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https://www.readbyqxmd.com/read/28550040/kras-g12d-expression-in-lung-resident-myeloid-cells-promotes-pulmonary-lch-like-neoplasm-sensitive-to-statin-treatment
#1
Tamihiro Kamata, Susan Giblett, Catrin Pritchard
Langerhans cell histiocytosis (LCH) is a rare histiocytic neoplasm associated with somatic mutations in the genes involved in the RAF/MEK/ERK signaling pathway. Recently, oncogenic mutations in NRAS/KRAS, upstream regulators of the RAF/MEK/ERK pathway, have been reported in pulmonary, but not in non-pulmonary, LCH cases, suggesting organ-specific contribution of oncogenic RAS to LCH pathogenesis. Using a mouse model expressing KRAS(G12D) in the lung by nasal delivery of adenoviral Cre, here we show that KRAS(G12D) expression in lung-resident myeloid cells induces pulmonary LCH-like neoplasms comprised of pathogenic CD11c(high)F4/80+CD207+ cells...
May 26, 2017: Blood
https://www.readbyqxmd.com/read/28548966/targeting-shp-1-stat3-signaling-a-promising-therapeutic-approach-for-the-treatment-of-cholangiocarcinoma
#2
Ming-Hung Hu, Li-Ju Chen, Yen-Lin Chen, Ming-Shen Tsai, Chung-Wai Shiau, Tzu-I Chao, Chun-Yu Liu, Jia-Horng Kao, Kuen-Feng Chen
Sorafenib is a multiple kinase inhibitor which targets Raf kinases, VEGFR, and PDGFR and is approved for the treatment of hepatocellular carcinoma (HCC). Previously, we found that p-STAT3 is a major target of SC-43, a sorafenib derivative. In this study, we report that SC-43-induced apoptosis in cholangiocarcinoma (CCA) via a novel mechanism. Three CCA cell lines (HuCCT-1, KKU-100 and CGCCA) were treated with SC-43 to determine their sensitivity to SC-43-induced cell death and apoptosis. We found that SC-43 activated SH2 domain-containing phosphatase 1 (SHP-1) activity, leading to p-STAT3 and downstream cyclin B1 and Cdc2 downregulation, which induced G2-M arrest and apoptotic cell death...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28546669/prevalence-clinical-and-laparoscopic-features-of-endometriosis-among-infertile-women
#3
Vineet V Mishra, Pradeep Bandwal, Ritu Agarwal, Rohina Aggarwal
OBJECTIVE: To study the prevalence, clinical and laparoscopic characteristics of endometriosis in infertile women. STUDY DESIGN: This is a hospital-based prospective study. PATIENTS: Five hundred and two (502) patients underwent diagnostic laparoscopy for evaluation of cause for infertility. Staging of endometriosis was done according to the rAFS scoring system. RESULTS: Out of 502 women, 276 (54.98 %) showed the presence of endometriosis, while 226 (45...
June 2017: Journal of Obstetrics and Gynaecology of India
https://www.readbyqxmd.com/read/28546431/disruption-of-mitochondrial-electron-transport-chain-function-potentiates-the-pro-apoptotic-effects-of-mapk-inhibition
#4
Andrew P Trotta, Jesse D Gelles, Madhavika N Serasinghe, Patrick Loi, Jack L Arbiser, Jerry E Chipuk
The mitochondrial network is a major site of ATP production through the coupled integration of the electron transport chain (ETC) with oxidative phosphorylation. In melanoma, arising from the Val600Glu mutation in the kinase v-RAF murine sarcoma viral oncogene homolog B (BRAFV600E), oncogenic signaling enhances glucose-dependent metabolism, while reducing mitochondrial ATP production. Likewise, when BRAFV600E is pharmacologically inhibited by targeted therapies (e.g. PLX-4032/Vemurafenib), glucose metabolism is reduced and cells increase mitochondrial ATP production to sustain survival...
May 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28546426/guanine-nucleotide-exchange-factor-epac2-dependent-activation-of-the-gtp-binding-protein-rap2a-mediates-camp-dependent-growth-arrest-in-neuroendocrine-cells
#5
Andrew C Emery, Wenqin Xu, Maribeth V Eiden, Lee E Eiden
First messenger-dependent activation of MAPKs in neuronal and endocrine cells is critical for cell differentiation and function and requires guanine nucleotide exchange factor (GEF)- mediated activation of downstream Ras-family small GTPases, which ultimately lead to ERK, JNK, and p38 phosphorylation. Because there are numerous GEFs and also a host of Ras-family small GTPases, it is important to know which specific GEF-small GTPase dyad functions in a given cellular process. Here, we investigated the upstream activators and downstream effectors of signaling via the GEF Epac2 in the neuroendocrine NS-1 cell line...
