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Objective:To evaluate the effects of pegylated interferon (Peg-IFN) alfa-2b combined with nucleotide analogues (NAs) on the recurrence of hepatitis B-related liver cancer after resection, and to explore the changes of HBsAg and HBV DNA in patients with chronic hepatitis B liver cancer during postoperative treatment.Methods:The prospective study was conducted. Clinical data of 43 patients with hepatitis B-related liver cancer who underwent radical resection treated in 900th Hospital of People′s Liberation Army were prospectively analyzed from January 2020 to December 2021. Among 43 patients, there were 39 males and 4 females, the age was 30-76 years. According to different treatment methods they were divided into two groups, the patients treated by Peg-IFN alfa-2b combined with NAs were devided into the IFN group( n=10), and those treated by NAs alone into the NAs group( n=33). Two-pair semi-quantitative were collected every 3 months after operation. The recurrence-free survival rate, recurrence time after 2 years in the two groups, the clearance rate and the negative rate of HBsAg and HBV DNA in the two groups. Peg-IFN alfa-2b was evaluated in improving the prognosis of hepatitis B-related liver cancer. The measurement data of normal distribution were expressed by mean±standard deviation ( ± s), and t-test was used for comparison between the two groups. Chi-square test was used for comparison between the two groups of count data. Repeated analysis of measurement variance was used for analysis HBsAg and HBV DNA changes of the interferon group overall survival time and recurrence-free surrival time of patients was estimated using Kaplan-Meier method and the difference between groups was assessed using Log-rank test. Results:HBsAg and HBV DNA: The HBsAg clearance rate at 24 weeks and that at 48 weeks in the IFN group were 24.6% and 59.0% respectively. The HBsAg negative rate at 48 weeks was 16.7%. The HBV DNA clearance rate at 24 weeks and that at 48 weeks were 33.9% and 53.8% respectively. The HBV DNA negative rate was 0 at 48 weeks. The levels of HBsAg and HBV DNA in the IFN group decreased gradually with time. There were statistically differences between the levels of HBsAg and HBV DNA at 0 weeks, 24 weeks and 48 weeks( P<0.05). The 2-year overall survival rates of IFN group and NAs group were 100% and 90.9% respectively. The 2-year recurrence-free survival rates were 90.0% and 63.6% respectively. There were no significant statistical differences in the overall survival rate and recurrence-free survival rate between the groups ( P>0.05). The postoperative recurrence time of the IFN group and the NAs group were (15.00±7.07) months and (5.78±3.39) months respectively. The difference between the two groups was statistically significant ( t=3.160, P<0.01). Conclusion:Long-term antiviral therapy of Peg-IFN alfa-2b combined with NAs can prolong the recurrence time of liver cancer, reduce the levels of HBsAg and HBV DNA in serum, and potentially improve the survival rate of the patients compared with therapy of NAs alone.
