Lenvatinib plus drug-eluting bead transarterial chemoembolization with/without hepatic arterial infusion chemotherapy for hepatocellular carcinoma larger than 7 cm with major portal vein tumor thrombosis: a multicenter retrospective cohort study.

BACKGROUND: The management of hepatocellular carcinoma (HCC) with high tumor burden and major portal vein tumor thrombosis (PVTT) remains a great challenge. We aimed to investigate the efficacy and safety of lenvatinib plus drug-eluting bead transarterial chemoembolization (DEB-TACE) and hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, fluorouracil and leucovorin (Len+DEB-TACE+HAIC) versus lenvatinib plus DEB-TACE (Len+DEB-TACE) for HCC > 7.0 cm accompanied with major PVTT. MATERIALS AND METHODS: This multicenter retrospective cohort study evaluated consecutive patients with HCC (> 7.0 cm) and major PVTT who received Len+DEB-TACE+HAIC (Len+DEB-TACE+HAIC group) or Len+DEB-TACE (Len+DEB-TACE group) between July 2019 and June 2021 from eight institutions in China. Objective response rate (ORR), time to progression (TTP), overall survival (OS), and treatment-related adverse events (TRAEs) were compared between the two groups by propensity score-matching (PSM). RESULTS: A total of 205 patients were included. After PSM, 85-paired patients remained in the study cohorts. Patients in the Len+DEB-TACE+HAIC group had higher ORR (61.2% vs. 34.1%, P < 0.001), longer TTP (median, 9.8 vs. 5.9 months, P < 0.001), and prolonged OS (median, 16.7 vs. 12.5 months, P < 0.001) than those in the Len+DEB-TACE group. The ORR and TTP of both intrahepatic tumor (ORR: 64.7% vs. 36.5%, P < 0.001; median TTP: 10.7 vs. 7.0 months, P < 0.001) and PVTT (ORR: 74.1% vs. 47.1%, P < 0.001; median TTP: 17.4 vs. 7.6 months, P < 0.001) were better in the Len+DEB-TACE+HAIC group than the Len+DEB-TACE group. The frequency of grade 3-4 TRAEs in the Len+DEB-TACE+HAIC group were comparable to those in the Len+DEB-TACE group (38.8% vs. 34.1%, P = 0.524). CONCLUSION: The addition of HAIC to Len+DEB-TACE significantly improved ORR, TTP, and OS over Len+DEB-TACE with an acceptable safety profile for large HCC with major PVTT.

Comparison of laparoscopic radiofrequency ablation with percutaneous radiofrequency ablation in the treatment of chronic hepatitis B-related hepatocellular carcinoma involving specific sites: A retrospective cohort study.

BACKGROUND: This study compared the effectiveness and safety of laparoscopic radiofrequency ablation (LRFA) and percutaneous radiofrequency ablation (PRFA) in the treatment of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) involving specific sites. METHODS: This retrospective cohort study included patients with HBV-related HCC involving specific sites treated with LRFA or PRFA between January 2012 and December 2020. The overall survival (OS), disease-free survival (DFS), and complications were compared between the LRFA and PRFA groups. The Cox proportional-hazards regression model was used to determine the factors affecting prognosis. RESULTS: This study included 109 patients: 69 in the LRFA group and 40 cases in the PRFA group. No significant differences were found in the 3-year OS rate between the two groups (73.7% vs. 70.0%, P = 0.514), but the LRFA group showed a higher 3-year DFS rate than the PRFA group (58.2% vs. 42.5%, P = 0.018). The RFA method was not associated with OS but was independently associated with DFS (LRPA vs. PRFA, HR = 2.078, P = 0.012). The common complications were ascites, pleural effusion, and fever in the two groups. The occurrence of complications in patients treated with LRFA or PRFA was similar (15.9% vs. 12.5%, P = 0.785). CONCLUSION: LRFA was associated with a better DFS in patients with HBV-related HCC involving specific sites. Thus, LRFA might have more advantages in treating liver cancer involving specific sites.

Genetic alterations of KRAS and TP53 in intrahepatic cholangiocarcinoma associated with poor prognosis.

