Impact of alternative splicing on mechanisms of resistance to anticancer drugs DOI Creative Commons
María Reviejo,

Meraris Soto,

Elisa Lozano

et al.

Biochemical Pharmacology, Journal Year: 2021, Volume and Issue: 193, P. 114810 - 114810

Published: Oct. 20, 2021

A shared characteristic of many tumors is the lack response to anticancer drugs. Multiple mechanisms pharmacoresistance (MPRs) are involved in permitting cancer cells overcome effect these agents. Pharmacoresistance can be primary (intrinsic) or secondary (acquired), i.e., triggered enhanced treatment. Moreover, MPRs usually result sensitivity several agents, which accounts for diverse multidrug-resistant (MDR) phenotypes. based on dynamic expression more than one hundred genes, constituting so-called resistome. Alternative splicing (AS) during pre-mRNA maturation results changes affecting proteins The resulting variants (SVs) reduce efficacy drugs by lowering intracellular levels active altering molecular targets, enhancing both DNA repair ability and defensive mechanism tumors, inducing balance between pro-survival pro-apoptosis signals, modifying interactions with tumor microenvironment, favoring malignant phenotypic transitions. Reasons accounting cancer-associated aberrant include mutations that create disrupt sites enhancers silencers, abnormal factors, impaired signaling pathways activity machinery. Here we have reviewed impact AS MPR cells.

Language: Английский

The Role of TLR4 in the Immunotherapy of Hepatocellular Carcinoma: Can We Teach an Old Dog New Tricks? DOI Open Access
Stavros P. Papadakos, Konstantinos Arvanitakis, Ioanna Ε. Stergiou

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(10), P. 2795 - 2795

Published: May 17, 2023

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and a leading cause cancer-related death worldwide. Immunotherapy has emerged as mainstay treatment option for unresectable HCC. Toll-like receptor 4 (TLR4) plays crucial role in innate immune response by recognizing responding primarily to bacterial lipopolysaccharides. In addition its system, TLR4 also been implicated adaptive immunity, including specific anti-tumor responses. particular, signaling pathway seems be involved regulation several hallmarks, such continuous activation cellular pathways that promote cell division growth, inhibition programmed death, promotion invasion metastatic mechanisms, epithelial-to-mesenchymal transition, angiogenesis, drug resistance, epigenetic modifications. Emerging evidence further suggests holds promise potential immunotherapeutic target The aim this review was explore multilayer aspects pathway, regarding diseases HCC, well utilization an immunotherapy

Language: Английский

Citations

19
A Glucose Metabolic Intervention Nanoplatform for Enhanced Chemodynamic Therapy and Sensitized Photothermal Therapy of Hepatocellular Carcinoma DOI
Lu Zhang,

Tian Hongwei,

Ying Guo

et al.

ACS Applied Materials & Interfaces, Journal Year: 2023, Volume and Issue: 15(21), P. 25437 - 25451

Published: May 18, 2023

Traditional treatments for hepatocellular carcinoma (HCC) still lack effectiveness. Recently, the combined mode of chemodynamic therapy (CDT) and photothermal (PTT) has shown great potential against HCC. However, insufficient Fenton reaction rates hyperthermia-induced heat shock responses greatly impair their efficiency, hindering further clinical application. Here, we constructed a cascade-amplified PTT/CDT nanoplatform by coating an IR780-embedded red blood cell membrane on glucose oxidase (GOx)-loaded Fe3O4 nanoparticles effective HCC treatment. On one hand, interfered with metabolism through action GOx to reduce synthesis ATP, which reduced expression proteins, thereby sensitizing IR780-mediated PTT. other hydrogen peroxide generated during catalysis thermal effect PTT accelerated Fe3O4-mediated reaction, realizing enhanced CDT. Consequently, sensitized CDT management could be simultaneously achieved interfering metabolism, providing alternative strategy treatment tumors.

