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https://www.readbyqxmd.com/read/29336315/a-high-neutrophil-to-lymphocyte-ratio-prior-to-braf-inhibitor-treatment-is-a-predictor-of-poor-progression-free-survival-in-patients-with-metastatic-melanoma
#1
Antoine Finon, Julia Zaragoza, Hervé Maillard, Nathalie Beneton, Guido Bens, Mahtab Samimi, Agnès Caille, Laurent Machet
Some studies have shown that a high neutrophil/lymphocyte ratio (NLR) ≥4 before initiating ipilimumab treatment is an independent prognostic indicator of poor survival in patients with metastatic melanoma (MM). To determine whether the NLR before starting BRAF inhibitor (BRAFi) treatment in patients with (MM) is associated with progression-free survival (PFS). This retrospective study included 49 patients consecutively receiving BRAFi for MM between July 2012 and December 2014. Cox proportional hazards regression was used to analyse the relationship between NLR and other factors, such as lactate dehydrogenase (LDH), performance status, BRAFi as first- or second-line therapy, and corticosteroid intake with PFS...
January 16, 2018: European Journal of Dermatology: EJD
https://www.readbyqxmd.com/read/29334172/silica-nanoparticle-induced-cytokine-responses-in-beas-2b-and-hbec3-kt-cells-significance-of-particle-size-and-signalling-pathways-in-different-lung-cell-cultures
#2
Marit Låg, Tonje Skuland, Anna Godymchuk, Thu H T Nguyen, Hang L T Pham, Magne Refsnes
We have previously reported that silica nanoparticles (SiNPs) of nominal size 50 nm (Si50) induce the pro-inflammatory cytokines CXCL8 and IL-6 in BEAS-2B cells, via mechanisms involving MAPK p38, TACE-mediated TGFα release and the NFκB pathway. In the present study, we examined whether these findings are cell-specific or might be extended to another epithelial lung cell model, HBEC3-KT, and also to SiNPs of a smaller size (nominal size of 10 nm; Si10). The TEM average size of Si10 and Si50 was 10.9 nm and 34...
January 15, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29332352/puerarin-leads-to-k562-cell-apoptosis-of-chronic-myelogenous-leukemia-via-induction-of-autophagy
#3
Da Gao, Zhen Xiao, Hui-Ping Li
PURPOSE: To study the effects of puerarin on the viability, apoptosis and autophagy of K562 cells of chronic myelogenous leukemia (CML), and to provide a basis for the study on antitumor mechanism of puerarin. METHODS: K562 cells of human CML were taken as the study material and puerarin was applied in different concentrations. The effect of puerarin on cell viability was detected via cholecystokinin-8 (CCK8) and lactate dehydrogenase (LDH). Flow cytometry and western blot (WB) were used to detect cell apoptosis, while Cyto-ID and WB were used to detect the cell autophagy level...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29330929/adipocytes-affect-castration-resistant-prostate-cancer-cells-to-develop-the-resistance-to-cytotoxic-action-of-nk-cells-with-alterations-of-pd-l1-nkg2d-ligand-levels-in-tumor-cells
#4
Lijun Xu, Mingjing Shen, Xiaodong Chen, Rongying Zhu, Dong-Rong Yang, Ying Tsai, Peter C Keng, Yuhchyau Chen, Soo Ok Lee
BACKGROUND: Obesity affects prostate cancer (PCa) progression, and the periprostatic adipose tissue adjacent to the prostate is considered a driving force of disease progression. Adipocytes are the main cell population in adipose tissues and their paracrine role contributes to PCa progression, however its implication in modulating immune reactions remains largely unknown. We investigated the adipocyte role in controlling the susceptibility of castration-resistant PCa (CRPC) cells to the cytotoxic action of natural killer (NK) cells...
