Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An essential event in the progression of adenocarcinoma is the loss of organized epithelial attachment (both to the basement membrane and to adjoining epithelial cells). The E-cadherin cell adhesion molecule has an established function in maintaining normal phenotype and tissue homeostasis, and loss of E-cadherin function has been implicated in tumorigenesis. Aberrations in E-cadherin are associated with prostate cancer progression; however, these aberrations are not simply a result of prodigious allelic loss. We have previously demonstrated a novel posttranslational truncation within the cytosolic domain of native Mr 120,000 E-cadherin to a membrane-bound Mr 97,000 species. We hypothesize that truncation of E-cadherin is an inactivating event that is significantly increased in localized prostate tumors and that it represents a novel molecular event that may distinguish prostate cancer from adjacent normal tissue. E-cadherin was characterized by Western blot analysis in matched normal and cancer tissue from 18 prostate cancer patients. Imaging and densitometry software were used to quantify the truncation of E-cadherin by measuring the ratio of Mr 97,000 E-cadherin to Mr 120,000 E-cadherin, which was significantly increased in the tumor aspect of the prostate gland. Herein, we report the first experiment comparing case-matched human normal and cancerous prostate tissue in the context of E-cadherin truncation.
 ...
PMID:Posttranslational truncation and inactivation of human E-cadherin distinguishes prostate cancer from matched normal prostate. 1121 38

Prostate-specific membrane antigen (PSMA) is a membrane-bound glycoprotein highly restricted to prostatic epithelial cells. PSMA expression is increased in association with prostatic cancer, particularly in hormone refractory disease. Given its membrane-bound character, PSMA is an ideal sentinel molecule for use in targeting prostatic cancer cells. Monoclonal antibodies specific for PSMA are available, beginning with the antibody 7E11.C5 which originally defined PSMA and which has been developed for use in cancer detection via immunoscintiscanning in the ProstaScint test. Newer second generation antibodies specific for both linear amino acid sequence epitopes and protein conformational epitopes on the extracellular domain of PSMA have been reported. Although most of these are murine antibodies, both humanised and fully human examples have been developed. These antibodies are beginning to work their way into clinical applications for potential improved diagnostic and therapeutic uses. Results to date suggest that antibodies specific for extracellular epitopes are significantly better for clinical uses in vivo than the 7E11.C5 antibody that is specific for an intracellular epitope. Current knowledge relating to PSMA-specific antibodies and their clinical uses and potential is described and evaluated.
 ...
PMID:PSMA specific antibodies and their diagnostic and therapeutic use. 1122 49

The bioadhesive properties of fluorescein-labeled plant lectins with different carbohydrate specificities were investigated by flow cytometry at 4 and 37 degrees C using Du-145 prostate cancer cells. At both temperatures the lectin association rate increased following the order: Dolichos biflorus agglutinin (DBA)<peanut agglutinin<Ulex europaeus isoagglutinin I<Lens culinaris agglutinin<Solanum tuberosum lectin << wheat germ agglutinin (WGA), reflecting the glycosylation pattern of Du-145 cells. Both, the BSA-binding capacity of the cells referring to nonspecific binding and inhibition studies using the complementary carbohydrate, assured specificity of the lectin-cell interactions except for DBA. The WGA-association rate of Du-145 cells was dependent on temperature indicative for cellular uptake of membrane-bound WGA. Intracellular enrichment of WGA was confirmed by confocal microscopy. As resulted from experiments in presence of ouabain active transport mechanisms were involved in cellular uptake of WGA. Equilibration of the intracellular pH with monensin pointed to accumulation of intracellular located WGA within acidic compartments of Du-145 cells such as the lysosomes or the trans-Golgi complex. Consequently the interaction of WGA with Du-145 cells at 37 degrees C is a one way process due to immediate active transport of membrane-bound lectin into acidic compartments of prostate cancer cells.
 ...
PMID:The interaction between wheat germ agglutinin and other plant lectins with prostate cancer cells Du-145. 1139 65

TENB2 encodes a putative transmembrane proteoglycan, related to the EGF/heregulin family of growth factors and follistatin, which has been identified through the application of a differential display technique to a xenograft model of prostate cancer. Northern analysis and competitive PCR were used to demonstrate significantly increased TENB2 expression (p = 0.0003) on the acquisition of androgen independence in the model system. TENB2 is also overexpressed in clinical prostate carcinoma vs. its benign counterpart (p < 0.0001), with particular prominence in high-grade tumours, and shows a high degree of tissue specificity, being detected on a multitissue Northern array exclusively in brain and prostate material. Studies of recombinant protein expression demonstrate that TENB2 is a chondroitin sulphate proteoglycan. The presence of an EGF and 2 follistatin domains suggests a role in the regulation of growth factor signalling either as a ligand precursor, a membrane-bound receptor or as a binding protein for growth factors. These data are indicative of a significant role for TENB2 in the progression of poorly differentiated tumour types, with implications for prostate cancer detection, prognosis and therapy.
 ...
PMID:TENB2, a proteoglycan identified in prostate cancer that is associated with disease progression and androgen independence. 1166 95

