-
International Journal of Medical... 2024The mitochondrial unfolded protein response (UPRmt) is a pivotal cellular mechanism that ensures mitochondrial homeostasis and cellular survival under stress conditions....
The mitochondrial unfolded protein response (UPRmt) is a pivotal cellular mechanism that ensures mitochondrial homeostasis and cellular survival under stress conditions. This study investigates the role of UPRmt in modulating the response of nasopharyngeal carcinoma cells to cisplatin-induced stress. We report that the inhibition of UPRmt via AEB5F exacerbates cisplatin cytotoxicity, as evidenced by increased lactate dehydrogenase (LDH) release and apoptosis, characterized by a surge in TUNEL-positive cells. Conversely, the activation of UPRmt with oligomycin attenuates these effects, preserving cell viability and reducing apoptotic markers. Immunofluorescence assays reveal that UPRmt activation maintains mitochondrial membrane potential and ATP production in the presence of cisplatin, countering the rise in reactive oxygen species (ROS) and inhibiting caspase-9 activation. These findings suggest that UPRmt serves as a cytoprotective mechanism in cancer cells, mitigating cisplatin-induced mitochondrial dysfunction and apoptosis. The data underscore the therapeutic potential of modulating UPRmt to improve the efficacy and reduce the side effects of cisplatin chemotherapy. This study provides a foundation for future research on the exploitation of UPRmt in cancer treatment, with the aim of enhancing patient outcomes by leveraging the cellular stress response pathways.
Topics: Humans; Unfolded Protein Response; Mitochondria; Cisplatin; Apoptosis; Cell Line, Tumor; Reactive Oxygen Species; Membrane Potential, Mitochondrial; Nasopharyngeal Neoplasms; Nasopharyngeal Carcinoma; Antineoplastic Agents; Cell Survival
PubMed: 38818479
DOI: 10.7150/ijms.95624 -
International Journal of Medical... 2024Interleukin-25 (IL-25) has been proved to play a role in the pathogenesis and metastasis of Hepatocellular carcinoma (HCC), but the relationship between the level of...
Interleukin-25 (IL-25) has been proved to play a role in the pathogenesis and metastasis of Hepatocellular carcinoma (HCC), but the relationship between the level of IL-25 and the metastasis and prognosis of HCC is still not clear. This study aimed to investigate the expression of IL-25 and other potential biochemical indicators among healthy people, HBV-associated HCC patients without lung metastasis and HBV-associated HCC patients with lung metastasis. From September 2019 to November 2021, 33 HCC patients without lung metastasis, 37 HCC patients with lung metastasis and 29 healthy controls were included in the study. IL-25 and other commonly used biochemical markers were measured to establish predictors of overall survival (OS) and progression-free survival (PFS) after treatment. The serum level of IL-25 was increased in HCC patients than healthy controls ( < 0.001) and HCC patients with lung metastasis had higher IL-25 level than HCC patients without metastasis ( = 0.035). Lung metastasis also indicated higher death rate ( < 0.001) by chi-square test, higher GGT level ( = 0.024) and higher AFP level ( = 0.049) by non-parametric test. Kaplan-Meier analysis demonstrated that IL-25 was negatively associated with PFS ( = 0.024). Multivariate Cox-regression analysis indicated IL-25 ( = 0.030) and GGT ( = 0.020) to be independent predictors of poorer PFS, while IL-25 showed no significant association with OS. The level of IL-25 was significantly associated with disease progression and lung metastasis of HBV-associated HCC. The high expression of IL-25 predicted high recurrence rate and death probability of HCC patients after treatment. Therefore, IL-25 may be an effective predictor of prognosis in HCC.
Topics: Humans; Liver Neoplasms; Carcinoma, Hepatocellular; Male; Female; Lung Neoplasms; Middle Aged; Biomarkers, Tumor; Case-Control Studies; Prognosis; Adult; China; Hepatitis B; Interleukin-17; Aged; East Asian People
PubMed: 38818476
DOI: 10.7150/ijms.90642 -
International Journal of Medical... 2024: Esophageal squamous cell carcinoma (ESCC), a gastrointestinal cancer, is associated with poor prognosis. Prognostic models predict the likelihood of disease...