January 12, 2018: Prostate
https://www.readbyqxmd.com/read/29329518/the-use-of-eculizumab-in-gemcitabine-induced-thrombotic-microangiopathy
#5
Vinod Krishnappa, Mohit Gupta, Haikoo Shah, Abhijit Das, Natthavat Tanphaichitr, Robert Novak, Rupesh Raina
BACKGROUND: Thrombotic microangiopathy (TMA) secondary to gemcitabine therapy (GiTMA) is a very rare pathology that carries a poor prognosis, with nearly half of the cases progressing to end stage renal disease. GiTMA is most commonly associated with adenocarcinomas, most notably pancreatic cancers. The mainstay of management is withdrawal of the offending drug and supportive care. Plasmapheresis has a limited role and hemodialysis may help in the management of fluid overload secondary to renal failure...
January 12, 2018: BMC Nephrology
https://www.readbyqxmd.com/read/29327044/association-of-the-lung-immune-prognostic-index-with-immune-checkpoint-inhibitor-outcomes-in-patients-with-advanced-non-small-cell-lung-cancer
#6
Laura Mezquita, Edouard Auclin, Roberto Ferrara, Melinda Charrier, Jordi Remon, David Planchard, Santiago Ponce, Luis Paz Ares, Laura Leroy, Clarisse Audigier-Valette, Enriqueta Felip, Jorge Zerón-Medina, Pilar Garrido, Solenn Brosseau, Gérard Zalcman, Julien Mazieres, Caroline Caramela, Jihene Lahmar, Julien Adam, Nathalie Chaput, Jean Charles Soria, Benjamin Besse
Importance: Derived neutrophils/(leukocytes minus neutrophils) ratio (dNLR) and lactate dehydrogenase (LDH) level have been correlated with immune checkpoint inhibitor (ICI) outcomes in patients with melanoma. Objective: To determine whether pretreatment dNLR and LDH are associated with resistance to ICIs in patients with advanced non-small cell lung cancer (NSCLC). Design, Setting, and Participants: Multicenter retrospective study with a test (n = 161) and a validation set (n = 305) treated with programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors in 8 European centers, and a control cohort (n = 162) treated with chemotherapy only...
January 11, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29320799/new-phenylethanoid-glycosides-from-cistanche-phelypaea-and-their-activity-as-inhibitors-of-monoacylglycerol-lipase-magl
#7
Khadidja Aya Beladjila, Djemaa Berrehal, Nunziatina De Tommasi, Carlotta Granchi, Giulia Bononi, Alessandra Braca, Marinella De Leo
Four new phenylethanoid glycosides (1: -4: ), 1-β-p-hydroxyphenyl-ethyl-2-O-acetyl-3,6-di-α-l-rhamnopyranosyl-β-d-glucopyranoside (1: ), 1-β-p-hydroxyphenyl-ethyl-3,6-O-di-α-l-rhamnopyranosyl-β-d-glucopyranoside (2: ), 1-β-p-hydroxyphenyl-ethyl-2-O-acetyl-3,6-di-α-l-rhamnopyranosyl-4-p-coumaroyl-β-d-glucopyranoside (3: ), and 1-β-p-hydroxyphenyl-ethyl-3,6-di-α-l-rhamnopyranosyl-4-p-coumaroyl-β-d-glucopyranoside (4: ), together with three known compounds, were isolated from the n-butanol extract of Cistanche phelypaea aerial parts...
