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https://www.readbyqxmd.com/read/28538872/melanoma-tumor-microenvironment-and-new-treatments
#1
Mara Huffenbaecher Giavina-Bianchi, Pedro Francisco Giavina-Bianchi, Cyro Festa
In the recent past years, many discoveries in the tumor microenvironment have led to changes in the management of melanoma and it is rising up hopes, specially, to those in advanced stages. FDA approved seven new drugs from 2011 to 2014. They are: Vemurafenib, Dabrafenib and Trametinib, kinases inhibitors used for patients that have BRAFV600E mutation; Ipilimumab (anti-CTLA4), Pembrolizumab (anti-PD-1) and Nivolumab (anti-PD-1), monoclonal antibodies that stimulate the immune system; and Peginterferon alfa-2b, an anti-proliferative cytokine used as adjuvant therapy...
March 2017: Anais Brasileiros de Dermatologia
https://www.readbyqxmd.com/read/28538834/characteristics-of-liver-fibrosis-with-different-etiologies-using-a-fully-quantitative-fibrosis-assessment-tool
#2
Q Wu, X Zhao, H You
This study aimed to test the diagnostic performance of a fully quantitative fibrosis assessment tool for liver fibrosis in patients with chronic hepatitis B (CHB), primary biliary cirrhosis (PBC) and non-alcoholic steatohepatitis (NASH). A total of 117 patients with liver fibrosis were included in this study, including 50 patients with CHB, 49 patients with PBC and 18 patients with NASH. All patients underwent liver biopsy (LB). Fibrosis stages were assessed by two experienced pathologists. Histopathological images of LB slices were processed by second harmonic generation (SHG)/two-photon excited fluorescence (TPEF) microscopy without staining, a system called qFibrosis (quantitative fibrosis) system...
May 18, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28538728/the-sunflower-genome-provides-insights-into-oil-metabolism-flowering-and-asterid-evolution
#3
Hélène Badouin, Jérôme Gouzy, Christopher J Grassa, Florent Murat, S Evan Staton, Ludovic Cottret, Christine Lelandais-Brière, Gregory L Owens, Sébastien Carrère, Baptiste Mayjonade, Ludovic Legrand, Navdeep Gill, Nolan C Kane, John E Bowers, Sariel Hubner, Arnaud Bellec, Aurélie Bérard, Hélène Bergès, Nicolas Blanchet, Marie-Claude Boniface, Dominique Brunel, Olivier Catrice, Nadia Chaidir, Clotilde Claudel, Cécile Donnadieu, Thomas Faraut, Ghislain Fievet, Nicolas Helmstetter, Matthew King, Steven J Knapp, Zhao Lai, Marie-Christine Le Paslier, Yannick Lippi, Lolita Lorenzon, Jennifer R Mandel, Gwenola Marage, Gwenaëlle Marchand, Elodie Marquand, Emmanuelle Bret-Mestries, Evan Morien, Savithri Nambeesan, Thuy Nguyen, Prune Pegot-Espagnet, Nicolas Pouilly, Frances Raftis, Erika Sallet, Thomas Schiex, Justine Thomas, Céline Vandecasteele, Didier Varès, Felicity Vear, Sonia Vautrin, Martin Crespi, Brigitte Mangin, John M Burke, Jérôme Salse, Stéphane Muños, Patrick Vincourt, Loren H Rieseberg, Nicolas B Langlade
The domesticated sunflower, Helianthus annuus L., is a global oil crop that has promise for climate change adaptation, because it can maintain stable yields across a wide variety of environmental conditions, including drought. Even greater resilience is achievable through the mining of resistance alleles from compatible wild sunflower relatives, including numerous extremophile species. Here we report a high-quality reference for the sunflower genome (3.6 gigabases), together with extensive transcriptomic data from vegetative and floral organs...
