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Huang J, Cheng X, Wang C, Gong F. Protein regulator of cytokinesis 1 regulates autophagy in hepatitis B virus‑associated liver cancer development. Oncol Rep 2025; 53:36. [PMID: 39930820 PMCID: PMC11795243 DOI: 10.3892/or.2025.8869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Accepted: 01/07/2025] [Indexed: 02/14/2025] Open
Abstract
Hepatitis B protein x (HBx) is considered a critical contributor to hepatitis B virus (HBV)‑associated liver cancer development. Protein regulator of cytokinesis 1 (PRC1) has been implicated in hepatocarcinogenesis. However, the clinical relevance, biological functions and related regulatory mechanisms of PRC1 in HBV‑associated liver cancer have not yet been clarified. PRC1 expression profiles in liver cancer were obtained from The Cancer Genome Atlas and Gene Expression Profiling Interactive Analysis database and through reverse transcription‑quantitative polymerase chain reaction and immunohistochemistry assays. A series of in vitro and in vivo assays were used to explore the function of the PRC1 gene and the possible mechanisms through which it affects HBV‑associated liver cancer. PRC1 was overexpressed in HBV‑positive liver cancer tissues. Functional studies in vitro demonstrated that HBx induced the expression of the PRC1 gene, which promoted cell autophagy and enhanced viability, invasion and migration. Furthermore, the knockdown of the PRC1 gene or treatment with the autophagosome inhibitor 3‑methyladenine blocked the HBx‑induced autophagic flux, disrupted the formation of autophagosomes, and promoted cell apoptosis. Liver cancer xenograft animal model experiments revealed that inhibition of autophagy by 3‑methyladenine or silencing of the PRC1 gene attenuated HBx‑induced malignant behavior in vivo. The absence of autophagy inhibited the expression of Bcl‑2, induced the expression of Bax, and regulated the levels of Th1 and Th2 cytokines. These results elucidate a mechanism wherein the PRC1 gene participates in the occurrence and development of HBV‑associated liver cancer by modulating autophagy. PRC1 could be a potential therapeutic target for liver cancer.
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Affiliation(s)
- Jingjing Huang
- Department of Infection, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, Heilongjiang157000, P.R. China
| | - Xianzhi Cheng
- Department of Pharmacy, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, Heilongjiang 157000, P.R. China
| | - Chuang Wang
- Department of Neurosurgery, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, Heilongjiang 157000, P.R. China
| | - Fangyan Gong
- Department of Clinical Laboratory, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, Heilongjiang 157000, P.R. China
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Capasso L, De Masi L, Sirignano C, Maresca V, Basile A, Nebbioso A, Rigano D, Bontempo P. Epigallocatechin Gallate (EGCG): Pharmacological Properties, Biological Activities and Therapeutic Potential. Molecules 2025; 30:654. [PMID: 39942757 PMCID: PMC11821029 DOI: 10.3390/molecules30030654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Revised: 01/26/2025] [Accepted: 01/29/2025] [Indexed: 02/16/2025] Open
Abstract
Epigallocatechin gallate (EGCG), the predominant catechin in green tea, comprises approximately 50% of its total polyphenol content and has garnered widespread recognition for its significant therapeutic potential. As the principal bioactive component of Camellia sinensis, EGCG is celebrated for its potent antioxidant, anti-inflammatory, cardioprotective, and antitumor properties. The bioavailability and metabolism of EGCG within the gut microbiota underscore its systemic effects, as it is absorbed in the intestine, metabolized into bioactive compounds, and transported to target organs. This compound has been shown to influence key physiological pathways, particularly those related to lipid metabolism and inflammation, offering protective effects against a variety of diseases. EGCG's ability to modulate cell signaling pathways associated with oxidative stress, apoptosis, and immune regulation highlights its multifaceted role in health promotion. Emerging evidence underscores EGCG's therapeutic potential in preventing and managing a range of chronic conditions, including cancer, cardiovascular diseases, neurodegenerative disorders, and metabolic syndromes. Given the growing prevalence of lifestyle-related diseases and the increasing interest in natural compounds, EGCG presents a promising avenue for novel therapeutic strategies. This review aims to summarize current knowledge on EGCG, emphasizing its critical role as a versatile natural bioactive agent with diverse clinical applications. Further exploration in both experimental and clinical settings is essential to fully unlock its therapeutic potential.
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Affiliation(s)
- Lucia Capasso
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138 Naples, Italy; (L.C.); (A.N.)
| | - Luigi De Masi
- National Research Council (CNR), Institute of Biosciences and BioResources (IBBR), Via Università 133, 80055 Portici, Italy;
| | - Carmina Sirignano
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131 Naples, Italy;
| | - Viviana Maresca
- Department of Life Science, Health, and Health Professions, Link Campus University, 00165 Rome, Italy;
| | - Adriana Basile
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy;
| | - Angela Nebbioso
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138 Naples, Italy; (L.C.); (A.N.)
| | - Daniela Rigano
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131 Naples, Italy;
| | - Paola Bontempo
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138 Naples, Italy; (L.C.); (A.N.)
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3
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Zhang Z, Wu Y, Xu J, Meng Z, Chen Q, Yin S. Quantitative Analysis of Hepatitis D Virus Using gRNA-Sensitive Semiconducting Polymer Dots. Anal Chem 2025; 97:1575-1583. [PMID: 39807540 DOI: 10.1021/acs.analchem.4c04147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2025]
Abstract
Hepatitis D virus (HDV) significantly influences the progression of liver diseases. Through clinical observations and database analyses, it has been established that patients coinfected with HDV and hepatitis B virus (HBV) experience accelerated progression toward cirrhosis, hepatocellular carcinoma (HCC), and liver failure compared to those infected solely with HBV. A higher viral load correlates with increased replicative activity, enhanced infectivity, and more severe disease manifestations. In this study, we use HDV gRNA-sensitive semiconducting polymer dots (Pdots) as the nanoprobes for the quantitative analysis of HDV copy number variations. The surface of the Pdots is engineered with a clamp design that includes a pair of reporter sequences, protection sequences, and capture sequences tailored to the conserved sequence length of the HDV genome. The capture sequence, comprising leading and trailing chains, specifically binds to the gRNA of the target virus. The protection sequence shields the Pdots from external interference, while the reporter sequence detects the presence of target gRNA through the degradation of fluorescent dye Cy5.5dt. We demonstrate the effectiveness of this assay in a stably transfected cell line derived from HepG2-HDV cells and its translational application in clinical samples from patients. Additionally, this nanobiosensor can accurately detect gRNA at femtomolar (fM) levels, a sensitivity unachievable by previously reported methods. This novel virus quantification system offers significant potential for clinical and virological applications, enhancing screening, early diagnosis, and personalized treatment strategies.
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Affiliation(s)
- Ze Zhang
- Department of Hepatobiliary and Pancreatic Surgery II, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin 130012, P. R. China
- State Key Laboratory of Integrated Optoelectronics, College of Electronics Science and Engineering, Jilin University, No. 2699 Qianjin Street, Changchun, Jilin 130012, P. R. China
| | - Yuyang Wu
- State Key Laboratory of Integrated Optoelectronics, College of Electronics Science and Engineering, Jilin University, No. 2699 Qianjin Street, Changchun, Jilin 130012, P. R. China
| | - Jinglun Xu
- Department of Hepatobiliary-Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130000, P. R. China
| | - Zihui Meng
- Department of Hepatobiliary-Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130000, P. R. China
| | - Qingmin Chen
- Department of Hepatobiliary and Pancreatic Surgery II, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin 130012, P. R. China
| | - Shengyan Yin
- State Key Laboratory of Integrated Optoelectronics, College of Electronics Science and Engineering, Jilin University, No. 2699 Qianjin Street, Changchun, Jilin 130012, P. R. China
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Zhen WC, Sun J, Bai XT, Zhang Q, Li ZH, Zhang YX, Xu RX, Wu W, Yao ZH, Pu CW, Li XF. Trends of alkaline phosphatase to prealbumin ratio in patients with hepatitis B linked to hepatocellular carcinoma development. World J Gastroenterol 2025; 31:99349. [PMID: 39811503 PMCID: PMC11684201 DOI: 10.3748/wjg.v31.i2.99349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2024] [Revised: 10/25/2024] [Accepted: 11/18/2024] [Indexed: 12/18/2024] Open
Abstract
BACKGROUND Chronic hepatitis B often progresses silently toward hepatocellular carcinoma (HCC), a leading cause of mortality worldwide. Early detection of HCC is crucial, yet challenging. AIM To investigate the role of dynamic changes in alkaline phosphatase to prealbumin ratio (APR) in hepatitis B progression to HCC. METHODS Data from 4843 patients with hepatitis B (January 2015 to January 2024) were analyzed. HCC incidence rates in males and females were compared using the log-rank test. Data were evaluated using Kaplan-Meier analysis. The Linear Mixed-Effects Model was applied to track the fluctuation of APR levels over time. Furthermore, Joint Modeling of Longitudinal and Survival data was employed to investigate the temporal relationship between APR and HCC risk. RESULTS The incidence of HCC was higher in males. To ensure the model's normality assumption, this study applied a logarithmic transformation to APR, yielding ratio. Ratio levels were higher in females (t = 5.26, P < 0.01). A 1-unit increase in ratio correlated with a 2.005-fold higher risk of HCC in males (95%CI: 1.653-2.431) and a 2.273-fold higher risk in females (95%CI: 1.620-3.190). CONCLUSION Males are more prone to HCC, while females have higher APR levels. Despite no baseline APR link, rising APR indicates a higher HCC risk.
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Affiliation(s)
- Wen-Chong Zhen
- School of Public Health, Dalian Medical University, Dalian 116044, Liaoning Province, China
| | - Jing Sun
- Graduate School, Dalian Medical University, Dalian 116044, Liaoning Province, China
| | - Xue-Ting Bai
- School of Public Health, Dalian Medical University, Dalian 116044, Liaoning Province, China
| | - Qian Zhang
- School of Public Health, Dalian Medical University, Dalian 116044, Liaoning Province, China
| | - Zi-Han Li
- School of Public Health, Dalian Medical University, Dalian 116044, Liaoning Province, China
| | - Yi-Xin Zhang
- School of Public Health, Dalian Medical University, Dalian 116044, Liaoning Province, China
| | - Rong-Xuan Xu
- School of Public Health, Dalian Medical University, Dalian 116044, Liaoning Province, China
| | - Wei Wu
- School of Public Health, Dalian Medical University, Dalian 116044, Liaoning Province, China
| | - Zhi-Han Yao
- School of Public Health, Dalian Medical University, Dalian 116044, Liaoning Province, China
| | - Chun-Wen Pu
- Dalian Public Health Clinical Center, Dalian Municipal Research Institute for Public Health, Dalian 116001, Liaoning Province, China
| | - Xiao-Feng Li
- Department of Epidemiology and Health Statistics, Dalian Medical University, Dalian 116044, Liaoning Province, China
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Borden ES, Jorgensen A, Natri HM, Hastings KT, Buetow KH, Wilson MA. HCV- and HBV-mediated liver cancer converge on similar transcriptomic landscapes and immune profiles. HGG ADVANCES 2025; 6:100373. [PMID: 39427232 PMCID: PMC11570839 DOI: 10.1016/j.xhgg.2024.100373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2023] [Revised: 10/17/2024] [Accepted: 10/17/2024] [Indexed: 10/21/2024] Open
Abstract
Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related deaths worldwide, and a large proportion is attributable to viral causes, including hepatitis B (HBV) and C viruses (HCV). The pathogenesis of viral-mediated HCC can differ between HBV and HCV, but it is unclear how much these differences influence the tumors' final molecular and immune profiles. Additionally, there are known sex differences in the molecular etiology of HCC, but sex differences have not been explored in the context of viral-mediated HCC. To determine the extent to which the viral status and sex impact the molecular and immune profiles of HCC, we performed differential expression and immune cell deconvolution analyses. We identified a large number of differentially expressed genes unique to the HBV or HCV tumor:tumor-adjacent comparison. Pathway enrichment analyses demonstrated that changes unique to the HCV tumor:tumor-adjacent tissue were dominated by changes in immune pathways. Immune cell deconvolution demonstrated that HCV tumor-adjacent tissue had the largest immune cell infiltrate, with no difference in the immune profiles within HBV and HCV tumor samples. Overall, this work demonstrates the convergence of HBV- and HCV-mediated HCC on a similar transcriptomic landscape and immune profile despite differences in the surrounding tissue.
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Affiliation(s)
- Elizabeth S Borden
- Department of Dermatology, College of Medicine-Phoenix, University of Arizona, Phoenix, AZ, USA; Phoenix Veterans Affairs Health Care System, Phoenix, AZ, USA
| | - Annika Jorgensen
- School of Life Sciences, Arizona State University, Tempe, AZ, USA
| | - Heini M Natri
- Translational Genomics Research Institute, Phoenix, AZ, USA
| | - Karen Taraszka Hastings
- Department of Dermatology, College of Medicine-Phoenix, University of Arizona, Phoenix, AZ, USA; Phoenix Veterans Affairs Health Care System, Phoenix, AZ, USA
| | - Kenneth H Buetow
- School of Life Sciences, Arizona State University, Tempe, AZ, USA; Center for Evolution and Medicine, Arizona State University, Tempe, AZ, USA.
| | - Melissa A Wilson
- School of Life Sciences, Arizona State University, Tempe, AZ, USA; Center for Evolution and Medicine, Arizona State University, Tempe, AZ, USA.
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Badshah Y, Shabbir M, Khan K, Zafar S, Afsar T, Husain FM, Amor H, Razak S. HCV and HBV genotypes: vital in the progression of HCV/ HBV co-infection. BMC Gastroenterol 2025; 25:6. [PMID: 39780058 PMCID: PMC11708002 DOI: 10.1186/s12876-025-03587-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Accepted: 01/01/2025] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND Viral hepatitis is the major contributor to liver cirrhosis and hepatocellular carcinoma (HCC). Studies indicated that the co-infection of hepatitis C and hepatitis B virus also prompts liver damage progression. Therefore, in the present study, the prevalence of HCV-HBV co-infection and the impact of HCV-HBV co-infection on the progression of liver damage was evaluated amongst the HCV-infected patients in Pakistan. METHODS In this study 2500 HCV-positive patients were recruited from Pakistan. The presence and prevalence of HCV and HBV was confirmed through ELISA and nested PCR. To determine the liver damage due to viral infection levels of ALT, ALP, and total bilirubin were also determined. Diagnostic history of patients was thoroughly documented through serological tests and liver biopsy reports. Viral genotypes and viral loads were determined through multiplex polymerase chain reaction (PCR) and time PCR, respectively. RESULTS The study outcomes showed that 12.5% of the HCV-infected patients were co-infected with HBV. Co-infection development was more common in females than in males, and females were at a higher risk of developing the infection (p-value = < 0.0001, OR = 2.437). Despite the variation among different age groups, there was no significant difference in co-infection prevalence. HCV genotype 3a was found to be most prevalent while in HBV genotype D was found to be prevalent among the patients. The HCV patients frequently developed co-infection with HBV genotype D. It was also determined that viral load for HBV genotype D was higher compared to non-D genotypes while for HCV viral load was higher in non-3a genotypes. CONCLUSIONS This study evaluated the prevalence of HCV and HBV co-infection among HCV-positive patients, revealing that 12.5% patients were co-infected with HBV. Co-infection was more common in females, who had a higher risk of developing it. The study also revealed that HBV genotype D was the most prevalent in co-infected patients, with no significant age-related differences in co-infection rates.
