Microvessel density in patients with gastrointestinal stromal tumors:A systematic review and meta-analysis

BACKGROUND Gastrointestinal stromal tumors(GISTs)are considered the most common mesenchymal tumors of the gastrointestinal tract.Microvessel density(MVD)constitutes a direct method of vascularity quantification and has been associated with survival rates in multiple malignancies.AIM To appraise the effect of MVD on the survival of patients with GIST.METHODS This study adhered to Systematic reviews and Meta-Analyses guidelines and the Cochrane Handbook for Systematic Reviews of Interventions.Electronic scholar databases and grey literature repositories were systematically screened.The Fixed Effects or Random Effects models were used according to the Cochran Q test.RESULTS In total,6 eligible studies were identified.The pooled hazard ratio(HR)for disease free survival(DFS)was 8.52(95%CI:1.69-42.84,P=0.009).The odds ratios of disease-free survival between high and low MVD groups at 12 and 60 mo did not reach statistical significance.Significant superiority of the low MVD group in terms of DFS was documented at 36 and 120 mo(OR:8.46,P<0.0001 and OR:22.71,P=0.0003,respectively)as well as at metastases rate(OR:0.11,P=0.0003).CONCLUSION MVD significantly correlates with the HR of DFS and overall survival rates at 36 and 120 mo.Further prospective studies of higher methodological quality are required.

Study on the Changes in Microvessel Density in Hepatocellular Carcinoma Following Transcatheter Arterial Chemoembolization

To study the changes in intratumoral microvessel density (MVD) in hepatocellular carcinoma (HCC) following transcatheter arterial chemoembolization (TACE), MVD in 42 HCC specimens histologically verified was studied by using immunohistochemical method. Of all the specimens, 20 were obtained from the patients treated with surgical resection alone, 22 from those with second stage surgical resection after TACE. The results showed that the MVD in HCC tissues was 53.4±21 9 in the TACE group and 27.6±9.2 in the single operating group, respectively, with the difference being significant between them ( P <0.001). It was suggested that TACE might contribute to angiogenesis of HCC, possibly due to anoxic stress and ischemia reperfusion injury.

Correlation of RUNX3 expression with microvessel density in colorectal adenocarcinoma tissues and clinical significance

Objective: To study the expression of RUNX3 in colorectal adenocarcinoma tissues and its correlation with microvessel density(MVD),and investigate the clinical pathological prognostic significance of RUNX3 and MVD in patients with colorectal cancer,Methods: The expression value of RUNX3 and MVD in 70 specimens' colorectal adenocarcinoma tissues were detected by immunohistochemistry staining technique,The correlation between their expression and the clinicopathologic features was also investigated,Results: The expression value of RUNX3 and the positive rates of RUNX3 in colorectal adenocarcinoma tissues were 3.25±1.14 and 25.71%(18/70),The expression value of MVD in colorectal adenocarcinoma tissues was 13.14±3.23,Expression of RUNX3 and MVD value were correlated with CEA,serosal invasion,liver metastasis,lymph node metastasis,and TNM stage(P<0.01),The expression value of RUNX3 had negative correlations with that of MVD,Conclusions: The high expression of RUNX3 could inhibit tumor microvascular generation in order to have negative control response on invasion and distant metastasis.

Microvessel density at different levels of normal or injured bile duct in dogs and its surgical implications

