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.
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.
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.
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.
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 investigate the clinicopathological significance of integrin α5β1 expression and microvessel density(MVD) in gastric cancer(GC) and the correlation of MVD with integrin α5β1. MethodsThe expression of integrin α5β1 was detected by means of immunohistochemical staining (SP method) on paraffinembeded tissue specimens from 35 primary gastric carcinoma(PGC), 10 metastasic lymph node of gastric cancer and 8 chronic superficial gastritis (CSG). Vascular endothelial cells were stained immunohistochemically using antiCD34 monoclonal antibody to recognize microvessel(MV) in 35 cases of PGC and 8 CSG, MV was counted in 4 hot spot per slide under lightmicroscope (×400) and the average was defined as MVD. The results combined with clinicopathological parameters were analyzed statistically to characterize the role of integrin α5β1 and MVD in the progression of gastric cancer. ResultsIntegrin α5β1 expression and MVD in PGC were significantly higher than those in CSG respectively （t=3.32, P lt;0.01; t=2.30, Plt;0.05）; the expression of integrin α5β1 in PGC showed only a correlation with the invasion depth of tumor (t=2.29, Plt;0.05） while MVD showed all correlations with invasion depth,lymph node status and TNM stage （t=3.07, Plt;0.01; t=2.48, Plt;0.05; t=2.94,Plt;0.01）. Neither integrin α5β1expression nor MVD showed a relation with differential of PGC （t=0.15, Pgt;0.05; t=0.41, Pgt;0.05）. Integrin α5β1 was significantly overexpressed in lymph node metastatic cancer compared with that in corresponding PGC （t=2.45, Plt;0.05）; the difference of MVD showed no statistical significance among levels of integrin α5β1 expression in PGC （F =1.43,P＞0.05） and it showed no correlation with integrin α5β1 expression（r= 0.156, P=0.37）.Conclusion Overexpression of integrin α5β1 is present in GC and associates with the progression of tumor, implying that it may be viewed as the indicator of invasion and metastasis and the candidate target of gene therapy of gastric cancer. However, integrin α5β1 may not play an important role in the vascularization of GC.
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.
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 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 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.