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Affiliation(s)
- Yasmin Badshah
- Department of Healthcare Biotechnology, Atta ur Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, 44000, Pakistan.
| | - Maria Shabbir
- Department of Healthcare Biotechnology, Atta ur Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, 44000, Pakistan
| | - Khushbukhat Khan
- Department of Healthcare Biotechnology, Atta ur Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, 44000, Pakistan
| | - Sameen Zafar
- Department of Healthcare Biotechnology, Atta ur Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, 44000, Pakistan
| | - Tayyaba Afsar
- Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, 11433, Saudi Arabia
| | - Fohad Mabood Husain
- Department of Food Science and Nutrition, College of Food and Agriculture Sciences, King Saud University, Riyadh, 11433, Saudi Arabia
| | - Houda Amor
- Department of Obstetrics, Gynecology and Reproductive Medicine, Saarland University Clinic, Homburg, Germany
| | - Suhail Razak
- Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, 11433, Saudi Arabia.
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Li J, Wang Y, Bao L, Chen G, Ye Q, He C, Liu L, Luo M. Taxifolin regulates SLC31A1-mediated cuproptosis and tumor progression in hepatocellular carcinoma. Hum Cell 2025; 38:37. [PMID: 39752031 DOI: 10.1007/s13577-024-01168-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Accepted: 12/25/2024] [Indexed: 01/04/2025]
Abstract
Hepatocellular carcinoma (HCC) is a primary malignant neoplasm exhibiting a high mortality rate. Taxifolin is a naturally occurring flavonoid compound that exhibits a range of pharmacological properties. The effects of taxifolin on HCC remain largely unexplored. Therefore, the aim of this study was to examine the potential roles of taxifolin in the development and progression of HCC. In this study, CCK-8 assay was utilized to examine the impact of taxifolin on the cell viability. The copper ions level and the activity of mitochondrial respiratory chain were determined by the correspondent kits. The biological properties of HCC cells were evaluated using colony formation, transwell, flow cytometry, and TUNEL assays, respectively. Transcriptome sequencing was carried out either with or without taxifolin treatment. The expression of cuproptosis-related proteins was determined by Western blot. We observed significant decrease of cell viability, Glutathione (GSH), and mitochondrial respiratory chain under the treatment of taxifolin, while an increase of copper ions level. Taxifolin was observed to suppress HCC progression both in vitro and in vivo. The intersection analysis was performed between upregulated genes and cuproptosis-related genes to obtain one intersection gene-SLC31A1. The knockdown of SLC31A1 reversed the tumor-suppressive effects induced by taxifolin. Taxifolin inhibited HCC progression through inducing cuproptosis in an SLC31A1-mediated manner.
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Affiliation(s)
- Jike Li
- Traditional Chinese Medicine Laboratory, Chengdu Public Health Clinical Center, Chengdu, 610061, People's Republic of China
| | - Yuelian Wang
- Center for Precision and Translational Medicine, Chengdu Public Health Clinical Center, Chengdu, 610061, People's Republic of China
| | - Lei Bao
- Department of Internal Medicine, Chengdu Public Health Clinical Center, Chengdu, 610061, People's Republic of China
| | - Guo Chen
- Department of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, People's Republic of China
| | - Qing Ye
- Department of Integrated Traditional & Western Medicine, Chengdu Public Health Clinical Center, Chengdu, 610061, People's Republic of China
| | - Chengshi He
- Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, People's Republic of China
| | - Lin Liu
- Department of Nephrology, Panzhihua Central Hospital, Panzhihua, 617067, Sichuan, People's Republic of China
| | - Mei Luo
- Infectious Disease Laboratory, Chengdu Public Health Clinical Center, Chengdu, 610061, People's Republic of China.
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Gavilán P, Gavilán JC, Arnedo R, Clavijo E, Viciana I, González-Correa JA. Prediction model of hepatocellular carcinoma development in chronic hepatitis B virus infection in a Spanish cohort. Med Clin (Barc) 2024; 163:609-616. [PMID: 39424472 DOI: 10.1016/j.medcli.2024.07.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Revised: 07/20/2024] [Accepted: 07/27/2024] [Indexed: 10/21/2024]
Abstract
INTRODUCTION AND OBJECTIVES To identify risk factors associated with the development of hepatocellular carcinoma (HCC) in an unselected cohort of patients with chronic B virus infection (CHB) in Spain. A predictive model was developed to assess the risk of HCC. MATERIAL AND METHODS A prospective open-cohort study recruited 446 unselected patients with chronic hepatitis B infection from two hospitals in Málaga (Spain). The follow-up time ranged from 0.5 to 31.5 years (mean: 13.8; SD: 9.5; median: 11.4 years). We used a Cox proportional hazard model to estimate the multivariable-adjusted hazard ratios of risk factors associated with the development of liver cancer and developed a clinical score, (HCCB score) to determine the risk of liver cancer, that categories patients into two risk levels for the development of HCC. We compared the diagnostic accuracy of our model with other previously published. RESULTS During the follow-up period, 4.80% of the patients developed liver cancer (21 out of 437), 0.33 cases per 100 patient-years. Multivariate Cox regression analysis revealed that age >45 years, male gender, hepatitis C coinfection, alkaline phosphatase >147IU/L, Child score >5 points, glucose >126mg/dL, and a viral load >4.3 log10 IU/mL were independent risk factors. A risk score has been developed with a high predictive capacity for identifying patients at high risk of developing hepatocellular carcinoma. AUROC 0.87 (95% CI: 0.79-0.95). CONCLUSIONS An HCCB score greater than 5.42 points identifies a subgroup of chronic hepatitis B patients at high risk of developing liver cancer, who could benefit from screening measures for the early diagnosis of HCC.
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Affiliation(s)
- Paula Gavilán
- Universidad de Málaga, IBIMA-Plataforma BIONAND, Departamento de Farmacología y Pediatría, Facultad de Medicina, Campus de Teatinos s/n, 29071 Málaga, Spain
| | - Juan-Carlos Gavilán
- Departamento de Medicina Interna, Hospital Universitario Virgen de la Victoria, Málaga, Spain; Hospital Internacional Vithas Xanit, Benalmádena, Spain.
| | - Rocío Arnedo
- Departamento de Medicina Interna, Hospital Universitario Virgen de la Victoria, Málaga, Spain; Hospital Internacional Vithas Xanit, Benalmádena, Spain
| | - Encarnación Clavijo
- Universidad de Málaga, IBIMA-Plataforma BIONAND, Departamento de Microbiología, Facultad de Medicina, Campus de Teatinos s/n, 29071 Málaga, Spain
| | - Isabel Viciana
- Departamento de Microbiología, Hospital Universitario Virgen de la Victoria, Málaga, Spain
| | - José-Antonio González-Correa
- Universidad de Málaga, IBIMA-Plataforma BIONAND, Departamento de Farmacología y Pediatría, Facultad de Medicina, Campus de Teatinos s/n, 29071 Málaga, Spain
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9
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Bai W, Wu X, Zhao S, Yu Y, Wang Z, Li X, Zhou N. Incidence and risk factors of hepatitis E virus infection in women with gynecological tumors in Eastern China. PeerJ 2024; 12:e18747. [PMID: 39713139 PMCID: PMC11662898 DOI: 10.7717/peerj.18747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Accepted: 12/02/2024] [Indexed: 12/24/2024] Open
Abstract
Background Recently, there has been increasing interest in the exploration of the association between the hepatitis E virus (HEV) infection and malignancies; however, epidemiological data for HEV infection among women with a gynecological tumors (GT) are limited. Herein, we investigated the correlation between HEV and GT in Chinese women. Methods We recruited 452 women diagnosed with a primary GT and 452 healthy volunteers to investigate the possible routes and risk factors for HEV infection. The serum antibody levels of anti-HEV IgG and IgM were measured by enzyme-linked immunoassays once a year. Results After a median follow-up time of 5.4 years (range 4 to 7 years), the overall detection rate of anti-HEV antibodies in patients with GT and in controls were 69/452 (15.27%) and 23/452 (5.09%) (P = 0.001), respectively. The seroprevalence of anti-HEV IgG antibodies was significant higher in patients with GT (15.27%) than in healthy controls (5.09%) (P = 0.001). Moreover, 13 (2.88%) patients with GT were positive for IgM antibodies, while only 4 (0.88%) healthy controls tested positive for anti-HEV IgM antibodies (P = 0.028). The highest prevalence of HEV antibodies were detected in patients with ovarian borderline tumors (40%), followed by patients with ovarian cancer (20.54%) and endometrial cancer (18.46%). Multivariable analysis revealed that contact with dogs (OR, 1.88; 95% CI [1.10-3.22]; P = 0.015) and a history of anti-tumor chemotherapy (OR, 1.85; 95% CI [1.07-3.20]; P = 0.028) were independent risk factors for HEV infection. Conclusion Overall, the present study showed that patients with GT are more susceptible to HEV infection in Eastern China, particularly in patients with ovarian borderline tumors. Thus, effective strategies are needed to reduce HEV infection in patients with GT.
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Affiliation(s)
- Wenye Bai
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xiao Wu
- Department of Clinical Laboratory, Qingdao Women and Children’s Hospital, Qingdao, China
| | - Shuchao Zhao
- Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yang Yu
- Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Zhongjun Wang
- Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xiu Li
- Department of Obstetrics and Gynecology, Qingdao Municipal Hospital, Qingdao, China
| | - Na Zhou
- Department of Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
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10
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Ibeanu GC, Rowaiye AB, Okoli JC, Eze DU. Microbiome Differences in Colorectal Cancer Patients and Healthy Individuals: Implications for Vaccine Antigen Discovery. Immunotargets Ther 2024; 13:749-774. [PMID: 39698218 PMCID: PMC11652712 DOI: 10.2147/itt.s486731] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Accepted: 12/02/2024] [Indexed: 12/20/2024] Open
Abstract
Background Colorectal cancer (CRC) is the third most prevalent cancer worldwide, with numerous risk factors contributing to its development. Recent research has illuminated the significant role of the gut microbiota in CRC pathogenesis, identifying various microbial antigens as potential targets for vaccine development. Aim This review aimed at exploring the potential sources of microbial antigens that could be harnessed to create effective CRC vaccines and understand the role of microbiome-CRC interactions in carcinogenesis. Methods A comprehensive search of original research and review articles on the pathological links between key microbial candidates, particularly those more prevalent in CRC tissues, was conducted. This involved extensive use of the PubMed and Medline databases, as well as the Google Scholar search engine, utilizing pertinent keywords. A total of one hundred and forty-three relevant articles in English, mostly published between 2018 and 2024, were selected. Results Numerous microbes, particularly bacteria and viruses, are significantly overrepresented in CRC tissues and have been shown to promote tumorigenesis by inducing inflammation and modulating the immune system. This makes them promising candidates for antigens in the development of CRC vaccines. Conclusion The selection of microbial antigens focuses on their capacity to trigger a strong immune response and their link to tumor presence and progression. Identifying and validating these antigens through preclinical testing is essential in developing a CRC vaccine.
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Affiliation(s)
- Gordon C Ibeanu
- Department of Pharmaceutical Sciences, North Carolina Central University, Durham, NC, 27707, USA
| | - Adekunle B Rowaiye
- Department of Pharmaceutical Sciences, North Carolina Central University, Durham, NC, 27707, USA
- Department of Agricultural Biotechnology, National Biotechnology Development Agency, Abuja, Nigeria
| | - Joy C Okoli
- Department of Pharmaceutical Sciences, North Carolina Central University, Durham, NC, 27707, USA
| | - Daniel U Eze
- Department of Pharmaceutical Sciences, North Carolina Central University, Durham, NC, 27707, USA
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11
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Bruni A, Castellana C, Dajti E, Barbara G, Marasco G, Maida M, Serviddio G, Facciorusso A. Epidemiological, diagnostic, therapeutic and prognostic impact of hepatitis B and D virus infection on hepatocellular carcinoma: A review of the literature. Virology 2024; 600:110273. [PMID: 39454228 DOI: 10.1016/j.virol.2024.110273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Revised: 10/17/2024] [Accepted: 10/21/2024] [Indexed: 10/28/2024]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) accounts for >90% of primary liver cancer cases, and chronic infections with hepatitis B virus (HBV) and hepatitis D virus (HDV) are major contributors. METHODS A comprehensive literature review was conducted using the MEDLINE (PubMed) database, focusing on studies related to HBV, HDV, and HCC. RESULTS HBV contributes to HCC through mechanisms like viral integration into the host genome, chronic inflammation, and immune modulation, leading to genomic instability and altered cell signaling. HDV exacerbates HBV-induced liver damage, accelerating fibrosis and cirrhosis, and significantly increasing HCC risk. Antiviral therapies and vaccinations have majorly reduced the burden of HBV-related HCC, but HDV remains challenging to treat due to limited therapeutic options. Emerging treatments like Bulevirtide showed promising results. CONCLUSION This review highlights the critical impact of HBV and HDV co-infections on HCC development, emphasizing the need for more effective therapeutic strategies. While advances in antiviral therapies have reduced the incidence of HBV-related HCC, the high burden of HDV-related complications persists. Future research should focus on improving treatments for HDV and understanding its unique contribution to HCC pathogenesis.
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Affiliation(s)
- Angelo Bruni
- Department of Medical and Surgical Sciences, Università di Bologna, Bologna, Italy
| | - Chiara Castellana
- Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Elton Dajti
- Department of Medical and Surgical Sciences, Università di Bologna, Bologna, Italy; Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Giovanni Barbara
- Department of Medical and Surgical Sciences, Università di Bologna, Bologna, Italy; Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Giovanni Marasco
- Department of Medical and Surgical Sciences, Università di Bologna, Bologna, Italy; Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Marcello Maida
- Department of Medicine and Surgery, University of Enna 'Kore', Enna, Italy; Gastroenterology Unit, Umberto I Hospital, Enna, Italy
| | - Gaetano Serviddio
- Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Antonio Facciorusso
- Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
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12
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Tudi M, Sawuti A, Abudurusuli M, Wu C, Chen X, Ailimu G, Wulayin K, Tuerxun M. Epitope-based therapeutic targets in HCV genotype 1 non-structural proteins: a novel strategy to combat emerging drug resistance. Front Cell Infect Microbiol 2024; 14:1480987. [PMID: 39575309 PMCID: PMC11578958 DOI: 10.3389/fcimb.2024.1480987] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Accepted: 10/04/2024] [Indexed: 11/24/2024] Open
Abstract
Introduction The hepatitis C virus (HCV) poses a major global health challenge, with its non-structural proteins being essential for viral replication and pathogenesis. Mutations in these proteins significantly contribute to drug resistance, necessitating innovative therapeutic strategies. This study aims to identify epitope-based therapeutic targets in the non-structural proteins of HCV genotype 1, employing in-depth in silico tools to counteract emerging drug resistance. Methods We retrieved approximately 250 sequences of each non-structural protein from the NCBI database, capturing a broad spectrum of variability and sequence alignments, variability analysis and physicochemical property analysis were conducted. We utilized the TEPITOOL server by IEDB to predict cytotoxic T lymphocyte (CTL) epitopes. Following this, we assessed the efficiency of TAP transport and proteasomal cleavage using IEDB's combined predictor tool. The epitopes were selected based on conservancy analysis, immunogenicity, allergenicity, and presence in non-glycosylated regions, ensuring high predictive scores and suitability as vaccine candidates. Epitopes were docked with the HLA-A*02:01 allele and Toll-like receptor-3 using the ClusPro server. The immune response potential of the epitopes was evaluated through in-silico immune stimulation. Results The study identified 27 potential CTL epitopes from the non-structural proteins, including NS3, NS4a, NS4b, NS5a, and NS5b. Out of these, three lead epitopes demonstrated high conservation (>90%), strong binding affinities to HLA-A*02:01 and TLR-3, and robust immune response potential. These epitopes also showed favorable characteristics such as being non-allergenic and non-glycosylated. Conclusion This comprehensive in-silico analysis provides a promising foundation for developing an epitope-based vaccine targeting HCV non-structural proteins, offering a novel approach to overcoming drug resistance in HCV treatment.