BACKGROUND:Ischemic recurrent stricture after surgical repair for iatrogenic bile duct injury(BDI)remains a challenge in clinical practice.The present study was designed to investigate whether ischemia is universal and of varied severity at different levels of the proximal bile duct after BDI. METHODS:A total of 30 beagle dogs were randomly divided into control,BDI,and BDI-repaired groups.The BDI animal model was established based on the classic pattern of laparoscopic cholecystectomy-related BDI.The animals were sacrificed on postoperative day 15,and bile duct tissue was harvested to assess microvessel density(MVD)at selected levels of the normal,post-BDI and BDI-repaired bile duct with the CD34 immunohistochemistry technique. RESULTS:In the control group,MVD at level H(high level) was remarkably higher than that at level L(low level).No significant difference was found between MVDs at levels H and M(middle level),as well as at levels M and L.However, the tendency was noted that the closer the level to the hilus, the greater the MVD at that level.In both the BDI and BDI-repaired groups,MVDs at level H were generally greater than those at level L,despite the unremarkable differences between MVDs at neighboring levels.In these two groups,a similar tendency of MVD distribution to that in the control group was found;the closer the level to the injury site,the lower was the MVD at that level.Moreover,compared with the MDVs at the levels M and L in the control group,MVDs at the corresponding levels in the BDI and BDI-repaired groups were all remarkably reduced(P<0.05).In addition,MVDs at all three levels in the BDI group significantly declined further after BDI repair.CONCLUSIONS:After BDI,universal ischemic damage in the injured proximal bile duct develops close to the injury site, while close to the hilus,ischemia is relatively slight.High hepaticojejunostomy,rather than low biloenterostomy or end-to-end duct anastomosis,should be recommended for BDI repair.Great care should be taken to protect the peribiliary plexus during repair.

Effect of Renin Angiotensin System Blockade on the Islet Microvessel Density of Diabetic Rats and Its Relationship with Islet Function

To investigate the effects of rennin angiotensin system blockade on the microvessel density in islets of diabetic rats and its relationship with islet function, diabetes model was created by feeding of high-caloric laboratory chow plus intraperitoneal injection of a small dose of streptozotocin （30 mg/kg）. After 8 weeks intervention with perindopril （AE, n=10） or valsartan （AR, n=10）, the islet function of the animals was evaluated by intravenous insulin release test （IVIRT）. The pancreases were immunohistochemically stained to analyze the content of insulin and vascular endothelial growth factor （VEGF） in the islets. The microvessel density （MVD） of islets was detected by counting CD34 positive cells. The hypoxia inducible factor （HIF）-1α mRNA expression in the islets was detected by RT-PCR. Compared with normal control group （NC, n=10）, the area under the curve for insulin from 0 to 30 min （AUCI0-30） of diabetes group （DM, n=8） was decreased by 66.3%; the insulin relative concentration （IRC） of βcell was decreased significantly; the relative content of VEGF was increased obviously [（–4.21±0.13） vs （–4.06±0.29）]; MVD in islets was decreased by 71.4%; the relative expression of HIF-1α mRNA was increased by 1.19 times （all P〈0.01）. Compared with DM group, the AUCI0-30 of AE and AR group was increased by 44.6% and 34.9% respectively; IRC was also increased significantly; the relative content of VEGF was decreased by 21.2% and 21.7% respectively; MVD was increased by 62.5% and 75.0% respectively; the relative expression of HIF-1α was decreased by 27.2% and 29.0% respectively （all P〈0.01 or P〈0.05）. There were no significant differences in the said indexes between group AE and AR. It is concluded that the blockade of RAS may ameliorate islets function of diabetic rats by increasing the MVD in islets.

Relationship between peritumoral lymphatic microvessel density and the clinical and pathological characteristics of invasive breast cancer

