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)

The interferon (IFN)-alpha and -gamma producing capacities were measured in 47 patients with prostatic cancer by the whole blood method. The mean IFN-alpha producing capacity in prostatic cancer patients was 3,657 IU/ml, which indicated a significantly (P less than 0.005) lower value than that in healthy male control aged 50 years or more (mean value, 4,988 IU/ml), while the IFN-gamma producing capacity was almost normal. The IFN-alpha and -gamma producing capacities in patients with stage D disease was decreased as compared with that in patients with stage A, B or C. The higher the grade of the diseases, the lower the IFN producing capacity tended to be. In patients with prostatic cancer, the prognosis was worse in low IFN producing capacity group than in normal or high IFN producing capacity group. These results suggest that the measurement of IFN producing capacity is useful for the estimation of the prognosis of patients with prostatic cancer, and that the IFN producing capacity may be a factor which decides the prognosis.
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PMID:[Interferon-producing capacity in patients with prostate cancer: prognosis value]. 214 3

Human recombinant tumor necrosis factor-alpha (rTNF-alpha, 10(-12)-10(-8) M) inhibited the proliferation of androgen-dependent LNCaP cells by 32-56%. In contrast, proliferation of androgen-independent PC-3 and JCA-1 cells was only slightly inhibited, or not inhibited at all, respectively. Human recombinant interferon-gamma (rIFN-gamma, 500 U/ml) decreased proliferation of PC-3 and JCA-1 cells by 35% and 53%, respectively, but had no effect on LNCaP cells. Interestingly, the combination of rIFN-gamma and TNF-alpha had greater antiproliferative effects on JCA-1 cells than treatment with either cytokine alone. However, the antiproliferative effects of this combination were similar to those observed for PC-3 or LNCaP cells treated with rIFN-gamma or TNF-alpha alone, respectively. These data suggest that some forms of androgen-independent prostate cancer may benefit from a combination therapy of IFN-gamma and TNF-alpha, while the use of IFN-gamma alone may be more efficacious in others.
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PMID:Effect of tumor necrosis factor-alpha and interferon-gamma on the growth of human prostate cancer cell lines. 853 4

We have identified that human prostatic cancer cell lines DU145, PC3, ND1, ALVA31 and JCA1 released soluble CD44 molecules and DU145, PC3 and ND1 released soluble CD54. Both soluble and surface CD44 were not found in LNCaP, and both forms of CD54 were not expressed in LNCaP and JCA1. CD54 was found to be highly expressed on cell surface in ALVA31, but these cells did not release soluble CD54. Expression of both cell surface and soluble forms were examined after treatment of cells with IFN-gamma, TGF-beta 1, or culturing in serum-free media. The concentration of soluble CD54 in supernatants changed to small extent after treatment with TGF-beta 1 and increased after treatment with IFN-gamma or in serum-free media. Cell surface expression of CD54 however, changed only minimally after treatment. The levels of cell surface and soluble CD44 also changed minimally after treatment with IFN-gamma and TGF-beta 1 but decreased in serum-free media and this was accompanied by marked elevation of soluble CD44 in supernatants. These data indicate that soluble CD44 might be released from cell surface by shedding whereas alternative splicing is the most likely mechanism of soluble CD54 release.
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PMID:Soluble forms of CD44 and CD54 (ICAM-1) cellular adhesion molecules are released by human prostatic cancer cell lines. 891 63

To assess the tumor targeting, safety, and efficacy of monoclonal antibody 131I-labeled CC49 in patients with androgen-independent prostate cancer, 16 patients received 75 mCi/m2 of the radiolabeled antibody after 7 days of IFN-gamma pretreatment. Sequential tumor biopsies in three patients showed a median 5-fold (range, 2-6-fold) increase in the proportion of cells staining positively for the TAG-72 antigen, whereas one showed a decrease in staining. Fourteen patients received 131I-labeled CC49, whereas 2 showed a disease-related decrease in performance status, precluding antibody treatment. The antibody localized to sites of metastatic androgen-independent prostate cancer in 86% (12 of 14; 95% confidence interval, 57-95%) of cases. Both osseous and extraosseous sites were visualized, and in six (42%) patients, more areas were visible when the radioimmunoconjugate was used than were apparent when conventional scanning techniques were used. The localization of the conjugate in the marrow cavity was usually a site not visualized by the radionuclide bone scan, in which the isotope localizes primarily to the tumor-bone interface. The dose-limiting toxicity was thrombocytopenia because five (36%) patients showed grade IV and seven (50%) showed grade III effects. In addition, six (42%) patients, four of whom were hospitalized, showed a flare in baseline pain, and four showed a decrease in pain. No patient showed a >50% decline in prostate-specific antigen, although radionuclide bone scans remained stable in four cases for a median of 4 months. The results are consistent with dosimetry estimates showing that the delivered dose to tumor was subtherapeutic and suggest that approaches that exclusively target the bone tumor interface or the marrow stroma may be unable to completely eradicate disease in the marrow cavity. For CC49, improving outcomes would require repetitive dosing, which was precluded by the rapid development of a human antimouse antibody response.
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PMID:Interferon-gamma and monoclonal antibody 131I-labeled CC49: outcomes in patients with androgen-independent prostate cancer. 953 32