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Objective:To explore the relationship between CD24 expression in preoperative peripheral blood as well as cancer tissue and clinical parameters and prognosis in patients with hepatocellular carcinoma (HCC) after liver transplantation (LT).Methods:From November 2018 to November 2019, clinical data were collected for 65 HCC patients and 41 patients with benign liver disease.The preoperative peripheral blood level of CD24 was detected by enzyme-linked immunosorbent assay (ELISA) and the expression of CD24 in cancerous foci and adjacent tissues examined by immunohistochemistry.Kaplan-Meier survival curves of differential CD24 expression were plotted and survival differences compared by Log-rank method.One-way ANOVA was utilized for examining the relationship between the expression level of CD24 and various clinicopathological parameters and multivariate Cox analysis for screening independent risk factors affecting patient prognosis.Results:The concentration of CD24 in preoperative peripheral blood (p-CD24) of HCC patients (6.51±2.33 μg/L) was significantly higher than that of patients with benign liver disease (4.10±0.91) μg/L, P<0.05.The positive rate of CD24 was obviously higher in cancerous tissues than that in adjacent tissues (87.7% vs. 4.6%, P<0.05). The peripheral blood level of CD24 was positively correlated with the expression intensity of CD24 in tumor tissues (t-CD24, r=0.570, P<0.001). The expression of CD24 (both in blood and cancer foci) was significantly correlated with preoperative level of gamma-glutamyl transferase (GGT), maximal tumor diameter, microvascular invasion, portal vein tumor thrombus, vessel carcinoma embolus and satellite focus ( P<0.05). The expression of CD24 in patients exceeding the Milan/UCSF criteria was higher than those fulfilling the criteria ( P<0.005). Patients with a higher expression of CD24 had worse overall survival and recurrence-free survival rates as compared to those a lower expression of CD24 ( P<0.05). Multivariate Cox analysis indicated that t-CD24 [OS: HR=3.661(1.005-13.333)], P=0.049; recurrence-free survival (RFS): [HR=4.331(1.887-9.942), P=0.001] and preoperative level of alpha fetoprotein (AFP) [OS: HR=4.900(1.590-15.097), P=0.006]; RFS: [HR=3.414(1.614-7.221), P=0.001] were independent risk factors for overall survival and recurrence-free survival in HCC patients undergoing LT. Conclusions:The preoperative peripheral blood level of CD24 in HCC patients undergoing LT indirectly reflects the expression of CD24 in cancerous tissues to a certain extent.And the expression of CD24 in cancerous tissue is one of the independent risk factors affecting OS and RFS of LT patients.
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Objective:To evaluate the long-term prognosis and recurrence of young liver transplant recipients with hepatocellular carcinoma(HCC).Methods:Based upon the database of liver transplantation center, clinical data were retrospectively reviewed for 39 young recipients(18~40 years)and 158 middle-aged and elderly recipients(over 40 years)from 2013 to 2017. The parameters of overall survival(OS), recurrence-free survival(RFS)and disease-specific survival(DSS)were compared between two groups.Cox's proportional hazard model was utilized for evaluating the prognostic factors.Results:Significant inter-group difference existed in recurrence rate of HCC. Kaplan-Meier analysis revealed no significant difference in OS rate(1/3-year OS, 82.1%, 66.7% and 86.1%, 74.7%, P>0.05)and DSS rate(1/3-year DSS, 94.9%, 82.1% and 99.4%, 91.1%, P=0.053); RFS rate(1/3-year RFS, 51.3%, 41.0% and 73.0%, 62.7%, P=0.008)showed significant differences; Cox multivariate analysis revealed that AFP>400 μg/L was an independent risk factor for OS, DSS and RFS; poorly differentiated tumors and positive micro-vascular invasion(MVI)were independent risk factor for DSS; poorly differentiated tumors and total tumor size >5 cm were independent risk factors for RFS. Conclusions:Although RFS of young adult group is worse than that in middle-aged and elderly group after LT, no significant inter-group difference exists in OS or DSS. And LT is still a quite effective treatment for young HCC patients.
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Aim To explore the mechanism of Fluspirilene inhibiting HCC through decreasing the expression of Akt.Methods The difference of mRNA was verified by the test of protein expression between Fluspirilenc treatment group and control group by HCC experiment in vivo and vitro, including Western blot, IHC after mRNA array.Results Akt expression was lower in Fluspirilene treatment group than that in control group by mRNA array.Protein expression of Akt, phosphorylate-CDK2 and phos- phorylate-Rb decreased massively in Fluspirilene treatment group in a concentration-dependent manner in HepG2 and Huh7 cells by Western blotting compared with those in control group.Declined expression of phosphorylate-Akt was proved in a concen- tration-dependent manner in xenograft tumor tissues in Fluspirilene treatment group compared with that in control group in IHC test.Conclusions Fluspirilene inhibits HCC by decreasing significantly the protein expression of Akt, phosphorylat-Akt, phos- phorylate-CDK2 and phosphorylate-Rb.
