tag:blogger.com,1999:blog-58474885668055250312024-03-13T10:11:35.186-05:00DIPG Discussion -- brought to you by Just One More Day for Love, Hope & a CureChristinehttp://www.blogger.com/profile/18348381365493843154noreply@blogger.comBlogger142125tag:blogger.com,1999:blog-5847488566805525031.post-61801705779920936362015-12-06T12:41:00.000-06:002015-12-06T12:41:28.527-06:00Holiday Toy Drive ~ In memory of Alicia Marie Martin<div class="separator" style="clear: both; text-align: center;">
<a href="http://2.bp.blogspot.com/-2eYFRPbBpCk/Um15pcbHGvI/AAAAAAAAAGc/No3CUNkJC5A/s1600/christmas%2Bpic.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" height="200" src="http://2.bp.blogspot.com/-2eYFRPbBpCk/Um15pcbHGvI/AAAAAAAAAGc/No3CUNkJC5A/s200/christmas%2Bpic.jpg" width="132" /></a></div>
<span lang="en-US" style="color: #00b050; font-family: Arial; font-size: 12pt; language: en-US; line-height: 114%; mso-ansi-language: en-US; mso-arabic-font-family: Arial; mso-armenian-font-family: Arial; mso-ascii-font-family: Arial; mso-currency-font-family: Arial; mso-cyrillic-font-family: Arial; mso-default-font-family: Arial; mso-greek-font-family: Arial; mso-hebrew-font-family: Arial; mso-latin-font-family: Arial; mso-latinext-font-family: Arial; mso-ligatures: none;">In August of 2005, a six year old girl named Alicia was very sick.<span style="mso-spacerun: yes;"> </span>Alicia spent a lot of time traveling to doctor’s appointments for blood work, scans and other tests.<span style="mso-spacerun: yes;"> </span>Alicia’s body was weak and when she got a simple cold it would make her so sick that she would need to go to the hospital.<span style="mso-spacerun: yes;"> </span>When Alicia was admitted to the hospital she would go to her room and find a stuffed animal on her bed waiting for her.<span style="mso-spacerun: yes;"> </span>Every time Alicia went to the hospital she would take her new stuffed animal and carefully choose who she would give it to.<span style="mso-spacerun: yes;"> </span>She would never keep them for herself.<span style="mso-spacerun: yes;"> </span>These animals made Alicia very happy.<span style="mso-spacerun: yes;"> </span>She enjoyed seeing them waiting for her on her bed but she also loved giving her animal to another person.</span><br />
<span lang="en-US" style="color: #00b050; font-family: Arial; font-size: 12pt; language: en-US; line-height: 114%; mso-ansi-language: en-US; mso-arabic-font-family: Arial; mso-armenian-font-family: Arial; mso-ascii-font-family: Arial; mso-currency-font-family: Arial; mso-cyrillic-font-family: Arial; mso-default-font-family: Arial; mso-greek-font-family: Arial; mso-hebrew-font-family: Arial; mso-latin-font-family: Arial; mso-latinext-font-family: Arial; mso-ligatures: none;"><o:p><span lang="en-US" style="color: #00b050; font-family: Arial; font-size: 12pt; language: en-US; line-height: 114%; mso-ansi-language: en-US; mso-arabic-font-family: Arial; mso-armenian-font-family: Arial; mso-ascii-font-family: Arial; mso-currency-font-family: Arial; mso-cyrillic-font-family: Arial; mso-default-font-family: Arial; mso-greek-font-family: Arial; mso-hebrew-font-family: Arial; mso-latin-font-family: Arial; mso-latinext-font-family: Arial; mso-ligatures: none;"></span><br />
<span lang="en-US" style="color: #00b050; font-family: Arial; font-size: 12pt; language: en-US; line-height: 114%; mso-ansi-language: en-US; mso-arabic-font-family: Arial; mso-armenian-font-family: Arial; mso-ascii-font-family: Arial; mso-currency-font-family: Arial; mso-cyrillic-font-family: Arial; mso-default-font-family: Arial; mso-greek-font-family: Arial; mso-hebrew-font-family: Arial; mso-latin-font-family: Arial; mso-latinext-font-family: Arial; mso-ligatures: none;">When a child is sick and has to stay in the hospital it affects the whole family.<span style="mso-spacerun: yes;"> </span>One of the most common problems is not having enough money for hospital bills, medicine, traveling and some parents have to take time off from work making the situation even worse.<span style="mso-spacerun: yes;"> </span>Some parents can’t afford gifts for their children at Christmas.<o:p></o:p></span><br />
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<span lang="en-US" style="color: #00b050; font-family: Arial; font-size: 12pt; language: en-US; line-height: 114%; mso-ansi-language: en-US; mso-arabic-font-family: Arial; mso-armenian-font-family: Arial; mso-ascii-font-family: Arial; mso-currency-font-family: Arial; mso-cyrillic-font-family: Arial; mso-default-font-family: Arial; mso-greek-font-family: Arial; mso-hebrew-font-family: Arial; mso-latin-font-family: Arial; mso-latinext-font-family: Arial; mso-ligatures: none;"><br />Christmas time is a special time for Alicia and her family.<span style="mso-spacerun: yes;"> </span>So every year, to carry on the tradition that Alicia started, Alicia’s family and friends bring toys to the hospitals that help children.<span style="mso-spacerun: yes;"> </span>They try to bring enough toys so that the children in the hospital will have toys for Christmas but also enough so that the brothers and sisters can have a special gift as well.</span></div>
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<span lang="en-US" style="color: #00b050; font-family: Arial; font-size: 12pt; language: en-US; line-height: 114%; mso-ansi-language: en-US; mso-arabic-font-family: Arial; mso-armenian-font-family: Arial; mso-ascii-font-family: Arial; mso-currency-font-family: Arial; mso-cyrillic-font-family: Arial; mso-default-font-family: Arial; mso-greek-font-family: Arial; mso-hebrew-font-family: Arial; mso-latin-font-family: Arial; mso-latinext-font-family: Arial; mso-ligatures: none;">The children in the hospital cannot go shopping for their brothers and sisters.<span style="mso-spacerun: yes;"> </span>This gives them the opportunity to give something to their siblings and get a few special gifts themselves.<span style="mso-spacerun: yes;"> </span>Being in the hospital during Christmas is not an enjoyable thing.<span style="mso-spacerun: yes;"> </span>These toys will help make the holiday a little brighter and hopefully put a few smiles on some little faces. <o:p></o:p></span></div>
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<a href="http://3.bp.blogspot.com/-YEjgaRYX8uE/VmSBJDsg15I/AAAAAAAAAHk/fTgKgQXSwxw/s1600/christmas%2Btradition%2B2015%2Bpg1.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="640" src="http://3.bp.blogspot.com/-YEjgaRYX8uE/VmSBJDsg15I/AAAAAAAAAHk/fTgKgQXSwxw/s640/christmas%2Btradition%2B2015%2Bpg1.jpg" width="492" /></a></div>
