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https://www.readbyqxmd.com/read/29330194/telotristat-ethyl-in-carcinoid-syndrome-safety-and-efficacy-in-the-telecast-phase-3-trial
#1
Marianne E Pavel, David J Gross, Marta Benavent, Petros Perros, Raj Srirajaskanthan, Richard R P Warner, Matthew H Kulke, Lowell Anthony, Pamela Kunz, Dieter Hörsch, Martin O Weickert, Pablo Lapuerta, Wenjun Jiang, Kenneth Kassler-Taub, Suman Wason, Rosanna Fleming, Douglas Fleming, Rocio García-Carbonero
Telotristat ethyl, a tryptophan hydroxylase inhibitor, was efficacious and well tolerated in the Phase 3 TELESTAR study in patients with carcinoid syndrome (CS) experiencing ≥4 bowel movements per day (BMs/day) while on somatostatin analogs (SSAs). TELECAST, a Phase 3 companion study, assessed safety and efficacy of telotristat ethyl in patients with CS (diarrhea, flushing, abdominal pain, nausea, or elevated urinary 5-hydroxyindoleacetic acid [u5-HIAA]) with <4 BMs/day on SSAs (or ≥1 symptom or ≥4 BMs/day if not on SSAs) during a 12-week double-blind treatment period followed by a 36-week open-label extension (OLE)...
January 12, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29328464/inhibition-of-gli-leads-to-antitumor-growth-and-enhancement-of-cisplatin-induced-cytotoxicity-in-large-cell-neuroendocrine-carcinoma-of-the-lung
#2
Tsukasa Ishiwata, Shunichiro Iwasawa, Takahiro Ebata, Mengmeng Fan, Yuji Tada, Koichiro Tatsumi, Yuichi Takiguchi
Large cell neuroendocrine carcinoma (LCNEC) of the lung is a highly aggressive tumor without established standard treatment. The Hedgehog (Hh) signal, which is critical in embryogenesis, is known to play important roles in maintaining a malignant phenotype in various cancers. The present study explored the possibility of targeting the Hh signal in the treatment of LCNEC by suppressing Hh downstream molecules, Smoothened (Smo) and GLI family zinc finger 1/2 (Gli1/2), in 3 human LCNEC cell lines. Smo inhibitor, BMS-833923, and Gli inhibitor, GANT61, downregulated Gli1 and 2, resulting in the suppression of the cell viability of the 3 cell lines as assessed using an MTT assay...
January 3, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29321066/perioperative-management-of-antiplatelet-therapy-in-patients-undergoing-non-cardiac-surgery-following-coronary-stent-placement-a-systematic-review
#3
Christopher P Childers, Melinda Maggard-Gibbons, Jesus G Ulloa, Ian T MacQueen, Isomi M Miake-Lye, Roberta Shanman, Selene Mak, Jessica M Beroes, Paul G Shekelle
BACKGROUND: The correct perioperative management of antiplatelet therapy (APT) in patients undergoing non-cardiac surgery (NCS) is often debated by clinicians. American College of Cardiology (ACC) and American Heart Association (AHA) guidelines recommend postponing elective NCS at least 3 months after stent implantation. Regardless of the timing of surgery, ACC/AHA guidelines recommend continuing at least ASA throughout the perioperative period and ideally continuing dual APT (DAPT) therapy "unless surgery demands discontinuation...
January 10, 2018: Systematic Reviews
https://www.readbyqxmd.com/read/29317226/oral-delivery-of-highly-lipophilic-poorly-water-soluble-drugs-self-emulsifying-drug-delivery-systems-sedds-to-improve-oral-absorption-and-enable-high-dose-toxicology-studies-of-a-cetp-inhibitor-in-preclinical-species
#4
Xue-Qing Chen, Theresa Ziemba, Christine Huang, Ming Chang, Carrie Xu, Jennifer X Qiao, Tammy C Wang, Heather J Finlay, Mark E Salvati, Leonard P Adam, Olafur Gudmundsson, Michael J Hageman
BMS-A is a highly lipophilic compound (clogP 10.5) with poor aqueous solubility (< 0.0001 mg/mL at pH 6.5). The compound exhibits low oral exposure when dosed as cosolvent solution formulations. The purpose of this study was to evaluate lipid-based formulations for enabling high-dose toxicology studies and enhancing toxicology margins of BMS-A in pre-GLP studies in non-rodent species. The solubility of BMS-A was screened in lipid and cosolvent/surfactant excipients and prototype formulations were developed...