We have previously identified (M. Wang et al., Oncol. Res., in press, 1998) an enhancer element [human tissue inhibitor of metalloproteinase-1 enhancer-1 (HTE)] for the human tissue inhibitor of metalloproteinase-1 promoter that binds a novel zinc finger, cysteine-rich transcription factor (CRTF). In this study, we have used electrophoretic mobility shift assays to examine the relative level of expression of CRTF, jun/fos, and IFN-gamma responsive signal transducer activators of transcription (STATs) that bind specific HTE, activator protein, and IFN-gamma (Fcy and interferon regulatory factor) response motifs in tumor lines and human prostate tissue [i.e., normal (n = 3); benign prostatic hyperplasia (BPH; n = 12); high grade prostate intraepithelial neoplasia (PIN; n = 10); and prostate cancer adenocarcinoma (PCA; n = 61) plus seminal vesicle (n = 10) tissues]. The data showed that CRTF was overexpressed in PCA (Gleason's score, 10>8>6>5>4) compared with BPH, PIN, seminal vesicle, and normal tissues. To a much lesser degree, jun/fos and STAT 1 were also elevated in PCA compared to BPH, PIN, and normal tissues. In addition, blinded studies showed that CRTF and jun/fos were present at low levels in organ-confined specimens but at significantly elevated levels (P < 0.001) in samples exhibiting capsular penetration and localized spread, which indicated that CRTF and perhaps jun/fos were markers for cancer progression.
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PMID:Specific transcription factors prognostic for prostate cancer progression. 974 34

To identify prostate cancer-associated Ags, tumor-reactive T lymphocytes were generated using iterative stimulations of PBMC from a prostate cancer patient with an autologous IFN-gamma-treated carcinoma cell line in the presence of IL-2. A CD8+ T cell line and TCR alphabeta+ T cell clone were isolated that secreted IFN-gamma and TNF-alpha in response to autologous prostate cancer cells but not to autologous fibroblasts or lymphoblastoid cells. However, these T cells recognized several normal and malignant prostate epithelial cell lines without evidence of shared classical HLA molecules. The T cell line and clone also recognized colon cancers, but not melanomas, sarcomas, or lymphomas, suggesting recognition of a shared epithelium-associated Ag presented by nonclassical MHC or MHC-like molecules. Although Ag recognition by T cells was inhibited by mAb against CD8 and the TCR complex (anti-TCR alphabeta, CD3, Vbeta12), it was not inhibited by mAb directed against MHC class Ia or MHC class II molecules. Neither target expression of CD1 molecules nor HLA-G correlated with T cell recognition, but beta2-microglobulin expression was essential. Ag expression was diminished by brefeldin A, lactacystin, and cycloheximide, but not by chloroquine, consistent with an endogenous/cytosolic Ag processed through the classical class I pathway. These results suggest that prostate cancer and colon cancer cells can process and present a shared peptidic Ag to TCR alphabeta+ T cells via a nonclassical MHC I-like molecule yet to be defined.
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PMID:Recognition of a shared human prostate cancer-associated antigen by nonclassical MHC-restricted CD8+ T cells. 1057 Mar 28

The therapeutic potential of IFN-gamma in prostatic cancer has been documented in several reports, although no immunohistochemical studies of this factor and its receptors in the prostate have been reported. The aim of the present study was to investigate the expression of IFN-gamma and its receptor components (IFN-gamma-Ralpha and IFN-gamma-Rbeta) in normal prostate, benign prostatic hyperplasia (BPH) and prostatic cancer (PC), as well as the possible relationship between this factor and the products of the p53 gene (the wild and mutant forms) and the oncogene c-myc, by means of immunochemical techniques (Western blot, ELISA, and quantification of immunostaining in histological sections). In normal prostate, IFN-gamma and its two receptors were expressed in the basal cells of the epithelium and some stromal cells. In BPH specimens, immunostaining of basal epithelial cells was significantly increased for IFN-gamma and its a receptor, whereas stromal cell immunostaining was significantly increased for IFN-gamma and its b receptor. In addition, columnar epithelial cells immunostained for IFNbeta-Rbeta. PC specimens differed from BPH specimens in the significantly increased immunostaining of epithelial cells for IFN-gamma and its two receptors, and the immunostaining of columnar epithelial cells for IFN-gamma-Ralpha. Immunodetection of wild-p53 was weak and limited to some stromal cells in the three types of specimens. Immunostainings for both mutant-p53 and c-myc were negative in normal prostate, and positive in the epithelium and stromal cells of both BPH and PC specimens. Immunostaining intensity in PC was significantly higher than in BPH. These observations suggest that the expression of both mutant-p53 and c-myc, together with other factors, might be involved in the development of prostatic hyperplasia and neoplasia, while the increased expression of IFN-gamma and its receptors could be regarded as an attempt, although insufficient, to inhibit the uncontrolled cell proliferation.
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PMID:Interferon-gamma and its functional receptors overexpression in benign prostatic hyperplasia and prostatic carcinoma: parallelism with c-myc and p53 expression. 1070 9

