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Aims: We aimed to determine whether lymphocyte activation gene 3 (LAG-3), also known as CD223, is associated with microvessel density (MVD) in primary hepatocellular carcinoma (HCC), as well as their clinical significance in predicting survival. Materials and methods: One hundred and twenty-seven patients were enrolled in the study. Samples were obtained on resection at the Department of Hepatobiliary Surgery of the Qingdao Municipal Hospital from June 2014 to June 2016. Immunohistochemistry was used to determine vessel density and LAG-3 abundance. Statistical analyses were performed to test for correlation of LAG-3 density and other clinicopathological variables with overall survival (OS). Results: High LAG-3 abundance was significantly correlated with increased MVD in primary HCC (P < 0.05). The ?2 test revealed a significant association of LAG-3 with preoperative AFP level, tumor diameter, N stage, and the presence of HBV infection (P < 0.05). Patients with high LAG-3 expression had shorter OS compared to those with low LAG-3 expression (P < 0.05). The Cox proportional hazards model showed that both higher LAG-3 and MVD density, age, the number of tumors, preoperative AFP level, tissue differentiation, Child–Pugh grade, and lymph node metastasis correlated with survival. Conclusions: High expression of LAG-3 is associated with angiogenesis and poor prognosis in HCC patients. With the deepening of research, LAG-3 is likely to become a novel biomarker for clinical diagnosis and prognosis and can even be a therapeutic target of HCC.
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@#AIM: To invesgate the expression of epidermal growth factor-like domain7(EGFL7)protein in several lacrimal gland tumor types and normal lacrimal gland tissues by immunohistochemical staining. And discuss the correlation of EGFL7 expression with tumor cell proliferation activity and the MVD in lacrimal gland epithelial tumors.<p>METHODS: A total of 46 paraffin-embedded specimens of common lacrimal gland epithelial tumors and other lacrimal gland tumor types, including 20 cases of lacrimal gland pleomorphic adenoma, 12 cases of pleomorphic adenocarcinoma, and 14 cases of adenoid cystic carcinoma, as well as ten normal lacrimal glands were analyzed for the expression of EGFL7 protein. For all specimens, the tumor microvascular networks were also labeled with anti-CD34 antibody and the tumor MVD was calculated. The proliferative activity of tumor cells containing Ki67.<p>RESULTS: EGFL7 protein was scored as positive with the presence of brown color in the cytoplasm, and was mainly observed in cells of lacrimal gland pleomorphic adenocarcinomas and adenoid cystic carcinomas. Immunohistochemical staining showed that EGFL7 was not expressed in normal lacrimal gland tissue. The rates of expression of EGFL7 in lacrimal gland pleomorphic adenomas, lacrimal gland pleomorphic adenocarcinomas, and lacrimal adenoid cystic carcinomas were 5%(1/20), 83%(10/12), and 86%(12/14), respectively. The EGFL7 expression in both malignant tumor types was significantly higher than that in pleomorphic adenomas and normal lacrimal gland tissues(<i>P</i><0.001). CD34 staining colored the tumor microvascular network brown-yellow in single cells or clustered cell populations. The expression of CD34 in lacrimal gland pleomorphic adenocarcinomas(32.58±14.46)and adenoid cystic carcinomas(43.43±4.60)was significantly higher than that in pleomorphic adenomas(4.20±1.19)(<i>P</i><0.001). Ki67 staining appeared as a brownish color in cell nuclei, indicating proliferative activity. The expression of Ki67 in lacrimal gland pleomorphic adenocarcinomas(44.83±13.68)and adenoid cystic carcinomas(26.29±8.44)was significantly higher than that in pleomorphic adenomas(2.80±3.14)and normal tissues(0.40±0.70)(<i>P</i><0.001). Furthermore, the expression of EGFL7 protein was positively correlated with high MVD and Ki67 expression in lacrimal epithelial tumors(<i>r</i>s=0.897,<i> P</i><0.001; <i>r</i>s=0.837, <i>P</i><0.001). <p>CONCLUSION: The correlation of EGFL7 expression with high MVD and Ki67 expression suggests that high EGFL7 expression plays an important role in promoting tumor angiogenesis and tumor proliferation.
