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https://www.readbyqxmd.com/read/29908468/first-report-on-the-pharmacokinetic-profile-of-nimbolide-a-novel-anticancer-agent-in-oral-and-intravenous-administrated-rats-by-lc-ms-method
#1
Shandilya Mahamuni Baira, Amit Khurana, Jaganmohan Somagoni, R Srinivas, Chandraiah Godugu, M V N Kumar Talluri
Nimbolide is a novel, natural compound with promising potential as a drug candidate for anticancer activity. It is isolated from the Indian traditional medicinal plant Azadirachta indica popularly known as neem. The present study was undertaken to explore the oral bioavailability and pharmacokinetic characteristics of nimbolide in rats using the LC/QTOF/MS method. A simple protein precipitation method using acetonitrile was employed for extracting nimbolide from rat plasma. The chromatographic separation of nimbolide and the internal standard (regorafenib) was attained on an Aquity BEH C18 column (100 × 2...
June 2, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29908231/haploidentical-bone-marrow-transplantation-with-post-transplant-cyclophosphamide-bendamustine-in-pediatric-and-young-adult-patients-with-hematologic-malignancies
#2
Emmanuel Katsanis, Lauren N Sapp, Nicole Varner, Shannon Koza, Baldassarre Stea, Yi Zeng
More than half of patients undergoing hematopoietic cell transplantation at our institution are ethnic or racial minorities, making the search for matched unrelated donors more challenging. Since the introduction of haploidentical bone marrow transplant (haplo-BMT) into our pediatric BMT program in 2015, 69.2% of the recipients have been minorities. Herein, we describe our experience with the first thirteen pediatric and young adult patients with hematologic malignancies who have undergone T-cell replete haplo-BMT following myeloablative conditioning (MAC) at our institution...
June 13, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29906232/novel-role-of-pkr-in-palmitate-induced-sirt1-inactivation-and-endothelial-cell-senescence
#3
Yapei Li, Yang-Fan PengZhou, Chunle Wang, Le Li, Yiping Leng, Ruifang Chen, Hong Yuan, Shenghua Zhou, Zhen Zhang, Alex F Chen
Endothelial cell senescence is regarded as a vital characteristic of cardiovascular diseases (CVDs). Elevated palmitate (PA) is an independent risk factor of CVDs, but its role in the endothelial cell senescence is currently unknown. During the course of studying pro-senescent role of PA, we discovered a key role of double-stranded RNA-dependent protein kinase PKR in endothelial senescence. Exposure of human umbilical vein endothelial cells (HUVECs) to PA induced cell senescence, characterized by increased levels of senescence-associated β-galactose glucosidase (SA-β-gal) activity, excessive reactive oxygen species (ROS) production, impaired cellular proliferation, and G1 phase arrest...
June 15, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29900565/in-vivo-affinity-and-target-engagement-in-skin-and-blood-in-a-first-time-in-human-study-of-an-anti-oncostatin-m-monoclonal-antibody
#4
Juliet Reid, Stefano Zamuner, Ken Edwards, Sally-Anne Rumley, Katherine Nevin, Maria Feeney, Chiara Zecchin, Disala Fernando, Nicolas Wisniacki
BACKGROUND: The oncostatin M (OSM) pathway drives fibrosis, inflammation and vasculopathy and is a potential therapeutic target for inflammatory and fibrotic diseases. METHODS: This was a Phase I, randomised, double-blind, placebo-controlled, single-dose escalation, first-time-in-human study of subcutaneously administered GSK2330811, an anti-OSM monoclonal antibody, in healthy adults (NCT02386436). Safety and tolerability, GSK2330811 pharmacokinetic profile, OSM levels in blood and skin and potential for anti-drug antibody formation were assessed...
