Research progress of long non-coding RNA in the invasion and metastasis of hepatocellular carcinoma / 医学研究生学报

Long non-coding RNA (LncRNA) refers to a class of RNA molecules that are not capable of encoding a protein that is greater than 200 nucleotides in length. It is suggested that LncRNA plays a promoting or inhibiting role in regulating tumor growth, invasion and metastasis through a variety of molecular mechanisms. Primary hepatocellular carcinoma (HCC) is the second leading cause of cancer death in China. Recurrence and metastasis of HCC after operation is the main cause of low survival rate. Therefore, systematically explore the mechanism of lncRNA that promotes or inhibits the invasion and metastasis of HCC, and contributes to the targeted therapy, prediction of recurrence and metastasis and prognosis of HCC. This article reviews the recent research on the mechanism of LncRNA and invasion and metastasis of HCC, in order to provide new ideas for the prevention and treatment of HCC.

Rehepatectomy and radiofrequency ablation for patients with recurrent hepatocellular carcinoma / 中国实用外科杂志

OBJECTIVE: To observe the safety and efficacy of rehepatectomy and radiofrequency ablation for patientswith recurrent hepatocellular carcinoma(HCC).METHODS: A consecutive sample of 159 recurrent HCC patients whounderwent rehepatectomy(n=77) or radiofrequency ablation(n=82) from January 2005 to December 2014 were analyzedretrospectively. Propensity score analysis was used. The Kaplan-Meier method was used for survival analysis.RESULTS: Propensity score analysis chose 41 pair patients. Patients in the radiofrequency ablation group were with lower rate ofperioperative mortality and morbidiy,shorter length of hospital stay. When calculate the survival time from the date ofrehepatectomy or radiofrequency ablation,or calculate the survival time from the date of the first hepatectomy,the twoarms showed similar overall survival(P=0.258,0.820). Moreover,overall survival were similar after propensity scoreanalysis(P=0.443,0.917).CONCLUSION: Radiofrequency ablation was safety,associated with shorter length of hospitalstay and similar long-term overall survival with rehepatectomy for recurrent HCC.

Traditional herbal medicine in preventing recurrence after resection of small hepatocellular carcinoma: a multicenter randomized controlled trial / 中西医结合学报

<p><b>BACKGROUND</b>Disease recurrence is a main challenge in treatment of hepatocellular carcinoma (HCC). There is no generally accepted method for preventing recurrence of HCC after resection.</p><p><b>OBJECTIVE</b>To compare the efficacy of a traditional herbal medicine (THM) regimen and transarterial chemoembolization (TACE) in preventing recurrence in post-resection patients with small HCC.</p><p><b>DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS</b>This is a multicenter, open-label, randomized, controlled study, which was undertaken in five centers of China. A total of 379 patients who met the eligibility criteria and underwent randomization were enrolled in this trial. One hundred and eighty-eight patients were assigned to the THM group and received Cinobufacini injection and Jiedu Granule, and the other 191 patients were assigned to the TACE group and received one single course of TACE.</p><p><b>MAIN OUTCOME MEASURES</b>Primary outcome measures were the annual recurrence rate and the time to recurrence. Incidence of adverse events was regarded as the secondary outcome measure.</p><p><b>RESULTS</b>Among the 364 patients who were included in the intention-to-treat analysis, 67 patients of the THM group and 87 of the TACE group had recurrence, with a hazard ratio of 0.695 (P = 0.048). Median recurrence-free survival of the patients in the THM and TACE groups was 46.89 and 34.49 months, respectively. Recurrence rates at 1, 2 and 3 years were 17.7%, 33.0% and 43.5% for the THM group, and 28.8%, 42.5% and 54.0% for the TACE group, respectively (P = 0.026). Multivariate analysis indicated that the THM regimen had a big advantage for prolonging the recurrence-free survival. Adverse events were mild and abnormality of laboratory indices of the two groups were similar.</p><p><b>CONCLUSION</b>In comparison with TACE therapy, the THM regimen was associated with diminished risk of recurrence of small-sized HCC after resection, with comparable adverse events. TRIAL REGISTRTION IDENTIFIER: This trial was registered in the Chinese Clinical Trial Registry with the identifier ChiCTR-TRC-07000033.</p>