January 10, 2018: Planta Medica
https://www.readbyqxmd.com/read/29312582/shexiang-tongxin-dropping-pill-protects-against-isoproterenol-induced-myocardial-ischemia-in-vivo-and-in-vitro
#8
Jianyong Qi, Wenjun Pan, Yafang Tan, Jiaru Luo, Dancai Fan, Juan Yu, Jiashin Wu, Minzhou Zhang
Shexiang Tongxin dropping pill (STDP) is a formulae of Chinese Medicine commonly used to treating angina pectoris in China. However, its mechanism of action is still yet unclear. This study investigated the roles of STDP on myocardial ischemia injury. We constructed a rat model of myocardial injury (isoproterenol subcutaneous injection, i.h, 85 mg/kg/day for 2 days), and compared among 4 groups: CON (control), ISO (ischemic injury model), MET (metoprolol), and STDP. Serum contents of Troponin I (cTnI), creatine kinase (CK), CK-MB, lactate dehydrogenase (LDH), alpha-hydroxybutyric dehydrogenase (α-HBD), and Aspartate Aminotransferase were detected and five STDP doses (1, 10, 100, 1000 and 10000 mg/kg/day) were chosen to obtain a dose-response curve...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29304479/microrna-140-5p-aggravates-doxorubicin-induced-cardiotoxicity-by-promoting-myocardial-oxidative-stress-via-targeting-nrf2-and-sirt2
#9
Lisha Zhao, Yan Qi, Lina Xu, Xufeng Tao, Xu Han, Lianhong Yin, Jinyong Peng
Clinical application of doxorubicin (DOX), an anthracycline antibiotic with potent anti- tumor effects, is limited because of its cardiotoxicity. However, its pathogenesis is still not entirely understood. The aim of this paper was to explore the mechanisms and new drug targets to treat DOX-induced cardiotoxicity. The in vitro model on H9C2 cells and the in vivo models on rats and mice were developed. The results showed that DOX markedly decreased H9C2 cell viability, increased the levels of CK, LDH, caused histopathological and ECG changes in rats and mice, and triggered myocardial oxidative damage via adjusting the levels of intracellular ROS, MDA, SOD, GSH and GSH-Px...
December 29, 2017: Redox Biology
https://www.readbyqxmd.com/read/29286061/cardioprotection-by-exenatide-a-novel-mechanism-via-improving-mitochondrial-function-involving-the-glp-1-receptor-camp-pka-pathway
#10
Guanglei Chang, Jian Liu, Shu Qin, Youqin Jiang, Peng Zhang, Hui Yu, Kai Lu, Nan Zhang, Li Cao, Ying Wang, Yong Li, Dongying Zhang
Accumulating evidence suggests that glucagon-like peptide-1 (GLP-1) and its analogues exert cardioprotective effects via modulating cardiomyocyte metabolism. Mitochondria play a pivotal role in the regulation of cell metabolism. It was hypothesized that treatment with exenatide, a GLP-1 analogue, may exert cardioprotective effects by improving mitochondrial function in an in vitro model of hypoxia/reoxygenation (H/R). H9c2 cells were employed to establish an in vitro model of H/R. Exenatide was added to the cells for 30 min prior to exposure to hypoxia...
December 12, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29277824/carcinoembryonic-antigen-as-a-predictive-biomarker-of-response-to-nivolumab-in-non-small-cell-lung-cancer
#11
Yuki Kataoka, Katsuya Hirano, Tomoko Narabayashi, Satoshi Hara, Daichi Fujimoto, Tae Tanaka, Noriyuki Ebi, Keisuke Tomii, Hiroshige Yoshioka
AIM: To find new predictive factors for the efficient use of immune checkpoint inhibitors in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: In this multicenter retrospective cohort study, we evaluated consecutive patients treated with nivolumab between January and October 2016 after second-line systemic chemotherapy. The endpoint was progression-free survival (PFS), as defined by Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: A total of 189 patients were included in the study...
January 2018: Anticancer Research
https://www.readbyqxmd.com/read/29275936/downregulation-of-akt2-attenuates-er-stress-induced-cytotoxicity-through-jnk-wnt-pathway-in-cardiomyocytes
#12
Yan-Xia Gao, Wen-Ting He, Long-Fei Pan, Hui Feng, Jiang-Li Sun, Bin Zhang, Lei Yu, Li-Jun Li
Akt, also known as protein kinase B (PKB), is a serine/threonine kinase that promotes survival and growth in response to extracellular signals. Akt1 has been demonstrated to play vital roles in cardiovascular diseases, but the role of Akt2 in cardiomyocytes is not fully understood. This study investigated the effect of Akt2 knockdown on tunicamycin (TM)-induced cytotoxicity in cardiomyocytes and the underlying mechanisms with a focus on the JNK-Wnt pathway. TM treatment significantly increased the expression of Akt2 at both mRNA and protein levels, which was shown to be mediated by the induction of reactive oxygen species (ROS)...
