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Cancer Initiation (cancer + initiation)
Selected AbstractsTargeting the development of resveratrol as a chemopreventive agent,DRUG DEVELOPMENT RESEARCH, Issue 6 2010Nian-Guang Li Abstract Tumor development consists of several separate, but closely linked, stages: tumor initiation, promotion, and progression. This long and complex process provides opportunities for intervention both in preventing cancer initiation and in treating the neoplasm during its premalignant stages. Resveratrol, a polyphenolic compound found in many plant species, including grapes, peanuts, and various herbs, has recently been investigated intensely for its cancer chemopreventive property. The present work is an overview of the chemopreventive mechanisms of resveratrol in anti-initiation, anti-promotion, and anti-progression. These, together with the low toxicity of resveratrol, suggest promise for novel chemopreventive agents. However, the low bioavailability and rapid clearance of resveratrol from the circulation require the design of new resveratrol-like chemopreventive agents, the structural modifications and the structure,activity relationship of which are also discussed in this review. Drug Dev Res 71:335,350, 2010. © 2010 Wiley-Liss, Inc. [source] ERBB2, TBX2, RPS6KB1, and MYC alterations in breast tissues of BRCA1 and BRCA2 mutation carriersGENES, CHROMOSOMES AND CANCER, Issue 1 2004Camilo Adem Breast cancer risk is greatly increased in women who carry mutations in the BRCA1 or BRCA2 genes. Because breast cancer initiation is different between BRCA1/2 mutation carriers and women who do not carry mutations, it is possible that the mechanism of breast cancer progression is also different. Histopathologic and genetic studies have supported this hypothesis. To test this hypothesis further, we utilized a large cohort of women who underwent therapeutic mastectomy (TM) and contralateral prophylactic mastectomy (PM). From this cohort, we developed case groups of women with a family history of breast cancer with BRCA1/2 deleterious mutations, with unclassified variant alterations, and with no detected mutation and matched these cases with sporadic controls from the same TM and PM cohort. Fluorescence in situ hybridization was performed on paraffin sections by use of dual-color probes for ERBB2/CEP17, MYC/CEP8, TBX2/CEP17, and RPS6KB1/CEP17. All malignant and benign lesions, including putative precursor lesions, were studied. The invasive cancers from deleterious mutation carriers had a higher prevalence of duplication of MYC (P = 0.006) and TBX2 (P = 0.0008) compared to controls and a lower prevalence of ERBB2 amplification (P = 0.011). Coduplication of MYC and TBX2 was common in the in situ and invasive lesions from the deleterious mutation carriers. The odds ratio of having a BRCA1/2 mutation is 31.4 (95% CI = 1.7,569) when MYC and TBX2 are coduplicated but ERBB2 is normal. Unclassified variant carriers/no mutation detected and sporadic controls had a similar prevalence of alterations, suggesting that hereditary patients with no deleterious mutations follow a progression pathway similar to that of sporadic cases. With the exception of one atypical ductal hyperplasia lesion, no putative precursor lesion showed any detectable alteration of the probes tested. There was no significant intratumoral heterogeneity of genetic alterations. Our data confirm that a specific pattern of genomic instability characterizes BRCA1/2 -related cancers and that this pattern has implications for the biology of these cancers. Moreover, our current and previous results emphasize the interaction between phenotype and genotype in BRCA1/2 -related breast cancers and that a combination of morphologic features and alterations of ERBB2, MYC, and TBX2 may better define mechanisms of tumor progression, as well as determine which patients are more likely to carry BRCA1/2 mutations. © 2004 Wiley-Liss, Inc. [source] Photochemoprevention of skin cancer by botanical agentsPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 2 2003Sleem F'guyer Photochemoprevention has become an important armamentarium in the fight against ultraviolet radiation (UVR)-induced damage to the skin. Among many UVR-induced damages, skin cancer is of the greatest concern as its rates have been steadily increasing in recent years and the same trend is expected to continue in the future. Ultraviolet radiation increases oxidative stress in skin cells by causing excessive generation of reactive oxygen species (ROS), leading to cancer initiation and promotion. Antioxidants have the capability to quench these ROS and much recent work shows that some of these can inhibit many UVR-induced signal transduction pathways. Thus, identifying nontoxic strong antioxidants , capable of preventing UVR-induced skin cancer , has become an important area of research. The use of botanical antioxidants in skin care products is growing in popularity. A wide range of such agents has been shown to prevent skin cancer in animal model systems. New agents are constantly