: Esophageal squamous cell carcinoma (ESCC), a gastrointestinal cancer, is associated with poor prognosis. Prognostic models predict the likelihood of disease progression and are important for the management of patients with ESCC. The objective of this study was to develop a prognostic model for ESCC using bioinformatics analysis. : Two transcriptome microarray Gene Expression Omnibus ESCC datasets (GSE53624 and GSE53622) were analyzed using bioinformatics methods. Differentially expressed genes (DEGs) were identified using the R package limma, and genes associated with survival outcomes in both datasets were identified by Kaplan-Meier analysis. Genes with diagnostic or prognostic value were selected for further analysis, and hazard ratios and their relationship with pathological TNM (pTNM) staging were investigated using univariate and multivariate Cox analysis. After selecting the independent factors from pTNM staging, Cox analysis and nomogram plotting were performed. The ability of the model to stratify risk and predict survival was evaluated and compared with the pTNM staging system to determine its potential clinical value. Key genes were analyzed by immunohistochemistry and RT-PCR. : Four candidate genes (B3GNT3, MACC1, NELL2, and USH1G) with prognostic value were identified from the two transcriptome microarray datasets. Age, pTNM stage, and B3GNT3, MACC1, and NELL2 were identified as independent factors associated with survival in the multivariate Cox analysis and used to establish a prognostic model. The model demonstrated significantly higher accuracy in predicting 3-year survival than the pTNM staging system and was useful for further risk stratification in patients with ESCC. B3GNT3 was significantly downregulated in ESCC tumor tissues and negatively associated with lymph node metastasis. Bioinformatics analysis indicated that B3GNT3 may play a role in immune regulation by regulating M2 macrophages. : This study developed a new prognostic model for ESCC and identified B3GNT3 as a potential biomarker negatively associated with lymph node metastasis, which warrants further validation.
Topics: Humans; Esophageal Squamous Cell Carcinoma; Computational Biology; Prognosis; Esophageal Neoplasms; Male; Female; Gene Expression Regulation, Neoplastic; Middle Aged; Biomarkers, Tumor; Gene Expression Profiling; Neoplasm Staging; Transcriptome; Kaplan-Meier Estimate; Aged; Nomograms
PubMed: 38818465
DOI: 10.7150/ijms.93423 -
World Journal of Hepatology May 2024Hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infection still involves 2.3 million patients worldwide of the estimated 37.7 million living with HIV,...
Hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infection still involves 2.3 million patients worldwide of the estimated 37.7 million living with HIV, according to World Health Organization. People living with HIV (PLWH) are six times greater affected by HCV, compared to HIV negative ones; the greater prevalence is encountered among people who inject drugs and men who have sex with men: the risk of HCV transmission through sexual contact in this setting can be increased by HIV infection. These patients experience a high rate of chronic hepatitis, which if left untreated progresses to end-stage liver disease and hepatocellular carcinoma (HCC) HIV infection increases the risk of mother to child vertical transmission of HCV. No vaccination against both infections is still available. There is an interplay between HIV and HCV infections. Treatment of HCV is nowadays based on direct acting antivirals (DAAs), HCV treatment plays a key role in limiting the progression of liver disease and reducing the risk of HCC development in mono- and coinfected individuals, especially when used at an early stage of fibrosis, reducing liver disease mortality and morbidity. Since the sustained virological response at week 12 rates were observed in PLWH after HCV eradication, the AASLD has revised its simplified HCV treatment algorithm to also include individuals living with HIV. HCV eradication can determine dyslipidemia, since HCV promotes changes in serum lipid profiles and may influence lipid metabolism. In addition to these apparent detrimental effects on the lipid profile, the efficacy of DAA in HCV/HIV patients needs to be considered in light of its effects on glucose metabolism mediated by improvements in liver function. The aim of the present editorial is to describe the advancement in HCV treatment among PLWH.
