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https://www.readbyqxmd.com/read/29441626/identification-of-metabolites-of-anticancer-candidate-salinomycin-using-liquid-chromatography-coupled-with-q-tof-and-hybrid-qqq-linear-ion-trap-mass-spectrometry
#1
Małgorzata Olejnik, Lidia Radko, Piotr Jedziniak
RATIONALE: Salinomycin is an ionophore antibiotic with potential anti-cancer activity. The history of its use in veterinary medicine show large differences in species susceptibility to its toxicity. At the same time, the results of so-far research suggest the correlation between the extent and pathways of ionophore biotransformation and its toxicity. The biotransformation pattern of salinomycin has not been studied so far. METHODS: The extracts from culture media of human hepatoma cells (HepG2) exposed to salinomycin were analysed with two mass spectrometry techniques...
February 14, 2018: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/29418080/insights-from-ion-binding-site-network-analysis-into-evolution-and-functions-of-proteins
#2
Blaž Škrlj, Tanja Kunej, Janez Konc
Many biological phenomena can be represented as complex networks. Using a protein binding site comparison approach, we generated a network of ion binding sites on the scale of all known protein structures from the Protein Data Bank. We found that this ion binding site similarity network is scale-free, indicating a network in which a few ion binding site scaffolds are the network hubs, and these are connected to hundreds of nodes, whereas the vast majority of nodes have only a few neighbors. Enrichment and statistical analysis of the network components and communities yielded insights into underlying processes from the functional and the structural perspective...
February 8, 2018: Molecular Informatics
https://www.readbyqxmd.com/read/29410996/modulation-of-thiol-dependent-redox-system-by-metal-ions-via-thioredoxin-and-glutaredoxin-systems
#3
REVIEW
Yanfang Ouyang, Yi Peng, Jing Li, Arne Holmgren, Jun Lu
The thioredoxin and glutaredoxin systems possess a variety of biological activities in mammalian cells, including the defense against oxidative stress, regulation of DNA synthesis, the cell cycle and the mediation of apoptosis. The thioredoxin system, comprised of NADPH, thioredoxin reductase (TrxR) and thioredoxin (Trx), exerts its activities via a disulfide-dithiol exchange reaction. Mammalian TrxRs are selenoproteins; the thiols and selenols in the active site of these enzymes confer the thioredoxin system to work as soft bases, which have a high affinity with soft acids, including numerous metal ions...
February 7, 2018: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29397400/cell-death-mechanisms-of-the-anti-cancer-drug-etoposide-on-human-cardiomyocytes-isolated-from-pluripotent-stem-cells
#4
Harshal Nemade, Umesh Chaudhari, Aviseka Acharya, Jürgen Hescheler, Jan Georg Hengstler, Symeon Papadopoulos, Agapios Sachinidis
Etoposide (ETP) and anthracyclines are applied for wide anti-cancer treatments. However, the ETP-induced cardiotoxicity remains to be a major safety issue and the underlying cardiotoxic mechanisms are not well understood. This study is aiming to unravel the cardiotoxicity profile of ETP in comparison to anthracyclines using physiologically relevant human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs). Using xCELLigence real-time cell analyser (RTCA), we found that single high dose of ETP induces irreversible increase in hPSC-CMs beating rate and decrease in beating amplitude...
February 3, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29396267/a-new-role-for-the-mitochondrial-pro-apoptotic-protein-smac-diablo-in-phospholipid-synthesis-associated-with-tumorigenesis
#5
Avijit Paul, Yakov Krelin, Tasleem Arif, Rina Jeger, Varda Shoshan-Barmatz
The mitochondrial pro-apoptotic protein SMAC/Diablo participates in apoptosis by negatively regulating IAPs and activating caspases, thus encouraging apoptosis. Unexpectedly, we found that SMAC/Diablo is overexpressed in cancer. This paradox was addressed here by silencing SMAC/Diablo expression using specific siRNA (si-hSMAC). In cancer cell lines and subcutaneous lung cancer xenografts in mice, such silencing reduced cell and tumor growth. Immunohistochemistry and electron microscopy of the si-hSMAC-treated residual tumor demonstrated morphological changes, including cell differentiation and reorganization into glandular/alveoli-like structures and elimination of lamellar bodies, surfactant-producing organs...
