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https://www.readbyqxmd.com/read/28927002/predicting-variation-of-dna-shape-preferences-in-protein-dna-interaction-in-cancer-cells-with-a-new-biophysical-model
#1
Kirill Batmanov, Junbai Wang
DNA shape readout is an important mechanism of transcription factor target site recognition, in addition to the sequence readout. Several machine learning-based models of transcription factor-DNA interactions, considering DNA shape features, have been developed in recent years. Here, we present a new biophysical model of protein-DNA interactions by integrating the DNA shape properties. It is based on the neighbor dinucleotide dependency model BayesPI2, where new parameters are restricted to a subspace spanned by the dinucleotide form of DNA shape features...
September 18, 2017: Genes
https://www.readbyqxmd.com/read/28926225/bridging-bio-nano-science-and-cancer-nanomedicine
#2
Mattias Björnmalm, Kristofer J Thurecht, Michael Michael, Andrew M Scott, Frank Caruso
The interface of bio-nano science and cancer medicine is an area experiencing much progress but also beset with controversy. Core concepts of the field-e.g., the enhanced permeability and retention (EPR) effect, tumor targeting and accumulation, and even the purpose of "nano" in cancer medicine-are hotly debated. In parallel, considerable advances in neighboring fields are occurring rapidly, including the recent progress of "immuno-oncology" and the fundamental impact it is having on our understanding and the clinical treatment of the group of diseases collectively known as cancer...
September 19, 2017: ACS Nano
https://www.readbyqxmd.com/read/28926093/pulmonary-hypertension-molecular-aspects-of-current-therapeutic-intervention-and-future-direction
#3
Taruna Katyal Arora, Amit KumarArora, Monika Katyal Sachdeva, Satyendra Kumar Rajput, Arun Kumar Sharma
Pulmonary hypertension (PH) is a life-threatening lung disorder with towering prevalence and risk for future has been gradually rising worldwide. Even, no specific medications are available for pulmonary hypertension; various classes of treatment based upon the origin and magnitude of hypertension are still used for the treatment of PH. Consideration of molecular or signaling modulation is the imperative approach that can offer a new notion for prevalent pharmacotherapeutic agents. Instead of concurrent targets, including endothelin receptor antagonists (ETA/ETB), phosphodiesterase 5 inhibitor (PDF-5), calcium channel blockers, anticoagulants, diuretics and long acting prostacyclin analogue, recent scientific reports revealed the numerous potential alternative therapeutic approaches that can significantly target the pathological signaling alteration associated with PH...
September 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28925926/resolution-of-treatment-resistant-subretinal-fluid-in-a-patient-with-exudative-age-related-macular-degeneration-following-endophthalmitis
#4
Peter M Kally, Yossi Sidikaro, Colin A McCannel
PURPOSE: This is the first report to the best of the authors' knowledge to show resolution of subretinal fluid and treatment requirement in a case of exudative age-related macular degeneration (eAMD) with persistent fluid despite treatment that resolved following an episode of culture-positive bacterial endophthalmitis. METHODS: A 73-year-old man with history of eAMD of the right eye presented with acute postinjection bacterial endophthalmitis 3 days after injection...
October 2017: Retinal Cases & Brief Reports
https://www.readbyqxmd.com/read/28925030/drug-repurposing-may-generate-novel-approaches-to-treating-depression
#5
REVIEW
Mohamed Elsaed Ebada
OBJECTIVES: The breakthrough advancements in scientific medical research have greatly improved our understanding of the pathogenesis of depression, encouraging drug discoverers to take a shorter path than ever through drug repurposing to generate new antidepressant medications. In addition to reduced noradrenergic and serotonergic neurotransmission in the brain, other coincidence features such as glutamate neurotoxicity, inflammation and/or cerebrovascular insufficiency are implicated in the pathogenesis of major depressive disorder and late-life depression...