May 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28543798/mucosal-melanoma-clinical-histological-and-c-kit-gene-mutational-profile-of-86-french-cases
#6
E Cinotti, J Chevallier, B Labeille, F Cambazard, L Thomas, B Balme, M T Leccia, M D'Incan, P Vercherin, C Douchet, P Rubegni, J L Perrot
BACKGROUND: Mucosal melanomas are rare and highly aggressive tumors. Few studies evaluated mucosal melanomas of locations other than the head and neck region, and other than those of the Asian population. OBJECTIVES: The objective of this study was to analyze the clinical and histological features, as well as the mutational status of c-kit and b-raf gene of mucosal melanoma in any localization in a French series. METHODS: We investigated clinical (sex, age, performance status, survival, treatment of the patients and lack of pigmentation of the tumors) and histopathologic features (ulceration, Breslow's index, mitotic rate), as well as the mutational status of c-kit and b-raf of 86 mucosal melanomas diagnosed in 15 years in four French University Hospitals...
May 22, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28540983/routine-angiographic-follow-up-versus-clinical-follow-up-after-percutaneous-coronary-intervention-in-acute-myocardial-infarction
#7
Yong Hoon Kim, Ae Young Her, Seung Woon Rha, Byoung Geol Choi, Minsuk Shim, Se Yeon Choi, Jae Kyeong Byun, Hu Li, Woohyeun Kim, Jun Hyuk Kang, Jah Yeon Choi, Eun Jin Park, Sung Hun Park, Sunki Lee, Jin Oh Na, Cheol Ung Choi, Hong Euy Lim, Eung Ju Kim, Chang Gyu Park, Hong Seog Seo, Dong Joo Oh
PURPOSE: Differences in the utility of routine angiographic follow-up (RAF) and clinical follow-up (CF) after percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI) are not well understood. The present study aimed to compare the 3-year clinical outcomes of RAF and CF in AMI patients who underwent PCI with drug-eluting stents (DES). MATERIALS AND METHODS: A total of 774 consecutive AMI patients who underwent PCI with DES were enrolled. RAF was performed at 6 to 9 months after index PCI (n=425)...
July 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/28539323/etv1-positive-cells-give-rise-to-brafv600e-mutant-gastrointestinal-stromal-tumors
#8
Leili Ran, Devan Murphy, Jessica Sher, Zhen Cao, Shangqian Wang, Edward Walczak, Youxin Guan, Yuanyuan Xie, Shipra Shukla, Yu Zhan, Cristina R Antonescu, Yu Chen, Ping Chi
Gastrointestinal Stromal Tumor (GIST) is the most common subtype of sarcoma. Despite clinical advances in the treatment of KIT/PDGFRA-mutant GIST, similar progress against KIT/PDGFRA-wild type GIST, including mutant BRAF-driven tumors, have been limited by a lack of model systems. ETV1 is a master regulator in the intestinal cells of Cajal (ICC), thought to be the cells of origin of GIST. Here we present a model in which the ETV1 promoter is used to specifically and inducibly drive Cre recombinase in ICC as a strategy to study GIST pathogenesis...
May 24, 2017: Cancer Research
https://www.readbyqxmd.com/read/28539143/incidence-of-g-induced-loss-of-consciousness-and-almost-loss-of-consciousness-in-the-royal-air-force
#9
Ellen Slungaard, Judith McLeod, Nicholas D C Green, Amit Kiran, Di J Newham, Stephen D R Harridge
INTRODUCTION: Exposure to sustained +Gz acceleration with inadequate G protection can result in G-induced loss of consciousness (G-LOC) or almost loss of consciousness (A-LOC). The UK Royal Air Force (RAF) last conducted a survey of G-LOC within their military aircrew in 2005 with interventions subsequently introduced. The aim of this study was to repeat the 2005 survey in order to evaluate the impact of those interventions. METHODS: An anonymous questionnaire requesting details of G-LOC and A-LOC events was mailed to all RAF pilots (N = 1878) and weapons systems operators (WSOs) (N = 473), irrespective of aircraft currently flown...
