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https://www.readbyqxmd.com/read/29342418/functional-characterization-of-9-cyp2a13-allelic-variants-by-assessment-of-nicotine-c-oxidation-and-coumarin-7-hydroxylation
#1
Masaki Kumondai, Hiroki Hosono, Masamitsu Maekawa, Hiroaki Yamaguchi, Nariyasu Mano, Akifumi Oda, Noriyasu Hirasawa, Masahiro Hiratsuka
Cytochrome P450 2A13 (CYP2A13) is responsible for the metabolism of chemical compounds such as nicotine, coumarin, and tobacco-specific nitrosamine. Several of these compounds have been recognized as procarcinogens activated by CYP2A13. We recently showed that CYP2A13*2 contributes to inter-individual variations observed in bladder cancer susceptibility because CYP2A13*2 might cause a decrease in enzymatic activity. Other CYP2A13 allelic variants may also affect cancer susceptibility. In this study, we performed an in vitro analysis of the wild-type enzyme (CYP2A13...
November 22, 2017: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29342230/metformin-as-an-anti-cancer-agent-actions-and-mechanisms-targeting-cancer-stem-cells
#2
Nipun Saini, Xiaohe Yang
Metformin, a first line medication for type II diabetes, initially entered the spotlight as a promising anti-cancer agent due to epidemiologic reports that found reduced cancer risk and improved clinical outcomes in diabetic patients taking metformin. To uncover the anti-cancer mechanisms of metformin, preclinical studies determined that metformin impairs cellular metabolism and suppresses oncogenic signaling pathways, including receptor tyrosine kinase, PI3K/Akt, and mTOR pathways. Recently, the anti-cancer potential of metformin has gained increasing interest due to its inhibitory effects on cancer stem cells (CSCs), which are associated with tumor metastasis, drug resistance, and relapse...
October 7, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29342159/prediction-of-novel-target-genes-and-pathways-involved-in-bevacizumab-resistant-colorectal-cancer
#3
Precious Takondwa Makondi, Chia-Hwa Lee, Chien-Yu Huang, Chi-Ming Chu, Yu-Jia Chang, Po-Li Wei
Bevacizumab combined with cytotoxic chemotherapy is the backbone of metastatic colorectal cancer (mCRC) therapy; however, its treatment efficacy is hampered by therapeutic resistance. Therefore, understanding the mechanisms underlying bevacizumab resistance is crucial to increasing the therapeutic efficacy of bevacizumab. The Gene Expression Omnibus (GEO) database (dataset, GSE86525) was used to identify the key genes and pathways involved in bevacizumab-resistant mCRC. The GEO2R web tool was used to identify differentially expressed genes (DEGs)...
2018: PloS One
https://www.readbyqxmd.com/read/29342137/corrigendum-mtorc1-dependent-amd1-regulation-sustains-polyamine-metabolism-in-prostate-cancer
#4
Amaia Zabala-Letona, Amaia Arruabarrena-Aristorena, Natalia Martín-Martín, Sonia Fernandez-Ruiz, James D Sutherland, Michelle Clasquin, Julen Tomas-Cortazar, Jose Jimenez, Ines Torres, Phong Quang, Pilar Ximenez-Embun, Ruzica Bago, Aitziber Ugalde-Olano, Ana Loizaga-Iriarte, Isabel Lacasa-Viscasillas, Miguel Unda, Verónica Torrano, Diana Cabrera, Sebastiaan M van Liempd, Ylenia Cendon, Elena Castro, Stuart Murray, Ajinkya Revandkar, Andrea Alimonti, Yinan Zhang, Amelia Barnett, Gina Lein, David Pirman, Ana R Cortazar, Leire Arreal, Ludmila Prudkin, Ianire Astobiza, Lorea Valcarcel-Jimenez, Patricia Zuñiga-García, Itziar Fernandez-Dominguez, Marco Piva, Alfredo Caro-Maldonado, Pilar Sánchez-Mosquera, Mireia Castillo-Martín, Violeta Serra, Naiara Beraza, Antonio Gentilella, George Thomas, Mikel Azkargorta, Felix Elortza, Rosa Farràs, David Olmos, Alejo Efeyan, Juan Anguita, Javier Muñoz, Juan M Falcón-Pérez, Rosa Barrio, Teresa Macarulla, Jose M Mato, Maria L Martinez-Chantar, Carlos Cordon-Cardo, Ana M Aransay, Kevin Marks, José Baselga, Josep Tabernero, Paolo Nuciforo, Brendan D Manning, Katya Marjon, Arkaitz Carracedo
This corrects the article DOI: 10.1038/nature22964.