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Affiliation(s)
| | | | | | | | | | | | | | - Maimaitiaili Tuerxun
- Department of Infectious Diseases, The First People’s Hospital of Kashi Prefecture, Kashi, China
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13
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Lu X, Chen Z, Mi W, Zheng J, Liu Y. MARK1 suppress malignant progression of hepatocellular carcinoma and improves sorafenib resistance through negatively regulating POTEE. Open Med (Wars) 2024; 19:20241060. [PMID: 39534429 PMCID: PMC11554448 DOI: 10.1515/med-2024-1060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Revised: 09/07/2024] [Accepted: 09/23/2024] [Indexed: 11/16/2024] Open
Abstract
Purpose This study aimed to investigate the role of microtubule-affinity regulatory protein kinase 1 (MARK1) in hepatocellular carcinoma (HCC) progression, its association with sorafenib sensitivity, and the interplay between MARK1 and POTE Ankyrin domain family member E(POTEE) in HCC cells. Methods Quantitative real-time polymerase chain reaction analysis was used to assess MARK1 and POTEE expression in 60 pairs of HCC tissues and cell lines. The correlation between MARK1 levels, clinicopathological features, and patient prognosis was analyzed. Sorafenib-resistant HCC cell models were developed, followed by MARK1 overexpression to evaluate its impact on cell functions. Luciferase reporter assays and rescue experiments were conducted to elucidate the MARK1-POTEE regulatory mechanism. Results MARK1 exhibited decreased mRNA expression in HCC tissues and cells, correlating with adverse clinicopathological features and poorer patient survival. Luciferase assays confirmed direct binding between MARK1 and POTEE. Sorafenib treatment increased MARK1 protein levels, reduced POTEE, and inhibited cell proliferation. Overexpressing MARK1 suppressed sorafenib-induced proliferation in resistant cells, while co-overexpression of MARK1 and POTEE reversed this effect. Conclusion MARK1 potentially restrains HCC progression and enhances sorafenib resistance by negatively modulating POTEE expression, highlighting its significance as a therapeutic target in HCC treatment.
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Affiliation(s)
- Xin Lu
- Department of Hepatobiliary Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Zhiyuan Chen
- Department of Hepatobiliary Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Wenting Mi
- Gastroenterology Department, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jianming Zheng
- Department of Hepatobiliary Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Yubin Liu
- Department of Hepatobiliary Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, 106 Zhongshan Second Road, Yuexiu District, Guangzhou, China
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14
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Yu Y, Li Y, Zhou L, Cheng X, Gong Z. Hepatic stellate cells promote hepatocellular carcinoma development by regulating histone lactylation: Novel insights from single-cell RNA sequencing and spatial transcriptomics analyses. Cancer Lett 2024; 604:217243. [PMID: 39260669 DOI: 10.1016/j.canlet.2024.217243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 08/23/2024] [Accepted: 09/06/2024] [Indexed: 09/13/2024]
Abstract
This study evaluated the cellular heterogeneity and molecular mechanisms of hepatocellular carcinoma (HCC). Single cell RNA sequencing (scRNA-seq), transcriptomic data, histone lactylation-related genes were collected from public databases. Cell-cell interaction, trajectory, pathway, and spatial transcriptome analyses were executed. Differential expression and survival analyses were conducted. Western blot, Real-time reverse transcription PCR (qRT-PCR), and Cell Counting Kit 8 (CCK8) assay were used to detect the expression of αSMA, AKR1B10 and its target genes, and verify the roles of AKR1B10 in HCC cells. Hepatic stellate cell (HSC) subgroups strongly interacted with tumor cell subgroups, and their spatial distribution was heterogeneous. Two candidate prognostic genes (AKR1B10 and RMRP) were obtained. LONP1, NPIPB3, and ZSWIM6 were determined as AKR1B10 targets. Besides, the expression levels of AKR1B10 and αSMA were significantly increased in LX-2 + HepG2 and LX-2 + HuH7 groups compared to those in LX-2 group, respectively. sh-AKR1B10 significantly inhibited the HCC cell proliferation and change the expression of AKR1B10 target genes, Bcl-2, Bax, Pan Kla, and H3K18la at protein levels. Our findings unveil the pivotal role of HSCs in HCC pathogenesis through regulating histone lactylation.
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Affiliation(s)
- Yifan Yu
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, 110004, China.
| | - Yongnan Li
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, 110004, China.
| | - Long Zhou
- Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, 110004, China.
| | - Xiaoli Cheng
- Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, 110004, China.
| | - Zheng Gong
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, 110004, China.
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15
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Mohammed OA, Youssef ME, Hamad RS, Abdel-Reheim MA, Saleh LA, Alamri MMS, Alharthi MH, Alfaifi J, Adam MIE, Eleragi AMS, Senbel A, Farrag AA, Rezigalla AA, El-wakeel HS, Attia MA, El-Husseiny HM, AL-Noshokaty TM, Doghish AS, Gaafar AGA, Saber S. Unlocking vinpocetine's oncostatic potential in early-stage hepatocellular carcinoma: A new approach to oncogenic modulation by a nootropic drug. PLoS One 2024; 19:e0312572. [PMID: 39480853 PMCID: PMC11527275 DOI: 10.1371/journal.pone.0312572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Accepted: 10/04/2024] [Indexed: 11/02/2024] Open
Abstract
The development of new drugs for the inhibition of hepatocellular carcinoma (HCC) development and progression is a critical and urgent need. The median survival rate for HCC patients remains disappointingly low. Vinpocetine is a safe nootropic agent that is often used to enhance cognitive function. The impact of vinpocetine on HCC development and progression has not been fully explored. Our main objective was to investigate the possible inhibitory role of vinpocetine in rats exposed to diethylnitrosamine. We observed that vinpocetine increased the survival rate of these rats and improved the ultrastructure of their livers. Additionally, vinpocetine reduced the liver weight index, mitigated liver oxidative stress, and improved liver function. In both in vitro and in vivo settings, vinpocetine demonstrated antiproliferative and apoptotic properties. It downregulated the expression of CCND1 and Ki-67 while exhibiting anti-BCL-2 effects and enhancing the levels of Bax and cleaved caspase-3. Vinpocetine also successfully deactivated NF-κB, STAT3, and HIF-1α, along with their associated transcription proteins, thereby exerting anti-inflammatory and anti-angiogenic role. Furthermore, vinpocetine showed promise in reducing the levels of ICAM-1 and TGF-β1 indicating its potential role in tissue remodeling. These findings strongly suggest that vinpocetine holds promise as a hepatoprotective agent by targeting a range of oncogenic proteins simultaneously. However, further approaches are needed to validate and establish causal links between our observed effects allowing for a more in-depth exploration of the mechanisms underlying vinpocetine's effects and identifying pivotal determinants of outcomes.
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Affiliation(s)
- Osama A. Mohammed
- Department of Pharmacology, College of Medicine, University of Bisha, Bisha, Saudi Arabia
| | - Mahmoud E. Youssef
- Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt
| | - Rabab S. Hamad
- Biological Sciences Department, College of Science, King Faisal University, Al Ahsa, Saudi Arabia
- Central Laboratory, Theodor Bilharz Research Institute, Giza, Egypt
| | - Mustafa Ahmed Abdel-Reheim
- Department of Pharmaceutical Sciences, College of Pharmacy, Shaqra University, Shaqra, Saudi Arabia
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni Suef, Egypt
| | - Lobna A. Saleh
- Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, Taif, Saudi Arabia
| | | | - Muffarah Hamid Alharthi
- Department of Family and Community Medicine, College of Medicine, University of Bisha, Bisha, Saudi Arabia
| | - Jaber Alfaifi
- Department of Child Health, College of Medicine, University of Bisha, Bisha, Saudi Arabia
| | - Masoud I. E. Adam
- Department of Medical Education and Internal Medicine, College of Medicine, University of Bisha, Bisha, Saudi Arabia
| | - Ali M. S. Eleragi
- Department of Microorganisms and Clinical Parasitology, College of Medicine, University of Bisha, Bisha, Saudi Arabia
| | - Ahmed Senbel
- Department of Surgical Oncology, Oncology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Alshaimaa A. Farrag
- Department of Histology and Cell Biology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Assad Ali Rezigalla
- Department of Anatomy, College of Medicine, University of Bisha, Bisha, Saudi Arabia
| | - Hend S. El-wakeel
- Physiology Department, Benha Faculty of Medicine, Benha University, Qalubyia, Egypt
- Physiology Department, Al-Baha Faculty of Medicine, Al-Baha University, Al-Baha, Saudi Arabia
| | - Mohammed A. Attia
- Department of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
- Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh, Saudi Arabia
| | - Hussein M. El-Husseiny
- Cooperative Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo, Japan
- Department of Surgery, Anesthesiology, and Radiology, Faculty of Veterinary Medicine, Benha University, Benha, Egypt
| | | | - Ahmed S. Doghish
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo, Cairo, Egypt
- Department of Biochemistry and Molecular Biology, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, Egypt
| | - Ahmed Gaafar Ahmed Gaafar
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Port Said University, Port Said, Egypt
| | - Sameh Saber
- Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt
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16
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La Marca JE, Kelly GL, Strasser A, Diepstraten ST. Don't fear the reaper: The role of regulated cell death in tumorigenesis and BH3-mimetics for cancer therapy. Dev Cell 2024; 59:2532-2548. [PMID: 39378839 DOI: 10.1016/j.devcel.2024.06.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Revised: 05/20/2024] [Accepted: 06/20/2024] [Indexed: 10/10/2024]
Abstract
From its earliest characterization, it has been recognized that there is a role for regulated (programmed) cell death in cancer. As our understanding of the different types of programmed cell death processes and their molecular control has advanced, so have the technologies that allow us to manipulate these processes to, for example, fight against cancer. In this review, we describe the roles of the different forms of regulated cell death in the development of cancer as well as their potential therapeutic exploitation. In that vein, we explore the development and use of BH3-mimetics, a unique class of drugs that can directly activate the apoptotic cell death machinery to treat cancer. Finally, we address key challenges that face the field to improve the use of these therapeutics and the efforts that are being undertaken to do so.
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Affiliation(s)
- John E La Marca
- The Walter and Eliza Hall Institute, Parkville, VIC, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia; Genome Engineering and Cancer Modelling Program, Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, Australia; School of Cancer Medicine, La Trobe University, Bundoora, VIC, Australia.
| | - Gemma L Kelly
- The Walter and Eliza Hall Institute, Parkville, VIC, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.
| | - Andreas Strasser
- The Walter and Eliza Hall Institute, Parkville, VIC, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.
| | - Sarah T Diepstraten
- The Walter and Eliza Hall Institute, Parkville, VIC, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.
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17
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Toner K, McCann CD, Bollard CM. Applications of cell therapy in the treatment of virus-associated cancers. Nat Rev Clin Oncol 2024; 21:709-724. [PMID: 39160243 DOI: 10.1038/s41571-024-00930-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/19/2024] [Indexed: 08/21/2024]
Abstract
A diverse range of viruses have well-established roles as the primary driver of oncogenesis in various haematological malignancies and solid tumours. Indeed, estimates suggest that approximately 1.5 million patients annually are diagnosed with virus-related cancers. The predominant human oncoviruses include Epstein-Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV), hepatitis B and C viruses (HBV and HCV), human papillomavirus (HPV), human T-lymphotropic virus type 1 (HTLV1), and Merkel cell polyomavirus (MCPyV). In addition, although not inherently oncogenic, human immunodeficiency virus (HIV) is associated with immunosuppression that contributes to the development of AIDS-defining cancers (specifically, Kaposi sarcoma, aggressive B cell non-Hodgkin lymphoma and cervical cancer). Given that an adaptive T cell-mediated immune response is crucial for the control of viral infections, increasing research is being focused on evaluating virus-specific T cell therapies for the treatment of virus-associated cancers. In this Review, we briefly outline the roles of viruses in the pathogenesis of these malignancies before describing progress to date in the field of virus-specific T cell therapy and evaluating the potential utility of these therapies to treat or possibly even prevent virus-related malignancies.
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Affiliation(s)
- Keri Toner
- Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA
- Department of Paediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA
| | - Chase D McCann
- Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA
- Department of Paediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA
| | - Catherine M Bollard
- Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA.
- Department of Paediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
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18
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Al-Amodi HS, Kamel HF. Altered Metabolites in Hepatocellular Carcinoma (HCC) Paving the Road for Metabolomics Signature and Biomarkers for Early Diagnosis of HCC. Cureus 2024; 16:e71968. [PMID: 39569240 PMCID: PMC11576499 DOI: 10.7759/cureus.71968] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/20/2024] [Indexed: 11/22/2024] Open
Abstract
Globally, hepatocellular carcinoma (HCC) is one of the most commonly encountered cancers. Because the current early diagnostic tests for HCC are not very sensitive, most cases of the disease are discovered late when it is in its terminal stage. Cellular metabolism changes during carcinogenesis to enable cancer cells to adapt to the hypoxic milieu, boost anabolic synthesis, promote survival, and evade apoptotic death signals. Omic techniques represent a breakthrough in the field of diagnostic technology. For example, Metabolomics analysis could be used to identify these metabolite alterations. Understanding the metabolic alterations linked to HCC is crucial for improving high-risk patients' surveillance and understanding the illness's biology. This review highlights the metabolic alterations linked to energy production in cancer cells, as well as the significantly altered metabolites and pathways associated with hepatocarcinogenesis, including acylcarnitines (ACs), amino acids, proteins, lipids, carbohydrates, glucose, and lactate, which reflect the anabolic and catabolic changes occurring in these cells. Additionally, it discusses the clinical implications of recent metabolomics that may serve as potential biomarkers for early diagnosis and monitoring of the progression of HCC.