Objective The aim of the study was to determine the morphological characteristics of lymphatic microvessels and the relationship between lymphatic microvessel density(LMVD) and clinical and pathological characteristics of invasive breast cancer.Methods Tissue specimens and clinical pathological data of 51 cases of female breast cancer were collected in the General Hospital of Shenyang Military Region(Shenyang, China) from January 2007 to October 2011. Another 20 breast fibroadenoma tissue samples were used as controls. All specimens were cut into 4-μm slices, and immunohistochemically stained using streptomycin-resistant avidin peroxidase antibody D2-40. SPSS 17.0 for Windows was used to perform all analyses.Results A total of 38 breast cancer tissue specimens showed varied staining with monoclonal antibody D2-40. The rate of positive staining was in these tissues was 74.5%(38/51), which is significantly higher than that observed in breast fibroadenoma tissues(chi-square = 35.197, P = 0.000). The average LMVD in 38 cases of breast cancer was(26.46 ± 10.06) microvessels/100× magnification field, which was higher than that in the control group(t = 10.74, P = 0.000). Microvessels in peritumoral tissues were abundant, with an average LMVD of(38.42 ± 11.38) microvessels/100× magnification field. Based on layered analysis, the expression level of peritumoral LMVD was correlated with metastasis of lymph nodes, tumor size, and the expression of C-erb B-2(P < 0.05); however, there was no correlation with age or expression of estrogen receptors or progesterone receptors(P > 0.05).Conclusion Lymphatic microvessels detected using D2-40 antibody are mainly present in the peritumoral region of breast cancer tissues, and LMVD showed a correlation with lymph node metastasis and the expression of C-erb B-2. Positive lymphatic vessels, especially in the peritumoral region, may provide a path for lymphatic metastasis in breast cancer. Peritumoral LMVD may be used to estimate the prognosis of patients with breast cancer and may aid in research on treatment methods.

STUDY ON THE CLINICAL-PATHOLOGICAL SIGNIFICANCE OF MICROVESSEL DENSITY AND VASCULAR ENDOTHILIAL GROWTHFACTOR EXPRESSION IN PRIMARY LIVER CANCER

Objective: To evaluate the clinical-pathological significance of intratumoral microvessel density (MVD) and Vascular Endothelial Growth Factor (VEGF) expression in primary liver cancer (PLC). Methods: A retrospective study from 63 postoperative patients all with small PLC (diameter ≤5 cm) was done. One group of 29 patients developed recurrence or metastasis within 2 years. The other group of 34 patients had no evidence of recurrence or metastasis within 2 years. Three sections were taken from each patient. One for H.E. staining, the other two for VEGF and Bio-UEA-I immunohistochemical staining respectively. MVD was counted by endothelial cells, which were highlighted by Bio-UEA-I. Results: The MVD of the recurrence (or metastasis) group (49.6±29.7) were significantly greater than the other, group (22.7±28.2) (P<0.01); The VEGF positive rate of the recurrence group was 86.2% (25/29), the rate of the other group was 47.1% (16/34). the difference between the 2 groups was stafistically significant (P<0.01). The stage of the tumor, the positive rate of satellite nodules and the positive rate of the portal vein embolus were all significantly different between the 2 groups. Conclusion: Besides tumor stage, satellite nodule and portal vein embolus, the MVD and VEGF are also of prognostic significance.

Effects of Brucine on Vascular Endothelial Growth Factor Expression and Microvessel Density in A Nude Mouse Model of Bone Metastasis Due to Breast Cancer

Objective： To study the effects of brucine on vascular endothelial growth factor （VEGF） expression and microvessel density （MVD） in a nude mouse model of bone metastasis due to breast cancer, and to assess the possible antitumor mechanism of brucine. Methods： A syringe needle was used to directly inject 0.2 mL monoplast suspension （with 2 × 106 human breast cancer cells contained） into the bony femoral cortex of the right hind leg for modeling. Twenty-five nude mice were randomized into five groups and administered with an intraperitoneal injection of saline or drug for 8 consecutive days： model group （0.2 mL normal saline）, low-dose brucine group （1.73 mg-kg^-1）, medium-dose brucine group （3.45 mgokg^-1）, high-dose brucine group （6.90 mg.kg^-1）, and thalidomide group （200 mg.kg^-1）. Diet and activity were recorded, and the tumors were harvested 5 weeks later. The percentage of VEGF-positive cells was determined with hematoxylin and eosin staining and immunohistochemical staining, and MVD expression was determined by optical microscopy. Results： The VEGF expressions in brucineor thalidomide-treated mice were significantly reduced as compared with mice in the model group （P〈0.01）. There were no significant difference between the high-dose brucine group and the thalidomide group （P〉0.05）. Significant difference was between the high- and low-dose brucine group （P〈0.05）. Further, VEGF expression was significantly increased in the low- and medium-dose brucine groups compared with the thalidomide group （P〈0.05）. The MVD values in the three brucine and thalidomide groups were significantly lower than that in the model group （P〈0.01）. The MVD values in the medium- and high-dose brucine groups were not significantly different from those in the thalidomide group （P〉0.05）, while the MVD value showed a significant increase in the low-dose group compared with the thalidomide group （P〈0.05）. Conclusion： Brucine could inhibit the growth of breast cancer to bone metastases, possibly by inhibiting tumor angiogenesis.

