Identification and validation of an anoikis-associated gene signature to predict clinical character, stemness, IDH mutation, and immune filtration in glioblastoma

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 25, 2022

Background Glioblastoma (GBM) is the most prominent and aggressive primary brain tumor in adults. Anoikis a specific form of programmed cell death that plays key role invasion metastasis. The presence anti-anoikis factors associated with aggressiveness drug resistance. Methods non-negative matrix factorization algorithm was used for effective dimension reduction integrated datasets. Differences microenvironment (TME), stemness indices, clinical characteristics between two clusters were analyzed. Difference analysis, weighted gene coexpression network analysis (WGCNA), univariate Cox regression, least absolute shrinkage selection operator regression leveraged to screen prognosis-related genes construct risk score model. Immunohistochemistry performed evaluate expression representative specimens. relationship TME, stemness, traits, immunotherapy response assessed GBM pancancer. Results Two definite identified on basis anoikis-related expression. Patients assigned C1 characterized by shortened overall survival, higher suppressive immune infiltration levels, lower indices. We further constructed scoring model quantify regulatory patterns genes. group poor prognosis, cells differentiated phenotype, whereas exhibited opposite effects. In addition, patients frequency isocitrate dehydrogenase (IDH) mutations more sensitive immunotherapy. Drug sensitivity performed, revealing may benefit from drugs targeting PI3K/mTOR signaling pathway. Conclusion revealed potential relationships features, IDH mutation, elucidated their therapeutic value.

Language: Английский

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New Directions in the Therapy of Glioblastoma

Cancers, Journal Year: 2022, Volume and Issue: 14(21), P. 5377 - 5377

Published: Oct. 31, 2022

Glioblastoma is the most common histologic type of all gliomas and contributes to 57.3% cases. Despite standard management based on surgical resection radiotherapy, it related poor outcome, with a 5-year relative survival rate below 6.9%. In order improve overall outcome for patients, new therapeutic strategies are needed. Herein, we describe current state knowledge novel targeted therapies in glioblastoma. Based recent studies, compared treatment efficacy measured by progression-free patients treated selected potential antitumor drugs. The results application analyzed inhibitors highly variable despite encouraging conclusions previous preclinical studies. This paper focused drugs that target major glioblastoma kinases. As far, some BRAF favorable. Vemurafenib demonstrated long-term clinical trials while combination dabrafenib trametinib improves PFS both vemurafenib alone. There no evidence any MEK inhibitor effective monotherapy. According knowledge, inhibition more advantageous than Moreover, mTOR (especially paxalisib) may be considered particularly important group. Everolimus partial response significant proportion when combined bevacizumab, however its actual role unclear. Neither nintedanib nor pemigatinib were efficient GBM. Among anti-VEGF drugs, bevacizumab monotherapy was well-tolerated option, significantly associated anti-GBM activity recurrent aflibercept pazopanib has not been demonstrated. Apatinib proven tolerable single trial, but research Lenvatinib under trial. Finally, promising from study regorafenib confirmed ongoing randomized AGILE studies conducted so far have provided relatively wide range which at least well tolerated trials. comprehensive understanding molecular biology promises further outcomes patients.

Language: Английский

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IDHwt glioblastomas can be stratified by their transcriptional response to standard treatment, with implications for targeted therapy

Genome biology, Journal Year: 2024, Volume and Issue: 25(1)

Published: Feb. 7, 2024

Glioblastoma (GBM) brain tumors lacking IDH1 mutations (IDHwt) have the worst prognosis of all neoplasms. Patients receive surgery and chemoradiotherapy but almost always fatally recur.

Language: Английский

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Comprehensive understanding of glioblastoma molecular phenotypes: classification, characteristics, and transition

Cancer Biology and Medicine, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 19

Published: May 6, 2024

Among central nervous system-associated malignancies, glioblastoma (GBM) is the most common and has highest mortality rate. The high heterogeneity of GBM cell types complex tumor microenvironment frequently lead to recurrence sudden relapse in patients treated with temozolomide. In precision medicine, research on treatment increasingly focusing molecular subtyping precisely characterize cellular heterogeneity, as well refractory nature toward therapy. Deep understanding different expression patterns subtypes critical. Researchers have recently proposed tetra fractional or tripartite methods for detecting subtypes. various show significant differences gene biological behaviors. These also exhibit plasticity their regulatory pathways, oncogene expression, alterations, differential responses standard Herein, we summarize current typing scheme major molecular/genetic characteristics each subtype. Furthermore, review mesenchymal transition mechanisms under regulators.

Language: Английский

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New mechanism of LncRNA: In addition to act as a ceRNA

Non-coding RNA Research, Journal Year: 2024, Volume and Issue: 9(4), P. 1050 - 1060

Published: June 4, 2024

Long non-coding RNAs (LncRNAs) are a class of RNA molecules with nucleic acid lengths ranging from 200 bp to 100 kb that cannot code for proteins, which diverse and widely expressed in both animals plants. Scholars have found lncRNAs can regulate human physiological processes at the gene protein levels, mainly through regulation epigenetic, transcriptional post-transcriptional levels genes as well immune response by regulating expression cells inflammatory factors, thus participate occurrence development variety diseases. From downstream targets lncRNAs, we summarize new research progress lncRNA mechanisms other than miRNA sponges recent years, aiming provide ideas directions study mechanisms.

