Single-cell integrative analysis reveals consensus cancer cell states and clinical relevance in breast cancer.

High heterogeneity and complex interactions of malignant cells in breast cancer has been recognized as a driver of cancer progression and therapeutic failure. However, complete understanding of common cancer cell states and their underlying driver factors remain scarce and challenging. Here, we revealed seven consensus cancer cell states recurring cross patients by integrative analysis of single-cell RNA sequencing data of breast cancer.

Discovery of novel 2-aminopyridine derivatives as ROS1 and ALK dual inhibitors to combat drug-resistant mutants including ROS1 and ALK.

Clinical treatment by FDA-approved ROS1/ALK inhibitor Crizotinib significantly improved the therapeutic outcomes. However, the emergence of drug resistance, especially driven by acquired mutations, have become an inevitable problem and worsened the clinical effects of Crizotinib. To combat drug resistance, some novel 2-aminopyridine derivatives were designed rationally based on molecular simulation, then synthesised and subjected to biological test.

Effect of Entecavir Combined with Adefovir Dipivoxil on Clinical Efficacy and TNF- and IL-6 Levels in Patients with Hepatitis B Cirrhosis.

Objective: The purpose of the study was to investigate the effect of entecavir combined with adefovir dipivoxil on clinical efficacy and TNF- and IL-6 levels in patients with hepatitis B cirrhosis.

Methods: A total of 100 patients with hepatitis B cirrhosis admitted to our hospital between January 2018 and June 2019 were randomly selected and divided into the control group ( = 50) and experimental group ( = 50) according to the order of admission. Among them, the control group patients were treated with entecavir, while the patients in the experimental group received entecavir combined with adefovir dipivoxil.

Design, synthesis, biological evaluation and molecular modeling of novel 2-amino-4-(1-phenylethoxy) pyridine derivatives as potential ROS1 inhibitors.

With the aim of discovering potential and selective inhibitors targeting ROS1 kinase, we rationally designed, synthesized and evaluated two series of novel 2-amino-pyridine derivatives with 1-phenylethoxy at C-3 and C-4 position. The enzymic assays results indicated that six of the new compounds 13b-13d and 14a-14c showed remarkably higher inhibitory activities against ROS1 kinase. The most promising compounds, 13d and 14c displayed the most desired ROS1 inhibitory activity with IC values of 440 nM and 370 nM respectively.

Molecular Simulation Studies on the Binding Selectivity of Type-I Inhibitors in the Complexes with ROS1 versus ALK.

ROS1 and ALK are promising targets of anticancer drugs for non-small-cell lung cancer. Since they have 49% amide acid sequence homology in the kinases domain and 77% identity at the ATP binding area, some ALK inhibitors also showed some significant responses for ROS1 in the clinical trial, such as the type-I binding inhibitor crizotinib and PF-06463922. As a newly therapeutic target, the selective ROS1 inhibitor is relatively rare.

Design, synthesis, anti-tumor activity, and molecular modeling of quinazoline and pyrido[2,3-d]pyrimidine derivatives targeting epidermal growth factor receptor.

Three series of novel quinazoline and pyrido[2,3-d]pyrimidine derivatives were designed, synthesized and evaluated for their ability to inhibit EGFR tyrosine kinase and a panel of five human cancer cell lines (MCF-7, A549, BT-474, SK-BR-3, and MDA-MB-231). Bioassay results indicated that five of these prepared compounds (12c-12e and 13c-13d) exhibited remarkably higher inhibitory activities against EGFR and SK-BR-3 cell line. Compounds 12c and 12e displayed the most potent EGFR inhibitory activity (IC50 = 2.