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https://www.readbyqxmd.com/read/29452121/an-open-label-pilot-study-to-evaluate-the-efficacy-of-tofacitinib-in-moderate-to-severe-patch-type-alopecia-areata-totalis-and-universalis
#1
A Jabbari, F Sansaricq, J Cerise, J C Chen, A Bitterman, G Ulerio, J Borbon, R Clynes, A M Christiano, J Mackay-Wiggan
Alopecia areata (AA) is a common autoimmune disease, with a lifetime risk of ∼2%. In AA, the immune systems targets the hair follicle, resulting in clinical hair loss. AA prognosis is unpredictable, and currently there is no definitive treatment. Our previous whole genome expression studies identified active immune circuits in AA lesions, including common γ-chain cytokine and IFN pathways. Since these pathways are mediated through JAK kinases, we prioritized clinical exploration of small molecule JAK inhibitors...
February 13, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29451706/insulin-degludec-insulin-aspart-lowers-fasting-plasma-glucose-and-rates-of-confirmed-and-nocturnal-hypoglycaemia-independent-of-baseline-hba-1c-levels-disease-duration-or-bmi-a-pooled-meta-analysis-of-phase-3-studies-in-patients-with-type-2-diabetes
#2
Martin Haluzík, Greg Fulcher, Thomas R Pieber, Lars Bardtrum, Deniz Tutkunkardas, Helena W Rodbard
AIMS: Previous studies demonstrated the co-formulation of insulin degludec (IDeg)/insulin aspart (IAsp) 'IDegAsp' offers lower rates of hypoglycaemia with smaller changes in weight compared with basal-bolus (IDeg once daily [OD] + IAsp [2-4 injections]) and premix insulin (BIAsp 30 twice daily [BID]) comparators. This study aimed to investigate whether the benefits of IDegAsp, given twice daily, extend across a wide spectrum of patients with diabetes. MATERIALS AND METHODS: This was a post hoc pooled analysis of five phase 3 randomised, 26-week, open-label, BID, treat-to-target trials comparing IDegAsp BID (n = 1111) with one of two 'comparators' - BIAsp 30 BID (n = 561) or IDeg OD + IAsp (n = 136)...
February 16, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29450140/jnk3-phosphorylates-bax-protein-and-induces-ability-to-form-pore-on-bilayer-lipid-membrane
#3
Rajeev Gupta, Subhendu Ghosh
Bax is a pro-apoptotic cytosolic protein. In this work native (unphosphorylated) and JNK3 phosphorylated Bax proteins are studied on artificial bilayer membranes for pore formation. Phosphorylated Bax formed pore on the bilayer lipid membrane whereas native one does not. In cells undergoing apoptosis the pore formed by the phosphorylated Bax could be important in cytochrome c release from the mitochondrial intermembrane space to the cytosol. The low conductance (1.5 nS) of the open state of the phosphorylated Bax pore corresponds to pore diameter of 0...
June 2017: Biochimie Open
https://www.readbyqxmd.com/read/29449710/oncologists-tap-the-microbiome-in-bid-to-improve-immunotherapy-outcomes
#4
Asher Mullard
No abstract text is available yet for this article.
February 16, 2018: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/29447329/randomised-phase-iii-trial-of-vinflunine-plus-capecitabine-versus-capecitabine-alone-in-patients-with-advanced-breast-cancer-previously-treated-with-an-anthracycline-and-resistant-to-taxane
#5
M Martin, M Campone, I Bondarenko, D Sakaeva, S Krishnamurthy, L Roman, L Lebedeva, J-C Vedovato, M Aapro
Background: Capecitabine is an approved standard therapy for anthracycline- and taxane-pretreated locally advanced or metastatic breast cancer (BC). Vinflunine has demonstrated single-agent activity in phase II studies in this setting, and activity and tolerability when combined with capecitabine. We compared the combination of vinflunine plus capecitabine (VC) with single-agent capecitabine. Patients and methods: Patients with locally recurrent/metastatic BC previously treated or resistant to an anthracycline and resistant to taxane therapy were randomly assigned to either vinflunine (280 mg/m2, day 1) plus oral capecitabine (825 mg/m2 twice daily [bid], days 1-14) every 3 weeks (q3w) or single-agent oral capecitabine (1250 mg/m2 bid, days 1-14) q3w...
February 10, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29446343/cost-utility-analysis-of-antiviral-use-under-pandemic-influenza-using-a-novel-approach-linking-pharmacology-epidemiology-and-heath-economics
#6
D B C Wu, N Chaiyakunapruk, C Pratoomsoot, K K C Lee, H Y Chong, R E Nelson, P F Smith, C M Kirkpatrick, M A Kamal, K Nieforth, G Dall, S Toovey, D C M Kong, A Kamauu, C R Rayner
Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) - dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility...
