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Objective:To investigate the protective effect of cerebrospinal fluid containing Tongqiao Huoxuetang (TQHXT) on oxygen-glucose deprivation/reoxygenation (OGD/R)-induced brain microvascular endothelial cells (BMECs), in order to explore the underlying mechanisms. Method:Primary BMECs were extracted by enzymatic digestion, and the cells were randomly divided into six groups: the normal control group, the OGD/R group, the TQHXT group（20%）, the nimodipine（NMDP） group (10 μmol·L-1), the cabozanix group (1 μmol·L-1) and the combination group. Except for the normal control group, the cells in the other groups were rapidly reoxygenated for 24 h after 2 h of oxygen-glucose deprivation, the OGD/R modeling was performed, and the rats were administered with drugs by groups. BMECs were identified by cell immunofluorescence staining, morphological and ultrastructural changes of OGD/R-induced BMECs were observed, and changes in cell transmembrane resistance (TEER) were detected. The levels of nitric oxide (NO), the activity of lactate dehydrogenase (LDH), the fluorescence intensity of reactive oxygen species (ROS) and the content of tissue-type plasminogen activator (tPA) were measured with kits. Intracellular Ca2+ concentration and cell apoptosis were detected by flow cytometry, and the expression of CD34 was observed. The protein expressions of zonula occluden-1 (ZO-1), vascular endothelial growth factor (VEGF), adhesion kinase (FAK), and Paxillin were detected by Western blot. Result:Compared with the normal control group, the cells in the OGD/R group were shrinking and rounded, TEER value and ZO-1 protein expression in cells were significantly decreased, the contents of NO, LDH and ROS in cells were significantly increased, the content of tPA was significantly decreased, the concentration of Ca2+ and the apoptosis in the cells were significantly increased, CD34 was expressed in cells, and the protein expressions of VEGF, FAK and Paxillin were significantly increased (P<0.01). Compared with the OGD/R group, cell damage in the TQHXT group was significantly improved, the TEER value and ZO-1 protein expression in cells were significantly increased, the contents of NO, LDH and ROS in cells were significantly reduced, the content of tPA was significantly increased, the concentration of Ca2+ and the apoptosis in the cells were significantly reduced, CD34 expression increased in cells, and the protein expressions of VEGF, FAK and Paxillin were significantly increased (P<0.05，P<0.01). Conclusion:CSF containing TQHXT protects BMECs from OGD/R injury possibly by promoting angiogenesis through the VEGF-VEGFR2/FAK/Paxillin signaling pathway.
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OBJECTIVE@#To investigate the effects of traditional Chinese medicine, Danzhi decoction, on the expression angiogenesis factors in human endometrial cells during the sequelae of pelvic inflammatory disease (SPID) and explore the role of Danzhi decction in improving the blood stasis microenvironment of SPID.@*METHODS@#A three-dimensional (3D) co-culture system including human vascular endothelial cells (VECs), endometrial stromal cells and glandular epithelial cells was established in vitro and treated with Danzhi decoction, sterilized water and aspirin respectively. A Milliplex multifunctional liquid chip technique was used to measure the expression levels of vascular endothelial growth factor (VEGF)-A/C/D, fibroblast growth factor -1/2, angiopoietin-2, epidermal growth factor (EGF), HB-EGF, bone morphogenetic protein-9, endoglin, endothelin-1, granulocyte colony stimulating factor, hepatocyte growth factor, interleukin-8, follistatin, placenta growth factor and leptin. The location of angiogenesis factors was monitored by immunofluorescence labeling and confocal laser scanning microscope 3D reconstruction.@*RESULTS@#Endometrial stromal cells and glandular epithelial cells were isolated and primary cultured for establishing a 3D co-culture system. The levels of VEGF-A/C/D in Danzhi decoction group and aspirin group were significantly lower than those in mock group (P0.05). Furthermore, the alterative location of VEGF-A/C/D was observed in the cytoplasm of endometrial glandular epithelial cells.@*CONCLUSIONS@#Danzhi decoction may inhibit the expression of VEGF in the blood stasis microenvironment of SPID by targeting the cytoplasm of endometrial glandular epithelial cell.