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@# Objective: To investigate the expressions of programmed death ligand 1（PD-L1）in triple-negative breast cancer (TNBC) and its correlation with angiogenesis. Methods: 120 cases of TNBC patients who underwent surgery in the Fourth Hospital of Hebei Medical University from March 1, 2011 to June 1, 2012 were collected. The tumor tissues of patients were surgically resected and confirmed by pathology. PD-L1 protein expression in TNBC tissues of 120 patients was detected by tissue microarray combined with immunohistochemistry, and its relationship with various clinical indicators was analyzed. Blood vessels and lymphatic vessels were labeled withCD34andD2-40todetectmicrovesseldensity(MVD)andlymphaticvesseldensity(LVD)inTNBC.Results:Thepositiveexpression rate of PD-L1 in the tumor cells and interstitial infiltrating lymphocytes fromTNBC was 56.7% (68/120); No correlation was found between PD-L1 protein expression and the gender, age, histological grade, clinical stage, or tumor size of patients with TNBC (P>0.05), but related to the lymph node metastasis (P<0.05) and vascular thrombus (P<0.05). TNBC with high PD-L1 expression exhibited high incidence of lymph node metastasis and formation of vascular thrombus, and the expression of PD-L1 was positively correlated with MVD (r=0.500, P=0.02) as well as LVD (r=0.662, P=0.01). Log-Rank test showed that the survival time of TNBC patients with positive PD-L1 protein expression was significantly shorter than that of patients with negative expression (P<0.05). Cox multivariate analysis suggested that PD-L1 protein expression could be an independent prognostic factor for TNBC overall survival. Conclusion: PD-L1 plays an important role in TNBC angiogenesis and lymphangiogenesis, and is closely related to TNBC invasion and metastasis; blocking PD1/PD-L1 signal pathway is expected to be an effective new strategy for TNBC treatment.
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OBJECTIVE: To study the inhibitory effect of Dendrobium nobile Lindl wall-broken powder on tumor growth and angiogenesis of transplanted human liver cancer cell line HepG2 in nude mice. METHODS: The transplant tumor model in nude mice for HepG2 was established. All tumor-bearing nude mice were randomly divided into control group (normal saline), positive group (bevacizumab,5 mg•kg-1, intraperitioneally), and low-,medium-, high-dose Dendrobium nobile Lindl wall-broken powder-treated groups(50,100 and 200 mg•kg-1,intragastrically).The tumor xenografts were harvested and measured for their weights. Immunohistochemistry was used to detected microvessel density (microvessel density, MVD) and vascular endothelial growth factor (vascular endothelial growth factor,VEGF) expression. RESULTS: After the administration, TV (tumor volume), RTV (relative tumor volume), and T/C(%) in Dendrobium nobile Lindl wall-broken powder treatment group decreased significantly, T/C(%) was 60.56%, 48.59%, and 47.15%, respectively. SABC assay showed that MVD in Dendrobium nobile Lindl wall-broken powder treatment group was sparse, MVD value decreased from (65.67±12.05) to (51.53±10.75),(45.89±9.24)and(40.76±8.93), Dendrobium nobile Lindl wall-broken powder can significantly reduce the positive expression of VEGF. The positive expression rate reduced from (82.25±15.59)% to(65.27±13.88)%,(48.02±12.14)% and (44.07±10.34)%. CONCLUSION: Dendrobium nobile Lindl wall-broken powder can inhibit tumor growth of transplanted liver cancer cell line HepG2 in nude mice in varying degrees, which may be related to reducing MVD value and the expression of VEGF in tumor tissue.
