Therapeutic Effect Of Hepatocellular Carcinoma Research Articles

The role of NLRP3 inflammasome in hepatocellular carcinoma.

Inflammasomes play an important role in innate immunity. As a signal platform, they deal with the excessive pathogenic products and cellular products related to stress and injury. So far, the best studied and most characteristic inflammasome is the NLR-family pyrin domain-containing protein 3(NLRP3) inflammasome, which is composed of NLRP3, apoptosis associated speck like protein (ASC) and pro-caspase-1. The formation of NLRP3 inflammasome complexes results in the activation of caspase-1, the maturation of interleukin (IL)-1β and IL-18, and pyroptosis. Many studies have demonstrated that NLRP3 inflammasome not only participates in tumorigenesis, but also plays a protective role in some cancers. Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality. Currently, due to the lack of effective treatment methods for HCC, the therapeutic effect of HCC has not been ideal. Therefore, it is particularly urgent to explore the pathogenesis of HCC and find its effective treatment methods. The increasing evidences indicate that NLRP3 inflammasome plays a vital role in HCC, however, the related mechanisms are not fully understood. Hence, we focused on the recent progress about the role of NLRP3 inflammasome in HCC, and analyzed the relevant mechanisms in detail to provide reference for the future in-depth researches.

An Unfolded Protein Response-Related mRNA Signature Predicting the Survival and Therapeutic Effect of Hepatocellular Carcinoma.

Tumorigenesis, metastasis, and treatment response of hepatocellular carcinoma (HCC) are regulated by unfolded protein responses (UPR) signaling pathways, including IRE1a, PERK, and ATF6, but little is known about UPR related genes with HCC prognosis and therapeutic indicators. We aimed to identify a UPR related prognostic signature (UPRRPS) for HCC and explore the potential effect of the current signature on the existing molecular targeted agents and immune checkpoint inhibitors (ICIs). We used The Cancer Genome Atlas (TCGA) database to screen candidate UPR genes (UPRGs), which are expressed differentially between hepatocellular carcinoma and normal liver tissue and associated with prognosis. A gene risk score for overall survival prediction was established using the least absolute shrinkage and selection operator (LASSO) regression analysis, which was validated using data from the International Cancer Genome Consortium (ICGC) database and evaluated by the C-index. Then immune and molecular characteristics stratified by the current UPRRPS were analyzed, and the corresponding drug sensitivity was conducted. Initially, 42 UPRGs from the TCGA database were screened as differentially expressed genes, which were also associated with HCC prognosis. Using the LASSO regression analysis, nine UPRGs (EXTL3, PPP2R5B, ZBTB17, EIF2S2, EIF2S3, HDGF, SRPRB, EXTL2, and TPP1) were used to develop a UPRRPS to predict the OS of HCC patients in the TCGA set with the Cindex of 0.763. The current UPRRPS was also well-validated in the ICGC set with the C-index of 0.700. Multivariate Cox regression analyses also confirmed that the risk score was an independent risk factor for HCC in both the TCGA and ICGC sets (both P<0.05). Functional analyses showed that low-risk score was associated with increased natural killer cells, T helpers, tumor immune dysfunction and exclusion score, microsatellite instability expression, and more benefit from ICIs; the high-risk score was associated with increased active dendritic cells, Tregs, T-cell exclusion score, and less benefit from ICIs. Gene set enrichment analyses showed that the signaling pathways of VEGF, MAPK, and mTOR were enriched in high UPRRPS, and the drug sensitivities of the corresponding inhibitors were all significantly higher in the high UPRRPS subgroup (all P<0.001). With the current findings, UPRRPS was a promising biomarker for predicting the prognosis of HCC patients. UPRRPS might also be taken as a potential indicator to guide the management of immune checkpoint inhibitors and molecular targeted agents.

