Applications of Focused Ultrasound for the Treatment of Glioblastoma: A New Frontier

Cancers, Год журнала: 2022, Номер 14(19), С. 4920 - 4920

Опубликована: Окт. 8, 2022

Glioblastoma (GBM) is an aggressive primary astrocytoma associated with short overall survival. Treatment for GBM primarily consists of maximal safe surgical resection, radiation therapy, and chemotherapy using temozolomide. Nonetheless, recurrence tumor progression the norm, driven by stem cell activity a high mutational burden. Focused ultrasound (FUS) has shown promising results in preclinical clinical trials treatment received regulatory approval other neoplasms. Here, we review range applications FUS GBM, which depend on parameters, including frequency, power, pulse duration, duty cycle. Low-intensity can be used to transiently open blood–brain barrier (BBB), restricts diffusion most macromolecules therapeutic agents into brain. Under guidance from magnetic resonance imaging, BBB targeted precise location permit molecules only at vicinity tumor, preventing side effects healthy tissue. opening also improve detection cell-free DNA liquid biopsies, allowing non-invasive diagnosis identification molecular mutations. High-intensity cause ablation via hyperthermic effect. Additionally, stimulate immunological attack cells, activate sonosensitizers exert cytotoxic tissue, sensitize tumors therapy. Finally, another mechanism under investigation, known as histotripsy, produces acoustic cavitation rather than thermal effects.

Язык: Английский

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Nrf2 signaling pathway: current status and potential therapeutic targetable role in human cancers

Frontiers in Oncology, Год журнала: 2023, Номер 13

Опубликована: Сен. 22, 2023

Cancer is a borderless global health challenge that continues to threaten human health. Studies have found oxidative stress (OS) often associated with the etiology of many diseases, especially aging process and cancer. Involved in OS reaction as key transcription factor, Nrf2 pivotal regulator cellular redox state detoxification. can prevent damage by regulating gene expression antioxidant response elements (ARE) promote process. generated an imbalance promotes accumulation mutations genome instability, thus establishment development different cancers. activation regulates plethora processes inducing proliferation, differentiation death, strongly OS-mediated What’s more, also involved anti-inflammatory effects metabolic disorders, neurodegenerative multidrug resistance. highly expressed multiple body parts digestive system, respiratory reproductive system nervous system. In oncology research, has emerged promising therapeutic target. Therefore, certain natural compounds drugs exert anti-cancer through signaling pathway, blocking pathway reduce some types tumor recurrence rates increase sensitivity chemotherapy. However, Nrf2’s dual role controversial impact cancer are inevitable consideration factors when treating this review, we summarized current biological characteristics its mechanism cells, discussed Keap1/Nrf2/ARE downstream genes, elaborated related pathways such AMPK/mTOR NF-κB. Besides, main target strategies using inhibitors or activators, well possible positive negative were reviewed. It be concluded serves important factor formation development, provides basis for targeted therapy

Язык: Английский

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Advancements in Glioma Care: Focus on Emerging Neurosurgical Techniques

Biomedicines, Год журнала: 2023, Номер 12(1), С. 8 - 8

Опубликована: Дек. 20, 2023

Background: Despite significant advances in understanding the molecular pathways of glioma, translating this knowledge into effective long-term solutions remains a challenge. Indeed, gliomas pose challenge to neurosurgical oncology because their diverse histopathological features, genetic heterogeneity, and clinical manifestations. Relevant sections: This study focuses on glioma complexity by reviewing recent management, also considering new classification systems emerging techniques. To bridge gap between approaches standards care, importance diagnosis use techniques such as laser interstitial thermal therapy (LITT) focused ultrasound (FUS) are emphasized, exploring how integration with can personalize improve treatment gliomas. Conclusions: The choice LITT FUS should be tailored each case, factors tumor characteristics patient health. is favored for larger, complex tumors, while standard smaller, deep-seated ones. Both equally small superficial tumors. Our provides clear guidance treating pediatric low-grade highlights crucial roles managing high-grade adults. research sets stage improved care future developments field neurosurgery.

