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Arquivos de Gastroenterologia 2024Recently, significant associations between non-alcoholic fatty liver disease (NAFLD) and extra-hepatic cancer have been reported. (Review)
Review
BACKGROUND
Recently, significant associations between non-alcoholic fatty liver disease (NAFLD) and extra-hepatic cancer have been reported.
OBJECTIVE
To carry out a comprehensive review of the current evidence in the literature on the association between NAFLD and extra-hepatic cancer.
METHODS
A narrative literature review was performed through an online search for the MeSH terms "fatty liver" and "cancer" in MEDLINE (via PubMed) and LILACS (via BVS). Original studies that described the impact of NAFLD on different types of extra-hepatic malignancies were included.
RESULTS
After careful analysis, nine prospective cohort studies, one retrospective cohort study, three case-control studies, and three cross-sectional studies were selected.
CONCLUSION
There is consistent evidence on the association between NAFLD and extra-hepatic carcinogenesis, especially in relation to colorectal, gastric, pancreatic, breast, prostate, and bladder cancers.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Neoplasms; Risk Factors; Male; Female
PubMed: 38896570
DOI: 10.1590/S0004-2803.24612023-027 -
ELife Jun 2024Untargeted metabolomic profiling through liquid chromatography-mass spectrometry (LC-MS) measures a vast array of metabolites within biospecimens, advancing drug...
Untargeted metabolomic profiling through liquid chromatography-mass spectrometry (LC-MS) measures a vast array of metabolites within biospecimens, advancing drug development, disease diagnosis, and risk prediction. However, the low throughput of LC-MS poses a major challenge for biomarker discovery, annotation, and experimental comparison, necessitating the merging of multiple datasets. Current data pooling methods encounter practical limitations due to their vulnerability to data variations and hyperparameter dependence. Here, we introduce GromovMatcher, a flexible and user-friendly algorithm that automatically combines LC-MS datasets using optimal transport. By capitalizing on feature intensity correlation structures, GromovMatcher delivers superior alignment accuracy and robustness compared to existing approaches. This algorithm scales to thousands of features requiring minimal hyperparameter tuning. Manually curated datasets for validating alignment algorithms are limited in the field of untargeted metabolomics, and hence we develop a dataset split procedure to generate pairs of validation datasets to test the alignments produced by GromovMatcher and other methods. Applying our method to experimental patient studies of liver and pancreatic cancer, we discover shared metabolic features related to patient alcohol intake, demonstrating how GromovMatcher facilitates the search for biomarkers associated with lifestyle risk factors linked to several cancer types.
Topics: Metabolomics; Humans; Chromatography, Liquid; Algorithms; Mass Spectrometry; Pancreatic Neoplasms; Liver Neoplasms; Metabolome
PubMed: 38896449
DOI: 10.7554/eLife.91597 -
Molecular Biology Reports Jun 2024MG132, a proteasome inhibitor, is widely used to inhibit nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity by proteasome-mediated...
BACKGROUND
MG132, a proteasome inhibitor, is widely used to inhibit nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity by proteasome-mediated degradation of IκB. It has been marketed as a specific, reversible, cell-permeable and low-cost inhibitor. However, adverse effects of the compound have been reported in the literature. We recently discovered and characterised a point mutation in the acute phase protein serum amyloid A (SAA) in chickens, by overexpressing the protein in chicken hepatocellular carcinoma (LMH) cells. This serine to arginine exchange at amino acid position 90 (SAA.R90S) leads to intra- and extracellular accumulation of SAA, which is surprisingly counteracted by MG132 treatment, independent of SAA's intrinsic promoter.
METHODS AND RESULTS
To test, whether low proteasomal degradation of SAA.R90S is responsible for the observed intra- and extracellular SAA accumulation, we intended to inhibit the proteasome in SAA wild type (SAA.WT) overexpressing cells with MG132. However, we observed an unexpected drastic decrease in SAA protein expression at the transcript level. NF-κB gene expression was unchanged by MG132 at the measured time point.
CONCLUSIONS
The observed results demonstrate that MG132 inhibits SAA expression at the transcript level, independent of its endogenous promoter. Further, the data might indicate that NF-κB is not involved in the observed MG132-induced inhibition of SAA expression. We, consequently, question in this brief report whether MG132 should truly be categorised as a specific ubiquitin proteasome inhibitor and recommend the usage of alternative compounds.