LncRNA TTN-AS1 intensifies sorafenib resistance in hepatocellular carcinoma by sponging miR-16-5p and upregulation of cyclin E1

Drug resistance has always been an important problem affecting the therapeutic effect of hepatocellular carcinoma (HCC). To investigate the potential role of lncRNA TTN-AS1 in HCC cells with sorafenib (SOR) resistance, and explore the underlying pathways, quantitative real time polymerase chain reaction (qRT-PCR) was used to test the expression of TTN-AS1 in HCC tissues and cells. Then, the expression of TTN-AS1 was down-regulated by shRNA, the activity changes, apoptosis and related protein expression in HCC cells with/without SOR treatment were observed in succession. Expression levels of the downstream target of TTN-AS1, miR-16-5p were studied by dual-luciferase binding assay, cell proliferation, and western blotting analysis. Nude mice models of human HCC with TTN-AS1 gene knockdown were established to observe the tumor growth. As the results revealed, TTN-AS1 silencing in HCC cells induced apoptosis by enhancing the sensitivity of cells to SOR, and the tumor in nude mice became smaller. The mechanism study showed that miR-16-5p was affected by TTN-AS1 sponge, up-regulated cyclin E1 expression, and regulated PTEN/Akt signaling pathway, thereby significantly alleviating the inhibition of apoptosis of HCC cells induced by TTN-AS1 gene. Collectively, our results provided TTN-AS1 as a potential therapeutic target for sorafenib resistance in HCC.

Expert consensus on multidisciplinary diagnosis and treatment of precancerous lesions of hepatocellular carcinoma (2020 edition)

Hepatocellular carcinoma (HCC) currently holds the second position for cause of cancer-related deaths in China. Most of the pathogenic characteristics of HCC in China follow the tri-step model of hepatitis B-cirrhosis-liver cancer. The screening of precancerous lesions of stomach cancer, colorectal cancer and cervical cancer has achieved remarkable results for the diagnosis and treatment of malignant tumors. Dysplastic nodules in the state of cirrhosis have strong potential for malignant changes, especially high-grade dysplastic nodules, have extremely high canceration rate. This expert consensus is based on the research results and clinical experience of foreign and native experts of this field. Furthermore, this consensus summarizes and defines high-grade dysplastic nodules of the liver as precancerous lesions of HCC through multidisciplinary collaboration in terms of conception, screening, diagnosis, treatment and follow-up, with the aim to reduce the HCC incidence and improve the overall therapeutic effect of HCC in China.

Research progress on heterogeneity and epigenetics of hepatocellular carcinoma

Tumor heterogeneity is one of the common phenomena of malignant tumors, and the heterogeneity of hepatocellular carcinoma is significant. Despite some treatments such as surgical resection, chemotherapy and radiotherapy in the primary phage of hepatocellular carcinoma have been used, the prognosis of patients remains poor, which is closely related to the heterogeneity of hepatocellular carcinoma. Therefore, exploring the heterogeneity of hepatocellular carcinoma has important clinical significance for improving the therapeutic effect of hepatocellular carcinoma. This article reviews the heterogeneity of hepatocellular carcinoma from an epigenetic perspective and explores the possible intrinsic epigenetic molecular mechanisms underlying the heterogeneity of hepatocellular carcinoma. Key words: Liver neoplasms; Genetic heterogeneity; Neoplastic stem cells; Epigenetics

Evaluating the therapeutic effect of hepatocellular carcinoma treated with transcatheter arterial chemoembolization by magnetic resonance perfusion imaging

