RESUMO
The Japanese guidelines for the treatment of gastric cancer recommend nivolumab as third-line chemotherapy for metastatic gastric cancer. We report a case of gastric cancer exhibiting a durable response after the discontinuation of nivolumab due to the early onset of immune-related adverse event (irAE). A 64-year-old man with advanced HER2-positive gastric cancer and distant lymph node metastasis received nivolumab as fourth-line therapy. After two courses of nivolumab, the lymph nodes showed progression. However, the treatment was discontinued because of interstitial pneumonia as an irAE. Disease regression was sustained for approximately 11 months without the readministration of nivolumab.
Assuntos
Doenças Pulmonares Intersticiais , Neoplasias Gástricas , Humanos , Doenças Pulmonares Intersticiais/induzido quimicamente , Linfonodos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Neoplasias Gástricas/tratamento farmacológicoRESUMO
Phthalates are a group of endocrine disrupting chemicals and may have contributed to the recent global obesity health crisis. Increased adipogenesis via the peroxisome proliferator-activated receptor γ (PPARγ)-CCAAT-enhancer binding protein α (C/EBPα) pathway could be one critical mechanism responsible for phthalate-induced weight gain. On the other hand, curcumin has been shown to inhibit adipogenesis in cells and animal models. The present study was undertaken to evaluate, for the first time, whether curcumin could reduce adipogenesis induced by benzyl butyl phthalate (BBP) via downregulation of the PPARγ-C/EBPα pathway. 3T3-L1 preadipocytes were differentiated by treating them with insulin, dexamethasone, and 3-isobutyl-1-methylxanthine in the presence of BBP, with or without curcumin. Cells that were grown in the presence of BBP alone showed a significant increase in triacylglycerol (TG) levels. In addition, the number of Oil Red O-stained cells and the mRNA expression levels of PPARγ, C/EBPα, adiponectin, and tumor necrosis factor-α (TNFα) were significantly increased. However, treatment with BBP in combination with curcumin resulted in major reductions in TG levels, the numbers of Oil Red O-stained cells, and the mRNA expression levels of the four proteins. These results suggest that curcumin might be an inhibitor of BBP-induced weight gain and inflammation via stimulation of adipocyte differentiation and TNFα generation. Curcumin may, therefore, be a potential medication for preventing the harmful effects of phthalates.
Assuntos
Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Fármacos Antiobesidade/farmacologia , Curcumina/farmacologia , Disruptores Endócrinos/toxicidade , Ácidos Ftálicos/toxicidade , Células 3T3-L1 , Adipócitos/metabolismo , Adipócitos/patologia , Adiponectina/genética , Adiponectina/metabolismo , Animais , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Citoproteção , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos , PPAR gama/efeitos dos fármacos , PPAR gama/genética , PPAR gama/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Triglicerídeos/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Cell culture models that mimic tissue environments are useful for cell and extracellular matrix (ECM) function analysis. Decellularized tissues with tissue-specific ECM are expected to be applied as cell culture scaffolds, however, it is often difficult for seeded cells to permeate their structures. In this study, we evaluated the adhesion and proliferation of mouse fibroblasts seeded onto decellularized bone marrow scaffolds that we fabricated from adult and fetal porcine. Decellularized fetal bone marrow displays more cell attachment and faster cell proliferation than decellularized adult bone marrow. Our findings suggest that decellularized fetal bone marrow is useful as a cell culture scaffold with bone marrow ECM and structure.
Assuntos
Adesão Celular , Técnicas de Cultura de Células , Proliferação de Células , Matriz Extracelular , Fibroblastos , Alicerces Teciduais , Animais , Alicerces Teciduais/química , Camundongos , Matriz Extracelular/química , Matriz Extracelular/metabolismo , Suínos , Fibroblastos/citologia , Técnicas de Cultura de Células/métodos , Engenharia Tecidual/métodos , Medula Óssea/metabolismo , Células da Medula Óssea/citologia , Matriz Extracelular Descelularizada/químicaRESUMO
Metastatic colorectal neuroendocrine carcinoma (NEC) is often treated using a chemotherapy protocol for small-cell lung cancer; however, the prognosis is extremely poor. A 55-year-old woman with BRAF V600E-mutated transverse colon NEC and liver metastases underwent colectomy followed by FOLFOXIRI plus bevacizumab. Consequently, the liver metastases markedly shrank. Owing to later worsening of the liver metastases, she received encorafenib and binimetinib plus cetuximab. Despite discontinuing binimetinib due to myalgia, she had a long-term response with a progression-free survival of 14 months and an overall survival of more than 27 months. A chemotherapy protocol for BRAF-mutated metastatic colorectal cancer may be a treatment option for BRAF V600E-mutated colorectal NEC.