Ultrasomics in liver cancer: Developing a radiomics model for differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma using contrast-enhanced ultrasound.

BACKGROUND: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) represent the predominant histological types of primary liver cancer, comprising over 99% of cases. Given their differing biological behaviors, prognoses, and treatment strategies, accurately differentiating between HCC and ICC is crucial for effective clinical management. Radiomics, an emerging image processing technology, can automatically extract various quantitative image features that may elude the human eye. Reports on the application of ultrasound (US)-based radiomics methods in distinguishing HCC from ICC are limited. AIM: To develop and validate an ultrasomics model to accurately differentiate between HCC and ICC. METHODS: In our retrospective study, we included a total of 280 patients who were diagnosed with ICC (n = 140) and HCC (n = 140) between 1999 and 2019. These patients were divided into training (n = 224) and testing (n = 56) groups for analysis. US images and relevant clinical characteristics were collected. We utilized the XGBoost method to extract and select radiomics features and further employed a random forest algorithm to establish ultrasomics models. We compared the diagnostic performances of these ultrasomics models with that of radiologists. RESULTS: Four distinct ultrasomics models were constructed, with the number of selected features varying between models: 13 features for the US model; 15 for the contrast-enhanced ultrasound (CEUS) model; 13 for the combined US + CEUS model; and 21 for the US + CEUS + clinical data model. The US + CEUS + clinical data model yielded the highest area under the receiver operating characteristic curve (AUC) among all models, achieving an AUC of 0.973 in the validation cohort and 0.971 in the test cohort. This performance exceeded even the most experienced radiologist (AUC = 0.964). The AUC for the US + CEUS model (training cohort AUC = 0.964, test cohort AUC = 0.955) was significantly higher than that of the US model alone (training cohort AUC = 0.822, test cohort AUC = 0.816). This finding underscored the significant benefit of incorporating CEUS information in accurately distinguishing ICC from HCC. CONCLUSION: We developed a radiomics diagnostic model based on CEUS images capable of quickly distinguishing HCC from ICC, which outperformed experienced radiologists.

PWP1 is overexpressed in hepatocellular carcinoma and facilitates liver cancer cell proliferation.

Identification of novel biomarkers for prediction of disease course and prognosis is needed to reduce morbidity of liver hepatocellular carcinoma (LIHC/HCC) patients. Although dysregulated Periodic tryptophan protein 1 homolog (PWP1/endonuclein) expression has been detected in several tumors, the potential regulatory effect of PWP1 on LIHC remains uncertain. Here we evaluated the expression of PWP1 using multiple online platforms, and demonstrated that PWP1 upregulation was consistently observed in LIHC relative to non-tumor liver tissues and correlated with unfavorable prognosis. Moreover, HCC prognosis was significantly influenced by the methylation status of various CpG sites in the PWP1 gene. Lastly, we provide direct evidence that PWP1 acts as a driver of HCC progression by showing that siRNA-mediated PWP1 silencing significantly suppressed HCC cell proliferation in vitro. These data strongly suggest that PWP1 silencing may be an effective therapeutic strategy to treat LIHC.

Treatment of colorectal cancer by traditional Chinese medicine: prevention and treatment mechanisms.

Colorectal cancer (CRC) is a significant global health burden, with high morbidity and mortality rates. It is often diagnosed at middle to advanced stage, affecting approximately 35% of patients at the time of diagnosis. Currently, chemotherapy has been used to improve patient prognosis and increase overall survival. However, chemotherapy can also have cytotoxic effects and lead to adverse reactions, such as inhibiting bone marrow hematopoiesis, causing digestive dysfunction, hand-foot syndrome, and even life-threatening conditions. In response to these adverse effects, researchers have proposed using Traditional Chinese Medicine (TCM) as an option to treat cancer. TCM research focuses on prescriptions, herbs, and components, which form essential components of the current research in Chinese medicine. The study and implementation of TCM prescriptions and herbs demonstrate its distinctive holistic approach to therapy, characterized by applying multi-component and multi-target treatment. TMC components have advantages in developing new drugs as they consist of single ingredients, require smaller medication dosages, have a precise measure of pharmacodynamic effects, and have a clear mechanism of action compared to TCM prescriptions and herbs. However, further research is still needed to determine whether TMC components can fully substitute the therapeutic efficacy of TCM prescriptions. This paper presents a comprehensive analysis of the research advancements made in TCM prescriptions, herbs, and components. The findings of this study can serve as a theoretical basis for researchers who are interested in exploring the potential of TCM for the treatment of colorectal cancer.

