Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostate cancer is a leading solid tumor among men in the Western world. Androgens play an important role in the carcinogenesis and treatment of prostate cancer. CYP3A5 is a cytochrome P450 superfamily member which also has activity in testosterone metabolism. In this study, we looked for two-gene interactions associated with clinical characteristics of prostate cancer in the Finnish population. We used multifactor-dimensionality reduction for the identification of the two-gene interactions in androgen metabolism pathway genes together with clinical characteristics of prostate cancer among 754 genotyped prostate cancer patients. The CYP3A5*3/*3 and SRD5A2 A49T GG genotype interaction was associated with the clinical tumor stage T2-T4 (T-stage, TNM classification) with odds ratio (OR) 2.14, 95% confidence interval (CI) 1.35-3.40. Patients with CYP3A5*3/*3 and KLK3 I179T CC/TC genotypes had increased OR 2.30, 95% CI 1.16-4.58 for metastatic disease. Further, two-gene interaction CYP3A5*3/*3 and KLK3 -252A > G AA was associated with Gleason scores >or=7 with OR 1.52, 95% CI 1.11-2.09. Prostate cancer patients with CYP3A5*3/*3 and KLK -252A > G GG/AG genotypes had decreased OR of 0.70 with 95% CI 0.50-0.98 for high prostate-specific antigen levels at diagnosis. For prostate cancer patients aged below 65 years, the OR for interaction of CYP3A5*1/*3 or *1/*1 and AKR1C3 Q5H CC genotypes was 1.84 with 95% CI 1.03-3.28. For prostate cancer, the best two-gene interaction included genotypes SRD5A2 V89L GG and AKR1C3 Q5H CC with OR 1.30, 95% CI 1.01-1.66. It remains to be clarified whether these polymorphism associations identified here are also present in other populations.
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PMID:The interaction of CYP3A5 polymorphisms along the androgen metabolism pathway in prostate cancer. 1830 54

Heparanase plays an important role in invasion and metastasis of tumor cells. In this study, we explored the expression and clinicopathological significance of heparanase protein in hepatocellular carcinogenesis to investigate their roles in invasion and the relationship between biological behavior and prognosis of hepatocellular carcinoma (HCC) in tissue microarrays (TMAs). Heparanase expression was examined by immunohistochemistry in TMAs comprising 120 cases of HCC, 48 cases of adjacent tumor liver, 62 cases of cirrhosis, and 23 cases of normal liver tissues. Statistical analyses were determined to access the correlation between heparanase expression and the clinicopathological features of HCC. The results showed a positive level of heparanase in HCC tissues that was significantly higher than that in adjacent tumor liver, cirrhosis, and normal liver tissue. Heparanase was expressed lower in clinical TNM stages I and II than in III and IV. Moreover, the expression of heparanase in cases without metastasis within 20 months was statistically lower than in those with metastasis. Furthermore, heparanase expression in groups of alpha-fetoprotein (AFP) > or = 400 microg/L, portal vein tumor emboli, multiple tumor nodes, and tumor diameter > or = 5 cm were significantly higher than those of corresponding groups, while it was not associated with patients' age, sex, histological classification, cirrhosis, or tumor capsular infiltration. In conclusion, TMA is a powerful tool for the rapid identification of molecular alterations in HCC. The overexpression of heparanase may play an important role in hepatocarcinogenesis, progression, and metastases of HCC. It could serve as a determining factor for clinical prognosis and curative effect.
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PMID:Expression of heparanase in hepatocellular carcinoma has prognostic significance: a tissue microarray study. 1877 63

Altered DNA methylation in cancer cells is characterized by focal CpG island hypermethylation and diffuse genomic hypomethylation. Both types of aberrant methylation are frequently found in human prostate adenocarcinoma (PCa). Prostatic intraepithelial neoplasm (PIN), a precursor lesion of PCa, has been demonstrated to contain CpG island hypermethylation, but little is known about the role of DNA hypomethylation. We analyzed the methylation status at 12 CpG island loci and at two repetitive DNA elements (LINE-1 and SAT2) from normal prostate (n = 20), PIN (n = 25), and PCa (n = 35) tissues using MethyLight assay or combined bisulfite restriction analysis. The methylation levels in LINE-1 and SAT2 decreased with progression of lesion types from normal prostate to PIN to PCa (P < 0.05), whereas promoter CpG island loci displayed increased methylation. Ten genes were found to be hypermethylated in a cancer-specific manner and were further analyzed in another set of PCa tissues (n = 64). The number of methylated genes was closely associated with TNM stage, Gleason sum, and preoperative serum PSA levels (P = 0.020, 0.073, 0.033, respectively). These results suggest that genomic hypomethylation and CpG island hypermethylation, common among PCas, are early events in prostate carcinogenesis and may be implicated in the development of PIN.
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PMID:Genomic hypomethylation and CpG island hypermethylation in prostatic intraepithelial neoplasm. 1904 91

