A prognostic signature of fatty acid metabolism-related genes for predicting survival of gastric cancer patients.

To analyze the expression profile of fatty acid metabolism (FAM)-related genes, identify a prognostic signature, and evaluate its clinical value for gastric cancer (GC) patients. The mRNA expression profiles of 493 FAM-related genes were obtained from TCGA database. Differentially expressed genes (DEGs) between cancer and non-cancer samples were identified, and their relationships with overall survival (OS) of GC patients were evaluated. A prognostic signature of FAM-related genes was identified by the LASSO regression model, and its predictive performance was tested by an independent external cohort. Ninety-three DEGs were identified, of which 44 were downregulated and 49 were upregulated. After optimizing risk characteristics, a prognostic signature of four FAM-related genes (ACBD5, AVPR1A, ELOVL4, and FAAH) were developed. All patients were divided into high-risk (>1.020) and low-risk groups (≤1.020) on the basis of the median risk score. Survival analysis indicated that high-risk patients had a shorter OS than low-risk patients (5-year OS rate, 26.3% vs. 45.0%, p < 0.001). The AUC values for the prediction of 3-year and 5-year OS were 0.664 and 0.624, respectively. In the GSE62254 data set, the 5-year OS rate of high-risk and low-risk patients were 44.7% versus 61.5%, respectively (p = 0.003). The AUC values were 0.632 and 0.627 at 3-year and 5-year prediction. The prognostic signature of FAM-related genes was an independent predictor of OS (hanzard ratio [HR] for TCGA cohort: 1.851, 95% confidence interval [CI]: 1.394-2.458, p < 0.001; HR for GSE62254: 1.549, 95% CI: 1.098-2.185, p = 0.013). The risk signature of four FAM-related genes was a valuable prognostic tool, and it might be helpful for clinical management and therapeutic decision of gastric cancer patients.

Which is the appropriate surgical procedure for appendiceal adenocarcinoma: appendectomy, partial colectomy or right hemicolectomy?

Objective The purpose of this study was to explore the appropriate surgical procedure and clinical decision for appendiceal adenocarcinoma. Methods A total of 1,984 appendiceal adenocarcinoma patients from 2004 to 2015 were retrospectively identified from the Surveillance, Epidemiology, and End Results (SEER) database. All patients were divided into three groups based on the extent of surgical resection: appendectomy (N = 335), partial colectomy (N = 390) and right hemicolectomy (N = 1,259). The clinicopathological features and survival outcomes of three groups were compared, and independent prognostic factors were assessed. Results The 5-year OS rates of patients who underwent appendectomy, partial colectomy and right hemicolectomy were 58.3%, 65.5% and 69.1%, respectively (right hemicolectomy vs appendectomy, P < 0.001; right hemicolectomy vs partial colectomy, P = 0.285; partial colectomy vs appendectomy, P = 0.045). The 5-year CSS rates of patients who underwent appendectomy, partial colectomy and right hemicolectomy were 73.2%, 77.0% and 78.7%, respectively (right hemicolectomy vs appendectomy, P = 0.046; right hemicolectomy vs partial colectomy, P = 0.545; partial colectomy vs appendectomy, P = 0.246). The subgroup analysis based on the pathological TNM stage indicated that there was no survival difference amongst three surgical procedures for stage I patients (5-year CSS rate: 90.8%, 93.9% and 98.1%, respectively). The prognosis of patients who underwent an appendectomy was poorer than that of those who underwent partial colectomy (5-year OS rate: 53.5% vs 67.1%, P = 0.005; 5-year CSS rate: 65.2% vs 78.7%, P = 0.003) or right hemicolectomy (5-year OS rate: 74.2% vs 53.23%, P < 0.001; 5-year CSS rate: 65.2% vs 82.5%, P < 0.001) for stage II disease. Right hemicolectomy did not show a survival advantage over partial colectomy for stage II (5-year CSS, P = 0.255) and stage III (5-year CSS, P = 0.846) appendiceal adenocarcinoma (AU)

Which is the appropriate surgical procedure for appendiceal adenocarcinoma: appendectomy, partial colectomy or right hemicolectomy?

