keyword
MENU ▼
Read by QxMD icon Read
search

cancer ion channel

keyword
https://www.readbyqxmd.com/read/28426996/design-synthesis-sar-discussion-in%C3%A2-vitro-and-in%C3%A2-vivo-evaluation-of-novel-selective-egfr-modulator-to-inhibit-l858r-t790m-double-mutants
#1
Haoyang Zhang, Wenkui Wu, Chao Feng, Zhaogang Liu, Enhe Bai, Xueyuan Wang, Meng Lei, Hao Cheng, Huayun Feng, Jingmiao Shi, Jia Wang, Zhao Zhang, Tao Jin, Shanshan Chen, Shihe Hu, Yongqiang Zhu
Based upon the modeling binding mode of marketed AZD9291 with T790M, a series of 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline derivatives were designed and synthesized with the purpose to overcome the drug resistance resulted from T790M/L858R double mutations. The most potent compound 8 showed excellent enzyme inhibitory activities and selectivity with sub nanomolar IC50 values for both the single L858R and double T790M/L858R mutant EGFRs, and was more than 8-fold selective for wild type EGFR. Compound 8 exhibited good microsomes stabilities and pharmacokinetic properties and lower binding affinity to hERG ion channel than AZD9291 and displayed strong antiproliferative activity against the H1975 non-small cell lung cancer (NSCLC) cells bearing T790M/L858R and in vivo anticancer efficacy in a human NSCLC (H1975) xenograft mouse model...
April 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28415575/ik-channel-activation-increases-tumor-growth-and-induces-differential-behavioral-responses-in-two-breast-epithelial-cell-lines
#2
Amy E Thurber, Michaela Nelson, Crystal L Frost, Michael Levin, William J Brackenbury, David L Kaplan
Many potassium channel families are over-expressed in cancer, but their mechanistic role in disease progression is poorly understood. Potassium channels modulate membrane potential (Vmem) and thereby influence calcium ion dynamics and other voltage-sensitive signaling mechanisms, potentially acting as transcriptional regulators. This study investigated the differential response to over-expression and activation of a cancer-associated potassium channel, the intermediate conductance calcium-activated potassium channel (IK), on aggressive behaviors in mammary epithelial and breast cancer cell lines...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28399409/direct-pharmacological-targeting-of-a-mitochondrial-ion-channel-selectively-kills-tumor-cells-in%C3%A2-vivo
#3
Luigi Leanza, Matteo Romio, Katrin Anne Becker, Michele Azzolini, Livio Trentin, Antonella Managò, Elisa Venturini, Angela Zaccagnino, Andrea Mattarei, Luca Carraretto, Andrea Urbani, Stephanie Kadow, Lucia Biasutto, Veronica Martini, Filippo Severin, Roberta Peruzzo, Valentina Trimarco, Jan-Hendrik Egberts, Charlotte Hauser, Andrea Visentin, Gianpietro Semenzato, Holger Kalthoff, Mario Zoratti, Erich Gulbins, Cristina Paradisi, Ildiko Szabo
The potassium channel Kv1.3 is highly expressed in the mitochondria of various cancerous cells. Here we show that direct inhibition of Kv1.3 using two mitochondria-targeted inhibitors alters mitochondrial function and leads to reactive oxygen species (ROS)-mediated death of even chemoresistant cells independently of p53 status. These inhibitors killed 98% of ex vivo primary chronic B-lymphocytic leukemia tumor cells while sparing healthy B cells. In orthotopic mouse models of melanoma and pancreatic ductal adenocarcinoma, the compounds reduced tumor size by more than 90% and 60%, respectively, while sparing immune and cardiac functions...
April 10, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28393180/fenofibrate-inhibits-tumour-intravasation-by-several-independent-mechanisms-in-a-3-dimensional-co-culture-model
#4
Chi Huu Nguyen, Nicole Huttary, Atanas G Atanasov, Waranya Chatuphonprasert, Stefan Brenner, Adryan Fristiohady, Junli Hong, Serena Stadler, Silvio Holzner, Daniela Milovanovic, Verena M Dirsch, Brigitte Kopp, Philipp Saiko, Liselotte Krenn, Walter Jäger, Georg Krupitza
Lymph node metastasis of breast cancer is a clinical marker of poor prognosis. Yet, there exist no therapies targeting mechanisms of intravasation into lymphatics. Herein we report on an effect of the antidyslipidemic drug fenofibrate with vasoprotective activity, which attenuates breast cancer intravasation in vitro, and describe the potential mechanisms. To measure intravasation in a 3-dimensional co-culture model MDA-MB231 and MCF-7 breast cancer spheroids were placed on immortalised lymphendothelial cell (LEC) monolayers...