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Objective: To investigate the possible role of astrocytes after brain infarction in stroke-prone, spontaneously hypertensive (SHR-SP) rats and the association with angiogenesis and the architecture. Methods: We maintained SHR-SP rats on high sodium water starting to accelerate the stroke onset. The 3D quantification of microvasculatures (diameter, branch number) by cofocal microscope after FITC-dextran was injected into the rats via the left femoral vein. Glial fibrillary acidic protein (GFAP) expression and microvessel density (MVD) using counting the number of factor -positive endothelial cells were evaluated by immunofluorescence and immunohistochemistry, respectively. Results: Cerebral infarction occurred at week 7 after high sodium water intake (13 g/L NaCl) in SHR-SP group. When compared with the non-infarcted contralateral hemisphere and SHR-SP on normal sodium intake and WKY rats, GFAP expression and MVD were significantly increased, respectively, and the diameter and the branch number of vessels were decreased, respectively, in cerebral infarcts with boundary zones of SHR-SP rats (P<0.01). Linear correlation analysis showed that GFAP expression was positively correlated with MVD and the diameter and the branch number of vessels in cerebral infarcts in SHR-SP (P<0.01). Conclusion: Astrocytes hyperplasia may be associated with increased regional angiogenesis and the changes of architecture in SHR-SP rats with high sodium water (13 g/L NaCl) that induces focal cerebral infarcts.
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Objective To investigate the expression of LRG1 (Leucine－rich alpha－2－glycoprotein 1) and CD105 (Endoglin) in normal cervical tissues , cervical intraepithelial neoplasia (CIN)Ⅱ－ Ⅲ and cervical carcinoma. Furthermore, to explore the function of LRG1 in cervical carcinoma pathogenesis and the relationship between LRG1 and microvessel density.Methods The expression levels of LRG1 and CD105 were detected by immunohistochemistry in 40 cervical carcinoma tissues, 20 CINⅡ－ Ⅲ tissues and 20 normal cervical tissues. Results Compared to the normal cervix, the expression of LRG1 in CINⅡ－ Ⅲ and cervical squamous cell carcinoma was significantly increased (P＜0.05).LRG1expression was correlated to clinical stage and lymph node metastasis (P＜0.05) . But there was no correlation between LRG1 expression and age, the size of tumor, pathologic grades and depth of invasion (P＞0.05).With the deepening of cervical lesions, CD105－MVD (X± s) increasedsignificantly (P＜0.05).The expression of CD105－MVD in cervical carcinomawas related to clinical stage, lymph node metastasis and the size of tumor. The difference was statistically significant (P＜0.05) . There was no correlation between CD105－MVD and age, pathologic grades and depth of invasion (P＞0.05).Positive correlation was found between the expression of LRG1 and CD105－MVD (r=0.944,P＜0.05).Conclusions The expression of LRG1 and CD105－MVD is up－regulated and shows a positive correlation, which suggests that the abnormal expression of LRG1 and CD105－MVD may involve in the occurrence and development of cervical squamous carcinoma.