OBJECTIVE: The purpose of this study was to explore the appropriate surgical procedure and clinical decision for appendiceal adenocarcinoma. METHODS: A total of 1,984 appendiceal adenocarcinoma patients from 2004 to 2015 were retrospectively identified from the Surveillance, Epidemiology, and End Results (SEER) database. All patients were divided into three groups based on the extent of surgical resection: appendectomy (N = 335), partial colectomy (N = 390) and right hemicolectomy (N = 1,259). The clinicopathological features and survival outcomes of three groups were compared, and independent prognostic factors were assessed. RESULTS: The 5-year OS rates of patients who underwent appendectomy, partial colectomy and right hemicolectomy were 58.3%, 65.5% and 69.1%, respectively (right hemicolectomy vs appendectomy, P < 0.001; right hemicolectomy vs partial colectomy, P = 0.285; partial colectomy vs appendectomy, P = 0.045). The 5-year CSS rates of patients who underwent appendectomy, partial colectomy and right hemicolectomy were 73.2%, 77.0% and 78.7%, respectively (right hemicolectomy vs appendectomy, P = 0.046; right hemicolectomy vs partial colectomy, P = 0.545; partial colectomy vs appendectomy, P = 0.246). The subgroup analysis based on the pathological TNM stage indicated that there was no survival difference amongst three surgical procedures for stage I patients (5-year CSS rate: 90.8%, 93.9% and 98.1%, respectively). The prognosis of patients who underwent an appendectomy was poorer than that of those who underwent partial colectomy (5-year OS rate: 53.5% vs 67.1%, P = 0.005; 5-year CSS rate: 65.2% vs 78.7%, P = 0.003) or right hemicolectomy (5-year OS rate: 74.2% vs 53.23%, P < 0.001; 5-year CSS rate: 65.2% vs 82.5%, P < 0.001) for stage II disease. Right hemicolectomy did not show a survival advantage over partial colectomy for stage II (5-year CSS, P = 0.255) and stage III (5-year CSS, P = 0.846) appendiceal adenocarcinoma. CONCLUSIONS: Right hemicolectomy may not always be necessary for appendiceal adenocarcinoma patients. An appendectomy could be sufficient for therapeutic effect of stage I patients, but limited for stage II patients. Right hemicolectomy was not superior to partial colectomy for advanced stage patients, suggesting omission of standard hemicolectomy might be feasible. However, adequate lymphadenectomy should be strongly recommended.

Identifying a Risk Signature of Methylation-Driven Genes as a Predictor of Survival Outcome for Colon Cancer Patients.

Aberrant expression of gene is driven by its promoter methylation and is the key molecular basis of carcinogenic processes. This study aimed at identifying a risk signature of methylation-driven (MD) genes and evaluating its prognostic value for colon cancer (CC) patients. The expression profiles of methylation and mRNA in CC samples were obtained from the TCGA database, and the MethylMix algorithm was used to identify MD genes. The relationships between their expression levels and overall survival (OS) of CC patients were analyzed, and a prognostic signature of MD genes was established. The risk score of gene signature was calculated, and the median was used to divide all patients into high (H) and low (L) risk groups. The prognostic value of gene signature was tested by the TCGA cohort and an independent validation cohort (GSE17538 dataset). In total, 69 MD genes were identified, and 7 were associated with OS of CC patients. Ultimately, 4 (TWIST1, LDOC1, EPHX3, and STC2) were screened out to establish a risk signature. The H-risk patients (>0.923) had a worse OS than L-risk patients (≤0.923) in both the TCGA (5-year cumulative survival: 52.9% vs 72.0%, P=0.005) and GSE17538 cohort (49.4% vs 69.3%, P=0.004). The AUC values of MD genes signature for the prediction of 3- and 5-year OS were 0.648 and 0.643 in the TCGA dataset and 0.634 and 0.624 in the GSE17538 dataset, respectively. The risk signature of four MD genes was identified as an independent predictor of OS for CC patients (HR for TCGA dataset: 2.071, 95% CI=1.196-3.586, P=0.009; HR for GSE17538 dataset: 2.021, 95% CI=1.290-3.166, P=0.002). The risk signature of four MD genes might be a useful prognostic tool and help doctors improve the clinical management of CC patients.

