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tumor metabolism

Toru Komatsu, Masahiro Shimoda, Yukiko Kawamura, Yasuteru Urano, Tetsuo Nagano
Diced electrophoresis gel (DEG) assay is a methodology to identify enzymes with a specified activity in complex cell or tissue lysates by means of two-dimensional separation using isoelectric focusing and native PAGE, followed by dicing of the gel into small pieces that are assayed separately, and digestion and peptide fingerprinting to identify the protein(s) of interest in positive wells. The existing hand-made system has some disadvantages, and here we describe the development and validation of an improved cutter-plate system that enables simple, reliable and reproducible DEG assay in a 384-well plate-based format with signal readout using fluorometric or LC-MS-based reaction monitoring...
June 18, 2018: Biochimica et Biophysica Acta
Ke Duan, Zhong-Jian Liu, Su-Qiong Hu, Hong-Yu Huo, Zhi-Ru Xu, Jian-Fei Ruan, Yang Sun, Li-Ping Dai, Chang-Bao Yan, Wei Xiong, Qing-Hua Cui, Hai-Jing Yu, Min Yu, Yang Qin
The Warburg effect is a dominant phenotype of most tumor cells. Recent reports have shown that the Warburg effect can be reprogrammed by the tumor microenvironment. Lactic acidosis and glucose deprivation are the common adverse microenvironments in solid tumor. The metabolic reprogramming induced by lactic acid and glucose deprivation remains to be elucidated in glioblastoma. Here, we show that, under glucose deprivation, lactic acid can preserve high ATP levels and resist cell death in U251 cells. At the same time, we find that MCT1 and MCT4 are significantly highly expressed...
June 18, 2018: Biochemical and Biophysical Research Communications
Shamir Cassim, Valérie-Ann Raymond, Benoit Lacoste, Pascal Lapierre, Marc Bilodeau
HCC (Hepatocellular carcinoma) cells exhibit greater metabolic plasticity than normal hepatocytes since they must survive in a dynamic microenvironment where nutrients and oxygen are often scarce. Using a metabolomic approach combined with functional in vitro and in vivo assays, we aimed to identify an HCC metabolic signature associated with increased tumorigenicity and patient mortality. Metabolite profiling of HCC Dt81Hepa1-6 cells revealed that their increased tumorigenicity was associated with elevated levels of glycolytic metabolites...
June 1, 2018: Oncotarget
Jian Yu, Yu Zhang, Dongxun Zhou, Jun Wu, Rong Luo
A-kinase anchoring protein 1 (AKAP1) plays important regulatory roles in the regulation of mitochondrial function, oxidative metabolism, and cell survival. However, the expression pattern and prognostic value of AKAP1 in hepatocellular carcinoma (HCC) remains unclear. AKAP1 expression levels in tumor and matched non-tumor tissues were evaluated using reverse transcription-quantitative polymerase chain reaction and immunohistochemical staining. Kaplan-Meier and Cox regression analyses were used to analyze the survival rates...
July 2018: Oncology Letters
Makoto Osanai, Akira Takasawa, Kumi Takasawa, Masaki Murata, Norimasa Sawada
Elevated expression of the retinoic acid-metabolizing enzyme cytochrome P450 26A1 (CYP26A1) has been demonstrated to have an oncogenic function in carcinogenesis. In order to address the oncogenic capacity of CYP26A1 in vivo , transgenic mice that ubiquitously overexpressed CYP26A1 driven by the cytomegalovirus promoter were generated in the present study. Since the growth of these animals was normal for ≤15 months and they presented no evident abnormalities, a two-stage skin carcinogenesis analysis was performed...
June 2018: Oncology Letters
Qingchun Cai, Qipeng Fan, Aaron Buechlein, David Miller, Kenneth P Nephew, Sheng Liu, Jun Wan, Yan Xu
The cure rate for late stage epithelial ovarian cancer (EOC) has not significantly improved over several decades. New and more effective targets and treatment modalities are urgently needed. RNA-seq analyses of a syngeneic EOC cell pair, representing more and less aggressive tumor cells in vivo were conducted. Bioinformatics analyses of the RNA-seq data and biological signaling and function studies have identified new targets, such as ZIP4 in EOC. Many up-regulated tumor promoting signaling pathways have been identified which are mainly grouped into three cellular activities: 1) cell proliferation and apoptosis resistance; 2) cell skeleton and adhesion changes; and 3) carbohydrate metabolic reprograming...
2018: PloS One
Kairui Zhang, Michael W Hast, Soutarou Izumi, Yu Usami, Snehal Shetye, Ngozi Akabudike, Nancy J Philp, Masahiro Iwamoto, Itzhak Nissim, Louis J Soslowsky, Motomi Enomoto-Iwamoto
BACKGROUND: Tendon injuries are common problems among athletes. Complete recovery of the mechanical structure and function of ruptured tendons is challenging. It has been demonstrated that upregulation of glycolysis and lactate production occurs in wounds, inflammation sites, and cancerous tumors, and these metabolic changes also control growth and differentiation of stem and progenitor cells. Similar metabolic changes have been reported in human healing tendons. In addition, lactate production has increased in progenitors isolated from injured tendons after treatment with IL-1β...
