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https://www.readbyqxmd.com/read/28427238/clinical-features-and-treatment-outcome-of-non-small-cell-lung-cancer-nsclc-patients-with-uncommon-or-complex-epidermal-growth-factor-receptor-egfr-mutations
#1
Stefano Frega, Martina Lorenzi, Matteo Fassan, Stefano Indraccolo, Fiorella Calabrese, Adolfo Favaretto, Laura Bonanno, Valentina Polo, Giulia Zago, Francesca Lunardi, Ilaria Attili, Alberto Pavan, Massimo Rugge, Valentina Guarneri, PierFranco Conte, Giulia Pasello
INTRODUCTION: Tyrosine-kinase inhibitors (TKIs) represent the best treatment for advanced non-small cell lung cancer (NSCLC) with common exon 19 deletion or exon 21 epidermal growth factor receptor mutation (EGFRm). This is an observational study investigating epidemiology, clinical features and treatment outcome of NSCLC cases harbouring rare/complex EGFRm. RESULTS: Among 764 non-squamous NSCLC cases with known EGFRm status, 26(3.4%) harboured rare/complex EGFRm...
March 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427224/ponatinib-promotes-a-g1-cell-cycle-arrest-of-merlin-nf2-deficient-human-schwann-cells
#2
Alejandra M Petrilli, Jeanine Garcia, Marga Bott, Stephani Klingeman Plati, Christine T Dinh, Olena R Bracho, Denise Yan, Bing Zou, Rahul Mittal, Fred F Telischi, Xue-Zhong Liu, Long-Sheng Chang, D Bradley Welling, Alicja J Copik, Cristina Fernández-Valle
Neurofibromatosis type 2 (NF2) is a genetic syndrome that predisposes individuals to multiple benign tumors of the central and peripheral nervous systems, including vestibular schwannomas. Currently, there are no FDA approved drug therapies for NF2. Loss of function of merlin encoded by the NF2 tumor suppressor gene leads to activation of multiple mitogenic signaling cascades, including platelet-derived growth factor receptor (PDGFR) and SRC in Schwann cells. The goal of this study was to determine whether ponatinib, an FDA-approved ABL/SRC inhibitor, reduced proliferation and/or survival of merlin-deficient human Schwann cells (HSC)...
March 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427216/the-challenge-in-treating-locally-recurrent-t3-4-nasopharyngeal-carcinoma-the-survival-benefit-and-severe-late-toxicities-of-re-irradiation-with-intensity-modulated-radiotherapy
#3
Yun-Ming Tian, Wei-Zeng Huang, Xia Yuan, Li Bai, Chong Zhao, Fei Han
BACKGROUND: Effective treatments for patients with advanced locally recurrent nasopharyngeal carcinoma (NPC) are limited. This investigation was to determine the potential benefits from re-irradiation by intensity-modulated radiotherapy (IMRT) on survival and the effects of severe late toxicities. METHODS: A retrospective study was conducted in 245 patients diagnosed with locally recurrent T3-T4 NPC who had undergone re-irradiation with IMRT. Follow-up data was colletedand factors associated with survival and severe late toxicities were analyzed...
March 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427213/clinical-benefit-of-continuing-crizotinib-therapy-after-initial-disease-progression-in-chinese-patients-with-advanced-alk-rearranged-non-small-cell-lung-cancer
#4
Xiangchan Hong, Qi Chen, Lingyu Ding, Ying Liang, Ningning Zhou, Wenfeng Fang, Xinru Chen, Haiying Wu
PURPOSE: Although most patients with ALK-positive non‒small-cell lung cancer (NSCLC) who benefit from treatment with crizotinib ultimately develop progressive disease (PD), continuing crizotinb beyond the initial PD (CBPD) in these patients may be beneficial. In this study, we investigated whether Chinese patients with advanced ALK-positive NSCLC benefit from CBPD, and whether any factors are predictive of a longer post-initial progression-free survival time (PFS2). MATERIALS AND METHODS: Data on 33 patients with ALK-positive NSCLC who achieved disease control with crizotinib were analyzed retrospectively...
