Jianpiyifei II granules (JPYF II), a herbal formula, are used for the treatment of chronic obstructive pulmonary disease (COPD) in Guangdong Provincial Hospital of Chinese Medicine. The protective effects of JPYF II against bronchial epithelial cell apoptosis in mice exposed to cigarette smoke (CS) and apoptosis of human bronchial epithelial cell lines (BEAS-2B and 16-HBE) stimulated with cigarette smoke extract (CSE) were investigated. Mice were exposed to CS generated from 4 cigarettes/day for 30 days and administered a dose of JPYF II (0.75, 1.5 and 3 g/kg/d) from the third week of CS exposure. In mice exposed to CS, JPYF II significantly inhibited CS-induced apoptosis and overexpression of endoplasmic reticulum (ER) stress-related markers in bronchial epithelial cells of the lung tissues. In CSE-stimulated BEAS-2B and 16-HBE cells, JPYF II attenuated apoptosis and cell cycle arrest in the G0/G1 phase. Mechanistically, CSE initially induced intracellular reactive oxygen species (ROS) production, which then triggered ER stress, leading to the release of Ca2+ from ER inositol trisphosphate receptor (IP3R)-mediated stores and finally cell death. Treatment with JPYF II resulted in a significant reduction in CSE-induced apoptosis through interruption of the ROS-ER stress-Ca2+ signaling pathway. Therefore, the results of this study have revealed the underlying mechanism of action of JPYF II in the treatment of COPD.
// Anish Thomas 1 , Yuanbin Chen 1 , Seth M. Steinberg 2 , Ji Luo 3 , Svetlana Pack 4 , Mark Raffeld 4 , Zied Abdullaev 4 , Christine Alewine 5 , Arun Rajan 1 , Giuseppe Giaccone 6 , Ira Pastan 5 , Markku Miettinen 4 , Raffit Hassan 1 1 Thoracic and GI Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA 2 Biostatistics and Data Management Section, Center for Cancer Research, National Institutes of Health, Bethesda, MD, USA 3 Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA 4 Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA 5 Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA 6 Lombardi Cancer Center, Georgetown University, Washington DC, USA Correspondence to: Raffit Hassan, e-mail: hassanr@mail.nih.gov Keywords: mesothelin, non-small cell lung cancer, KRAS, EGFR Received: January 12, 2015 Accepted: February 24, 2015 Published: April 13, 2015 ABSTRACT Mesothelin is a cell surface glycoprotein which is highly expressed in several epithelial cancers and may have a role in cell adhesion and metastases. In this study, we used prospectively obtained clinical and pathological data to characterize mesothelin expression in advanced lung adenocarcinoma. Tissue was obtained from patients who underwent molecular profiling of potentially actionable genes on a trial of molecular profiling and targeted therapies in advanced thoracic malignancies. We immunohistochemically evaluated the intensity, and the percentage of cells expressing mesothelin in 93 advanced lung adenocarcinomas. The evaluation was blinded for molecular data and outcome. Mutations of EGFR, KRAS, BRAF, AKT1, PIK3CA and HER2 were assessed by pyrosequencing; HER2 amplification and ALK translocation were assessed by fluorescence in situ hybridization. 53% of advanced lung adenocarcinomas expressed mesothelin to some degree; high mesothelin expression, defined as mesothelin positivity in more than 25% of cells, was found in 24% of patients. High mesothelin expression was associated with inferior survival (median 18.2 months vs. 32.9 months; P = 0.014). High mesothelin expression was strongly associated with mutant KRAS ( P < 0.0001) and wild-type EGFR ( P = 0.002). Our results provide strong rationale to explore anti-mesothelin targeted therapies in advanced lung adenocarcinoma especially in the KRAS -mutant subgroup.