June 13, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29895196/the-acid-base-transport-proteins-nhe1-and-nbcn1-regulate-cell-cycle-progression-in-human-breast-cancer-cells
#5
Mette Flinck, Signe Hoejland Kramer, Julie Schnipper, Anne P Andersen, Stine F Pedersen
Precise acid-base homeostasis is essential for maintaining normal cell proliferation and growth. Conversely, dysregulated acid-base homeostasis, with increased acid extrusion and marked extracellular acidification, is an enabling feature of solid tumors, yet the mechanisms through which intra- and extracellular pH (pHi , pHe ) impact proliferation and growth are incompletely understood. The aim of this study was to determine the impact of pH, and specifically of the Na+ /H+ exchanger NHE1 and Na+ , HCO3 - transporter NBCn1, on cell cycle progression and its regulators in human breast cancer cells...
June 12, 2018: Cell Cycle
https://www.readbyqxmd.com/read/29887576/-quality-characteristics-and-nonclinical-clinical-profiles-of-etanercept-bs-sc-ma
#6
Hiroshi Kyono, Kayo Haraguchi, Shota Kojima, Takumi Ota, Chulho Jung, Sung Mo Yang, Sangwoo Park, Jineon So, Sunyoung Kim, Jooncheol Kwon, Suyeon Ko, Minae Yun
Etanercept is a dimeric genetic recombinant glycoprotein consisting of Fc domain of human Immunoglobulin G1 and the extracellular domain of human tumor necrosis factor (TNF) receptor type II. Etanercept exerts therapeutic effects on inflammatory diseases such as rheumatoid arthritis and juvenile idiopathic arthritis by neutralizing biological activities of TNFα/Lymphotoxin (LT) α. Mochida Pharmaceutical and LG Chem have developed syringe, pen, and vial products of Etanercept BS (biosimilar) as the first biosimilar of Enbrel in Japan...
2018: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
https://www.readbyqxmd.com/read/29884132/a-first-in-human-study-investigating-biodistribution-safety-and-recommended-dose-of-a-new-radiolabeled-mab-targeting-fzd10-in-metastatic-synovial-sarcoma-patients
#7
Anne-Laure Giraudet, Philippe Alexandre Cassier, Chicaco Iwao-Fukukawa, Gwenaelle Garin, Jean-Noël Badel, David Kryza, Sylvie Chabaud, Laurence Gilles-Afchain, Gilles Clapisson, Claude Desuzinges, David Sarrut, Adrien Halty, Antoine Italiano, Masaharu Mori, Takuya Tsunoda, Toyomasa Katagiri, Yusuke Nakamura, Laurent Alberti, Claire Cropet, Simon Baconnier, Sandrine Berge-Montamat, David Pérol, Jean-Yves Blay
BACKGROUND: Synovial Sarcomas (SS) are rare tumors occurring predominantly in adolescent and young adults with a dismal prognosis in advanced phases. We report a first-in-human phase I of monoclonal antibody (OTSA-101) targeting FZD10, overexpressed in most SS but not present in normal tissues, labelled with radioisotopes and used as a molecular vehicle to specifically deliver radiation to FZD10 expressing SS lesions. METHODS: Patients with progressive advanced SS were included...
June 8, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29882481/novel-approach-to-stem-cell-therapy-in-parkinson-s-disease
#8
Ibon Garitaonandia, Rodolfo Gonzalez, Glenn Sherman, Andrey Semechkin, Andrew Evans, Russell Kern
In this commentary we discuss International Stem Cell Corporation's (ISCO's) approach to developing a pluripotent stem cell based treatment for Parkinson's disease (PD). In 2016, Cyto Therapeutics, ISCO's wholly-owned subsidiary, received approval to conduct the world's first clinical study of a pluripotent stem cell based therapy for PD. The Australian regulatory agency Therapeutics Goods Administration (TGA) and the Melbourne Health's Human Research Ethics Committee (HREC) independently reviewed ISCO's extensive preclinical data and granted approval for the evaluation of a novel human parthenogenetic derived neural stem cell line, ISC-hpNSC, in a PD Phase 1 clinical trial (ClinicalTrials...