September 18, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28925011/trends-in-active-surveillance-for-very-low-risk-prostate-cancer-do-guidelines-influence-modern-practice
#6
Rahul R Parikh, Sinae Kim, Mark N Stein, Bruce G Haffty, Isaac Y Kim, Sharad Goyal
As recommended by current NCCN guidelines, patients with very low-risk prostate cancer may be treated with active surveillance (AS), but this may be underutilized. Using the National Cancer Database (NCDB), we identified men (2010-2013) with biopsy-proven, very low-risk prostate cancer that met AS criteria as suggested by Epstein (stage ≤ T1c; Gleason score (GS) ≤ 6; PSA < 10; and ≤2 [or <33%] positive biopsy cores) and aged ≤76, and low comorbidity index (Charlson-Deyo score = 0). For those patients meeting this criteria, we performed generalized estimation equation (GEE) method with incorporation of correlation in patients clustered within facility to determine the likelihood of undergoing AS...
September 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28924972/targeting-nociceptive-trp-channels-to-treat-chronic-pain-current-state-of-the-field
#7
REVIEW
Magdalene M Moran, Arpad Szallasi
Control of chronic pain is frequently inadequate and/or associated with intolerable adverse effects, prompting a frantic search for new therapeutics and new therapeutic targets. Nearly two decades of preclinical and clinical research supports the involvement of Transient Receptor Potential (TRP) channels in temperature perception, nociception and sensitization. Although there has been considerable excitement around the therapeutic potential of this channel family since the cloning and identification of TRPV1 as the capsaicin receptor more than 20 years ago, only modulators of a few channels have been tested clinically...
September 19, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28924379/the-overexpression-of-carm1-promotes-human-osteosarcoma-cell-proliferation-through-the-pgsk3%C3%AE-%C3%AE-catenin-cyclind1-signaling-pathway
#8
Shijie Li, Dongdong Cheng, Bin Zhu, Qingcheng Yang
Osteosarcoma (OS) is a kind of malignant bone tumor that occurs frequently in the region surrounding the knee joint and poses a threat to the health of teenagers. Since the application of chemotherapy to treat OS, 5-year survival rate in patients has improved from 10% to 70%, but patient survival has not changed over the past four decades. Coactivator-associated arginine methyltransferase 1 (CARM1) is a member of the PRMT protein family; it acts as an oncogene in many cancers, but its function in OS is still unknown...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28924233/pharmacological-inhibition-of-camkk2-with-the-selective-antagonist-sto-609-regresses-nafld
#9
Brian York, Feng Li, Fumin Lin, Kathrina L Marcelo, Jianqiang Mao, Adam Dean, Naomi Gonzales, David Gooden, Suman Maity, Cristian Coarfa, Nagireddy Putluri, Anthony R Means
Binding of calcium to its intracellular receptor calmodulin (CaM) activates a family of Ca(2+)/CaM-dependent protein kinases. CaMKK2 (Ca(2+)/CaM-dependent protein kinase kinase 2) is a central member of this kinase family as it controls the actions of a CaMK cascade involving CaMKI, CaMKIV or AMPK. CaMKK2 controls insulin signaling, metabolic homeostasis, inflammation and cancer cell growth highlighting its potential as a therapeutic target for a variety of diseases. STO-609 is a selective, small molecule inhibitor of CaMKK2...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28923369/rapid-identification-and-validation-of-novel-targeted-approaches-for-glioblastoma-a-combined-ex-vivo-in-vivo-pharmaco-omic-model
#10
REVIEW
Ahmad Daher, John de Groot
Tumor heterogeneity is a major factor in glioblastoma's poor response to therapy and seemingly inevitable recurrence. Only two glioblastoma drugs have received Food and Drug Administration approval since 1998, highlighting the urgent need for new therapies. Profiling "omics" analyses have helped characterize glioblastoma molecularly and have thus identified multiple molecular targets for precision medicine. These molecular targets have influenced clinical trial design; many "actionable" mutation-focused trials are underway, but because they have not yet led to therapeutic breakthroughs, new strategies for treating glioblastoma, especially those with a pharmacological functional component, remain in high demand...