A novel miRNA-based signature as predictive tool of survival outcome of colorectal cancer patients.

It is great significance of identifying valuable biomarkers for early diagnosis and prognostic prediction of colorectal cancer (CRC) patients. This study aimed at developing and validating a miRNAs-based signature as prognostic tool for CRC patients. The miRNA expression profile of 624 CRC samples (613 tumor tissues and 11 normal tissues) was analyzed, and 523 differentially expressed miRNAs (DEmiRNAs) were identified, in which 191 were downregulated and 332 were upregulated. All patients were randomly divided into a training cohort (N = 308) and an internal validation cohort (N = 200). Using the least absolute shrinkage and selection operator (LASSO) and Cox regression model, a prognostic signature of 10 miRNAs (hsa-miR-149-5p, hsa-miR-193b-5p, hsa-miR-193a-3p, hsa-miR-3677-3p, hsa-miR-29a-3p, hsa-miR-200c-5p, hsa-miR-200a-5p, hsa-miR-6854-5p, hsa-miR-216a-5p and hsa-miR-891a-5p) was developed in the training cohort. The risk score was calculated by the product of the expression level and the coefficients of each miRNA. The prognostic value of 10 miRNAs-based signature for CRC patients was tested and validated. Survival analysis indicated that high-risk patients (> 1.10) had a worse overall survival (OS) than low-risk (≤ 1.10) patients (5-year OS rate for training cohort: 59.3% vs. 78.9%, p < .001; validation cohort: 48.3% vs. 69.3%, p = .011). The miRNA-based signature was an independent prognostic factor for CRC patients (HR for training cohort:2.476, 95% CI:1.202-5.098, p = .014; HR for validation cohort:2.050, 95% CI:1.087-3.869, p = .027). The AUC values for 3-year and 5-year OS prediction were 0.718 and 0.784 in the training cohort, 0.659 and 0.614 in the validation cohort, respectively. The 10 miRNAs-based signature provided a proper prognostic stratification for CRC patients, and it might be a promising tool for survival prediction.

Development and validation of a prognostic nomogram for rectal cancer patients who underwent surgical resection.

Objective: The purpose of this study was to develop and validate a nomogram model for the prediction of survival outcome in rectal cancer patients who underwent surgical resection. Methods: A total of 9,919 consecutive patients were retrospectively identified using the Surveillance, Epidemiology, and End Results (SEER) database. Significant prognostic factors were determined by the univariate and multivariate Cox analysis. The nomogram model for the prediction of cancer-specific survival (CSS) in rectal cancer patients were developed based on these prognostic variables, and its predictive power was assessed by the concordance index (C-index). Calibration curves were plotted to evaluate the associations between predicted probabilities and actual observations. The internal and external cohort were used to further validate the predictive performance of the prognostic nomogram. Results: All patients from the SEER database were randomly split into a training cohort (n = 6,944) and an internal validation cohort (n = 2,975). The baseline characteristics of two cohorts was comparable. Independent prognostic factors were identified as age, pT stage, lymph node metastasis, serum CEA level, tumor size, differentiation type, perineural invasion, circumferential resection margin involvement and inadequate lymph node yield. In the training cohort, the C-index of the nomogram was 0.719 (95% CI: 0.696-0.742), which was significantly higher than that of the TNM staging system (C-index: 0.606, 95% CI: 0.583-0.629). The nomogram had a C-index of 0.726 (95% CI: 0.691-0.761) for the internal validation cohort, indicating a good predictive power. In addition, an independent cohort composed of 202 rectal cancer patients from our institution were enrolled as the external validation. Compared with the TNM staging system (C-index: 0.573, 95% CI: 0.492-0.654), the prognostic nomogram still showed a better predictive performance, with the C-index of 0.704 (95% CI: 0.626-0.782). Calibration plots showed a good consistency between predicted probability and the actual observation in the training and two validation cohorts. Conclusion: The nomogram showed an excellent predictive ability for survival outcome of rectal cancer patients, and it might provide an accurate prognostic stratification and help clinicians determine individualized treatment strategies.