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Objective To investigate the effects of survivin shRNA-APC double gene co-expression stably transfected cell lines on the VEGF、COX-2 expressions and angiogenesis of subcutaneous exnotransplanted tumor tissues cell of HT-29 colon cancer in nude mice.Methods Forty nude mice were randomly divided into five groups,the negative control group,empty vector group,Survivin shRNA group,APC group,double-gene group.The stably transfected cell lines and HT-29 colon cancer cells were cultured,PBS suspension resulted in cell density of 2× 107/ml,injected with respective stably transfected cell lines to establish an SXT model.All the mice were sacrificed after six weeks in order to separate the subcutaneous tumor,the expressions of the VEGF,COX-2mRNA and protein were detected by Real time PCR and immunohistochemistry,CD34 antibody was used to mark the vascular endothelial cells,and the MVD values were detected by immunohistochemistry.Results Tumors were formed in the nude mice of each group.The expressions of VEGF,COX-2 mRNA in Survivin shRNA group ((50.84±3.64)％,(50.11±3.91)％),APC group((74.28±6.87)％,(72.39±6.55)％) and Survivin shRNA-APC double-gene group ((21.78±4.00) ％,(20.74±5.12) ％) were significantly lower than those in the empty vector groups((100.00±0.00) ％,(100.00±0.00) ％) or negative control group ((98.22±0.38) ％,(97.61 + 0.77)),the differences were statistically significant (P ＜ 0.05);the expressions of VEGF,COX-2 mRNA in Survivin shRNA-APC double-gene group were significantly lower than those in APC groups,Survivin shRNA group,the differences were statistically significant (P＜0.05).The expressions of VEGF,COX-2 protein in Survivin shRNA group (5.15 ± 1.02,5.26 ± 0.91),APC group (4.96 ± 1.12,4.93 ± 1.18),and Survivin shRNA-APC double-gene groups (1.81 ± 0.84,1.80± 0.81)were significantli lower than those in the negative control group (8.95± 0.55,8.77± 0.60) and empty vector group (9.17± 0.49,9.01 ± 0.80),the differences were statistically significant(P＜0.05),the expressions of VEGF,COX-2 protein in the Survivin shRNA-APC double-gene group were significantly lower than those than in APC group,Survivin shRNA group(P＜0.05);the expressions of MVD in APC group (12.14± 3.45),Survivin shRNA group (11.39 ± 2.94) and Survivin shRNA-APC double-gene group (3.96 ± 2.20) were lower than those in the negative control group (25.09 ± 5.59) and empty vector group (27.87 ± 7.36),the differences were statistically significant (P ＜ 0.05),the MVD in the Survivin shRNA-APC double-gene group was even lower than that in APC group,Survivin shRNA group,the differences were statistically significant (P ＜ 0.05).Conclusion Survivin shRNA-APC double gene coexpression stably transfected cell lines can significantly reduce the expression of the VEGF,COX-2 mRNA and protein and then inhibit the angiogenesis of transplanted tumor tissue,and its inhibitory effect is more effective than that og Survivin shRNA and APC single gene stable strain.
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Objective To investigate the prognostic impact of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and CD34 on invasion and metastasis of gastric cancer.Methods CEACAM1 and CD34 expressions were detected by immunhistochemistry in 90 cases of gastric cancer and 30 cases of normal gastric mucosa.Then the relationship among CEACAM1, MVD marked by CD34 antibody and gastric cancer patients` clinical pathological features and prognosis were analyzed.Results The positive rates of CEACAM1 and CD34 protein in gastric cancer were significantly higher than those in normal gastric mucosa (P<0.05).The positive rate of CEACAM1 was closely related to histological differentiation, tumor invasion, nodal metastasis and TNM stage.MVD marked by CD34 was related with tumor size, histological differentiation, tumor invasion, nodal metastasis and TNM stage(P<0.05).Conclusions In gastric cancer, CEACAM1 and CD34 promote its invasion and metastasis, and they are potential indicators of predicting development and prognosis.
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OBJECTIVE: To study the inhibitory effect of Ke-ai-xin pill on tumor growth and angiogenesis of transplanted colon cancer cell line HCT116 in nude mice. METHODS: To establish the transplant tumor model in nude mice for HCT116. All tumor-bearing nude mice were randomly divided into control group (normal saline), positive group (bevacizumab, 5 mg·kg-1, intraperitioneally), and low-, medium-, high-dose Ke-ai-xin pill-treated groups(200, 400 and 800 mg·kg-1, intragastrically). The tumor xenografts were harvested and measured for their weights. Immunohistochemistry was used to detecte microvessel density (MVD)and vascular endothelial growth factor(VEGF)expression. RESULTS: Ke-ai-xin pill inhibited tumor growth in nude mice in varying degrees. After the administration of each treatment group, TV, RTV, and T/C decreased significantly(P<0.05). SABC assay showed that MVD of Ke-ai-xin pill treatment group was sparse, MVD value decreased from (59.62±18.83) to (55.56±12.63), (46.72±11.57) and (41.35±10.27), Ke-ai-xin pill treatment group can significantly reduce the positive expression of VEGF. the positive expression rate reduced from(78.46±16.53)% to (58.64±14.19)%, (49.27±13.29)% and (43.68±11.71)%. CONCLUSION: Ke-ai-xin pill can inhibit tumor growth of transplanted colon cancer cell line HCT116 in nude mice in varying degrees, reduce MVD value and the expression of VEGF in tumor tissue, so its antitumor activity may be related to inhibiting angiogenesis.
