ABSTRACT
BACKGROUND/AIMS: In both SHARP and Asia-Pacific Study, sorafenib was proved to improve the overall survival of the patients with hepatocellular carcinoma. However, factors contributing to the improvement of overall survival of the patients treated by sorafenib have not been fully evaluated. In this study, patient-derived, background liver disease-derived and tumor-derived factors before treatment were evaluated whether they have contributed to the improvement of the overall survival. METHODOLOGY: Forty-seven cases with HCC treated by sorafenib between Sept 2009 and Feb 2011 were included in this analysis. The survival of these cases was analyzed by Kaplan-Meier Method. Factors used for univariate analysis were two patient-derived parameters, two background liver disease-derived, five tumor-derived. Factors related to the over-all survival were analyzed by multivariate analysis using Cox regression model. RESULTS: In the multivariate analysis, only background liver disease-derived parameter Child-Pugh class A vs. B, (p=0.007, HR=0.21 (0.07-0.65)) was significant. No other parameters including tumor-derived factors were statistically significant by multivariate analysis. CONCLUSIONS: We undertook the statistical analysis on the three categories. Surprisingly, no tumor derived parameter contributed to the overall survival. Background liver disease-derived parameter rather than tumor-derived parameter was found to define the prognosis of patients with advanced HCC treated by sorafenib.
Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Niacinamide/analogs & derivatives , Phenylurea Compounds/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Female , Humans , Japan , Kaplan-Meier Estimate , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Multivariate Analysis , Niacinamide/therapeutic use , Proportional Hazards Models , Retrospective Studies , Sorafenib , Time Factors , Treatment OutcomeABSTRACT
A 67-year-old man visited our hospital with a history of continuous hematochezia leading to hemorrhagic shock. An abdominal computed tomography scan revealed a large mass in the ascending colon invading the duodenum and pancreatic head as well as extravasation of blood from the gastroduodenal artery (GDA) into the colon. Colonoscopy revealed an irregular ulcerative lesion and stenosis in the ascending colon. Therefore, right hemicolectomy combined with pylorus-preserving pancreaticoduodenectomy was performed. Histologically, the tumor was classified as a moderately differentiated adenocarcinoma. Moreover, cancer cells were mainly located in the colon but had also invaded the duodenum and pancreas and involved the GDA. Immunohistochemically, the tumor cells were positive for cytokeratin (CK)20 and carcinoembryonic antigen (CEA) but not for CK7 and carbohydrate antigen (CA)19-9. The patient died 23 d after the surgery because he had another episode of arterial bleeding from the anastomosis site. Although En bloc resection of the tumor with pancreaticoduodenectomy and colectomy performed for locally advanced colon cancer can ensure long-term survival, patients undergoing these procedures should be carefully monitored, particularly when the tumor involves the main artery.
Subject(s)
Adenocarcinoma/genetics , Barrett Esophagus/genetics , Barrett Esophagus/surgery , Epigenesis, Genetic , Esophageal Neoplasms/genetics , Esophageal Neoplasms/surgery , Esophagoscopy , Neoplasms, Second Primary/genetics , Neoplasms, Second Primary/surgery , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Adenomatous Polyposis Coli Protein/genetics , Antibodies/analysis , Barrett Esophagus/pathology , DNA Methylation/genetics , Electrocoagulation , Esophageal Neoplasms/pathology , Esophagus/pathology , Esophagus/surgery , Genetic Loci/genetics , Humans , Lymphatic Metastasis/pathology , Male , Microsatellite Instability , Middle Aged , Neoplasm Invasiveness , Neoplasms, Second Primary/pathology , Phenotype , Promoter Regions, Genetic/geneticsABSTRACT
The present study identified several 4-alkynyl and 4-alkenylquinazolines that serve as novel and potent EGFR tyrosine kinase inhibitors. The IC(50) values of these compounds are in the nanomolar range. In addition, the 4-(4-phenylbut-1-yn/en-yl)quinazolines provided scaffolds for potent enzyme inhibition. Chiral discrimination was observed to occur in one of the 4-alkynylquinazoline derivatives with the (R)-isomer being more than 150 times as potent as the (S)-isomer.
Subject(s)
ErbB Receptors/antagonists & inhibitors , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/pharmacology , Quinazolines/chemical synthesis , Quinazolines/pharmacology , Chromatography, High Pressure Liquid , Crystallography, X-Ray , Models, Molecular , Protein Kinase Inhibitors/chemistry , Quinazolines/chemistryABSTRACT
The 12 wt% Pt-deposited carbon nanotube electrode gives 10% higher voltages than 29 wt% Pt-deposited carbon black and reduces the Pt usage by 60% in polymer electrolyte fuel cells with hydrogen and oxygen.