April 7, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28389731/esophageal-cancer-stem-cells-are-suppressed-by-tranilast-a-trpv2-channel-inhibitor
#5
Atsushi Shiozaki, Michihiro Kudou, Daisuke Ichikawa, Hitoshi Fujiwara, Hiroki Shimizu, Takeshi Ishimoto, Tomohiro Arita, Toshiyuki Kosuga, Hirotaka Konishi, Shuhei Komatsu, Kazuma Okamoto, Yoshinori Marunaka, Eigo Otsuji
BACKGROUND: Recent evidence suggests that the targeting of membrane proteins specifically activated in cancer stem cells (CSCs) is an important strategy for cancer therapy. The objectives of the present study were to investigate the expression and activity of ion-transport-related molecules in the CSCs of esophageal squamous cell carcinoma. METHODS: Cells exhibiting strong aldehyde dehydrogenase 1 family member A1 (ALDH1A1) activity were isolated from TE8 cells by fluorescence-activated cell sorting, and CSCs were then generated with the sphere formation assay...
April 7, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28379203/role-of-trpm7-in-cancer-potential-as-molecular-biomarker-and-therapeutic-target
#6
REVIEW
Nelson S Yee
The transient receptor potential melastatin-subfamily member 7 (TRPM7) is a ubiquitously expressed ion channel with intrinsic kinase activity. Molecular and electrophysiological analyses of the structure and activity of TRPM7 have revealed functional coupling of its channel and kinase activity. Studies have indicated the important roles of TRPM7 channel-kinase in fundamental cellular processes, physiological responses, and embryonic development. Accumulating evidence has shown that TRPM7 is aberrantly expressed and/or activated in human diseases including cancer...
April 5, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28377405/the-conformational-state-of-herg1-channels-determines-integrin-association-downstream-signaling-and-cancer-progression
#7
Andrea Becchetti, Silvia Crescioli, Francesca Zanieri, Giulia Petroni, Raffaella Mercatelli, Stefano Coppola, Luca Gasparoli, Massimo D'Amico, Serena Pillozzi, Olivia Crociani, Matteo Stefanini, Antonella Fiore, Laura Carraresi, Virginia Morello, Sagar Manoli, Maria Felice Brizzi, Davide Ricci, Mauro Rinaldi, Alessio Masi, Thomas Schmidt, Franco Quercioli, Paola Defilippi, Annarosa Arcangeli
Ion channels regulate cell proliferation, differentiation, and migration in normal and neoplastic cells through cell-cell and cell-extracellular matrix (ECM) transmembrane receptors called integrins. K(+) flux through the human ether-à-go-go-related gene 1 (hERG1) channel shapes action potential firing in excitable cells such as cardiomyocytes. Its abundance is often aberrantly high in tumors, where it modulates integrin-mediated signaling. We found that hERG1 interacted with the β1 integrin subunit at the plasma membrane of human cancer cells...
April 4, 2017: Science Signaling
https://www.readbyqxmd.com/read/28373572/bidirectional-kcnq1-%C3%AE-catenin-interaction-drives-colorectal-cancer-cell-differentiation
#8
Raphael Rapetti-Mauss, Viviana Bustos, Warren Thomas, Jean McBryan, Harry Harvey, Natalia Lajczak, Stephen F Madden, Bernard Pellissier, Franck Borgese, Olivier Soriani, Brian J Harvey
The K(+) channel KCNQ1 has been proposed as a tumor suppressor in colorectal cancer (CRC). We investigated the molecular mechanisms regulating KCNQ1:β-catenin bidirectional interactions and their effects on CRC differentiation, proliferation, and invasion. Molecular and pharmacologic approaches were used to determine the influence of KCNQ1 expression on the Wnt/β-catenin signaling and epithelial-to-mesenchymal transition (EMT) in human CRC cell lines of varying stages of differentiation. The expression of KCNQ1 was lost with increasing mesenchymal phenotype in poorly differentiated CRC cell lines as a consequence of repression of the KCNQ1 promoter by β-catenin:T-cell factor (TCF)-4...
