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https://www.readbyqxmd.com/read/28110019/cancer-cell-metabolism-and-mitochondria-nutrient-plasticity-for-tca-cycle-fueling
#1
REVIEW
Cyril Corbet, Olivier Feron
Warburg's hypothesis that cancer cells take up a lot of glucose in the presence of ambient oxygen but convert pyruvate into lactate due to impaired mitochondrial function led to the misconception that cancer cells rely on glycolysis as their major source of energy. Most recent (13)C-based metabolomic studies, including in cancer patients, indicate that cancer cells may also fully oxidize glucose. In addition to glucose-derived pyruvate, lactate, fatty acids and amino acids supply substrates to the TCA cycle to sustain mitochondrial metabolism...
January 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28107182/the-nitrobenzoxadiazole-derivative-mc3181-blocks-melanoma-invasion-and-metastasis
#2
Anastasia De Luca, Debora Carpanese, Maria Cristina Rapanotti, Tara Mayte Suarez Viguria, Maria Antonietta Forgione, Dante Rotili, Chiara Fulci, Egidio Iorio, Luigi Quintieri, Sergio Chimenti, Luca Bianchi, Antonio Rosato, Anna Maria Caccuri
The novel nitrobenzoxadiazole (NBD) derivative MC3181 is endowed with remarkable therapeutic activity in mice bearing both sensitive and vemurafenib-resistant human melanoma xenografts. Here, we report that subtoxic concentrations of this compound significantly reduced invasiveness of BRAF-V600D mutated WM115 and WM266.4 melanoma cell lines derived from the primary lesion and related skin metastasis of the same patient, respectively. The strong antimetastatic activity of MC3181 was observed in both 2D monolayer cultures and 3D multicellular tumor spheroids, and confirmed in vivo by the significant decrease in the number of B16-F10 melanoma lung metastases in drug-treated mice...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28103504/l-arginine-alters-the-effect-of-5-fluorouracil-on-breast-cancer-cells-in-favor-of-apoptosis
#3
Mozhgan Jahani, Mehri Azadbakht, Fatemeh Norooznezhad, Kamran Mansouri
Chemoresistance in breast cancer is a major obstacle, especially in p53 mutation types. The aim of this study was to evaluate if a combination therapy of l-arginine with 5-fluorouracil (5-FU) can alter the effect of this chemotherapy drug on breast cancer cells. The study was performed on BT-20 and MCF-7 cell lines. The effects of l-arginine alone and in combination with 5-FU were investigated on cell viability, apoptosis and nitric oxide (NO) production. Drugs effects on the cellular energetic metabolism were investigated through the lactate production and glucose-6-phosphate dehydrogenase (G6PD) activity assay...
January 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28102676/novel-antitumor-platinum-ii-conjugates-containing-the-nonsteroidal-anti-inflammatory-agent-diclofenac-synthesis-and-dual-mechanisms-of-antiproliferative-effects
#4
Francesco Paolo Intini, Juraj Zajac, Vojtech Novohradsky, Teresa Saltarella, Concetta Pacifico, Viktor Brabec, Giovanni Natile, Jana Kasparkova
One concept how to improve anticancer effects of conventional metallodrugs consists in conjugation of these compounds with other biologically (antitumor) active agents, acting by a different mechanism. Here, we present synthesis, biological effects, and mechanisms of action of new Pt(II) derivatives containing one or two nonsteroidal anti-inflammatory diclofenac (DCF) ligands also known for their antitumor effects. The antiproliferative properties of these metallic conjugates show that these compounds are potent and cancer cell selective cytotoxic agents exhibiting activity in cisplatin resistant and the COX-2 positive tumor cell lines...
January 19, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28101782/the-antineoplastic-drug-trastuzumab-dysregulates-metabolism-in-ipsc-derived-cardiomyocytes
#5
Brian M Necela, Bianca C Axenfeld, Daniel J Serie, Jennifer M Kachergus, Edith A Perez, E Aubrey Thompson, Nadine Norton
BACKGROUND: The targeted ERBB2 therapy, trastuzumab, has had a tremendous impact on management of patients with HER2+ breast cancer, leading to development and increased use of further HER2 targeted therapies. The major clinical side effect is cardiotoxicity but the mechanism is largely unknown. On the basis that gene expression is known to be altered in multiple models of heart failure, we examined differential gene expression of iPSC-derived cardiomyocytes treated at day 11 with the ERBB2 targeted monoclonal antibody, trastuzumab for 48 h and the small molecule tyrosine kinase inhibitor of EGFR and ERBB2...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28099979/milrinone-pharmacokinetics-and-pharmacodynamics-in-neonates-with-persistent-pulmonary-hypertension-of-the-newborn
#6
Annie Giaccone, Athena F Zuppa, Beena Sood, Meryl S Cohen, Michael L O'Byrne, Ganesh Moorthy, Amit Mathur, Haresh Kirpalani
Objective To describe the pharmacokinetics and pharmacodynamics of milrinone in infants with persistent pulmonary hypertension of the newborn (PPHN) and to explore the impact of age on milrinone disposition. Design Randomized, open label pilot study. Setting Multicenter; level 3 and level 4 neonatal intensive care units. Patients Six infants ≥34 weeks' gestational age and <10 days of life with persistent hypoxemia receiving inhaled nitric oxide. Intervention Intravenous milrinone lactate in one of two dosing regimens: (1) low dose, 20 mcg/kg bolus followed by 0...
