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https://www.readbyqxmd.com/read/28214977/braf-mutated-colorectal-cancer-what-is-the-optimal-strategy-for-treatment
#1
REVIEW
Romain Cohen, Pascale Cervera, Magali Svrcek, Anna Pellat, Chantal Dreyer, Aimery de Gramont, Thierry André
The BRAF activating mutation, harbored by approximately 10% of colorectal cancers (CRC), confers dramatic prognosis to advanced diseases. In early-stage setting, the identification of the BRAF mutation does not impact the therapeutic decision. Yet, the BRAF mutation could be considered as a stratification factor in adjuvant trials, because of its prognostic impact after relapse. Moreover, both BRAF mutation and mismatch repair (MMR) statuses should be determined in all CRC to help identify sporadic tumors versus Lynch syndrome-related tumors...
February 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28214895/development-of-cancer-vaccines-targeting-brachyury-a-transcription-factor-associated-with-tumor-epithelial-mesenchymal-transition
#2
Duane H Hamilton, Justin M David, Charli Dominguez, Claudia Palena
Epithelial-mesenchymal transition (EMT) is recognized as a relevant process during the progression of carcinomas towards metastatic disease. Epithelial cancer cells undergoing an EMT program may acquire mesenchymal features, motility, invasiveness, and resistance to a variety of anticancer therapeutics. Preventing or reverting the EMT process in carcinomas has the potential to minimize tumor dissemination and the emergence of therapeutic resistance. One of the strategies currently under investigation to target tumor cells undergoing EMT is the generation of a sustained immune response directed against an essential molecular driver of the process...
2017: Cells, Tissues, Organs
https://www.readbyqxmd.com/read/28214831/p38-mapk-pharmacological-inhibitor-sb203580-alleviates-total-parenteral-nutrition-induced-loss-of-intestinal-barrier-function-but-promotes-hepatocyte-lipoapoptosis
#3
Yong-Tao Xiao, Wei-Hui Yan, Yi Cao, Jun-Kai Yan, Wei Cai
BACKGROUND & AIMS: Our previous studies have provided evidence that p38 mitogen-activated protein kinase (MAPK) is involved in total parenteral nutrition (TPN)-associated complications, but its exact effects and mechanisms have not been fully understood. This study aimed to evaluate the roles of p38 MAPK inhibitor SB203580 in the TPN-induced loss of intestinal barrier function and liver disease. METHODS: A rodent model of TPN was used to analyze the roles of SB203580 in TPN-associated complications...
February 8, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28214773/the-usefulness-of-bone-biomarkers-for-monitoring-treatment-disease-a-comparative-study-in-osteolytic-and-osteosclerotic-bone-metastasis-models
#4
Marta Martín-Fernández, Karmele Valencia, Carolina Zandueta, Cristina Ormazábal, Susana Martínez-Canarias, Fernando Lecanda, Concepción de la Piedra
BACKGROUND: The skeleton is the most common site of colonization by metastatic cancers. Zoledronic acid (ZA) has been shown to be effective for the treatment of bone metastases regardless of whether the bone lesions are osteolytic or osteoblastic. Biochemical markers of bone turnover may be useful tools to quantify the degree of bone remodeling in the presence of bone metastases. The aim of this work was to establish the correlation between tumor dispersion (bioluminescence) and biochemical markers of bone turnover in two osteolytic and osteoblastic metastasis models in mice...
February 16, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28214688/h2s-causes-contraction-and-relaxation-of-major-arteries-of-the-rabbit
#5
Martin Caprnda, Tawar Qaradakhi, Joanne L Hart, Nazarii Kobyliak, Radka Opatrilova, Peter Kruzliak, Anthony Zulli
OBJECTIVE: Cardiovascular disease (CVD) caused by atherosclerosis remains a worldwide burden. Hydrogen sulfide is a promising new therapeutic avenue for the treatment of CVD, however reports show exogenous H2S has both vasodilator and vasoconstrictor effects depending on organ examined, and in vitro studies in animal models which are not resistant to developing atherosclerosis are limited. We sought to determine if rabbit arteries constricted or dilated to hydrogen sulfide. MATERIAL AND METHODS: The aorta, carotid, renal and iliac arteries were harvested from New Zealand White rabbits (n=4) and subjected to a concentration response curve to the fast H2S releaser NaHS...