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29342108/different-lipid-regulation-in-ovarian-cancer-inhibition-of-the-immune-system
#5
Christina Wefers, Tjitske Duiveman-de Boer, Petra L M Zusterzeel, Leon F A G Massuger, David Fuchs, Ruurd Torensma, Craig E Wheelock, I Jolanda M de Vries
Lipid metabolism is altered in several cancer settings leading to different ratios of intermediates. Ovarian cancer is the most lethal gynecological malignancy. Cancer cells disperse in the abdominal space and ascites occurs. T cells obtained from ascites are unable to proliferate after an antigenic stimulus. The proliferation of ascites-derived T cells can be restored after culturing the cells for ten days in normal culture medium. No pathway aberrancies were detected. The acellular fraction of ascites can inhibit the proliferation of autologous as well as allogeneic peripheral blood lymphocytes, indicating the presence of soluble factors that interfere with T cell functionality...
January 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29342094/telomeric-repeat-containing-rnas-terra-decrease-in-squamous-cell-carcinoma-of-the-head-and-neck-is-associated-with-worsened-clinical-outcome
#6
Valerio Vitelli, Paolo Falvo, Solomon G Nergadze, Marco Santagostino, Lela Khoriauli, Paola Pellanda, Giulia Bertino, Antonio Occhini, Marco Benazzo, Patrizia Morbini, Marco Paulli, Camillo Porta, Elena Giulotto
Telomeres are transcribed into noncoding telomeric repeat-containing RNAs (TERRA), which are essential for telomere maintenance. Deregulation of TERRA transcription impairs telomere metabolism and a role in tumorigenesis has been proposed. Head and neck cancer (HNC) is one of the most frequent cancers worldwide, with head and neck squamous cell carcinoma (HNSCC) being the predominant type. Since HNSCC patients are characterized by altered telomere maintenance, a dysfunction in telomere transcription can be hypothesized...
January 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29342092/metabolic-alterations-in-cancer-cells-and-the-emerging-role-of-oncometabolites-as-drivers-of-neoplastic-change
#7
REVIEW
Zhengqiu Zhou, Elochukwu Ibekwe, Yevgen Chornenkyy
The mitochondrion is an important organelle and provides energy for a plethora of intracellular reactions. Metabolic dysregulation has dire consequences for the cell, and alteration in metabolism has been identified in multiple disease states-cancer being one. Otto Warburg demonstrated that cancer cells, in the presence of oxygen, undergo glycolysis by reprogramming their metabolism-termed "aerobic glycolysis". Alterations in metabolism enable cancer cells to gain a growth advantage by obtaining precursors for macromolecule biosynthesis, such as nucleic acids and lipids...
January 17, 2018: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/29341016/oxygenation-imaging-by-nuclear-magnetic-resonance-methods
#8
Heling Zhou, Nuria Arias-Ramos, Pilar López-Larrubia, Ralph P Mason, Sebastián Cerdán, Jesús Pacheco-Torres
Oxygen monitoring is a topic of exhaustive research due to its central role in many biological processes, from energy metabolism to gene regulation. The ability to monitor in vivo the physiological distribution and the dynamics of oxygen from subcellular to macroscopic levels is a prerequisite to better understand the mechanisms associated with both normal and disease states (cancer, neurodegeneration, stroke, etc.). This chapter focuses on magnetic resonance imaging (MRI) based techniques to assess oxygenation in vivo...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29340974/inhibiting-6-phosphogluconate-dehydrogenase-selectively-targets-breast-cancer-through-ampk-activation
#9
Xiaoyu Yang, Xiaochun Peng, Jiangrong Huang
PURPOSE: 6-phosphogluconate dehydrogenase (6PGD), a key enzyme of the oxidative pentose phosphate pathway, is involved in tumor growth and metabolism. Although high 6PGD activity has been shown to be associated with poor prognosis, its role and therapeutic value in breast cancer remain unknown. METHODS: The levels and roles of 6PGD were analyzed in breast cancer cells and their normal counterparts. The underlying mechanisms of 6PGD's roles are also analyzed. RESULTS: We found that 6PGD is aberrantly activated in breast cancer as shown by its increased transcriptional and translational levels as well as enzyme activity in breast cancer tissues and cell lines compared to normal counterparts...
January 16, 2018: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29340859/comparative-proteomics-of-chromium-transformed-beas-2b-cells-by-2d-dige-and-maldi-tof-tof-ms
#10
Jian Lu, Miaomiao Tang, Yi Liu, Jin Wang, Zhanao Wu
Chromium (Cr) is a highly toxic, common heavy metal used in industrial production. There are two types of Cr in nature: hexavalent chromium (Cr(VI)) and chromium trichloride (Cr(III)). Cr(III) is involved in the metabolism of sugars and lipids, whereas Cr(VI) is absorbed through the respiratory tract and skin and generates free radicals that result in secondary toxicity. Cr(VI) leads to cancer in the occupational population and is therefore recognized as a human carcinogen by the International Agency for Research on Cancer...