Topics: Animals; Leupeptins; Chickens; Carcinoma, Hepatocellular; Cell Line, Tumor; Liver Neoplasms; Promoter Regions, Genetic; Serum Amyloid A Protein; NF-kappa B; Proteasome Endopeptidase Complex; Proteasome Inhibitors; Gene Expression Regulation, Neoplastic
PubMed: 38896168
DOI: 10.1007/s11033-024-09726-9 -
Journal of Cancer Research and Clinical... Jun 2024Metabolic reprogramming is an emerging hallmark that influences the tumour microenvironment (TME) by regulating the behavior of cancer cells and immune cells. The...
BACKGROUND
Metabolic reprogramming is an emerging hallmark that influences the tumour microenvironment (TME) by regulating the behavior of cancer cells and immune cells. The relationship between metabolism and immunity remains elusive. The purpose of this study was to explore the predictive value of immune- and metabolism-related genes in hepatocellular carcinoma (HCC) and their intricate interplay with TME.
METHODS
We established the immune- and metabolism-related signature (IMRPS) based on the LIHC cohort from The Cancer Genome Atlas (TCGA) dataset. Kaplan-Meier analysis, receiver operating characteristic (ROC) curve analysis and Cox regression analysis confirmed the prognostic value of IMRPS. We investigated differences in immune cell infiltration, clinical features, and therapeutic response between risk groups. The quantitative real-time PCR (qPCR) was used to confirm the expression of signature genes. Immunohistochemical staining was performed to evaluate immune infiltration features in HCC tissue samples. We conducted cell experiments including gene knockout, cell counting kit-8 (CCK-8), and flow cytometry to explore the role of the IMRPS key gene UCK2 in HCC. RNA-seq was used to further investigate the potential underlying mechanism involved.
RESULTS
The IMRPS, composed of four genes, SMS, UCK2, PFKFB4 and MAPT, exhibited significant correlations with survival, immune cell infiltration, clinical features, immune checkpoints and therapeutic response. The IMRPS was shown to be an excellent predictor of HCC prognosis. It could stratify patients appropriately and characterize the TME accurately. The high-risk HCC group exhibited an immunosuppressive microenvironment with abundant M-like macrophage infiltration, which was confirmed by the immunohistochemistry results. The results of qPCR revealed that the expression of signature genes in 20 HCC tissues was significantly greater than that in adjacent normal tissues. After the key gene UCK2 was knocked out, the proliferation of the Huh7 cell line was significantly inhibited, and monocyte-derived macrophages polarized towards an M1-like phenotype in the coculture system. RNA-seq and GSEA suggested that the phenotypes were closely related to the negative regulation of growth and regulation of macrophage chemotaxis.
CONCLUSIONS
This study established a new IMRS for the accurate prediction of patient prognosis and the TME, which is also helpful for identifying new targets for the treatment of HCC.
Topics: Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Tumor Microenvironment; Prognosis; Biomarkers, Tumor; Female; Gene Expression Regulation, Neoplastic; Male; Middle Aged; Gene Expression Profiling; Transcriptome
PubMed: 38896142
DOI: 10.1007/s00432-024-05849-5 -
Hepatology Communications Jul 2024Serum AFP-L3%, AFP, and DCP are useful biomarkers for HCC detection, but their utility in assessing treatment response remains unknown. We aim to evaluate the accuracy...
BACKGROUND
Serum AFP-L3%, AFP, and DCP are useful biomarkers for HCC detection, but their utility in assessing treatment response remains unknown. We aim to evaluate the accuracy of a biomarker model in the detection of posttreatment viable tumors.
METHODS
For model derivation, recipients with HCC undergoing liver transplant from 2018 to 2022 who had biomarkers collected within 3 months before transplant were included. We developed a generalized linear model for detecting posttreatment viable tumors with the 3 biomarkers as covariates, which we termed the "LAD Score." An independent cohort of 117 patients with HCC was used for external validation.
