Objective: To evaluate the value of inactivated bone replantation with preservation of the epiphysis following the effective chemotherapy in avoiding postoperative discrepancy of the affected limb in children with ost...Objective: To evaluate the value of inactivated bone replantation with preservation of the epiphysis following the effective chemotherapy in avoiding postoperative discrepancy of the affected limb in children with osteosarcoma. Methods: Two children (aged 5 and 10 years, 1 male and 1 female) with osteosarcoma underwent inactivated bone replantation with preserving epiphysis following chemotherapy (MMIA protocol, including high-dose methotrexate, adriamycin and ifosfamide). After two cycles of preop-erative chemotherapy, pain vanished, the local mass shrank and there was no pain on pressing the affected parts. Sera AKP and LDH were reduced to normal levels; marked shrinkage and sclerotic changes and good margin of lesions were seen on plain radiographs and MR images. Two courses of the same protocol as preoperative chemotherapy were administered postoperatively. Results: Postoperative histological examination of the specimens demonstrated absence of vital tumor cells. Incisions healed well and no complications occurred. The replanted inactivated bone healed with host at 6 months after operation. In the two patients, no evidence was seen of metastasis and recurrence and discrepancy of the affected limbs in postoperative 36 and 48 months. Functions of the affected limbs were satisfactory. Conclusion: Inactivated bone replantation with preserving epiphysis was a viable option for osteosarcoma in children. The long-term outcomes remain to be further proven.展开更多
Objective: To investigate the inhibitory effects of the Bcl-2 antisense oligodeoxynucleotides (ASODN) on tumor formation and growth of human lung carcinoma transplanted subcutaneously in nude mice. Methods: Human ...Objective: To investigate the inhibitory effects of the Bcl-2 antisense oligodeoxynucleotides (ASODN) on tumor formation and growth of human lung carcinoma transplanted subcutaneously in nude mice. Methods: Human NCI-H460 cells treated with Bcl-2 ASODN or nonesense oligodeoxynucleotide (NSODN) and untreated NCI-H460 cells were respectively implanted subcutaneously into nude mice. When the diameters of tumor were above 0.5 cm after untreated NCI-H460 cells injection, the mice bearing tumor were randomly divided into three groups: saline control group, Bcl-2 ASODN group, NSODN group. ODN was directly injected into the tumor body for 3 weeks. The weight and volume of subcutaneous tumors were measured, and the morphology of tumor cells was observed. Results: The tumorigenic ability of the treated NCI-H460 cells by Bcl-2 ASODN was reduced. The mean time at which tumor can be detected was prolonged up to 12.6 days (P〈0.01). The maximum tumor growth inhibitory rate was 87.5%. In therapeutic efficacy, growth of tumor was significantly inhibited in Bcl-2 ASODN group as compared with that in NSODN group, saline-treated group (P〈0.01). The NSODN control was ineffective. In comparison with NSODN-treated, saline-treated mice, those treated with Bcl-2 ASODN showed a significant decrease in median weight of subcutaneous tumors (P〈0.01). The growth inhibitory rate was 71.0% in ASODN group. Conclusion: Bcl-2 ASODN could inhibit tumor formation and tumor growth in nude mice.展开更多
AIM: To study the effect of the transfected Twist gene on invasion and metastasis of gastric carcinoma cells and the possible mechanisms involved. METHODS: Human gastric carcinoma MKN28 cells were stably transfected w...AIM: To study the effect of the transfected Twist gene on invasion and metastasis of gastric carcinoma cells and the possible mechanisms involved. METHODS: Human gastric carcinoma MKN28 cells were stably transfected with Twist sense plasmid, and MKN45 cells were stably transfected with Twist antisense plasmid using the lipofectamine transfection technique. RT-PCR, Western blotting, EMSA, gelatin zymography assay, and in vitro invasion and migration assays were performed. Nude mice metastasis models were established by the abdominal cavity transfer method. RESULTS: Cell models (TwistS-MKN28) that steadily expressed high Twist protein were obtained. Compared with MKN28 and pcDNA3-MKN28 cells, adherence, migration and invasion ability of TwistS -MKN28 cells were clearly raised. The number of cancer nodules was increased significantly in the abdominal cavity and liver of nude mice inoculated with TwistS-MKN28 cells. Overexpression of Twist in MKN28 cells increased Tcf-4/ Lef DNA binding activity, and promoted expression of Tcf-4’s downstream target genes cyclin D1 and MMP-2. However, suppression of Twist (TwistAS-MKN45) inhibited MKN45 cell invasion and the expression of cyclin D1 was reduced. The activity of MMP-2 was also decreased. CONCLUSION: These results indicate that Twist promotes gastric cancer cell migration, invasion and metastasis, and Twist may play an important role in Wnt/ Tcf-4 signaling.展开更多