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Objective: To investigate the effects of traditional Chinese medicine, Danzhi decoction, on the expression angiogenesis factors in human endometrial cells during the sequelae of pelvic inflammatory disease (SPID) and explore the role of Danzhi decction in improving the blood stasis microenvironment of SPID. Methods: A three-dimensional (3D) co-culture system including human vascular endothelial cells (VECs), endometrial stromal cells and glandular epithelial cells was established in vitro and treated with Danzhi decoction, sterilized water and aspirin respectively. A Milliplex multifunctional liquid chip technique was used to measure the expression levels of vascular endothelial growth factor (VEGF)-A/C/D, fibroblast growth factor -1/2, angiopoietin-2, epidermal growth factor (EGF), HB-EGF, bone morphogenetic protein-9, endoglin, endothelin-1, granulocyte colony stimulating factor, hepatocyte growth factor, interleukin-8, follistatin, placenta growth factor and leptin. The location of angiogenesis factors was monitored by immunofluorescence labeling and confocal laser scanning microscope 3D reconstruction. Results: Endometrial stromal cells and glandular epithelial cells were isolated and primary cultured for establishing a 3D co-culture system. The levels of VEGF-A/C/D in Danzhi decoction group and aspirin group were significantly lower than those in mock group (. P0.05). Furthermore, the alterative location of VEGF-A/C/D was observed in the cytoplasm of endometrial glandular epithelial cells. Conclusions: Danzhi decoction may inhibit the expression of VEGF in the blood stasis microenvironment of SPID by targeting the cytoplasm of endometrial glandular epithelial cell.
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This study was aimed to discuss the influence of specific acupoint acupuncture therapy to the serum angiogenesis factor of high fat diet obese mouse models. Mice were randomly divided into the blank control group , acupuncture control group , model control group , and acupuncture treatment group . There were 6 mice in each group . Obese mouse models were induced after 15-week high fat diet . The specific acupoint acupunc-ture therapy was used as an intervention treatment method for 10 days . The enzyme-linked immunosorbent as-say (ELISA) was used in the detection of serum insulin, vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor , leptin and the level of nitric oxide in mice . The results showed that the serum insulin , nitric oxide and leptin level in the obese mouse models were increased . However , there were no obvious changes on the vascular endothelial growth factor and soluble vascular endothelial growth fac-tor receptor level . The specific acupoint acupuncture therapy can obviously reduce the level of serum nitric ox-ide and leptin, and improve the content of vascular endothelial growth factor in obese mouse models. However, there were no influence on the level of blood glucose and soluble vascular endothelial growth factor receptor . It was concluded that the specific acupoint acupuncture therapy method had preferable antiobesity action . Its mechanism of action may be related to the regulation of angiogenesis .
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Objective To investigate the effects of recombinant human growth hormone (rhGH) on tumor growth and tumor angiogenesis factor relevant to Janus kinase 2-signal transducer and activator of transcription 3 of human gastric carcinoma xenografts in nude mice with different expressions of growth hormone receptor (GHR).Methods Immunocytochemical method was used to pick out one GHR-positive and one GHR-negative cell line. The cells were subcutaneously injected into 26 nude mice separately, then the patterns of xenografts in nude mice with different expressions of GHR were established. The nude mice bearing two different kinds of human gastric caicinoma were equally randomized into control group, low-dose rhGH group, and high-dose rhGH group,and were treated with drugs for 14 days. Changes of tumor volumes and body weight of nude mice were record. The protein and mRN A expressions of tumor angiogenesis factor in tumor tissue were detected by RT-PCR and Western blot, respectively. Results GHR was highly expressed in SGC-7901 celk but negative in MKN-45 cells. For nude mice bearing GHR+ SGC-7901 xenografts, the tumor volumes were significantly larger in low-dose rhGH group [(1. 141 ±0. 234) cm3] and high-dose rhGH group [(2. 106 ±0. 260) cm3] than in control group [(0.612±0. 156) cm3] (P = 0. 034, P = 0. 001), and the high-dose rhGH group revealed greater effect (P =0. 