The aim of this study is to investigate certain genetic features of intrahepatic cholangiocarcinoma (ICCA). A total of 12 eligible ICCA patients were enrolled, and tumor tissues from the patients were subjected to next-generation sequencing of a multi-genes panel. Tumor mutation burden (TMB), mutated genes, copy number variants (CNVs), and pathway enrichment analysis were performed. The median TMB was 2.76 Mutation/Mb (range, 0-36.62 Mutation/Mb) in ICCA patients. The top two most commonly mutated genes in ICCA were KRAS (33%) and TP53 (25%). The co-mutations of KRAS and TP53 were 16.7% (2/12) in ICCA patients. Notably, patient P6 with the highest TMB did not have KRAS and TP53 mutations. Additionally, TP53 and/or KRAS alterations were significantly associated with poor progression-free survival than those with wild type (1.4 months vs 18 months). DNA damage repair and homologs recombinant repair deficiencies were significantly associated with high TMB in ICCA cases. In conclusion, we found that certain genetic mutations of TP53 and KRAS could predict poor prognosis in ICCA patients.

Propofol mediates bone metastasis by regulating PC-derived exosomal miR-142-3p.

In this study we investigated the role of propofol in mediating prostate cancer (PCa) bone metastasis through regulating exosomal factors derived from PCa. We isolated exosomes from PCa cells and co-cultured them with mesenchymal stem cells (MSCs). PCa-derived exosomes increased calcium deposition of MSCs and upregulated ALPL'Alkaline phosphatase, tissue-nonspecific isozyme) and BGLAP (Bone Gamma-Carboxyglutamate Protein) expression. Propofol treatment reduced alkaline phosphatase (ALP) activity, and ALPL and BGLAP expression that was induced by PCa-derived exosomes in MSCs. miRNAs present in cancer cell-derived exosomes increased osteogenesis in these cells. We evaluated miRNA expression in PCa cells after treatment with propofol, and found that miR-142-3p was upregulated in PCa cells. Furthermore, we transfected MSCs with miR-142-3p mimics or inhibitors and revealed that miR-142-3p mimics reduced calcium deposition and downregulated ALP activity, and ALPL and BGLAP levels, while miR-142-3p inhibitors increased calcium deposition and increased ALP activity, and ALPL and BGLAP levels. Finally, we determined that MSCs co-cultured with PCa-derived exosomes and transfected with miR-142-3p mimic exhibited reduced calcium deposition and lower ALP activity, and expression of ALPL and BGLAP. These data demonstrate that propofol inhibits osteogenic differentiation and mineralization of MSCs induced by PCa-derived exosomes by regulation of miR-142-3p levels.

MicroRNAs: Crucial Players in the Differentiation of Human Pluripotent and Multipotent Stem Cells into Functional Hepatocyte-Like Cells.

Hepatic disease negatively impacts liver function and metabolism. Primary human hepatocytes are the gold standard for the prediction and successful treatment of liver disease. However, the sources of hepatocytes for drug toxicity testing and disease modeling are limited. To overcome this issue, pluripotent stem cells (PSCs) have emerged as an alternative strategy for liver disease therapy. Human PSCs, including embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) can self-renew and give rise to all cells of the body. Human PSCs are attractive cell sources for regenerative medicine, tissue engineering, drug discovery, and developmental studies. Several recent studies have shown that mesenchymal stem cells (MSCs) can also differentiate (or trans-differentiate) into hepatocytes. Differentiation of human PSCs and MSCs into functional hepatocytelike cells (HLCs) opens new strategies to study genetic diseases, hepatotoxicity, infection of hepatotropic viruses, and analyze hepatic biology. Numerous in vitro and in vivo differentiation protocols have been established to obtain human PSCs/MSCs-derived HLCs and mimic their characteristics. It was recently discovered that microRNAs (miRNAs) play a critical role in controlling the ectopic expression of transcription factors and governing the hepatocyte differentiation of human PSCs and MSCs. In this review, we focused on the role of miRNAs in the differentiation of human PSCs and MSCs into hepatocytes.