January 18, 2017: American Journal of Perinatology
https://www.readbyqxmd.com/read/28092695/absorption-distribution-and-excretion-of-the-anti-tuberculosis-drug-delamanid-in-rats-extensive-tissue-distribution-suggests-potential-therapeutic-value-for-extrapulmonary-tuberculosis
#7
Masakazu Shibata, Yoshihiko Shimokawa, Katsunori Sasahara, Noriaki Yoda, Hiroyuki Sasabe, Mitsunari Suzuki, Ken Umehara
Delamanid (OPC-67683, Deltyba(TM) , nitro-dihydro-imidazooxazoles derivative) is approved for the treatment of adult pulmonary multidrug-resistant tuberculosis. The absorption, distribution, and excretion of delamanid-derived radioactivity were investigated after a single oral administration of (14) C-delamanid at 3 mg/kg to rats. In both male and female rats, radioactivity in blood and all tissues reached peak levels by 8 or 24 hours postdose, and thereafter decreased slowly. Radioactivity levels were 3- to 5-fold higher in lung tissue at time to maximum concentration compared with plasma...
January 16, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28089921/penehyclidine-hydrochloride-prevents-anoxia-reoxygenation-injury-and-induces-h9c2-cardiomyocyte-apoptosis-via-a-mitochondrial-pathway
#8
Zhaoqi Wang, Duomao Lin, Liang Zhang, Wenjun Liu, Hongbao Tan, Jun Ma
Penehyclidine hydrochloride (PHC) is an anticholinergic drug that has been widely used in the clinic for years, evaluating for anesthetic premedication, anti-muscarinic, or improving microcirculation. However, very little is known about its protective effects against anoxia/reoxygenation (A/R) injury in myocardiocytes. The aim of our study was to investigate the protective effects of PHC pretreatment on A/R injury, as well as the underlying mechanisms involved. To investigate apoptosis, we used the cell viability assay, Annexin-V/PI assay, and lactate dehydrogenase (LDH) and creatine kinase (CK) activity measurements...
January 12, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28088425/short-communication-staphylococcus-aureus-infection-modulates-expression-of-drug-transporters-and-inflammatory-biomarkers-in-mouse-mammary-gland
#9
A Oskarsson, Y Yagdiran, S Nazemi, J Tallkvist, C H Knight
Mastitis is the most common disease in dairy herds worldwide and is often caused by Staphylococcus aureus. Little is known about the effect of mastitis on transporters in the mammary gland and the effect on transporter-mediated secretion of drugs into milk. We studied gene expressions of ATP-binding cassette and solute carrier transporters in S. aureus-infected mammary glands of mice. On d 7 of lactation, NMRI mice were inoculated with 1,000 cfu of S. aureus in 2 mammary glands and with a saline vehicle in 2 control glands...
January 11, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28079354/effect-of-excess-iodine-intake-on-thyroid-on-human-health
#10
Eftychia G Koukkou, Nikolaos D Roupas, Kostas B Markou
INTRODUCTION: The recommended daily intake of iodide, is 150 μg for adolescents and adults, 175 μg for pregnancy and 200 μg for lactation. Thyroid gland is an effective collector of iodine. EVIDENCE ACQUISITION: The active iodine uptake along the basolateral membrane of thyroid cell is followed by its transport to the apical edge of the cell and then to the follicle lumen. TSH acts through cAMP and stimulates NIS gene expression and protein synthesis. The major proportion of iodine in the thyroid gland is bound to Thyroglobulin...
January 12, 2017: Minerva Medica
https://www.readbyqxmd.com/read/28077256/montivipera-bornmuelleri-venom-selectively-exhibits-high-cytotoxic-effects-on-keratinocytes-cancer-cell-lines
#11
Saly Sawan, Tania Yaacoub, Souad Hraoui-Bloquet, Riyad Sadek, Walid Hleihel, Ziad Fajloun, Marc Karam
CONTEXT: The Viperidae family venom is a rich source of bioactive compounds such as many proteases, which cause tissue necrosis and affect mostly the vascular system. However, the venom exhibits therapeutic potentials and has contributed to the development of some medical drugs. Specifically, the Montivipera bornmuelleri venom has shown to exhibit antibacterial, pro-inflammatory and antifungal activities. OBJECTIVE: This work evaluates the cytotoxic effect of the M...
January 8, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/28068681/hypoxia-and-hyperoxia-affect-serum-angiogenic-regulators-in-t2dm-men-during-cycling
#12
C Brinkmann, A Metten, P Scriba, C V M Tagarakis, P Wahl, J Latsch, K Brixius, W Bloch
Exercise-induced transient increases in pro-angiogenic regulators can promote angiogenesis.This pilot study aims to analyze the potential of exercise to positively affect angiogenic regulators in patients with type 2 diabetes mellitus (T2DM), who often exhibit abnormal angiogenesis, under different environmental conditions. 9 overweight/obese men with uncomplicated T2DM (8 took anti-diabetic drugs) performed submaximal cycling for 40 min in normoxia (≈21 vol%O2), hypoxia (≈14 vol%O2) and during alternating hypoxia/hyperoxia (≈14 vol%O2/≈30 vol%O2, 5-min intervals) (3×3 crossover design)...
January 9, 2017: International Journal of Sports Medicine
https://www.readbyqxmd.com/read/28065220/effects-of-lianhua-qingwen-on-pulmonary-oxidative-lesions-induced-by-fine-particulates-pm2-5-in-rats
#13
Ping Fen, Li Zhen-Sheng, Zhang Feng-Rui, Li De-Xin, Han Shu-Zhi
Objective To investigate the antagonistic effects of different doses of Lianhua Qingwen on pulmonary injury induced by fine particulates PM2.5 in rats. Methods Fine particulates suspended in the environment were collected. Forty-eight healthy adult wistar rats were randomly divided into 6 groups with 8 rats in each group. Four groups of rats were exposed to PM2.5 by intratracheally dripping suspensions of fine particulates PM2.5 (7.5 mg/kg) as dust-exposed model rats. Among them 24 rats in three groups received Lianhua Qingwen treatment (crude drug) at a dose of 2 g/kg, 4 g/kg, 8 g/kg per day for 3 days before dust exposure and were defined as low-dose, middle-dose and high-dose Lianhua Qingwen treatment groups respectively...
November 20, 2016: Chinese Medical Sciences Journal, Chung-kuo i Hsüeh K'o Hsüeh Tsa Chih
https://www.readbyqxmd.com/read/28064509/acute-salicylate-poisoning-risk-factors-for-severe-outcome
#14
Rachel M Shively, Robert S Hoffman, Alex F Manini
CONTEXT: Salicylate poisoning remains a significant public health threat with more than 20,000 exposures reported annually in the United States. OBJECTIVE: We aimed to establish early predictors of severe in-hospital outcomes in Emergency Department patients presenting with acute salicylate poisoning. METHODS: This was a secondary data analysis of adult salicylate overdoses from a prospective cohort study of acute drug overdoses at two urban university teaching hospitals from 2009 to 2013...
January 9, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28056084/sbds-deficient-cells-have-an-altered-homeostatic-equilibrium-due-to-translational-inefficiency-which-explains-their-reduced-fitness-and-provides-a-logical-framework-for-intervention
#15
Piera Calamita, Annarita Miluzio, Arianna Russo, Elisa Pesce, Sara Ricciardi, Farhat Khanim, Cristina Cheroni, Roberta Alfieri, Marilena Mancino, Chiara Gorrini, Grazisa Rossetti, Ivana Peluso, Massimiliano Pagani, Diego L Medina, Johanna Rommens, Stefano Biffo
Ribosomopathies are a family of inherited disorders caused by mutations in genes necessary for ribosomal function. Shwachman-Diamond Bodian Syndrome (SDS) is an autosomal recessive disease caused, in most patients, by mutations of the SBDS gene. SBDS is a protein required for the maturation of 60S ribosomes. SDS patients present exocrine pancreatic insufficiency, neutropenia, chronic infections, and skeletal abnormalities. Later in life, patients are prone to myelodisplastic syndrome and acute myeloid leukemia (AML)...
January 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28052109/defining-surrogate-endpoints-for-clinical-trials-in-severe-falciparum-malaria
#16
Atthanee Jeeyapant, Hugh W Kingston, Katherine Plewes, Richard J Maude, Josh Hanson, M Trent Herdman, Stije J Leopold, Thatsanun Ngernseng, Prakaykaew Charunwatthana, Nguyen Hoan Phu, Aniruddha Ghose, M Mahtab Uddin Hasan, Caterina I Fanello, Md Abul Faiz, Tran Tinh Hien, Nicholas P J Day, Nicholas J White, Arjen M Dondorp
BACKGROUND: Clinical trials in severe falciparum malaria require a large sample size to detect clinically meaningful differences in mortality. This means few interventions can be evaluated at any time. Using a validated surrogate endpoint for mortality would provide a useful alternative allowing a smaller sample size. Here we evaluate changes in coma score and plasma lactate as surrogate endpoints for mortality in severe falciparum malaria. METHODS: Three datasets of clinical studies in severe malaria were re-evaluated: studies from Chittagong, Bangladesh (adults), the African 'AQUAMAT' trial comparing artesunate and quinine (children), and the Vietnamese 'AQ' study (adults) comparing artemether with quinine...
2017: PloS One
https://www.readbyqxmd.com/read/28052008/targeting-p-glycoprotein-function-p53-and-energy-metabolism-combination-of-metformin-and-2-deoxyglucose-reverses-the-multidrug-resistance-of-mcf-7-dox-cells-to-doxorubicin
#17
Chaojun Xue, Changyuan Wang, Yaoting Sun, Qiang Meng, Zhihao Liu, Xiaokui Huo, Pengyuan Sun, Huijun Sun, Xiaodong Ma, Xiaochi Ma, Jinyong Peng, Kexin Liu
Multidrug resistance(MDR) is a major obstacle to efficiency of breast cancer chemotherapy. We investigated whether combination of metformin and 2-deoxyglucose reverses MDR of MCF-7/Dox cells and tried to elucidate the possible mechanisms. The combination of metformin and 2-deoxyglucose selectively enhanced cytotoxicity of doxorubicin against MCF-7/Dox cells. Combination of the two drugs resumed p53 function via inhibiting overexpression of murine doubleminute 2(MDM2) and murine doubleminute 4(MDM4) leading to G2/M arrest and apoptosis in MCF-7/Dox cells...
December 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/28046175/acute-effects-of-general-anesthesia-with-propofol-pentobarbital-or-isoflurane-plus-propofol-on-plasma-metabolites-and-hormones-in-adult-pigs
#18
G Daş, A Vernunft, S Görs, E Kanitz, J M Weitzel, K-P Brüssow, C C Metges
Experimental setups for physiological research, in which acute operative interventions need to be performed, can require inclusion of general anesthesia (GA), which may interfere or confound with the effects of the experimental factors of interest on measured variables. It was recently shown that the most commonly used sedatives/anesthetics in pigs (e.g., ketamine, xylazine, azaperone) affect physiological responses and thus the primary metabolic readouts have the potential to be confounded. To extend the search for a physiologically-friendly anesthesia regime for such studies, we investigated effects of GA induced by propofol (Prop) or pentobarbital (Pent) or propofol plus isoflurane (Prop + Isof) on plasma concentrations of commonly measured metabolites and hormones...
December 2016: Journal of Animal Science
https://www.readbyqxmd.com/read/28043661/use-of-noninvasive-and-invasive-mechanical-ventilation-in-cardiogenic-shock-a-prospective-multicenter-study
#19
Mari Hongisto, Johan Lassus, Tuukka Tarvasmaki, Alessandro Sionis, Heli Tolppanen, Matias Greve Lindholm, Marek Banaszewski, John Parissis, Jindrich Spinar, Jose Silva-Cardoso, Valentina Carubelli, Salvatore Di Somma, Josep Masip, Veli-Pekka Harjola
BACKGROUND: Despite scarce data, invasive mechanical ventilation (MV) is widely recommended over non-invasive ventilation (NIV) for ventilatory support in cardiogenic shock (CS). We assessed the real-life use of different ventilation strategies in CS and their influence on outcome focusing on the use of NIV and MV. METHODS: 219 CS patients were categorized by the maximum intensity of ventilatory support they needed during the first 24h into MV (n=137; 63%) , NIV (n=26; 12%), and supplementary oxygen (n=56; 26%) groups...
December 27, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/28042534/effect-of-food-additive-citric-acid-on-the-growth-of-human-esophageal-carcinoma-cell-line-ec109
#20
Xiaoguang Chen, Qiongxia Lv, Yumei Liu, Wen Deng
OBJECTIVE: Today, esophageal cancer (EC) has become one of the most common cancer types in China. Therefore, new drug and therapeutic strategies are urgently needed to improve postoperative survival rate of patients with EC. As a food additive, several lines of evidence have shown that citric acid can be served as glycolysis suppressor to inhibit growth of some tumor cells. However, little is known about the effect of this organic acid on the growth of human esophageal carcinoma cell line, EC109...
2017: Cell Journal
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