Objective To explore the effect of cytotoxic T lymphocyte-associated antigen 4 (CTLA4-Ig) fusion protein on the function of orthotopic liver allograft. Methods Orthotopic liver allograft models of rhesus monkeys were established in this study. The survival time, liver function and morphologic changes of graft were observed, respectively. The levels of IL-2 and IL-10 were detected by ELISA. Apoptosis was monitored by TUNEL.Results The average survival of control group was 6.57 d, while the average survival of CTLA4-Ig group was 14.92 d, which was statistically prolonged (Plt;0.05). Serum ALT level was highly increased, and Alb level decreased obviously in control group. While the levels of ALT and Alb kept in normal in CTLA4-Ig group. After day 3-7, the expressions of IL-2 were highly expressed in control group, while the expressions of IL-10 in CTLA4-Ig group were higher than those of control group. The severity of rejection reaction after day 3 was weaker in CTLA4-Ig group than that of control group by histological assessment. The apoptosis index after day 3 in the liver cells was highly increased in control group as compared with the CTLA4-Ig group. Conclusions CTLA4-Ig fusion protein therapy can induce immunotolerance and prolong the survival of recipients. The increasing of cytokines IL-2 or the decreasing of cytokines IL-10 may be one of the laboratory indexes in monitoring immunotolerance of transplantation.
Objective To study the expression of proliferating cell nuclear antigen (PCNA) in the occurrence and development of hepatocellular carcinoma. Methods Sixty SD rats were randomly divided into control group and experimental group. 3′MeDAB was administrated into rats to establish the experimental model of hepatocarcinoma. The expressions of PCNA of different phases were detected by immunohistochemistry and the liver pathologic changes were observed by optical microscope. Results The process of canceration was divided into three stages: inflammation, proliferative fibrosis and hepatic carcinoma. The expression of PCNA firstly presented in the oval cells that located in the portal area at the stage of inflammation, and a part of PCNA were hyperexpressed in the portal area. The expression rate of PCNA in the middle phase of inflammatory stage was higher than that of any other phases but declined later. Yet, when it came to the stage of hepatic carcinoma, the rate increased again. Conclusion Under the experimental circumstance when liver cancer is caused by the carcinogenic agent, PCNA may be firstly expressed in the oval cells, and the dynamic expression of PCNA may be an indicator for the early diagnosis of hepatocarcinogenesis.
【Abstract】Objective To investigate the expression of PCNA in gastric cancer and its relationship with telomerase activity of peritoneal washings and peritoneal dissemination, and to compare the efficacy of telomerase activity and cytology of peritoneal washings for prediction of peritoneal metastasis of gastric cancer. MethodsTelomeric repeated amplification protocol (TRAP)enzymelinked immunosorbent assay (ELISA) was performed to measure the telomerase activity of peritoneal washings collected from 60 patients with gastric cancer. Exfoliate cytologic analysis of the corresponding samples was used for comparison.Expression of PCNA was measured with immunohistochemical staining.Their relationship with clinicopathologic features were evaluated. ResultsThe positive rate of telomerase activity in peritoneal washing collected from patients with gastric cancer was 41.7%,which well related to serosal invasion, histology types, depth of infiltration and peritoneal metastasis of gastric cancer. The positive rate of telomerase activity increased with the increased depth of infiltration and serosal involvement areas (P＜0.05).The positive rate of exfoliative cytology was 25.0%, which was obviously high in the group with macroscopic peritoneal metastasis (the group of P1-3). The positive rate of exfoliative cytology also increased with the increased depth of infiltration and serosal involvement areas (P＜0.05). Although the positive rate of telomerase activity in peritoneal washing collected from patients with gastric cancer was not significantly higher than that of exfoliative cytology in general, it was significantly higher than that of exfoliative cytology in the group of pT4, P1-3 and undifferentiated type.The PCNA proliferation index (PI) of positive telomerase activity group was significantly higher than that of negative. The PCNA PI was significantly higher in the group of P1-3 and serosal invasion thanthat of P0 and without serosal invasion. ConclusionTo detect telomerase activity in peritoneal washings and to detect tumor cells by cytologic method are useful to predict subclinical metastasis to the peritoneum in patients with gastric cancer,but telomerase activity is more sensitive than the other one.Telomerase activity is well related to proliferating activity of gastric cancer,which was the very important reason of peritoneal metastasis and serosal invasion.