Oncosis in human esophageal squamous cell carcinoma and its relationship with apoptosis and microvessel density

Background Previous studies have shown that oncosis in malignant tumors might be related to cellular energy supply. The aim of this study was to detect oncosis in human esophageal squamous cell carcinoma （ESCC）, and to investigate its relationship with apoptosis and microvessel density （MVD）. Methods ESCC specimens were obtained from 30 patients with ESCC after surgery. Transmission electron microscopy TUNEL, and immunohistochemistry were used to detect oncosis, apoptosis, and MVD. The relation of oncosis to apoptosis and MVD was analyzed by ANOVA, t test, and q test using SPSS 10.0. Results Transmission electron microscopy revealed both oncosis and apoptosis in the ECSS tissues. About 10% of the TUNEL-positive cells, which were considered apoptotic cells, showed the characteristics of oncosis. In the areas, where oncotic cells accumulated, apoptotic cells were rare; contrarily, where apoptotic cells gathered, oncotic cells were sparse. Compared with the tissues with a high MVD, the number of oncotic cells was increased and that of apoptotic cells was decreased in the tissues with a low MVD. Conclusions Cellular oncosis can be detected in human ESCC tissues. The distribution of oncotic cells presents a close relationship with cellular apoptosis and MVD. Oncosis might be induced by poor blood supply.

Expression and significance of pigment epithelium-derived factor and vascular endothelial growth factor in colorectal adenoma and cancer

BACKGROUND The incidence and mortality of colorectal cancer(CRC)are among the highest in the world,and its occurrence and development are closely related to tumor neovascularization.When the balance between pigment epithelium-derived factors(PEDF)that inhibit angiogenesis and vascular endothelial growth factors(VEGF)that stimulate angiogenesis is broken,angiogenesis is out of control,resulting in tumor development.Therefore,it is very necessary to find more therapeutic targets for CRC for early intervention and later treatment.AIM To investigate the expression and significance of PEDF,VEGF,and CD31-stained microvessel density values(CD31-MVD)in normal colorectal mucosa,adenoma,and CRC.METHODS In this case-control study,we collected archived wax blocks of specimens from the Digestive Endoscopy Center and the General Surgery Department of Chengdu Second People's Hospital from April 2022 to October 2022.Fifty cases of specimen wax blocks were selected as normal intestinal mucosa confirmed by electronic colonoscopy and concurrent biopsy(normal control group),50 cases of specimen wax blocks were selected as colorectal adenoma confirmed by electronic colonoscopy and pathological biopsy(adenoma group),and 50 cases of specimen wax blocks were selected as CRC confirmed by postoperative pathological biopsy after inpatient operation of general surgery(CRC group).An immunohistochemical staining experiment was carried out to detect PEDF and VEGF expression in three groups of specimens,analyze their differences,study the relationship between the two and clinicopathological factors in CRC group,record CD31-MVD in the three groups,and analyze the correlation of PEDF,VEGF,and CD31-MVD in the colorectal adenoma group and the CRC group.The F test or adjusted F test is used to analyze measurement data statistically.Kruskal-Wallis rank sum test was used between groups for ranked data.The chi-square test,adjusted chi-square test,or Fisher's exact test were used to compare the rates between groups.All differences between groups were compared using the Bonferroni method for multiple comparisons.Spearman correlation analysis was used to test the correlation of the data.The test level(α)was 0.05,and a two-sided P<0.05 was considered statistically significant.RESULTS The positive expression rate and expression intensity of PEDF were gradually decreased in the normal control group,adenoma group,and CRC group(100%vs 78%vs 50%,χ^(2)=34.430,P<0.001;++~++vs+~++vs-~+,H=94.059,P<0.001),while VEGF increased gradually(0%vs 68%vs 96%,χ^(2)=98.35,P<0.001;-vs-~+vs++~+++,H=107.734,P<0.001).In the CRC group,the positive expression rate of PEDF decreased with the increase of differen-tiation degree,invasion depth,lymph node metastasis,distant metastasis,and TNM stage(χ^(2)=20.513,4.160,5.128,6.349,5.128,P<0.05);the high expression rate of VEGF was the opposite(χ^(2)=10.317,13.134,17.643,21.844,17.643,P<0.05).In the colorectal adenoma group,the expression intensity of PEDF correlated negatively with CD31-MVD(r=-0.601,P<0.001),whereas VEGF was not significantly different(r=0.258,P=0.07).In the CRC group,the expression intensity of PEDF correlated negatively with the expression intensity of CD31-MVD and VEGF(r=-0.297,P<0.05;r=-0.548,P<0.05),while VEGF expression intensity was positively related to CD31-MVD(r=0.421,P=0.002).CONCLUSION It is possible that PEDF can be used as a new treatment and prevention target for CRC by upregulating the expression of PEDF while inhibiting the expression of VEGF.

