Evaluation of Antiangiogenic Effects of a New Synthetic Candidate Drug KR-31831 on Xenografted Ovarian Carcinoma Using Dynamic Contrast Enhanced MRI

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 in stage IIIB squamous cell carcinoma of uterine cervix: reproducibility of measurement and preliminary outcome as a prognostic factor.

This study was performed to determine the reliability and replicability of IMD analysis using the Factor VIII immunohistochemical method. The following purpose was determining the relationship between IMD and clinical outcome in individual cervical cancer patient treated with radical radiotherapy. Twenty nine patients with stage IIIB cervical cancer were enrolled. Phase one was performed by using two pieces of tissue biopsy from different locations in the tumor from each patient. The IMD value was counted by the two pathologists after counterstaining by Factor VIII immunohistochemical method. No interobserver disagreement between the two pathologists was found (correlation coefficient = 0.92, 95% CI 0.82-0.96 for the first piece of tissue and 0.85, 95% CI 0.67-0.93 for the second piece). There was no variability in the IMD between the 2 pieces of tissue specimens from different locations of the tumor Phase two followed to evaluate the relationship between IMD and clinical outcome in individual cervical cancer patients. Because of the small sample size, different patients' characteristics, different treatment protocol and short term follow up, there is no statistically significant conclusion.

Color Doppler sonography with contrast in the differentiation of ovarian tumors

The objective of this study was to differentiate benign ovarian tumors from malignant ones before surgery using color and pulsed Doppler sonography, and to compare results obtained before and after use of contrast medium, thereby verifying whether contrast results in an improvement in the diagnostic sensitivity. METHODS: Sixty two women (mean age 49.9 years) with ovarian tumors were studied, 45 with benign and 17 with malignant tumors. All women underwent a transvaginal color Doppler ultrasonographic exam. A study of the arterial vascular flow was made in all tumor areas, as well as an impedance evaluation of arterial vascular flow using the resistance index. RESULT: Localization of the vessels in the tumor revealed a greater proportion of malignant tumors with detectable internal vascular flows (64 percent) than benign tumors with such flows (22 percent). There was a considerable overlap of these findings. The use of contrast identified a greater number of vessels with confirmation in the totality of tumors, but did not improve the Doppler capacity in tumoral differentiation. Malignant tumors presented lower values of resistance index than the benign ones, whether or not contrast was used. The cutoff value for resistance index that better maximized the Doppler sensitivity and specificity was 0.55. Through this value, an increase of the sensitivity after contrast use was obtained, varying from 47 percent to 82 percent, while specificity remained statistically unchanged. CONCLUSION: Although the injection of a microbubble agent improved the sensitivity of the method detecting vascularization of tumors, a positive finding for vascularization by this method was not clinically useful in the differentiation of benign and malignant ovarian tumors

Evaluación de masas ováricas con doppler color transabdominal / Evaluation of ovaric masses with transabdominal color Doppler

Se estudian 21 pacientes con tumores ováricos mediante Doppler Color transabdominal con el fin de predecir su carácter benigno o maligno de acuerdo a su patrón vascular. En los 4 cánceres ováricos, el índice de resistencia (IR) está bajo 0,70. En 16 tumores benignos, el IR se encuentra sobre 0,70. Sólo un tumor benigno correspondiente a un quiste tecaluteínico hemorrágico tuvo un patrón vascular de baja resistencia. La sensibilidad del método fue de un 100%, la especificidad de un 94,1%, el valor predictivo de un examen anormal de un 80%y el valor predictivo de un examen normal de un 100%