Pharmacological targeting of the mitochondrial phosphatase PTPMT1 sensitizes hepatocellular carcinoma to ferroptosis DOI Creative Commons
Miaomiao Li, Yi Wang, Xinyan Li

и другие.

Cell Death and Disease, Год журнала: 2025, Номер 16(1)

Опубликована: Апрель 6, 2025

Abstract Protein tyrosine phosphatase mitochondrial 1 (PTPMT1), is a member of the protein superfamily localized on inner membrane, and regulates biosynthesis cardiolipin. Given important position PTPMT1 in function metabolism, pharmacological targeting considered promising manner disease treatments. In this study, we mainly investigated role hepatocellular carcinoma (HCC) ferroptosis, new type cell death accompanied by significant iron accumulation lipid peroxidation. Herein, inhibition was induced alexidine dihydrochloride (AD, dibiguanide compound). Human HCC lines with knockout overexpression were established using CRISPR/Cas9 lentiviral transduction methods, respectively. The regulating ferroptosis evaluated vitro vivo. Our results indicated that PTPMT1, facilitated AD treatment, heightens susceptibility to cystine deprivation-ferroptosis, treatment promoted conversion from ferritin-bound Fe 3+ free 2+ , which contributed labile pool cytoplasm. Meanwhile, also formation both swollen mitochondria donut mitochondria, enhanced metabolism process form succinate fumarate tricarboxylic acid (TCA) cycle, increased sensitivity cells deprivation-induced ferroptosis. total, our work reveals close association cysteine providing novel insight into chemotherapy strategies against human HCC.

Язык: Английский

Risk of hepatocellular carcinoma after viral clearance achieved by DAA treatment DOI Creative Commons
Shinya Maekawa, Shinichi Takano,

Nobuyuki Enomoto

и другие.

Journal of the Formosan Medical Association, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

The advent of direct-acting antiviral (DAA) therapy has revolutionized hepatitis C virus (HCV) treatment, enabling most HCV-infected patients to achieve a sustained viral response (SVR) easily and safely in short period. On the other hand, it is gradually being recognized that significant proportion are still at risk developing de novo recurrent hepatocellular carcinoma (HCC), even after HCV elimination, therefore, elucidation HCC, investigation its molecular basis, construction accurate prediction models emerging as new important clinical topics. In this review, we present recent advances regarding these issues.

Язык: Английский

Процитировано

6
Discovery of 5-(Piperidin-4-yl)-1,2,4-oxadiazole Derivatives as a New Class of Human Caseinolytic Protease P Agonists for the Treatment of Hepatocellular Carcinoma DOI
Song Liu, Jing Sui,

Baozhu Luo

и другие.

Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(13), С. 10622 - 10642

Опубликована: Июнь 21, 2024

Chemical agonism of human caseinolytic protease P (HsClpP) is increasingly being recognized as a potential anticancer strategy due to its critical role in maintaining mitochondrial homeostasis. We unveil the discovery 5-(piperidin-4-yl)-1,2,4-oxadiazole derivatives novel class HsClpP agonists and demonstrate for first time application treatment hepatocellular carcinoma (HCC) (Pace, A.; Pierro, P. The new era 1,2,4-oxadiazoles. Org. Biomol. Chem. 2009, 7 (21), 4337-4348). Compound SL44 exhibited potent agonistic activity α-casein hydrolysis assay (EC50 = 1.30 μM) inhibited proliferation HCCLM3 cells (IC50 3.1 μM, 21.4-fold higher than hit ADX-47273). Mechanistically, induces degradation respiratory chain complex subunits leads apoptosis HCC cells. In vivo results demonstrated that has tumor growth inhibitory superior safety profile compared kinase inhibitor sorafenib. Overall, we developed can potentially be used HCC.

Язык: Английский

Процитировано

6
A one-pot CRISPR-RCA strategy for ultrasensitive and specific detection of circRNA DOI

Xinxin Ke,

Ajuan Liang,

Chuanxia Chen

и другие.