Research on the prognosis of different types of microvessels in bladder transitional cell carcinoma

BACKGROUND At present,there is controversy on the role of microvessel density(MVD)in tumors as a prognostic indicator of bladder transitional cell carcinoma(BTCC).However,the MVD in tumors is simply classified based on the expression of several different vascular markers,which has not been related to analytical research on the prognosis of patients with BTCC.AIM To explore the classification of blood vessels in tumors and studied the relationship between MVD and the prognosis of patients with BTCC.METHODS The tissue mass was detected by tissue microarray and immunohistochemical analysis with monoclonal antibodies against CD31,CD34,CD105,and vascular smooth muscle actin to investigate the MVD in BTCC.The measurement data are expressed as the mean±SD.The difference between the groups was analyzed by the t-test,the counting data were analyzed byχ2 test.The Kaplan-Meier survival curve was estimated by the product-limit method.The log-rank time-series test was employed to compare the tumor-free survival curves.RESULTS The MVD was closely related to the pathological grade,invasive depth,and prognosis of BTCC.Significant differences were found between grade I and grade II,grade II and grade III,superficial and invasive type,and the tumor-free survival group and the recurrence or metastasis group(P<0.01).Multivariate analysis showed that undifferentiated MVD was an independent prognostic factor for patient survival time.An inverse correlation between undifferentiated tumor MVD and differentiated tumor MVD in BTCC was also shown.CONCLUSION The classification of blood vessels in BTCC could act as an important prognostic indicator and may also be of great significance in the treatment of cancer.

Microvessel changes in the gerbil hippocampus after cerebral ischemia and reperfusion by Buyang Huanwu decoction pretreatment

Buyang Huanwu decoction （BYHWD） is a classic recipe for the prevention and treatment of ischemic cerebrovascular disease. Gerbils were pretreated with BYHWD, and then subjected to cerebral ischemia and reperfusion. Microvascular changes were determined with laser Doppler monitoring, tannic acid-ferric chloride mordant, and electron microscopy. Results showed that BYHWD pretreatment could enhance the function of hippocampal microvessels, prevent injury, and increase microvasular density and microvasular area density. Thus, these results suggest that BYHWD pretreatment could prevent microvascular occlusion, enhance the capacity of microvascular reperfusion, increase cerebral blood flow, and inhibit neuronal damage, and may be an effective therapy against brain ischemic injury.

