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Cancer, metabolism

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https://www.readbyqxmd.com/read/29777783/accelerated-lipid-catabolism-and-autophagy-are-cancer-survival-mechanisms-under-inhibited-glutaminolysis
#1
Anna Halama, Michal Kulinski, Shaima S Dib, Shaza B Zaghlool, Kodappully S Siveen, Ahmad Iskandarani, Jonas Zierer, Kirti S Prabhu, Noothan J Satheesh, Aditya M Bhagwat, Shahab Uddin, Gabi Kastenmüller, Olivier Elemento, Steven S Gross, Karsten Suhre
Suppressing glutaminolysis does not always induce cancer cell death in glutamine dependent tumors because cells may switch to alternative energy sources. To reveal compensatory metabolic pathways, we investigated the metabolome-wide cellular response to inhibited glutaminolysis in cancer cells. Glutaminolysis inhibition with C.968 suppressed cell proliferation but was insufficient to induce cancer cell death. We found that lipid catabolism was activated as a compensation for glutaminolysis inhibition. Accelerated lipid catabolism, together with oxidative stress induced by glutaminolysis inhibition, triggered autophagy...
May 16, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29776993/tumor-immune-evasion-arises-through-loss-of-tnf-sensitivity
#2
Conor J Kearney, Stephin J Vervoort, Simon J Hogg, Kelly M Ramsbottom, Andrew J Freeman, Najoua Lalaoui, Lizzy Pijpers, Jessica Michie, Kristin K Brown, Deborah A Knight, Vivien Sutton, Paul A Beavis, Ilia Voskoboinik, Phil K Darcy, John Silke, Joseph A Trapani, Ricky W Johnstone, Jane Oliaro
Immunotherapy has revolutionized outcomes for cancer patients, but the mechanisms of resistance remain poorly defined. We used a series of whole-genome clustered regularly interspaced short palindromic repeat (CRISPR)-based screens performed in vitro and in vivo to identify mechanisms of tumor immune evasion from cytotoxic lymphocytes [CD8+ T cells and natural killer (NK) cells]. Deletion of key genes within the tumor necrosis factor (TNF) signaling, interferon-γ (IFN-γ) signaling, and antigen presentation pathways provided protection of tumor cells from CD8+ T cell-mediated killing and blunted antitumor immune responses in vivo...
May 18, 2018: Science Immunology
https://www.readbyqxmd.com/read/29776834/bet-bromodomain-ligands-probing-the-wpf-shelf-to-improve-brd4-bromodomain-affinity-and-metabolic-stability
#3
Laura E Jennings, Matthias Schiedel, David S Hewings, Sarah Picaud, Corentine M C Laurin, Paul A Bruno, Joseph P Bluck, Amy R Scorah, Larissa See, Jessica K Reynolds, Mustafa Moroglu, Ishna N Mistry, Amy Hicks, Pavel Guzanov, James Clayton, Charles N G Evans, Giulia Stazi, Philip C Biggin, Anna K Mapp, Ester M Hammond, Philip G Humphreys, Panagis Filippakopoulos, Stuart J Conway
Ligands for the bromodomain and extra-terminal domain (BET) family of bromodomains have shown promise as useful therapeutic agents for treating a range of cancers and inflammation. Here we report that our previously developed 3,5-dimethylisoxazole-based BET bromodomain ligand (OXFBD02) inhibits interactions of BRD4(1) with the RelA subunit of NF-κB, in addition to histone H4. This ligand shows a promising profile in a screen of the NCI-60 panel but was rapidly metabolised (t½  = 39.8 min). Structure-guided optimisation of compound properties led to the development of the 3-pyridyl-derived OXFBD04...
May 15, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29776373/metabolic-therapy-with-peg-arginase-induces-a-sustained-complete-remission-in-immunotherapy-resistant-melanoma
#4
Carmela De Santo, Paul Cheng, Andrew Beggs, Sharon Egan, Alberto Bessudo, Francis Mussai
BACKGROUND: Metastatic melanoma is an aggressive skin cancer with a poor prognosis. Current treatment strategies for high-stage melanoma are based around the use of immunotherapy with immune checkpoint inhibitors such as anti-PDL1 or anti-CTLA4 antibodies to stimulate anti-cancer T cell responses, yet a number of patients will relapse and die of disease. Here, we report the first sustained complete remission in a patient with metastatic melanoma who failed two immunotherapy strategies, by targeting tumour arginine metabolism...