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Affiliation(s)
| | - Hala F Kamel
- Biochemistry, Umm Al-Qura University, Makkah, SAU
- Medical Biochemistry and Molecular Biology, Ain Shams University, Cairo, EGY
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19
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Talubo NDD, Tsai PW, Tayo LL. Comprehensive RNA-Seq Gene Co-Expression Analysis Reveals Consistent Molecular Pathways in Hepatocellular Carcinoma across Diverse Risk Factors. BIOLOGY 2024; 13:765. [PMID: 39452074 PMCID: PMC11505157 DOI: 10.3390/biology13100765] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Revised: 09/04/2024] [Accepted: 09/24/2024] [Indexed: 10/26/2024]
Abstract
Hepatocellular carcinoma (HCC) has the highest mortality rate and is the most frequent of liver cancers. The heterogeneity of HCC in its etiology and molecular expression increases the difficulty in identifying possible treatments. To elucidate the molecular mechanisms of HCC across grades, data from The Cancer Genome Atlas (TCGA) were used for gene co-expression analysis, categorizing each sample into its pre-existing risk factors. The R library BioNERO was used for preprocessing and gene co-expression network construction. For those modules most correlated with a grade, functional enrichments from different databases were then tested, which appeared to have relatively consistent patterns when grouped by G1/G2 and G3/G4. G1/G2 exhibited the involvement of pathways related to metabolism and the PI3K/Akt pathway, which regulates cell proliferation and related pathways, whereas G3/G4 showed the activation of cell adhesion genes and the p53 signaling pathway, which regulates apoptosis, cell cycle arrest, and similar processes. Module preservation analysis was then used with the no history dataset as the reference network, which found cell adhesion molecules and cell cycle genes to be preserved across all risk factors, suggesting they are imperative in the development of HCC regardless of potential etiology. Through hierarchical clustering, modules related to the cell cycle, cell adhesion, the immune system, and the ribosome were found to be consistently present across all risk factors, with distinct clusters linked to oxidative phosphorylation in viral HCC and pentose and glucuronate interconversions in non-viral HCC, underscoring their potential roles in cancer progression.
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Affiliation(s)
- Nicholas Dale D. Talubo
- School of Chemical, Biological, and Materials Engineering and Sciences, Mapúa University, Manila 1002, Philippines;
- School of Graduate Studies, Mapúa University, Manila 1002, Philippines
| | - Po-Wei Tsai
- Department of Food Science, National Taiwan Ocean University, Keelung 202, Taiwan;
| | - Lemmuel L. Tayo
- Department of Biology, School of Health Sciences, Mapúa University, Makati 1203, Philippines
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20
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Qiu C, Fan H, Tao S, Deng Z, Luo H, Liu F. ST8SIA6-AS1, a novel lncRNA star in liver cancer. Front Cell Dev Biol 2024; 12:1435664. [PMID: 39211393 PMCID: PMC11358109 DOI: 10.3389/fcell.2024.1435664] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Accepted: 07/26/2024] [Indexed: 09/04/2024] Open
Abstract
Liver cancer is one of the most lethal gastrointestinal malignancies. Emerging evidence has underscored the pivotal role of long non-coding RNAs (lncRNAs) in tumorigenesis, with ST8SIA6-AS1 identified as a novel oncogenic lncRNA contributing to liver cancer progression. ST8SIA6-AS1 is consistently upregulated in hepatic cancer tissues and is strongly associated with unfavorable prognosis. Moreover, it demonstrates high diagnostic efficacy in detecting HCC. ST8SIA6-AS1 is involved in various cellular processes including proliferation, migration, and invasion, primarily through its function as a competing endogenous RNA (ceRNA), thereby facilitating hepatocarcinogenesis and disease advancement. This review provides a detailed examination of the molecular functions and regulatory mechanisms of ST8SIA6-AS1 in hepatocellular carcinoma (HCC) and highlights its potential as a promising biomarker for liver cancer, aiming to propel the development of innovative therapeutic strategies for HCC management.
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Affiliation(s)
- Cheng Qiu
- Department of General Surgery, Pingxiang People’s Hospital, Pingxiang, Jiangxi, China
| | - Haoran Fan
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Siyu Tao
- Second School of Clinical Medicine, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Ziqing Deng
- Department of General Surgery, Nanchang Third Hospital, Nanchang, Jiangxi, China
| | - Hongliang Luo
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Fangteng Liu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
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Chien YC, Lee HL, Chiang WL, Bai LY, Hung YJ, Chen SC, Wang HL, Yang SF, Yu YL. Analysis of ZNF208 Polymorphisms on the Clinicopathologic Characteristics of Asian Patients with Hepatocellular Carcinoma. J Cancer 2024; 15:5183-5190. [PMID: 39247597 PMCID: PMC11375538 DOI: 10.7150/jca.98520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Accepted: 07/29/2024] [Indexed: 09/10/2024] Open
Abstract
Hepatocellular carcinoma (HCC), a major form of liver cancer, is characterized by high lethality and a multifactorial etiology that includes hepatitis virus infections, lifestyle factors, and genetic predispositions. This study aimed to explore the impact of ZNF208 gene polymorphisms on the clinicopathological features of Taiwanese HCC patients, focusing on three specific single nucleotide polymorphisms (SNPs): rs2188971, rs2188972, and rs8105767. Our cohort consisted of 438 HCC patients and 1193 control individuals. Clinical staging was determined using the tumor/node/metastasis (TNM) system, and various clinical indicators were collected. Our analysis revealed a statistically significant increase in ZNF208 expression in HCC patients compared to controls, indicating a potential role in HCC progression. Although no substantial association was observed between ZNF208 SNPs and increased HCC risk, specific clinical features such as distant metastasis and vascular invasion showed significant associations with these SNPs, suggesting their influence on disease aggressiveness. Demographic analyses highlighted the importance of factors like alcohol consumption and viral hepatitis markers in HCC. Our study underscores the complexity of genetic influences on HCC, with ZNF208 polymorphisms potentially affecting tumor progression and patient outcomes.
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Affiliation(s)
- Yi-Chung Chien
- Institute of Translational Medicine and New Drug Development, China Medical University, Taichung 40402, Taiwan
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan
- Center for Molecular Medicine, China Medical University Hospital, Taichung 40402, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
| | - Hsiang-Lin Lee
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
- Department of Surgery, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
| | - Whei-Ling Chiang
- School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 40201, Taiwan
| | - Li-Yuan Bai
- Division of Hematology and Oncology, China Medical University Hospital, Taichung, 40402, Taiwan
| | - Yu-Ju Hung
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
- Department of Surgery, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
| | - Shuo-Chueh Chen
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung 40402, Taiwan
| | - Hsiang-Ling Wang
- Department of Beauty Science, National Taichung University of Science and Technology, Taichung 404336, Taiwan
| | - Shun-Fa Yang
- Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
- Department of Medical Research, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
| | - Yung-Luen Yu
- Institute of Translational Medicine and New Drug Development, China Medical University, Taichung 40402, Taiwan
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan
- Center for Molecular Medicine, China Medical University Hospital, Taichung 40402, Taiwan
- Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung 41354, Taiwan
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22
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Farhad SZ, Karbalaeihasanesfahani A, Dadgar E, Nasiri K, Esfahaniani M, Nabi Afjadi M. The role of periodontitis in cancer development, with a focus on oral cancers. Mol Biol Rep 2024; 51:814. [PMID: 39008163 DOI: 10.1007/s11033-024-09737-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Accepted: 06/18/2024] [Indexed: 07/16/2024]
Abstract
Periodontitis is a severe gum infection that begins as gingivitis and can lead to gum recession, bone loss, and tooth loss if left untreated. It is primarily caused by bacterial infection, which triggers inflammation and the formation of periodontal pockets. Notably, periodontitis is associated with systemic health issues and has been linked to heart disease, diabetes, respiratory diseases, adverse pregnancy outcomes, and cancers. Accordingly, the presence of chronic inflammation and immune system dysregulation in individuals with periodontitis significantly contributes to the initiation and progression of various cancers, particularly oral cancers. These processes promote genetic mutations, impair DNA repair mechanisms, and create a tumor-supportive environment. Moreover, the bacteria associated with periodontitis produce harmful byproducts and toxins that directly damage the DNA within oral cells, exacerbating cancer development. In addition, chronic inflammation not only stimulates cell proliferation but also inhibits apoptosis, causes DNA damage, and triggers the release of pro-inflammatory cytokines. Collectively, these factors play a crucial role in the progression of cancer in individuals affected by periodontitis. Further, specific viral and bacterial agents, such as hepatitis B and C viruses, human papillomavirus (HPV), Helicobacter pylori (H. pylori), and Porphyromonas gingivalis, contribute to cancer development through distinct mechanisms. Bacterial infections have systemic implications for cancer development, while viral infections provoke immune and inflammatory responses that can lead to genetic mutations. This review will elucidate the link between periodontitis and cancers, particularly oral cancers, exploring their underlying mechanisms to provide insights for future research and treatment advancements.
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Affiliation(s)
- Shirin Zahra Farhad
- Department of Periodontics, Faculty of Dentistry, Isfahan(Khorasgan) Branch, Islamic Azad University, Isfahan, Iran
| | | | - Esmaeel Dadgar
- Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Kamyar Nasiri
- Faculty of Dentistry, Islamic Azad University of Medical Sciences, Tehran, Iran
| | - Mahla Esfahaniani
- Faculty of Dentistry, Golestan University of Medical Sciences, Gorgan, Iran.
| | - Mohsen Nabi Afjadi
- Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
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23
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Hsu CY, Abdulrahim MN, Mustafa MA, Omar TM, Balto F, Pineda I, Khudair TT, Ubaid M, Ali MS. The multifaceted role of PCSK9 in cancer pathogenesis, tumor immunity, and immunotherapy. Med Oncol 2024; 41:202. [PMID: 39008137 DOI: 10.1007/s12032-024-02435-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 06/18/2024] [Indexed: 07/16/2024]
Abstract
Proprotein convertase subtilisin/kexin type 9 (PCSK9), a well-known regulator of cholesterol metabolism and cardiovascular diseases, has recently garnered attention for its emerging involvement in cancer biology. The multifunctional nature of PCSK9 extends beyond lipid regulation and encompasses a wide range of cellular processes that can influence cancer progression. Studies have revealed that PCSK9 can modulate signaling pathways, such as PI3K/Akt, MAPK, and Wnt/β-catenin, thereby influencing cellular proliferation, survival, and angiogenesis. Additionally, the interplay between PCSK9 and cholesterol homeostasis may impact membrane dynamics and cellular migration, further influencing tumor aggressiveness. The central role of the immune system in monitoring and controlling cancer is increasingly recognized. Recent research has demonstrated the ability of PCSK9 to modulate immune responses through interactions with immune cells and components of the tumor microenvironment. This includes effects on dendritic cell maturation, T cell activation, and cytokine production, suggesting a role in shaping antitumor immune responses. Moreover, the potential influence of PCSK9 on immune checkpoints such as PD1/PD-L1 lends an additional layer of complexity to its immunomodulatory functions. The growing interest in cancer immunotherapy has prompted exploration into the potential of targeting PCSK9 for therapeutic benefits. Preclinical studies have demonstrated synergistic effects between PCSK9 inhibitors and established immunotherapies, offering a novel avenue for combination treatments. The strategic manipulation of PCSK9 to enhance tumor immunity and improve therapeutic outcomes presents an exciting area for further investigations. Understanding the mechanisms by which PCSK9 influences cancer biology and immunity holds promise for the development of novel immunotherapeutic approaches. This review aims to provide a comprehensive analysis of the intricate connections between PCSK9, cancer pathogenesis, tumor immunity, and the potential implications for immunotherapeutic interventions.
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Affiliation(s)
- Chou-Yi Hsu
- Department of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan City, 71710, Taiwan.
- Thunderbird School of Global Management, Arizona State University Tempe Campus, Phoenix, AZ, 85004, USA.
| | | | - Mohammed Ahmed Mustafa
- Department of Medical Laboratory Technology, Imam Jaafar AL-Sadiq University, Baghdad, Iraq
- Department of Pathological Analyzes, College of Applied Sciences, University of Samarra, Samarra, Iraq
| | - Thabit Moath Omar
- Department of Medical Laboratory Technics, Al-Noor University College, Nineveh, Iraq
| | - Franklin Balto
- Department of Biotechnology and Genetics, Jain (Deemed-to-be) University, Bengaluru, Karnataka, 560069, India
- Department of Allied Healthcare and Sciences, Vivekananda Global University, Jaipur, Rajasthan, 303012, India
| | - Indira Pineda
- School of Basic & Applied Sciences, Shobhit University, Gangoh, Uttar Pradesh, 247341, India
- Department of Health & Allied Sciences, Arka Jain University, Jamshedpur, Jharkhand, 831001, India
| | - Teeba Thamer Khudair
- College of Nursing, National University of Science and Technology, Dhi Qar, Iraq
| | - Mohammed Ubaid
- Medical Technical College, Al-Farahidi University, Baghdad, Iraq
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24
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Borden ES, Jorgensen A, Natri HM, Hastings KT, Buetow KH, Wilson MA. HCV- and HBV-mediated liver cancer converge on similar transcriptomic landscapes and immune profiles. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.07.01.601493. [PMID: 39005337 PMCID: PMC11244919 DOI: 10.1101/2024.07.01.601493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/16/2024]
Abstract
Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related deaths worldwide, and a large proportion of HCC is attributable to viral causes including hepatitis B (HBV) and C virus (HCV). The pathogenesis of viral-mediated HCC can differ between HBV and HCV, but it is unclear how much these differences influence the tumors' final molecular and immune profiles. Additionally, there are known sex differences in the molecular etiology of HCC, but sex differences have not been explored in the context of viral-mediated HCC. To determine the extent to which the viral status and sex impact the molecular and immune profiles of HCC, we performed differential expression and immune cell deconvolution analyses. We identified a large number of differentially expressed genes unique to the HBV or HCV tumor:tumor-adjacent comparison. Pathway enrichment analyses demonstrated that the changes unique to the HCV tumor:tumor-adjacent tissue were predominated by changes in the immune pathways. Immune cell deconvolution demonstrated that HCV tumor-adjacent tissue had the largest immune cell infiltrate, with no difference in the immune profiles within HBV and HCV tumor samples. We subsequently segregated the differential expression analyses by sex, but demonstrated that the low number of female samples led to an overestimate of differentially expressed genes unique to male tumors. This limitation highlights the importance of additional sampling of female HCC tumors to allow for a more complete analysis of the sex differences in HCC. Overall, this work demonstrates the convergence of HBV- and HCV-mediated HCC on a similar transcriptomic landscape and immune profile despite differences in the surrounding tissue.