June 1, 2017: Aerospace Medicine and Human Performance
https://www.readbyqxmd.com/read/28538440/neurologic-injury-in-adults-supported-with-veno-venous-extracorporeal-membrane-oxygenation-for-respiratory-failure-findings-from-the-extracorporeal-life-support-organization-database
#10
Roberto Lorusso, Sandro Gelsomino, Orlando Parise, Michele Di Mauro, Fabio Barili, Gijs Geskes, Enrico Vizzardi, Peter T Rycus, Raf Muellenbach, Thomas Mueller, Antonio Pesenti, Alain Combes, Giles Peek, Bjorn Frenckner, Matteo Di Nardo, Justyna Swol, Jos Maessen, Ravi R Thiagarajan
OBJECTIVES: To assess in-hospital neurologic (CNS) complications in adult patients undergoing veno-venous extracorporeal membrane oxygenation for respiratory failure. DESIGN: Retrospective analysis of the Extracorporeal Life Support Organization's data registry. SETTING: Data reported to Extracorporeal Life Support Organization from 350 international extracorporeal membrane oxygenation centers during 1992-2015. PATIENTS: Adults (≥ 18 yr old) supported with veno-venous extracorporeal membrane oxygenation for respiratory failure...
May 22, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28537318/a-new-mechanism-for-the-low-dielectric-property-of-poss-nanocomposites-the-key-role-of-interfacial-effect
#11
LiLi Liu, Yuan Yuan, Yawen Huang, Hongtao Yu, Junxiao Yang
The low dielectric constant (ε) of polyhedral oligomeric silsesquioxanes (POSS) was generally attributed to its porous structure. In this work, we propose a new mechanism for the low ε of the POSS-based nanocomposites from the interfacial effect point of view. The investigation on a typical nanocomposite, polystyrene/POSS, found that POSS molecules take crystallization to form crystalline nanoplatelets (PCPs) in PS. Correspondingly, the dielectric constant can be reduced to around 2.30. A detailed investigation excluded the possible influence of the chain stacking and chain mobility of the polymers on ε...
May 24, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28536078/akt-is-critically-involved-in-the-antagonism-of-braf-inhibitor-sorafenib-against-dabrafenib-in-colorectal-cancer-cells-harboring-both-wild-type-and-mutant-v600e-braf-genes
#12
Hongbin Wang, Haitian Quan, Liguang Lou
BRAF, one of the key factors in mitogen-activated protein kinase (MAPK) signaling pathway, plays an important role in cell functions including growth and proliferation. Inhibition of BRAF represents a promising antitumor strategy. Dabrafenib, a type I inhibitor of BRAF interrupting RAF/MEK interaction, has been approved by FDA as a single agent or combined with MEK inhibitor trametinib for the treatment of patients with BRAF V600E mutation-positive advanced melanoma. In the present study, we investigated the feasibility of combined treatment with dabrafenib and sorafenib, type I and type II BRAF inhibitor respectively, on colorectal cancer cells with BRAF V600E mutation...
May 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28535653/-clinical-pathological-characteristics-of-resectable-papillary-thyroid-microcarcinoma
#13
C L Shi, Y Guo, Y C Lyu, Z A B Y S Nanding, W C Gao, T F Shi, H D Qin, S Y Liu
Objective: To investigate the difference of prognostic factors and recurrence rates between papillary thyroid microcarcinoma (PTMC) and lager papillary thyroid carcinoma (PTC) and analyze the clinical pathological characteristics of PTMC suitable for surgery. Methods: A retrospective analysis on the clinicopathological features, expression level of of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E gene mutation and pigment epithelium-derived factor (PEDF), and postoperative follow-up results of the 251 PTC patients who underwent surgical treatment from October 2011 to October 2013, including 169 cases with PTMC and 82 with lager PTC (Tumor diameter>1 cm)...
May 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28534510/targeting-group-i-p21-activated-kinases-to-control-malignant-peripheral-nerve-sheath-tumor-growth-and-metastasis
#14
G Semenova, D S Stepanova, C Dubyk, E Handorf, S M Deyev, A J Lazar, J Chernoff
Malignant peripheral nerve sheath tumors (MPNSTs) are devastating sarcomas for which no effective medical therapies are available. Over 50% of MPSNTs are associated with mutations in NF1 tumor suppressor gene, resulting in activation of Ras and its effectors, including the Raf/Mek/Erk and PI3K/Akt/mTORC1 signaling cascades, and also the WNT/β-catenin pathway. As Group I p21-activated kinases (Group I Paks, PAK1/2/3) have been shown to modulate Ras-driven oncogenesis, we asked if these enzymes might regulate signaling in MPNSTs...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28533659/braf-inhibitor-treatment-of-melanoma-causing-colonic-polyps-an-alternative-hypothesis
#15
EDITORIAL
Fergal C Kelleher, Grainne Callaghan, Catriona Gallagher, Hazel O'Sullivan
Colonic polyps may arise from BRAF inhibitor treatment of melanoma, possibly due to paradoxical activation of the mitogen-activated protein (MAP)-kinase pathway. In an alternative evidence based scenario, tubular colonic adenomas with APC gene mutations have also been identified in the context of BRAF inhibitor treatment, in the absence of mutations of MAPK genes. A minority of colorectal cancers develop by an alternative "serrated polyp pathway". This article postulates a novel hypothesis, that the established phenotypic and molecular characteristics of serrated colonic polyps/CRC offer an intriguing insight into the pathobiology of BRAF inhibitor induced colonic polyps...
