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https://www.readbyqxmd.com/read/28107190/radiosynthesis-and-validation-of-%C3%A2-18f-3-fluoro-2-hydroxypropionate-18f-flac-as-a-pet-tracer-of-lactate-to-monitor-mct1-dependent-lactate-uptake-in-tumors
#1
Vincent F Van Hée, Daniel Labar, Gwenaël Dehon, Debora Grasso, Vincent Grégoire, Giulio G Muccioli, Raphaël Frédérick, Pierre Sonveaux
Cancers develop metabolic strategies to cope with their microenvironment often characterized by hypoxia, limited nutrient bioavailability and exposure to anticancer treatments. Among these strategies, the metabolic symbiosis based on the exchange of lactate between hypoxic/glycolytic cancer cells that convert glucose to lactate and oxidative cancer cells that preferentially use lactate as an oxidative fuel optimizes the bioavailability of glucose to hypoxic cancer cells. This metabolic cooperation has been described in various human cancers and can provide resistance to anti-angiogenic therapies...
January 17, 2017: Oncotarget
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/28103993/-effects-of-hypertonic-sodium-saline-resuscitation-on-the-liver-damage-of-rats-at-early-stage-of-severe-scald
#3
J P Zhou, Z Gao, Y X Sun, X L Chen, X S Wu, F Wang
Objective: To explore the effects of hypertonic sodium saline (HSS) resuscitation on the liver damage of rats at early stage of severe scald. Methods: Fifty-six SD rats were divided into sham injury group (SI, n=8), lactated Ringer's solution group (LRS, n=24), and group HSS (n=24) according to the random number table. Rats in group SI were sham injured without resuscitation, while rats in the other two groups were reproduced deep partial-thickness to full-thickness scald model with 30% total body surface area on the back...
January 20, 2017: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
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/28101940/chronic-nasal-exposure-to-nanoparticulate-tio2-causes-pulmonary-tumorigenesis-in-male-mice
#5
Fashui Hong, Li Ji, Yingjun Zhou, Ling Wang
Chronic inhalation bioassays in rodents are used to assess pulmonary carcinogenicity for purposes of hazard identification and potentially for risk characterization. Numerous studies have been confirmed that exposure to titanium dioxide nanoparticles (TiO2 NPs) may result in chronic pulmonary inflammation in both mice and rats. However, very few studies have focused on the pulmonary tumorigenesis. In this study, to examine whether chronic TiO2 NP exposure induce tumorigenesis in the lung, forty mice (each group) were nasally exposed to 1...
January 19, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28099149/clinically-relevant-hif-1%C3%AE-dependent-metabolic-reprogramming-in-oropharyngeal-squamous-cell-carcinomas-includes-coordinated-activation-of-caix-and-the-mir-210-iscu-signaling-axis-but-not-mct1-and-mct4-upregulation
#6
Inés Sáenz-de-Santa-María, Cristóbal Bernardo-Castiñeira, Pablo Secades, Sandra Bernaldo-de-Quirós, Juan Pablo Rodrigo, Aurora Astudillo, María-Dolores Chiara
Metabolic reprogramming is a very heterogeneous phenomenon in cancer. It mostly consists on increased glycolysis, lactic acid formation and extracellular acidification. These events have been associated to increased activity of the hypoxia inducible factor, HIF-1α. This study aimed at defining the metabolic program activated by HIF-1α in oropharyngeal squamous cell carcinomas (SCC) and assessing its clinical impact. Global gene/miRNA expression was analyzed in SCC-derived cells exposed to hypoxia. Expression of HIF-1α, the carbonic anhydrase CAIX, and the lactate/H+ transporters MCT1 and MCT4 were analyzed by immunohistochemistry in 246 SCCs...
January 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28098871/lectin-pcl-inhibits-the-warburg-effect-of-pc3-cells-by-combining-with-egfr-and-inhibiting-hk2
#7
Hong Zhang, Xia Du, Ting-Ting Sun, Chun-Liu Wang, Ye Li, Shou-Zhen Wu
Prostatic carcinoma is the most aggressive tumor in adult men. Warburg effect is an important characteristic of tumor cell metabolism including prostate cancer cells, in which hexokinase 2 (HK2), a major rate-limiting enzyme involved in Warburg effect, is selectively upregulated. The lectin PCL is a mannose binding lectin which induces tumor cell apoptosis and autophagy. In the present study, we report that PCL could lower glucose consumption and lactate production, shift the Warburg effect by inhibiting the expression of HK2 in PC3 cells and the suppression of HK2 by siRNA reversed the effect of PCL on glucose consumption and lactate production...