February 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28214655/identification-of-microrna-biomarkers-for-response-of-advanced-soft-tissue-sarcomas-to-eribulin-translational-results-of-the-eortc-62052-trial
#6
Erik A C Wiemer, Agnieszka Wozniak, Herman Burger, Marcel Smid, Giuseppe Floris, Axelle Nzokirantevye, Raf Sciot, Stefan Sleijfer, Patrick Schöffski
BACKGROUND: Recent phase II and III clinical trials demonstrated anti-tumour activity of eribulin, a tubulin-interacting cytotoxic agent, in patients with metastatic soft tissue sarcoma (STS). In this exploratory study, we aimed to identify putative microRNA biomarkers that associate with eribulin sensitivity or resistance in STS. MATERIALS AND METHODS: Archival tumour tissue from primary tumours or metastatic lesions was collected prior to eribulin treatment, from 65 consenting patients involved in the EORTC trial 62052...
February 16, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28214556/isolated-limb-infusion-as-a-limb-salvage-strategy-for-locally-advanced-extremity-sarcoma
#7
John E Mullinax, Hidde M Kroon, John F Thompson, Neel Nath, Paul J Mosca, Jeffrey M Farma, Rajendra Bhati, Danielle Hardmann, Sean Sileno, Cristina O'Donoghue, Matthew Perez, Syeda Mahrukh Hussnain Naqvi, Y Ann Chen, Ricardo J Gonzalez, Jonathan S Zager
INTRO: Treatment-resistant, locally advanced soft tissue sarcomas (STS) often require amputation for complete tumor extirpation. Isolated limb infusion (ILI) selectively delivers high-dose chemotherapy to the extremity in an attempt to achieve limb salvage The aim of this study is to report perioperative and oncological outcomes after ILI in patients with extremity STS. METHODS: From 1994-2016, 77 patients underwent 84 ILI's at a total of 5 institutions. Melphalan and actinomycin D were circulated for 30 minutes after complete tourniquet occlusion of the limb, then actively washed out to prevent systemic exposure...
January 11, 2017: Journal of the American College of Surgeons
https://www.readbyqxmd.com/read/28214016/melk-expression-in-ovarian-cancer-correlates-with-poor-outcome-and-its-inhibition-by-otssp167-abrogates-proliferation-and-viability-of-ovarian-cancer-cells
#8
Reto S Kohler, Henriette Kettelhack, Alexandra M Knipprath-Mészaros, André Fedier, Andreas Schoetzau, Francis Jacob, Viola Heinzelmann-Schwarz
OBJECTIVE: Maternal embryonic leucine-zipper kinase (MELK) shows oncogenic properties in basal-like breast cancer, a cancer subtype sharing common molecular features with high-grade serous ovarian cancer. We examined the potential of MELK as a molecular and pharmacological target for treatment of epithelial ovarian cancer (EOC). METHODS/MATERIALS: Bioinformatic analysis was performed on nine OC transcriptomic data sets totaling 1241 patients. Effects of MELK depletion by shRNA or inhibition by OTSSP167 in cell lines were assessed by colony formation and MTT (proliferation) assays, Western blotting (apoptosis), and flow cytometry (cell cycle analysis)...
February 14, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28213687/ofatumumab-for-the-treatment-of-childhood-nephrotic-syndrome
#9
Chia-Shi Wang, Rochelle Schmidt Liverman, Rouba Garro, Roshan Punnoose George, Anastacia Glumova, Alana Karp, Stephanie Jernigan, Barry Warshaw
BACKGROUND: Ofatumumab is a humanized anti-CD20 monoclonal antibody that has recently garnered interest as a potential therapeutic agent for nephrotic syndrome. We report our center's experience in administering ofatumumab to five pediatric patients with idiopathic nephrotic syndrome. METHODS: Between March 2015 and November 2016, five patients were treated with ofatumumab. One patient had post-transplant recurrent focal segmental glomerulosclerosis (FSGS) which had been resistant to plasmapheresis and numerous immunosuppressive agents...
February 17, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28213613/an-atf4-atg5-signaling-in-hypothalamic-pomc-neurons-regulates-fat-mass-via-affecting-energy-expenditure
#10
Yuzhong Xiao, Yalan Deng, Feixiang Yuan, Tingting Xia, Hao Liu, Zhigang Li, Zhixue Liu, Hao Ying, Yi Liu, Qiwei Zhai, Shanghai Chen, Feifan Guo
Although many biological functions of activating transcription factor 4 (ATF4) have been identified, a role of hypothalamic ATF4 in the regulation of energy homeostasis is poorly understood. Here, we showed that hypothalamic pro-opiomelanocortin (POMC) neurons specific ATF4 knockout (PAKO) mice are lean and have higher energy expenditure. Furthermore, PAKO mice were resistant to high-fat diet (HFD)-induced obesity, glucose intolerance and leptin resistance. Moreover, the expression of autophagy protein 5 (ATG5) was increased or decreased by ATF4 knockdown or over-expression, respectively, and ATF4 inhibited the transcription of ATG5 by binding to the basic zipper-containing protein (bZIP) sites on its promoter...