The interaction of connexin 43 and E-cadherin may play an important role in carcinogenesis and malignant behaviour of tumours. In this study, we examined the relationship between connexin 43 and E-cadherin in human non-small cell lung cancers (NSCLC). Expression levels of connexin 43 and E-cadherin were examined in 107 NSCLC specimens by immunohistochemistry. The connexin 43 gene was transfected into lung cancer LH7 cells. The protein localizations and levels of connexin 43 and E-cadherin were detected using immunofluorescence staining and western blot. Cell cycle and proliferation of lung cancer cells were examined using flow cytometry and MTT. We found that reduced expression of both connexin 43 and E-cadherin significantly correlated to poor differentiation, advanced TNM stage, and lymph note metastasis of NSCLCs. Connexin 43 and E-cadherin expression significantly correlated with each other. Over-expression of connexin 43 significantly induced E-cadherin expression. Moreover, connexin 43-transfected LH7 cells showed significantly decreased cell proliferation. The percentage of cells in G1 phase increased, while the number of cells in S and G2 phases significantly decreased. We concluded that concurrent reduction of connexin 43 and E-cadherin may contribute to the development of lung cancer. Connexin 43 may induce E-cadherin expression and inhibit cell proliferation and progression of lung cancer.
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PMID:Connexin 43 recruits E-cadherin expression and inhibits the malignant behaviour of lung cancer cells. 1905 35

To study the expression and implication of HIF-1alpha and VEGF-C in non-small cell lung cancer (NSCLC) and its relationship with clinical pathological features of NSCLC, immunohistochemical SP was used to detect the expression of HIF-1alpha and VEGF-C proteins in 48 NSCLC tissues and the same para-cancerous tissues. The positive rates of HIF-1alpha and VEGF-C were 70.8% (34/48) and 68.8% (33/48) respectively. The expression of HIF-1alpha protein was detected in a significantly greater proportion in NSCLC carcinoma tissues than that in para-cancerous tissues (12.5% and 16.7%, P<0.05). The positive rates of HIF-1alpha and VEGF-C were correlated with lymph node metastasis and TNM stage. No relationship was found between the two factors and age, sex, pathological subtypes and histological grades. The positive rates between HIF-1alpha and VEGF-C were correlated (P<0.05). HIF-1alpha and VEGF-C were over-expressed in NSCLC. They may be involved in the carcinogenesis of NSCLC, and play an important role in invasion and metastasis of NSCLC. HIF-1alpha and VEGF-C work synergically in the process of NSCLC.
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PMID:Expression and clinical implication of HIF-1alpha and VEGF-C in non-small cell lung cancer. 1910 64

Epidemiological studies have shown that the inducible form of cyclooxygenase (COX-2) may be involved in colorectal carcinogenesis, but it is controversial whether its expression is a prognostic factor for colorectal cancer. The aim of the study was to examine the expression of COX-2 in colorectal cancer and investigate its prognostic relevance. Tissue sections of primary tumors from 132 patients undergoing curative resection for colorectal cancer were immunohistochemically examined for COX-2 expression. The levels of intensity and extent of COX-2 staining were quantified by use of a computerized image analysis system and correlated with various clinicopathological characteristics and survival. COX-2 immunoreactivity was observed in the cytoplasm of tumour epithelial cells of all colorectal cancer tissues examined. No significant correlation was found between levels of intensity and extent of COX-2 staining and various clinicopathological characteristics, including age, gender, tumor location, tumor size, tumor grade, depth of invasion, lymph node status and TNM stage. There was an inverse correlation between intensity and extent of COX-2 staining scores (Spearman's rho=-0.414; p<0.001). To analyze the prognostic value of intensity and extent of COX-2 staining, the patients were divided into four groups with respect to quartiles (< or =25; >25 to < or =50; >50 to < or =75; and >75). No significant disease-specific survival difference among the quartiles was found based on analysis of intensity (p=0.689) and extent (p=0.975) of COX-2 staining. These results suggest that the expression of COX-2 protein has no significant impact on the outcome of patients with colorectal cancer.
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PMID:Prognostic value of COX-2 immunohistochemical expression evaluated by quantitative image analysis in colorectal cancer. 1913 85

