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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/28938774/evaluation-of-encapsulated-sodium-butyrate-on-growth-performance-energy-digestibility-gut-development-and-salmonella-colonization-in-broilers
#2
J D Liu, H O Bayir, D E Cosby, N A Cox, S M Williams, J Fowler
Two experiments were conducted to determine the effect of an encapsulated sodium butyrate (Na-B) with targeted releasing times on broiler performance, energy digestibility, intestinal morphology, and ceca Salmonella colonization. In experiment 1, 3 different Na-B products (CMA, CMP, and CMS) were evaluated following a challenge with a nalidixic acid-resistant Salmonella typhimurium (STNAR). Cobb-Cobb male birds were placed 8 per pen into 6 replicates for each treatment. Treatments included 6 Na-B treatments (500 and 1,000 ppm of each product) plus 2 control (non-challenged and challenged)...
October 1, 2017: Poultry Science
https://www.readbyqxmd.com/read/28938745/a-closer-look-at-expanded-carrier-screening-from-a-pgd-perspective
#3
Carolina Vaz-de-Macedo, Joyce Harper
Conventionally, the search for carrier status was based on ethnicity and/or family history and targeted to a restricted number of genetic conditions and mutations. This is now being replaced by extended panels testing for hundreds of genetic disorders with a broad range of phenotypes, in what is called 'expanded carrier screening'. While the ultimate aim of these panels is to increase the reproductive autonomy of the individuals and couples by providing preconception knowledge that could lead to the broadest range of available options, including PGD, we argue that: (i) Given the number and heterogeneity of the conditions included in panels, it cannot be guaranteed that a couple who tests positive for one of those conditions will be eligible for PGD; patients should be informed of this potential limitation before undertaking screening...
October 1, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28938672/comparing-the-clinical-efficacy-of-abiraterone-acetate-enzalutamide-and-orteronel-in-patients-with-metastatic-castration-resistant-prostate-cancer-by-performing-a-network-meta-analysis-of-eight-randomized-controlled-trials
#4
Minyong Kang, Chang Wook Jeong, Cheol Kwak, Ja Hyeon Ku, Hyeon Hoe Kim
Various novel androgen receptor (AR) targeting drugs have been developed recently and have shown beneficial effects on survival in patients with metastatic castration-resistant prostate cancer (mCRPC). However, no consensus has been reached regarding which of these agents provides the most favorable oncological outcomes. Here, we aimed to compare the efficacy of novel AR-targeted agents by performing a network meta-analysis of randomized controlled trials (RCTs). We included eight RCTs for men with mCRPC treated with one of the AR targeting agents: abiraterone acetate, enzalutamide, or orteronel...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938657/a-network-meta-analysis-on-the-efficacy-of-targeted-agents-in-combination-with-chemotherapy-for-treatment-of-advanced-metastatic-triple-negative-breast-cancer
#5
Long Ge, Yan Tang, Qiu-Ning Zhang, Jin-Hui Tian, Xiao-Hu Wang, Dawid Pieper, Bei Pan, Lun Li, Juan Ling, Zhi-Tong Bing, Ke-Hu Yang
OBJECTIVE: Our network meta-analysis aimed to determine the assistant efficacy of targeted therapy in combined with chemotherapy for advanced/metastatic triple-negative breast cancer (TNBC). RESULTS: A total of 15 randomized controlled trials (RCTs), involving 2,410 patients, met our inclusion criteria. Eight targeted agents involving 11 treatment arms were included. The methodological quality of included RCTs was acceptable. The results of direct comparisons showed that progression-free survival (PFS) was significantly longer with bevacizumab+chemotherapy when compared to chemotherapy alone (hazard ratio [HR] = 0...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938641/potential-independent-action-of-sigma-receptor-ligands-through-inhibition-of-the-kv2-1-channel
#6
Xinying Liu, Yingmei Fu, Huan Yang, Timur Mavlyutov, Jun Li, Christopher R McCurdy, Lian-Wang Guo, Bikash R Pattnaik
