scholarly journals MRI-Based Characterization of Vascular Disruption by 5,6-Dimethylxanthenone-Acetic Acid in Gliomas

2009 ◽  
Vol 29 (8) ◽  
pp. 1373-1382 ◽  
Author(s):  
Mukund Seshadri ◽  
Michael J Ciesielski
Keyword(s):  
Acetic Acid ◽  
Relaxation Rate ◽  
Vascular Disrupting Agent ◽  
Vascular Disruption ◽  
Kaplan Meier ◽  
Apparent Diffusion ◽  
Adc Values ◽  
Magnetic Resonance Imaging Mri ◽  
Vascular Disrupting

The well-vascularized nature of gliomas has generated a lot of interest in antiangiogenic therapies. However, the potential of vascular disrupting agents (VDAs) against gliomas has not been investigated extensively. In this study, we examined the in vivo efficacy of the tumor-VDA 5,6-dimethylxanthenone-4-acetic acid (DMXAA) against gliomas. Contrast-enhanced magnetic resonance imaging (MRI) and diffusion-weighted MRI were used to characterize the vascular and cellular responses of GL261 and U87 gliomas to DMXAA treatment. Therapeutic efficacy was assessed by Kaplan-Meier survival analysis. Before VDA treatment, minimal enhancement was detected within the tumor in both models. Longitudinal relaxation rate ( R1 = 1/ T1) maps acquired 24 h after treatment showed marked extravasation and accumulation of the contrast agent in the tumor indicative of treatment-induced vascular disruption. Normalized change in relaxation rate (ΔR1) values of the tumor showed a significant increase ( P<0.01 GL261; P<0.05 U87) after therapy compared with baseline estimates. Mean apparent diffusion coefficient (ADC) values were significantly increased ( P = 0.015) 72 h after therapy in GL261 but not in U87 gliomas. Vascular disrupting agent therapy resulted in a significant ( P<0.01) increase in median survival in both models evaluated. The results highlight the potential of VDAs against gliomas and the utility of MRI in the assessment of glioma response to VDA therapy.

scholarly journals Activity of the Vascular-Disrupting Agent 5,6-Dimethylxanthenone-4-Acetic Acid against Human Head and Neck Carcinoma Xenografts

Neoplasia ◽  
2006 ◽  
Vol 8 (7) ◽  
pp. 534-542 ◽  
Author(s):  
Mukund Seshadri ◽  
Richard Mazurchuk ◽  
Joseph A. Spernyak ◽  
Arup Bhattacharya ◽  
Youcef M. Rustum ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Head And Neck ◽  
Head And Neck Carcinoma ◽  
Human Head ◽  
Vascular Disrupting Agent ◽  
Neck Carcinoma ◽  
Vascular Disrupting

Characterization of tumefactive demyelinating lesions using MR imaging and in-vivo proton MR spectroscopy

2008 ◽  
Vol 15 (2) ◽  
pp. 193-203 ◽  
Author(s):  
HS Malhotra ◽  
KK Jain ◽  
A Agarwal ◽  
MK Singh ◽  
SK Yadav ◽  
...  
Keyword(s):  
Resonance Spectroscopy ◽  
Post Contrast ◽  
Open Ring ◽  
Apparent Diffusion ◽  
Demyelinating Lesions ◽  
Fluid Attenuated Inversion Recovery ◽  
Adc Values ◽  
Mri Characteristics

Background and Objectives Diagnosis of tumefactive demyelinating lesions (TDLs) is challenging to both clinicians and radiologists. Our objective in this study was to analyze and characterize these lesions clinically, biochemically, electrophysiologically, and on imaging. Methods A retrospective analysis with prospective follow-up of 18 cases of TDLs was performed. Imaging included T2-, T1-weighted, fluid-attenuated inversion recovery (FLAIR), post-contrast T1-weighted, diffusion weighted imaging (DWI), and proton magnetic resonance spectroscopy (PMRS). Results All the lesions appeared hyperintense on T2 and FLAIR images. Increased Apparent diffusion coefficient (ADC) (0.93–2.21 × 10−3 mm2/s) in centre of the lesion was seen in 14/18 cases; however, peripheral restriction (ADC values 0.55–0.64 × 10−3 mm2/s) was noted in 11/18 cases. In all, 13/18 cases showed contrast enhancement with open ring ( n = 5), complete ring ( n = 1), minimal ( n = 4), and infiltrative ( n = 3) pattern of enhancement. Nine of these 13 cases also showed venular enhancement. On PMRS, nine showed glutamate/glutamine (Glx) at 2.4 ppm. Conclusion Clinical features along with several MRI characteristics such as open ring enhancement, peripheral restriction on DWI, venular enhancement, and presence of Glx on spectroscopy may be rewarding in differentiating TDLs from neoplastic lesions.

