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https://www.readbyqxmd.com/read/29775654/targeting-cancer-s-metabolic-co-dependencies-a-landscape-shaped-by-genotype-and-tissue-context
#1
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/29774420/lysophosphatidylcholine-as-a-predictor-of-postoperative-complications-after-colorectal-cancer-surgery
#2
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/29774096/gstm3-and-gstp1-novel-players-driving-tumor-progression-in-cervical-cancer
#3
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
#4
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
#5
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/29773495/metabolic-changes-in-bladder-cancer
#6
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/29772843/the-role-of-trp-channels-in-the-metastatic-cascade
#7
REVIEW
Benedikt Fels, Etmar Bulk, Zoltán Pethő, Albrecht Schwab
A dysregulated cellular Ca2+ homeostasis is involved in multiple pathologies including cancer. Changes in Ca2+ signaling caused by altered fluxes through ion channels and transporters (the transportome) are involved in all steps of the metastatic cascade. Cancer cells thereby "re-program" and "misuse" the cellular transportome to regulate proliferation, apoptosis, metabolism, growth factor signaling, migration and invasion. Cancer cells use their transportome to cope with diverse environmental challenges during the metastatic cascade, like hypoxic, acidic and mechanical cues...
May 17, 2018: Pharmaceuticals
https://www.readbyqxmd.com/read/29769529/methionine-metabolism-influences-genomic-architecture-and-gene-expression-through-h3k4me3-peak-width
#8
Ziwei Dai, Samantha J Mentch, Xia Gao, Sailendra N Nichenametla, Jason W Locasale
Nutrition and metabolism are known to influence chromatin biology and epigenetics through post-translational modifications, yet how this interaction influences genomic architecture and connects to gene expression is unknown. Here we consider, as a model, the metabolically-driven dynamics of H3K4me3, a histone methylation mark that is known to encode information about active transcription, cell identity, and tumor suppression. We analyze the genome-wide changes in H3K4me3 and gene expression in response to alterations in methionine availability in both normal mouse physiology and human cancer cells...
May 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29769046/%C3%AE-tocotrienol-induces-apoptosis-in-pancreatic-cancer-cells-by-upregulation-of-ceramide-synthesis-and-modulation-of-sphingolipid-transport
#9
Victoria E Palau, Kanishka Chakraborty, Daniel Wann, Janet Lightner, Keely Hilton, Marianne Brannon, William Stone, Koyamangalath Krishnan
BACKGROUND: Ceramide synthesis and metabolism is a promising target in cancer drug development. γ-tocotrienol (GT3), a member of the vitamin E family, orchestrates multiple effects that ensure the induction of apoptosis in both, wild-type and RAS-mutated pancreatic cancer cells. Here, we investigated whether these effects involve changes in ceramide synthesis and transport. METHODS: The effects of GT3 on the synthesis of ceramide via the de novo pathway, and the hydrolysis of sphingomyelin were analyzed by the expression levels of the enzymes serine palmitoyl transferase, ceramide synthase-6, and dihydroceramide desaturase, and acid sphingomyelinase in wild-type RAS BxPC3, and RAS-mutated MIA PaCa-2 and Panc 1 pancreatic cancer cells...
May 16, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29765540/could-a-plant-derived-protein-potentiate-the-anticancer-effects-of-a-stem-cell-in-brain-cancer
#10
Camila Ramalho Bonturi, Helena Motaln, Mariana Cristina Cabral Silva, Bruno Ramos Salu, Marlon Vilela de Brito, Luciana de Andrade Luz Cost, Heron Fernandes Vieira Torquato, Natalia Neto Dos Santos Nunes, Edgar Julian Paredes-Gamero, Tamara Lah Turnšek, Maria Luiza Vilela Oliva
Glioblastoma is the most aggressive brain tumor with poor overall survival bellow 2 years. The natural compounds with anti-cancer properties, are thus gaining attention for possible adjuvant GBM treatment. In various cancer models Enterolobium contortisiliquum Trypsin Inhibitor (EcTI) proved to have anti-cancer effects. Here, we investigated the EcTI effects on GBM U87 cells and on mesenchymal stem cells (MSC) compared to their direct coculture (MSC/U87). MSC are present in tumor stroma, modulating GBM cells phenotype, and also represent potential drug delivery vehicle due to their tumor tropism...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29765528/metabolic-changes-associated-with-metformin-potentiates-bcl-2-inhibitor-venetoclax-and-cdk9-inhibitor-bay1143572-and-reduces-viability-of-lymphoma-cells
#11
