Download to read offline
![Screening Synthetic Analogs of Pactamycin for Anti-Cancer
Properties in Melanoma
Asha Pantula1, Evan Carpenter2, Monet Miller2, Gitali Ganguli-Indra2,3,4, Arup Indra2,3,4,5
Background
Materials
Results
Future Developments
Acknowledgments
• Melanoma: One of the most
dangerous and treatment
resistant human cancers (1).
Before treatment 15 weeks of Vemurafenib (treatment) 32 weeks of
Vemurafenib
Need: To find a potent yet still
efficient therapy(2).
• Pactamycin: a natural
compound with many
anticancer properties and
high cytotoxicity levels (4).
• Synthetic analogs have been
produced, hoping to lower
toxicity levels (3,4).
Worked with A375 line of human melanoma cells
Added analogs of Pactamycin and Vehicle (DMSO)
1. TM026 is a positive control
2. TM117 and TM118: different analogs of Pactamycin
Screened compounds through high throughput characterization
Added cell titer glow reagent which measures ATP
(cell energy) and gives ATP count
Bright-field microscopy to identify impact on morphology
Immunocytochemistry to observe impact on proliferation
• Analogs showing anti-
cancer properties (TM026,
TM122, and TM123) will be
tested on normal human
melanocytes, to test toxicity
levels.
• There will also be new
research on the mechanism
of action of these
compounds as well as the
morphology of the cells.
• TM026 showed strong anti-
cancer properties against
melanoma like previously
shown in head and neck
squamous cell carcinoma
cells
• TM122, and TM123 showed
strong anti-cancer traits
against metastatic
melanoma.
• TM117, TM118, TM119,
TM120, TM121, TM124, and
TM125 analogs had no
impact on the growth of the
metastatic melanoma,
A375 line of Melanoma
containing BRAF (V600E)
mutation, analogs of Pactamycin,
Growth Media (DMEM),Vehicle
(DMSO), Cell Titer Glo Assay kit
Methods
Figure A: Graph shows
that TM026 has an IC-50
value of 3.045 uM . Neither
TM117 nor TM118 showed
any anti-cancer activity in
A375 cell line.
I would like to thank Saturday
Academy for the opportunity, the
College of Pharmacy at OSU,
and all the members of the Indra
lab for their help and support.
Objective
Figure B: TM122, TM123
and TM026 all showed
anti-cancer activity against
melanoma cells.
References
1Nikolaou, Vasiliki A. et al. Melanoma: New Insights and New Therapies." J Invest Dermatol.
2012 Mar;132(3 Pt 2):854-63.
2Wagle, Nikhil, et al. "Dissecting Therapeutic Resistance to RAF Inhibition in Melanoma by
Tumor Genomic Profiling." Journal of Clinical Onocology 29.22 (2011): 3085-096.
3Lu W, Roongsawang N, Mahmud T. Biosynthetic Studies and Genetic Engineering of
Pactamycin Analogs with Improved Selectivity toward Malarial Parasites. Chem Biol.
2011;18: 425–431. pmid:21513878
.
1Saturday Academy, 2College of Pharmacy, 3Linus Pauling Institute, Oregon State University; Corvallis, OR
4Dept. of Dermatology, 5Knight Cancer Institute, Oregon Health & Sciences University; Portland, OR
Conclusions
Figure C: Bright-field microscopy shows compound TM026’s
(right) ability to kill melanoma cells thereby reducing cell density,
and reduce cell size and shape.
Figure D: Immunocytochemistry using anti-Ki67 antibody exhibits
reduced proliferation of TM026 treated melanoma cells compared
to the vehicle control.
A.
B.
E.
Figure E: Graph shows less cells treated
with TM026 inhibit Ki67 (marker for
proliferation)
Effect of TM026 on
Proliferation
- 4 - 3 - 2 - 1 0 1 2
0
2 5
5 0
7 5
1 0 0
1 2 5
E f f e c t o f P a c t a m y c i n A n a l o g s o n A 3 7 5 l i n e
L o g D o s e C o n c e n t r a t i o n
%CellSurvival
T M 0 2 6
T M 1 1 7
T M 1 1 8
P a c t a m y c i n A n a l o g u e D o s e R e s p o n s e C u r v e i n A 3 7 5
l o g [ C o m p o u n d ] ( M )
%CellSurvival
- 4 - 3 - 2 - 1 0 1 2
0
2 5
5 0
7 5
1 0 0
1 2 5
T M 0 2 6
T M 1 1 7
T M 1 1 8
T M 1 1 9
T M 1 2 0
T M 1 2 1
T M 1 2 2
T M 1 2 3
T M 1 2 4
T M 1 2 5
U.S. Melanoma Incidence*. Digital image. Planning Cancer.
