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About OMICS Group

About OMICS Group.

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About OMICS Group

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  1. About OMICS Group OMICS Group International is an amalgamation of Open Access publications and worldwide international science conferences and events. Established in the year 2007 with the sole aim of making the information on Sciences and technology ‘Open Access’, OMICS Group publishes 400 online open access scholarly journals in all aspects of Science, Engineering, Management and Technology journals. OMICS Group has been instrumental in taking the knowledge on Science & technology to the doorsteps of ordinary men and women. Research Scholars, Students, Libraries, Educational Institutions, Research centers and the industry are main stakeholders that benefitted greatly from this knowledge dissemination. OMICS Group also organizes 300 International conferences annually across the globe, where knowledge transfer takes place through debates, round table discussions, poster presentations, workshops, symposia and exhibitions

  2. About OMICS Group Conferences OMICS Group International is a pioneer and leading science event organizer, which publishes around 400 open access journals and conducts over 300 Medical, Clinical, Engineering, Life Sciences, Phrama scientific conferences all over the globe annually with the support of more than 1000 scientific associations and 30,000 editorial board members and 3.5 million followers to its credit. OMICS Group has organized 500 conferences, workshops and national symposiums across the major cities including San Francisco, Las Vegas, San Antonio, Omaha, Orlando, Raleigh, Santa Clara, Chicago, Philadelphia, Baltimore, United Kingdom, Valencia, Dubai, Beijing, Hyderabad, Bengaluru and Mumbai.

  3. A natural biodrug targeting melanoma cells with varying p53 status August 5, 2014 2nd International Summit on Integrative Biology PhD Candidate: Neha Singh Principal Supervisor: Dr. Rupinder K Kanwar Associate Supervisor: Professor Jagat R Kanwar Nanomedicine laboratory of immunology, molecular and biomedical Research (NLIMBR), School of Medicine (SoM), Faculty of health, Deakin University, Geelong, Vicotria 3216 Australia sne@deakin.edu.au

  4. FACING MELANOMA AND ITS FACTS • Melanoma is defined as malignant (fatal) tumour of the melanocytes or skin cells. • It is one of the most rarely occurring skin cancers but accounts for 75% of the deaths caused due to skin cancer. • The highest rates of incidence of melanoma are in AUSTRALIA and NEW ZEALAND. • It is the most common cancer detected in people between the age group of 15-24. • Highly metastatic cancer- first organ of metastasis being the brain.

  5. CURRENT THERAPEUTIC OPTIONS- ITS LIMITATIONS • FDA approved only one drug for the treatment of metastatic melanoma- dacarbazine (DTIC). • Continuous chemotherapy- very painful for the patients. • Chemotherapeutics developed for melanoma fail to yield success rates due to primary and secondary mutations in genes like BRAF helping melanoma become drug resistant.

  6. Factors that contribute to MDR • Molecular players • P- glycoprotein (P-gp) • Member of the ATP binding cassette (ABC) transporters family. • Overexpressed in most cancer types. • Upon activation- pumps out drugs from the cancer cells leading to resistance towards those drugs. • One of the most crucial molecules that helps in acquiring drug resistance. • Other important players include survivin, ABCG2 & MDR2

  7. Anti-apoptotic protein-Survivin • Survivin- member of the inhibitor of apoptosis (IAP) family. • Aids in mitotic spindle assembly formation helping in cell division and proliferation. • Overexpressed in all the tumour cells and shown to play a role in drug resistance tumours. • Stem cells • One of the most recently understood markers that aid in Multiple-drug resistance (MDR). • Population of cells within a tumour that have the ability to sustain therapy hence helping in regrowth of the tumour. • More rigid population, hence difficult to target using conventional chemotherapeutic options.

  8. Role of P-gp in helping acquire MDR Kanwar JR, Singh N, Kanwar RK. Nanomedicine (2011)

  9. LACTOFERRIN- A POSSIBLE ANSWER? • Natural-bovine lactoferrin is a 80kDa milk protein, also called translactoferrin. • Long known therapeutic molecule with its antimicrobial, antiviral, anti-inflammatory, anti-oxidant and anticancer properties. • Previous studies from our lab have demonstrated the role of lactoferrin as • An anti-oxidant in human gut epithelial cells and colon cancer (Kanwar et al, Anticancer Agents Med Chem. (2011) 9:762-771). • An anticancer agent in mouse melanoma cell lines and lymphomas (Kanwar et al, Immunol Cell Biol. (2008) 86(3):277-288).

  10. Advantages of using lactoferrin as a therapeutic molecule • No side effects as it is a natural molecule. • Enhances the immune system against cancer. • Helps in targeting various conditions like oxidative stress in the tumour microenvironment.

  11. Aims • To isolate and characterize bovine lactoferrin protein – both iron-free form (Apo-bLf) and iron-saturated form (Fe-bLf). • To check the cytotoxic and apoptotic effects of Apo-bLf and Fe-bLf on p53 wild-type SK-MEL-2 cell line and p53 mutant-type SK-MEL-28 cell line. • To check the effects of p53 on stem cell markers like P-gp, CD133 and survivin to target drug resistance in melanoma.

  12. INTERNALISATION STUDIES SK-MEL-28 SK-MEL-2 a a A A b b c c a a B B b b c c A- Apo-bLf; B-Fe-bLf (a) 30 min (b) 4 h (c) 6h Time dependent internalisation of Apo-bLf and Fe-bLf CONCLUSION: Apo-bLf and Fe-bLf internalise into SK-MEL-2 and SK-MEL-28 within 30 min and this is through receptor mediated endocytosis.

