DIPG Dialogue

Introduction:

Dr. David Zagzag is an Associate Professor of Pathology and Neurosurgery, the Director of Microvascular and Molecular Neuro-Oncology Laboratory, and the Director of the Human Brain Tumor Bank at NYU Medical Center. His research and clinical interests include the pathology of nervous system, mechanisms of cerebral vasculogenesis and angiogenesis.


Questions & Answers:

What is a Brain Bank?

A brain tumor bank serves as a repository for tissues. These tissues are preserved in our bank by freezing or by fixation in different fixatives. Freezing and fixation help to assure that the tissues are safeguarded until needed for investigations.


Approximately how many brain tumor specimens do you have?

We currently have approximately 500 brain tumor specimens in our tumor bank.


How do you get these specimens- from surgery or from autopsy?

The specimens in the tumor bank are acquired from both surgery and autopsy.


Do you have any pediatric DIPG specimens?

We have specimens from approximately 250 pediatric brain tumor patients in our tumor bank. This includes approximately 15 pediatric patients diagnosed with DIPG.


What do you hope to do with these specimens?

We use these specimens to perform investigations into the pathogenesis of brain tumors. Our goal is to use the collected information to develop diagnostic and prognostic methods that can be translated into the clinic for therapeutic use in patients.


Is using the bank only open to those associated with NYU?

No, use of the brain tumor bank is not limited to those associated with NYU, investigators from any institution are welcome to request specimens from our bank.


Do you know of other brain banks for pediatric brain tumors?

Yes, though limited in number, other pediatric brain tumor banks have been established in universities, hospitals, and other medical institutions around the nation.


This endeavor is a team effort with Pediatric Neurosurgeons Drs. Jeffrey Wisoff, Howard Weiner and David Harter, and Pediatric Neurooncologists Drs. Jeffrey Allen, Sharon Gardner and Matthias Karajannis.

DIPG Digest

DIPG News brought to you by:
Just One More Day for Love, Hope & a Cure
http://www.justonemoreday.org/

July 18, 2009

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Medical News
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A human brainstem glioma xenograft model enabled for bioluminescence imaging.

J Neurooncol. 2009 Jul 8.

“There is a need for relevant brainstem tumor models that can be used to test new therapeutic agents and delivery systems in pre-clinical studies. We report the development of a brainstem-tumor model in rats and the application of bioluminescence imaging (BLI) for monitoring tumor growth and response to therapy as part of this model……This model is well suited for pre-clinical testing of therapeutics that are being considered for treatment of patients with brainstem tumors.”

An experimental brainstem tumor model using in vivo bioluminescence imaging in rat.

Childs Nerv Syst. 2009 May;25(5):527-33. Epub 2009 Jan 13

“This study demonstrates a robust rodent model with the ability to monitor brainstem tumor growth and response to chemotherapeutic agents.”

Anti-VEGF therapies for malignant glioma: treatment effects and escape mechanisms.

Expert Opin Ther Targets. 2009 Apr;13(4):455-68

“It should be kept in mind though that tumours can develop escape mechanisms. In particular invasive cells, which migrate away from the highly vascularized tumour core, are not targeted by anti-angiogenic therapies. In our opinion, the future of anti-angiogenic therapy will rely on a combination strategy including chemotherapy and drugs that target invasive glioma cells.”

Kinome profiling in pediatric brain tumors as a new approach for target discovery

Cancer Res. 2009 Jul 15;69(14):5987-95. Epub 2009 Jun 30

“this study describes a new high-throughput technique to generate clinically relevant tyrosine kinase activity profiles as has been shown here for pediatric brain tumors. In the era of a rapidly increasing number of small-molecule inhibitors, this approach will enable us to rapidly identify new potential targets in a broad range of human malignancies.”

Cancer Stem Cells in Pediatric Brain Tumors

Curr Stem Cell Res Ther. 2009 Dec 1. [Epub ahead of print]

“In this review, we describe the issues surrounding the identification and characterization of BTSC, the molecular biology of BTSC for different pediatric brain tumors, and suggest future avenues for the development of treatments for this devastating disease.”

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For past issues of DIPG Digest please visit

http://www.justonemoreday.org/DIPGDigest/DIPGDigest.html

Please submit information you feel will be helpful to DIPG families to JustOneMoreDay@cfl.rr.com subject: DIPG Digest

Copyright 2008 - 2009 Just One More Day for Love, Hope & a Cure, Inc. Allrights reserved. The materials and links provided on this site have beenprepared for information purposes only and should not be construed as advice oropinions on any specific facts or circumstances. Medical research concerningdisease and treatments is an ongoing process. Readers should not act upon thisinformation, but should obtain advice from physicians, medical institutions orother professionals, as appropriate.

DIPG Digest

DIPG News brought to you by:
Just One More Day for Love, Hope & a Cure
http://www.justonemoreday.org/

June 13, 2009

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Medical News
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Treatment of diffuse intrinsic brainstem gliomas: failed approaches and future strategies. :“The discussion includes a rationale for stereotactic biopsies as well as possible therapeutic options of local chemotherapy in these lesions.”

Neurological grading, survival, MR imaging, and histological evaluation in the rat brainstem glioma model. :“Local chemotherapy in the brainstem glioma model showed significant efficacy for histological changes and survival. Our neurological grading enables quantification of drug and tumor-related morbidity as an important factor for functional performance during therapy.”

