China CRO Comapny




2017-04-21 15:13:59 | 日記
Imaging-guided preclinical trials of vascular targeting in prostate cancer
All content on this webpage originated from other webpages,Please check the medicilon's website for details. Medicilon is a Preclinical Research Outsourcing (CRO) company. With our more than 10 years experience on preclinical research services, we dedicated to provide our clients with customized preclinical services program in drug metabolism, pharmacokinetics, efficacy studies, and toxicology. We provide our clients a high-quality data and rapid turnaround time to support their drug development, preclinical studies and clinical research and to help them to select the most valuable drug candidates into clinical trials stage. Our preclinical research services consist in three major parts: pharmacokinetics, disease transplantation models and drug safety evaluation. Our services cover all of the aspects including design, in vivo studies, sample analysis, professional data analysis, IACUC review, and the preparation of application materials.
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Prostate cancer is the most common non-cutaneous malignancy in American men and is characterized by dependence on androgens (Testosterone/Dihydrotestosterone) for growth and survival. Although reduction of serum testosterone levels by surgical or chemical castration transiently inhibits neoplastic growth, tumor adaptation to castrate levels of androgens results in the generation of castration-resistant prostate cancer (CRPC). Progression to CRPC following androgen deprivation therapy (ADT) has been associated with changes in vascular morphology and increased angiogenesis. Based on this knowledge, we hypothesized that targeting tumor vasculature in combination with ADT would result in enhanced therapeutic efficacy against prostate cancer.
To test this hypothesis, we examined the therapeutic activity of a tumor-vascular disrupting agent (tumor-VDA), EPC2407 (Crolibulin™), alone and in combination with ADT in a murine model of prostate cancer (Myc-CaP). A non-invasive multimodality imaging approach based on magnetic resonance imaging (MRI), bioluminescence imaging (BLI), and ultrasound (US) was utilized to characterize tumor response to therapy and to guide preclinical trial design. Imaging results were correlated with histopathologic (H&E) and immunohistochemical (CD31) assessment as well as tumor growth inhibition and survival analyses.
Results: Our imaging techniques were able to capture an acute reduction (within 24 hours) in tumor perfusion following castration and VDA monotherapy. BLI revealed onset of recurrent disease 5-7 days post castration prior to visible tumor regrowth suggestive of vascular recovery. Administration of VDA beginning 1 week post castration for 3 weeks resulted in sustained vascular suppression, inhibition of tumor regrowth, and conferred a more pronounced survival benefit compared to either monotherapy.
The high mortality rate associated with CRPC underscores the need for investigating novel treatment strategies for this patient population. The results of our preclinical studies demonstrated the therapeutic potential of vascular targeting in combination with ADT against prostate cancer as well as highlight the capability of imaging to guide study design. Further investigation into the utility of VDAs in combination with ADT in prostate cancer is warranted.
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