Effect of intraarterial chemotherapy on vascular endothelial growth factor expression and microvessel density in carcinoma of the cervix

Objective: To clarify the effect of intraarterial chemotherapy on vascular endothelial growth factor (VEGF) expres- sion and microvessel density (MVD) count in carcinoma of the cervix. Methods: Before intraarterial chemotherapy and after 2–3 weeks of therapy, the expression of VEGF and MVD count in 36 carcinoma tissues of locally advanced cervical cancer were determined by CD34. Results: Before intraarterial chemotherapy and after 2–3 weeks, the expression of VEGF were 75% (27/36) and 30.6% (11/36) respectively, and MVD were reduced obviously (P<0.001). Conclusion:?The intraarterial chemotherapy can reduce the expression of VEGF and MVD, and adjust malignancy of cervical cancer, and cut down the postoperative metastasis.

Vascular endothelial growth factor and microvessel density for detection and prognostic evaluation of invasive breast cancer

Objective The purpose of this study was to evaluate the distribution of vascular endothelial growth factor （VEGF） and CD105-microvessel density （MVD）in invasive breast carcinomas. We also aimed to analyze the relationship between VEGF and MVD expression with other standard prognostic parameters associated with invasive breast cancer, such as size, grade, stage of the cancer, metastases, and tumor recurrence. Methods immunohistochemistry via the Ultra SensitiveTM S-P method was used to detect VEGF and MVD expression in 128 cases of invasive breast carcinoma. Specimens were evaluated for CD105 expression. Positively stained microvessels were counted in dense vascular loci under 400x magnification, MVD in the peripheral area adjacent to the lesion and in the central, area within the lesion in invasive breast carcinomas and benign leisions groups were also assessed. Fifty cases of benign breast disease tissue were selected as the control group. Results Results showed that 64.1% of invasive breast cancer samples were VEGF-positive, higher than in benign breast disease tissue （22.0%, P 〈 0.05）. There was a positive correlation between VEGF overexpression and histological grade, lymph node metastasis, and distant metastasis of invasive breast cancer. VEGF expression was not related to age or size of the tumor （P 〉 0.05）. MVD of the peripheral area adjacent to the lesion was significantly higher than those central area within the lesion in both invasive breast cancer and benignbreast disease groups （P 〈 0.01 for each group）. There were significant differences in the mean CD105-MVD, between invasive breast tumors with a histological grade of Ⅰ or Ⅱ and grade Ⅲ; between tumors with lymph node or distant metastasis; and between patients with or without recurrence （P 〈 0.05）. However, there was no difference in the mean MVD between the two age groups （≤ 50 years vs. 〉 50 years） or the two tumor diameter groups （〈 2 cm vs. 〉 2 cm）, P 〉 0.05. Conclusion Overexpression of VEGF and MVD may be important biological.markers for invasion and lymph node and distant metastases of invasive breast cancer. Combined detection of the two tumor markers could provide better prognostic monitoring for disease recurrence and metastasis, as well as aid with clinical staging of breast tumors. Prediction of the risk for metastasis and recurrence, as well as recurrence patterns based on VEGF and MVD post-surgery, could aid design of better follow-up regimens and appropriate treatment strategies for breast cancer patients.

The effects of vascular endothelial growth factor and microvessel density in the fibromyoma uteri

Objective： To investigate vascular endothelial growth factor （VEGF） expression and microvessel density （MVD） on the fibromyoma uteri treated with mifepristone. Methods： VEGF expression and MVD were counted on 60 cases of the fibromyoma uteri by SP method, including 40 cases of mifepristone treated and 20 cases of untreated patients as controlled group. Results： VEGF positive expression rate and MVD in treated group were 3715% and 9.90 ＋ 5.95, which were lower than those in controlled group （80% and 16.36 ＋ 2.07; P 〈 0.05）. Meanwhile, in treated group, those in marked shrink in tumor size sub-group were lower than in not obvious sub-group （12.0% and 7.89 ＋ 4.36 vs. 80% and 11,29 ＋ 3.10; P 〈 0.05）. Conclusion： VEGF and MVD expression decreases in the fibromyoma uteri after treatment with mifepristone, suggesting that mifepristone could inhibit angiogenesis and blood supply resulting in tumor shrink.

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.

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.