May 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28529742/intraductal-tubulopapillary-neoplasm-accompanied-by-invasive-carcinoma-of-the-pancreas-a-case-report-and-review-of-the-literature
#16
Li Niu, Zhigao Xu, Huan Liu, Hong Cao, Guifang Yang
Intraductal tubulopapillary neoplasms (ITPNs) are rare pancreatic neoplasms accounting for ~0.4% of pancreatic tumors. However, their clinicopathological characteristics have not been clearly determined and the number of available clinical studies on this type of tumor is limited at present. Due to the rare incidence of ITPN, diagnosis is often delayed. We herein present a unique case of a 38-year-old man who was diagnosed with ITPN accompanied with invasive carcinoma of the pancreas and underwent total pancreatectomy...
May 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28529577/aggressiveness-of-the-tall-cell-variant-of-papillary-thyroid-carcinoma-is-independent-of-the-tumor-size-and-patient-age
#17
Rocío Villar-Taibo, Diego Peteiro-González, José Manuel Cabezas-Agrícola, Elvin Aliyev, Francisco Barreiro-Morandeira, Clara Ruiz-Ponte, José M Cameselle-Teijeiro
The tall cell variant (TCV) of papillary thyroid carcinoma (PTC) is characterized by tall columnar cells with a height of at least three times their width. TCV usually presents at an older age, has a larger size and exhibits more extrathyroidal extension and metastases than classical PTC. The current study compared TCV with the classical and follicular variants (CaFVs) of PTC to determine if, irrespective of the age at diagnosis and tumor size, TCV is more aggressive than its classical and follicular counterparts...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28529557/a-single-center-experience-of-sorafenib-monotherapy-in-patients-with-advanced-intrahepatic-cholangiocarcinoma
#18
Ting-Ting Pan, Wei Wang, Wei-Dong Jia, Ge-Liang Xu
Patients with advanced intrahepatic cholangiocarcinoma (ICC) have a poor prognosis and the therapeutic options available for treating ICC are limited. Sorafenib, a multikinase inhibitor of vascular endothelial growth factor receptor 2 and 3, platelet derived growth factor receptor-β, B-Raf proto-oncogene, serine/threonine kinase and C-Raf proto-oncogene, serine/threonine kinase, is a novel reference standard for the treatment of advanced hepatocellular carcinoma. Sorafenib has previously been demonstrated to exhibit significant antitumor activity in various cholangiocarcinoma cell lines and in xenograft ICC models...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28523409/factors-associated-with-a-poor-prognosis-for-the-ivf-icsi-live-birth-rate-in-women-with-rafs-stage-iii-and-iv-endometriosis
#19
Pauline Roux, Jeanne Perrin, Julien Mancini, Aubert Agostini, Léon Boubli, Blandine Courbiere
PURPOSE: To assess the factors associated with a poor prognosis for a cumulative IVF live birth rate (LBR) in women with stage III and IV endometriosis according to the revised classification of the American Fertility Society (rAFS). METHODS: A retrospective cohort study was conducted between January 1, 2010, and December 31, 2014, in our Reproductive Medicine Center. We analyzed different factors associated with a poor prognosis for a cumulative IVF LBR in women with rAFS stage III and IV endometriosis...
May 18, 2017: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/28521461/kras-and-braf-mutations-in-serum-exosomes-from-patients-with-colorectal-cancer-in-a-chinese-population
#20
Yi-Xin Hao, Yong-Mei Li, Ming Ye, Yan-Yan Guo, Qiu-Wen Li, Xiu-Mei Peng, Qi Wang, Shu-Fang Zhang, Hui-Xia Zhao, He Zhang, Guang-Hui Li, Jian-Hua Zhu, Wen-Hua Xiao
The efficacy of epidermal growth factor receptor- targeted therapy is significantly associated with Kirsten rat sarcoma viral oncogene homolog (KRAS) and B-raf serine/threonine kinase proto-oncogene (BRAF) mutation in patients with colorectal cancer (CRC), for which the standard gene testing is currently performed using tumor tissue DNA. The aim of the present study was to compare the presence of KRAS and BRAF mutations in the serum exosome and primary tumor tissue from patients with CRC. Genomic DNA were extracted from the tumor tissues of 35 patients with histologically-confirmed CRC and exosomal mRNA were obtained from peripheral blood, which were collected from the corresponding patients prior to surgery...
May 2017: Oncology Letters
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