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https://www.readbyqxmd.com/read/28219421/regulation-of-voltage-gated-potassium-channels-attenuates-resistance-of-side-population-cells-to-gefitinib-in-the-human-lung-cancer-cell-line-nci-h460
#1
Seon Young Choi, Hang-Rae Kim, Pan Dong Ryu, So Yeong Lee
BACKGROUND: Side-population (SP) cells that exclude anti-cancer drugs have been found in various tumor cell lines. Moreover, SP cells have a higher proliferative potential and drug resistance than main population cells (Non-SP cells). Also, several ion channels are responsible for the drug resistance and proliferation of SP cells in cancer. METHODS: To confirm the expression and function of voltage-gated potassium (Kv) channels of SP cells, these cells, as well as highly expressed ATP-binding cassette (ABC) transporters and stemness genes, were isolated from a gefitinib-resistant human lung adenocarcinoma cell line (NCI-H460), using Hoechst 33342 efflux...
February 21, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28217814/-effects-of-growth-differentiation-factor-15-gdf-15-on-neurological-systems-cardiovascular-diseases-and-cancer-progression
#2
Dong-Dong Liu, Yan-Ai Mei
Growth differentiation factor-15 (GDF-15) is a member of the transforming growth factor beta superfamily. GDF-15 expression is dramatically upregulated during acute brain injury, cancer, cardiovascular disease, and inflammation, suggesting its potential value as a disease biomarker. It has been suggested that GDF-15 has neurotropic effects in the nervous system. Our studies showed that GDF-15 modulated the expression of neuronal K(+) and Ca(2+) ion channels and increased the release of excitatory transmitter in the medial prefrontal cortex of mice...
February 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28205574/neuropathic-pain
#3
REVIEW
Luana Colloca, Taylor Ludman, Didier Bouhassira, Ralf Baron, Anthony H Dickenson, David Yarnitsky, Roy Freeman, Andrea Truini, Nadine Attal, Nanna B Finnerup, Christopher Eccleston, Eija Kalso, David L Bennett, Robert H Dworkin, Srinivasa N Raja
Neuropathic pain is caused by a lesion or disease of the somatosensory system, including peripheral fibres (Aβ, Aδ and C fibres) and central neurons, and affects 7-10% of the general population. Multiple causes of neuropathic pain have been described and its incidence is likely to increase owing to the ageing global population, increased incidence of diabetes mellitus and improved survival from cancer after chemotherapy. Indeed, imbalances between excitatory and inhibitory somatosensory signalling, alterations in ion channels and variability in the way that pain messages are modulated in the central nervous system all have been implicated in neuropathic pain...
February 16, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28198817/dynamic-properties-of-calcium-activated-chloride-currents-in-xenopus-laevis-oocytes
#4
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
#5
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/28185236/regulation-of-osmolality-for-cancer-treatment
#6
REVIEW
Atsushi Shiozaki, Daisuke Ichikawa, Toshiyuki Kosuga, Yoshinori Marunaka, Eigo Otsuji
Disseminated metastasis is associated with a poor prognosis, and its management in the peritoneal or pleural cavity is crucial in the treatment of cancer. Recent studies show that ion and water transporters play important roles in fundamental cellular functions, including the regulation of cell volume that would be involved in the cancer process. Here, we review the evidence for hypotonic treatments of cancer and evaluate the potential of the cellular physiological approach in clinical management. The regulation of extracellular osmolality is a promising method, with several studies demonstrating the cytocidal effects of hypotonic solution on cancer cells...
February 10, 2017: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/28179976/biobetters-from-an-integrated-computational-experimental-approach
#7
REVIEW
Serdar Kuyucak, Veysel Kayser
Biobetters are new drugs designed from existing peptide or protein-based therapeutics by improving their properties such as affinity and selectivity for the target epitope, and stability against degradation. Computational methods can play a key role in such design problems-by predicting the changes that are most likely to succeed, they can drastically reduce the number of experiments to be performed. Here we discuss the computational and experimental methods commonly used in drug design problems, focusing on the inverse relationship between the two, namely, the more accurate the computational predictions means the less experimental effort is needed for testing...
2017: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/28177286/sloppy-morphological-tuning-in-identified-neurons-of-the-crustacean-stomatogastric-ganglion
#8
Adriane G Otopalik, Marie L Goeritz, Alexander C Sutton, Ted Brookings, Cosmo Joseph Guerini, Eve Marder
Neuronal physiology depends on a neuron's ion channel composition and unique morphology. Variable ion channel compositions can produce similar neuronal physiologies across animals. Less is known regarding the morphological precision required to produce reliable neuronal physiology. Theoretical studies suggest that morphology is tightly tuned to minimize wiring and conduction delay of synaptic events. We utilize high-resolution confocal microscopy and custom computational tools to characterize the morphologies of four neuron types in the stomatogastric ganglion (STG) of the crab Cancer borealis...