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Affiliation(s)
- Elizabeth S Borden
- Department of Dermatology, College of Medicine-Phoenix, University of Arizona, Phoenix, AZ
- Phoenix Veterans Affairs Health Care System, Phoenix, AZ, USA
| | | | - Heini M Natri
- Translational Genomics Research Institute, Phoenix, AZ
| | - Karen Taraszka Hastings
- Department of Dermatology, College of Medicine-Phoenix, University of Arizona, Phoenix, AZ
- Phoenix Veterans Affairs Health Care System, Phoenix, AZ, USA
| | - Kenneth H Buetow
- School of Life Sciences, Arizona State University, Tempe, AZ
- Center for Evolution and Medicine, Arizona State University, Tempe, AZ
| | - Melissa A Wilson
- School of Life Sciences, Arizona State University, Tempe, AZ
- Center for Evolution and Medicine, Arizona State University, Tempe, AZ
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25
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Ma X, Cui M, Guo Y. Bioinformatics analysis of the association between obesity and gastric cancer. Front Genet 2024; 15:1385559. [PMID: 39011399 PMCID: PMC11246963 DOI: 10.3389/fgene.2024.1385559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Accepted: 06/11/2024] [Indexed: 07/17/2024] Open
Abstract
Background Obesity and gastric cancer (GC) are prevalent diseases worldwide. In particular, the number of patients with obesity is increasing annually, while the incidence and mortality rates of GC are ranked high. Consequently, these conditions seriously affect the quality of life of individuals. While evidence suggests a strong association between these two conditions, the underlying mechanisms of this comorbidity remain unclear. Methods We obtained the gene expression profiles of GSE94752 and GSE54129 from the Gene Expression Omnibus database. To investigate the associated biological processes, pathway enrichment analyses were conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes for the shared differentially expressed genes in obesity and GC. A protein-protein interaction (PPI) network was subsequently established based on the Search Tool for the Retrieval of Interacting Genes (STRING) database, followed by the screening of the core modules and central genes in this network using Cytoscape plug-in MCODE. Furthermore, we scrutinized the co-expression network and the interplay network of transcription factors (TFs), miRNAs, and mRNAs linked to these central genes. Finally, we conducted further analyses using different datasets to validate the significance of the hub genes. Results A total of 246 shared differentially expressed genes (209 upregulated and 37 downregulated) were selected for ensuing analyses. Functional analysis emphasized the pivotal role of inflammation and immune-associated pathways in these two diseases. Using the Cytoscape plug-in CytoHubba, nine hub genes were identified, namely, CXCR4, CXCL8, CXCL10, IL6, TNF, CCL4, CXCL2, CD4, and CCL2. IL6 and CCL4 were confirmed as the final hub genes through validation using different datasets. The TF-miRNA-mRNA regulatory network showed that the TFs primarily associated with the hub genes included RELA and NFKB1, while the predominantly associated miRNAs included has-miR-195-5p and has-miR-106a-5p. Conclusion Using bioinformatics methods, we identified two hub genes from the Gene Expression Omnibus datasets for obesity and GC. In addition, we constructed a network of hub genes, TFs, and miRNAs, and identified the major related TFs and miRNAs. These factors may be involved in the common molecular mechanisms of obesity and GC.
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Affiliation(s)
- Xiaole Ma
- Department of Gastrointestinal Surgery, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Miao Cui
- Department of Geriatrics, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Yuntong Guo
- Department of Gastrointestinal Surgery, First Hospital of Shanxi Medical University, Taiyuan, China
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26
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Zarlashat Y, Mushtaq H, Pham L, Abbas W, Sato K. Advancements in Immunotherapeutic Treatments for Hepatocellular Carcinoma: Potential of Combination Therapies. Int J Mol Sci 2024; 25:6830. [PMID: 38999940 PMCID: PMC11241106 DOI: 10.3390/ijms25136830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2024] [Revised: 06/16/2024] [Accepted: 06/17/2024] [Indexed: 07/14/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and a significant global health burden, with increasing incidence rates and limited treatment options. Immunotherapy has become a promising approach due to its ability to affect the immune microenvironment and promote antitumor responses. The immune microenvironment performs an essential role in both the progression and the development of HCC, with different characteristics based on specific immune cells and etiological factors. Immune checkpoint inhibitors, including programmed death-1/programmed death-ligand 1 inhibitors (pembrolizumab, nivolumab, and durvalumab) and cytotoxic T lymphocyte antigen-4 inhibitors (tremelimumab and ipilimumab), have the potential to treat advanced HCC and overcome adverse effects, such as liver failure and chemoresistance. Phase II and phase III clinical trials highlight the efficacy of pembrolizumab and nivolumab, respectively, in advanced HCC patients, as demonstrated by their positive effects on overall survival and progression-free survival. Tremelimumab has exhibited modest response rates, though it does possess antiviral activity. Thus, it is still being investigated in ongoing clinical trials. Combination therapies with multiple drugs have demonstrated potential benefits in terms of survival and tumor response rates, improving patient outcomes compared to monotherapy, especially for advanced-stage HCC. This review addresses the clinical trials of immunotherapies for early-, intermediate-, and advanced-stage HCC. Additionally, it highlights how combination therapy can significantly enhance overall survival, progression-free survival, and objective response rate in advanced-stage HCC, where treatment options are limited.
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Affiliation(s)
- Yusra Zarlashat
- Department of Biochemistry, Government College University Faisalabad, Faisalabad 38000, Pakistan
| | - Hassan Mushtaq
- Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering-C (NIBGE), Faisalabad 38000, Pakistan
- Pakistan Institute of Engineering and Applied Sciences (PIEAS), Islamabad 45650, Pakistan
| | - Linh Pham
- Department of Science and Mathematics, Texas A&M University-Central Texas, Killeen, TX 76549, USA
| | - Wasim Abbas
- Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering-C (NIBGE), Faisalabad 38000, Pakistan
- Pakistan Institute of Engineering and Applied Sciences (PIEAS), Islamabad 45650, Pakistan
| | - Keisaku Sato
- Department of Medicine, Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
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27
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Sallam M, Khalil R. Contemporary Insights into Hepatitis C Virus: A Comprehensive Review. Microorganisms 2024; 12:1035. [PMID: 38930417 PMCID: PMC11205832 DOI: 10.3390/microorganisms12061035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 05/15/2024] [Accepted: 05/20/2024] [Indexed: 06/28/2024] Open
Abstract
Hepatitis C virus (HCV) remains a significant global health challenge. Approximately 50 million people were living with chronic hepatitis C based on the World Health Organization as of 2024, contributing extensively to global morbidity and mortality. The advent and approval of several direct-acting antiviral (DAA) regimens significantly improved HCV treatment, offering potentially high rates of cure for chronic hepatitis C. However, the promising aim of eventual HCV eradication remains challenging. Key challenges include the variability in DAA access across different regions, slightly variable response rates to DAAs across diverse patient populations and HCV genotypes/subtypes, and the emergence of resistance-associated substitutions (RASs), potentially conferring resistance to DAAs. Therefore, periodic reassessment of current HCV knowledge is needed. An up-to-date review on HCV is also necessitated based on the observed shifts in HCV epidemiological trends, continuous development and approval of therapeutic strategies, and changes in public health policies. Thus, the current comprehensive review aimed to integrate the latest knowledge on the epidemiology, pathophysiology, diagnostic approaches, treatment options and preventive strategies for HCV, with a particular focus on the current challenges associated with RASs and ongoing efforts in vaccine development. This review sought to provide healthcare professionals, researchers, and policymakers with the necessary insights to address the HCV burden more effectively. We aimed to highlight the progress made in managing and preventing HCV infection and to highlight the persistent barriers challenging the prevention of HCV infection. The overarching goal was to align with global health objectives towards reducing the burden of chronic hepatitis, aiming for its eventual elimination as a public health threat by 2030.
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Affiliation(s)
- Malik Sallam
- Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan
- Department of Clinical Laboratories and Forensic Medicine, Jordan University Hospital, Amman 11942, Jordan
| | - Roaa Khalil
- Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan
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28
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Rahman MA, Yan F, Li R, Wang Y, Huang L, Han R, Jiang Y. Deep Learning Insights into the Dynamic Effects of Photodynamic Therapy on Cancer Cells. Pharmaceutics 2024; 16:673. [PMID: 38794335 PMCID: PMC11125085 DOI: 10.3390/pharmaceutics16050673] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 05/10/2024] [Accepted: 05/15/2024] [Indexed: 05/26/2024] Open
Abstract
Photodynamic therapy (PDT) shows promise in tumor treatment, particularly when combined with nanotechnology. This study examines the impact of deep learning, particularly the Cellpose algorithm, on the comprehension of cancer cell responses to PDT. The Cellpose algorithm enables robust morphological analysis of cancer cells, while logistic growth modelling predicts cellular behavior post-PDT. Rigorous model validation ensures the accuracy of the findings. Cellpose demonstrates significant morphological changes after PDT, affecting cellular proliferation and survival. The reliability of the findings is confirmed by model validation. This deep learning tool enhances our understanding of cancer cell dynamics after PDT. Advanced analytical techniques, such as morphological analysis and growth modeling, provide insights into the effects of PDT on hepatocellular carcinoma (HCC) cells, which could potentially improve cancer treatment efficacy. In summary, the research examines the role of deep learning in optimizing PDT parameters to personalize oncology treatment and improve efficacy.
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Affiliation(s)
- Md. Atiqur Rahman
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; (M.A.R.); (F.Y.); (R.L.); (Y.W.); (L.H.)
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Feihong Yan
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; (M.A.R.); (F.Y.); (R.L.); (Y.W.); (L.H.)
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Ruiyuan Li
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; (M.A.R.); (F.Y.); (R.L.); (Y.W.); (L.H.)
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Yu Wang
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; (M.A.R.); (F.Y.); (R.L.); (Y.W.); (L.H.)
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Lu Huang
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; (M.A.R.); (F.Y.); (R.L.); (Y.W.); (L.H.)
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Rongcheng Han
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; (M.A.R.); (F.Y.); (R.L.); (Y.W.); (L.H.)
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Yuqiang Jiang
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; (M.A.R.); (F.Y.); (R.L.); (Y.W.); (L.H.)
- University of Chinese Academy of Sciences, Beijing 100049, China
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29
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Ozturk NB, Pham HN, Mouhaffel R, Ibrahim R, Alsaqa M, Gurakar A, Saberi B. A Longitudinal Analysis of Mortality Related to Chronic Viral Hepatitis and Hepatocellular Carcinoma in the United States. Viruses 2024; 16:694. [PMID: 38793576 PMCID: PMC11125803 DOI: 10.3390/v16050694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 04/25/2024] [Accepted: 04/27/2024] [Indexed: 05/26/2024] Open
Abstract
(1) Background: Hepatocellular carcinoma (HCC) contributes to the significant burden of cancer mortality in the United States (US). Despite highly efficacious antivirals, chronic viral hepatitis (CVH) remains an important cause of HCC. With advancements in therapeutic modalities, along with the aging of the population, we aimed to assess the contribution of CVH in HCC-related mortality in the US between 1999-2020. (2) Methods: We queried all deaths related to CVH and HCC in the multiple-causes-of-death files from the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER) database between 1999-2020. Using the direct method of standardization, we adjusted all mortality information for age and compared the age-adjusted mortality rates (AAMRs) across demographic populations and by percentile rankings of social vulnerability. Temporal shifts in mortality were quantified using log-linear regression models. (3) Results: A total of 35,030 deaths were identified between 1999-2020. The overall crude mortality increased from 0.27 in 1999 to 8.32 in 2016, followed by a slight reduction to 7.04 in 2020. The cumulative AAMR during the study period was 4.43 (95% CI, 4.39-4.48). Males (AAMR 7.70) had higher mortality rates compared to females (AAMR 1.44). Mortality was higher among Hispanic populations (AAMR 6.72) compared to non-Hispanic populations (AAMR 4.18). Higher mortality was observed in US counties categorized as the most socially vulnerable (AAMR 5.20) compared to counties that are the least socially vulnerable (AAMR 2.53), with social vulnerability accounting for 2.67 excess deaths per 1,000,000 person-years. (4) Conclusions: Our epidemiological analysis revealed an overall increase in CVH-related HCC mortality between 1999-2008, followed by a stagnation period until 2020. CVH-related HCC mortality disproportionately affected males, Hispanic populations, and Black/African American populations, Western US regions, and socially vulnerable counties. These insights can help aid in the development of strategies to target vulnerable patients, focus on preventive efforts, and allocate resources to decrease HCC-related mortality.
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Affiliation(s)
- N. Begum Ozturk
- Department of Medicine, Beaumont Hospital, Royal Oak, MI 48073, USA
| | - Hoang Nhat Pham
- Department of Medicine, University of Arizona Tucson, Tucson, AZ 85721, USA
| | - Rama Mouhaffel
- Department of Medicine, University of Arizona Tucson, Tucson, AZ 85721, USA
| | - Ramzi Ibrahim
- Department of Medicine, University of Arizona Tucson, Tucson, AZ 85721, USA
| | - Marwan Alsaqa
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02130, USA
| | - Ahmet Gurakar
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross Research Building, Suite 918, Baltimore, MD 21205, USA
| | - Behnam Saberi
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02130, USA
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30
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Tian J, Bai X, Quek C. Single-Cell Informatics for Tumor Microenvironment and Immunotherapy. Int J Mol Sci 2024; 25:4485. [PMID: 38674070 PMCID: PMC11050520 DOI: 10.3390/ijms25084485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 04/12/2024] [Accepted: 04/16/2024] [Indexed: 04/28/2024] Open
Abstract
Cancer comprises malignant cells surrounded by the tumor microenvironment (TME), a dynamic ecosystem composed of heterogeneous cell populations that exert unique influences on tumor development. The immune community within the TME plays a substantial role in tumorigenesis and tumor evolution. The innate and adaptive immune cells "talk" to the tumor through ligand-receptor interactions and signaling molecules, forming a complex communication network to influence the cellular and molecular basis of cancer. Such intricate intratumoral immune composition and interactions foster the application of immunotherapies, which empower the immune system against cancer to elicit durable long-term responses in cancer patients. Single-cell technologies have allowed for the dissection and characterization of the TME to an unprecedented level, while recent advancements in bioinformatics tools have expanded the horizon and depth of high-dimensional single-cell data analysis. This review will unravel the intertwined networks between malignancy and immunity, explore the utilization of computational tools for a deeper understanding of tumor-immune communications, and discuss the application of these approaches to aid in diagnosis or treatment decision making in the clinical setting, as well as the current challenges faced by the researchers with their potential future improvements.
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Affiliation(s)
| | | | - Camelia Quek
- Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia; (J.T.); (X.B.)
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31
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Guo D, Zhang M, Wei T, Zhang X, Shi X, Tang H, Ding M, Li J, Zhang S, Guo W. NFKBIZ regulates NFκB signaling pathway to mediate tumorigenesis and metastasis of hepatocellular carcinoma by direct interaction with TRIM16. Cell Mol Life Sci 2024; 81:167. [PMID: 38581570 PMCID: PMC10998794 DOI: 10.1007/s00018-024-05182-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 01/30/2024] [Accepted: 02/20/2024] [Indexed: 04/08/2024]
Abstract
Hepatocellular carcinoma (HCC) is a malignant tumor with high incidence and mortality rates. NFKBIZ, a member of the nuclear factor kappa B inhibitory family, is closely related to tumor progression. However, the precise role of NFKBIZ in HCC remains unclear. To explore this, we conducted a series of experiments from clinic to cells. Western blot and qPCR revealed a significant downregulation of NFKBIZ in human HCC tissues. Clinical character analysis showed that the patients with lower NFKBIZ expression had poorer prognosis and higher clinical stage. By using CCK-8, wound healing, transwell invasion and migration assay, we discovered that NFKBIZ expression was reversely associated with the proliferation, invasion, and migration ability of HCC cells in vitro. Additionally, the results obtained from xenograft assay and lung metastasis models showed that NFKBIZ overexpression inhibited the growth and metastasis of HCC cells in vivo. Western blot and immunofluorescence assay further revealed that NFKBIZ mediated HCC cell growth and migration by regulating NFκB signaling transduction. Finally, flow cytometry, protein degradation assay and Co-immunoprecipitation indicated that TRIM16 can enhance NFKBIZ ubiquitination by direct interactions at its K48 site, which may thereby alleviate HCC cell apoptosis to induce the insensitivity to sorafenib. In conclusion, our study demonstrated that NFKBIZ regulated HCC tumorigenesis and metastasis by mediating NFκB signal transduction and TRIM16/NFKBIZ/NFκB axis may be the underlying mechanism of sorafenib insensitivity in HCC.