Vineela Chukkapalli, Leo I Gordon, Parameswaran Venugopal, Jeffrey A Borgia, Reem Karmali
Metformin exerts direct anti-tumor effects by activating AMP-activated protein kinase (AMPK), a major sensor of cellular metabolism in cancer cells. This, in turn, inhibits pro-survival mTOR signaling. Metformin has also been shown to disrupt complex 1 of the mitochondrial electron transport chain. Here, we explored the lymphoma specific anti-tumor effects of metformin using Daudi (Burkitt), SUDHL-4 (germinal center diffuse large B-cell lymphoma; GC DLBCL), Jeko-1 (Mantle-cell lymphoma; MCL) and KPUM-UH1 (double hit DLBCL) cell lines...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29764892/intense-exercise-for-survival-among-men-with-metastatic-castrate-resistant-prostate-cancer-interval-gap4-a-multicentre-randomised-controlled-phase-iii-study-protocol
#12
Robert U Newton, Stacey A Kenfield, Nicolas H Hart, June M Chan, Kerry S Courneya, James Catto, Stephen P Finn, Rosemary Greenwood, Daniel C Hughes, Lorelei Mucci, Stephen R Plymate, Stephan F E Praet, Emer M Guinan, Erin L Van Blarigan, Orla Casey, Mark Buzza, Sam Gledhill, Li Zhang, Daniel A Galvão, Charles J Ryan, Fred Saad
INTRODUCTION: Preliminary evidence supports the beneficial role of physical activity on prostate cancer outcomes. This phase III randomised controlled trial (RCT) is designed to determine if supervised high-intensity aerobic and resistance exercise increases overall survival (OS) in patients with metastatic castrate-resistant prostate cancer (mCRPC). METHODS AND ANALYSIS: Participants (n=866) must have histologically documented metastatic prostate cancer with evidence of progressive disease on androgen deprivation therapy (defined as mCRPC)...
May 14, 2018: BMJ Open
https://www.readbyqxmd.com/read/29764852/combined-hdac-and-bromodomain-protein-inhibition-reprograms-tumor-cell-metabolism-and-elicits-synthetic-lethality-in-glioblastoma
#13
Yiru Zhang, Chiaki Tsuge Ishida, Wataru Ishida, Sheng-Fu L Lo, Junfei Zhao, Chang Shu, Elena Bianchetti, Giulio Kleiner, Maria Sanchez-Quintero, Catarina M Quinzii, Mike-Andrew Westhoff, Georg Karpel-Massler, Peter Canoll, Markus D Siegelin
PURPOSE: Glioblastoma remain a challenge in oncology in part due to tumor heterogeneity. EXPERIMENTAL DESIGN: Patient-derived xenograft and stem-like glioblastoma cells were used as the primary model systems. RESULTS: Based on a transcriptome and subsequent gene set enrichment analysis (GSEA), we show by using clinically validated compounds that combined histone deacetylase (HDAC) inhibition and Bromodomain protein (BRD) inhibition results in pronounced synergistic reduction in cellular viability in patient-derived xenograft and stem-like glioblastoma cells...
May 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29761043/differential-expression-patterns-of-housekeeping-genes-increase-diagnostic-and-prognostic-value-in-lung-cancer
#14
Yu-Chun Chang, Yan Ding, Lingsheng Dong, Lang-Jing Zhu, Roderick V Jensen, Li-Li Hsiao
Background: Using DNA microarrays, we previously identified 451 genes expressed in 19 different human tissues. Although ubiquitously expressed, the variable expression patterns of these "housekeeping genes" (HKGs) could separate one normal human tissue type from another. Current focus on identifying "specific disease markers" is problematic as single gene expression in a given sample represents the specific cellular states of the sample at the time of collection. In this study, we examine the diagnostic and prognostic potential of the variable expressions of HKGs in lung cancers...
2018: PeerJ
https://www.readbyqxmd.com/read/29760869/metabolic-alterations-in-urine-extracellular-vesicles-are-associated-to-prostate-cancer-pathogenesis-and-progression
#15
Marc Clos-Garcia, Ana Loizaga-Iriarte, Patricia Zuñiga-Garcia, Pilar Sánchez-Mosquera, Ana Rosa Cortazar, Esperanza González, Verónica Torrano, Cristina Alonso, Miriam Pérez-Cormenzana, Aitziber Ugalde-Olano, Isabel Lacasa-Viscasillas, Azucena Castro, Felix Royo, Miguel Unda, Arkaitz Carracedo, Juan M Falcón-Pérez
Urine contains extracellular vesicles (EVs) that concentrate molecules and protect them from degradation. Thus, isolation and characterisation of urinary EVs could increase the efficiency of biomarker discovery. We have previously identified proteins and RNAs with differential abundance in urinary EVs from prostate cancer (PCa) patients compared to benign prostate hyperplasia (BPH). Here, we focused on the analysis of the metabolites contained in urinary EVs collected from patients with PCa and BPH. Targeted metabolomics analysis of EVs was performed by ultra-high-performance liquid chromatography-mass spectrometry...
