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.
Objective To investigate the expression of hypoxia inducing factor 1 alpha (HIF-1α) in human breast cancer and its relationships with microvessel density （MVD）, proliferating cell nuclear antigen (PCNA) protein, other tumor biomarkers and clinicopathologic factors. Methods Immunohistochemical staining (SP) was used to measure the expressions of HIF-1α and PCNA in human breast fibroadenoma, usual hyperplasia and adenocarcinoma, and the MVD was determined by anti-CD34 immunostaining. Results No HIF-1α was observed in the lesions of breast fibroadenoma and hyperplasia. However, the positive expression rate of HIF-1α in the ductal carcinoma in situ （DCIS） was 55.0% (11/20) and the infiltrative breast cancer was 85.0%(51/60). The total high expression rate of PCNA in breast cancer was 75.0% (60/80), in which the rate of DCIS counted for 65.0% (13/20) and the rate of infiltrative adenocarcinoma counted for 78.3% (47/60). There were positive correlations between the expresson of HIF-1α and the expression of PCNA (r=0.693， P＜0.01) and MVD in DCIS (r=0.682, P＜0.05), respectively, but there was no relation between HIF-1α and MVD in infiltrative breast cancer. The expression of HIF-1α was associated with tumor cell proliferation, lymph node metastasis, estrogen receptor status (P＜0.01). Conclusion The expression of HIF-1α increased in breast cancer and it is associated with tumor cell proliferation, lymph node metastasis, estrogen receptor status. Thus, HIF-1α may play an important role in the tumor cell proliferation, vasiformation, progression and metastasis of breast cancer, and may become a new target for tumor treatment.
Objective To explore the clinical significance of estrogen receptor α( ERα) , estrogen receptor β( ERβ) in non-small cell lung cancer( NSCLC) .Methods EnVision method was used to detect the expressions of ERα, ERβ, vascular endothelial growth factor( VEGF) , and microvessel density( MVD) in 54 NSCLC patients, 10 patients with lung benign lesions, and 10 normal controls. The interrelation between ERα, ERβ, VEGF, and MVD was analyzed. Results No obvious expressions of ERα and ERβwere observed in the normal lung tissues and lung benign lesions. The positive expression rates of ERα, ERβ, and VEGF in NSCLC were 20. 4% ( 11/54) , 64. 8% ( 35/54) , and 64. 8% ( 35/54) , respectively. There were no significant differences between ERαin regard to clinical parameters of NSCLC. But the expression of ERβwas dependent on pathological classification and differentiation of NSCLC. The expression of ERβ was significantly higher in adenocarcinoma than in squamous cell carcinoma( P lt; 0. 05) . The expression rate of ERβin well differentiated group was significantly higher than that in low, moderately differentiated group( P lt;0. 05) . There were significant differences between VEGF in regard to lymph node metastasis and TNM stage. The expression of ERαinterrelated with VEGF and MVD with r value of 0. 4 and 0. 685 respectively ( P lt;0. 05) . There was little correlation between ERβ and VEGF, MVD( P gt; 0. 05) . Conclusion Theexpression of ERβ correlates with pathological classification and differentiation of NSCLC, suggesting its significance in evaluating the pathological classification and malignant degree of NSCLC. The expression of ERαcorrelates with VEGF and MVD, suggesting that ERαpossibly promote micro-angiogenesis of NSCLC by VEGF pathway.
