RESUMO
A 68-year-old man underwent total gastrectomy for Type 3 gastric cancer with liver metastasis. The final finding was T3(SE), N1, H1, P0, CY0(class IV), Stage IV, Cur C. After surgery, he was treated with combination chemotherapy of weekly paclitaxel(PTX)/doxifluridine(5'-DFUR). Paclitaxel was administered at a dose of 80 mg/m(2) on day 1, 8 and 15, and doxifluridine was orally administered at a dose of 533 mg/m(2) day for five days followed by withdrawal for two days. This regimen was repeated every four weeks. After 2 courses, the tumor marker level normalized, and the size of the liver metastasis was remarkably decreased. After 5 courses, a CT scan revealed the liver metastasis had disappeared, and he has now survived without recurrence after the disappearance of the liver metastasis. No severe adverse reactions were observed, and the man can be treated as an outpatient. This therapy may thus be effective in the treatment of advanced gastric cancer following non-curative operation.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Floxuridina/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Paclitaxel/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais/sangue , Floxuridina/efeitos adversos , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Estadiamento de Neoplasias , Paclitaxel/efeitos adversos , Indução de Remissão , Neoplasias Gástricas/sangue , Neoplasias Gástricas/cirurgia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND: Aberrant activation of Wnt signaling caused by mutations in the tumor suppressor adenomatous polyposis coli or beta-catenin is a critical event in the development of human colorectal tumors. We have recently identified the ICAT gene, which encodes a small protein that interacts with beta-catenin and represses Wnt signaling. METHODS: We examined the prevalence of mutations in the entire ICAT coding sequence and intronic splice donor and acceptor regions of ICAT by PCR-SSCP and also the expression of the ICAT gene by RT-PCR. RESULTS: The ICAT gene was mapped to chromosome 1p36.1-p36.2, which is implicated in the pathogenesis of various types of cancers. However, no mutations in ICAT were detected among 128 colorectal tumors. Instead, ICAT was found to be overexpressed in almost half of colorectal carcinomas. Cases exhibiting ICAT overexpression showed a significantly higher incidence of well-differentiated adenocarcinoma and positive lymphatic permeation. CONCLUSION: Our results suggest that ICAT is not the putative tumor suppressor on 1p36.1-p36.2, although aberrant overexpression of ICAT may play a role in the pathogenesis of colorectal carcinomas.
Assuntos
Proteínas de Ciclo Celular , Neoplasias do Colo/genética , Proteínas do Citoesqueleto/biossíntese , Proteínas do Citoesqueleto/genética , Proteínas Musculares/genética , Mutação , Neoplasias Retais/genética , Proteínas Repressoras , Transativadores/biossíntese , Proteínas Adaptadoras de Transdução de Sinal , Polipose Adenomatosa do Colo/genética , Idoso , Neoplasias do Colo/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Genes APC , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Pessoa de Meia-Idade , Proteínas Musculares/biossíntese , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Neoplasias Retais/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , beta CateninaRESUMO
MBD4/MED1 is a newly identified mismatch repair gene, which is mutated in colon, endometrial, and pancreatic high-frequency microsatellite instability (MSI-H) tumors. To assess its role in gastric cancers, we investigated MBD4/MED1 mutations in sporadic gastric cancers, compared with colon cancers. Frameshift mutations were found in 29% of gastric and 20% of colon MSI-H cancers, but not in any low-frequency microsatellite instability/microsatellite stable cancers. MBD4/MED1 is mutated in gastric cancers as frequently as in colon cancers; these mutations reduce the accuracy of DNA repair, and may lead to cancer progression.
Assuntos
Endodesoxirribonucleases/genética , Idoso , Pareamento Incorreto de Bases , Neoplasias do Colo/genética , Análise Mutacional de DNA , Feminino , Mutação da Fase de Leitura , Humanos , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Neoplasias GástricasRESUMO
Aberrant activation of Wnt signaling caused by mutations in adenomatous polyposis coli (APC) or beta-catenin is a critical event in the development of human colorectal tumors. Wnt signaling stabilizes beta-catenin, which in turn associates with TCF/LEF family transcription factors, ultimately altering the expression of Wnt target genes. We have recently identified ICAT, a beta-catenin-interacting protein that interferes with the interaction between beta-catenin and TCF-4, thereby negatively regulating Wnt signaling. In the present study, we generated a recombinant adenovirus encoding ICAT and examined its effect on the growth of tumor cells. We found that Icat inhibits proliferation of colorectal tumor cells mutated in APC or beta-catenin and hepatocellular carcinoma cells mutated in AXIN: By contrast, Icat did not inhibit growth of either normal or tumor cells containing the wild-type APC, beta-catenin, and Axin genes. Icat also inhibited the anchorage-independent growth of colorectal tumor cells and tumorigenic growth of colorectal tumor xenografts. Furthermore, we found that Icat inhibits both dephosphorylation of Cdc2 and nuclear translocation of cyclin B1 and induces G(2) arrest followed by cell death in colorectal tumor cells. These results suggest that Wnt signaling is critical for the growth of colorectal tumors and some hepatocellular carcinomas and that expression of ICAT or drugs which mimic its effects may be useful in the treatment of these tumors.