043 ). Body weight was not significantly different among three groups. Compared with the control group, the mRNA expressions of tumor angiogenesis factor were significantly increased in low-does rhGH group, and the P values of GHR, Janus kinase 2, signal transducer and activator of transcription 3, vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1α (HIF-1α), fibroblast growth factor, and matrix metalloproteinases-2 (MMP-2) was 0.001, 0.011, 0.042, 0.045, 0.040, 0.002, and 0.003, respectively; however, the high-does rhGH group did not show the greater effects. The protein expressions were significantly increased in low-does rhGH group, and the P value of phosphorylation-signal transducer and activator of transcription 3, signal transducer and activator of transcription 3, VEGF, HIF-1α, and MMP-2 was 0. 015, 0.003, 0.010, 0.008,and 0. 005, respectively; furthermore, the high-does group revealed the further greater effects, and the P value of VEGF, HIF-1α, and MMP-2 was 0.012, 0.025, and 0.046, respectively. On the contrary, for nude mice bearing GHR- MKN-45 xenografts, the body weights of low-dose rhGH group [(24.94 ±0. 517) g] and high-dose rhGH group [(26.97 ±0.686) g] were significantly higher than that of control group [(22.78 ±0.418) g] (P =0. 040, P = 0.012 ) , while tumor growth as well as the expressions of mRNA and protein of tumor angiogenesis factor in tumor tissue were not significantly different Conclusions rhGH can promote tumor growth and up-regulate the expression of tumor angiogenesis factor in the GHR-highly-expressed SGC-7901 xenograft tumor model; However,such effects do not exist in GHR-negatively-expressed MKN-45 xenograft tumor model. The existence of GHR may be a key target by which rhGH influences the tumor growth and the expressions of tumor angiogenesis factor, which is probably achieved through Janus kinase 2-signal transducer and activator of transcription 3 activation.
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PURPOSE: Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are associated with increased angiogenesis, growth, and metastasis in solid tumors. But, until today, the importance of theses factors on leukemia, especially childhood acute lymphocytic leukemia (ALL) has received limited attention. Therefore, this study examined the bone marrow plasma VEGF and bFGF levels in ALL patients and normal controls. PATIENTS AND METHODS: Bone marrow plasmas at diagnosis from 33 ALL patients (median age 5.9 years; range 1.8-13.9 years) were used for analysis. The bone marrow levels of bFGF and VEGF were determined by enzyme-linked immunosorbent assay (R & D Systems) and compared with the bone marrow levels of 7 healthy control subjects (median age 11.98 years; 6 months -13.6 years). RESULTS: Average VEGF was higher in relapse ALL (N=7, 216.6 +/- 79.9pg/mL) compared to standard (N=9, 36.8 +/- 12.1pg/mL) (p=0.013) or high risk ALL (N=17, 80.0 +/- 12.2pg/mL) (p=0.023). bFGF levels were also significantly higher in relapse than standard-, or high-risk ALL patients (relapse ALL; 48.6 +/- 15.4pg/mL, standard risk ALL; 18.9 +/- 5.5pg/mL, high risk ALL; 19.0 +/- 3.5pg/mL, normal control; 18.6 +/- 4.0pg/mL) (p=0.003). Three patients with refractory relapse and death had much higher VEGF and bFGF values (VEGF; 420.0 +/- 81.6pg/ mL, bFGF; 85.6 +/- 3.2pg/mL). CONCLUSION: Our data suggest that the increased levels of VEGF and bFGF in bone marrow may play an important role in prognosis of childhood ALL.
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Non-small cell lung cancers (NSCLC) vary in their biologic behavior. Recurrence and tumor-related mortality may be attributable to molecular abnormalities in primary tumors. This study evaluated such immunophenotypes with regard to cell cycle regulation and proliferation, apoptosis, and angiogenesis, to determine their significance for patient outcome. Core biopsies from 219 patients with NSCLC were assembled on tissue microarrays, and the expressions of p16, p21, p27, cyclin B1, cyclin E, Ki-67, caspase-3, survivin, bcl-2, VEGF, and endostatin were evaluated by immunohistochemistry. Despite previously described prognostic relevance of some of the investigated molecules, many of those markers were not directly associated with recurrence or survival. However, there was a trend for p16 immunoreactivity to be associated with a good prognosis (57% vs. 42% in 5-yr survival) (p=0.071). bcl-2 expression was strongly correlated with a better outcome (65% vs. 45% in 5-yr survival) (p=0.029), and the hazard of death for bcl-2 positive patients was 0.42 times of that for bcl-2 negative patients (p=0.047). A multivariate analysis with Cox proportional hazards model confirmed that the lymph node status (p=0.043) and stage (p=0.003) were other independent prognostic factors. Our results suggest that p16 and bcl-2 provide prognostic information independent of the TNM stage in NSCLC.
