Computer modeling and in vitro experimental study of water-cooled microwave ablation array.

INTRODUCTION: Microwaves (MWs) quickly deliver relatively high temperatures into tumors and cover a large ablation zone. We present a research protocol for using water-cooled double-needle MW ablation arrays for tumor ablation here. MATERIAL AND METHODS: Our research program includes computer modeling, tissue-mimicking phantom experiments, and in vitro swine liver experiments. The computer modeling is based on the finite element method (FEM) to evaluate ablation temperature distributions. In tissue-mimicking phantom and in vitro swine liver ablation experiments, the performances of the new device and the single-needle MW device currently used in clinical practice are compared. RESULTS: FEM shows that the maximum transverse ablation diameter (MTAD) is 4.2 cm at 100 W output and 300 s (assessed at the 50 °C isotherm). In the tissue-mimicking phantom, the MTDA is 2.6 cm at 50 W and 300 s in single-needle MW ablation, and 4 cm in double needle MW ablation array. In in vitro swine liver experiments, the MTAD is 2.820 ± 0.127 cm at 100 W and 300 s in single-needle MW ablation, and 3.847 ± 0.103 cm in MW ablation array. CONCLUSION: A new type of water-cooled MW ablation array is designed and tested, and has potential advantages over currently used devices.

The effects of microRNA-1224-5p on hepatocellular carcinoma tumor endothelial cells.

AIM: The aim of this study was to investigate the effect of microRNA-1224-5p (miR-1224-5p) on tumor endothelial cells (TECs) of human hepatocellular carcinoma (HCC). SUBJECTS AND METHODS: Oligonucleotides were chemically synthesized and transfected into TECs using Lipofectamine 2000. TECs were divided into three groups, namely a control (CON) group without transfection, a negative control (NC) group transfected with negative control oligonucleotides and green fluorescent protein (GFP), and a micro-up (MU) group transfected with miR-1224-5p mimic and GFP. The expression of miR-1224-5p was quantified via quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The proliferation of TECs was detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the optical density value at 490 nm was measured after every 24 h. Apoptosis was detected via flow cytometry using a 7-aminoactinomycin/APC Annexin V kit. The migration and invasion of TECs were detected using transwell assay. The tube formation ability was evaluated using the tube formation assay. RESULTS: Oligonucleotides were successfully transduced into TECs, and the expression of miR-1224-5p was specifically upregulated. The results of qRT-PCR analysis showed that the expression of miR-1224-5p was significantly upregulated in the MU group (2-ΔΔCt = 3.27 ± 0.15) than in the CON group (2-ΔΔCt = 1) and NC group (2-ΔΔCt = 1.08 ± 0.11) (P < 0.01). The results of MTT assay showed that the cell proliferation was significantly inhibited in the MU group at four time points than in the CON and NC groups (P < 0.01). Flow cytometry analysis revealed the significant increase in apoptosis of cells from the MU group (19.29% ± 0.95%) than those from the CON (8.73% ± 0.64%) and NC (9.51% ± 0.56%) (P < 0.01) groups. The migration ability was significantly inhibited in MU group (51.0 ± 3.6) as compared with CON (77.7 ± 2.5) and NC (79.2 ± 3.5) groups (P < 0.01). The invasion ability of TECs was significantly inhibited in MU group (9.8 ± 1.3) than in CON (15.8 ± 0.8) and NC (15.4 ± 0.9) groups (P < 0.01). The ability of tube formation of TECs was completely inhibited in MU group but remained unaffected in CON and NC groups. CONCLUSIONS: miR-1224-5p may serve as a potential tumor suppressor in HCC. Upregulation in miR-1224-5p expression may decrease proliferation, induce apoptosis, inhibit migration and invasion, and suppress tube formation in TECs of human HCC.

Interferon-gamma induces autophagy-associated apoptosis through induction of cPLA2-dependent mitochondrial ROS generation in colorectal cancer cells.