May 22, 2017: Nature
https://www.readbyqxmd.com/read/28538604/acute-gastric-volvulus-successfully-treated-by-endoscopic-reduction-in-a-6-year-old-girl-and-a-review-of-the-japanese-literature
#4
Mitsuhiro Haga, Nobuyuki Sano, Takamichi Kamiyama, Naohiro Dairaku, Mari Ishii, Teruko Nemoto, Hoshiro Suzuki, Hiromi Fujie, Jun Suzuki
A previously healthy 6-year-old girl suddenly developed severe abdominal pain and nausea. She was diagnosed with acute gastric volvulus, and a nasogastric tube was inserted to decompress the stomach. The volvulus did not reduce spontaneously; therefore, we performed endoscopic reduction on day 3 and were able to treat her successfully. We reviewed the Japanese literature on endoscopic reduction for gastric volvulus in children. Fifteen cases have been reported since 1994. There are no reports of perforation during the procedure...
May 23, 2017: Pediatric Emergency Care
https://www.readbyqxmd.com/read/28538597/surgical-management-of-thoracolumbar-kyphosis-in-patients-with-mucopolysaccharidosis-a-systematic-review
#5
Nicole Williams, Peter Cundy, Deborah Eastwood
STUDY DESIGN: Systematic Review OBJECTIVE.: To determine the indications and outcomes for surgical treatment of thoracolumbar kyphosis in patients with mucopolysaccharidoses (MPS) in order to define future studies. SUMMARY OF BACKGROUND DATA: Improvements in the medical treatment of MPS have increased lifespan and improved quality of life for many patients, but with no effect on thoracolumbar kyphosis. A greater number of these challenging patients may now be considered spinal surgical candidates...
May 22, 2017: Spine
https://www.readbyqxmd.com/read/28538578/total-abdominal-wall-transplantation-an-anatomical-study-and-classification-system
#6
David Light, Neilendu Kundu, Risal Djohan, Cristiano Quintini, Namita Gandhi, Brian R Gastman, Richard Drake, Maria Siemionow, James E Zins
BACKGROUND: Candidates for multivisceral transplantation present with complex defects often beyond traditional reconstructive options. In this study, the authors describe a dissection technique for a total abdominal wall vascularized composite flap. In addition, the authors suggest a classification system for complex abdominal wall defects. METHODS: Forty fresh, cadaveric hemiabdomens were dissected, with care taken to preserve the iliofemoral, deep circumflex iliac, superficial circumflex iliac, deep inferior epigastric, and superficial inferior epigastric arteries and corresponding veins...
June 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28538370/radiographic-anatomical-relationship-between-spinous-process-and-pedicle-in-thoracolumbar-and-lumbar-spine
#7
Xingang Cui, Guodong Wang
Pedicle screws are widely used in spinal surgeries, but it remains technically demanding to place. There are numerous studies on the anatomy of pedicle; however, there is very little insight on the relationship between the pedicle and the spinous process, which is an important part of the spinal posterior column.The aim of the study was to investigate the radiographic anatomical relationship between spinous processes and pedicles in the thoracolumbar and lumbar spine, in order to reveal a novel entrance point for pedicle screw insertion...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28538289/a-three-dimensional-analysis-of-the-fracture-planes-in-pediatric-lateral-humeral-condyle-fractures-for-image-based-pin-positioning-during-fixation
#8
Do Young Park, Jae Ho Cho, Doo-Hyung Lee, Wan-Sun Choi, Jun Young Bang, Xiang Yun Yin
OBJECTIVE: To determine the 3 dimensional morphology of pediatric lateral condylar physeal fractures using 3-dimensional computed tomography (3D-CT) and to identify optimal pin positions for percutaneous pinning. DESIGN: Prospective case series of consecutively treated patients SETTING:: Tertiary university hospital setting. PATIENTS: Preoperative 3D-CTs in pediatric surgical candidates diagnosed with lateral condylar physeal fractures INTERVENTION:: Closed reduction and percutaneous pinning was performed...