Language: Английский

Citations

18
Patient-Derived Tumor Xenograft Models: Toward the Establishment of Precision Cancer Medicine DOI Open Access
Taichiro Goto

Journal of Personalized Medicine, Journal Year: 2020, Volume and Issue: 10(3), P. 64 - 64

Published: July 18, 2020

Patient-derived xenografts (PDXs) describe models involving the implantation of patient-derived tumor tissue into immunodeficient mice. Compared with conventional preclinical cancer cell lines mice, PDXs can be characterized by preservation heterogeneity, and microenvironment (including stroma/vasculature) more closely resembles that in patients. Consequently, use PDX has improved predictability clinical therapeutic responses to 80% or greater, compared approximately 5% for existing models. In future, molecular biological analyses, omics other experiments will conducted using recently prepared under strong expectation analysis pathophysiology, stem cells, novel treatment targets biomarkers improved, thereby promoting drug development. This review outlines methods preparing models, advances research perspectives establishment precision medicine within framework personalized medicine.

Language: Английский

Citations

47
The role of DNA damage and repair in liver cancer DOI
Rhys Gillman, Kylie Lopes Floro,

Miriam Wankell

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2020, Volume and Issue: 1875(1), P. 188493 - 188493

Published: Dec. 13, 2020

Language: Английский

Citations

45
Enhancing the chemosensitivity of HepG2 cells towards cisplatin by organoselenium pseudopeptides DOI
Saad Shaaban, Sameh M. Shabana, Yasair S. Al‐Faiyz

et al.

Bioorganic Chemistry, Journal Year: 2021, Volume and Issue: 109, P. 104713 - 104713

Published: Feb. 9, 2021

Language: Английский

Citations

40
Epigenetic modulation of neuroblastoma enhances T cell and NK cell immunogenicity by inducing a tumor-cell lineage switch DOI Creative Commons
Annelisa M. Cornel,

Ester Dünnebach,

Damon A. Hofman

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2022, Volume and Issue: 10(12), P. e005002 - e005002

Published: Dec. 1, 2022

Background Immunotherapy in high-risk neuroblastoma (HR-NBL) does not live up to its full potential due inadequate (adaptive) immune engagement caused by the extensive immunomodulatory capacity of HR-NBL. We aimed tackle one most notable processes (NBL), absence major histocompatibility complex class I (MHC-I) surface expression, a process greatly limiting cytotoxic T cell engagement. and others have previously shown that MHC-I expression can be induced cytokine-driven modulation. Here, we identify tolerable pharmacological repurposing strategies upregulate therewith enhance immunogenicity NBL. Methods Drug libraries were screened compounds enhancing NBL cells using high-throughput flow cytometry analyses optimized for adherent cells. The effect positive hits was confirmed panel lines patient-derived organoids. Compound-treated organoids cocultured with preferentially expressed antigen melanoma (PRAME)-reactive tumor-specific healthy-donor natural killer (NK) determine vitro on NK cytotoxicity. Additional effects histone deacetylase inhibitors (HDACi) identified transcriptome translatome analysis treated Results library screening revealed upregulation inhibitor apoptosis (IAPi)- HDACi drug classes. IAPi limited repression nuclear factor kappa B (NFκB) pathway activity NBL, while MHC-I-modulating widely translatable Pretreatment entinostat enhanced against vitro, which coincided increased additional players regulating cytotoxicity (eg, TAP1/2 immunoproteasome subunits). Moreover, MICA MICB, important cytotoxicity, also exposure. Intriguingly, this increase accompanied shift toward more mesenchymal lineage. Conclusions This study indicates combining (immuno)therapy both cell-driven NKcell-driven responses patients

Language: Английский

Citations

28
Evaluation and Application of Drug Resistance by Biomarkers in the Clinical Treatment of Liver Cancer DOI Creative Commons
Po-Shuan Huang, Ling‐Yu Wang, Yiwen Wang