May 18, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29775961/antioxidant-response-elements-discovery-classes-regulation-and-potential-applications
#5
REVIEW
Azhwar Raghunath, Kiruthika Sundarraj, Raju Nagarajan, Frank Arfuso, Jinsong Bian, Alan P Kumar, Gautam Sethi, Ekambaram Perumal
Exposure to antioxidants and xenobiotics triggers the expression of a myriad of genes encoding antioxidant proteins, detoxifying enzymes, and xenobiotic transporters to offer protection against oxidative stress. This articulated universal mechanism is regulated through the cis-acting elements in an array of Nrf2 target genes called antioxidant response elements (AREs), which play a critical role in redox homeostasis. Though the Keap1/Nrf2/ARE system involves many players, AREs hold the key in transcriptional regulation of cytoprotective genes...
May 7, 2018: Redox Biology
https://www.readbyqxmd.com/read/29775756/pkm2-a-potential-target-for-regulating-cancer
#6
REVIEW
Yu-Huan Li, Xiao-Feng Li, Jia-Tao Liu, Hua Wang, Lu-Lu Fan, Jun Li, Guo-Ping Sun
Aberrated glucose metabolism is a key future of cancer cells. Unlike normal cells, tumor cells favor glycolysis even in the presence of sufficient oxygen. Pyruvate kinase (PK), a key glucose metabolic enzyme, converts phosphoenolpyruvate (PEP) to pyruvate by transferring the high-energy phosphate group to adenosine diphosphate (ADP) to produce adenosine triphosphate (ATP). Pyruvate kinase M2 (PKM2), one of the four isozyme of PK, which universally expressed in rapidly proliferating cells such as embryonic cells and cancer cells...
May 15, 2018: Gene
https://www.readbyqxmd.com/read/29775654/targeting-cancer-s-metabolic-co-dependencies-a-landscape-shaped-by-genotype-and-tissue-context
#7
REVIEW
Junfeng Bi, Sihan Wu, Wenjing Zhang, Paul S Mischel
Tumors cells reprogram their metabolism to fuel rapid growth. The ability to trace nutrient fluxes in the context of specific alterations has provided new mechanistic insight into the process of oncogenic transformation. A broad array of complementary genetic, epigenetic, transcriptional and translational mechanisms has been identified, revealing a metabolic landscape of cancer. However, cancer metabolism is not a static or uniform process, including within a single tumor. Tumor cells adapt to changing environmental conditions, profoundly shaping the enzymatic dependencies of individual cells...
May 15, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29775610/monocarboxylate-transporters-in-breast-cancer-and-adipose-tissue-are-novel-biomarkers-and-potential-therapeutic-targets
#8
Zhiyu Li, Qi Wu, Si Sun, Juan Wu, Juanjuan Li, Yimin Zhang, Changhua Wang, Jingping Yuan, Shengrong Sun
Monocarboxylate transporters (MCTs) are transmembrane proteins that control the lactate metabolism and associated with poor prognosis in solid tumors including breast cancer (BC). This study aimed to evaluate the clinical and prognostic value of MCTs used by immunohistochemistry and quantum dots-based fluorescent imaging technique in BC and surrounding stroma with emphasis on the interaction between tumour and stroma. Moreover, the data from The Cancer Genome Atlas (TCGA) was analyzed to evaluate the association between MCTs mRNA expression and prognosis of breast cancer patients...
May 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29775571/effect-of-methylglyoxal-on-reactive-oxygen-species-ki-67-and-caspase-3-expression-in-mcf-7-cells
#9
Dyah Paramita, J D P Wisnubroto
BACKGROUND: Methylglyoxal (MG) is an extremely reactive α-ketoaldehyde endogenously produced by various metabolic pathways, including the dephosphorylation of glycolytic intermediates, metabolites of the polyol pathway, and aminoacetone metabolism. MG cytotoxicity occurs through the induction of apoptosis. There are multiple mechanisms by which MG can induce apoptosis, e.g., through the generation of reactive oxygen species (ROS), induction of oxidative DNA damage, or accumulation of a specific MG-derived advanced glycation end product (AGE)...
May 15, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29775456/maternal-obesogenic-diet-induces-endometrial-hyperplasia-an-early-hallmark-of-endometrial-cancer-in-a-diethylstilbestrol-mouse-model
#10
Theresa O Owuor, Michaela Reid, Lauren Reschke, Ian Hagemann, Suellen Greco, Zeel Modi, Kelle H Moley
Thirty-eight percent of US adult women are obese, meaning that more children are now born of overweight and obese mothers, leading to an increase in predisposition to several adult onset diseases. To explore this phenomenon, we developed a maternal obesity animal model by feeding mice a diet composed of high fat/ high sugar (HF/HS) and assessed both maternal diet and offspring diet on the development of endometrial cancer (ECa). We show that maternal diet by itself did not lead to ECa initiation in wildtype offspring of the C57Bl/6J mouse strain...