Colorectal cancer (CRC) is the second most commonly diagnosed cancer in females and the third in males. In this work, we aim to investigate the possible anti-cancer effects of interferon-gamma (IFN-γ) in CRC cells. We observed that IFN-γ induced mitochondria-derived reactive oxygen species (ROS) production in a time-dependent manner in SW480 and HCT116 cell lines. The IFN-γ-induced mitochondrial ROS generation was dependent on the activation of cytosolic phospholipase A2 (cPLA2). In addition, a mitochondria-targeted antioxidant SS31 and/or cPLA2 inhibitor AACOCF3 abolished the IFN-γ-induced ROS production and subsequent autophagy and apoptosis. Moreover, suppression of autophagy by CQ was able to reduce IFN-γ-induced cell apoptosis. Beclin-1 gene silencing resulted in caspase-3 inactivation, decreased Bax/Bcl-2 ratio and less population of apoptotic cells. Collectively, our results suggested that IFN-γ induces autophagy-associated apoptosis in CRC cells via inducing cPLA2-dependent mitochondrial ROS production.

Ηypoxia-inducible factor 1-α promotes colon cell proliferation and migration by upregulating AMPK-related protein kinase 5 under hypoxic conditions.

Hypoxia is a common characteristic of solid tumors. Previous studies have reported that the tumor invasion-associated factor, AMPK-related protein kinase 5 (ARK5), is associated with a poor prognosis in colon cancer. However, whether or not ARK5 is involved in hypoxia is unclear. The aim of present study was to investigate the association between the expression of ARK5 and that of hypoxia-inducible factor 1-α (HIF1-α). Samples from 60 patients with colon cancer were collected and immunohistochemistry was used to detect the expression of ARK5 and HIF1-α within them. Western blot analysis and reverse transcription polymerase chain reaction were used to detect the expression of ARK5 in an SW480 cell line under hypoxic conditions. Cell Counting kit-8 and Transwell assays were used to study the function of ARK5 under hypoxic conditions. According to the immunohistochemistry results, ARK5 and HIF1-α staining was significantly associated with Tumor-Node-Metastasis stage, tumor grade, lymph node metastasis and liver metastasis. Spearman's correlation analysis revealed a correlation between the expression of ARK5 and that of HIF1-α. This finding was also verified under hypoxic conditions in the SW480 cell line, in which the expression of ARK5 increased over time. Further cellular function experiments revealed that suppression of ARK5 inhibited cell viability and migration under hypoxic conditions. The present study has suggested that ARK5 expression in colon cancer cells is upregulated by HIF1-α under hypoxic conditions and that ARK5 serves an important role in cell proliferation and migration under hypoxic stress.

Microwave-assisted liver resection vs. clamp crushing liver resection in cirrhosis patients with hepatocellular carcinoma.

PURPOSE: This study aimed to evaluate the safety and effectiveness of microwave-ablation-assisted liver resection (MW-LR) and clamp crushing liver resection (CC-LR) in cirrhotic patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: From July 2005 to January 2015, cirrhotic HCC patients who underwent CC-LR (n = 191) or MW-LR (n = 112) were retrospectively analysed. We compared morbidity, mortality, disease-free survival (DFS) time and overall survival time between the CC-LR and MW-LR groups. RESULTS: The blood loss volume was significantly higher in the CC-LR group (mean of 752 ml) than that in the MW-LR group (mean of 253 ml, p < 0.001). The abdominal abscess rate was higher in the MW-LR group (8.9%) than that in the CC-LR group (3.1%, p = 0.029). The 30-day mortality rate (1.5% vs. 0.8%) and postoperative complication rate (32.9% vs. 25.0%) were both similar between the CC-LR and MW-LR groups. MW-LR provided a survival benefit over CC-LR at 1, 3 and 5 years in the entire population (93.5% vs. 87.0%, 77.0% vs. 62.5% and 50.0% vs. 36.5%, respectively; p = 0.003). In a subgroup analysis, MW-LR provided a survival benefit over CC-LR for Barcelona Clinic Liver Cancer stage A (BCLC-A) HCC (p = 0.026) and stage B (BCLC-B) HCC (p = 0.035) patients and provided DFS benefits for BCLC-A HCC patients (p = 0.036). CONCLUSIONS: MW-LR is a safe and feasible procedure for HCC patients with a cirrhotic liver history.

