Expression and role of programmed cell death ligand-1 in sorafenib-resistant hepatocellular carcinoma cells / 第二军医大学学报

Objective To explore the expression and role of programmed cell death ligand-1 (PD-L1) in sorafenib-resistant human hepatocellular carcinoma cells. Methods Sorafenib-resistant human hepatocellular carcinoma cell lines (Hep3B-SR, HepG2-SR) were established by the procedure of stepwise increase in sorafenib concentrations. CCK-8 assay was used to detect half inhibition concentration (IC50). The expressions of P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and PD-L1 were examined by Western blotting and qPCR. The expression of PD-L1 was silenced by transfecting siRNA into the drug-resistant cells, and the silencing efficiency was tested. After silencing the expression of PD-L1 in the drug-resistant cells, CCK-8 assay was used to detect IC50, the drug-resistance index was calculated, and the expressions of P-gp and MRP1 were examined. Then cell proliferation assay, wound healing assay, colony formation assay and flow cytometry were applied to examine cell proliferation, migration, clone formation and apoptosis, respectively. Results The drug-resistance indexes of Hep3B-SR and HepG2-SR were 5.4 and 5.2, respectively. The expressions of P-gp, MRP1 and PD-L1 in the drug-resistant cells were significantly up-regulated in comparison with the parental cells (all P0.01). After inhibiting the expression of PD-L1, the drug-resistance indexes of Hep3B-SR and HepG2-SR decreased to 1.8 and 1.5, respectively, and the expressions of P-gp and MRP1 were down-regulated (all P0.01). Silencing the PD-L1 expression could significantly inhibit the proliferation, migration and colony formation of drug-resistant cells, and could significantly promote the apoptosis (all P0.01); and these effects were strengthened by combining sorafenib. Conclusion PD-L1 is highly expressed in sorafenib-resistant hepatocellular carcinoma cells. Inhibition of PD-L1 expression can partially reverse the drug-resistance of the cells and significantly enhance the anticancer effect of sorafenib. Inhibiting the expression of PD-L1 can effectively repress the growth of sorafenib-resistant hepatocellular carcinoma cells, which is more if combining with sorafenib.

To evaluate the results of treatment of liver cell carcinoma by method of chemical plug of liver artery on 134 patients at Bach Mai Hospital

The study was performed on 134 patients of primary liver cell cancer, treated through 294 episodes of chemical plug using lipiodol through the arteries, in order to evaluate the efficacy of treatment by the method of chemical plug of liver artery and to give some imaging diagnostic factors related to the effect of treatment. Results showed that all cases were intervented favorably, without death by the technique. In majority of cases, chemical improvements were notified (weight gain, pain relief in the liver...) > 6 months survival reported in 82.35%, > 12 months survival 48.24%, mean survival duration 16 months. In comparison with palliative treatment, the method of liver artery chemical plug gave higher efficacy

Remarks on the results of tying esophage vena in patients with liver cell carcinoma associated with liver sclerosis

The study carries on 30 patients with hepatocellular carcinoma treated by embolism liver artery by thrombosis. Following clinical and laboratory on form includes: anamnesis, medical history, symptom and entity, immune, biochemical, endoscope. The result relies on scale of child-pugh A/B/C = 8/18/4. The result of hemostatic: good 73.3%, failed 26.6%. Association between the result of treatment and esophageal varices: the rate death of patients with esophageal varices 3 degree is 87.3%. Sign of clinical and paraclinical of hepatocellular carcinoma complicating liver cirrhosis and bleeding due to rupture of esophageal vein is also grave stage of disease. The effect hemostatic of esophageal varices knot using knot method on hepatocellular carcinoma is 73.3%. The death rate associated to varix level and red mark of esophageal vein

Effect of 1-A ( OH ) D3 on Steroid Induced Bone Loss in Frequently Relapsing Childhood Nephrotic Syndrome

CT guided percutaneous fine-needle aspiration (FNA) of the liver for both cytologic and histologic examination has great value in diagnosing liver malignancy. From March, 1986 to April, 1990, 62 patients with the clinical impression of liver mal- ignancy underwent CT guided percutaneous FNA biopsy. Of these, 43 cases were revi- ewed for this study, 19 were reported to be liver cell carcinoma, 2 were adenocarcinoma, 11 were reported as anaplastic cell present, and the rest (11 cases) were negative (9) or necrotic (2). Among the 11 cases of the last group, 9 were diagnosed as liver cell carcinoma and 2 were necrotic histologically. Retrospective review, in order to clarify the cause of cytologic diagnostic error, of both cytologic and histologic slides of all cases showed discordance of 23% between these diagnoses and sensitivity is 93.9% and specificity is 90.9%. The reasons were as follows ; 1) the lack of awareness of tumor cells of well differentiated liver cell carcinoma (4 cases), 2) missed tumor cells due to too scanty cellularity (1 case), 3) improper smear (2 cases) and no tumor cell in the cytologic smears (3 cases). In such cases, at the initiation of FNA, a correct diagnosis of liver malignancy could only be made by a combination of cytologic and histologic examinations. However after three years' exper- ience we can conclude that cytomorphologic features of liver cell carcinoma are sufficiently distinctive from other liver malignancies to be diagnostic.

The Aberrant Expression of p53 Protein in Liver Cell Carcinoma

This study was carried out to evaluate the aberrant expression of p53 protein using immunobistochemical method in 54 surgically resected liver cell carcinomas and to correlate it with clinical and pathological findings. Twenty five out of 54 cases(46%) showed positive reaction in the nucleus of liver cell carcinoma and negative reaction in associated 30 cases of cirrhosis, one case of adenoma and two cases of adenomatous hyperplasia. The p53 protein expression was associated with alpha-FP level(p<0.05), but not associated with HBsAg positivity. It was significantly associated with WHO classification, Edmondson-Steiner grade and nuclear grade p53(p<0.05), but not associated with tumor size, capsule formation, portal vein invasion, cirrhosis in surrounding tissue, Eggel classification, special cell type and mitosis. In conclusion, our results suggest that the aberrant expression of p53 protein can be an advisory factor, at least, for prognosis evaluation.

Cytologic Diagnosis of hepatocellular Carcinoma by Fine-Needle Aspiration Biopsy / 대한세포병리학회지

CT guided percutaneous fine-needle aspiration(FNA) of the liver for both cytologic and histologic examination has great value in diagnosing liver malignancy. From March, 1986 to April, 1990, 62 patients with the clinical impression of liver malignancy underwent CT guided percutaneous FNA biopsy. Of these, 43 cases were reviewed for this study, 19 were reported to be liver cell carcinoma, 2 were adenocarcinoma, 11 were reported as anaplastic cell present, and the rest (11 cases) were negative (9) or necrotic (2). Among the 11 cases of the last group, 9 were diagnosed as liver cell carcinoma and 2 were necrotic histologically. Retrospective review, in order to clarify the casuse of cytologic diagnostic error, of both cytologic and histologic slides of all cases showed discordance of 23% between these diagnoses and sensitivity is 93.9% and specificity is 90.9%. The reasons were as follows :1) the lack of awareness of tumor cells of well differentiated liver cell carcinoma (4 cases), 2) missed tumor cells due to too scanty cellularity (1 case), 3) improper smear (2 cases) and no tumor cell in the cytologic smears (3 cases). In such cases, at the initiation of FNA, a correct diagnosis of liveer malignancy could only be made by a combination of cytologic and histologic examinations. However after three years' experience we can conclude that cytomorphologic features of liver cell carcinoma are sufficiently distinctive from other liver malignancies to be diagnostic