September 15, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28921641/pharmacokinetic-guided-dosing-of-new-oral-cancer-agents
#11
Catherine J Lucas, Jennifer H Martin
Generally, licensed drug-dosing recommendations for chemotherapy are based on results from clinical trials in which subjects are usually of relatively normal body size, middle-aged, and are relatively racially homogeneous, with minimal comorbidity and specific tumor characteristics. Very few nontrial patients meet these characteristics, resulting in clinical practice having to extrapolate dosing recommendations to the specific patient. There is insufficient research on the impact of obesity-associated physiological changes prevalent in patients with common cancers on standard pharmacokinetic and pharmacodynamic parameters...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28921458/pharmacogenetics-and-pharmacogenomics-in-moderate-to-severe-psoriasis
#12
REVIEW
María C Ovejero-Benito, Ester Muñoz-Aceituno, Alejandra Reolid, Miriam Saiz-Rodríguez, Francisco Abad-Santos, Esteban Daudén
Pharmacogenetics is the study of variations in DNA sequence related to drug response. Moreover, the evolution of biotechnology and the sequencing of human DNA have allowed the creation of pharmacogenomics, a branch of genetics that analyzes human genes, the RNAs and proteins encoded by them, and the inter-and intra-individual variations in expression and function in relation to drug response. Pharmacogenetics and pharmacogenomics are being used to search for biomarkers that can predict response to systemic treatments, including those for moderate-to-severe psoriasis...
September 18, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28920959/targeting-mitochondrial-oxidative-phosphorylation-eradicates-therapy-resistant-chronic-myeloid-leukemia-stem-cells
#13
Elodie M Kuntz, Pablo Baquero, Alison M Michie, Karen Dunn, Saverio Tardito, Tessa L Holyoake, G Vignir Helgason, Eyal Gottlieb
Treatment of chronic myeloid leukemia (CML) with imatinib mesylate and other second- and/or third-generation c-Abl-specific tyrosine kinase inhibitors (TKIs) has substantially extended patient survival. However, TKIs primarily target differentiated cells and do not eliminate leukemic stem cells (LSCs). Therefore, targeting minimal residual disease to prevent acquired resistance and/or disease relapse requires identification of new LSC-selective target(s) that can be exploited therapeutically. Considering that malignant transformation involves cellular metabolic changes, which may in turn render the transformed cells susceptible to specific assaults in a selective manner, we searched for such vulnerabilities in CML LSCs...
September 18, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28919705/new-insight-into-the-pathogenesis-of-nail-psoriasis-and-overview-of-treatment-strategies
#14
REVIEW
Alessandra Ventura, Mauro Mazzeo, Roberta Gaziano, Marco Galluzzo, Luca Bianchi, Elena Campione
Psoriasis is a chronic inflammatory disease affecting up to 3% of the general population. The prevalence of nail involvement in psoriasis patients varies between 15% and 79%. While the nails represent a small portion of the body surface area, psoriasis in these areas can have a disproportionate influence on a patient's physical and psychosocial activities. Differential diagnosis between an onychomycosis and a psoriatic nail could be challenging; nevertheless, coexistence of onychomycosis and nail psoriasis also occurs and both are common disorders in the general population...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28919047/long-non-coding-rna-657-suppresses-hepatocellular-carcinoma-cell-growth-by-acting-as-a-molecular-sponge-of-mir-106a-5p-to-regulate-pten-expression
#15
Bingren Hu, Huajie Cai, Ru Zheng, Shouzhang Yang, Zhenxu Zhou, Jinfu Tu
Previous study has identified the aberrant expression of LINC00657, a long non-coding RNA (lncRNA), in human breast cancer. However, the expression pattern, biological function and underlying mechanism of LINC00657 in human hepatocellular carcinoma (HCC) remain obscure. The expression levels of LINC00657 in HCC tissues and cell lines were determined by quantitative real-time PCR. CCK-8 assay, cell colony formation assay, cell cycle analysis, Transwell assay were performed to determine whether LINC00657 could affect HCC progression...