Anti-Cancer Potency of Copper-Doped Carbon Quantum Dots Against Breast Cancer Progression.

Introduction: The anti-cancer potency of copper-doped carbon quantum dots (Cu-CDs) against breast cancer progression needs more detailed investigations. Methods: With urea and ethylene glycol applied as carbon sources and copper sulfate used as a reactive dopant, Cu-CDs were synthesized in the current study by a one-step hydrothermal synthesis method, followed by the characterization and biocompatibility evaluations of Cu-CDs. Subsequently, the anti-cancer potency of Cu-CDs against breast cancer progression was confirmed by these biochemical, molecular, and transcriptomic assessments, including viability, proliferation, migration, invasion, adhesion, clonogenicity, cell cycle distribution, apoptosis, redox homeostasis, and transcriptomic assays of MDA-MB-231 cells. Results: The biocompatibility of Cu-CDs was confirmed based on the non-significant changes in the pathological and physiological parameters in the Cu-CDs treated mice, as well as the noncytotoxic effect of Cu-CDs on normal cells. Moreover, the Cu-CDs treatments not only decreased the viability, proliferation, migration, invasion, adhesion, and clonogenicity of MDA-MB-231 cells but also induced the redox imbalance, cell cycle arrest, and apoptosis of MDA-MB-231 cells via ameliorating the mitochondrial dysfunctions and regulating the MAPK signaling pathway. Conclusion: Our findings confirmed the biosafety and excellent anti-cancer potency of Cu-CDs against breast cancer progression by tapping into mechanisms that disrupt malignant behaviors and oxidative homeostasis of breast cancer cells.

Stiffness on shear wave elastography as a potential microenvironment biomarker for predicting tumor recurrence in HBV-related hepatocellular carcinoma.

BACKGROUND: To explore the pathologic basis and prognostic value of tumor and liver stiffness measured pre-operatively by two-dimensional shear wave elastography (2D-SWE) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients who undergo hepatic resection. METHODS: A total of 191 HBV-infected patients with solitary resectable HCC were prospectively enrolled. The stiffness of intratumoral tissue, peritumoral tissue, adjacent liver tissue, and distant liver tissue was evaluated by 2D-SWE. The correlations between stiffness and pathological characteristics were analyzed in 114 patients. The predictive value of stiffness for recurrence-free survival (RFS) was evaluated, and Cutoff Finder was used for determining optimal cut-off stiffness values. Cox proportional hazards analysis was used to identify independent predictors of RFS. RESULTS: Pathologically, intratumoral stiffness was associated with stroma proportion and microvascular invasion (MVI) while peritumoral stiffness was associated with tumor size, capsule, and MVI. Adjacent liver stiffness was correlated with capsule and liver fibrosis stage while distant liver stiffness was correlated with liver fibrosis stage. Peritumoral stiffness, adjacent liver stiffness, and distant liver stiffness were all correlated to RFS (all p < 0.05). Higher peritumoral stiffness (> 49.4 kPa) (HR = 1.822, p = 0.023) and higher adjacent liver stiffness (> 24.1 kPa) (HR = 1.792, p = 0.048) were significant independent predictors of worse RFS, along with tumor size and MVI. The nomogram based on these variables showed a C-index of 0.77 for RFS prediction. CONCLUSIONS: Stiffness measured by 2D-SWE could be a tumor microenvironment and tumor invasiveness biomarker. Peritumoral stiffness and adjacent liver stiffness showed important values in predicting tumor recurrence after curative resection in HBV-related HCC. CLINICAL RELEVANCE STATEMENT: Tumor and liver stiffness measured by two-dimensional shear wave elastography serve as imaging biomarkers for predicting hepatocellular carcinoma recurrence, reflecting biological behavior and tumor microenvironment. KEY POINTS: • Stiffness measured by two-dimensional shear wave elastography is a useful biomarker of tumor microenvironment and invasiveness. • Higher stiffness indicated more aggressive behavior of hepatocellular carcinoma. • The study showed the prognostic value of peritumoral stiffness and adjacent liver stiffness for recurrence-free survival. • The nomogram integrating peritumoral stiffness, adjacent liver stiffness, tumor size, and microvascular invasion showed a C-index of 0.77.

