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Статті в журналах з теми "Therapeutic ion"

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Автор: Grafiati

Опубліковано: 14 березня 2023

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1

Hutchings, Catherine J., Paul Colussi, and Theodore G. Clark. "Ion channels as therapeutic antibody targets." mAbs 11, no. 2 (December 10, 2018): 265–96. http://dx.doi.org/10.1080/19420862.2018.1548232.

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2

Peixoto, Pablo M., Shin-Young Ryu, and Kathleen W. Kinnally. "Mitochondrial ion channels as therapeutic targets." FEBS Letters 584, no. 10 (February 20, 2010): 2142–52. http://dx.doi.org/10.1016/j.febslet.2010.02.046.

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3

Matsufuji, Naruhiro, Tetsuharu Matsuyama, Shinji Sato, and Toshiyuki Kohno. "Recombination characteristics of therapeutic ion beams on ion chamber dosimetry." International Journal of Modern Physics: Conference Series 44 (January 2016): 1660218. http://dx.doi.org/10.1142/s2010194516602180.

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Анотація:

In heavy ion radiotherapy, ionization chambers are regarded as a standard for determining the absorbed dose given to patients. In ion dosimetry, it is necessary to correct the radiation quality, which depends on the initial recombination effect. This study reveals for the radiation quality dependence of the initial recombination in air in ion dosimetry. Ionization charge was measured for the beams of protons at 40–160 MeV, carbon at 21–400 MeV/n, and iron at 23.5–500 MeV/n using two identical parallel-plate ionization chambers placed in series along the beam axis. The downstream chamber was used as a monitor operated with a constant applied voltage, while the other chamber was used for recombination measurement by changing the voltage. The ratio of the ionization charge measured by the two ionization chambers showed a linear relationship with the inverse of the voltage in the high-voltage region. The initial recombination factor was estimated by extrapolating the obtained linear relationship to infinite voltage. The extent of the initial recombination was found to increase with decreasing incident energy or increasing atomic number of the beam. This behavior can be explained with an amorphous track structure model: the increase of ionization density in the core region of the track due to decreasing kinetic energy or increasing atomic number leads to denser initial ion production and results in a higher recombination probability. For therapeutic carbon ion beams, the extent of the initial recombination was not constant but changed by 0.6% even in the target region. This tendency was quantitatively well reproduced with the track-structure based on the initial recombination model; however, the transitional change in the track structure is considered to play an important role in further understanding of the characteristics of the initial recombination.

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4

Zamponi, Gerald W. "Welcome to “Ion Channels: Key Therapeutic Targets”." Future Medicinal Chemistry 2, no. 5 (May 2010): 689–90. http://dx.doi.org/10.4155/fmc.10.184.

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5

Lambert, Mélanie, Véronique Capuano, Andrea Olschewski, Jessica Sabourin, Chandran Nagaraj, Barbara Girerd, Jason Weatherald, Marc Humbert, and Fabrice Antigny. "Ion Channels in Pulmonary Hypertension: A Therapeutic Interest?" International Journal of Molecular Sciences 19, no. 10 (October 14, 2018): 3162. http://dx.doi.org/10.3390/ijms19103162.

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Pulmonary arterial hypertension (PAH) is a multifactorial and severe disease without curative therapies. PAH pathobiology involves altered pulmonary arterial tone, endothelial dysfunction, distal pulmonary vessel remodeling, and inflammation, which could all depend on ion channel activities (K+, Ca2+, Na+ and Cl−). This review focuses on ion channels in the pulmonary vasculature and discusses their pathophysiological contribution to PAH as well as their therapeutic potential in PAH.

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6

Nisar, Areeba, Zubair Ahmed, and Hsiangkuo Yuan. "Novel Therapeutic Targets for Migraine." Biomedicines 11, no. 2 (February 15, 2023): 569. http://dx.doi.org/10.3390/biomedicines11020569.