N.p., n.d. Web.
To determine if synthetic analogs of
Pactamycin have anti-cancer
properties and less toxicity levels
against human metastatic melanoma.
Poster 1:](https://image.slidesharecdn.com/symprep2019online-190716201748/85/Saturday-Academy-ASE-Program-Symposium-Preparation-2019-14-320.jpg)
Uploaded byLibby Van Vleet
Saturday Academy ASE Program Symposium Preparation 2019
The document provides information about an upcoming ASE Symposium on August 16th where students will present their summer research accomplishments through oral presentations and posters. It outlines the schedule of events, which includes introductions, presentations, lunch, and a networking session. Students are given tips and guidelines for preparing their oral presentations, posters, summary reports, and thank you letters to share at the symposium. They are encouraged to practice their talks and rehearse their "pitch" for the poster session. Support resources are also listed to help students succeed at the symposium.
Saturday Academy ASE Program Symposium Preparation 2019
- 1. Showcase your accomplishments! StaceyJohnson, ASETeacher Monitor Preparing for the ASE Symposium, Friday, August 16th at UP
- 2. prepare * practice* prepare * practice What Happens AtThe Symposium? • Introductions and Keynote Speaker • Oral Presentations • Lunch and Recognitions • Poster Presentations • Networking
- 3.
- 4. • Dress • OralPresentations • SymposiumTitle & Registration • Poster • ASE Summary • ThankYou Letter saturdayacademy.org/ase-symposium What’s coming up?
- 5. Oral Presentations • Sessionshave 3-4 presentations • 10-30 attendees per session • Each talk is 12 minutes • Plus 3 minutes for questions • Joint talks allowed (doubles time) https://www.youtube.com/watch?v=S5c1susCPAE
- 6. • Model aspeaker you like • Pose a question or tell a story • Use simple terms & clean design • Think about your audience CyaberAcademy: ContentPreparing & Giving your Presentation
- 7.
- 8. Thinking about GoodPresentations • Prepare an outline • Use story, build background • Think about your title
- 9. • “We’ve GotYourRack: Discovering Engineering at Yakima Products Inc.” • “Risky Business” • “An Analysis of the Conductivity of Encap Polymer AdhesivesThrough Impedance Spectroscopy” • “Recovery and Digitization of HistoricTide Data“ Register online by July 22nd SymposiumTitle & Registration: examples
- 10. CyaberAcademy: Content saturdayacademy.org/current-interns MakingYour Poster– Details • Follow ASE poster rules • Check out the handbook… “Preparing for the ASE Symposium”
- 11. CyaberAcademy: ContentMakingYour Poster- Displays • Two posters will hang on a stand with binder clips. • Do NOT use cardboard or foam core board 3 ft 3 ft
- 12. CyaberAcademy: ContentExample Format Start Now!
- 13. CyaberAcademy: ContentPoster Activity •Look at the following posters • Focus on first impressions What do you like about these posters? What is distracting or hard to read about these posters?
- 14. Screening Synthetic Analogsof Pactamycin for Anti-Cancer Properties in Melanoma Asha Pantula1, Evan Carpenter2, Monet Miller2, Gitali Ganguli-Indra2,3,4, Arup Indra2,3,4,5 Background Materials Results Future Developments Acknowledgments • Melanoma: One of the most dangerous and treatment resistant human cancers (1). Before treatment 15 weeks of Vemurafenib (treatment) 32 weeks of Vemurafenib Need: To find a potent yet still efficient therapy(2). • Pactamycin: a natural compound with many anticancer properties and high cytotoxicity levels (4). • Synthetic analogs have been produced, hoping to lower toxicity levels (3,4). Worked with A375 line of human melanoma cells Added analogs of Pactamycin and Vehicle (DMSO) 1. TM026 is a positive control 2. TM117 and TM118: different analogs of Pactamycin Screened compounds through high throughput characterization Added cell titer glow reagent which measures ATP (cell energy) and gives ATP count Bright-field microscopy to identify impact on morphology Immunocytochemistry to observe impact on proliferation • Analogs showing anti- cancer properties (TM026, TM122, and TM123) will be tested on normal human melanocytes, to test toxicity levels. • There will also be new research on the mechanism of action of these compounds as