Expression of endothelial nitric oxide synthase and vascular endothelial growth factor in association with neovascularization in human primary astrocytoma

Objective: To investigate the relationship between the expression of endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) and angiogenesis in primary astrocytoma. Methods: Thirty-seven primary astrocytomas and 4 astrocytic hyperplasia samples were collected and divided into three groups according to histological grade. The expression of eNOS, VEGF and factorⅧ related antigen (FⅧRAg) were assayed by immunohistochemistry. Microvascular density was assessed by FⅧRAg immunoreactivity. The intensity of immunoreactivity was graded according to the percentage of positive tumor cells. Results: No eNOS and VEGF were expressed in the astrocytes and vascular endothelium in astrocytic hyperplasia. The expression of eNOS or VEGF was light in low-grade astrocytoma and strong in glioblastoma. eNOS expression in astrocytoma was very positively correlated with VEGF. eNOS and VEGF expression in anaplastic astrocytoma was median in contrast to the low grade astrocytoma and glioblastoma. Lower microvascular density was found in low grade astrocytoma than that in higher grade malignant ones. The expressions of eNOS and VEGF were correlated with microvascular density and tumor malignancy. Conclusion: This finding suggests that eNOS and VEGF may have cooperative effect in tumor angiogenesis and play an important role in the pathogenesis of primary astrocytoma.

Endocan-expressing microvessel density as a prognostic factor for survival in human gastric cancer

AIM: To investigate the expression of endocan in tumour vessels and the relationships between endocan and the expression of vascular endothelial growth factor(VEGF) and prognosis in gastric cancer.METHODS: This study included 142 patients with confirmed gastric cancer in a single cancer centre between 2008 and 2009. Clinicopathologic features were determined, and an immunohistochemical analysis of endocan-expressing microvessel density(MVD)(endocan-MVD), VEGF and vascular endothelial growth factor receptor 2(VEGFR2) was performed. Potential relationships between endocan-MVD and clinicopathological variables were assessed using a Student's t-test or an analysis of variance test. Spearman's rank correlation was applied to evaluate the relationship between endocan-MVD and the expression of VEGF/VEGFR2. long-term survival of these patients was analysed using univariate and multivariate analyses.RESULTS: Positive staining of endocan was observed in most of the gastric cancer tissues(108/142) and in fewer of the normal gastric tissues. Endocan-MVD was not associated with gender or histological type(P > 0.05), while endocan-MVD was associated with tumour size,Borrmann type, tumour differentiation, tumour invasion, lymph node metastasis and TNM stage(P < 0.05). According to the Spearman's rank correlation analysis, endocan-MVD had a positive correlation with VEGF(r = 0.167, P = 0.047) and VEGFR2(r = 0.410, P = 0.000). The univariate analysis with a log-rank test indicated that the patients with a high level of endocan-MVD had a significantly poorer overall survival rate than those with a low level of endocan-MVD(17.9% vs 64.0%, P = 0.000). The multivariate analysis showed that a high level of endocan-MVD was a valuable prognostic factor.CONCLUSION: Endocan-MVD significantly correlates with the expression of VEGF and VEGFR2 and is a valuable prognostic factor for survival in human gastric cancer.

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.

Expression levels and significance of hypoxia inducible factor-1 alpha and vascular endothelial growth factor in human colorectal adenocarcinoma

Background Hypoxia-inducible factor 1 (HIF-1), a transcription factor, is overexpressed in common human cancers and their metastases. This study aimed at determining the expression levels of HIF-1α and vascular endothelial growth factor (VEGF) in SW480 cells and in colorectal adenocarcinoma tissue and ascertaining whether HIF-1α and VEGF play important roles in tumor angiogenesis. Methods HIF-1α mRNA expression was analyzed using in situ hybridization and RT-PCR. HIF-1α and VEGF protein were detected in SW480 cells and colorectal adenomas and adenocarcinomas by immunohistochemistry using streptavidin/peroxidase (SP). Western blot was used to detect HIF-1α protein extracted from SW480 cells. Microvessel density (MVD) in colorectal carcinomas was determined by anti-CD_ 34 immunostaining in colorectal carcinomas. Results Optical density values representing HIF-1α mRNA expression levels were found to be significantly higher in SW480 cells in hypoxic conditions than in cells under normoxic conditions (P<0.05) or in hypoxic conditions but treated with genistein (P<0.05). The levels of HIF-1α and VEGF protein expression in SW480 cells were significantly higher in the hypoxia group than in the normoxia group (P<0.01, P<0.05, respectively) and hypoxia/genistein group (P<0.01, P<0.05, respectively). The positive expression rates of HIF-1α mRNA changed dramatically when comparing colorectal adenomas with adenocarcinomas of different Dukes’ stages (P<0.05). HIF-1α mRNA was also expressed at higher levels in adenocarcinomas than that in adenomas (P<0.01). HIF-1α protein expression correlated significantly with VEGF protein expression and MVD.Conclusions Hypoxia induces the expression of HIF-1α and VEGF in colorectal adenocarcinomas. HIF-1α may play an important role in angiogenesis and tumor progression by regulating the expression of VEGF in human colorectal carcinomas.