Glutathione ameliorates the meiotic defects of copper exposed ovine oocytes via inhibiting the mitochondrial dysfunctions.

Regardless of the essential role of copper (Cu) in the physiological regulation process of mammalian reproduction, excessive exposure to Cu triggers the meiotic defects of porcine oocytes via compromising the mitochondrial functions. However, the connections between the excessive Cu exposure and meiotic defects of ovine oocytes have not been reported. In this study, the effect of copper sulfate (CuSO4) exposure on the meiotic potentials of ovine oocytes was analyzed. Subsequently, the ameliorative effect of glutathione (GSH) supplementation on the meiotic defects of CuSO4 exposed ovine oocytes was investigated. For these purposes, the in vitro maturation (IVM) of ovine cumulus oocyte complexes (COCs) was conducted in the presence of 5, 10, 20 and 40 µg/mL of CuSO4 supplementation. Subsequently, different concentrations of GSH (2, 4 and 8 mM) were added to the IVM medium containing CuSO4 solution. After IVM, the assay, including nuclear maturation, spindle organization, chromosome alignment, cytoskeleton assembly, cortical granule (CGs) dynamics, mitochondrial function, reactive oxygen species (ROS) generation, apoptosis, epigenetic modification and fertilization capacity of ovine oocytes were performed. The results showed that excessive Cu exposure triggered the meiotic defects of ovine oocytes via promoting the mitochondrial dysfunction related oxidative stress damage. Moreover, the GSH supplementation, not only ameliorated the decreased maturation potential and fertilization defect of CuSO4 exposed oocytes, but inhibited the mitochondrial dysfunction related oxidative stress damage, ROS generation, apoptosis and altered H3K27me3 expression in the CuSO4 exposed oocytes. Combined with the gene expression pattern, the finding in the present study provided fundamental bases for the ameliorative effect of GSH supplementation on the meiotic defects of CuSO4 exposed oocytes via inhibiting the mitochondrial dysfunctions, further benefiting these potential applications of GSH supplementation in the mammalian IVM system and livestock breeding suffering from the excessive Cu exposure.

The "stiff rim" sign of hepatocellular carcinoma on shear wave elastography: correlation with pathological features and potential prognostic value.

PURPOSE: To explore the pathologic basis, the influencing factors and potential prognostic value of the stiff rim sign in two-dimensional shear wave elastography (2D-SWE) of hepatocellular carcinoma (HCC). METHODS: HCC patients who underwent tumor 2D-SWE examination before resection were prospectively enrolled. The stiff rim sign was defined as increased stiffness in the peritumoral region. Interobserver and intraobserver variability of the stiff rim sign was assessed. The correlation between the stiff rim sign and pathological characteristics was analyzed. Multivariate analysis was performed to examine clinical and radiological factors influencing the appearance of stiff rim sign. The Kaplan-Meier method was used to analyze the relationship between recurrence-free survival (RFS) and the stiff rim sign. RESULTS: The stiff rim sign on 2D-SWE was present in 44.7% of HCC lesions. Interobserver agreement and intraobserver agreement for the stiff rim sign were substantial (κ = 0.772) and almost perfect (κ = 0.895), respectively. Pathologically, the stiff rim sign was associated with capsule status, capsule integrity, capsule thickness, proportion of peritumoral fibrous tissue, and peritumoral fibrous arrangement. Multivariate analysis showed that tumor size was an independent clinical predictor for the appearance of stiff rim sign (OR 1.201, p = 0.008). Kaplan-Meier analysis showed RFS was significantly poorer in the stiff rim sign (+) group than the stiff rim sign (-) group in solitary tumors smaller than 5 cm (p = 0.007) and solitary tumors with intratumoral stiffness less than 33.7 kPa (p = 0.007). CONCLUSION: The stiff rim sign on 2D-SWE was mainly correlated with peritumoral fibrous tissue status and was a poor prognostic indicator for HCC.

