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)

Monoclonal antibodies were raised to PC-3 human prostate adenocarcinoma cells, and one hybridoma, designated F77-129, was extensively purified and used to characterize a PC-3 antigen. The F77-129 antibody also showed serological reactivity with the Du-145 prostate cancer line and with three of four breast carcinoma lines tested; it showed variable binding to a colon carcinoma line. Several other lines tested, including melanomas, fibrosarcomas, and leukemias, were completely negative. Immunoperoxidase staining of frozen surgical specimens showed binding to both normal and malignant prostate and breast tissue. Injection of radioiodinated F77-129 into tumor-bearing nude mice showed specific in vivo targeting to prostatic cancer implants. The antigen also showed surface modulation by bound antibody, suggesting possible clinical utility of this antibody in delivering immunotoxins to tumors.
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PMID:Monoclonal antibodies to tissue-specific cell surface antigens. I. Characterization of an antibody to a prostate tissue antigen. 648 92

We made an effort to identify a reliable source for obtaining large quantities of both free (PSA) and PSA-ACT complex for the preparation of the calibrator for the PSA assay. Using size exclusion chromatography, we found both free PSA and PSA-ACT complex in the conditioned cell medium of the LNCaP cell line, which was derived from a human metastatic adenocarcinoma of the prostate. An assay specific for PSA-ACT reacted only with the PSA-ACT complex from cells grown in serum-free medium, and not with the complex from the cell medium grown in 10% calf serum. We also found both free PSA and PSA-ACT complex in 15% of cytosols prepared from breast tumor tissues; the cytosol PSA concentrations ranged from 0.1 to 110 ng/ml. No correlation was found between cytosol PSA and concentrations of estrogen receptor, progestin receptor, epidermal growth factor receptor, cathepsin D, or the ectodomain of c-erbB-2 protein. Based on chromatographic characterizations and the slope of their dose-response curves, it appears that both free PSA and PSA-ACT complex found in the cytosols are similar to PSA complex from the cell medium and the serum of prostate cancer patients. Ectopic PSA was also detected in pooled sera from patients with breast, ovarian, pancreatic, and colon carcinoma. The PSA concentrations in these serum pools increased with the level of their dominant tumor marker. In any event, the LNCaP cell medium appears to be a reliable source for obtaining both free and ACT-complexed PSA of human tumor origin for the preparation of PSA assay calibrators.
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PMID:PSA immunoreactivity detected in LNCaP cell medium, breast tumor cytosol, and female serum. 756 42

Early dissemination of malignant cells is the main cause for metastatic relapse in patients with solid tumours. By use of monoclonal antibodies (mAbs) specific for cytokeratins, disseminated individual epithelial tumour cells can now be identified in mesenchymal organs such as bone marrow. Further to characterize such cells in patients with prostate cancer, an immunocytochemical procedure was developed for simultaneous labelling of cytokeratin component no. 18 (CK18) and prostate specific antigen (PSA). In a first step, cells were incubated with mAb ER-PR8 against PSA and secondary gold-conjugated goat anti-mouse antibodies. In a second step, biotinylated mAb CK2 to CK18 was applied as primary antibody and subsequently incubated with complexes of streptavidin-conjugated alkaline phosphatase, which were developed with the Newfuchsin substrate. The binding of gold-labelled antibodies was visualized by silver enhancement. The sensitivity and specificity of the technique was demonstrated on cryostat sections of hyperplastic prostatic tissue, and cytological preparations of LNCaP prostatic tumour cells. Double staining was restricted to cells derived from the secretory epithelium of the prostate. Cross-reactivity between both detection systems was excluded by several controls, including the use of unrelated antibodies of the same isotype and the staining of CK18+/PSA- HT29 colon carcinoma cells. CK18+ cells co-expressing PSA were found in bone marrow aspirates from 5 out of 13 patients with carcinomas of the prostate, a finding that is consistent with the relative fraction of double-positive LNCaP cells. The specificity of CK18 for epithelial tumour cells in bone marrow was supported by negative staining of 12 control aspirates from patients with benign prostatic hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunocytochemical double staining of cytokeratin and prostate specific antigen in individual prostatic tumour cells. 768 10

