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https://www.readbyqxmd.com/read/28941356/computational-approaches-to-identify-genetic-interactions-for-cancer-therapeutics
#1
Graeme Benstead-Hume, Sarah K Wooller, Frances M G Pearl
The development of improved cancer therapies is frequently cited as an urgent unmet medical need. Here we describe how genetic interactions are being therapeutically exploited to identify novel targeted treatments for cancer. We discuss the current methodologies that use 'omics data to identify genetic interactions, in particular focusing on synthetic sickness lethality (SSL) and synthetic dosage lethality (SDL). We describe the experimental and computational approaches undertaken both in humans and model organisms to identify these interactions...
September 23, 2017: Journal of Integrative Bioinformatics
https://www.readbyqxmd.com/read/28938700/liver-cancers-with-stem-progenitor-cell-features-a-rare-chemotherapy-sensitive-malignancy
#2
Bruno Christian Köhler, Nina Waldburger, Kai Schlamp, Dirk Jäger, Karl Heinz Weiss, Henning Schulze-Bergkamen, Peter Schirmacher, Christoph Springfeld
Primary liver tumors are a heterogeneous group of malignancies. Besides classical hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC), combined and intermediate forms of liver cancer exist and can express stem-cell markers like nuclear cell adhesion molecule (NCAM-1/CD56), c-kit (CD117) or epithelial cell adhesion molecule (EpCAM) together with high proliferative activity. Liver tumors with progenitor-cell features are associated with an unfavorable prognosis, but the phenotype has not resulted in therapeutic consequences so far...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938691/concomitant-eml4-alk-rearrangement-and-egfr-mutation-in-non-small-cell-lung-cancer-patients-a-literature-review-of-100-cases
#3
REVIEW
Giuseppe Lo Russo, Martina Imbimbo, Giulia Corrao, Claudia Proto, Diego Signorelli, Milena Vitali, Monica Ganzinelli, Laura Botta, Nicoletta Zilembo, Filippo de Braud, Marina Chiara Garassino
The discovery of EGFR mutations and EML4-ALK gene rearrangements has radically changed the therapeutic scenario for patients with advanced non-small cell lung cancer. ALK and EGFR tyrosine-kinase inhibitors showed better activity and efficacy than standard chemotherapy in the first and second line treatment settings, leading to a clear advantage in overall survival of advanced non-small cell lung cancer patients harboring these genetic alterations. Historically the coexistence of EGFR mutations and EML4-ALK rearrangements in the same tumor has been described as virtually impossible...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938688/drag-reducing-polymers-decrease-hepatic-injury-and-metastases-after-liver-ischemia-reperfusion
#4
Samer Tohme, Marina V Kameneva, Hamza O Yazdani, Vikas Sud, Julie Goswami, Patricia Loughran, Hai Huang, Richard L Simmons, Allan Tsung
INTRODUCTION: Surgery, a crucial therapeutic modality in the treatment of solid tumors, can induce sterile inflammatory processes which can result in metastatic progression. Liver ischemia and reperfusion (I/R) injury, an inevitable consequence of hepatic resection of metastases, has been shown to foster hepatic capture of circulating cancer cells and accelerate metastatic growth. Efforts to reduce these negative consequences have not been thoroughly investigated. Drag reducing polymers (DRPs) are blood-soluble macromolecules that can, in nanomolar concentrations, increase tissue perfusion, decrease vascular resistance and decrease near-wall microvascular concentration of neutrophils and platelets thereby possibly reducing the inflammatory microenvironment...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938687/mediastinal-lesions-across-the-age-spectrum-a-clinicopathological-comparison-between-pediatric-and-adult-patients
#5
Tingting Liu, Lika'a Fasih Y Al-Kzayer, Xiao Xie, Hua Fan, Shamil Naji Sarsam, Yozo Nakazawa, Lei Chen
The objective of this study was to identify the differences in histopathological distribution and clinical features of mediastinal lesions (MLs) across the age spectrum in Chinese series of patients and to compare with the available literature. A total of 409 cases of MLs, including 137 pediatric and 272 adult patients from a single institution, was reviewed and categorized into groups according to age. Among the 409 cases, the age showed a bimodal distribution with an increased incidence of MLs among (< 10 year) and (60-< 70 year) age groups...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938622/profiling-cancer-related-gene-mutations-in-oral-squamous-cell-carcinoma-from-japanese-patients-by-targeted-amplicon-sequencing
