T-type Ca2+ channels and their relationship with pre-neoplastic and neoplastic lesions in the human breast

The expression of T-type voltage-dependent Ca2+ channels (Cav3) has been previously observed in breast cancer, but their expression and subcellular localization were not evaluated in pre-neoplastic lesions. Therefore, this work aimed to evaluate protein expression and subcellular localization of T-type channel isoforms in human breast tissue samples. Protein expressions of CaV3.1, CaV3.2, and CaV3.3 were evaluated by immunohistochemistry in breast without alteration, in proliferative non-neoplastic lesions, and in neoplastic ductal epithelial lesions of the human breast. CaV3.1, CaV3.2, and CaV3.3 nuclear expressions were decreased in advanced stages of neoplastic transformation, whereas CaV3.1 and CaV3.2 cytoplasmic expression increased. Also, the decrease in nuclear expression was correlated with an increase in cytoplasmic expression for CaV3.1 isoform. The change in CaV3 protein expression and subcellular localization are consistent with the neoplastic transformation stages of mammary epithelial cells, evident in early neoplastic lesions, such as ductal carcinomas in situ. These results suggest a possible involvement of CaV3 in the carcinogenic processes and could be considered as a potential pharmacological target in new therapies for breast cancer treatment.

Oncogenes, genes supressores de tumores, microRNAs e o desenvolvimento de tumores / Oncogenes, tumor supressor genes, microRNA and tumor development

O câncer é um processo invasivo decorrente da transformação celular que ocorre em resposta a distúrbios genéticos provocados por mutações ou amplificações de alguns genes que codificam para proteínas capazes de controlar a proliferação e divisão celular, tais genes mutados são chamados oncogenes. Os genes normais (não alterados) constituintes do genoma são denominados proto-oncogenes. Neste artigo serão discutidos os mecanismos moleculares que estão envolvidos com a transformação de proto-oncogenes em oncogenes. A ação de microRNA no controle da expressão gênica representa um mecanismo essencial no controle de várias proteínas envolvidas com a carcinogênese, como consequência este tema também será abordado. Finalmente, será descrito o papel essencial que os genes supressores de tumores ou genes supressores da proliferação celular (antioncogenes) desempenham no controle do desenvolvimento do câncer. O melhor entendimento dos mecanismos celulares envolvidos na carcinogênese são essenciais para descobertas de novas moléculas que poderão servir como biomarcadores de diagnóstico e/ou prognóstico do câncer, além de poderem auxiliar significativamente para a descoberta de futuras terapias antitumorais.

The Clinicopathological Features of Gastric Hyperplastic Polyps with Neoplastic Transformations: A Suggestion of Indication for Endoscopic Polypectomy

BACKGROUND/AIMS: Although gastric hyperplastic polyps are usually considered as benign lesions, a low risk of carcinomatous conversion is currently recognized. We aimed to identify the characteristics of hyperplastic polyps undergoing neoplastic transformation. METHODS: A total of 269 gastric hyperplastic polyps from 216 patients removed by endoscopic polypectomy (EP) or surgical resection were enrolled in this study, and their endoscopic pictures and pathology slides were reviewed. RESULTS: Neoplastic transformation was detected on forceps biopsy specimen in 11 cases. However, the pathology findings from the EP or surgical specimen revealed neoplastic transformation in 14 cases (5.2%; 4 with dysplasia and 10 with adenocarcinoma). No significant difference was found between hyperplastic polyps with and without neoplastic transformation in age, sex, location, number of polyps or gross appearance. However, neoplastic transformations were more frequently found in gastric hyperplastic polyps >1 cm than in polyps 1 cm. Therefore, EP should be considered for gastric hyperplastic polyps >1 cm for the accurate diagnosis and definitive treatment.

Acrylamide-induced neoplastic transformation of human epithelial cells in culture

PURPOSE Acrylamide is present in significant quantities in a wide range of commonly consumed human foods. Carcinogenic risk of acrylamide through the consumption of food is a great public concern and in controversy, but it is not properly addressed due to the lack of evidence in humans. While a plenty of data is available on the carcinogenicity in animal models, the studies in humans are limited. Thus, the present study attempted to examine the carcinogenic potentials of acrylamide on the human epithelial cell, which is the target cell origin of the most cancers. MATERIAL AND METHOD & RESULT 1. Acrylamide was not cytotoxic up to 100 MICRO M as measured by MTT and LDH assays, indicating a relatively low toxicity of this substance in human epithelial cells. 2. The parameters of neoplastic cellular transformation such as cell saturation density, soft-agar colony formation and cell aggregation were analyzed to examine the carcinogenic potential of acrylamide. 3. The neoplastic transformation was further increased with the co-treatment of TPA 4. Antioxidants blocked the generation of Reactive Oxygen Species(ROS) and the GSH depleting agent dramatically increased the ROS production. 5. mRNA levels of fibronectin following acrylamide exposure was increased in a dose-dependent manner, indicating a possible biomarker of acrylamide-induced cellular transformation. CONCLUSION The present study will provide a valuable basis to compare the interspecies differences in response to carcinogenic potentials of acrylamide. The data on the interspecies differences are essential element in human risk assessment. Thus, our results obtained from the human epithelial cells will contribute to improving the risk assessment of human neoplasm including oral cancer.

High dose exposures of vinyl acetate induce neoplastic transformation of human epithelial cells in culture

Vinyl acetate has been widely used for the manufacture of polyvinyl alcohol emulsion, which is primary ingredient of adhesive, paints, textile, paperboard coatings, etc. Since these products are plentiful and frequently used around us, workers and consumers are at health risk. International Agency for Research on Cancer (IARC) classified vinyl acetate as group 2B (possibly carcinogenic to humans). Among the organs targeted, the oral cavity is the most vulnerable organ affected by the carcinogenic effects of vinyl acetate. Since the origin of most of oral cancer is derived from the epithelial cells, it is important to understand the carcinogenic potential of vinyl acetate in human epithelial cells. Thus, the present study has attempted to utilize the immortalized human epithelial cell model to assess the carcinogenic potency of this chemical and to understand the underlying mechanisms.

Neoplastic transformation of human osteoblast-like cell line HOS TE85 / 第三军医大学学报

Objective To establish human osteoblast-like cell lines TE85 model of neoplastic transformation for exploring molecular mechanism in canceration process of osteosarcoma.Methods HOS TE85 cells were treated by MNNG(initiated factor) and TPA(promotor).The malignancy of transformed cells was identified by observing the cell form,colony forming frequency on soft agar and tumorigenesis in nude mice.Results Continuous passage after induction of neoplastic transformation led to the formation of a few paramorph foci that exhibited an extensively random orientation.The agglomeration in experiment group was more than that in control group.As compared with that of negative control cells,colony formation efficiency of transformed cells in semisolid agar showed a significant increase and the transformed cells could form tumor subcutaneously in the nude mice.The tumors were a poorly differentiated osteosarcoma confirmed by histopathological examination.Conclusion Simulating the process of malignant transformation of human cells,we establish neoplastic transformation of human osteoblast-like cell lines TE85 model.