Erratum: pri-miR-34b/c rs4938723 polymorphism is associated with hepatocellular carcinoma risk: a case-control study in a Chinese population.

[This corrects the article on p. 1 in vol. 8, PMID: 28337312.].

High Expression of Retinoblastoma-Binding Protein 2 (RBP2) in Patients with Hepatocellular Carcinoma and Its Prognostic Significance.

BACKGROUND Recently, some studies have found that retinoblastoma-binding protein 2 (RBP2) is involved in the development and progression of many kinds of malignant tumors. This study aimed to explore the expression level of RBP2 in hepatocellular carcinoma (HCC) and its prognostic significance. MATERIAL AND METHODS Immunohistochemical analysis was used to evaluate the RBP2 expression level in 130 HCC patients and adjacent normal tissues. Tumor angiogenesis was marked by CD31 and vascular endothelial growth factor (VEGF) staining. Kaplan-Meier and Cox regression analyses were performed to examine the relationship between RBP2 expression and prognosis of HCC patients. RESULTS RBP2 expression was significantly higher in HCC tissues (positive expression rate: 72.3%, 94/130). Increased RBP2 expression was dramatically associated with AFP level (P=0.016), degree of differentiation (P=0.000), and TNM stage (P=0.035). Moreover, tumors with RBP2-positive expression showed significantly higher intratumoral MVD than those with RBP2-negative expression (P=0.000). Kaplan-Meier analysis revealed RBP2-positive expression was related to decreased disease-free survival (DFS) (P=0.000) and overall survival (OS) (P=0.000). Furthermore, RBP2 was an independent poor prognostic factor of DFS and OS (P=0.029 and 0.010, respectively) as demonstrated by multivariate analysis. CONCLUSIONS Increased RBP2 expression, as an independent poor prognostic factor for DFS and OS of HCC patients, is closely related to tumor angiogenesis. RBP2 is expected to become a new potential therapeutic target for HCC.

pri-miR-34b/c rs4938723 polymorphism is associated with hepatocellular carcinoma risk: a case-control study in a Chinese population.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. miR-34 induces changes of its downstream genes, and plays a key role in altering the apoptotic cycle and pathways of downstream cells, and finally influences the development of cancer. We assessed the relationship of the pri-miR-34b/c rs4938723 polymorphism with hepatocellular carcinoma risk in a Chinese population. During the period of January 2014 and December 2015, a total of 164 HCC patients and 305 healthy controls were recruited from the Inner Mongolia People's Hospital. Genotyping of the pri-miR-34b/c rs4938723 was determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Using χ2 test, we observed that HCC patients were likely to have a habit of alcohol consumption (χ2 = 10.24, P = 0.001) and infect with HBV or HCV (χ2 = 128.17, P < 0.001). In co-dominant model, the CC genotype of pri-miR-34b/c rs4938723 had a significant higher risk of HCC as compared with the TT genotype, and the corresponding adjusted OR (95% CI) was 4.14 (1.91-9.75). In dominant model, we observed that the TC+CC genotype were associated with an increased risk of HCC in comparison to the TT genotype (OR = 1.67, 95% CI = 1.17-2.55). In recessive model, the CC genotype was correlated with an elevated risk of HCC when compared with the TT+TC genotype (OR = 3.46, 95% CI = 1.62-8.54). The pri-miR-34b/c rs4938723 polymorphism was associated with a higher risk of HCC in the Chinese population examined. Further large-scale and multi-center studies are required to confirm these results.

Simultaneous hepatectomy and splenectomy versus hepatectomy alone for hepatocellular carcinoma complicated by hypersplenism: a meta-analysis.

