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https://www.readbyqxmd.com/read/29166610/cisd2-haploinsufficiency-disrupts-calcium-homeostasis-causes-nonalcoholic-fatty-liver-disease-and-promotes-hepatocellular-carcinoma
#1
Zhao-Qing Shen, Yi-Fan Chen, Jim-Ray Chen, Yuh-Shan Jou, Pei-Chun Wu, Cheng-Heng Kao, Chih-Hao Wang, Yi-Long Huang, Chian-Feng Chen, Ting-Shuo Huang, Yu-Chiau Shyu, Shih-Feng Tsai, Lung-Sen Kao, Ting-Fen Tsai
CISD2 is located within the chromosome 4q region frequently deleted in hepatocellular carcinoma (HCC). Mice with Cisd2 heterozygous deficiency develop a phenotype similar to the clinical manifestation of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Cisd2 haploinsufficiency causes a low incidence (20%) of spontaneous HCC and promotes HBV-associated and DEN-induced HCC; conversely, 2-fold overexpression of Cisd2 suppresses HCC in these models. Mechanistically, Cisd2 interacts with Serca2b and mediates its Ca(2+) pump activity via modulation of Serca2b oxidative modification, which regulates ER Ca(2+) uptake and maintains intracellular Ca(2+) homeostasis in the hepatocyte...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166603/caveolin1-is-required-for-th1-cell-infiltration-but-not-tight-junction-remodeling-at-the-blood-brain-barrier-in-autoimmune-neuroinflammation
#2
Sarah E Lutz, Julian R Smith, Dae Hwan Kim, Carl V L Olson, Kyle Ellefsen, Jennifer M Bates, Sunil P Gandhi, Dritan Agalliu
Lymphocytes cross vascular boundaries via either disrupted tight junctions (TJs) or caveolae to induce tissue inflammation. In the CNS, Th17 lymphocytes cross the blood-brain barrier (BBB) before Th1 cells; yet this differential crossing is poorly understood. We have used intravital two-photon imaging of the spinal cord in wild-type and caveolae-deficient mice with fluorescently labeled endothelial tight junctions to determine how tight junction remodeling and caveolae regulate CNS entry of lymphocytes during the experimental autoimmune encephalomyelitis (EAE) model for multiple sclerosis...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166504/moderate-to-severe-psoriasis-treatment-challenges-through-the-era-of-biological-drugs
#3
Júlia Vide, Sofia Magina
Biological therapy has revolutionized moderate to severe psoriasis treatment. However, despite being more effective than conventional systemic treatments, some patients do not respond or lose response to biotechnological treatments or develop drug-antibodies, interfering with its safety and efficacy. There are also clinical forms of the disease and patient profiles for which is pending further scientific evidence for more sustained therapeutic interventions. The continuous and more detailed knowledge of psoriasis pathophysiology has allowed identifying new therapeutic targets, which is expected to help overcome the challenges of individualized psoriasis treatment...
September 2017: Anais Brasileiros de Dermatologia
https://www.readbyqxmd.com/read/29165988/bioconjugate-strategies-for-the-induction-of-antigen-specific-tolerance-in-autoimmune-diseases
#4
Chunsong Yu, Jingchao Xi, Meng Li, Myunggi An, Haipeng Liu
Antigen-specific immunotherapy (ASI) holds great promise for the treatment of autoimmune diseases. In mice, administration of major histocompatibility complex (MHC) binding synthetic peptides which modulate T cell receptor (TCR) signaling under subimmunogenic conditions induces selective tolerance without suppressing the global immune responses. However, clinical translation has yielded limited success. It has become apparent that the TCR signaling pathway via synthetic peptide antigen alone is inadequate to induce an effective tolerogenic immunity in autoimmune diseases...
November 22, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29165981/layered-double-hydroxide-and-polypeptide-thermogel-nanocomposite-system-for-chondrogenic-differentiation-of-stem-cells
#5
Seon Sook Lee, Goeun Choi, Hyun Jung Lee, Yelin Kim, Jin-Ho Choy, Byeongmoon Jeong
Stem cell therapy for damaged cartilages suffers from the low rates of retention, survival, and differentiation into chondrocytes at the target site. To solve these problems, here we propose a two dimensional/three dimensional (2D/3D) nanocomposite system. As a new two dimensional (2D) material, hexagonal layered double hydroxides (LDHs) with a uniform lateral length of 2-3 μm were prepared by a hydrothermal process. And then, tonsil-derived mesenchymal stem cells (TMSCs), RGD-coated LDHs, and kartogenin (KGN) were incorporated into the gel through the thermal energy-driven gelation of the system...
