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      The Mechanisms of Current Platinum Anticancer Drug Resistance in the Glioma

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          Abstract

          Gliomas are the most common and malignant primary tumors of the central nervous system (CNS). Glioblastomas are the most malignant and aggressive form of primary brain tumors and account for the majority of brain tumor-related deaths. The current standard treatment for gliomas is surgical resection supplemented by postoperative chemotherapy. Platinum drugs are a class of chemotherapeutic drugs that affect the cell cycle, and the main site of action is the DNA of cells, which are common chemotherapeutic drugs in clinical practice. Chemotherapy with platinum drugs such as cisplatin, carboplatin, oxaliplatin, or a combination thereof is used to treat a variety of tumors. However, the results of gliomas chemotherapy are unsatisfactory, and resistance to platinum drugs is one of the important reasons. The resistance of gliomas to platinum drugs is the result of a combination of influencing factors. Decreased intracellular drug concentration, enhanced function of cell processing active products, enhanced repair ability of cellular DNA damage, and blockage of related apoptosis pathways play an important role in it. It is known that the pathogenic properties of glioma cells and the response of glioma towards platinum-based drugs are strongly influenced by non-coding RNAs, particularly, by microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). miRNAs and lncRNAs control drug sensitivity and the development of tumor resistance towards platinum drugs. This mini-review summarizes the resistance mechanisms of gliomas to platinum drugs, as well as molecules and therapies that can improve the sensitivity of gliomas to platinum drugs.

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          Most cited references89

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          mTOR signaling in growth control and disease.

          The mechanistic target of rapamycin (mTOR) signaling pathway senses and integrates a variety of environmental cues to regulate organismal growth and homeostasis. The pathway regulates many major cellular processes and is implicated in an increasing number of pathological conditions, including cancer, obesity, type 2 diabetes, and neurodegeneration. Here, we review recent advances in our understanding of the mTOR pathway and its role in health, disease, and aging. We further discuss pharmacological approaches to treat human pathologies linked to mTOR deregulation. Copyright © 2012 Elsevier Inc. All rights reserved.
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            Molecular mechanisms of cisplatin resistance.

            Platinum-based drugs, and in particular cis-diamminedichloroplatinum(II) (best known as cisplatin), are employed for the treatment of a wide array of solid malignancies, including testicular, ovarian, head and neck, colorectal, bladder and lung cancers. Cisplatin exerts anticancer effects via multiple mechanisms, yet its most prominent (and best understood) mode of action involves the generation of DNA lesions followed by the activation of the DNA damage response and the induction of mitochondrial apoptosis. Despite a consistent rate of initial responses, cisplatin treatment often results in the development of chemoresistance, leading to therapeutic failure. An intense research has been conducted during the past 30 years and several mechanisms that account for the cisplatin-resistant phenotype of tumor cells have been described. Here, we provide a systematic discussion of these mechanism by classifying them in alterations (1) that involve steps preceding the binding of cisplatin to DNA (pre-target resistance), (2) that directly relate to DNA-cisplatin adducts (on-target resistance), (3) concerning the lethal signaling pathway(s) elicited by cisplatin-mediated DNA damage (post-target resistance) and (4) affecting molecular circuitries that do not present obvious links with cisplatin-elicited signals (off-target resistance). As in some clinical settings cisplatin constitutes the major therapeutic option, the development of chemosensitization strategies constitute a goal with important clinical implications.
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              A Brief Review on the Mechanisms of miRNA Regulation

              MicroRNAs (miRNAs) are a class of short, endogenously-initiated non-coding RNAs that post-transcriptionally control gene expression via either translational repression or mRNA degradation. It is becoming evident that miRNAs are playing significant roles in regulatory mechanisms operating in various organisms, including developmental timing and host-pathogen interactions as well as cell differentiation, proliferation, apoptosis and tumorigenesis. Likewise, as a regulatory element, miRNA itself is coordinatively modulated by multifarious effectors when carrying out basic functions, such as SNP, miRNA editing, methylation and circadian clock. This mini-review summarized the current understanding of interactions between miRNAs and their targets, including recent advancements in deciphering the regulatory mechanisms that control the biogenesis and functionality of miRNAs in various cellular processes.
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                Author and article information

                Journal
                Curr Pharm Des
                Curr Pharm Des
                CPD
                Current Pharmaceutical Design
                Bentham Science Publishers
                1381-6128
                1873-4286
                30 August 2022
                30 August 2022
                : 28
                : 23
                : 1863-1869
                Affiliations
                [1 ] deptDepartment of Neurosurgery , The First Affiliated Hospital of Harbin Medical University , Harbin, , 150001 , China;
                [2 ] deptCentral Research Laboratory , Bashkir State Medical University , Ufa, , 450008 , Russia;
                [3 ] deptDepartment of Neurosurgery , Shenzhen University General Hospital , Shenzhen, , 518055 , China;
                [4 ] deptDepartment of Neurosurgery , Sechenov First Moscow State Medical University (Sechenov University) , Moscow, , Russia
                Author notes
                [* ]Address correspondence to these authors at the Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China; Tel: 18746072927; E-mail: yangguang@ 123456hrbmu.edu.cn and Department of Neurosurgery, Shenzhen University General Hospital, Shenzhen, 518055, China; E-mail: guangsz@ 123456hotmail.com
                [# ] These authors contributed equally to this work.
                Article
                CPD-28-1863
                10.2174/1381612828666220607105746
                10556399
                35674307
                32ede42a-d042-4629-9cf8-36b34f5a7402
                Copyright @ 2022

                This is an Open Access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode

                History
                : 02 February 2022
                : 12 April 2022
                Funding
                Funded by: China
                Award ID: (81971135) (YQ2020H014) (HLJ2019009) (HYD2020JQ0014)
                Award Recipient : This work was supported by the National Natural Science Foundations of China (81971135); Natural Science Foundations of Heilongjiang (YQ2020H014); “Chunhui Plan” of the Ministry of Education (HLJ2019009); Distinguished Young Foundations of the First Affiliated Hospital of Harbin Medical University (HYD2020JQ0014).
                Categories
                Pharmacology

                Pharmacology & Pharmaceutical medicine
                glioma,platinum drugs,resistance mechanisms,chemosensitivity,prognosis,micrornas,long non-coding rnas

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