Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Attainment of cell type-specific cytotoxicity with minimal side effects is the ultimate goal of cancer therapy. By employing the prostate-specific antigen promoter (PSAP), we investigated (1) whether PSAP-driven antisense genetic constructs targeting DNA polymerase-alpha and topoisomerase II alpha (Top II alpha), designated PSAP-antipol and PSAP-antitop respectively, could induce death of prostate cancer cells, and (2) whether the cytotoxicity is restricted to cells of prostate origin. A PSAP-driven beta-galactosidase gene, PSAP-LacZ, was also used to estimate the expression of the PSAP-driven transcripts. Lipofection-mediated gene transfers were performed with these 3 constructs and a control plasmid, pCDNA3, in 3 human prostate cancer cell lines (LNCaP, DU-145, PC-3) and 5 other cell lines (Cos-1 [monkey kidney], HL-60 [human myeloid leukemia], Hep G2 [human hepatoma], NCI H460 [human lung cancer] and SW 480 [human colon cancer]). On transfection with PSAP-LacZ, LNCaP, DU-145, and PC-3 showed a 10.8, 1.8, and 1.6 fold increase in beta-galactosidase activity, respectively. The remaining 5 cell lines showed no changes after transfection. Corresponding to the levels of the induced beta-galactosidase activity, LNCaP showed the strongest growth inhibition by the antisense constructs: 36% by PSAP-antipol, 39% by PSAP-antitop and 80% by PSAP-antipol+PSAP-antitop. DU-145 and PC-3 had minimal growth inhibition with PSAP-antipol alone or PSAP-antitop alone. However, when cotransfected with PSAP-antipol and PSAP-antitop, DU-145 and PC-3 displayed 42% and 55% growth inhibition, respectively. In contrast, no cytotoxicity was observed in the remaining 5 cell lines when transfected with PSAP-antipol, PSAP-antitop or both. Therefore, PSAP-driven antisense gene therapy targeting DNA polymerase-alpha and Top II alpha inhibits the growth of human prostate cancer cells and the cytotoxic effect is restricted in cells of prostate origin.
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PMID:Prostate-specific antigen promoter driven gene therapy targeting DNA polymerase-alpha and topoisomerase II alpha in prostate cancer. 871 4

Serum prostate-specific antigen (PSA) values above 10 ng/ml are considered highly sensitive and specific for prostatic carcinoma in the absence of prostatic inflammation or trauma. However, in rare instances, non-prostatic malignancies have also been associated with raised serum PSA values. We have encountered a patient with increased serum PSA concentration measured by monoclonal antibody assay who had no evidence of prostatic malignant involvement, but suffered from colon cancer. Before operation for colon cancer his PSA was always over 30 ng/ml on several examinations. After total removal of colon cancer serum PSA level fell down to 1.2 ng/ml. Although immunohistochemical staining of colon cancer with monoclonal PSA antibody was not performed, some relationship between raised PSA and colon cancer is strongly suspected. Substances like serine protease which can cross-react with the PSA antibody might be produced by malignant tumour of non-prostatic origin.
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PMID:Raised prostate-specific antigen in adenocarcinoma of the colon. 924 51

Nonsteroidal anti-inflammatory drugs (NSAIDs) play potential roles in chemoprevention of colon cancer and others by inhibiting prostaglandin synthesis. In this report, we used LNCaP cells, an androgen-responsive human prostate carcinoma cell line, to study the effects of two NSAIDs, flufenamic acid (FA) and piroxicam (PXM), on the cancer cell growth stimulated by androgens. We found that FA had much higher potency to inhibit LNCaP cell growth than PXM. FA dramatically reduced the expression of androgen inducible genes, such as prostate-specific antigen (PSA) and the homeo-domain transcription factor Nkx3.1, but PXM did not. In vitro transfection experiments showed that FA down regulated the PSA expression at the transcription level. Western and northern blot analyses demonstrated that FA inhibited the androgen receptor (AR) expression at mRNA and protein levels. Suppressed AR expression may be the cause of FA-mediated inhibition of the androgen inducible gene expression. Our data also showed that FA significantly reduced the AR promoter-mediated transcription activities. This study indicated that AR might be a target for FA to inhibit LNCaP cell growth. FA and other similar NSAIDs may be potential candidates for chemoprevention of human prostate cancer by modulating the expression of AR.
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PMID:A nonsteroidal anti-inflammatory drug, flufenamic acid, inhibits the expression of the androgen receptor in LNCaP cells. 1053 80