Subject(s)
Male , Humans , Female , Aged , Biomarkers, Tumor/analysis , Survival Rate , Survival Analysis , Statistics , Sensitivity and Specificity , Reproducibility of Results , Prognosis , Outcome Assessment, Health Care/methods , Neoplasm Proteins/analysis , Lung Neoplasms/diagnosis , Korea/epidemiology , Carcinoma, Non-Small-Cell Lung/diagnosisABSTRACT
Objective To investigate the relationships between Cyclooxygenase(COX-2) and angiogenesis and expressions of COX-2 and vascular endothelial growth factor(VEGF) in thyroid cancer and its clinical significance.Methods Immunohistochemistry was used to detect the expressions of COX-2 and VEGF in 60 thyroid cancer,(15 thyroid)adenomas and 10 normal thyroid tissues.Results The expression rates of COX-2 and VEGF in thyroid cancer were higher than those in thyroid adenomas and normal tissues(P
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BACKGROUND AND OBJECTIVES: Angiogenesis is important both in normal and pathologic processes, including wound healing and inflammation. Because proliferating tissues require an enhanced blood supply, angiogenesis appears to be a prerequisite for expansion of cholesteatoma. This study was aimed to investigate mRNA and protein expression of angiogenic growth factors such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor-alpha (TGF-alpha) and platelet derived-endothelial cell growth factor (PD-ECGF) in middle ear cholesteatoma. SUBJECTS AND METHOD: Cholesteatoma tissues and retroauricular skins were obtained from 12 patients during operation. The mRNA expression was detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), and the degree of expression was measured by comparing density ratio of beta-actin by NIH imaging analysis system. The protein expression was evaluated by immunohistochemistry, and the degrees of expression in epithelial, endothelial, inflammatory cells of cholesteatoma and retroauricular skin were judged by two pathologists and then converted on a 5-grade rating scale according to intensity of expression. RESULTS: The expression rate of mRNA in cholesteatoma and retroauricular skin was 67.7 and 33.3% in VEGF, 75.0 and 50.0% in bFGF, 53.8 and 8.3% in TGF-alpha, 67.7 and 75% in PD-ECGF. There was statistically significant difference only in TGF-alpha (p0.05). The degrees of VEGF, bFGF and PD-ECGF protein expression in cholesteatoma tissue were more intense at the inflammatory (p0.05) than in retroauricular skin. And the degree of TGF-alpha protein expression in cholesteatoma tissue was more intense at all three cells (p<0.05) than in the retroauricular skin. CONCLUSION: These results suggest that angiogenesis processes in cholesteatoma perimatrix and the expression of angiogenic growth factors are upregulated by mRNA. Further studies for evaluating the factors that can affect the expression of mRNA and also for disclosing the roles and control mechanisms of these factors in cholesteatoma angiogenesis must be followed.