Radiomics models for preoperative prediction of microvascular invasion in hepatocellular carcinoma: a systematic review and meta-analysis.

PURPOSE: To assess the methodological quality and to evaluate the predictive performance of radiomics studies for preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). METHODS: Publications between 2017 and 2021 on radiomic MVI prediction in HCC based on CT, MR, ultrasound, and PET/CT were included. The risk of bias was assessed using the prediction model risk of bias assessment tool (PROBAST). Methodological quality was assessed through the radiomics quality score (RQS). Fourteen studies classified as TRIPOD Type 2a or above were used for meta-analysis using random-effects model. Further analyses were performed to investigate the technical factors influencing the predictive performance of radiomics models. RESULTS: Twenty-three studies including 4947 patients were included. The risk of bias was mainly related to analysis domain. The RQS reached an average of (37.7 ± 11.4)% with main methodological insufficiencies of scientific study design, external validation, and open science. The pooled areas under the receiver operating curve (AUC) were 0.85 (95% CI 0.82-0.89), 0.87 (95% CI 0.83-0.92), and 0.74 (95% CI 0.67-0.80), respectively, for CT, MR, and ultrasound radiomics models. The pooled AUC of ultrasound radiomics model was significantly lower than that of CT (p = 0.002) and MR (p < 0.001). Portal venous phase for CT and hepatobiliary phase for MR were superior to other imaging sequences for radiomic MVI prediction. Segmentation of both tumor and peritumor regions showed better performance than tumor region. CONCLUSION: Radiomics models show promising prediction performance for predicting MVI in HCC. However, improvements in standardization of methodology are required for feasibility confirmation and clinical translation.

A nomogram based on multi-modal ultrasound for prediction of microvascular invasion and recurrence of hepatocellular carcinoma.

OBJECTIVE: To establish and validate a nomogram based on multi-modal ultrasound for preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC), and to assess the ability thereof to stratify recurrence-free survival (RFS). METHODS: A total of 287 HCC patients undergoing surgical resection were prospectively enrolled, including 210 patients in the training cohort and 77 patients in the test cohort. All patients underwent conventional ultrasound, contrast-enhanced ultrasonography, and shear wave elastography examinations within one week before surgery. Taking histopathological examination result as the reference standard, independent factors associated with MVI in HCC were determined by logistic regression and a nomogram was established and further evaluated. The Kaplan-Meier method was used to analyze the prognostic value of histologic MVI status and nomogram-predicted MVI status. RESULTS: Multivariate analysis showed that tumor diameter, echogenicity, tumor shape, arterial phase peritumoral enhancement and enhancement level in portal venous phase were independent predictors of MVI (all p < 0.05). The nomogram based on these variables showed good discrimination and calibration with the areas under the receiver operating characteristic curve (AUC) of 0.821 (0.762-0.870) and 0.789 (0.681-0.874) in the training and test cohorts. There was a significant difference in RFS between the nomogram-predicted MVI positive and the nomogram-predicted MVI negative groups in training and test cohorts (p < 0.001 and p = 0.004 respectively). CONCLUSIONS: The multimodal ultrasound features were effective imaging markers for preoperative prediction of MVI of HCC and the nomogram might be an effective tool to stratify the risk of recurrence and guide the individualized treatment of HCC.

The value of liver stiffness measured by two-dimensional shear wave elastography for predicting symptomatic posthepatectomy liver failure in patients with hepatocellular carcinoma.

