Objective To investigate relationship between hypoxia microenvironment and occurrence and development of hepatocellular carcinoma (HCC). Method The relevant literatures on researches of the relationship between the hypoxic microenvironment and the HCC were review and analyzed. Results The hypoxia microenvironment played an important role in inducing the drug resistance and angiogenesis of the HCC cells, and it was an important factor of affecting the ability of tumor metabolism, invasion, and migration. The hypoxia microenvironment could up-regulate the expression of hypoxia-inducible factors (HIFs) and promote its transcriptional activity, promote the expression of the vascular endothelial growth factor gene, and regulate the neovascularization in the tumor. Among them, the HIF-1α played a major role in regulating the angiogenesis, immune escape, tumor invasion and metastasis-related gene expression, participating in the glycolysis, regulating lysyl oxidase 2 and thus regulated epithelial-mesenchymal transition, then promoted the invasion and metastasis of the HCC; HIF-2α was a key regulator of the malignant phenotype involving in the cell proliferation, angiogenesis, apoptosis, metabolism, metastasis, and resistance to chemotherapy. The hypoxia microenvironment posed some difficulties for the treatment of HCC, but it was also a potential therapeutic breakthrough. Conclusion Hypoxia microenvironment can promote invasion and metastasis of HCC through various mechanisms, which provides new targets and strategies for clinical treatment of HCC.
Objective To investigate the association of the expression of CD15 mRNA with the invasion and prognosis of hepatocellular carcinoma (HCC) and the expression of nm23H1 mRNA. Methods In situ hybridization and immunohistochemistry methods were used to detect the expression of CD15 mRNA and protein nm23H1 mRNA in HCC.Results In 99 cases of HCC, the positive rate of CD15 mRNA,its protein and nm23H1 mRNA were 38.4%, 36.4% and 76.8%, respectively. The expression of CD15 mRNA was consistent with its protein and negatively correlated with the expression of nm23H1 mRNA. The expression of CD15 mRNA and its protein, nm23H1 mRNA were associated with the invasiveness and metastasis of HCC and the prognosis of HCC patients. Conclusion The detection of CD15 expression could be a new pathological biology index to judge the metastasis and prognosis of HCC.
ObjectiveTo investigate the expression and clinical significance of cytochromes b561 (CYB561) in hepatocellular carcinoma (HCC). MethodsThe expression of CYB561 mRNA in HCC tissues and its relationship with prognosis were analyzed by database data. Immunohistochemistry (IHC) was used to detect the expression of CYB561 protein in 61 matched HCC tissues and their adjacent tissues, and the relationship between CYB561 protein expression and clinicopathological features and prognosis of HCC was analyzed. Kaplan-Meier method was used to draw the survival curve and Cox proportional hazard regression model was used to analyze the correlation between the expression of CYB561 protein and the prognosis of HCC. ResultsThe analysis of database data showed that the relative expression of CYB561 mRNA in HCC tissues was higher than that in adjacent tissues (P<0.001). Compared with HCC patients with negative expression of CYB561 mRNA, HCC patients with positive expression of CYB561 mRNA had worse overall survival (OS), relapse-free survival, progression-free survival and disease-free survival (all P<0.05). The results of IHC showed that the positive rates of CYB561 protein in HCC tissues and adjacent tissues were 57.38% (35/61) and 21.31%(13/61), respectively. The former was higher than the latter, with statistical significance (χ2=16.624, P<0.001). Survival analysis showed that the OS of patients with positive expression of CYB561 protein was worse than that of patients with negative expression (P<0.05). Multivariate Cox proportional hazard regression analysis showed that the positive expression of CYB561 protein was a risk factor for postoperative OS in HCC patients [HR=3.308, 95%CI (1.344, 8.144), P=0.009]. ConclusionCYB561 is positively expressed in HCC and suggests a worse survival, and may serve as a potential prognostic biomarker for HCC.
Objective To study the clinical significance of DNA content and expression of nm23-H1, C-erb B-2 and p53 oncoproteins in hepatocellular carcinoma. Methods DNA content was measured after DNA feulgen’s dyeing, the expression of nm23-H1, C-erb B-2 and p53 oncoproteins was detected immunohistochemically. Results The incidence of aneuploid DNA content was 50.0% (12/24) in ≤5 cm group, and was 82.1% (23/28) in ＞5cm group; aneuploid DNA content was related with liver metastasis and cancerous thrombosis. The expression of nm23-H1 in HCC with liver metastasis was higher than that without metastasis. The positive rate of p53 in HCC with canerous thrombosis was higher than that without cancerous thrombosis. The positive rates of nm23-H1 and p53 in HCC with aneuploid DNA content were higher than those with diploid DNA content. The positive rate of C-erb B-2 did not have significantly difference between groups. Postoperative survival rates were possibly related with DNA content as well as expression of nm23-H1, and p53 oncoproteins. Conclusion Aneuploid DNA conten, expression of nm23-H1 and p53 oncoproteins are closely related with the invasiveness of HCC, and have remarkably clinical significance.