【Abstract】Objective This study was conducted to build experimental model of orthotopic liver transplantation in rat (ROLT) with the character of acute rejection; and to study the effect of cytotoxic T lymphocyte antigen 4 immunoglobulin G (CTLA4Ig) on prevention of rejection and the induction of immune tolerance of ROLT. Methods Build model of Wistar→SD ROLT(performed by the two cuff method) with character of acute rejection.Recipients were injected with CTLA4Ig 75 μg per ROLT into abdominal cavity after 2 days of operation. Contrast was made with no treatment group, the clinical characters, the liver function, the transplantated liver pathologic character and the concentrations of TNFα in serum were observed and measured on postoperative day 7. In treatment group, all above observation were done on postoperative month 4. Above all, determination of the effect of CTLA4Ig on preventing acute rejection and inducing tolerance in ROLT was observed.Results ①Recipients (no treatment group) died one by one within 6th～14th days; pathologic character of rejection in transplantation liver could be found; ② In treatment group, on postoperative day 7 and month 4, no clinical rejection character and no pathologic character of rejection in transplantation liver were found and serum concentration of cytokins related to TNFα found lower than that of contrast group(P＜0.05), and serum concentration of ALT、AST、TBIL、DBIL found lower too(P＜0.05); But serum concentration of TP and Alb was found higher than that of contrast group(P＜0.05). Conclusion ① CTLA4Ig treatment alone inhibits the rejection responce in ROLT. ② CTLA4Ig treatment can Prevent rejection and induce immune tolerance in ROLT model with characters of acute rejection; the serum concentration of cytokins related to TNFα can probably be used as evaluation standard of rejection in ROLT rejection.
【Abstract】ObjectiveTo inquire into the regulative effect of interferon (IFN) on human leucocyte antigen-DR(HLADR) expression in human colonic cancer cells. MethodsThe expression of HLA-DR in 4 colonic cancer cell lines HCT-8，lovo，SW-480 and Ls-174-T was detected with immunohistochemical SP and ELISA method before and after being stimulated by different doses of α-IFN or γ-IFN. ResultsAll cell lines except lovo cell were HLA-DR positive before stimulation with α-IFN or γ-IFN. HLA-DR expression was enhanced on all of the 4 cell lines after stimulation, and it was correlated with γ-IFN and the dose of γ-IFN. The effect of γ-IFN was more obvious than that of α-IFN. ConclusionIFN can enhance HLA-DR expression in human colonci cancer cells and clinical therapy of IFN for colon cancer has a certain applying prospect.
【Abstract】ObjectiveTo detect the spreading scope of rectal cancer to mesorectum by RT-PCR using carcinoembryonic antigen (CEA) mRNA as a marker and to investigate the excision scope of mesorectum in resection of rectal cancer. MethodsForty specimens from 40 rectal cancer patients who underwent curative operation was employed to detect the metastatic deposits scattered in the mesorectum by RT-PCR using CEA as a marker. ResultsNine of 40 (22.5%) specimens contained metastatic deposits scattered in the mesorectum. The metastasis was just within the range of 4cm mesorectum under the verge of tumor. The tumor spreading to mesorectum is correlated with Dukes stages，the infiltrated depth of bowel wall, tumor differentiation and tumor type(P＜0.05), and is not correlated with the size of tumor and the level of CEA(Pgt;0.05). ConclusionThe excision of mesorectum should be within the range of 5cm under the verge of tumor in surgical management of rectal cancer.