</span>Christinehttp://www.blogger.com/profile/18348381365493843154noreply@blogger.com0tag:blogger.com,1999:blog-5847488566805525031.post-82187813076474059652013-10-27T15:45:00.000-05:002013-10-27T15:45:01.767-05:00Holiday Toy Drive ~ In memory of Alicia Martin<div class="separator" style="clear: both; text-align: center;">
<a href="http://1.bp.blogspot.com/-2eYFRPbBpCk/Um15pcbHGvI/AAAAAAAAAGY/lTzKK7SbE4g/s1600/christmas+pic.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" height="200" src="http://1.bp.blogspot.com/-2eYFRPbBpCk/Um15pcbHGvI/AAAAAAAAAGY/lTzKK7SbE4g/s200/christmas+pic.jpg" width="132" /></a>
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<span lang="en-US" style="color: #00b050; font-family: Arial; font-size: 12pt; language: en-US; line-height: 114%; mso-ansi-language: en-US; mso-arabic-font-family: Arial; mso-armenian-font-family: Arial; mso-ascii-font-family: Arial; mso-currency-font-family: Arial; mso-cyrillic-font-family: Arial; mso-default-font-family: Arial; mso-greek-font-family: Arial; mso-hebrew-font-family: Arial; mso-latin-font-family: Arial; mso-latinext-font-family: Arial; mso-ligatures: none;">In August of 2005, a six year old girl named Alicia was very sick.<span style="mso-spacerun: yes;"> </span>Alicia spent a lot of time traveling to doctor’s appointments for blood work, scans and other tests.<span style="mso-spacerun: yes;"> </span>Alicia’s body was weak and when she got a simple cold it would make her so sick that she would need to go to the hospital.<span style="mso-spacerun: yes;"> </span>When Alicia was admitted to the hospital she would go to her room and find a stuffed animal on her bed waiting for her.<span style="mso-spacerun: yes;"> </span>Every time Alicia went to the hospital she would take her new stuffed animal and carefully choose who she would give it to.<span style="mso-spacerun: yes;"> </span>She would never keep them for herself.<span style="mso-spacerun: yes;"> </span>These animals made Alicia very happy.<span style="mso-spacerun: yes;"> </span>She enjoyed seeing them waiting for her on her bed but she also loved giving her animal to another person.</span></div>
<span lang="en-US" style="color: #00b050; font-family: Arial; font-size: 12pt; language: en-US; line-height: 114%; mso-ansi-language: en-US; mso-arabic-font-family: Arial; mso-armenian-font-family: Arial; mso-ascii-font-family: Arial; mso-currency-font-family: Arial; mso-cyrillic-font-family: Arial; mso-default-font-family: Arial; mso-greek-font-family: Arial; mso-hebrew-font-family: Arial; mso-latin-font-family: Arial; mso-latinext-font-family: Arial; mso-ligatures: none;"><o:p><div class="MsoNormal" style="line-height: 114%; margin-bottom: 10pt; mso-pagination: widow-orphan;">
<span lang="en-US" style="color: #00b050; font-family: Arial; font-size: 12pt; language: en-US; line-height: 114%; mso-ansi-language: en-US; mso-arabic-font-family: Arial; mso-armenian-font-family: Arial; mso-ascii-font-family: Arial; mso-currency-font-family: Arial; mso-cyrillic-font-family: Arial; mso-default-font-family: Arial; mso-greek-font-family: Arial; mso-hebrew-font-family: Arial; mso-latin-font-family: Arial; mso-latinext-font-family: Arial; mso-ligatures: none;">When a child is sick and has to stay in the hospital it affects the whole family.<span style="mso-spacerun: yes;"> </span>One of the most common problems is not having enough money for hospital bills, medicine, traveling and some parents have to take time off from work making the situation even worse.<span style="mso-spacerun: yes;"> </span>Some parents can’t afford gifts for their children at Christmas.<o:p></o:p></span></div>
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<span lang="en-US" style="color: #00b050; font-family: Arial; font-size: 12pt; language: en-US; line-height: 114%; mso-ansi-language: en-US; mso-arabic-font-family: Arial; mso-armenian-font-family: Arial; mso-ascii-font-family: Arial; mso-currency-font-family: Arial; mso-cyrillic-font-family: Arial; mso-default-font-family: Arial; mso-greek-font-family: Arial; mso-hebrew-font-family: Arial; mso-latin-font-family: Arial; mso-latinext-font-family: Arial; mso-ligatures: none;">Christmas time is a special time for Alicia and her family.<span style="mso-spacerun: yes;"> </span>So every year, to carry on the tradition that Alicia started, Alicia’s family and friends bring toys to the hospitals that help children.<span style="mso-spacerun: yes;"> </span>They try to bring enough toys so that the children in the hospital will have toys for Christmas but also enough so that the brothers and sisters can have a special gift as well.<o:p></o:p></span></div>
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<span lang="en-US" style="color: #00b050; font-family: Arial; font-size: 12pt; language: en-US; line-height: 114%; mso-ansi-language: en-US; mso-arabic-font-family: Arial; mso-armenian-font-family: Arial; mso-ascii-font-family: Arial; mso-currency-font-family: Arial; mso-cyrillic-font-family: Arial; mso-default-font-family: Arial; mso-greek-font-family: Arial; mso-hebrew-font-family: Arial; mso-latin-font-family: Arial; mso-latinext-font-family: Arial; mso-ligatures: none;">The children in the hospital cannot go shopping for their brothers and sisters.<span style="mso-spacerun: yes;"> </span>This gives them the opportunity to give something to their siblings and get a few special gifts themselves.<span style="mso-spacerun: yes;"> </span>Being in the hospital during Christmas is not an enjoyable thing.<span style="mso-spacerun: yes;"> </span>These toys will help make the holiday a little brighter and hopefully put a few smiles on some little faces. <o:p></o:p></span></div>
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<br />Christinehttp://www.blogger.com/profile/18348381365493843154noreply@blogger.com0tag:blogger.com,1999:blog-5847488566805525031.post-91209582358771229412013-05-30T08:18:00.001-05:002013-05-30T08:26:01.317-05:00DIPG in Adolescents- Presentation and OutcomesASCO starts tomorrow. It is the biggest professional cancer meeting in the world. There will be over 25,000 medical professionals from all over the globe to build bridges to conquer cancer. <br />
<br />
The <a href="http://chicago2013.asco.org/abstract-submission-statistics" target="_blank">2013 abstract statistics</a> are amazing. There were 5306 abstracts submitted from 75 countries. Of those, 2720 were accepted for presentation at the meeting and another 2034 were additionally accepted for ePublication. There were 172 abstracts submitted in the area of<a href="http://abstracts2.asco.org/CatAbstView_132_153_AA.html" target="_blank"> CNS Tumors</a> and 81 in the field <a href="http://abstracts2.asco.org/CatAbstView_132_128_AA.html" target="_blank">Pediatric Oncology</a>.<br />
