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.
This study was designed to define the microvessel density (MVD) in breast carcinoma and benign breast disease and the relationship of microvessel density with the tumor size, histologic grade, and lymph node status. Under light microscopy, the microvessels by staining their endothelial cells immunocytochemically for factor Ⅷ were highlighted. Results: The mean level of MVD of breast carcinoma was significantly higher than that of benign disease (Ｐ＜0.01); the MVD of breast carcinoma was associated with tumor size (Ｐ＜0.05), histologic grade (Ｐ＜0.05), and axillary node status (Ｐ＜0.05), but no association with estrogen receptor. These show that MVD of breast carcinoma is significantly higher than that of benign breast disease, and MVD of breast carcinoma is one of significant prognostic indicators.
ObjectiveTo investigate the expression of keratinocyte growth factor (KGF) and cyclooxygen-ase-2 (COX-2) protein and microvessel density (MVD), and to explore their function and mechanism in the multistep process of gastric cancer. MethodsThe expressions of KGF and COX-2 protein in 64 samples of gastric cancer and 30 cases of normal gastric mucosa tissues were detected by immunohistochemistry. The MVD was detected by staining the endothelial cells in microvessles using anti-CD34 antibody. ResultsThe positive rate of KGF and COX-2 protein expression in gastric cancer were 65.6% (42/64) and 79.7% (51/64), respectively, which was significantly higher than that in normal gastric mucosa tissues 〔(23.3%, 7/30), P=0.046; (13.3%, 4/30), P=0.008〕. The MVD of gastric cancer was 31.8±8.0, which was significantly higher than that of normal gastric mucosa tissues (14.3±6.1), P=0.000. The MVD in gastric cancer with coexpressive KGF and COX-2 protein was 35.9±5.7, which was significant higher than that with non-coexpressive KGF and COX-2 protein (25.7±7.0), P=0.000. Both the expression of KGF and COX-2 protein were related to the invasion of serosa, lymph node metastasis and TNM staging (Plt;0.05, Plt;0.01). The MVD of gastric cancer tissues was related to lymph node metastasis and TNM staging (Plt;0.05), but unrelated to patient’s age, gender, and differentiation of tumor (Pgt;0.05). The co-expression of KGF and COX-2 protein was frequently found in patients with deeper invasion of serosa, lymph node metastasis, and higher TNM staging (Plt;0.05), but which was not associated withpatient’sage, gender, and differentiation of tumor (Pgt;0.05). The expression of KGF protein was positively correlated to the expression of COX-2 protein (r=0.610, P=0.000). There was positive correlation between MVD and the expression of KGF (r=0.675, P=0.000) and COX-2 protein (r=0.657, P=0.000) in gastric cancer, respectively. ConclusionKGF and COX-2 highly expressed by gastric cancer, which may be involved in the invasion and metastasis of gastric cancer by synergisticly promoting 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 effects of sustained-release basic fibroblast growth factor (bFGF) on healing of bile duct defect. Methods A model of bile duct wall defect (2 cm in length and 1/3-2/3 of the bile duct circumference in width) was made in 24 pigs (male or female, weighing 15-30 kg), and then defect was repaired with sustained-release bFGF collagen membrane (2.0 cm × 1.0 cm × 0.5 cm in size) in the experimental group (n=12) or with collagen membrane (2.0 cm × 1.0 cm × 0.5 cm in size) alone in the blank control group (n=12). Another 4 healthy pigs were used to obtain normal bile duct as normal control group. The survival condition of pigs was observed after operation; at 1, 2, and 3 months after operation, the blood sampling was collected to test the changes of liver function, and the bile duct specimens were harvested to count the microvessel density (MVD) and submucosal gland by HE staining and immunohistochemistry staining; and at 3 months after operation, cholangiography examination was done. Results All the animals survived to completion of the experiment. Intra-abdominal adhesion was serious in the experimental and blank control groups at 1 week after operation, but the adhesion was markedly improved in the experimental group when compared with the blank control group with time passing. The liver function test showed that alkaline phosphatase in the experimental group was significantly lower than that in the blank control group at 2 and 3 months (P lt; 0.05), but no significant difference in aspartate aminortransferase, total bilirubin, and albumin was found among 3 groups (P gt; 0.05). The histology and immunohistochemistry staining observations showed that the regeneration rates of submucosal glands and epithelium in the experimental group were faster than those in the blank control group; defect was covered with the epithelium at 2 months, and the structure was similar to that of normal control group at 3 months; and the edema and inflammation infiltration were reduced when compared with the blank control group. The counts of MVD and submucosal gland were significantly higher than those in blank control group and normal control group at 1 month after operation (P lt; 0.05), and then decreased and remained at normal levels at 2 months after operation. There was a positive correlation between submucosal gland counting and MVD counting in 3 groups after operation (P lt; 0.01). The cholangiography examination showed no biliary dilatation or cholelithiasis after 3 months in experimental group and blank control group. Conclusion Sustained-release bFGF can promote healing of bile duct defect by accelerating the vascularization, gland regeneration, and epithelialization.