The landscape of PD-L1 expression and somatic mutations in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver, and becoming the third-leading cause of cancer-related mortality worldwide. Despite the immune checkpoint inhibitors and molecular targeted therapies have shown preferable efficacy in HCC, large number of HCC patients do not respond effectively to anti-PD-1 reagents. Besides, the accumulation of genetic mutations in cancer cells may lead to the therapy resistant. Hence, there are clinical gaps between genetic and transcriptomic biomarkers for the HCC treatment. METHODS: To investigate the genetic mapping of liver cancer, targeted deep sequencing (TDS) and bioinformatics analysis were performed on hepatocellular carcinoma (HCC) tumor tissues and matched blood samples. Furthermore, copy number variants (CNVs) and Tumor mutation burden (TMB) were calculated. Immunohistochemistry was applied to determine the PD-L1 expression in HCC tumor tissues. Clinical characteristic, PD-L1 expression, and the TMB were analyzed in 32 HCC patients. RESULTS: This study indicated that the PD-L1 positive patients exhibited a lower TMB compared to the PD-L1 negative group, and PD-L1 positive patients were more likely to suffer from aggressive clinicopathologic features than PD-L1 negative patients. We also verified the top 30 mutated genes, including TP53, CTNNB1, KMT2D, AXIN1, ALK, and NOTCH1, in our dataset. Our results indicated that PD-L1 positive patients possessed more tumors with vascular invasion and advanced CCLC stage. Moreover, PD-L1 positive patients exhibited a lower TMB compared to the PD-L1 negative group. CONCLUSIONS: These findings could improve our understanding of the effects of immune checkpoint therapies on prognosis, and could facilitate the monitoring of somatic mutations in HCC.

CDKN3 expression predicates poor prognosis and regulates adriamycin sensitivity in hepatocellular carcinoma in vitro.

OBJECTIVE: Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths worldwide. This study investigated the relationship between cyclin-dependent kinase inhibitor (CDKN)3 and prognosis and pathological characteristics in HCC patients to determine whether it could be used as a prognostic factor and/or therapeutic target for HCC drug development. METHODS: We previously showed that CDKN3 is deregulated in HCC tumor samples. Here, bioinformatics analysis was used to assess the relationship between CDKN3 gene expression and the characteristics of HCC patients from Gene Expression Omnibus and The Cancer Genome Atlas databases. Additionally, CDKN3 expression was silenced by small interfering RNA to determine its effect on HCC cell proliferation and on HCC cell sensitivity to adriamycin chemotherapy. RESULTS: Bioinformatics analysis showed a negative correlation between CDKN3 expression and both disease-free survival and overall survival. CDKN3 silencing did not significantly suppress the proliferation of HCC cells, but did decrease their sensitivity to adriamycin. CONCLUSIONS: CDKN3 may have a dual role during the development of HCC, and could be used as an independent prognostic factor and therapeutic target for HCC treatment.

Giant recurrent left inguinal hernia with femoral nerve injury: a report of a rare case.

BACKGROUND: Giant inguinal hernia(GIH), a rare disease, has brought great challenges to surgeons. GIH is defined as an inguinal hernia that extends below the midpoint of the inner thigh in standing position. However, a giant recurrent inguinal hernia resulting from previous operations that destroy the anatomical structure of the inguinal region is extremely rare. Nerve injury, a complication following inguinal hernia repair, is mostly found in ilioinguinal nerve and iliohypogastric nerve, which often presents as numbness and acute or chronic pain, while postoperative muscular dysfunction results from femoral nerve injury is rare. CASE PRESENTATION: A 77-years-old woman presented with a complaint of a reducible mass in the left inguinal of duration 1 year. The patient had three previous inguinal hernia repairs. Physical examination and auxiliary examination indicated a giant inguinal hernia with femoral nerve injury. After preoperative evaluation and preparation, a transabdominal partial extraperitoneal(TAPE) repair have performed. Finally, the patient recovered and was discharged. CONCLUSIONS: In conclusion, we reported a rare case of a giant recurrent inguinal hernia with femoral nerve injury and made a successful treatment for the patient via transabdominal partial extraperitoneal(TAPE) repair.

Identify potential clinical significance of long noncoding RNA forkhead box P4 antisense RNA 1 in patients with early stage pancreatic ductal adenocarcinoma.

