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Irena Misiewicz-Krzeminska, Luis Antonio Corchete, Elizabeta A Rojas, Joaquín Martínez-López, Ramón García-Sanz, Albert Oriol, Joan Bladé, Juan José Lahuerta, Jesús San Miguel, María Victoria Mateos, Norma C Gutiérrez
Protein analysis in bone marrow samples from patients with multiple myeloma has been limited by the low protein concentration obtained after CD138+ selection. A novel approach based on capillary nano-immunoassay could make it possible to automatically quantify dozens of proteins from each myeloma sample. Here, we present a method for the accurate and robust quantification of the expression of multiple proteins extracted from CD138-purified multiple myeloma samples frozen in RLT Plus buffer, which is commonly used for nucleic acid preservation and isolation...
March 15, 2018: Haematologica
Sara L Ackerman, Gato Gourley, Gem Le, Pamela Williams, Jinoos Yazdany, Urmimala Sarkar
OBJECTIVE: The aim of the study was to develop standards for tracking patient safety gaps in ambulatory care in safety net health systems. METHODS: Leaders from five California safety net health systems were invited to participate in a modified Delphi process sponsored by the Safety Promotion Action Research and Knowledge Network (SPARKNet) and the California Safety Net Institute in 2016. During each of the three Delphi rounds, the feasibility and validity of 13 proposed patient safety measures were discussed and prioritized...
March 14, 2018: Journal of Patient Safety
Hirofumi Maekawa, Katsuaki Noda, Keisuke Kuramochi, Tianyuan Zhang
Vinylsilanes were directly prepared from the corresponding vinyl triflates under magnesium-promoted reductive conditions in THF with no transition metal catalyst, and gem-bis-silylated compounds were obtained in NMP. Investigation of the redox potential of starting materials and products suggested that reductive coupling reactions of vinyl triflates might be controlled by the reduction potential. A variety of gem-bis-silylated compounds and 3-silyladipic acid esters were easily synthesized in only two steps from vinyl triflates in high yields...
March 14, 2018: Organic Letters
Wei Zhang, Luc Girard, Yu-An Zhang, Tomohiro Haruki, Mahboubeh Papari-Zareei, Victor Stastny, Hans K Ghayee, Karel Pacak, Trudy G Oliver, John D Minna, Adi F Gazdar
Background: Small cell lung cancer (SCLC) is a deadly, high grade neuroendocrine (NE) tumor without recognized morphologic heterogeneity. However, over 30 years ago we described a SCLC subtype with "variant" morphology which did not express some NE markers and exhibited more aggressive growth. Methods: To quantitate NE properties of SCLCs, we developed a 50-gene expression-based NE score that could be applied to human SCLC tumors and cell lines, and genetically engineered mouse (GEM) models...
February 2018: Translational Lung Cancer Research
Jiyan Mohammad, Harsharan Dhillon, Shireen Chikara, Sujan Mamidi, Avinash Sreedasyam, Kishore Chittem, Megan Orr, John C Wilkinson, Katie M Reindl
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers due to a late diagnosis and poor response to available treatments. There is a need to identify complementary treatment strategies that will enhance the efficacy and reduce the toxicity of currently used therapeutic approaches. We investigated the ability of a known ROS inducer, piperlongumine (PL), to complement the modest anti-cancer effects of the approved chemotherapeutic agent gemcitabine (GEM) in PDAC cells in vitro and in vivo . PDAC cells treated with PL + GEM showed reduced cell viability, clonogenic survival, and growth on Matrigel compared to control and individually-treated cells...
February 13, 2018: Oncotarget
Anne Harrison-Marchand, Jie Guang, Romain Duwald, Jacques Maddaluno, Hassan Oulyadi, Sami Lakhdar, Annie-Claude Gaumont
The synthesis and identification of unprecedented gem-dianionic phosphorus compounds, i.e. gem-dilithium phosphido-boranes Li2[RP*BH3], with R = Ph or Cy, are reported in THF solution. Those are obtained by double deprotonation of the corresponding primary phosphine-borane precursors RPH2*BH3. Their in-depth structural study, based on multinuclear (1H, 6Li, 7Li, 11B, 13C, 31P) mono- and bi-dimensional NMR analyses, indicates a strong influence of the phosphorus substituent on the structure of the gem-dianionic phosphorus structure: while a monomeric arrangement is obtained when R = phenyl, a cyclic oligomer is observed for R = cyclohexyl...
March 13, 2018: Chemistry: a European Journal
Hiroshi Ishii, Natsumi Yamashita, Makoto Ueno, Shinichi Ohkawa, Akiko M Saito, Mitsugu Sekimoto
Introduction: In Japan, the age of patients with pancreatic cancer has increased. Combination chemotherapies such as 5-fluorouracil/leucovorin, oxaliplatin and irinotecan therapy and gemcitabine hydrochloride (GEM) +nab paclitaxel therapy have been developed as the standard treatments for young patients with advanced recurrent pancreatic cancer. However, both therapies produce toxicity and their administration is limited by the patients' age or performance status. The efficacy and safety data obtained in the GEST study-a large-scale randomised controlled study conducted in patients with pancreatic cancer in Japan-suggested that GEM +S-1 (GS) combination therapy is a promising candidate for those aged between 75 and 80 years...
