Infliximab Inhibits Colitis Associated Cancer in Model Mice by Downregulating Genes Associated with Mast Cells and Decreasing Their Accumulation.

Inflammatory bowel diseases (IBDs), such as Crohn's disease or ulcerative colitis, can be treated with anti TNF-alpha (TNF-α) antibodies (Abs), but they also put patients with IBDs at risk of cancer. We aimed to determine whether the anti TNF-α Ab induces colon cancer development in vitro and in vivo, and to identify the genes involved in colitis-associated cancer. We found that TNF-α (50 ng/mL) inhibited the proliferation, migration, and invasion of HCT8 and COLO205 colon cancer cell lines and that anti TNF-α Ab neutralized TNF-α inhibition in vitro. The effects of anti TNF-α Ab, infliximab (10 mg/kg) were investigated in mouse models of colitis-associated cancer induced by intraperitoneally injected azoxymethane (AOM: 10 mg/kg)/orally administered dextran sodium sulfate (DSS: 2.5%) (AOM/DSS) in vivo. Infliximab significantly attenuated the development of colon cancer in these mice. Microarray analyses and RT-qPCR revealed that mast cell protease 1, mast cell protease 2, and chymase 1 were up-regulated in cancer tissue of AOM/DSS mice; however, those mast cell related genes were downregulated in cancer tissue of AOM/DSS mice with infliximab. These results suggested that mast cells play a pivotal role in the development of cancer associated with colitis in AOM/DSS mice.

Loss of BAP1 expression is associated with genetic mutation and can predict outcomes in gallbladder cancer.

BACKGROUND: BRCA-1 associated protein (BAP1) is a de-ubiquitinating enzyme that regulates gene expression. Recently, the BAP1 mutation and its involvement in cancer survival have been reported in a range of tumor types, including uveal melanoma, mesothelioma, renal cancers, and biliary tract cancers. However, the frequency of BAP1 mutation and down-regulation varies among tumor types, and little is known about the function of BAP1 silencing in cancer cells. Gallbladder carcinoma (GBC) is a type of biliary tract cancer with a poor prognosis. Few mutational studies have investigated the role of BAP1 in GBC, and no functional study in vitro-, or clinical studies about cancer survival have been done. METHODS: GBC cells were studied by following the small interfering RNA mediated silencing of BAP1 with regard to proliferation, migration, invasion, and drug sensitivity. We carried out genomic, epigenomic and immunohistochemical analyses to detect somatic BAP1 alterations in 47 GBC patients undergoing surgical resection. RESULTS: BAP1 depletion resulted in increased migration and invasion, but not proliferation, and also resulted in decreased sensitivity to bortezomib, a proteasome inhibitor. Suppressed expression of BAP1 occurred in 22 GBC cases (46.8%) and showed a strong trend toward a worse median survival time of 13.3 months (95% CI, 17.6-62.6) (p = 0.0034). Sanger sequencing revealed a loss-of-function mutation of BAP1 in 11 out of these 22 GBC cases (50%) with low BAP1 expression, whereas 2 out of 25 GBC cases (8%) were detected in cases with high BAP1 expression. Partial changes in methylation were observed in 6 out of 47 cases, but methylation did not show a strong relationship to BAP1 expression or to the prognosis. CONCLUSION: Our findings showed that genetic mutations are involved in BAP1 down-regulation, leading to promotion of the invasive character of cancer cells and poor prognosis in GBC.

[General anesthesia for a 100-year-old woman with chronic heart failure].

With the expanding elderly population in Japan, general anesthesia in patients above 80 years of age has become routine and is increasing. We report on a case of general anesthesia for a 100-year-old woman with chronic heart failure. This patient could not decide on anything about her own treatment plan because of dementia, and the operation was undertaken from strong request of her family. There was no cardiopulmonary instability during the operation, but heart failure became worse postoperatively, and it took nearly a month before the patient could leave the hospital. As for the operation and general anesthesia in the elderly, it is important not only to assess their perioperative physical risks but also to consider family background and postoperative course.

[Anesthetic management of surgery for a huge renal tumor with the inferior vena cava invasion--application of Vigileo as a hemodynamic monitor].

In anesthetic management of surgery for a huge renal tumor with the inferior vena cava invasion, maintaining circulatory state is one of the key points. Several hemodynamic parameters are required to evaluate the circulatory state, such as central venous oxygen saturation (ScvO2), cardiac output (CO) and direct arterial blood pressure, in addition to routine hemodynamic parameters like heart rate and central venous pressure. Pulmonary artery catheter is considered as a standard apparatus to obtain those parameters; however, the catheter is invasive and may cause possible pulmonary artery damage, cardiac penetration, or severe arrhythmia. Therefore, application of pulmonary artery catheter is a relative contraindication in some cases. We used Vigileo system to obtain similar hemodynamic parameters. This system provided an arterial based pressure-based cardiac output, central venous oxygen saturation, stroke volume variation (SVV) and so on. In the present case, the system was an alternative device to pulmonary artery catheter system.

Thermodynamic study on competitive solubilization of cholesterol and beta-sitosterol in bile salt micelles.

Differences in the preferential solubilization of cholesterol and competitive solubilizates (beta-sitosterol and aromatic compounds) in bile salt micelles was systematically studied by changing the molar ratio of cholesterol to competitive solubilizates. The cholesterol solubility in a mixed binary system (cholesterol and beta-sitosterol) was almost half that of the cholesterol alone system, regardless of the excess beta-sitosterol quantity added. On the other hand, the mutual solubilities of cholesterol and pyrene were not inhibited by their presence in binary mixed crystals. Finally, the cholesterol solubility was measured by changing the alkyl chain length of n-alkylbenzenes. When tetradecylbenzene was added to the bile solution, the cholesterol solubility decreased slightly and was below the original cholesterol solubility. Based on Gibbs energy change (DeltaG degrees ) for solubilization, chemicals that inhibit cholesterol solubility in their combined crystal systems showed a larger negative DeltaG degrees value than cholesterol alone.