March 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427205/mns16a-tandem-repeat-minisatellite-of-human-telomerase-gene-functional-studies-in-colorectal-lung-and-prostate-cancer
#5
Philipp Hofer, Cornelia Zöchmeister, Christian Behm, Stefanie Brezina, Andreas Baierl, Angelina Doriguzzi, Vanita Vanas, Klaus Holzmann, Hedwig Sutterlüty-Fall, Andrea Gsur
MNS16A, a functional polymorphic tandem repeat minisatellite, is located in the promoter region of an antisense transcript of the human telomerase reverse transcriptase gene. MNS16A promoter activity depends on the variable number of tandem repeats (VNTR) presenting varying numbers of transcription factor binding sites for GATA binding protein 1. Although MNS16A has been investigated in multiple cancer epidemiology studies with incongruent findings, functional data of only two VNTRs (VNTR-243 and VNTR-302) were available thus far, linking the shorter VNTR to higher promoter activity...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427200/idh1-r132h-mutation-regulates-glioma-chemosensitivity-through-nrf2-pathway
#6
Kaishu Li, Leping Ouyang, Mingliang He, Ming Luo, Wangqing Cai, Yalin Tu, Rongbiao Pi, Anmin Liu
PURPOSE: Numerous studies have reported that glioma patients with isocitrate dehydrogenase 1(IDH1) R132H mutation are sensitive to temozolomide treatment. However, the mechanism of IDH1 mutations on the chemosensitivity of glioma remains unclear. In this study, we investigated the role and the potential mechanism of Nrf2 in IDH1 R132H-mediated drug resistance. METHODS: Wild type IDH1 (R132H-WT) and mutant IDH1 (R132H) plasmids were constructed. Stable U87 cells and U251 cells overexpressing IDH1 were generated...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427198/hypoxia-activates-placental-growth-factor-expression-in-lymphatic-endothelial-cells
#7
Laura Tudisco, Augusto Orlandi, Valeria Tarallo, Sandro De Falco
Placental growth factor (PlGF), a proangiogenic member of vascular endothelial growth family, is active during pathological conditions like cancer, metastasis formation and hind limb ischemia and in wound healing. Endothelial cells express PlGF and hypoxia positively modulates in vitro its expression. To verify whether hypoxia modulates PlGF expression in different cellular contexts and in vivo, we first analyzed five human and five mouse cancer cell lines showing that in eight of them hypoxia positively modulates PlGF...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427196/breast-cancer-subtypes-predict-the-preferential-site-of-distant-metastases-a-seer-based-study
#8
Qi Wu, Juanjuan Li, Shan Zhu, Juan Wu, Chuang Chen, Qian Liu, Wen Wei, Yimin Zhang, Shengrong Sun
BACKGROUND AND AIMS: This study aimed to access possible relationships between breast cancer subtypes and sites of distant metastasis in breast cancer. RESULTS: A total of 243,896 patients, including 226,451 cases in control groups were identified. Bone metastasis was found in 8848 cases, compared with 1,000 brain metastasis cases, 3434 liver metastasis cases and 4167 lung metastasis cases. Patients with all subtypes were most prone to bone metastases, the incidence of bone metastasis in HR+/HER2+ subtype was up to 5...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427186/microrna-494-promotes-apoptosis-and-extracellular-matrix-degradation-in-degenerative-human-nucleus-pulposus-cells
#9
Liang Kang, Cao Yang, Yu Song, Kangcheng Zhao, Wei Liu, Wenbin Hua, Kun Wang, Ji Tu, Shuai Li, Huipeng Yin, Yukun Zhang
PURPOSE: This study investigated the expression and function of the microRNA-494 in intervertebral disc degeneration (IDD). RESULTS: MicroRNA-494 expression was upregulated during IDD progression; its overexpression increased the expression of ECM catabolic factors such as matrix metalloproteinase and A disintegrin and metalloproteinase with thrombospondin motif in NP cells while decreasing that of anabolic genes such as type II collagen and aggrecan; it also induced the apoptosis of NP cells, as determined by flow cytometry...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427184/kpnb1-mediated-nuclear-import-is-required-for-motility-and-inflammatory-transcription-factor-activity-in-cervical-cancer-cells
#10
Tamara Stelma, Virna D Leaner
Karyopherin β1 is a nuclear import protein involved in the transport of proteins containing a nuclear localisation sequence. Elevated Karyopherin β1 expression has been reported in cancer and transformed cells and is essential for cancer cell proliferation and survival. Transcription factors such as NFĸB and AP-1 contain a nuclear localisation sequence and initiate the expression of multiple factors associated with inflammation and cancer cell biology. Our study investigated the effect of inhibiting nuclear import via Karyopherin β1 on cancer cell motility and inflammatory signaling using siRNA and the novel small molecule, Inhibitor of Nuclear Import-43, INI-43...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427174/association-of-immunologic-markers-from-complete-blood-counts-with-the-response-to-preoperative-chemoradiotherapy-and-prognosis-in-locally-advanced-rectal-cancer
#11
Sung Woo Jung, In Ja Park, Se Heon Oh, Seung-Seop Yeom, Jong Lyul Lee, Yong Sik Yoon, Chan Wook Kim, Seok-Byung Lim, Jung Bok Lee, Chang Sik Yu, Jin Cheon Kim
We investigated retrospectively whether immunologic markers from a complete blood count (CBC) are associated with the responsiveness to preoperative chemoradiotherapy (PCRT) and oncologic outcomes in 984 patients with locally advanced rectal cancer (LARC) who also underwent radical surgery from 2005 to 2013. CBC parameters including the neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), and platelet to lymphocyte ratio (PLR) were recorded. Pathologic responses to PCRT were evaluated in the resected specimens using the tumor regression grade system...
