Hypoxia is a common characteristic of hepatocellular carcinoma (HCC) associated with reduced response to chemotherapy, thus increasing the probability of tumor recurrence. Astrocyte elevated gene-1 (AEG-1) has been involved in a wide array of cancer progression including proliferation, chemoresistance, angiogenesis and metastasis, but its effect on HCC chemoresistance induced by hypoxia is unclear. In this study, expression of AEG-1 and multiple drug resistance (MDR-1) were examined in HCC using immunohistochemical staining and RT-PCR. Furthermore, their expression levels were detected in HCC HepG2 cells in normoxia or hypoxia via RT-PCR and Western blot assays. Specific shRNAs were used to silence AEG-1 expression in HepG2 cells. Results showed AEG-1 and MDR-1 expression were higher in HCC tissues than in adjacent normal tissues. Incubation of HepG2 cells in hypoxia increased expression of AEG-1 and MDR-1, compared to incubation in normoxia. Exposure to hypoxia blunted sensitivity of HepG2 cells to Adriamycin, 5-fluorouracil and cis-platinum, as evidenced by modest alterations in cell viability and apoptosis rate, however the sensitivity was elevated with AEG-1 knockdown. PI3K/AKT/HIF-1/MDR-1 pathway was attenuated following AEG-1 knockdown in hypoxia. Based on these data, it was suggested that AEG-1 is associated with hypoxia-induced hepatocellular carcinoma chemoresistance via regulating PI3K/AKT/HIF-1/MDR-1 pathway. This study uncovered a novel potential target for development of an effective therapy against hypoxia-induced HCC chemoresistance.
To determine the influence of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) interference on SW579 cell lines in thyroid cancer.We designed 2 pairs of siRNA interference sequences, transfected them into SW579 cell line with liposome, and detected the interference with RT-PCR method. For successfully interfered cell lines, the changes in cell proliferation, cell cycle, and the expression of related proteins in mitogen-activated protein signal-regulated kinase /extracellular signal-regulated kinase (MEK/ ERK) signal pathway were detected.After 2 pairs of siRNA transfection, the expressions of BRAF mRNA and protein of SW579 cell lines were significantly inhibited (P<0.01). The proliferation was inhibited, the cell cycle was changed, G1/S phase increased, and MEK/ERK signal pathway was inhibited.Inhibition of growth and proliferation of SW579 cell lines by BRAF may be functioned by de-activating MEK/ERK signal pathway.
Engulfment and cell motility 1 (Elmo1) has been linked to the invasive phenotype of glioma cells. The use of Elmo1 inhibitors is currently being evaluated in hepato-cellular carcinoma (HCC), but the molecular mechanisms of their therapeutic effect have yet to be determined. Elmo1 expression in HCC tissue samples from 131 cases and in 5 HCC cell lines was determined by immunohistochemistry, quantitative RT-PCR and western blotting. To functionally characterize Elmo1 in HCC, Elmo1 expression in the HCCLM3 cell line was blocked by siRNA. Cell migration was measured by wound healing and transwell migration assays in vitro. Elmo1 overexpression was significantly correlated with cell invasion and the poor prognosis of HCC. Elmo1-siRNA-treated HCCLM3 cells demonstrated a reduction in cell migration. The present study demonstrated for the first time that the suppression of Elmo1 expression inhibits cell invasion in HCC.
To explore and summarize the experience of surgical treatment for primary retroperitoneal tumor (PRT)in children.Clinical data of 17 patients with PRT treated from January 2001 to January 2008 were retrospectively analyzed, including image examination, pathologic examination and surgical procedure.Seventeen patients underwent complete resection; 8 benign PRT, and 9 malignant PRT were diagnosed by operation and postoperative pathologic examination. Vascular surgery was done on 11 patients, 6 cases of multi-visceral resection, 1 vascular transplant, and 1 multi-visceral resection. Two patients had recurrent malignant PRT.For pediatric complex retroperitoneal tumors, complete resection can reduce the recurrence and improve the long-term survival.
Peliosis hepatis (PH) is a rare condition characterized by the presence of blood‑filled cavities within the liver. The etiology of PH remains unknown, but it has been reported to be associated with infections or malignancies. However, the cause of PH is not clear in 20‑50% of patients. The current study presents the case of a 19‑year‑old male who presented with right upper quadrant pain that had lasted for three days. The patient was a student with no previous medical history. Contrast‑enhanced computer tomography (CT) and ultrasonography showed a neoplasm in the right liver and a diagnosis of primary liver cancer was made due to the manifestation of the disease and the results of physical tests. The individual was treated successfully with an irregular right hemihepatectomy and was in good health at 6‑months post‑surgery. A tissue specimen was obtained and determined to be PH by pathological examination and immunohistochemistry analysis. Consequently, a diagnosis of PH must be considered in cases like this.