The sigma-1 receptor (σ1-R) and sigma-2 receptor (σ2-R) are potential drug targets for treatment of cancer, pain, depression, retinal degeneration and other neuronal diseases. Previous reports show that sigma-1 receptor modulates the activities of multiple channels. We are interested in possible sigma receptor modulation of Kv2.1, a K(+) channel abundant in retinal photoreceptors. We tested the effect of established sigma receptor ligands on Kv2.1 channels which were stably expressed in HEK293 cells. Surprisingly, σ1-R antagonists inhibited Kv2...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938633/mir-543-promotes-colorectal-cancer-proliferation-and-metastasis-by-targeting-klf4
#7
Fangbing Zhai, Chunhong Cao, Liang Zhang, Jianhua Zhang
Till now, miR-543 expression has been demonstrated to be involved in the development of some cancers. However, reports about its expression and mechanism in colorectal cancer (CRC) were conflicting [1, 2]. Here, we investigated clinical implications of miR-543 and mechanisms underlying miR-543-mediated CRC development. In this study, real-time quantitative PCR (qRT-PCR) validated miR-543 was highly expressed in CRC samples and cell lines. MiR-543 was closely associated with tumor size, TNM stage and metastasis...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938620/pathological-expression-of-tissue-factor-confers-promising-antitumor-response-to-a-novel-therapeutic-antibody-sc1-in-triple-negative-breast-cancer-and-pancreatic-adenocarcinoma
#8
Xuesai Zhang, Qingrou Li, Hui Zhao, Lanping Ma, Tao Meng, Jianchang Qian, Rui Jin, Jingkang Shen, Ker Yu
The pathological presence of tissue factor (TF) in cancer cells promotes tumor-initiated thrombosis and cancer metastasis. We found that TF is aberrantly present in large percentage of aggressive triple negative breast cancer (TNBC) and pancreatic adenocarcinoma (PaC), two most lethal forms of malignancy that urgently need effective treatment. TF expression in TNBC clustered with higher levels of vimentin, basal-type keratins KRT5/14 and caveolin-1 but lower levels of luminal-type biomarkers. We developed a novel and specific anti-TF therapeutic antibody SC1, which displayed an exceedingly high potency against TF extracellular domain (EC50: 0...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938613/high-phlpp1-expression-levels-predicts-longer-time-of-acquired-resistance-to-egfr-tyrosine-kinase-inhibitors-in-patients-with-lung-adenocarcinoma
#9
Youyou Xie, Dongqing Lv, Wei Wang, Minhua Ye, Xiaofeng Chen, Haihua Yang
BACKGROUND: In spite of an initial good response to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) in lung adenocarcinoma patients, resistance to treatment eventually occurs. Epidermal growth factor receptor (EGFR) activation stimulates Ras/Raf/Erk/MAPK and influences PI3K/Akt pathways, respectively. PHLPP negatively regulates PI3K/Akt and the RAF/RAS/ERK signaling pathways. Our study aimed to investigate the association between PH domain leucine-rich-repeats protein phosphatase (PHLPP) expression levels and the acquired resistance to EGFR TKIs in lung adenocarcinoma...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938607/hgfl-mediated-ron-signaling-supports-breast-cancer-stem-cell-phenotypes-via-activation-of-non-canonical-%C3%AE-catenin-signaling
#10
Sasha J Ruiz-Torres, Nancy M Benight, Rebekah A Karns, Elyse E Lower, Jun-Lin Guan, Susan E Waltz
Breast cancer stem cells (BCSCs), which drive tumor progression, recurrence, and metastasis, are considered a major challenge for breast cancer treatments, thus the discovery of novel pathways regulating BCSC maintenance remains essential to develop new strategies to effectively target this population and combat disease mortality. The HGFL-RON signaling is overexpressed in human breast cancers and is associated with increased breast cancer progression, metastasis, and poor prognosis. Here, we report that overexpression of RON/MST1R and HGFL/MST1 in cell lines and primary tumors increases BCSC self-renewal, numbers, and tumorigenic potential after syngeneic transplantation...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938606/oroxylin-a-inhibits-colitis-by-inactivating-nlrp3-inflammasome
#11
Wei Zhou, Xiuting Liu, Xin Zhang, Jingjing Tang, Zhiyu Li, Qing Wang, Rong Hu
