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https://www.readbyqxmd.com/read/28735458/the-efficacy-of-lapatinib-and-nilotinib-in-combination-with-radiation-therapy-in-a-model-of-nf2-associated-peripheral-schwannoma
#1
Iddo Paldor, Sara Abbadi, Nicolas Bonne, Xiaobu Ye, Fausto J Rodriguez, David Rowshanshad, MariaLisa Itzoe, Veronica Vigilar, Marco Giovannini, Henry Brem, Jaishri O Blakeley, Betty M Tyler
Neurofibromatosis type 2 (NF2), a neurogenetic condition manifest by peripheral nerve sheath tumors (PNST) throughout the neuroaxis for which there are no approved therapies. In vitro and in vivo studies presented here examine agents targeting signaling pathways, angiogenesis, and DNA repair mechanisms. In vitro dose response assays demonstrated potent activity of lapatinib and nilotinib against the mouse schwannoma SC4 (Nf2 (-/-)) cell line. We then examined the efficacy of everolimus, nilotinib, lapatinib, bevacizumab and radiation (RT) as mono- and combination therapies in flank and sciatic nerve in vivo NF2-PNST models...
July 22, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28735379/multidisciplinary-management-of-clival-chordomas-long-term-clinical-outcome-in-a-single-institution-consecutive-series
#2
Petter Förander, Jiri Bartek, Michael Fagerlund, Hamza Benmaklouf, Ernest Dodoo, Alia Shamikh, Pär Stjärne, Tiit Mathiesen
OBJECTIVE: Chordomas of the skull base have high recurrence rates even after radical resection and adjuvant radiotherapy. We evaluate the long-term clinical outcome using multidisciplinary management in the treatment of clival chordomas. METHODS: Between 1984 and 2015, 22 patients diagnosed with an intracranial chordoma were treated at the Karolinska University Hospital, Stockholm, Sweden. Sixteen of 22 were treated with Gamma Knife radiosurgery (GKRS) for tumour residual or progression during the disease course...
July 22, 2017: Acta Neurochirurgica
https://www.readbyqxmd.com/read/28735361/concentrations-source-identification-and-lung-cancer-risk-associated-with-springtime-pm2-5-bound-polycyclic-aromatic-hydrocarbons-pahs-in-nanjing-china
#3
Chong Chen, Zhonghuan Xia, Minmin Wu, Qianqian Zhang, Tao Wang, Liping Wang, Hao Yang
This study concentrated on the pollution level, sources, and lung cancer risk of PM2.5-bound polycyclic aromatic hydrocarbons (PAHs) in spring in Nanjing, China. The PM2.5 samples were collected in spring of the year 2016 in Nanjing. Sixteen United States Environmental Protection Agency priority PAHs were extracted and analyzed after sampling. The mean concentrations of PAHs and BaPeq were 3.98 ± 1.01 and 0.29 ± 0.08 ng/m(3), respectively, which is a low level among results from regions worldwide. The diurnal variations of PAHs and BaPeq concentrations showed a relatively high level in the early morning, at the morning rush time of work and traffic transportation, and in the evening traffic peak hours...
July 22, 2017: Archives of Environmental Contamination and Toxicology
https://www.readbyqxmd.com/read/28735217/zopiclone-concentrations-in-oral-fluid-and-blood-after-administration-of-therapeutic-doses-of-zopiclone
#4
Knut Hjelmeland, Ingebjørg Gustavsen, Elisabeth Leere Øiestad, Åse Marit Leere Øiestad, Gudrun Høiseth, Jørg Mørland
PURPOSE: Little is known about the relationship between concentrations in oral fluid (OF) and blood for the widely prescribed hypnotic drug zopiclone. The purpose of this study was to investigate the usefulness of OF zopiclone concentrations to predict blood zopiclone concentrations in order to introduce OF testing as an alternative to more cumbersome blood testing. METHODS: 16 healthy young male volunteers received capsules of either 5 or 10mg zopiclone on two different study days separated by at least one week...
