of control and tomato sauce-supplemented patients and the variability in the values of apoptotic cells in BPH and carcinomas, a much larger number of patients needs to be examined to support the data generated in this study.
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PMID:Effects of tomato sauce consumption on apoptotic cell death in prostate benign hyperplasia and carcinoma. 1476 36

Prostatic ductal adenocarcinoma represents a rare histological variant of prostatic carcinoma with features of a papillary lesion at cystoscopy. There are conflicts regarding the existence, origin, staging, grading, treatment and clinical behavior of this tumor. The aim of the present study is to examine the expression of Bcl-2 and p53 in prostatic ductal adenocarcinoma and to evaluate its origin by analyzing prostate specific antigen, prostate specific acid phosphatase, cytokeratins, epithelial membrane antigen and carcinoembryonic antigen expressions. The results confirmed the expression of prostate specific antigen and prostate specific acid phosphatase in prostatic ductal adenocarcinoma. The demonstrated expression of Bcl-2 was predominant in the better-differentiated tumor. Bcl-2 expression appears not to be associated with neuroendocrine differentiation as assessed by chromogranin A reactivity. Thus, the first case of a prostatic ductal adenocarcinoma showing Bcl-2 expression is presented. The tumor was negative for p53.
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PMID:Prostatic ductal adenocarcinoma showing Bcl-2 expression. 1537 52

FTY720, a derivative of fungus, has demonstrated dramatic anticancer effect in several malignancies recently. Our study evaluates the therapeutic potential of FTY720 in the treatment of androgen-independent prostate cancer using a human prostate cancer xenograft in nude mice. CWR22R, an androgen-independent human prostate tumor xenograft was inoculated into castrated nude mice and the animals were administrated with either normal saline or FTY720 (10 mg/kg) through intraperitoneal (i.p.) injection for 20 days. Body weight and tumor volume were recorded every 2 days, and serum prostate specific antigen (PSA) levels were also measured before and after the treatment. The effect of FTY720 on tumor cell proliferation was examined using antibodies against PCNA and Ki-67 by immunohistochemical staining, MTT assay and colony forming assay, whereas apoptotic effect of FTY720 was evaluated by TUNEL assay and immunostaining using antibodies against cleaved caspase 3 and Bcl-2. In addition, the potential inhibitory effect of FTY720 on prostate cancer angiogenesis and metastasis was investigated by immunostaining of CD31, VEGF, E-cadherin and beta-catenin. Our results showed that FTY720 treatment led to suppression of CWR22R tumor growth without causing any detectable side effects in nude mice. The FTY720-induced tumor suppression was correlated with decreased serum PSA level as well as reduced proliferation rate, suppression of angiogenic factors, and restoration of E-cadherin and beta-catenin expression. In addition, the FTY720-treated tumors showed increased apoptosis rate demonstrated by increased TUNEL- and cleaved caspase 3-positive cells, and decreased Bcl-2 expression. Our results suggest a potential novel agent in the suppression of androgen-independent prostate cancer.
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PMID:FTY720, a fungus metabolite, inhibits in vivo growth of androgen-independent prostate cancer. 1598 40

The taxoid analogue docetaxel is a potent inhibitor of microtubular depolymerisation and, in hormone-refractory metastatic prostate cancer, it also counters the effects of the anti-apoptotic protein Bcl-2. Overall survival was significantly increased in patients with hormone-refractory metastatic prostate cancer receiving intravenous docetaxel every 3 weeks plus oral prednisone or estramustine, compared with patients receiving intravenous mitoxantrone every 3 weeks plus prednisone in two large phase III trials (TAX 327 and SWOG [Southwest Oncology Group] 9916). In the TAX 327 study, patients receiving docetaxel 75 mg/m(2) every 3 weeks plus prednisone had a median overall survival duration of 18.9 months; in the SWOG 9916 study, median overall survival duration was 17.5 months with docetaxel 60 mg/m(2) every 3 weeks plus estramustine 280 mg three times daily on days 1-5. The median overall survival duration for the control arm of mitoxantrone 12 mg/m(2) every 3 weeks plus prednisone was 16-17 months. Compared with mitoxantrone plus prednisone, docetaxel plus prednisone improved prostate specific antigen response rate, pain and health-related quality of life, and docetaxel plus estramustine increased progression-free survival. Adverse events were more common with docetaxel- than mitoxantrone-based treatment regimens, but most events associated with docetaxel were mild-to-moderate in severity.
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PMID:Docetaxel in hormone-refractory metastatic prostate cancer. 1626 95

Cancer of the prostate gland (CaP), the most common invasive malignancy and a major cause of cancer related deaths in male population in the USA, is an ideal candidate disease for chemoprevention because it is typically detected in elderly population with a relatively slower rate of growth and progression. Many dietary phytochemicals are showing promising chemopreventive effects, at-least in pre-clinical models of CaP. Our published data in cell culture and animal studies, supported by the work from other laboratories, as well as epidemiological observations and case-control studies, suggest that polyphenols present in green tea possess CaP chemopreventive and possibly therapeutic effects. This present study was designed to compare CaP cancer chemopreventive effects of green tea polyphenols (GTP), water extract of black tea, and their major constituents epigallocatechin-3-gallate and theaflavins, respectively, in athymic nude mice implanted with androgen-sensitive human CaP CWR22Rnu1 cells. Our data demonstrated that the treatment with all the tea ingredients resulted in (i) significant inhibition in growth of implanted prostate tumors, (ii) reduction in the level of serum prostate specific antigen, (iii) induction of apoptosis accompanied with upregulation in Bax and decrease in Bcl-2 proteins, and (iv) decrease in the levels of VEGF protein. Furthermore, we also found that GTP (0.01 or 0.05% w/v; given after establishment of CWR22Rnu1 tumor) causes a significant regression of tumors suggesting therapeutic effects of GTP at human achievable concentrations.
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PMID:Inhibition of CWR22Rnu1 tumor growth and PSA secretion in athymic nude mice by green and black teas. 1638 39