PubMed: 38818300
DOI: 10.4254/wjh.v16.i5.661 -
World Journal of Hepatology May 2024In this editorial we comment on the review by Zhou reviewing the landscape of nanomedicine in the treatment of hepatocellular carcinoma (HCC). We focus on the immense...
In this editorial we comment on the review by Zhou reviewing the landscape of nanomedicine in the treatment of hepatocellular carcinoma (HCC). We focus on the immense potential of nanotechnology, particularly ligand-receptor mediated nanotherapy, in revolutionizing the treatment landscape of HCC. Despite advancements in multidisciplinary treatment, HCC remains a significant global health challenge. Ligand-mediated nanotherapy offers the opportunity for precise drug delivery to tumor sites, targeting specific receptors overexpressed in HCC cells, thereby enhancing efficacy and minimizing side effects. Overcoming drug resistance and aggressive tumor biology is facilitated by nanomedicine, bypassing traditional hurdles encountered in chemotherapy. Examples include targeting glypican-3, asialoglycoprotein, transferrin receptor or folic acid receptors, capitalizing on their over-expression in tumor cells. The ability for multi-receptor targeting through dual-ligand nanoparticle modification holds the prospect of further enhancement in specificity and efficacy of directed therapy. However, challenges including immune responses, reproducibility in nanoparticle synthesis, and production scalability remain. Future directions involve refining targeting strategies, improving drug release mechanisms, and streamlining production processes to enable personalized and multifunctional nanotherapies. Overall, the integration of nanotherapy in HCC treatment holds immense promise, but continued partnership and effort are needed in offering hope for more effective, precise, and accessible clinical care in the management of HCC.
PubMed: 38818296
DOI: 10.4254/wjh.v16.i5.684 -
World Journal of Hepatology May 2024Occult hepatitis B infection (OBI) is a globally prevalent infection, with its frequency being influenced by the prevalence of hepatitis B virus (HBV) infection in a...
BACKGROUND
Occult hepatitis B infection (OBI) is a globally prevalent infection, with its frequency being influenced by the prevalence of hepatitis B virus (HBV) infection in a particular geographic region, including Africa. OBI can be transmitted through blood transfusions and organ transplants and has been linked to the development of hepatocellular carcinoma (HCC). The associated HBV genotype influences the infection.
AIM
To highlight the genetic diversity and prevalence of OBI in Africa.
METHODS
This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and involved a comprehensive search on PubMed, Google Scholar, Science Direct, and African Journals Online for published studies on the prevalence and genetic diversity of OBI in Africa.
RESULTS
The synthesis included 83 articles, revealing that the prevalence of OBI varied between countries and population groups, with the highest prevalence being 90.9% in patients with hepatitis C virus infection and 38% in blood donors, indicating an increased risk of HBV transmission through blood transfusions. Cases of OBI reactivation have been reported following chemotherapy. Genotype D is the predominant, followed by genotypes A and E.
CONCLUSION
This review highlights the prevalence of OBI in Africa, which varies across countries and population groups. The study also demonstrates that genotype D is the most prevalent.
PubMed: 38818293
DOI: 10.4254/wjh.v16.i5.843 -
World Journal of Hepatology May 2024Liver cancer, primarily hepatocellular carcinoma, remains a global health challenge with rising incidence and limited therapeutic options. Genetic factors play a pivotal... (Review)
Review
Liver cancer, primarily hepatocellular carcinoma, remains a global health challenge with rising incidence and limited therapeutic options. Genetic factors play a pivotal role in the development and progression of liver cancer. This state-of-the-art paper provides a comprehensive review of the current landscape of genetic screening strategies for liver cancer. We discuss the genetic underpinnings of liver cancer, emphasizing the critical role of risk-associated genetic variants, somatic mutations, and epigenetic alterations. We also explore the intricate interplay between environmental factors and genetics, highlighting how genetic screening can aid in risk stratification and early detection using liquid biopsy, and advancements in high-throughput sequencing technologies. By synthesizing the latest research findings, we aim to provide a comprehensive overview of the state-of-the-art genetic screening methods for liver cancer, shedding light on their potential to revolutionize early detection, risk assessment, and targeted therapies in the fight against this devastating disease.
