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)

Metastatic prostate carcinomas in autopsy cases from three populations 49 cases of indigenous Japanese, 29 cases of Japanese Americans and 14 from whites in Hawaii) were compared in terms of their clinicopathological, immunohistochemical (tenascin and ras p21) and lectin binding (Helix Pomatia antigen, HPA) properties. Only the clinicopathological features were analyzed in the cases of whites in Hawaii. The results indicate that poorly differentiated carcinoma is less common, whereas distant metastasis is more frequent, in indigenous Japanese. Some of the Japanese-American cases with poorly differentiated carcinomas did not show any distant metastases. HPA and ras p21 expression are more common, but tenascin is less common in indigenous Japanese. HPA expression is more common in cases with metastasis, especially with metastasis to the bone and other organs, than nonmetastatic cases. Prostatic cancer cases in indigenous Japanese were more aggressive biologically than those in Japanese Americans, but no phenotypic differences were seen relevant to the presence or absence of bone metastases.
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PMID:Comparative study of prostatic carcinoma bone metastasis among Japanese in Japan and Japanese Americans and whites in Hawaii. 128 3

The LNCaP human prostate cancer cell line is dependent on androgen for in vitro growth. To discover genes that may be responsible for progression of prostate cancer from hormone dependence to hormone independence, we transfected LNCaP cells with expression vectors that contained either the v-rasH or c-rasH gene under the control of the cadmium (Cd2+)-inducible human metallothionein-IIA promoter. Numerous derivative cell lines were isolated which manifested inducible expression of rasH p21 protein when the cells were treated with Cd2+. None of the cell lines transfected with c-rasH were found to have an altered growth phenotype. Several derivative cell lines expressing inducible v-rasH manifested hormone-independent growth in culture when treated with 10(-7) M Cd2+ . Cd2+ induction of v-rasH p21 was also shown to increase anchorage-independent colony formation of the v-rasH-expressing cell lines tested. Expression of a dominant mutated oncogene can change the hormone-dependent growth phenotype of prostate cancer cells.
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PMID:v-rasH expression confers hormone-independent in vitro growth to LNCaP prostate carcinoma cells. 203 42

Activation of ras protooncogenes by any of several possible mutations in codons 12, 13 or 61 has been demonstrated in a variety of human malignancies, including acute non-lymphoblastic leukemia (ANLL). In situ staining for the ras gene product, p21, has been demonstrated in carcinomas of several sites. High levels of p21 expression have been associated with histologic anaplasia in prostate cancer and regional lymph node metastasis in breast cancer. We examined 16 marrow aspirates and blood smears from patients with acute leukemia, predominantly ANLL, and eight controls. Marrow aspirates or blood were smeared on glass slides and fixed immediately in 10% buffered formalin. p21 was examined with avidin-biotin linked immunoperoxidase visualization. Particular attention must be paid to antibody selection and fixation protocol to demonstrate p21, owing to its rapid degradation ex vivo. Three of 16 patients exhibited occasional high p21 expression primarily in leukemic blasts, but in no case were more than 10% of blast cells positive. Normal reticuloendothelial and myeloid cells occasionally exhibited mild to moderately heavy staining, but megakaryocytes, erythroid precursors, lymphocytes and plasma cells were consistently negative. Most patients, 5 normal volunteers and 3 patients with non-malignant disease, exhibited no reactivity, or only a faint blush. These data suggest that while point mutation and concomitant activation of c-N-ras occurs regularly in ANLL, high levels of ras p21 expression are rarely found with this technique.
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PMID:Ras gene product expression in blood and marrow smears of patients with acute leukemia: importance of fixation. 223 1