July 13, 2017: Forensic Science International
https://www.readbyqxmd.com/read/28735186/development-of-a-robust-reporter-gene-assay-to-measure-the-bioactivity-of-anti-pd-1-anti-pd-l1-therapeutic-antibodies
#5
Lan Wang, Chuanfei Yu, Yalan Yang, Kai Gao, Junzhi Wang
Being regarded as the 'cancer panacea', the anti-PD-1/anti-PD-L1 monoclonal antibodies (mAbs) have become the R&D focus of biopharmaceutical industries. Several marketed such mAbs have been proved particularly effective in treating various cancers. However, the cell-based bioassay to measure the biological activities of the anti-PD-1/anti-PD-L1 mAbs as the lot release or stability test has been a great challenge to quality control laboratories due to the immunomodulating nature of the mAbs. Here, we describe the development and validation of a reporter gene assay consisting of two-cell systems to measure the bioactivity of the anti-PD-1/anti-PD-L1 mAbs...
May 8, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28734929/aripiprazole-prevents-renal-ischemia-reperfusion-injury-in-rats-probably-through-nitric-oxide-involvement
#6
Hanieh Gholampour, Leila Moezi, Hamed Shafaroodi
Renal ischemia/reperfusion (I/R) injury is strongly related to morbidity and mortality. Oxidative stress, inflammation, and apoptosis play key roles in renal dysfunction following renal I/R. Aripiprazole is an atypical antipsychotic which used for the treatment of schizophrenia and bipolar disorder. Recent studies have reported aripiprazole as displaying certain anti-inflammatory effects. Regarding the underlying mechanisms of renal ischemia-reperfusion, therefore, nephroprotective effects might be predicted to be seen with aripiprazole...
July 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28734876/t-cell-depletion-as-an-alternative-approach-for-patients-55-years-undergoing-allogeneic-stem-cell-transplantation-as-curative-therapy-for-hematologic-malignancies
#7
Ann A Jakubowski, Erica Petrlik, Molly Maloy, Patrick Hilden, Esperanza Papadopoulos, James W Young, Farid Boulad, Hugo Castro-Malaspina, Roni Tamari, Parastoo B Dahi, Jenna Goldberg, Guenther Koehne, Miguel-Angel Perales, Craig S Sauter, Richard J O'Reilly, Sergio Giralt
T cell depleted allogeneic hematopoietic stem cell transplantation (TCD HSCT) is curative treatment for hematologic malignancies in adults, shown to reduce graft vs. host disease (GVHD) without increased relapse. We retrospectively reviewed a single center, 11yr experience of 214 patients ≥55yrs to determine tolerability and efficacy in the older adult. The majority (70%) had myeloid diseases and most acute leukemias were in remission. Median age was 61 yrs with related and unrelated donors > 8/10 HLA matched...
July 19, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28734868/a-single-and-multiple-dose-study-to-investigate-the-pharmacokinetics-and-pharmacodynamics-of-opicapone-a-novel-comt-inhibitor-in-rat
#8
Daniela Gonçalves, Gilberto Alves, Ana Fortuna, Maria João Bonifácio, Patrício Soares-da-Silva, Amílcar Falcão
Opicapone is a novel catechol-O-methyltransferase (COMT) inhibitor that emerged to fulfil the need of a safer and more efficacious COMT inhibitor. The present study was carried out in order to assess and compare the pharmacokinetics and pharmacodynamics (COMT inhibition) of opicapone after single and multiple oral administrations (30 mg/kg) to Wistar rats. For this purpose, at predefined time points up to 72 h post-dosing, blood, liver and kidneys were collected and, then, the concentrations of opicapone and its active metabolite (BIA 9-1079) were determined in plasma and in liver and kidney tissues, as well as the erythrocyte, liver and kidney COMT activity...