Existing prognostic algorithms for localized prostate cancer (PC) are hampered by poor validation for endpoints other than biochemical relapse such as clinical disease progression or survival. Therefore, the prognostic relevance of Her-2 (Her-2/neu, c-erbB2) protein expression in patients undergoing curative radiotherapy (RT) was compared to widely accepted prognostic factors such as pretreatment prostate-specific antigen (PSA) levels, biopsy Gleason score and T category of the primary tumor. Biopsies from 112 homogeneously treated patients with T1-4pN0M0 PC were examined by immunohistochemistry and 37% of cases showed membrane-bound Her-2 expression in more than 10% of cancer cells. No definite membrane staining was seen in normal prostate epithelium. With 25 patients dead of PC and a median follow-up of surviving patients of 71 months (range 48-144), the prognostic relevance of Her-2 expression was univariately associated with adverse outcome in terms of biochemical or clinical progression-free survival (B/C-PFS; p = 0.04), clinical progression-free survival (C-PFS; p = 0.02) and disease-specific survival (DSS; p = 0.02). In multivariate analysis, Her-2 expression, T category and Gleason score were independently associated with C-PFS, whereas only Her-2 expression and Gleason score were associated with DSS. Her-2 expression and Gleason score together discriminated 2 groups of patients with 5-year DSS of 95% and 79%, respectively (p < 0.001). Pretreatment PSA levels were associated only with B/C-PFS but not with C-PFS or DSS. Together the data show for the first time that expression of Her-2 is of prognostic relevance in localized PC undergoing RT and suggest that analysis for Her-2 may improve prognostic algorithms for clinically relevant endpoints other than biochemical relapse.
 ...
PMID:Independent prognostic significance of HER-2 oncoprotein expression in pN0 prostate cancer undergoing curative radiotherapy. 1194 99

A novel alpha-particle emitting ((213)Bi) plasminogen activator inhibitor type 2 construct, which targets the membrane-bound urokinase plasminogen activator on prostate cancer cells, was prepared and evaluated in vitro and in a xenograft animal model. The PC3 prostate cancer cell line expresses urokinase plasminogen activator which binds to its receptor on the cell membrane; plasminogen activator inhibitor type 2 is bound to urokinase plasminogen activator/urokinase plasminogen activator receptor to form stable complexes. In vitro, the cytotoxicity of (213)Bi-plasminogen activator inhibitor type 2 against prostate cancer cells was tested using the MTS assay and apoptosis was documented using terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick end-labelling (TUNEL) assay. In vivo, antiproliferative effects for tumours and prostate cancer lymph node metastasis were carried out in an athymic nude mouse model with a subcutaneous xenograft of PC3 cells. (213)Bi-plasminogen activator inhibitor type 2 was specifically cytotoxic to PC3 cells in a concentration-dependent fashion, causing the cells to undergo apoptosis. A single local or i.p. injection of (213)Bi-plasminogen activator inhibitor type 2 was able to completely regress the growth of tumours and lymph node metastases 2 days post subcutaneous inoculation, and obvious tumour regression was achieved in the therapy groups compared with control groups with (213)Bi-plasminogen activator inhibitor type 2 when the tumours measured 30-40 mm(3) and 85-100 mm(3). All control animals and one of five (20%) mice treated with 3 mCi kg(-1) (213)Bi-plasminogen activator inhibitor type 2 developed metastases in the lymph nodes while no lymphatic spread of cancer was found in the 6 mCi kg(-1) treated groups at 2 days and 2 weeks post-cell inoculation. These results demonstrate that this novel (213)Bi-plasminogen activator inhibitor type 2 conjugate selectively targets prostate cancer in vitro and in vivo, and could be considered for further development for the therapy of prostate cancer, especially for the control of micro-metastases or in minimal residual disease.
 ...
PMID:213Bi-PAI2 conjugate selectively induces apoptosis in PC3 metastatic prostate cancer cell line and shows anti-cancer activity in a xenograft animal model. 1195 71

