OBJECTIVE: To observe the effect of electroacupuncture (EA) on vascular endothelial growth factor-C (VEGF-C), vascular endothelial growth factor receptor-3 (VEGFR-3), proinflammatory factors and apoptosis in myocardial tissue in mice with acute myocardial ischemia (AMI), and to explore the mechanism of EA for AMI. METHODS: Fifty male C57BL/6 mice were randomly divided into a sham operation group, a model group, an EA group, an inhibitor group and an inhibitor+EA group, 10 mice in each group. Except for the sham operation group, the mice in the remaining groups were intervented with ligation at the left anterior descending (LAD) coronary artery to establish AMI model. The mice in the sham operation group were intervented without ligation after thoracotomy. The mice in the EA group were intervented with EA at "Shenmen" (HT 7) and "Tongli" (HT 5), disperse-dense wave, 2 Hz/15 Hz in frequency, 1 mA in current intensity, 30 min each time, once a day, for 3 d. The mice in the inhibitor group were treated with intraperitoneal injection of SAR 131675 (12.5 mg•kg^-1•d^-1, once a day for 3 d). The mice in the inhibitor+EA group were injected intraperitoneally with SAR 131675 30 min before EA. The ECG before modeling, 30 min after modeling and 3 d after intervention was detected, and the ST segment displacement was recorded; after the intervention, the ELISA method was applied to measure the contents of serum creatine kinase isoenzyme (CK-MB), aspartate aminotransferase (AST) as well as tumor necrosis factor-α (TNF-α) and interleukin-23 (IL-23) in myocardial tissue; the HE staining method was used to observe the morphological changes of myocardial tissue; the immunofluorescence double labeling method was applied to measure the number of co-expression positive cells of VEGF-C/VEGFR-3 in myocardial tissue; the TUNEL method was used to detect the level of cardiomyocyte apoptosis; the Western blot method was applied to measure the protein expressions of VEGF-C, VEGFR-3, b-lymphoma-2 (Bcl-2), activated caspase-3 (Cleaved Caspase-3) and activated poly adenosine diphosphate ribose polymerase-1 (Cleaved PARP-1). RESULTS: Compared with the sham operation group, in the model group the ST segment displacement was increased (P<0.01); the contents of CK-MB, AST, TNF-α and IL-23 were increased (P<0.01); the arrangement of myocardial fibers was disordered, and interstitial inflammatory cell infiltration was obvious; the number of co-expression positive cells of VEGF-C/VEGFR-3 was decreased (P<0.01); the number of cardiomyocyte apoptosis was increased (P<0.01); the expressions of VEGF-C, VEGFR-3 and Bcl-2 were decreased (P<0.01); the expressions of Cleaved Caspase-3 and Cleaved PARP-1 were increased (P<0.01). Compared with the model group, in the EA group the ST segment displacement was decreased (P<0.01); the contents of CK-MB, AST, TNF-α, IL-23 were decreased (P<0.01); the severity of myocardial pathological injury was reduced; the number of co-expression positive cells of VEGF-C/VEGFR-3 was increased (P<0.01); the number of cardiomyocyte apoptosis was reduced (P<0.01); the expressions of VEGF-C, VEGFR-3 and Bcl-2 were increased (P<0.01); the expressions of Cleaved Caspase-3 and Cleaved PARP-1 were reduced (P<0.01). There was no significant difference in all the indexes between the model group and the inhibitor group (P>0.05). Compared with the model group, the protein expression of VEGF-C was increased in the inhibitor+EA group (P<0.01). Compared with the inhibitor group, in the EA group the ST segment displacement was decreased (P<0.01); the contents of CK-MB, AST, TNF-α, IL-23 were decreased (P<0.01); the severity of myocardial pathological injury was reduced; the number of co-expression positive cells of VEGF-C/VEGFR-3 was increased (P<0.05); the number of cardiomyocyte apoptosis was reduced (P<0.01); the expressions of VEGF-C, VEGFR-3 and Bcl-2 were increased (P<0.01); the expressions of Cleaved Caspase-3 and Cleaved PARP-1 were reduced (P<0.01). Compared with the inhibitor+EA group, all the indexes in the EA group were improved except the protein expression of VEGF-C (P<0.01). CONCLUSION EA could relieve the inflammatory reaction and apoptosis in AMI mice, and its mechanism may be related to activating VEGF-C/VEGFR-3 pathway and promoting lymphangion genesis.
Mice ; Male ; Animals ; Electroacupuncture ; Vascular Endothelial Growth Factor Receptor-3 ; Caspase 3 ; Vascular Endothelial Growth Factor C ; Tumor Necrosis Factor-alpha/genetics* ; Vascular Endothelial Growth Factor A/genetics* ; Poly(ADP-ribose) Polymerase Inhibitors ; Mice, Inbred C57BL ; Myocardial Ischemia/metabolism* ; Apoptosis ; Interleukin-23 ; Proto-Oncogene Proteins c-bcl-2