<br />
One of those CNS abstracts happen to be on DIPGs! <br />
<br />
<u>Abstract:</u> <a href="http://abstracts2.asco.org/AbstView_132_118298.html" target="_blank">Diffuse intrinsic pontine gliomas (DIPG) in adolescents can have different prsentation but similar outcomes compared to middle childhood</a><br />
<u>Insitutions:</u> NIH and Lurie Children's Hopsital of Chicago<br />
<u>Authors: </u>Kathy Warren, Elad Jacoby and Jason Fangusaro<br />
<br />
In this study 46 children between the ages 10-20 years of age (median 13) were identified. There was a female to male ratio of 1:0.77.<br />
<br />
<u>Symptoms:</u> headache (39%); double vision (27%); cranial nerve issues (27%); dizziness (25%)<br />
Two were incidental<br />
<br />
<u>Onset of Symptoms to Diagnosis: </u> 2 days to 5 years (only 9 had symtoms less than 2 weeks)<br />
<br />
<u>Radiation:</u> 39/42 patients had radation; 36% did not improve or got worse during riadation: 63% remained on steroids at the end of radation<br />
<br />
<u>Time to Progression:</u> (n-32 for data available) 8 months median with a range of 2 months- 2.5 years; 2 alive and 1 in active treatment at time of abstract submission<br />
<br />
<u>Conclusion:</u> Adolescents are more like kids than adults with diffuse intrinsic pontine lesions with similarly abysmal survival stats.<br />
<br />
Reference:<br />
Diffuse intrinsic pontine gliomas (DIPG) in adolescents can have different prsentation but similar outcomes compared to middle childhood<br />
<a href="http://abstracts2.asco.org/AbstView_132_118298.html">http://abstracts2.asco.org/AbstView_132_118298.html</a><br />
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LAShttp://www.blogger.com/profile/10542398672724609734noreply@blogger.com0tag:blogger.com,1999:blog-5847488566805525031.post-9204089051217133402013-05-27T16:29:00.000-05:002013-05-27T16:29:49.559-05:00Prenatal DIPG- a case report!On May 16th the jounal Pediatric Radiology published an unsual case report of a a pre-natal DIPG written from the department of neurosurgery and diagnostic imaging t Brown University.<br />
<br />
In this situation a 33 year female who had previously delivered 3 children without complications had an ultrasound at 33 weeks gestation. Unfortunately the ultrasound revealed a markedly enlarged head of a size more than 40 weeks but with an abdominal circumference and femur length of 33 weeks. There was also triventricular hydrocephalus without evidence of spina bifida.<br />
<br />
A fetal MRI was then obtrained which showed a mass with the epicenter in the pons extending into the midbrain, medulla and cerebellar peduncles. The expansile mass had poor margins. There was severe hydrocephalus. No abnormalities were seen outside the brain. A diagnosis of diffuse pontine glioma was made. <br />
<br />
The chid was delivered at 36 weeks, 4 days becaue of the big head and had Apgar scores of 7 and 9. A repeat MRI was preformed and confirmed the prior findings. The boy underwent placement of an extraventricular drain because of signs of increased intracranial pressure. The child died from respiratory failure at day 3.<br />
<br />
At autospy the lesions was found to be primarily an infiltrative anaplastic oliogdendroglioma with areas of astroctyoma grade IV differentiation.<br />
<br />
Although I have posted on neonatal tumors in the past (<a href="http://dipg.blogspot.com/2013/04/10-and-15-year-survivors.html" target="_blank">click here for prior blog post</a>), the rarity of brainstem lesions in the neonatal period makes it difficult to know exactly what to do. Ther have been a few cases that have done well in the very young. There are other resports of the typically horrendous course of DIPG in the neonatal period. As researchers attempt to understand more about DIPG, this case adds to the library of knowledge regarding DIPG. The authors sugggest that autopsy studies should be strongly encouraged to learn more about this atypical situation. I would add that perhaps including this in the <a href="http://www.dipgregistry.org/" target="_blank">DIPG registry</a> would also be helpful. <br />
<br />
Reference-<br />
Prenatal MRI characterization of brainstem glioma<br />
in Pediatric Radiology<br />
<a href="http://www.ncbi.nlm.nih.gov/pubmed/23677423">http://www.ncbi.nlm.nih.gov/pubmed/23677423</a><br />
<br />
Spontaneous regression of a diffuse brainstem lesion in the neonate. Report of two cases and review of the literature<br />
<a href="http://www.ncbi.nlm.nih.gov/pubmed/16206736">http://www.ncbi.nlm.nih.gov/pubmed/16206736</a><br />
<br />
Lesion Regression<br />
<a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=AIREWELE+brainstem">http://www.ncbi.nlm.nih.gov/pubmed/?term=AIREWELE+brainstem</a><br />
<br />
Diffuse intrinsic brainstem tumors in neonates. Report of two case.<br />
<a href="http://www.ncbi.nlm.nih.gov/pubmed/18447673">http://www.ncbi.nlm.nih.gov/pubmed/18447673</a>LAShttp://www.blogger.com/profile/10542398672724609734noreply@blogger.com0tag:blogger.com,1999:blog-5847488566805525031.post-1825312928940928672013-05-22T09:38:00.000-05:002013-05-22T09:38:52.579-05:00Meagan's Walk 2014Well, the date has been set for 2014 Meagan's Walk! <br />
<br />
OK, I guess that shouldn't be a surprise as for more than a decade <a href="http://megswalk.squarespace.com/" target="_blank">Meagan's Walk</a> has been happening the Saturday of Mother's Day weekend in Toronto, Canada. I was remiss in posting earlier about this amazing event. Every year, thousands of people come out to for a leisurely 5K walk ending at The Hospital for Sick children. The partipants then form a human chain all around the hospital to give the hospital and the kids a loving hug. All this is done to raise awareness and funds for pediatric brain tumor research.<br />
<br />
Over the years, Meagan's Walk has raised more than 2.7 million dollars for Sick Kids brain tumor research. They directly fund preclinical research at the <a href="http://www.sickkids.ca/Research/BTRC/index.html" target="_blank">Arthur and Sonia Labatt Brain Tumour Research Center</a> lead by Dr James Rutka as well as clinical care and research initiative lead by Dr Eric Bouffet.<br />
<br />
So one might ask exactly why is this is a DIPG blog. Yes, Meagan had a diffuse brainstem glioma. The little girl's story is one that has been repeated again and again. She loved life playing with frineds and cuddling every little living creature. She died June 17, 2001 just about 7 months from diagnosis. Yet as we with so many of our kids, "Meagan's story is one of courage, spirit and hope." And as with so many parents, Denise- her mom, has continued to strive to make the story different for other families.<br />