January 16, 2018: Biological Trace Element Research
https://www.readbyqxmd.com/read/29340710/production-of-plant-derived-polyphenols-in-microorganisms-current-state-and-perspectives
#11
REVIEW
Lars Milke, Jennifer Aschenbrenner, Jan Marienhagen, Nicolai Kallscheuer
Plants synthesize several thousand different polyphenols of which many have the potential to aid in preventing or treating cancer, cardiovascular, and neurodegenerative diseases. However, plants usually contain complex polyphenol mixtures impeding access to individual compounds in larger quantities. In contrast, functional integration of biosynthetic plant polyphenol pathways into microorganisms allows for the production of individual polyphenols as chemically distinct compounds, which can be synthesized in large amounts and can be more easily isolated...
January 16, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29340111/effect-of-dihydropyrimidine-dehydrogenase-single-nucleotide-polymorphisms-on-prognosis-of-breast-cancer-patients-with-chemotherapy
#12
Fengxia Qin, Huikun Zhang, Yong Huang, Limin Yang, Feng Yu, Xiaoli Liu, Li Fu, Feng Gu, Yongjie Ma
Defining biomarkers that predict therapeutic effects and adverse events is a crucial mandate to guide patient selection for personalized cancer treatments. DPD (dihydropyrimidine dehydrogenase, encoded by DPYD gene) is the initial and rate-limiting enzyme of metabolic pathway of fluoropyrimidines, and fluoropyrimidines are common used drug therapies for breast cancer. Previous studies on DPYD polymorphism were mainly focused on its association with fluoropyrimidines toxicity. In our present study, 5 DPYD single nucleotide polymorphisms status was detected from tumor tissues of 331 invasive breast cancer patients using standard techniques...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340031/analyzing-the-influence-of-kinase-inhibitors-on-dna-repair-by-differential-proteomics-of-chromatin-interacting-proteins-and-nuclear-phospho-proteins
#13
Lisa Gleißner, Marcel Kwiatkowski, Laura Myllynen, Pascal Steffen, Cordula Petersen, Kai Rothkamm, Hartmut Schlüter, Malte Kriegs
The combination of radiotherapy and pharmacological inhibition of cellular signal transduction pathways offers promising strategies for enhanced cancer cell inactivation. However, the molecular effects of kinase inhibitors especially on DNA damage detection and repair after X-irradiation have to be understood to facilitate the development of efficient and personalized treatment regimens. Therefore, we applied differential proteomics for analyzing inhibitor-induced changes in either chromatin-bound or phosphorylated nuclear proteins...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340030/increased-efficacy-of-metformin-corresponds-to-differential-metabolic-effects-in-the-ovarian-tumors-from-obese-versus-lean-mice
#14
Jianjun Han, Weiya Z Wysham, Yan Zhong, Hui Guo, Lu Zhang, Kim M Malloy, Hallum K Dickens, Gene Huh, Douglas Lee, Liza Makowski, Chunxiao Zhou, Victoria L Bae-Jump
Obesity is a significant risk factor for ovarian cancer (OC) and associated with worse outcomes for this disease. We assessed the anti-tumorigenic effects of metformin in human OC cell lines and a genetically engineered mouse model of high grade serous OC under obese and lean conditions. Metformin potently inhibited growth in a dose-dependent manner in all four human OC cell lines through AMPK/mTOR pathways. Treatment with metformin resulted in G1 arrest, induction of apoptosis, reduction of invasion and decreased hTERT expression...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340028/high-resolution-microbiome-profiling-uncovers-fusobacterium-nucleatum-lactobacillus-gasseri-johnsonii-and-lactobacillus-vaginalis-associated-to-oral-and-oropharyngeal-cancer-in-saliva-from-hpv-positive-and-hpv-negative-patients-treated-with-surgery-and-chemo
#15
Rafael Guerrero-Preston, James Robert White, Filipa Godoy-Vitorino, Arnold Rodríguez-Hilario, Kelvin Navarro, Herminio González, Christina Michailidi, Anne Jedlicka, Sierra Canapp, Jessica Bondy, Amanda Dziedzic, Barbara Mora-Lagos, Gustavo Rivera-Alvarez, Carmen Ili-Gangas, Priscilla Brebi-Mieville, William Westra, Wayne Koch, Hyunseok Kang, Luigi Marchionni, Young Kim, David Sidransky
Microbiome studies show altered microbiota in head and neck squamous cell carcinoma (HNSCC), both in terms of taxonomic composition and metabolic capacity. These studies utilized a traditional bioinformatics methodology, which allows for accurate taxonomic assignment down to the genus level, but cannot accurately resolve species level membership. We applied Resphera Insight, a high-resolution methodology for 16S rRNA taxonomic assignment that is able to provide species-level context in its assignments of 16S rRNA next generation sequencing (NGS) data...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339836/the-role-of-metabolic-enzymes-in-mesenchymal-tumors-and-tumor-syndromes-genetics-pathology-and-molecular-mechanisms
#16
REVIEW
Inga-Marie Schaefer, Jason L Hornick, Judith V M G Bovée
The discovery of mutations in genes encoding the metabolic enzymes isocitrate dehydrogenase (IDH), succinate dehydrogenase (SDH), and fumarate hydratase (FH) has expanded our understanding not only of altered metabolic pathways but also epigenetic dysregulation in cancer. IDH1/2 mutations occur in enchondromas and chondrosarcomas in patients with the non-hereditary enchondromatosis syndromes Ollier disease and Maffucci syndrome and in sporadic tumors. IDH1/2 mutations result in excess production of the oncometabolite (D)-2-hydroxyglutarate...