Previous studies have shown that forkhead box P4 antisense RNA 1 (FOXP4-AS1) is dysregulated in tumor tissues and can serve as a prognostic indicator for multiple cancers. However, the clinical significance of FOXP4-AS1 in pancreatic ductal adenocarcinoma (PDAC) remains unclear. The goal of this study is to recognize the possible clinical significance of long noncoding RNA FOXP4-AS1 in patients with early stage PDAC. A total of 112 patients from The Cancer Genome Atlas (TCGA) PDAC cohort, receiving RNA sequencing, were involved in the study. Survival analysis, functional mechanism, and potential small molecule drugs of target therapy of FOXP4-AS1 were performed in this study. Survival analysis in TCGA PDAC cohort suggested that patients with high FOXP4-AS1 expression had significantly augmented possibility of death than in PDAC patients with lower FOXP4-AS1 expression (adjusted P = .008; adjusted HR = 2.143, 95% CI = 1.221-3.760). In this study, a genome-wide RNA sequencing dataset was used to identify 927 genes co-expressing with FOXP4-AS1 in PDAC tumor tissues. A total of 676 differentially expressed genes were identified between different FOXP4-AS1 expression groups. Functional enrichment analysis of these genes and gene set enrichment analysis for PDAC genome-wide RNA sequencing dataset was done. We have found that FOXP4-AS1 may function in PDAC by participating in biological processes and pathways including oxidative phosphorylation, tricarboxylic acid cycle, classical tumor-related pathways such as NF-kappaB as well as Janus kinase/signal transducers in addition to activators of transcription, cell proliferation, and adhesion. In addition, we also screened two potential targeted therapeutic small molecule drugs (dimenhydrinate and metanephrine) for FOXP4-AS1 in PDAC. In conclusion, our present study demonstrated that higher expression of FOXP4-AS1 in PDAC tumor tissues were related with an inferior medical outcome. Through multiple genome-wide approaches, we identified the potential molecular mechanisms of FOXP4-AS1 in PDAC and two targeted therapeutic drugs for it.

Dexmedetomidine protects aged rats from postoperative cognitive dysfunction by alleviating hippocampal inflammation.

The present study investigated the effect of dexmedetomidine on hippocampal inflammation and cognitive function in rats with postoperative cognitive dysfunction (POCD). A total of 80 healthy male Sprague Dawley rats were used, 72 of which developed POCD. The rats were randomly divided into four groups: The control, model, low­dose and high­dose dexmedetomidine anesthesia groups. A POCD model was established and dexmedetomidine was administered. Cognitive function tests were performed and expression levels of interleukin 1ß (IL­1ß), tumor necrosis factor­α (TNF­α) and NF­κB biomarkers were evaluated on the first, third and seventh day following modeling. The cognitive function of rats was measured using a Y­maze test. The expression levels of IL­1ß and TNF­α in the hippocampus were determined by ELISA. The protein expression levels of NF­κB p65 in the hippocampus were determined by western blotting. It was revealed that at 1, 3 and 7 days after surgery, there were no alterations in the exercise ability of rats in the different groups, as reflected by the number of rats passing the alternative arms in the Y­maze. On the first and third day after surgery, the cognitive dysfunction reflected by the alteration scores of the low­dose and high­dose dexmedetomidine anesthesia groups were significantly higher than those of the model group, and the increase in the high­dose group was more pronounced. Additionally, on the first day after surgery, the expression levels of IL­1ß, TNF­α and NF­κB in the hippocampi of rats in the low­ and high­dose dexmedetomidine anesthesia groups were significantly lower than those in the model group, and the decrease was more pronounced in the high­dose group. At 7 days after surgery, the differences in expression levels of IL­1ß, TNF­α and NF­κB in the hippocampus among groups were not identified to be statistically significantly different. Taken together, the results of the present study indicated that dexmedetomidine may inhibit hippocampal inflammation induced by surgical trauma, and that dexmedetomidine may effectively improve postoperative cognitive function in rats.

Propofol Reversed Hypoxia-Induced Docetaxel Resistance in Prostate Cancer Cells by Preventing Epithelial-Mesenchymal Transition by Inhibiting Hypoxia-Inducible Factor 1α.