February 17, 2017: Diabetes
https://www.readbyqxmd.com/read/28213434/malaria-during-pregnancy
#11
Michal Fried, Patrick E Duffy
One hundred and twenty-five million women in malaria-endemic areas become pregnant each year (see Dellicour et al. PLoS Med7: e1000221 [2010]) and require protection from infection to avoid disease and death for themselves and their offspring. Chloroquine prophylaxis was once a safe approach to prevention but has been abandoned because of drug-resistant parasites, and intermittent presumptive treatment with sulfadoxine-pyrimethamine, which is currently used to protect pregnant women throughout Africa, is rapidly losing its benefits for the same reason...
February 17, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28213404/hydrogen-sulfide-alleviates-hypertensive-kidney-dysfunction-through-an-epigenetic-mechanism
#12
Gregory Weber, Sathnur Pushpakumar, Utpal Sen
Hypertension is a major risk factor for chronic kidney disease (CKD) and renal inflammation is an integral part in this pathology. Hydrogen sulfide (H2S) has been shown to mitigate renal damage through reduction in blood pressure and reactive oxygen species; however, the exact mechanisms are not clear. While several studies have underlined the role of epigenetics in renal inflammation and dysfunction, the mechanisms through which epigenetic regulators play role in hypertension are not well defined. In this study, we sought to identify if microRNAs are dysregulated in response to angiotensin-II (Ang-II) induced hypertension in the kidney and whether H2S donor, GYY 4137, could reverse the microRNA alteration and kidney function...
February 17, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28213398/foxo-integration-of-insulin-signaling-with-glucose-and-lipid-metabolism
#13
Sojin Lee, Henry H Dong
The forkhead box O family consists of FoxO1, FoxO3, FoxO4 and FoxO6 proteins in mammals. Expressed ubiquitously in the body, the four FoxO isoforms share in common the amino DNA binding domain, known as "forkhead box" domain. They mediate the inhibitory action of insulin or insulin-like growth factor on key functions involved in cell metabolism, growth, differentiation, oxidative stress, senescence, autophagy and aging. Genetic mutations in FoxO genes or abnormal expression of FoxO proteins are associated with metabolic disease, cancer or altered lifespan in humans and animals...
February 17, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28213201/respiratory-load-perception-in-overweight-and-asthmatic-children
#14
Victoria MacBean, Lorna Wheatley, Alan C Lunt, Gerrard F Rafferty
Overweight asthmatic children report greater symptoms than normal weight asthmatics, despite comparable airflow obstruction. This has been widely assumed to be due to heightened perception of respiratory effort. Three groups of children (healthy weight controls, healthy weight asthmatics, overweight asthmatics) rated perceived respiratory effort throughout an inspiratory resistive loading protocol. Parasternal intercostal electromyogram was used as an objective marker of respiratory load; this was expressed relative to tidal volume and reported as a ratio of the baseline value (neuroventilatory activity ratio (NVEAR))...
February 14, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28213199/cardiovascular-risk-in-different-obesity-phenotypes-over-a-decade-follow-up-tehran-lipid-and-glucose-study
#15
Bita Mirzaei, Hengameh Abdi, Sara Serahati, Maryam Barzin, Mahtab Niroomand, Fereidoun Azizi, Farhad Hosseinpanah
BACKGROUND AND AIMS: Considering the inconsistent data available on cardiovascular (CV) risk of different obesity phenotypes, the aim of this study was to investigate the development of cardiovascular disease (CVD) in different obesity phenotypes over a median follow-up of 12 years. METHODS: In this large population-based cohort, 7842 participants (44.8% men), aged ≥ 30 years, were enrolled. Participants were divided into six phenotypes based on body mass index and metabolic status...
