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https://www.readbyqxmd.com/read/28207290/fatty-acid-and-mineral-receptors-as-drug-targets-for-gastrointestinal-disorders
#1
Pawin Pongkorpsakol, Aekkacha Moonwiriyakit, Chatchai Muanprasat
Nutrient-sensing receptors, including fatty acid receptors (FFA1-FFA4), Ca(2+)-sensing receptors and Zn(2+)-sensing receptors, are involved in several biological processes. These receptors are abundantly expressed in the GI tract, where they have been shown to play crucial roles in regulating GI function. This review provides an overview of the GI functions of fatty acid and mineral receptors, including the regulation of gastric and enteroendocrine functions, GI motility, ion transport and cell growth. Recently, several lines of evidence have implicated these receptors as promising therapeutic targets for the treatment of GI disorders, for example, inflammatory bowel disease, colorectal cancer, metabolic syndrome and diarrheal diseases...
February 16, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28202602/cancer-cell-behaviors-mediated-by-dysregulated-ph-dynamics-at-a-glance
#2
REVIEW
Katharine A White, Bree K Grillo-Hill, Diane L Barber
Dysregulated pH is a common characteristic of cancer cells, as they have an increased intracellular pH (pHi) and a decreased extracellular pH (pHe) compared with normal cells. Recent work has expanded our knowledge of how dysregulated pH dynamics influences cancer cell behaviors, including proliferation, metastasis, metabolic adaptation and tumorigenesis. Emerging data suggest that the dysregulated pH of cancers enables these specific cell behaviors by altering the structure and function of selective pH-sensitive proteins, termed pH sensors...
February 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28198817/dynamic-properties-of-calcium-activated-chloride-currents-in-xenopus-laevis-oocytes
#3
Ildefonso M De la Fuente, Iker Malaina, Alberto Pérez-Samartín, María Dolores Boyano, Gorka Pérez-Yarza, Carlos Bringas, Álvaro Villarroel, María Fedetz, Rogelio Arellano, Jesus M Cortes, Luis Martínez
Chloride is the most abundant permeable anion in the cell, and numerous studies in the last two decades highlight the great importance and broad physiological role of chloride currents mediated anion transport. They participate in a multiplicity of key processes, as for instance, the regulation of electrical excitability, apoptosis, cell cycle, epithelial secretion and neuronal excitability. In addition, dysfunction of Cl(-) channels is involved in a variety of human diseases such as epilepsy, osteoporosis and different cancer types...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28193528/cellular-acidification-as-a-new-approach-to-cancer-treatment-and-to-the-understanding-and-therapeutics-of-neurodegenerative-diseases
#4
REVIEW
Salvador Harguindey, Daniel Stanciu, Jesús Devesa, Khalid Alfarouk, Rosa Angela Cardone, Julian David Polo Orozco, Pablo Devesa, Cyril Rauch, Gorka Orive, Eduardo Anitua, Sébastien Roger, Stephan J Reshkin
During the last few years, the understanding of the dysregulated hydrogen ion dynamics and reversed proton gradient of cancer cells has resulted in a new and integral pH-centric paradigm in oncology, a translational model embracing from cancer etiopathogenesis to treatment. The abnormalities of intracellular alkalinization along with extracellular acidification of all types of solid tumors and leukemic cells have never been described in any other disease and now appear to be a specific hallmark of malignancy...
February 10, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28167419/comparative-pharmacokinetic-profiles-of-selected-irreversible-tyrosine-kinase-inhibitors-neratinib-and-pelitinib-with-apigenin-in-rat-plasma-by-uplc-ms-ms
#5
Hadir M Maher, Nourah Z Alzoman, Shereen M Shehata, Ashwag O Abahussain
Neratinib (NER) and pelitinib (PEL) are irreversible tyrosine kinase inhibitors (TKIs) that have been recently employed in cancer treatment. Apigenin (API), among other flavonoids, is known to have antioxidant, anti-proliferative, and carcinogenic effect. API can potentiate the antitumor effect of chemotherapeutic agents and/or alleviate the side effects of many anticancer agents. Since TKIs are mostly metabolized by CYP3A4 enzymes and that API could alter the enzymatic activity, potential drug interactions could be expected following their co-aministration...
