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Nature Communications Jun 2024Despite the importance of spliceosome core components in cellular processes, their roles in cancer development, including hepatocellular carcinoma (HCC), remain poorly...
Despite the importance of spliceosome core components in cellular processes, their roles in cancer development, including hepatocellular carcinoma (HCC), remain poorly understood. In this study, we uncover a critical role for SmD2, a core component of the spliceosome machinery, in modulating DNA damage in HCC through its impact on BRCA1/FANC cassette exons and expression. Our findings reveal that SmD2 depletion sensitizes HCC cells to PARP inhibitors, expanding the potential therapeutic targets. We also demonstrate that SmD2 acetylation by p300 leads to its degradation, while HDAC2-mediated deacetylation stabilizes SmD2. Importantly, we show that the combination of Romidepsin and Olaparib exhibits significant therapeutic potential in multiple HCC models, highlighting the promise of targeting SmD2 acetylation and HDAC2 inhibition alongside PARP inhibitors for HCC treatment.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Acetylation; Poly(ADP-ribose) Polymerase Inhibitors; Spliceosomes; Cell Line, Tumor; Phthalazines; Exons; Piperazines; Animals; BRCA1 Protein; Depsipeptides; Mice; DNA Damage; Gene Expression Regulation, Neoplastic
PubMed: 38890388
DOI: 10.1038/s41467-024-49573-7 -
Journal of Cancer Research and Clinical... Jun 2024Hepatocellular carcinoma (HCC) is a prevalent malignant tumor, often arising from hepatitis induced by the hepatitis B virus (HBV) in China. However, effective...
PURPOSE
Hepatocellular carcinoma (HCC) is a prevalent malignant tumor, often arising from hepatitis induced by the hepatitis B virus (HBV) in China. However, effective biomarkers for early diagnosis are lacking, leading to a 5-year overall survival rate of less than 20% among patients with advanced HCC. This study aims to identify serum biomarkers for early HCC diagnosis to enhance patient survival rates.
METHODS
We established an independent cohort comprising 27 healthy individuals, 13 patients with HBV-induced cirrhosis, 13 patients with hepatitis B-type HCC, and 8 patients who progressed from cirrhosis to hepatocellular carcinoma during follow-up. Serum metabolic abnormalities during the progression from cirrhosis to HCC were studied using untargeted metabolomics. Liquid chromatography-mass spectrometry-based metabolomics methods characterized the subjects' serum metabolic profiles. Partial least squares discriminant analysis (PLS-DA) was employed to elucidate metabolic profile changes during the progression from cirrhosis to HCC. Differentially expressed metabolites (DEMs) between cirrhosis and HCC groups were identified using the LIMMA package in the R language. Two machine learning algorithms, Least Absolute Shrinkage and Selection Operator (LASSO), and Random Forest Classifier (RF), were used to identify key metabolic biomarkers involved in the progression from cirrhosis to HCC. Key metabolic biomarkers were further validated using targeted metabolomics in a new independent validation cohort comprising 25 healthy individuals and 25 patients with early-stage hepatocellular carcinoma.
RESULTS
A total of 155 serum metabolites were identified, of which 21/54 metabolites exhibited significant changes in HCC patients compared with cirrhosis patients and healthy individuals, respectively. PLS-DA clustering results demonstrated a significant change trend in the serum metabolic profile of patients with HBV-induced cirrhosis during the progression to HCC. Utilizing LASSO regression and RF algorithms, we confirmed 10 key metabolic biomarkers. Notably, 1-Methylnicotinamide (1-MNAM) exhibited a persistent and significant decrease in healthy individuals, cirrhosis, and HCC patients. Moreover, 1-MNAM levels in developing patients were significantly higher during the cirrhosis stage than in the HCC stage. Targeted metabolomic validation in an external cohort further confirmed the good diagnostic performance of 1-MNAM in early HCC detection.
CONCLUSION
Our findings imply that 1-MNAM may be a specific biomarker for the progression of cirrhosis to HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Liver Cirrhosis; Disease Progression; Male; Biomarkers, Tumor; Female; Middle Aged; Niacinamide; Adult; Metabolomics; Cohort Studies; Aged
PubMed: 38890166
DOI: 10.1007/s00432-024-05848-6 -
Journal of Cancer Research and Clinical... Jun 2024Limited treatment options exist for unresectable intrahepatic cholangiocarcinoma (ICC), with systemic chemotherapy (SC) serving as the primary approach. This study aimed... (Comparative Study)
Comparative Study
First-line hepatic arterial infusion chemotherapy plus lenvatinib and PD-(L)1 inhibitors versus systemic chemotherapy alone or with PD-(L)1 inhibitors in unresectable intrahepatic cholangiocarcinoma.