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Sorafenib is an oral multi-kinase inhibitor used primarily in the treatment of hepatic cellular carcinoma, renal cell carcinoma, and thyroid carcinoma. Hand-foot syndrome also is known as palmar-plantar erythrodysesthesia causes reddening, numbness, swelling of palms of hands and soles of feet. In this report, a known case of renal cell carcinoma, post right nephrectomy patient on treatment with tab sorafenib had developed the hand-foot syndrome
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@#【Objective】To study retrospectively the serum hepatitis B surface antigen（HBsAg）and HBsAg normal⁃ ized to the same hepatic parenchyma cell volume（HPCV），namely，the same hepatic cell quantities，between HBeAg- positive and HBeAg-negative chronic hepatitis B（CHB）.【Methods】A total of 168 CHB patients who had undergone liv⁃ er biopsy and test of serum HBsAg levels due to their disease in the Third Affiliated Hospital of SunYat-sen University were selected as the study subjects. The serum HBsAg levels，as well as HBsAg levels normalized to HPCV（hepatic cell quantities）were compared between HBeAg-positive and HBeAg-negative CHB，respectively.【Results】There was statis⁃ tically significant difference in serum HBsAg levels between HBeAg-positive and HBeAg-negative CHB（P = 0.028）， while there was no statistical difference in HBsAg normalized to HPCV（P = 0.073）. There were no correlations between serum HBsAg and liver inflammation grades（HBeAg-positive：r s = 0.020，P = 0.876 & HBeAg-negative：r s = 0.037，P =0.711）. Similarly，there were no correlations between HBsAg and hepatic fibrosis stages（HBeAg-positive：r s = 0.087， P = 0.488 & HBeAg-negative：r s = 0.144，P = 0.148）. Nevertheless，statistically significant positive correlations were shown between HBsAg normalized to HPCV and liver inflammation grades（HBeAg-positive：r s = 0.309，P = 0.012 & HBeAg-negative：r s = 0.389，P < 0.001）. Similarly，the HBsAg normalized to HPCV and hepatic fibrosis stages were shown to be statistically significantly correlated（HBeAg-positive：r s = 0.490，P < 0.001 & HBeAg-negative：r s = 0.599， P < 0.001）.【Conclusions】Serum HBsAg normalized to HPCV but not HBsAg levels，is correlated with liver inflamma⁃ tion grades as well as hepatic fibrosis stages positively in both HBeAg-positive and HBeAg-negative CHB. But there is no difference in serum HBsAg levels normalized to HPCV between HBeAg-positive and HBeAg-negative CHB.
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Objective To investigate the effects of high fat diet on hepatic autophagy in mice and analyze the possi-ble mechanism.Methods C57BL male mice were fed with either normal diet or high-fat diet ( HFD) for 8,12 or 16 weeks .The mice were sacrificed after measuring the body weight .The mesentery and epididymal fat tissue weight ,the liver weight and the hepatic lipid accumulation were detected .The expression of hepatic AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) protein and autophagic markers including LC3Ⅱ, P 62 protein were measured by Western blot .Results HFD-fed mice displayed significantly heavier body weight at 16 weeks and significantly heavier intra abdominal fat weight and lipid overaccumulation in liver at 8,12, 16weeks(all P<0.01).Western blot showed hepatic LC3Ⅱexpression was up-regulated mildly in HFD fed mice at 8 weeks(P<0.05), but the change dramatically was reversed , hepatic LC3Ⅱ was significantly lower in HFD fed mice at 12,16 weeks, as well as P62 was increased in HFD fed animals (all P<0.05).HFD suppressed phos-phorylation of AMPK and increased phosphorylation of mTOR levels in liver at 8,12,16 weeks, compared to the normal-diet fed mice .Conclusions Our data demonstrate that hepatic autophagy is in dynamic change in high-fat diet mice , long term high-fat diet severely suppressed hepatic autophagy , which is associated with decreased p-AMPK and increased p-mTOR.