Язык: Английский

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Molecular Targeted Therapies in Glioblastoma Multiforme: A Systematic Overview of Global Trends and Findings

Brain Sciences, Год журнала: 2023, Номер 13(11), С. 1602 - 1602

Опубликована: Ноя. 17, 2023

This systematic review assesses current molecular targeted therapies for glioblastoma multiforme (GBM), a challenging condition with limited treatment options. Using PRISMA methodology, 166 eligible studies, involving 2526 patients (61.49% male, 38.51% female, male-to-female ratio of 1.59/1), were analyzed. In laboratory 52.52% primarily used human cell cultures (HCC), and 43.17% employed animal samples (mainly mice). Clinical participants ranged from 18 to 100 years, 60.2% using combined 39.8% monotherapies. Mechanistic categories included Protein Kinase Phosphorylation (41.6%), Cell Cycle-Related Mechanisms (18.1%), Microenvironmental Targets (19.9%), Immunological (4.2%), Other (16.3%). Key targets Epidermal Growth Factor Receptor (EGFR) (10.8%), Mammalian Target Rapamycin (mTOR) (7.2%), Vascular Endothelial (VEGF) (6.6%), Mitogen-Activated (MEK) (5.4%). provides comprehensive assessment GBM, highlighting their varied efficacy in clinical settings, ultimately impacting overall progression-free survival GBM management.

Язык: Английский

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Glioma Stem Cells as Promoter of Glioma Progression: A Systematic Review of Molecular Pathways and Targeted Therapies

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(14), С. 7979 - 7979

Опубликована: Июль 22, 2024

Gliomas’ aggressive nature and resistance to therapy make them a major problem in oncology. Gliomas continue have dismal prognoses despite significant advancements medical science, traditional treatments like surgery, radiation (RT), chemotherapy (CT) frequently prove be ineffective. After glioma stem cells (GSCs) were discovered, the view of gliomas as homogeneous masses changed. GSCs are essential for tumor growth, treatment resistance, recurrence. These cells’ distinct capacities differentiation self-renewal changing our knowledge biology gliomas. This systematic literature review aims uncover molecular mechanisms driving progression associated with GSCs. The adhered PRISMA guidelines, thorough search conducted on PubMed, Ovid MED-LINE, EMBASE. first was performed 1 March 2024, updated 15 May 2024. Employing MeSH terms Boolean operators, focused GCSs-mediated progression. Inclusion criteria encompassed English language studies, preclinical clinical trials. A number 957 papers initially identified, which 65 studies spanning from 2005 2024 finally included review. main GSC model distribution is arranged decreasing order frequency: U87: 20 (32.0%); U251: 13 (20.0%); A172: 4 (6.2%); T98G: 2 (3.17%). From most least frequent, primary pathway follows: Notch: 8 (12.3%); STAT3: 6 (9.2%); Wnt/β-catenin: HIF: 5 (7.7%); PI3K/AKT: (6.2%). effects, common, inhibition differentiation: 22 (33.8%); increased proliferation: 18 (27.7%); enhanced invasive ability: (23.1%); self-renewal: apoptosis: 3 (4.6%). work highlights heterogeneity dynamic interplay within glioblastoma microenvironment, underscoring need tailored approach. few key pathways influencing behavior JAK/STAT3, PI3K/AKT, Wnt/β-catenin, Notch. Therapy may target these pathways. research urges more study fill gaps translate findings into useful approaches that could improve GBM patient outcomes.

Язык: Английский

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Glioblastoma multiforme: insights into pathogenesis, key signaling pathways, and therapeutic strategies

Molecular Cancer, Год журнала: 2025, Номер 24(1)

Опубликована: Фев. 26, 2025

Glioblastoma multiforme (GBM) is the most prevalent and aggressive primary brain tumor in adults, characterized by a poor prognosis significant resistance to existing treatments. Despite progress therapeutic strategies, median overall survival remains approximately 15 months. A hallmark of GBM its intricate molecular profile, driven disruptions multiple signaling pathways, including PI3K/AKT/mTOR, Wnt, NF-κB, TGF-β, critical growth, invasion, treatment resistance. This review examines epidemiology, mechanisms, prospects targeting these pathways GBM, highlighting recent insights into pathway interactions discovering new targets improve patient outcomes.