January 16, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29339767/regulatory-t-cells-trigger-effector-t-cell-dna-damage-and-senescence-caused-by-metabolic-competition
#17
Xia Liu, Wei Mo, Jian Ye, Lingyun Li, Yanping Zhang, Eddy C Hsueh, Daniel F Hoft, Guangyong Peng
Defining the suppressive mechanisms used by regulatory T (Treg) cells is critical for the development of effective strategies for treating tumors and chronic infections. The molecular processes that occur in responder T cells that are suppressed by Treg cells are unclear. Here we show that human Treg cells initiate DNA damage in effector T cells caused by metabolic competition during cross-talk, resulting in senescence and functional changes that are molecularly distinct from anergy and exhaustion. ERK1/2 and p38 signaling cooperate with STAT1 and STAT3 to control Treg-induced effector T-cell senescence...
January 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29339647/proceedings-of-the-11th-congress-of-the-international-society-of-nutrigenetics-and-nutrigenomics-isnn-2017
#18
William T Barrington, Anna C Salvador, Jaana A Hartiala, Raffaele De Caterina, Martin Kohlmeier, J Alfredo Martinez, Carin B Kreutzer, David Heber, Aldons J Lusis, Zhaoping Li, Hooman Allayee
The International Society of Nutrigenetics and Nutrigenomics (ISNN) held its 11th annual Congress in Los Angeles, California, between September 16 and 19, 2017. In addition to 2 keynote lectures, 4 plenary sessions included presentations by internationally renowned speakers on cutting-edge areas of research and new discoveries in genetics/genomics, the microbiome, and nutrition. Scientific topics included multi-omics approaches; diet and the microbiome; cancer, longevity, and metabolism; moving the field forward; and translational/educational aspects and the future of medicine...
January 17, 2018: Journal of Nutrigenetics and Nutrigenomics
https://www.readbyqxmd.com/read/29339552/mechanisms-of-redox-metabolism-and-cancer-cell-survival-during-extracellular-matrix-detachment
#19
Mark A Hawk, Zachary T Schafer
Non-transformed cells that become detached from the extracellular matrix (ECM) undergo dysregulation of redox homeostasis and cell death. In contrast, cancer cells often acquire the ability to mitigate programmed cell death pathways and recalibrate the redox balance to survive after ECM detachment, facilitating metastatic dissemination. Accordingly, recent studies of the mechanisms by which cancer cells overcome ECM detachment-induced metabolic alterations have focused on mechanisms in redox homeostasis. The insights into these mechanisms may inform the development of therapeutics that manipulate redox homeostasis to eliminate ECM-detached cancer cells...
January 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29339540/radio-resistant-cervical-cancers-are-sensitive-to-inhibition-of-glycolysis-and-redox-metabolism
#20
Ramachandran Rashmi, Xiaojing Huang, John M Floberg, Adnan Elhammali, Michael L McCormick, Gary J Patti, Douglas R Spitz, Julie K Schwarz
Highly glycolytic cervical cancers largely resist treatment by cisplatin and co-administered pelvic irradiation as the present standard of care. In this study, we investigated the effects of inhibiting glycolysis and thiol redox metabolism to evaluate them as alternate treatment strategies in these cancers. In a panel of multiple cervical cancer cell lines, we evaluated sensitivity to inhibition of glycolysis (2-DG) with or without simultaneous inhibition of glutathione and thioredoxin metabolism (BSO/AUR)...
January 16, 2018: Cancer Research
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