Prostate cancer is the second most frequently diagnosed cancer worldwide. Hypoxia-induced epithelial-mesenchymal transition (EMT), driven by hypoxia-inducible factor 1α (HIF-1α), is involved in cancer progression and metastasis. The present study was designed to explore the role of propofol in hypoxia-induced resistance of prostate cancer cells to docetaxel. We used the Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine incorporation assay to measure cell viability and cell proliferation, respectively, in prostate cancer cell lines. Then, we detected HIF-1α, E-cadherin, and vimentin expression using western blotting. Propofol reversed the hypoxia-induced docetaxel resistance in the prostate cancer cell lines. Propofol not only decreased hypoxia-induced HIF-1α expression, but also reversed hypoxia-induced EMT by suppressing HIF-1α. Furthermore, small interfering RNA-mediated silencing of HIF-1α reversed the hypoxia-induced docetaxel resistance, although there was little change in docetaxel sensitivity between the hypoxia group and propofol group. The induction of hypoxia did not affect E-cadherin and vimentin expression, and under the siRNA knockdown conditions, the effects of propofol were obviated. These data support a role for propofol in regulating EMT in prostate cancer cells. Taken together, our findings demonstrate that propofol plays an important role in hypoxia-induced docetaxel sensitivity and EMT in prostate cancer cells and that it is a potential drug for overcoming drug resistance in prostate cancer cells via HIF-1α suppression.

CDKN3 expression is negatively associated with pathological tumor stage and CDKN3 inhibition promotes cell survival in hepatocellular carcinoma.

Aberrant expression of CDKN3 may be involved in carcinogenesis of liver cancer. The effect of CDKN3 on tumorigenesis and the molecular mechanisms involved have not been fully elucidated. Immunohistochemistry was performed to detect CDKN3 expression levels in tumor tissues. CDKN3 siRNA was used to knockdown CDKN3 in QGY7701 hepatocellular carcinoma (HCC) cells. Colony formation assay was used to measure the clonogenic capacity of the tumor cells. Cell viability was determined by MTT assay. Logistic regression was performed to analyze the association between CDKN3 expression level and the HCC clinical pathology index. The CDKN3 expression level was significantly decreased in HCC tumor tissues compared with normal liver tissue and liver cirrhosis tissue. Additionally, CDKN3 expression was negatively­associated with the pathological stage of the tumor. Inhibition of CKDN3 promoted the clonogenic capacity and chemotherapeutic tolerance in HCC tissues compared with controls. Knockdown of CDKN3 resulted in downregulation of p53 and p21 protein levels, whereas, AKT serine/threonine kinase 1 expression was upregulated. Thus, CDKN3 expression may reduce the survival of tumor cells and alter the sensitivity to therapeutic agents via the AKT/P53/P21 signaling pathway. Therefore, CDKN3 may be involved in tumor differentiation and self-renewal.

Diosmetin induces apoptosis by upregulating p53 via the TGF-ß signal pathway in HepG2 hepatoma cells.

Diosmetin (Dio) is a major active component of flavonoid compounds. A previous study demonstrated that Dio exhibited anticancer activity and induced apoptosis in HepG2 human hepatoma cells via cytochrome P450, family 1-catalyzed metabolism. The present study observed that cell proliferation of HepG2 cells was inhibited by Dio treatment and tumor protein p53 was significantly increased following Dio treatment. Following addition of recombinant transforming growth factor­ß (TGF­ß) protein to Dio­treated HepG2 cells, cell growth inhibition and cell apoptosis was partially reversed. These findings suggest a novel function for the TGF­ß/TGF­ß receptor signaling pathway and that it may be a key target of Dio­induced cell apoptosis in HepG2 cells.

Notch3 functions as a regulator of cell self-renewal by interacting with the ß-catenin pathway in hepatocellular carcinoma.