To investigate the expression of JAK/STAT signal pathway in human hepatocellular carcinoma, and to evaluate its clinical significance in the progression and prognosis in hepatocellular carcinoma.196 patients with hepatocellular carcinoma were examined for the expression of JAK-1 protein and STAT-3 protein by SABC immunohistochemistry.The positive expression rates of JAK-1 protein and STAT-3 protein in patients with hepatocellular carcinoma were significantly higher than those in 20 cases of normal liver tissue (P=0.02 and 0.01, respectively). There was no significant relation between the positive expression rates of JAK-1 protein and STAT-3 protein and patients'sex, age, tumor size, and cirrhosis of the hepatocellular carcinoma tissues (all P>0.05). The JAK-1 protein and STAT-3 protein were expressed more frequently in hepatocellular carcinoma tissues with incomplete capsule (P=0.01 and 0.008, respectively), venous tumor emboli (both P=0.02), poorly differentiated (P=0.01 and 0.009, respectively) or clinical III-IV stage (P=0.02 and 0.008, respectively) than in those with complete capsule, no venous tumor emboli, maturely differentiated or clinical I-II stage. Cox proportional hazard regression model analysis indicated that the expression of JAK-1 protein and STAT-3 protein was significantly correlated with the prognosis of patients with hepatocellular carcinoma.The results suggest that the over-expression of JAK/STAT signal pathway may be an important feature of hepatocellular carcinoma.
In our previous study, we reported that the cannabinoid receptors CB1 and CB2 are overexpressed in human hepatocellular carcinoma (HCC) tissues. Recently, the antitumor potential of the endogenous cannabinoid anandamide (AEA) has also been addressed. The present study was conducted to investigate the anti-proliferative effects of AEA in HCC cells. The human HCC cell line Huh7 was used. Cell proliferation was measured by MTT assay and flow cytometry. Apoptotic analysis was investigated by TUNEL assay. Real-time PCR and western blot analysis were used to analyze the expression of relevant molecules. The results of this study demonstrated that AEA inhibited the proliferation of Huh7 cells, resulted in G1 cell cycle arrest and induced apoptosis. Furthermore, downregulation of CDK4 and upregulation of p21 and Bak by AEA were observed. This study defines the anti-proliferative effects of anandamide in HCC cells and suggests that AEA has therapeutic potential in the management of HCC patients.
Objective To study the efficacy of emergency orthotopic liver transplantation(EOLT) for acute(hepatic) failure(ALT).Methods A retrospective review was undertaken on the clinical data of 8 patients undergoing emergency liver transplantation for ALT.Results The 8 patients completely regained consciousness in 12 to 72 hours after operation.No case developed central nervous complications.One case of severe(hepatitis) complicated by acute renal failure died of respiratory infection and ARDS on postoperative day 7.One case who refused to take medication died from chronic rejection 12 months after operation.One case was(complicated) by bile duct stricture and biliary sludge at 14 months postoperatively and survived for 18 months.Four of the other 5 cases were followed up for 17 months and 1 cases for 14 months,and thir quality of life was excellent.3 of them have returned to work.Conclusions Emergency orthotopic liver thansplantation is an effective means to treat ALF.Intensive care and effective treatment preoperatively are pre-requisite(conditions) to ensure the success of EOLT.
Hepatocellular carcinoma (HCC) is the fifth most common malignant tumor in men and the seventh in women and understanding the molecular mechanisms of HCC and establishing more effective therapies are critical and urgent issues. Our objective was to study the expression of ferroportin in hepatocellular carcinoma (HCC) tissue samples and the relationship between ferroportin expression and HCC characteristics. Sixty HCC tissues and their corresponding para-cancer liver tissues (PCLT) were obtained from sixty HCC patients who had undergone hepatectomy in the Second Xiangya Hospital of Central South University. Ten normal liver tissue samples were also obtained as a control. Immunohistochemistry (IHC) was performed to analyze the ferroportin expression in HCC, and the relationship between ferroportin expression and HCC clinical pathological characteristics also was analyzed. For the evaluation of IHC results, the comprehensive scoring criteria were met according to the staining intensity and the number of positive staining cells. Western blotting was performed to detect the expression level of ferroportin in HCC cell lines. Ferroportin expression in HCC tissue was significantly lower compared to PCLT and normal liver tissue (P <0.05). Moreover, ferroportin expression was related to liver cancer cell de-differentiation, the severity degree in TNM staging, Edmondson-Steiner grading, intrahepatic metastasis and portal vein invasion. In addition, high expression of ferroportin was observed in normal human liver cell lines L02 and HL7702, whereas weak positive expression and even negative expression of ferroportin were observed in HCC cell lines FOCUS, MHCC-97H, HepG2 and SMMC-7721. Furthermore, among the four kinds of HCC cell lines, the expression level of ferroportin was the lowest in MHCC-97H cells. Ferroportin expression level declines along with the progression of liver cancer, suggesting that the reduction of ferroportin may serve as an important marker for poor HCC prognosis and as a new therapeutic target.
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