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| Centre
for Mathematical Medicine Seminar Series 2004-2005 |
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 May
27, 2005 -- 4:30 p.m.
talk to be held at Bahen Centre (BA) , Univ. of Toronto,
Rm. 1190 at
(Map of campus)
J.
Carl Panetta, Department of Pharmaceutical Sciences,
St. Jude Children's Research Hospital and University
of Tennessee,
Modeling
Chemotherapy Induced Myelosuppression
Temozolomide (TMZ) and Topotecan (TPT) are currently
being evaluated for the treatment of several pediatric
cancers including high-grade gliomas, neuroblastoma,
medulloblastoma, rhabdomyosarcoma, and acute leukemias.
Myelosuppression is the dose-limiting toxicity for
both TMZ and TPT. Empirical methods (i.e. relations
between the percent change in absolute neutrophil
count (ANC) and the area under the plasma concentration
curve (AUC)) show poor results when attempting to
describe myelosuppression from serial data. Therefore,
to improve our understanding of the myelosuppressive
effects of TMZ and TPT in children we developed a
mechanistic mathematical model. The model describes
the progression of neutrophils from their production
in the bone marrow to their release in the plasma.
Included in the model are the feedback effects of
granulocyte colony stimulating factor (G-CSF), which
stimulates neutrophil production when there is a decrease
in circulating neutrophils. Post TMZ or TPT dose serial
ANC measurements are fit to the model. The model is
able to explain, among other things, the lag in ANC
reduction following a dose and a "rebound effect"
observed where the ANC recovers to levels greater
than pre-dose. The mathematical model is then used
to predict the extent of myelosuppression given various
TMZ/TPT/G-CSF dosing schedules. This model will be
useful for the prospective design of clinical trials
of TMZ and TPT in children with brain tumors.
Short
Bio:
Dr. J.C. Panetta completed his PhD in 1995 at Old
Dominion University and was subsequently Professor
of Mathematics at Penn State Erie, The Behrend College,
Erie PA. He is currently a Biomedical Modeller at
St. Jude Children's Research Hospital in Memphis,
Tennessee and Adjunct Professor in the Department
of Pharmaceutical Sciences at the University of Tennessee.
Dr. Panetta is also on the Board of Directors of the
Society for Mathematical Biology.
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March
2, 2005 - 4:00 p.m.
Kristin R. Swanson, PhD, Shaw Research Assistant
Professor, Pathology, University of Washington
Clinical
applications of quantitative modeling for invasive
brain tumors (gliomas)
Gliomas account for over half of all primary
brain tumors and have been studied extensively for
decades. Even with increasingly sophisticated medical
imaging technologies, gliomas remain uniformly fatal
lesions. A significant gap remains between the goal
of designing effective therapy and the present understanding
of the dynamics of glioma progression. It has become
increasingly clear that, along with the proliferative
potential of these neoplasms, it is the subclinically
diffuse invasion of gliomas that most contributes
to their resistance to treatment. That is, the inevitable
recurrence of these tumors is the result of diffusely
invaded but practically invisible tumor cells peripheral
to the abnormal signal on medical imaging and to
the limits of surgical, radiological and chemical
treatments.
In
this presentation, I will demonstrate how quantitative
modeling can not only shed light on the spatio-temporal
growth of gliomas but also can have specific clinical
application in real patients. Integration of our
quantitative model with the T1-weighted and T2-weighted
MR imaging characteristics of gliomas can provide
estimates of the extent of invasion of glioma cells
peripheral to the imaging abnormality. Further model
analysis reveals remarkable concordance with patient
survival rates. In summary, although current imaging
techniques remain woefully inadequate in accurately
resolving the true extent of gliomas, quantitative
modeling provides a new approach for the dynamic
assessment of real patients and helps direct the
way to novel therapeutic approaches.
Dr.
Kristin R. Swanson received her B. S. for Tulane
University in 1996 followed by her Ph.D. from the
University of Washington in 1999 under the direction
of Professor J.D. Murray, FRS. She is currently
the Shaw Research Assistant Professor of Neuropathology
in the University of Washington School of Medicine
as well as an adjunct research assistant professor
of Applied Mathematics. Her research focuses on
the application of quantitative modeling techniques
to biomedical problems including brain tumor invasion,
dynamics of serum markers for prostatic tumor growth,
wallerian degeneration in stroke victims, PET tracer
kinetics and thymic function following immunosuppression.
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