Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cancer of the prostate is an heterogenic, "epidemic" world-wide tumor, which represents the most common form of solid cancer in adult males, excluding nonmelanoma skin cancer. Prostate cancer now surpasses the incidence of lung cancer and becomes the second leading cause of male cancer death in the industrialized West countries. The incidence and mortality of prostate cancer are increasing to alarming rates (in the USA carcinoma prostate was projected to be responsible for 14% of all male cancer deaths in 1996). As the life expectancy of the male population increases over time, the incidence of clinical prostate cancer will also increase. There is a wide geographic variation in the incidence of clinical prostate cancer, with higher rates in the United States than in China. A difference in diagnostic practice with regard to prostate cancer can be the explanation for this wide divergence. One risk factor which could explain this fact is the high fat Western diet. It is also apparent that prostate cancer is now being detected at less advanced stages than in the past. It has become evident that there is a greater than expected incidence of this tumor in the male relatives of men who died from the disease. Hereditary prostate cancer is characterized by Mendelian autosomal dominant inheritance, and an early onset of the disease. Prostate specific antigen (PSA) represents the best serum marker for prostatic carcinoma and is considered as most perfect tumor marker available today. Nevertheless, the use of PSA to detect prostate cancer is clinically imprecise since benign and malignant prostate disease can cause elevations in PSA. The biological behaviour and the natural course of prostate cancer are poorly understood. There are far larger numbers of males who have a so-called latent, well-differentiated microscopic (clinically insignificant) prostate carcinoma that may never progress to invasive clinical disease with metastatic potential. These incidental cancers discovered histologically after the transurethral or open prostatectomy and as a result of the prostate biopsy in patients with the high level of PSA are currently not well understood. Results of the mass screening for prostate cancer are at present controversial and their benefit is still not confirmed. There is now strong evidence for the screening of first degree male relatives of men with prostate cancer, particularly male relatives of those developing the disease at a young age and those with a strong positive family history of the disease. There is no debate that the earlier diagnosis of prostate carcinoma, especially in young men give them the best chance to be cured. The "watchful waiting" seems the best treatment strategy for older men with so called insignificant carcinoma. The aggressive modalities of the therapy--radical prostatectomy, radiation therapy, interstitial brachy-therapy or interstitial cryotherapy--are the curable methods only for organ-confirmed tumors and advocated in patients with life expectancy longer than 10 years. Androgen ablation therapy is the treatment of choice for the palliation of patients with advanced prostate cancer. Maximal androgen ablation (combination of medical or surgical castration and an antiandrogen) has been shown to increase the survival of patients with metastatic prostate cancer. As the incidence and prevalence of prostate cancer have increased, so has mortality, though at a slower rate. This fact may more a reflection of earlier diagnosis rather than improvements in treatment. Five-year prostate cancer survival has improved for every stages of disease in the last decenium. Thanks to the screening programmes performed in many countries, urologists are faced with an increasing incidence of clinical less advanced prostate cancer and this trend is likely to continue. (ABSTRACT TRUNCATED)
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PMID:[Adenocarcinoma of the prostate]. 978 3