Analytical Methods, Год журнала: 2024, Номер 16(20), С. 3256 - 3262

Опубликована: Янв. 1, 2024

Accurate and precise detection of circular RNA (circRNA) is imperative for its clinical use. However, the inherent challenges in circRNA detection, arising from low abundance potential interference linear isomers, necessitate innovative solutions. In this study, we introduce, first time, application CRISPR/Cas12a system to establish a one-pot, rapid (30 minutes 2 hours), specific ultrasensitive strategy, termed RETA-CRISPR (reverse transcription-rolling circle amplification (RT-RCA) with CRISPR/Cas12a). This method comprises two steps: (1) RT-RCA process amplification, generating repeat units containing back-splicing junction (BSJ) sequences; (2) leveraging protospacer adjacent motif (PAM)-independent Cas12a/crRNA complex precisely recognize target sequences BSJ, thereby initiating collateral cleavage activity Cas12a generate robust fluorescence signal. Remarkably, approach exhibits capability detect circRNAs at concentration as 300 aM. The sensor has been successfully employed accurate hepatocellular carcinoma biomarker hsa_circ_0001445 (circRNA1445) various cell lines. conclusion, seamlessly integrates advantages exponential reaction Cas12a, positioning it compelling tool practical CRISPR-based diagnostics.

Язык: Английский

Процитировано

5
The Future Role of Abdominal US in Hepatocellular Carcinoma Surveillance DOI
Mishal Mendiratta‐Lala, David T. Fetzer,

Aya Kamaya

и другие.

Radiology, Год журнала: 2024, Номер 311(2)

Опубликована: Май 1, 2024

Abdominal US is currently the best-validated surveillance strategy for hepatocellular carcinoma (HCC) in at-risk patients. It only modality shown to have completed all five phases of validation and can achieve high sensitivity specificity HCC detection, especially when conducted by expert sonographers high-volume centers. However, also has limitations, including operator dependency varying clinical practice. Further, early-stage detection lower patients with obesity or nonviral liver disease, increasingly common populations undergoing surveillance. Imaging-based blood-based strategies, abbreviated MRI biomarker panels, may overcome some limitations US-based Both strategies promising test performance phase II III studies are prospective validation. Considering variation risk between patients, there will likely be a shift away from one-size-fits-all approach toward precision screening, which "best" selected based on individual patient characteristics. In this upcoming era screening among cirrhosis, continue an important, albeit reduced, role. © RSNA, 2024

Язык: Английский

Процитировано

5
Liver Cancer Etiology: Old Issues and New Perspectives DOI
Jianguo Chen,

Yong-Hui Zhang,

Jianhua Lu

и другие.

Current Oncology Reports, Год журнала: 2024, Номер 26(11), С. 1452 - 1468

Опубликована: Окт. 10, 2024

Язык: Английский

Процитировано

5
Novel Biomarkers for Early Detection of Hepatocellular Carcinoma DOI Creative Commons
Abdelrahman M. Attia, Mohammad Saeid Rezaee‐Zavareh, Soo Young Hwang

и другие.

Diagnostics, Год журнала: 2024, Номер 14(20), С. 2278 - 2278

Опубликована: Окт. 13, 2024

Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality globally. Most patients present with late diagnosis, to poor prognosis. This narrative review explores novel biomarkers for early HCC detection. We conducted comprehensive literature analyzing protein, circulating nucleic acid, metabolite, and quantitative proteomics-based biomarkers, evaluating the advantages limitations each approach. While established markers like alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin, AFP-L3 remain relevant, promising candidates include tumor DNA, microRNAs, long noncoding RNAs, extracellular vesicle, metabolomic biomarkers. Multi-biomarker panels GALAD score, Oncoguard, Helio liver test show promise improved diagnostic accuracy. Non-invasive approaches urine gut microbiome analysis are also emerging possibilities. Integrating these current screening protocols holds significant potential earlier detection patient outcomes. Future research should explore multi-biomarker panels, omics technologies, artificial intelligence further enhance diagnosis management.

Язык: Английский

Процитировано

5
Defining precancer: a grand challenge for the cancer community DOI
Jessica M. Faupel‐Badger, Indu Kohaar, Manisha Bahl

и другие.

Nature reviews. Cancer, Год журнала: 2024, Номер unknown

Опубликована: Окт. 1, 2024

Язык: Английский

Процитировано

4
Integrated investigation of the clinical implications and targeted landscape for RNA methylation modifications in hepatocellular carcinoma DOI Creative Commons

Jianping Zhang,

Jie Gao, Mingchao Hu

и другие.