BACKGROUND: This study systematically compared the efficacy and safety of simultaneous hepatectomy and splenectomy (HS) with hepatectomy (H) alone in patients with hepatocellular carcinoma (HCC) and hypersplenism. METHODS: The PubMed, Web of Science, Science Direct, EMBASE, and Cochrane Library databases were systematically searched by two independent researchers through to March 31, 2015 to identify relevant studies. All the extracted literature were managed by Bibliographic citation management software. Quality assessment of the included studies was performed using a modified Newcastle-Ottawa Scale judgment. The data were analyzed using RevMan5.2 software. RESULTS: Eight studies including a total of 761 patients with HCC and hypersplenism (360 in the HS group, 401 in the H group) were finally included in the analysis. Outcomes, including postoperative complications, perioperative mortality, operation time, 5-year survival rate, and need for blood transfusion did not differ significantly between the two groups. HS was associated with significantly more intraoperative bleeding (mean difference [MD] 57.15, 95% confidence interval [CI] 18.83-95.46, P=0.003), and CD4/CD8 ratio (MD 0.69, 95% CI 0.61-0.77, P<0.00001), CD4 subset, platelet count (MD 213.06, 95% CI 202.59-223.53, P<0.0001), white blood cell count (MD 4.85, 95% CI 4.58-5.13, P<0.0001), interferon-gamma levels (MD 18.52, 95% CI 13.93-23.11, P<0.00001), and interleukin-2 levels (MD 20.73, 95% CI 16.05-25.41, P<0.0001). In addition, lower CD8 subset (MD -7.85, 95% CI -9.07, -6.63, P<0.00001) and interleukin-10 levels (MD -18.56, 95% CI -22.61, -14.50, P<0.00001) were observed for HS. CONCLUSION: We identified that simultaneous HS do not increase postoperative complications, operation time, or perioperative mortality in patients with HCC and hypersplenism. Simultaneous splenectomy can increase postoperative white blood cell and platelet counts significantly, improve blood coagulation, reduce the incidence of postoperative bleeding, and enhance immunity. Therefore, HS is safe, effective, and feasible for patients with HCC and hypersplenism.

Effect of microRNA-1 on hepatocellular carcinoma tumor endothelial cells.

AIM: To investigate the effect of microRNA-1 (miR-1) on tumor endothelial cells (TECs) of human hepatocellular carcinoma (HCC). METHODS: MiR-1 specific short hairpin RNA (shRNA) was synthesized and cloned into a recombinant lentiviral vector. TECs were then infected by the miRNA-1-shRNA recombinant lentivirus. TECs were divided into three groups: a control (CON) group consisting of normal TECs without lentiviral infection, a negative control (NC) group consisting of normal TECs infected with a negative control virus, and a micro-down (MD) group consisting of normal TECs infected with the miR-1-inhibition virus containing the target gene. Silencing of miR-1 expression was quantified via quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The proliferation of TECs was detected using MTT (Thiazolyl Blue Tetrazolium Bromide) assay; the observations were continued for 5 d, and the optical density value at 490 nm was detected every day. Apoptosis was detected via flow cytometry using Annexin V-APC single staining. The migration and invasion of TECs were detected using transwell assays. RESULTS: Lentiviral miR-1 shRNA was successfully transduced into TECs, and specifically silenced the expression of miR-1. The results of qRT-PCR showed that the expression of miR-1 was significantly decreased in the MD group (2(-ΔΔCt) = 0.57 ± 0.14) compared with the CON group (2(-ΔΔCt) = 1) and the NC group (2(-ΔΔCt) = 1.05 ± 0.13) (P < 0.01). The results of MTT assay showed that the cell proliferation was all significantly inhibited in the MD group in the 5 days compared with the CON and NC groups (P < 0.01). The results of flow cytometry showed that the apoptosis was significantly increased in the MD group (6.32% ± 0.33%) compared with the CON group (2.03% ± 0.30%) and the NC group (2.18% ± 0.15%) (P < 0.01). The ability of cell migration was significantly inhibited in the MD group (62.0 ± 5.48) compared with the CON group (99.8 ± 3.11) and the NC group (97.2 ± 3.70) (P < 0.01). The ability of invasion of TECs was also significantly inhibited in the MD group (29.8 ± 2.39) compared with the CON group (44.6 ± 3.36) and the NC group (44.4 ± 5.17) (P < 0.01). CONCLUSION: MiR-1 might be a potential tumor activator. Inhibiting its expression could decrease proliferation, induce apoptosis, and inhibit the migration and invasion of TECs of human HCC.