Subject(s)
Humans , Actins , Angiogenesis Inducing Agents , Blood Platelets , Cholesteatoma , Cholesteatoma, Middle Ear , Ear, Middle , Epithelial Cells , Fibroblast Growth Factor 2 , Immunohistochemistry , Inflammation , Intercellular Signaling Peptides and Proteins , Pathologic Processes , RNA, Messenger , Skin , Thymidine Phosphorylase , Transforming Growth Factor alpha , Vascular Endothelial Growth Factor A , Wound HealingABSTRACT
BACKGROUND AND OBJECTIVES: Angiogenesis is the process of new blood vessel development from preexisting vessel. In many human solid tumor, the extent of angiogenesis is one of the most significant prognostic factors that can be used to predict the patient survival rate and metastasis. The aim of this study is to investigate the role of new blood vessel formation in the thyroid tumors. SUBJECTS AND METHOD: We analyzed the microvascular density and proliferation index in the 70 cases of thyroid tumors by double immunohistochemistry with anti-CD34 and anti-Ki67 antibody. The microvascular density and Ki67 index were compared with the clinical parameters such as sex, age, stage, tumor extension, cervical lymph node metastasis, and prognostic factors, which were obtained through the retrospective review of the medical records. RESULTS: The microvascular density and Ki67 index were higher in malignant tumors than in benign tumors. Higher microvascular density and Ki67 index were associated with tumor stage and increased risk of AMES, AGES and MACIS scores. CONCLUSION: The microvascular density and Ki67 index may serve as significant prognostic factors in the differentiated thyroid cancer.
Subject(s)
Humans , Angiogenesis Inducing Agents , Blood Vessels , Immunohistochemistry , Lymph Nodes , Medical Records , Neoplasm Metastasis , Retrospective Studies , Survival Rate , Thyroid Gland , Thyroid NeoplasmsABSTRACT
PURPOSE: HIF-1alpha (Hypoxia inducible factor-1alpha) and VEGF (vascular endothelial growth factor) have been reported to be involved in tumor growth and metastasis, but only a little data on the roles of HIF-1alpha and VEGF in renal cell carcinomas are available, and few studies have yet evaluated their prognostic values. The aim of the present study was to assess the HIF-1alpha and VEGF expression and evaluate the relationships between HIF-1alpha/VEGF and the histopathological characteristics in renal cell carcinomas. MATERIALS AND METHODS: HIF-1alpha and VEGF immunohistochemical stainings were performed on formalin-fixed, paraffin-embedded archival tissues from 22 renal cell carcinoma tissues and 13 normal kidney tissues, used as a control group. The interpretation of the immunohistochemical stainings were semi-quantitatively performed by one pathologist. RESULTS: The expressions of HIF-1alpha and VEGF were significantly higher in the patient than the control group. The HIF-1alpha and VEGF expressions were correlated to each other, and inclined to be positively correlated with the pathological stage and grade of the renal cell carcinoma. CONCLUSIONS: The HIF-1alpha and VEGF expressions might be independent predictors of the outcome, as well as the stage and grade of renal cell carcinomas. This study suggests that HIF-1alpha and VEGF may be potential prognostic factors in renal cell carcinomas.
Subject(s)
Humans , Angiogenesis Inducing Agents , Hypoxia , Carcinoma, Renal Cell , Kidney , Neoplasm Metastasis , Vascular Endothelial Growth Factor AABSTRACT
PURPOSE: HIF-1alpha(Hypoxia inducible factor-1alpha) and VEGF(vascular endothelial growth factor) have been reported to be involved in tumor growth and metastasis but little data concerning their role in transitional bladder cancer is available and few studies have yet evaluated their prognostic values. The aim of the present study was to assess HIF-1alpha and VEGF expression and to evaluate the relationship between HIF-1alpha/ VEGF and histopathologic characteristics in bladder tumors. MATERIALS AND METHODS: HIF-1alpha and VEGF immunohistochemical stainings were performed on formalin-fixed, paraffin-embedded archival tissues from 27 transitional bladder cancer tissues and from 4 normal bladder tissues as a control group. Interpretation of immunohistochemical staining was performed semi-quantitatively by one pathologist. RESULTS: Expressions of HIF-1alpha and VEGF tended to be higher in the patient group than in the control group. HIF-1alpha expression was correlated with VEGF expression. HIF-1alpha and VEGF tended to be positively correlated with pathologic stage and grade of transitional bladder cancer. CONCLUSIONS: HIF-1alpha and VEGF expression might be independent predictors of outcome, as well as stage and grade of transitional bladder cancer. This study suggests that HIF-1alpha and VEGF may be potential prognostic factors in bladder cancer.
