Trefoil Factor 1 Suppresses Stemness And Enhances Chemosensitivity Of Pancreatic Cancer

Abstract Pancreatic cancer is one of the most lethal malignancies, partly due to its high resistance to conventional chemotherapy. The aim of this study is to investigate the association between chemoresistance and trefoil factor family 1 (TFF1), a tumor-suppressive protein in pancreatic carcinogenesis. To investigate the role of TFF1 in human and mice, specimens of human pancreatic cancer and genetically engineered mouse model of pancreatic cancer (KPC/TFF1KO; Pdx1-Cre/ LSL-KRASG12D/ LSL-p53R172H/ TFF1-/-) were analysed. The expression of TFF1 in cancer cells was associated with better survival of the patients who underwent chemotherapy, and the deficiency of TFF1 increased EMT of cancer cells and deteriorated the benefit of gemcitabine in mice. To explore the efficacy of TFF1 treatment, recombinant and chemically synthesized TFF1 were administered to pancreatic cancer cell lines and mouse models. TFF1 inhibited gemcitabine-induced EMT, Wnt pathway activation and cancer stemness, eventually increased apoptosis of pancreatic cancer cells by gemcitabine. Combined treatment of gemcitabine and TFF1 arrested tumor growth and resulted in the better survival of mice. These results indicate that TFF1 can contribute to establishing a novel strategy to treat pancreatic cancer patients by enhancing chemosensitivity.  </jats:p

Electrogenic pump current of sarcoplasmic reticulum Ca2+-ATPase reconstituted at high lipid/protein ratio

AbstractWhen Ca2+-ATPase from sarcoplasmic reticulum was reconstituted with excess phospholipid (at a 1:800 weight ratio) in a monomeric state and activated by Ca2+ and ATP a transmembrane potential developed which could be continuously recorded by the fluorochrome oxonol VI. The results demonstrate the electrogenicity or active Ca2+ transport during continuous turnover. The fluorescence signal can be quantified in terms of net current electrical flow through the vesicular membranes and compared to the ATP hydrolysis to give the number of electrostatic charges transferred during Ca2+ transport. From such measurements a stoichiometry of 1.8±0.4 Ca2+ per ATP hydrolysed at pH 7.1 can be obtained. The method is also convenient for determination of the kinetics of Ca2+-ATPase activation by ATP and free Ca2+