Several risk factors for the development of laryngeal cancer have been identified, such as smoking and alcohol consumption, but the molecular mechanisms related to the carcinogenesis in the larynx remain under investigation. In this context, deregulations of the cell-cycle-controling mechanisms, Rb-pathway in particular, have been suggested to be involved in the pathogenesis of laryngeal carcinoma. Our purpose was to investigate 13q14 LOH and the expression of Rb protein and their possible prognostic value in laryngeal cancer. The group of 67 patients with laryngeal cancer, surgically treated with minimum 5 years observation, was multi-variously analysed. LOH for Rb was investigated by PCR-based techniques using two microsatellite markers, D13S263 and D13S126, flanking the Rb locus. Amplification products from each polymorphism were fractionated by denaturing gel electrophoresis and detected by audioradiography. Immunohistochemical staining of paraffin specimens of laryngeal cancers was supervised by the use of monoclonal mouse antibodies IgG1 (Anti-Human Retinoblastoma Gene Product of Dako) in dilution of 1:50. Inactivation of Rb protein was assumed to represent the expression in < or =10% tumour cells. The results of each examined individual factor were compared with clinicopathologic features and the results were statistically transformed (Chi-square test with Yates' correction, Mann-Whitney test). The Kaplan and Meier model was used for overall and disease free survival curves. Only p value of less than 0,05 was considered significant. 13q14 LOH was detected in 7/67 (10,4%) of informative tumours. No correlations were found between Rb genetic alteration (LOH) and gender, age, TNM staging, histological differentiation, nodal and local recurrences (p>0.05). There was a strong association between the loss of Rb and supraglottic localisation of tumour in the larynx (p<0.01). By univariate analysis 13q14 LOH proved to be significantly related to the overall survival whereas it was not related to the quicker relapse (p=0.01, p>0.05 respectively). The genetic data were correlated with the expression of the Rb protein (p=0.001). All tumours with Rb-LOH were immunohistochemically Rb-negative. Inactivation of Rb protein was observed in 9/67 cases (13.49%) and was significantly correlated with the polymorphism of cancer cells, but not with the histological grading. We also found the correlation between reduction of Rb protein and the size of primary tumour (T) (p=0.03) and local recurrence (p=0.035). There was no significant dependence between the level of Rb protein and other histopathological and clinical features (p>0.05). To conclude, analysis of 13q14 LOH enables the assessment of biology of laryngeal cancer and it can be a prognostic factor in overall survival. Immunohistochemical analysis of Rb protein expression in neoplastic cells made it easier to evaluate the mechanisms of cancerogenesis in laryngeal cancer and is closely related to genetic alteration in Rb locus.
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PMID:Loss of heterozygosity for Rb locus and pRb immunostaining in laryngeal cancer: a clinicopathologic, molecular and immunohistochemical study. 1914 2

One main etiology for oral squamous cell carcinoma (OSCC) is inflammation. Inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) are the important molecules showing close relation to not only inflammation but also carcinogenesis and angiogenesis. Angiogenesis is defined as the formation of new blood vessels from existing vasculature. It is necessary for tumor growth and progression and also involved in metastasis. The objective of this research was to study the expression and relationship among iNOS, VEGF, COX-2, angiogenesis and their clinico-pathological correlation in OSCC. In this study, standard indirect immunohistochemical technique using polyclonal antibodies specific to human iNOS, VEGF, COX-2 and CD31 was performed in formalin-fixed paraffin-embedded tissue sections of 66 OSCC samples. The staining patterns and intensity are measured and analyzed statistically. The results showed that epithelial components of squamous cell carcinomas demonstrated moderate to intense staining for iNOS, VEGF and COX-2. iNOS shows correlation with cervical lymph node metastasis and tumor staging (TNM) of the patients and angiogenesis. VEGF shows correlation with tumor grading, tumor staging and angiogenesis. COX-2 shows correlation with cervical lymph node metastasis. In conclusion, the expression of iNOS, VEGF and COX-2 exists in OSCC. The data provided show the expression of these chemical mediators associated with carcinogenesis and angiogenesis in OSCC. It can be the primary database before using angiogenesis drug against these mediators for OSCC treatment.
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PMID:Expression of pro-inflammatory protein, iNOS, VEGF and COX-2 in oral squamous cell carcinoma (OSCC), relationship with angiogenesis and their clinico-pathological correlation. 1930 Mar 68