Subject(s)
Humans , Angiogenesis Inducing Agents , Hypoxia , Neoplasm Metastasis , Urinary Bladder Neoplasms , Urinary Bladder , Vascular Endothelial Growth Factor AABSTRACT
BACKGROUND AND OBJECTIVES: The growth of tumor is dependent on angiogenesis. Expressions of vascular endothelial growth factor (VEGF) as a prognostic indicator has been documented for various types of human tumors. The purpose of this study was to investigate the relationship between the expression of VEGF and the differentiation and TNM stage of the laryngeal squamous cell carcinoma. MATERIALS AND METHOD: The VEGF expression was evaluated by immunohistochemical staining with monoclonal anti-VEGF antibody in 28 cases of the laryngeal squamous cell carcinoma. RESULTS: The positive staining for VEGF was observed in 5 (31.3%) out of 16 cases of well differentiated carcinomas and 7 (58.3%) out of 12 cases of moderately differentiated carcinomas. Comparing with the TNM staging system, no positive staining was found in any of the stage I cases; however, 2 out of 6 cases (33.3%) of stage II, 3 out of 7 cases (42.9%) of stage III and 6 out of 9 cases (66.7%) of stage IV showed positive staining for VEGF. There was statistical relationship between the differentiation and positive expression for VEGF, but not between the stage of the laryngeal squamous cell carcinoma and the VEGF expression. CONCLUSION: These results suggest that there is a clinical correlation of VEGF expression to the progress of differentiation and tumor stages.
Subject(s)
Humans , Angiogenesis Inducing Agents , Carcinoma, Squamous Cell , Larynx , Neoplasm Staging , Vascular Endothelial Growth Factor AABSTRACT
Coronary artery disease (CAD) and peripheral vascular disease (PVD) are significant medical problems worldwide, including Korea. Although substantial progress has been made in prevention and treatment of these diseases, particularly CAD, there are still a large number of patients, who despite maximal medical treatment have substantial symptomatology, so are not suitable for mechanical revascularization. Therapeutic angiogenesis represents a novel, conceptually appealing, treatment option for these patients. Consequently, there are several different products in clinical trials looking at the various angiogenic growth factors. A number of small, mostly open-labeled phase I or I/II, studies have been conducted with adeno- and plasmid-based vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) gene constructs in CAD and PVD. Although these studies have provided intriguing indications of the possibility of new vessel formation, and that these new vessels could be functional, these studies have been too small to allow definite conclusions on their potential efficacy to be drawn. Although, larger scale placebo-controlled studies of gene transfer are in progress. Future clinical studies will be required to determine the optimal dose, formulation, route of administration and combination of growth factors, as well as the requirement for endothelial progenitor cell, or stem cell supplementation, to provide effective and safe therapeutic angiogenesis. This exciting new field is reviewed, with special emphasis on clinical trials.
Subject(s)
Humans , Angiogenesis Inducing Agents , Cardiovascular Diseases , Coronary Artery Disease , Fibroblast Growth Factors , Genetic Therapy , Intercellular Signaling Peptides and Proteins , Korea , Myocardial Ischemia , Peripheral Vascular Diseases , Stem Cells , Vascular Endothelial Growth Factor AABSTRACT
BACKGROUND AND OBJECTIVES: Lymph node metastasis is believed to be the single most important prognostic factor in the head and neck squamous cell cancer. To identify potential biological parameters for predicting cervical lymph node metastasis, we evaluated the relationship between cervical nodal status and several parameters, such as microvessel density, p53, Ki67, and DNA ploidy, and compared it with the conventional clinical parameters including histologic grade of the tumors. MATERIALS AND METHOD: This study group included 26 specimens from the primary sites of patients who were diagnosed with squamous cell cancers of the head and neck. Immunohistochemstry and DNA flowcytometry were performed at almost the same sections of the primary sites. To quantify angiogenesis, the microvessel density was determined by counting the number of the vascular endothelial cells positively stained with CD-31 under the magnification filed power of 200 by two investigators; the cell number was determined by taking the average of the highest values of three counts made by each investigator. Immunohistochemical staining with Ki67 and p53 were also done to evaluate the cellular proliferation of tumors and the overexpression of mutated tumor suppressor gene. DNA flowcytometry was performed to evaluate the ploidy and proliferation index. These results were compared and analyzed with clinical parameters. RESULTS: All of the parameters failed to show a significant relationship to nodal status in this study. However, the microvessel density of the laryngeal cancers showed a statistically significant relationship with the cervical nodal metastasis (p=0.045). CONCLUSION: The microvessel density may have a correlation to the lymph nodal metastasis in the head and neck squamous cell cancer and may be regarded as an additional prognostic factor for planning treatment.