#6
Takafumi Nakagaki, Miyuki Tamura, Kenta Kobashi, Ryota Koyama, Hisayo Fukushima, Tomoko Ohashi, Masashi Idogawa, Kazuhiro Ogi, Hiroyoshi Hiratsuka, Takashi Tokino, Yasushi Sasaki
Somatic mutation analysis is a standard practice in the study of human cancers to identify mutations that cause therapeutic sensitization and resistance. We performed comprehensive genomic analyses that used PCR target enrichment and next-generation sequencing on Ion Proton semiconductor sequencers. Forty-seven oral squamous cell carcinoma (OSCC) samples and their corresponding noncancerous tissues were used for multiplex PCR amplification to obtain targeted coverage of the entire coding regions of 409 cancer-related genes (covered regions: 95...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938586/the-long-noncoding-rna-hotair-activates-the-hippo-pathway-by-directly-binding-to-sav1-in-renal-cell-carcinoma
#7
Guanghui Hu, Binbin Dong, Jingwei Zhang, Wei Zhai, Tiancheng Xie, Bisheng Huang, Chi Huang, Xudong Yao, Junhua Zheng, Jianping Che, Yun-Fei Xu
The long noncoding RNA HOTAIR promotes the development and progression of several tumors. Here, the clinical significance and role of HOTAIR in renal cell carcinoma (RCC) tumorigenesis were explored. The results showed that increased expression of HOTAIR predicted a poor prognosis of RCC after surgery. HOTAIR promoted RCC cell proliferation and growth in vitro and in vivo. The expressions of HOTAIR and Salvador homolog 1 (SAV1) were inversely correlated in clinical RCC samples. HOTAIR downregulated SAV1 by directly binding to the SAV1 protein and enhanced histone H3K27 methylation...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938584/bmpr2-promotes-invasion-and-metastasis-via-the-rhoa-rock-limk2-pathway-in-human-osteosarcoma-cells
#8
Shidong Wang, Tingting Ren, Guangjun Jiao, Yi Huang, Xing Bao, Fan Zhang, Kuisheng Liu, Bingxin Zheng, Kunkun Sun, Wei Guo
Bone morphogenetic protein receptor 2 (BMPR2) has been identified in several types of cancer. However, its role in osteosarcoma is largely unknown. We systematically investigated the role of BMPR2 in osteosarcoma cell lines, human tissue samples and xenograft models. The relationship between BMPR2 expression and osteosarcoma patients' survival was investigated by bioinformatics and clinical data. Wound healing assay and transwell assay were used to detect the changes of cell migration and invasion ability after BMPR2 transfection...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938522/mir-539-inhibits-human-colorectal-cancer-progression-by-targeting-runx2
#9
Dacheng Wen, Songhe Li, Weidong Jiang, Jiaming Zhu, Jingjing Liu, Shutao Zhao
Emerging evidence has shown that microRNAs (miRNAs) such as miR-539 play critical roles in carcinogenesis and progression in many types of cancer, including human colorectal cancer (CRC). However, the roles and underlying mechanism of miR-539 in CRC have not been well identified. The aims of this study were, therefore, to investigate the regulatory role and potential mechanism of miR-539 in human CRC. Here, we show that miR-539 expression is downregulated in CRC tissues and cell lines. The expression level of miR-539 is inversely associated with advanced clinical stage and lymph node metastasis...
September 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28938469/taming-the-flames-targeting-white-adipose-tissue-browning-in-hypermetabolic-conditions
#10
Abdikarim Abdullahi, Marc G Jeschke
In this era of increased obesity and diabetes prevalence, the browning of white adipose tissue (WAT) has emerged as a promising therapeutic target to induce weight loss and improve insulin sensitivity in this population. The browning process entails a shift in the WAT from primarily storing excess energy to the dissipation of energy as heat. However, this idealistic view of WAT browning being the saviour of the metabolic syndrome has been criticized by studies in burns and cancer patients that have shown browning to be detrimental rather than being beneficial...