Erythropoietin (EPO) regulates mammalian erythropoiesis by binding to its transmembrane receptor EPOR. Recent studies demonstrated functional EPOR expression in human cancer cells. Recombinant human EPO was reported to stimulate the proliferation of monolayer cultures of breast and renal carcinoma cells. Furthermore, administration of EPO-EPOR antagonists delayed the growth of uterine, ovarian, and mammary carcinoma cells in experimental animal models. In this study, we show EPOR transcript and protein expression in breast, colon, lung, ovary, and prostate cancer cells. Using reverse transcription-polymerase chain reaction, we isolated and characterized several novel cDNAs for EPOR splice variants expressed in cancer cells. Deduced amino acid sequences of the cDNAs revealed splice variants encoding soluble EPOR or membrane-bound EPOR peptides with intra-cytoplasmic, carboxy-terminal truncations. These findings indicate the expression of multiple EPOR isoforms in human cancer cells that may modulate the cellular effects of recombinant human EPO or EPO-EPOR antagonists.
 ...
PMID:Expression of erythropoietin receptor splice variants in human cancer. 1287 11

The abnormal activation of the epidermal growth factor (EGF) pathway is one of the most common findings in human cancer, and a number of molecular devices of laboratory and clinical relevance have been designed to block this transduction pathway. Because of the large number of cellular events that might be regulated through the activation of the four EGF receptor family members, it is possible that screening methodologies for the identification of new molecular targets working downstream of these pathways may provide new tools for cancer diagnosis and potentially prevention and therapy. In searching for EGF target genes, we have identified ERG1.2, the mouse homolog of the solid tumor-associated gene STAG1. Both in humans and in mice, it belongs to a new gene family that can give origin to several protein isoforms through alternative splicing and/or multiple translation starts. Sequence analysis and experimental data suggest that ERG1.2 is likely to function as a membrane-bound protein interacting with downstream signaling molecules through WW- and SH3-binding domains. ERG1.2 is a cell-cycle-regulated gene, and both ERG1.2 and STAG1 are induced by EGF and other growth factors at the transcript and protein levels. Finally, we have demonstrated that, besides prostate cancer and renal cell carcinoma, STAG1 was also overexpressed in breast and ovarian cancer cell lines and in breast primary tumors. Although in most cases STAG1 overexpression is probably due to the abnormal activation of the EGF pathway, we have also demonstrated genetic amplification and rearrangement of its locus in one breast cancer cell line and one primary ovarian cancer, suggesting that STAG1 might be a direct molecular target in the carcinogenetic process. Thus its overexpression might be regarded not only as a tumor marker but also as a potentially pathogenetic event.
 ...
PMID:EGF- and cell-cycle-regulated STAG1/PMEPA1/ERG1.2 belongs to a conserved gene family and is overexpressed and amplified in breast and ovarian cancer. 1463 58

Extracellular proteases are recognized as critical factors in the progression of a number of carcinomas, including prostate cancer. Matrix metalloproteases (MMP) are important in processes of tumor growth, invasion and dissemination, but other classes of proteases, such as serine and cysteine proteases, also contribute. We utilized the TRAMP model for prostate cancer to elucidate proteases involved in prostate cancer progression. General proteomic analysis was performed on normal murine prostate, early TRAMP tumors and advanced TRAMP tumors, as well as normal and involved lymph nodes. Zymography and antigenic analyses revealed increased expression of mainly pro-MMP in early TRAMP tumors but substantial elaboration of activated MMP only in late TRAMP tumors. Progressive increase in cysteine, serine and certain membrane-bound proteases from normal to early to advanced prostate tumors, was also seen. Our results implicate pericellular proteases as initiators of major proteolytic cascades during tumor progression and suggest targets for maximal therapeutic effect.
Prostate Cancer Prostatic Dis 2003
PMID:Patterns of protease production during prostate cancer progression: proteomic evidence for cascades in a transgenic model. 1466 66

Cyclooxygenase (COX)-2 plays an important role in the development of various cancers due to its angiogenic function. We have demonstrated that the expression of COX-2 was up-regulated in human renal cell carcinoma (RCC), bladder tumor (BT) and prostate cancer (PC). In this study, we examined the effects of COX-2 inhibitors on cell proliferation in RCC, BT and PC-derived cell lines using MTT assay and Hoechst staining. COX-2 inhibitors did not induce a reduction of cell viability with the half-maximal concentration of growth inhibition of RCC, BT and PC cell lines. Furthermore, counting cells at days 1, 2 and 3, showed no inhibition of cell proliferation using COX-2 inhibitors. COX-2 inhibitors could not stop the growth of RCC, BT and PC cells. Typical characteristics of apoptosis, i.e. chromatin condensation, cellular shrinkage, small membrane-bound bodies (apoptotic bodies) and cytoplasmic condensation, did not occur. Although the expression of COX-2 was up-regulated in human RCC, BT and PC tissues, COX-2 inhibitors have only slight anti-proliferative effects against RCC, BT and PC cells through differentiation. Thus, using only down-regulation of arachidonic acid (AA) metabolizing enzyme, COX may be an unsuccessful approach in providing new anti-cancer therapies.
 ...
PMID:The effects of cyclooxygenase-2 inhibitors on urological cancer cells. 1513 13


<< Previous 1 2 3 4 5 6 7 8 Next >>