Quantitative evaluation of colorectal tumour vasculature using contrast-enhanced ultrasound:Correlation with angiogenesis and prognostic significance

BACKGROUND Ultrasound is a vital tool for the diagnosis and management of colorectal cancer(CRC).Contrast-enhanced ultrasound(CEUS)is a non-invasive,safe,and cost-effective method for evaluating tumour blood vessels,that play a crucial role in tumour growth and progression.AIM To explore CEUS’s role in the quantitative evaluation of CRC blood vessels and their correlation with angiogenesis markers and prognosis.METHODS This study prospectively enrolled 100 patients with CRC confirmed by histo-pathology.All patients received preoperative CEUS examinations.Quantitative parameters,such as peak intensity(PI),time to peak(TTP),and area under the curve(AUC),were derived from time-intensity curve(TIC)analysis.Tumour tissue samples were obtained during surgery and examined immunohistochem-ically to assess the expression of angiogenesis markers,including vascular endo-thelial growth factor(VEGF)and microvessel density(MVD).The correlation between CEUS parameters,angiogenesis markers,and clinicopathological features was evaluated using appropriate statistical tests.RESULTS Quantitative CEUS parameters(PI,TTP,and AUC)showed significant correlations with VEGF expression(P<0.001)and MVD(P<0.001),indicating a strong link between tumour blood vessels and angiogenesis.Increased PI,reduced TTP,and expanded AUC values were significantly related to higher tumour stage(P<0.001),lymph node metastasis(P<0.001),and distant metastasis(P<0.001).Furthermore,these parameters were recognized as independent predictors of overall survival and disease-free survival in multivariate analysis(P<0.001).CONCLUSION CEUS has a high potential in guiding treatment planning and predicting patient outcomes.However,more com-prehensive,multicentre studies are required to validate the clinical utility of CEUS in CRC management.

High matrix metalloproteinase-9 expression induces angiogenesis and basement membrane degradation in stroke-prone spontaneously hypertensive rats after cerebral infarction

Basement membrane degradation and blood-brain barrier damage appear after cerebral infarc- tion, severely impacting neuronal and brain functioning; however, the underlying pathogenetic mechanisms remain poorly understood. In this study, we induced cerebral infarction in stroke- prone spontaneously hypertensive rats by intragastric administration of high-sodium water （1.3% NaC1） for 7 consecutive weeks. Immunohistochemical and immunofluorescence assays demonstrated that, compared with the non-infarcted contralateral hemisphere, stroke-prone spontaneously hypertensive rats on normal sodium intake and Wistar-Kyoto rats, matrix metalloproteinase-9 expression, the number of blood vessels with discontinuous collagen IV expression and microvessel density were significantly higher, and the number of continuous collagen IV-positive blood vessels was lower in the infarct border zones of stroke-prone sponta- neously hypertensive rats given high-sodium water. Linear correlation analysis showed matrix metalloproteinase-9 expression was positively correlated with the number of discontinuously collagen IV-labeled blood vessels and microvessel density in cerebral infarcts of stroke-prone spontaneously hypertensive rats. These results suggest that matrix metalloproteinase-9 upregula- tion is associated with increased regional angiogenesis and degradation of collagen IV, the major component of the basal lamina, in stroke-prone spontaneously hypertensive rats with high-sodi- um water-induced focal cerebral infarction.

Expression of Maspin in Non-small Cell Lung Cancer and Its Relationship to Vasculogenic Mimicry

