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Lactate AND Tumor

Soojung Lee, Trine V Axelsen, Nicolai Jessen, Stine F Pedersen, Pernille Vahl, Ebbe Boedtkjer
Metabolic acid production challenges cellular pH homeostasis in solid cancer tissue, and mechanisms of net acid extrusion represent promising new targets for breast cancer therapy. Here, we used genetically engineered mice to investigate the contribution of the Na+ ,HCO3 - -cotransporter NBCn1 (Slc4a7) to intracellular acid-base regulation in ErbB2-induced breast cancer tissue and the consequences of NBCn1 knockout for breast tumor development and growth. We demonstrate an approximately 2-fold increase of NBCn1 protein abundance in ErbB2-induced breast cancer tissue compared to normal breast tissue despite a 4-fold decrease in the NBCn1 mRNA level...
June 15, 2018: Oncogene
Xisi Wang, Lijun Wang, Yan Su, Zhixia Yue, Tianyu Xing, Wen Zhao, Qian Zhao, Chao Duan, Cheng Huang, Dawei Zhang, Mei Jin, Xianfeng Cheng, Shenglan Chen, Yi Liu, Xiaoli Ma
To evaluate plasma cell-free DNA (cfDNA) as a promising biomarker for neuroblastoma (NB) tumor burden. Seventy-nine eligible patients with newly diagnosed NB were recruited from Beijing Children's Hospital between April 2016 and April 2017. Additionally, from September 2011 to June 2017, 79 patients with stable NB were evaluated with a median follow-up time of 21 months. Approximately 2 mL of peripheral blood was drawn upon enrollment, and plasma cfDNA levels were measured via quantitative polymerase chain reaction (qPCR)...
June 14, 2018: Cancer Medicine
Rahul Bhattacharya, Susri Ray Chaudhuri, Sib S Roy
Ovarian cancer (OC) renders its lethality to enhanced metastasis and late detection. A plethora of growth factors including Vascular Endothelial Growth Factor (VEGF) and Fibroblast Growth Factor (FGF) stimulated signaling pathways regulate the invasive/metastatic behavior of ovarian tumors contributing to its aggressiveness. Autocrine VEGF-functioning by virtue of upregulated VEGFR2 contributes to the invasiveness of OC cells by modulating the MMPs. Studies have highlighted the interaction between FGF and VEGF signaling pathways during angiogenesis...
June 15, 2018: Journal of Cellular Biochemistry
Eva-Maria Ratai, Zheng Zhang, James Fink, Mark Muzi, Lucy Hanna, Erin Greco, Todd Richards, Daniel Kim, Ovidiu C Andronesi, Akiva Mintz, Lale Kostakoglu, Melissa Prah, Benjamin Ellingson, Kathleen Schmainda, Gregory Sorensen, Daniel Barboriak, David Mankoff, Elizabeth R Gerstner
A multi-center imaging trial by the American College of Radiology Imaging Network (ACRIN) "A Multicenter, phase II assessment of tumor hypoxia in glioblastoma using 18F Fluoromisonidazole (FMISO) with PET and MRI (ACRIN 6684)", was conducted to assess hypoxia in patients with glioblastoma (GBM). The aims of this study were to support the role of proton magnetic resonance spectroscopic imaging (1H MRSI) as a prognostic marker for brain tumor patients in multi-center clinical trials. Seventeen participants from four sites had analyzable 3D MRSI datasets acquired on Philips, GE or Siemens scanners at either 1...
2018: PloS One
Jiao Chen, Bomiao Cui, Yaping Fan, Xiaoying Li, Qian Li, Yue Du, Yun Feng, Ping Zhang
Protein kinase D1 (PKD1), one of the protein kinase D (PKD) family members, plays a prominent role in multiple bio-behaviors of cancer cells. Low pH and hypoxia are unique characteristics of the tumor microenvironment. The aim of this study was to investigate the role and mechanism of PKD1 in regulating metabolism in the human tongue squamous cell carcinoma (TSCC) cell line SCC25 under a hypoxic condition, as well as growth and apoptosis. Here, we found that hypoxia not only induced the expression of HIF-1α, but also induced the expression and activation of PKD1...