June 1, 2018: American Journal of Sports Medicine
P V Nikitin, A A Potapov, M V Ryzhova, V A Shurkhay, E E Kulikov, E S Zhvanskiy, I A Popov, E N Nikolaev
The relationship between molecular genetic and metabolic disorders is one of the challenges of modern oncology. In this review, we consider lipid metabolism and its changes as one of the factors of oncogenesis of glial tumors. Also, we demonstrate that the genome and the metabolome are interconnected by a large number of links, and the metabolic pathways, during their reorganization, are able to drastically affect the genetic structure of the cell and, in particular, cause its tumor transformation. Our own observations and analysis of the literature data allow us to conclude that mass spectrometry is a highly accurate current method for assessing metabolic disorders at the cellular level...
2018: Zhurnal Voprosy Neĭrokhirurgii Imeni N. N. Burdenko
Aatif Parvez, Noam Tau, Douglas Hussey, Manjula Maganti, Ur Metser
In the original publication of the article, the title was incorrectly.
June 20, 2018: Annals of Nuclear Medicine
Brendan W Lunn, Laurel A Littrell, Doris E Wenger, Stephen M Broski
OBJECTIVE: To examine the imaging characteristics of intramuscular myxomas (IM) and myxoid liposarcomas (MLS) on 18 F-FDG PET/CT and MRI. MATERIALS AND METHODS: With IRB approval, our institutional imaging database was searched for pathologically proven IM and MLS evaluated by 18 F-FDG PET/CT and MRI. PET/CT and MRI imaging characteristics were recorded and correlated with pathologic diagnosis. RESULTS: We found eight patients (2 M, 6 F) with IM (mean age 65...
June 20, 2018: Skeletal Radiology
Manjulata Singh, Katsuhiko Warita, Tomoko Warita, James R Faeder, Robin E C Lee, Shilpa Sant, Zoltán N Oltvai
Cell-to-cell differences in protein expression in normal tissues and tumors are a common phenomenon, but the underlying principles that govern this heterogeneity are largely unknown. Here, we show that in monolayer cancer cell-line cultures, the expression of the five metabolic enzymes of serine-glycine synthesis (SGS), including its rate-limiting enzyme, phosphoglycerate dehydrogenase (PHGDH), displays stochastic cell-to-cell variation. By contrast, in cancer cell line-derived three-dimensional (3D) microtumors PHGDH expression is restricted to the outermost part of the microtumors' outer proliferative cell layer, while the four other SGS enzymes display near uniform expression throughout the microtumor...
June 20, 2018: Scientific Reports
Tianliang He, Min Jin, Chenxi Xu, Zhongjun Ma, Fufang Wu, Xiaobo Zhang
The antiviral metabolites from bacterial stress response to bacteriophage infection can maintain homeostasis of host cells, while metabolism disorder is a remarkable characteristic of tumorigenesis. In the aspect of metabolic homeostasis, therefore, the antiviral homeostasis-maintaining metabolites of bacteria may possess anti-tumor activity. However, this issue has not been addressed. Here we show that the homeostasis-challenged maintaining metabolites from deep-sea bacteriophage-challenged thermophile can suppress tumor metastasis...
June 20, 2018: Oncogene
Emilia Metryka, Karina Chibowska, Izabela Gutowska, Anna Falkowska, Patrycja Kupnicka, Katarzyna Barczak, Dariusz Chlubek, Irena Baranowska-Bosiacka
The human immune system is constantly exposed to xenobiotics and pathogens from the environment. Although the mechanisms underlying their influence have already been at least partially recognized, the effects of some factors, such as lead (Pb), still need to be clarified. The results of many studies indicate that Pb has a negative effect on the immune system, and in our review, we summarize the most recent evidence that Pb can promote inflammatory response. We also discuss possible molecular and biochemical mechanisms of its proinflammatory action, including the influence of Pb on cytokine metabolism (interleukins IL-2, IL-4, IL-8, IL-1b, IL-6), interferon gamma (IFNγ), and tumor necrosis factor alpha (TNF-α); the activity and expression of enzymes involved in the inflammatory process (cyclooxygenases); and the effect on selected acute phase proteins: C-reactive protein (CRP), haptoglobin, and ceruloplasmin...
