DIPG/DIPT Discussion

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A searchable blog on DIPG research, DIPG news, recent publications, DIPG Foundations, DIPG researchers, clinical trials as well as other issues relating to Diffuse Intrinsic Pontine Tumors- both Diffuse Intrinsic Pontine Gliomas (DIPGs) and Atypical Pontine Lesions (APLs).

For parents, family and friends of children with DIPG looking for information and connection to others dealing with DIPG please check the buttons on the right hand side for resources.

Saturday, June 13, 2009

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.

Tuesday, June 9, 2009

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-

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

Thursday, June 4, 2009

DIPG Conference

Click here for workshop notes.
Research on Pontine Gliomas
Barcelona, February 26th 2009

Presentation videos:

Diffuse Intrinsic Pontine Glioma a Clinical Introduction by Ofelia Cruz

Pontine Glioma: By Darren Hargrave
Clinical Trials for Children with DIPG, a Critical View
To Biopsy or Not Biopsy: Diagnostic and Therapeutic Challenges
Investigational Avenues in UK

The Origin of Brainstem Tumors by Sebastian Pons
Wrong Cell or Just the Right Cell at Wrong Place

Molecular Gliomagenesis:Gene and Core Pathways by Joan Seoane
The Therapeutic TGF-Beta Approach

Molecular Medicine for Diffuse Intrinsic Pontine Gliomas by Mark W. Kieran

Murine Animal Models of Brainstem Tumors & Delivery Systems of Drugs to the Brainstem
by Ioannis Roussos

New Clinical Trials from St. Jude/PBTC by Alberto Broniscer
The St. Jude Protocol of Autopsies for Children with DIPG

Clinical Trials at Duke - So What is New? by Sri Gururangan

Gene Therapy Strategies by Manuel Ramirez

Development of Novel Therapeutics &Targeted Delivery in Pediatric Brainstem Glioma
by Viola Caretti & Dannis Van Vuurden