No Relationship between the Amount of DNA Damage and the Level of hMLH1 and RASSF1A Gene Expression in Bladder Cancer Cells Treated with Cisplatin and Gemcitabine

Tumor response to antineoplastic drugs is not always predictable. This is also true for bladder carcinoma, a highly recurrent neoplasia. Currently, the combination of cisplatin and gemcitabine is well accepted as a standard protocol for treating bladder carcinoma. However, in some cases, this treatment protocol causes harmful side effects. Therefore, we investigated the roles of the genes TP53, RASSF1A (a tumor suppressor gene) and hMLH1 (a gene involved in the mismatch repair pathway) in cell susceptibility to cisplatin/gemcitabine treatment. Two bladder transitional carcinoma cell (TCC) lines, RT4 (wild-type TP53) and 5637 (mutated TP53), were used in this study. First, we evaluated whether the genotoxic potential of cisplatin/gemcitabine was dependent on TP53 status. Then, we evaluated whether the two antineoplastic drugs modulated RASSF1A and hMLH1 expression in the two cell lines. Increased DNA damage was observed in both cell lines after treatment with cisplatin or gemcitabine and with the two drugs simultaneously, as depicted by the comet assay. A lack of RASSF1A expression and hypermethylation of its promoter were observed before and after treatment in both cell lines. On the other hand, hMLH1 downregulation, unrelated to methylation status, was observed in RT4 cells after treatment with cisplatin or with cisplatin and gemcitabine simultaneously (wild-type TP53); in 5637 cells, hMLH1 was upregulated only after treatment with gemcitabine. In conclusion, the three treatment protocols were genotoxic, independent of TP53 status. However, cisplatin was the most effective, causing the highest level of DNA damage in both wild-type and mutated TP53 cells. Gemcitabine was the least genotoxic agent in both cell lines. Furthermore, no relationship was observed between the amount of DNA damage and the level of hMLH1 and RASSF1A expression. Therefore, other alternative pathways might be involved in cisplatin and gemcitabine genotoxicity in these two bladder cancer cell lines.

DNA methylation patterns of steroid receptor genes ESR1, ESR2 and PGR in deep endometriosis compromising the rectum

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Indole-3-carbinol attenuates the deleterious gestational effects of bisphenol A exposure on the prostate gland of male F1 rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Progesterone as a morphological regulatory factor of the male and female gerbil prostate

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Segundo tumor em pacientes com neoplasias de cabeça e pescoço

Pós-graduação em Pesquisa e Desenvolvimento (Biotecnologia Médica) - FMB

Avaliação dos fatores preditivos dos pólipos endometriais em mulheres na pós-menopausa

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB

Perfil lipídico sérico e ede ácidos graxos do tecido adiposo em cadelas com tumores mamários: caso-controle

Pós-graduação em Biotecnologia Animal - FMVZ

Avaliação de biomarcadores moleculares em mulheres com câncer de ovário

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB

Estudo da viabilidade do tratamento de pacientes portadores de carcinoma epidermóide de lábio(T1nomo) por meio da radiação laser de dióxido de carbono (CO2)

Pós-graduação em Odontologia - ICT

Diagnóstico, tratamento e seguimento do carcinoma medular de tireoide: recomendações do Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

MORFOLOGIA E MORFOMETRIA DAS DILATAÇÕES GLANDULARES NO ENDOMÉTRIO DA ÉGUA

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Transporte placentário via cavéola na placenta de bovinos clonados e transgênicos

Pós-graduação em Ciência e Tecnologia Animal - FEIS

Análise histopatológica de biópsia prostática guiada pelo ultrassom transretal com 10 e 12 fragmentos: ensaio clínico prospectivo controlado

Pós-graduação em Bases Gerais da Cirurgia - FMB

Incidence of subclinical endometritis and its effects on reproductive performance of crossbred dairy cows

In dairy cattle, uterine infections are not life threatening and often unavoidable; however, they reduce fertility and increase the production costs of properties. The aim of this study was to evaluate the incidence of subclinical endometritis from 32 to 70 days in milk (DIM) and its effects on the reproductive performance of crossbred dairy cows. Lactating cows (Holstein/Gir; n = 172), with no history of retained placenta, without clinical signs of uterine infection were used. The body condition score (BCS) was evaluated on a scale from 1 to 5. Ultrasound examination was performed to evaluate uterine lining and ovarian activity, while vaginal mucus was analyzed by gloved hand. The diagnosis of subclinical endometritis was performed by endometrial cytobrush technique. The samples were collected, stained, and examined microscopically; positive cases for subclinical endometritis were considered with the presence of a parts per thousand yen5 % of neutrophils. Later, the cows were submitted to conventional artificial insemination or timed artificial insemination. The incidence of subclinical endometritis in the herd was 26 %, and this was not affected by the season of calving, presence of corpus luteum, DIM, and parity. Cows with a BCS a parts per thousand currency sign2.50 had a higher incidence of subclinical endometritis. The conception rate to first insemination and pregnancy rate at 150 days postpartum were not influenced by the presence of subclinical endometritis in crossbred dairy cows.

Dose and temporal effects on gene expression profiles of urothelial cells from rats exposed to diuron

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)