OBJECTIVE: Dexmedetomidine (DEX), the most specific α ₂-adrenergic receptor agonist widely used for its sedative and analgesic properties, has been reported to upregulate HIF-1α expression to protect hypoxic and ischemic tissues. However, it is largely unclear whether DEX can also upregulate Hypoxia-inducible factor-1 alpha (HIF-1α) expression and its downstream vascular endothelial growth factor-A (VEGFA) in cancer tissues with oxygen-deficient tumor microenvironment. METHODS: We used SMMC-7721 cells, MHCC97-H cells, and a mouse model of orthotopic hepatic carcinoma to explore the effect of DEX on angiogenesis and vasculogenic mimicry (VM) and its mechanism. Under normoxic (20% O ₂) and hypoxic (1% O ₂) conditions, DEX was used to intervene cells, and yohimbine was used to rescue them. RESULTS: The results showed that DEX promoted angiogenesis and VM in human liver cancer cells within a certain dose range, and the addition of yohimbine inhibited this effect. DEX could activate HIF-1α/VEGFA pathway, which was further verified by silencing HIF-1α. Consistently, in vivo results also showed that DEX can up-regulate HIF-1α/VEGFA expression, and enhance the number of VM channels and microvessel density (MVD). CONCLUSION We believe that HIF-1α/VEGFA might be an important signaling pathway by which DEX promotes angiogenesis and VM formation in human hepatocellular carcinoma, whereas α ₂-adrenergic receptor mediation might be the critical mechanisms.
Animals ; Humans ; Mice ; Adrenergic alpha-2 Receptor Agonists/pharmacology* ; Carcinoma, Hepatocellular ; Cardiovascular Physiological Phenomena ; Dexmedetomidine/pharmacology* ; Hypoxia ; Liver Neoplasms/drug therapy* ; Oxygen ; Tumor Microenvironment ; Vascular Endothelial Growth Factor A/genetics* ; Receptors, Adrenergic, alpha-2/metabolism*

OBJECTIVE: To analyze the expression and relationship of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and kinase insert domain receptor (KDR) in local skin tissues of pressure injury and investigate the possible mechanism of stage 3 pressure injury refractory wound. METHODS: Forty male SD rats were randomly divided into normal control group, compressed 3 d, 5 d, 7 d, and 9 d groups. Stage 3 pressure injury animal model were established by magnet compression. The morphology of skin was observed by HE staining. The expression of VEGF was detected by immunohistochemistry. The expression levels of HIF-1α, VEGF and KDR protein in skin tissue were detected by Western blot. One-way analysis of variance and LSD test were performed on the data. RESULTS: ①The HE results showed that compared with the normal control group, the epidermis of the compressed group was gradually thickened, the number of blood vessels was decreased, the collagen arrangement disordered and inflammatory cells infiltration were increased. ②Immunohistochemical results showed that the expression of VEGF protein in the 3 d group was significantly higher than that in the normal control group (P＜0.01). The expression of VEGF protein in the skin tissue of 5 d, 7 d and 9 d groups was lower than that in normal control group (P＜0.05). WB results were consistent with immunohistochemistry results. ③WB results showed that the expression of HIF-1α in the skin tissues of the rats in 3 d, 5 d and 7 d groups was higher than that in the normal control group (P＜0.01 or P＜0.05). The expression of KDR protein was lower than that of the normal control group (P＜0.05 or P＜0.01). CONCLUSION HIF-1α mediated reduction of VEGF and KDR protein expression and decreased tissue angiogenesis may be one of the important causes of chronic dysfunction of stage 3 pressure injury.
Animals ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; metabolism ; Male ; Pressure ; adverse effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Skin ; injuries ; Vascular Endothelial Growth Factor A ; genetics ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; genetics ; metabolism