Possible biological and translational significance of mast cells density in colorectal cancer

Mast cells (MCs), located ubiquitously near blood vessels, are descended from CD34+ hematopoietic stem cells. Initially, although their role has been well defined in hypersensitivity reactions, the discovery of their sharing in both innate and adaptive immunity has allowed to redefine their crucial interplay on the regulatory function between inflammatory and tumor cells through the release of mediators granule-associated (mainly tryptase and vascular endothelial growth factor). In particular, in several animal and human malignancies it has been well demonstrated that activated c-Kit receptor (c-KitR) and tryptase (an agonist of the proteinase-activated receptor-2) take pivotal part in tumor angiogenesis after the MCs activation, contributing to tumor cells invasion and metastasis. In this review, we focused on crucial MCs density (MCD) role in colorectal cancer (CRC) development and progression angiogenesis-mediated; then, we will analyze the principal studies that have focused on MCD as possible prognostic factor. Finally, we will consider a possible role of MCD as novel therapeutic target mainly by c-KitR tyrosine kinase inhibitors (imatinib, masitinib) and tryptase inhibitors (gabexate and nafamostat mesylate) with the aim to prevent CRC progression.

Issues of origin,morphology and clinical significance of tumor microvessels in gastric cancer

Gastric cancer(GC)remains a serious oncological problem,ranking third in the structure of mortality from malignant neoplasms.Improving treatment outcomes for this pathology largely depends on understanding the pathogenesis and biological characteristics of GC,including the identification and characterization of diagnostic,prognostic,predictive,and therapeutic biomarkers.It is known that the main cause of death from malignant neoplasms and GC,in particular,is tumor metastasis.Given that angiogenesis is a critical process for tumor growth and metastasis,it is now considered an important marker of disease prognosis and sensitivity to anticancer therapy.In the presented review,modern concepts of the mechanisms of tumor vessel formation and the peculiarities of their morphology are considered;data on numerous factors influencing the formation of tumor microvessels and their role in GC progression are summarized;and various approaches to the classification of tumor vessels,as well as the methods for assessing angiogenesis activity in a tumor,are highlighted.Here,results from studies on the prognostic and predictive significance of tumor microvessels in GC are also discussed,and a new classification of tumor microvessels in GC,based on their morphology and clinical significance,is proposed for consideration.

A Correlative Study between CT Perfusion Parameters and Angiogenesis in Rabbit VX2 Liver Tumors

Objective: The purpose of this study was to evaluate the correlation between CT perfusion parameters and the hypoxia-inducible factor-1 alpha (HIF-1α), vascular en-dothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and microvessel density (MVD) marked by CD34 molecular of rabbit VX2 liver tumors and to investigate the value of CT perfusion imaging in evaluating tumor angiogenesis. Material and methods: Twenty-four cases of rabbit VX2 liver tumor were performed by CT perfusion scanning. Hepatic artery perfusion (HAP), portal vein perfusion (PVP), total hepatic blood flow (THBF) and hepatic perfusion index (HPI) were measured by perfusion software. HIF-1α, VEGF and MMP-2 expression and MVD were detected in the 24 rabbit VX2 liver tumor tissue samples using immunohistochemical method. The correlation between the HIF-1α, VEGF, MMP-2 expression and MVD and CT perfusion parameters were analyzed. Results: Correlation analysis revealed that the expression of HIF-1α, MMP-2, MVD were positively related to the HAP, THBF, HPI (p < 0.01), but no relations with PVP (p > 0.05);and correlation analysis revealed that the expression of VEGF was positively related to the HAP, HPI (p 0.05). There was a positive relationship between the expression of HIF-1α, VEGF, MMP-2 and MVD (p < 0.01). Conclusions: CT perfusion imaging can reflect the blood perfusion of the rabbit VX2 liver tumors and evaluate the information of angiogenesis about tumors.