August 30, 2017: Endocrine Reviews
https://www.readbyqxmd.com/read/28938419/nocturnal-urinary-excretion-of-fsh-and-lh-in-children-and-adolescents-with-normal-and-early-puberty
#11
Nanna Kolby, Alexander S Busch, Lise Aksglaede, Kaspar Sørensen, Jorgen Holm Petersen, Anna-Maria Andersson, Anders Juul
Context: Clinical use of single serum gonadotropin measurements in children is limited by the pulsatile section of FSH and LH. However, first morning voided (FMV) urine may integrate the fluctuating gonadotropin serum levels. Objective: We aimed to evaluate urinary and serum gonadotropin levels according to age, sex and pubertal stage in healthy children and to assess the clinical use of FMV urinary gonadotropins in children with disordered puberty. Design: Cross-sectional part of the COPENHAGEN Puberty study and longitudinal study of patients...
August 15, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28938397/regulation-of-orbital-fibrosis-and-adipogenesis-by-pathogenic-th17-cells-in-graves-orbitopathy
#12
Sijie Fang, Yazhuo Huang, Sisi Zhong, Yangyang Li, Yidan Zhang, Yinwei Li, Jing Sun, Xingtong Liu, Yang Wang, Shuo Zhang, Tianle Xu, Xiaodong Sun, Ping Gu, Dan Li, Huifang Zhou, Bin Li, Xianqun Fan
Context: Th17 cells are correlated with many human autoimmune disorders including Graves' disease, and may play key roles in the pathogenesis of Graves' orbitopathy (GO). Objective: To study the phenotype of Th17 cells in patients with GO and healthy subjects, investigate the fibrosis and adipogenesis in orbital fibroblasts (OFs) modulated by IL-17A, and determine the interaction between Th17 cells and OFs. Design/Setting/Participants: Blood samples and orbital tissues from GO patients and healthy controls were collected...
August 16, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28938283/effect-of-tranexamic-acid-on-transfusion-a-randomized-clinical-trial-in-acetabular-fracture-surgery
#13
William D Lack, Brett D Crist, Rachel B Seymour, William Harvin, Madhav A Karunakar
OBJECTIVES: Given the increasing evidence that minimizing blood loss and limiting allogeneic transfusion can improve patient outcome, we are performing a randomized controlled trial of the use of tranexamic acid (TXA) during acetabular fracture surgery. DESIGN: Prospective, multicenter, and randomized. SETTING: Two level I trauma centers. PARTICIPANTS: Eighty-eight patients underwent randomization, with 42 assigned to the TXA group and 46 assigned to the placebo group...
October 2017: Journal of Orthopaedic Trauma
https://www.readbyqxmd.com/read/28938252/emotional-impact-of-end-of-life-decisions-on-professional-relationships-in-the-icu-an-obstacle-to-collegiality
#14
Alexandra Laurent, Magalie Bonnet, Gilles Capellier, Pierre Aslanian, Paul Hebert
OBJECTIVES: End-of-life decisions are not only common in the ICU but also frequently elicit strong feelings among health professionals. Even though we seek to develop more collegial interprofessional approaches to care and health decision-making, there are many barriers to successfully managing complex decisions. The aim of this study is to better understand how emotions influence the end-of-life decision-making process among professionals working in ICU. DESIGN: Qualitative study with clinical interviews...
September 21, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28938234/is-early-total-care-a-safe-and-effective-alternative-to-staged-protocol-for-the-treatment-of-schatzker-iv-vi-tibial-plateau-fractures-in-patients-older-than-50-years
#15
Amrut Borade, Harish Kempegowda, Raveesh Richard, Jove Graham, Michael Suk, Daniel S Horwitz
OBJECTIVES: To compare "Early Total Care" (ETC) with "Staged Protocol" (SP) for the treatment of Schatzker IV-VI tibial plateau fractures in patients older than 50 years regarding safety and effectiveness. DESIGN: Retrospective cohort study. SETTING: An academic level 1 US trauma center. PATIENTS/PARTICIPANTS: Eighty-one patients older than 50 years with Schatzker grade IV-VI tibial plateau fractures were included. INTERVENTION: Fifty-three patients were treated under SP with immediate external fixation followed by definitive internal fixation...
