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https://www.readbyqxmd.com/read/28916726/the-nqo1-bioactivatable-drug-%C3%AE-lapachone-alters-the-redox-state-of-nqo1-pancreatic-cancer-cells-causing-perturbation-in-central-carbon-metabolism
#1
Molly A Silvers, Stanislaw Deja, Naveen Singh, Robert A Egnatchik, Jessica Sudderth, Xiuquan Luo, Muhammad S Beg, Shawn C Burgess, Ralph J DeBerardinis, David A Boothman, Matthew E Merritt
Many cancer treatments, such as those for managing recalcitrant tumors like pancreatic ductal adenocarcinoma, cause off-target toxicities in normal, healthy tissue, highlighting the need for more tumor-selective chemotherapies. β-Lapachone is bioactivated by NAD(P)H:quinone oxidoreductase 1 (NQO1). This enzyme exhibits elevated expression in most solid cancers and therefore is a potential cancer-specific target. β-Lapachone's therapeutic efficacy partially stems from the drug's induction of a futile NQO1-mediated redox cycle that causes high levels of superoxide, then peroxide formation, which damages DNA and causes hyperactivation of poly (ADP-ribose) polymerase (PARP), resulting in extensive NAD+/ATP depletion...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28914667/metabolic-regulation-of-macrophages-in-tumor-microenvironment
#2
Jaehong Kim, Jong-Sup Bae
PURPOSE OF REVIEW: Insight into the metabolic changes in cancer has become so important that cancer is regarded as a disease entity full of metabolic implications. We summarize the recent findings pertaining to cancer cell-derived metabolic changes that regulate the function of macrophages to favor cancer cell survival, and the reported approaches to reverse these changes. RECENT FINDINGS: Since the observation and dramatic revitalization of the Warburg effect, metabolic changes were thought to be confined in cancer cells...
September 13, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28913935/induction-of-cancer-cell-stemness-by-depletion-of-macrohistone-h2a1-in-hepatocellular-carcinoma
#3
Oriana Lo Re, Caterina Fusilli, Francesca Rappa, Matthias Van Haele, Julien Douet, Jana Pindjakova, Sura Wanessa Rocha, Illar Pata, Barbora Valčíková, Stjepan Uldrijan, Raymond S Yeung, Christina Alves Peixoto, Tania Roskams, Marcus Buschbeck, Tommaso Mazza, Manlio Vinciguerra
Hepatocellular carcinomas (HCC) contain a sub-population of cancer stem cells (CSCs), which exhibit stem-cell like features and are responsible for tumor relapse, metastasis, and chemoresistance. The development of effective treatments for HCC will depend on a molecular-level understanding of the specific pathways driving CSC emergence and stemness. MacroH2A1 is a variant of the histone H2A and an epigenetic regulator of stem cell function, where it promotes differentiation and, conversely, acts as a barrier to somatic cell reprogramming...
September 15, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28911967/applications-of-nuclear-magnetic-resonance-in-lipid-analyses-an-emerging-powerful-tool-for-lipidomics-studies
#4
REVIEW
Jingbo Li, Thomas Vosegaard, Zheng Guo
The role of lipids in cell, tissue, and organ physiology is crucial; as many diseases, including cancer, diabetes, neurodegenerative, and infectious diseases, are closely related to absorption and metabolism of lipids. Mass spectrometry (MS) based methods are the most developed powerful tools to study the synthetic pathways and metabolic networks of cellular lipids in biological systems; leading to the birth of an emerging subject lipidomics, which has been extensively reviewed. Nuclear magnetic resonance (NMR), another powerful analytical tool, which allows the visualization of single atoms and molecules, is receiving increasing attention in lipidomics analyses...
September 11, 2017: Progress in Lipid Research
https://www.readbyqxmd.com/read/28910408/effects-of-tumour-necrosis-factor-%C3%AE-upon-the-metabolism-of-the-endocannabinoid-anandamide-in-prostate-cancer-cells
#5
Jessica Karlsson, Sandra Gouveia-Figueira, Mireille Alhouayek, Christopher J Fowler
Tumour necrosis factor α (TNFα) is involved in the pathogenesis of prostate cancer, a disease where disturbances in the endocannabinoid system are seen. In the present study we have investigated whether treatment of DU145 human prostate cancer cells affects anandamide (AEA) catabolic pathways. Additionally, we have investigated whether cyclooxygenase-2 (COX-2) can regulate the uptake of AEA into cells. Levels of AEA synthetic and catabolic enzymes were determined by qPCR. AEA uptake and hydrolysis in DU145 and RAW264...
