Objective To review the advances of target gene therapy of liver cancer. MethodsWe analyze and compare the tissuespecific carrier system or cellspecific gene expressing system from current researches of liver cancer gene therapy. ResultsArtificial synthetic DNA transfer system and modified viral vectors could efficiently transfect target cells and get highlevel expression. The ciselements of alpha fetal protein or albumin gene have been often adopted in the regulation of therapeutic gene and have shown their effectiveness. Some other gene therapy strategies also promised a good future. Conclusion Searching for more specific and universal liver cancer antigens is the key to improve the target gene therapy efficiency. The individual situation is the basis to select the best transfer system or regulatory elements in the future.
Objective To investigate the reasons and preventions of bleeding after percutaneous microwave ablation for liver cancer. Methods The data of 156 patients with liver cancer between September 2006 and December 2009 treated with percutaneous microwave ablation (226 times) were recorded. The reasons and preventions of bleeding after percutaneous microwave ablation were analyzed. Results Eleven patients (11 times) suffered from bleeding. The rate of bleeding is 4.87% (11/226), including 2 cases of biliary bleeding, 9 cases of intraperitoneal hemorrhage. All patients who suffered from bleeding firstly received medical therapy to control bleeding, 5 cases were successful; in the other 6 cases who failed in medical therapy, 1 case was stopped bleeding with opening procedures, 4 cases received transcatheter embolization to stop bleeding with gelatin sponge, 1 case died due to excessive blood loss. According to Chi-square test result, the bleeding was significantly related with liver cirrhosis, lower platelet count, obvious prolongation of prothrombin time, subcapsular tumor, Child-Pugh B/C grade, and re-ablation (P=0.044, 0.041, 0.028, 0.001, 0.016, 0.016). The multiple variables logistic regression analysis showed that liver cirrhosis, platelet count, prothrombin time, location of tumor, and Child-Pugh grade were the influential factors of bleeding after microwave ablation (OR=5.273, P=0.036; OR=8.534, P=0.043; OR=4.893, P=0.045; OR=7.747, P=0.010; OR=6.882, P=0.015). Conclusions There were some factors were significantly related with the bleeding after percutaneous microwave ablation: liver cirrhosis, abnormal blood clotting function (lower platelet count and prolongation of prothrombin time), tumor located on the surface of liver, and Child-Pugh C grade. When failed to stop bleeding with medical therapy, transcatheter embolization is an effective method to control bleeding.
ObjectiveTo understand the role of metformin on reducing incidence of type 2 diabetes mellitus (T2MD) patients complicated with liver cancer.
MethodThe related literatures of metformin treated patients with T2MD complicated with liver cancer at home and abroad in recent years were reviewed.
ResultsA large number of epidemiological and clinical data showed that the metformin might prevent the occurrence of the T2MD patients complicated with liver cancer, its mechanism was mainly inhibited the proliferation of hepatoma cells through the ATM-LKB1-AMPK-mTOR pathway, PI3K/Akt/mTOR pathway, or miRNA. The current controversy was the authenticity of the data, the influencing factors included the aging problem and characteristics of metformin user. The prospective study design rigorous remained to be clarified.
ConclusionMetformin could reduce the incidence of T2MD patients complicated with liver cancer, and could inhibit the growth of liver cancer cells, which provides a new way of thinking for the comprehensive treatment of liver cancer.