January 6, 2018: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29316397/discovery-of-potent-and-orally-bioavailable-dihydropyrazole-gpr40-agonists
#5
Jun Shi, Zhengxiang Gu, Elizabeth Anne Jurica, Ximao Wu, Lauren E Haque, Kristin N Williams, Andres S Hernandez, Zhenqiu Hong, Qi Gao, Marta Dabros, Akin H Davulcu, Arvind Mathur, Richard A Rampulla, Arun Kumar Gupta, Ramya Jayaram, Atsu Apedo, Douglas B Moore, Heng Liu, Lori K Kunselman, Edward J Brady, Jason J Wilkes, Bradley A Zinker, Hong Cai, Yue-Zhong Shu, Qin Sun, Elizabeth A Dierks, Kimberly A Foster, Carrie Xu, Tao Wang, Reshma Panemangalore, Mary Ellen Cvijic, Chunshan Xie, Gary G Cao, Min Zhou, John Krupinski, Jean M Whaley, Jeffrey A Robl, William R Ewing, Bruce Alan Ellsworth
G protein-coupled receptor 40 (GPR40) has become an attractive target for the treatment of diabetes since it was shown clinically to promote glucose-stimulated insulin secretion. Herein, we report our efforts to develop highly selective and potent GPR40 agonists with a dual mechanism of action, promoting both glucose-dependent insulin and incretin secretion. Employing strategies to increase polarity and the ratio of sp3/sp2 character of the chemotype, we identified BMS-986118 (compound 4), which showed potent and selective GPR40 agonist activity in vitro...
January 9, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29312855/systematic-review-of-bone-marrow-stimulation-for-osteochondral-lesion-of-talus-evaluation-for-level-and-quality-of-clinical-studies
#6
Youichi Yasui, Laura Ramponi, Dexter Seow, Eoghan T Hurley, Wataru Miyamoto, Yoshiharu Shimozono, John G Kennedy
AIM: To clarify the quality of the studies indicating lesion size and/or containment as prognostic indicators of bone marrow stimulation (BMS) for osteochondral lesions of the talus (OLT). METHODS: Two reviewers searched the PubMed/MEDLINE and EMBASE databases using specific terms on March 2015 in accordance with the Preferred Reporting Items for Systemic Reviews and Meta-Analyses guidelines. Predetermined variables were extracted for all the included studies. Level of evidence (LOE) was determined using previously published criteria by the Journal of Bone and Joint Surgery and methodological quality of evidence (MQOE) was evaluated using the Modified Coleman Methodology Score...
December 18, 2017: World Journal of Orthopedics
https://www.readbyqxmd.com/read/29311135/clinical-pharmacokinetics-and-the-impact-of-genetic-polymorphism-on-a-cyp2c19-substrate-bms-823778-in-healthy-subjects
#7
Jiachang Gong, Lars Hansen, Lisa Iacono
BMS-823778 is a potent and selective inhibitor of 11beta-HSD1, an enzyme that regulates tissue specific intracellular glucocorticoid metabolism and a compelling target for the treatment of metabolic diseases. Metabolism of BMS-823778 was mainly mediated by polymorphic CYP2C19 with minor contribution from CYP3A3/5 and UGT1A4. Clinical PK of BMS-823778 was first investigated in healthy volunteers after single and multiple ascending doses. BMS-823778 was rapidly absorbed after oral dose, and systemic exposure at steady state increased proportionally to the dose...
January 8, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29311016/the-development-of-brain-metastases-in-patients-with-renal-cell-carcinoma-epidemiologic-trends-survival-and-clinical-risk-factors-using-a-population-based-cohort
#8
Maxine Sun, Guillermo De Velasco, Priscilla K Brastianos, Ayal A Aizer, Allison Martin, Raphael Moreira, Paul L Nguyen, Quoc-Dien Trinh, Toni K Choueiri
BACKGROUND: The incidence of brain metastases (BM) in patients with renal cell carcinoma (RCC) is hypothesized to have increased in the last 2 decades. OBJECTIVE: To define incidence trends according to patient and clinical characteristics, to identify risk factors, and to describe outcomes of patients with BM for RCC. DESIGN, SETTING, AND PARTICIPANTS: Patients diagnosed with RCC between the years 2010 and 2013 within the Surveillance, Epidemiology, and End Results database...
January 5, 2018: European Urology Focus
https://www.readbyqxmd.com/read/29310720/direct-comparison-of-coronary-bare-metal-vs-drug-eluting-stents-same-platform-different-mechanics
#9
Wolfram Schmidt, Peter Lanzer, Peter Behrens, Christoph Brandt-Wunderlich, Alper Öner, Hüseyin Ince, Klaus-Peter Schmitz, Niels Grabow
BACKGROUND: Drug-eluting stents (DES) compared to bare metal stents (BMS) have shown superior clinical performance, but are considered less suitable in complex cases. Most studies do not distinguish between DES and BMS with respect to their mechanical performance. The objective was to obtain mechanical parameters for direct comparison of BMS and DES. METHODS: In vitro bench tests evaluated crimped stent profiles, crossability in stenosis models, elastic recoil, bending stiffness (crimped and expanded), and scaffolding properties...