<br />
Sick Kids has been a powerhouse of reasearch for DIPG and all pediatric brain tumors. I am sure Meagan's Walk has been part of the reason.<br />
<br />
Although this video is a few years old, pictures are worth more than all the words I could write here. Hearing the story from the mom and founder of Meagan's Walk is better than anything I could say.<br />
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<br />LAShttp://www.blogger.com/profile/10542398672724609734noreply@blogger.com0tag:blogger.com,1999:blog-5847488566805525031.post-87882429838236983702013-05-21T11:29:00.000-05:002013-05-21T11:31:14.046-05:00Jack's Angels Foundation Supporting CHLA DIPG ResearchI've always found that parents are the ones that care most about DIPG. It is the parents that are the ones that go on fighting against DIPG hoping that one day other parents will not have to endure the same fate as their family. And it has made a difference. The parents that have donated their children's tumors, started foundations, created DIPG awareness, funded DIPG research and have brought researchers together collaboratively have made a changed the landscape for DIPG. <br />
<br />
Jack's Angels Foundation is another parent-founded and led foundation in memory of a child who died from DIPG. The Foundation had their first fundraiser earlier this month hosting an art action ofchildren. student and trained artists' works. The proceeds are to go to Children's Hospital of Los Angeles DIPG Research.<br />
<br />
Jack was just 3 years old when on October 28, 2011 he was diagnosed with a DIPG. Having difficulties with hs speech and right side and a sudden fear of looking up he was admitted to CHLA. Like so many children Jack had radiation and steroids which gave him time to go to Disney and ride the bus to preschool. With an eye on quality of life and an eye on hope, the family relates the CHLA doctors gave the "wisest possible cousel concerning available chemotherapies" and that he avoided losing precious time pursuing other therapies that have not been effective. Just 9 months later, Jack was born into Light on July 30, 2012.<br />
<br />
Jack's Angels Foundation has formed to continue to fight agaisnt DIPG with funding of research at CHLA. <br />
<br />
CHLA is one of the <a href="http://www.pbtc.org/public/inst_contact_info.htm" target="_blank">Pediatric Brain Tumor Consortium institutions</a>. The physicians and researcher there have been quite interested in DIPG for some time. In fact, this has been one of the sites that has been <a href="http://justonemoreday.org/Research/ImagingResearch.html" target="_blank">specifically looking at imaging characteristics of these tumors</a>. Although the trial is not open yet at CHLA, they collaborators of the<a href="http://clinicaltrials.gov/show/NCT01182350" target="_blank"> upfront biopsy trial with molecularly determined treatment.</a> Through the PBTC they are participants in the <a href="http://clinicaltrials.gov/ct2/show/NCT01836549?term=dipg+los+angeles&rank=4" target="_blank">Imetelstat trial </a>for recurrent DIPG. And through COG they are participants in the <a href="http://clinicaltrials.gov/ct2/show/NCT01189266?term=dipg+los+angeles&rank=2" target="_blank">Vorinostat trial</a> for newly diagnosed children with DIPG.<br />
<br />
The news article says that CHLA and UCSF are working together and with other hopsitals in a loose consortium of researchers looking for new methods to treat DIPG. Clearly the upfront biopsy trial fits the bill as both institutions are involved. However, UCSF has also been doing great work on the advancement of understanding and treatment of pediatric brain tumors- from <a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=glioma+intranasal+san+francisco" target="_blank">intranasal administration of agents</a> to <a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=The+histone+H3.3K27M+mutation+in+pediatric+glioma+reprograms" target="_blank">unravelling the importance of the K27M mutation</a>. Since there are so few children with DIPGs, these collaborative efforts are important in pushing research forward as well as disseminating results as quickly as possible.<br />
<br />
I am glad to hear this first art auction was a success- hopefully one of many more to come.<br />
<br />
Reference-<br />
3-year old's death from rare brain tumor prompts Agua Dulce mom to help find a cure<br />
<a href="http://www.dailynews.com/ci_23211490/3-year-olds-death-from-rare-brain-tumor">http://www.dailynews.com/ci_23211490/3-year-olds-death-from-rare-brain-tumor</a><br />
<br />
Jack's Angels Foundation<br />
<a href="http://jacksangelsfoundation.com/">http://jacksangelsfoundation.com/</a><br />
<br />
Apparent Diffusional and Fractional Anisotrophy of Diffuse Intrinsic Brain Stem Gliomas<br />
<a href="http://www.ajnr.org/content/31/10/1879.long">http://www.ajnr.org/content/31/10/1879.long</a>LAShttp://www.blogger.com/profile/10542398672724609734noreply@blogger.com0tag:blogger.com,1999:blog-5847488566805525031.post-54910159698320111742013-05-18T15:04:00.001-05:002013-05-18T15:05:17.246-05:00K27M- Important in DIPG?It has been less than a year and a half since the St Jude and Canadian researchers came out <a href="http://www.genengnews.com/keywordsandtools/print/4/25908/" target="_blank">simultaneously with publications on histone H3 mutations in pediatric glioblastoma and DIPG</a>. These were the first ever reports on a "recurrent mutation in a regulatory histone in humans to case cancer and it seemed that those mutations may be drivers to alter the chromatinc architecture underlying the formation of pediatric GBMs and DIPGs. The H3 mutation specifically related to DIPGs seems to be K27M.<br />
<br />
This seemed to generate a huge amount of interest in pediatric high grade glioma/DIPG research as this SNO/PBTF Pediatric Neuro-Oncology Basic and Translational Research Conference held in Fort Lauderdale this week had several abstracts on this exact subject. In fact 4 of the 11 abstracts in the brainstem glioma section included K27M in their title.<br />
<br />
<a href="https://soc-neuro-onc.conference-services.net/reports/template/onetextabstract.xml?xsl=template/onetextabstract.xsl&conferenceID=3467&abstractID=740430" target="_blank">Functional Analysis of the H3.3-K27M Mutaton in DIPG</a><br />
University of Toronto, Duke University, The Hospital for Sick Children<br />
<br />
<a href="https://soc-neuro-onc.conference-services.net/reports/template/onetextabstract.xml?xsl=template/onetextabstract.xsl&conferenceID=3467&abstractID=740411" target="_blank">H3.3 K27M accelerates PDGR-induced brainstem gliomagenesis in vivo</a><br />
