Tolerance and chimerism and allogeneic bone marrow/stem cell transplantation in liver transplantation.

The liver has particular tolerogenic properties that allow its spontaneous acceptance in some animal species. Liver structure is considered to favor a tolerogenic environment. The peripheral tolerance mechanisms also play a role in spontaneous tolerance to liver graft. In a clinical setting, the main challenge nowadays facing liver transplantation is minimization of immunosuppression with the goal of donor-specific tolerance. Mechanisms involved in tolerance to transplanted organs are complex and partly unknown. A significant mechanism in tolerance induction is chimerism. Chimerism can be induced through transplantation of allogeneic donor bone marrow/stem cells under appropriate host conditioning. This review focuses on the tolerance mechanisms in liver transplantation and highlights the role of chimerism and allogeneic bone marrow/stem cell transplantation in tolerance development.

Resveratrol inhibits VEGF expression of human hepatocellular carcinoma cells through a NF-kappa B-mediated mechanism.

BACKGROUND/AIMS: Resveratrol, a polyphenolic phytochemical present in berries, grapes, and wine, has emerged as a promising chemopreventive candidate. The aim of the present study was to determine the inhibitory effect of resveratrol on vascular endothelial growth factor (VEGF) expression and angiogenesis in hepatocellular carcinoma (HCC) and to explore its mechanism. METHODOLOGY: VEGF protein was detected by western blot, whereas VEGF mRNA expression was investigated by RT-PCR. Nuclear factor-kappa B (NF-kappa B) was measured by electrophoretic mobility shift assay (EMSA). Xenograft sections were stained for CD34 to study microvessels in vivo. RESULTS: We found that VEGF protein and mRNA expressions in the cells treated with resveratrol were significantly decreased. The activation of NF-kappa B was also intensely inhibited by resveratrol. Growth of tumours in nude mice was inhibited by resveratrol. Microvessel density was decreased with resveratrol treatment. CONCLUSIONS: The inhibitory effect of resveratrol on VEGF activity may occur partly through suppression of the activation of NF-kappa B in HepG2 cells. Resveratrol also significantly inhibited tumour growth and angiogenesis.

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.

[Resveratrol increases sensitivity of CNE2 cells to chemotherapeutic drugs under hypoxia].

OBJECTIVE: To explore the sensitization effects of resveratrol on CNE2 nasopharyngeal carcinoma cell line with hypoxia-induced chemotherapy resistance and the potential mechanism. METHODS: Human CNE2 nasopharyngeal carcinoma cell line was cultured under hypoxic conditions (37 degrees centigrade, 5% CO(2), 2% O(2)) in vitro. The cultured cells were treated with different concentrations of resveratrol for 48 h. Reversal fold (RF) of reseratrol to chemotherapeutic drugs in CNE2 cells was measured by methyl thiazolyl tetrazolium (MTT) assay. Apoptotic rate of CNE2 cells was observed by flow cytometry. Reverse transcription-polymerase chain reaction (RT-PCR) method and Western blotting were used to investigate the expressions of multidrug resistance gene 1 (mdr1), multidrug resistance-associated protein 1 (MRP1) and hypoxia inducible factor 1alpha (HIF-1alpha) in CNE2 cells. RESULTS: Resveratrol combined with chemotherapeutics produced a synergistic effect. The RF of 200 micromol/L resveratrol to paclitaxel was 2.58. Combined with paclitaxel, 25, 50, 100 and 200 micromol/L of resveratrol increased the apoptotic rate of CNE2 cells from (22.14+/-1.09)% to (23.24+/-1.37)%, (27.57+/-2.01)%, and (30.36+/-2.31)%, respectively. Resveratrol could down-regulate the expressions of HIF-1alpha, mdr1 and MRP1 significantly. After being treated with resveratrol at different concentrations separately, the expressions of HIF-1alpha, mdr1 and MRP1 in CNE2 cells decreased significantly as compared with paclitaxel alone or paclitaxel plus verapamil (P<0.01). CONCLUSION: Resveratrol can enhance the sensitivity of CNE2 cells to chemotherapeutic drugs under hypoxia. The potential mechanism is partly attributed to inhibiting the gene expressions of HIF-1alpha, mdr1 and MRP1.