PURPOSE
Limited treatment options exist for unresectable intrahepatic cholangiocarcinoma (ICC), with systemic chemotherapy (SC) serving as the primary approach. This study aimed to assess the effectiveness of first-line hepatic arterial infusion chemotherapy (HAIC) in combination with lenvatinib and PD-(L)1 inhibitors (HLP) compared to SC combined with PD-(L)1 inhibitors (SCP) or SC alone in treating unresectable ICC.
METHODS
Patient with unresectable ICC who underwent first-line treatment with HLP, SCP or SC from January 2016 to December 2022 were retrospectively analyzed. The study evaluated and compared efficacy and safety outcomes across the three treatment groups.
RESULTS
The study comprised 42, 49, and 50 patients in the HLP, SCP, and SC groups, respectively. Median progression-free survival (PFS) times were 30.0, 10.2, and 6.5 months for HLP, SCP, and SC groups. While the SC group had a median overall survival (OS) time of 21.8 months, the HLP and SCP groups hadn't reached median OS. The HLP group demonstrated significantly superior PFS (p < 0.001) and OS (p = 0.014) compared to the others. Moreover, the HLP group exhibited the highest objective response rate (ORR) at 50.0% and the highest disease control rate (DCR) at 88.1%, surpassing the SC group (ORR, 6.0%; DCR, 52.0%) and SCP group (ORR, 18.4%; DCR, 73.5%) (p < 0.05). Generally, the HLP group reported fewer grades 3-4 adverse events (AEs) compared with others.
CONCLUSION
In contrast to systemic chemotherapy with or without PD-(L)1 inhibitors, the triple combination therapy incorporating HAIC, lenvatinib, and PD-(L)1 inhibitors showcased favorable survival benefits and manageable adverse events for unresectable ICC.
Topics: Humans; Cholangiocarcinoma; Female; Male; Quinolines; Middle Aged; Aged; Retrospective Studies; Phenylurea Compounds; Bile Duct Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Infusions, Intra-Arterial; Adult; Immune Checkpoint Inhibitors; B7-H1 Antigen; Aged, 80 and over; Hepatic Artery
PubMed: 38890157
DOI: 10.1007/s00432-024-05795-2 -
BMJ Case Reports Jun 2024Eclampsia spectrum disorders are a set of serious complications of pregnancy that commonly present after 20 weeks of gestation. There is an association between molar...
Eclampsia spectrum disorders are a set of serious complications of pregnancy that commonly present after 20 weeks of gestation. There is an association between molar pregnancy, a gestational trophoblastic disease resulting from abnormal fertilisation and gametogenesis, and eclampsia spectrum disorders which can result in manifestation of pre-eclamptic symptomatology earlier than 20 weeks of gestation. We report a case of a gravida 1 para 0 in her mid 20s at 16-weeks gestation presenting with partial hydatidiform mole who developed eclampsia, haemolysis, elevated liver enzymes and low platelets syndrome and posterior reversible encephalopathy syndrome. Ultrasound findings were consistent with molar pregnancy and pathology confirmed partial molar pregnancy with triploid 69, XYY karyotype. This case highlights the early onset potential of eclampsia spectrum disorders in molar pregnancies while suggesting screening such patients for hypertensive disorders.
Topics: Humans; Female; Hydatidiform Mole; Pregnancy; HELLP Syndrome; Eclampsia; Adult; Uterine Neoplasms; Posterior Leukoencephalopathy Syndrome
PubMed: 38890113
DOI: 10.1136/bcr-2023-258188 -
Veterinary Medicine and Science Jul 2024Dogs with retroperitoneal hemangiosarcoma (HSA) exhibit variable postoperative median survival times (MST). (Comparative Study)
Comparative Study
Prognostic value of tumour-related factors associated with canine retroperitoneal hemangiosarcoma in comparison with other anatomic presentations: A retrospective observational study.
BACKGROUND
Dogs with retroperitoneal hemangiosarcoma (HSA) exhibit variable postoperative median survival times (MST).