AIM: To evaluate the relationship between the expression of cell adhesion molecules (CAMs) and the biological behavior of gastric carcinoma. METHODS: Expression of syndecan-1, E-cadherin and integrin β3 were evaluate...AIM: To evaluate the relationship between the expression of cell adhesion molecules (CAMs) and the biological behavior of gastric carcinoma. METHODS: Expression of syndecan-1, E-cadherin and integrin β3 were evaluated by immunohistochemical study in a total of 118 gastric carcinomas and 20 non- tumor gastric mucosas. RESULTS: The expressions of syndecan-1 and E-cadherin were significantly lower in gastric carcinoma compared to non-tumor gastric mucosa, and the low expression rates were positively correlated to the tumor invasion depth, vessel invasion, lymph node metastasis and distant metastasis (P < 0.01 in all cases). However, the expression of integrin β3 was significantly higher in gastric carcinoma compared to non-tumor gastric mucosa, and the high expression rates were positively correlated to the tumor invasion depth, vessel invasion, lymph node metastasis and distant metastasis (P < 0.01 in all cases). In addition, the three protein expressions were correlated to the tumor growth pattern (P < 0.01, P < 0.01, and P < 0.05 respectively), but not correlated to tumor differentiation (P > 0.05, P > 0.05 and P > 0.05 respectively). Positive correlation was observed between the expressions of syndecan-1 and E-cadherin, but they which were negatively correlated to the expression of integrin β3 (P < 0.01 in all cases). Univariate analysis demonstrated that the mean survival time and 5-year survival rate were lower in the cases with low expressions of syndecan-1 and E-cadherin and high expression of integrin β3 (P < 0.01, in all cases). COX multivariate analysis showed that the expression level of syndecan-1 could be an independent prognostic index of gastric carcinoma (P < 0.01), whereas E-cadherin and integrin β3 could not be independent indexes (P > 0.05, P > 0.05 respectively). CONCLUSION: The low expression of syndecan-1 and E-cadherin and the high expression of integrin β3 are significantly correlated with the invasion and metastasis of gastric carcinoma, and they are highly correlated with each other. Therefore they may serve as important prognostic markers of gastric carcinoma.展开更多
The liver is an essential player in the pathway of coagulation in both primary and secondary haernostasis. Only yon Willebrand factor is not synthetised by the liver, thus liver failure is associated with impairment o...The liver is an essential player in the pathway of coagulation in both primary and secondary haernostasis. Only yon Willebrand factor is not synthetised by the liver, thus liver failure is associated with impairment of coagulation. However, recently it has been shown that the delicate balance between pro and antithrornbotic factors synthetised by the liver might be reset to a lower level in patients with chronic liver disease. Therefore, these patients might not be really anticoagulated in stable condition and bleeding may be caused only when additional factors, such as infections, supervene. Portal hypertension plays an important role in coagulopathy in liver disease, reducing the number of circulating platelets, but platelet function and secretion of thrornbopoietin have been also shown to be impaired in patients with liver disease. Vitamin K deficiency may coexist, so that abnormal clotting factors are produced due to lack of gamma carboxylation. Moreover during liver failure, there is a reduced capacity to clear activated haernostatic proteins and protein inhibitor complexes from the circulation. Usually therapy for coagulation disorders in liver disease is needed only during bleeding or before invasive procedures. When end stage liver disease occurs, liver transplantation is the only treatment available, which can restore normal haemostasis, and correct genetic clotting defects, such as haemophilia or factor V Leiden mutation. During liver transplantation haemorrage may occur due to the pre-existing hypocoagulable state, the collateral circulation caused by portal hypertension and increased fibrinolysis which occurs during this surgery.展开更多
AIM: To investigate the histological and ultra-structural characteristics of liver graft during different of warm ischemia time (WIT) in rats and to predict the maximum limitation of liver graft to warm ischemia. M...AIM: To investigate the histological and ultra-structural characteristics of liver graft during different of warm ischemia time (WIT) in rats and to predict the maximum limitation of liver graft to warm ischemia. METHODS: The rats were randomized into 7 groups undergoing warm ischemia injury for 0, 10, 15, 20, 30, 45 and 60 min, respectively. All specimens having undergone warm ischemia injury were investigated dynamically by light and electron microscopy, and histochemistry staining. After orthotopic liver transplantation (OLT), the recovery of morphology of liver grafts after 6, 24 and 48 h was observed. RESULTS: The donor liver from non-heart-beating donors (NHBD) underwent ischemia injury both in the warm ischemia period and in the reperfusion period. Morphological changes were positively related to warm ischemia injury in a time-dependent manner during the reperfusion period. The results demonstrated that different degrees of histocyte degeneration were observed when WIT was within 30 min, and became more severe with the prolongation of WIT, no obvious hepatocyte necrosis was noted in any specimen. In the group undergoing warm ischemia injury for 45 min, small focal necrosis occurred in the central area of hepatic Iobule first. In the group undergoing warm ischemia injury for 60 rain, patchy or diffused necrosis was observed and the area was gradually extended, while hepatic sinusoid endothelial cells were obviously swollen. Hepatic sinusoid was obstructed and microcirculation was in disorder.CONCLUSION: The rat liver graft undergoing warm ischemia injury is in the reversible stage when the WIT is within 30 min. The 45 min WIT may be a critical point of rat liver graft to endure warm ischemia injury. When the WIT is over 60 min, the damage is irreversible.展开更多