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Objective To evaluate the feasibility of contrast enhanced ultrasound (CEUS) in gallbladder carcinoma anti-angiogenesis treatment.Methods Subcutaneous gallbladder carcinoma model was consturcted.The mice were divided into intervention-drug group and control group randomly.The mice of intervention-drug group were treated with Endostar (10 mg · kg-1 · d-1) by intraperitoneal injection for two weeks.Two groups of mice were detected by CEUS,then the time of arrival (AT),peak time (TTP),peak intensity (PI),area under the curve (AUC) were measured via time-intensity curve.Expression of MVD and VEGF both in the intervention and control groups were studied through immunohistochemistry.and the correlations between MVD,VEGF and CEUS parameteres were further analyzed.Results The mean values of PI in drug intervention group and control group were 10.8 ± 5.5 and 16.8 ± 5.8,respectively.The values of PI in intervention-drug group were lower than that in control group significantly (P ＜ 0.05).There was no significant difference in AT,TTP,AUC between the two groups.The mean values of MVD on drug intervention group and control group were 8.5 ± 3.8 and 13.1 ± 3.5,respectively.The mean values of VEGF on drug intervention group and control group were 4.3 ± 0.5 and 4.7 ± 0.4,respectively.The values of MVD and VEGF in intervention-drug group were significant lower than that control group (P ＜ 0.05).MVD and VEGF values of intervention-drug group were correlated with PI (r =0.712,P ＜ 0.05;r =0.739,P ＜ 0.05).Conclusion Endostar can inhibit the growth of gallbladder carcinoma and PI can be used as an effective marker to evaluatethe effect of anti-angiogenic therapy in gallbladder carcinoma.
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Aim To observe the effects of thin recipe of Buyang Huanwu Decoction on angiogenesis and the signal pathway of Nrf2 / HO-1 after cerebral ischemic injury in rats. Methods Totally 120 SD rats were randomly divided into four groups: sham operation group,model group,Buyang Huanwu Decoction group and thin recipe of Buyang Huanwu Decoction group. The focal cerebral ischemia rat model was established by middle cerebral arterial occlusion. Each group was treated with corresponding treatment. Each group was detected after cerebral ischemia for day 1,day 3 and day 7, respectively. Immunohistochemical method was used to detect the plasma levels of factor VIII related antigen( vWF), determination of microvessel density (MVD). The expression of Nrf2,HO-1 gene and pro-tein in brain tissues was detected by Real-Time PCR (RT-PCR) and Western blot. Results ① Compared with sham-operation group, the expression of vWF in the model group was significantly increased on day 3(P< 0. 05). Compared with model group, the expression levels increased differently in each drug group on day 7 (P < 0. 05). ② The expression of Nrf2, HO-1 gene and protein in sham operation group showed a small a-mount of gamma expression. Compared with sham op-eration group at the same time point, the expression of Nrf2 protein was significantly increased on day 3(P <0. 01). Compared with model group at the same time point, the Nrf2mRNA and protein expression was up-regulated in each drug group. The Nrf2mRNA on day 1,the Nrf2 protein on day 1 and day 7 were significant-ly increased( P < 0. 01). Compared with sham opera-tion group at the same time point, the expression of HO-1mRNA and protein in the model group was signif-icantly increased on day 7(P < 0. 05). Compared with model group at the same time point, the HO-1mRNA on day 3, the HO-1 protein on day 3 and day 7 in each drug group were significantly increased (P < 0. 05,P <0. 01). Conclusions The thin recipe of Buyang Hua-nwu Decoction promotes brain angiogenesis after ische-mia. The effect may be related wih the expression of Nrf2 / HO-1 signal pathway.