Better understanding of the immunology of prostate cancer is needed for the development of new therapeutic approaches that can be used in conjunction with current treatment methods. The present study was designed to compare the immunological properties of a genetically matched pair of primary tumor- and metastasis-derived prostate cancer cell lines generated from the mouse prostate reconstitution (MPR) model. Only the primary prostate cancer cells were immunogenic in that prior immunization with irradiated primary but not the metastatic prostate cancer cells delayed the growth of subsequently injected live cancer cells. The lack of immunogenicity of the metastatic cells was not attributable to their inability to induce antitumor cytotoxic T cells. Both primary and metastatic cells induced antitumor CTLs in syngeneic hosts, but unlike the primary cells, the metastatic cells were resistant to CTL lysis. Differential resistance to cytolysis in metastatic versus primary prostate cancer cells was not attributable to the differential expression of molecules such as transporter associated with antigen processing (TAP)-1, TAP-2, low molecular weight protein of the proteasome complex (LMP)-2, and LMP-7 that contribute to antigen presentation by class I MHC. IFN-gamma induced surface class I MHC expression, as well as gene expression of TAP-1, TAP-2, LMP-2, and LMP-7 in the metastatic cells, yet the cells remained resistant to cell lysis induced by CTLs. Interestingly, although in comparison to the primary cells the metastatic cells were resistant to cytolysis, both cell types were susceptible to DNA fragmentation induced by CTLs. Cell fusion between primary and metastatic cancer cells resulted in hybrids that also resisted the cytolytic activity of CTLs. Therefore, there is a dominant factor(s) in the metastatic prostate cancer cells that confers specific protection against CTL cytolysis in this model system.
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PMID:Resistance to lysis by cytotoxic T cells: a dominant effect in metastatic mouse prostate cancer cells. 1076 82

The active vitamin D metabolite, 1,25-dihydroxyvitamin D3[1,25-(OH)2D3], exerts immunosuppressive activity. At a cellular and molecular level, the hormone preferentially targets helper T cell activity (Th1) by inhibiting the secretion of both IL-2 and IFN-gamma by Th1 and by suppressing the secretion pro-Th1 cytokine IL-12 by antigen-presenting cells. The active metabolite further inhibits class II antigen expression and enhances suppressor cell activity. In animal models of autoimmunity, 1,25-(OH)2D3 prevents the development of experimental autoimmune encephalomyelitis, reduces the incidence of diabetes, and attenuates murine lupus. The hormone also prolongs graft survival in animal models of transplantation. In humans, non-classical use of 1,25-(OH)2D3 has led to an anti-proliferative effect in psoriasis, antineoplastic effect in prostate cancer, and immunomodulatory effect in scleroderma. The development of less hypercalcemic analogs might open a new therapeutic area for vitamin D3.
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PMID:1,25-Dihydroxyvitamin D3--a hormone with immunomodulatory properties. 1076 31

Interferons (IFNs) are known to possess potent antitumor properties. Previous studies have indicated that IFNs are capable of modulating the expression of various tumor suppressor genes and oncogenes. In this study, we looked at the effect of IFN-gamma on the neu/HER-2 proto-oncogene in the DU145, LNCaP, and PC-3 prostate cancer cell lines. IFN-gamma inhibited cell proliferation in both DU145 and PC-3 cells in a dose-dependent manner, whereas no inhibition of proliferation was seen in LNCaP cells. Correspondingly, IFN-gamma treatment of DU145 and PC-3 cells resulted in an increased production of the cyclin-dependent kinase inhibitor p21(WAF1), whereas no increase in p21(WAF1) was seen in LNCaP cells. In addition, IFN-gamma induced phosphorylation of signal transducer and activator of transcription (STAT) 1 in DU145 and PC-3 cells, but not in LNCaP cells. Consistent with these findings, we found that IFN-gamma treatment of DU145 and PC-3 cells caused a reduction in neu/HER-2 expression, with no change seen in the LNCaP cell line. Transfection and overexpression of the transcriptional coactivator p300 in PC-3 cells suppressed the reduction in neu/HER-2 expression after IFN-gamma treatment, suggesting a role for p300 in neu/HER-2 expression. The antiproliferative activity and p21(WAF1) production of these cells after IFN-gamma treatment were found to be reduced as well. We propose that the down-regulation of neu/HER-2 by IFN-gamma occurs via the interaction of phosphorylated STAT1 with p300 because IFN-gamma activities requiring phosphorylated STAT1 are reduced in cells overexpressing p300. These findings suggest that neu/HER-2 may play a role in the growth of some prostate cancers and that IFN-gamma may suppress such cancers by down-regulation of neu/HER-2.
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PMID:Down-regulation of neu/HER-2 by interferon-gamma in prostate cancer cells. 1091 67


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