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Affiliation(s)
- Danfeng Guo
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
- Henan Key Laboratory for Digestive Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
| | - Ming Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
- Henan Key Laboratory for Digestive Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Tingju Wei
- Department of Cardiac Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Xiaodan Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
- Henan Key Laboratory for Digestive Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Xiaoyi Shi
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
- Henan Key Laboratory for Digestive Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Hongwei Tang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
- Henan Key Laboratory for Digestive Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Mingjie Ding
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
- Henan Key Laboratory for Digestive Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Jie Li
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
- Henan Key Laboratory for Digestive Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Shuijun Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
- Henan Key Laboratory for Digestive Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Wenzhi Guo
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
- Henan Key Laboratory for Digestive Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
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Yang X, Meng D, Jiang N, Wang C, Zhang J, Hu Y, Lun J, Jia R, Zhang X, Sun W. Curcumin-loaded pH-sensitive carboxymethyl chitosan nanoparticles for the treatment of liver cancer. JOURNAL OF BIOMATERIALS SCIENCE. POLYMER EDITION 2024; 35:628-656. [PMID: 38284334 DOI: 10.1080/09205063.2024.2304949] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Accepted: 11/10/2023] [Indexed: 01/30/2024]
Abstract
In this study, the pH-responsive API-CMCS-SA (ACS) polymeric nanoparticles (NPs) based on 1-(3-amino-propyl) imidazole (API), stearic acid (SA), and carboxymethyl chitosan (CMCS) were fabricated for the effective transport of curcumin (CUR) in liver cancer. CUR-ACS-NPs with various degrees of substitution (DS) were employed to prepare through ultrasonic dispersion method. The effect of different DS on NPs formation was discussed. The obtained CUR-ACS-NPs (DSSA=12.4%) had high encapsulation rate (more than 85%) and uniform particle size (186.2 ± 1.42 nm). The CUR-ACS-NPs showed better stability than the other groups. Drug release from the CUR-ACS-NPs was pH-dependent, and more than 90% or 65% of CUR was released in 48 h in weakly acid medium (pH 5.0 or 6.0, respectively). Additionally, the CUR-ACS-NPs increased the intracellular accumulation of CUR and demonstrated high anticancer effect on HepG2 cells compared with the other groups. CUR-ACS-NPs prolonged the retention time of the drug, and the area under the curve (AUC) increased significantly in vivo. The in vivo antitumor study further revealed that the CUR-ACS-NPs exhibited the capability of inhibiting tumor growth and lower systemic toxicity. Meanwhile, CUR, CUR-CS-NPs, and CUR-ACS-NPs could be detected in the evaluated organs, including tumor, liver, spleen, lung, heart, and kidney in distribution studies. Among them, CUR-ACS-NPs reached the maximum concentration at the tumor site, indicating the tumor-targeting properties. In short, the results suggested that CUR-ACS-NPs could act a prospective drug transport system for effective delivery of CUR in cancer treatment.
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Affiliation(s)
- Xinyu Yang
- College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang 154007, PR China
| | - Dongdong Meng
- College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang 154007, PR China
| | - Ning Jiang
- College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang 154007, PR China
| | - Chaoxing Wang
- College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang 154007, PR China
| | - Jinbo Zhang
- College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang 154007, PR China
| | - Yanqiu Hu
- College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang 154007, PR China
| | - Jiaming Lun
- College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang 154007, PR China
| | - Rui Jia
- College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang 154007, PR China
| | - Xueyun Zhang
- College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang 154007, PR China
| | - Weitong Sun
- College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang 154007, PR China
- Heilongjiang Provincial Key Laboratory of New Drug Development and Pharmacotoxicological Evaluation, Jiamusi, Heilongjiang 154007, PR China
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Lai YW, Chung CH. Epidemiology of Hepatocellular Carcinoma in Taiwan. Clin Pract 2024; 14:570-578. [PMID: 38666802 PMCID: PMC11048999 DOI: 10.3390/clinpract14020044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Revised: 03/14/2024] [Accepted: 03/19/2024] [Indexed: 04/28/2024] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a major contributor to the world's cancer burden. Understanding the HCC incidence rate in Taiwan is thus an interesting avenue of research. METHODS From an NHI database, those patients who had been newly diagnosed with HCC and who had been listed on a registry in a catastrophic illness dataset during the years 2013-2021 were enrolled in this study. Antineoplastic agent usage and comorbidities were also studied. RESULTS The incidence rate of HCC decreased from 57.77 to 44.95 in 100,000 from 2013 to 2021. The average age of patients with HCC increased from 65.54 years old with a CCI score of 4.98 in 2013 to 67.92 years old with a CCI score of 5.49 in 2021. Among these HCC patients, the patients under antineoplastic agent treatment decreased from 53.47% to 31.41% from 2013 to 2021. The presence of comorbidities in HCC patients was about 55.77-83.01% with mild liver disease and 29.93-37.30% with diabetes (without complications) in the period 2013-2021. CONCLUSIONS The incidence rate of HCC slightly decreased in Taiwan. Due to antineoplastic agent usage decreasing over time, these results may indicate that more early-stage HCC patients detected in recent years were mainly treated with surgeries.
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Affiliation(s)
- Yu-Wei Lai
- General Education Center, University of Taipei, Taipei 104, Taiwan;
- Division of Urology, Taipei City Hospital Renai Branch, Taipei 106, Taiwan
| | - Ching-Hu Chung
- Department of Medicine, Mackay Medical College, New Taipei City 252, Taiwan
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Poli E, De Martin E. Progression of liver disease and associated risk of hepatocellular carcinoma. HEPATOMA RESEARCH 2024. [DOI: 10.20517/2394-5079.2023.101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
Hepatocellular carcinoma (HCC) is the primary liver cancer type, often seen in individuals with chronic liver disease. Once the patient progresses to the cirrhotic stage, the annual incidence of HCC is approximately 2%-4%. As it exceeds the minimum threshold of 1.0%-1.5% per year, HCC screening every 6 months through abdominal ultrasound is indicated in the cirrhotic population. While the incidence of viral hepatitis-associated HCC is decreasing, there is a notable rise of HCC associated with metabolic dysfunction-related steatotic liver disease and alcohol-related liver disease, particularly in high-income countries. The most effective approach for oncological prevention remains addressing the cause of liver disease. The indications for HCC screening in patients without cirrhosis depend on the etiology of liver disease and the stage of fibrosis, assessed by liver biopsy or noninvasive tests such as FIB-4 or transient elastography. However, clear recommendations for HCC screening in patients without cirrhosis and for the different etiologies are currently unavailable. Research efforts should focus on identifying markers, or combinations thereof, to provide a more accurate estimate of HCC occurrence. Such advancements would enable the effective targeting of populations at the highest risk of HCC and the establishment of the correct timing to start the screening.
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Lin J, Guo H, Qin H, Zhang X, Sheng J. Integration of meta-analysis and network pharmacology analysis to investigate the pharmacological mechanisms of traditional Chinese medicine in the treatment of hepatocellular carcinoma. Front Pharmacol 2024; 15:1374988. [PMID: 38560356 PMCID: PMC10978761 DOI: 10.3389/fphar.2024.1374988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Accepted: 03/04/2024] [Indexed: 04/04/2024] Open
Abstract
Background: This study will explore the therapeutic value of traditional Chinese medicine (TCM) in Hepatocellular Carcinoma (HCC) through meta-analysis, combined with network pharmacology analysis. Methods: The results of randomized controlled trials on TCM and HCC were retrieved and summarized from multiple databases. The effective active com-pounds and target genes of the high-frequency TCM were obtained using the TCMSP database, and disease targets of HCC were acquired through the public disease database. The network pharmacology analysis was used to get the core genes and investigate the potential oncogenic molecular mechanism. Results: A total of 14 meta-analysis studies with 1,831 patients suggested that therapy combined TCM is associated with better clinical efficacy and survival prognosis, as well as avoiding many adverse events. A total of 156 compounds, 247 herbal target genes and 36 core genes were identified. The function analysis suggested above genes may participate development in HCC through regulating some pathways, such as HIF-1 pathway and PD-L1 immune-related pathway. Conclusion: TCM, as a novel, safe, and effective multi-mechanism therapy, holds greater value in the treatment of HCC.
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Affiliation(s)
- Jie Lin
- Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, Changchun, Jilin, China
| | - Huaijuan Guo
- Department of Oncology, The Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu, China
| | - Hanjiao Qin
- Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, Changchun, Jilin, China
| | - Xuewen Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, Changchun, Jilin, China
| | - Jiyao Sheng
- Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, Changchun, Jilin, China
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Ayaz H, Ahmad F, Ahmad S, Arfan Q, Alasmari AF, Siddique F, Rehman B, Zeb A, Crovella S, Ali SS, Waheed Y, Suleman M. Network-base approaches to identify therapeutic biomarkers in hepatocellular carcinoma and search for drug hunting utilizing molecular dynamics simulations. J Biomol Struct Dyn 2024:1-17. [DOI: 10.1080/07391102.2024.2326197] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Accepted: 02/27/2024] [Indexed: 12/06/2024]
Affiliation(s)
- Hassan Ayaz
- Centre for Biotechnology and Microbiology, University of Swat, Mingora, Pakistan
- Department of Biotechnology, Quaid-I-Azam University, Islamabad, Pakistan
| | - Faisal Ahmad
- Foundation University Medical College, Foundation University Islamabad, DHA-I, Islamabad, Pakistan
- School of Biology, Georgia Institute of Technology, Atlanta, GA, USA
| | - Sajjad Ahmad
- Department of Health and Biological Sciences, Abasyn University, Peshawar, Pakistan
- Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Beirut, Lebanon
- Department of Natural Sciences, Lebanese American University, Beirut, Lebanon
| | - Qaiser Arfan
- Department of Bioinformatics, Hazara University, Mansehra, Pakistan
| | - Abdullah F. Alasmari
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Farhan Siddique
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Bahauddin Zakriya University Multan, Multan, Pakistan
| | - Bushra Rehman
- Institute of Biotechnology and Microbiology, Bacha khan University, Charsadda, Pakistan
| | - Adnan Zeb
- Centre for Biotechnology and Microbiology, University of Swat, Mingora, Pakistan
| | - Sergio Crovella
- Laboratory Animal Research Centre, Qatar University, Doha, Qatar
| | - Syed Shujait Ali
- Centre for Biotechnology and Microbiology, University of Swat, Mingora, Pakistan
| | - Yasir Waheed
- Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Beirut, Lebanon
- Bridging Health Foundation, Rawalpindi, Pakistan
| | - Muhammad Suleman
- Centre for Biotechnology and Microbiology, University of Swat, Mingora, Pakistan
- Institute of Biotechnology and Microbiology, Bacha khan University, Charsadda, Pakistan
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Chen J, Shen L, Guo Q, Ma S, Zhang Y, Chen J, Qu L, Ng SS, Chen X. The downregulation of Tapasin in dendritic cell regulates CD8 + T cell autophagy to hamper hepatitis B viral clearance in the induced pluripotent stem cell-derived hepatocyte organoid. J Med Virol 2024; 96:e29546. [PMID: 38516804 DOI: 10.1002/jmv.29546] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Revised: 02/09/2024] [Accepted: 03/06/2024] [Indexed: 03/23/2024]
Abstract
Tapasin, a crucial molecular chaperone involved viral antigen processing and presentation, plays an important role in antivirus immunity. However, its impact on T cell differentiation in the context of virus clearance remains unclear. In this study, we employed induced pluripotent stem cells to differentiate into hepatocyte-like cell, which were subsequently inserted to the inverted colloidal crystal scaffolds, thus establishing a hepatocyte organoid (HO). By inoculating hepatitis B virus (HBV) particles in the system, we successfully engineered a robust in vitro HBV infection model for at least 3 weeks. Furthermore, we aimed to explore the effects of lentivirus-mediated short hairpin RNA (shRNA) targeting human Tapasin on the differentiation and antiviral function of CD8+ T cells. Specifically, we transfected dendritic cells (DCs) with Tapasin-shRNA and cocultured with T cells. The results demonstrated that Tapasin-shRNA transfected DCs effectively suppressed T cell proliferation and impeded HBV-specific cytotoxic T lymphocyte responses. Our investigation also revealed the role of mTOR pathway activation in reducing autophagy activity within CD8+ T cells. Expressions of autophagy-related proteins, beclin-1, LC3II/LC3I were decreased and PI3K/AKT/mTOR activity was increased in Tapasin-shRNA group. Collectively, our findings elucidate that shRNA targeting the Tapasin gene within DCs inhibits T cell differentiation by reducing autophagy activity to hamper viral clearance in the HBV-infected HO.
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Affiliation(s)
- Jinmei Chen
- Department of Infectious Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Leer Shen
- Department of Infectious Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qingxin Guo
- Department of Infectious Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Siyuan Ma
- Department of Infectious Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yi Zhang
- Department of Infectious Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jie Chen
- Department of Infectious Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lihong Qu
- Department of Infectious Diseases, Shanghai East Hospital, Tongji University, Shanghai, China
| | - Soon Seng Ng
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Xiaohua Chen
- Department of Infectious Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Kamali MJ, Salehi M, Mostafavi M, Morovatshoar R, Akbari M, Latifi N, Barzegari O, Ghadimi F, Daraei A. Hijacking and rewiring of host CircRNA/miRNA/mRNA competitive endogenous RNA (ceRNA) regulatory networks by oncoviruses during development of viral cancers. Rev Med Virol 2024; 34:e2530. [PMID: 38517354 DOI: 10.1002/rmv.2530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 03/04/2024] [Accepted: 03/11/2024] [Indexed: 03/23/2024]
Abstract
A significant portion of human cancers are caused by oncoviruses (12%-25%). Oncoviruses employ various strategies to promote their replication and induce tumourigenesis in host cells, one of which involves modifying the gene expression patterns of the host cells, leading to the rewiring of genes and resulting in significant changes in cellular processes and signalling pathways. In recent studies, a specific mode of gene regulation known as circular RNA (circRNA)-mediated competing endogenous RNA (ceRNA) networks has emerged as a key player in this context. CircRNAs, a class of non-coding RNA molecules, can interact with other RNA molecules, such as mRNAs and microRNAs (miRNAs), through a process known as ceRNA crosstalk. This interaction occurs when circRNAs, acting as sponges, sequester miRNAs, thereby preventing them from binding to their target mRNAs and modulating their expression. By rewiring the host cell genome, oncoviruses have the ability to manipulate the expression and activity of circRNAs, thereby influencing the ceRNA networks that can profoundly impact cellular processes such as cell proliferation, differentiation, apoptosis, and immune responses. This review focuses on a comprehensive evaluation of the latest findings on the involvement of virus-induced reprogramming of host circRNA-mediated ceRNA networks in the development and pathophysiology of human viral cancers, including cervical cancer, gastric cancer, nasopharyngeal carcinoma, Kaposi's sarcoma, hepatocellular carcinoma, and diffuse large B cell lymphoma. Understanding these mechanisms can improve our knowledge of how oncoviruses contribute to human tumourigenesis and identify potential targets for developing optimised therapies and diagnostic tools for viral cancers.