May 17, 2017: Journal of Orthopaedic Trauma
https://www.readbyqxmd.com/read/28538284/the-advance-study-a-groundbreaking-trial-to-evaluate-a-candidate-universal-antiretroviral-regimen
#9
Willem D F Venter, Polly Clayden, Celicia Serenata
PURPOSE OF REVIEW: Current WHO-recommended first-line therapy in low-income and middle-income countries has been very successful in saving millions of lives but still has toxicity concerns and a low barrier to resistance. RECENT FINDINGS: Two candidate antiretrovirals may substantially transform first-line therapy in low-income and middle-income countries, yielding a safer, more robust and cheaper regimen. Tenofovir alafenamide carries toxicity and cost benefits over tenofovir disoproxil fumarate...
May 19, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28538178/wolf-hirschhorn-syndrome-candidate-1-is-necessary-for-correct-hematopoietic-and-b-cell-development
#10
Elena Campos-Sanchez, Nerea Deleyto-Seldas, Veronica Dominguez, Enrique Carrillo-de-Santa-Pau, Kiyoe Ura, Pedro P Rocha, JungHyun Kim, Arafat Aljoufi, Anna Esteve-Codina, Marc Dabad, Marta Gut, Holger Heyn, Yasufumi Kaneda, Keisuke Nimura, Jane A Skok, Maria Luisa Martinez-Frias, Cesar Cobaleda
Immunodeficiency is one of the most important causes of mortality associated with Wolf-Hirschhorn syndrome (WHS), a severe rare disease originated by a deletion in chromosome 4p. The WHS candidate 1 (WHSC1) gene has been proposed as one of the main genes responsible for many of the alterations in WHS, but its mechanism of action is still unknown. Here, we present in vivo genetic evidence showing that Whsc1 plays an important role at several points of hematopoietic development. Particularly, our results demonstrate that both differentiation and function of Whsc1-deficient B cells are impaired at several key developmental stages due to profound molecular defects affecting B cell lineage specification, commitment, fitness, and proliferation, demonstrating a causal role for WHSC1 in the immunodeficiency of WHS patients...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28538000/revascularization-for-patients-with-diabetes-mellitus-and-stable-ischemic-heart-disease-an-update
#11
G B John Mancini, Michael Farkouh, Subodh Verma
PURPOSE OF REVIEW: To provide an update on the management of patients with diabetes mellitus and requiring coronary revascularization. RECENT FINDINGS: Evidence continues to show that patients with diabetes mellitus and ischemic heart disease represent a very high-risk group of patients. Choice of stent appears important for minimizing target lesion and target vessel adverse events with everolimus eluting stents having the best performance, particularly in patients being treated with insulin...
May 19, 2017: Current Opinion in Cardiology
https://www.readbyqxmd.com/read/28537927/wx-132-18b-a-novel-microtubule-inhibitor-exhibits-promising-anti-tumor-effects
#12
Fang Guan, Rui Ding, Qi Zhang, Wei Chen, Feifei Li, Long Long, Wei Li, Linna Li, Dexuan Yang, Lan Xie, Shoujun Yuan, Lili Wang
Cancer drug researchers have been seeking microtubule-inhibiting agents (MIAs) with higher bioactivity and lower toxicity than currently marketed drugs. WX-132-18B, a novel structural compound synthesized at our institute, specifically bound to the colchicine-binding site on tubulin rather than the vinblastine site, and concentration-dependently reduced microtubule content via depolymerization. It exhibited the same cellular phenotypic profiles as the classic MIAs (colchicine, vincristine, and taxol), including inducing cell cycle arrest at the G2/M phase, triggering tumor cell apoptosis, promoting nuclear membrane permeability, reducing mitochondrial membrane potential, and disrupting the redox system balance...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537878/biological-characterization-of-sn32976-a-selective-inhibitor-of-pi3k-and-mtor-with-preferential-activity-to-pi3k%C3%AE-in-comparison-to-established-pan-pi3k-inhibitors