2017: PloS One
https://www.readbyqxmd.com/read/28905102/digestive-system-in-psoriasis-an-update
#6
REVIEW
Daniel Pietrzak, Aldona Pietrzak, Dorota Krasowska, Andrzej Borzęcki, Kinga Franciszkiewicz-Pietrzak, Beata Polkowska-Pruszyńska, Maja Baranowska, Kristian Reich
Psoriasis is a chronic inflammatory immune-mediated disorder associated and often coexisting with many other immune-related clinical conditions including those affecting the gastrointestinal tract. Data obtained from the reviewed literature suggest an association between psoriasis and pathologies of the oral cavity, both psoriasis-specific lesions, as well as non-specific, such as geographic tongue or fissured tongue. These findings show the importance of thorough examination of oral mucosa in psoriatic patients...
September 13, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28904010/vitamin-d-supplementation-to-palliative-cancer-patients-protocol-of-a-double-blind-randomised-controlled-trial-palliative-d
#7
Maria Helde-Frankling, Jenny Bergqvist, Caritha Klasson, Marie Nordström, Jonas Höijer, Peter Bergman, Linda Björkhem-Bergman
BACKGROUND: According to a small pilot study on palliative cancer patients at our ward, vitamin D supplementation had beneficial effects on pain (measured as opioid consumption), infections and quality of life (QoL) without having any significant side effects. OBJECTIVE: The primary objective of the 'Palliative-D' study is to test the hypothesis that vitamin D supplementation for 12 weeks reduces opioid consumption. The secondary objectives are to study if reduction of antibiotic consumption and fatigue as well as improvement in QoL assessments can be observed...
September 13, 2017: BMJ Supportive & Palliative Care
https://www.readbyqxmd.com/read/28901484/molecular-iodine-impairs-chemoresistance-mechanisms-enhances-doxorubicin-retention-and-induces-downregulation-of-the-cd44-cd24-and-e-cadherin-vimentin-subpopulations-in-mcf-7-cells-resistant-to-low-doses-of-doxorubicin
#8
Alexander Bontempo, Brenda Ugalde-Villanueva, Evangelina Delgado-González, Ángel Luis Rodríguez, Carmen Aceves
One of the most dreaded clinical events for an oncology patient is resistance to treatment. Chemoresistance is a complex phenomenon based on alterations in apoptosis, the cell cycle and drug metabolism, and it correlates with the cancer stem cell phenotype and/or epithelial-mesenchymal transition. Molecular iodine (I2) exerts an antitumor effect on different types of iodine-capturing neoplasms by its oxidant/antioxidant properties and formation of iodolipids. In the present study, wild-type breast carcinoma cells (MCF-7/W) were treated chronically with 10 nM doxorubicin (DOX) to establish a low-dose DOX-resistant mammary cancer model (MCF-7/D)...
September 1, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28901272/disorders-of-mechanisms-of-calcium-metabolism-control-as-potential-risk-factors-of-prostate-cancer
#9
Dorota Skrajnowska, Barbara Bobrowska-Korczak, Andrzej Tokarz
Prostate cancer significantly affects the overall morbidity and mortality of malignant tumours in highly developed countries. Important risk factors include family predisposition and regional, racial and dietary determinants. The scientific literature contains a great deal of data on the role of calcium and dairy products in general in the process of neoplastic transformation of the prostate. This is most likely linked to the fact that changes in the concentration of calcium ions control such varied life processes as secretion of hormones and neurotransmitters, the level of cyclic nucleotides, and cell growth, division and differentiation...
September 12, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28900510/egln1-c-myc-induced-lymphoid-specific-helicase-inhibits-ferroptosis-through-lipid-metabolic-gene-expression-changes
#10
Yiqun Jiang, Chao Mao, Rui Yang, Bin Yan, Ying Shi, Xiaoli Liu, Weiwei Lai, Yating Liu, Xiang Wang, Desheng Xiao, Hu Zhou, Yan Cheng, Fenglei Yu, Ya Cao, Shuang Liu, Qin Yan, Yongguang Tao
Ferroptosis is a newly discovered form of non-apoptotic cell death in multiple human diseases. However, the epigenetic mechanisms underlying ferroptosis remain poorly defined. First, we demonstrated that lymphoid-specific helicase (LSH), which is a DNA methylation modifier, interacted with WDR76 to inhibit ferroptosis by activating lipid metabolism-associated genes, including GLUT1, and ferroptosis related genes SCD1 and FADS2, in turn, involved in the Warburg effect. WDR76 targeted these genes expression in dependent manner of LSH and chromatin modification in DNA methylation and histone modification...