February 15, 2018: Epidemiology and Infection
https://www.readbyqxmd.com/read/29444163/the-effect-of-nutramiltm-complex-food-for-special-medical-purpose-on-breast-and-prostate-carcinoma-cells
#7
Aneta A Koronowicz, Mariola Drozdowska, Barbara Wielgos, Ewelina Piasna-Słupecka, Dominik Domagała, Joanna Dulińska-Litewka, Teresa Leszczyńska
NutramilTM Complex is a multicomponent food product that meets the requirements of a food for special medical purpose. As a complete, high-energy diet it consists of properly balanced nutrients, vitamins and minerals. The aim of this study was to assess the effect of NutramilTM Complex on breast and prostate carcinoma cells. Our results showed that NutramilTM Complex reduced the viability and proliferation of breast and prostate cancer cells and that this process was associated with the induction of apoptosis via activation of caspase signalling...
2018: PloS One
https://www.readbyqxmd.com/read/29444104/shdcr3-sensitizes-trail-resistant-hcc-cells-by-inducing-caspase-dependent-apoptosis-while-suppressing-nf-%C3%AE%C2%BAb-dependent-cflipl-expression
#8
Dong-Yu Liang, Wei Huang, Qing Chang, Yan-Qiang Hou
Evidence has shown that most hepatocellular carcinoma (HCC) cells are resistant to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. However, the molecular mechanisms underlying TRAIL-mediated apoptosis resistance are not well understood. In this study, we reported that downregulation of Decoy receptor 3 (DcR3) expression by lentiviral vectors carrying shRNA against DcR3 (LV-ShDcR3, shDcR3) in Huh7 both greatly enhanced TRAIL-mediated apoptosis and reduced cell proliferation capability...
2018: PloS One
https://www.readbyqxmd.com/read/29440992/the-bcl-2-homology-3-domain-bh3-only-proteins-bid-dp5-hrk-and-bnip3l-are-upregulated-in-reactive-astrocytes-of-end-stage-mutant-sod1-mouse-spinal-cord
#9
Nathan Duval, Whitney A Sumner, Anna G Andrianakos, Josie J Gray, Ron J Bouchard, Heather M Wilkins, Daniel A Linseman
The molecular mechanisms leading to motor neuron death in amyotrophic lateral sclerosis (ALS) are unknown; however, several studies have provided evidence of a central role for intrinsic apoptosis. Bcl-2 homology-3 domain (BH3)-only proteins are pro-apoptotic members of the Bcl-2 family whose enhanced expression acts as a trigger for the intrinsic apoptotic cascade. Here, we compared the relative expression of BH3-only proteins in the spinal cord of end-stage G93A mutant SOD1 mice to age-matched wild-type (WT) mice...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29440708/differential-role-of-fl-bid-and-t-bid-during-verotoxin-1-induced-apoptosis-in-burkitt-s-lymphoma-cells
#10
Justine Debernardi, Emilie Hollville, Marc Lipinski, Joëlle Wiels, Aude Robert
The globotriaosylceramide Gb3 is a glycosphingolipid expressed on a subpopulation of germinal center B lymphocytes which has been recognized as the B cell differentiation antigen CD77. Among tumoral cell types, Gb3/CD77 is strongly expressed in Burkitt's lymphoma (BL) cells as well as other solid tumors including breast, testicular and ovarian carcinomas. One known ligand of Gb3/CD77 is Verotoxin-1 (VT-1), a Shiga toxin produced in specific E. coli strains. Previously, we have reported that in BL cells, VT-1 induces apoptosis via a caspase-dependent and mitochondria-dependent pathway...
February 14, 2018: Oncogene
https://www.readbyqxmd.com/read/29440181/a-first-in-human-study-of-the-new-oral-selective-estrogen-receptor-degrader-azd9496-for-hr-her2-advanced-breast-cancer
#11
Erika P Hamilton, Manish R Patel, Anne C Armstrong, Richard D Baird, Komal Jhaveri, Matthias Hoch, Teresa Klinowska, Justin P O Lindemann, Shethah Morgan, Gaia Schiavon, Hazel M Weir, Seock-Ah Im
PURPOSE: AZD9496 is an oral non-steroidal, small-molecule inhibitor of estrogen receptor alpha (ERα), and a potent and selective antagonist and degrader of ERα. This first in human Phase 1 study determined the safety and tolerability of ascending doses of oral AZD9496 in women with estrogen receptor (ER)+/HER2- advanced breast cancer, characterized its pharmacokinetic (PK) profile, and made preliminary assessment of antitumor activity. EXPERIMENTAL DESIGN: Forty-five patients received AZD9496 (20 mg once daily to 600 mg twice daily) in a dose-escalation, dose- expansion 'rolling 6' design...