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Migraine, a primary headache disorder involving a dysfunctional trigeminal vascular system, remains a major debilitating neurological condition impacting many patients’ quality of life. Despite the success of multiple new migraine therapies, not all patients achieve significant clinical benefits. The success of CGRP pathway-targeted therapy highlights the importance of translating the mechanistic understanding toward effective therapy. Ongoing research has identified multiple potential mechanisms in migraine signaling and nociception. In this narrative review, we discuss several potential emerging therapeutic targets, including pituitary adenylate cyclase-activating polypeptide (PACAP), adenosine, δ-opioid receptor (DOR), potassium channels, transient receptor potential ion channels (TRP), and acid-sensing ion channels (ASIC). A better understanding of these mechanisms facilitates the discovery of novel therapeutic targets and provides more treatment options for improved clinical care.

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7

Selvaraj, Chandrabose, Gurudeeban Selvaraj, Satyavani Kaliamurthi, William C. Cho, Dong-Qing Wei, and Sanjeev Kumar Singh. "Ion Channels as Therapeutic Targets for Type 1 Diabetes Mellitus." Current Drug Targets 21, no. 2 (January 22, 2020): 132–47. http://dx.doi.org/10.2174/1389450119666190920152249.

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Ion channels are integral proteins expressed in almost all living cells and are involved in muscle contraction and nutrient transport. They play a critical role in the normal functioning of the excitable tissues of the nervous system and regulate the action potential and contraction events. Dysfunction of genes encodes ion channel proteins, which disrupt the channel function and lead to a number of diseases, among which is type 1 diabetes mellitus (T1DM). Therefore, understanding the complex mechanism of ion channel receptors is necessary to facilitate the diagnosis and management of treatment. In this review, we summarize the mechanism of important ion channels and their potential role in the regulation of insulin secretion along with the limitations of ion channels as therapeutic targets. Furthermore, we discuss the recent investigations of the mechanism regulating the ion channels in pancreatic beta cells, which suggest that ion channels are active participants in the regulation of insulin secretion.

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8

Janssen, Luke J. "Membrane Currents in Airway Smooth Muscle: Mechanisms and Therapeutic Implications." Canadian Respiratory Journal 4, no. 1 (1997): 13–20. http://dx.doi.org/10.1155/1997/253424.

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Electrophysiological and pharmacological techniques were used to characterize the membrane conductance changes underlying spasmogen-evoked depolarization in airway smooth muscle (ASM). Changes included a transient activation of chloride ion channels and prolonged suppression of potassium ion channels; both changes are triggered by release of internally sequestered calcium ion and in turn cause opening of voltage-dependent calcium channels. The resultant influx of calcium ions contributes to contraction as well as to refilling of the internal calcium ion pool. Bronchodilators, on the other hand, act in part through activation of potassium channels, with consequent closure of calcium channels. The tools used to study ion channels in ASM are described, and the investigations of the roles of ion channels in ASM physiology (autacoid-evoked depolarization and hyperpolarization) and pathophysiology (airway hyperresponsiveness) are summarized. Finally, how the relationship between ion channels and ASM function/dysfunction may relate to the treatment of asthma and related breathing disorders is discussed.

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9

Griffin, Michaela, Raheela Khan, Surajit Basu, and Stuart Smith. "Ion Channels as Therapeutic Targets in High Grade Gliomas." Cancers 12, no. 10 (October 21, 2020): 3068. http://dx.doi.org/10.3390/cancers12103068.

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Glioblastoma multiforme (GBM) is a lethal brain cancer with an average survival of 14–15 months even with exhaustive treatment. High grade gliomas (HGG) represent the leading cause of CNS cancer-related death in children and adults due to the aggressive nature of the tumour and limited treatment options. The scarcity of treatment available for GBM has opened the field to new modalities such as electrotherapy. Previous studies have identified the clinical benefit of electrotherapy in combination with chemotherapeutics, however the mechanistic action is unclear. Increasing evidence indicates that not only are ion channels key in regulating electrical signaling and membrane potential of excitable cells, they perform a crucial role in the development and neoplastic progression of brain tumours. Unlike other tissue types, neural tissue is intrinsically electrically active and reliant on ion channels and their function. Ion channels are essential in cell cycle control, invasion and migration of cancer cells and therefore present as valuable therapeutic targets. This review aims to discuss the role that ion channels hold in gliomagenesis and whether we can target and exploit these channels to provide new therapeutic targets and whether ion channels hold the mechanistic key to the newfound success of electrotherapies.