Objective To study the interferencing and anti-tumor effects of lentiviral vector of siRNA targeting IGF1R and EGFR gene of the liver cancer cell. Methods The complementary DNA containing both sense and antisense Oligo DNA of the targeting sequence was designed, synthesized and connected to the pLVTHM vector, named pLVTHM-IGF1R, into whom the EGFR-siRNA expression frame containing H1 promotor synthesized by RT-PCR was cloned to generate pLVTHM-IGF1R-EGFR-siRNA. The 293T cells were cotransfected by 3 plasmids of pLVTHM-IGF1R-EGFR-siRNA, psPAX2 and pMD2G to enclose LVTHM-IGF1R-EGFR-siRNA, which was amplified in large amount and purified by caesium chloride density gradient centrifugation for measurement of virus titer. SMMC7721 cells infected by LVTHM-IGF1R-EGFR-siRNA were infection group, the untreated SMMC7721 cells and blank vector plasmid LVTHM were two control groups (SMMC7721 cell group and blank vector group). The effect of LVTHM-IGF1R-EGFR-siRNA on IGF1R and EGFR expressions of SMMC7721 cells were detected by RT-PCR and Western blot. The antitumor potential of LVTHM-IGF1R-EGFR-siRNA to SMMC7721 cells was evaluated by Cell Counting Kit-8 assay for cell growth and TUNEL for apoptosis respectively. Results LVTHM-IGF1R-EGFR-siRNA was constructed successfully. Functional pfu titers of LVTHM-IGF1R-EGFR-siRNA was 4.58×109 pfu/ml. Protein and mRNA expression of IGF1R and EGFR of infection group were less than those of blank vector group and SMMC7721 cell group (P<0.05), LVTHM-IGF1R-EGFR-siRNA was more effective to inhibit the proliferation and promote apoptosis of SMMC7721 cells (P<0.05). Conclusion LVTHM-IGF1R-EGFR-siRNA expressing IGF1R-EGFR-siRNA can inhibit the expression of IGF1R and EGFR, and may be used for further investigation of gene therapy of liver cancer.
Objective To explore the clinical value and experience of ultrasound guided combined with laparoscopic microwave ablation in treatment for special site liver cancer.Methods The clinical data of 9 patients with liver cancer treated by ultrasound guided combined with laparoscopic microwave ablation in our hospital from February 2008 to October 2010 were analyzed retrospectively.Results There were 6 cases of primary liver cancer, 3 cases of metastatic hepatic carcinoma. Eight cases of multiple tumors, 1 case of single tumor.There were one or more lesions invading liver capsular,a total of 13 lesions in all the patients. Among them,6 lesions located in diaphragm, 3 closed to bowel, 2 neared stomach,1 located in gallbladder bed and 1 in hilar.No serious complications and no death happened during operation.The following-up time was (9.2±4.7) months (4 to 18 months), there were 2 lesions of part residual, including 1 case of microwave ablation again,1 case of percutaneous ethanol ablation, and 11 lesions of complete ablation (84.6%,11/13) 1 month after operation by CT examination.Four cases recurred 3 months after operation by CT examination, including 2 cases of microwave ablation again,1 case of percutaneous ethanol ablation,1 patient with pulmonary metastasis and giving up treatment,1 patient with poor liver function and died of liver failure 6 months after operation;1 patient with multiple lesions died of brain metastases 10 months after operation; the rest were still alive.Conclusions Ultrasound guided combined with laparoscopic microwave ablation is a safe and effective method in the treatment for special site liver cancer,the curative effect is good and worth of spread.
Objective To overview the systematic reviews/meta-analyses of radiofrequency ablation combined with transcatheter arterial chemoembolization for primary liver cancer. Methods We searched China National Knowledge Infrastructure, Wanfang, Chongqing VIP, SinoMed, PubMed, Embase, and Web of Science databases using computers, with a search deadline of December 31, 2022 for systematic reviews/meta-analyses of radiofrequency ablation combined with transcatheter arterial chemoembolization for primary liver cancer. The AMSTAR 2 scale, PRISMA statement, and GRADE grading system were used to evaluate the reporting quality, methodological quality, and evidence level. Results A total of 13 systematic reviews/meta-analyses were included, published from 2011 to 2022. The evaluation results of the AMSTAR 2 scale showed that 4 systematic reviews/meta-analyses were of low quality, while the rest were of extremely low quality, without medium to high quality systematic reviews/meta-analyses. The evaluation results of PRISMA statement showed that the scores of 9 systematic reviews/meta-analyses were 15-21, with certain reporting defects, and only 4 were relatively complete. The GRADE system evaluation of 75 evidence bodies for 9 clinical outcome indicators showed that there was no high quality of evidence, with medium quality accounting for 29%, low quality accounting for 32%, and extremely low quality accounting for 39%. Conclusions Radiofrequency ablation combined with transcatheter arterial chemoembolization can improve the 1-year and 3-year overall survival rates of patients with primary liver cancer with medium quality of evidence. However, its impact on 5-year overall survival rate, recurrence-free survival rate, complications, and whether it is more effective for hepatocellular carcinoma with a diameter of 3-5 cm still require more high-quality clinical research and systematic evaluation to verify.