BACKGROUNDRecombinant human-erythropoietin (rh-EPO) has therapeutic efficacy for premature infants with brain damage during the active rehabilitation and anti-inflammation. In the present study, we found that the rh-EPO was related to the promotion of neovascularization. Our aim was to investigate whether rh-EPO augments neovascularization in the neonatal rat model of premature brain damage through the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway.

METHODSPostnatal day 5 (PD5), rats underwent permanent ligation of the right common carotid artery and were exposed to hypoxia for 2 h. All the rat pups were randomized into five groups as follows: (1) control group; (2) hypoxia-ischemic (HI) group; (3) HI + LY294002 group; (4) HI + rh-EPO group; and (5) HI + rh-EPO + LY294002 group. The phospho-Akt protein was tested 90 min after the whole operation, and CD34, vascular endothelial growth factor receptor 2 (VEGFR2), and vascular endothelial growth factor (VEGF) were also tested 2 days after the whole operation.

RESULTSIn the hypoxic and ischemic zone of the premature rat brain, the rh-EPO induced CD34+ cells to immigrate to the HI brain zone (P < 0.05) and also upregulated the VEGFR2 protein expression (P < 0.05) and VEGF mRNA level (P < 0.05) through the PI3K/Akt (P < 0.05) signaling pathway when compared with other groups.

CONCLUSIONSThe rh-EPO treatment augments neovascularization responses in the neonatal rat model of premature brain damage through the PI3K/Akt signaling pathway. Besides, the endogenous EPO may exist in the HI zone of rat brain and also has neovascularization function through the PI3K/Akt signaling pathway.

Animals ; Animals, Newborn ; Antigens, CD34 ; metabolism ; Brain ; drug effects ; metabolism ; pathology ; Disease Models, Animal ; Erythropoietin ; genetics ; metabolism ; therapeutic use ; Female ; Humans ; Hypoxia-Ischemia, Brain ; drug therapy ; metabolism ; Neovascularization, Physiologic ; drug effects ; Phosphatidylinositol 3-Kinase ; metabolism ; Pregnancy ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; genetics ; metabolism ; therapeutic use ; Signal Transduction ; drug effects ; Vascular Endothelial Growth Factor A ; genetics ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism

Marsdeniae tenacissimae extract (MTE), commonly known as Xiao-Ai-Ping in China, is a traditional Chinese herb medicine capable of inhibiting proliferation and metastasis and boosting apoptosis in various cancer cells. However, little is known about the contribution of MTE towards tumor angiogenesis and the underlying mechanism. The present study aimed to evaluate the effects of MTE on the proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs) and the molecular mechanism. 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium, inner salt (MTS) and PI-stained flow cytometry assays revealed that MTE dose-dependently reduced the proliferation of HUVECs by arresting cell cycle at S phase (P < 0.05). Annexin V-FITC/PI-stained flow cytometry confirmed that MTE (160 μL·L) enhanced the apoptosis of HUVECs significantly (P < 0.001). Real-time quantitative RT-PCR and Western blot analyses showed an increase in Bax expression and a sharply decline in Bcl-2 expression; caspase-3 was activated simultaneously in a dose-dependent manner (P < 0.05). Further study observed the dose-dependent down-regulation of vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2), P2Y6 receptor (P2Y6R), and chemokine (C-C motif) ligand 2 (CCL-2), along with the activation of PKC Δ and up-regulation of p53 in a dose-dependent manner in MTE-treated selected cells (P < 0.05). Collectively, the results from the present study suggested that MTE suppressed the proliferation by attenuating CCL-2-mediated VEGF/VEGFR2 interactions and promoted the apoptosis through PKCΔ-induced p53-dependent mitochondrial pathway in HUVECs, supporting that MTE may be developed as a potent anti-cancer medicine.
Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Human Umbilical Vein Endothelial Cells ; cytology ; drug effects ; metabolism ; Humans ; Marsdenia ; chemistry ; Plant Extracts ; pharmacology ; Protein Kinase C ; genetics ; metabolism ; Signal Transduction ; drug effects ; Vascular Endothelial Growth Factor A ; genetics ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; genetics ; metabolism