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10

Ben-Johny, Manu, and David T. Yue. "Calmodulin regulation (calmodulation) of voltage-gated calcium channels." Journal of General Physiology 143, no. 6 (May 26, 2014): 679–92. http://dx.doi.org/10.1085/jgp.201311153.

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Calmodulin regulation (calmodulation) of the family of voltage-gated CaV1-2 channels comprises a prominent prototype for ion channel regulation, remarkable for its powerful Ca2+ sensing capabilities, deep in elegant mechanistic lessons, and rich in biological and therapeutic implications. This field thereby resides squarely at the epicenter of Ca2+ signaling biology, ion channel biophysics, and therapeutic advance. This review summarizes the historical development of ideas in this field, the scope and richly patterned organization of Ca2+ feedback behaviors encompassed by this system, and the long-standing challenges and recent developments in discerning a molecular basis for calmodulation. We conclude by highlighting the considerable synergy between mechanism, biological insight, and promising therapeutics.

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11

Saltarella, Ilaria, Concetta Altamura, Aurelia Lamanuzzi, Benedetta Apollonio, Angelo Vacca, Maria Antonia Frassanito, and Jean-François Desaphy. "Ion Channels in Multiple Myeloma: Pathogenic Role and Therapeutic Perspectives." International Journal of Molecular Sciences 23, no. 13 (June 30, 2022): 7302. http://dx.doi.org/10.3390/ijms23137302.

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Ion channels are pore-forming proteins that allow ions to flow across plasma membranes and intracellular organelles in both excitable and non-excitable cells. They are involved in the regulation of several biological processes (i.e., proliferation, cell volume and shape, differentiation, migration, and apoptosis). Recently, the aberrant expression of ion channels has emerged as an important step of malignant transformation, tumor progression, and drug resistance, leading to the idea of “onco-channelopathy”. Here, we review the contribution of ion channels and transporters in multiple myeloma (MM), a hematological neoplasia characterized by the expansion of tumor plasma cells (MM cells) in the bone marrow (BM). Deregulation of ion channels sustains MM progression by modulating intracellular pathways that promote MM cells’ survival, proliferation, and drug resistance. Finally, we focus on the promising role of ion channels as therapeutic targets for the treatment of MM patients in a combination strategy with currently used anti-MM drugs to improve their cytotoxic activity and reduce adverse effects.

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12

D. Skaper, Stephen. "Ion Channels on Microglia: Therapeutic Targets for Neuroprotection." CNS & Neurological Disorders - Drug Targets 10, no. 1 (February 1, 2011): 44–56. http://dx.doi.org/10.2174/187152711794488638.

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13

Heusser, Stephanie A., and Stephan A. Pless. "Acid-sensing ion channels as potential therapeutic targets." Trends in Pharmacological Sciences 42, no. 12 (December 2021): 1035–50. http://dx.doi.org/10.1016/j.tips.2021.09.008.

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14

Ugawa, Shinya, Takashi Ueda, and Shoichi Shimada. "Acid-sensing ion channels and pain: therapeutic potential?" Expert Review of Neurotherapeutics 3, no. 5 (September 2003): 609–17. http://dx.doi.org/10.1586/14737175.3.5.609.

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15

Garcia, Maria L., and Gregory J. Kaczorowski. "Ion channels find a pathway for therapeutic success." Proceedings of the National Academy of Sciences 113, no. 20 (May 4, 2016): 5472–74. http://dx.doi.org/10.1073/pnas.1605669113.

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16

Charlton, Frank W., Hayley M. Pearson, Samantha Hover, Jon D. Lippiat, Juan Fontana, John N. Barr, and Jamel Mankouri. "Ion Channels as Therapeutic Targets for Viral Infections: Further Discoveries and Future Perspectives." Viruses 12, no. 8 (August 3, 2020): 844. http://dx.doi.org/10.3390/v12080844.

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Анотація:

Ion channels play key roles in almost all facets of cellular physiology and have emerged as key host cell factors for a multitude of viral infections. A catalogue of ion channel-blocking drugs have been shown to possess antiviral activity, some of which are in widespread human usage for ion channel-related diseases, highlighting new potential for drug repurposing. The emergence of ion channel–virus interactions has also revealed the intriguing possibility that channelopathies may explain some commonly observed virus induced pathologies. This field is rapidly evolving and an up-to-date summary of new discoveries can inform future perspectives. We herein discuss the role of ion channels during viral lifecycles, describe the recently identified ion channel drugs that can inhibit viral infections, and highlight the potential contribution of ion channels to virus-mediated disease.

