Aqueous Stability of Metal-Organic Frameworks Using ReaxFF-Based Metadynamics Simulations.

Aqueous stability is a critical property for the application of metal-organic framework (MOF) materials in humid conditions. The sampling of the free energy surface for a water reaction is challenging due to a lack of a reactive force field. Here, we developed a ReaxFF force field for simulating the reaction of zeolitic imidazole frameworks (ZIFs) with water. We carried out metadynamics simulations based on ReaxFF to study the reaction of water with a few different types of MOFs. We also conducted an experimental water immersion test and characterized the XRD, TG, and gas adsorption properties of the MOFs before and after the immersion test. By considering the energy barrier for a hydrolysis reaction, the simulation results are in good agreement with the experiments. MOFs with open structures and large pores are found to be unstable in metadynamics simulations, where the water molecule can attack or bond with the metallic node relatively easily. In contrast, it is more difficult for water to attack the Zn atom in the ZnN4 tetrahedral structure of ZIFs. We also found that ZIFs with the -NO2 functional groups have higher water stability. Discrepancies between the metadynamics simulation and gas adsorption experiments have been accounted for from the phase/crystallinity change of the structure reflected in the X-ray diffraction and thermogravimetry analysis of the MOF samples.

[A successfully resected case of liver metastasis of gastrointestinal stromal tumor responding to neoadjuvant chemotherapy with imatinib mesylate and interventional radiology].

A 75-year-old woman underwent resection of gastrointestinal stromal tumor (GIST) of small intestine in 1999. In January 2006, she suffered liver dysfunction and abdominal CT revealed she had a large liver metastasis. At first the tumor in the right lobe progressed to the medial segment and seemed unresectable. She twice underwent transarterial embolization and treatment with 400mg/day of imatinib mesylate. Then percutaneous transhepatic portal embolization was performed. As a result, liver metastasis markedly decreased in size, and extended right lobectomy of the liver was performed in June 2006. A large portion of the liver metastasis showed necrosis, but histopathological examination revealed focal remnants of viable tumor cells. In March 2007, radiofrequency ablation was performed for recurrence of remnant liver. The patient has been treated by imatinib mesylate and is alive with no evidence of tumor recurrence.

Caspase-3 expression in human gastric carcinoma and its clinical significance.

OBJECTIVES: Caspase-3 is one of the most important molecules in the apoptosis cascade, and the relationship between caspase-3 expression and prognosis has been reported in many types of malignancies. However, the involvement of caspase-3 in human gastric carcinoma is not fully understood. We evaluated caspase-3 expression in human gastric carcinoma to clarify the clinicopathological importance and investigated the apoptosis avoidance mechanism by an immunohistological method. METHODS: Specimens from 151 patients who underwent gastrectomy at the Department of Surgery and Surgical Basic Science of Kyoto University Hospital were investigated. Caspase-3 expression in cancer cells was evaluated by comparing its expression in the germinal center of the lymphoid follicle, and was quantified as the caspase-3 expression index (C3EI). C3EI was compared with the expression of Bcl-2 and the TdT-mediated dUTP biotin nick-end labeling (TUNEL) in 80 randomly selected cases. Actual activation of caspase-3 was determined by immunohistochemistry using monoclonal antibody that recognizes only activated caspase-3. RESULTS: C3EI correlated significantly with lymph node metastasis (negative 105.5-78.7, positive 153.8 +/- 66.1 p = 0.001) and the lower C3EI group had a better prognosis than the higher group (log-rank test, p = 0.0001). Cox multivariate analysis showed that age, operation curability, tumor invasion and C3EI were significant independent determinants of overall survival. Bcl-2 and TUNEL staining had no significant correlations with C3EI. Immunohistochemistry of activated caspase-3 revealed that most caspase-3 in gastric cancer cells was not activated, in accordance with TUNEL assay. CONCLUSIONS: Our results show that C3EI is a novel, independent prognostic factor in gastric cancer patients and cancer cells may avoid apoptosis by inhibiting caspase-3 activation.