17-DMAG对PD-1人源化小鼠肝癌移植瘤的抑制作用

目的 探讨17-二甲基胺乙基-17-去甲氧基格尔德霉素(17-DMAG)对PD-1人源化小鼠人肝癌移植肿瘤生长的抑制作用。方法 选取30只PD-1人源化小鼠,将HepG2细胞悬液注射于小鼠右侧腹股沟皮下组织,构建人肝癌移植瘤模型;将荷瘤人源化小鼠随机分为3组(每组10只):(1)模型组(注射生理盐水10 mg/kg);(2)17-DMAG组(按25 mg/kg腹腔注射17-DMAG,3次/周);(3)顺铂组(腹腔注射20 mg/kg, 2次/周),实验持续4周。注射结束后测量人源化小鼠移植瘤的长、短径计算体积,测量肿瘤质量计算抑瘤率,同时采用免疫组化方法检测肿瘤组织中CD31(以阳性细胞数计算肿瘤微血管密度(MVD))及血管内皮生长因子(VEGF)的表达。结果 17-DMAG组和顺铂组的肿瘤体积和质量均较模型组显著减小(P<0.05),17-DMAG组的抑瘤率略高于顺铂组,但17-DMAG组和顺铂组肿瘤质量和体积以及抑瘤率均不存在显著性差异。17-DMAG组和顺铂组MVD标记微血管数量及VEGF表达均低于模型组(P<0.05),且17-DMAG组又低于顺铂组(P<0.05)。结论 17-DMAG可显著降低肝癌移植瘤中VEGF的表达,抑制新生血管在肿瘤中发生发展,从而对人源化小鼠肝癌移植瘤发挥抑制作用。

原发性肝癌MRI肿瘤影像学表现与血管新生的关联性及预后影响因素分析

目的探讨原发性肝癌MRI肿瘤影像学表现与血管新生、临床病理特征的关联性,分析对肝癌的诊断、治疗和预后影响的因素。方法选取2020年1月—2022年1月于本院经手术病理的原发性肝癌患者286例,所有患者均行术前MRI影像学检查,通过ELISA法定量检测患者血浆中的血管内皮生长因子(VEGF)和微血管密度(MVD),并比对临床病理资料进行统计、分析、构建模型及验证。结果所有患者均完成了MRI扫描,MRI评估结果显示,肝癌以T2信号高为主,T1加权成像中肝癌的信号强度不一,病变处有毛刺状和结节状的强化效应。原发性肝癌MRI肿瘤影像参数表现结果显示:286例原发性肝癌患者中有包膜所占比66.43%,肿瘤大小≥3 cm所占比70.98%,有肿瘤血管所占比63.29%,肿瘤坏死所占比78.32%,多发结节所占比81.47%,门静脉癌栓所占比23.08%,肝硬化所占比24.83%。原发性肝癌MRI纹理特征一致性检验结果显示:286例原发性肝癌患者的病灶勾画的一致性很好(ICC>0.80,P<0.01)。原发性肝癌MRI肿瘤影像学表现(包膜、肿瘤大小、肿瘤血管、肿瘤坏死、肿瘤数目、门静脉癌栓、肝硬化、纹理参数)与血管新生(VEGF、MVD)有关(P<0.05)。随访结果显示,肿瘤发生复发/转移114例(39.86%),无转移/复发172例(60.14%);随访18个月,死亡49例。包膜、肿瘤大小、门静脉癌栓、肝硬化、纹理参数等表现与肝细胞肝癌患者预后相关(P<0.05)。肿瘤越大、门静脉癌栓、肝硬化、有包膜及纹理参数越小是原发性肝癌患者复发/转移的影响因素(P<0.05)。Hosmer-Lemeshow检验得出χ^(2)=2.277,P=0.864,提示模型与观测值拟合度较好。ROC分析结果显示,Logistic回归模型预测术后早期HCC复发的AUC为0.847,95%CI为0.754~0.905,说明该模型预测效能较好(P<0.05)。结论MRI肿瘤影像学表现能够很好地反映原发性肝癌的病理变化,VEGF和MVD的变化与肝癌的诊断、治疗和预后密切相关,是一个有价值的生物标志物。

