The regulatory and modulatory roles of TRP family channels in malignant tumors and relevant therapeutic strategies

Acta Pharmaceutica Sinica B, Journal Year: 2021, Volume and Issue: 12(4), P. 1761 - 1780

Published: Nov. 5, 2021

Transient receptor potential (TRP) channels are one primary type of calcium (Ca2+) permeable channels, and those relevant transmembrane intracellular TRP were previously thought to be mainly associated with the regulation cardiovascular neuronal systems. Nowadays, however, accumulating evidence shows that also responsible for tumorigenesis progression, inducing tumor invasion metastasis. However, overall underlying mechanisms possible signaling transduction pathways in malignant tumors might still remain elusive. Therefore, this review, we focus on linkage between significant characteristics such as multi-drug resistance (MDR), metastasis, apoptosis, proliferation, immune surveillance evasion, alterations micro-environment. Moreover, have discussed expression various forms cancer inhibitors' efficacy. The chemo-sensitivity anti-cancer drugs acting clinical applications presented. Furthermore, it would enlightening provide novel therapeutic approaches counteract regarding intervention type.

Language: Английский

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Receptor Tyrosine Kinase Signaling and Targeting in Glioblastoma Multiforme

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(4), P. 1831 - 1831

Published: Feb. 12, 2021

Glioblastoma multiforme (GBM) is amongst the deadliest of human cancers, with a median survival rate just over one year following diagnosis. Characterized by rapid proliferation and diffuse infiltration into brain, GBM notoriously difficult to treat, tumor cells showing limited response existing therapies eventually developing resistance these interventions. As such, there intense interest in better understanding molecular alterations guide development more efficient targeted therapies. tumors can be classified several subtypes which have distinct genetic signatures, they show aberrant activation numerous signal transduction pathways, particularly those connected receptor tyrosine kinases (RTKs) control glioma cell growth, survival, migration, invasion, angiogenesis. There are also non-canonical modes RTK signaling found GBM, involve G-protein-coupled receptors calcium channels. This review uses The Cancer Genome Atlas (TCGA) dataset combination data-mining approach summarize disease characteristics, focus on select pathways that drive pathogenesis. We present unique genomic survey RTKs frequently altered subtypes, as well catalog association scores for all RTKs. Lastly, we discuss current highlight emerging directions research.

Language: Английский

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Active constituents of saffron (Crocus sativus L.) and their prospects in treating neurodegenerative diseases (Review)

Experimental and Therapeutic Medicine, Journal Year: 2023, Volume and Issue: 25(5)

Published: April 3, 2023

Crocus sativus L. (saffron) is widely used as a traditional spice for flavoring, coloring and medicinal purposes. As Chinese herb, saffron promotes blood circulation, removes stasis, cools detoxifies the blood, relieves depression calms mind. According to modern pharmacological studies, active constituents of saffron, including crocetin, safranal crocus aldehyde, exhibit antioxidant, anti-inflammatory, mitochondrial function-improving antidepressant effects. Thus, has potential treat neurodegenerative diseases (NDs) associated with oxidative stress, inflammation impaired function, such Alzheimer's disease, Parkinson's multiple sclerosis cerebral ischemia. The present article provides review effects its in terms neuroprotective effects, antioxidant anti-inflammatory improvement dysfunction, well their clinical application treating NDs.

Language: Английский

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TRP Channels in Cancer: Signaling Mechanisms and Translational Approaches

Biomolecules, Journal Year: 2023, Volume and Issue: 13(10), P. 1557 - 1557

Published: Oct. 22, 2023

Ion channels play a crucial role in wide range of biological processes, including cell cycle regulation and cancer progression. In particular, the transient receptor potential (TRP) family has emerged as promising therapeutic target due to its involvement several stages development dissemination. TRP are expressed large variety cells tissues, by increasing cation intracellular concentration, they monitor mechanical, thermal, chemical stimuli under physiological pathological conditions. Some members superfamily, namely vanilloid (TRPV), canonical (TRPC), melastatin (TRPM), ankyrin (TRPA), have been investigated different types cancer, breast, prostate, lung, colorectal cancer. involved processes such proliferation, migration, invasion, angiogenesis, drug resistance, all related mechanistically associated with signaling pain. Understanding cellular molecular mechanisms which influence provides new opportunities for targeted strategies. Selective inhibitors initial scrutiny experimental animals anti-cancer agents. In-depth knowledge these their regulatory may lead strategies treatment, providing perspectives effective therapies.

