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Combined Elements Therapy

Junjie Xu, Longbo Zheng, Jiang Chen, Yin Sun, Hui Lin, Ren-An Jin, Minyue Tang, Xiao Liang, Xiujun Cai
Although sorafenib is currently used as a standard treatment for advanced hepatocellular carcinoma, low response rate, transient and limited efficacy, primary and acquired resistance and negative side-effects gain increasing attentions, suggesting the need for better efficacious combination therapy. Here, we demonstrated that the sorafenib-induced or hypoxia-induced hypoxia inducible factor (HIF)-2α could bind to an hypoxia responsive element within 500 bp region of androgen receptor (AR) promoter and thus transcriptionally suppress AR...
October 12, 2017: Cell Death & Disease
Klaus E Matzel, Emmanuel Chartier-Kastler, Charles H Knowles, Paul A Lehur, Arantxa Muñoz-Duyos, Carlo Ratto, Mona B Rydningen, Michael Sørensen, Philip van Kerrebroeck, Stefan de Wachter
INTRODUCTION: Sacral neuromodulation (SNM) (sacral nerve stimulation SNS) has become an established therapy for functional disorders of the pelvic organs. Despite its overall success, the therapy fails in a proportion of patients. This may be partially due to inadequate electrode placement with suboptimal coupling of the electrode and nerve. Based on these assumptions the technique of sacral spinal neuromodulation has been redefined. All descriptions relate to the only currently available system licensed for all pelvic indications (Medtronic Interstim(®) )...
October 4, 2017: Neuromodulation: Journal of the International Neuromodulation Society
Shan S Parikh, Daniel J Blackwell, Nieves Gomez-Hurtado, Michael Frisk, Lili Wang, Kyungsoo Kim, Christen P Dahl, Arnt E Fiane, Theis Tønnessen, Dmytro O Kryshtal, William E Louch, Bjorn C Knollmann
Rationale: Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CM) are increasingly being used for modeling heart disease and are under development for regeneration of the injured heart. However, incomplete structural and functional maturation of hiPSC-CM including lack of t-tubules, immature excitation-contraction (EC) coupling, and inefficient Ca-induced Ca release (CICR) remain major limitations. Objective: Thyroid and glucocorticoid hormones are critical for heart maturation. We hypothesized that their addition to standard protocols would promote t-tubule development and mature EC coupling of hiPSC-CM when cultured on extracellular matrix with physiological stiffness (Matrigel mattress)...
October 2, 2017: Circulation Research
Alireza Aghighi, Philippe Comtois
Self-organization of spontaneous activity of a network of active elements is important to the general theory of reaction-diffusion systems as well as for pacemaking activity to initiate beating of the heart. Monolayer cultures of neonatal rat ventricular myocytes, consisting of resting and pacemaker cells, exhibit spontaneous activation of their electrical activity. Similarly, one proposed approach to the development of biopacemakers as an alternative to electronic pacemakers for cardiac therapy is based on heterogeneous cardiac cells with resting and spontaneously beating phenotypes...
September 2017: Chaos
Trisevgeni Rapakoulia, Xin Gao, Yi Huang, Michiel de Hoon, Mariko Okada-Hatakeyama, Harukazu Suzuki, Erik Arner
Motivation: Drug combination therapy for treatment of cancers and other multifactorial diseases has the potential of increasing the therapeutic effect, while reducing the likelihood of drug resistance. In order to reduce time and cost spent in comprehensive screens, methods are needed which can model additive effects of possible drug combinations. Results: We here show that the transcriptional response to combinatorial drug treatment at promoters, as measured by single molecule CAGE technology, is accurately described by a linear combination of the responses of the individual drugs at a genome wide scale...
August 14, 2017: Bioinformatics
Jannik Donner, Michael Reck, Boyke Bunk, Michael Jarek, Constantin Benjamin App, Jan P Meier-Kolthoff, Jörg Overmann, Rolf Müller, Andreas Kirschning, Irene Wagner-Döbler
The myxobacterial secondary metabolite carolacton inhibits growth of Streptococcus pneumoniae and kills biofilm cells of the caries- and endocarditis-associated pathogen Streptococcus mutans at nanomolar concentrations. Here, we studied the response to carolacton of an Escherichia coli strain that lacked the outer membrane protein TolC. Whole-genome sequencing of the laboratory E. coli strain TolC revealed the integration of an insertion element, IS5, at the tolC locus and a close phylogenetic relationship to the ancient E...
September 2017: MSphere
Simon de Lusignan, Stacy Shinneman, Ivelina Yonova, Jeremy van Vlymen, Alex J Elliot, Frederick Bolton, Gillian E Smith, Sarah O'Brien
BACKGROUND: Infectious intestinal disease (IID) has considerable health impact; there are 2 billion cases worldwide resulting in 1 million deaths and 78.7 million disability-adjusted life years lost. Reported IID incidence rates vary and this is partly because terms such as "diarrheal disease" and "acute infectious gastroenteritis" are used interchangeably. Ontologies provide a method of transparently comparing case definitions and disease incidence rates. OBJECTIVE: This study sought to show how differences in case definition in part account for variation in incidence estimates for IID and how an ontological approach provides greater transparency to IID case finding...