Mixed adenoneuroendocrine carcinoma originating from the appendix and colorectum: a comparative analysis of a large population-based database.

PURPOSE: As a rare gastrointestinal neoplasm, the demographic, clinicopathological, and prognostic characteristics of mixed adenoneuroendocrine carcinoma (MANEC) remain unclear. The purpose of this study was to evaluate its biological features, survival outcome, and prognostic factors. METHODS: From the Surveillance, Epidemiology, and End Results (SEER) database, we retrospectively reviewed clinicopathological and survival data of 513 patients who were histopathologically diagnosed with MANEC of the appendix and colorectum bettween 2004 and 2015. The clinicopathological features and survival outcomes of MANEC located at different anatomical locations were compared, and predictive factors for cancer-specific survival (CSS) and overall survival (OS) were assessed. RESULTS: In terms of anatomical distribution of MANEC, the appendix (64.5%, 331/513) was more frequently involved, followed by colon (28.1%, 144/513) and rectum (7.4%, 38/513). The MANEC at different anatomical locations had a distinct clinicopathological characteristic, and colorectal MANEC was significantly associated with more aggressive biological features. The survival outcomes of appendiceal MANEC were significantly better than that of colorectal MANEC (3-year CSS rate 73.8% vs 59.4%, P = 0.010; 3-year OS 69.2% vs 48.3%, P < 0.001). In addition, hemicolectomy had a better survival benefit than appendicectomy for patients with appendiceal MANEC, regardless of lymph node metastasis (P < 0.05). Tumor location, histology grade III, tumor size > 2 cm, T3-T4 stage, lymph node metastasis, and distant metastasis were independent prognostic factors for patients with MANEC. CONCLUSIONS: Tumor location had an important prognostic significance for MANEC. As an uncommon clinical entity, colorectal MANEC had more aggressive biological features and worse prognosis than its appendiceal counterpart. The standard surgical procedure and clinical management strategy for MANEC need to be established.

MicroRNA-24 inhibits the proliferation, migration and invasion and enhances chemosensitivity of human gastric cancer by targeting DND1.

PURPOSE: Gastric cancer causes significant human mortality and is the fourth prevalent type of cancer across the globe. The gastric cancer treatment is hurdled by late diagnosis due to unavailability of biomarkers, lack of potent therapeutic targets and adverse effects of chemotherapy. Recent reports have indicated that miR-24 acts a tumor suppressor in different cancers. This study explored the role and therapeutic implications of miR-24 in gastric cancer. METHODS: Expression analysis was carried out in gastric cancer tissues and cell lines by qRT-PCR. Proliferation rate was monitored by WST-1 assay. Transwell assay was used to determine cell invasion and wound healing assay was used for cell migration. Protein expression analysis was carried out by western blot analysis. RESULTS: The results showed that miR-24 was significantly suppressed in gastric cancer tissues and cell lines. Overexpression of miR-24 in SNU-1 gastric cancer cells resulted in decline of proliferation rate in a time-dependent manner. In silico analysis together with the dual luciferase assay revealed RNA binding protein DND1 to be the target of miR-24. Expression analysis of DND1 was found to be significantly overexpressed in gastric cancer tissues and cell lines. Suppression of DND1 suppressed the proliferation of gastric cancer cells. Wound healing and transwell assay revealed that miR-24 overexpression also inhibited the migration and invasion and also enhanced the chemosensitivity of the SNU1 gastric cancer cells. CONCLUSION: Taken together, miR-24 may prove to be an important therapeutic target for the treatment of gastric cancer and warrants further studies.