AIM:The prognosis of early gastric carcinoma (EGC) is generally excellent after surgery. The presence or absence of lymph node metastasis in EGC is an important prognostic factor. The survival and recurrence rates of ...AIM:The prognosis of early gastric carcinoma (EGC) is generally excellent after surgery. The presence or absence of lymph node metastasis in EGC is an important prognostic factor. The survival and recurrence rates of node-negative EGC are much better than those of node-positive EGC. This study examined the factors related to lymph node metastasis in EGC to determine the appropriate treatment for EGC.METHODS: We investigated 748 patients with EGC who underwent surgery between January 1985 and December 1999 at the Division of Gastroenterologic Surgery, Department of Surgery, Chonnam National University Hospital. Several clinicopathologic factors were investigated to analyze their relationship to lymph node metastasis: age, sex, tumor location, tumor size, gross type, histologic type, depth of invasion, extent of lymph node dissection, type of operation,and DNA ploidy.RESULTS:Lymph node metastases were found in 75 patients (10.0%). Univariate analysis showed that male sex, tumor size larger than 2.0cm, submucosal invasion of tumor, histologic differentiation, and DNA ploidy pattern were risk factors for regional lymph node metastasis in EGC patients. However, a multivariate analysis showed that three risk factors were associated with lymph node metastasis:large tumor size, undifferentiated histologic type and submucosal invasion. No statistical relationship was found for age, sex, tumor location, gross type, or DNA ploidy in multivariate analysis. The 5-year survival rate was 94.2% for those without lymph node metastasis and 87.3% for those with lymph node metastasis, and the difference was significant (P<0.05).CONCLUSION: In patients with EGC, the survival rate of patients with positive lymph nodes is significantly worse than that of patients with no lymph node metastasis. Therefore,a standard D2 lymphadenectomy should be performed in patients at high risk of lymph node metastasis: large tumor size, undifferentiated histologic type and submucosal invasion.展开更多
Acute humoral rejection (AHR) is uncommon after ABO- compatible liver transplantation. Herein, we report two cases of AHR treated with plasmapheresis and rituximab in two ABO-compatible liver-transplant patients wit...Acute humoral rejection (AHR) is uncommon after ABO- compatible liver transplantation. Herein, we report two cases of AHR treated with plasmapheresis and rituximab in two ABO-compatible liver-transplant patients with preformed anti-human leukocyte antigen donor-specific antibodies. Patient 1 experienced a biopsy-proven AHR at day 10 post-transplant. She was treated by steroid pulses, and OKT3. Because of persisting signs of biopsy-proven AHR at day 26, she was treated by plasmapheresis and rituximab. Uver enzyme levels did not improve, and she died on day 41. Patient 2 experienced a biopsy-proven AHR on day 10 post-transplant. She was treated by steroid pulses, plasmapheresis, and rituximab. Liver enzymes returned to within normal range 18 d after diagnosis. Uver biopsies, at 3 and 9 mo post-transplant, showed complete resolution of AHR. We conclude that plasmapheresis should be started as soon as AHR is diagnosed, and be associated with a B-cell depleting agent. Rituximab may be considered as a first-line therapy.展开更多
AIM: To evaluate whether the Milan criteria are useful in patients with hepatocellular carcinoma (HCC) who received transarterial chemoembolization (TACE) before liver transplantation (LT). METHODS: Thirty-six HCC pat...AIM: To evaluate whether the Milan criteria are useful in patients with hepatocellular carcinoma (HCC) who received transarterial chemoembolization (TACE) before liver transplantation (LT). METHODS: Thirty-six HCC patients who fulfilled the Milan criteria after having received TACE and subsequently underwent LT were included (TACE + LT group) in the study. As controls, 21 patients who also met the Milan criteria and underwent LT without prior treatment were selected (LT group). Post-LT clinical outcomes, such as HCC recurrence, survival rate, and histologic features of explanted livers, were compared between the two groups. RESULTS: Baseline characteristics were not different between the two groups. Pre-LT maximal tumor diameter in TACE + LT group was similar to that of LT group (2.0 ± 0.6 cm vs 2.3 ± 0.9 cm; P = 0.10). Post-LT histologic findings also revealed similar maximal tumor diameter in the two groups (2.4 ± 1.4 cm vs 2.3 ± 0.9 cm; P = 0.70). Explanted livers showed similar incidence of unfavorable pathologic features. The morality within 60 d after transplantation was not different between the two groups (8.3% vs 9.5%; P = 0.99). Post-LT 5-year survival rate (57% vs 74%; P = 0.70) and cumulative recurrence rate (8.3% vs 4.8%; P = 0.90) were not significantly different between the two groups. CONCLUSION: The Milan criteria are still a useful selec- tion criteria showing favorable outcomes in HCC patientsreceiving TACE before LT.展开更多
In the following four articles, we will provide an overview of the current clinical work in different areas of liver transplantation. For many decades, this transplantation has been the treatment choice for patients ...In the following four articles, we will provide an overview of the current clinical work in different areas of liver transplantation. For many decades, this transplantation has been the treatment choice for patients suffering from chronic and acute liver diseases.展开更多