Diffuse pontine glioma in Jordan and impact of up-front prognosis disclosure with parents and families. :“Contrary to the common belief, our study showed that do not resuscitate should be addressed in Muslim patients with high-risk malignancies. We also found that diffuse pontine glioma warrants further study in developing countries.”

Continual reassessment method vs. traditional empirically based design: modifications motivated by Phase I trials in pediatric oncology by the Pediatric Brain Tumor Consortium. :“Compared to the TM, our simulations indicate that the modified version of CRM is more accurate, exposes fewer patients to potentially toxic doses, and tends to require fewer patients. "

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Medical Updates
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The FDA Biopsy MeetingOn April 27, 2009, the Committee met to discuss the scientific and ethical issues involved in obtaining and using brain biopsy specimens to evaluate gene expression patterns in children with diffuse pontine gliomas.The slides from this meeting can be viewed here

DIPG Conference Memorial “Alicia Pueyo” Workshop Research on Pontine Gliomas held in Barcelona Spain,on February 26th 2009Conference video is now available at Just One More Day

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Foundation News
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DIPG Dialogue - Talking with the ExpertsJust One More Day is starting a new feature called DIPG Dialogue which will contain interviews with researchers, physicians and other advocates in the DIPG community.

2nd Annual Smiles For Sophie Forever Birthday Bash and Dash5K and 1 Mile Run/WalkSaturday, July 4, 2009 at 9:00 a.m.Walker Road Park31621 Walker RoadAvon Lake, OH 44012

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For past issues of DIPG Digest please visit
http://www.justonemoreday.org/DIPGDigest/DIPGDigest.html

Please submit information you feel will be helpful to DIPG families to JustOneMoreDay@cfl.rr.com subject: DIPG Digest

Copyright 2008 - 2009 Just One More Day for Love, Hope & a Cure, Inc. Allrights reserved. The materials and links provided on this site have beenprepared for information purposes only and should not be construed as advice oropinions on any specific facts or circumstances. Medical research concerningdisease and treatments is an ongoing process. Readers should not act upon thisinformation, but should obtain advice from physicians, medical institutions orother professionals, as appropriate.

DIPG Dialogue

Dr. Maryam Rahman

June 2009

Introduction:

Dr. Maryam Rahman is a research fellow in Dr. Reynolds’ lab at the University of Florida. Dr. Rahman is also a 4th year neurosurgery resident with a strong interest in neuro-oncology and novel therapy development. She has been responsible for BMP receptor/pathway activation experiments and the application to the NIH and FDA for testing of BMP 4 in human malignant glioma.
Dr. Rahman’s research on BMP4 and cell lines has recently been funded through a collaborative effort within the United Forces Against Brain Tumors. Just One More Day along with Gunner’s Magic Train and the Musella Foundation joined together to support her research. BMP4 has been shown to cause human glioblastoma cancer stem cells to become end cells that have a limited number of cell divisions and are more easily killed. The question is whether this effect can occur with other types of glioma cells.

Questions & Answers:

Where do you get cancer cell lines from?

Cancer lines are created by taking fresh tumor tissue from a surgical specimen. This tissue is dissociated into single cells and then placed in culture with growth factors. These cultures are placed in an incubator at 37 degrees C (like all cultures) and nurtured with media and growth factors until they start proliferating. Once the cells start proliferating, after several days, they outgrow their culture flask and need to be "passed" which means that they are dissociated into single cell suspension. Some of these cells are placed in a new flask with media and growth factors. The other cells can also be placed in culture (to expand the number of cells you produce) or used for experiments. Here at the University of Florida, we obtain our tumor tissue from the Florida Center for Brain Tumor Research. They obtain consent from the patients pre-operatively. Tissue is collected intra-operatively and given to us for cell culture and experimentation.

Would each individual's tumor grow out a different type of cell line?

Absolutely. Every patient's tumor is unique and therefore, having multiple lines of a type of tumor is beneficial for experimentation. Even within a certain type of tumor, there is variation in behavior and response to drugs.

Why does one use a cell line?

Cell lines are useful because it gives you an endless supply of tumor cells to use for experiments. If the cells we obtain from tumor tissue are fixed and used immediately for experimentation (which we do if we have a lot of cells and have some left over after placing them in culture), it could only be used once. The cell lines allow us to experiment with the tumor indefinitely.

Are cell lines stable or do they change over time?

Cell lines do not usually change over time. However, culture conditions do select out certain cells that can grow in media and growth factors. Therefore, cell lines are not always completely representative of the original tumor. This is the biggest argument against cell line work. I think cell line work is an important first step in understanding tumor biology, but it has to be supplemented and followed by animal and finally human work.

If there is a biopsy is there enough tissue to do what is needed therapeutically and perhaps to grow out a cell line?

Unfortunately, there is usually not enough tissue from a biopsy to do anything other than pathologic analysis. We only get tissue that is given to us after the pathologist takes what is necessary for diagnosis.

Dr. Rahman, you are saying that there are no cell lines of diffuse intrinsic pontine gliomas. Since we do not have cell lines but we have had biopsy and autopsy tissue which show most of these tumors to be gliomas , but not all GBMs, then it could follow that it might be important to find an agent that works on a wide variety of gliomas to try to cure DIPGs?

I do think that experimentation using other low grade glioma cell lines may be relevant to the treatment of DIPGs. You are absolutely correct with that question. I think that's why it's important to experiment with BMP in gliomas other than GBM.

References-

Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells. Nature. 2006 Dec 7;444(7120):761-5

BMPing off glioma stem cells. Cancer Cell. 2008 Jan;13(1):3-4