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https://www.readbyqxmd.com/read/28817834/mdm2-promotes-epithelial-mesenchymal-transition-and-metastasis-of-ovarian-cancer-skov3-cells
#1
Ying Chen, Dan-Dan Wang, Ye-Ping Wu, Dan Su, Tian-Yi Zhou, Ren-Hua Gai, Ying-Ying Fu, Lin Zheng, Qiao-Jun He, Hong Zhu, Bo Yang
BACKGROUND: Metastasis accounts for the most lethal reason for the death of ovarian cancer patients, but remains largely untreated. Epithelial-mesenchymal transition (EMT) is critical for the conversion of early-stage ovarian tumours into metastatic malignancies. Thus the exploration of the signalling pathways promoting EMT would open potential opportunities for the treatment of metastatic ovarian cancer. Herein, the putative role of MDM2 in regulating EMT and metastasis of ovarian cancer SKOV3 cells was investigated...
August 17, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28817807/mir-21-promotes-cardiac-fibrosis-after-myocardial-infarction-via-targeting-smad7
#2
Jinxia Yuan, Hongtao Chen, Dawei Ge, Yu Xu, Haihua Xu, Yang Yang, Ming Gu, Yuhe Zhou, Jingdong Zhu, Ting Ge, Qun Chen, Yue Gao, Yanqing Wang, Xiaowei Li, Yanfang Zhao
BACKGROUND/AIMS: Cardiac fibrosis after myocardial infarction (MI) has been identified as an important factor in the deterioration of heart function. Previous studies have demonstrated that miR-21 plays an important role in various pathophysiological processes in the heart. However, the role of miR-21 in fibrosis regulation after MI remains unclear. METHODS: To induce cardiac infarction, the left anterior descending coronary artery was permanently ligated of mice...
August 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28817720/targeting-of-cdk9-with-indirubin-3-monoxime-safely-and-durably-reduces-hiv-viremia-in-chronically-infected-humanized-mice
#3
Sandra Medina-Moreno, Thomas C Dowling, Juan C Zapata, Nhut M Le, Edward Sausville, Joseph Bryant, Robert R Redfield, Alonso Heredia
Successful propagation of HIV in the human host requires entry into a permissive cell, reverse transcription of viral RNA, integration into the human genome, transcription of the integrated provirus, and assembly/release of new virus particles. Currently, there are antiretrovirals against each of these viral steps, except for provirus transcription. An inhibitor of HIV transcription could both increase potency of treatment and suppress drug-resistant strains. Cellular cyclin-dependent kinase 9 (CDK9) serves as a cofactor for the HIV Tat protein and is required for effective transcription of the provirus...
2017: PloS One
https://www.readbyqxmd.com/read/28817677/abnormal-expression-of-nrf2-may-play-an-important-role-in-the-pathogenesis-and-development-of-adenomyosis
#4
Ning Chen, Baoying Du, Hao Zhou, Fengxian Shen, Juan Li, Zhenwei Xie
OBJECTIVE: To explore the expression level of Nrf2 in adenomyosis and study the mechanism of abnormal expression of Nrf2 in the pathogenesis of adenomyosis. METHODS: Western blot, immunohistochemistry(IHC) and real time PCR were used to measure Nrf2 expression levels in tissue and cell samples. Knockdown and overexpression of Nrf2 were used to investigate the variation of migration ability of endometrial glandular cells as well as the regulatory mechanism. RESULTS: Nrf2 protein levels were significantly higher in the eutopic and ectopic endometrial glands when compared with control cases using IHC and western blot methods...
2017: PloS One
https://www.readbyqxmd.com/read/28817675/deaths-during-tuberculosis-treatment-among-paediatric-patients-in-a-large-tertiary-hospital-in-nigeria
#5
Aishatu L Adamu, Muktar H Aliyu, Najiba Aliyu Galadanci, Baba Maiyaki Musa, Muktar A Gadanya, Auwalu U Gajida, Taiwo G Amole, Imam W Bello, Safiya Gambo, Ibrahim Abubakar
BACKGROUND: Despite availability of effective cure, tuberculosis (TB) remains a leading cause of death in children. In many high-burden countries, childhood TB is underdiagnosed and underreported, and care is often accessed too late, resulting in adverse treatment outcomes. In this study, we examined the time to death and its associated factors among a cohort of children that commenced TB treatment in a large treatment centre in northern Nigeria. METHODS: This is a retrospective cohort study of children that started TB treatment between 2010 and 2014...
