Medical
Research
The wonderful people who are part
of Team TJ have done much to advance the basic research needed to
make progress against TJ’s disease – Juvenile Pilocytic
Astrocytomas and other pediatric low grade astrocytomas. Over the
past three years, Team TJ has raised over $730,000 through the BTS
Ride for Research, The Pan-Mass Challenge, and private donations.
All
of these funds have been directed specifically at children’s
brain tumor research and the projects has been selected by some of
the leading pediatric brain tumor researchers in the country.
We’ve provided below a full list of related research that has
been partially funded by Team TJ or our partner families. While you
can see we’ve made strong progress, we are really only in the
very early stages of the research that will be needed to develop
promising new therapies or a cure. The unfortunate reality is that
it takes many millions of dollars to make meaningful long term progress.
You’ll also note that this research has been done in coordination
with our new foundation, the Pediatric Low Grade Astrocytoma (“PLGA”)
foundation. For more information on the PLGA foundation click here
PLGA and Team TJ Funded Research
Dana-Farber Cancer Institute’s
Pediatric Low Grade Astrocytoma Program
May 2007
A $2 million grant provided by families associated with the Pediatric
Low Grade Astrocyoma Foundation created a new program at Dana-Faber
to focus on low grade tumors and to discover new and improved targeted
therapies that don’t risk impairing children’s bodies
and minds. The PLGA Program – under the direction of Charles
Stiles, PhD, and Mark Kieran, MD, PhD – will draw resources,
including personnel and technology, from Dana-Farber’s pediatric
neuro-oncology program, the Department of Neurobiology at Harvard
Medical School, Children's Hospital Boston, and the Broad Institute
of MIT and Harvard. In addition to many individual projects within
the LGA program, the flagship project of this program will analyze
50-60 JPA and Fibrillary Astrocytoma samples looking for mutated
genes by utilizing SNP arrays and a new technology, Shape–based
Gene Sequencing. The goal of the flagship project for the LGA Program
is to identify a drug-susceptible target for low grade astrocytoma
within a five-year period of time.
Note: There were several families that donated a significant amount
of money to fund this program. Ken and Charise Gainey were instrumental
in developing and funding this program (www.TeamJake.org).
To read the press release, click
here.
To learn more about the DFCI PLGA Program,
click here.
2007 Pediatric Low Grade Astrocytoma Grants Funded
We would like to thank the Brain Tumor Society (BTS) Boston for their
support of the following grants through the Pediatric Low Grade Glioma
Initiative. The following grants are made possible through the collective
efforts of the riders from Team TJ, Team Samantha, Team Jake, and
Team Lucy in the Brain Tumor Society’s 13th annual Ride for
Research which raised over $1.1 million for dedicated pediatric low
grade astrocytoma research. We would like to express our sincere
gratitude for the overwhelming support and generosity of all the
riders and donors who made the 2007 Ride for Research such a great
success.
The Biologic and Prognostic Role of Replicative and Oncogene Induced
Senescence in Pediatric Low Grade Gliomas.
Principal Investigator Dr. Uri Tabori, Hospital for Sick Children,
University of Toronto.
This study will study why some PLGA tumors stop growing. Using this
alternative research strategy, we will build on previous results
that demonstrated that a mechanism that controls tumor growth arrest,
defined as senescence, predicts outcome in PLGA. With the collaboration
between three of the leading pediatric neuro-oncology centers in
North America, we plan to expand our preliminary findings and to
determine the pathways that control senescence in PLGA. Upon completion
of this project, we will be able to better predict which patients
are unlikely to have tumor progression (and can thus be spared from
current toxic therapies). We will uncover novel targets as therapeutic
options for PLGA. Furthermore our findings will provide a framework
for a new understanding of astrocytoma behavior in children.
Molecular Prognostic Markers for Low-Grade Gliomas.
Principal Investigator Dr. Ian F. Pollack, Children's Hospital of
Pittsburgh, University of Pittsburgh.
This study will apply the prognostic markers in childhood high-grade
gliomas to analyze low-grade gliomas. We will evaluate a series of
hypothesis-based markers linked with glioma progression in previous
studies, such as MGMT status, proliferation index and genetic alterations.