PURPOSE: To assess and compare the value of liver stiffness measurement (LSM) by two-dimensional shear wave elastography (2D-SWE) with the diagnosis of clinically significant portal hypertension (CSPH) and pathological examination in predicting symptomatic posthepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC). METHOD: A total of 130 patients who underwent liver resection for HCC between August 2018 and July 2021 were enrolled. Preoperative assessments for LSM and other clinicopathological tests were performed in all patients. The performance of LSM, CSPH and fibrosis stage in predicting symptomatic PHLF was assessed and compared. Univariate and multivariate analyses were conducted on the risk factors for symptomatic PHLF. RESULTS: Symptomatic PHLF occurred in 40 patients (30.8%). The best LSM cutoff value for predicting symptomatic PHLF was 9.5 kPa. The areas under the receiver operating characteristic curve (AUCs) of LSM ≥ 9.5 kPa, fibrosis stage and CSPH for predicting symptomatic PHLF were 0.732 (95% CI: 0.638-0.826, p < 0.001), 0.655 (95% CI: 0.553-0.758, p = 0.005) and 0.594 (95% CI: 0.484-0.705, p = 0.086), respectively. The AUC of LSM ≥ 9.5 kPa was significantly higher than that of CSPH (p = 0.010), and was comparable to that of fibrosis stage (p = 0.073). Multivariate analysis identified LSM ≥ 9.5 kPa (p = 0.001), major hepatectomy (p = 0.007) and CSPH diagnosis (p = 0.040) as independent predictors of symptomatic PHLF. CONCLUSIONS: LSM by 2D-SWE was promising for predicting symptomatic PHLF in HCC patients. The predictive performance was higher than that of CSPH and comparable to that of pathological fibrosis stage.

MicroRNA-20a-5p regulates the epithelial-mesenchymal transition of human hepatocellular carcinoma by targeting RUNX3.

BACKGROUND: MicroRNA-20a (miR-20a) is dysregulated in many types of malignancies, including human hepatocellular carcinoma (HCC), but its expression level and functional significance in HCC are still disputed. We aimed to study the role of miR-20a-5p in HCC and its downstream molecular mechanisms. METHODS: We used real-time polymerase chain reaction to detect the expression of miR-20a-5p and runt-related transcription factor 3 ( RUNX3 ) in HCC and paraneoplastic tissue, transfected Huh7 and highly metastatic human hepatocellular carcinoma (MHCC97H) cells. A live cell workstation was used to observe the proliferation and migration of transfected cells. The invasiveness of transfected cells was verified by Transwell assay. Cell apoptosis was detected by flow cytometry. The expression levels of proteins after transfection were measured using simple western immunoblot measurements. Gene expression profiles between HCC and normal samples were obtained from The Cancer Genome Atlas. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results were processed by the database for annotation, visualization and integrated discovery. Potential target genes of miR-20a-5p were predicted to further investigate how miR-20a-5p regulates epithelial-mesenchymal transition (EMT) in HCC. RESULTS: MiR-20a-5p was significantly highly expressed in HCC tissues, and overexpression of miR-20a-5p significantly promoted HCC cell proliferation, migration, and invasion and inhibited apoptosis in vitro. The protein expression of E-cadherin was decreased and that of vimentin was increased after overexpression of miR-20a-5p in HCC cells. We discovered the intersection of genes from miRDB, miR TarBase, and TargetScan, obtained 397 target genes and finally focused on RUNX3. RUNX3 was not only reduced in HCC specimens but also drastically reduced in HCC cells overexpressing miR-20a-5p. RUNX3 expression decreased with elevated miR-20a-5p, which activated downstream EMT signaling and promoted cell proliferation, migration, and invasion. CONCLUSIONS: Since RUNX3 is involved in EMT in HCC, as proven by previous research, our findings provide further evidence for a novel regulatory pathway comprising the miR-20a/RUNX3/EMT axis that upregulates EMT signaling and enhances the migration of HCC cells.

Feasibility of liver stiffness measured using two-dimensional shear wave elastography in assessing preoperative liver function for patients with hepatocellular carcinoma.