NLRP3 inflammasome is a novel therapeutic target for inflammatory bowel disease (IBD). The aim of this study was to investigate the anti-inflammatory effect of a bioactive flavonoid-oroxylin A on the treatment of dextran sulfate sodium (DSS)-induced murine colitis via targeting NLRP3 inflammasome. In this study, we found that oroxylin A attenuated experimental colitis in mice, including loss of body weights, shortening of the colon lengths and infiltration of inflammatory cells. The production of IL-1β, IL-6 and TNF-α in colon was also markedly reduced by oroxylin A...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938602/activation-of-cancerous-inhibitor-of-pp2a-cip2a-contributes-to-lapatinib-resistance-through-induction-of-cip2a-akt-feedback-loop-in-erbb2-positive-breast-cancer-cells
#12
Ming Zhao, Erin W Howard, Amanda B Parris, Zhiying Guo, Qingxia Zhao, Zhikun Ma, Ying Xing, Bolin Liu, Susan M Edgerton, Ann D Thor, Xiaohe Yang
Lapatinib, a small molecule ErbB2/EGFR inhibitor, is FDA-approved for the treatment of metastatic ErbB2-overexpressing breast cancer; however, lapatinib resistance is an emerging clinical challenge. Understanding the molecular mechanisms of lapatinib-mediated anti-cancer activities and identifying relevant resistance factors are of pivotal significance. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified oncoprotein that is overexpressed in breast cancer. Our study investigated the role of CIP2A in the anti-cancer efficacy of lapatinib in ErbB2-overexpressing breast cancer cells...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938600/application-of-dual-targeting-drug-delivery-system-for-the-improvement-of-anti-glioma-efficacy-of-doxorubicin
#13
Zhenliang Sun, Xuebing Yan, YiBo Liu, Linsheng Huang, Cheng Kong, Xiao Qu, Man Wang, Renyuan Gao, Huanlong Qin
Chemotherapy of glioma is always hampered by the unsatisfactory tumor accumulation of drugs, of which the most noticeable obstacle is the limited drug permeability from vessels into tumor inner. In the present study, we developed a novel nanocarrier for the delivery of doxorubicin to brain tumor. Such novel drug delivery system was mainly composed of a tumor homing peptide and DOX-loaded PLA nanoparticles (AP1-NP-DOX). CRKRLDRNC peptide, named as AP1, was a newly glioma affinity peptide which could specifically binds to interleukin-4 receptor (IL-4R), highly expressing on both glioma cells and angiogenesis...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938567/gemcitabine-induced-heparanase-promotes-aggressiveness-of-pancreatic-cancer-cells-via-activating-egfr-signaling
#14
Jin-Wen Song, Ying-Xia Tan, Su-Bo Li, Shi-Kun Zhang, Lu-Ming Wan, Shou-Ping Ji, Hong Zhou, Zhi-Hang Zhou, Feng Gong
Pancreatic cancer (PC), characterized by aggressive local invasion and metastasis, is one of the most malignant cancers. Gemcitabine is currently used as the standard drug for the treatment of advanced and metastatic PC, but with limited efficacy. In this study, we demonstrated that gemcitabine increased the expression of heparanase (HPA1), the only known mammalian endoglycosidase capable of cleaving heparan sulfate, both in vitro and in vivo. Furthermore, overexpression of HPA1 in PC cell lines enhanced proliferation and invasion, accompanied with elevated phosphorylation of EGFR...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938563/a-novel-immunotherapy-targeting-mmp-14-limits-hypoxia-immune-suppression-and-metastasis-in-triple-negative-breast-cancer-models
#15
Binbing Ling, Kathleen Watt, Sunandan Banerjee, Daniel Newsted, Peter Truesdell, Jarrett Adams, Sachdev S Sidhu, Andrew W B Craig
Matrix metalloproteinase-14 (MMP-14) is a clinically relevant target in metastatic cancers due to its role in tumor progression and metastasis. Since active MMP-14 is localized on the cell surface, it is amenable to antibody-mediated blockade in cancer, and here we describe our efforts to develop novel inhibitory anti-MMP-14 antibodies. A phage-displayed synthetic humanized Fab library was screened against the extracellular domain of MMP-14 and a panel of MMP14-specific Fabs were identified. A lead antibody that inhibits the catalytic domain of MMP-14 (Fab 3369) was identified and treatment of MDA-MB-231 breast cancer cells with Fab 3369 led to significant loss of extracellular matrix degradation and cell invasion abilities...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938559/doxorubicin-loaded-platelets-conjugated-with-anti-cd22-mabs-a-novel-targeted-delivery-system-for-lymphoma-treatment-with-cardiopulmonary-avoidance
