Background: Glioblastoma (GBM) is a very frequent primary tumour in the cerebrospinal nervous system. Temozolomide (TMZ) is the first-line treatment for patients with GBM. However, some of GBM patients do not respond to TMZ. O6-methylguanine-DNA-methytransferase (MGMT) remains a major cause. In a previous study, we detected antibodies against MGMT peptides in patients with glioma, and five highly responsive autoantibodies anti-MGMT-02, anti-MGMT-04, anti-MGMT-07, anti-MGMT-10, and anti-MGMT-18 were identified that could be used to dynamically assess chemotherapy-resistant TMZ. Therefore, targeting MGMT peptides may be a potential therapeutic approach for GBM to fight TMZ resistance.
Methods: First, MGMT-02 and MGMT-04 polypeptides with cell-penetrating peptides were designed and connected to FITC tracer for immunofluorescence localisation. CCK-8 and colony formation assay were performed to evaluate cell proliferation ability. Western blot and immunofluorescence analysis were used to detected the expression of apoptosis-related protein. Flow cytometry was used to detect the proportion of apoptosis in cells. TMZ-resistant effect of MGMT-02/04 peptides was assessed in intracranial xenograft nude mouse model.
Results: We also found reduced apoptosis of cells treated with MGMT-02 and MGMT-04 peptides and TMZ compared with those treated separately with TMZ and experiences.
Conclusion: The results of this study indicate that MGMT-02 and MGMT-04 peptides have a role in glioma resistance and that MGMT peptides may serve as a precise target for TMZ-resistant GBM.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9672402 | PMC |
| http://dx.doi.org/10.1016/j.bbrep.2022.101386 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Loss of O-methylguanine DNA methyltransferase (MGMT) in macrophages alters responses to TLR3 stimulation and enhances DNA double-strand breaks and mitophagy.
Sci Rep
November 2024
Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand.
O-methylguanine-DNA methyltransferase (MGMT) is a DNA damage repair enzyme. The roles of this enzyme in immune cells remain unclear. In this study, we explored the roles of MGMT in bone marrow-derived murine macrophages (BMMs) via the use of MGMT knockout (KO) mice.
View Article and Find Full Text PDFAP-2α decreases TMZ resistance of recurrent GBM by downregulating MGMT expression and improving DNA damage.
Life Sci
November 2024
The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Science, Hunan Normal University, Changsha 410081, China; State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha 410081, China. Electronic address:
Aims: The incidence of recurrent gliomas is high, exerting low survival rates and poor prognoses. Transcription factor AP-2α has been reported to regulate the progression of primary glioblastoma (GBM). However, the function of AP-2α in recurrent gliomas is largely unclear.
View Article and Find Full Text PDFPDCD10 Is a Key Player in TMZ-Resistance and Tumor Cell Regrowth: Insights into Its Underlying Mechanism in Glioblastoma Cells.
Cells
August 2024
Department of Neurosurgery and Spine Surgery, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.
Overcoming temozolomide (TMZ)-resistance is a major challenge in glioblastoma therapy. Therefore, identifying the key molecular player in chemo-resistance becomes urgent. We previously reported the downregulation of PDCD10 in primary glioblastoma patients and its tumor suppressor-like function in glioblastoma cells.
View Article and Find Full Text PDFFramework nucleic acid-based nanoparticles enhance temozolomide sensitivity in glioblastoma.
Drug Resist Updat
September 2024
Department of Neurosurgery, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China. Electronic address:
O-methylguanine DNA methyltransferase (MGMT) is a crucial determinant of temozolomide (TMZ) sensitivity in patients with glioblastoma (GBM). The therapeutic potential of small interfering RNA (siRNA) targeting MGMT to enhance TMZ sensitivity has been hampered by serum nuclease degradation, off-target effects, poor accumulation at tumor sites, and low circulation in blood stream. In this study, we developed a framework nucleic acid-based nanoparticles (FNN), which is constructed from a six-helix DNA bundle, to encapsulate and protect siMGMT for improving TMZ sensitivity in GBM treatment.
View Article and Find Full Text PDFTreatment, Prognostic Markers, and Survival in Thymic Neuroendocrine Tumors, with Special Reference to Temozolomide-Based Chemotherapy.
Cancers (Basel)
July 2024
Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing 100029, China.
Article Synopsis
- Thymic neuroendocrine tumors (Th-NETs) are rare, aggressive cancers, and this study aimed to evaluate how prognostic markers and TMZ-based chemotherapy affect patient survival.
- The research involved reviewing records of 32 patients diagnosed with Th-NETs from 2013 to 2023, highlighting median progression-free survival of 12.5 months for those on TMZ and 51.0 months for surgical patients.
- Key findings showed that the neutrophil-to-lymphocyte ratio (NLR) is a vital prognostic indicator, while high Ki67 levels and lack of surgery correlate with worse survival outcomes; suggesting that surgical treatment remains the primary therapy, with further focus needed on specific biomarkers.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!