[Reversal effect of resveratrol on chemotherapy resistance in KBv200 cell line and underlying mechanisms].

OBJECTIVE: To explore the reversal effect and potential mechanism of resveratrol on multidrug resistance of human oral epidermoid carcinoma KBv200 cells. METHODS: MTT assay was used to investigate reversal index of resveratrol to vincristine, adriamycin and paclitaxel. Cell apoptosis were measured by flow cytometry. RT-PCR and Western blot were used to detect mRNA and protein expression of multidrug resistant 1 (MDR1) and B cell lymphoma leukemia-2 (Bcl-2). RESULTS: Resveratrol produced a synergistic effect with chemotherapeutics and obviously reversed the multidrug resistant phenotype of KBv200 cells. The reversal fold (RF) of 200 micromol/L resveratrol to vincristine, paclitaxel and adriamycin were 77.1, 61.3 and 5.9, respectively. The gene array results showed that resveratrol greatly downregulated expression levels of Bcl-2 and MDR1. After treated with 100 micromol/L, 200 micromol/L resveratrol, the expression level of Bcl-2 and MDR1 in KBv200 cells were markedly decreased in comparison with those untreated (t were 2.98, 3.51 and 3.12, 4.56, P < 0.05). CONCLUSIONS: Resveratrol can efficiently reverse multidrug resistance in KBv200 cells. The potential mechanism may be via inhibiting the multidrug resistant gene expressions and/or promoting cell apoptosis.

[Expression of heparin-binding epidermal growth factor-like growth factor in patients with gastric carcinoma].

OBJECTIVE: To investigate the expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in patients with gastric carcinoma in different stages. METHODS: The expressions of HB-EGF protein and mRNA in normal gastric tissues, metaplasic intestinal mucosa, early-stage gastric cancer and advanced-stage gastric cancer tissues were detected by immunohistochemistry and in situ hybridization. RESULTS: HB-EGF expression was only detected in the parietal cells of the gastric fundic glands and in gastrin cells of the pyloric glands in normal gastric tissues. Weak HB-EGF expression was detected in the epithelial cells of the gastric mucosa in intestinal metaplasic mucosa, and the expression increased in all layers of the gastric mucosa in early-stage gastric cancer. Intense HB-EGF expression was observed in advanced gastric cancer. CONCLUSION: Increased HB-EGF expression may be implicated in the pathogenesis and development of gastric carcinoma.

[Construction and identification of recombinant adeno-associated virus vector harboring fusion gene NT4-Ant-Shepherdin[79-87]].

AIM: To construct a recombinant adeno-associated virus vector harboring fusion gene NT4-Ant-Shepherdin[79-87] and investigate Survivin as a anticancer therapeutic target by use of Shepherdin[79-87]. METHODS: The gene of Ant-Shepherdin[79-87] was obtained by PCR and T-vector method. After inserted in PBV220-NT4 vector and digested with restricted enzyme, The fusion gene of NT4-Ant-Shepherdin[79-87] was sub-cloned into the shuttle plasmid of adeno-associated virus; the products were co-transferred into HEK-293 cell line with helper plasmid pAAV-Ad and adeno-plasmid pFG140. The recombinant adeno-associated virus was produced by homologous recombination of above 3 plasmids in HEK-293 cells and its titer was measured by Dot-blot hybridization. The effect of rAAV-NT4-Ant-Shepherdin[79-87] on A549 cell line was measured by a colorimetric 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay. RESULTS: DNA sequencing results verified that the sequence of Ant-Shepherdin[79-87] was consistent with that we had designed. After transformed E.coli DH5alpha, a fragment of 321 bp was confirmed. High titer of recombinant adeno-associated virus was obtained by homologous recombination in HEK-293 cell lines (3.4x10(13)pfu/L). rAAV-NT4-Ant-Shepherdin[79-87] had strong induce apoptosis effect on A549 cells. CONCLUSION: The recombinant adeno-associated virus vector encoding fusion gene NT4-Ant-Shepherdin[79-87] is successfully constructed in this experiment by molecular cloning and in vitro recombination techniques, which provided the basis of further research of Survivin for cancer gene therapy.