#13
Gordon W Rewcastle, Sharada Kolekar, Christina M Buchanan, Swarna A Gamage, Anna C Giddens, Kit Y Tsang, Jackie D Kendall, Ripudaman Singh, Woo-Jeong Lee, Greg C Smith, Weiping Han, David J Matthews, William A Denny, Peter R Shepherd, Stephen M F Jamieson
Multiple therapeutic agents have been developed to target the phosphatidylinositol 3-kinase (PI3K) signaling pathway, which is frequently dysregulated in cancer promoting tumor growth and survival. These include pan PI3K inhibitors, which target class Ia PI3K isoforms and have largely shown limited single agent activity with narrow therapeutic windows in clinical trials. Here, we characterize SN32976, a novel pan PI3K inhibitor, for its biochemical potency against PI3K isoforms and mTOR, kinase selectivity, cellular activity, pharmacokinetics, pharmacodynamics and antitumor efficacy relative to five clinically-evaluated pan PI3K inhibitors: buparlisib, dactolisib, pictilisib, omipalisib and ZSTK474...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537846/uremic-toxins-affect-the-imbalance-of-redox-state-and-overexpression-of-prolyl-hydroxylase-2-in-human-adipose-tissue-derived-mesenchymal-stem-cells-involved-in-wound-healing
#14
Vuong Cat Khanh, Kinuko Ohneda, Toshiki Kato, Toshiharu Yamashita, Fujio Sato, Kana Tachi, Osamu Ohneda
Chronic kidney disease (CKD) results in a delay in wound healing because of its complications such as uremia, anemia, and fluid overload. Mesenchymal stem cells (MSCs) are considered to be a candidate for wound healing because of the ability to recruit many types of cells. However, it is still unclear whether the CKD-adipose tissue-derived MSCs (CKD-AT-MSCs) have the same function in wound healing as healthy donor-derived normal AT-MSCs (nAT-MSCs). In this study, we found that uremic toxins induced elevated reactive oxygen species (ROS) expression in nAT-MSCs, resulting in the reduced expression of hypoxia-inducible factor-1α (HIF-1α) under hypoxic conditions...
May 24, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28537748/pesticide-interactions-mechanisms-benefits-and-risks
#15
John E Casida
Interactions between pesticides at common molecular targets and detoxification systems often determine their effectiveness and safety. Compounds with the same mode of action or target are candidates for cross resistance and restrictions in their recommended uses. Discovery research is therefore focused on new mechanisms and modes of action. Interactions in detoxification systems also provide cross resistance and synergist and safener mechanisms illustrated with serine hydrolases and inhibitors, cytochrome P450s and insecticide synergists, and glutathione S-transferases and herbicide safeners...
May 24, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28537728/antimalarial-inhibitors-targeting-serine-hydroxymethyltransferase-shmt-with-in-vivo-efficacy-and-analysis-of-their-binding-mode-based-on-x-ray-cocrystal-structures
#16
Geoffrey Schwertz, Matthias C Witschel, Matthias Rottmann, Roger Bonnert, Ubolsree Leartsakulpanich, Penchit Chitnumsub, Aritsara Jaruwat, Wanwipa Ittarat, Anja Schäfer, Raphael A Aponte, Susan A Charman, Karen L White, Abhijit Kundu, Surajit Sadhukhan, Mel Lloyd, Gail M Freiberg, Myron Srikumaran, Marc Siggel, Adrian Zwyssig, Pimchai Chaiyen, François Diederich
Target-based approaches towards new antimalarial treatments are highly valuable to prevent resistance development. We report several series of pyrazolopyran-based inhibitors targeting the enzyme serine hydroxymethyltransferase (SHMT), designed to improve microsomal metabolic stability and to identify suitable candidates for in vivo efficacy evaluation. The best ligands inhibited Plasmodium falciparum (Pf) and Arabidopsis thaliana (At) SHMT in target assays and PfNF54 strains in cell-based assays with values in the low nanomolar range (3...