两种方法建立肝癌皮下瘤块模型的比较

目的:采用注射Walker-256肿瘤细胞的方法建立Wistar鼠和BALB/c裸鼠皮下瘤块模型。方法:抽取含Walker-256肿瘤细胞的BALB/c裸鼠腹水,进行离心洗涤,将洗涤液分别接种于Wistar鼠及BALB/c裸鼠腹股沟区皮下形成皮下瘤块。观察并比较两种不同实验鼠所建立的皮下瘤块模型成瘤率及瘤体生长速度。实验结束后,采用免疫组织化学法检测皮下瘤的微血管密度(MVD)及血管内皮生长因子(VEGF)的表达。结果:两种方法成瘤率均为100%,但是裸鼠皮下瘤块生长速度快于Wistar鼠皮下瘤;裸鼠组的MVD与VEGF表达均高于Wistar组,差异有统计学意义(t=8.52、5.13,P<0.05)。结论:用Wistar鼠或裸鼠作为肝癌皮下瘤块模型均可以满足临床试验研究的需要,但由于裸鼠为免疫缺陷动物,瘤块生长速度会明显快于Wistar鼠,且肿瘤血管生成指标更高,故选择肝癌瘤块生长模型时,裸鼠为最佳选择。

川芎嗪对小鼠肺癌血管生长和VEGF表达的抑制

目的 观察川芎嗪对实体肿瘤及其血管生长的抑制作用及作用环节。方法 用C57BL小鼠接种Lewis肺癌细胞造模 ,川芎嗪注射液 5 0、10 0、2 0 0mg·kg-1·d-1腹腔注射2 1d后 ,检测肿瘤体积、重量、肺转移灶数及微血管密度 ,并用WesternBlot法和免疫组化法分析肿瘤细胞VEGF的表达。结果 川芎嗪能减少小鼠Lewis肺癌肿瘤体积、重量和肺转移灶数 ,并能降低肿瘤微血管密度 ,抑制肿瘤细胞VEGF的表达。结论 川芎嗪能抑制小鼠Lewis肺癌的生长与转移 ,其机制可能与抑制VEGF表达 ,降低肿瘤微血管密度有关。

大肠腺瘤和腺癌组织中缺氧诱导因子-1α的表达及其与VEGF、微血管密度的关系

背景与目的:缺氧诱导因子-1α(hypoxia-inducible factor 1 alpha,HIF-1α)是肿瘤细胞适应缺氧而产生的一种核转录因子,在促进肿瘤新生血管生成中起重要作用。本研究旨在探讨大肠腺瘤和腺癌组织中HIF-1α的表达及其与血管内皮生长因子(vascular endothelial growth factor,VEGF)、微血管密度(microvessel density,MVD)的关系。方法:采用原位杂交技术检测HIF-1α mRNA,应用免疫组织化学方法检测VEGF蛋白的表达,用CD34单克隆抗体标记血管内皮细胞并计数MVD。结果:大肠腺癌组织HIF-1α mRNA阳性表达率为67.8％(42/62),腺瘤组织为44.4％(8/18)。腺癌组织从Dukes’A期到Dukes’C+D期HIF-lα mRNA表达阳性率不断增加(P<0.05)。HIF-1α mRNA表达平均阳性率为:腺瘤44.4％;腺癌Dukes’A期41.2％,Dukes’B期72.2％,Dukes’C+D期81.5％。腺癌组VEGF阳性表达率高于腺瘤组(59.7％ vs 33.3％,P<0.005).HIF-1α表达与VEGF呈正相关(r_s=0.768,P<0.01),与MVD呈正相关(r_s=0.683,P<0.05)。结论:HIF-1α及其靶基因 VEGF的过度表达与肿瘤新生血管形成呈正相关,这在大肠腺瘤癌变及大肠腺癌发展过程中可能起重要作用。

桂枝茯苓丸对子宫内膜异位症大鼠血管生成的影响

目的:探讨桂枝茯苓丸对子宫内膜异位症(EM)模型大鼠血管生成因子(VEGF)和异位内膜微血管密度(MVD)的影响。方法:SD大鼠建模,3周后将建模成功的大鼠随机分为不用药组(U)、桂枝茯苓丸组(GFW)、丹那唑组(D)和联合用药组(S),设假手术组(C)为对照,予相应处理4周后,观察各组异位子宫内膜体积和形态学的变化,计数腹腔液巨噬细胞,放射免疫法测定各组大鼠外周血、腹腔液及巨噬细胞培养液白细胞介素-8(IL-8)、肿瘤坏死因子(TNF-α),免疫组化法测定血管内皮生长因子(VEGF)在异位内膜中的表达,并通过CD34标记异位子宫内膜血管,测定其微血管密度(MVD)。结果:GFW组、D组和S组异位内膜呈现不同程度萎缩,腺体明显减少,腹腔液巨噬细胞计数减少,GFW组、D组及S组大鼠外周血、腹腔液及巨噬细胞培养液IL-8、TNF-α降低,异位内膜VEGF表达减弱,MVD也明显减少,其中以S组最为明显。结论:桂枝茯苓丸和丹那唑可以抑制EM模型大鼠异位内膜的血管生成,使异位内膜萎缩,当二者联合用药时,作用更强。