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Objective: To investigate the effect of the gene interfering technology on fatty acid synthase (FAS) gene silencing for lipid contents in human hepatic cell line HepG2 and to study the lipid metabolism related gene expression in HepG2 cells. Methods: A total of 3 pairs of small interfering RNA (siRNA) targeting different sequences of FAS mRNA were synthesized as FAS-siRNA-1, FAS-siRNA-2 and FAS-siRNA-3, meanwhile, 2 controls were established as Blank control group, in which HepG2 cells were not treated, and Negative control group, in which HepG2 cells were transfected by non-effective siRNA. The mRNA, and protein expression levels of FAS in HepG2 cells were examined by real-time lfuorescence quantitative RCR and Western blot analysis to screen the most effective pair of siRNA for FAS gene silencing; and that speciifc siRNA was transtected to HepG2 cells for 48 hours to detect the intra-/extra-cellular TG, TC levels and the mRNA expression related to lipid metabolism in HepG2 cells. Results: The screening experiment indicated that FAS-siRNA-3 was most effective for FAS gene silencing. Compared with Blank control group, the mRNA and protein expressions in FAS-siRNA-3 transfected HepG2 cells (Transfected group)decreased to (52.33 ± 3.07) % and (51.57 ± 3.14) % respectively. Compared with Blank control group, Transfected group had the reduced intra-/extra-cellular TG levels and reduced extracellular TC level; while increased mRNA expression of hepatic lipase,P<0.0001 and decreased mRNA expression of TG transfer protein in HepG2 microsome,P<0.05. Conclusion: FAS gene silencing could signiifcantly decrease the intra-/extra- cellular TG level and extracellular TC level in HepG2 cells, those ifndings need to be conifrmed by furtherin vivo andin vitro studies.
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<p><b>OBJECTIVE</b>To observe the change in the number of antibodies of preneoplastic hepatocellular carcinoma (HCC) using early treatment by Compound Phyllanthus Urinaria L. (CPUL) on patients with preneoplastic hepatitis B virus (HBV)-associated HCC.</p><p><b>METHODS</b>A total of 102 cirrhosis patients with regenerative or dysplastic nodules whose sera were tested positive for at least one of these six proteins (five up-regulated genes URG4, URG7, URG11, URG12 and URG19, and one down-regulated gene DRG2) were assigned randomly to two groups using continual random codes by SPSS software. Fifty-two patients were in the treatment group and 50 patients were in the control group. CPUL was used in the treatment group for 3 years, while the control group did not receive any treatment. The changes in HBV-DNA level, number of antibodies, and hepatocarcinogenesis occurred were observed. Patients who did not develop HCC were followed up for another 2 years.</p><p><b>RESULTS</b>HBV-DNA levels decreased ⩾2log in 22.2% (10/45) of patients in the treatment group in contrast to only 5.0% (2/40) of patients in the control group (P=0.0228). The number of antibodies that were tested positive in the treatment group (1.08±1.01) was significantly lower compared with the control group (2.11±1.12) after 24 months of drug treatment (P<0.01). Both the positive rates of anti-URG11 (33/52) and anti-URG19 (31/52) were over 60% at baseline in the two groups, and were decreased to 48.1% (25/52) and 46.2% (24/52) respectively at 36 months of drug treatment, while the rates increased to 68.0% (34/50) and 66.0% (33/50) respectively (P=0.0417, P=0.0436) in the control group. The positive rate of anti-DRG2 was increased to 55.8% (29/52) at 36 months of drug treatment, while in the control group was decreased to 36.0% (18/50, P=0.0452). Among the 102 patients who developed HCC, 2 were in the treatment group and 9 were in the control group, meaning that a significant difference between the two groups (P=0.0212). In 11 patients who developed HCC, anti-URG11 and anti-URG19 were always positive, while anti-DRG2 was negative. Patients newly developing HCC were 6 (20.0%) in the control group, and only one (2.5%) in the treatment group (P=0.0441) during 2-year follow-up after the end of the treatment.</p><p><b>CONCLUSIONS</b>Anti-URG11, anti-URG19 and anti-DRG2 could be used as early markers in the prediction of the therapeutic efficacy of CPUL in treating preneoplastic HCC. CPUL is useful in preventing or delaying the development of HBV-associated cirrhosis to HCC.</p>
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Humans , Antibodies, Viral , Blood , Carcinoma, Hepatocellular , Therapeutics , Virology , DNA, Viral , Hep G2 Cells , Hepatitis B virus , Genetics , Allergy and Immunology , Virulence , Liver Neoplasms , Therapeutics , Virology , Phyllanthus , Chemistry , Plant Extracts , Therapeutic Uses , Precancerous Conditions , VirologyABSTRACT