January 31, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28111813/chemometric-based-identification-and-validation-of-specific-chemical-markers-for-geographical-seasonal-and-gender-variations-in-tinospora-cordifolia-stem-using-hplc-esi-qtof-ms-analysis
#6
Vikas Bajpai, Sunil Kumar, Awantika Singh, Jyotsana Singh, M P S Negi, Sumit Kumar Bag, Nikhil Kumar, Rituraj Konwar, Brijesh Kumar
INTRODUCTION: Tinospora cordifolia is a widely distributed medicinal plant used in various traditional and commercial Ayurvedic formulations. Due to the wide use of this plant it is important to know the extent of variability in the metabolite profile resulting from geographical location, season and gender. OBJECTIVE: To develop a statistical approach based on phytochemical markers for confident prediction of variations in metabolic profile and cytotoxicity due to geographical, seasonal and gender difference in T...
January 23, 2017: Phytochemical Analysis: PCA
https://www.readbyqxmd.com/read/28104391/na-h-exchanger-mediated-hydrogen-ion-extrusion-as-a-carcinogenic-signal-in-triple-negative-breast-cancer-etiopathogenesis-and-prospects-for-its-inhibition-in-therapeutics
#7
REVIEW
Schammim Ray Amith, Larry Fliegel
Breast cancer is the leading cause of cancer-related death in women in Europe and North America, and metastasis is the primary cause of fatality in patients with breast cancer. While some breast cancers are quite treatable, the triple-negative breast cancers are more metastatic and resistant to chemotherapy. There is clearly an urgent need for better treatments for this form of the disease. Breast cancer is characterized by genetically complex intra-tumour heterogeneity, particularly within the triple-negative clinical subtype...
January 16, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28101932/amino-acid-profiling-of-zinc-resistant-prostate-cancer-cell-lines-associations-with-cancer-progression
#8
Monika Kratochvilova, Martina Raudenska, Zbynek Heger, Lukas Richtera, Natalia Cernei, Vojtech Adam, Petr Babula, Marie Novakova, Michal Masarik, Jaromir Gumulec
BACKGROUND: Failure in intracellular zinc accumulation is a key process in prostate carcinogenesis. Nevertheless, epidemiological studies of zinc administration have provided contradicting results. In order to examine the impact of the artificial intracellular increase of zinc(II) ions on prostate cancer metabolism, PNT1A, 22Rv1, and PC-3 prostatic cell lines-depicting different stages of cancer progression-and their zinc-resistant counterparts were used. To determine "benign" and "malignant" metabolic profiles, amino acid patterns, gene expression, and antioxidant capacity of these cell lines were assessed...
January 19, 2017: Prostate
https://www.readbyqxmd.com/read/28088622/reactive-oxygen-species-and-cancer-paradox-to-promote-or-to-suppress
#9
REVIEW
Sehamuddin Galadari, Anees Rahman, Siraj Pallichankandy, Faisal Thayyullathil
Reactive oxygen species (ROS), a group of highly reactive ions and molecules, are increasingly being appreciated as powerful signaling molecules involved in the regulation of a variety of biological processes. Indeed, their role is continuously being delineated in a variety of pathophysiological conditions. For instance, cancer cells are shown to have increased ROS levels in comparison to their normal counterparts. This is partly due to an enhanced metabolism and mitochondrial dysfunction in cancer cells. The escalated ROS generation in cancer cells contributes to the biochemical and molecular changes necessary for the tumor initiation, promotion and progression, as well as, tumor resistance to chemotherapy...
January 11, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28039486/cd147-a-small-molecule-transporter-ancillary-protein-at-the-crossroad-of-multiple-hallmarks-of-cancer-and-metabolic-reprogramming
#10
Agnieszka A Kendrick, Johnathon Schafer, Monika Dzieciatkowska, Travis Nemkov, Angelo D'Alessandro, Deepika Neelakantan, Heide L Ford, Chad G Pearson, Colin D Weekes, Kirk C Hansen, Elan Z Eisenmesser
Increased expression of CD147 in pancreatic cancer has been proposed to play a critical role in cancer progression via CD147 chaperone function for lactate monocarboxylate transporters (MCTs). Here, we show for the first time that CD147 interacts with membrane transporters beyond MCTs and exhibits a protective role for several of its interacting partners. CD147 prevents its interacting partner's proteasome-dependent degradation and incorrect plasma membrane localization through the CD147 transmembrane (TM) region...
