Xenograft model ppt.pptx
- 1. • Animals model is important in this study to evaluate clinical performance of the potential drug lead, being more accurate representation of conditions mimicking human body. • For cancer studies most frequently used models are human tumor xenograft models in which immunodeficient mice are engrafted with human cells or tissues. • Thus, to bridge the translational gap between preclinical and clinical research, and validation of in vitro results animal studies is of utmost importance. RATIONALE
- 2. STUDY DESIGN •Species: Athymic female BALB-c/ nu-nu •Gender: Female •Age: 6 weeks (n=35) •Source: ACTREC Mumbai • Sample size was calculated using “resource equation method”, keeping 20% expected attrition factor and 5 groups, sample size calculated was n=7 for each group, resulting in total 35 mice. • Group I (C): corn oil as vehicle by oral gavage (n = 7) • Group II: bioactive compound 1 intraperitoneally (n=7) • Group III: bioactive compound 2 intraperitoneally (n=7) • Group IV: bioactive compound 1 + Doxorubicin intraperitoneally (n=7) • Group V: bioactive compound 2 + Doxorubicin intraperitoneally (n=7)
- 3. •Tumors progression was monitored •Body weights were recorded •Tumor volume measured= 613 mm3, 413 mm3 and 301 mm3 •1x106 MDA-MB-231 cells + matrigel (1:1 ratio) in PBS/media was made •0.1 mL of this suspension was injected subcutaneously on right flank of each mouse in each group. Tumor visible after 10 days in 3 mice. Mice divided into five groups i.e. control and treatment. PROCEDURES Full Blood Count (FBC) parameters , liver and kidney function will be checked using auto-analyzer
- 4. Substances Sites MDA-MB 231 breast cancer cell line Right flank Isolated Bio-active compound Intraperitoneal Injections Isolated Bio-active compound + Doxorubicin Intraperitoneal Injections • Details of Invasive Procedure/Therapeutic interventions: Tumors from treated and untreated mice will be harvested, and Histopathologic analyses for cancer markers will be done All experiments will be carried out in accordance with CPCSEA guidelines. All results and data will be reported according to the ARRIVE guidelines for Animal Research: For reporting in vivo experiments.
- 5. • A novel anti-cancer bio-active compound/s that is potent and can be used alone or in combination with existing chemotherapeutics as a chemo-preventive agent. • Identified bio-active compound/s to be screened for its absorption, dissolution, metabolism, excretion, and toxicity (ADMET) to serve as a New Chemical Entity (NCE). EXPECTED OUTCOMES