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 observe the expression levels of nuclear factor kappa B （NF-κB）， vascular endothelial growth factor （VEGF）， and CD31 in portal vein and surrounding tissues of rats during the formation process of cavernoustransformation of portal vein （CTPV）， and try to search the relationship between NF-κB， VEGF， and the angiogenesisof portal areas， as well as the significance and the role of NF-κB and VEGF in the formation process of CTPV. Methods One hundred and ten Sprague-Dawley （SD） rats were randomly （random number method） divided into sham operation group and model group. The partial constriction operations on portal vein were performed in model rats with a blunt 21Gcaliber to establish CTPV animal models （model group）， while the exploratory operations on portal vein， not constriction，were performed in rats of sham operation group. All specimens （portal vein and surrounding tissues） were fixed in formalinand made into paraffin blocks. Each specimen was tested by immunohistochemistry for the expressions of NF-κB， VEGF， and CD31， then optical density （OD） of NF-κB expression and the mean integral optical density （IOD） of VEGF expressionwere measured by using Image Pro Plus 6.0 software， and microvessel density （MVD） was calculated under microscope. Results Nucleoplasm ratio of OD value of NF-κB， mean IOD value of VEGF， and MVD value in 1， 2， 3， 4， and 6 weeks after operation didn’t significantly differed from that of before operation in sham operation group （P＞0.05）， but higher at all time points after operation in model group （P＜0.01）. Compared with sham operation group， nucleoplasm ratio of OD value of NF-κB， mean IOD value of VEGF， and MVD value were significantly higher in 1， 2， 3， 4， and 6 weeks after operation in model group （P＜0.01）. NF-κB and VEGF， NF-κB and MVD， VEGF and MVD were positively correlated with each other （r=0.654 6，P＜0.01；r=0.620 7， P＜0.01；r=0.636 9， P＜0.01） in model group. Conclusion NF-κB and VEGF may relate to the formation of CTPV， and may involve in the angiogenesis.
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.
Objective To investigate the enhancement of the transverse rectusabdominis musculocutaneous (TRAM) flap survival in local ischemic area by recombinant adenovirus mediated vascular endothelial growth factor 165 gene(Ad-VEGF-165). Methods The vascular pedicle TRAM flaps were made in the right abdomin of30 SD rats and they were randomly divided into 5 groups. The Ad-VEGF-165 was injected into the subcutaneous tissue of epigastra(group 1), the subcutaneous tissue of epigastria and rectus abdominis muscle (group 2), and the rectus abdominis muscle(group 3); Adenovirus mediated green fluorescent protein(Ad-GFP) and DMEMwere injected into the subcutaneous tissue of epigastria and rectus abdominis muscle as autocontrol(group 4) and blank control(group 5), respectively. The survival areas of TRAM flap was measured after 7 days of operation. The microvascular density(MVD) and the integral optical density (IOD) were tested with anti-rat CD34 and with VEGF immunohistochemistry and insitu hybridization histochemistry (ISHH), respectively. Results The survivalareas of TRAM flap in groups 1, 2 and 3 (14.19±2.77, 15.18±2.18 and 8.30±1.28 cm2) were higher than those in groups 4 and 5(4.12±186 and 3.60±1.95 cm2), being significant differences(Plt;0.05).The CD34 MVD of the TRAMflap in groups 1, 2 and 3 was higher than that in groups 4 and 5; the positiveexpression for VEGF and ISHH were shown in groups 1, 2 and 3 and there was significant difference when compared with groups 4 and 5 (Plt;0.05). Conclusion Treatment by recombinant Ad-VEGF165gene is an effective option for enhancement of the TRAM flap survival in the local ischemic area.
ObjectiveTo discuss the feasibility of treating noumenon tumor by antiangiogenesis.MethodsRelated literatures of recent 5 years was reviewed.ResultsTumor angiogenesis were related closely with growth, development, metastasis and prognosis of noumenon tumor. It was possible to inhibit the growth and metastasis of noumenon tumor with antiangiogenesis in vitro and vivo.ConclusionAntiangiogenesis will be a new therapy of treating noumenon tumor.
ObjectiveTo assess the feasibility of intravoxel incoherent motion diffusion-weighted imaging (IVIM) in evaluating microvessel density (MVD) and microvascular invasion (MVI) of hepatocellular carcinoma (HCC).MethodsRat models were established to be scanned by IVIM. HCC lesions corresponding to IVIM image were examined pathologically to get data of MVD and MVI. Spearman correlation analysis was used to compare the apparent diffusion coefficient (ADC), D, D*, and f with MVD, independent samples t test was used to compare ADC, D, D*, and f between MVI (+) and MVI (–) groups.ResultsFifty HCC lesions were included finally. ADC and D values both showed a negative correlation with MVD (r=–0.406, P=0.003; r=–0.468, P=0.001), D* and f showed no statistical correlation with MVD (P=0.172, 0.074, respectively). The differences in ADC and all the IVIM parameters (D, D*, and f) between MVI (+) and MVI (–) HCCs were not statistically significant (P=0.393, 0.395, 0.221, 0.550).ConclusionADC and D can be used to evaluate MVD of HCC, but ADC and IVIM parameters were limited in evaluating MVI.