January 8, 2018: European Journal of Medical Research
https://www.readbyqxmd.com/read/29305674/comparable-osteogenic-capacity-of-mesenchymal-stem-or-stromal-cells-derived-from-human-amnion-membrane-and-bone-marrow
#10
Mehran Ghasemzadeh, Ehteramolsadat Hosseini, Mohammadhossein Ahmadi, Maedeh Kamalizad, Naser Amirizadeh
So far, substantial attentions have been attracted to the application of mesenchymal stem or stromal cells (MSCs) in different therapeutic approaches. Although human bone marrow is commonly considered as a major source for MSCs, having an invasive collection method, ethical consideration and donor availability create a challenge for scientists, leading them to explore better alternative sources for MSCs. The study presented here aimed to characterize and compare osteogenic capacity of MSCs obtained from the amnion membrane (AM) with those originated from BM...
January 5, 2018: Cytotechnology
https://www.readbyqxmd.com/read/29285790/drug-eluting-stents-are-superior-to-bare-metal-stents-to-reduce-clinical-outcome-and-stent-related-complications-in-ckd-patients-a-systematic-review-meta-analysis-and-network-meta-analysis
#11
REVIEW
Gabriele Crimi, Valeria Gritti, Vincenzo Alessandro Galiffa, Valeria Scotti, Sergio Leonardi, Maurizio Ferrario, Marco Ferlini, Gaetano Maria De Ferrari, Luigi Oltrona Visconti, Catherine Klersy
AIMS: To compare clinical outcome in Chronic kidney disease (CKD) patients receiving coronary stents according to stent type BMS versus DES and 1st generation versus 2nd generation DES. METHODS AND RESULTS: PubMed, Cinhal, Cochrane, Embase, and Web of Science were searched for studies including CKD patients. CKD was defined as eGFR < 60 mL/min. We selected n = 35 articles leading to 376 169 patients, of which 76 557 CKD patients receiving BMS n = 35,807, 1st generation DES n = 37,650, or 2nd generation DES n = 3100...
December 28, 2017: Journal of Interventional Cardiology
https://www.readbyqxmd.com/read/29284330/clinical-characterization-of-women-with-burning-mouth-syndrome-in-a-case-control-study
#12
Shikha Acharya, Anette Carlén, Bengt Wenneberg, Mats Jontell, Catharina Hägglin
OBJECTIVE: Burning mouth syndrome (BMS) is a chronic orofacial pain disorder that is defined by a burning sensation in the oral mucosa. The aim of this study was to investigate the underlying factors, clinical characteristics and self-reported oral and general health factors associated with BMS. MATERIAL AND METHODS: Fifty-six women with BMS (mean age: 67.7) and their age-matched controls were included in the study. A general questionnaire, an OHRQL index and BMS-specific questionnaires were used...
December 28, 2017: Acta Odontologica Scandinavica
https://www.readbyqxmd.com/read/29284024/diabetes-related-changes-in-the-protein-composition-and-the-biomechanical-properties-of-human-retinal-vascular-basement-membranes
#13
Willi Halfter, Suzette Moes, Daphne O Asgeirsson, Kathrin Halfter, Philipp Oertle, Esther Melo Herraiz, Marija Plodinec, Paul Jenoe, Paul Bernhard Henrich
Basement membranes (BMs) are specialized sheets of extracellular matrix that outline epithelial cell layers, muscle fibers, blood vessels, and peripheral nerves. A well-documented histological hallmark of progressing diabetes is a major increase in vascular BM thickness. In order to investigate whether this structural change is accompanied by a change in the protein composition, we compared the proteomes of retinal vascular BMs from diabetic and non-diabetic donors by using LC-MS/MS. Data analysis showed that seventeen extracellular matrix (ECM)-associated proteins were more abundant in diabetic than non-diabetic vascular BMs...
2017: PloS One
https://www.readbyqxmd.com/read/29279529/optical-frequency-domain-imaging-of-very-late-stent-thrombosis-following-bare-metal-stent-implantation-for-acute-myocardial-infarction
#14
Shinichiro Masuda, Takashi Shibui, Ryuki Kawamura, Hitoshi Saiki, Akihiro Hata
A 43-year-old man was admitted to our hospital with ST-segment elevation acute coronary syndrome. He had experienced myocardial infarction 19 months previously, and a bare-metal stent (BMS) had been implanted in the culprit distal right coronary artery at another hospital. Emergency coronary angiography showed thrombotic in-stent occlusion of the BMS. Intravascular ultrasound revealed an undersized stent compared with the size of the vessel and late stent malapposition (LSM) with abundant thrombi. The lesion was successfully recanalized via thrombectomy and plain old balloon angioplasty...
