Purpose: Combining gemcitabine with CHK1 inhibition has shown promise in preclinical models of pancreatic ductal adenocarcinoma (PDAC). Here, we report the findings from a phase I expansion cohort study (NCT02632448) investigating low-dose gemcitabine combined with the CHK1 inhibitor LY2880070 in patients with previously treated advanced PDAC.
Patients And Methods: Patients with metastatic PDAC were treated with gemcitabine intravenously at 100 mg/m2 on days 1, 8, and 15, and LY2880070 50 mg orally twice daily on days 2-6, 9-13, and 16-20 of each 21-day cycle.
A critical determinant of DNA repair pathway choice is REV7, an adaptor that binds to various DNA repair proteins through its C-terminal seatbelt domain. The REV7 seatbelt binds to either REV3, activating translesion synthesis, or to SHLD3, activating non-homologous end joining (NHEJ) repair. Recent studies have identified another REV7 seatbelt-binding protein, CHAMP1 (chromosome alignment-maintaining phosphoprotein 1), though its possible role in DNA repair is unknown.
View Article and Find Full Text PDFThe Plk1-interacting checkpoint helicase (PICH) protein localizes to ultrafine anaphase DNA bridges in mitosis along with a complex of DNA repair proteins. Previous studies show PICH deficiency-induced embryonic lethality in mice. However, the function of PICH that is required to suppress embryonic lethality in PICH-deficient mammals remains to be determined.
View Article and Find Full Text PDFSeveral studies have reported that gut and lung microbiomes are involved in the process of asthma pathogenesis. However, it remains unclear how perinatal or early-life antibiotic intervention affect adult allergic airway inflammation. We assigned C57BL/6 mice randomly to four experimental groups: normal saline control (NS), ovalbumin (OVA), vancomycin pretreated NS (VAN-NS), and vancomycin pretreated OVA (VAN-OVA).
View Article and Find Full Text PDFOleandrin is a monomeric compound extracted from leaves and seeds of Nerium oleander. It had been reported that oleandrin could effectively inhibit the growth of human cancer cells. However, the specific mechanisms of the oleandrin-induced anti-tumor effects remain largely unclear.
View Article and Find Full Text PDF