Ursodeoxycholic Acid Decreases Incidence of Primary Biliary Cholangitis and Biliary Complications After Liver Transplantation.

Content available: Audio Recording.

Using A Customized SMS Program to Promote Colonoscopy Adherence and Support Bowel Cleanliness for Spanish-speaking Patients.

INTRODUCTION: Low colorectal cancer (CRC) screening rates among Hispanic and Latino patients result in advanced disease at the time of diagnosis and decreased survival chances. METHODS: We performed a prospective study at an academic endoscopy center in Boston, Massachusetts from May 1, 2019 to January 31, 2020. We identified 887 Spanishspeaking patients as controls and enrolled 412 (59%) Spanish-speaking patients in a short message service (SMS) program for pre-procedure instructions. RESULTS: Intervention and control group participants were similar in age, sex, and indications. Patients receiving SMS messages were less likely to no-show or cancel last minute (OR=1.66, 95%CI=0.44-0.83, p=.002) and had more adequate bowel preparations compared with the control arm (OR=1.55, 95%CI=0.45-0.92, p=.01). Overall, 93% (117/126) of patients stated they would "highly recommend" the program to others. CONCLUSIONS: Our automated SMS reminders for colonoscopy preparation increased appointment adherence, bowel preparation quality, and showed good patient satisfaction among Spanish speakers.

Gamma secretase inhibitors enhance vincristine-induced apoptosis in T-ALL in a NOTCH-independent manner.

Activating mutations in the NOTCH1 gene are found in over 50 % of T-ALL cases. Since Notch signaling contributes to the leukemia cell survival and growth, targeting Notch signaling using γ-secretase inhibitors (GSI) has been proposed as a molecularly targeted therapy for the treatment of T-ALL. However, not all T-ALL with NOTCH1 activating mutations respond to GSI treatment. We examined whether GSI could enhance the cytotoxic effect of anti-leukemic agents in the GSI-resistant T-ALL cells although GSI does not have anti-tumor effect as a single agent. GSI significantly increased cell death induced by Vincristine (VCR) but not other anti-leukemic drugs (Methotrexate, Asparaginase, and Cytarabine). The GSI effect in enhancing VCR efficacy was not the result of inhibition of Notch signaling. GSI augmented VCR-induced mitotic arrest, followed by apoptosis. GSI accelerated VCR-triggered loss of mitochondrial membrane potential and caspase-mediated apoptosis. Our finding suggests that GSI has other functions besides inhibiting Notch signaling in T-ALL and incorporating GSI into the conventional regimen containing VCR may offer therapeutic advantage by potentiating VCR treatment in leukemia patients.

CD9 may contribute to the survival of human germinal center B cells by facilitating the interaction with follicular dendritic cells.

The germinal center (GC) is a dynamic microenvironment where antigen (Ag)-activated B cells rapidly expand and differentiate, generating plasma cells (PC) that produce high-affinity antibodies. Precise regulation of survival and proliferation of Ag-activated B cells within the GC is crucial for humoral immune responses. The follicular dendritic cells (FDC) are the specialized stromal cells in the GC that prevent apoptosis of GC-B cells. Recently, we reported that human GC-B cells consist of CD9+ and CD9- populations and that it is the CD9+ cells that are committed to the PC lineage. In this study, we investigated the functional role of CD9 on GC-B cells. Tonsillar tissue section staining revealed that in vivo CD9+ GC-B cells localized in the light zone FDC area. Consistent this, in vitro CD9+ GC-B cells survived better than CD9- GC-B cells in the presence of HK cells, an FDC line, in a cell-cell contact-dependent manner. The frozen tonsillar tissue section binding assay showed that CD9+ GC-B cells bound to the GC area of tonsillar tissues significantly more than the CD9- GC-B cells did and that the binding was significantly inhibited by neutralizing anti-integrin ß1 antibody. Furthermore, CD9+ cells bound to soluble VCAM-1 more than CD9- cells did, resulting in activation and stabilization of the active epitope of integrin ß1. All together, our data suggest that CD9 on GC-B cells contributes to survival by strengthening their binding to FDC through the VLA4/VCAM-1 axis.

GSI promotes vincristine-induced apoptosis by enhancing multi-polar spindle formation.

Gamma secretase inhibitors (GSI), cell-permeable small-molecule inhibitors of gamma secretase activity, had been originally developed for the treatment of Alzheimer disease. In recent years, it has been exploited in cancer research to inhibit Notch signaling that is aberrantly activated in various cancers. We previously found that GSI could synergize with anti-microtubule agent, vincristine (VCR) in a Notch-independent manner. Here, we delineate the underlying cell cycle-related mechanism using HeLa cells, which have strong mitotic checkpoints. GSI enhanced VCR-induced cell death, although GSI alone did not affect cell viability at all. GSI augmented VCR-induced mitotic arrest in a dose-dependent manner, which was preceded by apoptotic cell death, as shown by an increase in Annexin V-positive and caspase-positive cell population. Furthermore, GSI amplified multi-polar spindle formation triggered by VCR. Altogether, we show the evidence that GSI enhances VCR-induced apoptosis in HeLa cells via multi-polar mitotic spindle formation, independent of Notch signaling. These data suggest that one or more GS substrates, yet to be identified, in a post-GS processed form, may play a role in maintaining functional centrosomes/mitotic spindles. More significantly, the synergistic effect of GSI in combination with VCR could be exploited in clinical setting to improve the efficacy of VCR.