Objective To study the achievements and safety of Transcatheter arterial chemoembolization (TACE) associated Portal Vein Chemo-therapy (PVC) per-drug delivery system (DDS) program in preventing the recurrence of hepatic cell cancer (HCC) and Portal Vein Tumor Thrombus (PVTT).Methods 97 cases with HCC and PVTT were treated from Januay 2009 to January 2011.Patients with tumor or tumor thrombus were resected on all the cases and randomly divided into 3 groups.TACE,PVC per-DDS TACE and PVC per-DDS were given to group A,group B,and group C,respectively.Patients in the 3 groups were followed and compared on the Disease Free Survivals (DFS) and the accumulative survival rates,at 6 months,1 year and 2 years after the operation.Results After the surgery was completed in June,the 1-year,2-year,3-year survival rates and cummulative survival rate in group C was higher than in group A or group.Significant differences did no appeare in June but did show in 1 year after the surgery (P＞0.05) as well as in both 2 and 3 years,after the surgery (P＜0.01).Conclusion Patients with HCC and PVTT,the TACE chemotherapy in association with PVC per-DDS could increase both the DFSs and accumulative survival rates,when compared to the either single TACE or PVC per-DDS,after the tumor or tumor thrombus were resected.
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Objective To investigate the effect of Emodin on intracellular calcium concentration ([Ca~(2+)]i) and apoptosis of hepatic cells after simulated cold ischemia-reperfusion. Methods Glucose-oxygen deprivation, low temperature, subsequent reoxygenation and rewarming were used to induce ischemia-reperfusion injury model in cultured hepatic cells which were divided into 4 groups: control group and Emodin-treated group(100, 10 and apoptosis rate were determined by flow cytometry (FCM) respectively; the content of lactate dehydrogenase (LDH) in supernatant was tested. Results Intracellular calcium fluorescence intensity in Emodin-treated groups of high, medium and low density was 24.12±0.51, 26.35±1.34 and 39.12±1.94, respectively, which were significantly lower than 105.29±1.01 in control group(P<0.01). Apoptosis rate in Emodin-treated groups of high, (179.67±18.57)u/L in Emodin-treated groups of medium and high density respectively, which were significantly lower than (351.33±34.16)u/L in control group(P<0.01). Conclusion Emodin could reduce [Ca~(2+)]i and inhibit apoptosis of hepatic cells after simulated cold ischemia-reperfusion, thus protecting hepatic cells effectively.
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OBJECTIVE: To observe the effect of Chaihu on the hepatic cell apoptosis of experimental liver-injured mice and to discuss its mechanism. METHODS: 24 mice were randomly divided into 4 groups : blank control group, model control group, low dosage of Chaihu group and high dosage of Chaihu group, each administered with relevant medications and then killed. The expressions of Bax and Bcl-2 in the hepatic tissue of mice were measured by immunohistochemical method. RESULTS: The expression of Bax in Chaihu treatment group was significantly stronger than that in model control group (P
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0.05). The protein abundance of leptin receptor in rat hepatic cells was significantly decreased compared with the control after incubated with palmitate and oleate for 36 hours( P 0.05),but significantly decreased after 24 or 36 hours( P
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Two-stage carcinogenesis has been widely used as a method for evaluating precancerous lesion on animal experiments. Here we used diethylnitrosamine (DEN), a tumor trigger, and carbon tetrachloride (CCl4), a tumor promoter, to mimic the first two stages of hepatic carcinogenesis. Single intra-peritoneal injection of DEN 1% in combination with repeated intra-peritoneal injection of CCl4 4% for 16 weeks led to the formation of hyperplasia nodules on mouse livers. Microscopic examination also revealed dramatic changes in hepatocellular morphology and architecture: increased cell density and proliferation, abnormalities in cell division and nucleus structure. These changes were not observed in animal treated with NaCI or DEN alone. Repeated injection of CCl4 alone led to alterations on microscopic pictures but did not cause hyperplasia nodules. Our results indicate that DEN in combination of CCl4 causes abnormal proliferation of hepatic cells and evokes hepatic hyperplasia
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Hepatocytes , Cell Proliferation , Carbon TetrachlorideABSTRACT
Objective To analyze the time-density curve of the small HCCs in the arterial phase and to find out its unique features.Methods All lesions were imaged with single-level serial SCT.The attenuations of the lesion,hepatic artery and hepatic parenchyma were measured.The time-density curve was built with these CT values and their corresponding times.Results The time-density curves of the lesion and liver parenchyma were divided into three kinds:the first kind had two intersects(73%).The first one was seen at the time when the curve of the lesion went up over the one of the parenchyma and the second was seen at the point the curve came down below the parenchyma's.There was no second intersecting point in the second type(19.2%) and the curve of the lesion was below that of the parenchyma in the third (7.7%). Conclusion The initial time of the enhancement of small SHCC is (21.6?6) s.The optimal time of the enhancement of SHCC is (36?8) s.