January 16, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28093985/ketogenic-diet-and-other-dietary-intervention-strategies-in-the-treatment-of-cancer
#8
Matteo Vergati, Eriseld Krasniqi, Girolamo Del Monte, Silvia Riondino, Doriana Vallone, Fiorella Guadagni, Patrizia Ferroni, Mario Roselli
Pre-clinical and clinical studies have investigated the role of a dysregulated metabolism in the sustainability of tumor initiation and progression. One of the most familiar metabolic alterations encountered in several types of cancers is the upregulation of glycolysis, which is also maintained in conditions of normal oxygen tension (aerobic glycolysis, Warburg effect) while oxidative phosphorylation is apparently reduced. As a result, cancer cells convert most incoming glucose to lactate. Although more rapid, adenosine triphosphate (ATP) production by glycolysis is less efficient in terms of ATP generated per unit of glucose consumed than oxidative phosphorylation...
January 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28093122/sequential-enzymatic-derivatization-coupled-with-online-microdialysis-sampling-for-simultaneous-profiling-of-mouse-tumor-extracellular-hydrogen-peroxide-lactate-and-glucose
#9
Cheng-Kuan Su, Po-Jen Tseng, Hsien-Ting Chiu, Andrea Del Vall, Yu-Fen Huang, Yuh-Chang Sun
Probing tumor extracellular metabolites is a vitally important issue in current cancer biology. In this study an analytical system was constructed for the in vivo monitoring of mouse tumor extracellular hydrogen peroxide (H2O2), lactate, and glucose by means of microdialysis (MD) sampling and fluorescence determination in conjunction with a smart sequential enzymatic derivatization scheme-involving a loading sequence of fluorogenic reagent/horseradish peroxidase, microdialysate, lactate oxidase, pyruvate, and glucose oxidase-for step-by-step determination of sampled H2O2, lactate, and glucose in mouse tumor microdialysate...
March 1, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28092823/ph-lactate-and-hypoxia-reciprocity-in-regulating-high-affinity-monocarboxylate-transporter-expression-in-glioblastoma
#10
James P Caruso, Brandon J Koch, Philip D Benson, Elsa Varughese, Michael D Monterey, Amy E Lee, Ajal M Dave, Sam Kiousis, Andrew E Sloan, Saroj P Mathupala
Highly malignant brain tumors harbor the aberrant propensity for aerobic glycolysis, the excessive conversion of glucose to lactic acid even in the presence of ample tissue oxygen. Lactic acid is rapidly effluxed to the tumor microenvironment via a group of plasma-membrane transporters denoted monocarboxylate transporters (MCTs) to prevent "self-poisoning." One isoform, MCT2, has the highest affinity for lactate and thus should have the ability to respond to microenvironment conditions such as hypoxia, lactate, and pH to help maintain high glycolytic flux in the tumor...
January 13, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28087332/exo-mfa-a-13c-metabolic-flux-analysis-to-dissect-tumor-microenvironment-secreted-exosome-contributions-towards-cancer-cell-metabolism
#11
Abhinav Achreja, Hongyun Zhao, Lifeng Yang, Tae Hyun Yun, Juan Marini, Deepak Nagrath
Dissecting the pleiotropic roles of tumor micro-environment (TME) on cancer progression has been brought to the foreground of research on cancer pathology. Extracellular vesicles such as exosomes, transport proteins, lipids, and nucleic acids, to mediate intercellular communication between TME components and have emerged as candidates for anti-cancer therapy. We previously reported that cancer-associated fibroblast (CAF) derived exosomes (CDEs) contain metabolites in their cargo that are utilized by cancer cells for central carbon metabolism and promote cancer growth...