December 24, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29383104/chac1-degradation-of-glutathione-enhances-cystine-starvation-induced-necroptosis-and-ferroptosis-in-human-triple-negative-breast-cancer-cells-via-the-gcn2-eif2%C3%AE-atf4-pathway
#6
Meng-Shian Chen, Sheng-Fan Wang, Chih-Yi Hsu, Pen-Hui Yin, Tien-Shun Yeh, Hsin-Chen Lee, Ling-Ming Tseng
Cancer cells exhibit an abnormal amino acid metabolism and a dependence on specific amino acids, which might provide potential targets for treating cancer patients. In this study, we demonstrated that human triple negative breast cancer (TNBC) cells were highly susceptible to cystine starvation. We found that necrostatin-1 (Nec-1, a RIP1 inhibitor), necrosulfonamide (an MLKL inhibitor), deferoxamine (an ion chelator), ferrostatin-1 (a ferroptosis inhibitor) and RIP1 knockdown can prevent cystine-starvation-induced cell death, suggesting that cystine starvation induces necroptosis and ferroptosis in TNBC cells...
December 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29382206/tof-sims-analysis-of-an-isocitrate-dehydrogenase-1-mutation-associated-oncometabolite-in-cancer-cells
#7
Jungdae Park, Hee-Kyung Na, Hyun Kyong Shon, Hye Young Son, Yong-Min Huh, Sang-Won Lee, Tae Geol Lee
The development of analytical tools for accurate and sensitive detection of intracellular metabolites associated with mutated metabolic enzymes is important in cancer diagnosis and staging. The gene encoding the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) is mutated in various cancers, and mutant IDH1 could represent a good biomarker and potent target for cancer therapy. Owing to a mutation in an important arginine residue in the catalytic pocket, mutant IDH1 catalyzes the production of 2-hydroxyglutarate (2-HG) instead of its wild type product α-ketoglutarate (α-KG), which is involved in multiple cellular pathways involving the hydroxylation of proteins, ribonucleic acid, and deoxyribose nucleic acid (DNA)...
January 30, 2018: Biointerphases
https://www.readbyqxmd.com/read/29358341/temporal-effects-of-combined-birinapant-and-paclitaxel-on-pancreatic-cancer-cells-investigated-via-large-scale-ion-current-based-quantitative-proteomics-ionstar
#8
Xue Wang, Jin Niu, Jun Li, Xiaomeng Shen, Shichen Shen, Robert M Straubinger, Jun Qu
Despite decades of effort, pancreatic adenocarcinoma (PDAC) remains an intractable clinical challenge. An insufficient understanding of mechanisms underlying tumor cell responses to chemotherapy contributes significantly to the lack of effective treatment regimens. Here, paclitaxel, a first-line chemotherapeutic agent, was observed to interact synergistically with birinapant, a Second Mitochondrial-derived Activator of Caspases mimetic. Therefore, we investigated molecular-level drug interaction mechanisms using comprehensive, reproducible, and well-controlled ion-current-based MS1 quantification (IonStar)...
January 22, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29303993/endolysosomal-cation-channels-and-cancer-a-link-with-great-potential
#9
REVIEW
Christian Grimm, Karin Bartel, Angelika M Vollmar, Martin Biel
The endolysosomal system (ES) consists of lysosomes; early, late, and recycling endosomes; and autophagosomes. It is a key regulator not only of macromolecule degradation and recycling, plasma membrane repair, homeostasis, and lipid storage, but also of antigen presentation, immune defense, cell motility, cell death signaling, tumor growth, and cancer progression. In addition, it plays a critical role in autophagy, and the autophagy-lysosome pathway is intimately associated with the hallmarks of cancer, such as escaping cell death pathways, evading immune surveillance, and deregulating metabolism...
January 5, 2018: Pharmaceuticals
https://www.readbyqxmd.com/read/29303978/telomere-homeostasis-interplay-with-magnesium
#10
REVIEW
Donogh Maguire, Ognian Neytchev, Dinesh Talwar, Donald McMillan, Paul G Shiels
Telomere biology, a key component of the hallmarks of ageing, offers insight into dysregulation of normative ageing processes that accompany age-related diseases such as cancer. Telomere homeostasis is tightly linked to cellular metabolism, and in particular with mitochondrial physiology, which is also diminished during cellular senescence and normative physiological ageing. Inherent in the biochemistry of these processes is the role of magnesium, one of the main cellular ions and an essential cofactor in all reactions that use ATP...
