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https://www.readbyqxmd.com/read/28431428/computational-and-in-vitro-experimental-investigation-of-intrathecal-drug-distribution-parametric-study-of-the-effect-of-injection-volume-cerebrospinal-fluid-pulsatility-and-drug-uptake
#1
Kevin M Tangen, Roxanne Leval, Ankit I Mehta, Andreas A Linninger
BACKGROUND: Intrathecal drug delivery is an attractive option to circumvent the blood-brain barrier for pain management through its increased efficacy of pain relief, reduction in adverse side effects, and cost-effectiveness. Unfortunately, there are limited guidelines for physicians to choose infusion or drug pump settings to administer therapeutic doses to specific regions of the spine or the brain. Although empiric trialing of intrathecal drugs is critical to determine the sustained side effects, currently there is no inexpensive in vitro method to guide the selection of spinal drug delivery parameters...
May 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28431407/prognositic-value-of-cd73-adenosinergic-pathway-in-solid-tumor-a-meta-analysis-and-systematic-review
#2
Rong Wang, Yingying Zhang, Xia Lin, Yalin Gao, Ying Zhu
CD73 is a glycosylphosphatidylinositol (GPI) anchored cell surface protein that is encoded by NT5E gene, plays multiple roles in tumor processes. Previous studies have presented a potential value of CD73 served as a detectable biomarker for prognosis of several solid tumors, but the results were more controversially. A comprehensive meta-analysis was conducted to precisely evaluate the prognostic role of CD73 in solid tumors. The included studies were searched in PubMed, Web of Science and EBSCO from Jan 1990 to Jan 2016...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28431405/usp5-functions-as-an-oncogene-for-stimulating-tumorigenesis-in-hepatocellular-carcinoma
#3
Yi Liu, Wei-Mao Wang, Ying-Fei Lu, Lu Feng, Li Li, Ming-Zhu Pan, Yu Sun, Chun-Wai Suen, Wei Guo, Jian-Xin Pang, Jin-Fang Zhang, Wei-Ming Fu
As deubiquitinases, several ubiquitin specific protease members have been reported to mediate tumorigenesis. Although ubiquitin specific protease 5 (Usp5) was previously demonstrated to suppress p53 transcriptional activity and DNA repair, its role in carcinogenesis remains elusive. In this study, we sought to define a novel role of Usp5 in tumorigenesis. It was found that Usp5 was significantly upregulated in hepatocellular carcinoma (HCC) cells and most clinical specimens. Further functional investigation also showed that Usp5 knockdown suppressed cell proliferation, migration, drug resistance and induced apoptosis; on the other hand, Usp5 overexpression promoted colony formation, migration, drug resistance and tumorigenesis...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28431395/correlation-of-genomic-alterations-assessed-by-next-generation-sequencing-ngs-of-tumor-tissue-dna-and-circulating-tumor-dna-ctdna-in-metastatic-renal-cell-carcinoma-mrcc-potential-clinical-implications
#4
Andrew W Hahn, David M Gill, Benjamin Maughan, Archana Agarwal, Lubina Arjyal, Sumati Gupta, Jessica Streeter, Erin Bailey, Sumanta K Pal, Neeraj Agarwal
INTRODUCTION: Tumor tissue and circulating tumor DNA (ctDNA) next-generation sequencing (NGS) testing are frequently performed to detect genomic alterations (GAs) to help guide treatment in metastatic renal cell carcinoma (mRCC), especially after progression on standard systemic therapy. Our objective was to assess if GAs detected by ctDNA NGS are different from those detected by tumor tissue NGS, specifically in patients with mRCC, and if these platforms are interchangeable or complimentary...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28431353/discovery-of-potential-anticancer-multi-targeted-ligustrazine-based-cyclohexanone-and-oxime-analogs-overcoming-the-cancer-multidrug-resistance
#5
Gao-Feng Zha, Hua-Li Qin, Bahaa G M Youssif, Muhammad Wahab Amjad, Maria Abdul Ghafoor Raja, Ahmed H Abdelazeem, Syed Nasir Abbas Bukhari
The drug research and development nowadays is focusing on multi-target drugs. In the treatment of cancer, therapies using drugs inhibiting one numerous targets signify a novel viewpoint. In comparison with traditional therapy, multi-targeted drugs directly aim cell subpopulations which are involved in progression of tumor. The current study comprises the synthesis of 34 novel ligustrazine-containing α, β-unsaturated carbonyl-based compounds and oximes. The growth of 5 various cancer cell types was strongly inhibited by ligustrazine-containing oximes as revealed by biological evaluation...
