OBJECTIVETo analyze the correlation between the perfusion data and microvessel density (MVD) in ovarian tumors, and investigate the hemodynamic features of the tumors in terms of anatomy and functional CT imaging.

METHODSSix patients with surgically confirmed benign ovarian tumors and 6 with malignant ovarian tumors underwent multi-slice CT perfusion imaging to acquire the perfusion parameters including perfusion, PEI, TTP, BV peak enhancement image(PEI), time to peak(TTP) and blood volume(BV). The tumors were stained and counted by Immunohistochemical staining of the microvessels in the tumor was performed to detect the MVD.

RESULTSs The time-density curves of the benign ovarian tumors increased slowly, reaching the peak at 40 s; the curves of the malignant tumors rose rapidly and continuously and reached the peak at 25 s. The differences in the perfusion data (PEI, TTP, BV) were statistically significant between the benign and malignant tumors (P<0.05). The MVD of the malignant tumors was significantly greater than that of the benign tumors (P<0.05). The mean BV of the malignant ovarian tumor was positively correlated to MVD (r=0.786, P<0.05).

CONCLUSIONMulti-slice spiral CT perfusion imaging can provide accurate enhancement data of the ovarian tumors and helps in the diagnosis and differential diagnosis of the ovarian tumors by presenting the changes of the hemodynamic features in the tumors.

Adult ; Aged ; Capillaries ; pathology ; Cystadenocarcinoma ; blood supply ; diagnostic imaging ; Female ; Fibroma ; blood supply ; diagnostic imaging ; Humans ; Middle Aged ; Ovarian Neoplasms ; blood supply ; diagnostic imaging ; Tomography, Spiral Computed ; methods

OBJECTIVETo clarify the association of EGFR expression with angiogenesis and chemoresistance in ovarian cancer.

METHODSImmunohistochemical PV-6000 staining was used to detect the expression of EGFR, LRP protein and MVD in 102 ovarian tumor specimens.

RESULTSEGFR, LRP positive rates and MVD in borderline and malignant ovarian specimens were significantly higher than those in the normal and benign ones (P < 0.01). EGFR positive expression rate in stage III-IV carcinoma tissues, poor differentiation and with ascites was higher than that in stage I-II carcinomas of well differentiation and without ascites (P < 0.05). MVD was related to histological grade, residual tumor and ascites, LRP positive expression had no correlation with the clinicopathologic parameters (P > 0.05). The effective rate of chemotherapy in patients with EGFR and LRP-positive expression were 57.1% and 53.7%, respectively, significantly lower than that in cases with EGFR and LRP-negative expression (85.0% and 90.9%, P < 0.05). In the 64 cases with complete data, the three-year survival rate was 53.0%. The survival time was shorter in the cases with EGFR and LRP-positive expression, poor differentiation, ascites and chemoresistance (P < 0.01), and only LRP-positive expression and chemotherapeutic effect were independently related to survival time (P < 0.05). There was a correlation between EGFR and MVD (r = 0.548, P < 0.01), EGFR and LRP positive expression (P = 0.020).

CONCLUSIONThe expression of EGFR in ovarian cancer is related to angiogenesis and chemoresistance. EGFR and LRP-positive expression are related to chemoresistance, and detection of the two proteins may be helpful in guiding chemotherapy choice for ovarian cancer. LRP-positive expression and chemotherapeutic effect may be independent prognostic factors.

Antigens, CD34 ; metabolism ; Ascites ; pathology ; Cystadenocarcinoma, Mucinous ; blood supply ; drug therapy ; metabolism ; pathology ; Cystadenocarcinoma, Serous ; blood supply ; drug therapy ; metabolism ; pathology ; Cystadenoma, Mucinous ; blood supply ; drug therapy ; metabolism ; pathology ; Cystadenoma, Serous ; blood supply ; drug therapy ; metabolism ; pathology ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Neovascularization, Pathologic ; pathology ; Ovarian Neoplasms ; blood supply ; drug therapy ; metabolism ; pathology ; Receptor, Epidermal Growth Factor ; metabolism ; Survival Rate ; Vault Ribonucleoprotein Particles ; metabolism

OBJECTIVETo evaluate the correlations of microvessel density (MVD), vascular endothelial growth factor (VEGF), thrombospodin1 (TSP1) and p53 protein with prognosis in epithelial ovarian cancer.

METHODSSamples from 57 patients with primary epithelial ovarian cancer were examined by immunohistochemical staining using anti-VEGF, anti-TSP1, anti-p53 and anti-CD34 antibodies. The correlation of MVD, expression of VEGF, TSP1 and p53 protein with postoperative recurrence and overall survival were analyzed retrospectively.