January 5, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29225692/recent-advances-in-radiation-oncology
#11
REVIEW
Cristina Garibaldi, Barbara Alicja Jereczek-Fossa, Giulia Marvaso, Samantha Dicuonzo, Damaris Patricia Rojas, Federica Cattani, Anna Starzyńska, Delia Ciardo, Alessia Surgo, Maria Cristina Leonardi, Rosalinda Ricotti
Radiotherapy (RT) is very much a technology-driven treatment modality in the management of cancer. RT techniques have changed significantly over the past few decades, thanks to improvements in engineering and computing. We aim to highlight the recent developments in radiation oncology, focusing on the technological and biological advances. We will present state-of-the-art treatment techniques, employing photon beams, such as intensity-modulated RT, volumetric-modulated arc therapy, stereotactic body RT and adaptive RT, which make possible a highly tailored dose distribution with maximum normal tissue sparing...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/29216863/ccl5-ccr5-interactions-modulate-metabolic-events-during-tumor-onset-to-promote-tumorigenesis
#12
Darrin Gao, Lisa H Cazares, Eleanor N Fish
BACKGROUND: In earlier studies we have shown that CCL5 activation of CCR5 induces the proliferation and survival of breast cancer cells in a mechanistic target of rapamycin (mTOR)-dependent manner and that this is in part due to CCR5-mediated increases in glycolytic metabolism. METHODS: Using the MDA-MB-231 triple negative human breast cancer cell line and mouse mammary tumor virus - polyomavirus middle T-antigen (MMTV-PyMT) mouse primary breast cancer cells, we conducted in vivo tumor transplant experiments to examine the effects of CCL5-CCR5 interactions in the context of regulating tumor metabolism...
December 8, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29210434/nano-confinement-driven-enhanced-magnetic-relaxivity-of-spions-for-targeted-tumor-bioimaging
#13
Tuyen Duong Thanh Nguyen, Arunkumar Pitchaimani, Colin Ferrel, Ravindra Thakkar, Santosh Aryal
Superparamagnetic iron oxide nanoparticles (SPIONs) are highly biocompatible and have a versatile synthetic technique based on coprecipitation, reduction-precipitation, and hydrothermal methods, where Fe3+ and Fe2+ react in aqueous solutions; both these ions are present in our body and have clear metabolic pathways; therefore, they have attracted extensive research interest and development in the field of diagnostic imaging and therapy. However, most SPION-based clinical diagnostic contrast agents are discontinued due to severe pain, low transverse magnetic relaxivity range of 80-180 mM-1 s-1, shorter circulation half-life, and lack of disease specificity...
December 6, 2017: Nanoscale
https://www.readbyqxmd.com/read/29182572/aberrant-lipid-metabolism-in-hepatocellular-carcinoma-revealed-by-liver-lipidomics
#14
Zhao Li, Ming Guan, Yu Lin, Xiao Cui, Yangyang Zhang, Zhenwen Zhao, Jiye Zhu
BACKGROUND: The aim of this study was to characterize the disorder of lipid metabolism in hepatocellular carcinoma (HCC). HCC is a worldwide disease. The research into the disorder of lipid metabolism in HCC is very limited. Study of lipid metabolism in liver cancer tissue may have the potential to provide new insight into HCC mechanisms. METHODS: A lipidomics study of HCC based on Ultra high performance liquid chromatography-electronic spray ionization-QTOF mass spectrometer (UPLC-ESI-QTOF MS) and Matrix assisted laser desorption ionization-fourier transform ion cyclotron resonance mass spectrometer (MALDI-FTICR MS) was performed...
November 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29155562/quantification-of-nanomaterial-nanomedicine-trafficking-in-vivo
#15
Liming Wang, Liang Yan, Jing Liu, Chunying Chen, Yuliang Zhao
Absorption, distribution, metabolism and excretion (ADME) of nanomaterials (NMs) or nanomedicines (NMs), are fundamental biological processes that dominate their nanomedical functions or nanotoxicities. Mostly, NMs exist in biological systems as a form of nanoparticles (NPs). However, to determine the composition, spatial distribution, and states of existence of NMs/NPs in vivo, upon entry into the body, as well as to monitor the dynamic changes of these information over time remain a challenge for the current analytical methodology due to their limited efficiently in characterizing interactions between these complex(nano)-complex(bio) systems...