Language: Английский

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Molecular mechanisms of resveratrol as chemo and radiosensitizer in cancer

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 10, 2023

One of the primary diseases that cause death worldwide is cancer. Cancer cells can be intrinsically resistant or acquire resistance to therapies and drugs used for cancer treatment through multiple mechanisms action favor cell survival proliferation, becoming one leading causes failure against A promising strategy overcome chemoresistance radioresistance co-administration anticancer agents natural compounds with properties, such as polyphenolic compound resveratrol (RSV). RSV has been reported able sensitize chemotherapeutic radiotherapy, promoting death. This review describes molecular by which sensitizes tumor radiotherapy chemotherapy treatment.

Language: Английский

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Targeting Transcription Factors ATF5, CEBPB and CEBPD with Cell-Penetrating Peptides to Treat Brain and Other Cancers

Cells, Journal Year: 2023, Volume and Issue: 12(4), P. 581 - 581

Published: Feb. 11, 2023

Developing novel therapeutics often follows three steps: target identification, design of strategies to suppress activity and drug development implement the strategies. In this review, we recount evidence identifying basic leucine zipper transcription factors ATF5, CEBPB, CEBPD as targets for brain other malignancies. We describe that exploit structures create inhibitory dominant-negative (DN) mutant forms selectively growth survival cancer cells. then discuss compare four peptides (CP-DN-ATF5, Dpep, Bpep ST101) in which DN sequences are joined with cell-penetrating domains drugs pass through tissue barriers into The peptide show both efficacy safety suppressing cancers vivo, ST101 is currently clinical trials solid tumors, including GBM. further consider known mechanisms by act how these have been exploited rationally designed combination therapies. additionally lacunae our knowledge about merit research. Finally, suggest short- long-term directions creating new generations targeting CEBPD, treating

Language: Английский

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A positive feedback between PDIA3P1 and OCT4 promotes the cancer stem cell properties of esophageal squamous cell carcinoma

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 22, 2024

Abstract Background Increasing evidence has indicated that long non-coding RNAs (lncRNAs) have been proven to regulate esophageal cancer progression. The lncRNA protein disulfide isomerase family A member 3 pseudogene 1 (PDIA3P1) shown promote stem cell properties; however, its mechanism of action remains unclear. In this study, we investigated the regulation properties by interaction PDIA3P1 with proteins. Methods GEPIA2 and Gene Expression Omnibus databases were used analyze gene expression. expression in human squamous carcinoma (ESCC) tissues lines was detected quantitative real-time polymerase chain reaction (qRT-PCR). Loss-of-function experiments performed determine effects on ESCC proliferation, migration, invasion. sphere formation assay, number side population cells, CD271 + /CD44 cells flow cytometry identify properties. RNA immunoprecipitation (RIP), pull-down, co-immunoprecipitation (co-IP), dual luciferase reporter, cleavage under targets tagmentation (CUT&Tag) assays elucidate underlying molecular mechanisms. Results upregulated tissues. Functionally, higher promoted invasion, metastasis inhibited apoptosis cancer. Importantly, ESCC. Mechanistically, interacted stabilized octamer-binding transcription factor 4 (OCT4) eliminating ubiquitination ubiquitinating enzyme WW domain-containing 2 (WWP2). Moreover, as a factor, OCT4 bound promoter transcription. Conclusions Our research revealed novel which positive feedback loop exists between OCT4. It also demonstrated PDIA3P1-WWP2-OCT4 is beneficial for promoting Owing regulatory relationship, PDIA3P1-WWP2-OCT4-positive might be diagnosis prognosis, well development therapeutics

Language: Английский

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Targeting STAT3 potentiates CDK4/6 inhibitors therapy in head and neck squamous cell carcinoma

Cancer Letters, Journal Year: 2024, Volume and Issue: 593, P. 216956 - 216956

Published: May 11, 2024

Language: Английский

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Long Non-Coding RNAs in Malignant Human Brain Tumors: Driving Forces Behind Progression and Therapy

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 694 - 694

Published: Jan. 15, 2025

Long non-coding RNAs (lncRNAs) play a pivotal role in regulating gene expression and are critically involved the progression of malignant brain tumors, including glioblastoma, medulloblastoma, meningioma. These lncRNAs interact with microRNAs (miRNAs), proteins, DNA, influencing key processes such as cell proliferation, migration, invasion. This review highlights multifaceted impact lncRNA dysregulation on tumor underscores their potential therapeutic targets to enhance efficacy chemotherapy, radiotherapy, immunotherapy. The insights provided offer new directions for advancing basic research clinical applications tumors.

Language: Английский

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