April 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28431280/interleukin-1-receptor-associated-kinase-1-is-a-potential-therapeutic-target-of-anti-inflammatory-therapy-for-systemic-lupus-erythematosus
#6
Mingfang Li, Datang Yu, Bing Ni, Fei Hao
Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease and currently has no effective therapy. The genome-wide analyses indicate that interleukin-1 receptor associated kinase 1 (IRAK1) is associated with the susceptibility of SLE in humans. In the present study, we identified that IRAK1 was overexpressed and hyper-activated in splenic mononuclear cells from B6.MRL-Fas(lpr)/Nju (B6.lpr) mice and peripheral blood mononuclear cells (PBMCs) from SLE patients. Intraperitoneal treatment with a small molecular inhibitor of IRAK1 (IRAK1/4 inhibitor or IRAK-Inh) significantly mitigated inflammatory responses and renal injury in B6...
April 18, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28431263/epigenetic-therapy-and-chemosensitization-in-solid-malignancy
#7
REVIEW
Sean M Ronnekleiv-Kelly, Anup Sharma, Nita Ahuja
Epigenetic modifications result in dynamic shifts between transcriptionally active and suppressed states. The potentially reversible nature of epigenetic changes underlies the concept of epigenetic therapy, which serves to reprogram cancer cells as opposed to inducing cytotoxicity that occurs with standard chemotherapeutics. There are numerous enzymes involved in epigenetic changes and each can be potentially targetable. Although many investigations have evaluated the clinical potential of the various epigenetic therapies, currently only histone deacetylase inhibitors and DNA methyltransferase inhibitors are approved for use in specific hematologic malignancies...
April 8, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28431262/immunologic-approaches-for-the-treatment-of-multiple-myeloma
#8
REVIEW
Leo Rasche, Niels Weinhold, Gareth J Morgan, Frits van Rhee, Faith E Davies
The FDA approval of two monoclonal antibodies in 2015has heralded a new era of targeted immunotherapies for multiple myeloma (MM). In this review we discuss the recent approaches using different immunological components to treat MM. In particular, we review current monoclonal antibody based therapies, engineered T- and NK cell products, 'off-target' immunomodulation, and strategies utilizing allogeneic cell transplantation in MM. We discuss how an immunologic approach offers promise for the treatment of this genetically heterogeneous disease, and how patients with acquired drug resistance may particularly benefit from these therapies...
April 6, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28431079/precision-pain-medicine-can-we-deliver-targeted-pain-therapies-for-the-oncologic-patient-in-the-21st-century
#9
Amitabh Gulati
No abstract text is available yet for this article.
April 20, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28431070/emerging-molecular-therapies-targeting-myocardial-infarction-related-arrhythmias
#10
Helen E Driessen, Toon A B van Veen, Gerard J J Boink
Cardiac disease is the leading cause of death in the developed world. Ventricular arrhythmias associated with myocardial ischaemia and/or infarction are a major contributor to cardiovascular mortality, and require improved prevention and treatment. Drugs, devices, and radiofrequency catheter ablation have made important inroads, but have significant limitations ranging from incomplete success to undesired toxicities and major side effects. These limitations derive from the nature of the intervention. Drugs are frequently ineffective, target the entire heart, and often do not deal with the specific arrhythmia trigger or substrate...
April 1, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28430990/three-dimensional-dose-prediction-and-validation-with-the-radiobiological-gamma-index-based-on-a-relative-seriality-model-for-head-and-neck-imrt
#11
Noriaki Hamatani, Iori Sumida, Yutaka Takahashi, Michio Oda, Yuji Seo, Fumiaki Isohashi, Keisuke Tamari, Kazuhiko Ogawa
This study proposes a quality assurance (QA) method incorporating radiobiological factors based on the QUANTEC-determined tumor control probability and the normal tissue complication probability (NTCP) of head-and-neck intensity-modulated radiation therapy (HN-IMRT). Per-beam measurements were conducted for 20 cases using a 2D detector array. Three-dimensional predicted dose distributions within targets and organs at risk were reconstructed based on the per-beam QA results derived from differences between planned and measured doses...