The Notch signaling pathway plays a role in cell proliferation, differentiation. Emerging data have revealed aberrant Notch3 expression in hepatocellular carcinoma (HCC). However, whether Notch3 plays a role in tumorigenesis or tumor progression is unclear. In this study, we found that over 71.8% of the cases studied had high Notch3 expression levels (n = 32); Notch3 expression positively correlated with alpha-fetoprotein (AFP) levels (p = 0.0311) and negatively correlated with the differentiation grade (p = 0.042). We demonstrated that the patients with higher levels of Notch3 expression commonly had a poor prognosis. We discovered that Notch3 expression is inversely correlated with ß-catenin content but positively associated with the protein level of Nanog. In parallel, we found that Notch3 attenuation resulted in the upregulation of ß-catenin and the downregulation of Nanog in the hepatoma cell lines QGY7701 and HepG2. The downregulation of Notch3 enhanced the sensitivity to cisplatin in the QGY7701 and HepG2 cells and inhibited the ability of QGY7701 cells to form tumors. The Notch3-positive cells had higher levels of aldehyde dehydrogenase (ALDH) activity, and a tendency to differentiate into Notch3-negative cells. In conclusion, our study demonstrated that Notch3 plays a role in modulating the stemness of tumor cells via the inactivation of the Wnt/ß-catenin pathway.

Dihydromyricetin induces mouse hepatoma Hepal-6 cell apoptosis via the transforming growth factor-ß pathway.

Dihydromyricetin (DHM) is a flavonoid compound which possesses potent antitumor activity. In the present study, it was demonstrated that DHM significantly inhibited proliferation and induced apoptosis in mouse hepatocellular carcinoma Hepal­6 cells. Transforming growth factor ß (TGF­ß) is recognized as a major profibrogenic cytokine and is therefore a common target for drugs in the treatment of liver disease. The present study aimed to investigate whether TGF­ß was involved in DHM­triggered cell­viability inhibition and apoptosis induction. An MTT assay was used to evaluate the viability of Hepal­6 cells following DHM treatment. TGF­ß signalling is mediated by Smads and nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) is a crucial regulator of reactive oxygen species ROS production. TGF­ß, Smad3, phosphorylated (p)­Smad2/3 and NOX4 protein expression levels were evaluated by western blot analysis. TGF­ß and NOX4 gene expression levels were determined by quantitative polymerase chain reaction. The results indicated that DHM downregulated TGF­ß, Smad3, p­Smad2/3 and NOX4 in a concentration­dependent manner. A cell counting assay indicated that DHM also inhibited Hepal­6 cell growth in a concentration­dependent manner. TGF­ß expression was significantly decreased following DHM treatment. In conclusion, the results of the present study defined and supported a novel function for DHM, indicating that it induced cell apoptosis by downregulating ROS production via the TGF­ß/Smad3 signaling pathway in mouse hepatocellular carcinoma Hepal­6 cells.

Resveratrol inhibits the proliferation of human melanoma cells by inducing G1/S cell cycle arrest and apoptosis.

Resveratrol (Res), a natural plant extract, is an effective inducer of cell apoptosis and cell cycle arrest in multiple carcinoma cell types, which has been demonstrated by its ability to inhibit the proliferation of multiple human tumor cells in vitro. Although Res possesses chemopreventive properties against several types of cancer, the molecular mechanism underlying its anticancer activity remains to be fully elucidated. The present study demonstrated that Res induced cell cycle arrest and inhibited the proliferation of human melanoma A375 (IC50=23 µM after 48 h; P<0.05) and SK-MEL-31 (IC50=15 µM after 48 h; P<0.05) cells. Western blot analysis demonstrated that Res induced the apoptosis of human melanoma A375 and SK-MEL-31 cells by upregulating the expression of Bcl-2-associated X protein and B-cell lymphoma 2, possibly via the p53 pathway and activation of caspase-9 and caspase-3.

Resveratrol inhibits proliferation in human colorectal carcinoma cells by inducing G1/S­phase cell cycle arrest and apoptosis through caspase/cyclin­CDK pathways.