July 19, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28734858/safety-review-of-5-grass-pollen-tablet-from-pooled-data-of-clinical-trials
#9
Thomas B Casale, Linda S Cox, Ulrich Wahn, David B K Golden, Brigitte Bons, Alain Didier
BACKGROUND: The 5-grass pollen sublingual tablet has been approved for the treatment of grass pollen-induced allergic rhinoconjunctivitis in subjects with or without intermittent asthma. OBJECTIVE: To provide a comprehensive analysis of the safety profile of the 5-grass tablet on the basis of pooled data from 8 clinical trials. METHODS: Subjects (5-65 years old) with medically confirmed grass pollen-induced allergic rhinoconjunctivitis were included in the double-blind studies...
July 19, 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28734844/tlr3-blockade-in-rhinovirus-induced-experimental-asthma-exacerbations-a-randomized-controlled-study
#10
Philip E Silkoff, Susan Flavin, Robert Gordon, Mathew J Loza, Peter J Sterk, Rene Lutter, Zuzana Diamant, Ronald B Turner, Brian J Lipworth, David Proud, Dave Singh, Andreas Eich, Vibeke Backer, James E Gern, Christian Herzmann, Scott A Halperin, Tjeert T Mensinga, Alfred M Del Vecchio, Patrick Branigan, Lani San Mateo, Frédéric Baribaud, Elliot S Barnathan, Sebastian L Johnston
BACKGROUND: Human rhinoviruses (HRV) commonly precipitate asthma exacerbations. TLR3, an innate pattern-recognition receptor, is triggered by HRV driving inflammation that may worsen asthma. OBJECTIVE: To evaluate an inhibitory monoclonal antibody to TLR3, CNTO3157, on experimental HRV-16 inoculation in healthy and asthmatic subjects. METHODS: In this double-blind multicenter randomized parallel-group study in North America and Europe, healthy and mild-moderate stable asthmatic subjects received single or multiple doses of CNTO 3157 or placebo, respectively, and were then inoculated with HRV-16 within 72 hours...
July 19, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28734720/rectal-nonsteroidal-anti-inflammatory-drugs-administration-is-effective-for-the-prevention-of-post-ercp-pancreatitis-an-updated-meta-analysis-of-randomized-controlled-trials
#11
Chong Yang, Yanting Zhao, Wentao Li, Shikai Zhu, Hongji Yang, Yu Zhang, Xi Liu, Nan Peng, Ping Fan, Xin Jin
BACKGROUND: Acute pancreatitis is one of the most common complications of endoscopic retrograde cholangiopancreatography (ERCP). Whether the prophylactic administration of rectal non-steroidal anti-inflammatory drugs (NSAIDs) peri-ERCP is effective in preventing post-ERCP pancreatitis (PEP) remains controversial. The aim of this study was to assess the effect of rectal NSAIDs on PEP. METHODS: A systematic search of literature databases (Cochrane Library, PubMed, EMBASE, and Web of Science) was performed to identify eligible randomized controlled trials (RCTs)...
July 17, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28734620/treatment-of-dogs-with-compensated-myxomatous-mitral-valve-disease-with-spironolactone-a-pilot-study
#12
M J Hezzell, A Boswood, J López-Alvarez, N Lötter, J Elliott
OBJECTIVES: Spironolactone improves outcome in dogs with advanced myxomatous mitral valve disease (MMVD). Its efficacy in preclinical MMVD is unknown. The hypothesis was the administration of spironolactone to dogs with compensated MMVD demonstrating risk factors for poorer prognosis will decrease the rate of disease progression. The aim was to provide pilot data to evaluate preliminary effects and sample size calculation for a definitive clinical trial. ANIMALS: Twenty-five client-owned dogs with MMVD with at least one of the following; left atrial to aortic ratio (LA:Ao) ≥ 1...