Beckwith-Wiedemann syndrome, familial atypical multiple mole melanoma syndrome, and hereditary tylosis are bona fide genodermatoses with malignant potential. Each of these conditions is associated with an increased incidence of certain tumors: Wilms' tumor, adrenocortical carcinomas, pancreatoblastomas, and hepatoblastomas in Beckwith-Wiedemann syndrome; intraocular malignant melanoma, pancreatic carcinoma, and noncolorectal gastrointestinal cancers in familial atypical multiple mole melanoma syndrome; and squamous cell carcinoma of the esophagus in hereditary tylosis. Other cancer-related genodermatoses are Birt-Hogg-Dube syndrome (associated with medullary carcinoma of the thyroid and renal cell carcinoma) and its variant, Hornstein-Knickenberg syndrome (associated with colon carcinoma). Kidney tumors (Wilms' tumor and malignant rhabdoid tumor), leukemias (acute myelogenous and acute myelomonocytic), retinoblastoma, and paratesticular rhabdomyosarcoma have been reported recently in children with another genodermatosis-incontinentia pigmenti. Supernumerary nipples (polythelia) may be sporadic or familial in occurrence; their presence has been associated with an increased incidence of renal adenocarcinoma, testicular cancer, prostate cancer, and urinary bladder carcinoma. The general characteristics, mucosal and skin manifestations, and noncutaneous features of all these conditions are reviewed. Also, the associated malignancies of these genodermatoses and other conditions that are characterized by dermatologic manifestations and may be either familial or secondary to an inherited gene defect are summarized.
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PMID:Miscellaneous genodermatoses: Beckwith-Wiedemann syndrome, Birt-Hogg-Dube syndrome, familial atypical multiple mole melanoma syndrome, hereditary tylosis, incontinentia pigmenti, and supernumerary nipples. 771 45

Digital image analysis provides objective measurements of tissue and cell analytes previously interpreted subjectively. Both analyte concentration determination and morphometric analyses are possible. Calibration of the instrument and the use of standards and controls are essential for precise and reproducible quantitation of the analyte. Multi-tissue blocks ensure reproducible staining of the batch in quantitative immunohistochemical assays such as breast cancer estrogen and progesterone receptors. These multi-tissue blocks can be shared among laboratories to reduce interlaboratory variation and to objectively quantitate estrogen and progesterone receptors in clinical trials. In colon carcinoma, p53 can be quantitated objectively by image analysis. In prostate carcinoma, morphometric analysis of nuclear shape, nuclear roundness factor, and variations in nuclear size are objective measurements which constitute the pathologist's nuclear grade. Developments in instrumentation have now made it possible to combine analyte determination (such as DNA ploidy) and morphologic analysis of tumors, a diagnostic improvement over either method alone. A study employing image analysis to detect and quantitate androgen receptors and p53 in formalin-fixed, paraffin-embedded prostate cancer biopsies is underway to determine the utility of androgen receptors in predicting response to hormonal therapy. Histopathological features such as nuclear size, shape, and pleomorphism must be converted to image features such as area, shape factor, and variance of the area; this feature vector must be correlated with the pathologist's expert opinion or diagnosis. Other applications of image analysis include quantitation of immunofluorescent assays such as anti-nuclear antigen or anti-cytoplasmic nuclear antigen. Fluorescent image analysis provides more precision and greater reproducibility, as well as reduced test costs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Quantitation and morphometric analysis of tumors by image analysis. 782 83