February 3, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28213130/dipeptidyl-peptidase-4-impairs-insulin-signalling-and-promotes-lipid-accumulation-in-hepatocytes
#16
Kerstin Rufinatscha, Bernhard Radlinger, Jochen Dobner, Sabrina Folie, Claudia Bon, Elisabeth Profanter, Claudia Ress, Karin Salzmann, Gabriele Staudacher, Herbert Tilg, Susanne Kaser
Dipeptidyl-peptidase 4 [DPP-4) has evolved into an important target in diabetes therapy due to its role in incretin hormone metabolism. In contrast to its systemic effects, cellular functions of membranous DPP-4 are less clear. Here we studied the role of DPP-4 in hepatic energy metabolism. In order to distinguish systemic from cellular effects we established a cell culture model of DPP-4 knockdown in human hepatoma cell line HepG2. DPP-4 suppression was associated with increased basal glycogen content due to enhanced insulin signalling as shown by increased phosphorylation of insulin-receptor substrate 1 (IRS-1), protein kinase B/Akt and mitogen-activated protein kinases (MAPK)/ERK, respectively...
February 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28213010/the-pathogenesis-and-pathophysiology-of-gestational-diabetes-mellitus-deductions-from-a-three-part-longitudinal-metabolomics-study-in-china
#17
REVIEW
Kai P Law, Hua Zhang
Gestational diabetes mellitus (GDM) is a form of diabetes that is first recognised during pregnancy, with no evidence of pre-existing type 1 or type 2 diabetes. The prevalence of GDM has been rising steadily over the past few decades, coinciding with the ongoing epidemic of obesity and type 2 diabetes. Although GDM normally disappears after delivery, women who have been previously diagnosed with GDM are at a greater risk of developing gestational diabetes in subsequent pregnancies, and type 2 diabetes later in life...
February 14, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28213001/predictive-factors-for-egfr-tyrosine-kinase-inhibitor-retreatment-in-patients-with-egfr-mutated-non-small-cell-lung-cancer-a-multicenter-retrospective-sequence-study
#18
Gee-Chen Chang, Chien-Hua Tseng, Kuo-Hsuan Hsu, Chong-Jen Yu, Cheng-Ta Yang, Kun-Chieh Chen, Tsung-Ying Yang, Jeng-Sen Tseng, Chien-Ying Liu, Wei-Yu Liao, Te-Chun Hsia, Chih-Yen Tu, Meng-Chih Lin, Ying-Huang Tsai, Meng-Jer Hsieh, Wen-Shuo Wu, Yuh-Min Chen
BACKGROUND: Acquired resistance occurs in most non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations experiencing a response to EGFR-tyrosine kinase inhibitor (TKI) initially. We investigated EGFR-TKI retreatment in patients who had previously received EGFR-TKI followed by chemotherapy. MATERIALS AND METHODS: This was a retrospective multicenter study. Patients with locally advanced or metastatic adenocarcinoma or TTF-1 (+) NSCLC, positive EGFR sensitive mutation, and EGFR-TKI reuse after initial EGFR-TKI followed by chemotherapy were enrolled...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28212995/heterogeneity-of-circulating-tumor-cells-ctcs-in-patients-with-recurrent-small-cell-lung-cancer-sclc-treated-with-pazopanib
#19
I Messaritakis, E Politaki, M Plataki, V Karavassilis, N Kentepozidis, F Koinis, E Samantas, V Georgoulias, A Kotsakis
OBJECTIVES: To investigate the effect of pazopanib on different CTCs subpopulations in patients with recurrent SCLC and evaluate their clinical relevance. METHODS: Peripheral blood was obtained before the administration of pazopanib (n=56 patients), after the first cycle (n=35 patients) and at disease progression (n=45 patients). CTCs were detected by CellSearch and double immunofluorescent staining using antibodies against the cytokeratins (CK), TTF-1, CD56 and VEGFR2...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28212833/dietary-administration-of-pontogammarus-maeoticus-extract-affects-immune-responses-stress-resistance-feed-intake-and-growth-performance-of-caspian-roach-rutilus-caspicus-fingerlings
#20
Rudabeh Rufchaei, Seyed Hossein Hoseinifar, Alireza Mirzajani, Hien Van Doan
Dietary administration of immunostimulants showed promising results for elevation of immune responses and disease resistance. The aim of the present study was to investigate the effects of dietary Pontogammarus (Pontogammarus maeoticus) extract on innate immune response, stress resistance, feed intake and growth performance of the Caspian roach fingerling. Two levels of P. maeoticus extract dilution with distilled water 1:25 [T1] and 1:50 [T2] were prepared. Experimental diets were prepared by top-spraying the basal diet with equal amount (2%) of diluted extracts...
February 14, 2017: Fish & Shellfish Immunology
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