TRIP6 promotes cell proliferation in hepatocellular carcinoma via suppression of FOXO3a.

Thyroid hormone receptor-interacting protein 6 (TRIP6), a member of LIM family, acts as an adaptor protein and is overexpressed in several tumor types. However, the clinical significance and biological role of TRIP6 in HCC remains unknown. In our study, we found that TRIP6 was markedly overexpressed in HCC cells and clinical specimens compared with normal hepatocytes and adjacent non-tumor tissues. Immunohistochemical and statistical analysis showed that the expression of TRIP6 significantly correlated with HCC patients' clinical stage and poor survival. Moreover, we demonstrated that overexpressing TRIP6 significantly enhanced, whereas silencing endogenous TRIP6 inhibited, the proliferation and the anchorage-independent growth ability of HCC cells. In addition, overexpression of TRIP6 accelerated, while inhibition of TRIP6 retarded, G1-S phase transition in HCC cells. We further found that overexpression of TRIP6 increased the activation of AKT and suppressed the transactivity of FOXO3a. Meanwhile, overexpression of TRIP6 leaded to the decreased expression of cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1 and increased expression of the cell cycle regulator cyclin D1. While silencing TRIP6 triggered the opposite effect. Taken together, these findings showed that TRIP6 plays an important role in promoting HCC cells proliferation and may serve as a novel prognostic biomarker and therapeutic target in HCC.

Puerarin Induces Hepatocellular Carcinoma Cell Apoptosis Modulated by MAPK Signaling Pathways in a Dose-dependent Manner.

BACKGROUND/AIM: Puerarin possesses a battery of therapeutic values in diverse disorders, including pro-apoptotic actions in multiple cancers. Herein, we investigated the effects of puerarin on hepatocellular carcinoma (HCC) in vitro. MATERIALS AND METHODS: MTT and flow cytometry were carried out to evaluate the viability and apoptosis of SMMC-7721 HCC cells in the presence of different concentrations of puerarin. Moreover, expression levels, as well as phosphorylation status of several canonical components in mitogen-activated protein kinase (MAPK) pathways, including extracellular signal-regulated kinase 1/2 (ERK1/2), c- Jun N-terminal kinase (JNK), p38, were measured by reverse transcription and quantitative real-time polymerase chain reaction (RT-PCR) and western blot analysis at indicated time intervals. RESULTS: Puerarin inhibited proliferation of SMMC-7721 cells and promoted their apoptosis in a dose- and time-dependent fashion (p<0.05). Both the expression and phosphorylation levels of MAPK proteins were dramatically increased on puerarin treatment. CONCLUSION: Puerarin could be employed as a potential anti-carcinogen that exhibits pro-apoptotic effects on HCC cells, in a dose- and time-dependent manner, with emphasis on MAPK pathways whose initiation may contribute to this process.

Puerarin inhibits growth and induces apoptosis in SMMC-7721 hepatocellular carcinoma cells.