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Affiliation(s)
- Mohammad Javad Kamali
- Department of Medical Genetics, School of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Mohammad Salehi
- Department of Medical Genetics, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran
| | - Mehrnaz Mostafavi
- Department of Physics, Faculty of Allied Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Reza Morovatshoar
- Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Mitra Akbari
- Eye Department, Eye Research Center, Amiralmomenin Hospital, School of Medicine, Guilan University of Medical Science, Rasht, Iran
| | - Narges Latifi
- Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran
| | - Omid Barzegari
- Department of Medical Genetics, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran
| | - Fatemeh Ghadimi
- Department of Medical Genetics, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran
| | - Abdolreza Daraei
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
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Gao Y, Feng C, Ma J, Yan Q. Protein arginine methyltransferases (PRMTs): Orchestrators of cancer pathogenesis, immunotherapy dynamics, and drug resistance. Biochem Pharmacol 2024; 221:116048. [PMID: 38346542 DOI: 10.1016/j.bcp.2024.116048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 01/15/2024] [Accepted: 02/06/2024] [Indexed: 02/16/2024]
Abstract
Protein Arginine Methyltransferases (PRMTs) are a family of enzymes regulating protein arginine methylation, which is a post-translational modification crucial for various cellular processes. Recent studies have highlighted the mechanistic role of PRMTs in cancer pathogenesis, immunotherapy, and drug resistance. PRMTs are involved in diverse oncogenic processes, including cell proliferation, apoptosis, and metastasis. They exert their effects by methylation of histones, transcription factors, and other regulatory proteins, resulting in altered gene expression patterns. PRMT-mediated histone methylation can lead to aberrant chromatin remodeling and epigenetic changes that drive oncogenesis. Additionally, PRMTs can directly interact with key signaling pathways involved in cancer progression, such as the PI3K/Akt and MAPK pathways, thereby modulating cell survival and proliferation. In the context of cancer immunotherapy, PRMTs have emerged as critical regulators of immune responses. They modulate immune checkpoint molecules, including programmed cell death protein 1 (PD-1), through arginine methylation. Drug resistance is a significant challenge in cancer treatment, and PRMTs have been implicated in this phenomenon. PRMTs can contribute to drug resistance through multiple mechanisms, including the epigenetic regulation of drug efflux pumps, altered DNA damage repair, and modulation of cell survival pathways. In conclusion, PRMTs play critical roles in cancer pathogenesis, immunotherapy, and drug resistance. In this overview, we have endeavored to illuminate the mechanistic intricacies of PRMT-mediated processes. Shedding light on these aspects will offer valuable insights into the fundamental biology of cancer and establish PRMTs as promising therapeutic targets.
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Affiliation(s)
- Yihang Gao
- Department of Laboratory Medicine, the Second Hospital of Jilin University, Changchun 130000, China
| | - Chongchong Feng
- Department of Laboratory Medicine, the Second Hospital of Jilin University, Changchun 130000, China.
| | - Jingru Ma
- Department of Laboratory Medicine, the Second Hospital of Jilin University, Changchun 130000, China
| | - Qingzhu Yan
- Department of Ultrasound Medicine, the Second Hospital of Jilin University, Changchun 130000, China
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40
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Zhou XQ, Li YP, Dang SS. Precision targeting in hepatocellular carcinoma: Exploring ligand-receptor mediated nanotherapy. World J Hepatol 2024; 16:164-176. [PMID: 38495282 PMCID: PMC10941735 DOI: 10.4254/wjh.v16.i2.164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 01/10/2024] [Accepted: 01/18/2024] [Indexed: 02/27/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and poses a major challenge to global health due to its high morbidity and mortality. Conventional chemotherapy is usually targeted to patients with intermediate to advanced stages, but it is often ineffective and suffers from problems such as multidrug resistance, rapid drug clearance, nonspecific targeting, high side effects, and low drug accumulation in tumor cells. In response to these limitations, recent advances in nanoparticle-mediated targeted drug delivery technologies have emerged as breakthrough approaches for the treatment of HCC. This review focuses on recent advances in nanoparticle-based targeted drug delivery systems, with special attention to various receptors overexpressed on HCC cells. These receptors are key to enhancing the specificity and efficacy of nanoparticle delivery and represent a new paradigm for actively targeting and combating HCC. We comprehensively summarize the current understanding of these receptors, their role in nanoparticle targeting, and the impact of such targeted therapies on HCC. By gaining a deeper understanding of the receptor-mediated mechanisms of these innovative therapies, more effective and precise treatment of HCC can be achieved.
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Affiliation(s)
- Xia-Qing Zhou
- Department of Infectious Diseases, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
| | - Ya-Ping Li
- Department of Infectious Diseases, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
| | - Shuang-Suo Dang
- Department of Infectious Diseases, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
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Apostolo D, Ferreira LL, Vincenzi F, Vercellino N, Minisini R, Latini F, Ferrari B, Burlone ME, Pirisi M, Bellan M. From MASH to HCC: the role of Gas6/TAM receptors. Front Immunol 2024; 15:1332818. [PMID: 38298195 PMCID: PMC10827955 DOI: 10.3389/fimmu.2024.1332818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 01/02/2024] [Indexed: 02/02/2024] Open
Abstract
Metabolic dysfunction-associated steatohepatitis (MASH) is the replacement term for what used to be called nonalcoholic steatohepatitis (NASH). It is characterized by inflammation and injury of the liver in the presence of cardiometabolic risk factors and may eventually result in the development of hepatocellular carcinoma (HCC), the most common form of primary liver cancer. Several pathogenic mechanisms are involved in the transition from MASH to HCC, encompassing metabolic injury, inflammation, immune dysregulation and fibrosis. In this context, Gas6 (Growth Arrest-Specific 6) and TAM (Tyro3, Axl, and MerTK) receptors may play important roles. The Gas6/TAM family is involved in the modulation of inflammation, lipid metabolism, fibrosis, tumor progression and metastasis, processes which play an important role in the pathophysiology of acute and chronic liver diseases. In this review, we discuss MASH-associated HCC and the potential involvement of the Gas6/TAM system in disease development and progression. In addition, since therapeutic strategies for MASH and HCC are limited, we also speculate regarding possible future treatments involving the targeting of Gas6 or TAM receptors.
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Affiliation(s)
- Daria Apostolo
- Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
| | - Luciana L. Ferreira
- Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
| | - Federica Vincenzi
- Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
| | - Nicole Vercellino
- Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
| | - Rosalba Minisini
- Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
| | - Federico Latini
- Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
| | - Barbara Ferrari
- Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
| | - Michela E. Burlone
- Department of Internal Medicine, Azienda Ospedaliero-Universitaria Maggiore Della Carità, Novara, Italy
| | - Mario Pirisi
- Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
- Department of Internal Medicine, Azienda Ospedaliero-Universitaria Maggiore Della Carità, Novara, Italy
- Center on Autoimmune and Allergic Diseases, Università del Piemonte Orientale, Novara, Italy
| | - Mattia Bellan
- Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
- Department of Internal Medicine, Azienda Ospedaliero-Universitaria Maggiore Della Carità, Novara, Italy
- Center on Autoimmune and Allergic Diseases, Università del Piemonte Orientale, Novara, Italy
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Zhang B, Zhou B, Huang G, Huang J, Lin X, Li Z, Lian Y, Huang Q, Ye Y. Nitidine chloride inhibits G2/M phase by regulating the p53/14-3-3 Sigma/CDK1 axis for hepatocellular carcinoma treatment. Heliyon 2024; 10:e24012. [PMID: 38283241 PMCID: PMC10818205 DOI: 10.1016/j.heliyon.2024.e24012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Revised: 12/29/2023] [Accepted: 01/02/2024] [Indexed: 01/30/2024] Open
Abstract
Background Liver cancer had become the sixth most common cancer. Nitidine chloride (NC) has demonstrated promising anti-HCC properties; however, further elucidation of its mechanism of action is necessary. Methods The anti-HCC targets of NC were identified through the utilization of multiple databases and ChIPs data analysis. The GO and KEGG analyses to determine the specific pathway affected by NC. The Huh 7 and Hep G2 cells were subjected to a 24-h treatment with NC, followed by evaluating the impact of NC on cell proliferation and cell cycle. The involvement of the p53/14-3-3 Sigma/CDK1 axis in HCC cells was confirmed by qPCR and WB analysis of the corresponding genes and proteins. Results The GO and KEGG analysis showed the targets were related to cell cycle and p53 signaling pathways. In vitro experiments showed that NC significantly inhibited the proliferation of HCC cells and induced G2/M phase arrest. In addition, qPCR and WB experiments showed that the expression of p53 in HCC cells increased after NC intervention, while the expression of 14-3-3 Sigma and CDK1 decreased. Conclusion NC can inhibit the proliferation of HCC cells and induce G2/M cell cycle arrest, potentially by regulating the p53/14-3-3 Sigma/CDK1 axis.
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Affiliation(s)
- Bo Zhang
- Scientific Research Center, Guilin Medical University, Guilin, China
| | - Bo Zhou
- Scientific Research Center, Guilin Medical University, Guilin, China
| | - Guihong Huang
- Department of Pharmacy, The Second Affiliated Hospital of Guilin Medical University, Guilin, China
- Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders, Key Laboratory of Diabetic Systems Medicine, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, 541199, China
- Guangxi Key Laboratory of Drug Discovery and Optimization, Guangxi Engineering Research Center for Pharmaceutical Molecular Screening and Druggability Evaluation, School of Pharmacy, Guilin Medical University, Guilin, Guangxi, 541199, China
| | - Jing'an Huang
- Scientific Research Center, Guilin Medical University, Guilin, China
| | - Xiaoxin Lin
- Scientific Research Center, Guilin Medical University, Guilin, China
| | - Zonghuai Li
- Scientific Research Center, Guilin Medical University, Guilin, China
| | - Yuanchu Lian
- Scientific Research Center, Guilin Medical University, Guilin, China
| | - Qiujie Huang
- Guangxi University of Chinese Medicine, Teaching Experiment and Training Center, Nanning, China
| | - Yong Ye
- School of Pharmacy, Guangxi Medical University, Guangxi, China
- Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, China
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Liu T, Guo Y, Liao Y, Liu J. Mechanism-guided fine-tuned microbiome potentiates anti-tumor immunity in HCC. Front Immunol 2023; 14:1333864. [PMID: 38169837 PMCID: PMC10758498 DOI: 10.3389/fimmu.2023.1333864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 12/05/2023] [Indexed: 01/05/2024] Open
Abstract
Microbiome, including bacteria, fungi, and viruses, plays a crucial role in shaping distal and proximal anti-tumor immunity. Mounting evidence showed that commensal microbiome critically modulates immunophenotyping of hepatocellular carcinoma (HCC), a leading cause of cancer-related death. However, their role in anti-tumor surveillance of HCC is still poorly understood. Herein, we spotlighted growing interests in how the microbiome influences the progression and immunotherapeutic responses of HCC via changing local tumor microenvironment (TME) upon translocating to the sites of HCC through different "cell-type niches". Moreover, we summarized not only the associations but also the deep insight into the mechanisms of how the extrinsic microbiomes interplay with hosts to shape immune surveillance and regulate TME and immunotherapeutic responses. Collectively, we provided a rationale for a mechanism-guided fine-tuned microbiome to be neoadjuvant immunotherapy in the near future.
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Affiliation(s)
- Tao Liu
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Ya Guo
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Yanxia Liao
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jinping Liu
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
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Zulian V, Fiscon G, Paci P, Garbuglia AR. Hepatitis B Virus and microRNAs: A Bioinformatics Approach. Int J Mol Sci 2023; 24:17224. [PMID: 38139051 PMCID: PMC10743825 DOI: 10.3390/ijms242417224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Revised: 11/20/2023] [Accepted: 12/05/2023] [Indexed: 12/24/2023] Open
Abstract
In recent decades, microRNAs (miRNAs) have emerged as key regulators of gene expression, and the identification of viral miRNAs (v-miRNAs) within some viruses, including hepatitis B virus (HBV), has attracted significant attention. HBV infections often progress to chronic states (CHB) and may induce fibrosis/cirrhosis and hepatocellular carcinoma (HCC). The presence of HBV can dysregulate host miRNA expression, influencing several biological pathways, such as apoptosis, innate and immune response, viral replication, and pathogenesis. Consequently, miRNAs are considered a promising biomarker for diagnostic, prognostic, and treatment response. The dynamics of miRNAs during HBV infection are multifaceted, influenced by host variability and miRNA interactions. Given the ability of miRNAs to target multiple messenger RNA (mRNA), understanding the viral-host (human) interplay is complex but essential to develop novel clinical applications. Therefore, bioinformatics can help to analyze, identify, and interpret a vast amount of miRNA data. This review explores the bioinformatics tools available for viral and host miRNA research. Moreover, we introduce a brief overview focusing on the role of miRNAs during HBV infection. In this way, this review aims to help the selection of the most appropriate bioinformatics tools based on requirements and research goals.
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Affiliation(s)
- Verdiana Zulian
- Virology Laboratory, National Institute for Infectious Diseases “Lazzaro Spallanzani” IRCCS, 00149 Rome, Italy;
| | - Giulia Fiscon
- Department of Computer, Control and Management Engineering, Sapienza University of Rome, 00185 Rome, Italy; (G.F.); (P.P.)
- Institute for Systems Analysis and Computer Science “Antonio Ruberti”, National Research Council, 00185 Rome, Italy
| | - Paola Paci
- Department of Computer, Control and Management Engineering, Sapienza University of Rome, 00185 Rome, Italy; (G.F.); (P.P.)
- Institute for Systems Analysis and Computer Science “Antonio Ruberti”, National Research Council, 00185 Rome, Italy
| | - Anna Rosa Garbuglia
- Virology Laboratory, National Institute for Infectious Diseases “Lazzaro Spallanzani” IRCCS, 00149 Rome, Italy;
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Sheng M, Zhang Y, Wang Y, Liu W, Wang X, Ke T, Liu P, Wang S, Shao W. Decoding the role of aberrant RNA alternative splicing in hepatocellular carcinoma: a comprehensive review. J Cancer Res Clin Oncol 2023; 149:17691-17708. [PMID: 37898981 DOI: 10.1007/s00432-023-05474-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Accepted: 10/10/2023] [Indexed: 10/31/2023]
Abstract
During eukaryotic gene expression, alternative splicing of messenger RNA precursors is critical in increasing protein diversity and regulatory complexity. Multiple transcript isoforms could be produced by alternative splicing from a single gene; they could eventually be translated into protein isoforms with deleted, added, or altered domains or produce transcripts containing premature termination codons that could be targeted by nonsense-mediated mRNA decay. Alternative splicing can generate proteins with similar, different, or even opposite functions. Increasingly strong evidence indicates that abnormal RNA splicing is a prevalent and crucial occurrence in cellular differentiation, tissue advancement, and the development and progression of cancer. Aberrant alternative splicing could affect cancer cell activities such as growth, apoptosis, invasiveness, drug resistance, angiogenesis, and metabolism. This systematic review provides a comprehensive overview of the impact of abnormal RNA alternative splicing on the development and progression of hepatocellular carcinoma.
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Affiliation(s)
- Mengfei Sheng
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China
| | - Yuanyuan Zhang
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China
| | - Yaoyun Wang
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China
| | - Weiyi Liu
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China
| | - Xingyu Wang
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China
| | - Tiaoying Ke
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China
| | - Pingyang Liu
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA
| | - Sihan Wang
- Department of Clinical Medicine, Bengbu Medical College, Bengbu, China
| | - Wei Shao
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China.