The in vitro cell culture experiment was conducted to study the effect of Danqi Piantan capsule (DPC) and DPC dislodge the antelope horn with artificial bezoar double (DPCBD) on nerve regeneration and blood vessel regeneration and preliminarily investigate the possibility of substituting antelope horn in DPC with artificial bezoar. In this experiment, rats were randomly divided into 5 groups: the blank serum control group, the model group, DPC groups (0.306 g x kg(-1) x d(-1), the same below), DPC remove of antelope horn (DPCRA) groups and DPCBD groups. Brain microvascular endothelial cells cultured in vitro (BMEC), astrocytes and neural stem cells (NSC) were co-cultured to simulate neurovascular unit, label neurons with microtubule associated protein III (β-tubulin III) antibody and lable astrocytes with glial fibrillary acidicprotein (GFAP). ELISA was used for the detection of the content of BMEC lactate dehydrogenase instrument method (LDH), the inverted phase contrastmicroscope was adopted to observe the formation of BMEC tube like structure, the number of leukocytes and leukocytes adherent to BMEC were counted under the microscope, the expression levels of β-tubulin III and the ratio of GFAP positive cells was detected with inimmunofluorescence, and RT-PCR method was used to detect NGF, BDNF, VEGF and VEGFr-2 mRNA. According to the result, compared with the model group, both DPC and DPCBD can reduce LDH leakage, promote the formation of BMEC tube like structure, inhibit leukocytes and their adhesion to BMEC, increase the β-tubulin III positive cell differentiation proportion (P < 0. 01), reduce the proportion of GFAP positive cells (P < 0.01), increase the expressions of co-cultured NGF, VEGF, BDNF and VEGFr-2 mRNA to a certain extent, with the most significant difference on NGF and VEGF mRNA expressions (P < 0.05) and the same efficacy in both groups. DPCRA groups showed less impact on all indexes than that of DPCBD and DPC groups. The same efficacy of DPCBD and DPC on nerve regeneration and angiogenesis suggested that antelope horn in DPC can be substituted by artificial bezoar.
Animals ; Antelopes ; Brain-Derived Neurotrophic Factor ; genetics ; metabolism ; Cattle ; Cells, Cultured ; Drug Substitution ; Endothelial Cells ; drug effects ; metabolism ; Gallstones ; chemistry ; Horns ; chemistry ; Male ; Medicine, Chinese Traditional ; Nerve Growth Factor ; genetics ; metabolism ; Neural Stem Cells ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Vascular Endothelial Growth Factor Receptor-2 ; genetics ; metabolism

OBJECTIVE: To explore the association of VEGFR2 gene polymorphisms (rs2305948 and rs1870377) with the effect of levodopa (L-dopa) and dyskinesia in Chinese population and to provide theoretical basis for clinical treatment.
 METHODS: By using Taqman MGB analysis and gene sequencing, the rs2305948 and rs1870377 polymorphisms of 69 enrolled Parkinson's disease (PD) patients were detected. Among them, 32 cases developed dyskinesia during 5 years and 37 cases did not develop dyskinesia during 8 years (as the control).
 RESULTS: There was no significant association between the occurrence of dyskinesia and VEGFR2 polymorphisms at rs2305948 and rs1870377. However, rs1870377 polymorphism of AA showed greater maximum L-dopa dose [(565.00±163.55) mg/d vs (396.88±200.39) mg/d, (300.00±80.18) mg/d, P=0.038] and higher value of Modified Abnormal Involuntary Movement Scale (mAIMS) compared with that with polymorphisms of AT and TT [17.00±5.24 vs 8.94±6.53, 7.86±4.45, P=0.026]. 
 CONCLUSION VEGFR2 genes polymorphism (rs1870377) is associated with maximum L-dopa dose and mAIMS value in PD patients.
Antiparkinson Agents ; pharmacology ; Humans ; Levodopa ; pharmacology ; Parkinson Disease ; drug therapy ; genetics ; Polymorphism, Genetic ; Vascular Endothelial Growth Factor Receptor-2 ; genetics