June 20, 2018: International Journal of Molecular Sciences
Mohsen Hosseini, Léa Dousset, Walid Mahfouf, Martin Serrano-Sanchez, Isabelle Redonnet-Vernhet, Samir Mesli, Zeinab Kasraian, Emilie Obre, Marc Bonneu, Stephane Claverol, Marija Vlaski, Zoran Ivanovic, Walid Rachidi, Thierry Douki, Alain Taieb, Anne-Karine Bouzier-Sore, Rodrigue Rossignol, Hamid Reza Rezvani
Although growing evidence indicates that bioenergetic metabolism plays an important role in the progression of tumorigenesis, little information is available on the contribution of reprogramming of energy metabolism in cancer initiation. By applying a quantitative proteomic approach and targeted metabolomics, we find that specific metabolic modifications precede primary skin tumor formation. Using a multistage model of ultraviolet B (UVB) radiation-induced skin cancer, we show that glycolysis, tricarboxylic acid (TCA) cycle, and fatty acid β-oxidation are decreased at a very early stage of photocarcinogenesis, while the distal part of the electron transport chain (ETC) is upregulated...
June 19, 2018: Cell Reports
Zhao-Hui Jin, Atsushi B Tsuji, Mélissa Degardin, Aya Sugyo, Yukie Yoshii, Kotaro Nagatsu, Ming-Rong Zhang, Yasuhisa Fujibayashi, Pascal Dumy, Didier Boturyn, Tatsuya Higashi
BACKGROUND: The present study proposed a new concept for targeted radionuclide therapy (TRT) to improve the intratumoral distribution of radioactivity using two different radiopharmaceuticals. We examined the efficacy of a combination of a tetrameric cyclic Arg-Gly-Asp (cRGD) peptide-based radiopharmaceutical, 64 Cu-cyclam-RAFT-c(-RGDfK-)4 (64 Cu-RaftRGD, an αV β3 integrin [αV β3 ] tracer), and 64 Cu-diacetyl-bis (N4 -methylthiosemicarbazone) (64 Cu-ATSM, a supposed tracer for hypoxic metabolism) in a small animal tumor model...
June 19, 2018: EJNMMI Research
Robert D Leone, Im-Meng Sun, Min-Hee Oh, Im-Hong Sun, Jiayu Wen, Judson Englert, Jonathan D Powell
Adenosine signaling via the A2a receptor (A2aR) is emerging as an important checkpoint of immune responses. The presence of adenosine in the inflammatory milieu or generated by the CD39/CD73 axis on tissues or T regulatory cells serves to regulate immune responses. By nature of the specialized metabolism of cancer cells, adenosine levels are increased in the tumor microenvironment and contribute to tumor immune evasion. To this end, small molecule inhibitors of the A2aR are being pursued clinically to enhance immunotherapy...
June 19, 2018: Cancer Immunology, Immunotherapy: CII
Vusala Snyder, Tamika C Reed-Newman, Levi Arnold, Sufi Mary Thomas, Shrikant Anant
Malignant tumors contain heterogeneous populations of cells in various states of proliferation and differentiation. The presence of cancer stem or initiating cells is a well-established concept wherein quiescent and poorly differentiated cells within a tumor mass contribute to drug resistance, and under permissive conditions, are responsible for tumor recurrence and metastasis. A number of studies have identified molecular markers that are characteristic of tissue-specific cancer stem cells (CSCs). Isolation of CSCs has enabled studies on the metabolic status of CSCs...
2018: Frontiers in Oncology
Shourong Wu, Huimin Wang, Yanjun Li, Yudan Xie, Can Huang, Hezhao Zhao, Makoto Miyagishi, Vivi Kasim
Tumor cells alter their metablosim to meet their demand for macromolecules, support a high rate of proliferation as well as cope with oxidative stress. The transcription factor yin yang 1 (YY1) is upregulated in various types of tumors and is crucial for tumor cell proliferation and metastasis. However, its role in tumor cell metabolic reprogramming is poorly understood. Here we show that YY1 alters tumor cell metabolism by activating glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme in the pentose phosphate pathway...
June 19, 2018: Cancer Research
Na Li, Xiaohan Zhan, Xianquan Zhan
BACKGROUND: Malignant tumors are heterogeneous diseases characterized by different metabolic phenotypes. These were revealed by Warburg effect and reverse Warburg effect phenotypes. However, the molecular mechanism remains largely unknown. METHODS: Isobaric tag for relative and absolute quantification (iTRAQ) proteomics was used to identify mitochondrial differentially expressed proteins (DEPs) of ovarian cancers relative to controls, followed by bioinformatic analysis...
June 16, 2018: Gynecologic Oncology
Yifeng Qin, An Kang, Guisheng Zhou, Huan Wang, Wei Wei, Yujie Cao, Yanyan Chen, Jing Wang, Yajun Shi, Yuping Tang, Jianqin Jiang
Carboxylesterase and UDP-glucuronosyltransferases mediated metabolism of irinotecan (CPT-11) has long been proposed to be responsible for its anti-tumor activity and toxicity, like delayed-onset diarrhea. However, recent studies failed to gain more comprehensive in vivo and in vitro pharmacokinetic profiles of irinotecan. Herein, we choose rat plasma, human liver microsomes and immortalized HepG2 cell as experimental subjects to describes an sensitive and versatile UHPLC-MS/MS method for simultaneously quantify CPT-11 and its metabolites, including SN-38 and SN-38G...
June 19, 2018: Biomedical Chromatography: BMC
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