Objective To explore the mechanism of TPT1-AS1 targeting miR-324/TWIST1 axis to regulate the proliferation, invasion, migration and angiogenesis of epithelial ovarian cancer (EOC) cells, thereby affecting ovarian cancer (OC) progression. Methods RT-qPCR was used to detect the expression of TPT1-AS1 and miR-324 in 29 OC lesions and adjacent tissue samples. The two OC cell models of TPT1-AS1 overexpression and miRNA324 knockdown were constructed, and the cell proliferation, invasion and migration abilities were detected by CCK-8, Transwell^TM and scratch test. Western blot analysis was used to detect the protein expression levels of TWIST1, epithelial cadherin (E-cadherin), Vimentin, and vascular endothelial growth factor A (VEGF-A) in OC cells. Fluorescence in situ hybridization (FISH) and RNA pull-down experiments were used to verify the interaction between TPT1-AS1 and miR-324. Immunohistochemistry and Targetscan bioinformatics analysis were used to verify the negative regulatory role of miR-324 in the epithelial-mesenchymal transition (EMT) process. Results The TPT1-AS1 expression was significantly higher in OC tissues than that in para-cancerous tissues, while the miR-324 expression was significantly lower. In SKOV3 cells with TPT1-AS1 overexpression, the miR-324 expression decreased significantly, and TPT1-AS1 was negatively correlated with miR-324. It was also found that TPT1-AS1 and miR-324 were co-expressed in OC cells, and there was a direct binding relationship between them. Down-regulation of miR-324 significantly promoted the proliferation, invasion and migration of SKOV3 cells. Further studies revealed that miR-324 had a binding site at the 3'-UTR end of the TWIST1, a key transcription factor for EMT. Inhibiting miR-324 expression increased the transcription level of TWIST1, leading to a decrease in E-cadherin protein expression and an increase in Vimentin protein expression. Additionally, the downregulation of miR-324 resulted in an increased expression level of VEGF-A protein, which in turn enhanced angiogenesis of OC. Conclusion TPT1-AS1 promotes EOC cell proliferation, invasion, migration and angiogenesis by negatively regulating the miR-324/TWIST1 axis, thus promoting the development of OC. These findings provide new potential targets for the diagnosis and treatment of OC.
Humans ; MicroRNAs/metabolism* ; Female ; Cell Movement/genetics* ; Ovarian Neoplasms/blood supply* ; Twist-Related Protein 1/metabolism* ; Cell Line, Tumor ; Neovascularization, Pathologic/genetics* ; Neoplasm Invasiveness ; Carcinoma, Ovarian Epithelial/metabolism* ; Nuclear Proteins/metabolism* ; Cell Proliferation/genetics* ; Epithelial-Mesenchymal Transition/genetics* ; Gene Expression Regulation, Neoplastic ; RNA, Long Noncoding/metabolism* ; Cadherins/genetics* ; Vascular Endothelial Growth Factor A/genetics* ; Vimentin/genetics* ; Angiogenesis

OBJECTIVETo investigate the anti-angiogenic effects and mechanisms of Zengmian Yiliu Granule (ZMYLG) on ovarian carcinoma xenograft.

METHODSThe SKOV3 ovarian carcinoma bearing mouse model was established. The tumor-bearing mice were randomly divided into the control group, the paclitaxel group, the high, medium, and low dose ZMYLG group, 8 in each group. The medication was lasted for ten days. The microvessel density (MVD) in the xenograft was calculated by the method of using cell membrane differentiation antigen 34 (CD34) antibody marking new vascular endothelial cells. The protein and mRNA expressions of vascular endothelial growth factor (VEGF) and its receptor fetal liver kinase-1 (FLK-1), hypoxia inducible factor-1alpha (HIF-1alpha) in the tumor were determined using immunohistochemical assay and RT-PCR.

RESULTSThe MVD of ovarian carcinoma xenografts in the paclitaxel group, the high, medium, and low dose ZMYLG group obviously decreased, showing statistical difference when compared with the control group (P < 0.01, P < 0.05). Each ZMYLG dose group could down-regulate the protein and mRNA expressions of VEGF, FLK-1, and HIF-1alpha (P < 0.01, P < 0.05).

CONCLUSIONSZMYLG could inhibit neogenesis of tumor vessels. Its mechanisms might be associated with down-regulating the expression of HIF-1alpha, modifying the hypoxic state, inhibiting the expressions of VEGF and FLK-1, and exerting its anti-angiogenic effects.

Angiogenesis Inhibitors ; pharmacology ; Animals ; Cell Line, Tumor ; Drugs, Chinese Herbal ; pharmacology ; Female ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Mice ; Mice, Inbred BALB C ; Neoplasms, Glandular and Epithelial ; blood supply ; drug therapy ; Neovascularization, Pathologic ; prevention & control ; Ovarian Neoplasms ; blood supply ; drug therapy ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism ; Xenograft Model Antitumor Assays

BACKGROUNDAppendectomy is the traditional surgical procedure for correcting torsion of the adnexa. Although it prevents pulmonary embolism, ovarian necrosis, and secondary infection, it can have critical adverse effects on the ovarian function.

METHODSWe performed surgery for adnexal torsion in 12 patients, using high ligation of the ovarian vein, followed by removal of the ovarian tumor.