January 10, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28087305/circulating-interleukin-18-il-18-is-a-predictor-of-response-to-gemcitabine-based-chemotherapy-in-patients-with-pancreatic-adenocarcinoma
#12
Çiğdem Usul Afsar, Mehmet Karabulut, Senem Karabulut, Halil Alis, Murat Gonenc, Nergiz Dagoglu, Murat Serilmez, Faruk Tas
BACKGROUND: This study was conducted to investigate the serum levels of interleukin-18 (IL-18) in patients with pancreatic adenocarcinoma (PA) and the relationship with tumor progression and known prognostic parameters. METHODS: Thirty-three patients with PA were studied. Serum samples were obtained on first admission before any treatment. Serum IL-18 levels were analyzed using enzyme-linked immunosorbent assay (ELISA). Age- and sex-matched 30 healthy controls were included in the analysis...
January 10, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/28086949/nek2-promotes-aerobic-glycolysis-in-multiple-myeloma-through-regulating-splicing-of-pyruvate-kinase
#13
Zhimin Gu, Jiliang Xia, Hongwei Xu, Ivana Frech, Guido Tricot, Fenghuang Zhan
BACKGROUND: Aerobic glycolysis, a hallmark of cancer, is characterized by increased metabolism of glucose and production of lactate in normaxia. Recently, pyruvate kinase M2 (PKM2) has been identified as a key player for regulating aerobic glycolysis and promoting tumor cell proliferation and survival. METHODS: Tandem affinity purification followed up by mass spectrometry (TAP-MS) and co-immunoprecipitation (Co-IP) were used to study the interaction between NIMA (never in mitosis gene A)-related kinase 2 (NEK2) and heterogeneous nuclear ribonucleoproteins (hnRNP) A1/2...
January 13, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28079606/relationship-between-alternative-resuscitation-strategies-host-response-and-injury-biomarkers-and-outcome-in-septic-shock-analysis-of-the-protocol-based-care-for-early-septic-shock-study
#14
John A Kellum, Francis Pike, Donald M Yealy, David T Huang, Nathan I Shapiro, Derek C Angus
OBJECTIVES: The Protocol-based Care for Early Septic Shock trial found no differences across alternative resuscitation strategies in all-cause mortality. A separate aim was to determine whether differences in resuscitation strategies affected trajectories of biomarkers of key pathways associated with downstream clinical outcomes of sepsis and whether there were differences in survival across treatment arms for patients with different baseline biomarker profiles. DESIGN: Secondary analysis of a large randomized clinical trial...
January 10, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28077268/development-of-high-resolution-3d-hyperpolarized-carbon-13-mr-molecular-imaging-techniques
#15
Eugene Milshteyn, Cornelius von Morze, Galen D Reed, Hong Shang, Peter J Shin, Zihan Zhu, Hsin-Yu Chen, Robert Bok, Andrei Goga, John Kurhanewicz, Peder E Z Larson, Daniel B Vigneron
The goal of this project was to develop and apply techniques for T2 mapping and 3D high resolution (1.5mm isotropic; 0.003cm(3)) (13)C imaging of hyperpolarized (HP) probes [1-(13)C]lactate, [1-(13)C]pyruvate, [2-(13)C]pyruvate, and [(13)C,(15)N2]urea in vivo. A specialized 2D bSSFP sequence was implemented on a clinical 3T scanner and used to obtain the first high resolution T2 maps of these different hyperpolarized compounds in both rats and tumor-bearing mice. These maps were first used to optimize timings for highest SNR for single time-point 3D bSSFP acquisitions with a 1...