April 19, 2017: Journal of Radiation Research
https://www.readbyqxmd.com/read/28430908/late-thrombotic-events-after-bioresorbable-scaffold-implantation-a-systematic-review-and-meta-analysis-of-randomized-clinical-trials
#12
Carlos Collet, Taku Asano, Yosuke Miyazaki, Erhan Tenekecioglu, Yuki Katagiri, Yohei Sotomi, Rafael Cavalcante, Robbert J de Winter, Takeshi Kimura, Runlin Gao, Serban Puricel, Stéphane Cook, Davide Capodanno, Yoshinobu Onuma, Patrick W Serruys
Aims: To compare the long-term safety and efficacy of bioresorbable vascular scaffold (BVS) with everolimus-eluting stent (EES) after percutaneous coronary interventions. Methods and Results: A systematic review and meta-analysis of randomized clinical trials comparing clinical outcomes of patients treated with BVS and EES with at least 24 months follow-up was performed. Adjusted random-effect model by the Knapp-Hartung method was used to compute odds ratios (OR) and 95% confidence intervals (CI)...
April 18, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28430874/developmental-sall2-transcription-factor-a-new-player-in-cancer
#13
Viviana E Hermosilla, Matias I Hepp, David Escobar, Carlos Farlas, Elizabeth N Riffo, Ariel F Castro, Roxana Pincheira
SALL2, also known as Spalt-like transcription factor 2, is a member of the SALL family of transcription factors involved in development and conserved through evolution. Since its identification in 1996, findings indicate that SALL2 plays a role in neurogenesis, neuronal differentiation and eye development. Consistently, SALL2 deficiency associates with neural tube defects and coloboma, a congenital eye disease. Relevant to cancer, clinical studies indicate that SALL2 is deregulated in various cancers, and is a specific biomarker for Synovial Sarcoma...
April 18, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28430717/multilateral-functional-alterations-of-human-neutrophils-in-sepsis-from-the-point-of-diagnosis-to-the-seventh-day
#14
Akira Endo, Miko Okamura, Shunsuke Yoshikawa, Yasuhiro Otomo, Tomohiro Morio
Neutrophil functional changes caused by sepsis itself and their time-course variation have not been fully elucidated because previous studies targeted patients who had received therapeutic interventions. We explored the multilateral functions of circulating neutrophils in patients with severe sepsis or septic shock who had not yet undergone interventions, and followed their changes. Patients were treated based on the Surviving Sepsis Campaign Guidelines 2012. Neutrophil functions were evaluated on days 0 (before therapeutic intervention), 3, and 7 in fifty-nine sepsis patients...
April 20, 2017: Shock
https://www.readbyqxmd.com/read/28430673/antimicrobial-resistant-streptococcus-pneumoniae-prevalence-mechanisms-and-clinical-implications
#15
Regine Cherazard, Marcia Epstein, Thien-Ly Doan, Tanzila Salim, Sheena Bharti, Miriam A Smith
BACKGROUND: Streptococcus pneumoniae is a major cause of pneumonia, meningitis, sepsis, bacteremia, and otitis media. S. pneumoniae has developed increased resistance to multiple classes of antibiotics. STUDY DESIGN: Systematic literature review of prevalence, mechanisms, and clinical implications in S. pneumoniae resistance. AREAS OF UNCERTAINTY: Since S. pneumoniae resistance to penicillin was first reported with subsequent development of resistance to other classes of drugs, selection of appropriate antibiotic treatment is challenging...