OBJECTIVE
To retrospectively evaluate the prognostic value of selected tumour-related factors, such as tumour size, rupture, invasion into adjacent tissue, involvement of lymph node and distant metastasis, they were analysed in dogs with retroperitoneal HSA.
METHODS
Ten dogs with retroperitoneal HSA managed solely with surgical excision were reviewed and compared with spleen (71) and liver (9) HSA. The Kaplan-Meier method and log-rank analysis were used compare MSTs between factors. Multivariable Cox proportional-hazard analysis was used to compare differences between arising sites.
RESULTS
Retroperitoneal HSA showed comparatively longer postoperative MST compared with that of spleen and liver HSA and demonstrated significantly longer MST (p = 0.003) for tumours ≥5 cm (195 days) than <5 cm (70 days). Spleen HSA revealed significantly shorter MSTs in involvement of distant lymph nodes (23 days) and distant metastasis (39 days) than those in negative (83 days, p = 0.002 and 110 days, p < 0.001, respectively). Liver HSA also revealed significantly shorter MST (16.5 days compared with 98 days, p = 0.003) for distant metastasis. Additionally, hazard ratios (HRs) and their forest plot for overall HSA revealed as poor prognostic factors, arising sites (spleen; HR 2.78, p = 0.016 and liver; HR 3.62, p = 0.019), involvement of distant lymph nodes (HR 2.43, p = 0.014), and distant metastasis (HR 2.86, p < 0.001), and as better prognostic factor of tumour size ≥5 cm (HR 0.53, p = 0.037).
CONCLUSION
In combination with overall HSA, retroperitoneal HSA shows comparatively longer postoperative MST compared to spleen and liver HSA, associated with tumour size ≥5 cm suggesting better prognostic factor.
Topics: Animals; Dogs; Hemangiosarcoma; Retrospective Studies; Dog Diseases; Male; Female; Retroperitoneal Neoplasms; Prognosis; Splenic Neoplasms; Liver Neoplasms
PubMed: 38889089
DOI: 10.1002/vms3.1495 -
Cancer Medicine Jun 2024Penile cancer (PC) is a lethal malignancy with no effective prognostic biomarker. We aim to investigate associations between trajectories of squamous cell carcinoma...
Trajectories of squamous cell carcinoma antigen and outcomes of patients with advanced penile cancer after chemotherapy based on paclitaxel, ifosfamid, and cisplatin regimen.
INTRODUCTION
Penile cancer (PC) is a lethal malignancy with no effective prognostic biomarker. We aim to investigate associations between trajectories of squamous cell carcinoma antigen (SCC-A) and patient outcomes after chemotherapy based on paclitaxel, ifosfamid, and cisplatin (TIP) regimen.
METHODS
Consecutive AJCC staging III/IV PC patients who received TIP chemotherapy and repeated SCC-A measurements in 2014-2022 were analyzed. Latent class growth mixed (LCGM) models were employed to characterize patients' serum SCC-A trajectories. Patient survival, and clinical and pathological tumor responses were compared. Inverse probability treatment weighting was used to adjust confounding factors.
RESULTS
Eighty patients were included. LCGM models identified two distinct trajectories of SCC-A: low-stable (40%; n = 32) and high-decline (60%; n = 48). Overall survival (HR [95% CI]: 3.60 [1.23-10.53], p = 0.019), progression-free survival (HR [95% CI]: 11.33 [3.19-40.3], p < 0.001), objective response rate (37.5% vs. 62.5% p = 0.028), disease control rate (60.4% vs. 96.9% p < 0.00), and pathological complete response rate (21.2% vs. 51.9%, p = 0.014) were significantly worse in the high-decline arm.
CONCLUSION
PC patients' SCC-A change rate was associated with tumor response and patient survival after TIP chemotherapy. SCC-A might assist tumor monitoring after systemic therapies.
Topics: Humans; Male; Penile Neoplasms; Middle Aged; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Paclitaxel; Cisplatin; Serpins; Aged; Neoplasm Staging; Biomarkers, Tumor; Prognosis; Retrospective Studies; Adult
PubMed: 38888362
DOI: 10.1002/cam4.7353 -
Frontiers in Immunology 2024Multiple investigations and scholarly articles have presented compelling evidence indicating that tertiary lymphoid structures (TLS) play a pivotal role in inhibiting... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Multiple investigations and scholarly articles have presented compelling evidence indicating that tertiary lymphoid structures (TLS) play a pivotal role in inhibiting and controlling the advancement of tumors. While there is an abundance of information highlighting the importance of TLS in different cancer types, their prognostic significance specifically in hepatocellular carcinoma (HCC) cancers remains unclear. Thus, this meta-analysis aimed to explore the prognostic relevance of TLS in HCC.