European journal of medical research, Год журнала: 2023, Номер 28(1)

Опубликована: Янв. 27, 2023

Abstract Background RNA methylation (RM) is a crucial post-translational modification (PTM) that directs epigenetic regulation. It mostly consists of N 1 -methyladenosine (m A), 5-methylcytosine 5 C), 3 -methylcytidine 6 and 2′-O-methylation (Nm). The “writers” mainly act as intermediaries between these modifications associated biological processes. However, little known about the interactions potential functions RM writers in hepatocellular carcinoma (HCC). Methods expression properties genetic alterations 38 were assessed HCC samples from five bioinformatic datasets. Two patterns with identified using consensus clustering. Then, utilizing differentially expressed genes (DEGs) different subtypes, we built risk model called RM_Score. Additionally, investigated correlation RM_Score clinical characteristics, tumor microenvironment (TME) infiltration, molecular therapeutic response, immunotherapy effectiveness, competing endogenous (ceRNA) network. Results correlated TME cell infiltration prognosis. Cluster_1/2 gene.cluster_A/B shown to be capable distinguishing patients poor prognosis after unsupervised clustering writers. constructed pattern-specific subdivided cases into high low subgroups. In individual cohorts or merged datasets, was related worse overall survival patients. also exhibited correlations immune proliferation pathways. response anti-cancer treatments, had negative (drug sensitive) drugs focused on MAPK/ERK metabolism signaling, positive resistant) compounds targeting RKT PI3K/mTOR signaling pathway. Notably, connected effectiveness PD-L1 blockage, implying may target optimize outcomes. ceRNA network generated including 2 lncRNAs, 4 miRNAs, 7 mRNAs Conclusions We thoroughly established an RM_patterns-based for This study emphasized critical targeted therapy, immunotherapy, providing targets HCC.

Язык: Английский

Процитировано

10
Habitat radiomics based on CT images to predict survival and immune status in hepatocellular carcinoma, a multi-cohort validation study DOI Creative Commons
Kun Chen, Chunxiao Sui, Ziyang Wang

и другие.

Translational Oncology, Год журнала: 2025, Номер 52, С. 102260 - 102260

Опубликована: Янв. 5, 2025

Язык: Английский

Процитировано

0
Porous Silicon Particle-Assisted Mass Spectrometry Technology Unlocks Serum Metabolic Fingerprints in the Progression From Chronic Hepatitis B to Hepatocellular Carcinoma DOI

Xinrong Jiang,

Liye Tao,

Shuo Cao

и другие.

ACS Applied Materials & Interfaces, Год журнала: 2025, Номер unknown

Опубликована: Янв. 15, 2025

Hepatocellular carcinoma (HCC) is a common malignancy and generally develops from liver cirrhosis (LC), which primarily caused by the chronic hepatitis B (CHB) virus. Reliable liquid biopsy methods for HCC screening in high-risk populations are urgently needed. Here, we establish porous silicon-assisted laser desorption ionization mass spectrometry (PSALDI-MS) technology to profile metabolite information hidden human serum high throughput manner. Serum metabolites can be captured pore channel of APTES-modified silicon (pSi) particles well-preserved during storage or transportation. Furthermore, APTES-pSi directly detected on LDI-MS without addition an organic matrix, thus greatly accelerating acquisition metabolic fingerprints samples. The PSALDI-MS displays capability (5 min per 96 samples), reproducibility (coefficient variation <15%), sensitivity (LOD ∼ 1 pmol), tolerance background salt proteins. In multicenter cohort study, 1433 subjects including healthy controls (HC), CHB, LC, volunteers were enrolled nontargeted metabolomic analysis was performed platform. After selection feature metabolites, stepwise diagnostic model classification different disease stages constructed machine learning algorithm. external testing, accuracy 91.2% HC, 71.4% 70.0% 95.3% achieved chemometrics. Preliminary studies indicated that fingerprint also good predictive performance prospective observation. We believe combination may serve as efficient tool clinical practice.

Язык: Английский

Процитировано

0