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Andrographolide is a main bioactive substance in Andrographis paniculata, and extensively used in anti-inflammatory drugs. In order to increase andrographolide production in plant, three 1260 bp ORFs encoding mevalonate disphosphate decarboxylases with 419 amino acids were cloned from A. paniculata by RACE method and analyzed by bioinformatic software. Their tissue expression patterns were predicted by real time PCR. Eleven conserved amino acid residues determining specificity and activity of these MVDs were predicted in these amino acid sequences, but no plastid targeted signal peptides were detected. These MVDs have high similarities with the MVD protein (GenBank number: AEZ55675.1) from Salvia miltiorrhiza. In stems and leaves, expression levels of these MVD genes were constant, and reached the highest level at bud stage and the beginning of flowering. The MVD genes we have cloned from A. paniculata could be used in genetic engineering of andrographolide biosynthsis pathway in future.
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Objective:To investigate the correlations of Lauren classification and world health organization (WHO) classification of gastric cancer (GC) with microvascular density (MVD), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 1 (VEGFR1), vascular endothelial growth factor receptor 2 (VEGFR2), and p53. Methods:The clinical data of 89 patients with GC were collected. The collected specimens were categorized on the basis of Lauren classification and WHO classification. CD34/periodic acid-Schiff (PAS) double staining was performed to validate MVD. Immunohistochemistry was conducted to investigate the expression levels of MMP-2, MMP-9, VEGF, VEGFR1, VEGFR2, and p53. Results:MVD was not correlated with Lauren classification or WHO classification (P>0.05). Lauren typing was associated with the expression levels of MMP-9, VEGFR1, and p53 (P0.05). Cox proportional hazards model revealed that Lauren classification and WHO classification were the prognostic factors of overall survival (P<0.05). Conclusion:This research on tumor related factors, angiogenesis, and different classifications of GC may provide new methods to treat this disease.
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Objective To investigate the expressions of cycloxygenase-2 (COX-2 ),vascular endothelial growth factor (VEGF),matrix metalloproteinase (MMP2 )and micro-vessel density (MVD)in papillary thyroid carcinoma (PTC)and the relationship between their expressions and clinicopathological features,so as to evaluate the malignancy and prognosis of PTC.Methods The expressions of COX-2,MMP2 and VEGF and MVD count in 32 cases of PTC and 18 cases of normal thyroid tissues were detected by immunohistochemical staining.Their relationship with clinicopathological characteristics was analyzed.Results ① The expression of COX-2,MMP2, VEGF and MVD in PTC was as follows:M(Q 3 -Q 1 )=5(1),M(Q 3 -Q 1 )=5.5(2),M(Q 3 -Q 1 )=5.5(1)and M (Q 3 -Q 1 )= 28 (5.75 ),respectively.It differed significantly from that in control group (P 0.5).Conclusion The high expressions of COX-2, VEGF and MMP2 in thyroid tissues may result in the occurrence of PTC and lymph node metastasis,which is related to the regulation of tumor new vessels.Detecting these expressions are of value in evaluating the malignancy and prognosis of PTC.