2017: PloS One
https://www.readbyqxmd.com/read/28817601/bortezomib-initiates-endoplasmic-reticulum-stress-elicits-autophagy-and-death-in-echinococcus-granulosus-larval-stage
#6
María Celeste Nicolao, Julia A Loos, Christian Rodriguez Rodrigues, Viviana Beas, Andrea C Cumino
Cystic echinococcosis (CE) is a worldwide distributed helminthic zoonosis caused by Echinococcus granulosus. Benzimidazole derivatives are currently the only drugs for chemotherapeutic treatment of CE. However, their low efficacy and the adverse effects encourage the search for new therapeutic targets. We evaluated the in vitro efficacy of Bortezomib (Bz), a proteasome inhibitor, in the larval stage of the parasite. After 96 h, Bz showed potent deleterious effects at a concentration of 5 μM and 0.5 μM in protoscoleces and metacestodes, respectively (P < 0...
2017: PloS One
https://www.readbyqxmd.com/read/28817585/selecting-targets-for-the-diagnosis-of-schistosoma-mansoni-infection-an-integrative-approach-using-multi-omic-and-immunoinformatics-data
#7
Gardenia B F Carvalho, Daniela M Resende, Liliane M V Siqueira, Marcelo D Lopes, Débora O Lopes, Paulo Marcos Z Coelho, Andréa Teixeira-Carvalho, Jeronimo C Ruiz, Cristina T Fonseca
In order to effectively control and monitor schistosomiasis, new diagnostic methods are essential. Taking advantage of computational approaches provided by immunoinformatics and considering the availability of Schistosoma mansoni predicted proteome information, candidate antigens of schistosomiasis were selected and used in immunodiagnosis tests based on Enzime-linked Immunosorbent Assay (ELISA). The computational selection strategy was based on signal peptide prediction; low similarity to human proteins; B- and T-cell epitope prediction; location and expression in different parasite life stages within definitive host...
2017: PloS One
https://www.readbyqxmd.com/read/28817550/role-of-microrna-93-i-in-pathogenesis-of-left-ventricular-remodeling-via-targeting-cyclin-d1
#8
Jingjing Zhang, Li Qin, Ling Han, Ying Zhao, Hongfeng Jing, Wei Song, Haili Shi
BACKGROUND The objective of this study was to identify the pathway responsible for ventricular remodeling. MATERIAL AND METHODS We collected remodeling myocardium tissue (n=18) and control myocardium tissue (n=22), and detected the expression of 4 miRNAs in these 2 groups using real-time PCR. We then searched the miRNA database online to find the candidate genes of miR-93. Real-time PCR and Western blot analysis were used to confirm the regulatory relationship. RESULTS We found that only miR-93 was decreased in remodeling myocardium tissue, and validated CCND1 to be the direct target gene of miR-93, with the "seed sequence" located within the 3'-UTR of the target gene via luciferase reporter assay system...
August 17, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28817465/new-insights-into-the-recognition-classification-and-management-of-systemic-sclerosis-associated-pulmonary-hypertension
#9
Christopher J Mullin, Stephen C Mathai
PURPOSE OF REVIEW: Pulmonary hypertension is a common complication of systemic sclerosis (SSc), and remains a leading cause of morbidity and mortality. We will review recent developments in the recognition, classification and treatment of pulmonary hypertension in SSc. RECENT FINDINGS: Advances in screening for pulmonary arterial hypertension (PAH) and use of exercise haemodynamics may help to identify pulmonary vascular disease earlier in SSc. Recent studies have led to changes in recommendations for adjunct therapy and selection of pulmonary vasodilators for the treatment of SSc-associated PAH...
August 16, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28817464/biologics-for-idiopathic-inflammatory-myopathies
#10
Siamak Moghadam-Kia, Rohit Aggarwal, Chester V Oddis
PURPOSE OF REVIEW: As treatment of refractory cases of idiopathic inflammatory myopathies (IIMs) has been challenging, there is growing interest in assessing novel biologics that target various pathways implicated in the pathogenesis of IIM. RECENT FINDINGS: In the largest clinical trial in adult and juvenile IIM assessing the effectiveness of rituximab, the primary outcome was not met but 83% of this refractory group of IIM patients met a predefined definition of improvement and rituximab demonstrated a significant glucocorticoid-sparing effect...
