Objective To detect the expression of thromhospondin-1 （TSP-1） in gastric cancer and metastaticlymph node tissues， and to study its relationship of TSP-1 to clinicopathologic parameters or tumor angiogenesis. Methods The TSP-1 and vascular endothelial growth factor （VEGF） expressions and microvessel density （MVD） were evaluated by immunohistochemistry in 72 specimens obtained by gastric resection from patients with gastric cancer， including corres-ponding adjacent normal gastric mucosa tissues （distant from cancer ≥5 cm） and lymph nodes surrounding cancer. A semiquantitative scoring system was used for evaluating the staining. The relationship of TSP-1 to VEGF expression， MVD， or clinicopathologic parameters was analyzed. Results ① TSP-1 positive expression rate was 45.8% （33/72） in the primary gastric cancer tissues， 90.3% （65/72） in the corresponding adjacent normal gastric mucosa tissues， and 50.8% （30/59） in the metastatic lymph nodes tissues. The expressions of TSP-1 in the primary gastric cancer tissues and metastatic lymph nodes tissues were significantly lower than those in the adjacent normal gastric mucosa tissues （χ2=32.710，P=0.000；χ2=25.298， P=0.000）. The expression of TSP-1 had no statistical significance in the primary gastric cancer tissues as compared with in the metastatic lymph nodes tissues （χ2=0.327， P=0.568）. ② The expression of TSP-1 in the metastatic lymph nodes tissues was significantly lower than that in the non-metastatic lymph nodes tissues （Z=-2.573， P=0.010）. ③The expression of TSP-1 in the primary gastric cancer tissues and metastatic lymph nodes tissues suggested a negative correlation with VEGF （rs=-0.309， P=0.008；rs=-0.269， P=0.040） and MVD （rs=-0.348， P=0.003；rs=-0.272， P=0.037）. Conclusions TSP-1 expression is down-regulated and has a negative correlation with VEGF and MVD in the primary gastric cancer and the metastatic lymph nodes tissues. According to the present results， it seems likely that TSP-1 is a tumor angiogenesis inhibitor.
Objective To investigate the effects of adenovirus-mediated melanoma differentiation-associated gene-7 (mda-7)/IL-24 and/or adriamycin (ADM) on transplanted human hepatoma in nude mice and to explore a new way for hepatoma gene therapy combined with chemotherapy. Methods The recombinant adenovirus vector carrying Ad.mda-7 was constructed; Ad.mda-7 and/or ADM were injected into the tumor-bearing mice. Their effects on the growth of the tumor and the survival time of the mice were observed. The expressions of VEGF and TGF-β1 were detected by an immunohistochemistry method. Results Ad.mda-7 was constructed and expressed in vivo successfully. Compared with other three groups 〔control group (43.4±1.67) d, ADM group (64.2±4.14) d, Ad.mda-7 group (61.4±1.67) d〕, the mice treated with Ad.mda-7 combined with ADM had longer average survival time 〔(83.8±4.82) d, P＜0.01〕; the average size of tumor treated with Ad.mda-7 combined with ADM diminished significantly compared with that treated with ADM or Ad.mda-7 separately (P＜0.01). VEGF and TGF-β1 expressions of Ad.mda-7 group were (56.2±7.7)%, (35.2±4.5)%, respectively, and were lower than those in ADM group (VEGF: P＜0.05; TGF-β1: P＜0.01). VEGF expression of Ad.mda-7+ADM group was (37.3±5.0)%, and was significantly lower than that in other three groups (P＜0.01). TGF-β1 expression of Ad.mda-7+ADM group was (31.2±3.1)% and significantly lower than that in control group and ADM group (P＜0.01), however, there was no significant difference compared with Ad.mda-7 group (Pgt;0.05). Conclusion Ad.mda-7 combined with ADM has b antitumor potency and synergistic effects and suppresses the growth of human HCC xenograft in nude mice, possibly by inducing the apoptosis of hepatoma cell lines and suppressing tumor angiogenesis.