RESULTSBlood flow in the residual ovary gradually returned to normal within 1 - 3 months, and a dominant follicle could be seen in the residual ovary within 2 - 6 months post-surgery in all the 12 cases. Menstruation recovered in these three cases within 2 - 3 months. Postoperative intrauterine pregnancies occurred in two cases, with a corpus luteum graviditatis in the residual ovary in one case, while the other patient underwent labor after 13 months and a normal ovary on the affected side was seen at cesarean section.

CONCLUSIONSThis new surgical technique involving high ligation of the ovarian vein for adnexal torsion allowed successful preservation of the residual ovary and ovarian blood distribution, and can thus be used for the treatment of primary diseases of the ovary. The surgical procedure is simple, safe, and effective, and warrants extensive application in clinical practice.

Adolescent ; Adult ; Female ; Humans ; Ligation ; Ovarian Neoplasms ; physiopathology ; surgery ; Ovary ; blood supply ; physiopathology ; Torsion Abnormality ; surgery ; Ultrasonography, Doppler, Color

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 evaluate the efficacy and safety of transcatheter arterial embolization (TAE) of the ovarian arteries (OA) additionally supplying the tumor of pelvic cavity.

METHODSTAE of OA was performed in 63 patients with a pelvic tumor additionally supplied by the OA. The mean age of those patients was 43.6 years (range, 16 - 66 years). In this series, there were 28 cervical carcinomas, 22 uterus fibroids, 6 ovarian cancers, 3 choriocarcinomas, 2 uterine sarcomas, 1 fibrosarcoma, and 1 rectal carcinoma infiltrating the uterus and adnexa. Emergency TAE was performed in 8 patients due to colporrhagia. The embolization materials consisted of polyvinyl alcohol particles (PVA) in 24 patients, gelatin sponge particles in 10 cases, PVA + gelatin sponge particles in 26; and PVA + gelatin sponge particles + microcoils in 3 cases.

RESULTSThe OA embolization was successfully performed in all the 63 cases, including bilateral in 19 cases and unilateral in 44 cases (left 27, right 17). No complications related to the procedure were observed. Bleeding from the vagina in 8 patients ceased immediately after supplemental OA embolization, and no re-bleeding occurred in any of them during their hospital stay.

CONCLUSIONPelvic tumors may be supplied additionally by the ovarian arteries. Therefore, routine internal iliac artery/uterine artery chemoembolization or embolization may not effectively cure the tumors. Ovarian artery angiography should be routinely performed before interventional treatment. A supplementary selective ovarian artery chemoembolization or embolization is safe and effective in the management of pelvic tumors with additional blood supply from the ovarian arteries.

Adolescent ; Adult ; Aged ; Choriocarcinoma ; blood supply ; therapy ; Female ; Gelatin Sponge, Absorbable ; therapeutic use ; Humans ; Middle Aged ; Ovarian Neoplasms ; blood supply ; therapy ; Ovary ; blood supply ; Polyvinyl Alcohol ; therapeutic use ; Uterine Artery Embolization ; methods ; Uterine Cervical Neoplasms ; blood supply ; therapy ; Uterine Neoplasms ; blood supply ; therapy ; Young Adult

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 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 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 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

OBJECTIVETo evaluate the ability of multidetector computed tomography (MDCT) in differentiating ovarian tumors from non-ovarian masses.

METHODSForty-two cases with pelvic masses were examined with 16-row MDCT. All source image of each case was put into workstation for multi-planar reconstruction (MPR) and curved planar reconstruction(CPR). Axial image combined with 2D image was used for determining the relationship of the mass to ovarian vascular pedicle and identifying the normal ovary, which was compared with postoperative pathologic result and the finding during operation. All the data was compared using Fisher's exact test.

RESULTSThere were 28 ovarian tumors and 14 non-ovarian tumors in this series. If the ovarian vascular pedicle sign was used for determining whether the tumor was from the ovary or not, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy was 89.3%, 85.7%, 92.6%, 80.0% and 88.1%, respectively, with a significant difference in differentiating the tumor from the ovary or non-ovarian organs (P <0.05). If the identification of full normal ovary was used to determine non-ovarian origin of the tumor, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy was 50.0%, 100.0%, 100.0%, 80.0% and 83.3%, respectively, also with a significant difference in differentiating the tumors from the ovary or non-ovarian organs (P <0.05).

CONCLUSIONMDCT can clearly show the relationship of the tumor to the normal ovary and its vascular pedicle, which is very helpful in differentiating the ovarian tumors from a non-ovarian masses.

Adult ; Aged ; Cystadenocarcinoma, Mucinous ; diagnostic imaging ; Cystadenocarcinoma, Serous ; diagnostic imaging ; Cystadenoma, Mucinous ; diagnostic imaging ; Cystadenoma, Serous ; diagnostic imaging ; Diagnosis, Differential ; Female ; Gastrointestinal Stromal Tumors ; diagnostic imaging ; Humans ; Leiomyoma ; diagnostic imaging ; Middle Aged ; Ovarian Neoplasms ; diagnostic imaging ; Ovary ; blood supply ; diagnostic imaging ; Retroperitoneal Neoplasms ; diagnostic imaging ; Teratoma ; diagnostic imaging ; Tomography, X-Ray Computed ; methods ; Uterine Neoplasms ; diagnostic imaging ; Young Adult