To compare the characteristics of magnetic resonance perfusion-weighted imaging (MRPWI) scans before and after transcatheter arterial chemoembolization (TACE) treatment of hepatocellular carcinoma (HCC) and to apply MRPWI in evaluating the therapeutic effect of TACE and prognosis of HCC. Thirty-five patients with HCC undergoing their first TACE treatment were enrolled in this study. T2WI, T1WI, and PWI of MRI were performed 24-48 h before TACE and 48-168 h after TACE. Perfusion parameters calculated with the maximum slope were used to create a time-signal intensity curve (TSC). The efficacy of TACE treatment in HCC was evaluated by examining the hemodynamic changes in TSC caused by TACE treatment. TSC before TACE showed a pattern of a quick decrease and a slow increase in the tumor region of interest in 34 patients with HCC, whereas the TSC for normal liver tissues showed a pattern of slow decrease and slow increase. After TACE, the fluctuating range of TSC was significantly reduced in 31 patients, slightly reduced in three, and did not change significantly in one. The 3-year survival rate was 28.6%. MRPWI of the liver does not only show the anatomy of HCC lesions but also reflects hemodynamic changes of HCC before and after TACE to a certain extent. It is very useful for clinical evaluation of the efficacy of TACE for HCC.

Contrast-Enhanced Ultrasound in the Characterization of Hepatocellular Carcinomas Treated by Ablation: Comparison with Contrast-Enhanced Magnetic Resonance Imaging

The purpose of this study was to evaluate the clinical utility of low-mechanical-index contrast-enhanced ultrasound (CEUS) in assessing the response to percutaneous microwave ablation in patients with hepatocellular carcinoma by comparing the results with those of contrast-enhanced magnetic resonance imaging (CEMRI). Between August 2005 and July 2011, 182 patients with 231 lesions treated by microwave ablation were included in the study. One month after microwave ablation, CEUS and CEMRI were performed to evaluate therapeutic responses. The difference in diagnostic accuracy between the two methods was analyzed to evaluate the value of contrast-enhanced ultrasound after microwave ablation. The final diagnosis was based on computed tomography and MRI typical findings of therapeutic response of hepatocellular carcinoma, proven serum tumor marker levels and additional follow-up. The sensitivity of CEUS and CEMRI in evaluating the therapeutic effect of hepatocellular carcinoma was 86.5% and 84.6%; the specificity, 98.3% and 98.9%; and the accuracy, 95.7% and 95.7%.There was no significant statistical disparity between CEUS and CEMRI (p > 0.05).The sensitivity, specificity and accuracy were 98.1, 97.2 and 97.8% when CEUS was used in combination with CEMRI to evaluate the therapeutic response of hepatocellular carcinoma to microwave ablation. CEUS examination was proven to be a tolerable and easy modality for assessment of the therapeutic effect of microwave ablation and can provide results comparable to those obtained with CEMRI. Combining the results of these two examinations may reduce false-positive and false-negative diagnoses.

The quantitative evaluation of contrast harmonic imaging in the differential diagnosis of hepatic tumors and the therapeutic effect of hepatocellular carcinoma (HCC) with B-mode second harmonic ultrasonography: Naoki Hori, Saiseikai Kyoto Hospital, Nagaokakyo, Kyoto Japan; Motonari Sakai, Saiseikai Kyoto Hospital, Nagaokakyo, Kyoto Japan; Masaharu Ohta, Saiseikai Kyoto Hospital, Nagaokakyo, Kyoto Japan

The quantitative evaluation of contrast harmonic imaging in the differential diagnosis of hepatic tumors and the therapeutic effect of hepatocellular carcinoma (HCC) with B-mode second harmonic ultrasonography: Naoki Hori, Saiseikai Kyoto Hospital, Nagaokakyo, Kyoto Japan; Motonari Sakai, Saiseikai Kyoto Hospital, Nagaokakyo, Kyoto Japan; Masaharu Ohta, Saiseikai Kyoto Hospital, Nagaokakyo, Kyoto Japan

The quantative evaluation of contrast harmonic imaging in the differential diagnosis of hepatic tumors and the therapeutic effect of hepatocellular carcinoma (HCC) with B-mode second harmonicultrasonography (US)

The quantative evaluation of contrast harmonic imaging in the differential diagnosis of hepatic tumors and the therapeutic effect of hepatocellular carcinoma (HCC) with B-mode second harmonicultrasonography (US)

An assessment of therapeutic effect of hepatocellular carcinoma by the serial change of serum AFP value

An assessment of therapeutic effect of hepatocellular carcinoma by the serial change of serum AFP value