February 8, 2017: ELife
https://www.readbyqxmd.com/read/28167212/recruitment-of-rna-molecules-by-connexin-rna-binding-motifs-implication-in-rna-and-dna-transport-through-microvesicles-and-exosomes
#9
REVIEW
Marta Varela-Eirin, Adrian Varela-Vazquez, Marina Rodríguez-Candela Mateos, Anton Vila-Sanjurjo, Eduardo Fonseca, José L Mascareñas, M Eugenio Vázquez, Maria D Mayan
Connexins (Cxs) are integral membrane proteins that form high-conductance plasma membrane channels, allowing communication from cell to cell (via gap junctions) and from cells to the extracellular environment (via hemichannels). Initially described for their role in joining excitable cells (nerve and muscle), gap junctions (GJs) are found between virtually all cells in solid tissues and are essential for functional coordination by enabling the direct transfer of small signalling molecules, metabolites, ions, and electrical signals from cell to cell...
February 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28165322/when-complex-neuronal-structures-may-not-matter
#10
Adriane G Otopalik, Alexander C Sutton, Matthew Ryan Banghart, Eve Marder
Much work has explored animal-to-animal variability and compensation in ion channel expression. Yet, little is known regarding the physiological consequences of morphological variability. We quantify animal-to-animal variability in cable lengths (CV = 0.4) and branching patterns in the Gastric Mill (GM) neuron, an identified neuron type with highly-conserved physiological properties in the crustacean stomatogastric ganglion (STG) of Cancer borealis. We examined passive GM electrotonic structure by measuring the amplitudes and apparent reversal potentials (Erevs) of inhibitory responses evoked with focal glutamate photo-uncaging in the presence of TTX...
February 6, 2017: ELife
https://www.readbyqxmd.com/read/28161478/identification-of-tg100-115-as-a-new-and-potent-trpm7-kinase-inhibitor-which-suppresses-breast-cancer-cell-migration-and-invasion
#11
Chiman Song, Yeonju Bae, JinJoo Jun, Hyomin Lee, Nam Doo Kim, Kyung-Bok Lee, Wooyoung Hur, Jae-Yong Park, Taebo Sim
BACKGROUND: Transient receptor potential melastatin 7 (TRPM7) regulates breast cancer cell proliferation, migration, invasion and metastasis in its ion channel- and kinase domain-dependent manner. The pharmacological effects of TRPM7 ion channel inhibitors on breast cancer cells have been studied, but little is known about the effects of TRPM7 kinase domain inhibitors due to lack of potent TRPM7 kinase inhibitors. METHODS: Screening was performed by using TRPM7 kinase assay...
February 1, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28161459/peptide-microarray-based-characterization-of-antibody-responses-to-host-proteins-after-bacille-calmette-gu%C3%A3-rin-vaccination
#12
REVIEW
Davide Valentini, Martin Rao, Lalit Rane, Sayma Rahman, Rebecca Axelsson-Robertson, Rainer Heuchel, Matthias Löhr, Daniel Hoft, Susanna Brighenti, Alimuddin Zumla, Markus Maeurer
BACKGROUND: Bacille Calmette-Guérin (BCG) is the world's most widely distributed vaccine, used against tuberculosis (TB), in cancer immunotherapy, and in autoimmune diseases due to its immunomodulatory properties. To date, the effect of BCG vaccination on antibody responses to host proteins has not been reported. High-content peptide microarrays (HCPM) offer a unique opportunity to gauge specific humoral immune responses. METHODS: The sera of BCG-vaccinated healthy adults were tested on a human HCPM platform (4953 randomly selected epitopes of human proteins) to detect specific immunoglobulin gamma (IgG) responses...
February 2, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28134257/a-quantized-mechanism-for-activation-of-pannexin-channels
#13
Yu-Hsin Chiu, Xueyao Jin, Christopher B Medina, Susan A Leonhardt, Volker Kiessling, Brad C Bennett, Shaofang Shu, Lukas K Tamm, Mark Yeager, Kodi S Ravichandran, Douglas A Bayliss
Pannexin 1 (PANX1) subunits form oligomeric plasma membrane channels that mediate nucleotide release for purinergic signalling, which is involved in diverse physiological processes such as apoptosis, inflammation, blood pressure regulation, and cancer progression and metastasis. Here we explore the mechanistic basis for PANX1 activation by using wild type and engineered concatemeric channels. We find that PANX1 activation involves sequential stepwise sojourns through multiple discrete open states, each with unique channel gating and conductance properties that reflect contributions of the individual subunits of the hexamer...
January 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/28119804/targeting-calcium-signaling-in-cancer-therapy
#14
REVIEW
Chaochu Cui, Robert Merritt, Liwu Fu, Zui Pan
The intracellular calcium ions (Ca(2+)) act as second messenger to regulate gene transcription, cell proliferation, migration and death. Accumulating evidences have demonstrated that intracellular Ca(2+) homeostasis is altered in cancer cells and the alteration is involved in tumor initiation, angiogenesis, progression and metastasis. Targeting derailed Ca(2+) signaling for cancer therapy has become an emerging research area. This review summarizes some important Ca(2+) channels, transporters and Ca(2+)-ATPases, which have been reported to be altered in human cancer patients...