RESULTSVEGF, TSP1 and p53 protein was positively detected in 40 (70.2%), 27 (47.4%) and 35 (61.4%) of those patients, respectively. The mean MVD in this series was 30.3 +/- 8.5. High MVD, positive VEGF expression and negative TSP1 expression were positively correlated with postoperative recurrence. Univariate analysis showed that patients with high MVD, positive expression of VEGF and p53 had shorter median overall survival time than those with lower MVD, negative expression of VEGF and p53 (P = 0.0187, P = 0.010 and P = 0.005, respectively), while TSP1 expression was revealed as a protective factor for prognosis. Patients with positive expression of TSP1 had longer median overall survival time than those with negative TSP1 expression (P = 0.042). Multivariate analysis showed that MVD and p53 expression were two independent prognostic factors in epithelial ovarian cancer (P = 0.018 and P = 0.009, respectively).

CONCLUSIONVEGF, TSP1 and p53 protein may play an important role in the angiogenesis of epithelial ovarian cancer. High MVD level and p53 protein expression are two independent poor prognostic factors.

Adenocarcinoma, Clear Cell ; blood supply ; metabolism ; pathology ; Adult ; Aged ; Aged, 80 and over ; Cystadenocarcinoma, Serous ; blood supply ; metabolism ; pathology ; Female ; Humans ; Lymphatic Metastasis ; Microvessels ; pathology ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local ; Ovarian Neoplasms ; blood supply ; metabolism ; pathology ; Retrospective Studies ; Survival Rate ; Thrombospondin 1 ; metabolism ; Tumor Suppressor Protein p53 ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVE: The purpose of this research was to investigate the anti-angiogenic inhibitory effect of KR-31831, a newly developed anti-angiogenic agent, on an in vivo human ovarian carcinoma model using dynamic contrast-enhanced (DCE) MRI. MATERIALS AND METHODS: Xenografted ovarian tumors were established by subcutaneous injection of SKOV3 cells into mice. The mice were treated daily with KR-31831 at 50 mg/kg for 21 days. Tumor tissues were excised corresponding to the DCE-MRI sections for evaluation of MVD with CD31 immunohistochemistry. All in vivo MRIs were performed on a 7.0 Tesla micro-MRI System. DCE-MRI was acquired prior to initiating treatment with KR-31831 and again on days 3 and 21 after treatment. The permeability parameters (Ktrans, ve, and vp) were estimated using a pharmacokinetic model. RESULTS: Qualitatively, the Ktrans parametric mapping showed different changes before and after treatment with KR-31831 in the treatment group. For quantification of this change, the median of Ktrans values were compared before and after treatments in the control and KR-31831-treated groups. A non-parametric statistical test (Wilcoxon signed-rank test) showed decreasing Ktrans values on day 21 compared to days 0 and 3 in the KR-31831-treated group (p < 0.05), whereas there was no significant difference in the control group (p = 0.84). CONCLUSION: Our results suggest that DCE-MRI can be a useful tool by which to evaluate the anti-angiogenic effect of KR-31831 on a xenografted human ovarian carcinoma model.
Angiogenesis Inhibitors/*pharmacology ; Animals ; Benzopyrans/*pharmacology ; Cell Line, Tumor ; *Contrast Media ; Female ; Humans ; Imidazoles/*pharmacology ; Immunohistochemistry ; *Magnetic Resonance Imaging ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Microvessels/pathology ; Neoplasm Transplantation ; Ovarian Neoplasms/*blood supply/pathology

OBJECTIVETo observe the effects of angiostatin gene combined with chemotherapy on implanted human ovarian carcinoma of nude mouse.

METHODSThe mice were randomly divided into four groups after 7 days of the intraperitoneal injection of tumor cells (4 x 10(6)), and injected respectively with empty plasmid pcDNA3.0, angiostatin plasmid, cisplatin, and angiostatin plasmid + cisplatin. For combinational treatment, reagents were delivered in a timed fashion, where angiostatin plasmid was injected first, followed by cisplatin 24h later. The tumor samples were prepared to be used in the examinations of the expression of angiostatin with immunohistochemistry, of MVD in the tumor with immunohistochemistry, and of cell apoptosis with TUNEL staining.

RESULTSTumor growth and ascites formation were inhibited in all 3 groups except for the control group. The therapeutic effectiveness in the combined group was more significant than in the other two groups. In this group, MVD (32.5 +/- 4.3) was the lowest and apoptosis index (5.12 +/- 0.63) was the highest (P < 0.01).

CONCLUSIONSAngiostatin gene therapy combined with chemotherapy has a synergistic effect on the inhibition of ovarian cancer angiogenesis and ascites formation. Combining multiple therapies to treat ovarian cancer is an effective strategy.

Angiostatins ; biosynthesis ; genetics ; Animals ; Antineoplastic Agents ; therapeutic use ; Cisplatin ; therapeutic use ; Combined Modality Therapy ; Female ; Humans ; Injections, Intraperitoneal ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Ovarian Neoplasms ; blood supply ; pathology ; therapy ; Peritoneum ; Random Allocation ; Transplantation, Heterologous

OBJECTIVETo investigate whether basic fibroblast growth factor (bFGF) can induce the proliferation, invasion and angiogenesis of ovarian cancer or not.