June 7, 2018: Oncology Reports
Satoshi Sugita, Hideki Enokida, Hirofumi Yoshino, Kazutaka Miyamoto, Masaya Yonemori, Takashi Sakaguchi, Yoichi Osako, Masayuki Nakagawa
The active form of the small GTPase RAS binds to downstream effectors to promote cell growth and proliferation. RAS signal enhancement contributes to tumorigenesis, invasion, and metastasis in various different cancers. HRAS proto-oncogene GTPase (HRAS), one of the RAS isoforms, was the first human oncogene for which mutations were reported in T24 bladder cancer (BC) cells in 1982, and HRAS mutation or upregulation has been reported in several cancers. According to data from The Cancer Genome Atlas, HRAS expression was significantly upregulated in clinical BC samples compared to healthy samples (P=0...
June 11, 2018: International Journal of Oncology
Amanda C Warken, Leandro S Lopes, Nathieli B Bottari, Patrícia Glombowsky, Gabriela M Galli, Vera M Morsch, Maria Rosa C Schetinger, Aleksandro S DA Silva
The aim of this study was to evaluate whether the use of subcutaneous mineral supplementation would affect metabolic parameters, immunological response, milk quality and composition of dairy cows in the postpartum period. Twelve pregnant primiparous Holstein cows, were divided into two groups: six animals supplemented with the mineral complex (magnesium, phosphorus, potassium, selenium and copper), and six animals used as controls. Milk samples were collected every two other weeks postpartum up to sixty days of lactation to analyze composition and quality...
April 2018: Anais da Academia Brasileira de Ciências
Ran Tao, Min Gao, Fang Liu, Xuliang Guo, Aiping Fan, Dan Ding, Deling Kong, Zheng Wang, Yanjun Zhao
Nanocarriers have been extensively utilized to enhance the anti-tumor performance of chemotherapy, but it is very challenging to eliminate the associated hepatotoxicity. This was due to the significant liver accumulation of cytotoxic drug-loaded nanocarriers as a consequence of systemic biodistribution. To address this, we report a novel type of nanocarrier that was made of hepatoprotective compound (oleanolic acid/OA) with a model drug (methotrexate/MTX) being physically encapsulated. OA was covalently connected with methoxy poly(ethylene glycol) (mPEG) via a hydrazone linker, generating amphiphilic mPEG-OA prodrug conjugate that could self-assemble into pH-responsive micelles (ca...
June 13, 2018: ACS Applied Materials & Interfaces
Jun-Qiang Yin, Yi-Wei Fu, Xian-Biao Xie, Xiao-Yu Cheng, Xiao-Yu Yang, Wei-Hai Liu, Jian Tu, Zhen-Hua Gao, Jing-Nan Shen
Background and purpose: Telangiectatic osteosarcoma (TOS), a rare variant of osteosarcoma, may be easily misdiagnosed as aneurysmal bone cyst (ABC). The aims of this study were to investigate the diagnostic and prognostic factors of TOS by reviewing our experience with TOS and to develop a diagnostic model that may distinguish TOS from ABC. Materials and methods: We identified 51 cases of TOS treated at the First Affiliated Hospital of Sun Yat-Sen University from March 2001 to January 2016 and reviewed their records, imaging information and pathological studies...
June 2018: Journal of Bone Oncology
Biao Xu, Zhimei Yu, Sichuan Xiang, Yunshan Li, Shao-Lin Zhang, Yun He
Herein, triphenylphosphonium cation moieties were incorporated into a dichloroacetophenone derivative, leading to the discovery of novel mitochondria-targeted and tumor-specific pyruvate dehydrogenase kinase 1 (PDK1) inhibitors. Biological studies suggested that all these synthesized compounds had significant in vitro activities, in particular compound 1f, which inhibited PDK1 with an EC50 value of 0.12 μM, and reduced the proliferation of NCI-H1650 cell with an IC50 value of 0.21 μM, but showed marginal effect against non-cancerous BEAS-2B cell (IC50  = 3...