Growth inhibition of hepatocellular carcinoma tumor endothelial cells by miR-204-3p and underlying mechanism.

AIM: To investigate the mechanism by which miR-204-3p inhibits the growth of hepatocellular carcinoma (HCC) tumor endothelial cells (TECs). METHODS: Flow cytometry was used to identify HCCTECs and analyze their purity. Differentially expressed miRNAs in HCC TECs as compared to normal hepatic sinusoidal endothelial cells (HSECs) were examined using the HmiOA v4 Human miRNA OneArray microarray. miR-204-3p showed the most significant decrease in expression and was further studied. Over-expression of miR-204-3p was achieved using lentiviral transduction into TECs of HCC. The biological changes in HCC TECs before and after transduction were detected using MTT and apoptosis assays. The association between miR-204-3p and fibronectin 1 (FN1) was determined using the dual luciferase activity assay. Changes in FN1 protein expression before and after transduction were detected using Western blot analysis. RESULTS: Microarray results showed that compared to normal HSECs, 15 miRNAs were differentially expressed in HCC TECs, including 6 miRNAs with increased expression and 9 miRNAs with decreased expression. Among them, miR-204-3p showed the most significant decrease in expression (log2 = -1.233477, P = 0.000307). Over-expression of miR-204-3p in HCC TECs via lentiviral transduction significantly inhibited the proliferation of HCC TECs and promoted apoptosis. Results from the dual luciferase activity experiment showed that the luciferase intensity in the wild type FN1 group was significantly inhibited (P < 0.05), while that in the mutant FN1 group was not obviously affected. This observation indicated that FN1 was one of the potential targets of miR-204-3p. After over-expression of miR-204-3p in HCC TECs, Western blot analysis showed that the expression of FN1 protein was significantly inhibited. CONCLUSION: MiR-204-3p acts on its potential target gene, FN1, and inhibits its expression, thus blocking the adhesion function of FN1 in promoting the growth of TECs.

17ß-estradiol attenuates reduced-size hepatic ischemia/reperfusion injury by inhibition apoptosis via mitochondrial pathway in rats.

The aim of this study was to investigate the effect of 17ß-estradiol (E2) on hepatocyte apoptosis after reduced-size hepatic ischemia/reperfusion (I/R) injury and its mechanism. A rat model of reduced-size hepatic I/R injury was established. Sprague-Dawley rats were randomly allocated into sham, I/R, and E2 + I/R group. 17ß-Estradiol (4 mg/kg) or the vehicle was administered i.p. 1 h before ischemia and immediately after operation. For each group, 10 rats were used to investigate the survival during a week after reperfusion. Blood samples and liver tissues were obtained in the remaining animals after 3, 6, 12, and 24 h of reperfusion to assess serum aspartate aminotransferase and alanine aminotransferase levels, liver tissue malondialdehyde concentration, superoxide dismutase activity, and histopathologic changes. Apoptosis ratio; expression of cytochrome c, Bcl-2, and Bax proteins; and enzymatic activities of caspase 9 and caspase 3 were performed in the samples at 12 h after reperfusion. The serum aspartate aminotransferase and alanine aminotransferase levels and tissue malondialdehyde concentration were increased in the I/R group, whereas the increase was significantly reduced by E2. The superoxide dismutase activity, depressed by I/R injury, was elevated back to normal levels by treatment with E2. Severe hepatic damage was observed by light microscopy in the I/R group, whereas administration of E2 resulted in tissue and cellular preservation. Furthermore, E2 inhibited hepatocellular apoptosis by upregulating the ratio of Bcl-2 and Bax expression, reduced cytosolic cytochrome c level, and decreased caspase 9 and caspase 3 activities. The 7-day survival rate was significantly higher in the E2 + I/R group than in the I/R group. These results indicated that E2 protects liver tissues from reduced-size hepatic I/R injury by suppressing mitochondrial apoptotic pathways.

