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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of multiple tumor markers could better predict the behavior of malignant tumors. In prostate cancer, there are no reliably predictive markers for metastatic behavior but the histologic grade and clinical stage of tumor do influence prognosis. We have determined the expression of blood group antigens A, B, H, Lewis-a and Lewis-b and the proto-oncogene proteins v-erbB, c-fos and v-H-ras in both benign and malignant prostate tissues by immunohistochemistry. We determined the relationship between these markers and the grade of malignancy and by inference, clinical behavior. There was reduced expression of blood group antigens A, Lewis-a and Lewis-b in all grades of prostatic adenocarcinoma. We also found that the expression of v-erbB was greater in tumors of high grade. We suggest that loss of blood group antigens may be correlated with elevated v-erbB oncoprotein expression (related to epidermal growth factor receptor) and increasing grade of prostatic malignancy.
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PMID:Correlation of blood group antigen expression and oncogene-related proteins in malignant prostatic tissues. 171 71

The growth of human prostate cancer and its relationship to the surrounding stroma are controlled by complex mechanisms that are incompletely understood. Clearly, peptide growth factors appear to have crucial roles in these processes. One of these factors, TGF-beta, and its family members are notable for their wide spectrum of biological effects. In terms of growth, TGF-beta inhibits the growth of prostate cancer cells in a cytostatic fashion while stimulating the growth of critical stromal cells, such as fibroblasts. Since the inhibitory effects of TGF-beta on prostate cancer cells appear to diminish as the process of transformation progresses towards less differentiated states, the net effect on prostate tumour growth may be positive. Recent evidence suggests that the inhibitory effects of TGF-beta on growth, at least, might be mediated through the RB tumour suppressor gene product and the proto-oncogene c-myc. Beyond its direct growth effects, TGF-beta also alters the response of prostate cancer cells to positive mitogenic factors, such as members of the EGF and FGF families, suggesting that growth control is a delicate balance between positive and negative influences. Non-mitogenic responses to TGF-beta by prostate cancer cells, the immune system, the stroma and the vascular system provide evidence that TGF-beta might also be important in the processes of carcinogenesis, tumour establishment and metastases. In addition, TGF-beta appears to influence metabolic pathways important to drug metabolism and steroidogenesis. In vivo, limited evidence suggests that TGF-beta can alter the growth and differentiation of some tumour types but appears to be very toxic when administered in high doses. A better understanding of the response of prostate cancer cells to members of the TGF-beta family may open new avenues of treating and controlling this disease.
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PMID:Response of prostate cancer cells to peptide growth factors: transforming growth factor-beta. 184 49

Prostatic cancer is an increasing medical problem. Investigations of the biology of the prostate and the development of prostate cancer have shown that the prostate gland contains high levels of polypeptide growth factors, especially members of the fibroblast growth factor (FGF) and transforming growth factor (TGF)-beta family. Activated oncogenes and elevated proto-oncogene activities including ras and myc have been detected in human prostate cancer tissues, but there is no consensus as to the predominant genetic alterations involved in the progression of this disease. In vivo animal models have shown that relevant growth factors and oncogenes can induce both premalignant and malignant changes in prostate tissue. Additional experimental and clinical studies are needed to present a clearer molecular profile of this important malignancy.
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PMID:Growth factors and oncogenes in prostate cancer. 228 50

We have investigated the structure and expression of the c-myc proto-oncogene in DNA isolated from the immortal cell line LNCaP. This cell line was derived from a lymph node metastasis of human prostate cancer. Msp I digest of LNCaP DNA when hybridized to a human c-myc probe showed a 1.45 kb band of intensity about two-fold greater than that observed in normal lymphocytes. In addition, the LNCaP cells contain rearranged and amplified c-myc structures which are not present in normal lymphocytes. Quantitation of these bands by scanning densitometry is consistent with an approximately 10-fold amplification of c-myc. To determine whether this amplification was accompanied by increased expression, RNA was isolated from these cells and compared to RNA isolated from a control cell line in which c-myc was not amplified. Northern blot analysis showed that the RNA transcripts from LNCaP cells were approximately 50-fold higher. Although androgens modulate the cell growth of LNCaP, there was no change in the level of c-myc RNA transcripts in serum-free medium in the presence or absence of androgens. Further investigation to determine whether altered structure, amplification, and overexpression of c-myc constitute a common characteristic of metastatic human prostate cancer might prove profitable in understanding this disease.
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PMID:Amplification, rearrangement, and elevated expression of c-myc in the human prostatic carcinoma cell line LNCaP. 267 39