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17

Picci, Giacomo, Silvia Marchesan, and Claudia Caltagirone. "Ion Channels and Transporters as Therapeutic Agents: From Biomolecules to Supramolecular Medicinal Chemistry." Biomedicines 10, no. 4 (April 12, 2022): 885. http://dx.doi.org/10.3390/biomedicines10040885.

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Ion channels and transporters typically consist of biomolecules that play key roles in a large variety of physiological and pathological processes. Traditional therapies include many ion-channel blockers, and some activators, although the exact biochemical pathways and mechanisms that regulate ion homeostasis are yet to be fully elucidated. An emerging area of research with great innovative potential in biomedicine pertains the design and development of synthetic ion channels and transporters, which may provide unexplored therapeutic opportunities. However, most studies in this challenging and multidisciplinary area are still at a fundamental level. In this review, we discuss the progress that has been made over the last five years on ion channels and transporters, touching upon biomolecules and synthetic supramolecules that are relevant to biological use. We conclude with the identification of therapeutic opportunities for future exploration.

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18

Bista and Imlach. "Pathological Mechanisms and Therapeutic Targets for Trigeminal Neuropathic Pain." Medicines 6, no. 3 (August 22, 2019): 91. http://dx.doi.org/10.3390/medicines6030091.

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Trigeminal neuropathic pain is a chronic pain condition caused by damage or inflammation of the trigeminal nerve or its branches, with both peripheral and central nervous system dysfunction contributing to the disorder. Trigeminal pain conditions present with diagnostic and therapeutic challenges to healthcare providers and often require multiple therapeutic approaches for pain reduction. This review will provide the overview of pathophysiology in peripheral and central nociceptive circuits that are involved in neuropathic pain conditions involving the trigeminal nerve and the current therapeutics that are used to treat these disorders. Recent advances in treatment of trigeminal pain, including novel therapeutics that target ion channels and receptors, gene therapy and monoclonal antibodies that have shown great promise in preclinical studies and clinical trials will also be described.

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19

Daniel, Neha Hanna, Ananya Aravind, and Poonam Thakur. "Are ion channels potential therapeutic targets for Parkinson’s disease?" NeuroToxicology 87 (December 2021): 243–57. http://dx.doi.org/10.1016/j.neuro.2021.10.008.

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20

Beraud, Evelyne, and K. George Chandy. "Therapeutic Potential of Peptide Toxins that Target Ion Channels." Inflammation & Allergy - Drug Targets 10, no. 5 (October 1, 2011): 322–42. http://dx.doi.org/10.2174/187152811797200696.

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21

Bagal, Sharan K., Alan D. Brown, Peter J. Cox, Kiyoyuki Omoto, Robert M. Owen, David C. Pryde, Benjamin Sidders, et al. "Ion Channels as Therapeutic Targets: A Drug Discovery Perspective." Journal of Medicinal Chemistry 56, no. 3 (November 29, 2012): 593–624. http://dx.doi.org/10.1021/jm3011433.

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22

Wemmie, John A., Margaret P. Price, and Michael J. Welsh. "Acid-sensing ion channels: advances, questions and therapeutic opportunities." Trends in Neurosciences 29, no. 10 (October 2006): 578–86. http://dx.doi.org/10.1016/j.tins.2006.06.014.

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23

Akar, Fadi G., and Gordon F. Tomaselli. "Ion channels as novel therapeutic targets in heart failure." Annals of Medicine 37, no. 1 (March 2005): 44–54. http://dx.doi.org/10.1080/07853890510007214.

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24

Oosterwijk, E., and R. J. Gillies. "Targeting ion transport in cancer." Philosophical Transactions of the Royal Society B: Biological Sciences 369, no. 1638 (March 19, 2014): 20130107. http://dx.doi.org/10.1098/rstb.2013.0107.