A phase I/II study of the vascular disrupting agent BNC105P in combination with gemcitabine-carboplatin in partially platinum-sensitive ovarian cancer patients in first or second relapse: An international collaborative group trial of ANZGOG and HOG.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS5612-TPS5612
Author(s):  
Danny Rischin ◽  
Daniela Matei ◽  
Jeffrey C. Goh ◽  
Michelle Margaret Vaughan ◽  
Philip James Beale ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase I ◽  
Phase Ii ◽  
Objective Response ◽  
Collaborative Group ◽  
Synergistic Activity ◽  
Vascular Disrupting Agent ◽  
Platinum Based Chemotherapy ◽  
Vascular Disrupting

TPS5612 Background: BNC105P is a tubulin polymerization inhibitor and a vascular disrupting agent (VDA). In vivo exposure to BNC105P leads to selective damage of tumor vasculature in both primary and metastatic lesions, causing disruption of blood flow to tumors, hypoxia, and associated tumor necrosis. BNC105P also has a direct anti-proliferative action on cancer cells, including ovarian cancer cell lines. Pre-clinical data has demonstrated synergistic activity of BNC105P when combined with platinum or with gemcitabine, supporting the proposed study design. This study will determine the safety and efficacy of BNC105P in ovarian cancer when used in combination with gemcitabine-carboplatin. The target population is women with ovarian or primary peritoneal cancers who progressed 4 to 9 months after first-line platinum based chemotherapy, or 4 to 12 months after second line platinum based chemotherapy. Methods: A single arm phase I will be used to determine the phase II dose for the triplet combination (3-6 subjects per dose level, maximum of 24 subjects). Four dose levels of BNC105P (12-16 mg/m2) and gemcitabine (800-1000 mg/m2) will be assessed. The dose of carboplatin will be set at AUC 4. Enrolment to cohort 2 started in January 2013. The phase II component will consist of a 2-arm, randomized (1:1) study of BNC105P, gemcitabine and carboplatin versus gemcitabine and carboplatin alone. The primary endpoint for the phase II trial is objective response rate (ORR, according to RECIST 1.1 and/or GCIG CA125 criteria. An ORR of 40% or more with the experimental regimen would be considered worthy of further investigation, assuming an ORR of 20% with the control regimen. 110 phase II participants are planned (N = 55/arm). Treatment allocation will be balanced using minimization for the study site, target lesions according to RECIST (present vs. absent), progression free interval from last platinum based chemotherapy regimen (<6 months vs 6 months or more), and first relapse vs. second relapse. Biomarker (tissue and blood-borne) sampling and PK analysis will also be undertaken. Clinical trial information: NCT01624493.

Differentiation of prostate cancer and stromal hyperplasia in the transition zone with histogram analysis of the apparent diffusion coefficient

2017 ◽  
Vol 58 (12) ◽  
pp. 1528-1534 ◽  
Author(s):  
Liu Xiaohang ◽  
Zhou Bingni ◽  
Zhou Liangping ◽  
Peng Weijun ◽  
Yang Xiaoqun ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Diffusion Coefficient ◽  
Apparent Diffusion Coefficient ◽  
Transition Zone ◽  
B Value ◽  
Histogram Analysis ◽  
Apparent Diffusion ◽  
Adc Values ◽  
The Mean ◽  
Magnetic Resonance Imaging Mri

Background Prostate cancer and stromal hyperplasia (SH) in the transition zone (TZ) are difficult to discriminate by conventional magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI). Purpose To investigate the apparent diffusion coefficient (ADC) of prostate cancer and SH in the TZ with histogram analysis and the ability of ADC metrics to differentiate between these two tissues. Material and Methods Thirty-three cancer and 29 SH lesions in the TZ of 54 patients undergoing preoperative DWI (b-value 0, 1000 s/mm2) were analyzed. All the lesions on the MR images were localized based on histopathologic correlations. The 10th, 25th, and 50th percentiles, and the mean ADC values were calculated for the two tissues and compared. The efficiencies of the 10th, 25th, and 50th ADC percentiles in differentiating the two tissues were compared with that of the mean ADC with receiver operating characteristic (ROC) analysis. Results The 10th, 25th, and 50th percentiles and mean ADC values (×10−3 mm2/s) were 0.86 ± 0.15, 0.89 ± 0.16, 0.94 ± 0.16, and 1.03 ± 0.17 in SH and 0.64 ± 0.12, 0.69 ± 0.12, 0.72 ± 0.16, and 0.83 ± 0.15 in TZ cancer, respectively. The parameters were all significantly lower in cancer than SH. The 10th ADC percentile yielded an area under the ROC curve (AUC) of 0.87 for the differentiation of carcinomas from SH, which was higher than the mean ADC (0.80) ( P < 0.05), and the AUCs of the 25th (0.82) and 50th (0.83) percentiles exhibited no differences from those of the mean ADC ( P > 0.05). Conclusion Histogram analysis of ADC values may potentially improve the differentiation of prostate cancer from SH in the TZ.