Subject(s)
Humans , Angiogenesis Inducing Agents , Cell Count , Cell Proliferation , DNA , Endothelial Cells , Genes, Tumor Suppressor , Head and Neck Neoplasms , Head , Laryngeal Neoplasms , Lymph Nodes , Microvessels , Neck , Neoplasm Metastasis , Neoplasms, Squamous Cell , Ploidies , Research PersonnelABSTRACT
BACKGROUND AND OBJECTIVES: Angiogenesis is a necessary process for solid tumor to grow in human body, and thought to play an important role in metastasis. In some solid tumor such as the breast cancer and prostatic cancer, the angiogenesis is thought to be one of the most significant prognostic factors that predict the patient survival rate and metastasis. The purpose of this study is to define the significance of angiogenesis in the head and neck squamous cell carcinoma (HNSCC). SUBJECTS AND METHOD: We measured the microvascular density (MVD) using immunohistochemistry with anti-CD34 antibody in 40 HNSCC. The maximal and average MVD was compared with the clinical parameters such as stage, cervical lymph node metastasis, recurrence, and survival rate, obtained through the retrospective review of the medical records. RESULTS: 1) The maximal and average MVD correlated with overall stage, T stage and N stage statistically. The MVD were increased according to the increasement of the T and N stage. 2) The maximal and average MVD showed a significant relationship with 3 year survival rate. 3) There were no relationship between maximal and average MVD and local or regional recurrence. CONCLUSION: The maximal and average MVD may be a significant prognostic factors which can predict the survival rate of the patients with HNSCC.
Subject(s)
Humans , Angiogenesis Inducing Agents , Breast Neoplasms , Carcinoma, Squamous Cell , Head , Human Body , Immunohistochemistry , Lymph Nodes , Medical Records , Neck , Neoplasm Metastasis , Prostatic Neoplasms , Recurrence , Retrospective Studies , Survival RateABSTRACT
BACKGROUND AND OBJECTIVES: Normal angiogenesis occurs as a part of the body's repair processes like the healing of wounds and fractures. By contrast, uncontrolled angiogenesis can often be pathological. Vascular remodelling could therefore play an important role in the growth process of solid tumors. The aim of this study was to detect the expression of platelet-derived endothelial cell growth factor (PD-ECGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF), and investigate the correlation between these factors. Also, we studied the relationships between the expressions of these factors and the clinical stage, nodal involvement, and histologic grade in the squamous cell carcinoma of larynx. MATERIALS AND METHOD: The authors examined the expression of three angiogenic factors in specimens of laryngeal squamous cell carcinoma (n=17). The mRNA expressions of angiogenic factors were detected by the semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). Statistics were analysed using the Fisher's exact test, the Wilcoxon signed rank test, and the Spearman correlation coefficiency. RESULTS: PD-ECGF and bFGF were significantly higher in the stages III and IV cancers than in the stages I and II cancers, and thus shows that bFGF was related to severity of the nodal involvement. The expression of more than one factor was significantly related with stages III and IV cancer. PD-ECGF and VEGF were related with each other. CONCLUSION: The authors suggest that angiogenic factors, especially, PD-ECGF and bFGF, may be used as prognostic factors for the squamous cell carcinoma of larynx.