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(6), P. 869 - 869

Published: March 10, 2023

Liver cancer is one of the most lethal cancers in world, mainly owing to lack effective means for early monitoring and treatment. Accordingly, there considerable research interest various clinically applicable methods addressing these unmet needs. At present, commonly used biomarker diagnosis liver alpha-fetoprotein (AFP), but AFP sensitive interference from other factors cannot really be as basis determining cancer. Treatment options addition surgery (resection, transplantation) include radiation therapy, chemotherapy, targeted therapy. However, even more expensive drug therapies have a limited impact on clinical outcome One big reasons rapid emergence resistance. Therefore, finding biomarkers diagnosis, an important focus current discussions how effectively adjust select strategies guidelines treatment patients. In this review, we bring thought process resistance problem faced by different strategies, approaching it perspective gene expression molecular biology possibility solutions.

Language: Английский

Citations

16
Oxysophocarpine suppresses FGFR1-overexpressed hepatocellular carcinoma growth and sensitizes the therapeutic effect of lenvatinib DOI
Zhongwei Zhao, Jingjing Song, Dengke Zhang

et al.

Life Sciences, Journal Year: 2020, Volume and Issue: 264, P. 118642 - 118642

Published: Oct. 24, 2020

Language: Английский

Citations

35
Crocetin imparts antiproliferative activity via inhibiting STAT3 signaling in hepatocellular carcinoma DOI Creative Commons
Chakrabhavi Dhananjaya Mohan,

Chulwon Kim,

Kodappully Sivaraman Siveen

et al.

IUBMB Life, Journal Year: 2021, Volume and Issue: 73(11), P. 1348 - 1362

Published: Sept. 13, 2021

Abstract STAT3 is a key oncogenic transcription factor, often overactivated in several human cancers including hepatocellular carcinoma (HCC). modulates the expression of genes that are connected with cell proliferation, antiapoptosis, metastasis, angiogenesis, and immune evasion tumor cells. In this study, we investigated effect crocetin on growth HCC cells dissected its underlying molecular mechanism imparting cytotoxic effect. Crocetin suppressed promoted apoptosis, counteracted invasive capacity Besides, downregulated constitutive/inducible activation (STAT3 Y705 ), nuclear accumulation along suppression DNA binding activity no STAT5 activation. upstream kinases such as Src, JAK1, JAK2. Sodium pervanadate treatment terminated crocetin‐propelled inhibition suggesting involvement tyrosine phosphatases. increased SHP‐1 siRNA‐mediated silencing resulted negation crocetin‐driven inhibition. Further investigation revealed inhibited regulated (Bcl‐2, Bcl‐xL, cyclin D1, survivin, VEGF, COX‐2, MMP‐9). Taken together, report presents novel abrogator pathway lines.

Language: Английский

Citations

31
Upregulation of USP22 and ABCC1 during Sorafenib Treatment of Hepatocellular Carcinoma Contribute to Development of Resistance DOI Creative Commons

Yung‐Sheng Chang,

Chien‐Wei Su, San‐Chi Chen

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(4), P. 634 - 634

Published: Feb. 11, 2022

Sorafenib is a small molecule that blocks tumor proliferation by targeting the activity of multi-kinases for treatment advanced hepatocellular carcinoma (HCC). Increasing sorafenib resistance following long-term frequently encountered. Mechanisms underlying remain not completely clear. To further understand mechanism in HCC, we established sorafenib-resistant cell lines slowly increasing concentration culture medium. Upregulation USP22 and ABCC1 were found Sorafenib-resistant cells. cells treated with siRNA showed significant reduction endogenous mRNA protein levels ABCC1. During treatment, upregulation increases expression subsequently contributes to HCC Immunohistochemical analysis revealed positive correlation between tissue samples from patients (Pearson’s = 0.59, p 0.03). Our findings indicate during contribute has strong potential as therapeutic target overcoming patients.

Language: Английский

Citations

21