Histogram analysis of volume-based apparent diffusion coefficient in breast cancer

2017 ◽  
Vol 58 (11) ◽  
pp. 1294-1302 ◽  
Author(s):  
Ga Eun Park ◽  
Sung Hun Kim ◽  
Eun Jeong Kim ◽  
Bong Joo Kang ◽  
Mi Sun Park
Keyword(s):  
Breast Cancer ◽  
Diffusion Coefficient ◽  
Apparent Diffusion Coefficient ◽  
Ductal Carcinoma ◽  
Histogram Analysis ◽  
Invasive Ductal Cancer ◽  
Diffusion Weighted Images ◽  
Apparent Diffusion ◽  
Adc Values ◽  
Magnetic Resonance Imaging Mri

Background Breast cancer is a heterogeneous disease. Recent studies showed that apparent diffusion coefficient (ADC) values have various association with tumor aggressiveness and prognosis. Purpose To evaluate the value of histogram analysis of ADC values obtained from the whole tumor volume in invasive ductal cancer (IDC) and ductal carcinoma in situ (DCIS). Material and Methods This retrospective study included 201 patients with confirmed DCIS (n = 37) and IDC (n = 164). The IDC group was divided into two groups based on the presence of a DCIS component: IDC–DCIS (n = 76) and pure IDC (n = 88). All patients underwent preoperative breast magnetic resonance imaging (MRI) with diffusion-weighted images at 3.0 T. Histogram parameters of cumulative ADC values, skewness, and kurtosis were calculated and statistically analyzed. Results The differences between DCIS, IDC–DCIS, and pure IDC were significant in all percentiles of ADC values, in descending order of DCIS, IDC–DCIS, and pure IDC. IDC showed significantly lower ADC values than DCIS, and ADC50 was the best indicator for discriminating IDC from DCIS, with a threshold of 1.185 × 10–3 mm2/s (sensitivity of 82.9%, specificity of 75.7%). However, multivariate analysis of obtained ADC values showed no significant differences between DCIS, IDC–DCIS, and pure IDC ( P > 0.05). Conclusion Volume-based ADC values showed association with heterogeneity of breast cancer. However, there was no additional diagnostic performance in histogram analysis for differentiating between DCIS, IDC–DCIS, and pure IDC.

scholarly journals Vascular Disrupting Agent Arsenic Trioxide Enhances Thermoradiotherapy of Solid Tumors

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Robert J. Griffin ◽  
Brent W. Williams ◽  
Nathan A. Koonce ◽  
John C. Bischof ◽  
Chang W. Song ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Solid Tumors ◽  
Therapeutic Efficacy ◽  
Vascular Disrupting Agent ◽  
Vascular Disruption ◽  
Control Tumor Growth ◽  
Powerful Means ◽  
Control Tumor ◽  
Hypofractionated Radiation

Our previous studies demonstrated arsenic trioxide- (ATO-) induced selective tumor vascular disruption and augmentation of thermal or radiotherapy effect against solid tumors. These results suggested that a trimodality approach of radiation, ATO, and local hyperthermia may have potent therapeutic efficacy against solid tumors. Here, we report the antitumor effect of hypofractionated radiation followed by ATO administration and local 42.5 °C hyperthermia and the effects of cisplatin and thermoradiotherapy. We found that the therapeutic efficacy of ATO-based thermoradiotherapy was equal or greater than that of cisplatin-based thermoradiotherapy, and marked evidence ofin vivoapoptosis and tumor necrosis were observed in ATO-treated tumors. We conclude that ATO-based thermoradiotherapy is a powerful means to control tumor growth by using vascular disruption to augment the effects of thermal and radiation therapy.

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