Cyclooxygenase 2 Modulates Killing of Cytotoxic T Lymphocytes by Colon Cancer Cells

Although anti-cancer effects of cyclooxygenase 2 (COX2) inhibitors have been reported, most studies focused on the direct effects of COX2 inhibiters on colon cancer cells. On the other hand, several types of cancers express Fas ligand (FasL) and/or TRAIL and mediate apoptosis of T cells in vitro. The “counter-attack” machinery may account for the mechanisms by which tumors evade host immune surveillance. In this study we determined if COX2 inhibitor could modulate effector molecules of cell death on colon cancer cells changing their effects on cytotoxic T lymphocytes. Colon adenocarcinoma cells, HCA7 and HCT116, the former COX2-positive and the latter COX2-negative, were pre-incubated with/without a COX2 inhibitor, NS398. Subsequently, the cells were co-cultured with Jurkat T cell leukemia cells and damage to Jurkat cells was determined. Treatment with NS398 resulted in reduction of expression of FasL and TRAIL in HCA7 cells, whereas NS398 did not affect the expression of FasL and TRAIL in HCT116 cells. The number of viable Jurkat cells was diminished when cells were co-cultured with naive, non-pretreated HCA7 or HCA116 cells. Preincubation of HCA7 cells with NS398 before co-culture blunted the HCA7 cell-induced cell toxicity on Jurkat cells. In contrast, pretreatment with NS398 failed to inhibit the HCT116-induced Jurkat cell killing. Our results suggest that COX2 regulates the expression of FasL and TRAIL on COX2-positive colon cancer cells thereby evoking a counter-attack against cytotoxic T cells, which may lead to compromised host immune responses

Affinity-based screening of MDM2/MDMX-p53 interaction inhibitors by chemical array: Identification of novel peptidic inhibitors.

MDM2 and MDMX are oncoproteins that negatively regulate the activity and stability of the tumor suppressor protein p53. The inhibitors of protein-protein interactions (PPIs) of MDM2-p53 and MDMX-p53 represent potential anticancer agents. In this study, a novel approach for identifying MDM2-p53 and MDMX-p53 PPI inhibitor candidates by affinity-based screening using a chemical array has been established. A number of compounds from an in-house compound library, which were immobilized onto a chemical array, were screened for interaction with fluorescence-labeled MDM2 and MDMX proteins. The subsequent fluorescent polarization assay identified several compounds that inhibited MDM2-p53 and MDMX-p53 interactions

The Relationship between H. pylori

Background and Objective. H. pylori infection causes a chronic inflammation in the gastric mucosa. However, this local inflammation may result in extra-digestive conditions. Our aim is to investigate the relationship between H. pylori infection and osteoporosis in Japan. Methods. This cross-sectional study was conducted among outpatients at the Juntendo University Hospital between 2008 and 2014. Participants for patient profile, H. pylori infection status, comorbidity, internal medical therapies, lumbar dual-energy X-ray absorptiometry (DXA), and bone turnover marker were collected and upper gastrointestinal endoscopy for reflux esophagitis, hiatal hernia, peptic ulcer disease (PUD), and endoscopic gastric mucosal atrophy (EGA) was performed. The diagnosis of osteoporosis was performed in accordance with the Japanese criteria. We investigated risk factors of osteoporosis. Results. Of the eligible 200 study subjects, 41 cases were of osteoporosis. Bivariate analysis showed that age, being female, BMI, alcohol, smoking, H. pylori, bone-specific ALP, PUD, and EGA were related to osteoporosis. Multivariate analysis showed that age (OR 1.13; 95%CI 1.07–1.20), being female (OR 4.77; 95%CI 1.78–12.77), BMI (OR 0.79; 95%CI 0.68–0.92), H. pylori (OR 5.33; 95%CI 1.73–16.42), and PUD (OR 4.98; 95%CI 1.51–16.45) were related to osteoporosis. Conclusions. H. pylori infection may be a risk factor of osteoporosis in Japan

Comprehensive Prospective Analysis of the Factors Contributing to Aspiration Pneumonia Following Endoscopic Submucosal Dissection in Patients with Early Gastric Neoplasms

Endoscopic submucosal dissection (ESD) has become the first-line treatment for early gastric neoplasms; however, a subset of patients treated by this method develop aspiration pneumonia. We conducted a comprehensive prospective analysis of the factors contributing to post-ESD aspiration pneumonia in early gastric neoplasms in this study, with special focus on whether pre-treatment oral care can prevent aspiration pneumonia. Sixty-one patients who underwent ESD for gastric neoplasms were randomly assigned to the oral care or control groups. ESD was performed under deep sedation. Of 60 patients whose data were available for analysis, 5 (8.3%) experienced pneumonia confirmed either by chest radiography or computed tomography. Although no difference in the rate of pneumonia was found between the control and oral care groups, the post-oral care bacteria count was significantly higher in the saliva of patients who developed pneumonia compared to those without pneumonia. In addition, the presence of vascular brain diseases and the dose of meperidine were also significantly associated with the occurrence of pneumonia. These results suggest that the number of oral bacteria as well as pre-existing vascular brain diseases and high-dose narcotics can affect the incidence of post-ESD pneumonia

Clinical Study A Randomized Prospective Study of Bowel Preparation for Colonoscopy with Low-Dose Sodium Phosphate Tablets versus Polyethylene Glycol Electrolyte Solution

Optimal bowel preparation is essential for the safety and outcome of colonoscopy. A solution containing polyethylene glycol (PEG) is often used as a bowel cleansing agent, but some patients are intolerant of PEG, and this may lead to discontinuation of colonoscopy. Sodium phosphates (NaP) tablets are designed to improve patient acceptance and compliance. The objective of this study was to compare bowel preparation efficiency and patient acceptance of a 30 NaP tablet preparation (L-NaP) and a 2 L PEG preparation. Patients were randomized into either the L-NaP or PEG group. The primary endpoint was the efficiency of colon cleansing as assessed by a validated four-point scale according to the Aronchick scale by endoscopists and was verified by blinded investigators. The secondary endpoints were patients' tolerability and acceptance. Colon-cleansing efficiency was not significantly different between the two preparations. However, patients' overall judgment was significantly in favor of L-NaP, reflecting better acceptance of L-NaP than PEG. Additionally, more patients favored L-NaP over PEG in a hypothetical future occasion requiring colonoscopy

Successful remission of ulcerative colitis flare-up during pregnancy with adsorptive granulomonocytapheresis plus tacrolimus

Ulcerative colitis (UC) is 1 of the 2 major phenotypes of chronic inflammatory bowel disease (IBD), which afflicts millions of individuals throughout the world with debilitating symptoms that impair function and quality of life. Further, IBD often affects women during childbearing age. Indeed, UC activity frequently increases during pregnancy, and the medications used to induce remission may adversely affect the health of the mother and the unborn child. We report successful induction of a remission in a UC case who experienced a flare-up in the first trimester of pregnancy. Upon relapse, she was treated with steroids and adsorptive granulomonocytapheresis (GMA) with the Adacolumn plus tacrolimus. This combination therapy induced a stable remission that was maintained during her entire pregnancy. She gave birth to a healthy child at 36 weeks of pregnancy with no maternal or fetal complications. Our experience indicates that GMA, as a non-drug therapeutic intervention with a favorable safety profile, plus tacrolimus might be a relevant treatment option for patients with active IBD during pregnancy. A future study of a large cohort of pregnant patients should strengthen our findings