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Objective: To study the effects of PDGF-Rb antagonists imatinib on endometrial injury repairing in the mouse model. Methods: The cultured MSCs cells from male mice were marked with BrdU in vitro, and then transplanted to the female mice which suffered from radiation injury through tail vein, PDGF-Rb antagonists imatinib was injected through abdominal cavity. Four groups were arranged, which were radiation transplantation group, normal control group, imatinib intervention group and radiation control group. BrdU incorporation, SRY expression and MVD status were detected in uterus of mice. Results: SRY gene was negative expressed in normal control group and radiation control group. SRY gene presented positive in radiation transplantation group and imatinib intervention group; BrdU incorporation showed negative in radiation control group and normal control group which died in the early stage in mice; the incorporation of BrdU was higher in radiation transplantation group compared with imatinib intervention group; CD34 was positive on the uterus of all the four groups, which showed highest in radiation control group and lowest in radiation control group; The MVD in imatinib intervention group was lower than radiation control group; the difference of MVD was significantly compared with normal control group (P < 0.05). Conclusions: PDGF-Rb antagonists imatinib could inhibit the repairing function of MSCs in the endometrial lesions in mice.
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OBJECTIVE@#To study the effects of PDGF-Rb antagonists imatinib on endometrial injury repairing in the mouse model.@*METHODS@#The cultured MSCs cells from male mice were marked with BrdU in vitro, and then transplanted to the female mice which suffered from radiation injury through tail vein, PDGF-Rb antagonists imatinib was injected through abdominal cavity. Four groups were arranged, which were radiation transplantation group, normal control group, imatinib intervention group and radiation control group. BrdU incorporation, SRY expression and MVD status were detected in uterus of mice.@*RESULTS@#SRY gene was negative expressed in normal control group and radiation control group. SRY gene presented positive in radiation transplantation group and imatinib intervention group; BrdU incorporation showed negative in radiation control group and normal control group which died in the early stage in mice; the incorporation of BrdU was higher in radiation transplantation group compared with imatinib intervention group; CD34 was positive on the uterus of all the four groups, which showed highest in radiation control group and lowest in radiation control group; The MVD in imatinib intervention group was lower than radiation control group; the difference of MVD was significantly compared with normal control group (P < 0.05).@*CONCLUSIONS@#PDGF-Rb antagonists imatinib could inhibit the repairing function of MSCs in the endometrial lesions in mice.
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Objective:To explore the reversal effect of Docetaxel and Capecitabine on rat breast precancerous from angiogenesis and expression of related regulatory factors VEGF mRNA in rats.Methods: 350 SD rats were divided into 7 groups.Model of rats mammary was induced by DMBA and was treated by Docetaxel and Capecitabine for 4 weeks.All of them were killed from 8th week.The microvascular were detected in the specimens, examination of histopathology was performed and the expression of VEGF mRNA was measured by in situ hybridization.Results:The rat mortality and the incidence of precancerous lesions increased obviously, and the incidence of precancerous lesion of the high-dose group and the middle dose reduced.The positive rate of the expression of MVD,TGF-αand VEGF mRNA tend to increase in all the groups.The positive-cell rate of VEGF mRNA of Docetaxel,Capecitabine, Docetaxel and Capecitabine in ADH was lower than in the model group,and the positive-cell rate of VEGF mRNA of Docetaxel and Capecitabine was lower than Capecitabine and Docetaxel separately.Conclusion: Combination of Docetaxel and Capecitabinecan decrease the expression of VEGF mRNA in precancerouslesion of rats mammary.