July 19, 2017: Journal of Veterinary Cardiology: the Official Journal of the European Society of Veterinary Cardiology
https://www.readbyqxmd.com/read/28734271/development-and-validation-of-sensitive-lc-ms-ms-method-for-the-quantification-of-suvn-502-and-its-metabolite-and-its-application-for-first-in-human-pharmacokinetic-study
#13
Ramakrishna Nirogi, Devender Reddy Ajjala, Raghupathi Aleti, Lakshmiprasanna Rayapati, Hanumanth Rao Pantangi, Rajesh Kumar Boggavarapu, Naga Surya Prakash Padala
A sensitive and rapid LC-MS/MS method was developed and validated for the quantification of SUVN-502 and M1 of SUVN-502, a 5-HT6 receptor antagonist for the treatment of dementia associated with Alzheimer's disease. Following solid-phase extraction, SUVN-502 and M1 of SUVN-502 and IS were eluted with 10mM ammonium acetate (pH 4.0) and acetonitrile using a rapid gradient program on reverse phase column. Multiple reaction monitoring mode was used to monitor the respective transitions of m/z 478.2→377.7 for SUVN-502 and m/z 464...
April 14, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28733791/current-clinical-evidence-of-tocilizumab-for-the-treatment-of-anca-associated-vasculitis-a-prospective-case-series-for-microscopic-polyangiitis-in-a-combination-with-corticosteroids-and-literature-review
#14
REVIEW
Ryota Sakai, Tsuneo Kondo, Takahiko Kurasawa, Eiko Nishi, Ayumi Okuyama, Kentaro Chino, Akiko Shibata, Yusuke Okada, Hirofumi Takei, Hayato Nagasawa, Koichi Amano
The purpose of this study is to report the efficacy and safety of a combination of tocilizumab (TCZ) and high-dose corticosteroid (CS) in two patients with microscopic polyangiitis (MPA) and review the published current clinical evidence on TCZ in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), except for large vessel vasculitis (LVV) and polymyalgia rheumatica (PMR). Two MPA patients were treated with TCZ at 8 mg/kg every month for 1 year and CS (prednisolone 1 mg/kg/day for 2 weeks, followed by tapering) in a prospective single-arm, single-center, cohort, open-label pilot study (UMIN clinical trials: 000012072)...
July 21, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28733736/effects-of-steroid-use-for-stenosis-prevention-after-wide-endoscopic-submucosal-dissection-for-gastric-neoplasm
#15
Yoshihiro Kishida, Naomi Kakushima, Kohei Takizawa, Masaki Tanaka, Noboru Kawata, Masao Yoshida, Sayo Ito, Kenichiro Imai, Hirotoshi Ishiwatari, Kinichi Hotta, Hiroyuki Matsubayashi, Hiroyuki Ono
BACKGROUND: Stenosis is a troublesome complication after wide endoscopic submucosal dissection (ESD). As steroids are known to prevent post-ESD esophageal stenosis, this study aimed to clarify the gastric effects. METHODS: This was a retrospective single-institution study. Between September 2002 and June 2015, 132 patients with a post-ESD mucosal defect exceeding three-fourths of the circumference were identified. Among them, 107 patients who did not undergo additional surgery for non-curative resection were reviewed...
July 21, 2017: Surgical Endoscopy
https://www.readbyqxmd.com/read/28733700/feasibility-of-olanzapine-multi-acting-receptor-targeted-antipsychotic-agent-for-the-prevention-of-emesis-caused-by-continuous-cisplatin-or-ifosfamide-based-chemotherapy
#16
Seiko Bun, Kan Yonemori, Toru Akagi, Emi Noguchi, Tatsunori Shimoi, Akihiko Shimomura, Mayu Yunokawa, Chikako Shimizu, Yasuhiro Fujiwara, Yoshinori Makino, Yoshikazu Hayashi, Kenji Tamura
Background To determine the feasibility and efficacy of olanzapine, which is approved by the Pharmaceuticals and Medical Devices Agency as multi acting receptor targeted antipsychotic agent of the thienobenzodiazepine class, for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients undergoing continuous five-day chemotherapy. Patients and methods This study was a prospective dose escalation study at a single center (UMIN ID: UMIN000015386). Patients received a combination of adriamycin and ifosfamide (AI) or a combination of bleomycin, etoposide, and cisplatin (BEP)...