The human prostatic carcinoma cell line DU 145 was grown as multicellular spheroids in vitro. The volume doubling time during the early exponential growth phase was about 5 days. The saturation volume, in the plateau phase of the growth curve, was in the order of 1.4 mm3. The spheroids developed a central degenerative region surrounded by a 0.1-0.3 mm layer of viable cells. The DU 145 spheroid system is planned to be used as a model in studies on chemotherapy and targeted radiotherapy of micrometastases of prostatic cancer. Some effects of the drug estramustine, EM, a conjugate of estradiol and nornitrogen mustard, were analysed in this introductory study. Tritium-labelled estramustine, 3H-EM, bound both in the viable cell layers and in the degenerative region of the spheroid already after 1 hour of incubation which indicated good penetration. The viable cells bound only low levels of 3H-EM while the degenerative region bound 3H-EM to a higher extent. The amount of bound 3H-EM increased after incubation for 24 hours. The binding was nonspecific since it could not be inhibited by pretreatment with an excess of non-radioactive EM. Furthermore, 3H-EM bound to a similar extent in glioma and colon carcinoma spheroids used for comparison. Incubation of DU 145 spheroids for 24 hours with EM (20 mg/ml) induced a growth delay of 6-7 days and a transient increase in the volume of the extracellular spaces for a few days following the treatment. The results showed that the binding of EM to prostate DU 145 cells growing as spheroids was not specific and that the toxic action was limited. An interesting result was that EM works as an extracellular space expander. This might be exploited in combination treatments with other agents.
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PMID:Growth of prostatic cancer cells, DU 145, as multicellular spheroids and effects of estramustine. 823 95

Galectin-1 has been implicated in the process of vertebrate developmental regulation. Sodium butyrate is an established differentiation-inducing agent and has been shown to increase galectin-1 expression in colon carcinoma cells. We studied the roles of butyrate and galectin-1 in the induction of differentiation and apoptosis in the prostate cancer cell line LNCaP. Treatment of LNCaP cells with butyrate resulted in induction of galectin-1 expression in a time- and dose-dependent manner. Treatment with butyrate also resulted in inhibition of proliferation, morphologic changes consistent with a differentiated phenotype, and induction of apoptosis. Prostate specific antigen expression was transiently reduced. To determine which of these effects might be secondary to the induction of galectin-1, LNCaP cells were transfected with a galectin-1 expression vector. The transfected cells displayed growth inhibition and an increased rate of apoptosis. PSA expression was not affected. We conclude that galectin-1 may be responsible for many of the phenotypic changes resulting from butyrate treatment and may function downstream in the pathway of butyrate-induced differentiation. We also found PSA to be somewhat inconsistent as an indicator of differentiation of LNCaP cells, likely due to other factors influencing its expression.
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PMID:Induction of differentiation and apoptosis in the prostate cancer cell line LNCaP by sodium butyrate and galectin-1. 991 96

Okadaic acid (OA), a toxin from the black sponge Halicondria okadai, is a specific inhibitor of serine/threonine protein phosphatases 1 (PP1) and 2A (PP2A). OA is a tumor promoter but also induces apoptosis in some tumor cell lines. In this study, we determined whether ras mutation and/or p53 status are characteristics associated with the cell's sensitivity to the induction of apoptosis by OA. Several cell lines that differed in ras and p53 mutations were treated with OA (10-100 nM). At 24 to 48 h after treatment, the percentage of cells undergoing apoptosis was quantitated. The cell lines with mutations in either H-ras (human bladder carcinoma cell line T24 and mouse keratinocyte cell line 308), or K-ras (human colon carcinoma cell lines DLD-1 and HCT116; human prostate cancer cell lines LNCaP and PC-3; human lung cancer cell lines Calu-6 and SKLU-1; and human pancreatic cancer cell line MIAPaCa2) were more sensitive to OA-induced apoptosis (3- to 10-fold) than the cell lines that lacked the ras mutation (mouse epidermal cell lines C50 and JB6; murine fibroblast cell line NIH3T3; human colon cancer cell line HT29; human kidney epithelial cell line Hs715.K; and human pancreatic cancer cell line Bx-PC3). Similarly, using isogenic cell lines we found that overexpression of mutated H-ras in NIH3T3 and in SV40 immortalized human uroepithelial cells (SVHUC) enhanced their sensitivity to undergo apoptosis in response to OA treatment. The T24, DLD-1, SKLU-1, Calu-6, and MIAPaCa2 cell lines express mutated p53. The SVHUC as well as their ras-transfected counterparts have inactive p53 due to complex formation between large "T" antigen and p53. Taken together, these results imply that OA-induced apoptosis may involve a p53-independent pathway. The transfectants (NIH3T3-ras and SVHUC-ras), which express mutated H-ras, have up-regulated PP2A activity. OA treatment inhibited in vivo the levels of PP1 and PP2A activity, and induced apoptosis in SVHUC-ras and other cell lines. We conclude that OA-induced cell death pathway in ras-activated cell lines may involve a cross talk between PP1 and PP2A and ras signaling pathways. In light of the present results, the current theory that OA promotes mouse skin tumor formation by selective expansion of initiated cells that harbor ras mutations needs reevaluation.
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PMID:Ras mutation, irrespective of cell type and p53 status, determines a cell's destiny to undergo apoptosis by okadaic acid, an inhibitor of protein phosphatase 1 and 2A. 1046 39