Duke Univeristy and Laboratory of Chromatin Biology and Epigenetic (NY)<br />
<br />
<a href="https://soc-neuro-onc.conference-services.net/reports/template/onetextabstract.xml?xsl=template/onetextabstract.xsl&conferenceID=3467&abstractID=738702" target="_blank">Targeting the histone H3.3-K27M mutation for the treatment of diffuse intrinsic pontine gliomas</a><br />
UCSF and Georgetown<br />
<br />
<a href="https://soc-neuro-onc.conference-services.net/reports/template/onetextabstract.xml?xsl=template/onetextabstract.xsl&conferenceID=3467&abstractID=740130" target="_blank">The type of histone H3-variant K27M mutation drives the agressiveness of Diffuse Intrinsic Pontine Gliomas</a><br />
France and UK<br />
<br />
In addition, another abstract lists that all the 20 previsously untreated DIPG specimens in their study had the K27M mutition. This abstract entitled <a href="https://soc-neuro-onc.conference-services.net/reports/template/onetextabstract.xml?xsl=template/onetextabstract.xsl&conferenceID=3467&abstractID=738496" target="_blank">"The genomic landscape of treatment naive DIPG biopsy samples"</a> was a combined effort from Paris, France; Barcelona, Spain; London, UK and Vancouver, Canada. <br />
<br />
It would seem that this K27M mutation is going to dominant upcoming discussions regarding DIPG. The Allis-Becher research alliance has already produced an <a href="http://www.ncbi.nlm.nih.gov/pubmed/23539183" target="_blank">elegant paper coming out electronically ahead of print the end of March in Science</a>. This article found that the K27M point mutation is specific to the for the mistake of methionine for lysine at that location. No other amino acid mistake in production causes the same problems. These authors propose that this mutation inhibits a specific complex which promotes tumor formation. It is more complex than that but that is the general idea.<br />
<br />
The potential of importance is varied when looking at these abstacts. This K27M mutation could be:<br />
-"one of the first prognositic markers when judging results of prospective trials"<br />
-"a target for novel intervention"<br />
-and a mechanism for DIPG formation.<br />
<br />
For those interested in DIPG research, I predict the K27M and other histone mutation research is going to be in the forefront in the near future.<br />
<br />
Reference:<br />
Brainstem Tumors, Radiaiton Therapy and Medulloblastoma (Platform Presentation Abstracts)<br />
<a href="https://soc-neuro-onc.conference-services.net/programme.asp?conferenceID=3467&action=prog_list&session=26434">https://soc-neuro-onc.conference-services.net/programme.asp?conferenceID=3467&action=prog_list&session=26434</a><br />
<br />
Inhibition of PRC2 Activity by a Gain of Function H3 Mutation Found in Pediatric Glioblastoma<br />
<a href="http://www.ncbi.nlm.nih.gov/pubmed/23539183">http://www.ncbi.nlm.nih.gov/pubmed/23539183</a><br />
<br />
Exceptional new Allis lab Science paper on exploding area of histone H3.3 in pedaitric brain cancer<br />
<a href="http://www.ipscell.com/tag/h3-3-k27m/">http://www.ipscell.com/tag/h3-3-k27m/</a>LAShttp://www.blogger.com/profile/10542398672724609734noreply@blogger.com0tag:blogger.com,1999:blog-5847488566805525031.post-8561432704302540622013-05-17T17:34:00.000-05:002013-05-18T08:17:15.929-05:00Feasibility, safety, and indications for surgical biopsy of intrinsic brainstem tumors in childrenThe USCF pediatric neurosurgical department this week had a publication come out electronically ahead of print regarding biopsy issues for intrinsic brainstem lesions. These doctors note that the situation with pediatric brainstem tumors is "virtually unlike any other location in the brain" because for these other areas the first step is obtaining a tissue diagnosis to devise an appropriate treatment course. The reason for the lack of biopsy has been the perception of excessive risk of pediatric brainstem biopsy. The article also notes that the current approach of investigating a wide array of chemotherapeutic options in multitudinous trials without biologic tumor analysis has not lead to any increased survival in the last two decade. The authors evaluated the feasibility and safety of pediatric brainstem biopsy at their institution.<br />
<br />
Nine children ( 4 male and 5 female witht he average age of 5.7 years) underwent brainstem biopsy between 2000 and 2011 under approval from the Committee for Human Research. Children were exlcuded from the study if the tumor originated from the cerebellum or cerebral hemispheres, were exophytic or well defined lesions. All included children had typical DIPG imaging features. The included children presented with cranial nerve palsies (7/9), ataxia (5/9) and headache (3/9). Rarer symptoms included head tilt, nausea, weakness on one side and respiratory distress.<br />
<br />
The authors did discuss target selection. All children had stereotactic biospies via a transcerebellar approach. The course was chosen to minimize passing through the brainstem avoiding the lateral edge of the 4th ventical, pontine tegmentum and ventral corticospinal tracts. In some cases diffusion tensor imaging was used to locate the corticospinal tracts. Unless there was an obviously enhancing, aggressive area the site selection was just deep to the middle cerebellar penduncle. One to four specimens were taken.<br />
<br />
All cases were gliomas. Five of the children had high grade gliomas and four were low grade. None of the children suffered intraoperative complications. One of hte children developed seizures and hypercephalus postoperative which was treated with a shunt. Seven of the patients underwent radiation and chemotherapy and two underwent chemotherapy only. All children did experience the natural progresssion of DIPG with decline in neurologic and functional status. At the time of the publication writing 4 children had died- 2 high grade at 12 months and 2 low grade at 6 and 11 months.<br />
<br />
The authors point out the the tremendous lack of progress with DIPG statitics has lead to "therapeutic nihilism". However, they point out ther are many targeted biologic agents that might have potential on the horizon. The problem is for phase II trials there will "certainly require tissue in order to determine molecular pheontype prior to treatment assignement". <br />
<br />
It seems that this publication is looking specificially forward to those biologic agent trials so that DIPG children will not be excluded just on the basis of not having a tissue analysis. Although biopsy did not aid the children in this study, it did outline that biopsy can be preformed safely in children with DIPG and gives some tips on the approach of such biospies.<br />
