Morphological alterations and gene and protein expression profiling of bladder tumor cells after treatment with gemcitabine.

Chemical agents used in cancer therapy are associated with cell cycle arrest, activation or deactivation of mechanisms\ud associated to DNA repair and apoptosis. However, due to the complexity of biological systems, the molecular\ud mechanisms responsible for these activities are not fully understood. Thus, studies about gene and protein expression\ud have shown promising results for understanding the mechanisms related to cellular responses and regression of cancer\ud after chemotherapy. This study aimed to evaluate the gene and protein expression profiling in bladder transitional cell\ud carcinoma (TCC) with different TP53 status after gemcitabine (1.56 μM) treatment. The RT4 (grade 1, TP53 wild\ud type), 5637 (grade 2, TP53 mutated) and T24 (grade 3, TP53 mutated) cell lines were used. PCR arrays and mass\ud spectrometry were used to analyze gene and protein expression, respectively. Morphological alterations were observed\ud using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The results of PCR array\ud showed that gemcitabine activity was mainly related to CDKN1A, GADD45A and SERTDA1 overexpression, and BAX\ud overexpression only in the wild type TP53 cells. Mass spectrometry demonstrated that gemcitabine modulated the protein\ud expression, especially those from genes related to apoptosis, transport of vesicles and stress response. Analyses using SEM\ud and TEM showed changes in cell morphology independently on the cell line studied. The observed decreased number of\ud microvillus suggests low contact among the cells and between cell and extracellular matrix; irregular forms might indicate\ud actin cytoskeleton deregulation; and the reduction in the amount of organelles and core size might indicate reduced\ud cellular metabolism. In conclusion, independently on TP53 status or grade of bladder tumor, gemcitabine modulated\ud genes related to the cell cycle and apoptosis, that reflected in morphological changes indicative of future cell death.FAPESPCNP

CHO cell adhesion on modified surfaces of different materials.

Epithelial cells are mainly responsible for the formation of tissues that cover the external and internal surfaces of organs like skin, lining of the lungs and intestines. The cells must adhere to substrates and to each other in compliance with certain stimulus. In this way, adhesion properties can be regulated by the cell which simultaneously senses the chemical and mechanical properties of its environment. Their adhesion and growth on biomaterials depends on substrate properties such as surface wettability, topography and chemistry. The aim of this study is to investigate cell-surface interactions using several materials and different surfaces

Relationship between head and neck cancer therapy and some genetic endpoints

Head and neck cancer (HNC) is the sixth most common human malignancy worldwide. The main forms of treatment for HNC are surgery, radiotherapy (RT) and chemotherapy (CT). However, the choice of therapy depends on the tumor staging and approaches, which are aimed at organ preservation. Because of systemic RT and CT genotoxicity, one of the important side effects is a secondary cancer that can result from the activity of radiation and antineoplastic drugs on healthy cells. Ionizing radiation can affect the DNA, causing single and double-strand breaks, DNA-protein crosslinks and oxidative damage. The severity of radiotoxicity can be directly associated with the radiation dosimetry and the dose-volume differences. Regarding CT, cisplatin is still the standard protocol for the treatment of squamous cell carcinoma, the most common cancer located in the oral cavity. However, simultaneous treatment with cisplatin, bleomycin and 5-fluorouracil or treatment with paclitaxel and cisplatin are also used. These drugs can interact with the DNA, causing DNA crosslinks, double and single-strand breaks and changes in gene expression. Currently, the late effects of therapy have become a recurring problem, mainly due to the increased survival of HNC patients. Herein, we present an update of the systemic activity of RT and CT for HNC, with a focus on their toxicogenetic and toxicogenomic effects

Disperse Red 1 (textile dye) induces cytotoxic and genotoxic effects in mouse germ cells