September 28, 2017: JMIR Medical Informatics
Sai Yendamuri, Athar Battoo, Grace Dy, Hongbin Chen, Jorge Gomez, Anurag K Singh, Mark Hennon, Chukwumere E Nwogu, Elisabeth U Dexter, Miriam Huang, Anthony Picone, Todd L Demmy
BACKGROUND: Accurate staging of the mediastinum is a critical element of therapeutic decision making in non-small cell lung cancer. We sought to determine the utility of transcervical extended mediastinal lymphadenectomy (TEMLA) in staging non-small cell lung cancer for large central tumors and after induction therapy. METHODS: A retrospective record review was performed of all patients who underwent TEMLA at our institution from 2010 to 2015. Clinical stage as assessed by positron emission tomography integrated with computed tomography (PET-CT), stage as assessed by TEMLA, final pathologic stage, lymph node yield, and clinical characteristics of tumors were assessed along with TEMLA-related perioperative morbidity...
September 21, 2017: Annals of Thoracic Surgery
Michael Berk, Robert Post, Aswin Ratheesh, Emma Gliddon, Ajeet Singh, Eduard Vieta, Andre F Carvalho, Melanie M Ashton, Lesley Berk, Susan M Cotton, Patrick D McGorry, Brisa S Fernandes, Lakshmi N Yatham, Seetal Dodd
Illness staging is widely utilized in several medical disciplines to help predict course or prognosis, and optimize treatment. Staging models in psychiatry in general, and bipolar disorder in particular, depend on the premise that psychopathology moves along a predictable path: an at-risk or latency stage, a prodrome progressing to a first clinical threshold episode, and one or more recurrences with the potential to revert or progress to late or end-stage manifestations. The utility and validity of a staging model for bipolar disorder depend on its linking to clinical outcome, treatment response and neurobiological measures...
October 2017: World Psychiatry: Official Journal of the World Psychiatric Association (WPA)
Tao Zhang, Xiao-Hang Li, Dian-Bao Zhang, Xiao-Yu Liu, Feng Zhao, Xue-Wen Lin, Rui Wang, Hong-Xin Lang, Xi-Ning Pang
Identifying molecular mechanisms that regulate insulin expression in bone marrow-derived mesenchymal stem cells (bmMSCs) can provide clues on how to stimulate the differentiation of bmMSCs into insulin-producing cells (IPCs), which can be used as a therapeutic approach against type 1 diabetes (T1D). As repression factors may inhibit differentiation, the efficiency of this process is insufficient for cell transplantation. In this study, we used the mouse insulin 2 (Ins2) promoter sequence and performed a DNA affinity precipitation assay combined with liquid chromatography-mass spectrometry to identify the transcription factor, chicken ovalbumin upstream promoter transcriptional factor I (COUP-TFI)...
September 15, 2017: Molecular Therapy. Nucleic Acids
K Wada, Y Wada, Y Iwasaki, T Ikemura
Oligonucleotides are key elements of nucleic acid therapeutics such as small interfering RNAs (siRNAs). Influenza and Ebolaviruses are zoonotic RNA viruses mutating very rapidly, and their sequence changes must be characterized intensively to design therapeutic oligonucleotides with long utility. Focusing on a total of 182 experimentally validated siRNAs for influenza A, B and Ebolaviruses compiled by the siRNA database, we conducted time-series analyses of occurrences of siRNA targets in these viral genomes...
September 14, 2017: Gene Therapy
S Dressel, M-C Gosselin, M H Capstick, E Carrasco, M S Weyland, S Scheidegger, E Neufeld, N Kuster, S Bodis, C Rohrer Bley
Hyperthermia (HT) as an adjuvant to radiation therapy (RT) is a multimodality treatment method to enhance therapeutic efficacy in different tumours. High demands are placed on the hardware and treatment planning software to guarantee adequately planned and applied HT treatments. The aim of this prospective study was to determine the effectiveness and safety of the novel HT system in tumour-bearing dogs and cats in terms of local response and toxicity as well as to compare planned with actual achieved data during heating...
September 11, 2017: Veterinary and Comparative Oncology
Michael J Bottery, A Jamie Wood, Michael A Brockhurst
Bacteria gain antibiotic resistance genes by horizontal acquisition of mobile genetic elements (MGE) from other lineages. Newly acquired MGEs are often poorly adapted causing intragenomic conflicts, resolved by compensatory adaptation of the chromosome, the MGE or reciprocal coadaptation. The footprints of such intragenomic coevolution are present in bacterial genomes, suggesting an important role promoting genomic integration of horizontally acquired genes, but direct experimental evidence of the process is limited...