Management of spontaneous rupture of hepatocellular carcinoma.

BACKGROUND: Management of patients with spontaneous rupture of hepatocellular carcinoma in a single centre is reported and the diagnosis and treatment are discussed. METHODS: The clinical presentations, diagnosis and treatment of 28 cases of spontaneous rupture of hepatocellular carcinoma were reviewed. RESULTS: Twenty-six patients had sudden right upper-quadrant abdominal pain and 53.5% patients were in hypovolaemic shock on admission. The median survival of the patients who received one-stage, two-stage tumour resection and only transarterial embolization was 370, 483.5 and 60 days, respectively. The prognosis of the patients who underwent only conservative treatment or surgical haemostasis was poor. CONCLUSION: Transarterial embolization is the treatment of choice for those who are haemodynamically unstable on admission. Careful evaluations, including functional liver reserve, coagulopathy, tumour size and location should be made before tumour resection.

[Effects of resveratrol on matrix metalloproteinase-9 expression in hepatoma cells].

OBJECTIVE: To observe the effects of resveratrol on proliferation of human hepatocellular carcinoma cell line SMMC-7721 cells and expression of matrix metalloproteinase-9 (MMP-9) in vitro. METHODS: SMMC-7721 cells were treated with different concentrations of resveratrol for 24, 48 and 72 h, respectively. The effect of resveratrol on proliferation of SMMC-7721 cells was assessed with methyl thiazolyl tetrazolium (MTT). The expression of MMP-9 mRNA was determined by reverse transcription polymerase chain reaction (RT-PCR). MMP-9 protein was identified by Western blot analysis. RESULTS: Resveratrol could inhibit the proliferation of SMMC-7721 cells with dose- and time-dependent effects. Moreover, both MMP-9 mRNA expression and MMP-9 protein production were markedly reduced after resveratrol treatment. CONCLUSION: Resveratrol can inhibit the proliferation of SMMC-7721 cells and down-regulate MMP-9 expression. It is presumed that resveratrol may suppress the invasion and metastasis of hepatocellular carcinoma.

Heparanase expression in gallbladder carcinoma and its correlation to prognosis.

BACKGROUND AND AIM: Heparanase is an endo-beta-glucuronidase that cleaves heparan sulfate and has been implicated in tumor angiogenesis and metastasis. The present study was to analyze the expression of and explore the prognostic value of heparanase and two important transcriptional factors, namely hypoxia-inducible factor-1alpha (HIF-1alpha) and nuclear transcriptional factor kappa B p65 (NF-kappaB p65) in gallbladder cancer. METHODS: Heparanase, HIF-1alpha and NF-kappaB p65 protein levels in 38 patients with gallbladder carcinoma were detected by immunohistochemistry and analyzed for clinicopathological significance. RESULTS: The heparanase, HIF-1alpha and NF-kappaB p65 proteins were found in 24 (63.2%), 13 (34.2%) and 22 (57.9%) specimens, respectively. High heparanase expression was closely related to advanced TNM stage (P = 0.007), depth of tumor invasion (P = 0.016), lymph node metastasis (P = 0.040) and decreased postoperative survival at 3 years (50.0% vs 20.8%, P = 0.001). Both HIF-1alpha and NF-kappaB p65 proteins were correlated with tumor size (P = 0.039 and P = 0.027, respectively) and patients positive for HIF-1alpha expression had a decreased survival rate compared with those negative for HIF-1alpha expression (40.0% vs 15.4%, P = 0.035). In addition, heparanase-positive cases had high expression of NF-kappaB p65 compared with the heparanase-negative cases (P = 0.047). CONCLUSION: Heparanase and HIF-1alpha are frequently expressed in gallbladder carcinoma and are associated with decreased survival. High expression of heparanase, combined with NF-kappaB p65, may contribute to the highly invasive and metastatic behavior of gallbladder carcinoma.

[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.

Iatrogenic bile duct injuries from biliary tract surgery.