<br />
With biospy and convection enhanced delivery I would hope that more pediatric neurosurgeons will become increasingly interested in options for children with DIPG.<br />
<br />
References:<br />
Feasibility, safety and indications for surgical biopsy of intrinsic brainstem tumors in children<br />
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LAShttp://www.blogger.com/profile/10542398672724609734noreply@blogger.com1tag:blogger.com,1999:blog-5847488566805525031.post-78137589570630738542013-05-09T16:20:00.000-05:002013-05-09T16:20:46.964-05:00Stanford's Big News- Anti CD47Recently there has been quite a bit of press over Stanford's research on an anti-CD 47 drug because of a recent publication and potential of upcoming clinical trials. Now it seems that the FDA has approved this- human clinical trials. Because I am primarily interested in pediatric brain tumors, I rarely get excited about this type of news as in the past it often has taken years to go from first in man studies to our kids. However, this might not be the case with this new agent. It seems that DIPG has been on the minds of the developers of this anti- CD47 antibody already. Stanford already lists this as a topic in their <a href="http://www.lpch.org/clinicalSpecialtiesServices/COE/BrainBehavior/Neurosurgery/ccbt.html" target="_blank">pediatric brain tumor research program</a>!<br />
<br />
So what is so special about this anti-CD47 antibody that it has been called the <a href="http://www.nypost.com/p/news/international/every_cancer_kills_tumor_them_kind_L9lppJmy9gCoS848cSzqbP" target="_blank">"Holy Grail" of cancer research</a>?<br />
<br />
Apparently cells have these proteins on them called CD47 which tell a person's body "don't eat me". Those things that are foreign don't have these proteins so the idea is that the immune system will get destroy them. Cancer cells have alot of these CD47 proteins on them which allows them to continue to survive by tricking the immune system.<br />
<br />
A decade ago a Stanford researcher, Irving Weissman, found that leukemia cells had more CD47 on them than normal healthy cells. Later the researchers found that every type of cancer they tested had high levels of CD47 than healthy cells. They developed an anti-CD 47 antibody and tested it on tumor cells in petri dishes. Without the antibody the macrophages (those cells which eating up stuff that shouldn't be there) ignored the cancer cells. However, when the samples had the anit-CD47 antibody included the macrophages destroyed all types of cancer cells. They then tested the agent on mice with similar effects.<br />
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There has been some concern that since all cells have CD47 that there could be some significant side effects in normal tissue. Although there has been some transient decreases in blood counts other effects were not seen in mice. The hope is that this will hold true in people as well.<br />
<br />
The Stanford team has recieved a four-year $20 million grant for California Institute for Regenerative Medicine to translate these findings from mice to humans. Since Stanford seems to have the funding, the approval and the interest in DIPG this might be research to watch as sometime in the future this agent might become a clinical trial option for kids with DIPG.<br />
<br />
<i>Names to Know: It seems the Stanford <a href="http://ludwigcenter.stanford.edu/research/beachy.html" target="_blank">researchers involved in this project</a> and interested in pediatric DIPG included Michelle Monje, Hans Vogel, Paul Fisher, Albert Wong, Irving Weissman and Phillip Beachy as well as David Rowitch (UCSF).</i><br />
<br />
References:<br />
Antidote: On Cancer and CD47<br />
<a href="http://www.mmm-online.com/antidote-on-cancer-and-cd47/article/291840/">http://www.mmm-online.com/antidote-on-cancer-and-cd47/article/291840/</a><br />
<br />
CD47 Antibody treatment shrinks or eliminate human cancer tumors in mice (Stanford Video)<br />
<a href="https://www.youtube.com/watch?v=EyGWZbmjeR0">https://www.youtube.com/watch?v=EyGWZbmjeR0</a><br />
<!--EndFragment-->LAShttp://www.blogger.com/profile/10542398672724609734noreply@blogger.com0tag:blogger.com,1999:blog-5847488566805525031.post-11932218939528459162013-05-08T21:07:00.001-05:002013-05-08T23:25:30.290-05:00Their Ultimate Last Stand- McKenna Claire Foundation<span style="font-family: Times, Times New Roman, serif;">When the beautiful, green-eyed, blond 7 year-old California kid, McKenna Claire Wetzel, started to throw up in January 2011 it was just thought to be the flu that had been going around. After of week of illness and a couple visits to the doctor, her parents started to notice a wandering left eye. The CT Scan that followed found the DIPG.</span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">Good friends and good times- two of life's greatest gifts. MckKenna's parents worked hard for both. They had been told that this tumor was not survivable. Thus, they told their oldest child that they were doing thing to make Mckenna feel better- sadly not to cure her. She traveled to Hawaii, to tapings of both American Idol and Dancing with the Stars and sat on the floor at the Laker's game. She continued to go to second grade and every Tuesday night was "homework parties" at her house. The parties were more about community and friendship than homework. As things worsened her friend, Katie, would sit for hours holding McKenna's hand in silence. </span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">Just six months from hearing DIPG, McKenna passed away. As devastating as this was, the Wetzel's were making one "last stand" against the tumor. They decided to donate Mckenna's tumor to Michele Monje's lab at Stanford. A lab tech from Stanford flew down as a guardian for this precious gift as it came to a new home- a place striving to learn how get rid of "that stupid tumor".</span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">However, the Wetzel's realized that funded research would be able to do more. To honor McKenna and "perpetuate the sense of community", the McKenna Claire Foundation was born. In less than 2 years the foundation has raised approximately a half million dollars. One amazing thing was last May (Brain Cancer Awareness Month) the Chevron Corporation raised $292,466 at some of their California convenience stores.</span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">These funds have been provided to Michele Monje's lab at Stanford which had grown a cell line from McKenna's tumor. And although cell lines haven't been easy to transport, Michele Monje's lab seems to have overcome this hurdle. McKenna's tumor now is also being studied by researchers in England and Australia!</span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">Some of that funding had gone to fund the position of "tumor cell line guardian". OK, Anitha Pannuswami's official title is<span style="background-color: white; line-height: 21.59375px;"> laboratory manager at Monje’s lab at Stanford. Often times salary funding is not part of grants, but I believe this has been a important factor in being able to do more in DIPG research. Anitha Pannuswami's job is to watch over McKenna's tumor as well as 5 other children's at the Monje lab. She also handles shipping</span><span style="background-color: white; line-height: 21.59375px;"> them in ice to any researcher in the world who wishes to study DIPG. This is defnitely increasing DIPG reasearch internationally.</span></span><br />