December 14, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29251317/ethanol-extract-of-patrinia-scabiosaefolia-induces-the-death-of-human-renal-cell-carcinoma-786-o-cells-via-sirt-1-and-mtor-signaling-mediated-metabolic-disruptions
#13
Zeyan Li, Yueqing Tang, Shiqin Zhu, Dawei Li, Xiao Han, Gangli Gu, Naidong Xing, Juchao Ren, Zhaoxin Guo, Wei Jiao, Lei Yan, Zhonghua Xu, Wenhua Zhang
Recently, natural plant extracts have shown tremendous potential as novel antitumor drugs. Patrinia scabiosaefolia, a traditional prescription for inflammatory diseases, has been reported to effectively suppress various types of cancers. However, the mechanisms underlying its antitumor properties remain elusive. In the present study, we investigated the antitumor effects of an ethanol extract of Patrinia scabiosaefolia (EPS) on human renal cell carcinoma 786-O cells. After 24 h of incubation with EPS, the cell viability and colony number of 786-O cells were significantly decreased in a concentration-dependent manner as compared to the control group as determined by MTT and colony formation assays, respectively...
February 2018: Oncology Reports
https://www.readbyqxmd.com/read/29233027/effects-of-phosphodiestrase-type-5-inhibitors-in-epinephrine-induced-arrhythmia-in-rats-involvement-of-lactate-dehydrogenase-and-creatine-kinase-downregulation-and-adiponectin-expression
#14
Aaa Salama, R E Mostafa, E A Omara
Cardiac arrhythmia is a common cause of mortality, and its progression may be due to abnormal sympathetic nerve activity and catecholamine release. Besides, lactate dehydrogenase (LDH) and creatine kinase (CK) downregulation and adiponectin expression play important roles in promoting coronary artery disease. The study aimed to examine the possible cardioprotective effect of members of phosphodiesterase type 5 (PDE-5) inhibitors in epinephrine-induced arrhythmia in rats. Arrhythmia was induced by cumulative boluses of epinephrine (4, 8, 16, 32, 64, and 128 mg/kg) given at 10-min intervals...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29212219/microrna-126a-5p-enhances-myocardial-ischemia-reperfusion-injury-through-suppressing-hspb8-expression
#15
Bimei Jiang, Yanjuan Liu, Pengfei Liang, Yuanbin Li, Zhenguo Liu, Zhongyi Tong, Qinglan Lv, Meidong Liu, Xianzhong Xiao
Previously, we found several genes are involved in myocardial ischemia-reperfusion (M-I/R) injury. In this report, we first developed a mouse model of M-I/R injury and demonstrated microRNA-126a-5p was associated with the M-I/R injury by using high-throughput microRNA expression analysis. We further investigated the expression and function of microRNA-126a-5p during mouse M-I/R injury. We observed high expression of microRNA-126a-5p in the M-I/R mice and increased levels of LDH and CK-MB (damage markers) in the serum...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29203244/microrna-126-alleviates-endothelial-cells-injury-in-atherosclerosis-by-restoring-autophagic-flux-via-inhibiting-of-pi3k-akt-mtor-pathway
#16
Feng Tang, Tian-Lun Yang
MicroRNAs (miRNAs) have emerged as critical modulators of ECs function and play a vital role in the development of cardiovascular disease. Among them, miR-126 is a crucial regulator of atherosclerosis. Endothelial cells (ECs) death and autophagy have been described in cells to cope with the progression of atherosclerosis. Hence, the aim of this study is to investigate the effects of miR-126 on atherosclerosis in oxidized low-density lipoprotein (ox-LDL)-stimulated human umbilical vein endothelial cells (HUVECs) and the potential roles of autophagy flux in these processes...