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The metabolism of cancer cells differs substantially from normal cells, including ion transport. Although this phenomenon has been long recognized, ion transporters have not been viewed as suitable therapeutic targets. However, the acidic pH values present in tumours which are well outside of normal limits are now becoming recognized as an important therapeutic target. Carbonic anhydrase IX (CAIX) is fundamental to tumour pH regulation. CAIX is commonly expressed in cancer, but lowly expressed in normal tissues and that presents an attractive target. Here, we discuss the possibilities of exploiting the acidic, hypoxic tumour environment as possible target for therapy. Additionally, clinical experience with CAIX targeting in cancer patients is discussed.

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25

Reinhart, Anna Merle, Claudia Katharina Spindeldreier, Jan Jakubek, and Mária Martišíková. "Three dimensional reconstruction of therapeutic carbon ion beams in phantoms using single secondary ion tracks." Physics in Medicine and Biology 62, no. 12 (May 22, 2017): 4884–96. http://dx.doi.org/10.1088/1361-6560/aa6aeb.

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26

Fraser, Scott P., and Luis A. Pardo. "Ion channels: functional expression and therapeutic potential in cancer. Colloquium on Ion Channels and Cancer." EMBO reports 9, no. 6 (May 2, 2008): 512–15. http://dx.doi.org/10.1038/embor.2008.75.

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27

Hutchings, Catherine J. "Mini-review: antibody therapeutics targeting G protein-coupled receptors and ion channels." Antibody Therapeutics 3, no. 4 (December 2020): 257–64. http://dx.doi.org/10.1093/abt/tbaa023.

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Abstract Antibodies are now well established as therapeutics with many additional advantages over small molecules and peptides relative to their selectivity, bioavailability, half-life and effector function. Major classes of membrane-associated protein targets include G protein-coupled receptors (GPCRs) and ion channels that are linked to a wide range of disease indications across all therapeutic areas. This mini-review summarizes the antibody target landscape for both GPCRs and ion channels as well as current progress in the respective research and development pipelines with some example case studies highlighted from clinical studies, including those being evaluated for the treatment of symptoms in COVID-19 infection.

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28

Remigante, Alessia, Sara Spinelli, Angela Marino, Michael Pusch, Rossana Morabito, and Silvia Dossena. "Oxidative Stress and Immune Response in Melanoma: Ion Channels as Targets of Therapy." International Journal of Molecular Sciences 24, no. 1 (January 3, 2023): 887. http://dx.doi.org/10.3390/ijms24010887.

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Oxidative stress and immune response play an important role in the development of several cancers, including melanoma. Ion channels are aberrantly expressed in tumour cells and regulate neoplastic transformation, malignant progression, and resistance to therapy. Ion channels are localized in the plasma membrane or other cellular membranes and are targets of oxidative stress, which is particularly elevated in melanoma. At the same time, ion channels are crucial for normal and cancer cell physiology and are subject to multiple layers of regulation, and therefore represent promising targets for therapeutic intervention. In this review, we analyzed the effects of oxidative stress on ion channels on a molecular and cellular level and in the context of melanoma progression and immune evasion. The possible role of ion channels as targets of alternative therapeutic strategies in melanoma was discussed.

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29

Horne, Jesse, Shomit Mansur, and Yuping Bao. "Sodium ion channels as potential therapeutic targets for cancer metastasis." Drug Discovery Today 26, no. 5 (May 2021): 1136–47. http://dx.doi.org/10.1016/j.drudis.2021.01.026.

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30

Gladkikh, Irina N., Oksana V. Sintsova, Elena V. Leychenko, and Sergey A. Kozlov. "TRPV1 Ion Channel: Structural Features, Activity Modulators, and Therapeutic Potential." Biochemistry (Moscow) 86, S1 (January 2021): S50—S70. http://dx.doi.org/10.1134/s0006297921140054.

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31

Baartscheer, Antonius, and Marcel van Borren. "Sodium Ion Transporters as New Therapeutic Targets in Heart Failure." Cardiovascular & Hematological Agents in Medicinal Chemistry 6, no. 4 (October 1, 2008): 229–36. http://dx.doi.org/10.2174/187152508785909546.

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32

Wang, Yinghong, Hong Zhou, Yancai Sun, and Yan Huang. "Acid-sensing ion channel 1: potential therapeutic target for tumor." Biomedicine & Pharmacotherapy 155 (November 2022): 113835. http://dx.doi.org/10.1016/j.biopha.2022.113835.