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Yin X, Kan F. Hepatitis E virus infection and risk of hepatocellular carcinoma: A systematic review and meta-analysis. Cancer Epidemiol 2023; 87:102457. [PMID: 37797398 DOI: 10.1016/j.canep.2023.102457] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 09/12/2023] [Accepted: 09/22/2023] [Indexed: 10/07/2023]
Abstract
BACKGROUND The potential role of hepatitis E virus (HEV) infection in developing hepatocellular carcinoma (HCC) is controversial and poorly investigated. We conducted a meta-analysis of observational studies to evaluate whether HEV infection increases the risk of HCC. METHODS We searched international databases (PubMed/Medline, Web of Science Collection, Embase, and Scopus) for peer-reviewed research articles published from inception to May 1, 2023. The pooled estimates of the odds ratios (ORs) and corresponding 95% confidence intervals (95%CIs) were calculated using random-effects models. Between-study heterogeneity was measured using I² and Q-statistic. Sensitivity and cumulative analyses were performed to examine the stability of our results. RESULTS We identified seven eligible studies involving 1873 HCC cases and 8679 control subjects; the latter included 7382 healthy controls and 1297 patients with chronic liver diseases (CLD). Overall, we observed statistically significant associations between HEV infection and risk of HCC (OR 1.94; 95%CI 1.26-3.0). According to the types of the controls, the association was significant when healthy individuals were the controls (OR 2.28, 95%CI 1.43-3.64), whereas the association was not significant when the patients had CLD (OR 1.66, 95%CI 0.76-3.61). The Egger's test and funnel plot indicated that there is no publication bias (p = 0.1) in the studies included in the meta-analysis. Sensitivity and cumulative analyses also indicated stability of our results. CONCLUSIONS Our findings indicate that individuals with HEV infection had an increased risk of HCC; however, further well-designed clinical and experimental studies are needed to confirm these observations. Furthermore, whether various genotypes of HEV differ in promoting HCC also needs to be investigated.
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Affiliation(s)
- Xia Yin
- Department of Interventional Therapy, Zibo First Hospital, Zibo 255200, China
| | - Fanggong Kan
- Department of Oncology, Zibo First Hospital, Zibo 255200, China.
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Kalantari L, Ghotbabadi ZR, Gholipour A, Ehymayed HM, Najafiyan B, Amirlou P, Yasamineh S, Gholizadeh O, Emtiazi N. A state-of-the-art review on the NRF2 in Hepatitis virus-associated liver cancer. Cell Commun Signal 2023; 21:318. [PMID: 37946175 PMCID: PMC10633941 DOI: 10.1186/s12964-023-01351-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2023] [Accepted: 10/09/2023] [Indexed: 11/12/2023] Open
Abstract
According to a paper released and submitted to WHO by IARC scientists, there would be 905,700 new cases of liver cancer diagnosed globally in 2020, with 830,200 deaths expected as a direct result. Hepatitis B virus (HBV) hepatitis C virus (HCV), and hepatitis D virus (HDV) all play critical roles in the pathogenesis of hepatocellular carcinoma (HCC), despite the rising prevalence of HCC due to non-infectious causes. Liver cirrhosis and HCC are devastating consequences of HBV and HCV infections, which are widespread worldwide. Associated with a high mortality rate, these infections cause about 1.3 million deaths annually and are the primary cause of HCC globally. In addition to causing insertional mutations due to viral gene integration, epigenetic alterations and inducing chronic immunological dysfunction are all methods by which these viruses turn hepatocytes into cancerous ones. While expanding our knowledge of the illness, identifying these pathways also give possibilities for novel diagnostic and treatment methods. Nuclear factor erythroid 2-related factor 2 (NRF2) activation is gaining popularity as a treatment option for oxidative stress (OS), inflammation, and metabolic abnormalities. Numerous studies have shown that elevated Nrf2 expression is linked to HCC, providing more evidence that Nrf2 is a critical factor in HCC. This aberrant Nrf2 signaling drives cell proliferation, initiates angiogenesis and invasion, and imparts drug resistance. As a result, this master regulator may be a promising treatment target for HCC. In addition, the activation of Nrf2 is a common viral effect that contributes to the pathogenesis, development, and chronicity of virus infection. However, certain viruses suppress Nrf2 activity, which is helpful to the virus in maintaining cellular homeostasis. In this paper, we discussed the influence of Nrf2 deregulation on the viral life cycle and the pathogenesis associated with HBV and HCV. We summed up the mechanisms for the modulation of Nrf2 that are deregulated by these viruses. Moreover, we describe the molecular mechanism by which Nrf2 is modulated in liver cancer, liver cancer stem cells (LCSCs), and liver cancer caused by HBV and HCV. Video Abstract.
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Affiliation(s)
- Leila Kalantari
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | | | - Arsalan Gholipour
- Nanotechnology Research Institute, School of Chemical Engineering, Babol Noshirvani University of Technology, Babol, Iran
| | | | - Behnam Najafiyan
- Faculty of Pharmacy, Shiraz University of Medical Science, Shiraz, Iran
| | - Parsa Amirlou
- Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | | | | | - Nikoo Emtiazi
- Department of Pathology, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran.
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Romualdo GR, Heidor R, Bacil GP, Moreno FS, Barbisan LF. Past, present, and future of chemically induced hepatocarcinogenesis rodent models: Perspectives concerning classic and new cancer hallmarks. Life Sci 2023; 330:121994. [PMID: 37543357 DOI: 10.1016/j.lfs.2023.121994] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 07/25/2023] [Accepted: 07/29/2023] [Indexed: 08/07/2023]
Abstract
Hepatocellular carcinoma (HCC), the main primary liver cancer, accounts for 5 % of all incident cases and 8.4 % of all cancer-related deaths worldwide. HCC displays a spectrum of environmental risk factors (viral chronic infections, aflatoxin exposure, alcoholic- and nonalcoholic fatty liver diseases) that result in molecular complexity and heterogeneity, contributing to a rising epidemiological burden, poor prognosis, and non-satisfactory treatment options. The emergence of HCC (i.e., hepatocarcinogenesis) is a multistep and complex process that addresses many (epi)genetic alterations and phenotypic traits, the so-called cancer hallmarks. "Polymorphic microbiomes", "epigenetic reprogramming", "senescent cells" and "unlocking phenotypic plasticity" are trending hallmarks/enabling features in cancer biology. As the main molecular drivers of HCC are still undruggable, chemically induced in vivo models of hepatocarcinogenesis are useful tools in preclinical research. Thus, this narrative review aimed at recapitulating the basic features of chemically induced rodent models of hepatocarcinogenesis, eliciting their permanent translational value regarding the "classic" and the "new" cancer hallmarks/enabling features. We gathered state-of-art preclinical evidence on non-cirrhotic, inflammation-, alcoholic liver disease- and nonalcoholic fatty liver-associated HCC models, demonstrating that these bioassays indeed express the recently added hallmarks, as well as reflect the interplay between classical and new cancer traits. Our review demonstrated that these protocols remain valuable for translational preclinical application, as they recapitulate trending features of cancer science. Further "omics-based" approaches are warranted while multimodel investigations are encouraged in order to avoid "model-biased" responses.
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Affiliation(s)
- Guilherme Ribeiro Romualdo
- São Paulo State University (UNESP), Botucatu Medical School, Experimental Research Unit (UNIPEX), Multimodel Drug Screening Platform - Laboratory of Chemically Induced and Experimental Carcinogenesis (MDSP-LCQE), Botucatu, SP, Brazil; São Paulo State University (UNESP), Biosciences Institute, Department of Structural and Functional Biology, Laboratory of Chemically Induced and Experimental Carcinogenesis (LCQE), Botucatu, SP, Brazil; São Paulo State University (UNESP), Botucatu Medical School, Botucatu, SP, Brazil
| | - Renato Heidor
- University of São Paulo (USP), Faculty of Pharmaceutical Sciences, Department of Food and Experimental Nutrition, Laboratory of Diet, Nutrition, and Cancer, São Paulo, SP, Brazil
| | - Gabriel Prata Bacil
- São Paulo State University (UNESP), Biosciences Institute, Department of Structural and Functional Biology, Laboratory of Chemically Induced and Experimental Carcinogenesis (LCQE), Botucatu, SP, Brazil; São Paulo State University (UNESP), Botucatu Medical School, Botucatu, SP, Brazil
| | - Fernando Salvador Moreno
- University of São Paulo (USP), Faculty of Pharmaceutical Sciences, Department of Food and Experimental Nutrition, Laboratory of Diet, Nutrition, and Cancer, São Paulo, SP, Brazil
| | - Luís Fernando Barbisan
- São Paulo State University (UNESP), Botucatu Medical School, Experimental Research Unit (UNIPEX), Multimodel Drug Screening Platform - Laboratory of Chemically Induced and Experimental Carcinogenesis (MDSP-LCQE), Botucatu, SP, Brazil; São Paulo State University (UNESP), Biosciences Institute, Department of Structural and Functional Biology, Laboratory of Chemically Induced and Experimental Carcinogenesis (LCQE), Botucatu, SP, Brazil; São Paulo State University (UNESP), Botucatu Medical School, Botucatu, SP, Brazil.
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Nemteanu R, Clim A, Hincu CE, Gheorghe L, Ciortescu I, Plesa A. Interferon-Free Regimens and Direct-Acting Antiviral Agents for Delta Hepatitis: Are We There Yet? Curr Issues Mol Biol 2023; 45:7878-7890. [PMID: 37886941 PMCID: PMC10605217 DOI: 10.3390/cimb45100498] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 09/23/2023] [Accepted: 09/26/2023] [Indexed: 10/28/2023] Open
Abstract
Chronic delta hepatitis is a global health problem. Although a smaller percentage of chronic HBV-infected patients are coinfected with the hepatitis delta virus, these patients have a higher risk of an accelerated progression to fulminant "delta hepatitis", cirrhosis, hepatic decompensation, and hepatocellular carcinoma, putting a financial strain on the healthcare system and increasing the need for a liver transplant. Since its discovery, tremendous efforts have been directed toward understanding the intricate pathogenic mechanisms, discovering the complex viral replication process, the essential replicative intermediates, and cell division-mediated viral spread, which enables virion viability. The consideration of the interaction between HBV and HDV is crucial in the process of developing novel pharmaceuticals. Until just recently, interferon-based therapy was the only treatment available worldwide. This review aims to present the recent advancements in understanding the life cycle of HDV, which have consequently facilitated the development of innovative drug classes. Additionally, we will examine the antiviral strategies currently in phases II and III of development, including bulevirtide (an entry inhibitor), lonafarnib (a prenylation inhibitor), and REP 2139 (an HBsAg release inhibitor).
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Affiliation(s)
- Roxana Nemteanu
- Medical I Department, Grigore T. Popa University of Medicine and Pharmacy, 700100 Iasi, Romania; (A.C.); (L.G.); (A.P.)
- Institute of Gastroenterology and Hepatology, “Sfantul. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Andreea Clim
- Medical I Department, Grigore T. Popa University of Medicine and Pharmacy, 700100 Iasi, Romania; (A.C.); (L.G.); (A.P.)
| | - Corina Elena Hincu
- Department of Radiology, “Sfantul Spiridon” Hospital, 700111 Iasi, Romania;
| | - Liliana Gheorghe
- Medical I Department, Grigore T. Popa University of Medicine and Pharmacy, 700100 Iasi, Romania; (A.C.); (L.G.); (A.P.)
- Department of Radiology, “Sfantul Spiridon” Hospital, 700111 Iasi, Romania;
| | - Irina Ciortescu
- Medical I Department, Grigore T. Popa University of Medicine and Pharmacy, 700100 Iasi, Romania; (A.C.); (L.G.); (A.P.)
- Institute of Gastroenterology and Hepatology, “Sfantul. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Alina Plesa
- Medical I Department, Grigore T. Popa University of Medicine and Pharmacy, 700100 Iasi, Romania; (A.C.); (L.G.); (A.P.)
- Institute of Gastroenterology and Hepatology, “Sfantul. Spiridon” University Hospital, 700111 Iasi, Romania
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Arshad K, Hanan SD, Younis MN, Badar R, Imran M, Numair N, Imran A. Detection of Primary Hepatocellular Carcinoma on 18F-Fluorodeoxyglucose Positron Emission Tomography-computed Tomography. Euroasian J Hepatogastroenterol 2023; 13:66-72. [PMID: 38222944 PMCID: PMC10785142 DOI: 10.5005/jp-journals-10018-1409] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2023] [Accepted: 11/03/2023] [Indexed: 01/16/2024] Open
Abstract
Aims and background Hepatocellular carcinoma (HCC), ranks as the third most prevalent malignancy contributing to cancer-related death on a global scale. Hepatocellular carcinoma is known to be the fifth most frequently diagnosed malignancy of the males while among females, it is ranked as the seventh most common malignancy. The study was conducted to detect the sensitivity of primary HCC using 18F-flourodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) scan. Materials and methods This prospective study was conducted to identify the primary HCC in a sample size of 51 patients, in whom FDG PET-CT scan was performed between May 2022 and December 2022. Results Among the cohort of 51 patients, primary HCC was detected on FDG PET-CT in 43 individuals representing true-positive cases. Conversely, FDG PET-CT was unable to detect HCC in 8 cases, representing false-negative. Out of 51 patients, 74.5% of HCC cases exhibited multifocal pattern. The maximum standardized uptake value (SUV max) of the primary malignant site ranged from 1.9 to 16.1, with a mean of 3.7 ± 2.8. The FDG PET-CT revealed abnormal sites of the uptake outside liver in 23 individuals. The research confirmed the tumor recurrence in four previously treated patients. In the conducted investigation, FDG PET-CT showed 84.3% sensitivity for the diagnosis of HCC. Conclusion The study demonstrates that FDG PET-CT is a viable option for the detection of HCC. The sensitivity of FDG PET-CT in our population is comparable and in agreement with international data for diagnosis of HCC thereby favoring its reproducibility among geographical and ethnic groups. However, owing to the reduced ability of FDG PET-CT scan to identify well-differentiated/low-grade HCC, the routine use of FDG PET-CT scan may not be considered in cases requiring evaluation of primary disease only. How to cite this article Arshad K, Hanan SD, Younis MN, et al. Detection of Primary Hepatocellular Carcinoma on 18F-Fluorodeoxyglucose Positron Emission Tomography-computed Tomography. Euroasian J Hepato-Gastroenterol 2023;13(2):66-72.
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Affiliation(s)
- Kiran Arshad
- Department of Allied Health Sciences, Fatima Memorial Hospital, Lahore, Punjab, Pakistan
| | - Sheikh Danial Hanan
- Department of Medical Imaging Technology, NUR International University, Lahore, Punjab, Pakistan
| | - Muhammad Numair Younis
- Department of Nuclear Medicine and PET Imaging, Institute of Nuclear Medicine and Oncology (INMOL), Lahore, Punjab, Pakistan
| | - Rimsha Badar
- Department of Allied Health Sciences, Fatima Memorial Hospital, Lahore, Punjab, Pakistan
| | - Minahil Imran
- East Lancashire Hospitals NHS Trust, Lancashire, United Kingdom
| | - Nefal Numair
- Shaikh Khalifa Bin Zayed Al-Nahyan Medical and Dental College, Lahore, Punjab, Pakistan
| | - Abubakar Imran
- Department of Allied Health Sciences, Fatima Memorial Hospital, Lahore, Punjab, Pakistan
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