The role of prophylactic antibiotics in laparoscopic cholecystectomy in preventing postoperative infection: a meta-analysis.

BACKGROUND: Although laparoscopic cholecystectomy (LC) is a common and widely applied technique, the use of antibiotics during the perioperative period in infection prevention remains controversial. In our study, a meta-analysis was performed to assess the impact of antibiotic prophylaxis on the postoperative infection rate in LC. METHODS: A literature search was conducted on studies published between January 1966 and March 2010 that involved LC and prophylactic administration of antibiotics. Only randomized trials that compared perioperative antibiotic prophylaxis with placebo or no treatment in low-risk patients undergoing LC were selected. Eighteen studies qualified according to the inclusion criteria, but only 12 were of adequate quality according to the Jadad scale to be included for the meta-analysis. Data were analyzed via the Peto odds ratio (OR) method and run using RevMan 4.2 software. The precision of the estimation of OR by individual studies was used to calculate their contribution (or weighting) to the pooled OR. RESULTS: The results of the 12 studies did not have significant heterogeneity, and thus, the fixed effect model was used for data analysis. Compared with placebo or no treatment, there was no significant risk reduction in the antibiotic prophylaxis group with regard to overall infections (OR=1.11; 95% confidence interval [CI], 0.68-1.82; P=.67), wound infections (OR=1.07; 95% CI, 0.59-1.94; P=.99), major infections (OR=2.88; 95% CI, 0.3-28.09; P=.36), distant infections (OR=1.01; 95% CI, 0.43-2.36; P=.99), or positive bile cultures (OR=0.76; 95% CI, 0.54-1.08; P=.12). However, prophylactic antibiotics did shorten length of hospital stay (weighted mean difference=-0.16; 95% CI, -0.22 to -0.09; P<.01). CONCLUSION: Prophylactic antibiotics are not necessary for elective LC in low-risk patients.

The angiogenic and prognostic implications of VEGF, Ang-1, Ang-2, and MMP-9 for hepatocellular carcinoma with background of hepatitis B virus.

The objective of this study was to investigate the expressions of angiogenic factors and elucidate their angiogenic and prognostic roles in hepatocellular carcinoma (HCC) with background of hepatitis B virus (HBV). We evaluated microvessel density (MVD) of HCC, and investigated immunohistochemical expression of vascular endothelial growth factor (VEGF), angiopoietins (Ang-1 and Ang-2), and matrix metalloproteinases-9 (MMP-9) in 67 specimens of surgically resected HCC, which were all positive for hepatitis B surface antigen. We investigated the relationship between their expressions and clinicopathological factors or prognosis. The microvessel density (MVD) of tumor tissue and surrounding normal liver tissue was 93.1 +/- 43.8/mm2 and 30.4 +/- 14.8/mm2, respectively. The MVD of well-differentiated HCC was significantly less than that of poorly differentiated HCC. MVD was positively correlated with VEGF and Ang-2 expression (P = 0.0023 and 0.0265, respectively). There was less tumor recurrence in low Ang-2 and low MMP-9 group than high Ang-2 and/or high MMP-9 group (P = 0.002). In Cox regression model, portal vein thrombus and intrahepatic metastasis was the risk factors of tumor recurrence (P = 0.003 and 0.001, respectively). Our study showed that the expression of VEGF and Ang-2 were positively correlated with MVD. Ang-2 expression and/or MMP-9 expression might be a significant predictive factor for recurrence after resection in HCC patients with the background of HBV.

Expression and clinical significance of NET-1 and PCNA in hepatocellular carcinoma.