Puerarin, a predominant isoflavonoid compound extracted from the Chinese medicinal herb Radix Puerariae, is considered to exhibit an antitumor effect. In the present study, the effects of puerarin on SMMC-7721 human hepatocellular carcinoma cells were investigated. Cell viability was assessed by MTT assay. Apoptosis was detected by flow cytometry with Annexin V-fluorescein isothiocyante staining and morphological observation of nuclear changes by Hoechst staining. The mitochondrial membrane potential (MMP) was monitored using rhodamine 123. The generation of reactive oxygen species (ROS) was quantified using dichloro­dihydro­fluorescein diacetate. Polymerase chain reaction and western blot analysis were used to detect the expression levels of apoptosis­associated genes. The results revealed that high concentrations of puerarin (500, 1,000 and 1,500 µg/ml) significantly inhibited the proliferation of SMMC-7721 cells in a time- and dose-dependent manner. Simultaneously, apoptotic rates were increased and cell morphology was changed following puerarin treatment. Furthermore, puerarin­induced apoptosis of SMMC-7721 cells was associated with loss of MMP and generation of ROS. Puerarin treatment increased caspase­3,8,9 and apoptosis­inducing factor (AIF) mRNA expression levels in SMMC­7721 cells, while the phosphorylation levels of P38, extracellular signal­regulated kinase (ERK1) and c-Jun N­terminal kinase were also increased. Furthermore, caspase-9 and AIF protein expression was upregulated. In conclusion, puerarin inhibited proliferation and induced apoptosis in SMMC­7721 cells via the mitochondria­dependent pathway; however, the specific mechanisms require further investigation.

Clinical characteristics and surgical prognosis of hepatocellular carcinoma with bile duct invasion.

Objectives. Bile duct invasion (BDI) is a rare event in hepatocellular carcinoma (HCC). The present study aimed at investigating clinical characteristics and surgical outcome of HCC patients with bile duct invasion. Methods. 413 patients with HCC undergoing curative surgery were divided into two groups with (B(+)) and without BDI (B(-)). BDI was further classified as central type (B1) and peripheral type (B2). Survival was compared, and risk factors affecting prognosis were identified. Results. 35 (8.5%) patients were diagnosed BDI. Total bilirubin was significantly higher in B(+) group than in B(-) group (P < 0.001). Multiple lesions and large nodules (>5 cm) were predominantly identified in B(+) group (P < 0.01, resp.). Portal vein invasion was more frequently observed in B(+) than in B(-) group (P = 0.003). Univariate and multivariate analyses identified central BDI as a significant factor affecting prognosis of HCC patients (risk 1.3, 95% CI 1.1-2.2, P = 0.015). The gross overall survival of patients in B(+) was significantly worse than in B(-) (P = 0.001), which, however, was not different between B2 and B(-) (P > 0.05). Conclusions. Central but not peripheral BDI was associated with poorer prognosis of HCC patients. Curative surgical resection of tumors and invaded bile duct supplies the only hope for long-term survival of patients.

Hypoxia activates heparanase expression in an NF-kappaB dependent manner.

Hypoxia was shown to increase tumor cell invasion into the extracellular matrix in vitro. This result suggests that heparanase (Hpa), one of the key enzymes involved in tumor invasion and metastasis, may be regulated by hypoxia. RT-PCR, Western blot and Matrigel invasive assays were used to study the regulation of Hpa under hypoxia in human pancreatic MIA PaCa-2 cancer cells. Compared with those in normoxia (20% O2), Hpa mRNA, protein and enzymatic activity levels, were up-regulated by a reduction in the oxygen level (1% O2). Invasion by tumor cells into the extracellular matrix was found to be significantly enhanced. A reduction in Hpa protein levels was observed when nuclear factor kappaB (NF-kappaB) activation was blocked by pyrrolidine dithiocarbamate. The levels of Hpa were also reduced when Hpa was inhibited by an Hpa-specific antisense oligonucleotide. The MMP-9 mRNA, protein and gelatinase B activity levels in supernatants decreased significantly when Hpa was inhibited. We conclude that up-regulation of Hpa by hypoxia is NF-kappaB-dependent in MIA PaCa-2 cells and inhibition of Hpa reduces MMP-9 activity. This reduction in MMP-9 activity may be an important mechanism in tumor metastasis.

[Expression of heparanase and nuclear factor kappa B in pancreatic adenocarcinoma].