RESULTS
Among 205 recipients of transplant, 70.2% had evidence of viable tumor on explant. The median LAD score was higher among patients with viable versus nonviable tumors (1.06 vs. 0.465, p < 0.001). The LAD score had a sensitivity of 55.6% and a specificity of 85.1% at the cutoff of 0.927, which was more accurate than imaging for detecting posttreatment viable tumors (AUROC 0.736 vs. 0.643, respectively; p = 0.045). The superior performance of the LAD score over imaging is primarily driven by its greater accuracy in detecting tumors <2 cm in diameter (AUROC of the LAD score 0.721 vs. imaging 0.595, p = 0.02). In the validation data set, the LAD score had an AUROC of 0.832 (95% CI: 0.753, 0.911) with a sensitivity of 72.5% and a specificity of 89.4% at the cutoff of 0.927.
CONCLUSIONS
Our findings suggest the utility of LAD score in treatment response assessment after locoregional therapy for HCC, particularly in detecting small tumors. A larger prospective study is in progress to validate its accuracy and evaluate its performance in recurrence monitoring.
Topics: Humans; Liver Neoplasms; Carcinoma, Hepatocellular; Female; Male; Middle Aged; Biomarkers, Tumor; Liver Transplantation; alpha-Fetoproteins; Aged; Treatment Outcome; Sensitivity and Specificity; Retrospective Studies
PubMed: 38896084
DOI: 10.1097/HC9.0000000000000466 -
Landmark analysis of the risk of recurrence after resection or ablation for HCC: A nationwide study.Hepatology Communications Jul 2024The risk of HCC recurrence at particular landmarks since the initial treatment is unknown. With this registry-based study, we aimed to provide a nuanced description of...
BACKGROUND
The risk of HCC recurrence at particular landmarks since the initial treatment is unknown. With this registry-based study, we aimed to provide a nuanced description of the prognosis following resection or ablation for HCC, including landmark analyses.
METHODS
Using the Danish nationwide health care registries, we identified all patients who received resection or ablation in 2000-2018 as the first HCC treatment. HCC recurrence was defined as a new HCC treatment > 90 days after the first treatment. We conducted competing risk landmark analyses of the cumulative risk of recurrence and death.
RESULTS
Among 4801 patients with HCC, we identified 426 patients who received resection and 544 who received ablation. The 2 treatment cohorts differed in cirrhosis prevalence and tumor stage. The 5-year recurrence risk was 40.7% (95% CI 35.5%-45.8%) following resection and 60.7% (95% CI: 55.9%-65.1%) following ablation. The 1-year recurrence risk decreased over the landmarks from 20.4% (95% CI: 16.6%-24.6%) at the time of resection to 4.7% (95% CI: 0.9%-13.9%) at the 5-year landmark. For ablation, the risk decreased from 36.1% (95% CI: 31.9%-40.4%) at the time of treatment to 5.3% (95% CI: 0.4%-21.4%) at the 5-year landmark. The risk of death without recurrence was stable over the landmarks following both resection and ablation.
CONCLUSIONS
In conclusion, the risk of recurrence or death following resection or ablation for HCC is high from the treatment date, but the risk of recurrence decreases greatly over the survival landmarks. This information is valuable for clinicians and their patients.
Topics: Humans; Liver Neoplasms; Neoplasm Recurrence, Local; Carcinoma, Hepatocellular; Male; Female; Denmark; Middle Aged; Aged; Registries; Hepatectomy; Catheter Ablation; Risk Assessment; Prognosis; Risk Factors
PubMed: 38896083
DOI: 10.1097/HC9.0000000000000472 -
Journal of Investigative Medicine High... 2024Immune checkpoint inhibitors have become essential antineoplastic agents in medical oncology over the past decade. However, they are associated with potentially fatal...
Immune checkpoint inhibitors have become essential antineoplastic agents in medical oncology over the past decade. However, they are associated with potentially fatal multisystem abnormalities, with increasing concern in gastrointestinal tract and its associated organs. We present a patient with advanced renal cell carcinoma, who presented with acute liver failure after the first dose of combined immunotherapy with nivolumab and ipilimumab. A thorough evaluation for viral, metabolic, and autoimmune causes was unremarkable. He was managed with steroids and made significant improvement. To our knowledge, this is the first documented case of acute liver failure following ipilimumab and nivolumab.
Topics: Humans; Nivolumab; Liver Failure, Acute; Male; Ipilimumab; Immune Checkpoint Inhibitors; Carcinoma, Renal Cell; Kidney Neoplasms; Middle Aged
PubMed: 38895944
DOI: 10.1177/23247096241261505 -
Sensors (Basel, Switzerland) May 2024Aiming at the shortcomings of artificial surgical path planning for the thermal ablation of liver tumors, such as the time-consuming and labor-consuming process, and...