November 22, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29165888/molecular-pathology-and-thyroid-fna
#6
REVIEW
D N Poller, S Glaysher
This review summarises molecular pathological techniques applicable to thyroid FNA. The molecular pathology of thyroid tumours is now fairly well understood. Molecular methods may be used as a rule-in test for diagnosis of malignancy in thyroid nodules, eg BRAF V600E point mutation, use of a seven-gene mutational panel (BRAF V600E, RAS genes, RET/PTC or PAX8/PPARG rearrangement), or as a comprehensive multigene next-generation sequencing panel, eg ThyroSeq v2. Molecular methods can also be applied as rule-out tests for malignancy in thyroid nodules, eg Afirma or ThyroSeq v2 or as markers of prognosis, eg TERT promoter mutation or other gene mutations including BRAF V600E, TP53 and AKT1, and as tests for newly defined tumour entities such as non-invasive follicular thyroid neoplasm with papillary like nuclei, or as a molecular marker(s) for targeted therapies...
December 2017: Cytopathology: Official Journal of the British Society for Clinical Cytology
https://www.readbyqxmd.com/read/29165794/leptomeningeal-metastasis-from-systemic-cancer-review-and-update-on-management
#7
REVIEW
Nancy Wang, Mia S Bertalan, Priscilla K Brastianos
Leptomeningeal metastasis is an uncommon and typically late complication of cancer with a poor prognosis and limited treatment options. Diagnosis is often challenging, with nonspecific presenting symptoms ranging from headache and confusion to focal neurologic deficits, such as cranial nerve palsies. Standard diagnostic evaluation involves a neurologic examination, magnetic resonance imaging of the brain and spine with gadolinium, and cytologic evaluation of the cerebral spinal fluid. Therapy entails a multimodal approach focused on palliation with surgery, radiation, and/or chemotherapy, which may be administered systemically or directly into the cerebral spinal fluid...
November 22, 2017: Cancer
https://www.readbyqxmd.com/read/29165736/the-spartacus-trial-controversies-and-unresolved-issues
#8
Felix Beuschlein, Paolo Mulatero, Evelyn Asbach, Silvia Monticone, Cristiana Catena, Leonardo A Sechi, Michael Stowasser
Adrenal vein sampling (AVS) is considered the gold standard for the differential diagnosis in patients with primary aldosteronism (PA). The distinction between unilateral and bilateral disease dictates the targeted therapeutic approach with surgery for aldosterone producing adenomas and medical therapy for patients with bilateral hyperplasia. Thereby, this diagnostic step is crucial in clinical care. As AVS is an invasive, not well standardized procedure that is restricted to few specialized centers, several attempts have been made to simplify diagnostic algorithms...
November 17, 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/29165700/epigenetic-therapy-novel-translational-implications-for-arrest-of-environmental-dioxin-induced-disease-in-females
#9
Zaraq Khan, Ye Zheng, Tiffanny L Jones, Abigail A Delaney, Luiz F Correa, Chandra C Shenoy, Khashayarsha Khazaie, Gaurang S Daftary
Increased toxicant exposure and resultant environmentally-induced diseases are a tradeoff of industrial productivity. Dioxin (TCDD: 2,3,7,8 tetrachlorodibenzo-p-dioxin), a ubiquitous by-product is associated with a spectrum of diseases including endometriosis, a common, chronic disease in women. TCDD activates cytochrome p450 (CYP) metabolic enzymes, which alters organ function to cause disease. In contrast, the transcription factor, Krüppel-Like Factor (KLF) 11 represses these enzymes via epigenetic mechanisms...
November 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/29165638/feasibility-of-real-time-molecular-profiling-for-patients-with-newly-diagnosed-glioblastoma-without-mgmt-promoter-hypermethylation-the-nct-neuro-master-match-n2m2-pilot-study
#10
Elke Pfaff, Tobias Kessler, Gnana Prakash Balasubramanian, Anne Berberich, Daniel Schrimpf, Antje Wick, Jürgen Debus, Andreas Unterberg, Martin Bendszus, Christel Herold-Mende, David Capper, Irini Schenkel, Andreas Eisenmenger, Susan Dettmer, Benedikt Brors, Michael Platten, Stefan M Pfister, Andreas von Deimling, David T W Jones, Wolfgang Wick, Felix Sahm
Introduction: O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status is a predictive biomarker in glioblastoma patients. Glioblastoma without hypermethylated MGMT promoter are largely resistant to treatment with temozolomide. These patients are in particular need of new treatment approaches, which are offered by biomarker-driven clinical trials with targeted drugs based on molecular characterization of individual tumors. Methods: In preparation for an upcoming clinical study, a comprehensive molecular profiling approach was undertaken on tissues from 43 glioblastoma patients harboring an unmethylated MGMT promoter at diagnosis...