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Objective To determine the expression of macrophage migration inhibitory factor (MIF)in different molecular subtypes of breast cancer and its clinical significance so as to detect the biological markers of different molecular subtypes of breast cancer.Methods We divided 100 breast cancer patients into four molecular subtypes by immunostaining:luminal subtype,HER-2(+)subtype,basal-like (BLs)subtype and normal breast-like (NBLs)subtype,and then compared the expression of MIF in the groups.We analyzed the associations of MIF-positive expression rate with age,menstruation,tumor size,auxiliary lymph node metastasis,histological type and grade,and clinical stage of the breast cancer patients.We also compared MVD level and 5-year overall survival rate between MIF-positive patients and MIF-negative ones.Results The positive expression of MIF was correlated with HER2(+)subtype breast cancer and auxiliary lymph node metastasis (P < 0.05 ).The patients with MIF-positive expression had a significantly higher level of MVD than those with MIF-negative expression (P < 0.05 ). Kaplan-Meier method showed that MIF-positive patients had a poor prognosis than MIF-negative ones (Log-rank=1 9.5 1 6,P = 0.000).Conclusion Breast cancer patients with MIF-positive expression may be mostly of HER2 (+)subtype,and tend to develop auxiliary lymph node metastasis.These patients have a significantly higher level of MVD and poor prognosis than those with MIF-negative expression.
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Objective To detect the expressions of chemokine CXCL5 and its receptor CXCR2 in hepatocellular carcinoma (HCC), investigate their relationships between CXCL5, CXCR2 and clinicopathologic features and probe into the significance in the evaluation of prognosis. Methods Immunohistochemical Envision method was utilized to detect the expressions of CXCL5 and CXCR2 in HCC , to explore their relationship between CXCL5, CXCR2 and clinicopathologic features and MVD in HCC. Results (1) The high expression rates of CXCL5 and CXCR2 protein was 64.7% and 68.6%, respectively, significantly higher than those in adjacent tissues of HCC(17.6%, 15.7%, P < 0.05). The overexpression of CXCL5 protein had correlation with tumor size, differentiation, TNM stage and vascular invasion (P < 0.05) and the overexpression of CXCR2 protein did with tumor grade and vascular invasion (P < 0.05). (2) The value of MVD was higher in HCC than that in the adjacent tissues of HCC (P < 0.05), and had positive correlation with the expressions of CXCL5, and CXCR2 proteins. (3) The higher rates of recurrence and metastasis were in the groups of higher expression of CXCL5 and CXCR2 proteins (P < 0.05). Conclusions The overexpressions of CXCL5 and CXCR2 may promote the occurrence and development of HCC as well as the neovasculation in HCC. Therefore, they can be used as markers to evaluate the prognosis of HCC.
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Background and purpose:Thalidomide can enhance the radiation sensitivity on tumor effectively, but the mechanism of radiosensitization is still unclear. The present study aimed to investigate whether thalidomide could enhance the radiation sensitivity on colon cancer transplanted tumor of mouse, and to investigate the underlying mechanism. Methods: We established the model of colon26 colonic carcinoma, and the mice were divided into 4 groups:Control group, the thalidomide group, the radiotherapy group and thalidomide+radiotherapy group. From the day of treatment, tumors were measured every other day. Then, the xenograft tumor growth curve was depicted. Tumor volumes were measured in different treatment groups, then, the inhibitory rates of tumor growth were calcutated. Using immunohistochemical method in to detect the expression of microvessel density (MVD) in tumor tissue. Results:The mean tumor volumes at day 22 were (4.97±1.20)cm3 (control group), (2.90±0.92)cm3 (T group), (2.66±0.88)cm3 (R group), and (1.89±0.76)cm3 (T+R group). The tumor inhibition rate in the combination group (61.9%) was signiifcantly higher than the other groups (41.7%, 46.5%, P<0.05). The radiotherapy sensitization enhancement ratio of the combined treatment group was 2.27 times than in the radiotherapy group. Thalidomide combined with radiation therapy can significantly inhibit microvessel density of tumor:The decreasing MVD of T+R group, T group and R group were respectively 46.8%, 40.7%and 37.7%, and there was statistical significance between T+R group and T group (P<0.05 ), so as between T+R group and R group. It could be found more necrotic cells in tumor of group, and there was statistical signiifcance between T+R group and control group (P<0.05). Conclusion:Thalidomide can enhance the radiosensitivity mice of colonic carcinoma, and its mechanism may be related to the inhibition of tumor angiogenesis related.