April 19, 2017: American Journal of Therapeutics
https://www.readbyqxmd.com/read/28430642/immunocompetent-mouse-allograft-models-for-development-of-therapies-to-target-breast-cancer-metastasis
#16
Yuan Yang, Howard H Yang, Ying Hu, Peter H Watson, Huaitian Liu, Thomas R Geiger, Miriam R Anver, Diana C Haines, Philip Martin, Jeffrey E Green, Maxwell P Lee, Kent W Hunter, Lalage M Wakefield
Effective drug development to combat metastatic disease in breast cancer would be aided by the availability of well-characterized preclinical animal models that (a) metastasize with high efficiency, (b) metastasize in a reasonable time-frame, (c) have an intact immune system, and (d) capture some of the heterogeneity of the human disease. To address these issues, we have assembled a panel of twelve mouse mammary cancer cell lines that can metastasize efficiently on implantation into syngeneic immunocompetent hosts...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430601/growth-suppressive-activity-of-raloxifene-on-liver-cancer-cells-by-targeting-il-6-gp130-signaling
#17
Yina Wang, Haiyan Ma, Chongqiang Zhao, Tianshu Liu, Dan Yan, David Jou, Huameng Li, Cuntai Zhang, Jiagao Lü, Chenglong Li, Jiayuh Lin, Sheng Li, Li Lin
BACKGROUND: Interleukin-6 (IL-6) is a multifunctional cytokine, which is involved in the regulation of differentiation and growth of certain types of tumor cells. Constitutive activation of Signal Transducer and Activator of Transcription 3 (STAT3) induced by IL-6 is frequently detected in liver cancer and has emerged as a viable molecular target for liver cancer treatment. However, few inhibitors targeting up-streams of STAT3 are available for the therapy of liver cancer. We reported the discovery of EVISTA (Raloxifene HCl) as novel inhibitor of IL-6/GP130 protein-protein interactions (PPIs) using multiple ligand simultaneous docking (MLSD) and drug repositioning...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430590/treatment-of-esophageal-cancer-with-radiation-therapy-a-pan-chinese-survey-of-radiation-oncologists
#18
Yun Zhang, Jing Liu, Wencheng Zhang, Weiye Deng, Jinbo Yue
Lots of controversies were found about the treatment in relation to radiation therapy (RT) for esophageal squamous cell carcinoma (ESCC). We designed a questionnaire of these controversies to do a pan-Chinese survey of radiation oncologists (ROs). For operable ESCC, 53% ROs chose surgery plus postoperative chemoradiotherapy (CRT), while 40% chose preoperative CRT plus surgery. For target volume of postoperative RT, most ROs (92%) would delineate tumor bed plus involved lymph nodes region before surgery. For definitive RT, most ROs (81%) would give patients higher RT dose to 60-65Gy...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430580/expression-status-of-folate-receptor-alpha-is-a-predictor-of-survival-in-pancreatic-ductal-adenocarcinoma
#19
Lei Cai, Theodoros Michelakos, Cristina R Ferrone, Liyuan Zhang, Vikram Deshpande, Qi Shen, Albert De Leo, Teppei Yamada, Gong Zhang, Soldano Ferrone, Xinhui Wang
Pancreatic ductal adenocarcinoma (PDAC) has one of the poorest prognosis among malignancies. Thus, the identification of markers useful in developing innovative diagnostic and therapeutic methods is an imperative need. Folate receptor alpha (FRα) has been associated with prognosis in several cancers and has served as a target of novel anti-tumor therapies. However, FRα expression in PDAC and its correlation with the clinical course of the disease has not been thoroughly investigated. In this study, we analyzed FRα expression in 140 PDAC specimens and 7 PDAC cell lines in order to define the significance of FRα expression in PDAC and its potential role as a target for immunotherapy...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430577/synthetic-lethal-interaction-between-the-tumour-suppressor-stag2-and-its-paralog-stag1
#20
Lorena Benedetti, Matteo Cereda, LeeAnn Monteverde, Nikita Desai, Francesca D Ciccarelli
Cohesin is a multi-protein complex that tethers sister chromatids during mitosis and mediates DNA repair, genome compartmentalisation and regulation of gene expression. Cohesin subunits frequently acquire cancer loss-of-function alterations and act as tumour suppressors in several tumour types. This has led to increased interest in cohesin as potential target in anti-cancer therapy. Here we show that the loss-of-function of STAG2, a core component of cohesin and an emerging tumour suppressor, leads to synthetic dependency of mutated cancer cells on its paralog STAG1...
April 5, 2017: Oncotarget
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