AIM: To investigate the effect of inducible nitric oxide synthase inhibitor, aminoguanidine, on pancreas transplantation in rats. METHODS: A model of pancreas transplantation was established in rats. Streptozotocin-in...AIM: To investigate the effect of inducible nitric oxide synthase inhibitor, aminoguanidine, on pancreas transplantation in rats. METHODS: A model of pancreas transplantation was established in rats. Streptozotocin-induced diabetic male Wistar rats were randomly assigned to sham-operation control group (n= 6), transplant control group (n= 6), and aminoguanidine (AG) treatment group (n=18). In the AG group, aminoguanidine was added to intravascular infusion as the onset of reperfusion at the dose of 60 mg/kg, 80 mg/kg, 100 mg/kg body weight, respectively. Serum nitric oxide (NO) level, blood sugar and amylase activity were detected. Nitric oxide synthase (NOS) test kit was used to detect the pancreas cNOS and inducible NOS (iNOS) activity. Pancreas sections stained with HE and immunohistochemistry were evaluated under a light microscope. RESULTS: As compared with the transplant control group, the serum NO level and amylase activity decreased obviously and the evidence for pancreas injury was much less in the AG group. The AG (80 mg/kg body weight) group showed the most signifi cant difference in NO and amylase (NO: 66.0 ± 16.6 vs 192.3 ± 60.0, P < 0.01 and amylase: 1426 ± 177 vs 4477 ± 630, P < 0.01). The expression and activity of tissue iNOS, and blood sugar in the AG (80 mg/kg body weight) group were much lower than those in the transplant control group (iNOS: 2.01 ± 0.23 vs 26.59 ± 5.78, P < 0.01 and blood sugar: 14.2 ± 0.9 vs 16.8 ± 1.1, P < 0.01). CONCLUSION: Selective iNOS inhibitor, aminoguanidine as a free radical, has a protective effect on pancreas transplantation in rats by inhibiting NO and reducing its toxicity.展开更多
AIM:To evaluate survival and recurrence after salvage liver transplantation(SLT) for the treatment of hepatocellular carcinoma(HCC) compared with primary liver transplantation(PLT) using a meta-analysis.METHODS:Litera...AIM:To evaluate survival and recurrence after salvage liver transplantation(SLT) for the treatment of hepatocellular carcinoma(HCC) compared with primary liver transplantation(PLT) using a meta-analysis.METHODS:Literature on SLT versus PLT for the treatment of HCC published between 1966 and July 2011 was retrieved.A meta-analysis was conducted to estimate pooled survival and disease-free rates.A fixed or random-effect model was established to collect the data.RESULTS:The differences in overall survival and disease-free survival rates at 1-year,3-year and 5-year survival rates were not statistically significant between SLT group and PLT group(P > 0.05).After stratifying the various studies by donor source and Milan criteria,we found that:(1) Living donor liver transplantation recipients had significantly higher 1-year survival rate,lower 3-year and 5-year survival rates compared with deceased-donor liver transplantation(DDLT) recipients.And in DDLT recipients they had better 1-year and 5-year disease-free survival rate in SLT group;and(2) No difference was seen in 1-year,3-year and 5-year survival rates between two groups who beyond Milan criteria at the time of liver transplantation.CONCLUSION:SLT can be effectively performed for patients with recurrence or deterioration of liver function after hepatectomy for HCC.It does not increase the perioperative mortality and has a similar long-term survival rates compared to PLT.展开更多
Hepatitis B (HBV) reactivation induced by chemotherapy is problem encountered recently in the management of malignant diseases. Chemotherapy-induced HBV reacti- vation may ultimately lead to terminal acute liver fai...Hepatitis B (HBV) reactivation induced by chemotherapy is problem encountered recently in the management of malignant diseases. Chemotherapy-induced HBV reacti- vation may ultimately lead to terminal acute liver failure. Liver transplantation (LT) currently remains the only definitive treatment option for such cases, but is generally denied to patients suffering from malignancy. Here, the authors describe 2 cases of cancer-free and HBV graft renfection-free survival after LT performed for terminal liver failure arising from HBV reactivation induced by chemotherapy for advanced stage lymphoma. These 2 cases, and some other reports in the literature, may suggest that patients suffering from hematologic malignan- cies and terminal liver disease can be considered for LT if the prognosis of their hematologic malignancy is good.展开更多
Objective To evaluate the efficacy and safety of the combination of XELOX regimen (oxaliplatin plus capecitabine) with thalidomide for the first-line treatment of metastatic colorectal cancer (MCRC). Methods All o...Objective To evaluate the efficacy and safety of the combination of XELOX regimen (oxaliplatin plus capecitabine) with thalidomide for the first-line treatment of metastatic colorectal cancer (MCRC). Methods All of the 89 patients with MCRC who fulfilled eligibility criteria were randomly assigned to treatment group (n=44) and control group (n=45). The treatment group received a combination of XELOX with thalidomide and the control group received XELOX alone. Each patient received at least 2 cycles of treatment (1 cycle=21 d). The primary endpoint was progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR) as well as disease control rate (DCR). Drug safety and quality of life were also assessed. Results The median PFS of the treatment and control groups were 5.6 and 5.2 months, respectively. The difference did not have a statistical significance (P=0.307). The ORRs of the two groups also had no statistical difference (34.1% vs. 26.7%, P=0.446). The addition of thalidomide to XELOX significantly improved the DCR (63.6% vs. 42.2%, P=0.043). Among 24 patients with hepatic metastasis in the treatment group, 2 patients satisfied the surgical criteria after treatment but none of 23 patients in the control group did. Grade 3 or 4 constipation in patients treated with thalidomide was significantly increased (20.5% vs. 4.4%, P=0.022) but didn't result in treatment interruption. The rate of lethargy was increased but the difference between the two groups had no statistical significance (13,6% vs. 4.4%, P=0.130). The quality of life had no statistical difference between the two groups. Conclusions The combination of XELOX with thalidomide for the first-line treatment of MCRC was well tolerated. Statistically significant improvement was achieved for time DCR but not for PFS.展开更多
