Loss of Von Hippel–Lindau (VHL) Tumor Suppressor Gene Function: VHL–HIF Pathway and Advances in Treatments for Metastatic Renal Cell Carcinoma (RCC)

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(18), P. 9795 - 9795

Published: Sept. 10, 2021

Renal cell carcinoma (RCC) is a malignancy of the kidney originating from tubular epithelium. Inactivation von Hippel-Lindau tumor-suppressor gene (VHL) found in most clear renal carcinomas (ccRCCs). The VHL-HIF-VEGF/VEGFR pathway, which involves tumor suppressor protein (VHL), hypoxia-inducible factor (HIF), vascular endothelial growth (VEGF), and its receptor (VEGFR), well-studied therapeutic target for metastatic ccRCC. Therefore, over past decade, anti-angiogenic agents targeting VEGFR have served as standard treatment RCC. Recently, based on immunomodulatory effect anti-VEGFR therapy, immune checkpoint inhibitor combination strategies also emerged strategies. These advances were made possible by improved understanding VHL-HIF pathway. In this review, we summarize historical evolution ccRCC treatments, with focus involvement

Language: Английский

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Multifunctional Au Modified Ti₃C₂-MXene for Photothermal/Enzyme Dynamic/Immune Synergistic Therapy

Nano Letters, Journal Year: 2022, Volume and Issue: 22(20), P. 8321 - 8330

Published: Oct. 12, 2022

Ti3C2-MXene-based composites provide multifunctional interfaces in diagnosis and treatment of tumors. Herein, we proposed a nanoplatform based on Ti3C2-MXene–Au nanocomposites, which combines photothermal properties peroxidase-like activity, accomplishing synergistic therapy (PTT) enzyme dynamic (EDT) accompanied by photoacoustic (PA) thermal dual-mode imaging vivo. Furthermore, PTT induces immunogenic cell death, EDT promotes apoptosis, facilitating dendritic (DC) maturation T infiltration into the tumor. On this basis, antibody OX40 (αOX40) was utilized to further contribute immune for reversing immunosuppressive tumor microenvironment activating CD4+ CD8+ cells. In summary, triune PTT/EDT/antitumor is achieved combining nanocomposites αOX40, possesses several strong features good biocompatibility, NIR-controlled targeting, significant cancer killing, satisfactory biosafety vitro Our work might highlight promising application MXene-based nanoplatforms therapy.

Language: Английский

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Reinforcing the Induction of Immunogenic Cell Death Via Artificial Engineered Cascade Bioreactor‐Enhanced Chemo‐Immunotherapy for Optimizing Cancer Immunotherapy

Small, Journal Year: 2021, Volume and Issue: 17(37)

Published: Aug. 6, 2021

Traditional chemo-immunotherapy can elicit T cell immune response by inducing immunogenic death (ICD), however, insufficient ICD limits the lasting antitumor immunotherapeutic efficacy. Herein, tadpole-ovoid manganese-doped hollow mesoporous silica coated gold nanoparticles (Au@HMnMSNs) as biodegradable catalytic cascade nanoreactors are constructed to generate intratumoral high-toxic hydroxyl radicals combined with DOX and Aspirin (ASA) for enhancing induction of maturation dendritic cells (DCs). The released Mn2+ catalyze endogenous H2 O2 radicals, while internal mimetic glucose oxidase (GOx) converted into accelerate generation radicals. On other hand, tadpole oval-structured Au@HMnMSNs avoid inactivation due strong protein adsorption. introduction ASA is recruit DCs cytotoxic lymphocytes (CTLs) tumor sites restrain infiltration immunosuppressive decreasing expression prostaglandin E2 (PGE2 ). Accordingly, this work presents a novel insight introduce GOx-like nano-inducer immunotherapy synergistic therapy.

Language: Английский

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How to improve photodynamic therapy-induced antitumor immunity for cancer treatment?

Theranostics, Journal Year: 2022, Volume and Issue: 12(10), P. 4629 - 4655

Published: Jan. 1, 2022

Photodynamic therapy (PDT) is a promising method of tumor ablation and function-preserving oncological intervention, which minimally invasive, repeatable, has excellent function cosmetic effect, with no cumulative toxicity.More importantly, PDT can induce immunogenic cell death local inflammation, thus stimulating the body's immune response.However, weak immunity induced by alone insufficient to trigger systemic response towards cancer cells.To overcome this obstacle, multiple strategies have been investigated, including microenvironment remodeling, vaccines, subcellular-targeted PDT, synergistic therapies.This review summarizes latest progress in development improve PDT-induced effect for enhanced treatment.

Language: Английский

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Crosstalk among m6A RNA methylation, hypoxia and metabolic reprogramming in TME: from immunosuppressive microenvironment to clinical application

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: July 6, 2022

Abstract The tumor microenvironment (TME), which is regulated by intrinsic oncogenic mechanisms and epigenetic modifications, has become a research hotspot in recent years. Characteristic features of TME include hypoxia, metabolic dysregulation, immunosuppression. One the most common RNA N6-methyladenosine (m 6 A) methylation, widely involved regulation physiological pathological processes, including development. Compelling evidence indicates that m A methylation regulates transcription protein expression through shearing, export, translation, processing, thereby participating dynamic evolution TME. Specifically, methylation-mediated adaptation to phenotypic shift immune cells synergistically promote formation an immunosuppressive supports proliferation metastasis. In this review, we have focused on involvement tumor-adaptive described detailed linking change cell biological functions. view collective data, advocate treating as complete ecosystem components crosstalk with each other achieve adaptive changes. Finally, describe potential utility methylation-targeted therapies immunotherapy clinical applications challenges faced, aim advancing research.

Language: Английский

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