2018: PloS One
https://www.readbyqxmd.com/read/29774420/lysophosphatidylcholine-as-a-predictor-of-postoperative-complications-after-colorectal-cancer-surgery
#11
Akihisa Matsuda, Marina Yamada, Satoshi Matsumoto, Nobuyuki Sakurazawa, Takeshi Yamada, Takeshi Matsutani, Masao Miyashita, Eiji Uchida
PURPOSE: Lysophosphatidylcholine (LPC), which is generated from phosphatidylcholine (PC) and metabolized by autotaxin (ATX), modulates immune responses via its anti-inflammatory property. We investigated the association between LPC and postoperative complications (POCs) after colorectal cancer surgery (CRC). METHODS: The subjects of this study were 43 patients who underwent surgery for CRC. Peripheral blood samples were collected preoperatively and immediately after surgery, and on postoperative days (PODs) 1, 3, 5, and 7...
May 17, 2018: Surgery Today
https://www.readbyqxmd.com/read/29774118/proteomic-profiling-of-skeletal-and-cardiac-muscle-in-cancer-cachexia-alterations-in-sarcomeric-and-mitochondrial-protein-expression
#12
Angie M Y Shum, Anne Poljak, Nicholas L Bentley, Nigel Turner, Timothy C Tan, Patsie Polly
Background: Cancer cachexia is observed in more than 50% of advanced cancer patients, and impairs quality of life and prognosis. A variety of pathways are likely to be dysregulated. Hence, a broad-spectrum understanding of the disease process is best achieved by a discovery based approach such as proteomics. Results: More than 300 proteins were identified with > 95% confidence in correct sequence identification, of which 5-10% were significantly differentially expressed in cachectic tissues ( p -value of 0...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774104/use-of-baseline-18f-fdg-pet-scan-to-identify-initial-sub-volumes-with-local-failure-after-concomitant-radio-chemotherapy-in-head-and-neck-cancer
#13
Floriane Legot, Florent Tixier, Minea Hadzic, Thomas Pinto-Leite, Christelle Gallais, Rémy Perdrisot, Xavier Dufour, Catherine Cheze-Le-Rest
Introduction: Head and neck squamous cell carcinoma (HNSCC) treated by radio-chemotherapy have a significant local recurrence rate. It has been previously suggested that 18F-FDG PET could identify the high uptake areas that can be potential targets for dose boosting. The purpose of this study was to compare the location of initial hypermetabolic regions on baseline scans with the metabolic relapse sites after radio-chemotherapy in HNSCC. Results: The initial functional tumor volume was significantly higher for patients with proven local recurrence or residual disease (23...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774096/gstm3-and-gstp1-novel-players-driving-tumor-progression-in-cervical-cancer
#14
Alberto Checa-Rojas, Luis Fernando Delgadillo-Silva, Martín Del Castillo Velasco-Herrera, Andrés Andrade-Domínguez, Jeovanis Gil, Orlando Santillán, Luis Lozano, Alfredo Toledo-Leyva, Alberto Ramírez-Torres, Patricia Talamas-Rohana, Sergio Encarnación-Guevara
The molecular processes and proteomic markers leading to tumor progression (TP) in cervical cancer (CC) are either unknown or only partially understood. TP affects metabolic and regulatory mechanisms that can be identified as proteomic changes. To identify which proteins are differentially expressed and to understand the mechanisms of cancer progression, we analyzed the dynamics of the tumor proteome in CC cell lines. This analysis revealed two proteins that are up-regulated during TP, GSTM3 and GSTP1. These proteins are involved in cell maintenance, cell survival and the cellular stress response via the NF-κB and MAP kinase pathways during TP...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774014/oral-microbiota-community-dynamics-associated-with-oral-squamous-cell-carcinoma-staging
#15
Chia-Yu Yang, Yuan-Ming Yeh, Hai-Ying Yu, Chia-Yin Chin, Chia-Wei Hsu, Hsuan Liu, Po-Jung Huang, Song-Nian Hu, Chun-Ta Liao, Kai-Ping Chang, Yu-Liang Chang
Oral squamous cell carcinoma (OSCC) is a highly aggressive cancer and the fourth leading malignancy among males in Taiwan. Some pathogenic bacteria are associated with periodontitis and oral cancer. However, the comprehensive profile of the oral microbiome during the cancer's progression from the early stage to the late stage is still unclear. We profiled the oral microbiota and identified bacteria biomarkers associated with OSCC. The microbiota of an oral rinse from 51 healthy individuals and 197 OSCC patients at different stages were investigated using 16S rRNA V3V4 amplicon sequencing, followed by bioinformatics and statistical analyses...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29773816/experimental-investigation-of-radiobiology-in-head-and-neck-cancer-cell-lines-as-a-function-of-hpv-status-by-mtt-assay