The major neoplastic transformation-inducing genes of human solid tumors are members of the ras oncogene family. We used an immunohistochemical assay to assess expression of both the unaltered and the mutated ras oncogene protein (p21) in normal and neoplastic prostatic cells. With the concentration of monoclonal antibody used in this study, epithelial and stromal cells from subjects with normal prostates and from 19 patients with benign prostatic hyperplasia were negative for p21 antigen. This antigen was detected in 2 of 6 prostates with Grade I carcinoma, 4 of 6 with Grade II, and all of 17 with higher grades. A semiquantitative immunohistochemical method demonstrated that expression of the p21 antigen in a carcinoma strongly correlated with nuclear anaplasia and was inversely related to the degree of glandular differentiation. However, markedly anaplastic tumors were often more heterogeneous in expression of p21 and contained areas of low staining for the antigen. Comparison of p21 antigen with tumor carcinoembryonic antigen and prostate-specific antigen demonstrated that ras p21 was the only phenotypic marker that correlated with histologic tumor grade. Thus, ras oncogene p21 may represent a new class of biologically relevant tumor markers and may be a useful adjunct to histopathologic examination in determining the prognosis of patients with prostate cancer.
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PMID:Expression of ras oncogene p21 in prostate cancer. 241 18

A total of 124 specimens of prostate tissue (25 normal prostate, 41 benign prostatic hyperplasia, 58 adenocarcinoma) was immunostained for ras p21 using a commercially available monoclonal antibody directed against a peptide sequence conserved among all members of the ras gene family. Of normal prostate specimens, 76% showed no staining while the remainder showed only weak epithelial (glandular) staining. No significant stromal staining was noted in any normal prostate specimen. In contrast most benign prostatic hyperplasia specimens showed abundant staining. Epithelial staining was observed in 88% and stromal staining in 73% of specimens. A majority of prostate carcinoma specimens also stained, with 62% and 36% showing epithelial and stromal staining, respectively. No association was noted between staining and either tumor grade or clinical stage. These data argue against any clinical usefulness of immunostaining for ras p21 in the diagnosis or grading of prostate cancer.
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PMID:Immunohistochemical staining of ras p21: staining in benign and malignant prostate tissue. 752 5

The present study assessed the immunohistochemical expression of ras p21 oncoprotein in 41 cases of benign and cancerous lesions of the prostate gland and correlated p21 expression with survival of patients operated for prostate cancer. Our results show that p21 is detected in both categories of patients, the expression being weak in adenomatous hyperplasia and more intense in cancer. We were also able to show an inverse relation between ras p21 positivity and the degree of differentiatin. Follow-up study revealed a statistically significant (p < 0.05) correlation between 5 year survival and p21 expression.
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PMID:Comparative immunohistochemical study of ras-p21 oncoprotein in adenomatous hyperplasia and adenocarcinoma of the prostate gland. 753 Sep 30

The multifocal origin of prostate cancer suggests a pan-organ defect in a tumor suppressor pathway. Although structural mutations in the p53 gene have been implicated in late-stage prostate cancer, little is known about the p53 response to genotoxic stress in normal human prostatic epithelial cells from which adenocarcinomas originate. We found that the majority (10 of 12) of epithelial cell cultures derived from histologically normal tissues of radical prostatectomy specimens failed to exhibit p53 accumulation in response to ionizing radiation. Epithelial cell cultures derived from benign prostatic hyperplasia and a primary prostatic adenocarcinoma also failed to accumulate p53 in response to ionizing radiation. In contrast, cultures of prostatic stromal cells derived from normal, benign prostatic hyperplasia, or adenocarcinoma tissues exhibited a 3-9-fold induction of p53 within 1-3 h after irradiation. Since p53 regulates a cell cycle checkpoint through the induction of the cyclin-cdk inhibitor p21, we examined p21 accumulation and cell cycle arrest following exposure to ionizing radiation. With one exception, epithelial cells that did not display increased p53 or p21 induction did not demonstrate a significant G1-S arrest in response to ionizing radiation, whereas stromal cells that accumulated p53 and p21 exhibited a large cell cycle arrest. These results indicate a functional difference between the DNA damage response of epithelial and stromal prostatic cells and suggest a possible mechanism for the increased susceptibility of prostatic epithelial cells to accumulate genetic alterations.
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PMID:Attenuated response of p53 and p21 in primary cultures of human prostatic epithelial cells exposed to DNA-damaging agents. 754 16