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear hormone receptor that plays a key role in the differentiation of adipocytes. Activation of this receptor in liposarcomas and breast and colon cancer cells also induces cell growth inhibition and differentiation. In the present study, we show that PPARgamma is expressed in human prostate adenocarcinomas and cell lines derived from these tumors. Activation of this receptor with specific ligands exerts an inhibitory effect on the growth of prostate cancer cell lines. Further, we show that prostate cancer and cell lines do not have intragenic mutations in the PPARgamma gene, although 40% of the informative tumors have hemizygous deletions of this gene. Based on our preclinical data, we conducted a phase II clinical study in patients with advanced prostate cancer using troglitazone, a PPARgamma ligand used for the treatment of type 2 diabetes. Forty-one men with histologically confirmed prostate cancer and no symptomatic metastatic disease were treated orally with troglitazone. An unexpectedly high incidence of prolonged stabilization of prostate-specific antigen was seen in patients treated with troglitazone. In addition, one patient had a dramatic decrease in serum prostate-specific antigen to nearly undetectable levels. These data suggest that PPARgamma may serve as a biological modifier in human prostate cancer and its therapeutic potential in this disease should be further investigated.
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PMID:Effects of ligand activation of peroxisome proliferator-activated receptor gamma in human prostate cancer. 1098 6

Trypsinogen is a serine proteinase produced mainly by the pancreas, but it has recently been found to be expressed also in several cancers such as ovarian and colon cancer and in vascular endothelial cells. In this study, we found that trypsinogen-1 and -2 are present at high concentrations (median levels, 0.4 and 0.5 mg/L, respectively) in human seminal fluid and purified them to homogeneity by immunoaffinity and anion exchange chromatography. Purified trypsinogen isoenzymes displayed a M(r) of 25 to 28 kd in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting. Most of the trypsinogen-1 purified from seminal fluid was enzymatically active whereas trypsinogen-2 occurred as the proform, which could be activated by enteropeptidase in vitro. Immunohistochemically, trypsinogen protein was detected in the human prostate, urethra, utriculus, ejaculatory duct, seminal vesicles, deferent duct, epididymal glands, and testis. Expression of trypsinogen mRNA in the same organs was demonstrated by in situ hybridization. Trypsinogen mRNA was also detected in the prostate and seminal vesicles by reverse transcriptase-polymerase chain reaction and Northern blotting. Isolated trypsin was shown to activate the proenzyme form of prostate-specific antigen. These results suggest that trypsinogen isoenzymes found in seminal fluid are produced locally in the male genital tract and that they may play a physiological role in the semen.
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PMID:Expression and characterization of trypsinogen produced in the human male genital tract. 1110 74

Biomarkers of trans-fatty acid consumption have been associated with increased risks of breast and colon cancer, although no studies have examined their associations with prostate cancer risk. Using data from the beta-Carotene and Retinol Efficacy Trial, this nested case-control study examined the relationships between serum phospholipid trans-fatty acids and prostate cancer incidence in 272 case and 426 control men. Trans-fatty acids were measured using organic extraction followed by separations with TLC and gas chromatography. Adjusted odds ratios for risk of prostate cancer with increasing levels of trans-fatty acids were calculated using logistic regression. There were consistent trends for increasing prostate cancer risk with higher levels of C18 but not C16 trans-fatty acids, although only trends for Delta11t 18:1 trans-vaccenic and Delta9c,12t 18:2 fatty acids reached statistical significance. Odds ratios (95% confidence interval) contrasting low versus high quartiles for these fatty acids were 1.69 (1.03-2.77) and 1.79 (1.02-3.15), respectively. There were no consistent differences in associations between low-grade and high-grade cancer among the subset of 209 cases with information on tumor grade. Additional studies are needed to confirm these findings and better control for factors, such as use of prostate-specific antigen screening, which may confound this association.
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PMID:Serum trans-fatty acids are associated with risk of prostate cancer in beta-Carotene and Retinol Efficacy Trial. 1582 75

Prostate-specific antigen (PSA) is a representative of the prostate-related antigens, and has been considered to be a tumor marker of prostate cancer. However, some studies suggest that PSA could be produced by several types of tumors. In the present study, we attempted to determine whether or not PSA could be a target molecule in specific immunotherapy for patients with colon cancer. Five colon cancer cell lines were examined for their PSA expression at the mRNA and protein levels by RT-PCR and immunocytostaining, respectively. As a result, four cell lines were found to be positive for PSA at both the mRNA and protein levels. We also attempted to determine whether PSA-reactive cytotoxic T lymphocytes (CTLs) could be induced from the peripheral blood mononuclear cells (PBMCs) of HLA-A24+ colon cancer patients by in vitro stimulation with PSA-derived peptides. As a consequence, PSA peptide-specific CTLs could be generated from the PBMCs of male and female colon cancer patients. Their cytotoxicity against HLA-A24+ PSA-expressing colon cancer cells was dependent on HLA class I-restricted and CD8+ T cells. These findings indicate that PSA-reactive CTL precursors are present in the periphery of colon cancer patients, and that PSA could be a target molecule in specific immunotherapy to colon cancer.
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PMID:Prostate-specific antigen-reactive cytotoxic T lymphocyte precursors in colon cancer patients. 1639 48