METHODSHuman ovarian cancer cell lines SKOV(3) 1 x 10(4)/ml were plated in 24-well dishes, bFGF at 5, 10,15 and 20 ng/ml was added and crystal violet staining was given daily for 8 days, cell numbers were counted by determining OD490. SKOV(3) cells were plated in the center of 50% extra cellular matrix gel, bFGF at 5 and 10 ng/ml was added and the migration distance of cells was measured daily. SKOV(3) 5 x 10(7)/ml were transplanted to BALB/c nude mice subcutaneous. One week later, bFGF, bFGF-MAb or 0.9% nature sodium was injected subcutaneously surrounding the tumor twice a week. Eight weeks later, the experiment ended and the volume of the tumors were measured. Intratumoral microvessel density (MVD) was measured by immunohistochemistry staining for factor VIII.

RESULTSbFGF at 0-10 ng/ml could stimulate the proliferation of SKOV(3) concentration dependently (P<0.05). On the fifth day, the cell proliferation in 10 ng/ml group was 121% above control. bFGF could stimulate the invasion of SKOV(3) concentration dependently (P<0.05). On the seventh day, the migration distance in 5 ng/ml group was 1.16 cm and 153% above control, and that in 10 ng/ml group was 1.86 cm and 245% above control. The average volume of transplanted tumors and MVD in bFGF group were 180% and 146% above control respectively those in bFGF-MAb group were 63.7% and 62.8% above control respectively.

CONCLUSIONbFGF can stimulate proliferation, invasion and angiogenesis of ovarian cancer markedly; bFGF-MAb can inhibit the angiogenesis and growth of ovarian cancer.

Animals ; Cell Division ; drug effects ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Female ; Fibroblast Growth Factor 2 ; pharmacology ; Humans ; Mice ; Mice, Nude ; Neoplasm Invasiveness ; Neovascularization, Pathologic ; etiology ; Ovarian Neoplasms ; blood supply ; pathology

BACKGROUNDGinsenoside Rg3, the main component isolated from ginseng, inhibits some kinds of tumour growth and angiogenesis. The combination of low dose chemotherapy and antiangiogenesis inhibitors suppresses growth of experimental tumours more effectively than conventional therapy. The effect of this combination on ovarian cancer remains to be evaluated. Therefore, we investigated the synergism of ginsenoside Rg3 and cyclophosphamide (CTX) on growth and angiogenesis of human ovarian cancer.

METHODSTwenty-eight female athymic mice were divided randomly into 4 groups of 7: ginsenoside Rg3, CTX, ginsenoside Rg3 and CTX combination and control, after being transplanted with ovarian cancer cells (SKOV-3). The mice were given intraperitoneal injection of ginsenoside Rg3 and CTX for the 10 days following inoculation of SKOV-3 cells. The life quality and number of living days of mice were recorded. The size of tumour, tumour inhibitive rate, life elongation rate, proliferating cell nuclear antigen labelling index (PCNALI), expression of vascular endothelial cell growth factor (VEGF) and microvessel density (MVD) of the tumour tissues were estimated.

RESULTSLife quality of mice in ginsenoside Rg3 and combined treatment groups were better and number of living days longer than control. Average tumour weights of each treated group were less than control and there was no significant difference among the treated groups. PCNALI of treated groups was lower than control. The MVD value and VEGF expression in treated groups were significantly lower than control and the MVD values of ginsenoside Rg3 and combined treatment groups were lower than that of CTX group.

CONCLUSIONSGinsenoside Rg3 significantly inhibited growth and angiogenesis of ovarian cancer when used alone or combined with CTX. Ginsenoside Rg3 and CTX combination reinforced the antitumour effect each other and improved the living quality and survival time of mice with tumour.

Animals ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclophosphamide ; administration & dosage ; Female ; Ginsenosides ; administration & dosage ; Humans ; Immunohistochemistry ; Mice ; Neovascularization, Pathologic ; drug therapy ; pathology ; Ovarian Neoplasms ; blood supply ; drug therapy ; pathology ; Proliferating Cell Nuclear Antigen ; analysis ; Vascular Endothelial Growth Factor A ; analysis

Both the morbidity and mortality of ovarian cancer, among malignant tumors ot temale genital organs, are quite high. The traditional therapeutic methods on ovarian cancer are surgical operation, chemotherapy, radiotherapy and combination of these methods mentioned above. In recent years, some components of traditional Chinese medicine, such as genistein, semen Coicis, phytosterols, curcumin, quercetin, ginsenoside, etc. have been found to exert anticancer actions of inhibiting proliferation and inducing apoptosis of cancer cells, increasing the sensitivity of patients to chemotherapeutic agents in viva and/or in vitro, the mechanisms involve such aspects as inhibiting activity of key enzymes in cell metabolism, affecting gene expression, antioxidation, and inhibiting tumor angiogenesis, etc. As an adjuvant therapeutic means, the bioactive components of traditional Chinese medicine have broad future of clinical application.
Angiogenesis Inhibitors ; pharmacology ; Animals ; Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Curcumin ; isolation & purification ; pharmacology ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Female ; Genistein ; isolation & purification ; pharmacology ; Humans ; Ovarian Neoplasms ; blood supply ; pathology ; Quercetin ; isolation & purification ; pharmacology ; Tumor Cells, Cultured