RESUMO
Objetivos: Nos últimos anos foram desenvolvidos diversos trabalhos visando entender o comportamento biológico e definir a melhor forma de abordagem para os Tumores de Estroma Gastrointestinal. Nessa revisão, são organizadas informações atualizadas sobre o assunto. Métodos: Foi realizado levantamento bibliográfico, sem restrição de período, nas bases de dados PubMed e LILACS. Foi utilizada a palavra- -chave "Tumores de Estroma Gastrointestinal", que deveria aparecer no título dos artigos. Foram encontrados 1619 artigos e, depois da leitura dos resumos, foram selecionados 20 artigos publicados entre 1998 e 2018. Resultados: Foram levantados dados relevantes e atualizados sobre a epidemiologia, histopatologia, apresentação clínica, diagnóstico, prognóstico e tratamento dos Tumores de Estroma Gastrointestinal. Conclusões: Apesar de ser considerada uma neoplasia rara, é um assunto que deve ser estudado e discutido pela definição recente do diagnóstico e da abordagem terapêutica.
Objectives: In recent years, several studies have been developed to understand the biological behavior and to define the best therapeutic approach for Gastrointestinal Stromal Tumor. In this review, we have organized up-to-date information on the subject. Methods: A bibliographic survey was carried out, without period restriction, in PubMed and LILACS databases. The key word "Gastrointestinal Stromal Tumors" was used, which should appear in the title of the articles. A total of 1619 articles were found and, after reading the abstracts, 20 papers published between 1998 and 2018 were selected. Results: We collected relevant and updated data on the epidemiology, histopathology, clinical presentation, diagnosis, prognosis and treatment of Gastrointestinal Stromal Tumors. Conclusions: Despite being considered a rare neoplasm, it is a subject that must be studied and discussed because of the recent definition of diagnosis and the therapeutic approach.
Assuntos
Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/terapia , Neoplasias GastrointestinaisRESUMO
Molecular evidence indicates that alterations in genes involved in the maintenance of genome stability may be related to susceptibility to bladder carcinoma. Our goal was to evaluate the prognostic role of base excision repair (BER) genes in a cohort of patients diagnosed with primary urothelial carcinoma of the bladder (UCB). The levels of all APE1, XRCC1 and POLB transcripts were detected by quantitative real-time PCR (qPCR) technique in tumor samples from 52 patients undergoing transurethral resection (TUR) for primary UCB at the Department of Urology, Brazilian National Cancer Institute, Rio de Janeiro. Increased levels of APE1, XRCC1 and POLB transcripts were significantly associated with high-grade tumors when compared to these levels in low-grade tumors (p<0.01) and could be attributed to different mechanisms of transcriptional regulation as a response to tumorigenesis and oxidative stress. By analyzing the collected data in the present study, regardless of pathological grade or stage, univariate analysis revealed that the reduced levels of APE1 transcripts were significantly associated with cancer-specific mortality (p=0.032). Furthermore, the variant genotype (TG/GG) of the APE1 T1349G polymorphism was observed in 75% of a subset of patients who concomitantly experienced reduced levels of the APE1 transcript and death and/or recurrence events. Taken together, our data reinforce the idea that human DNA repair mechanisms must be finely regulated in order to avoid instability leading to tumorigenesis and poor clinical outcomes in UCB patients.
Assuntos
DNA Polimerase beta/genética , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/genética , Proteínas de Ligação a DNA/genética , Recidiva Local de Neoplasia/genética , Neoplasias da Bexiga Urinária/genética , Idoso , Idoso de 80 Anos ou mais , Brasil , DNA Polimerase beta/biossíntese , Reparo do DNA/genética , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/biossíntese , Proteínas de Ligação a DNA/biossíntese , Feminino , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Polimorfismo de Nucleotídeo Único , Prognóstico , Análise de Sobrevida , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
Cisplatin is currently used in tumor chemotherapy to induce the death of malignant cells through blockage of DNA replication. It is a commonly used chemotherapeutic agent binding mono- or bifunctionally to guanines in DNA. Escherichia coli K12 mutant strains deficient in nucleotide excision repair (NER) were submitted to increasing concentrations of cisplatin, and the results revealed that uvrA and uvrB mutants are sensitive to this agent, while uvrC and cho mutants remain as the wild type strain. The time required for both gene expression turn-off and return to normal weight DNA in wild-type E. coli was not accomplished even after 4 h post-treatment with cisplatin, while the same process takes place within 1.5 h after ultraviolet radiation (UV). Besides, a heavily damaging action of cisplatin can be seen not only by persistent nicks on genomic DNA, but also by NER gene expression exceeding manifold that seen after equivalent lethal doses of UV. Moreover, cisplatin caused an increase in uvrB gene expression from its putative upstream promoter P3 in an SOS-independent manner.