OBJECTIVE: To detect the expressions of heparanase and nuclear factor kappa B p65 (NF-kappaB p65) in pancreatic adenocarcinomas and analyze their relation to patients' prognosis and the regulatory mechanism of NF-kappaB on heparanase expression. METHODS: Heparanase and NF-kappaB p65 proteins in the tumor and adjacent tissues were detected by immunohistochemistry in 48 patients with pancreatic adenocarcinoma and analyzed for their clinicopathological significance. RESULTS: Heparanase and NF-kappaB p65 proteins were found in 30 (62.5%) and 22 (45.9%) tumor specimens, respectively, a rate significantly higher than that in the adjacent tissues. High heparanase expression was closely related to advanced TNM stage (P=0.031), lymph node metastasis (P=0.003) and decreased 3-year postoperative survival (20.0% vs 0%, P=0.001). NF-kappaB p65 expression was associated with lymph node metastasis (P=0.017) and distant metastasis (P=0.031), but had a higher positive rate in heparanase-positive cases than in heparanase-negative cases (P=0.018). Multivariate analysis showed that neither heparanase nor NF-kappaB p65 was the independent prognostic factors. CONCLUSION: Heparanase is overexpressed in pancreatic adenocarcinomas in association with decreased postoperative survival. NF-kappaB may up-regulate heparanase expression and promote heparanase-dependent tumor invasion and metastasis.

[The significance and expresssion of fractalkine in acute rejection after rat orthotopic liver transplantation].

OBJECTIVE: To establish the rat orthotopic liver transplantation model by characterizing the blood supply of hepatic artery with the Cuff skill and the modified arterial sleeve anastomosis, to explore the possible mechanisms of acute rejection and the express of Fractalkine (Fkn) in the early stage after hepatic allograft operation. METHODS: SD rats were selected as donors and Wistar rats as receptor for the rejection model of orthotopic liver transplantation. Recipient rats were divided into 2 groups randomly after operation and the drugs were given intraperitoneally once a day in each group. In the experimental group, cyclosporine A (CsA) was delivered with 3 mg/kg. In the control group, only normal saline was given with 3 ml/kg. Condition of survivals were observed. The rejection activity index (RAI) and the expression of Fkn of liver tissue were observed after 3rd, 5th and 7th days in 5 rats. The rest of rats in each group were fed and given drug or normal saline until they were died and the mean survival time were recorded. RESULTS: There were 18 survivals in control group, and 19 in experimental group after liver transplantation. Condition of survivals in experimental group was better than that of control group. The mean survival times of experimental group (19.50+/-4.51 days) was significantly longer than that of control group (7.60+/-1.60 days), showing statistically significant difference (P<0.05). After 3rd, 5th and 7th days of transplantation, RAI of control group were 3.80+/-0.35, 5.90+/-0.87 and 7.50+/-1.30, respectively; RAI of experimental group were 3.10+/-0.21, 3.90+/-0.41 and 4.50+/-0.52. There was statistically significant difference in RAI between 2 groups on the 7th day after transplantation (P<0.01). On the 3rd, 5th and 7th days after transplantation, the Fkn of control group was 8.20+/-0.57, 21.30+/-3.30 and 25.70+/-4.91, and that of experimental group was 8.30+/-0.56, 10.30+/-0.67 and 11.70+/- 1.23. There were statistically significant differences in Fkn between 2 groups on the 5th, 7th days after transplantation (P< 0.01). CONCLUSION: Fkn is a participant in acute rejection after the rat orthotopic liver transplantation and can be chosen as a useful target in the diagnosis of acute rejection. CsA has immunosuppressive property in the condition of acute rejection in the rat orthotopic liver transplantation, which may be result from the decreased the level of Fkn.

Apoptosis of lymphocytes in allograft in a rat liver transplantation model induced by resveratrol.