Artículo de publicación ISIDisperse Red 1 (DR1), which is widely used in the textile industry, is an azo dye that contributes to the toxicity and pollution of wastewater. To assess the toxic effects of DR1 on reproduction, sexually mature male mice (Mus musculus, strain CF-1) were orally (gavage) treated with single doses of the compound at 20, 100 and 500 mg/kg body weight. Testicular features and sperm parameters were evaluated 8.3, 16.6 and 24.9 days after treatments. In addition to testicular toxicity caused by the dye, the data clearly showed an increased frequency of sperm with abnormal morphology and decreased fertility. An increased amount of DNA damage was also detected in testis cells 16.6 and 24.9 days after treatments with 100 and 500 mg/kg. This study demonstrated the toxic and genotoxic effects of DR1, indicating the harmful activity of this dye on reproductive health.FAPESP 08/10449-

Biopatologia do Helicobacter pylori

A infecção pelo Helicobacter pylori (H. pylori) induz inflamação persistente na mucosa gástrica com diferentes lesões orgânicas em humanos, tais como gastrite crônica, úlcera péptica e câncer gástrico. Os fatores determinantes desses diferentes resultados incluem a intensidade e a distribuição da inflamação induzida pelo H. pylori na mucosa gástrica. Evidências recentes demonstram que cepas do H. pylori apresentam diversidade genotípica, cujos produtos acionam o processo inflamatório por meio de mediadores e citocinas, que podem levar a diferentes graus de resposta inflamatória do hospedeiro, resultando em diferentes destinos patológicos. Cepas H. pylori com a ilha de patogenicidade cag induzem resposta inflamatória mais grave, através da ativação da transcrição de genes, aumentando o risco para desenvolvimento de úlcera péptica e câncer gástrico. O estresse oxidativo e nitrosativo induzido pela inflamação desempenha importante papel na carcinogênese gástrica como mediador da formação ou ativação de cancerígenos, danos no DNA, bem como de alterações da proliferação celular e da apoptose.Helicobacter pylori (H. pylori)-infection causes persistent inflammation with different clinical outcomes in humans, including chronic gastritis, peptic ulcer, and gastric cancer. The key determinants of these outcomes are the severity and distribution of the H. pylori-induced inflammation. Recent evidence has demonstrated that H. pylori strains possess genotypic diversity whose products trigger inflammatory process and the main mediators and cytokines, which may engender differential host inflammatory responses with distintict clinical outcomes. H. pylori strains that possess the cag pathogenecity island induce more severe inflammation via activation of gene transcription, thus enhancing the risk for peptic ulcer and distal gastric cancer. The oxidative and nitrosative stress induced by inflammation plays an important role in gastric carcinogenesis as a mediator of carcinogen formation, DNA damage, and imbalances between cell proliferation and apoptosis

Biopatologia do Helicobacter pylori

A infecção pelo Helicobacter pylori (H. pylori) induz inflamação persistente na mucosa gástrica com diferentes lesões orgânicas em humanos, tais como gastrite crônica, úlcera péptica e câncer gástrico. Os fatores determinantes desses diferentes resultados incluem a intensidade e a distribuição da inflamação induzida pelo H. pylori na mucosa gástrica. Evidências recentes demonstram que cepas do H. pylori apresentam diversidade genotípica, cujos produtos acionam o processo inflamatório por meio de mediadores e citocinas, que podem levar a diferentes graus de resposta inflamatória do hospedeiro, resultando em diferentes destinos patológicos. Cepas H. pylori com a ilha de patogenicidade cag induzem resposta inflamatória mais grave, através da ativação da transcrição de genes, aumentando o risco para desenvolvimento de úlcera péptica e câncer gástrico. O estresse oxidativo e nitrosativo induzido pela inflamação desempenha importante papel na carcinogênese gástrica como mediador da formação ou ativação de cancerígenos, danos no DNA, bem como de alterações da proliferação celular e da apoptose

Does fluoride cause DNA damage? An in vitro evaluation using rats oral mucosa cells

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