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Anticancer Drug Screening ‘ Cancer’: a fatal disease of uncontrolled proliferation of genetically altered cells. In all known cases, cancer cells are derived from the repeated divisions of a mutant cell. Some of these mutations may be due to the effects of carcinogens, such as tobacco smoke, radiation, chemicals or infectious agents. A few other cancer-promoting mutations may be acquired through errors in DNA replication.  Genetic alterations that render a normal cell cancerous usually arise in two classes of genes termed the oncogenes and tumors suppressors.  Activate the cancer promoting oncogenes and/or inactivate the tumor suppressor genes.  Cancer
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Need for Novel Anticancer Agents ,[object Object],[object Object],[object Object],[object Object]
In vitro cytotoxicity studies ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object]
[object Object],[object Object],[object Object],[object Object]
Figure-1: Normal (Control) HeLa cells  showing no signs of necrosis or apoptosis Figure-2: Effect of Doxorubicin on HeLa cells showing cell shrinkage, nuclear condensation  Figure-3: Effect of compound - 6 on HeLa cells showing apoptosis and cell necrosis Figure-4: Effect of Com -4 on HeLa cells showing cell shrinkage and nuclear condensation
Cell Cycle Analysis Control R6 R3 R4 R5 DOX R6 R3 R4 R5 Phase Sub-G 0 G 0 -G1 S G 2 -M Phase Sub-G 0 G 0 -G 1 S G 2 -M % cells 1.15 74.27 6.34 18.65 % cells 2.22 16.62 4.01 76.76 Figure-7: Control HeLa cells  showing normal cell cycle  Figure-8: Doxorubicin showing prominent G 2 -M phase arrest
BE-7 R5 R2 R3 R4 BE-4 R6 R3 R4 R5 Phase Sub-G 0 G 0 -G 1 S G 2 -M Phase Sub-G 0 G 0 -G 1 S G 2- M % cells 27.87 44.46 9.73 17.91 % cells 0.62 88.41 1.04 9.72 Figure-9: Com-6 treated  HeLa cells  showing sub G 0  (apoptotic) arrest Figure-10: Com-4 treated HeLa cells showing prominent  G 0 -G 1   phase arrest
 
In Vivo Study Goals: Animal Models ,[object Object],[object Object],[object Object],[object Object],[object Object]
Animal Models Proof of Principle ,[object Object],[object Object],[object Object],[object Object]
Ideal Animal Model ,[object Object],[object Object],[object Object],[object Object],“ There is no perfect tumor model”
Animal Models in Cancer ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
IN VIVO  ANTICANCER ACTIVITY   ,[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],Group No. Treatment Dose Route 1 Control-S (2% gum acacia) Equivolume i.p 2 Cisplatin 3.5 mg/kg i.p 3 Control-A (2% gum acacia) Equivolume i.p 4 Compound-A 50 mg/kg i.p 5 Control-B Equivolume i.p 6 Compound-B 50 mg/kg i.p 7 Control-C Equivolume i.p 8 Compound-C 50 mg/kg i.p
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Solid tumor model using DLA cell lines ,[object Object],[object Object],[object Object],[object Object],[object Object]
Parameters Monitored ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Human Tumor Xenografts ,[object Object],[object Object],[object Object],[object Object],[object Object]
Murine Xenograft Sites ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Xenograft Study Endpoints ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Xenograft Tumor Weight Change ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Xenograft Advantages ,[object Object],[object Object],[object Object],[object Object]
Xenograft Disadvantages ,[object Object],[object Object],[object Object],[object Object],[object Object]
Other Animal Models ,[object Object],[object Object],[object Object],[object Object],[object Object]
In Vivo Hollow Fiber Assay ,[object Object],[object Object],[object Object],[object Object],[object Object]
Thank you

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Anticancer drug screening

  • 1. Anticancer Drug Screening ‘ Cancer’: a fatal disease of uncontrolled proliferation of genetically altered cells. In all known cases, cancer cells are derived from the repeated divisions of a mutant cell. Some of these mutations may be due to the effects of carcinogens, such as tobacco smoke, radiation, chemicals or infectious agents. A few other cancer-promoting mutations may be acquired through errors in DNA replication. Genetic alterations that render a normal cell cancerous usually arise in two classes of genes termed the oncogenes and tumors suppressors. Activate the cancer promoting oncogenes and/or inactivate the tumor suppressor genes. Cancer
  • 2.
  • 3.
  • 4.
  • 5.
  • 6.
  • 7. Figure-1: Normal (Control) HeLa cells showing no signs of necrosis or apoptosis Figure-2: Effect of Doxorubicin on HeLa cells showing cell shrinkage, nuclear condensation Figure-3: Effect of compound - 6 on HeLa cells showing apoptosis and cell necrosis Figure-4: Effect of Com -4 on HeLa cells showing cell shrinkage and nuclear condensation
  • 8. Cell Cycle Analysis Control R6 R3 R4 R5 DOX R6 R3 R4 R5 Phase Sub-G 0 G 0 -G1 S G 2 -M Phase Sub-G 0 G 0 -G 1 S G 2 -M % cells 1.15 74.27 6.34 18.65 % cells 2.22 16.62 4.01 76.76 Figure-7: Control HeLa cells showing normal cell cycle Figure-8: Doxorubicin showing prominent G 2 -M phase arrest
  • 9. BE-7 R5 R2 R3 R4 BE-4 R6 R3 R4 R5 Phase Sub-G 0 G 0 -G 1 S G 2 -M Phase Sub-G 0 G 0 -G 1 S G 2- M % cells 27.87 44.46 9.73 17.91 % cells 0.62 88.41 1.04 9.72 Figure-9: Com-6 treated HeLa cells showing sub G 0 (apoptotic) arrest Figure-10: Com-4 treated HeLa cells showing prominent G 0 -G 1 phase arrest
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