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Signaling Pathways Produced
By Combining DsRNA with
Paclitaxal to treat Ovarian
Cancer
Switu Patel
Ovarian Cancer
Fifth in, malignant deaths of US women
Cause unknown
Common Therapy: surgery +
chemotherapy
Dual treatments
In Van et al. they combined Double
stranded RNA (DsRNA) with therapeutic
agents like paclitaxel and carboplatin to
get a significant decrease in cell viability
DsRNA is known to stop the
immunosuppression signals caused by
ovarian tumor cells and activate four
innate immune receptors
Cell response to dsRNA
When stimulated within a cell, it activates
four receptors.
Cell response to dsRNA
DsRNA activates Protein Kinase and gives it a pro-apoptotic
or cell killing response
Cell response to dsRNA
Which then phosphorylates EIF2S which stops translation
Cell response to dsRNA
PKR also activates FADD which
further activates caspase 8
Apoptosis
Cell response to dsRNA
Other pathways that influence
apoptosis
Apoptosis
Individual vs. Combined treatments
Proposal question
What essential pathways related to apoptosis
are activated by dsRNA + paclitaxel?
◦ These pathways will serve as biomarkers for
individual patients
Experiment
Apoptotic PCR Array
For:
◦ Untreated
◦ Treated: dsRNA, paclitaxel, dsRNA + paclitaxel
Hypothetical Results
Caspase 3
Results
We expect that the samples treated with
combined therapeutic agents will have a
higher levels of apoptotic pathway
molecules or lower CT values, than the
individual treated samples.
However, it may cause down regulation of
anti-apoptotic proteins or cause up
regulation of pro-apoptotic or cell death
proteins.