NADPH oxidase promotes glioblastoma radiation resistance in a PTEN-dependent manner DOI Creative Commons
Kirsten Ludwig,

Janel E. Le Belle,

Sree Deepthi Muthukrishnan

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: June 17, 2022

ABSTRACT Aims The goal of this study was to determine whether NADPH oxidase (NOX)-produced reactive oxygen species enhances brain tumor growth glioblastoma (GBM) under hypoxic conditions and during radiation treatment. Results Exogenous ROS promoted in gliomasphere cultures that expressed functional PTEN, but not tumors were PTEN deficient. Hypoxia induced the production endogenous cytoplasmic cell via activation NOX. NOX resulted oxidation downstream Akt activation. Radiation also which, turn, cellular protection could be abrogated by knockdown key component, p22. Knockdown p22 inhibited enhanced efficacy PTEN-expressing GBM cells. Innovation While other studies have implicated function models, these demonstrate physiological hypoxia following GBM, two are seen patients. plays an important role a model system, PTEN-non-functional systems provide potential, patient-specific therapeutic opportunity. Conclusions This provides strong basis for pursuing inhibition cells as possible adjunct therapy.

Language: Английский

Glioblastoma Therapy: Past, Present and Future DOI Open Access
Elena Obrador, Paz Moreno-Murciano, María Oriol‐Caballo

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2529 - 2529

Published: Feb. 21, 2024

Glioblastoma (GB) stands out as the most prevalent and lethal form of brain cancer. Although great efforts have been made by clinicians researchers, no significant improvement in survival has achieved since Stupp protocol became standard care (SOC) 2005. Despite multimodality treatments, recurrence is almost universal with rates under 2 years after diagnosis. Here, we discuss recent progress our understanding GB pathophysiology, particular, importance glioma stem cells (GSCs), tumor microenvironment conditions, epigenetic mechanisms involved growth, aggressiveness recurrence. The discussion on therapeutic strategies first covers SOC treatment targeted therapies that shown to interfere different signaling pathways (pRB/CDK4/RB1/P16

Language: Английский

Citations

65
microRNAs (miRNAs) in Glioblastoma Multiforme (GBM)—Recent Literature Review DOI Open Access
Marianna Makowska, Beata Smolarz, Hanna Romanowicz

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3521 - 3521

Published: Feb. 9, 2023

Glioblastoma multiforme (GBM) is the most common, malignant, poorly promising primary brain tumor. GBM characterized by an infiltrating growth nature, abundant vascularization, and a rapid aggressive clinical course. For many years, standard treatment of gliomas has invariably been surgical supported radio- chemotherapy. Due to location significant resistance conventional therapies, prognosis glioblastoma patients very poor cure rate low. The search for new therapy targets effective therapeutic tools cancer current challenge medicine science. microRNAs (miRNAs) play key role in cellular processes, such as growth, differentiation, cell division, apoptosis, signaling. Their discovery was breakthrough diagnosis diseases. Understanding structure miRNAs may contribute understanding mechanisms regulation dependent on miRNA pathogenesis diseases underlying these short non-coding RNAs, including glial tumors. This paper provides detailed review latest reports relationship between changes expression individual formation development gliomas. use this also discussed.

Language: Английский

Citations

60
DNA Alkylation Damage by Nitrosamines and Relevant DNA Repair Pathways DOI Open Access
Jörg Fahrer, Markus Christmann

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4684 - 4684

Published: Feb. 28, 2023

Nitrosamines occur widespread in food, drinking water, cosmetics, as well tobacco smoke and can arise endogenously. More recently, nitrosamines have been detected impurities various drugs. This is of particular concern are alkylating agents that genotoxic carcinogenic. We first summarize the current knowledge on different sources chemical nature with a focus relevant nitrosamines. Subsequently, we present major DNA alkylation adducts induced by upon their metabolic activation CYP450 monooxygenases. then describe repair pathways engaged adducts, which include base excision repair, direct damage reversal MGMT ALKBH, nucleotide repair. Their roles protection against carcinogenic effects highlighted. Finally, address translesion synthesis tolerance mechanism to adducts.

Language: Английский

Citations

39
Tumor-derived small extracellular vesicles: potential roles and mechanism in glioma DOI Creative Commons
Xu Guo,

Rui Sui,

Haozhe Piao

et al.

Journal of Nanobiotechnology, Journal Year: 2022, Volume and Issue: 20(1)

Published: Aug. 23, 2022

Abstract Small extracellular vesicles (SEVs) are containing DNA, RNA, and proteins involved in intercellular communication function, playing an essential role the growth metastasis of tumors. SEVs present various body fluids can be isolated extracted from blood, urine, cerebrospinal fluid. Under both physiological pathological conditions, released by some cells, such as immune, stem, tumor a cytosolic manner. secreted cells called tumor-derived exosomes (TEXs) because their origin corresponding parent cells. Glioma is most common intracranial tumor, accounting for approximately half primary tumors, characterized insidious onset, high morbidity, mortality rate. Complete removal tissues surgery difficult. Chemotherapy improve survival quality patients to certain extent; however, gliomas prone chemoresistance, which seriously affects prognosis patients. In recent years, TEXs have played vital occurrence, development, associated immune response, chemotherapy resistance, radiation therapy glioma. This article reviews glioma progression, drug clinical diagnosis.