January 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28038952/metabotypes-of-breast-cancer-cell-lines-revealed-by-non-targeted-metabolomics
#11
Sébastien Dubuis, Franziska Baenke, Nina Scherbichler, Leila T Alexander, Almut Schulze, Nicola Zamboni
We present an analysis of intracellular metabolism by non-targeted, high-throughput metabolomics profiling of 18 breast cell lines. We profiled >900 putatively annotated metabolite ions for >100 samples collected under both normoxic and hypoxic conditions and revealed extensive heterogeneity across all metabolic pathways and cell lines. Cell line-specific metabolome profiles dominated over patterns associated with malignancy or with the clinical nomenclature of breast cancer cells. Such characteristic metabolome profiles were reproducible across different laboratories and experiments and exhibited mild to robust changes with change in experimental conditions...
December 27, 2016: Metabolic Engineering
https://www.readbyqxmd.com/read/28034363/the-screening-of-novel-inhibitors-against-leishmania-donovani-calcium-ion-channel-to-fight-leishmaniasis
#12
Mohammad Kashif, Partha Pratim Manna, Yusuf Akhter, Mohammed Alaidarous, Abdur Rub
Leishmania is an intracellular protozoan parasite which causes Leishmaniasis, a global health problem affecting millions of people throughout 89 different countries in the world. The current treatment which includes use of amphotericin B, antimonials, and others has major drawbacks due to toxicity, resistance, and extraordinary high cost. So there is an urgent need of development of new drug targets to fight against leishmaniasis. In this regard we have selected Leishmania donovani Ca2+ ion channel (Ld-CC) as potential drug target...
December 30, 2016: Infectious Disorders Drug Targets
https://www.readbyqxmd.com/read/28017863/metabolomic-profiling-of-prostate-cancer-by-matrix-assisted-laser-desorption-ionization-fourier-transform-ion-cyclotron-resonance-mass-spectrometry-imaging-using-matrix-coating-assisted-by-an-electric-field-mcaef
#13
Xiaodong Wang, Jun Han, Darryl B Hardie, Juncong Yang, Jingxi Pan, Christoph H Borchers
In this work, we combined the use of two MALDI matrices (quercetin and 9-aminoacridine), a recently developed new matrix coating technique - matrix coating assisted by an electric field (MCAEF), and matrix-assisted laser desorption/ionization - Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICRMS) to detect and image endogenous compounds in the cancerous and non-cancerous regions of three human prostate cancer (stage II) tissue specimens. After three rounds of imaging data acquisitions (i...
December 23, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27999995/lipid-glycosylation-a-primer-for-histochemists-and-cell-biologists
#14
REVIEW
Jürgen Kopitz
Glycolipids are glycoconjugates that are predominantly found on the extracellular surface of cells ranging from bacteria to men. In bacteria and plants, glycoglycerolipids represent the main glycolipid species. Ceramides as carrier for glycans, termed glycosphingolipids (GSLs), are characteristic for vertebrates and insects. The glycan part is involved in a variety of biological activities including cell adhesion and initiation of signaling. Most of these functions rest on two basic principles: (1) GSLs spontaneously contribute to organize lipid rafts in biological membranes, thereby forming functional complexes ('glycosynapses') with receptor proteins and ion channels and (2) their glycans are bound by receptors like galectins (protein-glycan recognition) or cognate glycans (glycan-glycan recognition)...
February 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/27917942/chemical-imaging-of-platinum-based-drugs-and-their-metabolites
#15
Xin Liu, Amanda B Hummon
Platinum-based drugs (cisplatin, carboplatin, and oxaliplatin) are widely used therapeutic agents for cancer treatment. Even though the platinum (Pt)-drugs are routinely used clinically, a clear picture of their distribution within tumor tissues is lacking. The current methods to image the distribution of Pt drugs are limited and do not enable the discrimination of the drug from its metabolites. In this manuscript, we demonstrate a methodology that enables chemical imaging of a Pt drug and its metabolites simultaneously and specifically...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27890939/the-metal-face-of-protein-tyrosine-phosphatase-1b
#16
REVIEW
Elisa Bellomo, Kshetrimayum Birla Singh, Alberto Massarotti, Christer Hogstrand, Wolfgang Maret
A new paradigm in metallobiochemistry describes the activation of inactive metalloenzymes by metal ion removal. Protein tyrosine phosphatases (PTPs) do not seem to require a metal ion for enzymatic activity. However, both metal cations and metal anions modulate their enzymatic activity. One binding site is the phosphate binding site at the catalytic cysteine residue. Oxyanions with structural similarity to phosphate, such as vanadate, inhibit the enzyme with nanomolar to micromolar affinities. In addition, zinc ions (Zn(2+)) inhibit with picomolar to nanomolar affinities...