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33

Arnold, R., W. Huynh, M. C. Kiernan, and A. V. Krishnan. "Ion Channel Modulation as a Therapeutic Approach in Multiple Sclerosis." Current Medicinal Chemistry 22, no. 38 (December 28, 2015): 4366–78. http://dx.doi.org/10.2174/0929867322666151029104452.

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34

Li, Zhiyuan, Dong Liang, and Ling Chen. "Potential Therapeutic Targets for ATP-Gated P2X Receptor Ion Channels." ASSAY and Drug Development Technologies 6, no. 2 (April 2008): 277–84. http://dx.doi.org/10.1089/adt.2007.121.

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35

Anumanthan, Govindaraj, Suneel Gupta, Michael K. Fink, Nathan P. Hesemann, Douglas K. Bowles, Lindsey M. McDaniel, Maaz Muhammad, and Rajiv R. Mohan. "KCa3.1 ion channel: A novel therapeutic target for corneal fibrosis." PLOS ONE 13, no. 3 (March 19, 2018): e0192145. http://dx.doi.org/10.1371/journal.pone.0192145.

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36

Attal, Nadine. "CME Information: Ion Channels as Therapeutic Targets in Neuropathic Pain." Journal of Pain 7, no. 1 (January 2006): S48—S54. http://dx.doi.org/10.1016/j.jpain.2005.09.009.

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37

Li, Qiang, and Lembit Sihver. "Therapeutic techniques applied in the heavy-ion therapy at IMP." Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms 269, no. 7 (April 2011): 664–70. http://dx.doi.org/10.1016/j.nimb.2011.01.125.

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38

Wu, Yufei, Jun Li, Liang Xu, Li Lin, and Yi-Han Chen. "Mechanistic and therapeutic perspectives for cardiac arrhythmias: beyond ion channels." Science China Life Sciences 60, no. 4 (March 24, 2017): 348–55. http://dx.doi.org/10.1007/s11427-016-9005-6.

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39

Nasiripourdori, Adak, Valérie Taly, Thomas Grutter, and Antoine Taly. "From Toxins Targeting Ligand Gated Ion Channels to Therapeutic Molecules." Toxins 3, no. 3 (March 21, 2011): 260–93. http://dx.doi.org/10.3390/toxins3030260.

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40

Vay, Laura, Chunjing Gu, and Peter A. McNaughton. "The thermo-TRP ion channel family: properties and therapeutic implications." British Journal of Pharmacology 165, no. 4 (January 25, 2012): 787–801. http://dx.doi.org/10.1111/j.1476-5381.2011.01601.x.

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41

Selvaraj, Stalin, Sridharan Krishnaswamy, Venkappayya Devashya, Swaminathan Sethuraman, and Uma Maheswari Krishnan. "Flavonoid-Metal Ion Complexes: A Novel Class of Therapeutic Agents." Medicinal Research Reviews 34, no. 4 (August 29, 2013): 677–702. http://dx.doi.org/10.1002/med.21301.

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42

Schumacher, Sarah M., and Jeffrey R. Martens. "Ion channel trafficking: A new therapeutic horizon for atrial fibrillation." Heart Rhythm 7, no. 9 (September 2010): 1309–15. http://dx.doi.org/10.1016/j.hrthm.2010.02.017.

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43

Sharma, Purnima, and Liao Ping. "Calcium ion influx in microglial cells: Physiological and therapeutic significance." Journal of Neuroscience Research 92, no. 4 (January 24, 2014): 409–23. http://dx.doi.org/10.1002/jnr.23344.

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44

Wilkinson, Trevor C. I. "Discovery of functional monoclonal antibodies targeting G-protein-coupled receptors and ion channels." Biochemical Society Transactions 44, no. 3 (June 9, 2016): 831–37. http://dx.doi.org/10.1042/bst20160028.