OBJECTIVES: To evaluate the feasibility of liver stiffness (LS) measured using two-dimensional shear wave elastography (2D SWE) in assessing preoperative liver function for patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 143 patients who underwent surgical resection for HCC between August 2018 and December 2019 were enrolled prospectively. LS measurement, liver function tests including serum biochemical indicators, and indocyanine green (ICG) clearance test were performed preoperatively. Child-Pugh (CP) score, Albumin-bilirubin (ALBI) score and Model for End-Stage Liver Disease score were calculated. ICG retention rate at 15 min (ICG R15) and ICG elimination rate constant (ICG K) were determined automatically. Fibrosis stage was determined based on pathological findings. The association between LS and serum biochemical indicators, liver function scores, and the ICG results were analyzed. RESULTS: Weak to moderate correlations were identified between LS and biochemical indicators of liver function (all p < 0.01). Weak correlation was identified between LS and CP score, and between LS and ALBI score (all p < 0.001). Moderate correlation was identified between LS and ICG R15 (Pearson r = 0.62, p < 0.001), and between LS and ICG K value (Pearson r = - 0.49, p < 0.001). The best cutoff of LS to discriminate a normal ICG R15 was 10.6 kPa, with area under the curve (AUC), sensitivity, specificity of 0.874, 0.900 and 0.724, respectively. CONCLUSIONS: LS determined using 2D SWE could be a potential tool for the preoperative evaluation of liver function in patients with HCC.

Liver Stiffness Measured by Two-Dimensional Shear Wave Elastography for Predicting Symptomatic Post-hepatectomy Liver Failure in Patients with Hepatocellular Carcinoma.

OBJECTIVES: To evaluate the ability of liver stiffness (LS) measured by two-dimensional shear wave elastography (2D SWE) to predict symptomatic post-hepatectomy liver failure (SPHLF) in patients with hepatocellular carcinoma (HCC). METHODS: A total of 119 patients who underwent hepatectomy for HCC between August 2018 and July 2019 were enrolled. Preoperative assessments for LS and other clinicopathological tests were performed in all patients. Univariate and multivariate analyses were conducted for the risk factors of SPHLF. Further subgroup analysis was performed according to multivariate analysis results. RESULTS: SPHLF occurred in 38 patients (31.9%). The best cutoff value of LS for predicting SPHLF was 9.5 kPa. Multivariate analysis identified LS ≥ 9.5 kPa, greater Child-Turcotte-Pugh (CTP) grade, and major hepatectomy as independent predictors of SPHLF. Based on the extent of hepatectomy, CTP grade could stratify the risk of SPHLF in the minor hepatectomy group (12.2% vs. 100.0%, p = 0.001), whereas LS was superior in predicting SPHLF in the major hepatectomy group (18.9% vs. 72.4%, p < 0.001). In patients with CTP grade A, LS could further stratify the risks of SPHLF in both the minor and major hepatectomy groups (3.7% vs. 22.7%, p = 0.043; 17.6% vs. 70.4%, p < 0.001, respectively). CONCLUSIONS: LS measured using 2D SWE could predict SPHLF using the best cutoff value of 9.5 kPa. CTP grade was a stronger indicator of SPHLF in minor hepatectomy, whereas LS was more effective in selecting candidates for major hepatectomy. LS could further stratify the risk of SPHLF in CTP grade A patients, regardless of the extent of hepatectomy.

ACBP suppresses the proliferation, migration, and invasion of colorectal cancer via targeting Wnt/beta-catenin signaling pathway.

Anticancer bioactive peptide (ACBP), a novel bioactive peptide isolated from spleens of goats immunized with tumor extracts in our lab, can inhibit the proliferation of CRC in vitro and vivo. However, it remains unclear how the proliferation of CRC is inhibited by ACBP at the molecular level. Here, we provide evidences showing that ACBP significantly inhibits the expression of Wnt/ß-catenin related genes (cyclin D1, met and c-myc) through pharmacotranscriptomic and qRT-PCR analysis in CRCs. Active ß-catenin, a key protein within Wnt pathway, was compromised remarkably by ACBP in three CRCs, including HCT116, RKO and HT29. Thus nuclear accumulation of active ß-catenin was retarded and finally lead to the decreased expression of oncogenes cyclin D1, met, and c-myc. In addition, we proved that active ß-catenin reduction was mainly due to the inhibition of phospho-LRP6 and stimulation of phospho-ß-catenin by ACBP. Based on the detection of Met and C-Myc in CRC tumor tissue without prior radiotherapy or chemotherapy, our results demonstrated that ACBP can act as a promising anticancer agent for CRC by targeting Wnt/ß-catenin pathway, especially active ß-catenin.