The present study compared the effect of resveratrol on HCT116 and Caco-2 human colon cancer cells. Annexin V/propidium iodide staining, MTT assay and western blot analysis revealed that resveratrol induced cycle arrest in the two cell lines, which was evidenced by cell cycle analysis and changes in the expression of the cell cycle proteins cyclin-dependent kinase (CDK) 2, CDK4, cyclin D1, proliferating cell nuclear antigen and P21. Furthermore, resveratrol was found to have a strong apoptosis-inducing effect, which was evidenced through the high percentage of annexin V positive cells and high protein expression of cleaved­caspase­7, cleaved­caspase­9 and cleaved­poly(ADP-ribose) polymerase in the resveratrol-treated cancer cells. In conclusion, these results demonstrated that resveratrol had greater growth inhibitory and cell cycle arrest effects on Caco-2 cells than HCT116 cells, through caspase-dependent and cyclin-CDK pathways.

Acoustic radiation force impulse elastography for efficacy evaluation after hepatocellular carcinoma radiofrequency ablation: a comparative study with contrast-enhanced ultrasound.

AIM: To explore acoustic radiation force impulse (ARFI) elastography in assessing residual tumors of hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA). MATERIALS AND METHODS: There were 83 HCC lesions among 72 patients. All patients were examined with ARFI, contrast enhanced ultrasound (CEUS), and CT or MRI. Tumor brightness on virtual touch tissue imaging (VTI) and shear wave velocity (SWV) were assessed before and approximately one month after RFA. RESULTS: There were 14 residual tumors after RFA. VTI showed that all the tumors were darker after RFA. VTI was not able to distinguish the ablated lesions and the residual tumors. 13 residual tumor lesions were detected by CEUS. All completely ablated nodules had SWV demonstration of x.xx., while with those residual nodules, 6 tumors had x.xx measurement and 8 tumors had measurable SWV. nine lesions with residual tumors occurred in cirrhosis subjects and 5 lesions with residual tumors occurred in fibrosis subjects; there was no residual tumor in the normal liver subjects. CONCLUSION: VTI technique cannot demonstrate residual tumor post RFA. While SWV measurement of less than x.xx is likely associated with residual tumors, measurement of less than x.xx cannot exclude residual tumors. Liver cirrhosis is associated with decreased chance of a complete ablation.

Dihydromyricetin promotes hepatocellular carcinoma regression via a p53 activation-dependent mechanism.

The development of antitumor chemotherapy drugs remains a key goal for oncologists, and natural products provide a vast resource for anti-cancer drug discovery. In the current study, we found that the flavonoid dihydromyricetin (DHM) exhibited antitumor activity against liver cancer cells, including primary cells obtained from hepatocellular carcinoma (HCC) patients. In contrast, DHM was not cytotoxic to immortalized normal liver cells. Furthermore, DHM treatment resulted in the growth inhibition and remission of xenotransplanted tumors in nude mice. Our results further demonstrated that this antitumor activity was caused by the activation of the p53-dependent apoptosis pathway via p53 phosphorylation at serine (15Ser). Moreover, our results showed that DHM plays a dual role in the induction of cell death when administered in combination with cisplatin, a common clinical drug that kills primary hepatoma cells but not normal liver cells.

AZD8055 induces cell death associated with autophagy and activation of AMPK in hepatocellular carcinoma.

AZD8055 is a potent inhibitor of mTORC1 and mTOR2 and shows inhibitory effects in several types of cancer cells in vitro and in vivo. However, the effect of AZD8055 on hepatocellular carcinoma (HCC) cells has not been studied. We report that AZD8055 inhibits cell proliferation and colony formation of Hep3B and Huh7 cells but does not cause PARP cleavage, or caspase activation, suggesting that classical apoptosis is not its main mechanism of cell death. By contrast, AZD8055-induced cell death was associated with several characteristics of autophagy, including an increase in acidic vesicular organelle content, conversion of cytosolic LC3-I to membrane-bound LC3-II and elevation of the levels of Atg-5/12, BECN1 and LC3-II. Inhibition of autophagy by 3-methyladenine (3-MA) partially inhibited AZD8055-induced cell death. Furthermore, AZD8055 caused the activation of AMPK and co-treatment with the AMPK inhibitor dorsomorphin also caused a partial but significant reduction of AZD8055-induced cell death. In conclusion, AZD8055-induced HCC cell death is associated with induction of autophagy and activation of AMPK.