川芎嗪和丹参对小鼠Lewis肺癌生长的抑制作用与抑制血管生成的关系

目的 观察川芎嗪注射液 (TMP)、丹参注射液对小鼠 L ewis肺癌生长和转移及肿瘤血管生成的影响。方法 用 C57BL小鼠 L ewis肺癌模型 ,分别 ip TMP 5 0 ,10 0 ,2 0 0 mg/(kg· d) ,丹参注射液 5 ,10 ,2 0 g/(kg· d) ,共2 1d,检测小鼠 L ewis肺癌移植瘤体积、质量、肺转移灶数、肿瘤微血管密度 (MVD)和血管内皮生长因子 (VEGF)的表达。结果 与模型组相比 ,TMP组小鼠 L ewis肺癌移植瘤的体积、质量、肺转移灶数、肿瘤 MVD和 VEGF的表达均显著降低 ;丹参组与模型组比较差异无显著性。结论 TMP可抑制小鼠 L ewis肺癌移植瘤的生长和转移 ,其作用机制与抑制 VEGF的表达、抑制血管生成有关。丹参对小鼠 L ewis肺癌移植瘤的生长和转移无明显影响。

肝癌衍生生长因子和血管内皮生长因子在脑胶质瘤中的表达及其与肿瘤微血管密度的相关性研究

目的：探讨肝癌衍生生长因子（HDGF）和血管内皮生长因子（VEGF）在脑胶质瘤中的表达及其与肿瘤微血管密度（MVD）的相关性。方法选取2008年3月—2013年6月于右江民族医学院附属医院诊治的脑胶质瘤患者52例为脑胶质瘤组，另选取同期于本院行颅脑损伤内减压术患者52例为对照组。收集脑胶质瘤组肿瘤组织和对照组正常脑组织，冷冻保存。实时荧光定量反转录 PCR 法测定 HDGF、VEGF mRNA表达水平。将肿瘤组织和正常脑组织裂解后提取蛋白，分别采用酶联免疫吸附试验（ELISA）和 Western blotting 测定 HDGF、VEGF 表达水平。以 CD105作为血管内皮细胞的特异性标志物，显微镜下观察5个视野内微血管数计算 MVD。自病理检查确诊起，追踪随访观察脑胶质瘤患者至2015-07-30，随访终点为死亡。结果脑胶质瘤组 HDGF、VEGF mRNA表达水平高于对照组，经ELISA、Western blotting 测定的 HDGF、VEGF 表达水平均高于对照组，差异有统计学意义（ P ＜0.05）。脑胶质瘤组MVD 为（74.3±10.4）个/视野，高于对照组的（9.6±1.4）个/视野，差异有统计学意义（t ＝15.941，P ＜0.001）。脑胶质瘤组HDGF mRNA、蛋白（分别经 ELISA、Western blotting 测定）表达水平与 MVD 呈正相关（r ＝0.562、0.382、0.225，P ＜0.05），VEGF mRNA、蛋白（分别经 ELISA、Western blotting 测定）表达水平与 MVD 呈正相关（ r＝0.676、0.471、0.184，P ＜0.05）。HDGF 表达低水平、高水平的脑胶质瘤患者中位生存时间分别为13.6〔95％ CI （11.0，16.1）〕、8.4〔95％ CI（6.6，10.2）〕个月，其生存曲线比较，差异有统计学意义（χ2＝9.938，P ＝0.002）。VEGF 表达低水平、高水平的脑胶质瘤患者中位生存时间分别为14.3〔95％ CI（12.2，16.8）〕、12.6〔95％ CI（10.0，15.1）〕个月，其生存曲线比较，差异无统计学意义（χ2＝0.735，P ＝0.391）。MVD 低水平、高水平的脑胶质瘤患者中位生存时间分别为14.8〔95％ CI（12.3，17.3）〕、10.4〔95％ CI（8.1，12.6）〕个月，其生存曲线比较，差异有统计学意义（χ2＝4.307，P ＝0.038）。结论脑胶质瘤组织中 HDGF、VEGF 表达水平异常升高与肿瘤微血管形成紧密相关，可作为判断肿瘤血管生成和疾病预后的参考标志物。