2018: BMJ Open Gastroenterology
Benjamin Levin, Emily P Balskus
Propanediol dehydratase (PD), a recently characterized member of the glycyl radical enzyme (GRE) family, uses protein-based radicals to catalyze the chemically challenging dehydration of (S)-1,2-propanediol. This transformation is also performed by the well-studied enzyme B12-dependent propanediol dehydratase (B12-PD) using an adenosylcobalamin cofactor. Despite the prominence of PD in anaerobic microorganisms, it remains unclear if the mechanism of this enzyme is similar to that of B12-PD. Here we report oxygen-18 labeling experiments that suggest PD and B12-PD employ distinct mechanisms...
March 12, 2018: Biochemistry
Evgeniy R Galimov, Rosina E Pryor, Sarah E Poole, Alexandre Benedetto, Zachary Pincus, David Gems
Organismal death is a process of systemic collapse whose mechanisms are less well understood than those of cell death. We previously reported that death in C. elegans is accompanied by a calcium-propagated wave of intestinal necrosis, marked by a wave of blue autofluorescence (death fluorescence). Here, we describe another feature of organismal death, a wave of body wall muscle contraction, or death contraction (DC). This phenomenon is accompanied by a wave of intramuscular Ca2+ release and, subsequently, of intestinal necrosis...
March 6, 2018: Cell Reports
Xiaoting Wu, Fang Xie, Ilya D Gridnev, Wanbin Zhang
An efficient copper-catalyzed reductive defluorination of β-trifluoromethylated enones via an oxidative homocoupling of Grignard reagents is reported. The reaction proceeded smoothly with a wide range of substrates, including the ones bearing aromatic heterocycles, such as furyl and thienyl ring systems in high yields (80-92%, except one example) under mild conditions. This provides a practical method for synthesis of gem-difluoroolefin ketones. It is also worth noting that this homocoupling process of Grignard reagents using β-trifluoromethylated enones as "oxidizing reagents" is effective for both the Csp2 -Csp2 and Csp3 -Csp3 bond formations, including for substrates whose β-hydride elimination of the corresponding transition metal alkyl complex is particularly facile, affording coupling products with high yields (83-95%), simultaneously...
March 7, 2018: Organic Letters
Jennifer L Fulton, Matthew A Horwitz, Ericka L Bruske, Jeffrey S Johnson
An asymmetric sulfa-Michael addition of alkyl thiols to enone diesters is reported. The reaction is catalyzed by a bifunctional triaryliminophosphorane-thiourea organocatalyst and provides a range of α-sulfaketones in high yields and enantioselectivities. Leveraging the gem-diester functional handle via a subsequent diastereotopic group discrimination generates functionalized lactones with three contiguous stereocenters.
March 7, 2018: Journal of Organic Chemistry
Mohan Pal, Nicole M Easton, Hannah Yaphe, Stephen L Bearne
Rational approaches for the design of enzyme inhibitors furnish powerful strategies for developing pharmaceutical agents and tools for probing biological mechanisms. A new strategy for the development of gem-disubstituted substrate-product analogues as inhibitors of racemases and epimerases is elaborated using α-methylacyl-coenzyme A racemase from Mycobacterium tuberculosis (MtMCR) as a model enzyme. MtMCR catalyzes the epimerization at C2 of acyl-CoA substrates, a key step in the metabolism of branched-chain fatty acids...
February 7, 2018: Bioorganic Chemistry
Yago Nieto, Peter F Thall, Junsheng Ma, Benigno C Valdez, Sairah Ahmed, Paolo Anderlini, Uday Popat, Roy B Jones, Elizabeth J Shpall, Chitra Hosing, Muzaffar Qazilbash, Partow Kebriaei, Amin Alousi, Melissa Timmons, Alison Gulbis, Alan Myers, Yasuhiro Oki, Michelle Fanale, Bouthaina Dabaja, Chelsea Pinnix, Sarah Milgrom, Richard Champlin, Borje S Andersson
We conducted a prospective phase 2 trial of gemcitabine, busulfan and melphalan (Gem/Bu/Mel) with autologous stem-cell transplantation (ASCT) in Hodgkin's lymphoma (HL) patients with primary refractory or poor-risk relapsed disease (extranodal relapse or within 1 year of frontline therapy). The trial was powered to detect a 2-year progression-free survival (PFS) rate improvement from a historical 50% (using BEAM) to 65%. We compared the study population with all other concurrent patients who were eligible for the trial but instead received BEAM at our center...