Androgen ablation has been an effective treatment in patients with advanced prostate cancer. However, most treated patients develop hormonally resistant disease and do not respond to conventional chemotherapy. Immunotherapy against prostate cancer is an alternative approach in overcoming hormonal/drug-resistant prostate cancer. Cytotoxic immune lymphocytes kill target cells via the perforin/granzyme and the Fas-ligand (Fas-L) pathways. We hypothesize that tumor cells respond poorly to immunotherapy by developing resistance to killing by the Fas-L mechanism. This study investigated whether prostate tumor cells are sensitive to Fas-mediated killing. The human prostate carcinoma cell lines DU145, PC-3, and LnCAP were examined for their sensitivity to killing and apoptosis by the Fas-L agonist anti-Fas antibody and CTLs. All three lines moderately expressed the Fas antigen on the cell surface; however, all three lines were relatively resistant to cytotoxicity mediated by anti-Fas (CH-11) antibody. Pretreatment of DU145 and PC-3 with subtoxic concentrations of drugs followed by anti-Fas antibody resulted in synergistic cytotoxicity and apoptosis, whereas only an additive effect was obtained with LnCAP. Chemosensitization with drugs and anti-Fas was completely blocked by the addition of neutralizing anti-Fas antibody. The murine CTL hybridoma, PMMI, which kills only via the Fas-L pathway, was able to kill chemosensitized PC-3 and DU145 but not LnCAP cells. Furthermore, this cytotoxicity was blocked by anti-Fas neutralizing antibody. Chemosensitization of PC-3 and DU145 prostate tumor cells was not due to up-regulation of Fas-receptor antigen expression. Treatment of tumor cells with cisplatin did not down-regulate the antiapoptotic genes bcl-2, FAP-1, and c-myc. Further, there was no induction by cisplatin of Fas-L on the tumor cells, thus ruling out Fas/Fas-L-mediated autologous killing. These findings demonstrate that pretreatment of drug-resistant/CTL-resistant prostate DU145 and PC-3 tumor cells with subtoxic concentrations of certain chemotherapeutic drugs sensitizes the tumor cells to Fas-mediated cytotoxicity. These findings suggest that chemosensitization of tumor cells should optimize the response to immunotherapeutic interventions in the treatment of hormone-resistant/drug-resistant prostate cancer.
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PMID:Chemosensitization of human prostate carcinoma cell lines to anti-fas-mediated cytotoxicity and apoptosis. 981 72

Androgen-independent growth of prostate cancer is correlated with expression of bcl-2. The impact of bcl-2 expression on the growth of prostate cancer cells following androgen ablation, was examined in the androgen-sensitive prostatic carcinoma cell line, LNCaP. Vector control and bcl-2 expressing LNCaP cells were grown subcutaneously in male nude mice. Tumor volume, apoptosis, and proliferation were assessed following castration. The levels of c-myc, p53, p21, bax, and bcl-2 protein were assessed by Western blotting. Bcl-2 expressing tumors exhibited a significant augmentation in growth compared to controls (p 0.01). No difference in the spontaneous rate of proliferation was observed between bcl-2 and control tumors, however, bcl-2 expressing tumors exhibited lower rates of apoptosis. Following orchiectomy the apoptotic index remained significantly lower in bcl-2 expressing tumors (p 0.002 at day 3). The proliferative index was maintained in bcl-2 expressing, but not control tumors following castration. This resulted in a significant growth advantage in bcl-2 tumors subsequent to androgen ablation (p 0.001). These changes were accompanied by alterations in the levels of gene products known to regulate the cell cycle and/or apoptosis. These results emphasize the significance of bcl-2 expression during prostate cancer progression and suggest possible mechanisms for the acquisition of androgen-independent tumor growth.
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PMID:Molecular correlates of bcl-2-enhanced growth following androgen-ablation in prostate carcinoma cells in vivo. 985 30

Protein kinase CK2, a messenger-independent serine/threonine kinase, has been implicated in cell growth. Androgenic stimulus in rat prostate modulates its association with nuclear matrix (NM) and chromatin. Because the growth of human prostate carcinoma cells is influenced by androgens and/or growth factors, we determined the nature of CK2 signaling in the NM in response to androgen and growth factor stimuli. Androgen-sensitive LNCaP and androgen-insensitive PC-3 cells were cultured in media to regulate their growth in the presence of 5alpha-dihydrotestosterone (5alpha-DHT) or growth factors (epidermal growth factor, keratinocyte growth factor, and transforming growth factor alpha). The activity of CK2 was measured in the cytosolic and NM fractions isolated from these cells after treatment with growth stimuli. The changes in CK2 in various fractions were also confirmed by immunoblotting with a specific antibody. LNCaP cells responded to both 5alpha-DHT and growth factors for growth. The presence of these agents in the culture medium evoked a translocation of CK2 to the NM from the cytosol. The PC-3 cells did not respond to 5alpha-DHT for growth but did respond to growth factors. Under these conditions, there was also a translocation of CK2 to the NM concomitant with a decrease in the cytosolic fraction. These results suggest that CK2 translocation to the NM occurs in response to various growth stimuli in cells in culture. Thus, CK2 is a common downstream signal transducer in response to diverse growth stimuli that may relate to the pathobiology of prostate cancer cells.
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PMID:Nuclear matrix targeting of the protein kinase CK2 signal as a common downstream response to androgen or growth factor stimulation of prostate cancer cells. 1007 Sep 76