June 8, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29879283/safety-and-efficacy-of-panitumumab-plus-neoadjuvant-chemotherapy-in-patients-with-primary-her2-negative-inflammatory-breast-cancer
#9
Naoko Matsuda, Xiaoping Wang, Bora Lim, Savitri Krishnamurthy, Ricardo H Alvarez, Jie S Willey, Charla A Parker, Juhee Song, Yu Shen, Jianhua Hu, Wenhui Wu, Nan Li, Gildy V Babiera, James L Murray, Banu K Arun, Abenaa M Brewster, James M Reuben, Michael C Stauder, Chad M Barnett, Wendy A Woodward, H T Carisa Le-Petross, Anthony Lucci, Sarah M DeSnyder, Debu Tripathy, Vicente Valero, Naoto T Ueno
Importance: Combining conventional chemotherapy with targeted therapy has been proposed to improve the pathologic complete response (pCR) rate in patients with inflammatory breast cancer (IBC). Epidermal growth factor receptor (EGFR) expression is an independent predictor of low overall survival in patients with IBC. Objective: To evaluate the safety and efficacy of the anti-EGFR antibody panitumumab plus neoadjuvant chemotherapy in patients with primary human epidermal growth factor receptor 2 (HER2)-negative IBC...
June 7, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29878583/pharmacokinetics-safety-and-tolerability-of-the-novel-chymase-inhibitor-bay-1142524-in-healthy-male-volunteers
#10
Friederike Kanefendt, Uwe Thuß, Michael Becka, Stefanie Boxnick, Matthias Berse, Armin Schultz, Christiane Otto
The orally available chymase inhibitor BAY 1142524 is currently being developed as a first-in-class treatment for left-ventricular dysfunction after myocardial infarction. Results from 3 randomized, single-center, phase 1 studies in healthy male volunteers examining the safety, tolerability, and pharmacokinetics of BAY 1142524 are summarized. In this first-in-human study, single oral doses of 1-200 mg were administered in fasted state as liquid service formulation or immediate release (IR) tablets. The relative bioavailability and the effect of a high-fat/high-calorie meal were investigated at the 5-mg dose...
June 7, 2018: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29874291/pharmacokinetic-properties-of-a-novel-inosine-analog-4-cyano-2-deoxyinosine-after-oral-administration-in-rats
#11
Mai Hashimoto, Kazuaki Taguchi, Takako Ishiguro, Satoru Kohgo, Shuhei Imoto, Keishi Yamasaki, Hiroaki Mitsuya, Masaki Otagiri
4'-cyano-2'-deoxyinosine (SK14-061a), a novel nucleoside analog based on inosine, has antiviral activity against the human immunodeficiency virus type 1 that has the ability to acquire resistance against many types of reverse transcriptase inhibitors based on nucleosides. The aim of this study was to investigate the pharmacokinetics studies after its oral administration to rats. For this purpose, we first developed and validated an analytical method for quantitatively determining SK14-061a levels in biological samples by a UPLC system interfaced with a TOF-MS system...
2018: PloS One
https://www.readbyqxmd.com/read/29874228/shortening-intradermal-rabies-post-exposure-prophylaxis-regimens-to-1-week-results-from-a-phase-iii-clinical-trial-in-children-adolescents-and-adults
#12
Phirangkul Kerdpanich, Pornthep Chanthavanich, Mari Rose De Los Reyes, Jodor Lim, Delia Yu, Ma Cecilia Ama, Zenaida Mojares, Daniela Casula, Ashwani Kumar Arora, Michele Pellegrini
BACKGROUND: This phase III clinical trial compared the immunogenicity and safety of a purified chick-embryo cell rabies vaccine (PCECV) administered according to a shortened post-exposure prophylaxis (PEP) 4-site/1-week intradermal regimen, compared with the currently recommended 2-site/Thai Red Cross (TRC). METHODOLOGY/PRINCIPAL FINDINGS: This controlled, open-label, multi-center study (NCT02177032) enrolled healthy individuals ≥1 year of age, randomized into 4 groups to receive intradermal PCECV according to one of the 2 regimens, with or without human rabies immunoglobulin (HRIG) administration at first visit (in adults only)...