Feasibility and outcomes of percutaneous radiofrequency ablation for intrahepatic recurrent hepatocellular carcinoma after liver transplantation: a single-center experience.

PURPOSE: To evaluate the feasibility, effectiveness, and treatment outcomes of percutaneous radiofrequency ablation (RFA) in the application of intrahepatic recurrent hepatocellular carcinoma (r-HCC) after liver transplantation (LT). METHODS: From April 2008 to December 2019, a total of 37 patients (34 male and 3 female, mean age: 48.7 ± 10.5 years) with 61 r-HCCs after LT treated by RFA as a first-line option were enrolled. The technical success, recurrence-free survival (RFS), overall survival (OS) and complications were evaluated. RESULTS: After the first session of RFA, three patients were detected with residual foci. All of them received additional session of RFA and two tumors were successfully ablated. Therefore, the technical success was 97.3% (36/37). During the follow-up period, a total of 7 tumors developed local tumor progression (LTP) after 2.2-10.8 months. The LTP rate was 11.7% for r-HCC in the transplanted liver. The median RFS was 4.8 months (95% confidence interval [CI]: 2.2-7.3 months). The 1-, 3-, and 5-year cumulative OS rates were 68.5%, 40.3%, and 40.3%, respectively. Multivariate analyses revealed that tumor size was the only independent predictor for RFS (hazard ratio [HR] = 2.557, 95% CI, 1.015-6.444; p = .046) and limited extrahepatic metastasis was the only independent prognostic factors of OS after RFA for post-LT r-HCC (HR = 4.031, 95%CI, 1.218-13.339; p = .022). Major complications after RFA occurred in two patients (2/37, 5.4%). CONCLUSION: Percutaneous RFA is safe and effective for intrahepatic r-HCC after LT, especially for those without limited extrahepatic metastasis.

Deep Learning Radiomics Based on Contrast-Enhanced Ultrasound Might Optimize Curative Treatments for Very-Early or Early-Stage Hepatocellular Carcinoma Patients.

BACKGROUND: We aimed to evaluate the performance of a deep learning (DL)-based Radiomics strategy designed for analyzing contrast-enhanced ultrasound (CEUS) to not only predict the progression-free survival (PFS) of radiofrequency ablation (RFA) and surgical resection (SR) but also optimize the treatment selection between them for patients with very-early or early-stage hepatocellular carcinoma (HCC). METHODS: We retrospectively enrolled 419 patients examined by CEUS within 1 week before receiving RFA or SR (RFA: 214, SR: 205) from January 2008 to 2016. Two Radiomics signatures were constructed by the Radiomics model R-RFA and R-SR to stratify PFS of different treatment groups. Then, RFA and SR nomograms were built by incorporating Radiomics signatures and significant clinical variables to achieve individualized 2-year PFS prediction. Finally, we applied both Radiomics models and both nomograms to each enrolled patient to investigate whether there were space for treatment optimization and how much prognostic improvement could be expected. RESULTS: R-RFA and R-SR showed remarkable discrimination (C-index: 0.726 for RFA, 0.741 for SR). RFA and SR nomograms provided good 2-year PFS prediction accuracy and good calibrations. We identified 17.3% RFA patients and 27.3% SR patients should swap their treatment, so their average probability of 2-year PFS would increase 12 and 15%, respectively. CONCLUSIONS: The proposed Radiomics models and nomograms achieved accurate preoperative prediction of PFS for RFA and SR, and they could facilitate the optimized treatment selection between them for patients with very-early or early-stage HCC.

PBRM1 suppresses tumor growth as a novel p53 acetylation reader.