OBJECTIVE: Objective of this study was to detect the expression of neuroepithelial transforming gene-1 (NET-1) and proliferating cell nuclear antigen (PCNA) in hepatocellular carcinoma (HCC) and adjacent tissues, and to investigate the relation of the expression of NET-1 in HCC tissue with cancer proliferation, metastasis and clinic stages. METHODS: The expression of NET-1 mRNA was detected by reverse transcription-polymerase chain reaction method in 34 human HCC tissues, and it was matched with 34 paracarcinoma tissues. The expression of PCNA in HCC was analyzed by immunohistochemistry. Meanwhile, the relation of the expression with clinic pathological features of HCC was evaluated, and the correlation between the expression of NET-1 and PCNA in HCC was investigated. RESULTS: Expression of NET-1 was significantly higher in HCC than that in matched paracarcinoma tissues. The expression of NET-1 was significantly higher in TMN III-IV HCC tissues when compared with TMN I-II HCC tissues (P<0.05). The expression level of NET-1 in HCC tissues was related to intrahepatic metastasis and portal vein infiltration. The expression of NET-1 in HCC tissues was positively correlated with PCNA. CONCLUSIONS: The expression of NET-1 may relate to proliferation, metastasis and clinic stages of HCC. The expression of NET-1 in HCC tissues may positively correlate to the TMN stages.

Microvessel damage may play an important role in tumoricidal effect for murine h(22) hepatoma cells with hyperthermia in vivo.

BACKGROUND: In the present study, murine H(22) hepatoma cells were provided hyperthermia with different thermal dose in vitro and in vivo, thereafter we investigated the apoptosis, necrosis rates, and intratumoral microvessel density (MVD) to determine that microvessel damage plays an important role in the tumoricidal effect of hyperthermia. METHODS: H(22) hepatoma cells were inoculated in the right hind legs of mice with immunosuppression. Local hyperthermia was administered to these mice for 15, 30, and 45 min, respectively. After hyperthermia, some mice with heat treatment of 30 min were killed at 3, 6, 12, 24, 48, 72, and 96 h after operation and others were immediately sacrificed. All tumor tissues were removed. They were analyzed for the death rate of tumor cells by flow cytometer (FCM) and observed MVD by immunohistochemistry. H(22) hepatoma cells in vitro were also given hyperthermia for 15, 30, and 45 min, respectively, and analyzed for the death rate by FCM. RESULTS: Most of the dead cells were apoptotic cells in the initiation phase of hyperthermia, then the necrosis rates rose gradually. The difference of death rates between in vivo and in vitro was significant for hyperthermia for 15 min, 30 min, and 45 min (P < 0.05). A strong positive linear correlation (r = -0.879) was observed between the death rate of tumor cells and MVD. CONCLUSION: Our study has shown that microvessel damage may play an important role in tumoricidal effect of hyperthermia.

Protective effect of curcumin against liver warm ischemia/reperfusion injury in rat model is associated with regulation of heat shock protein and antioxidant enzymes.

AIM: To investigate the hypothesis that the protective effects of curcumin in hepatic warm ischemia/reperfusion (I/R) injury are associated with increasing heat shock protein 70 (Hsp70) expression and antioxidant enzyme activity. METHODS: Sixty Sprague-Dawley male rats were randomly divided into sham, I/R, C + I/R groups. The model of reduced-size liver warm ischemia and reperfusion was used. Curcumin (50 mg/kg) was administered by injection through a branch of superior mesenteric vein at 30 min before ischemia in C + I/R group. Five rats were used to investigate the survival during 1 wk after operation in each group. Blood samples and liver tissues were obtained in the remaining animals after 3, 12, and 24 h of reperfusion to assess serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver tissue NO(2)(-) + NO(3)(-), malondialdehyde (MDA) content, superoxide dismutase (SOD), catalase (CAT), nitricoxide synthase (NOS) and myeloperoxidase (MPO) activity, Hsp70 expression and apoptosis ratio. RESULTS: Compared with I/R group, curcumin pretreatment group showed less ischemia/reperfusion-induced injury. CAT and SOD activity and Hsp70 expression increased significantly. A higher rate of apoptosis was observed in I/R group than in C + I/R group, and a significant increase of MDA, NO(2)(-) + NO(3)(-) and MPO level in liver tissues and serum transaminase concentration was also observed in I/R group compared to C + I/R group. Curcumin also decreased the activity of inducible NO synthase (iNOS) in liver after reperfusion, but had no effect on the level of endothelial NO synthase (eNOS) after reperfusion in liver. The 7 d survival rate was significantly higher in C + I/R group than in I/R group. CONCLUSION: Curcumin has protective effects against hepatic I/R injury. Its mechanism might be related to the overexpression of Hsp70 and antioxidant enzymes.

