Study on synergistic inhibitory effect of ruxolitinib and decitabine on growth of HEL cells with TET2 knockdown / 中国药理学通报

Aim To explore the cytotoxic and synergistic effects of decitabine and ruxolitinib on HEL cells with TET2 knockdown. Methods Stable TET2 knockdown by shRNA was established in HEL cell line. The change of cell proliferation was measured by CCK-8 assay. The median lethal dose (IC50) and colony formation assay were used to evaluate the cytotoxic effects of decitabine and ruxolitinib, the synergistic effects of which was further analyzed by Chou-Talalay method. Results The inhibition of TET2 increased the proliferative capacity of HEL cells. HEL cell lines became resistant to decitabine following shRNA-media- ted TET2 inactivation. Colony formation assay showed that the drug sensitivity of decitabine and ruxolitinib both decreased in TET2 knockdown HEL cells. The synergistic inhibitory effects of ruxolitinib and decitabine on TET2 knockdown HEL cells were observed. Conclusion The combination of ruxolitinib and decitabine may be an effective therapeutic strategy for accelerated or blast phase MPN patients with JAK2V6m and TET2 mutations.

An Attempt at Objective Evaluation of the Current Situation of Concomitant Drug Use for Dementia Outpatients at Community Pharmacies / 医薬品情報学

<b>Objectives: </b>The objectives of this study are to evaluate the current situation of concomitant drug use by community-dwelling elderly dementia patients, and to extract factors influencing the presence of potentially inappropriate medications (PIMs).<br><b>Method: </b>The research subjects were patients 65 years of age or older for whom concomitant drugs were prescribed on the same prescription form as donepezil hydrochloride.  One hundred and twenty community pharmacies randomly selected from 28 of the 47 prefectures throughout Japan.  Main research topics were sex, age, the clinical department to which the prescribing physician belonged, daily dosage of donepezil, and concomitant drugs.  Concomitant drugs were evaluated using the Beers Criteria: the Japanese Version. Furthermore, to search factors influencing the presence of PIMs, logistic regression analysis was used.<br><b>Results: </b>Data for 335 patients were extracted.  The average number of concomitant drug cases per patient were 4.2 (SD 2.6), and 109 patients (32.5%) were prescribed PIMs.  A logistic regression analysis confirmed that significant factors influencing the presence of PIMs were “the clinical department to which the prescribing physician belonged” (OR 4.80, 95%CI 1.01-22.72), “concomitant drug cases” (OR 1.26, 95%CI 1.13-1.41) and “the presence of concomitant use of central nervous system agents” (OR 5.82, 95%CI 3.35-10.11).<br><b>Conclusion: </b>This study revealed that more than a few cases of community-dwelling elderly patients of dementia were using concomitant drugs with potential risks.  It suggested that influencing factors were “the specialty of the prescribing physician” and “the presence of concomitant use of central nervous system agents.”