November 20, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29155210/transition-from-androgenic-to-neurosteroidal-action-of-5%C3%AE-androstane-3%C3%AE-17%C3%AE-diol-through-the-type-a-%C3%AE-aminobutyric-acid-receptor-in-prostate-cancer-progression
#16
Ding Xia, Doan V Lai, Weijuan Wu, Zachary D Webb, Qing Yang, Lichao Zhao, Zhongxin Yu, Jessica E Thorpe, Bryan C Disch, Michael A Ihnat, Muralidharan Jayaraman, Danny N Dhanasekaran, Kelly L Stratton, Michael S Cookson, Kar-Ming Fung, Hsueh-Kung Lin
Androgen ablation is the standard of care prescribed to patients with advanced or metastatic prostate cancer (PCa) to slow down disease progression. Unfortunately, a majority of PCa patients under androgen ablation progress to castration-resistant prostate cancer (CRPC). Several mechanisms including alternative intra-prostatic androgen production and androgen-independent androgen receptor (AR) activation have been proposed for CRPC progression. Aldo-keto reductase family 1 member C3 (AKR1C3), a multi-functional steroid metabolizing enzyme, is specifically expressed in the cytoplasm of PCa cells; and positive immunoreactivity of the type A γ-aminobutyric acid receptor (GABAAR), an ionotropic receptor and ligand-gated ion channel, is detected on the membrane of PCa cells...
November 15, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29149404/the-translational-controlled-tumour-protein-tctp-biological-functions-and-regulation
#17
Ulrich-Axel Bommer
The Translational Controlled Tumour Protein TCTP (gene symbol TPT1, also called P21, P23, Q23, fortilin or histamine-releasing factor, HRF) is a highly conserved protein present in essentially all eukaryotic organisms and involved in many fundamental cell biological and disease processes. It was first discovered about 35 years ago, and it took an extended period of time for its multiple functions to be revealed, and even today we do not yet fully understand all the details. Having witnessed most of this history, in this chapter, I give a brief overview and review the current knowledge on the structure, biological functions, disease involvements and cellular regulation of this protein...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29137386/mitochondrial-calcium-uniporter-as-a-target-of-microrna-340-and-promoter-of-metastasis-via-enhancing-the-warburg-effect
#18
Changhui Yu, Yuhao Wang, Jiawen Peng, Qiang Shen, Mimi Chen, Wei Tang, Xiumei Li, Chunqing Cai, Bin Wang, Shaoxi Cai, Xiaojing Meng, Fei Zou
Background: A shift from oxygen phosphorylation to aerobic glycolysis was known as the Warburg effect and a characteristic of cancer cell metabolism facilitating metastasis. Mitochondrial calcium uniporter (MCU), a key ion channel that mediates Ca(2+) uptake into mitochondria, was found to promote cancer progression and metastasis. However, its explicit role in shifting metabolism of breast cancer cells has not been defined. Methods: We evaluated MCU overexpression or knock-down on migration, invasion and glucose metabolismin breast cancer cells...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29080017/safety-pharmacokinetics-metabolism-and-radiation-dosimetry-of-18-f-tetrafluoroborate-18-f-tfb-in-healthy-human-subjects
#19
Huailei Jiang, Nicholas R Schmit, Alex R Koenen, Aditya Bansal, Mukesh K Pandey, Robert B Glynn, Bradley J Kemp, Kera L Delaney, Angela Dispenzieri, Jamie N Bakkum-Gamez, Kah-Whye Peng, Stephen J Russell, Tina M Gunderson, Val J Lowe, Timothy R DeGrado
BACKGROUND: (18)F-Tetrafluoroborate ((18)F-TFB) is a promising iodide analog for PET imaging of thyroid cancer and sodium/iodide symporter (NIS) reporter activity in viral therapy applications. The aim of this study was to evaluate the safety, pharmacokinetics, biodistribution, and radiation dosimetry of high-specific activity (18)F-TFB in healthy human subjects. METHODS: (18)F-TFB was synthesized with specific activity of 3.2 ± 1.3 GBq/μmol (at the end of synthesis)...
October 27, 2017: EJNMMI Research
https://www.readbyqxmd.com/read/29028058/protein-protein-interaction-networks-as-a-new-perspective-to-evaluate-distinct-functional-roles-of-voltage-dependent-anion-channel-isoforms
#20
REVIEW
Marianna Caterino, Margherita Ruoppolo, Annalisa Mandola, Michele Costanzo, Stefania Orrù, Esther Imperlini
Voltage-dependent anion channels (VDACs) are a family of three mitochondrial porins and the most abundant integral membrane proteins of the mitochondrial outer membrane (MOM). VDACs are known to be involved in metabolite/ion transport across the MOM and in many cellular processes ranging from mitochondria-mediated apoptosis to the control of energy metabolism, by interacting with cytosolic, mitochondrial and cytoskeletal proteins and other membrane channels. Despite redundancy and compensatory mechanisms among VDAC isoforms, they display not only different channel properties and protein expression levels, but also distinct protein partners...
November 21, 2017: Molecular BioSystems
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