Maspin belongs to the serine protease inhibitor （serpin） family and has been proven to be a suppressor of tumor growth and metastasis in many types of tumors. The purpose of this study was to investigate the expression of maspin in non-small cell lung cancer （NSCLC） and its relationship to vasculogenic mimicry （VM）. A total of 160 specimens of NSCLC were involved in this study and 20 specimens of normal lung tissue served as controls. VM, microvessel density （MVD） and the expression of maspin were detected by using immunohistochemical staining. The results showed that the positive rates of maspin and VM in the NSCLC group were 48.1% （77/160） and 36.9% （59/160）, respectively, which were significantly different from those in the control group with the positive rates of maspin and VM being 100% and 0% respectively （P〈0.05）. VM, MVD and the expression level of maspin were significantly related to tumor differentiation, lymph node metastasis, clinical stages and postoperative survival time （all P〈0.05）. The maspin expression in patients with squamous cell carcinoma was significantly higher than that in those with adenocarcinoma （P〈0.05）. The maspin expression was negatively correlated with VM and MVD, and there was a positive correlation between VM and MVD. Maspin-negative expression, VM and high MVD score were negatively related to the 5-year-survival rate. PTNM stages, VM, MVD and maspin expression were independent prognostic factors for NSCLC （P〈0.05）. It was suggested that the loss of expression of maspin may participate in the invasion and metastasis of NSCLC and it has a positive relationship to VM in NSCLC. Combined detection of maspin, VM and MVD may help predict the progression and prognosis of NSCLC.

A systematic review of the effects and mechanisms of preoperative 5α-reductase inhibitors on intraoperative haemorrhage during surgery for benign prostatic hyperplasia

5α-reductase inhibitors （5α-RIs）, including finasteride and dutasteride, are commonly used medical therapies for benign prostatic hyperplasia （BPH）. Many studies reported that preoperative 5α-RI had impact on intraoperative haemorrhage during surgery for BPH, but it was still in controversial. So, we conducted a systematic review of the effects and mechanisms of 5α-RIs on intraoperative bleeding for BPH. MEDLINE, EMBASE, the Cochrane Controlled Trail Register of Controlled Trials and the reference lists of retrieved studies were searched in the analysis. Sixteen publications involving 15 different randomized controlled trials （RCTs） and a total of 1156 patients were used in the analysis, including 10 RCTs for finasteride and five RCTs for dutasteride. We found that preoperative finasteride treatment decreases microvessel density （MVD） in resected prostate specimens. Total blood loss, blood loss per gram of resected prostate tissue and decreases in haemoglobin were all greatly reduced in the finasteride group as compared to controls. Dutasteride appeared to have no effect on bleeding. This meta-analysis shows that preoperative finasteride treatment could decrease intraoperative haemorrhage during surgery for BPH. Preoperative dutasteride had no effect on intraoperative haemorrhage, but further high-qualitv prospective studies are still needed to confirm this observation.

Relationsip between PTEN and VEGF Expression and Clinicopathological Characteristics in HCC

To investigate the expressions and significance of the tumor suppressor gene phosphatase and tensin homlog deleted on chromosome ten protein （PTEN） and vascular endothelial growth factor （VEGF） in hepatocellular carcinoma （HCC）, and to analyze the relationship between their expressions and the tumor＇s invasion and their pericarcinomatous tissues, the correlation of their expressions with the tumor＇s clinicopathological characteristics and invasion potential were studied. Our study showed that the expression level of PTEN in HCC was remarkably lower than that in pericarcinomatous liver tissues, while the expressions of both VEGF and MVD were higher than that in pericarcinomatous liver tissues. Correlation analysis revealed that the expression of PTEN was negatively related to the progression of the pathological differentiation and invasion of tumor, whereas the expressions of VEGF and MVD were positively related. Moreover, there was a negative relationship between the expression of PTEN and the expressions of VEGF and MVD, and a positive one between VEGF and MVD. The expressions of PTEN and VEGF may reveal the degree of differentiation and the invasive potential of HCC tissues. The mechanism by which the lack of PTEN expression probably induces abnormal hyperexpression of VEGF may play an important role in the invasion and metastasis of HCC.