August 16, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28817456/role-of-various-semiquantitative-parameters-of-18f-fdg-pet-ct-studies-for-interim-treatment-response-evaluation-in-non-small-cell-lung-cancer
#11
Akshima Sharma, Anant Mohan, Ashu Seith Bhalla, Sreenivas Vishnubhatla, Anil Kumar Pandey, Chandra Sekhar Bal, Rakesh Kumar
PURPOSE: The aim of this study was to prospectively evaluate the role of various semiquantitative parameters obtained from fluorine-18 fluorodeoxyglucose (F-FDG) PET/CT in interim treatment response assessment in biopsy-proven non-small-cell lung cancer (NSCLC) and to find the best parameter, if any. MATERIALS AND METHODS: Totally, 32 patients (male/female: 25/7) with biopsy proven NSCLC and a mean age of 54.71±12.65 years were enrolled in the study. Each patient underwent whole-body F-FDG PET/CT scan after injecting 5...
August 16, 2017: Nuclear Medicine Communications
https://www.readbyqxmd.com/read/28817445/the-safety-of-pembrolizumab-in-metastatic-melanoma-and-rheumatoid-arthritis
#12
Akshjot Puri, Jade Homsi
Immunotherapy has been in use for the treatment of melanoma since a very long time, but only recently have the cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody ipilimumab and programmed cell death-1 inhibitors such as nivolimumab and pembrolizumab been shown to induce marked improvements in survival in patients with metastatic melanoma. An important concern arises in terms of the safety of the use of these agents in patients with autoimmune diseases, solid organ transplant recipients on immunosuppression, patients with a history of previous hepatitis B or C, and patients with HIV infections as these patients were excluded from pivotal immunotherapy studies...
August 16, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28817418/neuromodulation-and-neurofeedback-treatments-in-eating-disorders-and-obesity
#13
Bethan Dalton, Iain C Campbell, Ulrike Schmidt
PURPOSE OF REVIEW: Psychological interventions are the treatment of choice for most eating disorders; however, significant proportions of patients do not recover with these. Advances in understanding of the neurobiology of eating disorders have led to the development of targeted treatments, such as deep brain stimulation (DBS), noninvasive brain stimulation (NIBS), and neurofeedback. We review the emerging clinical evidence for the use of these interventions in eating disorders and obesity, together with their theoretical rationale...
August 16, 2017: Current Opinion in Psychiatry
https://www.readbyqxmd.com/read/28817385/novel-molecular-defects-associated-with-very-early-onset-inflammatory-bowel
#14
Sara Ciullini Mannurita, Eleonora Gambineri
PURPOSE OF REVIEW: Immune dysregulation disorders present with common clinical features of multiorgan autoimmunity. Gastrointestinal involvement is the hallmark of an impaired immune homeostasis. This review will give an overview on the novel phenotypes, highlighting the major points that will help to enable early diagnosis and treatment. RECENT FINDINGS: The rapid progress on DNA sequencing technologies have led to the identification of monogenic defects that adversely impact the control of immune homeostasis...
August 16, 2017: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28817373/cabozantinib-as-salvage-therapy-for-patients-with-tyrosine-kinase-inhibitor-refractory-differentiated-thyroid-cancer-results-of-a-multicenter-phase-ii-international-thyroid-oncology-group-trial
#15
Maria E Cabanillas, Jonas A de Souza, Susan Geyer, Lori J Wirth, Michael E Menefee, Stephen V Liu, Komal Shah, John Wright, Manisha H Shah
Purpose Sorafenib and lenvatinib are oral multikinase inhibitors targeting vascular endothelial growth factor receptor (VEGFR) and approved for radioiodine (RAI)-refractory differentiated thyroid cancer (DTC). However, there are no approved second- or third-line therapies. MET is implicated in resistance to VEGFR inhibitors. Cabozantinib is an oral multikinase inhibitor targeting MET in addition to VEGFR and is approved for medullary thyroid cancer. In a phase I study of cabozantinib, five of eight patients with DTC previously treated with a VEGFR-targeted therapy had an objective response to cabozantinib...
August 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28817371/phase-i-ii-trial-of-labetuzumab-govitecan-anti-ceacam5-sn-38-antibody-drug-conjugate-in-patients-with-refractory-or-relapsing-metastatic-colorectal-cancer
#16
Efrat Dotan, Steven J Cohen, Alexander N Starodub, Christopher H Lieu, Wells A Messersmith, Pamela S Simpson, Michael J Guarino, John L Marshall, Richard M Goldberg, J Randolph Hecht, William A Wegener, Robert M Sharkey, Serengulam V Govindan, David M Goldenberg, Jordan D Berlin
Purpose The objectives were to evaluate dosing schedules of labetuzumab govitecan, an antibody-drug conjugate targeting carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) for tumor delivery of 7-ethyl-10-hydroxycamptothecin (SN-38), in an expanded phase II trial of patients with relapsed or refractory metastatic colorectal cancer. Patients and Methods Eligible patients with at least one prior irinotecan-containing therapy received labetuzumab govitecan once weekly at 8 and 10 mg/kg, or two times per week at 4 and 6 mg/km on weeks 1 and 2 of 3-week repeated cycles...