June 6, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29871690/a-survey-of-microrna-single-nucleotide-polymorphisms-identifies-novel-breast-cancer-susceptibility-loci-in-a-case-control-population-based-study-of-african-american-women
#13
Jeannette T Bensen, Mariaelisa Graff, Kristin L Young, Praveen Sethupathy, Joel Parker, Chad V Pecot, Kevin Currin, Stephen A Haddad, Edward A Ruiz-Narváez, Christopher A Haiman, Chi-Chen Hong, Lara E Sucheston-Campbell, Qianqian Zhu, Song Liu, Song Yao, Elisa V Bandera, Lynn Rosenberg, Kathryn L Lunetta, Christine B Ambrosone, Julie R Palmer, Melissa A Troester, Andrew F Olshan
BACKGROUND: MicroRNAs (miRNAs) regulate gene expression and influence cancer. Primary transcripts of miRNAs (pri-miRNAs) are poorly annotated and little is known about the role of germline variation in miRNA genes and breast cancer (BC). We sought to identify germline miRNA variants associated with BC risk and tumor subtype among African-American (AA) women. METHODS: Under the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium, genotyping and imputed data from four studies on BC in AA women were combined into a final dataset containing 224,188 miRNA gene single nucleotide polymorphisms (SNPs) for 8350 women: 3663 cases and 4687 controls...
June 5, 2018: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29867224/safety-pharmacokinetics-and-preliminary-efficacy-of-e6201-in-patients-with-advanced-solid-tumours-including-melanoma-results-of-a-phase-1-study
#14
Raoul Tibes, Mitesh J Borad, Corina E Dutcus, Larisa Reyderman, Kevie Feit, Andrew Eisen, David A Verbel, Daniel D Von Hoff
BACKGROUND: This phase 1 first-in-human study aimed to determine the maximum-tolerated dose (MTD), dose-limiting toxicities, and safety of E6201, and to establish recommended dosing in patients with advanced solid tumours, expanded to advanced melanoma. METHODS: Part A (dose escalation): sequential cohorts received E6201 intravenously (IV) over 30 min (once-weekly [qw; days (D)1 + 8 + 15 of a 28-day cycle]), starting at 20 mg/m2 , increasing to 720 mg/m2 or the MTD...
June 5, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29863954/effects-of-warm-temperatures-on-metabolic-rate-and-evaporative-water-loss-in-tuatara-a-cool-climate-rhynchocephalian-survivor
#15
Scott Jarvie, Tim Jowett, Michael B Thompson, Philip J Seddon, Alison Cree
The thermal sensitivity of physiological rates is a key characteristic of organisms. For tuatara (Sphenodon punctatus), the last surviving member of the reptilian order Rhynchocephalia and an unusually cold-tolerant reptile, we aimed to clarify responses in indices of metabolic rate (oxygen consumption [[Formula: see text]] and carbon dioxide production [[Formula: see text]]) as well as rates of total evaporative water loss (TEWL) to temperatures at the warmer end of the known tolerated range; currently, patterns for metabolic rate are unclear above 25°C, and TEWL has not been measured above 25°C...
July 2018: Physiological and Biochemical Zoology: PBZ
https://www.readbyqxmd.com/read/29862060/protective-activity-of-erythropoyetine-in-the-cognition-of-patients-with-parkinson-s-disease
#16
Ivonne Pedroso, Marité Garcia, Enrique Casabona, Lilia Morales, Maria Luisa Bringas, Leslie Pérez, Teresita Rodríguez, Ileana Sosa, Yordanka Ricardo, Arnoldo Padrón, Daniel Amaro
Introduction: Treatment strategies in Parkinson's disease (PD) can improve a patient's quality of life but cannot stop the progression of PD. We are looking for different alternatives that modify the natural course of the disease and recent research has demonstrated the neuroprotective properties of erythropoietin. In Cuba, the Center for Molecular Immunology (CIM) is a cutting edge scientific center where the recombinant form (EPOrh) and recombinant human erythropoietin with low sialic acid (NeuroEPO) are produced...