Expression and Clinical Significance of Vascular Endothelial Growth Factor in Benign and Malignant Tissues of Breast

Objective： To detect the expression of vascular endothelial growth factor （VEGF） and microvessel density （MVD） count in breast benign affection, breast atypical hyperplasia and breast carcinoma in situ, and to clarify the relationship between VEGF expression, MVD and the clinicopathological features of these diseases. Methods： The expression of VEGF and MVD count in 115 cases breast benign diseases （including 40 breast fibroid tumor, 40 breast cystic hyperplasia and 35 intraductal papilloma, 19 breast atypical hyperplasias and 32 breast carcinomas in situ were examined by immunohistochemistry staining （SP-method）. Results： The positive rate of VEGF in breast benign diseases, breast atypical hyperplasia and breast carcinoma in situ were 21.74%（25/115）, 31.58.% （6/19）and 53.13%（17/32） respectively. It was the lowest in breast benign affection group, and was the highest breast carcinoma in situ group. The expression of VEGF increased gradually in the three groups （P〈0.05）. The MVD count of the three groups were 14.41 ± 2.59, 18.89± 4.47 and 21.13 ± 4.12 respectively, It was the lowest in breast benign affection group, and was the highest breast carcinoma in situ group. The MVD count of the three groups increased gradually （P〈0.05）. In VEGF positive group, MVD count was 19.41 ±4.78; In VEGF negative group, MVD count was 14.91±3.15. The MVD count was higher in VEGF positive group than that in VEGF negative group （P〈0.05）. Conclusion： The results of this study suggested that VEGF could promote microvessel growth in breast tumors. The occurrence and progression of breast cancer might be related with the expression of VEGF.

Effects of Bu-Shen-An-Tai Recipe and Its Two Components on Endometrial Morphology during Peri-implantation in Superovulated Mice

The aim of this study was to investigate the effect of Bu-Shen-An-Tai recipe （BSATR） and its two components （Bushen recipe, and Huoxue recipe） on endometrial morphology during peri-implantation in superovulated mice. Mice were randomly divided into five groups, including the normal （N）, model （M）, Bushen （BS）, Huoxue （HX） and Bu-Shen-An-Tai （BH） groups. The uteri were collected on day 4 of pregnancy, and the endometrium thickness, microvessel density （MVD） and number of pinopodes observed. Compared with the M group, the endometrial thickness in the BS, HX and BH groups was significantly increased and there was a significant difference in endometrial thickness between the BS and the BH groups. The mean MVD was significantly lower in the M group than in the N group, and there was a significant increase in MVD in the BS, HX and BH groups as compared with the M group. Compared with the M group, the pinopode scores in the en- dometrium were significantly increased in the HX and BH groups; and the BS group had significantly higher pinipode scores than the HX and BH groups. In conclusion, the results of the present study demonstrated that the recipes （Bushen, Huoxue and BSATR） could improve the endometrial envi- ronment by regulating the endometrial thickness, MVD and the number of pinopodes at the window of implantation. Moreover, the Huoxue recipe and the BSATR were more efficient than the Bushen recipe, with the BSATR tending to have the most beneficial effects.

UP-REGULATION OF CYCLOOXYGENASE-2 GENE EXPRESSION CORRELATES WITH TUMOR ANGIOGENESIS IN HUMAN BREAST CANCER

Objective: To study the relationship between cyclooxygenase-2 (COX-2) expression and tumor angiogenesis in human breast cancer. Methods: Archival primary breast carcinomas (n = 62), adjacent ductal carcinoma in situ (DCIS, n = 13) and DCIS alone (n = 5) were analyzed for COX-2 and VEGF expression by immunohistochemistry using specific monoclonal antibodies. Microvessel density (MVD) was also examined the using CD34 staining. Results: A significant correlation was found between COX-2 and VEGF expression (P<0.01). Both COX-2 and VEGF were significantly correlated with MVD (P<0.05) and P<0.01, respectively). COX-2 and VEGF genes were overexpressed in tumor specimens as compared with normal epithelia. Conclusion: COX-2 is related to tumor angiogenesis in breast cancer. It is likely that VEGF is one of the most important mediators of the COX-2 angiogenic pathway.