METHODS
We conducted a thorough search across four databases, namely Web of Science, PubMed, Embase, and the Cochrane Library, to identify pertinent studies. The search utilized the keywords "tertiary lymphoid structures" and "hepatocellular carcinoma." The primary outcomes of interest encompassed overall survival (OS), recurrence-free survival (RFS), early recurrence, and late recurrence. The statistical effect size for these measures was expressed in terms of hazard ratios (HR).
RESULTS
Six studies were incorporated into the analysis. Among them, four studies, encompassing 6 datasets and involving 1490 patients, and three studies, comprising 5 datasets and involving 656 patients, respectively, investigated the correlation between intratumoral and peritumoral TLSs and the prognosis in HCC patients. The meta-analysis revealed that the presence of intratumoral TLSs is linked to longer RFS and reduced early recurrence (HR, 0.60; 95% CI, 0.50-0.67; p <0.001 and HR, 0.49; 95% CI, 0.36-0.65; p <0.001, respectively). However, no significant association was observed with OS and late recurrence. Sensitivity analysis demonstrated the robustness of these findings, and heterogeneities were minimal. Additionally, the meta-analysis did not detect a relationship between peritumoral TLSs and OS or RFS in HCC patients.
CONCLUSION
The presence of intratumoral TLSs is correlated with better RFS and reduced early recurrence in HCC patients. Further investigation is warranted to elucidate the roles of peritumoral TLSs in the prognosis of HCC patients.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42023466793.
Topics: Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Tertiary Lymphoid Structures; Prognosis; Neoplasm Recurrence, Local
PubMed: 38887293
DOI: 10.3389/fimmu.2024.1390938 -
Cancer Imaging : the Official... Jun 2024The Response Evaluation Criteria in Solid Tumors (RECIST) are often inadequate for the early assessment of the response to cancer therapy, particularly bevacizumab-based...
Prognostic value of the tumor-to-liver density ratio in patients with metastatic colorectal cancer treated with bevacizumab-based chemotherapy. A post-hoc study of the STIC-AVASTIN trial.
BACKGROUND
The Response Evaluation Criteria in Solid Tumors (RECIST) are often inadequate for the early assessment of the response to cancer therapy, particularly bevacizumab-based chemotherapy. In a first cohort of patients with colorectal cancer liver metastases (CRLM), we showed that variations of the tumor-to-liver density (TTLD) ratio and modified size-based criteria determined using computed tomography (CT) data at the first restaging were better prognostic criteria than the RECIST. The aims of this study were to confirm the relevance of these radiological biomarkers as early predictors of the long-term clinical outcome and to assess their correlation with contrast-enhanced ultrasound (CEUS) parameters in a new patient cohort.
METHODS
In this post-hoc study of the multicenter STIC-AVASTIN trial, we retrospectively reviewed CT data of patients with CRLM treated with bevacizumab-based regimens. We determined the size, density and TTLD ratio of target liver lesions at baseline and at the first restaging and also performed a morphologic evaluation according to the MD Anderson criteria. We assessed the correlation of these parameters with progression-free survival (PFS) and overall survival (OS) using the log-rank test and a Cox proportional hazard model. We also examined the association between TTLD ratio and quantitative CEUS parameters.
RESULTS
This analysis concerned 79 of the 137 patients included in the STIC-AVASTIN trial. PFS and OS were significantly longer in patients with tumor size reduction > 15% at first restaging, but were not correlated with TTLD ratio variations. However, PFS was longer in patients with TTLD ratio > 0.6 at baseline and first restaging than in those who did not reach this threshold. In the multivariate analysis, only baseline TTLD ratio > 0.6 was a significant survival predictor. TTLD ratio > 0.6 was associated with improved perfusion parameters.
CONCLUSIONS
Although TTLD ratio variations did not correlate with the long-term clinical outcomes, TTLD absolute values remained a good predictor of survival at baseline and first restaging, and may reflect tumor microvascular features that might influence bevacizumab-based treatment efficiency.
TRIAL REGISTRATION
NCT00489697, registration number of the STIC-AVASTIN trial.
