Home About us Contact
|
Home About us Contact | ||
|
|
||
Human Carcinogenesis (human + carcinogenesi)
Selected AbstractsHypermethylation of RAS effector related genes and DNA methyltransferase 1 expression in endometrial carcinogenesisINTERNATIONAL JOURNAL OF CANCER, Issue 2 2008Xiaoyun Liao Abstract Epigenetic aberration is known to be important in human carcinogenesis. Promoter methylation status of RAS effector related genes, RASSF1A, RASSF2A, hDAB2IP (m2a and m2b regions) and BLU, was evaluated in 76 endometrial carcinomas and their non-neoplastic endometrial tissue by methylation specific PCR. Hypermethylation of at least one of the 5 genes was detected in 73.7% of carcinomas. There were significant correlations between methylation of hDAB2IP and RASSF1A, RASSF2A (p = 0.042, p = 0.012, respectively). Significantly, more frequent RASSF1A hypermethylation was found in Type I endometrioid carcinomas than Type II carcinomas (p = 0.049). Among endometrioid cancers, significant association between RASSF1A hypermethylation and advanced stage, as well as between methylation of hDAB2IP at m2a region with deep myometrial invasion (p < 0.05) was observed. mRNA expression of RASSF1A, RASSF2A and BLU in endometrial cancer cell lines significantly increased after treatment with the demethylating agent 5-Aza-2,-deoxycytidine supporting the repressive effect of hypermethylation on their transcription. Immunohistochemical study of DNMT1 on eight normal endometrium, 16 hyperplastic endometrium without atypia, 40 atypical complex hyperplasia and 79 endometrial carcinomas showed progressive increase in DNMT1 immunoreactivity from normal endometrium to endometrial hyperplasia and endometrioid carcinomas (p = 0.001). Among carcinomas, distinctly higher DNMT1 expression was observed in Type I endometrioid carcinomas (p < 0.001). DNMT1 immunoreactivity correlated with RASSF1A and RASSF2A methylation (p < 0.05). The data suggested that hypermethylation of RAS related genes, particularly RASSF1A, was involved in endometrial carcinogenesis with possible divergent patterns in different histological types. DNMT1 protein overexpression might contribute to such aberrant DNA hypermethylation of specific tumor suppressor genes in endometrial cancers. © 2008 Wiley-Liss, Inc. [source] RNT-1 regulation in C. elegansJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2005Yon Ju Ji Abstract RUNXs are important transcription factors, which are involved in animal development and human carcinogenesis. RNT-1, the only homologue of RUNXs, in Caenorhabditis elegans (C. elegans) has been identified and viable mutant animals of rnt-1 gene have been isolated and characterized recently. Genetic analyses using rnt- 1 mutants have shown that RNT-1 is regulated by TGF,- and Wnt-signaling pathways in the body size regulation and male tail development. Here, we review our current understanding of RNT-1 functions in these signaling pathways. Furthermore, future prospects of RNT-1 and BRO-1 studies in C. elegans are discussed in this review. © 2005 Wiley-Liss, Inc. [source] Association between Waste Management and Cancer in Companion AnimalsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2009L. Marconato Background: Increased cancer rates have been documented in people residing in areas around Naples characterized by illegal dumping and incineration of waste. Hypothesis: Risk of cancer in dogs and cats is associated with waste management. Animals: Four hundred and fifty-three dogs and cats with cancer and 1,554 cancer-free animals. Methods: Hospital-based case-control study in Naples (low danger) and nearby cities having a history of illegal waste dumping (high danger). Odds ratio (OR) between high- and low-danger areas was calculated for all tumors and various malignancies in dogs and cats. Results: An increased risk for cancer development was identified in dogs but not in cats residing in high-danger areas (OR: 1.55; 95% confidence interval: 1.18,2.03; P < .01). A 2.39-fold increased risk of lymphoma (P < .01) accounted for the greater tumor frequency in dogs residing in high-danger areas. The risk of mast cell tumor and mammary cancer did not differ in dogs residing in high- or low-danger areas. Conclusions and Clinical Importance: Waste emission from illegal dumping sites increases cancer risk in dogs residing in high-danger areas. An increased prevalence of lymphoma has been previously recognized in humans living close to illegal waste dumps. Thus, epidemiological studies of spontaneous tumors in dogs might suggest a role for environmental factors in canine and human carcinogenesis and can predict health hazards for humans. [source] Cyclooxygenase-2 expression on urothelial and inflammatory cells of cystoscopic biopsies and urine cytology as a possible predictive marker for bladder carcinomaAPMIS, Issue 1 2009MONA MOUSSA Cyclooxygenase-2 (COX-2) is a key inducible enzyme involved in the production of prostaglandins. It contributes to human carcinogenesis by various mechanisms. The aim of the current study was to elucidate the possible involvement of