This study was aimed to investigate the mRNA and protein expression of CTGF, CYR61, VEGF-C and VEGFR-2 in bone marrow of patients with leukemia, and to analyze the role and clinical significance of these 4 factors in genesis and development of leukemia, infiltration and metastasis of leukemic cells. A total of 100 cases of newly diagnosed leukemia, 26 cases of acute leukemia in complete remission and 30 controls were enrolled in this study. The mononuclear cells of bone marrow were collected, the mRNA and protein expression levels of CTGF, CYR61, VEGF-C, VEGFR-2 in leukemia patients and controls were detected by real time PCR and Western blot, respectively. The results showed that the mRNA and protein expression levels of above mentioned 4 factors were significantly higher than those in control (P < 0.05), only CTGF mRNA expression in AL patients after complete remission showed statistical difference as compared with control (P < 0.05), but the expression of CTGF mRNA showed statistical significance in different bone marrow hyperplasia of acute leukemia (P < 0.05). The expression level of CTGF protein showed difference in different chromosome karyotypes of leukemia (P < 0.05). The expression levels of CYR61 and VEGF-C proteins showed statistical difference in different bone marrow hyperplasia of acute leukemia (P < 0.05). The expression level of CTGF, CYR61, VEGF-C mRNA and protein in CML group were higher than that in control group. The expression levels of CTGF and CYR61 protein were higher than that in control. The mRNA and protein expression levels of above-mentioned 4 factors in sex and infiltration lf leukemic cells did not show statistical significance(P < 0.05). In correlative analysis, the mRNA expressions of above mentioned 4 factors were positively correlated with bone marrow blast count(P < 0.05), the protein expression of CTGF, CYR61 and VEGF-C were positively correlated with bone marrow blast count. It is concluded that the CTGF, CYR61, VEGF-C and VEGFR-2 mRNA and protein play a role in acute leukemia. In acute leukemia (AML/ALL), the expression of above mentioned factor was high, but except VEGFR-2. Most of them were positively correlated with bone marrow blast count. Joint block of these angiogenesis-related factors is likely to play an important role in targeting treatment of leukemia.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bone Marrow ; metabolism ; pathology ; Case-Control Studies ; Child ; Child, Preschool ; Connective Tissue Growth Factor ; metabolism ; Cysteine-Rich Protein 61 ; metabolism ; Female ; Humans ; Leukemia ; metabolism ; pathology ; Male ; Middle Aged ; RNA, Messenger ; genetics ; Vascular Endothelial Growth Factor C ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism ; Young Adult

AIM: The compound B19 (C21H22O5) is a newly synthesized, mono-carbonyl analog of curcumin that has exhibited potential antitumor effects. This present study was performed to identify the anti-angiogenic activity of this compound. METHODS AND RESULTS: B19 inhibited migration and tube formation of human umbilical vein endothelial cells, and arrested microvessel outgrowth from rat aortic rings. In addition, B19 suppressed the neovascularization of chicken chorioallantoic membrane. Mechanistic studies revealed that B19 suppressed the downstream protein kinase activation of vascular endothelial growth factor (VEGF) by decreasing phosphorylated forms of serine/threonine kinase Akt, extracellular signal-regulated kinase, and p38 mitogen-activated protein kinase, with or without stimulating vascular endothelial growth factor (VEGF). CONCLUSIONS B19 exerted anti-angiogenic activity in vitro and ex vivo, which suggests that it merits further investigation as a promising anticancer angiogenesis compound.
Angiogenesis Inhibitors ; chemistry ; pharmacology ; Animals ; Aorta ; drug effects ; metabolism ; Cell Movement ; drug effects ; Curcumin ; analogs & derivatives ; pharmacology ; Extracellular Signal-Regulated MAP Kinases ; genetics ; metabolism ; Human Umbilical Vein Endothelial Cells ; cytology ; drug effects ; metabolism ; Humans ; In Vitro Techniques ; Rats ; Rats, Sprague-Dawley ; Vascular Endothelial Growth Factor A ; genetics ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; genetics ; metabolism