2017: Theranostics
https://www.readbyqxmd.com/read/28899208/the-regulation-of-nrf2-by-nutrient-responsive-signaling-and-its-role-in-anabolic-cancer-metabolism
#11
Sae Bom Lee, Brianna Sellers, Gina DeNicola
SIGNIFICANCE: The stress-responsive transcription factor nuclear factor erythroid 2 p45-related factor 2, or NRF2, regulates the expression of many cytoprotective enzymes to mitigate oxidative stress under physiological conditions. NRF2 is activated in response to oxidative stress, growth factor signaling, and changes in nutrient status. In addition, somatic mutations that disrupt the interaction between NRF2 and its negative regulator Kelch-like erythroid cell-derived protein with CNC homology (ECH)- associated 1 (KEAP1) commonly occur in cancer and are thought to promote tumorigenesis...
September 13, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28898813/insight-into-the-modulation-of-intestinal-proteome-of-juvenile-common-carp-cyprinus-carpio-l-after-dietary-exposure-to-zno-nanoparticles
#12
Latifeh Chupani, Hamid Niksirat, Vanessa Lünsmann, Sven-Bastiaan Haange, Martin von Bergen, Nico Jehmlich, Eliska Zuskova
ZnO nanoparticles (NPs) are widely used in industrial and consumer products. Therefore understanding their interaction with biological systems is key to their safe application. Proteomics was applied to assess the sub-lethal effects of dietary ZnO NPs on two parts of carp intestine, the intestinal folds and the muscular parts. A commercial carp feed containing 500mgkg(-1) of ZnO NPs was fed to fish for six weeks. The abundances of 32 proteins in the treated intestinal folds were significantly changed and in addition, 28 proteins were significantly changed in the muscular parts...
September 9, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28898588/micrornas-in-the-pathogenesis-of-type-2-diabetes-new-research-progress-and-future-direction
#13
Chenggui Miao, Guoxue Zhang, Zhongwen Xie, Jun Chang
MicroRNA (miRNA) is a short non-coding RNA that can influence messenger RNA (mRNA) processing at the post-transcriptional level. A large number of miRNAs have been found in virtually all species so far, and these small molecules play an important role in many different physiological processes and various pathologic conditions, such as cell metabolism, cancer, autoimmune disease, and diabetes mellitus. Type 2 diabetes (T2D) arises from a dysregulated response to the elevated glucose level in the circulation...
September 12, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28893623/cyp17a1-inhibitor-abiraterone-an-anti-prostate-cancer-drug-also-inhibits-the-21-hydroxylase-activity-of-cyp21a2
#14
Jana Malikova, Simone Brixius-Anderko, Sameer S Udhane, Shaheena Parween, Bernhard Dick, Rita Bernhardt, Amit V Pandey
Abiraterone is an inhibitor of CYP17A1 which is used for the treatment of castration resistant prostate cancer. Abiraterone is known to inhibit several drug metabolizing cytochrome P450 enzymes including CYP1A2, CYP2D6, CYP2C8, CYP2C9, CYP2C19, CYP3A4 and CYP3A5, but its effects on steroid metabolizing P450 enzymes are not clear. In preliminary results, we had observed inhibition of CYP21A2 by 1μM abiraterone. Here we are reporting the effect of abiraterone on activities of CYP21A2 in human adrenal cells as well as with purified recombinant CYP21A2...
September 8, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28891933/tyrosine-kinase-inhibitors-therapies-with-mainly-anti-angiogenic-activity-in-advanced-renal-cell-carcinoma-value-of-pet-ct-in-response-evaluation
#15
REVIEW
Girolamo Ranieri, Ilaria Marech, Artor Niccoli Asabella, Alessandra Di Palo, Mariangela Porcelli, Valentina Lavelli, Giuseppe Rubini, Cristina Ferrari, Cosmo Damiano Gadaleta
Renal cell carcinoma (RCC) is the most frequent renal tumor and the majority of patients are diagnosed with advanced disease. Tumor angiogenesis plays a crucial role in the development and progression of RCC together with hypoxia and glucose metabolism. These three pathways are strictly connected to the cell growth and proliferation, like a loop that is self-feeding. Over the last few years, the ever-deeper knowledge of its contribution in metastatic RCC led to the discovery of numerous tyrosine kinase inhibitors (TKIs) targeting pro-angiogenic receptors at different levels such as sunitinib, sorafenib, pazopanib, axitinib, tivozanib, and dovitinib...