November 15, 2016: Coordination Chemistry Reviews
https://www.readbyqxmd.com/read/27890727/synthetic-tambjamine-analogues-induce-mitochondrial-swelling-and-lysosomal-dysfunction-leading-to-autophagy-blockade-and-necrotic-cell-death-in-lung-cancer
#17
Ananda M Rodilla, Luís Korrodi-Gregório, Elsa Hernando, Pilar Manuel-Manresa, Roberto Quesada, Ricardo Pérez-Tomás, Vanessa Soto-Cerrato
Current pharmacological treatments for lung cancer show very poor clinical outcomes, therefore, the development of novel anticancer agents with innovative mechanisms of action is urgently needed. Cancer cells have a reversed pH gradient compared to normal cells, which favours cancer progression by promoting proliferation, metabolic adaptation and evasion of apoptosis. In this regard, the use of ionophores to modulate intracellular pH appears as a promising new therapeutic strategy. Indeed, there is a growing body of evidence supporting ionophores as novel antitumour drugs...
February 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27882891/a-comparative-mass-spectrometric-study-of-fatty-acids-and-metals-in-some-seed-extracts
#18
Sonia Niculina Suvar, R Bleiziffer, P Podea, A Iordache, C Voica, R Zgavarogea, M Culea
A major cause of cardiovascular diseases and cancer is diet content, so the optimization of micronutrients in food is very important. Omega-3 fatty acids supplementation for patients had beneficial effects on subjective global assessment score and metabolic profiles. Fatty acids content and the metal ions in different seeds (e.g. linseed, poppy, grape, hemp, nuts, pumpkin, sesame, watermelon, chia) recommended as food supplements, purchased on the Romanian market, were compared. Gas chromatography coupled to mass spectrometry (GC-MS) was used as an excellent technique for fatty acids identification and quantitation, and inductively coupled plasma mass spectrometer (ICP-MS) for analytical measurements of metals...
2016: European Journal of Mass Spectrometry
https://www.readbyqxmd.com/read/27856537/phosphocysteine-in-the-prl-cnnm-pathway-mediates-magnesium-homeostasis
#19
Irina Gulerez, Yosuke Funato, Howie Wu, Meng Yang, Guennadi Kozlov, Hiroaki Miki, Kalle Gehring
PRLs (phosphatases of regenerating liver) are frequently overexpressed in human cancers and are prognostic markers of poor survival. Despite their potential as therapeutic targets, their mechanism of action is not understood in part due to their weak enzymatic activity. Previous studies revealed that PRLs interact with CNNM ion transporters and prevent CNNM4-dependent Mg(2+) transport, which is important for energy metabolism and tumor progression. Here, we report that PRL-CNNM complex formation is regulated by the formation of phosphocysteine...
December 2016: EMBO Reports
https://www.readbyqxmd.com/read/27804847/the-warburg-effect-and-the-hallmarks-of-cancer
#20
REVIEW
Laurent Schwartz, Claudiu T Supuran, Khalid O Alfarouk
It is a longstanding debate whether cancer is one disease or a set of very diverse diseases. The goal of this paper is to suggest strongly that most of (if not all) the hallmarks of cancer could be the consequence of the Warburg's effect. As a result of the metabolic impairment of the oxidative phosphorylation, there is a decrease in ATP concentration. To compensate the reduced energy yield, there is massive glucose uptake, anaerobic glycolysis, with an up-regulation of the Pentose Phosphate Pathway resulting in increased biosynthesis leading to increased cell division and local pressure...
2017: Anti-cancer Agents in Medicinal Chemistry
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