February 13, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29439069/moving-towards-a-better-path-a-mixed-method-examination-of-china-s-reforms-to-remedy-medical-corruption-from-pharmaceutical-firms
#12
Jianwei Shi, Rui Liu, Hua Jiang, Chunxu Wang, Yue Xiao, Nana Liu, Zhaoxin Wang, Leiyu Shi
OBJECTIVES: Few studies have systematically examined the effects of the existing regulations for alleviating corruption in China. This study assesses the effectiveness of China's reforms to curb medical corruption. METHODS: We used mixed methods for the evaluation of existing countermeasures. First, qualitative informant interviews based on the Donabedian model were conducted to obtain experts' evaluation of various kinds of countermeasures. Second, using data from 'China Judgements Online', we analysed the trend of occurrence and the characteristics of the medical corruption cases in recent years to reflect the overall effects of these countermeasures in China...
February 8, 2018: BMJ Open
https://www.readbyqxmd.com/read/29436761/a-52-week-extension-study-of-switching-from-gemigliptin-vs-sitagliptin-to-gemigliptin-only-as-an-add-on-to-patients-with-type-2-diabetes-inadequately-controlled-on-metformin-alone
#13
Chan-Hee Jung, Eun-Jung Rhee, Won-Young Lee, Kyung Wan Min, Vyankatesh K Shivane, Aravind R Sosale, Hak Chul Jang, Choon Hee Chung, Il Seong Nam-Goong
We investigated the long-term efficacy and safety of gemigliptin and the efficacy and safety of gemigliptin treatment after once daily treatment with sitagliptin 100 mg, in patient with type 2 diabetes. This study was a 28-week, extension of a 24-week, randomized, double-blind, parallel study of gemigliptin or sitagliptin, added to ongoing metformin therapy. After randomized to sitagliptin 100 mg qd(S), gemigliptin 25 mg bid (G1), or gemigliptin 50 mg qd(G2) groups and completing treatment of 24 weeks, 118 patients switched from gemigliptin 25 mg bid to 50 mg qd(G1/G2), 111 patients continued gemigliptin 50 mg qd(G2/G2), and 106 patients switched from sitagliptin 100 mg qd to gemigliptin 50 mg qd(S/G2)...
February 13, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29434218/association-of-cytosolic-sialidase-neu2-with-plasma-membrane-enhances-fas-mediated-apoptosis-by-impairing-pi3k-akt-mtor-mediated-pathway-in-pancreatic-cancer-cells
#14
Shalini Nath, Chhabinath Mandal, Uttara Chatterjee, Chitra Mandal
Modulation of sialylation by sialyltransferases and sialidases plays essential role in carcinogenesis. There are few reports on sialyltransferase, however, the contribution of cytosolic sialidase (Neu2) remains unexplored in pancreatic ductal adenocarcinoma (PDAC). We observed lower expression of Neu2 in different PDAC cells, patient tissues, and a significant strong association with clinicopathological characteristics. Neu2 overexpression guided drug-resistant MIAPaCa2 and AsPC1 cells toward apoptosis as evidenced by decreased Bcl2/Bax ratio, activation of caspase-3/caspase-6/caspase-8, PARP reduction, reduced CDK2/CDK4/CDK6, and cyclin-B1/cyclin-E with unaffected caspase-9...
February 12, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29431470/economic-evaluation-of-safflower-yellow-injection-for-the-treatment-of-patients-with-stable-angina-pectoris-in-china-a-cost-effectiveness-analysis
#15
Jianwei Xuan, Min Huang, Yongji Lu, Libo Tao
OBJECTIVE: The purpose of this study was to evaluate the cost-effectiveness of Safflower Yellow Injection (SYI) plus conventional treatment (SYI group) versus conventional treatment only (conventional group) for the treatment of stable angina pectoris (SAP) patients in China. METHODS: A decision-tree model was constructed and the treatment impact was estimated for up to 1 year. The data, including treatment effectiveness, episodes of angina pectoris (AP)-associated hospitalization and its in-hospital mortality, mortality rate of heart diseases, and cost of hospitalization, were obtained from literature...
