1.Surgery combined with intraoperative radiotherapy compared with surgery alone for rectal carcinoma
Yuewu GUO ; Qiang ZHANG ; Su LIU
China Oncology 1998;0(01):-
Purpose:To assess the effect of surgery combined with intraoperative radiotherapy (IORT) in the treatment of rectal carcinoma.Methods:97 patients with rectal carcinoma underwent IORT with 10~30Gy by 9~16MeV elect ro n beam to the tumor bed and local lymphatic regions. Another 122 patients treate d by surgery alone served as control.Results:Surgery combined w ith IORT did not improve the 5-year survival rate and local recurrence rate in the stage Dukes A patients. IORT have increased the 3-year and the 5-year surv ival rates in the stage Dukes B patients to 19.9%?27.2%, decreased their local recurrence rates to 19%?20.2%(P
2.Effects of rhubarb aglycone on matrix metalloproteinase in cerebral ischemic tissue in rats with bone marrow mesenchymal stem cell transplantation
Jiansheng LI ; Jingxia LIU ; Jie SUN ; Yuewu ZHAO ; Jing SU ; Ning LI ; Xiaoyan GUO
Journal of Integrative Medicine 2008;6(8):810-6
OBJECTIVE: To observe the effects of rhubarb aglycone on pathological changes and activity of matrix metalloproteinase in cerebral ischemic tissue in rats with bone marrow mesenchymal stem cell (BMSC) transplantation, and to explore the action mechanisms of rhubarb aglycone in protecting against brain micrangium injury in rats. METHODS: The BMSCs were purified and amplified by methods of adherence and selection in vitro. One hundred and ninety rats were randomly divided into sham-operated group, untreated group, rhubarb aglycone group, BMSC transplantation group (abbreviated as transplantation group) and BMSCs combined with rhubarb aglycone group (abbreviated as combination group). Middle cerebral artery occlusion (MCAO) model was duplicated with nylon thread. Rats of transplantation and combination group were transplanted with BMSCs via carotid artery after 24-hour reperfusion. Rhubarb aglycone was used by intragastric administration in the rhubarb aglycone group and the combination group. The brain samples were taken at 7, 14 and 28 days after transplantation. Brain micrangium pathological changes were observed by light microscope, and immunohistochemical method was used to determine the expressions of immunoglobulin G (IgG), type IV collagen (Col IV), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1). RESULTS: Comparison with the normal control group revealed that brain micrangium in rats in the untreated group was obviously mutilated and damaged, the expression of IgG and MMP-9 increased, and showed a progressively enhanced tendency following the prolongation of reperfusion, while the expressions of Col IV and TIMP-1 were decreased, and TIMP-1 showed a attenuated tendency following the prolongation of reperfusion. Comparing with the untreated group, the improvements of brain micrangium structure in the rhubarb aglycone group (7 days after transplantation), the transplantation group (14 and 28 days after transplantation) and the combination group were significant; expression of IgG and activity of MMP-9 were decreased, while expressions of Col IV and TIMP-1 were increased in the rhubarb aglycone group and the combination group at each time point. The brain micrangium was integral and the expression of Col IV was enhanced in combination group (7 days after transplantation) as compared with those in transplantation group. MMP-9 activity in combination group (14 days after transplantation) was lower than that in the rhubarb aglycone group (14 days after transplantation), while expression of TIMP-1 in combination group also increased significantly as compared with that in transplantation group (28 days after transplantation). CONCLUSION: Rhubarb aglycone can decrease the degradation of basal lamina Col IV and the permeability of brain micrangium in cerebral ischemic rats with BMSC transplantation, and its mechanisms may be related to regulating the balance of MMP-9, especially by increasing the expression of TIMP-1.
3.Study of adeno-associated virus carrying the HGFK1 gene(AAV-HGFK1) in treating rat hepatocellular carcinoma
Chunrong GU ; Yuewu GUO ; Hui ZHAO ; Yuanjue SUN ; Yang YAO ; Zan SHEN ; Jiami LINLI
China Oncology 2009;19(6):416-422
Background and purpose: Hepatocellular carcinoma (HCC) is a hypervascular tumor associated with a poor prognosis and lack of effective treatments. Consequently, identifying novel therapeutic strategies are urgently needed. We have previously shown that the kringle 1 domain of human hepatocyte growth factor (HGFK1) is a more effective anti-angiogenesis molecule than angiostatin. In this study, we observed the effects and mechanisms of HGFK1 gene on the HCC. Methods: A recombinant adeno-associated vires carrying the HGFK1 gene (rAAV-HGFK1) was constructed.HCC of rat was induced by McA-RH7777. rAAV-HGFK1 was used to treat the rat, median survival time and metastasis rate were observed. Results: Ten days after tumor cell inoculation, surgery were performed to confirm the tumor formation, PBS, rAAV-EGFP or rAAV-HGFK1 was injected directly into the tumor nodule followed by portal vein injection. Results from our study demonstrated that rAAV-HGFK1 treatment significantly prolonged the median survival time of the HCC bearing rats from 30 days (PBS and rAAV-EGFP groups) to 49 days (rAAV-HGFK1 group). More importantly rAAV-HGFK1 inhibited tumor growth and completely prevented liver, lung and peritoneal metastasis. In the controlled PBS and AAV-EGFP group, liver and peritoneal metastasis rate were both 100%, and lung metastasis rate was 100% and 83%, respectively. While there was no metastasis found in treatment group, with only 33% of ascites happened. This was most possibly due to the primary tumor in liver but not due to the metastasis. Moreover, at a higher magnification (1000×), it was clear that the HGFK1 protein was expressed mainly in the cytoplasma of liver cells. In parallel, IHC staining of CD31 also demonstrated a significantly lower level of microvessel density (MVD) (6.21±1.6) in the liver tumor of the AAV-HGFK1 treatment group, as compared to the two control PBS and AAV-EGFP groups (25.1±2.1 and 26.8±2.5, respectively, P<0.01). HE staining showed that AAV-HGFK1 treatment induced large areas of necrosis in the tumor tissues, while minimal areas of necrosis were observed in the tumor tissue in the control groups. In addition, no toxicity appeared when high dosage (4.8× 1012 vg/rat) of rAAV-HGFK1 was administered in rats. Conclusion: Results from this study demonstrated that HGFK1 inhibited the growth and metastasis of HCC and prolonged the survival time of animals with HCC through anti-angiogenesis effects. No obvious toxicity was observed. It might be the novel promising treatment for HCC and other cancers.