May 2018: Behavioral Sciences
https://www.readbyqxmd.com/read/29858066/microrna-411-downregulation-enhances-tumor-growth-by-upregulating-mllt11-expression-in-human-bladder-cancer
#17
Honglei Jin, Wenrui Sun, Yuanmei Zhang, Huiying Yan, Huating Liufu, Shuai Wang, Caiyi Chen, Jiayan Gu, Xiaohui Hua, Lingli Zhou, Guosong Jiang, Dapang Rao, Qipeng Xie, Haishan Huang, Chuanshu Huang
Although several previous studies have reported the implication of various microRNAs (miRNAs) in regulation of human bladder cancer (BC) development, alterations and function of many miRNAs in bladder cancer growth are not explored yet at present. Here, we screened 1,900 known miRNAs and first discovered that miR-411 was one of the major miRNAs, which was down-regulated in n-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced BCs. This miR-411 down-regulation was also observed in human BC tissues and cell lines...
June 1, 2018: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/29845501/solving-the-delivery-problems-of-triclabendazole-using-cyclodextrins
#18
Daniel Real, Darío Leonardi, Robert O Williams, Michael A Repka, Claudio J Salomon
Triclabendazole is the first-line drug of choice to treat and control fasciolasis, a neglected parasitic human disease. It is a class II/IV compound according to the Biopharmaceutics Classification System. Thus, the aim of this study was to improve aqueous solubility and dissolution rate of triclabendazole complexed with 2-hydroxylpropyl-β-cyclodextrin (HP-β-CD) and methyl-β-cyclodextrin (Me-β-CD) at 1:1 and 1:2 M ratio. The impact of storage on the solubility, dissolution profile, and solid-state properties of such complexes was also investigated...
May 29, 2018: AAPS PharmSciTech
https://www.readbyqxmd.com/read/29845093/expanded-autologous-regulatory-t-lymphocyte-infusions-in-als-a-phase-i-first-in-human-study
#19
Jason R Thonhoff, David R Beers, Weihua Zhao, Milvia Pleitez, Ericka P Simpson, James D Berry, Merit E Cudkowicz, Stanley H Appel
Objective: To determine whether autologous infusions of expanded regulatory T lymphoctyes (Tregs) into patients with amyotrophic lateral sclerosis (ALS) are safe and tolerable during early and later stages of disease. Methods: Three patients with ALS, with no family history of ALS, were selected based on their differing sites of disease onset and rates of progression. Patients underwent leukapheresis, and Tregs were subsequently isolated and expanded ex vivo. Tregs (1 × 106 cells/kg) were administered IV at early stages (4 doses over 2 months) and later stages (4 doses over 4 months) of disease...
July 2018: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/29843719/the-ramazzini-institute-13-week-study-on-glyphosate-based-herbicides-at-human-equivalent-dose-in-sprague-dawley-rats-study-design-and-first-in-life-endpoints-evaluation
#20
Simona Panzacchi, Daniele Mandrioli, Fabiana Manservisi, Luciano Bua, Laura Falcioni, Marcella Spinaci, Giovanna Galeati, Giovanni Dinelli, Rossella Miglio, Alberto Mantovani, Stefano Lorenzetti, Jianzhong Hu, Jia Chen, Melissa J Perry, Philip J Landrigan, Fiorella Belpoggi
BACKGROUND: Glyphosate-based herbicides (GBHs) are the most widely used pesticides worldwide, and glyphosate is the active ingredient of such herbicides, including the formulation known as Roundup. The massive and increasing use of GBHs results in not only the global burden of occupational exposures, but also increased exposure to the general population. The current pilot study represents the first phase of a long-term investigation of GBHs that we are conducting over the next 5 years...
May 29, 2018: Environmental Health: a Global Access Science Source
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