Subject(s)
Angiogenesis Inducing Agents , Carcinoma, Squamous Cell , Endothelial Cells , Fibroblast Growth Factor 2 , Fibroblasts , Larynx , RNA, Messenger , Thymidine Phosphorylase , Vascular Endothelial Growth Factor A , Wounds and InjuriesABSTRACT
BACKGROUND: Angiogenesis is crucial for many biological processes such as embryogenesis, cyclic changes in the endometrium and wound healing. It is also critical for the growth, invasion and metastasis of solid tumors. Vascular endothelial growth factor (VEGF) acts as a mitogen for endothelial cells and is expressed by the presence of various tumor cells. The objective of this study is to evaluate if angiogenesis is involved in the mouse skin carcinogenesis and if VEGF is related to angiogenesis. METHODS: We induced premalignant and malignant lesions on mouse (BALB/c) skin using the two stage chemical carcinogenesis moedl, DMBA (7,12-dimethylbenzanthracene) initiation and TPA (tetra decanoyl-phorbol-acetate) promotion. And we analysed the microvessel densities (MVD) and expression of VEGF in various stages of premalignant and malignant lesions by immunohistochemical studies. RESULTS: Squamous papillomas, keratoacanthoma, dermatofibroma, and squamous cell carcinomas were developed in 20 weeks. There were no differences in the incidence of benign and malignant tumors between 10-week and 20-week promotion groups. There were significant increases in MVD from normal and hyperplastic skin through premalignant lesion to invasive squamous cell carcinoma (p<0.0005). But the degree of VEGF expression neither correlated with neither MVD nor the tumor groups. CONCLUSIONS: Increased angiogenesis begins from the hyperplastic stage. VEGF produced by tumor cells may not play major roles in the angiogenesis in the two stage chemical carcinogenesis model of the mouse skin.
Subject(s)
Animals , Female , Mice , Pregnancy , 9,10-Dimethyl-1,2-benzanthracene , Biological Phenomena , Carcinogenesis , Carcinoma, Squamous Cell , Embryonic Development , Endometrium , Endothelial Cells , Histiocytoma, Benign Fibrous , Incidence , Keratoacanthoma , Microvessels , Neoplasm Metastasis , Papilloma , Skin , Vascular Endothelial Growth Factor A , Wound HealingABSTRACT
BACKGROUND: Increased expression of nitric oxide synthase (NOS) isotypes is present in human tumor cell lines and solid tumor tissues. Hypoxia upregulates NOS expression, and nitric oxide (NO) induces mitogenesis among endothelial cells. NO has been known to induce vascular endothelial growth factor (VEGF) expression in carcinoma cells and to induce neovascularization in tumors. METHODS: The expression and cellular localization of 3 isotypes of NOS was detected by immunohistochemistry in 73 advanced gastric carcinoma tissues along with adjacent normal gastric mucosa; and the relationship to known clinicopathologic parameters, microvascular density, and VEGF expression was analysed. RESULTS: Forty-four (60.3%), 56 (76.7%), and 52 (71.2%) of the 73 cases revealed eNOS, nNOS, and iNOS expression, respectively. Intestinal type adenocarcinomas tended to have higher activity of eNOS (p=0.000) and nNOS (p=0.001) activities than did the diffuse type adenocarcinomas. All isotypes of NOS (eNOS, p=0.001; nNOS, p=0.005; iNOS, p=0.044) tended to be highly expressed when the tumor was differentiated. There was no significant relationship between any of the 3 NOS isotypes and microvascular density, whereas VEGF was closely related with microvascular density (p=0.000). The expression of VEGF was not related to with any of the NOS isotype expressions. CONCLUSIONS: From the above results, we speculated that NO may be implicated in the early stage of the gastric carcinogenesis rather than the growth and progression stages, and NO does not appear to affect angiogenesis or VEGF expression in the advanced gastric carcinoma.
Subject(s)
Humans , Adenocarcinoma , Angiogenesis Inducing Agents , Hypoxia , Carcinogenesis , Cell Line, Tumor , Endothelial Cells , Gastric Mucosa , Immunohistochemistry , Nitric Oxide Synthase , Nitric Oxide , Stomach Neoplasms , Vascular Endothelial Growth Factor AABSTRACT
Objective To study the effect of vascular endothelial growth factor(VEGF) on portal hypertensive gastropathy(PHG). Methods The incidence,location, and severity of PHG and the changes of VEGF in PHG were analysed in 44 cases. Results VEGF in the severe or moderate PHG group was significantly higher than that in the control group and in patients with portal hypertension without PHG(all P