Objective To examine the effects of newly designed LY52 on the expression of matrix metalloproteinases and invasive ability of hepatocellular carcinoma HepG2 cells. Methods The effects of LY52 on the proliferations of HepG2 cells were detected by MTT assay. Gelatin zymography and Western blot were used to detect the effects of LY52 on matrix metalloproteinase-2 expression in the cell line. Transwell chamber assay was used to detect the effects of LY52 on the invasion of the cells. Results No obvious inhibitory or cytotoxicity effects of LY52 was found in lower concentrations (lt;200 μg/ml) of LY52. Gelatin zymography and Western blot showed that matrix metalloproteinase-2 expression were inhibited by LY52 in a dose-dependent manner in HepG2 cells. Furthermore, transwell chamber assay showed that LY52 could significantly inhibit the invasion of the cell line in a dose-dependent manner.Conclusion The results suggest that LY52 may inhibit the invasion of hepatocellular carcinoma cells by suppressing the matrix metalloproteinase-2 activity.
ObjectiveTo investigate the value of multi-disciplinary team (MDT) for the diagnosis and treatment of postoperative recurrence of hepatocellular carcinoma (HCC). MethodThe clinicopathologic data of a patient with giant HCC (66 mm×60 mm×102 mm) who was multiple intrahepatic metastases with portal vein tumor thrombus after radical resection, admitted to the Department of Hepatobiliary Surgery of Sichuan Provincial People’s Hospital, were gathered. ResultsThe patient was a middle-aged male. The multiple recurrent intrahepatic metastases combined with portal vein right branch thrombosis was found at 1 month after radical hepatectomy. After MDT discussion and evaluation, the hepatic arterial infusion chemotherapy combined with immunotherapy and targeted therapy (chemical drugs regimen was FOLFOX, immunotherapy drug was sindilizumab, targeted therapy drug was lenvatinib) was administered. After 3 times conversion therapy, and most of the intrahepatic lesions liquefied and necrotic and shrunk markedly or disappeared. After further discussion and evaluation by MDT, radical surgical resection was performed. The postoperative pathological examination results showed granulomatous inflammation with necrosis, and no exact liver cancer cells were detected. At 6 months after surgery, no tumor recurrence was observed.ConclusionsFor early recurrence combined with portal vein thrombosis after radical resection for HCC, hepatic arterial infusion chemotherapy combined with immunotherapy and targeted therapy may still be effective and even has an opporunity of surgical therapy. MDT discussion can provide the best treatment plan for patient with recurrent liver cancer, leading to a better clinical outcome for them.
Laparoscopic hepatectomy is routinely used in the surgical treatment of hepatocellular carcinoma, and has formed a standardized operating procedure. Tumors located in the segments Ⅶ and Ⅷ of liver as well as the paracaval subsegment of caudate lobe are considered to be difficult sites for laparoscopic hepatectomy due to the deep anatomical location, proximity to important vascular structures, difficulty in exposing the visual field under laparoscopy, and limited operating space. Based on the experience of our team and related research reports, the authors analyzed and summarized countermeasures for the difficulties of laparoscopic hepatectomy in the treatment of hepatocellular carcinoma in difficult sites. Adhering to the tumor-centered and margin-based principles, accurate preoperative assessment, selection of the correct surgical approach, designing liver resection plane guided by hepatic vena while taking into account portal vein territory, and giving preference to ananatomical hepatectomy while preserving functional liver parenchyma as much as possible are the prerequisites for ensuring minimally invasive and oncology benefits for patients with hepatocellular carcinoma in difficult sites.
Objective To explore the effects of overexpression of human tissue inhibitors of metalloproteinase-1 (hTIMP-1) on proliferation of human liver cancer cell line HepG2 in vitro. Methods A recombinant adenoviral vector containing full-length cDNA of hTIMP-1 was generated and transfected into HepG2. The viral titer was checked by measuring GFP, and the expression of hTIMP-1 in vitro was detected by the techniques of Western blot and semi-quantitative RT-PCR. The ultrastructure was observed by transmission electron microscope and the effects of overexpression of hTIMP-1 on proliferation of HepG2 in vitro was analyzed by MTT assay and growth curve. Results The resultant AdhTIMP-1 was successfully constructed and the expression of hTIMP-1 was detected by Western blot and RT-PCR. The growth and proliferation of HepG2, which had been transfected with AdhTIMP-1, was significantly inhibited. Conclusion The proliferation of HepG2 was markedly inhibited by recombinant adenovirus-mediated overexpression of hTIMP-1, which may pave the way for further application in liver gene therapy.
Objective To investigate the value of contrast enhanced ultrasound (CEUS) in evaluating the short term therapeutic response to radiofrequency ablation (RFA) of primary hepatocellular carcinoma. Methods One hundred and ten lesions were studied in 96 patients. Each patient underwent CEUS within a week before RFA, the number, size, border, inner echo and perfusion pattern of lesions were observed. One month after ultrasound-guided RFA, color Doppler flow imaging, CEUS and contrast enhanced computed tomography (CECT, reference standard) were performed to assess the therapeutic response. Results Before RFA, in 96 cases with 110 lesions, 83 lesions showed homogeneous hyper-enhancement and the other 27 heterogeneous hyper-enhancement in arterial phase, and 98 lesions were hypo-enhanced in portal venous phase and late phase and the other 12 iso-enhanced. One month after RFA, 99 of 110 lesions were found no-enhancement in entire CEUS procedure, while 11 lesions showed local enhancement on the edge of lesion. Ninety-six of 110 lesions showed no-enhancement and other 14 with irregular enhancement by CECT. There was no statistical significance between CEUS and CECT (χ2=0.406, Pgt;0.05). Fourteen lesions as tumor residual by CECT were underwent RFA again, and then 1 month after RFA no-enhancement was showed by both CECT and CEUS. Conclusion CEUS can play a role in assessing the short term therapeutic response to RFA of hepatocellular carcinoma.