May 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28535608/antifungal-activities-of-dimeric-sesquiterpenes-shizukaols-c-and-f-isolated-from-chloranthus-japonicus-sieb
#17
Tae Hoon Kang, Yun Mi Lee, Won Jung Lee, Eui Il Hwang, Ki Duk Park, Gyang Ja Choi, Jae Sun Moon, Ho-Yong Park, Sung Uk Kim
Two dimeric sesquitepenes were separated from Chloranthus japonicus Sieb. and identified as shizukaols C and F. They exhibited potent antifungal activities (MICs = 4-16 μg/ml) in vitro against various plant pathogenic fungi Pythium ultimum, Phytophthora infestans, Botrytis cinerea, Colletotrichum lagenarium, Alternaria kikuchana, and Magnaporthe grisea. Shizukaol C showed 88% and 91% protective activities in the greenhouse against Puccinia recondite (wheat leaf rust) and Phytophthora infestans (tomato late blight), respectively, at 100 µg/ml; shizukaol F exhibited 93% antifungal activity against Puccinia recondite at the same concentration...
May 24, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28535443/independent-validation-of-body-fluid-specific-cpg-markers-and-construction-of-a-robust-multiplex-assay
#18
Hannah Holtkötter, Vanessa Beyer, Kristina Schwender, Alina Glaub, Kristina Schulze Johann, Marianne Schürenkamp, Ursula Sibbing, Sabrina Banken, Peter Wiegand, Heidi Pfeiffer, Lynn Dennany, Marielle Vennemann, Marielle Vennemann
Potential forensic use of tissue-specific DNA methylation markers has recently been discussed for the identification of the biological source of a stain. In this study 13 promising markers were evaluated to identify suitable candidate markers for the development of a robust and reliable multiplex assay. The results of this study suggest that a combination of only four highly informative markers will be enough for clear body fluid identification. A multiplex assay was developed for the identification of menstrual blood, saliva, semen, and venous blood...
May 9, 2017: Forensic Science International. Genetics
https://www.readbyqxmd.com/read/28535374/discovery-of-stromal-regulatory-networks-that-suppress-ras-sensitized-epithelial-cell-proliferation
#19
Huayang Liu, James A Dowdle, Safiya Khurshid, Nicholas J Sullivan, Nicholas Bertos, Komal Rambani, Markus Mair, Piotr Daniel, Esther Wheeler, Xing Tang, Kyle Toth, Michael Lause, Markus E Harrigan, Karl Eiring, Connor Sullivan, Matthew J Sullivan, Serena W Chang, Siddhant Srivastava, Joseph S Conway, Raleigh Kladney, Joseph McElroy, Sooin Bae, Yuanzhi Lu, Ali Tofigh, Sadiq M I Saleh, Soledad A Fernandez, Jeffrey D Parvin, Vincenzo Coppola, Erin R Macrae, Sarmila Majumder, Charles L Shapiro, Lisa D Yee, Bhuvaneswari Ramaswamy, Michael Hallett, Michael C Ostrowski, Morag Park, Helen M Chamberlin, Gustavo Leone
Mesodermal cells signal to neighboring epithelial cells to modulate their proliferation in both normal and disease states. We adapted a Caenorhabditis elegans organogenesis model to enable a genome-wide mesodermal-specific RNAi screen and discovered 39 factors in mesodermal cells that suppress the proliferation of adjacent Ras pathway-sensitized epithelial cells. These candidates encode components of protein complexes and signaling pathways that converge on the control of chromatin dynamics, cytoplasmic polyadenylation, and translation...
May 22, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28535276/live-attenuated-pertussis-vaccine-bpze1-protects-baboons-against-b-pertussis-disease-and-infection
#20
Camille Locht, James F Papin, Sophie Lecher, Anne-Sophie Debrie, Marcel Thalen, Ken Solovay, Keith Rubin, Nathalie Mielcarek
Evidence suggests that the resurgence of pertussis in many industrialized countries may result from the failure of current vaccines to prevent nasopharyngeal colonization by Bordetella pertussis, the principal causative agent of whooping cough. Here, we used a baboon model to test the protective potential of the novel, live attenuated pertussis vaccine candidate BPZE1. A single intranasal/intratracheal inoculation of juvenile baboons with BPZE1 resulted in transient nasopharyngeal colonization and induction of IgG and IgA to all antigens tested, while causing no adverse symptoms or leukocytosis...
May 23, 2017: Journal of Infectious Diseases
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