Objective To investigate the relationship of vascular endothelial growth factor (VEGF), microvessel density (MVD) and progression of gastric carcinoma (GC). Methods The expression of VEGF and MVD in archival waxembedded specimens of 80 cases of GC and 20 gastric benign disease (GBD) were examined by using immunohistochemical staining. ResultsThe positive expression rate (PER) of VEGF in GC was 75.0%, and in GBD 5.0% (P＜0.05). The PER of VEGF in GC with invasive serosa was 95.5%, in those without serosal invasion 50.0% (P＜0.05). 82.8% was the PER of VEGF in GC with lymph node metastasis, 54.5% without lymph node metastasis (P＜0.05).The PER of VEGF in GC accompanied by distant metastasis was 100%, higher than that without distant metastasis (71.0%, P＜0.05). PER of VEGF in pTNM Ⅰ+Ⅱ was 53.1%, in Ⅲ+Ⅳ 89.6% (P＜0.05). MVD correlated significantly with depth of invasion, lymph node metastasis,distant metastasis and pTNM stages (P＜0.05). There was correlationship between MVD and VEGF (P＜0.05).Conclusion VEGF expression upregulation and MVD contribute to the progression of gastric carcinoma.
ObjectiveTo observe the effects of hydroxysafflor yellow A (HSYA) on microvessel density (MVD) of mice transplanted Lewis lung cancer and mRNA expression of vascular endothelial growth factor (VEGF) so as to explore the tumor-inhibiting mechanism of HSYA. MethodsSixty tumor-bearing C57/BL mice were randomly divided into five groups, with 12 mice in each group, namely a control group, a cyclophosphamide (CTX) group (25mg/kg), a large dose HSYA group (112mg/L), a medium dose HSYA group (56mg/L), and a small dose HSYA group (28mg/L). These different drugs were administered by intraperitoneal injection. The mice were sacrificed 22 days after the treatment. Tumor tissues were sampled and examined by immunohistochemical method and quantitative real-time PCR to detect the expression of MVD and VEGF mRNA. ResultsThe MVD of the medium and small dose HSYA groups and CTX group were 30.01±3.12, 22.56±2.11 and 16.21±2.40, respectively, which were significantly lower than 41.10±2.93 of the control group and 37.66±3.04 of the large dose HSYA group (χ2=2.82, P=0.010;χ2=3.16, P=0.007;χ2=4.58, P=0.000) and (χ2=1.98, χ2=0.038;χ2=2.45, P=0.016;χ2=3.82, P=0.001). The difference in VEGF amplified fluorescence expression threshold between the HSYA groups and the control group was not significant. However, after amplification, the expression of VEGF mRNA in the small dose HSYA group was only 0.43±0.16, which was obviously lower than 0.82±0.06 in the control group (F=0.77, P=0.038). ConclusionHSYA can significantly reduce MVD in mice transplanted Lewis lung cancer and down-regulate expression of VEGF mRNA to achieve tumor-inhibiting effect.
ObjectiveTo study the mechanism of reducing the intratumoral microvessel density (MVD) by Ginsenoside Rg3 (Rg3) combined with cytotoxic agent in xenotransplanted human breast infiltrating duct carcinoma in nude mice. MethodsSixteen female nude mice were randomly divided into 4 groups to receive cyclophosphamid (16 mg/kg,qd) combined with Rg3 (10 mg/kg, qd),Rg3(10 mg/kg,qd) alone,cyclophosphamid (16 mg/kg,qd) alone and 0.5% sodium carboxymethyl cellulose (0.5 ml,qd) respectively for 55 days. Breast cancer mass were weighed and sampled for light microscopic observation. The intratumor MVD was examined by immunohistochemical staining. ResultsThe tumor weight of treated group was significantly lower than that of control group. The tumor weight of the Rg3 combined with CTX group was lower than that of Rg3 group. The MVD value of Rg3 group was significantly lower than that of CTX group and control group. The MVD was significantly reduced in the Rg3 combined with CTX group than that in the others.ConclusionRg3 combined with CTX can inhibit the growth of xenotransplanted human breast infiltrating duct carcinoma, and reduce the intratumoral MVD.