AIM:To assess the validity of the Milan and University of California San Francisco(UCSF) criteria and examine the long-term outcome of orthotopic liver transplantation(OLT) in patients with hepatocellular carcinoma(HC...AIM:To assess the validity of the Milan and University of California San Francisco(UCSF) criteria and examine the long-term outcome of orthotopic liver transplantation(OLT) in patients with hepatocellular carcinoma(HCC) in a single-center study.METHODS:This study is a retrospective review of prospectively collected data.Between 1998 and 2009,56 of 356 OLTs were performed in patients with HCC.Based on pathological examination of liver explants,patients were retrospectively categorized into 3 groups:Milan +(n = 34),Milan-/UCSF +(n = 7) and UCSF-(n = 14).RESULTS:Median follow-up period was 39.5(1-124) mo.The 5-year overall survival rates in the Milan +,Milan-/UCSF + and UCSF-groups were 87.7%,53.6% and 33.3%,respectively(P < 0.000).Within these groups,tumor recurrence was determined in 5.8%,14.3% and 40% of patients,respectively(P < 0.011).Additionally,the presence of microvascular invasion within the explanted liver had a negative effect on the 5-year disease free survival(74.7% vs 46.7%,P < 0.044).CONCLUSION:The Milan criteria are reliable in the selection of suitable candidates for OLT for the treatment of HCC.For cases of OLT involving living donors,the UCSF criteria may be applied.展开更多
文摘Objective: To evaluate the value of inactivated bone replantation with preservation of the epiphysis following the effective chemotherapy in avoiding postoperative discrepancy of the affected limb in children with osteosarcoma. Methods: Two children (aged 5 and 10 years, 1 male and 1 female) with osteosarcoma underwent inactivated bone replantation with preserving epiphysis following chemotherapy (MMIA protocol, including high-dose methotrexate, adriamycin and ifosfamide). After two cycles of preop-erative chemotherapy, pain vanished, the local mass shrank and there was no pain on pressing the affected parts. Sera AKP and LDH were reduced to normal levels; marked shrinkage and sclerotic changes and good margin of lesions were seen on plain radiographs and MR images. Two courses of the same protocol as preoperative chemotherapy were administered postoperatively. Results: Postoperative histological examination of the specimens demonstrated absence of vital tumor cells. Incisions healed well and no complications occurred. The replanted inactivated bone healed with host at 6 months after operation. In the two patients, no evidence was seen of metastasis and recurrence and discrepancy of the affected limbs in postoperative 36 and 48 months. Functions of the affected limbs were satisfactory. Conclusion: Inactivated bone replantation with preserving epiphysis was a viable option for osteosarcoma in children. The long-term outcomes remain to be further proven.
基金This project was supported by Natural Science Program Foundation of the Guangdong Provincial (021195) and The GuangzhouCity Key Foundation of Science and Technology Program (2001-Z-037-01)
文摘Objective: To investigate the inhibitory effects of the Bcl-2 antisense oligodeoxynucleotides (ASODN) on tumor formation and growth of human lung carcinoma transplanted subcutaneously in nude mice. Methods: Human NCI-H460 cells treated with Bcl-2 ASODN or nonesense oligodeoxynucleotide (NSODN) and untreated NCI-H460 cells were respectively implanted subcutaneously into nude mice. When the diameters of tumor were above 0.5 cm after untreated NCI-H460 cells injection, the mice bearing tumor were randomly divided into three groups: saline control group, Bcl-2 ASODN group, NSODN group. ODN was directly injected into the tumor body for 3 weeks. The weight and volume of subcutaneous tumors were measured, and the morphology of tumor cells was observed. Results: The tumorigenic ability of the treated NCI-H460 cells by Bcl-2 ASODN was reduced. The mean time at which tumor can be detected was prolonged up to 12.6 days (P〈0.01). The maximum tumor growth inhibitory rate was 87.5%. In therapeutic efficacy, growth of tumor was significantly inhibited in Bcl-2 ASODN group as compared with that in NSODN group, saline-treated group (P〈0.01). The NSODN control was ineffective. In comparison with NSODN-treated, saline-treated mice, those treated with Bcl-2 ASODN showed a significant decrease in median weight of subcutaneous tumors (P〈0.01). The growth inhibitory rate was 71.0% in ASODN group. Conclusion: Bcl-2 ASODN could inhibit tumor formation and tumor growth in nude mice.
文摘AIM: To study the effect of the transfected Twist gene on invasion and metastasis of gastric carcinoma cells and the possible mechanisms involved. METHODS: Human gastric carcinoma MKN28 cells were stably transfected with Twist sense plasmid, and MKN45 cells were stably transfected with Twist antisense plasmid using the lipofectamine transfection technique. RT-PCR, Western blotting, EMSA, gelatin zymography assay, and in vitro invasion and migration assays were performed. Nude mice metastasis models were established by the abdominal cavity transfer method. RESULTS: Cell models (TwistS-MKN28) that steadily expressed high Twist protein were obtained. Compared with MKN28 and pcDNA3-MKN28 cells, adherence, migration and invasion ability of TwistS -MKN28 cells were clearly raised. The number of cancer nodules was increased significantly in the abdominal cavity and liver of nude mice inoculated with TwistS-MKN28 cells. Overexpression of Twist in MKN28 cells increased Tcf-4/ Lef DNA binding activity, and promoted expression of Tcf-4’s downstream target genes cyclin D1 and MMP-2. However, suppression of Twist (TwistAS-MKN45) inhibited MKN45 cell invasion and the expression of cyclin D1 was reduced. The activity of MMP-2 was also decreased. CONCLUSION: These results indicate that Twist promotes gastric cancer cell migration, invasion and metastasis, and Twist may play an important role in Wnt/ Tcf-4 signaling.