April 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28368405/connexin-43-channels-are-a-pathway-for-discharging-lactate-from-glycolytic-pancreatic-ductal-adenocarcinoma-cells
#9
T H Dovmark, M Saccomano, A Hulikova, F Alves, P Swietach
Glycolytic cancer cells produce large quantities of lactate that must be removed to sustain metabolism in the absence of oxidative phosphorylation. The only venting mechanism described to do this at an adequate rate is H(+)-coupled lactate efflux on monocarboxylate transporters (MCTs). Outward MCT activity is, however, thermodynamically inhibited by extracellular acidity, a hallmark of solid tumours. This inhibition would feedback unfavourably on metabolism and growth, raising the possibility that other venting mechanisms become important in under-perfused tumours...
April 3, 2017: Oncogene
https://www.readbyqxmd.com/read/28367272/eag1-k-channel-endogenous-regulation-and-functions-in-nervous-system
#10
REVIEW
Bo Han, Tursonjan Tokay, Guangming Zhang, Peng Sun, Shangwei Hou
Ether-à-go-go1 (Eag1, Kv10.1, KCNH1) K(+) channel is a member of the voltage-gated K(+) channel family mainly distributed in the central nervous system and cancer cells. Like other types of voltage-gated K(+) channels, the EAG1 channels are regulated by a variety of endogenous signals including reactive oxygen species, rendering the EAG1 to be in the redox-regulated ion channel family. The role of EAG1 channels in tumor development and its therapeutic significance have been well established. Meanwhile, the importance of hEAG1 channels in the nervous system is now increasingly appreciated...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28365825/inhibition-of-inwardly-rectifying-kir2-x-channels-by-the-novel-anti-cancer-agent-gambogic-acid-depends-on-both-pore-block-and-pip2-interference
#11
Daniel Scherer, Benedikt Schworm, Claudia Seyler, Panagiotis Xynogalos, Eberhard P Scholz, Dierk Thomas, Hugo A Katus, Edgar Zitron
The caged xanthone gambogic acid (GA) is a novel anti-cancer agent which exhibits anti-proliferative, anti-inflammatory and cytotoxic effects in many types of cancer tissues. In a recent phase IIa study, GA exhibits a favourable safety profile. However, limited data are available concerning its interaction with cardiac ion channels. Heteromeric assembly of Kir2.x channels underlies the cardiac inwardly rectifying IK1 current which is responsible for the stabilization of the diastolic resting membrane potential...
April 2, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28355609/emerging-role-of-cav1-2-channels-in-proliferation-and-migration-in-distinct-cancer-cell-lines
#12
Gustavo Martínez-Delgado, Ricardo Felix
Extensive research is currently underway, seeking better diagnostic methods and treatments and a better understanding of the molecular mechanisms involved in cancer, from the role of specific genetic mutations to the intricate biochemical and molecular pathways involved. Because of their role in regulating relevant physiological events such as cell proliferation, migration, and invasion, ion channels have recently been recognized as important elements in cancer initiation and progression. Moreover, it has been reported that pharmacological intervention in ion channel activity might provide protection against diverse types of cancer, and that ion channels could be used as targets to counteract tumor growth, prevent metastasis, and overcome the therapy resistance of tumor cells...
March 30, 2017: Oncology
https://www.readbyqxmd.com/read/28350326/reply-to-the-letter-to-the-editor-by-d-d-arcangelo-et-al-ion-channels-in-brain-metastasis-ion-channels-in-cancer-set-up-and-metastatic-progression-ion-channels-in-brain-metastasis
#13
Lukas Klumpp, Efe C Sezgin, Franziska Eckert, Stephan M Huber
n/a.
March 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28350105/inflammatory-role-of-high-salt-level-in-tumor-microenvironment-review
#14
Suneetha Amara, Venkataswarup Tiriveedhi
Chronic inflammation is known to play a critical role in cancer development and progression. High salt is known to mediate several chronic inflammatory diseases including hypertension, myocardial infarction, neurological ischemic attack, autoimmune diseases and cancers. High salt level is shown to induce angiogenesis and immune-dysfunction, both of which play a direct role in cancer proliferation. Furthermore, salt has been suggested to enhance Warburg-like metabolic phenotype in cancer cells and at the same time also induce pro-tumor MΦ2-macrophage phenotype...