Language: Английский

Citations

31
The landscape of circRNAs in gliomas temozolomide resistance: Insights into molecular pathways DOI Creative Commons
Alireza Mafi, Neda Hedayati,

Samaneh Kahkesh

et al.

Non-coding RNA Research, Journal Year: 2024, Volume and Issue: 9(4), P. 1178 - 1189

Published: May 21, 2024

As the deadliest type of primary brain tumor, gliomas represent a significant worldwide health concern. Circular RNA (circRNA), unique non-coding molecule, seems to be one most alluring target molecules involved in pathophysiology many kinds cancers. CircRNAs have been identified as prospective targets and biomarkers for diagnosis treatment numerous disorders, particularly malignancies. Recent research has established clinical link between temozolomide (TMZ) resistance certain circRNA dysregulations glioma tumors. may play therapeutic role controlling or overcoming TMZ provide guidance novel kind individualized therapy. To address biological characteristics circRNAs their potential induce TMZ, this review highlighted summarized possible roles that molecular pathways drug resistance, including Ras/Raf/ERK PI3K/Akt signaling pathway metabolic processes gliomas.

Language: Английский

Citations

8
Radiotherapy of high-grade gliomas: dealing with a stalemate DOI Open Access
Guido Fròsina

Critical Reviews in Oncology/Hematology, Journal Year: 2023, Volume and Issue: 190, P. 104110 - 104110

Published: Aug. 30, 2023

Language: Английский

Citations

11
Modulation of diverse oncogenic signaling pathways by oroxylin A: An important strategy for both cancer prevention and treatment DOI
Anjana Sajeev, Mangala Hegde, Uzini Devi Daimary

et al.

Phytomedicine, Journal Year: 2022, Volume and Issue: 105, P. 154369 - 154369

Published: Aug. 1, 2022

Language: Английский

Citations

17
EGFRvIII Promotes the Proneural–Mesenchymal Transition of Glioblastoma Multiforme and Reduces Its Sensitivity to Temozolomide by Regulating the NF-κB/ALDH1A3 Axis DOI Open Access

Zhongfang Shi,

Guanzhang Li, You Zhai

et al.

Genes, Journal Year: 2023, Volume and Issue: 14(3), P. 651 - 651

Published: March 4, 2023

(1) Background: Glioblastoma multiforme (GBM) is the most common and malignant intracranial tumor in adults. At present, temozolomide (TMZ) recognized as preferred chemotherapeutic drug for GBM, but some patients have low sensitivity to TMZ or chemotherapy resistance TMZ. Our previous study found that GBM with EGFRvIII (+) However, reasons possible mechanisms of chemoradiotherapy are not clear. (2) Methods: In this study, tissue samples cell lines, glioma stem NSG mice were used explore causes (+)-GBM. (3) Results: The promoted proneural–mesenchymal transition reduced its TMZ, regulated expression ALDH1A3. (4) Conclusions: activated NF-κB pathway further ALDH1A3 promote reduce which will provide an experimental basis selection clinical drugs (+).

Language: Английский

Citations

10
The role of lncRNAs in the interplay of signaling pathways and epigenetic mechanisms in glioma DOI
Can Bora Yildiz,

Jian Du,

K. Naga Mohan

et al.

Epigenomics, Journal Year: 2025, Volume and Issue: 17(2), P. 125 - 140

Published: Jan. 19, 2025

Gliomas, highly aggressive tumors of the central nervous system, present overwhelming challenges due to their heterogeneity and therapeutic resistance. Glioblastoma multiforme (GBM), most malignant form, underscores this clinical urgency dismal prognosis despite treatment regimens. Recent advances in cancer research revealed signaling pathways epigenetic mechanisms that intricately govern glioma progression, offering multifaceted targets for intervention. This review explores dynamic interplay between events regulation context glioma, with a particular focus on crucial roles played by non-coding RNAs (ncRNAs). Through direct indirect targeting, ncRNAs emerge as key regulators shaping molecular landscape glioblastoma across its various stages. By dissecting these intricate regulatory networks, novel patient-tailored strategies could be devised improve patient outcomes devastating disease.

Language: Английский

Citations

0
The Clinical Role of miRNAs in the Development and Treatment of Glioblastoma DOI Open Access
Samantha Epistolio, Paolo Spina, Ismail Zaed

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2723 - 2723

Published: March 18, 2025

Glioblastoma multiforme (GBM) is the most common brain tumor and one of aggressive, with a median overall survival (OS) only 15–18 months. These characteristics make it necessary to identify new targets for improvement prognosis better prediction response therapies currently available GBM patients. One possible candidate target could be evaluation miRNAs. miRNAs are small non-coding RNAs that play important roles in post-transcriptional gene regulation. Due their functions, also control biological processes underlying development may considered clinical role. This narrative review introduces concept from molecular perspective then addresses specific described literature as relevant development, prognosis, patients affected by GBM.

Language: Английский

Citations

0