<span style="font-family: Times, Times New Roman, serif;"><span style="background-color: white; line-height: 21.59375px;"><br /></span></span>
<span style="font-family: Times, Times New Roman, serif;"><span style="background-color: white; line-height: 21.59375px;">This May's Brain Cancer Awareness Month, the Chevron Corporation has expanded their support through their convenience stores throughout California. The Mckenna Claire Foundation has several <a href="http://mckennaclairefoundation.org/events/" target="_blank">other events already planned for 2013</a>. </span></span><br />
<br />
<span style="font-family: Times, Times New Roman, serif;"><span style="line-height: 21.59375px;">McKenna's tumor is flying like a butterfly around the world. Without a doubt, the McKenna Claire Foundation and the targeted partnership with Stanford is changing the landscape for DIPG Research. I predict both will be well worth watching.</span></span><br />
<br />
<span style="font-family: Times, Times New Roman, serif;">References:</span><br />
<span style="font-family: Times, Times New Roman, serif;">Tumor that killed girl could keep others alive</span><br />
<span style="font-family: Times, Times New Roman, serif;"><a href="http://www.bendbulletin.com/article/20130427/NEWS0107/304270355/">http://www.bendbulletin.com/article/20130427/NEWS0107/304270355/</a></span><br />
<span style="font-family: Times, 'Times New Roman', serif;"><br /></span>
<span style="font-family: Times, 'Times New Roman', serif;">Chevron customers raise $292,466 for McKenna Clair Foundation fight against pediatric cancer</span><br />
<a href="http://www.orangecounty.com/articles/chevron-41266-foundation-claire.html%23" style="font-family: Times, 'Times New Roman', serif;">http://www.orangecounty.com/articles/chevron-41266-foundation-claire.html#</a><br />
<span style="font-family: Times, 'Times New Roman', serif;"><br /></span>
<span style="font-family: Times, 'Times New Roman', serif;">Mckenna Claire Foundation</span><br />
<a href="http://mckennaclairefoundation.org/"><span style="font-family: Times, Times New Roman, serif;">http://mckennaclairefoundation.org/</span></a>LAShttp://www.blogger.com/profile/10542398672724609734noreply@blogger.com0tag:blogger.com,1999:blog-5847488566805525031.post-71573410754546838782013-05-07T19:01:00.000-05:002013-05-07T19:02:30.812-05:00Part 2- Do the efflux transporters protect the glioma cells?One of the longstanding questions for DIPG has been."Why doesn't chemo work?" <br />
There have been dozens of trials using all kinds of agents and all of them have virtually the identical Kaplan Meier Curve. The think we don't know is why that is. Often times one hears about something in the blood brain barrier that limits chemotherapy effectiveness. Other times one wonders if it is something in the glioma cells themselves that make them more resistant. The Netherlands paper tried to answer one part of this in better defining ABC transporters in pediatric glioma.<br />
<br />
ABC transporters essentially function as little door ways in the cell's membrane either usher substances into the cell (importers) or out of the cells (exporters). The exporters are tone ones that are a problem withe drug resistance. The transporters pump drugs and toxins out of the cells. <br />
<br />
There have been 3 different ABC transporters found that escort drugs out of cells. These include P-glcyoprotein (P-gp, ABCB1), breast cancer resistance protein (BCRP, ABCG2) and multidrug resistance associated proteins (MRPs, ABCC1).<br />
<br />
This Netherlands study looked at the above 3 ABC transporters in each of the glioma cell lines. All cell lines were negative for P-gp. Only one supratentorial pediatric glioma cell line had BRCP1. High levels of MRP1 was found in 4 of the 9 glioma cell lines. That included 2 of 3 of the DIPG cell lines.<br />
<br />
The researchers then looked at actual tumor sample sections to try to determine the amount of ABC transporters in the glioma cells versus the blood vessels. They found that P-gp was not present in most of the glioma cells but was presesnt moderately in the tumor's blood vessels. BCRP1 was not present in the glioma cells but was highly pressent in the blood vessels. Only MRP1 was seen in both the glioma cells and the blood vessels. A chart on the cell lines tested (including 2 of the 3 DIPG samples) is available (click <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639279/table/pone-0061512-t004" target="_blank">here </a>to see chart).<br />
<br />
So, what does this mean for DIPG now? <br />
<br />
That is hard to say. So far tying to inhibit the ABC transporters with different agents have been problematic because of significant toxic side effects. These ABC transporters are meant to protect normal cells as well. However, since most of the ABC transporters seem to be in the blood vessels a way around this blood-brain barrier could be direct tumor delivery (i.e., convenction enhanced delivery). The researchers also suggest developing drugs that are not a substract for these transporters could also increase chemotherapy effectiveness.<br />
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It does tell us that in trying to find a cure for DIPG that we can not just focus on finding targets within the cancer biology but also need to work on finding ways for new agents to be able reach these targets.<br />
<br />
Note: The ATP-binding cassette transporters issue was featured in a <a href="http://abc%20transporters%20limit%20dasatinib%20efficacy%20in%20mice/" target="_blank">recent blogspot</a> regarding a new abstract out of Oren Becher's lab in Duke. <br />