August 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28817370/conko-005-adjuvant-chemotherapy-with-gemcitabine-plus-erlotinib-versus-gemcitabine-alone-in-patients-after-r0-resection-of-pancreatic-cancer-a-multicenter-randomized-phase-iii-trial
#17
Marianne Sinn, Marcus Bahra, Torsten Liersch, Klaus Gellert, Helmut Messmann, Wolf Bechstein, Dirk Waldschmidt, Lutz Jacobasch, Martin Wilhelm, Bettina M Rau, Robert Grützmann, Arndt Weinmann, Georg Maschmeyer, Uwe Pelzer, Jens M Stieler, Jana K Striefler, Michael Ghadimi, Sven Bischoff, Bernd Dörken, Helmut Oettle, Hanno Riess
Purpose Gemcitabine is standard of care in the adjuvant treatment of resectable pancreatic ductal adenocarcinoma (PDAC). The epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in combination with gemcitabine has shown efficacy in the treatment of advanced PDAC and was considered to improve survival in patients with primarily resectable PDAC after R0 resection. Patients and Methods In an open-label, multicenter trial, patients were randomly assigned to one of two study arms: gemcitabine 1,000 mg/m(2) days 1, 8, 15, every 4 weeks plus erlotinib 100 mg once per day (GemErlo) or gemcitabine (Gem) alone for six cycles...
August 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28817343/suppression-of-choroidal-neovascularization-in-mice-by-subretinal-delivery-of-multigenic-lentiviral-vectors-encoding-anti-angiogenic-micrornas
#18
Anne Louise Askou, Josephine Natalia Esther Benckendorff, Andreas Holmgaard, Tina Storm, Lars Aagaard, Toke Bek, Jacob Giehm Mikkelsen, Thomas Juhl Corydon
Lentivirus-based vectors have been used for the development of potent gene therapies. Here, application of a multigenic lentiviral vector (LV) producing multiple anti-angiogenic microRNAs following subretinal delivery in a laser-induced choroidal neovascularization (CNV) mouse model is presented. This versatile LV, carrying back-to-back RNApolII-driven expression cassettes, enables combined expression of microRNAs targeting vascular endothelial growth factor A (Vegfa) mRNA and fluorescent reporters. In addition, by including a vitelliform macular dystrophy 2 (VMD2) promoter, expression of microRNAs is restricted to the retinal pigment epithelial (RPE) cells...
August 2017: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/28817313/ccr7-mediates-tgf-%C3%AE-1-induced-human-malignant-glioma-invasion-migration-and-epithelial-mesenchymal-transition-by-activating-mmp2-9-through-the-nuclear-factor-kappab-signaling-pathway
#19
Yanyan Zheng, Yiting Miu, Xiaokai Yang, Xiaoguo Yang, Meijia Zhu
Chemokine receptor 7 (CCR7) has emerged as an inducer of invasion, migration, and epithelial-mesenchymal transition (EMT) in cancer. In this research, human malignant glioma cells were stimulated with transforming growth factor beta 1 (TGF-β1) and siCCR7. The data show that CCR7 mediates TGF-β1-induced EMT, migration, and invasion in U251 and U87 cells and that these effects of TGF-β1 were reversed by treatment with siCCR7 or a CCR7 neutralizing antibody. Importantly, the TGF-β1-mediated increase in nuclear factor kappaB (NF-κB) activity in human glioma cells was reduced by treatment with siCCR7 or a CCR7 neutralizing antibody...
August 17, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28817303/chrna7-deletions-are-enriched-in-risperidone-treated-children-and-adolescents
#20
Madelyn A Gillentine, Janson J White, Christopher M Grochowski, James R Lupski, Christian P Schaaf, Chadi A Calarge
OBJECTIVE: Aggression is among the most common indications for referral to child and adolescent mental health services and is often challenging to treat. Understanding the biological underpinnings of aggression could help optimize treatment efficacy. Neuronal nicotinic acetylcholine receptors (nAChRs), specifically the α7 nAChR, encoded by the gene CHRNA7, have been implicated in aggressive behaviors in animal models as well as humans. Copy number variants (CNVs) of CHRNA7 are found in individuals with neuropsychiatric disorders, often with comorbid aggression...
August 17, 2017: Journal of Child and Adolescent Psychopharmacology
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