We introduced the gene for wild-type human p53 or p21, a critical downstream mediator of p53-induced growth suppression, into a p53-deficient mouse prostate cancer cell line using a recombinant adenoviral vector (Ad5CMV-p53 or Ad5CMV-p21). Elevated levels of endogenous mouse p21 mRNA provided evidence for the functional activity of virally transduced p53. Functional activity of viral-transduced p21 was demonstrated through immunoprecipitation of cellular protein extracts, which showed that the viral-transduced p21 associates with cyclin-dependent kinase 2 and was sufficient to down-regulate the activity of the cyclin-dependent kinase by approximately 65%. In vitro growth assays revealed significantly higher growth suppression after Ad5CMV-p21 infection compared to Ad5CMV-p53. In vivo studies in syngeneic male mice with established s.c. prostate tumors demonstrated that the rate of growth and final tumor volume were reduced to a much greater extent in mice that received intratumor injection of Ad5CMV-p21 compared to Ad5CMV-p53. In addition, the survival of host animals bearing tumors that were infected with Ad5CMV-p21, but not Ad5CMV-p53, was significantly extended. These data suggest that Ad5CMV-p21 may be effective as a therapeutic agent for prostate cancer.
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PMID:In vivo gene therapy with p53 or p21 adenovirus for prostate cancer. 758 63

Human prostate cancers frequently show loss of heterozygosity at loci on the short arm of chromosome 8. In order to take a step toward isolation of the putative tumor suppressor gene(s) on 8p via positional cloning, we performed high-resolution deletion mapping in 46 prostate cancers (stage B, 20 cases; stage C, 8 cases; endocrine therapy-resistant cancer death, 18 cases) using new 12 restriction fragment length polymorphism markers for this chromosomal region. Allelic losses were observed in 25 of the 44 cases (57%) that were informative with at least one locus. Detailed deletion mapping defined a 1.2 Mb commonly deleted region at 8p22-p21.3 flanked by markers cMSR-32 and C18-1051. A second region of common deletion was identified between C18-1312 and C18-494 at 8p21-8p11.22, suggesting that at least two tumor suppressor genes associated with prostate cancer are present on chromosome arm 8p. Allelic losses on 8p were observed more frequently in the cancer death cases (14/17, 82%) than in early-stage tumors (11/27, 40%; P < 0.01, Fisher's exact test). In two out of 7 patients for whom DNA was available from metastatic cancers as well as from normal tissues and primary tumors, the primary cancer foci had no detectable abnormality of 8p, but the metastatic tumors showed loss of heterozygosity. These results suggest that inactivation of tumor suppressor genes on 8p plays an important role in the progression of prostate cancer.
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PMID:Localization of a tumor suppressor gene associated with progression of human prostate cancer within a 1.2 Mb region of 8p22-p21.3. 766 36

We have measured the product of the ras oncogene, ras p21, in random un-timed urine samples using an immunoblotting method which relies upon enhanced chemiluminescence for visualisation of the nitrocellulose filter. Urine samples were analysed from groups of patients with prostate (n = 10) or bladder (n = 25) cancer and a control group (n = 30) with no apparent urological disease. The mean concentration of urinary ras p21 in the groups with either bladder or prostate cancer was not significantly higher than that of the control group. The most striking difference between the control and clinical groups was the presence of a previously un-reported ras p21 "doublet" in the electrophoretic patterns obtained from 20% of the bladder cancer group and 10% of the prostate cancer group. This doublet was not present in any of the control samples analysed. This doublet is strongly suggestive of a mutation within the ras oncogene.
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PMID:Measurement of ras p21 in the urine of patients with urological tumours. 777 39


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