December 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29199484/symmetric-molecules-with-1-4-triazole-moieties-as-potent-inhibitors-of-tumour-associated-lactate-dehydrogenase-a
#17
Abdul-Malek S Altamimi, Ahmed M Alafeefy, Agnese Balode, Igor Vozny, Aleksandrs Pustenko, Mohey Eldin El Shikh, Fatmah A S Alasmary, Sherif A Abdel-Gawad, Raivis Žalubovskis
A series of symmetric molecules incorporating aryl or pyridyl moieties as central core and 1,4-substituted triazoles as a side bridge was synthesised. The new compounds were investigated as lactate dehydro-genase (LDH, EC 1.1.1.27) inhibitors. The cancer associated LDHA isoform was inhibited with IC50 = 117-174 µM. Seven compounds exhibited better LDHA inhibition (IC50 117-136 µM) compared to known LDH inhibitor - galloflavin (IC50 157 µM).
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/29193406/online-1-h-mrs-measurements-of-time-varying-lactate-production-in-an-animal-model-of-glioma-during-administration-of-an-anti-tumoral-drug
#18
Yannick Crémillieux, Roberto Salvati, Ursule Dumont, Noël Pinaud, Véronique Bouchaud, Stéphane Sanchez, Stefan Glöggler, Alan Wong
The aims of this study were to implement a magnetic resonance spectroscopy (MRS) protocol for the online profiling of subnanomolar quantities of metabolites sampled from the extracellular fluid using implanted microdialysis and to apply this protocol in glioma-bearing rats for the quantification of lactate concentration and the measurement of time-varying lactate concentration during drug administration. MRS acquisitions on the brain microdialysate were performed using a home-built, proton-tuned, microsolenoid with an active volume of 2 μL...
November 29, 2017: NMR in Biomedicine
https://www.readbyqxmd.com/read/29193391/dihydromyricetin-inhibits-nlrp3-inflammasome-dependent-pyroptosis-by-activating-the-nrf2-signaling-pathway-in-vascular-endothelial-cells
#19
Qin Hu, Ting Zhang, Long Yi, Xi Zhou, Mantian Mi
Increasing evidence demonstrates that pyroptosis, pro-inflammatory programmed cell death, is linked to atherosclerosis; however, the underlying mechanisms remain to be elucidated. Dihydromyricetin (DHM), a natural flavonoid, was reported to exert anti-oxidative and anti-inflammatory bioactivities. However, the effect of DHM on atherosclerosis-related pyroptosis has not been studied. In the present study, palmitic acid (PA) treatment led to pyroptosis in human umbilical vein endothelial cells (HUVECs), as evidenced by caspase-1 activation, LDH release, and propidium iodide-positive staining; enhanced the maturation and release of proinflammatory cytokine IL-1β and activation of the NLRP3 inflammasome; and markedly increased intracellular reactive oxygen species (ROS) and mitochondrial ROS (mtROS) levels...
November 29, 2017: BioFactors
https://www.readbyqxmd.com/read/29187017/anti-apoptotic-effect-of-3-aminobenzamide-an-inhibitor-of-poly-adp-ribose-polymerase-against-multiple-organ-damage-induced-by-gamma-irradiation-in-rats
#20
Marwa M El-Sheikh, Rania M El-Hazek, Aiman S El-Khatib, Mona A El-Ghazaly
PURPOSE: This study aimed to investigate the effect of 3-aminobenzamide (3-AB) in doses of 5, 10 and 15 mg/kg on the inhibition of Poly (ADP-ribose) polymerase (PARP) when combined with ionizing radiation (IR). MATERIAL AND METHODS: Rats were treated intraperitonealy, 1 hour prior to irradiation at a dose level of 6 Gray (Gy) and were sacrificed 24 hours after irradiation. Control groups were run concurrently. RESULTS: IR led to an increase of thiobarbituric acid reactive substance (TBARS), nitrite as well as a decrease in total antioxidant capacity associated increase in myeloperoxidase (MPO) with expression of cyclooxygenase-2 (COX-2)...
November 30, 2017: International Journal of Radiation Biology
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