Objective To investigate the effect of gut bacteria under chronic colitis on the progression of hepatoma in mice.Methods 22 hepatitis B virus (HBV) -transgenic mice ( male, 8 weeks) were randomly divided into two groups, one group (n =10) was fed the drinking water containing 2% dextran sodium sulphate(DSS)to induce chronic colitis and the control group(n =12)was fed with normal drinking water.In order to investigate the effect of gut microbes, 7 male HBV-transgenic mice(8 weeks, with no detectable hepatoma under microscopy) were cohoused with 4 mice with hepatoma for 16 weeks.Results No significant liver cell damage was observed in the group of the mice fed with 2% DSS-containing drinking water.By the 22 -week old,9 of the 10 mice(90.0%) fed with 2% DSS-containing drinking water, 2 of the 12 mice(16.7%) fed with normal drinking had hepatoma.Both the hepatoma incidence and the tumor numbers in the group of mice fed with DSS-containing water were significantly higher than that in the controls (P =0.002 and P =0.028respetively).Compared to controls, the bacteria family Prevotella (P =0.022) and Anaeroplasma (P =0.014) reduced significantly in the mice with induced chronic colitis.All the mice (n =7) cohoused with the mice with hepatoma had the liver tumor developed at 24 -week-old.Conclusion Alterations of gut bacteria under chronic colitis may promote the development of liver cancer.

OBJECTIVETo investigate the role of CCL20/CCR6/Th17 axis in vascular invasion and metastasis of primary hepatocellular carcinoma (HCC).

METHODSExpression levels of CCL20 mRNA in the normal human liver cell line L-02, and human hepatocellular carcinoma cell lines Hep3B, Huh7 and HepG2 were quantified by using SYBR green real time PCR. CCL20 secretions from these cell lines were quantified by using ELISA. The chemotactic effect of HCC cell line Hep3B on human peripheral blood mononuclear cells was determined by using transwell chemotaxis assay. Pre-therapy serum levels of IL-1α, IL-1β, IL-6, IL-8, IL-10, IL-17, IL-23, IFN-γ, TNF-α and CCL20 in 93 patients with HCC were measured by using 9-plex array and ELISA. All the patients were chronic hepatitis B virus associated HCC, and 51 cases were those with vascular invasion and metastasis (metastasis group) and 42 cases were not (non-metastasis group). CCL20 and CCR6 mRNA expressions in the HCC and tumor-adjacent tissues were determined by using SYBR Green real time PCR in 41 patients, among them, 20 cases were from the group of patients with metastasis and 21 cases were from the group of patients without metastasis. The CCL20 expression was further determined by immunohistochemistry.

RESULTSThe HCC cell lines expressed and secreted higher amount of CCL20, which effectively recruited CCR6(+) T cells. Pre-therapy serum levels of CCL20 in 93 HCC patients were (38.2 ± 28.4)pg/ml, significantly increased than those with benign hepatic hemangiomas [(7.8 ± 17.8)pg/ml, P < 0.01]. In addition, the serum levels of CCL20 were positively correlated with the tumor diameters in HCC patients (r = 0.32, P = 0.0018). CCL20 was dominantly expressed in the cytoplasm in HCC cells, and it was also expressed by some infiltrating immune cells. The mRNA expression levels of CCL20 of the tumor tissues were significantly higher than that in the tumor-adjacent tissues (P < 0.05). Multivariate logistic regression analysis showed that serum levels of IL-17 and CCL20 were independent risk factors of metastasis in HCC patients (P < 0.05 for both). CCL20 mRNA showed no statistically significant differences between patients with metastasis and without metastasis in both tumor tissues and tumor-adjacent tissues (P > 0.05 for both). But the patients with metastasis showed significantly higher expressions of CCR6 both in their tumor [5.75 (1.79, 19.13)]and tumor-adjacent tissues [7.99 (4.49, 19.54)] than those with non-metastasis [1.69 (0.76, 2.87) and 3.58 (1.84, 4.32), P < 0.05 for both].

CONCLUSIONCCL20/CCR6/Th17 axis may promote vascular invasion and metastasis hepatocellular carcinoma.

Bile Duct Neoplasms ; Carcinoma, Hepatocellular ; metabolism ; Chemokine CCL20 ; metabolism ; Humans ; Interleukin-10 ; metabolism ; Interleukin-17 ; metabolism ; Interleukin-23 ; metabolism ; Interleukin-6 ; metabolism ; Interleukin-8 ; metabolism ; Leukocytes, Mononuclear ; Liver Neoplasms ; metabolism ; RNA, Messenger ; Th17 Cells ; Tumor Necrosis Factor-alpha ; metabolism

Advanced hepatocellular carcinoma (HCC) has limited treatment options and poor prognosis. Only two tyrosine kinase inhibitors have been approved as single agents for first-line treatment over the last decade. In 2020, atezolizumab combined with bevacizumab was appro-ved for first-line treatment of advanced HCC. As the first brand-new therapy to surpass sorafenib, atezolizumab combined with bevacizumab showed good safety and life quality in patients. The authors introduced the diagnosis and treatment of a China Liver Cancer Staging Ⅲb HCC patient receiving atezolizumab combined with bevacizumab, in order to provide references for patient management.

