Aug
12
Mon
2013
Invited Talk : Preclinical Outsourcing to India @ Sathyam Hall
Aug 12 @ 10:35 am – 11:00 am

ganeshGanesh Sambasivam, Ph.D.
CSO & Co-Founder, Anthem Biosciences India


Preclinical Outsourcing to India

The outsourcing segment is witnessing rapid changes with respect to the nature of work outsourced and the location. Cost is the major driver but other considerations such as infrastructure and government policies can also be important drivers for decision making. The last couple of years have been a trying time for all CROs. The global economic meltdown has hit research budgets especially hard. The new challenges facing Contract Research Organizations call for a radically revised approach and a new model that would push the boundaries of this business further and would blur the line between client and vendor further. I believe the term Contract Research Organization (CRO), is a misnomer to begin with (often confused with Clinical Research Organization), has now morphed into a new type of company viz Contract Innovation Services (CIS). Clients are no longer just happy to outsource odds and ends of the development piece but are looking to their vendors for a massive amount of innovation input. This input is increasingly across both the chemistry and discovery domains. This new paradigm calls for CIS companies to develop new platforms, create intellectual propertythat is of service to clients andinnovate processes to meet new found customer expectations.

Aug
13
Tue
2013
Invited Talk: Cancer Stem Cells – Target Colon Cancer @ Acharya Hall
Aug 13 @ 4:25 pm – 5:04 pm

ShrikantShrikant Anant, Ph.D.
The Department of Molecular & Integrative Physiology, Kansas University Medical Center, USA


Cancer Stem Cells: Target Colon Cancers

Shrikant Anant, Deep Kwatra and Dharmalingam Subramaniam

Colon cancer is a leading cause of cancer related deaths in the US, and its rate is increasing at an alarming rate in lndia. Recent studies have suggested the drug resistance role for a mall number of cells within a tumor called cancer stem cells. We identified the colon cancer stem cell marker DCLK1, a member of the protein kinase superfamily and the doublecortin family. The protein encodes a Cterminal serinethreonine protein kinase domain, which shows substantial homology to Ca2calmodulindependent protein kinase. Our current studies have been to identify compounds that can either affect DCLK1 expression or inhibits its activity as a way to inhibit cancer stem cells. Honokiol is a biphenolic compound that has been used in the traditional Chinese Medicine for treating various ailments. In vitro kinase assays with recombinant DCLK1 demonstrated that honokiol inhibits its kinase activity in a dose dependent manner. We therefore determined the effect of honokiol on stem cells. One method to look at effects on stem cells is perform a spheroid assay, where spheroids formation is suggested to maintain stemlike characteristic of cancer cells. Honokiol significantly suppressed colonosphere formation of two colon cancer cell lines HCT116 and SW480. Flow cytometry studies confirmed that honokiol reduced the number of DCLK1cells. A critical signaling pathway known to modulate intestinal stem cell proliferation is the Hippo signaling pathway, and deregulation of the pathway leads to tumor development. DCLK1cells had high levels of YAP1, the nuclear target of Hippo signaling. We determined the effect of honokiol on components of the hipposignaling pathway. Honokiol reduced the phosphorylation of Mst1/2, Lats1/2 and YAP1. Furthermore, honokiol treatment resulted in downregulation of YAPTEAD complex protein TEAD-1. Ectopic expression of the TEAD-1 partially rescued the cells from honokiol mediated growth suppression. To determine the effect of honokiol on tumor growth in vivo, nude mice harboring HCT116 tumor xenografts in their flanks were administered the compound intraperitoneally every day for 21 days. Honokiol treatment significantly inhibited tumor xenograft growth. Western blot and immunohistochemistry analyses demonstrated significant inhibition in the expression of stem marker and Hippo signaling proteins in the honokioltreated xenograft tissues. Taken together, these data suggest that honokiol is a potent inhibitor of colon cancer that targets DCLK1 stem cells by inhibiting Hippo signaling pathway.