Lung cancer is one of the most common cancer in the world. In 2018, there were over 2 million new cases of lung cancer and over 1.7 million deaths were attributed to lung cancer. Targeted therapy has emerged as an important mean of the disease management for patients with non-small-cell lung cancer (NSCLC). Herein, we review and analyze recent literature, discuss the targeting pathways and ongoing clinical trials in lung cancer. Chemotherapy is no longer the best available treatment for all patients. Therapeutic decisions should be guided by an understanding of the molecular features of patient's tumor tissues. The future gains will likely emerge from finding optimal ways of combining targeted therapy, immunotherapy, and chemotherapy.
Suberoylanilide hydroxamic acid (SAHA) is a novel histone deacetylase inhibitor with high potency in inducing di erentiation of cultured murine erythroleukemia cells. We have recently demonstrated that SAHA induces cell cycle arrest and apoptosis in human breast cancer cells, accompanied by up-regulation of the cyclindependent kinase inhibitor, p21 WAF1/CIP1 , via a p53-independent mechanism. In this study, we used p21 gene expression as a model system to elucidate the molecular mechanism(s) underlying SAHA-mediated gene activation. Treatment of human breast cancer cell line MCF7 cells with SAHA induced p21 mRNA as a consequence of an immediate-early gene activation. Moreover, SAHA activated the p21 promoter primarily through two Sp1 sites located at 782 and 769 relative to the transcription start site. Furthermore, Sp1 and Sp3 proteins were the major factors binding to the Sp1 site of the p21 promoter. However, SAHA did not alter their DNA binding activities, suggesting that SAHA mediates p21 promoter activity by a mechanism other than altering the DNA binding activities of Sp1 and Sp3. Further studies using the GAL4 luciferase assay system demonstrated that both GAL4-Sp1 and GAL4-Sp3 fusion proteins supported SAHA-mediated gene activation from a promoter driven by ®ve GAL4 DNA binding sites, and that GAL4-Sp3 fusion protein was suppressive in the absence of SAHA treatment. Collectively, our results suggest that SAHA activates the p21 promoter through the Sp1 sites, and that both Sp1 and Sp3 proteins can mediate SAHA-induced gene activation.
The use of mobile and wireless technologies and wearable devices for improving health care processes and outcomes (mHealth) is promising for health promotion among patients with chronic diseases such as obesity and diabetes. This study comprehensively examined published mHealth intervention studies for obesity and diabetes treatment and management to assess their effectiveness and provide recommendations for future research. We systematically searched PubMed for mHealth-related studies on diabetes and obesity treatment and management published during 2000-2016. Relevant information was extracted and analyzed. Twenty-four studies met inclusion criteria and varied in terms of sample size, ethnicity, gender, and age of the participating patients and length of follow-up. The mHealth interventions were categorized into 3 types: mobile phone text messaging, wearable or portable monitoring devices, and applications running on smartphones. Primary outcomes included weight loss (an average loss ranging from -1.97 kg in 16 wk to -7.1 kg in 5 wk) or maintenance and blood glucose reduction (an average decrease of glycated hemoglobin ranging from -0.4% in 10 mo to -1.9% in 12 mo); main secondary outcomes included behavior changes and patient perceptions such as self-efficacy and acceptability of the intervention programs. More than 50% of studies reported positive effects of interventions based on primary outcomes. The duration or length of intervention ranged from 1 wk to 24 mo. However, most studies included small samples and short intervention periods and did not use rigorous data collection or analytic approaches. Although some studies suggest that mHealth interventions are effective and promising, most are pilot studies or have limitations in their study designs. There is an essential need for future studies that use larger study samples, longer intervention (≥ 6 mo) and follow-up periods (≥ 6 mo), and integrative and personalized innovative mobile technologies to provide comprehensive and sustainable support for patients and health service providers.
Measures of pulsatile GH secretion require frequent collection and analysis of blood samples at regular intervals. Due to blood volume constraints, repeat measures of circulating levels of GH in mice remain challenging. Consequently, few observations exist in which the pulsatile pattern of GH secretion in mice have been characterized. To address this, we developed a technique for the collection and analysis of circulating levels of GH at regular and frequent intervals in freely moving mice. This was achieved through the development of a sensitive assay for the detection of GH in small (2 μl) quantities of whole blood. The specificity and accuracy of this assay was validated following guidelines established for single-laboratory validation as specified by the International Union of Pure and Applied Chemistry. We incorporated an established method for tail-clip blood sample collection to determine circulating levels of GH secretion in 36 whole blood samples collected consecutively over a period of 6 h. Resulting measures were characterized by peak secretion periods and interpulse stable baseline secretion periods. Periods characterized by elevated whole blood GH levels consisted of multicomponent peaks. Deconvolution analysis of resulting measures confirmed key parameters associated with pulsatile GH secretion. We show a striking decrease in pulsatile GH secretion in mice after 12-18 h of fasting. This model is necessary to characterize the pulsatile profile of GH secretion in mice and will significantly contribute to current attempts to clarify mechanisms that contribute to the regulation of GH secretion.
, 1a, 2a, 2b, 3a, 4a, 5b, X, and Y, found that all belong to a new sequence type (ST), ST91. Pulsed-field gel electrophoresis revealed 154 pulse types with 655 S. flexneri isolates analyzed and identified 57 serotype switching events. The data suggest that S. flexneri epidemics in China have been caused by a single epidemic clone, ST91, with frequent serotype switching to evade infection-induced immunity to serotypes to which the population was exposed previously. The clone has also acquired resistance to multiple antibiotics. These findings underscore the challenges to the current vaccine development and control strategies for shigellosis.
SAHA induced growth inhibition, cell cycle arrest, and eventual apoptosis in human breast cancer cells, possibly by modulating cell cycle and apoptosis regulatory proteins, such as CDK inhibitors p21 and p27, pRb, and other differentiation and/or growth inhibition-associated genes, including gelsolin, IDI1 and VDUP1. This, together with the low toxicity in normal cells, suggests that SAHA might have therapeutic potential for the treatment of human breast cancers.
We characterized 208 human Salmonella isolates from 2006 to 2007 and 27 human Salmonella enterica serovar Typhimurium isolates from 1987 to 1993 from Henan Province, China, by serotyping, by antimicrobial susceptibility testing, and, for the most common serovars, by pulsed-field gel electrophoresis (PFGE). The most common serovars among the 2006-2007 isolates were S. enterica serovar Typhimurium (27%), S. enterica serovar Enteritidis (17%), S. enterica serovar Derby (10%), S. enterica serovar Indiana (6%), and S. enterica serovar Litchfield (6%). A high percentage of the isolates were multiple-drug resistant, and 54% were resistant to both nalidixic acid and ciprofloxacin. Of these, 42% were resistant to a high level of ciprofloxacin (MIC > 4 g/ml), whereas for the remaining isolates, the MICs ranged from 0.125 to 2 g/ml. Five isolates (2%) were ceftiofur resistant and harbored bla CTX-M14 or bla CTX-M15 . With the possible exception of the quinolones and cephalosporins, the 1987-1993 S. enterica serovar Typhimurium isolates were almost as resistant as the recent isolates. PFGE typing of S. enterica serovar Typhimurium showed that the most common cluster predominated over time. Two other clusters have emerged, and another cluster has disappeared.
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