The protective effects of 17beta-estradiol on hepatic ischemia-reperfusion injury in rat model, associated with regulation of heat-shock protein expression.

BACKGROUND: Ischemia-reperfusion (I/R) injury, which was commonly seen in the field of hepatic surgical intervention, impaired liver regeneration and predisposed to liver failure. Previous studies have shown gender dimorphic response of the liver for various hepatic stresses including I/R injury, hemorrhagic shock-resuscitation, liver cirrhosis, endotoxemia, and chronic alcoholic consumption, and demonstrated gender dimorphism in hepatocellular dysfunction after experimental trauma and hemorrhage. The objective of this study was to examine the hypothesis that the protective effects of 17beta-estradiol (E2) in hepatic I/R injury were associated with increasing heat-shock protein 70 expression. MATERIALS AND METHODS: Sprague-Dawley male and female rats were randomly divided into male and female sham, I/R, and E2 + I/R groups. The model of reduced-size liver ischemia and reperfusion was used. Except for the sham-operated groups, all rats were subjected to 70% liver ischemia for 45 min followed by resection of the remaining 30% nonischemic lobes and reperfusion of ischemic tissue. For each group, five rats were used to investigate the survival during a week after operation; blood samples and liver tissues were obtained in the remaining animals after 3, 12, and 24 h of reperfusion to assess serum alanine aminotransferase, aspartate aminotransferase, liver tissue NO(2)(-) + NO(3)(-), malondialdehyde content, superoxide dismutase, nitric oxide synthase, and myeloperoxidase activity, Hsp70 expression, and apoptosis ratio. RESULTS: Compared with I/R groups, male and female E2 + I/R groups showed less I/R-induced injury, and SOD and eNOS activity and Hsp70 expression were increased significantly (P < 0.01). A higher rate of apoptosis was observed in the I/R group versus the E2 + I/R group, a significant increase of MDA, NO(2)(-) + NO(3)(-), and MPO of liver tissues and serum transaminase were also observed in the I/R group versus the E2 + I/R group. The survival rate was significantly higher in the male E2 + I/R group than in the male I/R group. CONCLUSION: E2 pretreatment had protective effects on liver in hepatic I/R injury. The mechanism of this protection might be related to overexpression of Hsp70.

Intraoperative radiofrequency thermal ablation combined with portal vein infusion chemotherapy and transarterial chemoembolization for unresectable HCC.

BACKGROUND/AIMS: We conducted a preliminary study to determine the feasibility of therapy consisting of intraoperative radiofrequency thermal ablation combined with portal vein infusion chemotherapy and transarterial chemoembolization (IRFAPA) for unresectable hepatocellular carcinoma (HCC). METHODOLOGY: Between September 2001 and June 2004, 34 patients with unresectable HCC were enrolled into a prospective study. 18 cases underwent IRFAPA (group I and 16 cases underwent percutaneous RF ablation (PRFA, group II). Patients' outcomes for IRFAPA and PRFA were recorded and compared. RESULTS: Patients undergoing IRFAPA or PRFA were similar in age, liver function, tumor size, serum AFP, distribution of tumor, mortality, complication and complete ablation rates. In five patients in group II seven new lesions were found during operation. The rate of distant intrahepatic recurrence between the two groups had differences (11.1% vs. 50.0%, P=0.023) although the cumulative recurrence-free survival between the two groups had no differences (P=0.7808). There was a significant difference in the overall survival (P=0.0407). The 1-year and 3-year cumulative overall survival rate was 87.5% and 73.3%, 52.2% and 20.4% in group I and group II, respectively. CONCLUSIONS: IRFAPA is an effective and safe procedure for unresectable HCC. IRFAPA is preferred to PRFA therapy if the patients' conditions can tolerate laparotomy.