Objective To investigate the growth of tumors and the natural life length of the rats after the adriamycinethylcellulose microspheres(ADM-EC mc) were injected in the rats bearing transplantable liver cancer through their hepatic arteries.Methods ADM-EC mc were infused into the proper hepatic arteries of the Wistar rats (W256). All of the rats were divided randomly into five groups, group 1: control, group 2: normal saline, group 3: conventional ADM, group 4: placebo ethylcellulose microspheres, and group 5: ADM-EC mc. Results As compared with other four groups, the ADM-EC mc (group 5) showed the best inhibition of the growth of tumors and the longest mean life length of the rats. Conclusion Hepatic arterial infusion of ADM-EC mc can inhibit the growth of the tumor, aggravate the necrosis, and improve the effects of the chemotherapy of liver cancer.
ObjectiveTo investigate the methodology of a newly developed highpressure liquid chromatography electrochemical system in urinary 8hydroxydeoxyguanosine (8OHdG) quantification. MethodsQuantification of urinary 8OHdG with ESA 5600 Coularray system among 21 children from liver cancer highrisk areas, Fusui country, in contrast with 63 controls from Nanning city, Guangxi province.ResultsThe resolution, sensitivity, linearity, precision and recovery of this approach all fully meet the requirement of routine urinary 8OHdG quantification. The mean 8OHdG level of this population was (5.26±0.41) ng/mg creatinine, higher than previous report 〔(4.62±0.091) ng/mg creatinine〕 by similar method.ConclusionWith cautious design and modification, this method is reliable and accurate in high throughput quantification of urinary 8OHdG.
Objective
To determine the value of contrast-enhanced ultrasound (CEUS) in the differentiation of primary liver cancer (PLC) and hepatic alveolar echinococcosis (HAE).
Methods
The data of 56 patients with PLC or HAE were collected between January 2010 and May 2015. Grayscale and CEUS features of the patients were analyzed retrospectively. The frequency of each imaging finding, including calcification, arterial enhancement, and internal enhancement were evaluated and compared.
Results
Statistically significant difference of the proportion of gender and age were detected between the two groups (P=0.013, 0.002). Thirty-eight PLC lesions were detected in 32 patients. The diameters of PLC lesions were 3-10 cm with an average of (5.6±2.1) cm. Thirty-two HAE lesions were found in 24 patients. The diameters of HAE lesions were 4-12 cm with an average of (9.1±4.4) cm. Statistically significant difference of lesion size and the incidence rate of calcification (5.3% vs. 75.0%) were seen between PLC and HAE (P<0.001). Peripheral enhancement were seen in 100.0% (38/38) PLC lesions, including 84.2% (32/38) hyperenhancement and 15.8% (6/38) dendritic hyperenhancement. All PLC lesions demonstrated hypoenhancement in late phase. Irregular peripherally hyperenhancement both in arterial and late phase were detected in 43.8% (14/32) HAE lesions. The other 56.2% (18/32) HAE lesions showed no peripheral enhancement both in arterial and late phase. No internal enhancement were seen in HAE lesions. The presence of arterial enhancement (100.0% vs. 43.8%) and absence of internal enhancement (0 vs. 100.0%) were significantly different between PLC and HAE (P<0.001).
Conclusions
PLC is predicted by arterial phase hyperenhancement and late phase hypoenhancement on CEUS. HAE is predicted with calcification on baseline sonography and internal non-enhancement on CEUS. Arterial phase enhancement is less common and less intensive in HAE than in PLC which also contributes to the differentiation of these lesions.
Objective To study the mechanism of high intensity focused ultrasound (HIFU) and discuss its clinical significance in the treatment of mid-late stage liver cancer. Methods The patients with mid-late stage liver cancer were treated with HIFU. The changes of photography, pathology and immunology after operation were evaluated. Results It was shown that the results of the photographic, pathologic and immunologic examinations changed during the treatment of the patients with HIFU. Conclusion HIFU is effective and safe for the treatment of mid-late stage liver cancer.