Language: Английский

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IL-12-Overexpressed Nanoparticles Suppress the Proliferation of Melanoma Through Inducing ICD and Activating DC, CD8+ T, and CD4+ T Cells

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 2755 - 2772

Published: March 1, 2024

Purpose: The drug resistance and low response rates of immunotherapy limit its application. This study aimed to construct a new nanoparticle (CaCO 3 -polydopamine-polyethylenimine, CPP) effectively deliver interleukin-12 (IL-12) suppress cancer progress through immunotherapy. Methods: size distribution CPP zeta potential were measured using Malvern Zetasizer Nano-ZS90. morphology electrophoresis tentative delay analyzed JEM-1400 transmission electron microscope an ultraviolet spectrophotometer, respectively. Cell proliferation was by MTT assay. Proteins Western blot. IL-12 HMGB1 levels estimated ELISA kits. Live/dead staining assay performed Calcein-AM/PI kit. ATP production detected xenografts in vivo C57BL/6 mice. CD80 + /CD86 , CD3 /CD4 /CD8 flow cytometry. Results: could express EGFP or increase ROS levels. Laser treatment promoted CPP-IL-12 induced the number dead apoptotic cell. laser further enhance CALR extracellular decrease intracellular levels, indicating that it may induce immunogenic cell death (ICD). tumors weights laser-treated mice significantly reduced than controls. expression, expression DC from lymph glands, T cells spleen increased CPP-IL-12-treated compared with granzyme B, IFN-γ, TNF-α serum increased. Interestingly, local back inhibit growth distant untreated tumor. Conclusion: novel overexpress melanoma achieve inducing ICD, activating CD4 cell, enhancing function tumor-reactive CD8 cells. Keywords: immunotherapy, CaCO nanoparticle, interleukin-12, death, tumor therapy

Language: Английский

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Molecular Pathways Implicated in Radioresistance of Glioblastoma Multiforme: What Is the Role of Extracellular Vesicles?

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4883 - 4883

Published: March 2, 2023

Glioblastoma multiforme (GBM) is a primary brain tumor that very aggressive, resistant to treatment, and characterized by high degree of anaplasia proliferation. Routine treatment includes ablative surgery, chemotherapy, radiotherapy. However, GMB rapidly relapses develops radioresistance. Here, we briefly review the mechanisms underpinning radioresistance discuss research stop it install anti-tumor defenses. Factors participate in are varied include stem cells, heterogeneity, microenvironment, hypoxia, metabolic reprogramming, chaperone system, non-coding RNAs, DNA repair, extracellular vesicles (EVs). We direct our attention toward EVs because they emerging as promising candidates diagnostic prognostication tools basis for developing nanodevices delivering anti-cancer agents directly into mass. relatively easy obtain manipulate endow them with desired properties administer using minimally invasive procedures. Thus, isolating from GBM patient, supplying necessary agent capability recognizing specified tissue-cell target, reinjecting original donor appears, at this time, reachable objective personalized medicine.

Language: Английский

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Drug Repurposing - Hypothesis, Molecular Aspects and Therapeutic Applications

IntechOpen eBooks, Journal Year: 2020, Volume and Issue: unknown

Published: April 9, 2020

France.Dr. Badria has 20 patents, 250 publications, more than a dozen books, several marketed pharmaceutical products, and many plenary lectures workshops to his credit.He continues lead

Language: Английский

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Roles of TRPM channels in glioma

Cancer Biology & Therapy, Journal Year: 2024, Volume and Issue: 25(1)

Published: April 29, 2024

Gliomas are the most common type of primary brain tumor. Despite advances in treatment, it remains one aggressive and deadly tumor central nervous system (CNS). characterized by high malignancy, heterogeneity, invasiveness, resistance to radiotherapy chemotherapy. It is urgent find potential new molecular targets for glioma. The TRPM channels consist TRPM1-TPRM8 play a role many cellular functions, including proliferation, migration, invasion, angiogenesis, etc. More more studies have shown that can be used as therapeutic In this review, we first introduce structure, activation patterns, physiological functions channels. Additionally, pathological mechanism glioma mediated TRPM2, 3, 7, 8 related signaling pathways described. Finally, discuss targeting

Language: Английский

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Subtype specific targeting of calcium signaling in breast cancer

Cell Calcium, Journal Year: 2019, Volume and Issue: 85, P. 102109 - 102109

Published: Nov. 12, 2019

Language: Английский

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Glioblastoma pharmacotherapy: A multifaceted perspective of conventional and emerging treatments (Review)

Experimental and Therapeutic Medicine, Journal Year: 2021, Volume and Issue: 22(6)

Published: Oct. 6, 2021

Due to its localisation, rapid onset, high relapse rate and resistance most currently available treatment methods, glioblastoma multiforme (GBM) is considered be the deadliest type of all gliomas. Although surgical resection, chemotherapy radiotherapy are among therapeutic strategies used for GBM, survival rates achieved not satisfactory, there an urgent need novel effective options. In addition single‑target therapy, multi‑target therapies under development. Furthermore, drugs being optimised improve their ability cross blood‑brain barrier. present review, main applied GBM in terms recent agents approaches that pre‑clinical clinical testing were discussed. addition, recently reported experimental data following therapies, including stem cell immunotherapy, gene genomic correction precision medicine, reviewed, advantages drawbacks also summarised.

Language: Английский

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