Epigenetic modifications play an important role during carcinogenesis. The main goal of this study was to examine expression levels of two critical enzymes, DNA methyltransferase-1 (DNMT1) and histone deacetylase-1 (HDAC1), by immunohistochemistry (IHC) in human pancreatic cancer and precancerous lesions: 20 foci containing normal ductal epithelial cells without an inflammatory back-ground (DE), 30 containing ductal epithelial cells with an inflammatory background (DEI), 48 of pancreatic intraepithelial neoplasia-1A (PanIN-1A), 103 of PanIN-1B, 99 of PanIN-2, 30 of PanIN-3, 18 of intraductal papillary mucinous neoplasm A (IPMA), 10 of IPMB, 20 of IPMC, and 54 of pancreatic ductal adenocarcinoma (PDAC). The expression levels of both DNMT1 and HDAC1 increased from normal to precancerous lesions to pancreatic cancer, in a malignancy-dependent manner. Correlations between expression levels and clinicopathological features of the 54 PDAC patients were also analyzed. The expression of DNMT1 significantly correlated with nerve infiltration, degree of tumor differentiation and TNM staging (p<0.05), while that of HDAC1 correlated with proliferative activity, degree of tumor differentiation and TNM staging (p<0.05). Patients with higher expression of DNMT1 and/or HDAC1 had an overall lower survival than those with lower expression (p<0.05). Higher expression of DNMT1 and HDAC1 correlated with advanced stages of the disease and reflect the malignancy of pancreatic carcinoma. They may become new prognostic markers and potential therapeutic targets for pancreatic cancer.
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PMID:Significance of DNA methyltransferase-1 and histone deacetylase-1 in pancreatic cancer. 1942 21

Our previous studies revealed that cytokine induced apoptosis inhibitor 1 (CIAPIN1), which was reported to be essential in mouse definitive hematopoiesis, was related to multidrug resistance in gastric cancer cells and that the distribution of CIAPIN1 in normal human tissues was similar to the distribution of Ras. This study aimed to explore whether CIAPIN1 plays a role in gastric carcinogenesis. Expression of CIAPIN1 in normal, inflammatory gastric mucosa, gastric precancerous lesions and gastric adenocarcinoma was detected by immunohistochemistry and western blotting and, influence of CIAPIN1 on the proliferation of gastric cancer cells was investigated by ectopic expression of CIAPIN1 and RNA interference (RNAi). Our immunohistochemical results demonstrated that the expression of CIAPIN1 in gastric antral mucosa was progressively reduced along the sequence of normal/inflammatory gastric mucosa-atrophy-intestinal metaplasia-dysplasia-adenocarcinoma. The downregulation of CIAPIN1 in cancerous tissues was further confirmed by western blotting. No relationship between the expression level of CIAPIN1 and the clinicopathological parameters such as age, gender, differentiation, TNM stage and the existence of metastasis was found in gastric cancer patients. In in vitro cellular experiments, ectopic expression of CIAPIN1 by cDNA transfection resulted in suppression of cell proliferation and inhibition of cell cycle progression while knockdown of CIAPIN1 with siRNA accelerated cell proliferation and promoted cell cycle progression in SGC7901 and MKN28 gastric cancer cells. These results suggest that downregulated CIAPIN1 expression may contribute to gastric carcinogenesis by accelerating cell proliferation and promoting cell cycle progression.
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PMID:Downregulated expression of CIAPIN1 may contribute to gastric carcinogenesis by accelerating cell proliferation and promoting cell cycle progression. 1947 Nov 13


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