MHY218-induced apoptotic cell death is enhanced by the inhibition of autophagy in AGS human gastric cancer cells.

We previously reported the anticancer effects of MHY218, which is a hydroxamic acid derivative, in HCT116 human colon cancer cells. In the present study, the involvement of autophagy in the MHY218-induced apoptotic cell death of AGS human gastric cancer cells was investigated. MHY218 treatment induced growth inhibition and apoptotic cell death in a concentration- and time-dependent manner. The induction of apoptosis was confirmed by observations of decreased viability, DNA fragmentation, and an increase in late apoptosis and sub-G1 DNA, which were detected with a flow cytometric analysis. Western blot analyses showed that MHY218 treatment resulted in decreased protein levels of procaspase-8, -9, and -3; cleavage of poly(ADP-ribose) polymerase (PARP); and alterations in the ratio of Bax/Bcl-2 protein expression. Apoptosis induced by MHY218 was involved in the activation of caspase-8, -9, and -3, and it was blocked by the addition of Z-VAD­FMK, a pan-caspase inhibitor. In addition, autophagy-inducing effects of MHY218 were indicated by cytoplasmic vacuolation, the accumulation of acidic vesicular organelles, the appearance of green fluorescent protein-light-chain 3 (LC3) punctate dots, and increased levels of Beclin-1 and LC3-II protein expression. Pretreatment with the autophagy inhibitors LY294002, 3-methyladenine, chloroquine, and bafilomycin A1 enhanced the induction of apoptosis by MHY218, and this was accompanied by an increase in PARP cleavage. Taken together, these results provide new insights into the role of MHY218 as a potential antitumor agent. The combination of MHY218 with an autophagy inhibitor might be a useful candidate for the chemoprevention and/or treatment of gastric cancer.

Prognostic factors for metastatic colorectal cancer after first-line chemotherapy with FOLFOX-4 or FOLFIRI regimen.

BACKGROUND/AIMS: Information on prognostic factors for metastatic colorectal cancer is an important basis for planning the treatment and predicting the outcomes of the patients; however, it has not been well established. The aim of this study was to identify factors that predict results of chemotherapy and to establish a plan for treatment of patients whose tumors are inoperable due to metastatic colorectal cancer. METHODS: We conducted a retrospective review of records from 75 patients treated for colorectal cancer in Kosin University Gospel Hospital, from October 2004 to September 2008. Patients with inoperable tumors due to metastasis at the time of diagnosis who were treated with oxaliplatin or irinotecan as the first-line treatment were included in this study. We investigated the factors that might have an effect on overall survival. RESULTS: A total of 75 patients were included in this study. Results of univariate analysis showed that hemoglobin (Hb) ≥10 g/dL at the time of diagnosis, no increase in CEA on the follow-up examination after chemotherapy, chemotherapy plus surgery, and better response to chemotherapy were significant prognostic factors. Results of multivariate analysis showed that Hb ≥10 g/dL at the time of diagnosis (p<0.001), surgery after chemotherapy (p=0.001), and better response to chemotherapy (p=0.014) were significant prognostic factors. CONCLUSIONS: In this study, Hb ≥10 g/dL at the time of diagnosis, surgery after chemotherapy, and better response to chemotherapy were significant prognostic factors for metastatic colorectal cancer.

[A case of idiopathic pancreatitis in a patient with Crohn's disease].

Pancreatitis has been occasionally associated with Crohn's disease (CD). A definite etiology of pancreatitis can be identified in most patients, but a very small proportion remain idiopathic. We report a case of idiopathic pancreatitis resolved along with the clinical improvement of CD in a 25-year-old man. He presented with abdominal pain and diarrhea for 8 years. Ileocolonoscopy and enteroclysis showed multiple, longitudinal ulcers and strictures at the ileojejunum. The laboratory findings showed elevated serum amylase (951 IU/L) and lipase (326 IU/L) without positive autoantibodies. Esophagogastroduodenoscopy, enhanced pancreatic CT, and MRCP showed no abnormalities at ampulla of Vater, pancrease, and pancreaticobiliary duct. With the treatment with antibiotics, 5-aminosalicylic acid, steroid, and azathioprine, as a whole, decreasing pattern and intermittent fine coordinated fluctuation of the levels of amylase and lipase along with the decrease of Crohn's disease activity index (CDAI) and the CRP levels were observed. Then, three months after the start of the treatment, normalization of the pancreatic enzymes was observed, and there was recurrent elevation of pancreatic engyme during 12 months maintenance therapy. This report supports the concept of an association between idiopathic pancreatitis and CD, based on a significant and close relation between the levels of serum amylase and lipase, and CDAI.