High-grade prostatic intraepithelial neoplasia is the most likely precursor of prostatic adenocarcinoma, according to virtually all available evidence. It has a high predictive value as a marker for adenocarcinoma, and its identification in biopsy specimens of the prostate warrants further search for concurrent invasive carcinoma. Androgen deprivation therapy and radiation therapy decrease its prevalence and extent, suggesting a role in chemoprevention.
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PMID:Reversibility of prostatic intraepithelial neoplasia: implications for chemoprevention. 1032 11

Epidemiologic studies have suggested that nutrition plays an important role in carcinogenesis and that 30% of cancer morbidity and mortality can potentially be prevented with proper adjustment of diets. Resveratrol, a polyphenol present in red wines and a variety of human foods, has recently been reported to exhibit chemopreventive properties when tested in a mouse skin cancer model system. In this study, we investigated the effects of resveratrol on growth, induction of apoptosis, and modulation of prostate-specific gene expression using cultured prostate cancer cells that mimic the initial (hormone-sensitive) and advanced (hormone-refractory) stages of prostate carcinoma. Androgen-responsive LNCaP and androgen-nonresponsive DU-145, PC-3, and JCA-1 human prostate cancer cells were cultured with different concentrations of resveratrol (2. 5 x 10(-5)-10(-7) M). Cell growth, cell cycle distribution, and apoptosis were determined. Addition of 2.5 x 10(-5) M resveratrol led to a substantial decrease in growth of LNCaP and in PC-3 and DU-145 cells, but only had a modest inhibitory effect on proliferation of JCA-1 cells. Flow cytometric analysis showed resveratrol to partially disrupt G1/S transition in all three androgen-nonresponsive cell lines, but had no effect in the androgen-responsive LNCaP cells. In difference to the androgen-nonresponsive prostate cancer cells however, resveratrol causes a significant percentage of LNCaP cells to undergo apoptosis and significantly lowers both intracellular and secreted prostate-specific antigen (PSA) levels without affecting the expression of the androgen receptor (AR). These results suggest that resveratrol negatively modulates prostate cancer cell growth, by affecting mitogenesis as well as inducing apoptosis, in a prostate cell-type-specific manner. Resveratrol also regulates PSA gene expression by an AR-independent mechanism.
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PMID:Differential effects on growth, cell cycle arrest, and induction of apoptosis by resveratrol in human prostate cancer cell lines. 1032 58

C-CAM is an epithelial cell adhesion molecule with two major splice variants that differ in the length of the cytoplasmic domain. C-CAM1 (long (L)-form) strongly suppresses the tumorigenicity of human prostate carcinoma cells. In contrast, C-CAM2 (short (S)-form) does not exhibit tumor-suppressive activity. In the present study we have investigated the functional significance of L-form and S-form C-CAM in rat prostate by examining their expression and distribution in different prostate lobes and their response to androgen deprivation. RNase protection assays with a probe for both C-CAM isoforms detected high levels of C-CAM messages in the rat dorso-lateral prostate (DLP). L- and S-form proteins, localized by indirect immunofluorescence using isoform-specific antipeptide antibodies, were co-expressed on the apical surface of prostate epithelial cells in normal DLP. Androgen depletion did not significantly change the steady state levels of C-CAM message and protein expression in the DLP, although there was a change in the pattern of protein expression in these lobes. In contrast, C-CAM isoform messages and proteins were undetectable in normal ventral prostate (VP) but increased markedly in this lobe in response to castration, producing isoform ratios similar to those in DLP. These results demonstrate that coordinate expression of C-CAM isoforms is maintained in the VP following androgen depletion and suggest that androgen suppresses C-CAM expression in VP but not in DLP. These results suggest that balanced expression of L- and S-form C-CAM is important for normal prostate growth and differentiation.
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PMID:Expression and androgen regulation of C-CAM cell adhesion molecule isoforms in rat dorsal and ventral prostate. 1035 31