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.
【摘要】 目的 比較酸性成纖維細胞生長因子(acid fibroblast growth factor,aFGF或FGF1)在正常乳腺組織、乳腺良性腫瘤及乳腺癌中的表達差異,探討FGF1與乳腺癌血管生成的關系。方法 應用免疫組織化學(immunohistochemistry,IHC)SP法檢測FGF1在40例乳腺癌組織、12例良性乳腺腫瘤組織及12例正常乳腺組織中的表達情況；以CD34抗體標記血管內皮細胞CD34抗原行乳腺癌組織微血管密度(micro vessel density,MVD)計數。〖HTH〗結果〖HTSS〗 FGF1在40例乳腺癌中的陽性表達率（57.5%，23/40)顯著高于12例乳腺良性腫瘤組織中陽性表達率(16.7%,2/12)以及正常乳腺組織陽性表達率(0,0/12),差異有統計學意義(Plt;0.05)；良性腫瘤組FGF1表達率和正常乳腺組織比較無統計學意義(Pgt;0.05)。40例乳腺癌組織MVD計數為(70.17±29.33)個/HP,在23例FGF1陽性組中MVD計數為(89.48±23.23)個/HP,顯著高于17例陰性組(44.06±12.53)個/HP,差異有統計學意義(Plt;0.05)。〖HTH〗結論 〖HTSS〗FGF1可能參與乳腺癌微血管生成。
ObjectiveTo detect the expressions of microvessel density (MVD)-CD34 and vascular endothelial growth factor (VEGF) in hepatic alveolar hydatid tissue in gerbil model and explore their clinical significances. MethodsSixty health gerbils were randomly equally divided into two groups, an experimental group and a sham operation group, each gerbil was given liver vaccination by opening their abdominal. Each gerbil in the experimental group was injected with approximately 400 echinococcus protoscoleces (0.1 mL), and each gerbil in the sham operation group received a corresponding volume of physiological saline. Six gerbils were sacrificed on day 20, 40, 60, 80, and 100. The hepatic alveolar hydatid tissue (AE) and its surrounding liver tissue (HSAE) were collected from the experimental group and the normal liver tissue (NL) was collected from the sham operation group, and the expressions of MVD-CD34 and VEGF were detected by immunohistochemistry staining (EnVision method). ResultsEchioncoccus multilocularis hydatid tissues were observed over the liver and in the partly abdominal cavity in the experimental group each gerbil by general observation. The expressions of CD34 and VEGF were observed in the AE at each time point after infection and located in the cytoplasmic of endothelial cells. The number of MVD-CD34 of AE at each time point in the AE was (9.83±3.87)/HP, (25.33±6.71)/HP, (34.50±5.50)/HP, (37.67±5.71)/HP and (44.67±4.93)/HP, respectively, which were significantly higher than those in the HSAE〔0/HP, (1.17±0.98)/HP, (3.50±1.38)/HP, (5.83±2.71)/HP, and(8.83±2.48)/HP, respectively〕and NL (all were 0), P < 0.05. The point of VEGF at each time point in the AE was 2.95±0.46, 3.90±0.68, 4.27±1.05, 5.33±0.95, and 4.50±0.81 respectively, which were significantly higher than those in the HSAE(1.07±0.63, 1.38±0.75, 1.55±0.83, 1.67±0.47, 2.10±0.55, respectively) and NL (1.02±0.83, 1.12±0.63, 1.26±0.26, 1.20±0.74, 1.21±0.28), P < 0.05. ConclusionAngiogenesis might be involved in infiltrated growth of alveococcus, and VEGF might contribute to angiogenesis of alveolar hydatid tissue.