With various kinds of intelligent metering equipment coming into service, there has been an urgent need for a set of examination system in the electric power industry to check the staff's level of measuring electric energy. In this paper, we design and implement a random test paper generation algorithm for this examination system, and analyze the experiment's data, based on the practical requirement of a training system for the electric energy measurement in a certain electric company. At the same time, in order to get a set of test papers to satisfy the given conditions, this paper discusses how to use optimized genetic algorithm to generate test papers from the question bank. This paper introduce fishnet algorithm to generate test papers automatically for getting a better, more fair and more objective test paper.
Supplementary Legends 1-5 and Table 1 Legend from Oxygen Concentration Determines the Biological Effects of NOTCH-1 Signaling in Adenocarcinoma of the Lung
"HSR23-105: Real-World Dosing Patterns in Patients With Anaplastic Lymphoma Kinase Positive (ALK+) Non–Small Cell Lung Cancer (NSCLC) Treated With Brigatinib in the Front-Line (FL) Setting in the United States: A Claims Database Analysis" published on 31 Mar 2023 by National Comprehensive Cancer Network.
8562 Background: Nal-IRI is investigated as monotherapy in patients with SCLC who progressed on or after platinum regimen. The RESILIENT study is a Part 1 study of a Phase 2/3 trial to assess safety, tolerability, and efficacy of Irinotecan Liposome Injection in patients with SCLC. Methods: Nal-IRI is evaluated in patients ≥18 yrs with advanced SCLC with an ECOG performance status ≤1 and adequate organ function; prior exposure to immunotherapy is allowed. Safety and tolerability at dose levels of 85 mg/m 2 and 70 mg/m 2 are the primary endpoints, with assessment of exploratory efficacy signal. Results: At 24 Dec 2018 safety cutoff 12 patients in Part 1 received ≥1 dose of nal-IRI (Cohort 1 [C-1] at 85 mg/m 2 dose n=4; Cohort 2 [C-2] at 70 mg/m 2 dose n=8; median age 60.0 yrs; range 49–73 yrs). Three patients experienced ≥1 DLT (Cohort 1 n=3/4; Cohort 2 n=0/8). Most frequent treatment-emergent adverse events (TEAE) were gastrointestinal (GI) disorders (any grade): diarrhea (91.7%), nausea (58.3%), vomiting (41.7%), decreased appetite (58%), abdominal pain (33%) manageable by antidiarrheal regimen and antiemetics; as well as fatigue (50%) and asthenia (37.5%). Overall, hematologic toxicity was neutropenia (any grade) at 16.7% and anemia (any grade) at 16.7%. At 11 Dec 2018 efficacy cutoff the best objective response was partial response (PR) at 33.3% in 4/12 patients (C-1 n=1/4; C-2 n=3/8), median time to response was 6 wks. Overall disease control rate (DCR) was 58.3%; progressive disease (PD) was observed in 2 patients (16.7%), and 3 patients were non-evaluable (25%). Conclusions: Initial assessment suggests that nal-IRI at 70 mg/m 2 dose given bi-weekly is well-tolerated and has promising antitumor activity in patients with SCLC who progressed on or after platinum regimen. Part 1 dose expansion is ongoing. Clinical trial information: NCTN03088813. [Table: see text]
Bladder cancer belongs to one of the most common cancers and is a leading cause of deaths in our society. Urothelial carcinoma of the bladder (UCB) is the main type of this cancer, and the estrogen receptors in UCB remain to be studied. Our experiment aimed to investigate the possible biological effect of 17 β -estradiol on human bladder-derived T24 carcinoma cells and to indicate its related mechanisms. T24 cells were treated with various doses of 17 β -estradiol, and cell proliferation was detected using MTT assays. 17 β -estradiol promoted T24 cell proliferation independent of ER β /GPR30-regulated EGFR-MAPK pathway, while it inhibited cell growth via GPR30. Furthermore, the expression levels of downstream genes ( c-FOS, BCL-2, and CYCLIN D1 ) were increased by 17 β -estradiol and this effect was independently associated with activity of the EGFR-MAPK pathway. The two estrogen receptors might be potential therapeutic targets for the treatment of bladder cancer.
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