BACKGROUND: Cholecystectomy is the most commonly performed procedure in general surgery. However, bile duct injury is a rare but still one of the most common complications. These injuries sometimes present variably after primary surgery. Timely detection and appropriate management decrease the morbidity and mortality of the operation. METHODS: Five cases of iatrogenic bile duct injury (IBDI) were managed at the Department of Surgery, First Affiliated Hospital, Xi'an Jiaotong University. All the cases who underwent both open and laparoscopic cholecystectomy had persistent injury to the biliary tract and were treated accordingly. RESULTS: Recovery of the patients was uneventful. All patients were followed-up at the surgical outpatient department for six months to three years. So far the patients have shown good recovery. CONCLUSIONS: In cases of IBDI it is necessary to perform the operation under the supervision of an experienced surgeon who is specialized in the repair of bile duct injuries, and it is also necessary to detect and treat the injury as soon as possible to obtain a satisfactory outcome.

[Research of beta-elemene interventional treatment on VX2 carcinoma transplanted on kidney in rabbits].

OBJECTIVE: To investigate the curative effect and mechanism of beta-elemene interventional treatment on VX2 carcinoma transplanted on kidney in rabbits. METHODS: The rabbits were all transplanted with VX2 carcinoma on kidney. Fifty-five rabbits were randomly divided into 11 groups. Rabbits in these groups were administered interventional treatment of normal saline, iodinated oil, mitomycin, 5-fluorouracil, beta-elemene, cisplatin, carboplatin, adriamycin, thiotepa, cyclophopsphamide, and vincristine, respectively. After corresponding intervention, the tumor volume in each group was measured by ultrasonography and spiral computed tomography, and the tumor growth rate (TGR) was calculated. Nenal and hepatic functions of the rabbits in each group were compared 1 day, 7 and 14 days after the interventional treatment. Morphologic change of the tumor was observed by a light microscopy and a transmission electron microscopy 14 days after interventional treatment. The expressions of Bax and Bcl-2 were measured by immunohistochemical straining. RESULTS: There was statistical significance in the effects of different medicines intervened on VX2 kidney transplanted carcinoma. The VX2 carcinoma of rabbits had high-sensitivity to iodized oil embolism, mitomycin, cisplatin and carboplatin, which showed serious damage to the kidney function, medium-sensitivity to beta-elemene, adriamycin and 5-fluorouracil, in which beta-elemene showed slight damage to the kidney function, and resistance to thiotepa, cyclohosphamide and vincristine. Most tumor cells displayed apoptosis in the beta-elemene interventional treatment group under light microscopy and transmission electron microscopy, and only few tumor cells displayed necrosis. The Bax expression was up-regulated (P<0.05) and the Bcl-2 expression had no significant difference (P>0.05) in the beta-elemene interventional treatment group. CONCLUSION: Intervention treatment of beta-elemene has significant effect on VX2 kidney transplanted carcinoma and little side effect on the kidney function. Its mechanism is related to enhancing the apoptosis of tumor cells, and Bax gene participates in this action.

[Radiosensitization of beta-elemene on VX2 carcinoma transplanted on kidney in rabbits in vivo].

OBJECTIVE: To investigate the radiosensitization of beta-elemene on VX2 carcinoma transplanted on kidney in rabbits in vivo. METHODS: The rabbits were all transplanted with VX2 carcinoma on kidney. The appropriate dose of beta-elemene infusion via renal artery for further study on radiosensitization was determined. Then fifty-five rabbits were divided into three groups: untreated group, radiation group and radiation plus beta-elemene-treated group. After corresponding intervention for each group, the tumor volume was measured by ultrasonography and spiral computed tomography. The sensitization enhancement ratio (SER) of beta-elemene was calculated. The pathological change of tumor tissue in kidney was observed by light microscopy and electron transmission microscopy. The apoptotic index was also examined by TdT-mediated dUTP-biotin nick end labeling method. RESULTS: The most significant radiosensitivity was observed in the radiation plus beta-elemene-treated group with 6 Mev X-ray radiation dose of 3 Gy.Fx(-1).d(-1) x 5 d and beta-elemene dose of 10 mg.kg(-1).d(-1). The average time delayed for tumor growth was obviously longer in the radiation plus beta-elemene-treated group than those in the untreated group and radiation group. The SER of beta-elemene was 1.89. The apoptotic index of tumor cells in the radiation plus beta-elemene-treated group was also significantly higher than those in the untreated group and radiation group. CONCLUSION: The beta-elemene can enhance the effects of irradiation on VX2 carcinoma transplanted to kidney in rabbits in vivo by inducing apoptosis of tumor cells.