February 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427172/the-amelioration-of-cartilage-degeneration-by-photo-crosslinked-gelha-hydrogel-and-crizotinib-encapsulated-chitosan-microspheres
#12
Pengfei Chen, Sheng Mei, Chen Xia, Ren Zhu, Yichuan Pang, Jiying Wang, Jianfeng Zhang, Fangchun Shao, Shunwu Fan
The present study aimed to investigate the synergistic therapeutic effect of decreaseing cartilage angiogenesis via exposure to crizotinib encapsulated by chitosan microspheres and photo-crosslinked hydrogel, with the goal of evaluating crizotinib as a treatment for osteoarthritis. First, we developed and evaluated the characteristics of hydrogels and chitosan microspheres. Next, we measured the effect of crizotinib on the cartilage degeneration induced by interleukin-1β in chondrocytes. Crizotinib ameliorated the pathological changes induced by interleukin-1β via its anti-angiogenesis function...
February 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427157/the-anti-tumor-efficacy-of-3c23k-a-glyco-engineered-humanized-anti-misrii-antibody-in-an-ovarian-cancer-model-is-mainly-mediated-by-engagement-of-immune-effector-cells
#13
Pauline Estupina, Alexandre Fontayne, Jean-Marc Barret, Nathalie Kersual, Olivier Dubreuil, Marion Le Blay, Alexandre Pichard, Marta Jarlier, Martine Pugnière, Maëva Chauvin, Thierry Chardès, Jean-Pierre Pouget, Emmanuel Deshayes, Alexis Rossignol, Toufik Abache, Christophe de Romeuf, Aurélie Terrier, Lucie Verhaeghe, Christine Gaucher, Jean-François Prost, André Pèlegrin, Isabelle Navarro-Teulon
Ovarian cancer is the leading cause of death in women with gynecological cancers and despite recent advances, new and more efficient therapies are crucially needed. Müllerian Inhibiting Substance type II Receptor (MISRII, also named AMHRII) is expressed in most ovarian cancer subtypes and is a novel potential target for ovarian cancer immunotherapy. We previously developed and tested 12G4, the first murine monoclonal antibody (MAb) against human MISRII. Here, we report the humanization, affinity maturation and glyco-engineering steps of 12G4 to generate the Fc-optimized 3C23K MAb, and the evaluation of its in vivo anti-tumor activity...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427136/-effects-and-related-mechanism-of-bivalirudin-on-the-survival-of-random-skin-flap-on-the-back-of-rat
#14
L Y Cai, T Wang, D S Lin, D Lu
Objective: To investigate the effects and related mechanism of bivalirudin on the survival of random skin flap on the back of rat. Methods: Thirty SD rats were divided into bivalirudin group and normal saline group according to the random number table, with 15 rats in each group. The random flap model with size of 9 cm×3 cm was reproduced on the back of rats in two groups. Immediately post injury, rats in bivalirudin group were intraperitoneally injected with 5 mg/mL bivalirudin (0.8 mL/kg), while rats in normal saline group were intraperitoneally injected with normal saline (0...