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Анотація:

The development of recombinant antibody therapeutics is a significant area of growth in the pharmaceutical industry with almost 50 approved monoclonal antibodies on the market in the US and Europe. Despite this growth, however, certain classes of important molecular targets have remained intractable to therapeutic antibodies due to complexity of the target molecules. These complex target molecules include G-protein-coupled receptors and ion channels which represent a large potential target class for therapeutic intervention with monoclonal antibodies. Although these targets have typically been addressed by small molecule approaches, the exquisite specificity of antibodies provides a significant opportunity to provide selective modulation of these target proteins. Given this opportunity, substantial effort has been applied to address the technical challenges of targeting these complex membrane proteins with monoclonal antibodies. In this review recent progress made in the strategies for discovery of functional monoclonal antibodies for these challenging membrane protein targets is addressed.

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45

Yogo, Katsunori, Masato Tsuneda, Ryo Horita, Hikaru Souda, Akihiko Matsumura, Hiromichi Ishiyama, Kazushige Hayakawa, Tatsuaki Kanai, and Seiichi Yamamoto. "Three-dimensional dose-distribution measurement of therapeutic carbon-ion beams using a ZnS scintillator sheet." Journal of Radiation Research 62, no. 5 (May 17, 2021): 825–32. http://dx.doi.org/10.1093/jrr/rrab036.

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Abstract The accurate measurement of the 3D dose distribution of carbon-ion beams is essential for safe carbon-ion therapy. Although ionization chambers scanned in a water tank or air are conventionally used for this purpose, these measurement methods are time-consuming. We thus developed a rapid 3D dose-measurement tool that employs a silver-activated zinc sulfide (ZnS) scintillator with lower linear energy transfer (LET) dependence than gadolinium-based (Gd) scintillators; this tool enables the measurement of carbon-ion beams with small corrections. A ZnS scintillator sheet was placed vertical to the beam axis and installed in a shaded box. Scintillation images produced by incident carbon-ions were reflected with a mirror and captured with a charge-coupled device (CCD) camera. A 290 MeV/nucleon mono-energetic beam and spread-out Bragg peak (SOBP) carbon-ion passive beams were delivered at the Gunma University Heavy Ion Medical Center. A water tank was installed above the scintillator with the water level remotely adjusted to the measurement depth. Images were recorded at various water depths and stacked in the depth direction to create 3D scintillation images. Depth and lateral profiles were analyzed from the images. The ZnS-scintillator-measured depth profile agreed with the depth dose measured using an ionization chamber, outperforming the conventional Gd-based scintillator. Measurements were realized with smaller corrections for a carbon-ion beam with a higher LET than a proton. Lateral profiles at the entrance and the Bragg peak depths could be measured with this tool. The proposed method would make it possible to rapidly perform 3D dose-distribution measurements of carbon-ion beams with smaller quenching corrections.

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46

Azimi, Iman, and Gregory R. Monteith. "Plasma membrane ion channels and epithelial to mesenchymal transition in cancer cells." Endocrine-Related Cancer 23, no. 11 (November 2016): R517—R525. http://dx.doi.org/10.1530/erc-16-0334.

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A variety of studies have suggested that epithelial to mesenchymal transition (EMT) may be important in the progression of cancer in patients through metastasis and/or therapeutic resistance. A number of pathways have been investigated in EMT in cancer cells. Recently, changes in plasma membrane ion channel expression as a consequence of EMT have been reported. Other studies have identified specific ion channels able to regulate aspects of EMT induction. The utility of plasma membrane ion channels as targets for pharmacological modulation make them attractive for therapeutic approaches to target EMT. In this review, we provide an overview of some of the key plasma membrane ion channel types and highlight some of the studies that are beginning to define changes in plasma membrane ion channels as a consequence of EMT and also their possible roles in EMT induction.

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47

Molenaar, Remco J. "Ion Channels in Glioblastoma." ISRN Neurology 2011 (November 29, 2011): 1–7. http://dx.doi.org/10.5402/2011/590249.

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Glioblastoma is the most common primary brain tumor with the most dismal prognosis. It is characterized by extensive invasion, migration, and angiogenesis. Median survival is only 15 months due to this behavior, rendering focal surgical resection ineffective and adequate radiotherapy impossible. At this moment, several ion channels have been implicated in glioblastoma proliferation, migration, and invasion. This paper summarizes studies on potassium, sodium, chloride, and calcium channels of glioblastoma. It provides an up-to-date overview of the literature that could ultimately lead to new therapeutic targets.