being investigated; however, only a few have been tested for their efficacy in humans. Animal model and cell culture studies have clarified that antioxidants act by several mechanisms at various stages of skin carcinogenesis. This review focuses on skin cancer photochemopreventive effects of selected botanical antioxidants. [source] Epidemiology of pleural mesothelioma in a population with non-occupational asbestos exposureRESPIROLOGY, Issue 1 2008Muzaffer METINTAS Background and objective: This study describes the epidemiology of malignant pleural mesothelioma (MPM) in a rural population with environmental asbestos exposure. Methods: Patients with diagnosed MPM were recruited and their relevant demographic and exposure data were analysed. Results: A total of 131 patients with MPM (59 men, 72 women) were studied. The patients' mean age was 57.8 years and the mean exposure duration was 28.9 years. The cumulative fibre count of the villagers ranged from 0.19 to 14.61 fibre/mL-years. Of the 131 patients, 85 had epithelial cell type, 20 had mixed, and eight had sarcomatous pleural mesothelioma. No significant relationship was found between asbestos fibre type and age, exposure period, or cellular type of MPM; similarly, no significant relationship could be found between the cellular type and age or exposure period. Patients with sarcomatous mesotheliomas were considerably older. Only five of 131 (3.8%) patients had a family history of mesothelioma. Conclusions: Environmental exposure to asbestos begins at birth and this may be important in the age of disease onset, if a threshold model for cancer initiation is operative. Both men and women had an excess risk of mesothelioma. Given that a family history of MPM was not common in this relatively homogenous patient group, a genetic predisposition to mesothelioma appears unlikely. [source] The roles of microRNA in cancer and apoptosisBIOLOGICAL REVIEWS, Issue 1 2009Niamh Lynam-Lennon Abstract microRNAs (miRNAs) are highly conserved, non-protein-coding RNAs that function to regulate gene expression. In mammals this regulation is primarily carried out by repression of translation. miRNAs play important roles in homeostatic processes such as development, cell proliferation and cell death. Recently the dysregulation of miRNAs has been linked to cancer initiation and progression, indicating that miRNAs may play roles as tumour suppressor genes or oncogenes. The role of miRNAs in apoptosis is not fully understood, however, evidence is mounting that miRNAs are important in this process. The dysregulation of miRNAs involved in apoptosis may provide a mechanism for cancer development and resistance to cancer therapy. This review examines the biosynthesis of miRNA, the mechanisms of miRNA target regulation and the involvement of miRNAs in the initiation and progression of human cancer. It will include miRNAs involved in apoptosis, specifically those miRNAs involved in the regulation of apoptotic pathways and tumour suppressor/oncogene networks. It will also consider emerging evidence supporting a role for miRNAs in modulating sensitivity to anti-cancer therapy. [source] Hereditary diffuse gastric cancer: A manifestation of lost cell polarityCANCER SCIENCE, Issue 7 2009Bostjan Humar Hereditary diffuse gastric cancer is a cancer syndrome caused by germline mutations in the gene for the cell adhesion protein E-cadherin (CDH1). E-cadherin plays a central role in the maintenance of cell polarity and its loss during tumorigenesis is associated with poorly differentiated cancers and a poor prognosis. Hereditary diffuse gastric cancer is dominated by diffuse-type gastric adenocarcinoma, often with signet ring cell morphology. Large numbers of stage T1a signet ring cell carcinomas exist in the stomachs of CDH1 mutation carriers from a young age, and these foci sometimes show enrichment to the transition zone between the body and antrum. Generally these signet ring cell carcinomas are hypoproliferative, lack Wnt pathway activation, and are relatively indolent. However, a small proportion of the T1a foci contain cells that are poorly differentiated, display mesenchymal features, and express activated c-Src and its downstream targets. These same features are observed in more advanced stages of hereditary diffuse gastric cancer progression, suggesting that an epithelial,mesenchymal transition is required for tumor invasion beyond the muscularis mucosae. Hereditary diffuse gastric cancer initiation requires somatic down-regulation of the second CDH1 allele, which in most cases is caused by DNA promoter hypermethylation. Subsequent to CDH1 down-regulation, lost polarity in gastric stem or progenitor cells would be predicted to interfere with mitotic spindle orientation and the segregation of cell fate determinants. We predict that this disruption of cell division results in daughter cells being deposited in the lamina propria where their population expands and partially differentiates, resulting in the formation of foci of signet ring cells. (Cancer Sci 2009; 100: 1151,1157) [source] | ||||||||||