Synthesis of colon-specific prodrug of indomethacin and its inhibitory effect on liver metastasis from colon cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To develop a colon-specific prodrug of Indomethacin microbially triggered, carry out in vitro/in vivo evaluation of drug release, and appraise its inhibitory effect on liver metastasis from colon cancer.</p><p><b>METHODS</b>Indomethacin prodrugs were synthesized and characterized by FTIR and NMR, and dissolution test simulating gastrointestinal tract was employed to screen the colon-specific prodrug. Then, the pharmacokinetic profile of portal vein and peripheral blood in Sprague-Dawley rats was studied. Lastly, the inhibitory effect on liver metastasis from colon cancer in nude mice was observed.</p><p><b>RESULTS</b>The chemical structure characterized by FTIR and NMR demonstrated that six kinds of indomethacin-block-amylose with different drug loading (IDM-AM-1-6) were synthesized, among which IDM-AM-3 was degraded 1.3%, 9.3% and 95.3%, respectively, in simulated gastric fluid for 4 h, small intestine for 6 h, and colon for 36 h. The pharmacokinetic test of IDM-AM-3 showed that absorption was delayed significantly (P < 0.01), peak time [(11.35 + or - 2.45) h], elimination half-life [(16.74 + or - 4.04) h] and mean residence time [(22.27 + or - 0.52) h] were significantly prolonged (P < 0.01), as well as peak serum concentrations [(9.69 + or - 2.40) mg/L] and AUC(0-t) [(236.7 + or - 13.1) mg x L(-1) x h] were decreased markedly (P < 0.01) as compared with those of IDM regarding to portal vein. Additionally, its AUC(0-t) in peripheral blood was remarkably lower than that in Portal vein (P < 0.01). The tumor suppression observation showed that it could remarkably reduce the number of liver metastases in contrast to IDM (P < 0.05).</p><p><b>CONCLUSION</b>Colon-specific IDM-AM-3 possesses advantage of sustained release in portal vein providing some experimental basis for colon-specific delivery system applied to sustained release in the portal vein.</p>

Diagnosis and treatment of primary clear cell carcinoma of the liver / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathological features, diagnosis, treatment and prognosis of primary clear cell carcinoma of the liver (PCCCL).</p><p><b>METHODS</b>The clinicopathological data of 24 cases with pathologically proven PCCCL in the First Affiliated Hospital of Guangxi Medical University from May 1996 to December 2003 were collected and analyzed.</p><p><b>RESULTS</b>There were 21 males and 3 females in this group, with an average age of 46 years (range: 30 approximately 78 years). HBV infection was detected in 83.3%, and AFP expression was found in 75.0% of them. Of the 24 cases, 28 tumors were found with an average size of (6.64 +/- 5.54) cm. Liver cirrhosis was found in 75.0% of the patients. Macroscopic and microscopic tumor thrombi were found in 20.8% and 29.2%, respectively. Lymph node metastasis was found in 4.2% of the patents. The 1-, 3-, and 5-year overall survival rates of the 24 cases were 75.0%, 41.7% and 27.8%, respectively, with a median survival time of 29 months.</p><p><b>CONCLUSION</b>The clinical characteristics of primary clear cell carcinoma of the liver are similar to that of common hepatocellular carcinoma. It is difficult to be diagnosed preoperatively and final diagnosis depends on pathological examination. Surgical resection is an effective way to achieve favorable treatment outcome and even long-term survival.</p>

Comparative proteomic approach in differentiating multicentric occurrence and intrahepatic metastasis in multinodular hepatocellular carcinomas / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Multinodular hepatocellular carcinoma(HCC) might originate from multicentric occurrence (MO) or intrahepatic metastasis(IM). This study was to find out proteins which play important roles in clonal origin of multinodular hepatocellular carcinoma bt screening the differentially expressed proteins between the MO and IM tissues using comparative proteomic analysis.</p><p><b>METHODS</b>Total protein extracted was separated by two-dimensional gel electrophoresis. Comparative analyses of the 2-DE protein patterns between the two groups were carried out using computerized imaging techniques. Proteins exhibiting significant alternations were subsequently isolated and identified by mass spectrometry.</p><p><b>RESULTS</b>A total 1025+/-52 and 900+/-98 spots were detected in the protein profile in IM and MO, respectively. Twenty-five protein spots were statistically different at expression levels between the two groups. Twenty of them were identified by MALDI-TOF-MS and bioinformatics.</p><p><b>CONCLUSIONS</b>The protein profile of MO HCC tissues is different from that in IM HCC tissues. The twenty differentially expressed proteins might play a key role in the carcinogenesis and progression of multinodular HCC. These newly identified proteins might be potential and valuable biomarkers for identifying the multinodular HCC of clonal origin.</p>

Application of polymerase chain reaction with confronting two-pair primers in aldehyde dehydrogenase-2 typing / 中华预防医学杂志