OBJECTIVE
Aiming at the shortcomings of artificial surgical path planning for the thermal ablation of liver tumors, such as the time-consuming and labor-consuming process, and relying heavily on doctors' puncture experience, an automatic path-planning system for thermal ablation of liver tumors based on CT images is designed and implemented.
METHODS
The system mainly includes three modules: image segmentation and three-dimensional reconstruction, automatic surgical path planning, and image information management. Through organ segmentation and three- dimensional reconstruction based on CT images, the personalized abdominal spatial anatomical structure of patients is obtained, which is convenient for surgical path planning. The weighted summation method based on clinical constraints and the concept of Pareto optimality are used to solve the multi-objective optimization problem, screen the optimal needle entry path, and realize the automatic planning of the thermal ablation path. The image information database was established to store the information related to the surgical path.
RESULTS
In the discussion with clinicians, more than 78% of the paths generated by the planning system were considered to be effective, and the efficiency of system path planning is higher than doctors' planning efficiency.
CONCLUSION
After improvement, the system can be used for the planning of the thermal ablation path of a liver tumor and has certain clinical application value.
Topics: Humans; Liver Neoplasms; Tomography, X-Ray Computed; Imaging, Three-Dimensional; Ablation Techniques; Algorithms; Image Processing, Computer-Assisted; Surgery, Computer-Assisted; Liver
PubMed: 38894328
DOI: 10.3390/s24113537 -
Diagnostics (Basel, Switzerland) May 2024The emergence of endoscopic ultrasound (EUS) has significantly impacted the diagnosis and management of pancreatic cancer and its associated sequelae. While the... (Review)
Review
The emergence of endoscopic ultrasound (EUS) has significantly impacted the diagnosis and management of pancreatic cancer and its associated sequelae. While the definitive role of EUS for pancreatic cancer remains incompletely characterized by currently available guidelines, EUS undoubtedly offers high diagnostic accuracy, the precise staging of pancreatic neoplasms, and the ability to perform therapeutic and palliative interventions. However, current challenges to EUS include limited specialized expertise and variability in operator proficiency. As the technology and techniques continue to evolve and become more refined, EUS is poised to play an increasingly integral role in shaping pancreatic cancer care.
PubMed: 38893682
DOI: 10.3390/diagnostics14111156 -
Molecules (Basel, Switzerland) Jun 2024Oleoresin of Roxb. ex G. Don (DA) has been traditionally used for local medicinal applications. Several in vitro studies have indicated its pharmacological potential....
Oleoresin of Roxb. ex G. Don (DA) has been traditionally used for local medicinal applications. Several in vitro studies have indicated its pharmacological potential. However, the low water solubility hinders its use and development for pharmaceutical purposes. The study aimed to (1) formulate oil-in-water (/) Pickering emulsions of DA oleoresin and (2) demonstrate its activities in cancer cells. The Pickering emulsions were formulated using biocompatible carboxylated cellulose nanocrystal (cCNC) as an emulsifier. The optimized emulsion comprised 3% (F1) and 4% (/) (F2) of oleoresin in 1% cCNC and 0.1 M NaCl, which possessed homogeneity and physical stability compared with other formulations with uniform droplet size and low viscosity. The constituent analysis indicated the presence of the biomarker dipterocarpol in both F1 and F2. The pharmacological effects of the two emulsions were demonstrated in vitro against two cancer cell lines, HepG2 and HCT116. Both F1 and F2 suppressed cancer cell viability. The treated cells underwent apoptosis, as demonstrated by distinct nuclear morphological changes in DAPI-stained cells and Annexin V/PI-stained cells detected by flow cytometry. Our study highlights the prospect of Pickering emulsions for oleoresin, emphasizing enhanced stability and potential pharmacological advantages.
Topics: Humans; Hep G2 Cells; Cell Proliferation; Emulsions; HCT116 Cells; Apoptosis; Plant Extracts; Colonic Neoplasms; Cell Survival; Liver Neoplasms; Antineoplastic Agents, Phytogenic
PubMed: 38893569
DOI: 10.3390/molecules29112695