ObjectiveTo explore the relation between vascular endothelial growth factor （VEGF） and the formation of tumor thrombosis in the main trunks of portal vein (PVTT). MethodsTumor specimens were collected from 36 patients (16 patients with PVTT, the other patients without PVTT and metastasis) undergoing resection of hepatocellular carcinoma (HCC) and portal thrombectemy, PVTT specimens of 16 patients named group A1, the same patients’ with HCC named group A2, tumor specimens of the other patients named group B. In situ hybridization and immunohistochemistry were used to investigate VEGF mRNA, protein and microvessel density (MVD) on surgical specimens. The intensity was evaluated using a computer image analyzercell analysis system.ResultsVEGF mRNA expression was detected in the tumor’ cell of the specimens. The expression rates of VEGF mRNA in the group B, A2, A1 were 30%, 100%, 100% respectively, and the expression rates of VEGF mRNA in group A2 and A1 were higher than that in group B （P＜0.01）. The intensity of VEGF mRNA in group A2 （0.078 5±0.019 6） were lower than in group A1 （0.194 4±0.059 0） （P＜0.01）. VEGF protein expression was often detected in the tumor cell, vascular endothelial cell and fibroblast cells. Invasion was detected in small vein in group A2, more tumor cell colony detected in group A1. The expression rates of VEGF protein in group B, A2, A1 were same as VEGF mRNA; the intensity of VEGF protein in A1 （0.165 6± 0.034 5） was higher than in group A2 （0.108 1±0.024 3） （P＜0.01）. MVD in group B, A2, A1 was 31.9±14.4, 63.3±15.1, 116±27.6/view of 200 microscopefield, MVD in group A1 was higher than group A2 （P＜0.01）, higher in group A2 than in group B. There was a statistically significant correlation between the intensity of VEGF expression and MVD in group B,A2 and A1. ConclusionVEGF could play an important role in the invasion, metastasis of HCC and the formation of PVTT. Angiogenesis in tumor is correlated well with the progression of HCC.
ObjectiveTo study the effects of the expressions of endostatin, basic fibroblast growth factor (bFGF) and CD34 on oncogenesis and progression of gallbladder cancer, and to explore some valuable criterias for its biotherapy. Methods The expressions of endostatin, bFGF and CD34 were studied by means of immunohistochemistry (SP) in 61 cases of gallbladder cancer and 10 cases of normal cholecystic tissue, and microvessel density (MVD) was calculated by the expression of CD34. Their relationships with clinical pathological features were also investigated. Results The expression rates of endostatin in normal cholecystic tissue and in gallbladder cancer tissue were 40.00% (4/10) and 77.05% (47/61) respectively, which had statistical difference (P＜0.05). The expression of endostatin in 61 cases of caner was relational to clinical stage and metastasis of lymph nodes (P＜0.05), while no significant correlation was detected with sex and age of patient, location of tumor, size of tumor and histologic grade (P＞0.05). The expression rates of bFGF in normal cholecystic tissue and in gallbladder cancer tissue were 20.00%（2/10） and 67.21% （41/61） respectively, which had statistical difference (P＜0.05). The expression of bFGF in 61 cases of caner was relational to clinical stage and metastasis of lymph nodes (P＜0.05), while no significant correlation was detected with sex and age of patient, location of tumor, size of tumor and histologic grade (P＞0.05). MVD in gallbladder cancer tissue and in normal cholecystic tissue was （76.66±20.15） piece/HP and (29.53±5.03) piece/HP respectively, showing significant difference (P＜0.01). In 61 cases of cancer, MVD in clinical stage Ⅲ～Ⅴ 〔(80.53±17.98) piece/HP〕 was much higher than that in stage Ⅰ+Ⅱ 〔(46.79±5.38) piece/HP〕, P＜0.01; MVD was higher in those with lymph nodes metastasis 〔(94.60±7.28) piece/HP〕 than those without metastasis 〔(58.12±9.24) piece/HP〕, P＜0.01; and MVD was (60.59±14.71) piece/HP in histologic grade G1， (83.08±15.30) piece/HP in G2， and (96.53±6.92) piece/HP in G3, the difference was significant among them （P＜0.01）. There was no significant correlation between MVD and sex and age of patient, location of tumor and size of tumor (P＞0.05). There were statistically significant correlations between expressions of endostatin and MVD （P＜0.01）, expressions of bFGF and MVD （P＜0.01）. Conclusions The result suggests that endostatin, bFGF and CD34 play roles in oncogenesis and progression of gallbladder cancer. Detection of these proteins has positive effects on diagnosis, malignant degree determination and treatment of gallbladder cancer.