September 2017: Nature ecology & evolution
Andras Polyak, Tobias L Ross
PET and SPECT imaging methods can be of excellent assistance for the development of new nanoparticle drug delivery systems, and at the same time, these investigations also offer the opportunity to produce exceptional new diagnostic and therapeutic radiopharmaceuticals, as well. With a multifunctional, nano-scaled drug delivery system, the diagnostic (imaging) methods and the therapy (delivering drugs or beta-emitter radionuclides) can be carried out using the same biological and pharmacological mechanisms. By combining therapy and diagnostics in one method or in one specifically targeted nanoparticle system, we can product theranostic pharmaceuticals, and its applications are important elements of personalized medicine...
August 29, 2017: Current Medicinal Chemistry
Mona P Tan
Contemporary data suggests that breast conservation treatment (BCT) may confer a survival advantage when compared to mastectomy. Hence, it would be logical to adopt strategies which increase eligibility of successful BCT without compromising oncologic principles or cosmetic outcome. With respect to achieving good aesthetics, inferiorly sited breast cancers pose a particular technical challenge. A vast array of techniques, collectively referred to as oncoplastic breast surgery (OBS) have been developed to minimise post treatment distortion...
August 2017: Gland Surgery
Veshara Malapermal, Izel Botha, Suresh Babu Naidu Krishna, Joyce Nonhlanhla Mbatha
The role of silver nanoparticles (AgNps) is an attractive proposition for advancing modern diabetes therapies and applied science. Stable AgNps with a size range of 3-25 nm were synthesized using aqueous leaf extracts from Ocimum basilicum, Ocimum sanctum, and in combination. The concentration of the extracts facilitated the reduction of silver nitrate that led to the rapid formation of AgNps at room temperature, indicating a higher reaction rate as opposed to harsh chemical methods, and high conversion energy usually involved in the synthesis...
September 2017: Saudi Journal of Biological Sciences
V E Goldberg, T Yu Polyakova, N O Popova, V V Vysotskaya, E I Simolina, Yu V Belevich, T P Tuzikova, A V Goldberg, V V Zhdanov, L A Miroshnichenko, E V Udut, E V Simanina, A M Dygai, G N Zyuz'kov
The toxic effects of combined cisplatin/docetaxel therapy cycles on erythroid and granulocytic hematopoietic lineages as well as their intercycle recovery were examined in patients with stage III-IV non-small-cell lung carcinoma. Responsiveness of the blood system to this therapy remained at a high level. Combined therapy pronouncedly activated the key elements of the erythroid and granulocytic hematopoietic lineages leading to accumulation of immature and mature myelokaryocytes in the bone marrow, enlargement of the medullary pool of mature neutrophils, and increase in the count of medullary erythroid and granulocytic precursor cells under conditions of their accelerated maturation...
August 29, 2017: Bulletin of Experimental Biology and Medicine
Yiwei Zhou, Yong Hu, Wenjie Sun, Benqing Zhou, Jianzhi Zhu, Chen Peng, Mingwu Shen, Xiangyang Shi
We report the facile synthesis of polyaniline (PANI)-loaded γ-polyglutamic acid (γ-PGA) nanogels (NGs) for photoacoustic (PA) imaging-guided photothermal therapy (PTT) of tumors. In this work, γ-PGA NGs were first formed via a double emulsion approach, followed by crosslinking with cystamine dihydrochloride (Cys) via 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride coupling chemistry. The formed γ-PGA/Cys NGs were employed as a nanoreactor to load aniline monomers via an electrostatic interaction for subsequent in situ polymerization in the presence of ammonium persulfate...
August 31, 2017: Nanoscale
Yan Zhao, Ren-Ping Xiong, Xing Chen, Ping Li, Ya-Lei Ning, Nan Yang, Yan Peng, Yu-Lin Jiang, Yuan-Guo Zhou
Glucocorticoids are commonly used for the treatment of pancreatitis and complicated acute lung injury and help to reduce the mortality rates of both. The effect of gene variants in heat shock protein 90 (Hsp90), a key chaperone molecule of the glucocorticoid receptor (GR), on the therapeutic effect of glucocorticoids is unclear. Our study aims to investigate the different susceptibility to glucocorticoid treatment in BALB/c and C57BL/6 mice carrying different Hsp90 genotypes in an animal model of pancreatitis-induced lung injury...
August 21, 2017: Molecular and Cellular Biochemistry
Sisi Qin, James N Ingle, Mohan Liu, Jia Yu, D Lawrence Wickerham, Michiaki Kubo, Richard M Weinshilboum, Liewei Wang
BACKGROUND: We previously performed a case-control genome-wide association study in women treated with selective estrogen receptor modulators (SERMs) for breast cancer prevention and identified single nucleotide polymorphisms (SNPs) in ZNF423 as potential biomarkers for response to SERM therapy. The ZNF423rs9940645 SNP, which is approximately 200 bp away from the estrogen response elements, resulted in the SNP, estrogen, and SERM-dependent regulation of ZNF423 expression and, "downstream", that of BRCA1...
August 18, 2017: Breast Cancer Research: BCR
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