Topics: Humans; Bevacizumab; Colorectal Neoplasms; Liver Neoplasms; Male; Female; Middle Aged; Aged; Retrospective Studies; Prognosis; Tomography, X-Ray Computed; Antineoplastic Combined Chemotherapy Protocols; Adult; Ultrasonography; Liver
PubMed: 38886836
DOI: 10.1186/s40644-024-00722-7 -
BMC Medical Education Jun 2024To investigate the effectiveness of problem-based learning (PBL) and case-based learning (CBL) teaching methods in clinical practical teaching in transarterial... (Meta-Analysis)
Meta-Analysis
The effectiveness of problem-based learning and case-based learning teaching methods in clinical practical teaching in TACE treatment for hepatocellular carcinoma in China: a bayesian network meta-analysis.
PURPOSE
To investigate the effectiveness of problem-based learning (PBL) and case-based learning (CBL) teaching methods in clinical practical teaching in transarterial chemoembolization (TACE) treatment in China.
MATERIALS AND METHODS
A comprehensive search of PubMed, the Chinese National Knowledge Infrastructure (CNKI) database, the Weipu database and the Wanfang database up to June 2023 was performed to collect studies that evaluate the effectiveness of problem-based learning and case-based learning teaching methods in clinical practical teaching in TACE treatment in China. Statistical analysis was performed by R software (4.2.1) calling JAGS software (4.3.1) in a Bayesian framework using the Markov chain-Monte Carlo method for direct and indirect comparisons. The R packages "gemtc", "rjags", "openxlsx", and "ggplot2" were used for statistical analysis and data output.
RESULTS
Finally, 7 studies (five RCTs and two observational studies) were included in the meta-analysis. The combination of PBL and CBL showed more effectiveness in clinical thinking capacity, clinical practice capacity, knowledge understanding degree, literature reading ability, method satisfaction degree, learning efficiency, learning interest, practical skills examination scores and theoretical knowledge examination scores.
CONCLUSIONS
Network meta-analysis revealed that the application of PBL combined with the CBL teaching mode in the teaching of liver cancer intervention therapy significantly improves the teaching effect and significantly improves the theoretical and surgical operations, meeting the requirements of clinical education.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Chemoembolization, Therapeutic; China; Bayes Theorem; Problem-Based Learning; Network Meta-Analysis; Teaching; Clinical Competence
PubMed: 38886707
DOI: 10.1186/s12909-024-05615-8 -
Scientific Reports Jun 2024Patients diagnosed with hepatocellular carcinoma (HCC) often present with multimorbidity, significantly contributing to adverse outcomes, particularly in-hospital...
Patients diagnosed with hepatocellular carcinoma (HCC) often present with multimorbidity, significantly contributing to adverse outcomes, particularly in-hospital mortality. This study aimed to develop a predictive nomogram to assess the impact of comorbidities on in-hospital mortality risk in HCC patients undergoing palliative locoregional therapy. We retrospectively analyzed data from 345 hospitalized HCC patients who underwent palliative locoregional therapy between January 2015 and December 2022. The nomogram was constructed using independent risk factors such as length of stay (LOS), hepatitis B virus (HBV) infection, hypertension, chronic obstructive pulmonary disease (COPD), anemia, thrombocytopenia, liver cirrhosis, hepatic encephalopathy (HE), N stage, and microvascular invasion. The model demonstrated high predictive accuracy with an AUC of 0.908 (95% CI: 0.859-0.956) for the overall dataset, 0.926 (95% CI: 0.883-0.968) for the training set, and 0.862 (95% CI: 0.728-0.994) for the validation set. Calibration curves indicated a strong correlation between predicted and observed outcomes, validated by statistical tests. Decision curve analysis (DCA) and clinical impact curves (CIC) confirmed the model's clinical utility in predicting in-hospital mortality. This nomogram offers a practical tool for personalized risk assessment in HCC patients undergoing palliative locoregional therapy, facilitating informed clinical decision-making and improving patient management.
Topics: Humans; Carcinoma, Hepatocellular; Nomograms; Liver Neoplasms; Male; Female; Hospital Mortality; Middle Aged; Aged; Palliative Care; Retrospective Studies; Risk Factors; Comorbidity; Risk Assessment; Aged, 80 and over
PubMed: 38886455
DOI: 10.1038/s41598-024-64457-y