March 1, 2018: Biology of Blood and Marrow Transplantation
Kazuki Takasaki, Morikazu Miyamoto, Masashi Takano, Hiroaki Soyama, Tadashi Aoyama, Hiroko Matsuura, Kento Kato, Takahiro Sakamoto, Mika Kuwahara, Hideki Iwahashi, Hiroki Ishibashi, Tomoyuki Yoshikawa, Kenichi Furuya
PURPOSE: To compare a cohort of patients with platinum-resistant recurrent ovarian cancer (PROC) treated with bevacizumab and gemcitabine (Bev-Gem) to that of patients treated only with gemcitabine (Gem). METHODS: Between 2011 and 2017, we identified the Bev-Gem and Gem PROC groups. The regimen included 1000 mg/m2 of Gem on days 1, 8, and 15, and 15 mg/m2 of Bev on day 1, every 4 weeks. Progression-free survival (PFS) and overall survival (OS) were calculated from the date of the administration of Bev-Gem or Gem until disease progression or death...
March 2, 2018: Cancer Chemotherapy and Pharmacology
Shamaila Fraz, Abigail H Lee, Joanna Y Wilson
Gemfibrozil (GEM) and carbamazepine (CBZ) are two environmentally relevant pharmaceuticals and chronic exposure of fish to these compounds has decreased androgen levels and fish reproduction in laboratory studies. The main focus of this study was to examine the effects of GEM and CBZ on testicular steroid production, using zebrafish as a model species. Chronic water borne exposures of adult zebrafish to 10 μg/L of GEM and CBZ were conducted and the dosing was confirmed by chemical analysis of water as 17...
February 10, 2018: Aquatic Toxicology
Anna Kalbarczyk, Nina A Martin, Emily Combs, Marie Ward, Peter J Winch
BACKGROUND: Global Health is an inherently interdisciplinary field but overseas training in global health, particularly among health science institutions, has been an 'individual' or 'individual discipline' experience. Team-based training is an approach to global health education which is increasing in popularity; research on team-training demonstrates that teams are more productive than individuals. In 2015, the Johns Hopkins Center for Global Health (CGH) developed the Global Established Multidisciplinary Sites (GEMS) program, an interdisciplinary training program which was designed to establish a new norm in global health training by bringing interdisciplinary teams of faculty and students together to identify and solve complex global health challenges...
March 1, 2018: Globalization and Health
Charlotte Oris, Yoan Clavel, Matthieu Jabaudon, Annick Pialat, Hadj Abdelkader Mohamed, Frédérique Lioret, Vincent Sapin, Damien Bouvier
Background: Blood gas analyzers are o0.ften integrated into point-of-care testing provisions. International standards (ISO 22870 and 15189) as adapted to French COFRAC regulations make accreditation of point-ofta-care testintag obligatory. We installed and assessed 12 GEM PREMIER 4000 analyzers for pH, p CO2 , p O2 , Na+ , K+ , Cl- , Ca2+ , lactate, hemoglobin and oxyhemoglobin (O2 Hb) at Clermont-Ferrand Hospital. These instruments were distributed across 11 care sites in the hospital...
March 2018: Practical Laboratory Medicine
Kentaro Igarashi, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Miyake, Masuyo Miyake, Yunfeng Li, Scott D Nelson, Sarah M Dry, Arun S Singh, Irmina A Elliott, Tara A Russell, Mark A Eckardt, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Hiroyuki Tsuchiya, Fritz C Eilber, Robert M Hoffman
Relapsed osteosarcoma is a recalcitrant tumor. A patient's cisplatinum (CDDP)-resistant relapsed osteosarcoma lung metastasis was previously established orthotopically in the distal femur of mice to establish a patient-derived orthotopic xenograft (PDOX) model. In the present study, the PDOX models were randomized into the following groups when tumor volume reached 100 mm3 : G1, control without treatment; G2, CDDP (6 mg/kg, intraperitoneal (i.p.) injection, weekly, for 2 weeks); gemcitabine (GEM) (100 mg/kg, i...
January 30, 2018: Oncotarget
K S Funder, L S Rasmussen, V Siersma, N Lohse, R Hesselfeldt, F Pedersen, O M Hendriksen, J Steinmetz
BACKGROUND: Implementation of the first Danish helicopter emergency medical service (HEMS) was associated with reduced time from first medical contact to treatment at a specialized centre for patients with suspected ST elevation myocardial infarction (STEMI). We aimed to investigate effects of HEMS on mortality and labour market affiliation in patients admitted for primary percutaneous coronary intervention (PCI). METHODS: In this prospective observational study, we included patients with suspected STEMI within the region covered by the HEMS from January 1, 2010, to April 30, 2013, transported by either HEMS or ground emergency medical services (GEMS) to the regional PCI centre...
February 27, 2018: Acta Anaesthesiologica Scandinavica
Koji Kase, Ryo Okada, Makoto Muto, Junichiro Watanabe, Naoya Sato, Yasuhide Kofunato, Teruhide Ishigame, Takashi Kimura, Akira Kenjo, Tatsuo Shimura, Shigeru Marubashi
We hereby report a case of long-term survival of the pancreatic tail cancer with a synchronous small liver metastasis. A 62- year-old male with pancreatic tail cancer was incidentally diagnosed with single tiny metastasis in the left medial section of the liver duringthe distal pancreatectomy. The lesion was also resected together with primary lesion. Since then, systemic chemotherapies such as gemcitabine(GEM)plus S-1 combination therapy, GEM alone therapy and S-1 alone therapy had been given to escape from recurrence...
February 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
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