September 19, 2017: Journal of Orthopaedic Trauma
https://www.readbyqxmd.com/read/28938163/tumor-cell-targeted-delivery-of-crispr-cas9-by-aptamer-functionalized-lipopolymer-for-therapeutic-genome-editing-of-vegfa-in-osteosarcoma
#16
Chao Liang, Fangfei Li, Luyao Wang, Zong-Kang Zhang, Chao Wang, Bing He, Jie Li, Zhihao Chen, Atik Badshah Shaikh, Jin Liu, Xiaohao Wu, Songlin Peng, Lei Dang, Baosheng Guo, Xiaojuan He, D W T Au, Cheng Lu, Hailong Zhu, Bao-Ting Zhang, Aiping Lu, Ge Zhang
Osteosarcoma (OS) is a highly aggressive pediatric cancer, characterized by frequent lung metastasis and pathologic bone destruction. Vascular endothelial growth factor A (VEGFA), highly expressed in OS, not only contributes to angiogenesis within the tumor microenvironment via paracrine stimulation of vascular endothelial cells, but also acts as an autocrine survival factor for tumor cell themselves, thus making it a promising therapeutic target for OS. CRISPR/Cas9 is a versatile genome editing technology and holds tremendous promise for cancer treatment...
September 13, 2017: Biomaterials
https://www.readbyqxmd.com/read/28938091/targeting-metabolism-for-cancer-therapy
#17
REVIEW
Alba Luengo, Dan Y Gui, Matthew G Vander Heiden
Metabolic reprogramming contributes to tumor development and introduces metabolic liabilities that can be exploited to treat cancer. Chemotherapies targeting metabolism have been effective cancer treatments for decades, and the success of these therapies demonstrates that a therapeutic window exists to target malignant metabolism. New insights into the differential metabolic dependencies of tumors have provided novel therapeutic strategies to exploit altered metabolism, some of which are being evaluated in preclinical models or clinical trials...
September 21, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28938090/small-molecule-targets-in-immuno-oncology
#18
REVIEW
Dashyant Dhanak, James P Edwards, Ancho Nguyen, Peter J Tummino
Advances in understanding the role and molecular mechanisms underlying immune surveillance and control of (pre)malignancies is revolutionizing clinical practice in the treatment of cancer. Presently, multiple biologic drugs targeting the immune checkpoint proteins PD(L)1 or CTLA4 have been approved and/or are in advanced stages of clinical development for many cancers. In addition, combination therapy with these agents and other immunomodulators is being intensively explored with the aim of improving primary response rates or prolonging overall survival...
September 21, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28938089/drug-discovery-and-chemical-biology-of-cancer-epigenetics
#19
REVIEW
Scott Ribich, Darren Harvey, Robert A Copeland
Comprehensive whole-exome sequencing, DNA copy-number determination, and transcriptomic analyses of diverse cancers have greatly expanded our understanding of the biology of many tumor types. In addition to mutations in the common cell-of-origin specific driver mutations, these studies have also revealed a large number of loss-of-function and gain-of-function mutations in chromatin-modifying proteins (CMPs). This has revealed that epigenetic dysregulation is a common feature of most pediatric and adult cancers...
September 21, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28938087/emerging-opportunities-for-target-discovery-in-rare-cancers
#20
REVIEW
Tanaz Sharifnia, Andrew L Hong, Corrie A Painter, Jesse S Boehm
Rare cancers pose unique challenges to research due to their low incidence. Barriers include a scarcity of tissue and experimental models to enable basic research and insufficient patient accrual for clinical studies. Consequently, an understanding of the genetic and cellular features of many rare cancer types and their associated vulnerabilities has been lacking. However, new opportunities are emerging to facilitate discovery of therapeutic targets in rare cancers. Online platforms are allowing patients with rare cancers to organize on an unprecedented scale, tumor genome sequencing is now routinely performed in research and clinical settings, and the efficiency of patient-derived model generation has improved...
September 21, 2017: Cell Chemical Biology
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