Assuntos
Antineoplásicos/toxicidade , Cisplatino/toxicidade , Quebras de DNA de Cadeia Simples , Escherichia coli/genética , Resposta SOS em Genética/genética , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , DNA Helicases/genética , DNA Helicases/metabolismo , DNA Bacteriano/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Endodesoxirribonucleases/genética , Endodesoxirribonucleases/metabolismo , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Regulação Bacteriana da Expressão Gênica , Mutação , Regiões Promotoras Genéticas , Transcrição Gênica , Raios Ultravioleta , Regulação para CimaRESUMO
The evaluation of the treatment for chronic Chagas disease faces the absence of any clear-cut criterion of cure. The low degree of parasitemia and the persistence of positive immunologic reactions represent some of the difficulties involved in addressing therapeutic efficacy. Our aim was to define whether PCR could be used as a laboratory method for evaluating cure in Chagas disease after specific treatment. We tested the utility of PCR amplification of the variable regions of minicircles from Trypanosoma cruzi kinetoplast DNA, in 76 xenopositive chronic Brazilian patients who been treated with benznidazole in Mambai (Goias State) and São Felipe (Bahia State). We observed a positive amplification result in only 25 out 76 treated patients (33 per cent). Therefore, the performance of one single PCR after therapy revealed parasite clearance in 67 per cent of the treated individuals, while xenodiagnosis was negative in 84 per cent. These observations suggest that PCR is the most sensitive technique available for directed detection of T. cruzi in chagasic patients and that it can be a very useful instrument for the follow-up of patients after specific chemotherapy. In this sense, we are now developing a quatitative approach based on the use of fluorogenic probes and reat-time measurements of the amplification reaction (TacMan Technology) in order to precisely estimate the parasite load in chronic chagasic patients before and after treatment. This may be the basis for the futuer establishment of reliable criteria of cure for patients undergoing therapy.
Assuntos
Humanos , Doença de Chagas/tratamento farmacológico , Nitroimidazóis/uso terapêutico , Reação em Cadeia da Polimerase , Tripanossomicidas/uso terapêutico , Doença de Chagas/imunologia , Doença Crônica , DNA de Protozoário/análise , Estudo de Avaliação , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
The evaluation of the treatment for chronic Chagas disease faces the absence of any clear-cut criterion of cure. The low degree of parasitemia and the persistence of positive immunologic reactions represent some of the difficulties involved in addressing therapeutic efficacy. Our aim was to define whether PCR could be used as a laboratory method for evaluating cure in Chagas disease after specific treatment. We tested the utility of PCR amplification of the variable regions of minicircles from Trypanosoma cruzi kinetoplast DNA, in 76 xenopositive chronic Brazilian patients who been treated with benznidazole in Mambai (Goias State) and Sõo Felipe (Bahia State). We observed a positive amplification result in only 25 out 76 treated patients (33 per cent). Therefore, the performance of one single PCR after therapy revealed parasite clearance in 67 per cent of the treated individuals, while xenodiagnosis was negative in 84 per cent. These observations suggest that PCR is the most sensitive technique available for directed detection of T. cruzi in chagasic patients and that it can be a very useful instrument for the follow-up of patients after specific chemotherapy. In this sense, we are now developing a quatitative approach based on the use of fluorogenic probes and reat-time measurements of the amplification reaction (TacMan Technology) in order to precisely estimate the parasite load in chronic chagasic patients before and after treatment. This may be the basis for the futuer establishment of reliable criteria of cure for patients undergoing therapy. (AU)
