dabur

Est.1979

Providing Integrated Research Solutions in Preclinical Biology

Modules

In Vitro Pharmacology

Oncology


  • India’s largest tumor bank repository with human cancer cell lines representing 15 – 20 different cancer types
  • Characterized cell lines from authenticated sources
  • Inclusive of untransformed cell lines to enable early safety assessment
  • Drug resistant cell lines & primary cultures from human biopsies
  • Complete repertoire of viability & cytotoxicity assessment screens
  • Customized Molecular target based screens
  • Combination index studies for assessment of synergy

In Vitro Services

Model Evaluation of drug interactions in combination cancer chemotherapy by combination index method
Test system
  • Cancer cell lines
Methods
    Determination of % cytotoxicity & IC50 of individual drugs Selection of concentrations around IC50 for combination studies Testing all possible combinations of drugs for combined cytotoxicities Calculation of Combination Index (CI)
  • CI=1 – Synergy
  • CI=1 – Additive
  • CI=1 – Antagonism
End points
Categorization of drug combinations as synergistic/additive/antagonistic for each combination tested.
 
Model DETERMINATION OF SYNERGISTICALLY EFFICACIOUS COMBINATION(S) OF CISPLATIN AND DOXORUBICIN IN HepG-2 CELL LINE IN VITRO BY COMBINATION INDEX METHOD
Test system
    Hepatocellular carcinoma (HepG-2)
Methods
  • Cisplatin
  • Doxorubicin
End points
Cells were treated at fixed IC50 of one drug (Cisplatin/Doxorubicin) in combination with variable concentrations of the other (Cisplatin/Doxorubicin). MTT assay CI value was calculated to assess the synergistic effect of test items Synergism, additive or antagonism was based on the following criteria:
  • CI = 1 Synergism
  • CI=1 Additive
  • CI=1 Antagonism
Modelin vivo: model to quantitate intracellular uptake and localization of drugs (e.g. Nanoparticle/liposomal formulations)
Test system
  • Human tumor cell lines
  • Human normal cells/cell lines
Methods
  • Treatment of target cell lines with drug
  • Quantitative analysis – Visualization of Cellular uptake, delivery and subcellular distribution of drugs in target cell lines by TEM Transmission Electron Microscopy)/ Fluorescence microscopy
  •  Quantitative analysis – Measurement of intracellular concentrations of drug by bioanalytical methods (HPLC and LC/MS)
End points
  • Intracellular accumulation of drugs
  • Sub cellular distribution/localization
  • Uptake in non target tissues
  • Dose/Time kinetic profiles for drug uptake
  • Correlation with biological activity
  • Uptake/Transport by endocytotic/Non endocytotic routes
ModelAssessment of anti-cancer activity of the compounds using tube formation assay
Test system
  • HUVEC Cells
Methods
  • Seeding of HUVEC cells on matrigel
  • Application of vehicle and compound of interest at appropriate concentrations
  • Validation with Combretastatin A4 or client defined reference standards
End points
    Quantitative analysis of –
  • Branch area
  • Branch points
  • Tube length
  • Photomicrographs

Cell Migration assay

ModelAssessment of anti-cancer activity of the compounds using cell migration assay
Test systemHUVEC Cells
Method
  • Seeding of HUVEC cells
  • Creation of wound on surface of culture
  • Application of vehicle and Test item at appropriate concentrations
End points
  • Number of cells migrated to wound area

In vitro Angiogenesis model

ModelAssessment of anti-cancer activity of the compounds using tube formation assay
Test systemHUVEC Cells
Method
  • Seeding of HUVEC cells on matrigel
  • Application of vehicle and compound of interest at appropriate concentrations
  • Validation with Combretastatin A4 or client defined reference standards
End points
Quantitative analysis of –
  • Branch area
  • Branch points
  • Tube length
  • Photomicrographs

In vitro angiogenesis VEGF

ModelAssessment of VEGF, bFGF & Endostatin
Test systemHUVEC, MDA-MB-231, MCF-7, HCT-116 etc
Method
  • Seeding of predetermined number of Cell Type
  • Application of vehicle and Test item at appropriate concentrations
  • Incubation for 48 to 72hr
  • Estimation of VEGF, bFGF & endostatin concentration in culture supernatants
End points
  • % Inhibition
  • IC50 value

ModelComplete repertoire of Screens for assessment of Programmed cell death to enable selection of Proapoptotic & antiapoptotic molecules
Test system
  • Human normal cells/cell lines
  • Human cancer cell lines
Apoptotic Pathways
  • Death receptor and mitochondrial pathway
End points
  • Externalization of Phosphatidyl Serine (PS) on plasma membrane by Annexin-V staining
  • Loss of transmembrane mitochondrial potential by JC-1 staining
  • Quantitation of Reactive oxygen species (ROS)
  • Levels of pro-apoptotic and anti-apoptotic proteins
  • Ras-ERK kinases
  • Caspase-3 activation
  • PARP cleavage
  • DNA fragmentation
  • Micronuclei staining
  • Cell Cycle analysis

ModelAssessment of anti-leukemic activity of the compounds in SCID mice
Test systemSCID mice
Models
  • Intravenous inoculation of leukemic cell line
  • Administration of test item and reference item at predetermined time
  •  Observation of animals for defined time period
  •  Observation of animals in satellite group for occurrence of chloroma
End points
  • Percentage Change in body weight
  • Survival rate of animals
  • Clinical signs & symptoms
  •  Quantification by flow cytometry analysis in bone marrow & peripheral blood
    — Standard surface specific antigen staining – CD45
    — Lineage specific antigen staining
  •  Histopathology

Core team of Biochemists, Cell biologists & Molecular Biologists to Develop customized client defined target based screens Repertoire of screens
  • Enzyme assays
  • Cell based methods
  • Cell free screens
  • Functional assays
  • Semi-automatic Homogeneous screens for focused targets
Target Classes
  • Cytoskeletal proteins
  • Enzymes
  • Nuclear receptors
  • Kinases
  • Phosphatases
  • Hormones

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