March 27, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28334543/-functional-impact-of-herg-from-physiological-role-to-target-of-anticancer-therapy
#15
Júlia Šatková, Markéta Bébarová
The human ether-à-go-go related gene (hERG; officially designated as KCNH2) encodes the structure of protein forming α-subunit of voltage-gated ion channel which conducts the rapid component of delayed rectifier K+ current (IKr). This current plays an important role namely in the cardiac repolarization. Mutations in hERG result in inherited arrhythmogenic syndromes characterized by a lenghtening or shortening of QT interval on the electrocardiogram and by an increased occurrence of life-threatening arrhythmias...
2017: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/28315265/sigma-1-receptor-and-ion-channel-dynamics-in-cancer
#16
Olivier Soriani, Raphaël Rapetti-Mauss
SigmaR1 is a multitasking chaperone protein which has mainly been studied in CNS physiological and pathophysiological processes such as pain, memory, neurodegenerative diseases (amyotrophic lateral sclerosis , Parkinson's and Alzheimer's diseases, retinal neurodegeneration ), stroke and addiction . Strikingly, G-protein and ion channels are the main client protein fami lies of this atypical chaperone and the recent advances that have been performed for the last 10 years demonstrate that SigmaR1 is principally activated following tissue injury and disease development to promote cell survival...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28300784/the-molecular-basis-of-toxins-interactions-with-intracellular-signaling-via-discrete-portals
#17
REVIEW
Adi Lahiani, Ephraim Yavin, Philip Lazarovici
An understanding of the molecular mechanisms by which microbial, plant or animal-secreted toxins exert their action provides the most important element for assessment of human health risks and opens new insights into therapies addressing a plethora of pathologies, ranging from neurological disorders to cancer, using toxinomimetic agents. Recently, molecular and cellular biology dissecting tools have provided a wealth of information on the action of these diverse toxins, yet, an integrated framework to explain their selective toxicity is still lacking...
March 16, 2017: Toxins
https://www.readbyqxmd.com/read/28286483/long-term-effects-pathophysiological-mechanisms-and-risk-factors-of-chemotherapy-induced-peripheral-neuropathies-a-comprehensive-literature-review
#18
REVIEW
Nicolas Kerckhove, Aurore Collin, Sakahlé Condé, Carine Chaleteix, Denis Pezet, David Balayssac
Neurotoxic anticancer drugs, such as platinum-based anticancer drugs, taxanes, vinca alkaloids, and proteasome/angiogenesis inhibitors are responsible for chemotherapy-induced peripheral neuropathy (CIPN). The health consequences of CIPN remain worrying as it is associated with several comorbidities and affects a specific population of patients already impacted by cancer, a strong driver for declines in older adults. The purpose of this review is to present a comprehensive overview of the long-term effects of CIPN in cancer patients and survivors...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28283400/vdac-in-cancer
#19
REVIEW
N M Mazure
The voltage-dependent anion channel (VDAC) is a pore located at the outer membrane of the mitochondrion. It allows the entry and exit of numerous ions and metabolites between the cytosol and the mitochondrion. Flux through the pore occurs in an active way: first, it depends on the open or closed state and second, on the negative or positive charges of the different ion species passing through the pore. The flux of essential metabolites, such as ATP, determines the functioning of the mitochondria to a noxious stimulus...
March 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28277613/activation-of-mutated-trpa1-ion-channel-by-resveratrol-in-human-prostate-cancer-associated-fibroblasts-caf
#20
Eric Vancauwenberghe, Lucile Noyer, Sandra Derouiche, Loïc Lemonnier, Pierre Gosset, Laura R Sadofsky, Pascal Mariot, Marine Warnier, Alexandre Bokhobza, Christian Slomianny, Brigitte Mauroy, Jean-Louis Bonnal, Etienne Dewailly, Philippe Delcourt, Laurent Allart, Natalia Prevarskaya, Morad Roudbaraki
Previous studies showed the effects of resveratrol (RES) on several cancer cells, including prostate cancer (PCa) cell apoptosis without taking into consideration the impact of the tumor microenvironment (TME). The TME is composed of cancer cells, endothelial cells, blood cells and cancer-associated fibroblasts (CAF), the main source of growth factors. The latter cells might modify in the TME the impact of RES on tumor cells via secreted factors. Recent data clearly show the impact of CAF on cancer cells apoptosis resistance via secreted factors...
March 9, 2017: Molecular Carcinogenesis
keyword
keyword
84326
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"