OBJECTIVE: To analyze the expression of vascular endothelial growth factor (VEGF), miR-205, Ezrinand Lamin A/C in ovarian cancer tissues. METHODS: The expression of VEGF in the serum of epithelial ovarian cancer and that of healthy volunteers were detected by enzyme-linked immunosorbent assay; the expressions of vascular endothelial growth factor receptor 1 (VEGFR-1), VEGFR-2, Ezrin and Lamin A/C were detected by immunohistochemistry and the micro-vessel density (MVD) of CD31 was detected by immunohistochemistry in epithelial ovarian cancer, benign ovarian and normal ovarian specimens; and the expression of miR-205, Ezrin and Lamin A/C were detected by real-time PCR in epithelial ovarian cancer, benign ovarian and normal ovarian specimens. RESULTS: The expression of VEGF in the serum of epithelial ovarian cancer patients (116.10± 11.94) was significantly higher than that of healthy volunteers (40.04±4.97, P<0.05). The positive expression rates of VEGFR-1 and VEGFR-2 in the epithelial ovarian cancer specimens were 75.9% and 91.4% respectively, which were significantly higher than that in the benign ovarian and the normal ovarian specimens (P<0.05). No differences were observed in the positive expression rates of VEGFR-1 and VEGFR-2 between the benign ovarian and the normal ovarian specimens (P>0.05). The average length of MVD in the epithelial ovarian cancer specimens (7.56±0.51), was significantly higher than that in the normal ovarian specimens (1.22±0.56, P<0.05) and in the benign ovarian specimens (0.7±0.39, P<0.05). No differences were observed in the average length of MVD between the benign ovarian and the normal ovarian specimens (P>0.05). The relative expression level of miR-205 was 0.106±0.035 in the epithelial ovarian cancer specimens, which was significantly higher than that in the normal ovarian specimens (0.0007±0.0005, P<0.05); the relative expression level of miR-205 in the benign ovarian specimens was (0.0002±0.0002), higher than that in the normal ovarian specimens, but with no significance (P>0.05). The positive expression rates of Ezrin and Lamin A/C in the epithelial ovarian cancer specimens were 51.7% and 60.3%, respectively, which were significantly lower than those in the benign ovarian and the normal ovarian specimens (P<0.05). No differences were observed in the positive expression rates of Ezrin and Lamin A/C between the benign ovarian and the normal ovarian specimens (P>0.05). The relative expression levels of Ezrin and Lamin A/C mRNA in the epithelial ovarian cancer specimens were (0.026±0.003) and (0.060±0.007), respectively, which were significantly lower than those in the normal ovarian specimens (P<0.05). There was no statistical significance between the relative expression level of Ezrin and Lamin A/C mRNA in the epithelial ovarian cancer specimens and that in the benign ovarian specimens (0.029± 0.011, 0.089 ± 0.019; P>0.05) . CONCLUSION VEGF is significantly expressed in the serum of epithelial ovarian cancer patients; and miR-205 is up-regulated in the epithelial ovarian cancer specimens. Ezrin and Lamin A/C are down-regulated in the epithelial ovarian cancer samples. VEGF, miR-205 and target protein may be associated with the invasion and metastasis of epithelial ovarian cancer.
Carcinoma, Ovarian Epithelial ; Cytoskeletal Proteins ; genetics ; metabolism ; Down-Regulation ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Immunohistochemistry ; Lamin Type A ; genetics ; metabolism ; MicroRNAs ; genetics ; metabolism ; Neoplasms, Glandular and Epithelial ; genetics ; metabolism ; Ovarian Neoplasms ; genetics ; metabolism ; RNA, Messenger ; Real-Time Polymerase Chain Reaction ; Vascular Endothelial Growth Factor A ; blood ; Vascular Endothelial Growth Factor Receptor-1 ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism