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Ldh a inhibitors

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https://www.readbyqxmd.com/read/28327969/circulating-tumour-dna-predicts-response-to-anti-pd1-antibodies-in-metastatic-melanoma
#1
J H Lee, G V Long, S Boyd, S Lo, A M Menzies, V Tembe, A Guminski, V Jakrot, R A Scolyer, G J Mann, R F Kefford, M S Carlino, H Rizos
Background: Programmed death 1 (PD1) inhibitors are now a foundation of medical management of metastatic melanoma. This study sought to determine whether circulating tumour DNA (ctDNA) provides useful early response and prognostic information. Patients and methods: We evaluated the relationship between pre-treatment and early on treatment ctDNA and outcome in melanoma patients treated with PD1 inhibitors alone or in combination with ipilimumab. Results: ctDNA was detected in 40/76 patients (53%) at baseline, and correlated with stage, LDH levels, disease volume and ECOG performance...
January 24, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28323904/pyrrolidine-dithiocarbamate-administered-during-ex-vivo-lung-perfusion-promotes-rehabilitation-of-injured-donor-rat-lungs-obtained-after-prolonged-warm-ischemia
#2
Cyril Francioli, Xingyu Wang, Roumen Parapanov, Etienne Abdelnour, Jérôme Lugrin, Fabrizio Gronchi, Jean Perentes, Philippe Eckert, Hans-Beat Ris, Lise Piquilloud, Thorsten Krueger, Lucas Liaudet
Damaged lung grafts obtained after circulatory death (DCD lungs) and warm ischemia may be at high risk of reperfusion injury after transplantation. Such lungs could be pharmacologically reconditioned using ex-vivo lung perfusion (EVLP). Since acute inflammation related to the activation of nuclear factor kappaB (NF-κB) is instrumental in lung reperfusion injury, we hypothesized that DCD lungs might be treated during EVLP by pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB. Rat lungs exposed to 1h warm ischemia and 2 h cold ischemia were subjected to EVLP during 4h, in absence (CTRL group, N = 6) or in presence of PDTC (2...
2017: PloS One
https://www.readbyqxmd.com/read/28322131/soluble-flt-1-has-cytotoxic-effects-on-bewo-choriocarcinoma-cells
#3
Michiko Yamashita, Keiichi Kumasawa, Tatsuya Miyake, Hitomi Nakamura, Tadashi Kimura
BACKGROUND: Vascular endothelial growth factor (VEGF) plays a pivotal role in angiogenesis and is overexpressed in many kinds of malignant tumors. Soluble VEGF receptor 1 (sVEGFR-1/ soluble fms-like tyrosine kinase 1 [sFlt-1]) plays a role as an inhibitor of VEGF, and an antitumor effect has been shown in several studies using sFlt-1. Recently, in addition to its antiangiogenic effect, it was reported that sFlt-1 has direct cytotoxicity. MATERIALS AND METHODS: Transfection of sFlt-1 plasmid DNA was performed in the BeWo choriocarcinoma cell line...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28296232/inhibitors-of-soluble-epoxide-hydrolase-minimize-ischemia-reperfusion-induced-cardiac-damage-in-normal-hypertensive-and-diabetic-rats
#4
Oliul Islam, Prashanth Patil, Sumanta K Goswami, Rema Razdan, Mohammed N Inamdar, Mohammed Rizwan, Jubin Mathew, Bora Inceoglu, Kin S Stephen Lee, Sung H Hwang, Bruce D Hammock
AIM: We designed a study to evaluate the cardioprotective effect of two soluble epoxide hydrolase (sEH) inhibitors, 1-(1-propanoylpiperidin-4-yl)-3-(4-trifluoromethoxy)phenyl)urea (TPPU) and trans-4-{4-[3-(4-trifluoromethoxyphenyl)-ureido]cyclohexyloxy}benzoic acid (t-TUCB), in ischemia-reperfusion (IR) model. METHODS: Cardioprotective effects of the sEH inhibitors were evaluated against IR-induced myocardial damage in hearts from normal, hypertensive and diabetic rats using Langendorff's apparatus...
March 15, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28292981/vaginal-heparan-sulfate-linked-to-neutrophil-dysfunction-in-the-acute-inflammatory-response-associated-with-experimental-vulvovaginal-candidiasis
#5
Junko Yano, Mairi C Noverr, Paul L Fidel
Despite acute inflammation by polymorphonuclear neutrophils (PMNs) during vulvovaginal candidiasis (VVC), clearance of Candida fails to occur. The purpose of this study was to uncover the mechanism of vaginal PMN dysfunction. Designs included assessing PMN migration, proinflammatory mediators, and tissue damage (by analysis of the activity of lactate dehydrogenase [LDH]) in mice susceptible (C3H/HeN-C57BL/6) or resistant (CD-1) to chronic VVC (CVVC-S or CVVC-R) and testing morphology-specific Candida albicans strains under conditions of preinduced PMN migration (CVVC-S mice) or PMN depletion (CVVC-R mice)...
March 14, 2017: MBio
https://www.readbyqxmd.com/read/28281186/calcium-sensing-receptor-mediated-mitogen-activated-protein-kinase-pathway-improves-the-status-of-transplanted-mouse-embryonic-stem-cells-in-rats-with-acute-myocardial-infarction
#6
Jian Sun, Tao Wei, Shuzhi Bai, Hongtao Zhao, Xiaoqin Liu, Jinfeng Yu, Li Li, Gaochen Song, Hairong Luan, Changqing Xu
Several studies have identified the critical role of calcium-sensing receptors (CaSRs) in cardiac ischaemia/reperfusion injury and cardiac hypertrophy and have demonstrated that CaSRs induce myocardial apoptosis by activating MAPKs. Using acute myocardial infarction rat models, we found that a combination therapy of CaSR inhibition and embryonic stem cell (ESC) transplantation after acute myocardial infarction (AMI) leads to a dramatic reduction in the infarct size; a significant increase in the maximum rising and falling rate (+dp/dtmax and -dp/dtmax, respectively) of left ventricular pressure; a significant decrease in left ventricular end-diastolic pressure; a significant decrease in the mRNA expression level of CaSR, Bax, Bcl-2, cleaved caspase-3, cleaved caspase-9, p-ERK, p-JNK and p-P38 protein together with apoptosis indexes in the C and E groups; and a significant decrease in cTnT levels as well as LDH and CK activity...
March 9, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28274156/folic-acid-ameliorates-celecoxib-cardiotoxicity-in-a-doxorubicin-heart-failure-rat-model
#7
Shafique Ahmad, Bibhu Prasad Panda, Kanchan Kohli, Mohammad Fahim, Kiran Dubey
CONTEXT: The cardiotoxic effect of selective cyclo-oxygenase-2 inhibitors is well known. While rofecoxib and valdecoxib have been withdrawn, celecoxib remains on the market. Folic acid, a naturally occurring vitamin, has been shown to reduce myocardial ischemia and post-reperfusion injury in rats. OBJECTIVE: This study examined the cardiac effects of celecoxib and folic acid on doxorubicin-induced cardiomyopathy in rats. MATERIALS AND METHODS: Cardiomyopathy was induced in male Wistar rats with six intraperitoneal injections of 2...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28250059/netrin-1-restores-cell-injury-and-impaired-angiogenesis-in-vascular-endothelial-cells
#8
Ying Xing, Jingbo Lai, Xiangyang Liu, Nana Zhang, Jie Ming, Hengxin Liu, Xi Zhang
Diabetic foot ulceration (DFU) represents a common vascular complication of diabetes mellitus (DM) with high morbidity and disability resulting from amputation. Netrin-1 level was decreased in type 2 DM patients and has been identified as a protective regulator against diabetes-triggered myocardial infarction and nephropathy. Unfortunately, its role and molecular mechanism in DFU remain poorly elucidated. Here, netrin-1 levels were reduced in DM and DFU patients relative to healthy controls, with netrin-1 levels being lowest in DFU patients...
March 1, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28243322/targeting-metabolic-remodeling-in-triple-negative-breast-cancer-in-a-murine-model
#9
Verónica García-Castillo, Eduardo López-Urrutia, Octavio Villanueva-Sánchez, Miguel Á Ávila-Rodríguez, Alejandro Zentella-Dehesa, Carlo Cortés-González, César López-Camarillo, Nadia J Jacobo-Herrera, Carlos Pérez-Plasencia
Background: Chemotherapy is the backbone of systemic treatment for triple negative breast cancer (TNBC), which is one of the most relevant breast cancers molecular types due to the ability of tumor cells to develop drug resistance, highlighting the urgent need to design newer and safer drug combinations for treatment. In this context, to overcome tumor cell drug resistance, we employed a novel combinatorial treatment including Doxorubicin, Metformin, and Sodium Oxamate (DoxMetOx). Such pharmacological combination targets indispensable hallmarks of cancer-related to aerobic glycolysis and DNA synthesis...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28243141/bay11-7082-attenuates-neuropathic-pain-via-inhibition-of-nuclear-factor-kappa-b-and-nucleotide-binding-domain-like-receptor-protein-3-inflammasome-activation-in-dorsal-root-ganglions-in-a-rat-model-of-lumbar-disc-herniation
#10
Ailiang Zhang, Kun Wang, Lianghua Ding, Xinnan Bao, Xuan Wang, Xubin Qiu, Jinbo Liu
Lumbar disc herniation (LDH) is an important cause of radiculopathy, but the underlying mechanisms are incompletely understood. Many studies suggested that local inflammation, rather than mechanical compression, results in radiculopathy induced by LDH. On the molecular and cellular level, nuclear factor-kappa B (NF-κB) and nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome have been implicated in the regulation of neuroinflammation formation and progression. In this study, the autologous nucleus pulposus (NP) was implanted in the left L5 dorsal root ganglion (DRG) to mimic LDH in rats...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28238530/a-membrane-associated-adenylate-cyclase-modulates-lactate-dehydrogenase-and-creatine-kinase-activities-required-for-bull-sperm-capacitation-induced-by-hyaluronic-acid
#11
Silvina Fernández, Mariana Córdoba
Hyaluronic acid, as well as heparin, is a glycosaminoglycan present in the female genital tract of cattle. The aim of this study was to evaluate oxidative metabolism and intracellular signals mediated by a membrane-associated adenylate cyclase (mAC), in sperm capacitation with hyaluronic acid and heparin, in cryopreserved bull sperm. The mAC inhibitor, 2',5'-dideoxyadenosine, was used in the present study. Lactate dehydrogenase (LDH) and creatine kinase (CK) activities and lactate concentration were determined spectrophotometrically in the incubation medium...
April 2017: Animal Reproduction Science
https://www.readbyqxmd.com/read/28236683/extraction-and-isolation-of-potential-anti-stroke-compounds-from-flowers-of-pueraria-lobata-guided-by-in-vitro-pc12-cell-model
#12
Sainan Li, Senlin Li, Chengyu Liu, Chunming Liu, Yuchi Zhang
A simple and efficient method based on ultrafiltration liquid chromatography-mass spectrometry (UFLC-MS) was applied to rapidly screen and identify ligands for lactate dehydrogenase (LDH) from the flowers of Pueraria lobata, and the compounds were assessed for anti-stroke activity using a PC12 cell model. Seven major isoflavones, kakkalide, 3'-hydroxy puerarin, puerarin, puerarin xyloside, tectoridin, tectorigenin, and ononin, were identified as potent LDH inhibitors. A continuous online method, which consisted of microwave-assisted extraction and countercurrent chromatography (MAE-CCC), was newly developed for scaled-up production of these compounds with high purity and efficiency...
March 24, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28203523/glutathione-peroxidase-4-plays-an-important-role-in-oxidative-homeostasis-and-wound-repair-in-corneal-epithelial-cells
#13
Osamu Sakai, Takatoshi Uchida, Hirotaka Imai, Takashi Ueta
Oxidative stress is involved in the pathologies of corneal epithelial cells. However, the importance of specific antioxidant enzymes in corneal epithelial cells is not fully understood. The purpose of this study is to elucidate the role of glutathione peroxidase 4 (GPx4) in corneal epithelial cells. For in vitro experiments, an immortalized human corneal epithelial cell line was used. Cytotoxicity measured through LDH activity, lipid peroxidation immunostained for 4-hydroxynonenal, cell viability, and cell death were compared between cells transfected with either GPx4 siRNA or scrambled control siRNA...
December 2016: FEBS Open Bio
https://www.readbyqxmd.com/read/28194544/exploring-the-role-of-trpv-and-cgrp-in-adenosine-preconditioning-and-remote-hind-limb-preconditioning-induced-cardioprotection-in-rats
#14
Amritpal Singh, Puneet Kaur Randhawa, Anjana Bali, Nirmal Singh, Amteshwar Singh Jaggi
The cardioprotective effects of remote hind limb preconditioning (RIPC) are well known, but mechanisms by which protection occurs still remain to be explored. Therefore, the present study was designed to investigate the role of TRPV and CGRP in adenosine and remote preconditioning-induced cardioprotection, using sumatriptan, a CGRP release inhibitor and ruthenium red, a TRPV inhibitor, in rats. For remote preconditioning, a pressure cuff was tied around the hind limb of the rat and was inflated with air up to 150 mmHg to produce ischemia in the hind limb and during reperfusion pressure was released...
February 14, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28187451/gsk1059615-kills-head-and-neck-squamous-cell-carcinoma-cells-possibly-via-activating-mitochondrial-programmed-necrosis-pathway
#15
Jing Xie, Quan Li, Xi Ding, Yunyun Gao
This study tested the anti-head and neck squamous cell carcinoma (HNSCC) cell activity by GSK1059615, a novel PI3K and mTOR dual inhibitor. GSK1059615 inhibited survival and proliferation of established (SCC-9, SQ20B and A253 lines) and primary human HNSCC cells. GSK1059615 blocked PI3K-AKT-mTOR activation in HNSCC cells. Intriguingly, GSK1059615 treatment in HNSCC cells failed to provoke apoptosis, but induced programmed necrosis. The latter was tested by mitochondria depolarization, ANT-1-cyclophilin-D mitochondrial association and lactate dehydrogenase (LDH) release...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28183261/lactate-dehydrogenase-inhibition-biochemical-relevance-and-therapeutical-potential
#16
Giuseppina Laganà, Davide Barreca, Antonella Calderaro, Ersilia Bellocco
Lactate dehydrogenase (LHD) is a key enzyme of anaerobic metabolism in almost all living organisms and it is also a functional checkpoint for glucose restoration during gluconeogenesis and single-stranded DNA metabolism. This enzyme has a well preserved structure during evolution and among the species, with little, but sometimes very useful, changes in the amino acid sequence, which makes it an attractive target for the design and construction of functional molecules able to modulate its catalytic potential and expression...
February 8, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28173817/pigment-epithelium-derived-factor-alleviates-endothelial-injury-by-inhibiting-wnt-%C3%AE-catenin-pathway
#17
Shouyuan Ma, Shutong Yao, Hua Tian, Peng Jiao, Nana Yang, Ping Zhu, Shucun Qin
BACKGROUND: Oxidized low-density lipoprotein (ox-LDL) can induce endothelial injury and plays a vital role in the procession and development of atherosclerosis. Little is known regarding whether Wnt/β-catenin pathway is involved in ox-LDL-induced endothelial injury or whether it further promotes atherosclerosis via increased oxidative stress. This study aimed to investigate the role of Wnt/β-catenin pathway in ox-LDL-induced vascular endothelial injury and determine whether pigment epithelium-derived factor (PEDF) could alleviate ox-LDL-induced endothelial injury by inhibiting Wnt/β-catenin pathway...
February 7, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28144882/efficacy-and-toxicity-of-transarterial-chemoembolization-therapy-using-cisplatin-and-gelatin-sponge-in-patients-with-liver-metastases-from-uveal-melanoma-in-an-asian-population
#18
Yoshitsugu Shibayama, Kenjiro Namikawa, Miyuki Sone, Akira Takahashi, Arata Tsutsumida, Shunsuke Sugawara, Yasuaki Arai, Yukiko Aihara, Shigenobu Suzuki, Juichiro Nakayama, Shinichi Imafuku, Naoya Yamazaki
BACKGROUND: Although both immune-checkpoint inhibitors and targeted therapies such as MEK inhibitors have been evaluated in metastatic uveal melanoma, the efficacy of these therapies is modest to date. The purpose of this study was to evaluate the efficacy and toxicity of transarterial chemoembolization (TACE) therapy for liver metastasis from uveal melanoma in an Asian population. METHODS: We retrospectively assessed the clinical data of patients with liver metastases from uveal melanoma who received TACE therapy using cisplatin (70 mg/m(2)) and gelatin sponge between 1997 and 2008...
January 31, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28142224/effects-of-sulforaphane-on-neural-stem-cell-proliferation-and-differentiation
#19
Zhenxian Han, Qian Xu, Changfu Li, Hong Zhao
Sulforaphane (SFN) is a natural organosulfur compound with anti-oxidant and anti-inflammation properties. The objective of this study is to investigate the effect of SFN on the proliferation and differentiation of neural stem cells (NSC). NSCs were exposed to SFN at the concentrations ranging from 0.25 to 10 µM. Cell viability was evaluated with MTT assay and lactate dehydogenase (LDH) release assay. The proliferation of NSCs was evaluated with neurosphere formation assay and Ki-67 staining. The level of Tuj-1 was evaluated with immunostaining and Western blot to assess NSC neuronal differentiation...
January 31, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/28114833/a-mechanistic-kinetic-description-of-lactate-dehydrogenase-elucidating-cancer-diagnosis-and-inhibitor-evaluation
#20
Peifeng Tang, Jianlin Xu, Christopher L Oliveira, Zheng Jian Li, Shijie Liu
As a key enzyme for glycolysis, lactate dehydrogenase (LDH) remains as a topic of great interest in cancer study. Though a number of kinetic models have been applied to describe the dynamic behavior of LDH, few can reflect its actual mechanism, making it difficult to explain the observed substrate and competitor inhibitions at wide concentration ranges. A novel mechanistic kinetic model is developed based on the enzymatic processes and the interactive properties of LDH. Better kinetic simulation as well as new enzyme interactivity information and kinetic properties extracted from published articles via the novel model was presented...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
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