January 7, 2017: Magnetic Resonance Imaging
https://www.readbyqxmd.com/read/28076790/the-anti-warburg-effect-elicited-by-the-camp-pgc1%C3%AE-pathway-drives-differentiation-of-glioblastoma-cells-into-astrocytes
#16
Fan Xing, Yizhao Luan, Jing Cai, Sihan Wu, Jialuo Mai, Jiayu Gu, Haipeng Zhang, Kai Li, Yuan Lin, Xiao Xiao, Jiankai Liang, Yuan Li, Wenli Chen, Yaqian Tan, Longxiang Sheng, Bingzheng Lu, Wanjun Lu, Mingshi Gao, Pengxin Qiu, Xingwen Su, Wei Yin, Jun Hu, Zhongping Chen, Ke Sai, Jing Wang, Furong Chen, Yinsheng Chen, Shida Zhu, Dongbing Liu, Shiyuan Cheng, Zhi Xie, Wenbo Zhu, Guangmei Yan
Glioblastoma multiforme (GBM) is among the most aggressive of human cancers. Although differentiation therapy has been proposed as a potential approach to treat GBM, the mechanisms of induced differentiation remain poorly defined. Here, we established an induced differentiation model of GBM using cAMP activators that specifically directed GBM differentiation into astroglia. Transcriptomic and proteomic analyses revealed that oxidative phosphorylation and mitochondrial biogenesis are involved in induced differentiation of GBM...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28072864/1h-nmr-metabolomics-reveals-association-of-high-expression-of-inositol-1-4-5-trisphosphate-receptor-and-metabolites-in-breast-cancer-patients
#17
Aru Singh, Raj Kumar Sharma, Megha Chagtoo, Gaurav Agarwal, Nelson George, Neeraj Sinha, Madan M Godbole
1H NMR is used to detect alterations in metabolites and their linkage to metabolic processes in a number of pathological conditions including breast cancer. Inositol 1, 4, 5 trisphosphate (IP3R) receptor is an intracellular calcium channel known to regulate metabolism and cellular bioenergetics. Its expression is up regulated in a number of cancers. However, its linkage to metabolism in disease conditions has not been evaluated. This study was designed to determine the association if any, of these metabolites with altered expression of IP3R in breast cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28072830/protective-effects-of-dexrazoxane-against-doxorubicin-induced-cardiotoxicity-a-metabolomic-study
#18
Yang QuanJun, Yang GenJin, Wan LiLi, Han YongLong, Huo Yan, Li Jie, Huang JinLu, Lu Jin, Gan Run, Guo Cheng
Cardioprotection of dexrazoxane (DZR) against doxorubicin (DOX)-induced cardiotoxicity is contentious and the indicator is controversial. A pairwise comparative metabolomics approach was used to delineate the potential metabolic processes in the present study. Ninety-six BALB/c mice were randomly divided into two supergroups: tumor and control groups. Each supergroup was divided into control, DOX, DZR, and DOX plus DZR treatment groups. DOX treatment resulted in a steady increase in 5-hydroxylysine, 2-hydroxybutyrate, 2-oxoglutarate, 3-hydroxybutyrate, and decrease in glucose, glutamate, cysteine, acetone, methionine, asparate, isoleucine, and glycylproline...
2017: PloS One
https://www.readbyqxmd.com/read/28070044/-expression-of-lactate-dehydrogenase-5-in-non-hodgkin-lymphoma-and-its-clinical-significance
#19
Fei Dong, Aixia Sui, Hongmei Jing
To determine expression of lactate dehydrogenase (LDH)-5 in non-Hodgkin lymphoma and its clinical significance.
 Methods: LDH-5 levels and LDH levels in NHL patients were examined by agarose gel electrophoresis and enzymatic method (n=63), respectively. Positive rates of LDH-5 and LDH were statistically analyzed.
 Results: The median age of NHL patients was 56(19-84) years old, including 36 males and 27 females. The positive numbers for LDH-5 and LDH in the initial treatment group (n=43) were significantly different (P<0...
December 28, 2016: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/28068151/prognostic-impact-of-pretreatment-neutrophil-to-lymphocyte-ratio-in-castration-resistant-prostate-cancer-patients-treated-with-first-line-docetaxel
#20
Consuelo Buttigliero, Chiara Pisano, Marcello Tucci, Francesca Vignani, Valentina Bertaglia, Davide Iaconis, Pamela Guglielmini, Gianmauro Numico, Giorgio V Scagliotti, Massimo Di Maio
BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), a measure of systemic inflammatory response, has been associated with poor outcome in several solid tumors, including prostate cancer. We retrospectively investigated the prognostic role of pretreatment NLR in metastatic castration-resistant prostate cancer (mCRPC) patients treated with first-line docetaxel. METHODS: All CRPC patients treated with first-line docetaxel at two Italian institutions, with available data about baseline neutrophil and lymphocyte values, were included in this retrospective analysis...
January 9, 2017: Acta Oncologica
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