基金The Grant of Zhejiang Province Natural Science Foundation, No. M303843
文摘AIM: To evaluate the relationship between the expression of cell adhesion molecules (CAMs) and the biological behavior of gastric carcinoma. METHODS: Expression of syndecan-1, E-cadherin and integrin β3 were evaluated by immunohistochemical study in a total of 118 gastric carcinomas and 20 non- tumor gastric mucosas. RESULTS: The expressions of syndecan-1 and E-cadherin were significantly lower in gastric carcinoma compared to non-tumor gastric mucosa, and the low expression rates were positively correlated to the tumor invasion depth, vessel invasion, lymph node metastasis and distant metastasis (P < 0.01 in all cases). However, the expression of integrin β3 was significantly higher in gastric carcinoma compared to non-tumor gastric mucosa, and the high expression rates were positively correlated to the tumor invasion depth, vessel invasion, lymph node metastasis and distant metastasis (P < 0.01 in all cases). In addition, the three protein expressions were correlated to the tumor growth pattern (P < 0.01, P < 0.01, and P < 0.05 respectively), but not correlated to tumor differentiation (P > 0.05, P > 0.05 and P > 0.05 respectively). Positive correlation was observed between the expressions of syndecan-1 and E-cadherin, but they which were negatively correlated to the expression of integrin β3 (P < 0.01 in all cases). Univariate analysis demonstrated that the mean survival time and 5-year survival rate were lower in the cases with low expressions of syndecan-1 and E-cadherin and high expression of integrin β3 (P < 0.01, in all cases). COX multivariate analysis showed that the expression level of syndecan-1 could be an independent prognostic index of gastric carcinoma (P < 0.01), whereas E-cadherin and integrin β3 could not be independent indexes (P > 0.05, P > 0.05 respectively). CONCLUSION: The low expression of syndecan-1 and E-cadherin and the high expression of integrin β3 are significantly correlated with the invasion and metastasis of gastric carcinoma, and they are highly correlated with each other. Therefore they may serve as important prognostic markers of gastric carcinoma.
文摘The liver is an essential player in the pathway of coagulation in both primary and secondary haernostasis. Only yon Willebrand factor is not synthetised by the liver, thus liver failure is associated with impairment of coagulation. However, recently it has been shown that the delicate balance between pro and antithrornbotic factors synthetised by the liver might be reset to a lower level in patients with chronic liver disease. Therefore, these patients might not be really anticoagulated in stable condition and bleeding may be caused only when additional factors, such as infections, supervene. Portal hypertension plays an important role in coagulopathy in liver disease, reducing the number of circulating platelets, but platelet function and secretion of thrornbopoietin have been also shown to be impaired in patients with liver disease. Vitamin K deficiency may coexist, so that abnormal clotting factors are produced due to lack of gamma carboxylation. Moreover during liver failure, there is a reduced capacity to clear activated haernostatic proteins and protein inhibitor complexes from the circulation. Usually therapy for coagulation disorders in liver disease is needed only during bleeding or before invasive procedures. When end stage liver disease occurs, liver transplantation is the only treatment available, which can restore normal haemostasis, and correct genetic clotting defects, such as haemophilia or factor V Leiden mutation. During liver transplantation haemorrage may occur due to the pre-existing hypocoagulable state, the collateral circulation caused by portal hypertension and increased fibrinolysis which occurs during this surgery.
基金Supported by the Key Clinical Project of Minister of Public Health, No. 97040230
文摘AIM: To investigate the histological and ultra-structural characteristics of liver graft during different of warm ischemia time (WIT) in rats and to predict the maximum limitation of liver graft to warm ischemia. METHODS: The rats were randomized into 7 groups undergoing warm ischemia injury for 0, 10, 15, 20, 30, 45 and 60 min, respectively. All specimens having undergone warm ischemia injury were investigated dynamically by light and electron microscopy, and histochemistry staining. After orthotopic liver transplantation (OLT), the recovery of morphology of liver grafts after 6, 24 and 48 h was observed. RESULTS: The donor liver from non-heart-beating donors (NHBD) underwent ischemia injury both in the warm ischemia period and in the reperfusion period. Morphological changes were positively related to warm ischemia injury in a time-dependent manner during the reperfusion period. The results demonstrated that different degrees of histocyte degeneration were observed when WIT was within 30 min, and became more severe with the prolongation of WIT, no obvious hepatocyte necrosis was noted in any specimen. In the group undergoing warm ischemia injury for 45 min, small focal necrosis occurred in the central area of hepatic Iobule first. In the group undergoing warm ischemia injury for 60 rain, patchy or diffused necrosis was observed and the area was gradually extended, while hepatic sinusoid endothelial cells were obviously swollen. Hepatic sinusoid was obstructed and microcirculation was in disorder.CONCLUSION: The rat liver graft undergoing warm ischemia injury is in the reversible stage when the WIT is within 30 min. The 45 min WIT may be a critical point of rat liver graft to endure warm ischemia injury. When the WIT is over 60 min, the damage is irreversible.