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48

Lee, Dongun, and Jeong Hee Hong. "Nanoparticle-Mediated Therapeutic Application for Modulation of Lysosomal Ion Channels and Functions." Pharmaceutics 12, no. 3 (March 2, 2020): 217. http://dx.doi.org/10.3390/pharmaceutics12030217.

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Applications of nanoparticles in various fields have been addressed. Nanomaterials serve as carriers for transporting conventional drugs or proteins through lysosomes to various cellular targets. The basic function of lysosomes is to trigger degradation of proteins and lipids. Understanding of lysosomal functions is essential for enhancing the efficacy of nanoparticles-mediated therapy and reducing the malfunctions of cellular metabolism. The lysosomal function is modulated by the movement of ions through various ion channels. Thus, in this review, we have focused on the recruited ion channels for lysosomal function, to understand the lysosomal modulation through the nanoparticles and its applications. In the future, lysosomal channels-based targets will expand the therapeutic application of nanoparticles-associated drugs.

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49

Altamura, Concetta, Paola Gavazzo, Michael Pusch, and Jean-François Desaphy. "Ion Channel Involvement in Tumor Drug Resistance." Journal of Personalized Medicine 12, no. 2 (February 3, 2022): 210. http://dx.doi.org/10.3390/jpm12020210.

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Over 90% of deaths in cancer patients are attributed to tumor drug resistance. Resistance to therapeutic agents can be due to an innate property of cancer cells or can be acquired during chemotherapy. In recent years, it has become increasingly clear that regulation of membrane ion channels is an important mechanism in the development of chemoresistance. Here, we review the contribution of ion channels in drug resistance of various types of cancers, evaluating their potential in clinical management. Several molecular mechanisms have been proposed, including evasion of apoptosis, cell cycle arrest, decreased drug accumulation in cancer cells, and activation of alternative escape pathways such as autophagy. Each of these mechanisms leads to a reduction of the therapeutic efficacy of administered drugs, causing more difficulty in cancer treatment. Thus, targeting ion channels might represent a good option for adjuvant therapies in order to counteract chemoresistance development.

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50

Griffin, Michaela, Stuart Smith, Raheela Khan, Surajit Basu, and Joshua Branter. "EXTH-34. ION CHANNELS AS A THERAPEUTIC TARGET IN PAEDIATRIC HIGH-GRADE GLIOMAS." Neuro-Oncology 23, Supplement_6 (November 2, 2021): vi170—vi171. http://dx.doi.org/10.1093/neuonc/noab196.673.

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Abstract Pediatric Glioblastoma Multiforme (GBM) is a leading cause of CNS cancer-related death in children. The scarcity of treatments for GBM has opened the field to new pathways in adults, such as tumour treating fields(TTF). Studies have identified the clinical benefit of electrotherapy in combination with chemotherapeutics, however the mechanistic action is unclear. Increasing evidence suggests that ion channels not only regulate electrical signalling of excitable cells, but are also crucial in the development/progression of brain tumours. Ion channels are essential in cell-cycle control, invasion and migration of cancer cells, therefore presenting as valuable therapeutic targets. Candidate ion channel genes(ICG) associated with high-grade glioma (HGG) were identified via analysis of inhouse and publicly available data sets. Expression patterns of selected ICGs were assessed along with clinician correlations.. Protein and RNA expression of target ICGs was assessed in pGBM cell lines/ TMAs. Finally, the Human ClariomTMS array was used for whole transcriptome gene expression analysis of paediatric GBM cell lines treated with tumour treating fields or low frequency electrical fields via deep brain stimulating electrodes. Paediatric brain tumour cells were exposed to genetic and pharmacological manipulation of CLIC1 and CLIC4 ion channels individually or in combination. We have shown that HGG exhibit increased expression of CLIC4 and CLIC1 at protein and RNA levels in both publically available data sets and inhouse cell lines / TMAs. Clinical correlation determined that high CLIC4 and CLIC1 expression was associated with poor overall survival. Further to this, DNA array analysis revealed a downregulation of CLIC1 and CLIC4 ion channels genes in KNS42 cells when treated with electrotherapy compared to untreated cells. Inhibition of CLIC1 and CLIC4 reduces Cl- flux across cell membranes and reduces cell proliferation. These data provide rationale that manipulation of ICGs will reduce the capacity of childhood brain tumours to proliferate and invade.

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