September 14, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28918565/forward-genetic-screens-identify-a-role-for-the-mitochondrial-her2-in-e-2-hexenal-responsiveness
#16
Alessandra Scala, Rossana Mirabella, Joachim Goedhart, Michel de Vries, Michel A Haring, Robert C Schuurink
This work adds a new player, HER2, downstream of the perception of E-2-hexenal, a green leaf volatile, and shows that E-2-hexenal specifically changes the redox status of the mitochondria. It is widely accepted that plants produce and respond to green leaf volatiles (GLVs), but the molecular components involved in transducing their perception are largely unknown. The GLV E-2-hexenal inhibits root elongation in seedlings and, using this phenotype, we isolated E-2-hexenal response (her) Arabidopsis thaliana mutants...
September 16, 2017: Plant Molecular Biology
https://www.readbyqxmd.com/read/28918190/autophagy-inflammation-and-immune-dysfunction-in-the-pathogenesis-of-pancreatitis
#17
REVIEW
Anna S Gukovskaya, Ilya Gukovsky, Hana Algül, Aida Habtezion
Pancreatitis is a common disorder with significant morbidity and mortality, yet little is known about its pathogenesis and there is no specific or effective treatment. Its development involves dysregulated autophagy and unresolved inflammation, demonstrated by studies in genetic and experimental mouse models. Disease severity depends on whether the inflammatory response resolves or amplifies, leading to multi-organ failure. Dysregulated autophagy might promote the inflammatory response in the pancreas. We discuss the roles of autophagy and inflammation in pancreatitis, mechanisms of deregulation, and connections among disordered pathways...
September 13, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28918031/anti-adenoviral-artificial-micrornas-expressed-from-aav9-vectors-inhibit-human-adenovirus-infection-in-immunosuppressed-syrian-hamsters
#18
Katrin Schaar, Anja Geisler, Milena Kraus, Sandra Pinkert, Markian Pryshliak, Jacqueline F Spencer, Ann E Tollefson, Baoling Ying, Jens Kurreck, William S Wold, Robert Klopfleisch, Karoly Toth, Henry Fechner
Infections of immunocompromised patients with human adenoviruses (hAd) can develop into life-threatening conditions, whereas drugs with anti-adenoviral efficiency are not clinically approved and have limited efficacy. Small double-stranded RNAs that induce RNAi represent a new class of promising anti-adenoviral therapeutics. However, as yet, their efficiency to treat hAd5 infections has only been investigated in vitro. In this study, we analyzed artificial microRNAs (amiRs) delivered by self-complementary adeno-associated virus (scAAV) vectors for treatment of hAd5 infections in immunosuppressed Syrian hamsters...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28916337/angiotensin-ii-induces-calcium-mediated-autophagy-in-podocytes-through-enhancing-reactive-oxygen-species-levels
#19
Na Gao, Hui Wang, Hongqiang Yin, Zhuo Yang
As well known, abnormalities of Angiotensin II (Ang II) is closely related with glomerular damage. This study was to investigate whether Ang II could affect autophagy in podocytes via oxidative stress, and whether autophagy had a positive role in protecting podocytes impaired by Ang II. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that Ang II induced podocyte death. The measurements of malondialdehyde (MDA) and H2O2 levels, and flow cytometry assay revealed that Ang II considerably increased ROS generation in podocytes...
September 12, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28915721/dramatic-response-of-ctnnb1-and-vegfr-2-mutant-temporal-bone-squamous-cell-carcinoma-to-bevacizumab-in-combination-with-pemetrexed
#20
Lai Wei, Lizhi Wang, Ziye Liu, Meiyi Wang, Weili Lu, Dewei Zhao, Bin Yang, Xuejun Kong, Yan Ding, Zhiqiang Wang
High recurrence rates and poor survival rates for late stage/advanced temporal bone squamous cell carcinoma with the standard treatments continues to be a significant challenge to otolaryngologists. Targeted therapy for temporal bone squamous cell carcinoma after relapse has not been reported. Here we present a 58-year-old man who was diagnosed with recurrent temporal bone squamous cell carcinoma and treated with a regimen developed using whole exome sequencing. Somatic mutations in genes encoding catenin beta 1 and vascular endothelial growth factor receptor 2 were identified in the patient's tumor sample compared to the normal tissue...
August 22, 2017: Oncotarget
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