文摘AIM:The prognosis of early gastric carcinoma (EGC) is generally excellent after surgery. The presence or absence of lymph node metastasis in EGC is an important prognostic factor. The survival and recurrence rates of node-negative EGC are much better than those of node-positive EGC. This study examined the factors related to lymph node metastasis in EGC to determine the appropriate treatment for EGC.METHODS: We investigated 748 patients with EGC who underwent surgery between January 1985 and December 1999 at the Division of Gastroenterologic Surgery, Department of Surgery, Chonnam National University Hospital. Several clinicopathologic factors were investigated to analyze their relationship to lymph node metastasis: age, sex, tumor location, tumor size, gross type, histologic type, depth of invasion, extent of lymph node dissection, type of operation,and DNA ploidy.RESULTS:Lymph node metastases were found in 75 patients (10.0%). Univariate analysis showed that male sex, tumor size larger than 2.0cm, submucosal invasion of tumor, histologic differentiation, and DNA ploidy pattern were risk factors for regional lymph node metastasis in EGC patients. However, a multivariate analysis showed that three risk factors were associated with lymph node metastasis:large tumor size, undifferentiated histologic type and submucosal invasion. No statistical relationship was found for age, sex, tumor location, gross type, or DNA ploidy in multivariate analysis. The 5-year survival rate was 94.2% for those without lymph node metastasis and 87.3% for those with lymph node metastasis, and the difference was significant (P<0.05).CONCLUSION: In patients with EGC, the survival rate of patients with positive lymph nodes is significantly worse than that of patients with no lymph node metastasis. Therefore,a standard D2 lymphadenectomy should be performed in patients at high risk of lymph node metastasis: large tumor size, undifferentiated histologic type and submucosal invasion.
文摘Acute humoral rejection (AHR) is uncommon after ABO- compatible liver transplantation. Herein, we report two cases of AHR treated with plasmapheresis and rituximab in two ABO-compatible liver-transplant patients with preformed anti-human leukocyte antigen donor-specific antibodies. Patient 1 experienced a biopsy-proven AHR at day 10 post-transplant. She was treated by steroid pulses, and OKT3. Because of persisting signs of biopsy-proven AHR at day 26, she was treated by plasmapheresis and rituximab. Uver enzyme levels did not improve, and she died on day 41. Patient 2 experienced a biopsy-proven AHR on day 10 post-transplant. She was treated by steroid pulses, plasmapheresis, and rituximab. Liver enzymes returned to within normal range 18 d after diagnosis. Uver biopsies, at 3 and 9 mo post-transplant, showed complete resolution of AHR. We conclude that plasmapheresis should be started as soon as AHR is diagnosed, and be associated with a B-cell depleting agent. Rituximab may be considered as a first-line therapy.
文摘AIM: To evaluate whether the Milan criteria are useful in patients with hepatocellular carcinoma (HCC) who received transarterial chemoembolization (TACE) before liver transplantation (LT). METHODS: Thirty-six HCC patients who fulfilled the Milan criteria after having received TACE and subsequently underwent LT were included (TACE + LT group) in the study. As controls, 21 patients who also met the Milan criteria and underwent LT without prior treatment were selected (LT group). Post-LT clinical outcomes, such as HCC recurrence, survival rate, and histologic features of explanted livers, were compared between the two groups. RESULTS: Baseline characteristics were not different between the two groups. Pre-LT maximal tumor diameter in TACE + LT group was similar to that of LT group (2.0 ± 0.6 cm vs 2.3 ± 0.9 cm; P = 0.10). Post-LT histologic findings also revealed similar maximal tumor diameter in the two groups (2.4 ± 1.4 cm vs 2.3 ± 0.9 cm; P = 0.70). Explanted livers showed similar incidence of unfavorable pathologic features. The morality within 60 d after transplantation was not different between the two groups (8.3% vs 9.5%; P = 0.99). Post-LT 5-year survival rate (57% vs 74%; P = 0.70) and cumulative recurrence rate (8.3% vs 4.8%; P = 0.90) were not significantly different between the two groups. CONCLUSION: The Milan criteria are still a useful selec- tion criteria showing favorable outcomes in HCC patientsreceiving TACE before LT.
文摘In the following four articles, we will provide an overview of the current clinical work in different areas of liver transplantation. For many decades, this transplantation has been the treatment choice for patients suffering from chronic and acute liver diseases.
基金Supported by The Natural Science Foundation of Liaoning Province, No. 00225001
文摘AIM: To investigate the effect of inducible nitric oxide synthase inhibitor, aminoguanidine, on pancreas transplantation in rats. METHODS: A model of pancreas transplantation was established in rats. Streptozotocin-induced diabetic male Wistar rats were randomly assigned to sham-operation control group (n= 6), transplant control group (n= 6), and aminoguanidine (AG) treatment group (n=18). In the AG group, aminoguanidine was added to intravascular infusion as the onset of reperfusion at the dose of 60 mg/kg, 80 mg/kg, 100 mg/kg body weight, respectively. Serum nitric oxide (NO) level, blood sugar and amylase activity were detected. Nitric oxide synthase (NOS) test kit was used to detect the pancreas cNOS and inducible NOS (iNOS) activity. Pancreas sections stained with HE and immunohistochemistry were evaluated under a light microscope. RESULTS: As compared with the transplant control group, the serum NO level and amylase activity decreased obviously and the evidence for pancreas injury was much less in the AG group. The AG (80 mg/kg body weight) group showed the most signifi cant difference in NO and amylase (NO: 66.0 ± 16.6 vs 192.3 ± 60.0, P < 0.01 and amylase: 1426 ± 177 vs 4477 ± 630, P < 0.01). The expression and activity of tissue iNOS, and blood sugar in the AG (80 mg/kg body weight) group were much lower than those in the transplant control group (iNOS: 2.01 ± 0.23 vs 26.59 ± 5.78, P < 0.01 and blood sugar: 14.2 ± 0.9 vs 16.8 ± 1.1, P < 0.01). CONCLUSION: Selective iNOS inhibitor, aminoguanidine as a free radical, has a protective effect on pancreas transplantation in rats by inhibiting NO and reducing its toxicity.