June 5, 2018: European Journal of Medicinal Chemistry
Wenbo Chen, Shiyu Luo, Peng Xie, Tingting Hou, Tian Yu, Xiaoyun Fu
Background: Mitochondrial flashes (mitoflashes) are transient signals from transient bursts of reactive oxygen species (ROS) and changes in pH that occur in certain physiological or pathological conditions. Mitoflashes are closely related to metabolism, cell differentiation, stress response, diseases, and aging. Sepsis can trigger mitochondrial dysfunction in myocardial cells, which leads to ROS overproduction, while uncoupling protein 2 (UCP2) can reduce ROS production. This study aims to observe whether UCP2 overexpression can regulate the frequency of mitoflashes in cardiomyocytes during sepsis and thereby play a protective role...
2018: American Journal of Translational Research
Jenne De Koster, Clarissa Strieder-Barboza, Jonas de Souza, Adam L Lock, G Andres Contreras
Intense lipolysis triggers an inflammatory response within adipose tissue characterized by adipose tissue macrophage (ATM) infiltration; however, the mechanisms triggering this process are poorly characterized in transition dairy cows. The aim of this study was to determine the association between ATM infiltration and body fat mobilization in the transition period, markers of excessive lipolysis, and adipose tissue expression of genes related to chemotactic and inflammatory responses. Subcutaneous adipose tissue samples were taken from the tailhead of 9 multiparous Holstein cows, 27 ± 2...
June 6, 2018: Journal of Dairy Science
Georg Gdynia, Tadeusz Robak, Jürgen Kopitz, Anette Heller, Svetlana Grekova, Katarina Duglova, Gloria Laukemper, Monika Heinzel-Gutenbrunner, Cornelius Gutenbrunner, Wilfried Roth, Anthony D Ho, Peter Schirmacher, Michael Schmitt, Peter Dreger, Leopold Sellner
A higher capacity to grow under hypoxic conditions can lead to a more aggressive behavior of tumor cells. Determining tumor activity under hypoxia may identify chronic lymphocytic leukemia (CLL) with aggressive clinical course and predict response to chemo-immunotherapy (CIT). A metabolic score was generated by determining pyruvate kinase and lactate dehydrogenase, key enzymes of glycolysis, ex vivo in primary CLL samples under normoxic and hypoxic conditions. This score was further correlated with clinical endpoints and response to CIT in 96 CLL patients...
June 5, 2018: EBioMedicine
Yong Yang, Ke Yu, Yan-Min Zhang
The 4-ACGC isolated from BP was prepared to investigate the cardioprotective effects on attenuating chronic heart failure in-vivo and in-vitro . A chronic heart failure (CHF) rat model was established to investigate the cardioprotective effects of 4-ACGC. From this, several cardiac function indexes were recorded. The inflammatory markers including tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), and Interleukin-1β (IL-1β) were evaluated by enzyme-linked immunosorbent assay (ELISA). Subsequently, serum levels of myocardial enzymes lactate dehydrogenase (LDH) and creatine kinase (CK) were also assessed by ELISA kits...
2018: Iranian Journal of Pharmaceutical Research: IJPR
Shili Xu, Arthur Catapang, Hanna M Doh, Nicholas A Bayley, Jason T Lee, Daniel Braas, Thomas G Graeber, Harvey R Herschman
Although absent in most adult tissues, hexokinase 2 (HK2) is expressed in a majority of tumors and contributes to increased glucose consumption and to in vivo tumor 18 F-FDG PET signaling. Methods: Both HK2 knockdown and knockout approaches were used to investigate the role of HK2 in cancer cell proliferation, in vivo xenograft tumor progression and 18 F-FDG tumor accumulation. BioProfiler analysis monitored cell culture glucose consumption and lactate production; 18 F-FDG PET/CT monitored in vivo tumor glucose accumulation...