February 12, 2018: Journal of Alternative and Complementary Medicine: Research on Paradigm, Practice, and Policy
https://www.readbyqxmd.com/read/29427923/hg30-a-tetrahydroanthraquinone-compound-isolated-from-the-roots-of-prismatomeris-connate-induces-apoptosis-in-human-non-small-cell-lung-cancer-cells
#16
Shixiu Feng, Zhenzhen Wang, Min Zhang, Xiaohui Zhu, Zhanjun Ren
HG30, a tetrahydroanthraquinone compound isolated from the roots of Prismatomeris connate, was previously shown to inhibit the proliferation of A549 cells. The aim of this study was to evaluate the antitumor activity of HG30 in two non-small cell lung cancer cell lines, A549 and H1299, and to explore potential underlying mechanisms. In cell viability and colony formation assays, HG30 treatment suppressed the proliferation and number of colonies formed by A549 and H1299 cells. Western blot analysis further demonstrated that induction of apoptosis by HG30 in A549 and H1299 cells involves both caspase-dependent apoptosis pathways, including mitochondria- and death receptor-mediated pathways, and an apoptosis-inducing factor (AIF) -associated caspase-independent apoptosis pathway...
February 7, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29425631/combining-spatial-information-and-optimization-for-locating-emergency-medical-service-stations-a-case-study-for-lower-austria
#17
Robert Fritze, Anita Graser, Markus Sinnl
OBJECTIVES: Emergency medical services have been established in many countries all over the world. Good first care improves the outcome of patients in terms of hospital stay duration, chances of full recovery and of treatment costs. In this paper, we present an integrated approach combining spatial information and integer optimization for emergency medical service location planning. The research is motivated by a recent call for bids to restructure the location of emergency medical services in the Austrian federal state of Lower Austria by the local state government...
March 2018: International Journal of Medical Informatics
https://www.readbyqxmd.com/read/29423046/vitexin-induces-apoptosis-by-suppressing-autophagy-in-multi-drug-resistant-colorectal-cancer-cells
#18
Monika Bhardwaj, Hee Jun Cho, Souren Paul, Rekha Jakhar, Imran Khan, Seon-Jin Lee, Bo-Yeon Kim, Manigandan Krishnan, Tejinder Pal Khaket, Hee Gu Lee, Sun Chul Kang
Cancer treatment is limited due to the diverse multidrug resistance acquired by cancer cells and the collateral damage caused to adjacent normal cells by chemotherapy. The flavonoid compound vitexin exhibits anti-oxidative, anti-inflammatory and anti-tumor activity. This study elucidated the antitumor effects of vitexin and its underlying mechanisms in a multi-drug resistant human colon cancer cell line (HCT-116 DR ), which exhibits higher levels of multidrug-resistant protein 1 (MDR1) expression as compared with its parental cell line (HCT-116)...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29421383/latrunculin-b-and-substratum-stiffness-regulate-corneal-fibroblast-to-myofibroblast-transformation
#19
Sara M Thomasy, Vijay Krishna Raghunathan, Hidetaka Miyagi, Alexander T Evashenk, Jasmyne C Sermeno, Geneva K Tripp, Joshua T Morgan, Christopher J Murphy
The transformation of keratocytes and fibroblasts to myofibroblasts is important to corneal wound healing as well as formation of stromal haze. The purpose of this study was to determine the effect of latrunculin B, an actin cytoskeleton disruptor in conjunction with a fundamental biophysical cue, substrate stiffness, on myofibroblast transformation in vitro and in vivo. Rabbit corneal fibroblasts were cultured on substrates of differing compliance (1.5, 22, and 71 kPa) and tissue culture plastic (TCP; > 1 GPa) in media containing 0 or 10 ng/ml TGFβ1 for 72 h...
February 5, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29420993/glucagon-like-peptide-2-improves-intestinal-immune-function-and-diminishes-bacterial-translocation-in-a-mouse-model-of-parenteral-nutrition
#20
Qiucheng Lei, Jingcheng Bi, Huanwei Chen, Feng Tian, Xuejin Gao, Ning Li, Xinying Wang
Parenteral nutrition (PN) is associated with increased infectious risks due to impaired intestinal immunity. Although glucagon-like peptide-2 (GLP-2) enhances the gut barrier function, it is uncertain whether it improves mucosal immunologic barrier function. We hypothesized that injecting the PN mouse model with GLP-2 improved innate and acquired immunity, and prevented bacterial translocation. Forty-eight hours after venous cannulation, male Institute of Cancer Research mice were randomly divided into 3 groups based on their diet: chow with saline (n = 10), PN (n = 9), or PN + GLP-2 (30 μg bid per mouse, n = 10) provided for 5 days...
January 2018: Nutrition Research
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