<p><b>OBJECTIVE</b>To study the distribution of aldehyde dehydrogenase-2 (ALDH2) polymorphisms between healthy Zhuang and Han ethnic individuals in Guangxi Autonomous Region and its influence to the behaviors of alcohol consumption.</p><p><b>METHODS</b>Polymerase chain reaction with confronting two-pair primers (PCR-CTPP) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques were used to genotype ALDH2, respectively, and alcohol consumption was recorded in a constructed questionnaire.</p><p><b>RESULTS</b>The frequencies of ALDH2 alleles (ALDH2(1)/ALDH2(2)) among Zhuang and Han ethnics were 0.511, 0.489 and 0.508, 0.492 respectively (chi2 = 0.001, P > 0.05). The ALDH2 genotypes were verified with PCR-RFLP method. The frequencies of ALDH2(1) genotype in alcoholics (> or = 3 times drinking per week) were 35.59% and 15.67% in Zhuang and Han groups respectively (chi2 = 5.800, P = 0.016).</p><p><b>CONCLUSION</b>There was no significant different distribution of ALDH2 genotype among healthy Zhuang and Han ethnic people. The genotype of ALDH2 in different ethnicity might influence individual behavior of alcohol consumption.</p>

Synergistic effect of HBV infection, alcohol and raw fish consumption on oncogenisis of primary hepatic carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the correlation of eating raw fish with primary hepatic carcinoma (PHC), and to investigate the synergistic effect of HBV infection, alcohol consumption and eating raw fish on the oncogenesis of PHC.</p><p><b>METHODS</b>A hospital-based case-control study was conducted among 500 PHC patients and 500 non-cancerous patients in order to compare the history of eating raw fish. The synergistic pathogenetic action of eating raw fish, HBV infection and alcohol consumption on carcinogenesis of PHC was analyzed by crossover analysis and multiple logistic regression.</p><p><b>RESULTS</b>The rates of eating raw fish in the past between the case (54.8%) and the control group (8.4%) were significantly different (P < 0.001). OR value of suffering PHC in the patients who ate raw fish in the past was 13.6 (95% CI: 9.1-19.5) when compared with the non-cancerous patient. HBV infection, alcohol consumption and eating raw fish showed an interactive effect on the development of PHC, with a relative excessive risk of interaction(RERI) of 195.3 and 17.8; attributable proportion of interaction (API) of 0.8630 and 0.5251; and synergy index (S) of 7.5 and 2.8, respectively.</p><p><b>CONCLUSION</b>A history of eating raw fish may be an important risk factor for suffering primary hepatic carcinoma. HBV infection, alcohol consumption and eating raw fish may have a synergistic effect on the developing of primary hepatic carcinoma.</p>

Associated factors in modulating aflatoxin B1-albumin adduct level in three Chinese populations.

To elucidate the potential factors modulating exposure to aflatoxin B1 (AFB1) in three Chinese populations, an epidemiologic study was conducted in Fusui County and Nanning City of Guangxi Province and Chengdu City of Sichuan Province. The incidence rates of hepatocelluar carcinoma (HCC) for males in these three regions were 92-97 per 100,000, 32-47 per 100,000, and 21 per 100,000, respectively. Eighty-nine residents from Fusui, 196 residents from Nanning, and 118 residents from Chengdu were screened for AFB1-albumin adduct (AAA) levels and hepatitis virus (HBV, HCV, HDV, HEV, and HGV) infections, as well as liver biochemistry (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], y-glutamyl transpeptidase [GGT], 5'-nucleotidase, globulin [GLO], direct bilirubin, indirect bilirubin, and bile acid levels). At least one marker of hepatitis virus (HV) infection was present in 47.2% (42/89) of subjects from Fusui, while in Nanning and Chengdu the values were 15.8% (31/196) and 22.0% (26/118), respectively. In contrast to females, a higher level of AAA was observed in males; the difference was statistically significant in both the Nanning (P = 0.023) and the Chengdu (P = 0.026) subjects. In the Chengdu group, there was a significantly higher level of AAA in cases with HV infection (P = 0.041). There was a close association between AAA level and BMI in the adults without HV infection (r = 0.148, P = 0.044). Also, AAA was closely associated with DBIL and GGT in non-HV-infected minors (P < 0.05), closely associated with ALB, GLO, and GGT in HV-infected minors (P < 0.05), and closely associated with IBIL, GLO, TBA, and AST in non-HV-infected adults (P < 0.01). The co-effect of HV infection and AFB1 exposure may be responsible for the high risk of HCC in the Fusui region, whereas age, gender, BMI, and HV infection may modify individual aflatoxin levels. The relationship between AAA level and liver biochemistry indicates injury induced by aflatoxin to both hepatic parenchyma and biliary tract. But the associations vary with age and HV infection status.