ObjectiveTo study the expression and significance of proliferating cell nuclear antigen (PCNA) and argyrophilia nucleolar organizer regions (AgNORs) in colorectal carcinoma (CRC) and carcinoma adjacent mucosa (CAM).MethodsThe expression of PCNA in 48 cases of colorectal carcinoma tissue, CAM and 10 cases of normal mucosa was detected by immunohistochemistry techniques. AgNORs was determined with argyrophilia stain. ResultsThe PCNAlabeling index (PCNALI) and AgNORs count in CRC were higher than that in CAM and normal mucosa(P＜0.01).The PCNALI in Dukes C and D stage was higher than that in Dukes A(P＜0.05). The AgNORs count in 3 cmCAM was higher than 6 cmCAM (P＜0.01) and normal mucosa(P＜0.05). ConclusionSome cells proliferative activity were abnormal in CAM. It indicates that CAM is in an unstable premalignant state, which might have some correlation with the relapse of colorectal carcinoma.
ObjectiveTo study the expression of survivin protein in primary hepatocellular carcinoma(PHC) and its relationship to the proliferation of the tumor cells and prognosis of PHC. MethodsThe expression of survivin protein and the proliferation of tumor cells marked by proliferating cell nuclear antigen (PCNA) in 48 cases of PHC were determined by immunohistochemical method. ResultsThe survivin protein was expressed in 31 of 48 cases of PHC (64.6%). The expression of PCNA was significantly higher in hepatocellular carcinoma (HCC) with positive survivin expression than in HCC with negative survivin expression. The patients with positive survivin expression had the worse prognosis than those with negative survivin expression. ConclusionThe expression of survivin may play an important role in the proliferation of PHC cells and closely associate with the prognosis of PHC, and probably become the prognostic factor and an important target of therapy.
ObjectiveTo study the relationship between the expression of sialyl Lewisx (SLeX) antigen and CD44v6 products and biological behaviors in cholangiocarcinomas. MethodsThe expression of SLeX and CD44v6 in 43 cases of cholangiocarcinoma tissue was respectively investigated by catalyzed signal amplification immunohistochemical technique.The relationship between expression of SLeX and CD44v6 and the clinicopathological factors of cholangiocarcinoma was analyzed.ResultsThe positive expression rate of SLeX and CD44v6 in cholangiocarcinoma was 67.4% and 62.8% respectively,which was significantly higher than that in control group (20.0%,P＜0.05).The high level expression of SLeX and CD44v6 were correlated with the TNM phase, differentiation degree,metastasis to lymph nodes and viscera in cholangiocarcinoma (P＜0.05). Moreover,there was a positive correlation between the SLeX and CD44v6 expression in cholangiocarcinoma (r=0.49,P＜0.001).Conclusion Expression of SLeX and CD44v6 could be helpful in predicting the biological behavior and prognosis of cholangiocarcinoma.
ObjectiveTo investigate the expression of vascular endothelial growth factor （VEGF） and proliferating cell nuclear antigen (PCNA) in colorectal cancer and its relationship with metastasis and recurrence. MethodsParaffinembedded specimens from 59 patients with colorectal cancer, 16 patients with adenomas and 12 normal colonic tissues were examined and compared by SP immunohistochemical method. ResultsThe positive rate of VEGF in colorectal cancer were significantly higher than that in adenomas (P＜0.05). The positive rate of VEGF in Dukes A and B stage of colorectal cancer were significantly higher than those in Dukes C and D (P＜0.05). Expression of VEGF in postoperative recurrence group was markedly higher than that in the group with no recurrence (P＜0.05). Proliferative activity expression suggested that the poorer the differentiation, the more PCNA increased in case of lymphnode or hepatic metastasis. The PCNA showed marked difference between postoperative and nonpostoperative recurrences (P＜0.05). Conclusion The expression of VEGF and PCNA is closely related to the invasion and metastasis of tumor during the operation. The increased VEGF and high PCNA implies that there may be some potential metastasis present.