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.

[Efficacy of activated charcoal-epirubicin suspension for treatment of breast cancer with axillary metastasis].

OBJECTIVE: To investigate the effect of activated charcoal-epirubicin suspension (Epi-CH) for treatment of breast cancer and clearance of axillary lymph node metastasis. METHODS: Sixty patients with breast cancer of stages II-III were randomized into Epi-CH group (n=40) receiving injection with 10 mg Epi-CH in the tissue around the primary tumor 72 h before modified radical resection and control group (n=20) with 10 mg of aqueous epirubicin injection in the same region. The dissected axillary lymph nodes and the staining lymph nodes were counted. The concentration of epirubicin in the lymph nodes was detected by high-performance liquid chorography, and the specimens of lymph nodes were observed microscopically. RESULTS: In comparison with the control group, Epi-CH injection allowed dissection of 4.04 more lymph nodes (P<0.01) and resulted in the staining rate of the axillary lymph nodes of 86.9% (565/650). The proportion of the staining lymph nodes with diameter>1.0 cm was significantly lower than that with diameter 0.05). In Epi-CH group, the concentration of epirubicin in the stained lymph nodes was significantly higher than that in non-stained ones (443.0-/+123.1 vs 31.8-/+11.9 ng/g, P<0.01). Remarkable degeneration and necrosis could be observed microscopically in the stained lymph nodes. CONCLUSION: Epi-CH allows more effective treatment of breast cancer and clearance of axiliary metastasis by increasing the dissected lymph nodes and raising the concentration of epirubicin in the axillary lymph nodes.

[Impact of preoperative lymphatic chemotherapy on relapse and metastasis of breast cancer and its mechanism].

BACKGROUND & OBJECTIVE: Although it is reported that lymphatic chemotherapy could raise drug concentrations in local lymph nodes and prolong survival time of patients with gastrointestinal tumors, its effect on breast cancer has not been explored. This study was to explore the impact of lymphatic chemotherapy on relapse and metastasis of breast cancer, and to investigate the mechanism. METHODS: Sixty patients with breast cancer of stage II-III were randomized into 2 groups: 40 patients in Epi-CH (carbon activated absorbing epirubicin) group were injected with 10 mg of Epi-CH in the tissue around primary tumor 72 h before modified radical resection; 20 patients in control group were injected with 10 mg of aqueous epirubicin in the same region. The stained nodes full of tumor cells in Epi-CH group and non-stained nodes in control group were selected. The apoptotic index (AI) of cancer cells in metastatic axillary lymph node was calculated by TUNEL method; the expression of Fas/Fas-L proteins was examined by SP immunohistochemistry; the relapse and metastatic rate was compared. RESULTS: The AI of cancer cells in metastatic axillary lymph node was significantly higher in Epi-CH group than in control group [(9.5+/-2.7)% vs. (3.8+/-1.4)%, P<0.01]. The expression of Fas protein was significantly higher in Epi-CH group than in control group (P<0.05), but the expression of Fas-L protein had no difference between the 2 groups (P>0.05). No chemotherapy-related local and whole body reaction occurred in both groups. The relapse and metastatic rate was significantly lower in Epi-CH group than in control group (P<0.05). CONCLUSION: Preoperative Epi-CH lymphatic chemotherapy could suppress relapse and metastasis of breast cancer, which might through up-regulating expression of Fas protein and inducing apoptosis of axillary metastasis cells.

[Effect of preoperative lymphatic chemotherapy on Bcl-2 and Bax expression in axillary metastasis of breast cancer].