AIM: To study the effect of resveratrol (RES) on the apoptosis of lymphocytes in allograft in a rat liver transplantation model. METHODS: Male Sprague-Dawley (SD) rats were selected as donors and male Wistar rats as recipients for a rejection model. The recipients were divided into four groups after orthotopic liver transplantation (OLTx). In the RES A, B, and C groups, RES was given intraperitoneally once a day (25, 50, and 100 mgkg(-1), respectively) after OLTx, whereas in the control group vehicle buffer was given intraperitoneally once a day. The survival period, lymphocytes apoptosis, expressions of Bcl-2/Bax proteins in lymphocytes, and histopathological findings were then compared among these groups. RESULTS: The mean survival period after OLTx in RES C group was significantly longer than that in control group (P < 0.05). On the seventh post-transplant day, the apoptosis index (AI) of lymphocytes in portal area and the positive rate of Bax protein in lymphocytes in RES C group were significantly increased in comparison with those in control group (both P < 0.05), whereas there is no obvious difference in the expression of Bcl-2 protein in lymphocytes between the control group and various drug groups (all P < 0.05), and a histological examination revealed apparent difference in the severity of rejection between the RES C group and control group (P < 0.05). CONCLUSION: RES has an immunosuppressive effect on lymphocytes under allograft rejection in rat. Inducing apoptosis of lymphocytes and upregulating the ratio of Bax/bcl-2 proteins in lymphocytes in allograft liver may be part of the mechanisms.

Resveratrol prolongs allograft survival after liver transplantation in rats.

AIM: To study the immuno-modulatory effect of resveratrol (RES) on allograft rejection after liver transplantation in rats. METHODS: Male Sprague-Dawley (SD) rats were selected as donors and male Wistar rats as recipients for a rejection model. The recipients were divided into four groups after orthotopic liver transplantation (OLTx). In the RES A, B, and C groups, RES was given intra-peritoneally once a day (25, 50, and 100 mg/kg, respectively) after OLTx, whereas in the control group, vehicle buffer was given intra-peritoneally once a day. The survival time, serum chemistry, production of cytokines, activation of transcription factor NF-kappaB, and histopathologic findings were then compared among these groups. RESULTS: The mean survival time after OLTx in the RES C group was significantly longer than that in the control group (16.7+/-1.2 d vs 9.3+/-0.6 d, P<0.01). On the 7th post-transplant day the serum albumin level significantly improved in the RES C group, the serum total bile acid and alanine aminotransferase (ALT) levels were significantly lower in the RES C group, the serum IL-2 and INF-gamma levels were significantly lower in the RES C group, and the activation of transcription factor NF-kappaB in peripheral blood T lymphocytes was significantly suppressed in the RES A, B, and C groups in comparison to those in the control group. On the 7th post-transplant day, a histological examination revealed apparent difference in the severity of rejection between the RES C group and control group. CONCLUSION: RES has an immuno-suppressive property as well as protective effect on hepatocytes under allograft rejection. It might serve as a novel agent for reducing the severity of hepatic allograft rejection in rats.

[To reconstruct the blood supply of hepatic artery by a modified arterial "sleeve" anastomoses].

OBJECTIVE: To reconstruct the blood supply of hepatic artery of the recipient rat by a modified arterial "sleeve" anastomoses. METHODS: SD-SD and SD-Wistar rats liver transplantation were performed in 30 and 50 cases, respectively. The donor splenic artery, left gastric artery, right gastric artery and gastroduodenal artery were ligated, meanwhile the proper hepatic arteries were reserved. The celiac trunk of donors and the stump of right kidney artery of recipient were anastomosed by using 8-0 suture with "sleeve" technique. RESULTS: The mean time of artery anastomoses was 4.00 +/- 1.31 min. The rate of success was 96.3%. The longest survival time in the model SD-SD (29 survived) was more than 2 months. In SD-Wistar (48 survived), acute rejection was observed 3-5 days after operation and the mean survival time of rat was 9 d. CONCLUSION: The modified arterial "sleeve" anastomoses is an effective method to reconstruct blood supply of hepatic artery of rat recipient in rat liver transplantation.