Objective To investigate perfusion features of gastric antrum cancer by 64-multidetector CT and to assess the correlation between perfusion CT parameters and immunohistochemical markers of angiogenesis in gastric cancer. Methods Perfusion CT was performed in 30 patients with gastric antrum cancer （gastric antrum cancer group） and 24 patients with normal stomach (control group), and postoperative specimens were stained using a polyclonal antibody to VEGF and CD34. The correlation between perfusion parameters and microvessel density (MVD), and VEGF were analyzed. Results Blood volume (BV) increased in the gastric antrum cancer group (Plt;0.01). There was no significant difference in perfusion (PF), peak enhancement (PE), or time to peak (TTP) between the gastric antrum cancer and the normal groups (Pgt;0.05). BV was positively significantly correlated with MVD （r=0.522, P=0.02), but no significant correlation was found between PF （r=0.072, P=0.78), PE （r=0.253, P=0.31), or TTP （r=0.235, P=0.35) and MVD. No correlation was found between PF （r=-0.208, P=0.45), PE （r=-0.251, P=0.37), TTP（r=-0.284, P=0.31), or BV（r=-0.472, P=0.09) and VEGF.Conclusion Blood volume can evaluate the angiogenesis of tumor and perfusion CT can be a tool to assess microvessel status in gastric antrum cancer.
Objective To explore the effect of toremifene on estrogen receptor （ER） expression and tumor micro-angiogenesis in rat Lewis lung carcinoma. Methods Cell suspension of rat Lewis lung carcinoma was implanted into 40 female Wistar rats subcutaneously. The rats were randomly divided into a control group，a estradiol group （0.006 mg/mL），a low dose toremifene group （0.25 mg/mL） and a high dose toremifene group （5 mg/mL）. Tumor size was measured every 3 days and the tumor growth curve was charted. On 15th day，the tumor weight and the growth inhibition rate were measured. Immunohistochemical method was used to detect the expressions of estrogen receptor α （ERα），estrogen receptor β （ERβ），vascular endothelial growth factor （VEGF），and platelet endothelial cell adhesion molecule-1 （PECAM-1）. Integral optical density （IOD） of ERα，ERβ and VEGF was calculated by image analysis software. Quantitative method of Weidner with PECAM-1 was employed for microvessel density （MVD） count. Results Tumor size of the four groups all presented a quadratic function growth trend with time （Plt;0.05）. Tumor growth speed was slower in toremifene groups of low and high doses than that in the control group and the estradiol group. The growth inhibition rate of the estradiol group，the low dose toremifene group and the high dose toremifene group was －15.1%，22.6%，and 45.1%，respectively. The expressions of ERα，VEGF，and MVD in the estradiol group were significantly higher than those in the control group，the low dose toremifene group and the high dose toremifene group （all Plt;0.05）. The expressions of ERα，VEGF，and MVD in the low dose toremifene group were significantly lower than those in control group，but higher than those in high dose toremifene group （all Plt;0.05）.The expression of ERα was positively related to VEGF （r=0.664，Plt;0.05） and MVD（r=0.593，Plt;0.05）. Conclusion Toremifene can inhibit tumor growth，which maybe involved in inhibiting ERα mediated VEGF expression.
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.
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 investigate the expression of tumor necrosis factor-α (TNF-α) in prostate cancer tissue and explore its relations with tumor angiogenesis. MethodsThe expression of TNF-α and CD105 were detected with two-step immunohistochemical staining technique in 20 cases of benign prostatic hyperplasia and 50 cases of prostate cancer between January 2010 and January 2012, and microvessel density (MVD) marked with CD105 was also measured. ResultsThe expressions of TNF-α and CD105 were higher in prostate cancer (41.72±8.67, 20.15±2.67) than those in benign prostatic hyperplasia (21.01±3.85, 4.34±1.67) (t'=13.990, P<0.001; t'=29.771, P<0.001). TNF-α and MVD were not correlated with age and size of tumor, but were positively correlated with tumor differentiation degree (rs=0.847, P<0.001; rs=0.776, P<0.001) and negatively correlated with clinical grades (rs=-0.769, P<0.001; rs=-0.842, P<0.001). ConclusionThe result indicates that over expression of TNF-α exists in prostate cancer. It may play an important role in the anginogenesis and carcinogenesis of prostate cancer.