In this report, a novel inhibitor of farnesyl protein transferase (FPTase) is described. The compound, XR3054, is structurally similar to farnesol, a component of the reaction in which FPTase catalyses transfer of farnesol pyrophosphate to the CAAX recognition motif on proteins. The compound was selected initially because of its ability to inhibit in vitro farnesylation of CAAX recognition peptides with an IC50 of 50 microM. The farnesylation of p21 ras was reduced in a dose-dependent manner in the presence of XR3054. Similarly XR3054 was able to reduce the anchorage-independent growth of V12 H-ras transformed NIH 3T3 cells in a focus formation assay in soft agar, with an IC50 value of 30 microM, whilst not affecting the anchorage-independent growth of v-raf transformed cells. XR3054 reduced the phosphorylation of p42 mitogen activated protein (MAP) kinase in parental NIH 3T3 cells and V12 H-ras transformed NIH 3T3 cells, but constitutively active v-raf transformed cells showed no reduction in phosphorylation of ERK2 in the presence of XR3054. XR3054 inhibited the proliferation of the prostatic cancer cell lines LnCAP and PC3 and the colon carcinoma SW480 and HT1080 (IC50 values of 12.4, 12.2, 21.4 and 8.8 microM, respectively) but was relatively inactive when tested against a panel of breast carcinoma cell lines. The activity did not relate to the presence of mutant or wild-type ras in the cell lines tested. In conclusion XR3054 inhibits ras farnesylation, MAP kinase activation and anchorage-independent growth in NIH 3T3 transformed with v12 H-ras. Since the antiproliferative effect of the compound is not related to the ras phenotype, XR3054 may also have effects on other cell signalling mechanisms.
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PMID:XR3054, structurally related to limonene, is a novel inhibitor of farnesyl protein transferase. 1053 87

Resveratrol, a natural phytoestrogen, has been reported to promote differentiation of murine MC3T3-E1 osteoblasts and to inhibit proliferation of prostate cancer cell lines. In the present study we tested the effects of resveratrol on the increased proliferation of human AHTO-7 osteoblastic cell line induced by conditioned media (CM) from a panel of carcinoma cell lines. This compound was found to modulate AHTO-7 proliferation in a tamoxifen-sensitive mechanism at lower concentrations, but failed to induce the osteoblast differentiation marker alkaline phosphatase (ALP) in contrast to vitamin D3. The proliferative response of AHTO-7 cells to conditioned media from carcinoma cell lines was diminished (30-71.4% inhibition) upon pretreatment with 0.5 microM resveratrol. Highest inhibition was demonstrated for pancreas (BxPC3, Panc-1), breast (ZR75-1) and renal (ACHN) carcinoma cell line supernatants whereas the effect on colon carcinoma (SW620, Colo320DM) cell CM and prostate cancer (PC3, DU145 and LNCaP) CM was less pronounced. Direct addition of resveratrol affected only supernatants of cell lines (<25% inhibition) exhibiting growth stimulatory activity for normal WI-38 lung fibroblasts. Resveratrol inhibited proliferation of DU145 and LNCaP cells in concentrations exceeding 5 microM, altered cell cycle distribution of all prostate cancer cell lines in concentrations as low as 0.5 microM, but did not inhibit the production of osteoblastic factors by these lines. In conclusion, resveratrol failed to induce ALP activity as marker of osteoblast differentiation in human osteoblastic AHTO-7 cells, however, inhibited their response to osteoblastic carcinoma-derived growth factors in concentrations significantly lower than those to reduce growth of cancer cells, thus effectively modulating tumor - osteoblast interaction.
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PMID:Resveratrol pretreatment desensitizes AHTO-7 human osteoblasts to growth stimulation in response to carcinoma cell supernatants. 1053 79


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