Objective:To investigate the efficacy and safety of different transcatheter arterial chemoembolization(TACE)-based regimens in patients with unresectable hepatocellular carcinoma(uHCC)and explore the optimal timing for combining TACE with tyrosine kinase inhibit-ors(TKIs)and immune checkpoint inhibitors(ICIs).Methods:A retrospective analysis was conducted on data from 555 patients with uHCC who underwent TACE-based treatment between April 2016 and December 2021 in Nanfang Hospital,Southern Medical University.The pa-tients were assigned into the following four groups according to different treatment regimens:TACE group(n=317),TACE combined with TKIs group(TACE+TKIs,n=66),TACE combined with ICIs group(TACE+ICIs,n=33),and TACE combined with TKIs+ICIs group(TACE+TKIs+ICIs,n=139).Subgroup analysis was performed within the TACE+TKIs+ICIs group,with patients being assigned into"pre-TACE"and"post-TACE"groups based on the timing of the combination therapy.Univariate and multivariate Cox regression analyses were conducted to identify pro-gnostic factors influencing overall survival(OS).Results:The TACE+TKIs+ICIs group showed the longest OS(21.9 months,95%confidence in-terval[CI]:17.2-26.6,P=0.030)and progression-free survival(PFS)(8.3 months,95%CI:7.3-9.3,P=0.004)compared to those in the other three groups.In the subgroup analysis,the"post-TACE"group had longer OS than the"pre-TACE"group(26.8 months vs.19.2 months,P = 0.011).The objective response rate(ORR)was 32.8%,41.1%,42.4%,and 52.5%(P=0.001)and the disease control rate(DCR)was 59.6%,71.2%,69.7%,and 82.7%(P<0.001)in the TACE,TACE+TKIs,TACE+ICIs,and TACE+TKIs+ICIs groups,respectively.The adverse events were similar to those reported in previous studies.Cox regression analysis revealed that tumor number,extrahepatic metastasis,and treatment regimen were independent factors influencing OS in patients(all P<0.05).Conclusions:TKIs or ICIs can improve OS and PFS in patients with uHCC receiving TACE,and the combination of TKIs+ICIs with TACE achieves better beneficial outcomes.The greatest OS was observed when the combination therapy TKIs+ICIs was initiated within 3 months after the first TACE procedure.

Objective To investigate the efficacy of continuous hepatic arterial infusion chemotherapy (HAIC) with the FOLFOX regimen and its multimodality therapeutic regimen in the treatment of patients with advanced hepatocellular carcinoma, as well as the influencing factors for prognosis. Methods A retrospective analysis was performed for the clinical data of 66 patients with advanced hepatocellular carcinoma who received continuous HAIC with FOLFOX regimen in Nanfang Hospital, Southern Medical University, from September 2018 to November 2021. The patients were observed in terms of objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), and median overall survival (mOS) after treatment, and treatment-related adverse reactions were recorded. For the patients with portal vein tumor thrombus, the effect of the treatment on portal vein tumor thrombus was assessed. The Kaplan-Meier method was used for survival analysis, and the Cox regression analysis was used to investigate the influencing factors for prognosis. Results According to the RECIST1.1 criteria, FOLFOX-HAIC and its multimodality therapeutic regimen achieved an ORR of 33.3% (22/66) and a DCR of 86.4% (57/66) in the treatment of 66 patients with advanced hepatocellular carcinoma, with an mPFS time of 8.2 months and an mOS time of 22.1 months. Among the 39 patients with portal vein tumor thrombus, 2 achieved complete remission, 8 achieved partial remission, 24 achieved stable disease, and 5 had disease progression, with an ORR of 25.6% (10/39) and a DCR of 87.2% (34/39). The main adverse reactions included gastrointestinal reactions (16.7%, 11/66), pyrexia (12.1%, 8/66), liver area pain (10.6%, 7/66), bone marrow suppression (3.0%, 2/66), and contrast agent allergy (3.0%, 2/66), and there were no grade > Ⅳ toxic or side effects or deaths caused by such complications. The Cox regression analysis showed that extrahepatic metastasis (hazard ratio [ HR ]=2.668, 95% confidence interval [ CI ]: 1.357-5.245, P < 0.05) and prothrombin time (PT) ( HR =1.282, 95% CI : 1.080-1.630, P < 0.05) were independent risk factors for PFS, and aspartate aminotransferase level ( HR =1.008, 95% CI : 1.002-1.013, P < 0.05) and PT ( HR =1.303, 95% CI : 1.046-1.630, P < 0.05) were independent risk factors for OS. Conclusion FOLFOX-HAIC and its multimodality therapeutic regimen has a certain clinical effect with controllable adverse reactions in the treatment of advanced hepatocellular carcinoma.