December 27, 2017: International Heart Journal
https://www.readbyqxmd.com/read/29261656/nicotinic-alpha-7-receptor-agonists-evp-6124-and-bms-933043-attenuate-scopolamine-induced-deficits-in-visuo-spatial-paired-associates-learning
#15
Michael R Weed, Joseph Polino, Laura Signor, Mark Bookbinder, Deborah Keavy, Yulia Benitex, Daniel G Morgan, Dalton King, John E Macor, Robert Zaczek, Richard Olson, Linda J Bristow
Agonists at the nicotinic acetylcholine alpha 7 receptor (nAChR α7) subtype have the potential to treat cognitive deficits in patients with Alzheimer's disease (AD) or schizophrenia. Visuo-spatial paired associates learning (vsPAL) is a task that has been shown to reliably predict conversion from mild cognitive impairment to AD in humans and can also be performed by nonhuman primates. Reversal of scopolamine-induced impairment of vsPAL performance may represent a translational approach for the development of nAChR α7 agonists...
2017: PloS One
https://www.readbyqxmd.com/read/29260023/definition-prevalence-and-predictive-factors-of-benign-multiple-sclerosis
#16
REVIEW
Tatjana Reynders, Miguel D'haeseleer, Jacques De Keyser, Guy Nagels, Marie B D'hooghe
Background: Multiple sclerosis (MS) is characterized by a great inter-individual variability in disease course and severity. Some patients experience a rather mild course, controversially called 'benign MS' (BMS). The usefulness of this entity in clinical practice remains unclear. Methods: We performed a literature search in PubMed, Web of Science and Cochrane Library databases from November 1980 to December 2015, using the following key words: benign multiple sclerosis, diagnosis, imaging, prognosis, predictive, natural history and predefined inclusion criteria...
June 2017: ENeurologicalSci
https://www.readbyqxmd.com/read/29247157/a-case-of-subacute-bioresorbable-vascular-scaffold-thrombosis-what-was-wrong
#17
Seraj A Abualnaja, Hanan M Alrammah, Bayan A Alsaif, Malak O Almulla, Bayan A Alzahrani
BACKGROUND The introduction of bioresorbable vascular scaffolds (BVS) into the field of percutaneous coronary intervention (PCI) was thought to be a promising step in solving the issues raised with the use of early bare metal stents (BMS) and drug eluting stents (DES); however, studies have raised concerns regarding thrombosis risk associated with the use of these stents. CASE REPORT A 42-year-old male presented with acute coronary syndrome (ACS), on diagnostic coronary angiography he had 75% and 70% stenosis in mid and distal left anterior descending artery (LAD) respectively, PCI with BVS implantation was done...
December 16, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/29239195/-immunotherapy-of-colorectal-and-anal-carcinoma
#18
J Tomášek, I Kiss
BACKGROUND: The lower part of the digestive tract includes the large intestine, rectum and anus. Treatment algorithms of cancers in these localities have significant differences in both early and advanced stages. The vast majority of metastatic cases are incurable. A few years ago, it was generally accepted that gastrointestinal tumors are poorly immunogenic and modern immunotherapy would not work in gastrointestinal cancers. The breakthrough has become the recognition of the mismatch repair system (MMR) that affects the microsatellite instability (MSI) and its role in the development of colorectal carcinoma (CRC)...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/29237923/systemic-therapy-after-radiotherapy-significantly-reduces-the-risk-of-mortality-of-patients-with-1-3-brain-metastases-a-retrospective-study-of-250-patients
#19
Bo Li, Zhao-Xia Dai, Yi-Dong Chen, Yan-Wei Liu, Shuai Liu, Xue-Nan Gu, Xiao-Guang Qiu
BACKGROUND: For patients with a brain metastasis (BM), systemic therapy is usually administered after the completion of radiotherapy, especially in cases of multiple BMs. However, the role of systemic therapy in patients with a limited number of BMs is not clear. Therefore, we conducted a retrospective study to explore this question. METHODS: Consecutive patients with a pathologically confirmed malignancy and 1-3 intracranial lesions that had been documented within the last decade were selected from the databases of three hospitals in China...
December 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/29237903/clinicopathological-features-and-prognostic-evaluation-of-bone-metastasis-in-triple-negative-breast-cancer
#20
Anqi Luo, Fang Wu, Rui Han, Shangke Huang, Yujiao Zhang, Xin Jing, Xinhan Zhao
BACKGROUND: Bone metastases (BMs) are common for breast cancer patients. However, triple-negative breast cancer (TNBC) with BM is relatively rare and few data on it are available. In this study, we aim to investigate the incidence and clinicopathological features and to evaluate the prognosis of TNBC patients with BM. MATERIALS AND METHODS: A total of 616 patients with TNBC (120 out of them had BM) between 2007 and 2011 were involved in the study. Clinicopathological characteristics were statistically analyzed...
2017: Journal of Cancer Research and Therapeutics
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