Objective To investigate the serum levels of endostatin and vascular endothelial growth factor ( VEGF) at different therapy stages of mouse Lewis lung carcinoma, and elucidate the relation to the progress and prognosis of tumor. Methods Forty-four Lewis lung carcinoma-bearing C57BL/6 mice were randomly divided into 4 groups, ie. a non-therapy group, a chemotherapy group, a gene therapy group, and a combination therapy group ( chemotherapy plus gene therapy) . Eleven healthy mice were included as normal control group. Serum was collected on the 0th, 5th, 19th day after therapy for measurement of endostatin and VEGF by ELISA. The correlations were analysed between endostatin and VEGF levels in each group. Results ( 1) The serum endostatin levels had no significant difference in all groups on the 0th day,but increased significantly on the 5th day in the gene and combination therapy groups than those in other three groups ( all P lt;0. 01) . Then the endostatin level decreased on the 19th day in the gene and combination therapy groups, but still higher than those in the chemotherapy group and the normal group. ( 2 ) On the contrary, serum VEGF levels of the gene and combination therapy groups decreased significantly on the 5th day and increased little on the 19th day, which were both significant lower than those in chemotherapy group on the 5th and 19th day( all P lt; 0. 05) . There were significant diferences between the three therapy groups and the non-therapy group( all P lt;0. 05) . ( 3) Negative correlations between VEGF and endostatin levels were revealed in the gene and combination therapy groups ( r = - 0. 77 and - 0. 761 respectively) .Correlation was not found in the non-therapy and chemotherapy groups. Conclusion The serum levels of endostatin and VEGF might be used as monitoring indices of antiangiogenesis therapy.
Objective To investigate clinical significance of serum VEGF-C level and C-erbB-2 protein expression in patients with breast cancer. Methods Sixty-two female patients with breast invasive ductal cancer and breast benign lesion were respectively selected. Serum VEGF-C level was detected by enzyme-linked immunosorbent assay (ELISA) before operation and at one month after operation, and C-erbB-2 protein expression in tissues of breast cancer was detected by immunohistochemistry. Then, the relationship between serum VEGF-C level and clinicopathologic characteristics and C-erbB-2 protein expressions wereas analyzed. Results The serum VEGF-C level before operation in breast cancer patients〔(279.65±17.34) pg/ml〕 was significantly higher than that in breast benign lesions patients 〔(167.26±12.15) pg/ml〕, P＜0.01. In breast cancer patients, the serum VEGF-C level before operation was higher than that at one month after operation 〔(209.45±15.23) pg/ml〕, P＜0.01. The serum VEGF level was related to tumor stage (P＜0.05) but not to patient age, tumor size, menopause status , lymph node metastasis or not and ER and PR expression (Pgt;0.05). The positive expression rate of C-erbB-2 protein in breast cancer patients (54.84%, 34/62) was significantly higher than that in breast benign lesion patients (11.29%, 7/62), P＜0.01. Moreover, the positive expression rate of C-erbB-2 protein in breast cancer patients with axilla lymph node metastasis (69.44%) was significantly higher than that without axilla lymph node metastases (34.62%), P＜0.05. The serum VEGF level increased with increasing expression intensity of C-erbB-2 protein and there was positive correlation between them (r=0.813，P＜0.05). Conclusions The serum VEGF-C level in breast cancer may be conducted as an assisted marker to differential diagnosis of breast tumor. C-erbB-2 is related to lymph node metastasis of breast cancer patients. There is synergistic effect between VEGF-C and C-erbB-2 in the lymph node metastasis way of breast cancer.
Abstract: Objective To evaluate the significance of expression of vascular endothelial growth factor-C （VEGF-C） and cytokeratin 19 （CK19） in patients with stage I non-small cell lung cancer （NSCLC）. Methods A total of 269 patients with NSCLC who underwent standard lobectomy and lymph node dissection by the same surgical team in our hospital from January 2004 to June 2005 were included in this study. All the clinical data and follow-up results were complete, and all the pathological specimens were well kept. No preoperative or postoperative adjuvant therapy such as radiotherapy and chemotherapy was administered to those patients. Expressions of VEGF-C in cancer tissues was detected by immunohistochemical streptavidin-peroxidase （S-P） method, and CK19 was marked to examine micrometastasis in hilar and mediastinal lymph nodes. Clinical outcomes, pathological results and follow-up data were analyzed in combination with VEGF-C and CK19 expression. Results VEGF-C expression was not statistically different between different category in sex（Hc=1.722，P=0.084）, age （Hc=0.914，P=0.360）, smoking （Hc=2.440，P=0.295）, pathology type （Hc=5.668，P=0.058）or tumor size （Hc=0.165，P=0.920） . VEGF-C expression was statistically different between different groups of pathological differentiation （Hc=29.178，P=0.000). CK19 expression was not statistically different between different category in sex（χ2=0.000，P=0.999）, age （χ2=0.005，P=0.999）, smoking （χ2=2.294，P=0.317）, pathology type （χ2=0.573，P=0.289）, tumor size（χ2=0.006，P=0.999）, and pathological differentiation （χ2=2.927，P=0.231）. Five-year survival rate was statistically different between different grade of VEGF-C expression （χ2=37.318，P=0.000), and was also statistically different between positive group and negative group of CK19 （χ2=39.987，P=0.000). There was statistical difference between different grade of VEGF-C expression and positive rate of CK19 （χ2=25.954，P=0.000). Conclusion Expression of VEGF-C and CK19 is closely related to postoperative 5-year survival of patients with stage I NSCLC. Detection of VEGF-C and CK19 is of great clinical significance as it is helpful to predict patient prognosis and choose proper postoperative adjuvant therapy.