OBJECTIVE: To observe the expression of Bcl-2 and Bax proteins and cell apoptosis induced by preoperative lymphatic chemotherapy with epirubicin-activated carbon suspension (Epi-CH) in the cells of axillary metastatic lymph node of breast cancer and investigate the mechanism. METHODS: Sixty patients with breast cancer of stages II-III were randomly divided into two groups. Forty patients in Epi-CH group were injected with 10 mg Epi-CH in the tissue around the primary tumor or biopsy excision 72 h before operation. Twenty patients in the control group were injected with 10 mg epirubicin solution in the same region. The stained lymph nodes full of tumor cells in Epi-CH group and the non-stained nodes in the control group were selected for apoptotic detection by TUNEL method. The expression of Bcl-2 and Bax proteins were examined by SP immunohistochemistry. RESULTS: The apoptotic index of the metastatic cancer cells in Epi-CH group was increased remarkably in comparison with that in the control group [(9.5+/-2.7) % vs (3.8+/-1.4) %, P<0.01). Compared with the control group, the expression of Bcl-2 and Bax proteins were up-regulated significantly in Epi-CH group (P<0.05 and P<0.01, respectively), resulting in decreased ratio of Bcl-2/Bax. CONCLUSION: Lymphatic chemotherapy can promote cell apotosis in axillary metastasis of breast cancer, which may result from decreased ratio of Bcl-2/Bax.

Effect of resveratrol and in combination with 5-FU on murine liver cancer.

AIM: To study the anti-tumor effect of resveratrol and in combination with 5-FU on murine liver cancer. METHODS: Transplantable murine hepatoma22 model was used to evaluate the anti-tumor activity of resveratrol (RES) alone or in combination with 5-FU in vivo. H22 cell cycles were analyzed with flow cytometry. RESULTS: Resveratrol could inhibit the growth of murine hepatoma22, after the mice bearing H22 tumor were treated with 10 mg/kg or 15 mg/kg resveratrol for ten days, and the inhibition rates were 36.3% (n = 10) and 49.3% (n = 9), respectively, which increased obviously compared with that in control group (85+/-22 vs 68+/-17, P<0.01). RES could induce the S phase arrest of H22 cells, and increase the percentage of cells in S phase from 59.1% (n = 9) to 73.5% (n = 9) in a dose-dependent manner (P<0.05). The enhanced inhibition of tumor growth by 5-FU was also observed in hepatoma22 bearing mice when 5-FU was administered in combination with 10 mg/kg resveratrol. The inhibition rates for 20 mg/kg or 10 mg/kg 5-FU in combination with 10 mg/kg resveratrol were 77.4% and 72.4%, respectively, compared with the group of 20 mg/kg or 10 mg/kg 5-FU alone, in which the inhibition rates were 53.4% and 43.8%, respectively (n = 8). There was a statistical significance between the combination group and 5-FU group. CONCLUSION: RES could induce the S phase arrest of H22 cells and enhance the anti-tumor effect of 5-FU on murine hepatoma22 and antagonize its toxicity markedly. These results suggest that resveratrol, as a biochemical modulator to enhance the therapeutic effects of 5-FU, may be potentially useful in cancer chemotherapy.

Effects of Antiadhesion preparation on free fibrinogen and fibrin degrading products in abdominal exudates of rabbits postoperatively.

AIM: To observe effects of ACOL on fibrinogen (FIB), fibrin degrading products (FDP) and changes of FIB and FDP concentration in rabbits with intro-abdominal exudates during 7 d after major abdominal surgery. METHODS: Sixty New Zealand rabbits were randomly divided into 4 groups: ACOL group, the control group, DCT group and the normal group. After being modeled, except the normal group, the other 3 groups were treated with different ways for a week; the intro-abdominal exudates of rabbits in the 4 groups were drawn for FIB and FDP measurement once daily during 7 d after major abdominal surgery. RESULTS: FIB and FDP in the intro-abdominal exudates altered in a regular way and ACOL could change the concentration of FIB and FDP in the intra-abdominal exudates after major abdominal surgery. CONCLUSION: ACOL can prevent intestinal adhesion by reducing the concentration of FIB and raising that of FDP in the intro-abdominal exudates after major abdominal surgery.