#16
Paul Reid, Puthenparampil Wilson, Yanrui Li, Loredana G Marcu, Alexander H Staudacher, Michael P Brown, Eva Bezak
Head and neck cancers (HNCs) are aggressive epithelial tumours frequently treated using radiation. HNC biology shows distinctions dependent on the oncologic involvement of the human papilloma virus (HPV). Clinically, HPV positive HNCs respond better to radiotherapy but few in vitro data demonstrate radiobiological differences explaining differences in clinical outcomes. This pilot study examined radiobiological responses to irradiation and subsequent regeneration in two HNC cell lines (HPV positive and negative)...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29773553/intratumoral-androgen-levels-are-linked-to-tmprss2-erg-fusion-in-prostate-cancer
#17
Matias Knuuttila, Arfa Mehmood, Jenni Mäki-Jouppila, Henrik Ryberg, Pekka Taimen, Juha Knaapila, Otto Ettala, Peter J Bostrom, Claes Ohlsson, Mikko S Venäläinen, Asta Laiho, Laura L Elo, Petra Sipilä, Sari Makela, Matti Poutanen
Intratumoral androgen biosynthesis is one of the mechanisms involved in the progression of prostate cancer, and an important target for novel prostate cancer therapies. Using gas chromatography-tandem mass spectrometry and genome-wide RNA sequencing, we have analyzed androgen concentrations and androgen-regulated gene expression in cancerous and morphologically benign prostate tissue specimens and serum samples obtained from 48 primary prostate cancer patients. Intratumoral DHT concentrations were significantly higher in the cancerous tissues compared to benign prostate (p<0...
May 17, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29773495/metabolic-changes-in-bladder-cancer
#18
REVIEW
Benjamin L Woolbright, Matthew Ayres, John A Taylor
INTRODUCTION AND OBJECTIVE: Bladder cancer is a common solid tumor. Outcomes are poor in advanced disease, with few novel clinical therapeutics introduced over the previous several decades. Otto Warburg's original hypothesis that cancer cells use aerobic glycolysis to produce ATP instead of traditional oxidative phosphorylation in the mitochondria was a landmark discovery in its time. Recent studies indicate metabolic changes in cancer are far more complex than originally anticipated though...
May 14, 2018: Urologic Oncology
https://www.readbyqxmd.com/read/29773177/participation-of-selenoproteins-localized-in-the-er-in-the-processes-occurring-in-this-organelle-and-in-the-regulation-of-carcinogenesis-associated-processes
#19
REVIEW
Elena Gennadyevna Varlamova
The functions performed by the ER are diverse: synthesis of steroid hormones, synthesis of proteins for the plasma membrane, lysosomes, as well as proteins meant for exocytosis, protein folding, formation of disulfide bonds, N-linked glycosylation, etc. Selenoproteins localized in this organelle are definitely involved in the processes occurring in it, and the most common of them include participation in protein degradation, regulation of ER stress and redox metabolism. ER stress has been registered in many types of cancer cells...
July 2018: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/29773061/development-of-novel-therapeutics-targeting-isocitrate-dehydrogenase-mutations-in-cancer
#20
Horrick Sharma
Isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) are key metabolic enzymes that catalyze the conversion of isocitrate to α-ketoglutarate (αKG). IDH 1 and IDH2 regulate several cellular processes, including oxidative respiration, glutamine metabolism, lipogenesis, and cellular defense against oxidative damage. Mutations in IDH1 and IDH2 have recently been observed in multiple tumor types, including gliomas, acute myeloid leukemia, myelodysplastic syndromes, and chondrosarcoma. IDH1 and IDH2 mutations involve a gain in neomorphic activity that catalyze αKG conversion to (R)-2-hydroxyglutarate ((R)-2HG)...
May 17, 2018: Current Topics in Medicinal Chemistry
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