ObjectiveTo study the effects of angiogenesis inhibitor SU5416 on the microvessel density(MVD) of pancreatic cancer and to evaluate its influence on the growth and metastasis of pancreatic cancer. Methods A rat model of pancreatic cancer was established with dimethylbenzanthracine(DMBA). 60 rats with pancreatic cancer were randomly divided into 4 groups: saline group, 5-Fu group, SU5416 group, 5-Fu and SU5416 group. Thirteen weeks after injection, the microvascular density (MVD) of pancreatic cancer was detected.Results The microvascular densities (MVD) were (12.3±3.2)%, (11.4±3.8)%, (2.1±1.5)% and (1.8±1.1)% in the saline group, 5-Fu group, SU5416 group and 5-Fu+SU5416 group respectively. The MVDs in the SU5416 group and 5Fu+SU5416 group were statistically lower than those in the saline group and 5-Fu group(P＜0.05). There was no significant difference between the 5-Fu group and saline group(Pgt;0.05). ConclusionSU5416 can inhibit the microvascular growth in pancreatic cancer. And the inhibition can be enhanced when combined with chemotheraputic drugs.
摘要:目的: 探討選擇性內皮素A受體拮抗劑BQ123對人喉癌Hep2細胞裸鼠種植瘤的生長及血管形成的影響。 方法 :將實驗動物裸鼠隨機分為3組:BQ123［n =8,2mg/(kg·day)］、氟尿嘧啶組［n =8,2mg/(kg·day)］、生理鹽水組(n =8),比較各組裸鼠成瘤體積、微血管密度(MVD)。 結果 :BQ123組腫瘤體積為(162±053)cm3,明顯小于生理鹽水組及氟尿嘧啶組,差異具有統計學意義;BQ123組的腫瘤組織中MVD高倍鏡下為232,明顯低于生理鹽水組(586)及氟尿嘧啶組(395),差異具有統計學意義。 結論 :BQ123對人喉癌Hep2細胞在裸鼠體內有明顯抑瘤作用,腫瘤的體積、腫瘤組織MVD顯著低于對照組,表明BQ123可通過抑制腫瘤血管生成而顯著抑制腫瘤生長。Abstract: Objective: To study the effects of endothelin A receptor blockade BQ123 on the implanted human laryngeal carcinoma angiogenesis of nude mouse. Methods : From March 2008 to July 2009, 24 Balb/c nude mice were randomly divided into three groups: BQ123 group ［〖WTBX〗n =8, BQ123 at 2mg/(kg·day)］, 5Fu group ［〖WTBX〗n =8, fluorouracil at 2mg/(kg·day)］ and the control group (〖WTBX〗n =8, normal saline). The carcinoma volume and microvascular density of each group were compared. Results : The tumor size of BQ123 group, which was (162±053)cm3 in average, was significant smaller than the tumor sizes of the other two group s. The average microvascular density score of the tumors in BQ123 group was 232 per hyper power len (HP), which was also significantly less than the average scores of control groups (586 and 395 respectively). Conclusion : Nude mouse experiments show that the carcinoma volume and microvascular density of BQ123 group are significantly lower than those of the control groups. BQ123 inhibits the growth of carcinoma by its inhibition of carcinoma angiogenesis.