January 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28111260/down-regulation-of-asic1-suppressed-gastric-cancer-via-inhibiting-autophagy
#15
Qiong Zhang, Shiwu Wu, Jinhai Zhu, Damin Chai, Huaiyong Gan
As autophagy has anti-apoptosis effect and accelerates cell survival, many studies start to target autophagy as a therapeutic strategy for cancer. Acid-sensing ion channels (ASICs) was reported to activate autophagy. However, whether ASICs can regulate gastric cancer through autophagy is unknown. The differentially expressed genes in normal gastric tissue and gastric cancer tissue in patients were investigated by RNA-seq. Expression of ASIC1 and autophagy related 5 (ATG5) was further confirmed by real-time PCR...
January 19, 2017: Gene
https://www.readbyqxmd.com/read/28109880/dynamics-of-the-eag1-k-channel-selectivity-filter-assessed-by-molecular-dynamics-simulations
#16
Harald Bernsteiner, Michael Bründl, Anna Stary-Weinzinger
EAG1 channels belong to the KCNH family of voltage gated potassium channels. They are expressed in several brain regions and increased expression is linked to certain cancer types. Recent cryo-EM structure determination finally revealed the structure of these channels in atomic detail, allowing computational investigations. In this study, we performed molecular dynamics simulations to investigate the ion binding sites and the dynamical behavior of the selectivity filter. Our simulations suggest that sites S2 and S4 form stable ion binding sites, while ions placed at sites S1 and S3 rapidly switched to sites S2 and S4...
January 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28103434/analgesic-effect-of-quetiapine-in-a-mouse-model-of-cancer-induced-bone-pain
#17
Mi Hwa Heo, Jin Young Kim, Ilseon Hwang, Eunyoung Ha, Keon Uk Park
Background/Aims: Cancer-induced bone pain (CIBP) is one of the most common pains in patients with advanced neoplasms. Because of treatment-associated side effects, more than half of cancer patients are reported to have inadequate and undermanaged pain control. New mechanism-based therapies must be developed to reduce cancer pain. Quetiapine is a commonly used atypical antipsychotic drug. We report a study of the potential analgesic effects of quetiapine in a mouse model of CIBP and examine the mechanism of bone pain by analyzing the expression of various nociceptors...
January 20, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28101241/potential-role-of-melastatin-related-transient-receptor-potential-cation-channel-subfamily-m-gene-expression-in-the-pathogenesis-of-urinary-bladder-cancer
#18
Gülay Güleç Ceylan, Ebru Etem Önalan, Tuncay Kuloğlu, Gülten Aydoğ, İbrahim Keleş, Şenol Tonyali, Cavit Ceylan
Urinary bladder cancer is one of the most common malignancies of the urinary tract. Ion channels and calcium homeostasis are involved in almost all basic cellular mechanisms. The transient receptor potential cation channel subfamily M (TRPM) takes its name from the melastatin protein, which is classified as potential tumor suppressor. To the best of our knowledge, there have been no previous studies in the literature investigating the role of these ion channels in bladder cancer. The present study aimed to determine whether bladder cancer is associated with mRNA expression levels of TRPM ion channel genes, and whether there is the potential to conduct further studies to establish novel treatment modalities...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28096238/activation-of-trpa1-channel-by-antibacterial-agent-triclosan-induces-vegf-secretion-in-human-prostate-cancer-stromal-cells
#19
Sandra Derouiche, Pascal Mariot, Marine Warnier, Eric Vancauwenberghe, Gabriel Bidaux, Pierre Gosset, Brigitte Mauroy, Jean-Louis Bonnal, Christian Slomianny, Philippe Delcourt, Etienne Dewailly, Natalia Prevarskaya, Morad Roudbaraki
Accruing evidence indicates that exposure to environmental compounds may adversely impact human health and promote carcinogenesis. Triclosan (TCS), an antimicrobial agent widely used as a preservative in personal care products, has been shown to act as an endocrine disruptor in hormone-dependent tissues. Here we demonstrate a new molecular mechanism by which TCS stimulates the secretion by human prostate cancer stromal cells of Vascular Endothelial Growth Factor (VEGF), a factor known to promote tumour growth...
January 17, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28039451/high-throughput-proteome-analysis-reveals-targeted-trpm8-degradation-in-prostate-cancer
#20
Swapna Asuthkar, Lusine Demirkhanyan, Samuel Robert Mueting, Alejandro Cohen, Eleonora Zakharian
The Ca2+-permeable ion channel TRPM8 is a hallmark of the prostate epithelium. We recently discovered that TRPM8 is an ionotropic testosterone receptor. This finding suggested that testosterone-induced TRPM8 activity regulates Ca2+ homeostasis in the prostate epithelium. Since androgens are significantly implicated in prostate cancer development, the role of the novel testosterone receptor TRPM8 in cancer was assessed in our study. Although TRPM8 mRNA levels increase at the early prostate cancer stages, we found that it is not proportionally translated into TRPM8 protein levels...
December 26, 2016: Oncotarget
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