  13. Gene expression patterns of various lactoferrin receptors Lane 1: Untreated Control Lane 2: Native-bLf 20 nM Lane 3: Native-bLf 40 nM Lane 4: Apo-bLf 20 nM Lane 5: Apo-bLf 40 nM Lane 6: Fe-bLf 20 nM Lane 7: Fe-bLf 40 nM CONCLUSION: Treatment with lactoferrin enhances the expression of transferrin receptor in SK-MEL-28 and LRP-1, TfR1 and LfR in SK-MEL-2 proving that lactoferrin requires these receptors for internalisation

  14. CYTOTOXICITY AND PROLIFERATIVE EFFECTS OF BOVINE LACTOFERRIN • Native-bLf was cytotoxic to both SK-MEL-2 and SK-MEL-28 at concentrations of 10 nM, 20 nM and 40 nM. • Apo-bLf was cytotoxic to SK-MEL-28 at 20 nM and 40 nM. • Fe-bLf was cytotoxic to SK-MEL-2 at 10 nM, 20 nM and 40 nM concentrations.

  15. PROLIFERATIVE EFFECTS OF BOVINE LACTOFERRIN • Dose-dependent decrease in the cell proliferation was noted with Native-bLf. • Apo-bLf showed reduced proliferation of SK-MEL-28 with treatments. • Fe-bLf reduced the proliferative capacity of SK-MEL-2.

  16. ANNEXIN-V STUDIES TO CONFIRM CELL DEATH IN MELANOMA CELLS • CONCLUSIONS • The mode of cell death in SK-MEL-28 cells was mainly through necrosis. • Maximum cells were noted in the early apoptotic region in SK-MEL-2 cells with bLf treatments. FACS graphs and histograms representing ANNEXIN-V staining

  17. Effect of Apo-bLf and Fe-bLf on metastatic potential of SK-MEL-2 and SK-MEL-28 CONCLUSION: bLf was able to reduce migratory potential of SK-MEL-28 and SK-MEL-2.

  18. CONCLUSION: bLf was able to reduce invasive potential of SK-MEL-28 and SK-MEL-2.

  19. 3D culture studies of SK-MEL-2 and SK-MEL-28 • CONCLUSIONS • Reduction in the area of tumour spheroids was noted with Apo-bLf treatments in SK-MEL-28 cells. • Fe-bLf significantly reduced the tumour spheroid size in SK-MEL-2 cells in a dose-dependent manner.

  20. Effect of bLf on drug resistant marker P-gp in SK-MEL-28 Cells CONCLUSION: A significant decrease in P-gp in SK-MEL-28 cells was noted with bLf treatments (p≤0.001) proving the role of bLf as an agent in targeting drug resistant markers.

  21. Effect of bLf on drug resistant markers P-gp in SK-MEL-2 Cells CONCLUSION: A significant decrease in P-gp in SK-MEL-2 cells was noted with bLf treatments (p≤0.001) proving the role of bLf as an agent in targeting drug resistant markers.

  22. Effect of bLf on drug resistant marker CD133 CONCLUSION: A significant decrease in CD133 was noted with bLf treatments (p≤0.001) proving the role of bLf as an agent in targeting drug resistant markers.

  23. Effect of bLf on drug resistant marker Survivin CONCLUSION: A significant decrease in Survivin was noted with bLf treatments (p≤0.001) proving the role of bLf as an agent in targeting drug resistant markers.

  24. Study of mechanism of apoptosis in SK-MEL-2 CONCLUSION: Upregulation of TRAIL, FADD and Fas receptors along with significant upregulation of p53 protein was noted with Native-bLf, Apo-bLf and Fe-bLf treatments indicating extrinsic pathway of apoptosis in SK-MEL-2.

  25. Study of mechanism of apoptosis in SK-MEL-28 CONCLUSION: Upregulation of TRAIL, FADD and Fas receptors along with significant upregulation of 3 isoforms of p53 protein was noted with Native-bLf, Apo-bLf and Fe-bLf treatments indicating extrinsic pathway of apoptosis in SK-MEL-28.

  26. CONCLUSIONS AND FUTURE PERSPECTIVE • Both Apo-bLf and Fe-bLf were significant in causing cytotoxicity to SK-MEL-2 and SK-MEL-28 cells. • Apo-bLf and Fe-bLf were able to reduce the migratory, invasive and clonogenic potential of SK-MEL-28 and SK-MEL-2 respectively. • These proteins also proved effective in reducing the 3D tumour spheroid area proving its potential anti-tumour effect in an in vivo condition. • Extrinsic pathway of apoptosis was more prominent with Apo-bLf and Fe-bLf treatments in both the cell lines. • Receptor mediated internalisation of these cells caused activation of TRAIL, FADD and Fas leading to upregulation of p53 in both the cell lines.

  27. ACKNOWLEDGEMENTS • Dr. Rupinder K Kanwar (Principal Supervisor) • Professor Jagat R Kanwar (Associate Supervisor) • Elizabeth Laidlaw and Helen Barry (Technical Officers) • Helen Woodall (International Partnerships Coordinator) • School of Medicine (SoM) • Deakin University Post Graduate Research Scholarship • Australia-India Strategic Research Fund (AISRF-2009-2011) • All lab mates • 2nd International Summit on Integrative Biology • Paul Wesley (for all the communication and help)

  28. THANK YOU

  29. Let Us Meet Again We welcome you all to our future conferences of OMICS Group International Please Visit:www.omicsgroup.com www.conferenceseries.com www.pharmaceuticalconferences.com

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