COX-2 in human bladder carcinoma by examining its expression on both urothelial and inflammatory cells in tissue biopsies and urine cytology samples of different urinary bladder lesions. A total of 65 patients were included in the study and were selected from cases admitted to Urology Department, Theodor Bilharz Research Institute (TBRI), Giza, Egypt. They represented seven control cases with almost normal-looking bladder tissue; pure chronic cystitis (n=12); premalignant lesions (18) in the form of squamous metaplasia (n=8) or urothelial dysplasia (n=10) as well as transitional cell carcinoma (TCC) (n=18), and squamous cell carcinoma (SqCC) (n=10). Immunohistochemistry of formalin-fixed, paraffin-embedded tissue sections and urine cytology samples was performed for all cases using COX-2 (H-62): sc-7951, a rabbit polyclonal antibody. The study revealed positive COX-2 expression on the urothelial and inflammatory cells of cystoscopic biopsies from all cases of pure chronic cystitis, squamous metaplasia and SqCC compared with 42.8% and 71.4% of normal controls, respectively. The score of urothelial COX-2 expression was sequentially up-regulated from normal to chronic cystitis (either pure or associated with premalignant changes) (p<0.05) to malignant changes (p<0.05). However, the inflammatory cellular expression was down-regulated with malignant transformation compared with chronic cystitis (p<0.05). In TCC, COX-2 was over-expressed on both urothelial and inflammatory cells in advanced tumors. Urine cytology samples were positive for COX-2 in a comparable manner to that observed in cystoscopic biopsies. Accordingly, the results of the current study have provided new information in two aspects: First, is the possibility of using the differential COX-2 expression on both inflammatory and urothelial cells as markers for premalignant or malignant transformation; second, besides cystoscopy, urine cytology was found to have a high sensitivity for COX-2 expression and hence proved to be valuable in malignancy as a non-invasive substitute for cystoscopy. [source] ,-Herpesviruses and cellular signaling in AIDS-associated malignanciesCANCER SCIENCE, Issue 9 2007Kohji Noguchi ,-Herpesviruses, Epstein,Barr virus (EBV/HHV-4) and Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8), are involved in human carcinogenesis, particularly in immunocompromised patients. Virus-associated malignancies are becoming of significant concern for the mortality of long-lived immunocompromised patients, and therefore, research of advanced strategies for AIDS-related malignancies is an important field in cancer chemotherapy. Detailed understanding of the EBV and KSHV lifecycle and related cancers at the molecular level is required for novel strategies of molecular-targeted cancer chemotherapy. The present review gives a simple outline of the functional interactions between KSHV- and EBV-viral gene products and host cell deregulated signaling pathways as possible targets of chemotherapy against AIDS-related malignancies. (Cancer Sci 2007; 98: 1288,1296) [source] Cell adhesion system and human cancer morphogenesisCANCER SCIENCE, Issue 7 2003Setsuo Hirohashi Cell-cell adhesion determines the polarity of cells and participates in the maintenance of the cell societies called tissues. Cell-cell adhesiveness is generally reduced in human cancers. Reduced intercellular adhesiveness allows cancer cells to disobey the social order, resulting in destruction of histological structure, which is the morphological hallmark of malignant tumors. Reduced intercellular adhesiveness is also indispensable for cancer invasion and metastasis. A tumor-suppressor gene product, E-cadherin, and its undercoat proteins, catenins, which connect cadherins to actin filaments, are located at lateral borders, concentrating on adherens junctions, of epithelial cells and establish firm cell-cell adhesion. The E-cadherin cell adhesion system in cancer cells is inactivated by various mechanisms that reflect the morphological and biological characteristics of the tumor. Silencing of the E-cadherin gene by DNA hypermethylation around the promoter region occurs frequently, even in precancerous conditions. In diffuse infiltrating cancers, mutations are found in the genes for E-cadherin and ,-and ,-catenins. At the invading front of cancers, the E-cadherin cell adhesion system is inactivated by tyrosine phosphorylation of ,-catenin; an oncogene product, c- erb B-2 protein, is found to associate directly with ,-catenin. The E-cadherin cell adhesion system cross-talks with the Wingless/Wnt signaling pathway through ,-catenin, and expression of genes, which participate in cancer morphogenesis, may be regulated in conjunction with the Wingless/Wnt signaling pathway. Dysadherin, a newly identified cancer-associated cell membrane glycoprotein, down-regulates E-cadherin and promotes cancer metastasis. In conclusion, inactivation of the E-cadherin cell adhesion system by both genetic and epigenetic mechanisms plays a significant role during multistage human carcinogenesis. [source] | ||||||||||