Язык: Английский

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Wnt Signaling in Brain Tumors: A Challenging Therapeutic Target

Biology, Год журнала: 2023, Номер 12(5), С. 729 - 729

Опубликована: Май 16, 2023

The involvement of Wnt signaling in normal tissue homeostasis and disease has been widely demonstrated over the last 20 years. In particular, dysregulation pathway components suggested as a relevant hallmark several neoplastic malignancies, playing role cancer onset, progression, response to treatments. this review, we summarize current knowledge on instructions provided by during organogenesis and, particularly, brain development. Moreover, recapitulate most mechanisms through which aberrant activation may impact tumorigenesis tumor aggressiveness, with particular focus mutual interdependency existing between microenvironment. Finally, latest anti-cancer therapeutic approaches employing specific targeting are extensively reviewed discussed. conclusion, here provide evidence that signaling, due its pleiotropic features, represent target context, although additional efforts will be needed to: (i) demonstrate real clinical inhibition these tumors; (ii) overcome some still unsolved concerns about potential systemic effects such approaches; (iii) achieve efficient penetration.

Язык: Английский

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Oncolytic herpes simplex viruses for the treatment of glioma and targeting glioblastoma stem-like cells

Frontiers in Cellular and Infection Microbiology, Год журнала: 2023, Номер 13

Опубликована: Май 31, 2023

Glioblastoma (GBM) is one of the most lethal cancers, having a poor prognosis and median survival only about 15 months with standard treatment (surgery, radiation, chemotherapy), which has not been significantly extended in decades. GBM demonstrates remarkable cellular heterogeneity, glioblastoma stem-like cells (GSCs) at apex. GSCs are subpopulation that possess ability to self-renew, differentiate, initiate tumor formation, manipulate microenvironment (TME). no longer considered static population specific markers but quite flexible phenotypically driving heterogeneity therapeutic resistance. In light these features, they critical target for successful therapy. Oncolytic viruses, particular oncolytic herpes simplex viruses (oHSVs), have many attributes therapy promising agents GSCs. oHSVs genetically-engineered selectively replicate kill cancer cells, including GSCs, normal cells. Moreover, oHSV can induce anti-tumor immune responses synergize other therapies, such as chemotherapy, DNA repair inhibitors, checkpoint potentiate effects reduce GSC populations partly responsible chemo- radio-resistance. Herein, we present an overview activity different oHSVs, clinical trial results, combination strategies enhance efficacy, arming oHSV. Throughout, focus will be on studies specifically targeting Recent trials approval G47Δ Japan patients recurrent glioma demonstrate efficacy promise

Язык: Английский

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Osmotic Pressure and Its Biological Implications

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(6), С. 3310 - 3310

Опубликована: Март 14, 2024

Gaining insight into osmotic pressure and its biological implications is pivotal for revealing mechanisms underlying numerous fundamental processes across scales will contribute to the biomedical pharmaceutical fields. This review aims provide an overview of current understanding, focusing on two central issues: (i) how determine theoretically (ii) affects important activities. More specifically, we discuss representative theoretical equations models different solutions, emphasizing their applicability limitations, summarize effect lipid phase separation, cell division, differentiation, dependence these processes. We highlight that new theory applicable all experimentally feasible temperatures solute concentrations needs be developed, further studies regarding role in other should also carried out improve our comprehensive in-depth understanding. Moreover, point importance challenges developing techniques vivo measurement pressure.

Язык: Английский

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Harnessing the potential of nanoengineered siRNAs carriers for target responsive glioma therapy: Recent progress and future opportunities

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 266, С. 131048 - 131048

Опубликована: Март 23, 2024

Язык: Английский

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