Microelectronics-Photonics (microEP) Graduate Program
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Research Document for Seth Shumate
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Student Information Fields:
Student Name: Seth Shumate
Student ID: 005193192
Research Professor: Magda El-Shenawee
Thesis/Dissertation Committee
Chairman: Magda El-Shenawee
Member: Doug Rhoads
Member: Mack Ivey
Dept: ELEG
Dept: BIOL
Dept: BIOL
Background of research topic area:
The area of modeling tumorigenesis first developed early last century with mathematical
techniques which described tumor growth kinetics based on gross observation. At this time, the
underlying biological processes driving tumor growth were a subject of speculation. The past
quarter century has brought a wealth of knowledge regarding the factors driving tumor growth
and shape formation. Such factors include the acquisition of hallmark mutation types [1], the
pressures felt by the tumor from its local environment [2], and nutrient gradients [3]. To the best
of my knowledge, there are no models which incorporate all of these characteristics for breast
cancer. The practical applications of modeling breast cancer, specifically tumor growth
associated with Invasive Ductal Carcinoma (IDC) and Ductal Carcinoma in situ (DCIS), range
from detection evaluation to drug treatment strategies. The overall research goal will be to create
a three-dimensional growth model of Ductal Carcinoma.
Descriptive overview of research to be performed:
The work described by Sansone et al. [2]-[3] will serve as a starting point for model development
since the techniques emphasize the importance of two of the three aforementioned factors: by
assuming tumors are fully invasive, the importance of mutation acquisition is neglected. Also
the results of these methods were found to be both qualitatively and quantitatively adequate for
describing tumor growth morphologies for neoplasms near the jaw and larynx. The following
research phases briefly describe the major steps toward a complete model.
1. Reproducing the results, which are two-dimensional, reported by Sansone et al. in [2] will be
the first necessary task. The case of jaw cancer will be considered. (Accomplished)
2. Conversion to two-dimensional (2D) Cellular Automaton (CA) model of DCIS: This
model has been created. It includes modified versions of the nutrient diffusion system and cell
nutrient uptake system for individual cells rather than cell densities. Incorporated into the model
was the idea that E-cadherin mediated contact inhibition leads to the formation of the complex
growth patterns of DCIS. (Accomplished)
3. 3D model of DCIS
This step will involve converting the 2D model to three dimensions while maintaining
morphological pattern integrity. (Current Activity) (End of required material for inclusion in
M.S. thesis)
3. Invasive Model: In the final model, as the simulated tumor grows, it will eventually develop
the ability to invade into the surrounding tissue. For example, IDC tumors have acquired certain
mutations which allow them to spread beyond their original tissue boundaries. This results in
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Research Description Document
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Microelectronics-Photonics (microEP) Graduate Program
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Research Document for Seth Shumate
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complex shapes that are markedly different than those associated with DCIS. This is due to the
cancer cells’ interactions with a different types of tissues and cells. Recently, research into
applying the hallmarks paradigm to breast cancer for treatment and diagnosis purposes was
published [4].
4. Inhomogeneous Tissue Environment: Cell functions such as mitosis, apoptosis, and
motility will also depend on the availability of nutrients and the physical pressures from the
surrounding tissues. As in the model from Sansone et al. [2], nutrient and oxygen gradients will
be determined by the spatial distribution of blood supply present in and around the growing
tumor. The ability of mutated cells to induce new blood vessel growth, angiogenesis, has been
established as a necessary step for tumors to grow to detectable sizes [1]. The final model will
take into account the characteristic vasculature of the mammary tissue regions of interest [5].
Quantification of proposed research boundaries (currently planned experimental space,
including range of planned input variables and expected range of measured output):
Simulation results will be compared with available clinical data for IDC and DCIS. The patterns
for DCIS, along with the biological background supporting the simulation of those patterns, will
help determine the behavior of the progression from in situ disease to invasive disease. Required
results include completed models of DCIS in two and three dimensions.
Listing of high-risk components of research effort:
No high-risk components are foreseeable.
Alternative research topic/output should some high-risk element cause a significant time
delay to completion schedule:
N/A
Journal/Meeting(s) targeted for publication:
IEEE Region 5 Conference (April, 2007)
Arkansas Biosciences Institute Fall Symposium poster presentation (October, 2007)
IEEE TBME Journal paper (December, 2007)
ACES 2008 Conference (March 30-April 04, 2008)
Progress made toward completion of research investigation:
A successful model of ductal carcinoma in-situ of the breast was developed in two dimensions.
This model relates the phenomena of changing E-cadherin expression with pattern formation
within the duct. The model has been programmed for three dimensions and preliminary results
have been obtained.
[1] D. Hanahan, R.A. Weinberg, “The Hallmarks of Cancer,” Cell, vol. 100, pp. 57-70, 2000.
[2] B.C. Sansone, P.P Delsanto, M. Magnano, M. Scalerandi, “Effects of anatomical constraints
on tumor growth,” Phys. Rev. E, vol. 64, no. 2, pp. 021903-1-8, 2001.
[3] M. Scalerandi, A. Romano, P. Pescarmona, P.P. Delsanto, C.A. Condat, “Nutrient
competition as a determinant for cancer growth,” Phys. Rev. E, vol. 59, no. 2, pp. 2206-2217,
1999.
[4] G.W. Sledge Jr., K.D. Miller, “Exploiting the hallmarks of cancer: the future conquest of
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Research Description Document
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breast cancer,” European Journal of Cancer, vol. 39, no. 12, pp. 1668-1675, 2003.
[5] Gasparini, Giampietro, “Biological and clinical role of angiogenesis in breast cancer,” Breast
Cancer Research and Treatment, vol. 36, no.2, pp. 103-107, 1995.
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Research Description Document
December 4, 2007
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Research Document for Seth Shumate
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The undersigned agree that this document describes the current status of the research
investigation planned to meet microEP student Seth Shumate’s MS Thesis requirement for
graduation. Any significant change in the overall scope of the investigation will be made only
with the full review and agreement of the original signatories or their designee.
microEP Student:
______________________________
Seth Shumate
Date: __________
microEP Director:
______________________________
Ken Vickers
Date: __________
Research Professor:
(Chairman)
______________________________
Magda El-Shenawee
Date: __________
Committee Member: ______________________________
Doug Rhoads
Date: __________
Committee Member: ______________________________
Mack Ivey
Date: __________
microEP Graduate Program
master document revision 2
Research Description Document
December 4, 2007