2018: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/29760165/the-impact-of-transcription-on-metabolism-in-prostate-and-breast-cancers
#16
Ninu Poulose, Ian G Mills, Rebecca E Steele
Metabolic dysregulation is regarded as an important driver in cancer development and progression. The impact of transcriptional changes on metabolism have been intensively studied in hormone-dependent cancers, and in particular in prostate and breast cancer. These cancers have strong similarities in the function of important transcriptional drivers, such as the estrogen and androgen receptor, at the level of dietary risk and epidemiology, genetics and therapeutically. In this review we will focus on the function of these nuclear hormone receptors and their downstream impact on metabolism, with a particular focus on lipid metabolism...
May 14, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29760045/gfpt2-expressing-cancer-associated-fibroblasts-mediate-metabolic-reprogramming-in-human-lung-adenocarcinoma
#17
Weiruo Zhang, Gina Bouchard, Alice Yu, Majid Shafiq, Mehran Jamali, Joseph B Shrager, Kelsey Ayers, Shaimaa Bakr, Andrew J Gentles, Maximilian Diehn, Andrew Quon, Robert B West, Viswam Nair, Matt van de Rijn, Sandy Napel, Sylvia K Plevritis
Metabolic reprogramming of the tumor microenvironment is recognized as a cancer hallmark. To identify new molecular processes associated with tumor metabolism, we analyzed the transcriptome of bulk and flow-sorted human primary non-small cell lung cancer (NSCLC) together with 18FDG-positron emission tomography scans, which provide a clinical measure of glucose uptake. Tumors with higher glucose uptake were functionally enriched for molecular processes associated with invasion in adenocarcinoma (AD) and cell growth in squamous cell carcinoma (SCC)...
May 14, 2018: Cancer Research
https://www.readbyqxmd.com/read/29759594/liquid-chromatography-mass-spectrometry-based-metabolomics-and-lipidomics-reveal-toxicological-mechanisms-of-bisphenol-f-in-breast-cancer-xenografts
#18
Chao Zhao, Peisi Xie, Hailin Wang, Zongwei Cai
Bisphenol F (BPF) is a major alternative to bisphenol (BPA) and has been widely used. Although BPA exposure is known to generate various toxic effects, toxicity of BPF remains under-explored. A comprehensive method involving mass spectrometry (MS)-based global lipidomics and metabolomics, and matrix-assisted laser desorption/ionization-mass spectrometry (MALDI)- MS imaging (MSI) was used to study toxic effects of BPF and the underlying mechanisms on tumor metastasis-related tissues (liver and kidney) in breast cancer xenografts...
May 5, 2018: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/29759108/a-western-dietary-pattern-is-prospectively-associated-with-cardio-metabolic-traits-and-incidence-of-the-metabolic-syndrome
#19
Isabel Drake, Emily Sonestedt, Ulrika Ericson, Peter Wallström, Marju Orho-Melander
The aim of this study was to derive dietary patterns associated with cardio-metabolic traits and to examine whether these predict prospective changes in these traits and incidence of the metabolic syndrome (iMetS). Subjects from the Malmö Diet and Cancer Study cardiovascular cohort without cardio-metabolic disease and related drug treatments at baseline (n 4071; aged 45-67 years, 40 % men) were included. We applied reduced rank regression on thirty-eight foods to derive patterns that explain variation in response variables measured at baseline (waist circumference, TAG, HDL- and LDL-cholesterol, systolic and diastolic blood pressure, fasting glucose and insulin)...
May 2018: British Journal of Nutrition
https://www.readbyqxmd.com/read/29758944/the-conundrum-of-gsk3-inhibitors-is-it-the-dawn-of-a-new-beginning
#20
Ratan V Bhat, Ulf Andersson, Shalini Andersson, Laurent Knerr, Udo Bauer, Anna Sundgren Andersson
Spanning over three decades of extensive drug discovery research, the efforts to develop a potent and selective GSK3 inhibitor as a therapeutic for the treatment of type 2 diabetes, Alzheimer's disease (AD), bipolar disorders and cancer have been futile. Since its initial discovery in 1980 and subsequent decades of research, one cannot underscore the importance of the target and the promise of a game changing disease modifier. Several pharmaceutical companies, biotech companies, and academic institutions raged in a quest to unravel the biology and discover potent and selective GSK3 inhibitors, some of which went through clinical trials...
May 11, 2018: Journal of Alzheimer's Disease: JAD
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