September 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28891034/rheb1-insufficiency-in-aged-male-mice-is-associated-with-stress-induced-seizures
#16
Qi Tian, Pavel Gromov, Joachim H Clement, Yingming Wang, Marc Riemann, Falk Weih, Xiao-Xin Sun, Mu-Shui Dai, Lev M Fedorov
The mechanistic target of rapamycin (mTOR), a protein kinase, is a central regulator of mammalian metabolism and physiology. Protein mTOR complex 1 (mTORC1) functions as a major sensor for the nutrient, energy, and redox state of a cell and is activated by ras homolog enriched in brain (RHEB1), a GTP-binding protein. Increased activation of mTORC1 pathway has been associated with developmental abnormalities, certain form of epilepsy (tuberous sclerosis), and cancer. Clinically, those mTOR-related disorders are treated with the mTOR inhibitor rapamycin and its rapalogs...
September 10, 2017: GeroScience
https://www.readbyqxmd.com/read/28888995/mtor-signaling-in-immune-cells-and-its-implications-for-cancer-immunotherapy
#17
Hu Zeng
The realization that cellular metabolism dictates immune cell development, differentiation and function affords metabolic intervention as a potential venue for cancer immunotherapy. mTOR signaling, as a metabolic master regulator, controls immune cell biology in a cell type-specific and context dependent manner. Furthermore, mTOR activity needs to be fine-tuned to maintain proper immune function. These properties may be exploited for therapeutic purpose, yet caution should be taken against radical changes of mTOR activity...
September 6, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28886030/analysis-of-the-whole-transcriptome-from-gingivo-buccal-squamous-cell-carcinoma-reveals-deregulated-immune-landscape-and-suggests-targets-for-immunotherapy
#18
Richa Singh, Navonil De Sarkar, Sumanta Sarkar, Roshni Roy, Esita Chattopadhyay, Anindita Ray, Nidhan K Biswas, Arindam Maitra, Bidyut Roy
BACKGROUND: Gingivo-buccal squamous cell carcinoma (GBSCC) is one of the most common oral cavity cancers in India with less than 50% patients surviving past 5 years. Here, we report a whole transcriptome profile on a batch of GBSCC tumours with diverse tobacco usage habits. The study provides an entire landscape of altered expression with an emphasis on searching for targets with therapeutic potential. METHODS: Whole transcriptomes of 12 GBSCC tumours and adjacent normal tissues were sequenced and analysed to explore differential expression of genes...
2017: PloS One
https://www.readbyqxmd.com/read/28884042/aberrant-control-of-nf-%C3%AE%C2%BAb-in-cancer-permits-transcriptional-and-phenotypic-plasticity-to-curtail-dependence-on-host-tissue-molecular-mode
#19
Spiros A Vlahopoulos
The role of the transcription factor NF-κB in shaping the cancer microenvironment is becoming increasingly clear. Inflammation alters the activity of enzymes that modulate NF-κB function, and causes extensive changes in genomic chromatin that ultimately drastically alter cell-specific gene expression. NF-κB regulates the expression of cytokines and adhesion factors that control interactions among adjacent cells. As such, NF-κB fine tunes tissue cellular composition, as well as tissues' interactions with the immune system...
August 2017: Cancer Biology & Medicine
https://www.readbyqxmd.com/read/28883079/folate-dietary-insufficiency-and-folic-acid-supplementation-similarly-impair-metabolism-and-compromise-hematopoiesis
#20
Curtis J Henry, Travis Nemkov, Matias Casas-Selves, Ganna Bilousova, Vadym Zaberezhnyy, Kelly C Higa, Natalie J Serkova, Krik C Hansen, Angelo D' Alessandro, James DeGregori
While dietary folate deficiency is associated with increased risk for birth defects and other diseases, evidence suggests that supplementation with folic acid can contribute to predisposition to some diseases, including immune dysfunction and cancer. Here we show that diets supplemented with folic acid both below and above the recommended levels led to significantly altered metabolism in multiple tissues in mice. Surprisingly, both low and excessive dietary folate induced similar metabolic changes, which were particularly evident for nucleotide biosynthetic pathways in B-progenitor cells...
September 7, 2017: Haematologica
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