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  1. Article ; Online: MGMT in TMZ-based glioma therapy: Multifaceted insights and clinical trial perspectives.

    Shaw, Rajni / Basu, Malini / Karmakar, Subhajit / Ghosh, Mrinal K

    Biochimica et biophysica acta. Molecular cell research

    2024  Volume 1871, Issue 3, Page(s) 119673

    Abstract: Temozolomide (TMZ) is the most preferred and approved chemotherapeutic drug for either first- or second-line chemotherapy for glioma patients across the globe. In glioma patients, resistance to treatment with alkylating drugs like TMZ is known to be ... ...

    Abstract Temozolomide (TMZ) is the most preferred and approved chemotherapeutic drug for either first- or second-line chemotherapy for glioma patients across the globe. In glioma patients, resistance to treatment with alkylating drugs like TMZ is known to be conferred by exalted levels of MGMT gene expression. On the contrary, epigenetic silencing through MGMT gene promoter methylation leading to subsequent reduction in MGMT transcription and protein expression, is predicted to have a response favoring TMZ treatment. Thus, MGMT protein level in cancer cells is a crucial determining factor in indicating and predicting the choice of alkylating agents in chemotherapy or choosing glioma patients directly for a second line of treatment. Thus, in-depth research is necessary to achieve insights into MGMT gene regulation that has recently enticed a fascinating interest in epigenetic, transcriptional, post-transcriptional, and post-translational levels. Furthermore, MGMT promoter methylation, stability of MGMT protein, and related subsequent adaptive responses are also important contributors to strategic developments in glioma therapy. With applications to its identification as a prognostic biomarker, thus predicting response to advanced glioma therapy, this review aims to concentrate on the mechanistic role and regulation of MGMT gene expression at epigenetic, transcriptional, post-transcriptional, and post-translational levels functioning under the control of multiple signaling dynamics.
    MeSH term(s) Humans ; Temozolomide/therapeutic use ; Epigenesis, Genetic ; Glioma/drug therapy ; Glioma/genetics ; Promoter Regions, Genetic ; Signal Transduction ; DNA Modification Methylases/genetics ; Tumor Suppressor Proteins/genetics ; DNA Repair Enzymes/genetics
    Chemical Substances Temozolomide (YF1K15M17Y) ; MGMT protein, human (EC 2.1.1.63) ; DNA Modification Methylases (EC 2.1.1.-) ; Tumor Suppressor Proteins ; DNA Repair Enzymes (EC 6.5.1.-)
    Language English
    Publishing date 2024-01-18
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 60-7
    ISSN 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    ISSN (online) 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
    ISSN 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    DOI 10.1016/j.bbamcr.2024.119673
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uc I Zs.247: Show issues Location:
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  2. Article ; Online: DDX5 (p68) orchestrates β-catenin, RelA and SP1 mediated MGMT gene expression in human colon cancer cells: Implication in TMZ chemoresistance.

    Shaw, Rajni / Karmakar, Subhajit / Basu, Malini / Ghosh, Mrinal K

    Biochimica et biophysica acta. Gene regulatory mechanisms

    2023  Volume 1866, Issue 4, Page(s) 194991

    Abstract: DDX5 (p68) upregulation has been linked with various cancers of different origins, especially Colon Adenocarcinomas. Similarly, across cancers, MGMT has been identified as the major contributor of chemoresistance against DNA alkylating agents like ... ...