The oncoprotein encoded by bc1-2 is unique because of its intracellular location (a mitochondrial membrane protein) and apparent mode of action (suppression of apoptosis). To date, this oncogene has been associated only with the development of certain forms of human B-cell lymphoma. In this report, we describe our experience with a monoclonal antibody made against a synthetic peptide for bc1-2 that can recognize the bc1-2 protein and identify cells in human prostate glands expressing this proto-oncogene with in situ immunohistochemical procedures. These procedures were utilized to survey a series of 62 human tissues to evaluate whether bc1-2 might have a role in the developing prostate gland or in prostate oncogenesis. While all primordial epithelial cells in a fetal prostate gland immunostain for bc1-2, normal and hypertrophic prostate glands of the adult show bc1-2 expression restricted to the basal cells. All epithelial cells in areas of prostatic intraepithelial neoplasia were stained by this antibody, as were most (62%) localized invasive prostatic carcinomas. In contrast, all primary prostatic carcinomas and metastases obtained from metastatic prostate cancer patients after hormone treatment (hormone-refractory tumors) stained positive for bc1-2. This study demonstrates that the oncoprotein encoded by bc1-2 can be detected at sequential stages in the natural history of human prostate cancer. Since the bc1-2 oncoprotein is known to suppress the cellular response to apoptotic stimuli, it will be important to determine whether bc1-2 expression is a factor in the development of prostate cancers and in the survival of hormone-refractory prostate cancer cells.
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PMID:Detection of the apoptosis-suppressing oncoprotein bc1-2 in hormone-refractory human prostate cancers. 768 82

The c-erbB-2 proto-oncogene product is expressed in adenocarcinomas of breast cancer and ovarian cancer, and its significance as a prognostic factor has been increasingly noted. We immunohistochemically studied the expression of c-erbB-2 proto-oncogene product using anti-c-erbB-2 gene product polyclonal antibody (Nichirei), which was produced using a synthetic peptide at the C-terminal portion as the immunogen. The subjects consisted of 52 patients with prostatic cancer who were treated at the Department of Urology, Shiga University of Medical Science, from 1982 to 1990. The expression of c-erbB-2 gene was observed in 40 of the 52 patients (76.9%). The positive rate was highest in patients with poorly differentiated cancer and in stage D2 patients, but there were no significant differences in positive rates among patients with different histological types or clinical stages. The probability that progression would occur was significantly (p < 0.05) lower in the group that tested positive for c-erbB-2 than in the group that tested negative among 33 stage D2 patients after 5 years of treatment. When cause specific survival rates were calculated using the Kaplan-Meier method, the group that tested positive had a significantly (p < 0.001) poorer outcome than the group that tested negative after 3 years and 6 months of treatment. The above results suggest that c-erbB-2 expression in prostatic cancer may be useful in predicting the prognosis of the disease.
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PMID:[Immunohistochemical study of c-erbB-2 proto-oncogene product in prostatic cancer]. 790 85

Prostatic adenocarcinoma has a divergent response to androgen ablation and a varied long-term prognosis. BCL-2 is a proto-oncogene that prevents programmed cell death. Since androgen withdrawal induces apoptosis, it has been postulated that BCL-2 may play a role in androgen resistance. Neuroendocrine cells have been demonstrated in prostate cancer and have an adverse influence on long-term prognosis. This study demonstrates a proportional relationship between the tissue levels of BCL-2 and the neuroendocrine marker, neuron-specific enolase in 11 of 13 cases of primary prostate cancer. This relationship does not appear to exist in metastatic prostate cancer or in most nonprostate cancers. Direct immunohistochemical staining confirmed BCL-2 in six of the primary tumors, and these BCL-2-containing cells appeared to be intimately associated with tumor neuroendocrine cells.
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PMID:BCL-2 proto-oncogene expression in prostate cancer and its relationship to the prostatic neuroendocrine cell. 820 7