Androgen receptors (AR) are present in normal skin being localized to the basal and differentiating cells of the sebaceous gland, and as such, sebaceous glands are androgen sensitive tissue. Androgen receptor expression was examined in 43 sebaceous neoplasms including 8 sebaceous carcinomas, 22 sebaceous adenomas, 12 specimens showing sebaceous hyperplasia, and 1 sebaceous epithelioma, as well as in 14 squamous cell carcinomas, 2 clear cell acanthomas, and 35 basal cell carcinomas. Epithelial membrane antigen (EMA) expression was also examined in all of the sebaceous neoplasms. All specimens were fixed in formalin and embedded in paraffin. Diffuse positive nuclear androgen receptor antibody immunohistochemical staining was observed in all samples of sebaceous neoplasms, whereas approximately 60% of basal cell carcinomas showed only focal positivity for nuclear androgen receptor immunoreactivity. Clear cell acanthomas and squamous cell carcinomas were uniformly negative. Whereas all sebaceous neoplasms exhibited immunoreactivity for androgen receptors, the staining pattern was more marked in the nuclei of seboblasts and differentiating sebocytes in the adenomatous, hyperplastic, and epitheliomatous lesions than in the nuclei of the less differentiated sebaceous carcinoma cells. All the sebaceous neoplasms except for sebaceous carcinomas exhibited immunoreactivity for EMA. In the sebaceous carcinomas, EMA staining was absent in the most poorly differentiated specimen, but with increasing differentiation, the carcinomas became immunoreactive to EMA. We have shown that the nuclei of sebaceous neoplasms, including sebaceous gland carcinomas, show immunoreactivity for androgen receptors (AR), that immunohistochemical staining for the presence of AR may be a reliable marker of sebaceous differentiation, and that the AR may be a better marker of sebaceous differentiation than EMA, particularly in poorly differentiated sebaceous carcinomas.
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PMID:Immunohistochemical staining for androgen receptors: a sensitive marker of sebaceous differentiation. 1053 70

High-grade prostatic intraepithelial neoplasia (PIN) is now accepted as the most likely preinvasive stage of adenocarcinoma, a decade after its first formal description. PIN has a high predictive value as a marker for adenocarcinoma, and its identification warrants repeat biopsy for concurrent or subsequent invasive carcinoma. The only method of detection is biopsy; PIN does not significantly elevate serum PSA concentration or its derivatives and cannot be detected by ultrasonography. Most studies suggest that most patients with PIN will develop carcinoma within 10 years. PIN is associated with progressive abnormalities of phenotype and genotype, which are similar to cancer rather than normal prostatic epithelium, indicating impairment of cell differentiation with advancing stages of prostatic carcinogenesis. Androgen deprivation therapy decreases the prevalence and extent of PIN, suggesting that this form of treatment may play a role in chemoprevention.
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PMID:Prostatic intraepithelial neoplasia is a risk factor for cancer. 1063 20

The possible role of activin in the regulation of malignant prostatic growth was studied using RNAase protection assays of activin receptors, inhibin/activin subunits and follistatin mRNAs in the human prostatic carcinoma cell lines LNCaP-FGC, -R and -LNO, in human prostatic carcinoma xenografts and in human prostatic tissue. Activin receptor types IA (ActRIA), IB (ActRIB), IIA (ActRIIA) and IIB (ActRIIB) mRNAs were generally expressed in prostate epithelial cells, with significantly lower levels of ActRIB mRNA in prostate tumour material when compared to non-malignant tissue (P < 0.05; Mann-Whitney U-test). Inhibin/activin betaA- and betaB-subunit mRNA expression was also found in prostate tissue. Androgen-independent xenografts expressed significantly lower amounts of betaB-subunit mRNA when compared to androgen-dependent xenografts (P< 0.05). While betaB-subunit mRNA was expressed by LNCaP-FGC and -LNO cells, virtually no expression was found in the androgen-independent LNCaP-R line. Inhibin alpha-subunit mRNA levels were low or undetectable in all samples investigated. Follistatin mRNA was undetectable in LNCaP-sublines, while low levels were found in prostatic tissues. In androgen-independent LNCaP-R cells, activin inhibited cell growth in a dose-dependent manner. These results suggest that prostate tumour progression is accompanied by a decrease of the inhibitory effect of locally produced activin by either a decrease in the expression of activin betaB-subunit mRNA or by a decrease of ActRIB mRNA levels.
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PMID:Variations in activin receptor, inhibin/activin subunit and follistatin mRNAs in human prostate tumour tissues. 1063 76


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