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Objective To investigate the ischemic injury of hepatic cell caused by hepatic artery occlusion.Methods The hepatic artery was occluded in 20 dogs via operation,while the portal vein remained patent.Specimens were gained from the right liver at four time points:before occlusion of the hepatic artery,20(minutes),40 minutes and 60 minutes after artery occlusion.Each specimen was examined by HE and BCL-2 by immunohistochemistry.The gray scale of BCL-2 in HE sections was detected.Results Hepatic cellular injury was obvious 20 minutes after occlusion of the hepatic artery.Irreversible hepatic cellular injury was(observed) 60 minutes after hepatic artery occlusion.The results showed that the gray scale of BCL-2 at every time point after hepatic artery occlusion were significantly different from that before hepatic artery occlusion(P
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0.05). ConclusionsAdriamycin can induce apoptosis of cancer cells, and this is an important mechanism for its anticancer effect. This effect may be related to the down regulation of Bel-2 (expression).
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Objective:To study the expression of COX-2 and Survivin in HCC tissues and their relationship for supplying experimental evidence for gene diagnosis and treatment of HCC.Methods:The expression of COX-2 and Survivin was detected in 30 cases of hepatocellular carcinoma and 10 normal liver tissue by Flow cytometry (FCM) and immunohistochemistry (SP).Results:Two experimental methods showed that the positive expression of COX-2 and Survivin in HCC was significanly higher than that in normal liver tissue and there was significanly positive correlation between the expression of COX-2 and Survivin.Conclusion:The hyper-expression of COX-2 and Survivin in tissue can reflex the biological behavior of HCC and there are synergistic effect between them during the development of HCC.A possible mechanism is inhibition of tumor cell apoptosis through upregulating Survivin by COX-2,and promoting abnormal cell proliferation in development of hepatocellular carcinoma.
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Objective To investigate the cytotoxic effect of 103 palladium( 103 Pd) particle radiotherapy combined with 41℃ heating on human hepatocarcinoma cell line Bel-7402. Methods Human hepatocarcinoma cells (Bel-7402) were treated by water-heating and/or 103 Pd particle. The cell growth was determined with MTT assay, and the cell apoptosis was detected by the fluorescent stain of Hoechst33258. Results The cytotoxic effect of 103 Pd radiotherapy combinded with 41℃ heating on Bel-7402 cells was stronger than that of only 103 Pd radiotherapy. Conclusion 103 Pd radiotherapy and 41℃ heating had a synergistic effect on hepatocarcinoma cell Bel-7402, and 103 Pd radiotherapy had the cytotoxic effect on the surviving Bel-7402 cells after hot therapy.
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0.05). The positive rates of PDGF and PDGFR in the HCC patients with the tumor emboli of portal vein and/or biliary duct were 76.9% and 76.9%, respectively, which were significantly higher than those(25.0% and 16.7%, respectively) in the ones without(P