The TMPRSS2-ETS fusion prostate cancers comprise 50-70% of the prostate-specific antigen (PSA)-screened hospital-based prostate cancers examined to date, making it perhaps the most common genetic rearrangement in human cancer. The most common variant involves androgen-regulated TMPRSS2 and ERG, both located on chromosome 21. Emerging data from our group and others suggests that TMPRSS2-ERG fusion prostate cancer is associated with higher tumour stage and prostate cancer-specific death. The goal of this study was to determine if this common somatic alteration is associated with a morphological phenotype. We assessed 253 prostate cancer cases for TMPRSS2-ERG fusion status using an ERG break-apart FISH assay. Blinded to gene fusion status, two reviewers assessed each tumour for presence or absence of eight morphological features. Statistical analysis was performed to look for significant associations between morphological features and TMPRSS2-ERG fusion status. Five morphological features were associated with TMPRSS2-ERG fusion prostate cancer: blue-tinged mucin, cribriform growth pattern, macronucleoli, intraductal tumour spread, and signet-ring cell features, all with p-values < 0.05. Only 24% (n=30/125) of tumours without any of these features displayed the TMPRSS2-ERG fusion. By comparison, 55% (n=38/69) of cases with one feature (RR=3.88), 86% (n=38/44) of cases with two features (RR=20.06), and 93% (n=14/15) of cases with three or more features (RR=44.33) were fusion positive (p<0.001). To our knowledge, this is the first study that demonstrates a significant link between a molecular alteration in prostate cancer and distinct phenotypic features. The strength of these findings is similar to microsatellite unstable colon cancer and breast cancer involving BRCA1 and BRCA2 mutations. The biological effect of TMPRSS2-ERG overexpression may drive pathways that favour these common morphological features that pathologists observe daily. These features may also be helpful in diagnosing TMPRSS2-ERG fusion prostate cancer, which may have both prognostic and therapeutic implications.
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PMID:Morphological features of TMPRSS2-ERG gene fusion prostate cancer. 1738 88

To quantify the risk of prostate cancer after colorectal cancer and the risk of colorectal cancer after prostate cancer and to examine the impact of radiation therapy on subsequent cancer risk, we conducted retrospective cohort studies using data from the Surveillance, Epidemiology and End Results program from 1973 to 2005. Standardized incidence ratios (SIR) and 95% confidence intervals (95% CI) were calculated, adjusting for age, ethnicity, and calendar year. The subsequent risk of developing a prostate cancer was significantly elevated in patients diagnosed with colon cancer before age 50 years (SIR, 1.38; 95% CI, 1.18-1.60). The risk of subsequent prostate cancer was decreased for men with rectal cancer who received radiation therapy (SIR, 0.57; 95% CI, 0.52-0.63). Interestingly, this beneficial effect of radiation therapy was only observed in the prostate-specific antigen (PSA) era (1988+). In addition, the prostate cancer cases developed in the radiation therapy group tended to have higher-grade, later-stage tumors, higher PSA levels, and worse survival than those developed in the nonradiation therapy group. In the cohort of prostate cancer patients, the risk of colon cancer was elevated in patients diagnosed with prostate cancer before age 50 years (SIR, 1.51; 95% CI, 1.03-2.20). In conclusion, a diagnosis of colon or prostate cancer in men of younger ages may be an indication for screening of prostate or colon cancer, respectively. The decreased prostate cancer risk in men who received radiation therapy for rectal cancer may be related to the use of PSA for prostate cancer screening or the cure of occult prostate cancer.
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PMID:Association of colorectal cancer and prostate cancer and impact of radiation therapy. 1953 78

Cancer prevention sometimes referred to as tertiary prevention or chemoprevention makes use of specific xenobiotics or drugs to prevent, delay, or retard the development of cancer. Over the last two decades or so cancer prevention has made significant strides. For example, prevention of lung cancer through smoking cessation; cervical cancer prevention through regular Pap smear tests; colon cancer prevention through screening colonoscopy; and prostate cancer reductions by prostate-specific antigen measurements in conjunction with regular prostate examinations. The seminal epidemiological observation that nonsteroidal anti-inflammatory drugs (NSAIDs) prevent colon and other cancers has provided the impetus to develop novel chemoprevention approaches against cancer. To that end, a number of "designer drugs" have been synthesized that are in different stages of development, evaluation, and deployment. Some include the cyclooxygenase-2-specific inhibitors (coxibs), nitric oxide-releasing NSAIDs (NO-NSAIDs and NONO-NSAIDs), hydrogen sulfide-releasing NSAIDs, modulators of the lipoxygenase pathway, prostanoid receptor blockers, and chemokine receptor antagonists. In addition to these novel agents, there are also a host of naturally occurring compounds/micronutrients that have chemopreventive properties. This chapter reviews these classes of compounds, their utility and mechanism(s) of action against the background of mediators that link inflammation and cancer.
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PMID:Anti-inflammatory agents as cancer therapeutics. 2023 Jul 59


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