June 7, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
David Carr, Rosanna Lau, Alexandra D Hnatykiw, Gwendoline C D Ward, Manijeh Daneshmand, Miguel A Cabrita, M A Christine Pratt
Cellular inhibitor of apoptosis proteins-1 and -2 (cIAP1/2) are integral to regulation of apoptosis and signaling by the tumor necrosis factor (TNF) and related family of receptors. The expression of cIAP2 in tissues is typically low and considered functionally redundant with cIAP1, however cIAP2 can be activated by a variety of cellular stresses. Members of the TNFR family and their ligands have essential roles in mammary gland biology. We have found that cIAP2-/- virgin mammary glands have reduced ductal branching and delayed lobuloalveogenesis in early pregnancy...
June 6, 2018: Journal of Mammary Gland Biology and Neoplasia
Baoyu Chen, Man Luo, Jianming Liang, Chun Zhang, Caifang Gao, Jue Wang, Jianxin Wang, Yongji Li, Desheng Xu, Lina Liu, Ning Zhang, Huijun Chen, Jing Qin
Exploiting cells as vehicles combined with nanoparticles combined with therapy has attracted increasing attention in the world recently. Red blood cells, leukocytes and stem cells have been used for tumor immunotherapy, tissue regeneration and inflammatory disorders, and it is known that neutrophils can accumulate in brain lesions in many brain diseases including depression. N -Acetyl Pro-Gly-Pro (PGP) peptide shows high specific binding affinity to neutrophils through the CXCR2 receptor. In this study, PGP was used to modify baicalein-loaded solid lipid nanoparticles (PGP-SLNs) to facilitate binding to neutrophils in vivo ...
January 2018: Acta Pharmaceutica Sinica. B
Di Chen, Hui Wang, Jie Chen, Zhe Li, Shengli Li, Zhixiang Hu, Shenglin Huang, Yingjun Zhao, Xianghuo He
Tumor cells increase their glucose consumption through aerobic glycolysis to manufacture the necessary biomass required for proliferation, commonly known as the Warburg effect. Accumulating evidences suggest that microRNAs (miRNAs) interact with their target genes and contribute to metabolic reprogramming in cancer cells. By integrating high-throughput screening data and the existing miRNA expression datasets, we explored the roles of candidate glycometabolism-regulating miRNAs in gastric cancer (GC). Subsequent investigation of the characterized miRNAs indicated that miR-129-5p inhibits glucose metabolism in GC cells...
2018: Frontiers in Pharmacology
Lian Hui, Jingru Zhang, Xing Guo
Laryngeal squamous cell carcinoma (LSCC) is the most common form of laryngeal carcinoma with poor prognosis. Exploring novel factors involved in the progression of LSCC is quite necessary for understanding the mechanisms and designing therapeutic strategies for LSCC. In this study, we showed that miR-125b-5p was significantly down-regulated in LSCC tissues and cell lines. The decreased expression of miR-125b-5p was associated with the tumor differentiation, metastasis and high clinical stage of the LSCC patients...
July 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Zhan-Jun Ma, Hu Yan, Ya-Jiao Wang, Yang Yang, Xiao-Bin Li, An-Cheng Shi, Xu Jing-Wen, Lu Yu-Bao, Lu Li, Xue-Xi Wang
Rosmarinic acid (RA), isolated from herbal balm mint plants, has demonstrated potent anti-tumor properties against liver cancer. However, the precise underlying mechanisms remain unclear. This study aimed to investigate the molecular mechanisms of RA in HepG2 cells. RA anti-tumor activity was assessed using 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, and Hoechst 33258 staining. Apoptosis and the cell cycle distribution were evaluated by flow cytometry...
June 1, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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