well as the morphology of the cells. • TM026 showed strong anti- cancer properties against melanoma like previously shown in head and neck squamous cell carcinoma cells • TM122, and TM123 showed strong anti-cancer traits against metastatic melanoma. • TM117, TM118, TM119, TM120, TM121, TM124, and TM125 analogs had no impact on the growth of the metastatic melanoma, A375 line of Melanoma containing BRAF (V600E) mutation, analogs of Pactamycin, Growth Media (DMEM),Vehicle (DMSO), Cell Titer Glo Assay kit Methods Figure A: Graph shows that TM026 has an IC-50 value of 3.045 uM . Neither TM117 nor TM118 showed any anti-cancer activity in A375 cell line. I would like to thank Saturday Academy for the opportunity, the College of Pharmacy at OSU, and all the members of the Indra lab for their help and support. Objective Figure B: TM122, TM123 and TM026 all showed anti-cancer activity against melanoma cells. References 1Nikolaou, Vasiliki A. et al. Melanoma: New Insights and New Therapies." J Invest Dermatol. 2012 Mar;132(3 Pt 2):854-63. 2Wagle, Nikhil, et al. "Dissecting Therapeutic Resistance to RAF Inhibition in Melanoma by Tumor Genomic Profiling." Journal of Clinical Onocology 29.22 (2011): 3085-096. 3Lu W, Roongsawang N, Mahmud T. Biosynthetic Studies and Genetic Engineering of Pactamycin Analogs with Improved Selectivity toward Malarial Parasites. Chem Biol. 2011;18: 425–431. pmid:21513878 . 1Saturday Academy, 2College of Pharmacy, 3Linus Pauling Institute, Oregon State University; Corvallis, OR 4Dept. of Dermatology, 5Knight Cancer Institute, Oregon Health & Sciences University; Portland, OR Conclusions Figure C: Bright-field microscopy shows compound TM026’s (right) ability to kill melanoma cells thereby reducing cell density, and reduce cell size and shape. Figure D: Immunocytochemistry using anti-Ki67 antibody exhibits reduced proliferation of TM026 treated melanoma cells compared to the vehicle control. A. B. E. Figure E: Graph shows less cells treated with TM026 inhibit Ki67 (marker for proliferation) Effect of TM026 on Proliferation - 4 - 3 - 2 - 1 0 1 2 0 2 5 5 0 7 5 1 0 0 1 2 5 E f f e c t o f P a c t a m y c i n A n a l o g s o n A 3 7 5 l i n e L o g D o s e C o n c e n t r a t i o n %CellSurvival T M 0 2 6 T M 1 1 7 T M 1 1 8 P a c t a m y c i n A n a l o g u e D o s e R e s p o n s e C u r v e i n A 3 7 5 l o g [ C o m p o u n d ] ( M ) %CellSurvival - 4 - 3 - 2 - 1 0 1 2 0 2 5 5 0 7 5 1 0 0 1 2 5 T M 0 2 6 T M 1 1 7 T M 1 1 8 T M 1 1 9 T M 1 2 0 T M 1 2 1 T M 1 2 2 T M 1 2 3 T M 1 2 4 T M 1 2 5 U.S. Melanoma Incidence*. Digital image. Planning Cancer. N.p., n.d. Web. To determine if synthetic analogs of Pactamycin have anti-cancer properties and less toxicity levels against human metastatic melanoma. Poster 1:
- 15. CyaberAcademy: Content • Symposiumprep = HOMEWORK • Review poster and presentation with mentor(s) • Practice your talk and timing • Practice some more… • …then, practice again • Rehearse but don’t recite . Tips for Presentation Success Poster 2:
- 16. CyaberAcademy: Content • Standto the side of poster – not in front • Remember the tips from the presentation video • Remain at your poster entire session • Prepare your “pitch” ahead of time… Tips for Poster Session
- 17. CyaberAcademy: ContentSupport forSymposium Success • ASE Symposium Handbook • Teacher Monitor • Mentors
- 18. CyaberAcademy: ContentSummary Report Inyour words… • Your work and contributions over the summer. • Likely to share content with poster and talk. Submit Online Wed., Aug. 21st
- 19. CyaberAcademy: ContentThankYou Letters:Expressing Gratitude Personalized & Specific “ Your patience and sense of humor made the long hours seem short” Sincere & Heartfelt “Seeing you and other scientists enthusiastic about science has inspired my own interest.” Gratitude & Appreciation “I appreciate you giving me this amazing opportunity and mentoring me!”
- 21. Discuss titleand content with mentor ASAP Register by Mon., Jul. 22nd ASE will email you a list of thank you letter recipients by end of July Email your letters to yourTeacher Monitor by Friday., Aug. 9th Bring signedThankYou Letters to Symposium on Fri., Aug. 16th Submit Summary by Wed., Aug. 21st Next Steps
- 22. … follow yourcuriosity! Questions???