Objective To evaluate the effect of vascular endothelial growth factor (VEGF) on tumor angiogenesis, and its usage in tumor therapy.Methods The recent literatures about VEGF and angiogenesis were reviewed and analyzed. The advances of VEGF study were summarized. The effects of anti-angiogenesis in tumor biological therapy were introduced.Results Angiogenesis had been identified as an important factor for promoting tumor growth. VEGF was a basic and pivotal factor in tumor angiogenesis. The anti-angiogenesis treatments aimed at VEGF, including the applications of VEGF inhibitor and gene therapy of adenovirus medium, had got great progress. Conclusion VEGF is a leading factor of tumor angiogenesis, the anti-angiogenesis therapy aimed at VEGF has probably provided a new chance to malignant tumor treatment.
【Abstract】Objective To observe the changeable expressions of vascular endothelial growth factor (VEGF) and integrin β3 during the angiogenetic process of granulation tissue. Methods mRNA and protein of VEGF and integrin β3 in human normal subcutaneous tissue, proliferative granulation tissue and mature granulation tissue were observed by RT-PCR and immunohistochemistry staining. Results The expressions VEGF and integrin β3 were low in normal subcutaneous tissue and were much higher in proliferative granulation tissue. When the granulation tissue was mature, the expression was decreased again. Conclusion VEGF and integrin β3 are important regulating factors in ngiogenesis.
Objective To investigate the effect of the vascular endothelial growth factor (VEGF) gene therapy, the surgical delay, and the combination of the two therapeutic approaches on the survival of the rat over-area abdominal axial skin flap. Methods In 48 male Wistar rats (weight, 400-450 g), a model of the abdominal axial skin flap supplied by the superficial epigastric blood vessel was created. The rats were randomly divided into 6 groups: Group A (the blank group), Group B (the gene-therapy-during-operation group), Group C (the gene-therapy-before-operation group), Group D (themerely-surgical-delay group), Group E (the gene-therapy-during-surgical-delay group), and Group F (the gene-therapy-aftersurgical-delay group). Seven days after operation, the survival rate of the skin flap was measured; the specimens were harvested from the skin flap for a histological investigation of themicrovessels and for an immunohistochemical staining to observe the expression of VEGF165. Results The average survival rate of the skinflap was significantly greater in each of the treated groups than in Group A (Plt;0.05); the rate was the greater in Group E (Plt;0.05), but with no statistically significant difference between the other treated groups (Pgt;0.05). The average number of the microvessels was significantly greater in Groups B, C, E andF than in Groups A and D (Plt;0.05), but with no statistically significant difference between Groups B, C, E and F and between Groups A and D (Pgt;0.05). The lumen diameter of the microvessels was significantly greater in Group D than in Groups E and F (Plt;0.05), and the diameter was significantly greater in Groups D, E andF than in the other groups (Plt;0.05). More deposition of VEGF DNA detected by the immunohistochemical staining was in Groups B, C, E and F than in Groups A and D. There was no newly-formed blood vessel in the rat cornea in the treated groups.Conclusion Both the administration of pcDNA4-VEGF165 and the surgical delay can improve the survival of the rat abdominal axial skin flap, but the mechanism of the effect is different in explanation. The combination of the two therapeutic approaches can achieve a better effect.