Incidental prostate cancer (PCa) has been demonstrated at autopsy in about 80% of men aged 80 years and above and also in 10%-15% of younger men aged 30-50 years in the United States. These data imply a wide variation in aggressiveness of prostate cancer, from indolent tumors to aggressive cancers that kill the patients. The use of prostate specific antigen (PSA) in screening for PCa may detect even indolent disease for which radical prostatectomy may not be necessary. Currently available criteria such as histological grade, PSA level, stage of the disease do not always predict outcome. Furthermore, only about 80% of men with metastatic PCa will respond to first line hormone manipulation and once the patient develops hormone resistant prostate cancer (HRPCa), survival remains poor. Recent genomic and proteomic studies have provided many novel molecular markers that may help to redefine prognostic parameters. This paper is a review of studies using these novel markers in order to determine whether prostate cancer patients with the following characteristics have more aggressive cancer than those without: a) high serum levels of cathepsin B, survivin, Her - 2 / neu, IGFBP-2; b) low serum stefin A, IGFBP-3, c) positive immuno-staining of primary tumors for Her-2/neu, survivin and cathepsin B / stefin A ratio > 1 and d) gene expression of AMACR, HER-2/neu, high Bcl-2: Bax ratio and EZH2 in cancer cells. These markers have been chosen for review because they are among the most promising markers emerging currently.
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PMID:The importance of determining the aggressiveness of prostate cancer using serum and tissue molecular markers. 1840 43

Accumulating epidemiological data suggest that Asian men have lower incidences of prostate cancer and benign prostate hyperplasia (BPH) compared with American and European populations and may have benefited from their higher intake of phytoestrogens in their diet. However, how these phytochemicals affect prostatic diseases is still unclear. In this study, we isolated six lignans from a plant, Campylotropis hirtella (Franch.) Schindl., which has been used as a folk medicine for treatment of BPH in China, through bioassay guided fractionation. They were dehydrodiconiferyl alcohol (C1), 4-[(-6-hydroxy-2,3-dihydro-1-benzofuran-3-yl)methyl]-5-methoxybenzene-1,3-diol (C2), erythro-guaiacylglycerol-beta-O-4'-coniferyl ether (C3), threo-guaiacylglycerol-beta-O-4'-coniferyl ether (C4), secoisolariciresinol (C5), and prupaside (C6), where C2 was identified as a new lignan analog. Their IC50 values for inhibition of prostate specific antigen (PSA) secretion were 19, 45, 110, 128, 137, and 186 microM, respectively, from C1 to C6 in LNCaP cells. Further study showed that C1-5 down-regulated cellular PSA expression and C1-4 also decreased androgen receptor (AR) expression in LNCaP cells. Furthermore, we investigated the proapoptotic effect of C1 on LNCaP cells. The active forms of caspase 3 associated with the specific proteolysis of poly (ADP-ribose) polymerase (PARP) were detected, and the antiapoptotic protein Bcl-2 was down-regulated after the treatment with C1. These results collectively indicated that these lignans may have chemopreventive or therapeutic actions for prostate cancer through suppressing AR signaling pathway and inducing apoptosis.
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PMID:Lignans isolated from Campylotropis hirtella (Franch.) Schindl. decreased prostate specific antigen and androgen receptor expression in LNCaP cells. 1865 36

Aqueous extract of Psidium guajava L. budding leaves (PE) has been shown to possess anti-prostate cancer activity in a cell line model. We examined whether its bioactivity could be conserved either in the presence or the absence of synthetic androgen R1881. In both cases, PE was shown to inhibit LNCaP cell proliferation and down-regulate expressions of androgen receptor (AR) and prostate specific antigen (PSA). The cytotoxicity of PE was shown by enhanced LDH release in LNCaP cells. The flow cytometry analysis revealed cell cycle arrests at G(0)/G(1) phase with huge amount of apoptotic LNCaP cells after treatment with PE for 48 h in a dose-responsive manner, which was also confirmed by TUNEL assay. From the results of decreased Bcl-2/Bax ratio, inactivation of phosphor-Akt, activation of phosphor-p38, phospho-Erk1/phospho-Erk2, the molecular action mechanism of PE to induce apoptosis in LNCaP cells was elucidated. Compatible with the in vitro study findings, treatment with PE (1.5 mg/mouse/day) significantly diminished both the PSA serum levels and tumor size in a xenograft mouse tumor model. Conclusively, PE is a promising anti-androgen-sensative prostate cancer agent.
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PMID:Action mechanism and signal pathways of Psidium guajava L. aqueous extract in killing prostate cancer LNCaP cells. 2009 1


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