November 18, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29165636/reducing-redundant-anaerobic-therapy-through-spaced-education-and-antimicrobial-stewardship-interventions
#11
Kelly B Flett, Athos Bousvaros, Jane Carpenter, Carly E Millrinen, Patricia Martin, Thomas J Sandora
Background: Decreasing the use of redundant anaerobic therapy is a key target for antimicrobial stewardship. Education techniques that optimize knowledge retention could be an important component of reducing these regimens. Methods: We implemented a quality improvement project that incorporated spaced education to reduce the use of redundant anaerobic therapy. The initial interventions (November through December 2015) included education in a hospital-wide newsletter and review of redundant anaerobic regimens by the antimicrobial stewardship program...
November 20, 2017: Journal of the Pediatric Infectious Diseases Society
https://www.readbyqxmd.com/read/29165620/comparative-effectiveness-of-allopurinol-febuxostat-and-benzbromarone-on-renal-function-in-chronic-kidney-disease-patients-with-hyperuricemia-a-13-year-inception-cohort-study
#12
Hsu-Wen Chou, Hsien-Tsai Chiu, Ching-Wei Tsai, I-Wen Ting, Hung-Chieh Yeh, Han-Chun Huang, Chin-Chi Kuo
Background: Direct comparisons of the effectiveness of allopurinol with that of other urate-lowering agents in chronic kidney disease (CKD) populations, as well as guideline recommendations for clinical practice, are lacking. Methods: We constructed a pharmacoepidemiology cohort study by including patients from Taiwan's long-term integrated CKD care program to compare the effectiveness among allopurinol, febuxostat and benzbromarone in reducing the risk of progression to dialysis...
November 17, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29165619/comparison-of-response-of-passive-dosimetry-systems-in-scanning-proton-radiotherapy-a-study-using-paediatric-anthropomorphic-phantoms
#13
Ž Kneževic, I Ambrozova, C Domingo, M De Saint-Hubert, M Majer, I Martínez-Rovira, S Miljanic, N Mojzeszek, P Porwol, O Ploc, M Romero-Expósito, L Stolarczyk, S Trinkl, R M Harrison, P Olko
Proton beam therapy has advantages in comparison to conventional photon radiotherapy due to the physical properties of proton beams (e.g. sharp distal fall off, adjustable range and modulation). In proton therapy, there is the possibility of sparing healthy tissue close to the target volume. This is especially important when tumours are located next to critical organs and while treating cancer in paediatric patients. On the other hand, the interactions of protons with matter result in the production of secondary radiation, mostly neutrons and gamma radiation, which deposit their energy at a distance from the target...
November 18, 2017: Radiation Protection Dosimetry
https://www.readbyqxmd.com/read/29165498/tomographic-magnetic-particle-imaging-of-cancer-targeted-nanoparticles
#14
Hamed Arami, Eric Teeman, Alyssa Troksa, Haydin Bradshaw, Katayoun Saatchi, Asahi Tomitaka, Sanjiv Sam Gambhir, Urs O Häfeli, Denny Liggitt, Kannan M Krishnan
Magnetic Particle Imaging (MPI) is an emerging, whole body biomedical imaging technique, with sub-millimeter spatial resolution and high sensitivity to a biocompatible contrast agent consisting of an iron oxide nanoparticle core and a biofunctionalized shell. Successful application of MPI for imaging of cancer depends on the nanoparticles (NPs) accumulating at tumors at sufficient levels relative to other sites. NPs' physiochemical properties such as size, crystallographic structure and uniformity, surface coating, stability, blood circulation time and magnetization determine the efficacy of their tumor accumulation and MPI signal generation...
November 22, 2017: Nanoscale
https://www.readbyqxmd.com/read/29165391/micrornas-associated-with-von-hippel-lindau-pathway-in-renal-cell-carcinoma-a-comprehensive-review
#15
REVIEW
Lisa-Maria Schanza, Maximilian Seles, Michael Stotz, Johannes Fosselteder, Georg C Hutterer, Martin Pichler, Verena Stiegelbauer
Renal cell carcinoma (RCC) are the most common renal neoplasia and can be divided into three main histologic subtypes, among which clear cell RCC is by far the most common form of kidney cancer. Despite substantial advances over the last decade in the understanding of RCC biology, surgical treatments, and targeted and immuno-therapies in the metastatic setting, the prognosis for advanced RCC patients remains poor. One of the major problems with RCC treatment strategies is inherent or acquired resistance towards therapeutic agents over time...