April 20, 2017: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/28427134/-role-of-bone-marrow-tyrosine-kinase-on-chromosome-x-in-the-production-of-pro-inflammatory-cytokines-from-mouse-mononuclear-macrophages-raw264-7-induced-by-endotoxin-lipopolysaccharide-and-its-mechanism
#15
X Fang, Y Hu, Y Wang, S Liu, F Wang, X L Chen
Objective: To investigate the role of bone marrow tyrosine kinase on chromosome X (BMX) in the production of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) from mouse mononuclear-macrophages induced by endotoxin/lipopolysaccharide (LPS) and its related mechanism. Methods: Mouse mononuclear-macrophages RAW264.7 were inoculated in 6-well plates and routinely cultured for the following experiments. (1) Cells were collected and divided into blank control group, LPS control group, and 75, 750, 7 500, 75 000 nmol/L BMX-IN-1 pretreatment groups according to the random number table, with 8 wells in each group...
April 20, 2017: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/28427124/-contemporary-use-of-ticagrelor-in-patients-with-acute-coronary-syndrome-after-discharge
#16
J Liu, H B Yan, L Song, Y H Hua, H J Zhao, C Liu, P Zhou, J N Li, Y Tan, Y M Yang, Y Wu
Objective: To investigate the degree and determinants of using ticagrelor among discharged patients with acute coronary syndrome (ACS). Methods: Patients with ACS in Fuwai hospital who were given ticagrelor after discharge between Jan. 2015 to Jun. 2015 were analyzed.The clinical characteristics and adherence to ticagrelor of these patients were collected by reviewing the electronic medical records and telephone interview.Date were statistically-analyzed. Results: Among all screened 404 patients, 158 (39.1%) patients prematurely stopped ticagrelor within 12 months, while 119(29...
April 18, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28427101/tanshinol-alleviates-osteoporosis-and-myopathy-in-glucocorticoid-treated-rats
#17
Guanghua Chen, Xinle Zhang, Han Lin, Guizhi Huang, Yahui Chen, Liao Cui
Tanshinol is a major water-soluble active component of Salvia miltiorrhiza. In this study, we aimed to investigate whether tanshinol has potential therapeutic effects against glucocorticoid-induced osteoporosis and glucocorticoid-induced myopathy. Ninety-six female Sprague-Dawley rats were randomly assigned to five groups: a control group, a model group, and three model groups treated with 25 or 50 mg/kg of tanshinol, or calcitriol. All model groups received prednisone acetate for 90 days to induce glucocorticoid-induced osteoporosis...
April 20, 2017: Planta Medica
https://www.readbyqxmd.com/read/28427067/intravitreal-aflibercept-in-diabetic-macular-edema-long-term-outcomes
#18
Ugo Introini, Giuseppe Casalino
For decades, macular laser photocoagulation has been the standard of care in the treatment of diabetic macular edema (DME). With the relatively recent advent of anti-vascular endothelial growth factor (VEGF) agents, DME treatment has entered a new era. VEGF is a well-known pro-angiogenic and pro-permeability factor involved in the pathogenesis of DME. VEGF blockade has proven remarkably effective at reducing DME and improving visual acuity (VA) in eyes with center involved DME causing VA loss in several randomized controlled trials (RCTs)...
2017: Developments in Ophthalmology
https://www.readbyqxmd.com/read/28427061/emerging-insights-into-pathogenesis
#19
Edoardo Midena, Elisabetta Pilotto
Diabetic retinopathy (DR) is a frequent complication of diabetes mellitus (DM). Persistent hyperglycemia leads to the activation of multiple cellular pathways involved in the pathogenesis of DR, resulting in increased inflammation, oxidative stress, and vascular dysfunction. DR has been considered a "chronic, low-grade inflammatory disease of the retina". However, an increasing body of evidence suggests that inflammation and neurodegeneration both occur in human diabetes even before the development of clinical signs of DR...
2017: Developments in Ophthalmology
https://www.readbyqxmd.com/read/28427049/predictive-validity-of-two-physical-frailty-phenotype-specifications-developed-for-investigation-of-frailty-pathways-in-older-people
#20
Yew Yoong Ding
BACKGROUND: For investigating the relationship of frailty with physical, psychological, and social conditions on pathways, the frailty definition should ideally exclude these conditions. Based on the frailty phenotype, 2 candidate physical frailty specifications or instruments with 3 indicators, namely slowness, weakness, and exhaustion, and 4 indicators with addition of weight loss were previously developed, and had their construct and concurrent validity demonstrated. OBJECTIVE: This study seeks to evaluate the predictive validity of 2 candidate physical frailty specifications with respect to death, functional impairment, and poor quality of life in older people...
April 21, 2017: Gerontology
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