The reader(s) for acetylated tumor antigen p53 remains elusive. Here, PBRM1 (polybromo-1) is identified as a reader for acetylated lysine382 on p53 through its bromodomain 4 (BD4). PBRM1 BD4 mutants fail to support p53 transcriptional activity and suppress tumor growth. Thus PBRM1 suppresses tumor growth through p53 in kidney cancer.

Perioperative Nursing of Patients with Pancreatic Cancer Treated with a Nanoknife.

To summarize the experience of 40 patients with pancreatic adenocarcinoma treated with irreversible electroporation ablation (IRE), their experiences with surgical nurses, and to explore the best nursing methods before and during IRE ablation. Preoperative visits were conducted to assess the condition of patients, and psychological counseling was subsequently given to them. All material and medication required for the operation were prepared in advance, and placed in appropriate locations. All 40 patients were treated successfully. The mean time of IRE ablation was 63.33±12.26 (range, 37-87) minutes, and mean blood loss was 2.09±0.49 (range: 1.0-2.8) mL. There were no ablation-related deaths. Skillful mastery of nanoknife usage and troubleshooting methods, intensive observation of patients' vital signs during ablation, and active cooperation with surgeons can ensure successful ablation and can reduce the influence of improper nursing during ablation on patients' prognosis.

Trichomicin Suppresses Colorectal Cancer via Comprehensive Regulation of IL-6 and TNFα in Tumor Cells, TAMs, and CAFs.

Trichomicin, a small-molecule compound isolated from fungi, has been identified with bioactivity of antitumor. In this study, a colon cancer subcutaneous mice model was used to evaluate the antitumor effects of Trichomicin in vivo. Treatment with Trichomicin significantly inhibited tumor growth in a xenograft mouse colon cancer model. The underlying molecular mechanism has also been investigated through the quantification of relevant proteins. The expression levels of IL-6 and TNFα were reduced in tumor tissues of mice treated with Trichomicin, which was consistent with results of in vitro experiments in which Trichomicin suppressed the expression of IL-6 and TNFα in tumor and stromal cells. In addition, Trichomicin inhibited TNFα-induced activation of NF-κB and basal Stat3 signaling in vitro, which resulted in reduced expression of the immune checkpoint protein PD-L1 in tumor and stromal cells. Conclusively, Trichomicin, a promising new drug candidate with antitumor activity, exerted antitumor effects against colon cancer through inhibition of the IL-6 and TNFα signaling pathways.

Supramolecular Photothermal Nanomedicine Mediated Distant Tumor Inhibition via PD-1 and TIM-3 Blockage.

Supramolecular nanoparticles for photothermal therapy (PTT) have shown promising therapeutic efficacy in the primary tumor and great potential for turning the whole-body immune microenvironment from "cold" to "hot," which allows for the simultaneous treatment of the primary tumor and the metastatic site. In this work, we develop a liposome-based PTT nanoparticle through the self-assembly of FDA-approved intravenous injectable lipids and a photothermal agent, indocyanine green (ICG). The obtained ICG-liposome shows long-term storage stability, high ICG encapsulation efficiency (>95%), and enhanced near-infrared (NIR) light-triggered photothermal reaction both in vitro and in vivo. The ICG-liposome efficiently eradicated the primary tumor upon laser irradiation in two colon cancer animal models (CT26 and MC38) and promoted the infiltration of CD8 T cells to distant tumors. However, PTT from ICG-liposome shows only a minimal effect on the inhibition of distant tumor growth in long-term monitoring, predicting other immunosuppressive mechanisms that exist in the distant tumor. By immune-profiling of the tumor microenvironment, we find that the distant tumor growth after PTT highly correlates to compensatory upregulation of immune checkpoint biomarkers, including program death-1 (PD-1), T-cell immunoglobulin, and mucin domain-containing protein 3 (TIM-3), in tumor-infiltrating CD8 T cells. Based on this mechanism, we combine dual PD-1 and TIM-3 blockade with PTT in an MC38 tumor model. This combo successfully clears the primary tumor, generates a systemic immune response, and inhibits the growth of the distant tumor. The ICG-liposome-combined PD-1/TIM-3 blockade strategy sheds light on the future clinical use of supramolecular PTT for cancer immunotherapy.