November 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29165358/understanding-the-molecular-genetics-of-basal-cell-carcinoma
#16
REVIEW
Cristina Pellegrini, Maria Giovanna Maturo, Lucia Di Nardo, Valeria Ciciarelli, Carlota Gutiérrez García-Rodrigo, Maria Concetta Fargnoli
Basal cell carcinoma (BCC) is the most common human cancer and represents a growing public health care problem. Several tumor suppressor genes and proto-oncogenes have been implicated in BCC pathogenesis, including the key components of the Hedgehog pathway, PTCH1 and SMO, the TP53 tumor suppressor, and members of the RAS proto-oncogene family. Aberrant activation of the Hedgehog pathway represents the molecular driver in basal cell carcinoma pathogenesis, with the majority of BCCs carrying somatic point mutations, mainly ultraviolet (UV)-induced, and/or copy-loss of heterozygosis in the PTCH1 gene...
November 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29165322/treatment-planning-with-intensity-modulated-particle-therapy-for-multiple-targets-in-stage-iv-non-small-cell-lung-cancer
#17
Kristjan Anderle, Joep Stroom, Sandra Vieira, Nuno Pimentel, Carlo Greco, Marco Durante, Christian Graeff
Intensity modulated particle therapy (IMPT) can produce highly conformal plans, but is limited in advanced lung cancer patients with multiple lesions due to motion and planning complexity. A 4D IMPT optimization including all motion states was expanded to include multiple targets, where each target (isocenter) is designated to specific field(s). Furthermore, to achieve stereotactic treatment planning objectives, target and OAR weights plus objective doses were automatically iteratively adapted. Finally, 4D doses were calculated for different motion scenarios...
November 22, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/29165288/treatment-related-noncontiguous-radiologic-changes-in-children-with-diffuse-intrinsic-pontine-glioma-treated-with-expanded-irradiation-fields-and-antiangiogenic-therapy
#18
Zoltan Patay, Thomas E Merchant, Rosa Nguyen, Christopher R Pierson, Arzu Onar-Thomas, Alberto Broniscer
PURPOSE: We previously reported the cases of 3 children with diffuse intrinsic pontine glioma (DIPG) in whom noncontiguous treatment-related abnormalities (NCTRAs) developed in the brain after expanded-field radiation therapy (RT). To investigate the occurrence and putative mechanism of NCTRAs, we reviewed brain magnetic resonance imaging studies of patients with DIPG treated in 2 consecutive phase I clinical trials (trials 1 and 2). METHODS AND MATERIALS: The 55 children included in these trials received small-molecule inhibitors: vandetanib in trial 1 (n=32; mean age 6...
December 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29165285/hypofractionated-nodal-radiation-therapy-for-breast-cancer-was-not-associated-with-increased-patient-reported-arm-or-brachial-plexopathy-symptoms
#19
Nelson Leong, Pauline T Truong, Keith Tankel, Winkle Kwan, Lorna Weir, Ivo A Olivotto
PURPOSE: To determine whether nodal radiation therapy (RT) for breast cancer using modest hypofractionation (HF) with 2.25 to 2.5 Gy per fraction (fx) was associated with increased patient-reported arm symptoms, compared with conventional fractionation (CF) ≤2 Gy/fx. METHODS AND MATERIALS: Two cancer registries were used to identify subjects who received computed tomography-planned nodal RT for pT1-3, pN0-2, M0 breast cancer, from 2007 to 2010 at 2 cancer institutions...
December 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29165072/mpeg-pla-micelle-for-delivery-of-effective-parts-of-andrographis-paniculata
#20
Hailu Yao, Shiyong Song, Xiaolu Miao, Xiao Liu, Zhen Wang, Xiaoting Shao, Yu Zhang, Guang Han
Many studies have shown that Andrographis paniculata (Burm. f.) Nees has a good anti-tumor effect, but poor solubility in water and poor bioavailability hinder the modernization of it. To formulate the effective parts (mainly diterpene lactones) of Andrographis paniculata (AEP) into targeting drug delivery system, a series of poly(ethylene glycol)-poly(D.L-lactic acid)(mPEG-PLA) with different ratio of hydrophilic and hydrophobic segment were synthetized to encapsulate AEP. AEP micelles were prepared by a simple solvent-evaporation method...
November 19, 2017: Current Drug Delivery
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