文摘AIM:To evaluate survival and recurrence after salvage liver transplantation(SLT) for the treatment of hepatocellular carcinoma(HCC) compared with primary liver transplantation(PLT) using a meta-analysis.METHODS:Literature on SLT versus PLT for the treatment of HCC published between 1966 and July 2011 was retrieved.A meta-analysis was conducted to estimate pooled survival and disease-free rates.A fixed or random-effect model was established to collect the data.RESULTS:The differences in overall survival and disease-free survival rates at 1-year,3-year and 5-year survival rates were not statistically significant between SLT group and PLT group(P > 0.05).After stratifying the various studies by donor source and Milan criteria,we found that:(1) Living donor liver transplantation recipients had significantly higher 1-year survival rate,lower 3-year and 5-year survival rates compared with deceased-donor liver transplantation(DDLT) recipients.And in DDLT recipients they had better 1-year and 5-year disease-free survival rate in SLT group;and(2) No difference was seen in 1-year,3-year and 5-year survival rates between two groups who beyond Milan criteria at the time of liver transplantation.CONCLUSION:SLT can be effectively performed for patients with recurrence or deterioration of liver function after hepatectomy for HCC.It does not increase the perioperative mortality and has a similar long-term survival rates compared to PLT.
文摘Hepatitis B (HBV) reactivation induced by chemotherapy is problem encountered recently in the management of malignant diseases. Chemotherapy-induced HBV reacti- vation may ultimately lead to terminal acute liver failure. Liver transplantation (LT) currently remains the only definitive treatment option for such cases, but is generally denied to patients suffering from malignancy. Here, the authors describe 2 cases of cancer-free and HBV graft renfection-free survival after LT performed for terminal liver failure arising from HBV reactivation induced by chemotherapy for advanced stage lymphoma. These 2 cases, and some other reports in the literature, may suggest that patients suffering from hematologic malignan- cies and terminal liver disease can be considered for LT if the prognosis of their hematologic malignancy is good.
文摘Objective To evaluate the efficacy and safety of the combination of XELOX regimen (oxaliplatin plus capecitabine) with thalidomide for the first-line treatment of metastatic colorectal cancer (MCRC). Methods All of the 89 patients with MCRC who fulfilled eligibility criteria were randomly assigned to treatment group (n=44) and control group (n=45). The treatment group received a combination of XELOX with thalidomide and the control group received XELOX alone. Each patient received at least 2 cycles of treatment (1 cycle=21 d). The primary endpoint was progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR) as well as disease control rate (DCR). Drug safety and quality of life were also assessed. Results The median PFS of the treatment and control groups were 5.6 and 5.2 months, respectively. The difference did not have a statistical significance (P=0.307). The ORRs of the two groups also had no statistical difference (34.1% vs. 26.7%, P=0.446). The addition of thalidomide to XELOX significantly improved the DCR (63.6% vs. 42.2%, P=0.043). Among 24 patients with hepatic metastasis in the treatment group, 2 patients satisfied the surgical criteria after treatment but none of 23 patients in the control group did. Grade 3 or 4 constipation in patients treated with thalidomide was significantly increased (20.5% vs. 4.4%, P=0.022) but didn't result in treatment interruption. The rate of lethargy was increased but the difference between the two groups had no statistical significance (13,6% vs. 4.4%, P=0.130). The quality of life had no statistical difference between the two groups. Conclusions The combination of XELOX with thalidomide for the first-line treatment of MCRC was well tolerated. Statistically significant improvement was achieved for time DCR but not for PFS.
文摘AIM:To assess the validity of the Milan and University of California San Francisco(UCSF) criteria and examine the long-term outcome of orthotopic liver transplantation(OLT) in patients with hepatocellular carcinoma(HCC) in a single-center study.METHODS:This study is a retrospective review of prospectively collected data.Between 1998 and 2009,56 of 356 OLTs were performed in patients with HCC.Based on pathological examination of liver explants,patients were retrospectively categorized into 3 groups:Milan +(n = 34),Milan-/UCSF +(n = 7) and UCSF-(n = 14).RESULTS:Median follow-up period was 39.5(1-124) mo.The 5-year overall survival rates in the Milan +,Milan-/UCSF + and UCSF-groups were 87.7%,53.6% and 33.3%,respectively(P < 0.000).Within these groups,tumor recurrence was determined in 5.8%,14.3% and 40% of patients,respectively(P < 0.011).Additionally,the presence of microvascular invasion within the explanted liver had a negative effect on the 5-year disease free survival(74.7% vs 46.7%,P < 0.044).CONCLUSION:The Milan criteria are reliable in the selection of suitable candidates for OLT for the treatment of HCC.For cases of OLT involving living donors,the UCSF criteria may be applied.