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 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 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.
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 observe the morphological changes of macular capillary in type 2 diabetic mellitus (DM) patients without clinical features of diabetic retinopathy (DR) by optical coherence tomography angiography (OCTA). Methods This is a prospective clinical case-control study. Forty-three eyes of 22 patients with DM without clinical features of DR (case group) and 40 control eyes of 20 age- and sex-matched healthy physical examination subjects (control group) were enrolled in this study. All subjects underwent OCTA examination with mode of retinal blood flow imaging, macular 3 mm×3 mm and 6 mm×6 mm area, signal strength ＞45. Foveal avascular zone (FAZ) area, foveal capillary density, parafovea capillary non-perfusion, and micro-aneurysm in shallow capillary vessel layer were evaluated. Results In case group, the mean FAZ area was (0.397±0.141) mm2 and the mean foveal capillary density was (44.6±0.62) %. In control group, the mean FAZ area was (0.253±0.112) mm2 and the mean foveal capillary density was (48.6±0.58) %. FAZ area of eyes in case group was larger than that in control group (t=1.017,P＜0.05). There was no difference of foveal capillary density between two groups (t=1.499,P＞0.05). The spider web-like FAZ and normal foveolar avascular zone were observed in eyes of control group. The parafovea capillary non-perfusion, abnormal foveolar avascular zone, micro-aneurysm and tortuosity of vessels were observed in eyes of case group. Parafovea capillary non-perfusion (χ2=4.542), micro-aneurysms (χ2=5.183) were seen more often in case group than control group (P＜0.05). Conclusion Type 2 DM patients have abnormal retinal vascular microcirculation before DR using OCTA, including larger FAZ area, parafovea capillary non-perfusion, abnormal foveolar avascular zone, micro-aneurysm and tortuosity of vessels.
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.
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.
Microvascular dysfunction is a key pathological mechanism of diabetic retinopathy (DR). In recent years, it has been found that the phenomenon of "metabolic memory" is prevalent in diabetic patients, and diabetic microangiopaplasia cannot be avoided even if patients’ blood glucose is well controlled. Therefore, it is necessary to explore DR from a genetic perspective. miR-126 is the unique microRNA specifically expressed in vascular endothelial cells, which is closely related to the formation of neovascularization and can affect the stability of DR microvessels as well as the germination and migration of endothelial cells, and its gene level is significantly negatively correlated with the expression of vascular endothelial cell growth factor. The potential value of intracellular and circulating miR-126 in the regulation of DR microvascular homeostasis, early diagnosis and treatment, and monitoring of disease course has attracted great attention. However, studies in this area are mostly hypothesis-driven and still have some limitations. It is believed that with the rapid development of genomics, the miRNA spectrum and its molecular mechanism in eye development and eye diseases will gradually become clear, which may lead to a breakthrough in the intervention of individual refractory retinal diseases and establish a new miRNA diagnosis and treatment method in the future.
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.
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.