    Abstract DDX5 (p68) upregulation has been linked with various cancers of different origins, especially Colon Adenocarcinomas. Similarly, across cancers, MGMT has been identified as the major contributor of chemoresistance against DNA alkylating agents like Temozolomide (TMZ). TMZ is an emerging potent chemotherapeutic agent across cancers under the arena of drug repurposing. Recent studies have established that patients with open MGMT promoters are prone to be innately resistant or acquire resistance against TMZ compared to its closed conformation. However, not much is known about the transcriptional regulation of MGMT gene in the context of colon cancer. This necessitates studying MGMT gene regulation which directly impacts the cellular potential to develop chemoresistance against alkylating agents. Our study aims to uncover an unidentified mechanism of DDX5-mediated MGMT gene regulation. Experimentally, we found that both mRNA and protein expression levels of MGMT were elevated in response to p68 overexpression in multiple human colon cancer cell lines and vice-versa. Since p68 cannot directly interact with the MGMT promoter, transcription factors viz., β-catenin, RelA (p65) and SP1 were also studied as reported contributors. Through co-immunoprecipitation and GST-pull-down studies, p68 was established as an interacting partner of SP1 in addition to β-catenin and NF-κB (p50-p65). Mechanistically, luciferase reporter and chromatin-immunoprecipitation assays demonstrated that p68 interacts with the MGMT promoter via TCF4-LEF, RelA and SP1 sites to enhance its transcription. To the best of our knowledge, this is the first report of p68 as a transcriptional co-activator of MGMT promoter and our study identifies p68 as a novel and master regulator of MGMT gene expression.
    MeSH term(s) Humans ; Temozolomide/pharmacology ; beta Catenin/genetics ; beta Catenin/metabolism ; Drug Resistance, Neoplasm/genetics ; Cell Line, Tumor ; Colonic Neoplasms/drug therapy ; Colonic Neoplasms/genetics ; Alkylating Agents ; Gene Expression ; DNA Modification Methylases/genetics ; Tumor Suppressor Proteins/genetics ; DNA Repair Enzymes/genetics
    Chemical Substances Temozolomide (YF1K15M17Y) ; beta Catenin ; Alkylating Agents ; MGMT protein, human (EC 2.1.1.63) ; DNA Modification Methylases (EC 2.1.1.-) ; Tumor Suppressor Proteins ; DNA Repair Enzymes (EC 6.5.1.-)
    Language English
    Publishing date 2023-10-02
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2918786-2
    ISSN 1876-4320 ; 1874-9399
    ISSN (online) 1876-4320
    ISSN 1874-9399
    DOI 10.1016/j.bbagrm.2023.194991
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 7156: Show issues Location:
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    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
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  3. Article ; Online: Anti-SSTR2 peptide based targeted delivery of potent PLGA encapsulated 3,3'-diindolylmethane nanoparticles through blood brain barrier prevents glioma progression.

    Bhowmik, Arijit / Chakravarti, Sayak / Ghosh, Aparajita / Shaw, Rajni / Bhandary, Suman / Bhattacharyya, Satyaranjan / Sen, Parimal C / Ghosh, Mrinal K

    Oncotarget

    2017  Volume 8, Issue 39, Page(s) 65339–65358

    Abstract: Current therapy for Glioblastoma is insufficient because of the presence of blood brain barrier. It limits the transport of essential drugs to the tumor sites. To overcome this limitation we strategized the delivery of an anticancer compound 3,3'- ... ...

    Abstract Current therapy for Glioblastoma is insufficient because of the presence of blood brain barrier. It limits the transport of essential drugs to the tumor sites. To overcome this limitation we strategized the delivery of an anticancer compound 3,3'-diindolylmethane by encapsulation in poly (lactic-co-glycolic acid) nanoparticles. These nanoparticles were tagged with a novel peptide against somatostatin receptor 2 (SSTR2), a potential target in glioma. The nanoformulation (27-87nm) had loading and encapsulation efficiency of 7.2% and 70% respectively. It was successfully internalized inside the glioma cells resulting in apoptosis. Furthermore, an
    Language English
    Publishing date 2017-09-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2560162-3
    ISSN 1949-2553 ; 1949-2553
    ISSN (online) 1949-2553
    ISSN 1949-2553
    DOI 10.18632/oncotarget.18689
    Database MEDical Literature Analysis and Retrieval System OnLINE

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