July 21, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28733196/proteasome-subunit-beta-type-1-p11a-polymorphism-is-a-new-prognostic-marker-in-multiple-myeloma
#17
Gergely Varga, Gábor Mikala, Katalin Piroska Kiss, Éva Kosóczki, Edit Szabó, Nóra Meggyesi, Katalin Balassa, Petra Kövy, Bálint Tegze, Gergely Szombath, Attila Tordai, Hajnalka Andrikovics, László Homolya, Tamás Masszi
BACKGROUND: Proteasome subunit beta type 1 (PSMB1) rs12717 polymorphism, a single nucleotide polymorphism with unknown functional effect, was recently reported to influence response to bortezomib-based therapy in follicular lymphoma. PATIENTS AND METHODS: We retrospectively analyzed the prognostic impact of this polymorphism in 211 consecutively diagnosed multiple myeloma cases, and performed in vitro experiments to look into its functional consequences. RESULTS: On univariate analysis, patients carrying the variant G allele showed significantly shorter progression-free survival (PFS) with a pattern suggestive of a gene-dose effect (PFS 26...
June 30, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28733145/adipocytes-promote-nicotine-induced-injury-of-endothelial-cells-via-the-nf-%C3%AE%C2%BAb-pathway
#18
Xiu Liu, Chao-Nan Wang, Chen-Yang Qiu, Wei Song, Lin-Fang Wang, Bao Liu
Cigarette smoking is one of the most important risk factors of atherosclerosis, which can induce endothelial injury. Meanwhile, adipocytes are the main cell type of perivascular adipose tissue (PVAT), the largest endocrine and paracrine organ and direct anatomical connection to adventitia, which may play a key role in the injury of endothelial cells. We used nicotine to induce dysfunctional HUVECs and adipocytes. In addition, we used a novel model to co-culture HUVECs and adipocytes in vitro by the transwell co-culture system to determine the effect of adipocytes on endothelial injury...
July 18, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28733043/perioperative-hypotension-and-discharge-outcomes-in-non-critically-injured-trauma-patients-a-single-centre-retrospective-cohort-study
#19
Nadav Sheffy, Itay Bentov, Brianna Mills, Bala G Nair, G Alec Rooke, Monica S Vavilala
BACKGROUND: There is a lack of information on the effect of age on perioperative care and outcomes after minor trauma in the elderly. We examined the association between perioperative hypotension and discharge outcome among non-critically injured adult patients. METHODS: We conducted a retrospective study of non-critically ill patients (ISS <9 or discharged within less than 24h) who received anaesthesia care for surgery and Recovery Room care at a level-1 trauma centre between 5/1/2012 and 11/30/2013...
June 24, 2017: Injury
https://www.readbyqxmd.com/read/28732386/a-phase-i-trial-of-nk-92-cells-for-refractory-hematological-malignancies-relapsing-after-autologous-hematopoietic-cell-transplantation-shows-safety-and-evidence-of-efficacy
#20
Brent A Williams, Arjun Datt Law, Bertrand Routy, Neal denHollander, Vikas Gupta, Xing-Hua Wang, Amélie Chaboureau, Sowmya Viswanathan, Armand Keating
BACKGROUND: Autologous NK cell therapy can treat a variety of malignancies, but is limited by patient-specific variations in potency and cell number expansion. In contrast, allogeneic NK cell lines can overcome many of these limitations. Cells from the permanent NK-92 line are constitutively activated, lack inhibitory receptors and appear to be safe based on two prior phase I trials. MATERIALS AND METHODS: We conducted a single-center, non-randomized, non-blinded, open-label, Phase I dose-escalation trial of irradiated NK-92 cells in adults with refractory hematological malignancies who relapsed after autologous hematopoietic cell transplantation (AHCT)...
July 12, 2017: Oncotarget
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