PubMed: 38818292
DOI: 10.4254/wjh.v16.i5.716 -
World Journal of Hepatology May 2024In recent years, approximately half of the newly diagnosed cases and mortalities attributed to hepatocellular carcinoma (HCC) have been reported in China. Despite the...
BACKGROUND
In recent years, approximately half of the newly diagnosed cases and mortalities attributed to hepatocellular carcinoma (HCC) have been reported in China. Despite the high incidence of HCC, there remains a paucity of data regarding the natural growth pattern and the determination of optimal surveillance intervals specific to the Chinese population.
AIM
To quantify the natural tumor growth pattern of HCC in regional China.
METHODS
A retrospective analysis was performed on patients from a single institution in Southwest China who had undergone two or more serial dynamic computed tomography or magnetic resonance imaging scans between 2014 and 2020, without having received any anti-cancer therapy. Tumor growth was assessed using tumor volume doubling time (TVDT) and tumor growth rate (TGR), with volumes measured manually by experienced radiologists. Simple univariate linear regression and descriptive analysis were applied to explore associations between growth rates and clinical factors.
RESULTS
This study identifies the median TVDT for HCC as 163.4 d, interquartile range (IQR) 72.1 to 302.3 d, with a daily TGR of 0.42% (IQR 0.206%-0.97%). HCC growth patterns reveal that about one-third of tumors grow indolently with TVDT exceeding 270 d, another one-third of tumors exhibit rapid growth with TVDT under 90 d, and the remaining tumors show intermediate growth rates, with TVDT ranging between 3 to 9 months.
CONCLUSION
The identified TGRs support biannual surveillance and follow-up for HCC patients in certain regions of China. Given the observed heterogeneity in HCC growth, further investigation is warranted.
PubMed: 38818290
DOI: 10.4254/wjh.v16.i5.800 -
World Journal of Hepatology May 2024The development of type 2 diabetes mellitus is a major contributing factor to the worldwide health burden of metabolic dysfunction-associated steatotic liver disease...
The development of type 2 diabetes mellitus is a major contributing factor to the worldwide health burden of metabolic dysfunction-associated steatotic liver disease (MASLD). Insulin resistance, subclinical inflammation, dyslipidemia, obesity, and hypertension are all factors in this reciprocal interaction that contribute to the development of MASLD, which includes hepatocellular carcinoma, advanced fibrosis/cirrhosis, and non-alcoholic steatohepatitis (NASH). A new risk factor for MASLD/NASH that affects the course of the disease independently throughout life is gestational diabetes mellitus (GDM). Women with a history of GDM had a higher chance of developing NASH, according to a recent study that used a large-scale database. Although the precise etiology is yet unknown, temporary disruption of pancreatic beta cell activity during pregnancy may set off systemic inflammation, affecting distant organs including the liver. Early screening and management strategies are crucial in mitigating MASLD progression and preventing adverse cardiovascular events in affected individuals.
PubMed: 38818285
DOI: 10.4254/wjh.v16.i5.860 -
World Journal of Hepatology May 2024Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer associated with an appalling prognosis. The diagnosis and management of this entity... (Review)
Review
Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer associated with an appalling prognosis. The diagnosis and management of this entity have been challenging to physicians, radiologists, surgeons, pathologists, and oncologists alike. The diagnostic and prognostic value of biomarkers such as the immunohistochemical expression of nestin, a progenitor cell marker, have been explored recently. With a better understanding of biology and the clinical course of cHCC-CCA, newer treatment modalities like immune checkpoint inhibitors are being tried to improve the survival of patients with this rare disease. In this review, we give an account of the recent developments in the pathology, diagnostic approach, and management of cHCC-CCA.
PubMed: 38818284
DOI: 10.4254/wjh.v16.i5.766