We previously reported that a transgenic mouse line containing the fetal globin promoter linked to the SV40 T antigen (T Ag) viral oncogene (Ggamma/T-15) resulted in prostate tumors. In this study, we further explored tumor origin, frequency, invasiveness, androgen sensitivity, and gene expression pattern. T Ag was detected in adult but not fetal and neonatal prostates, suggesting a role for androgens in tumor progression. However, castration shortly after prostate morphogenesis did not prevent tumor development, suggesting an androgen-independent phenotype. Tumors originated within ventral or dorsal prostate lobes and involved intraepithelial neoplasia, rapid growth in the pelvic region, and metastasis to lymph nodes and distant sites. In addition, the primary cancers could be propagated in nude mice or nontransgenic mice. Seventy-five percent of hemizygous and 100% of homozygous transgenic males developed prostate tumors, suggesting a T Ag dosage effect. Biochemical characterization of advanced tumors revealed markers of both neuroendocrine and epithelial phenotypes; markers of terminal differentiation are lost early in tumorigenesis. Tumor suppressor genes (p53 and Rb), normally bound to T Ag, were up-regulated; bcl-2 proto-oncogene, which prevents apoptosis, was slightly up-regulated. Myc, a stimulus to cell cycle progression, was unchanged. We propose the Ggamma/T-15 transgenic line as a model of highly aggressive androgen-independent metastatic prostate carcinoma with features similar to end-stage prostate cancer in humans.
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PMID:Prostate cancer progression, metastasis, and gene expression in transgenic mice. 904 Nov 92

Luteinizing Hormone Releasing Hormone (LHRH) agonists exert both "in vitro" and "in vivo" a direct inhibitory action on the growth of both androgen-dependent (LNCaP) and androgen-independent (DU 145) human prostatic cancer cell lines. The present experiments have been performed to investigate the mechanisms involved in this direct antiproliferative action of LHRH agonists. In particular, the aim was to study whether these compounds might exert their antiproliferative effect by interfering with the stimulatory action of epidermal growth factor (EGF) both "in vitro" and "in vivo". To this purpose, the effects of LHRH agonist, Zoladex (LHRH-A), on the mitogenic action of EGF, on EGF-activated intracellular signaling mechanisms (tyrosine phosphorylation of EGF receptor and c-fos proto-oncogene expression), and on the concentration of EGF receptors have been evaluated in both LNCaP and DU 145 cells. The results of these "in vitro" studies show that in LNCaP cells LHRH-A counteracts the mitogenic action of EGF, abrogates the EGF-induced c-fos expression and reduces the concentration of EGF-binding sites, without modifying the EGF induced tyrosine phosphorylation. In DU 145 cells, LHRH-A antagonizes the proliferative action of EGF, inhibits tyrosine phosphorylation of EGF receptor induced by EGF and significantly reduces the number of EGF binding sites, without altering the stimulation of c-fos expression induced by EGF. For the "in vivo" experiments, male nude mice were s.c. injected in the flank with DU 145 cells and treated for 14 days with LHRH-A (100 micrograms/days). At the end of the treatment, the concentration of EGF receptors on membrane preparations as well as on tumor volume were found to be significantly lower in LHRH-A treated animals than in control mice. The mitotic index and the expression of the proliferation-associated antigen Ki67 were found similar in control as well as in treated animals. In addition no modification of apoptotic index (expression of p53) was observed. These data suggest that LHRH agonists may inhibit the proliferation of the tumor cells by interfering with the stimulatory actions of EGF.
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PMID:Effects of LHRH agonists on the growth of human prostatic tumor cells: "in vitro" and "in vivo" studies. 939 87

For prostate cancer, allelic deletions from the long arm of chromosome 10 (#10q23-25), the locus of the putative tumor suppressor gene MXI1 (#10q24-25), have been identified as a frequently occurring genetic event. During the development of several human malignancies, the c-myc proto-oncogene has been identified to enhance cellular transformation, mitogenesis and cell proliferation. The MXI1 gene, belonging to the helix-loop-helix (bHLH) gene family, was demonstrated to display tumor suppressor function by antagonizing c-myc induced transcriptional activities. Due to the detection of point mutations in the retained alleles of four primary adenocarcinomas of the prostate, MXI1 gene alterations have been suggested to be involved in the development and/or the progression of prostate cancer. To evaluate the role of MXI1 gene alterations for the development of adenocarcinoma of the prostate, 42 primary prostate cancers of different stage (T1-4) and histological grade (G1-3) were investigated for alterations within exons 4 and 5 of the MXI1 gene (spanning 6 exons in total), encoding for the functional HLH-Zip domain, by RNA-SSCP analysis and direct PCR-DNA-sequencing following the microscopically guided tumor cell dissection from 5 microm fresh-frozen buffer-soaked tissue sections. Even by application of this highly elaborated technical approach, MXI1 gene alterations could not be deleted in any of the tumor specimens investigated. Therefore, a substantial involvement of MXI1 gene alterations in the development of prostate cancer appears unlikely. The newly identified putative tumor suppressor gene PTEN, located at #10q23, might be responsible for the frequently observed allelic deletions from #10q23-25 in prostate cancer.
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PMID:The MXI1 tumor suppressor gene is not mutated in primary prostate cancer. 945 79


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