#16
Peipei Xu, Huaqin Zuo, Rongfu Zhou, Fan Wang, Xu Liu, Jian Ouyang, Bing Chen
B-cell lymphoma accounts for approximately 85% of all adult non-Hodgkin's lymphoma cases. Doxorubicin (DOX) is an indispensable drug for the treatment of non-Hodgkin's lymphoma. However, DOX causes severe cardiotoxicity, which limits its use in conventional treatment strategies. In this study, we developed a novel drug delivery system for lymphoma treatment: DOX-loaded platelets that were conjugated with anti-CD22 monoclonal antibodies (mAbs) (DOX-platelet-CD22). Platelets are bio- and immune-compatible drug carriers that can prolong the circulation time of drugs...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938558/human-menstrual-blood-derived-mesenchymal-stem-cells-as-a-cellular-vehicle-for-malignant-glioma-gene-therapy
#17
Xiao-Jun Wang, Bing-Yu Xiang, Ya-Hui Ding, Lu Chen, Hai Zou, Xiao-Zhou Mou, Charlie Xiang
Despite many advances in conventional treatment strategies, there is no effective treatment modality for malignant gliomas. Gene therapy may offer a promising option for gliomas and several gene therapy approaches have shown anti-tumor efficiency in previous studies. Mesenchymal stem cell-based gene therapies, in which stem cells are genetically engineered to express therapeutic molecules, have shown tremendous potential because of their innate homing ability. In this study, human menstrual blood-derived MSCs (MenSC), a novel type of multipotential MSCs displays tropism for human malignant glioma when used as a gene delivery vehicle for therapeutics...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938546/the-highly-expressed-col4a1-genes-contributes-to-the-proliferation-and-migration-of-the-invasive-ductal-carcinomas
#18
Rongzhong Jin, Jia Shen, Tiancheng Zhang, Qiliang Liu, Caihua Liao, Hailin Ma, Sijing Li, Zhaoxia Yu
BACKGROUND: Invasive ductal carcinoma is a kind of very typical breast cancer. The goal of our research was to figure out the molecular mechanism of Invasive ductal carcinoma and to find out its potential therapy targets. RESULTS: The total amount of 478 differentially expressed genes in Invasive ductal carcinoma which compared with normal breast epithelial cells were recognized. Functional enrichment analysis proved the most part of differentially expressed genes had connection with ECM-receptor interaction...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938545/overexpression-of-leptin-receptor-in-human-glioblastoma-correlation-with-vasculogenic-mimicry-and-poor-prognosis
#19
Guosheng Han, Yanan Li, Yiqun Cao, Zhijian Yue, Yuhui Zhang, Laixing Wang, Jianmin Liu
Vasculogenic mimicry (VM) was an important tumor blood supply to complement the endothelial cell-dependent angiogenesis, while leptin and receptor (ObR) involved in angiogenesis in glioblastoma has been reported on previous study, but the relationship between ObR expression and VM formation in human glioblastoma tissues, as well as their prognostic significance still remains unclear. In our study, we found that VM recognized by CD31-/PAS+ immunohistochemical staining in glioblastoma tissues showed a positive correlation with leptin expression (r = 0...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938542/the-immune-checkpoint-molecule-v-set-ig-domain-containing-4-is-an-independent-prognostic-factor-for-multiple-myeloma
#20
Jin Roh, Youkyoung Jeon, A-Neum Lee, Sang Min Lee, YeonMee Kim, Chang Ohk Sung, Chan-Jeoung Park, Jung Yong Hong, Dok Hyun Yoon, Cheolwon Suh, Jooryung Huh, Inhak Choi, Chan-Sik Park
Multiple myeloma (MM) remains as an incurable disease, despite recent substantial improvements in treatment. Therefore, development of novel biomarkers for risk stratification and new therapeutic targets are imperative. One of the emerging treatments for MM is the immune checkpoint blockades. V-set Ig domain-containing 4 (VSIG4) is a lately studied B7-related immune checkpoint modulator. We assessed the VSIG4 expression in patients with MM and its prognostic impact. We analyzed 81 bone marrow and 66 extramedullary biopsy samples of MM patients using immunohistochemistry...
August 29, 2017: Oncotarget
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