These results would be amenable to comparison with results from high-throughput
allelotyping. We will evaluate 100 favorable-risk" (e.g., grossly
resected) tumors in parallel with 100 "higher-risk" (unresectable
brainstem and diencephalic) lesions. This analysis should have s
sufficient statistical power to identify meaningful prognostic associations,
and would provide new insights into biological correlates of prognosis
in pediatric gliomas and therapeutic targets to improve the chances
of curing these tumors.
Development of Permanent Juvenile Pilocytic Astrocytoma Cell Lines
for Preclinical Trails.
Principal Investigator Dr. Kwong-Kwok Wong, University of Texas M.D.
Anderson Cancer Center.
This study will investigate different methods to immortalize JPA
primary cells which have limited growth potential. Cell culture method
will involve the expressing of telomerase gene into JPA primary cells
with limited growth potential. Over-expression of telomerase has
previously shown to increase the life span of human cells. Additionally,
we will attempt to inject fresh JPA tumor tissue into SCID mice which
are severely immunodeficient to investigate whether JPA tumor cells
can be propagated inside the brain of the SCID mice. The successful
development of these resources will allow us to perform various pre-clinical
trials of various therapeutic strategies in the future.
Controlling Pilocytic Astrocytoma Growth: Effects of location, age
and Telomerase.
Principal Investigator Dr. Jeffrey Leonard, Washington University.
This study will evaluate three growth characteristics of JPA that
might offer clues for research. First, JPA is primarily a disease
of childhood. Second, JPAs behave differently when they occur in
different parts of the brain. Third, JPAs grow slowly and often stop
growing spontaneously, possibly because JPAs cannot bypass the 'biological
clock' that stops non-cancer cells from growing indefinitely. We
will implant JPA cells taken from children undergoing surgical removal
of their tumor into the brains of mice. We will determine if these
cells grow preferentially when they are implanted into the brains
of very young mice in places that correspond to the original location
of the tumor in the patient, and if so, why. We will also put telomerase,
a gene that bypasses the 'biological clock' into JPA cells and see
if this allows tumor growth in mice brains. This project could identify
proteins or genes that are important for JPA growth that could be
used as targets for drugs or therapies to cure JPA.
Identification of Key Genetic and Growth Control Pathway Changes
in Pediatric Fibrillary Astrocyoma (PFA) that Represent Potential
Molecular Targets for Therapuetic Intervention.
Principal Investigator Dr. David Gutmann and Dr. Tobey MacDonald,
Washington University
This study represents a collaborative project that builds upon the
2006 BTS-funded project focused on juvenile pilocytic astrocytomas
(JPAs). The 2006 project boasted the first truly comprehensive genomic,
genetic and proteomic analysis of JPAs. This year’s project
will focus on pediatric fibrillary astrocytomas (PFA) as it continues
to employ multiple complementary highthroughput technologies to identify
key molecular genetic changes (DNA, RNA and protein) and growth control
pathways that represent potential molecular targets for future therapeutic
drug design. This approach, leading to “targeted therapeutics,” has
had great success in a number of adult cancers. Unfortunately, unlike
some of the other common childhood tumors, PFA has not been subjected
to the same rigorous and comprehensive molecular analysis that constitutes
the necessary first step for the development of targeted therapeutics.
No single study has analyzed a sufficiently large enough sample size,
and more importantly, no investigation has concurrently studied the
DNA, RNA and corresponding protein expression of each individual
tumor to make definitive and statistically valid conclusions regarding
the molecular basis of PFA.
2006 Pediatric Low Grade Astrocytoma Grant
Identification of Key Genetic and Growth Control Pathway Changes
in JPA that Represent Potential Molecular Targets for Therapuetic
Intervention.
Principal Investigator Dr. David Gutmann and Dr. Tobey MacDonald,
Washington University
A collaborative project conducting the first truly comprehensive
genomic, genetic and proteomic analysis of JPAs. The project is being
conducted by Dr. David Gutmann and Dr. Tobey MacDonald. This project
will apply cutting edge bioinformatics techniques to proven genetic,
genomic and proteomic analyses which have helped lead to the development
of "targeted therapeutics" in a number of adult cancers. All Related Medical Research
A full list of all related research is provided by the PLGA Foundation
at the following link: http://fightplga.org/research]
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