<i style="background-color: white; color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.545454025268555px; line-height: 18.18181800842285px;"><span style="font-family: Times, 'Times New Roman', serif;"><br /></span></i>
<i style="background-color: white; color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.545454025268555px; line-height: 18.18181800842285px;"><span style="font-family: Times, 'Times New Roman', serif;">This work was funded by<a href="http://www.kika.nl/" style="color: #445594; text-decoration: none;" target="_blank"> KiKa "Stichting Kinderen Kankervrij"</a>- Dutch Children Cancer-free Foundation.</span></i><br />
<i style="background-color: white; color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.545454025268555px; line-height: 18.18181800842285px;"><span style="font-family: Times, 'Times New Roman', serif;"><br /></span></i>
<span style="background-color: white; color: #333333; font-family: Times, 'Times New Roman', serif; font-size: 14.545454025268555px; line-height: 18.18181800842285px;">References:</span><br />
<span style="background-color: white; color: #333333; font-family: Times, 'Times New Roman', serif; font-size: 14.545454025268555px; line-height: 18.18181800842285px;">In vitro drug response and efflux transporters associated with drug resistance in pediatric high grade glioma and diffuse intrinsic pontine glioma</span><br />
<span style="background-color: white; color: #333333; font-family: Times, 'Times New Roman', serif; font-size: 14.545454025268555px; line-height: 18.18181800842285px;"><span role="menubar" style="line-height: 15.954861640930176px;"><a abstractlink="yes" alsec="jour" alterm="PLoS One." aria-expanded="false" aria-haspopup="true" href="http://www.ncbi.nlm.nih.gov/pubmed/23637844#" role="menuitem" style="border-bottom-width: 0px; color: #660066; text-decoration: none;" title="PloS one.">PLoS One.</a></span><span style="line-height: 15.954861640930176px;"> 2013 Apr 29;8(4):e61512. doi: 10.1371/journal.pone.0061512. Print 2013.</span></span><br />
<span style="background-color: white; color: #333333; font-family: Times, 'Times New Roman', serif; font-size: 14.545454025268555px; line-height: 18.18181800842285px;"><span style="line-height: 15.954861640930176px;">Free Full Text- </span><a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639279/" style="color: #445594; text-decoration: none;">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639279/</a></span><br />
<span style="background-color: white; color: #333333; font-family: Times, 'Times New Roman', serif; font-size: 14.545454025268555px; line-height: 18.18181800842285px;"><br /></span><span style="background-color: white; color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.545454025268555px; line-height: 18.18181800842285px;"></span><span style="background-color: white; color: #333333; font-family: Times, 'Times New Roman', serif; font-size: 14.545454025268555px; line-height: 18.18181800842285px;">KiKa Stichting Kinderen Kankervrij- Dutch Children Cancer-free Foundation</span><br />
<span style="background-color: white; color: #445594; font-family: Times, 'Times New Roman', serif; font-size: 14.545454025268555px; line-height: 18.18181800842285px; text-decoration: none;"><a href="http://www.kika.nl/" style="background-color: white; color: #445594; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.545454025268555px; line-height: 18.18181800842285px; text-decoration: none;">http://www.kika.nl/</a></span><br />
<br />
ABC transporters limit dansantinib efficacy in mice<br />
<a href="http://dipg.blogspot.com/2013/04/abc-transported-limit-dasatinib.html">http://dipg.blogspot.com/2013/04/abc-transported-limit-dasatinib.html</a>LAShttp://www.blogger.com/profile/10542398672724609734noreply@blogger.com0tag:blogger.com,1999:blog-5847488566805525031.post-27856979495490504052013-05-06T13:38:00.000-05:002013-05-06T13:38:38.347-05:00New Publication- Are DIPGs just resistant to chemo? No!<span style="font-family: Times, Times New Roman, serif;">Last week the highly productive, DIPG-focused Netherlands group from VU University Medical Center in Amsterdam put forth another publication which happens to have <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639279/" target="_blank">free full text available</a>!</span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">This research focuses on unravelling the reasons why chemotherapy has not been beneficial against DIPGs and pediatric high-grade gliomas. Are DIPGs just resistant to the agents? Or, is it that something is protecting the cells which causes an otherwise good option to be ineffective?</span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<b><u><span style="font-family: Times, Times New Roman, serif;">Part 1- Are glioma cells just resistant to chemotherapy?</span></u></b><br />
<span style="font-family: Times, Times New Roman, serif;">To look at the first question, the researchers evaluated 9 pediatric glioma cell lines to eliminate questions of adequate drug delivery. Three of these cell lines were from children with DIPGs and 6 were from supratentorial high grade gliomas. Of the 3 DIPG cell lines, all were of different histologic grades- one GBM, one anaplastic astrocytoma and one diffuse fibrillary asrocytomas. Two of these DIPG cell lines came from children who had not had any treatment. The other cell line came from an autopsy donation done approximately 2 hours after death.</span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">In the screening of these cell lines, several agents had high level of killing tumor cells. </span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">When looking at targeted small molecule agents, these did not fare as well as classical chemotherapies. Some did show some efficacy . The best of these was bortezomib which resulted in more than 50% reduction in cell line surival in 6/9 cell lines. There was little or no effect with erlotinib and everolimus. A hypothesis for this result include that the cell lines were not checked for the targets. If there was a matching of targets and agents the results might have been better. Also since there are multiple messed up pathways combined therapy is generally thought to be needed and a single agents is very unlikely to be effective.</span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="line-height: 23.328125px;"><span style="font-family: Times, Times New Roman, serif;">In looking at classic chemotherapy agents, melphalan was the only drug that had significiant toxicity in all cell lines. Interestly that is the exact agent of the <a href="http://www.hopkinsmedicine.org/interventional_neuroradiology/conditions_procedures/progressive_diffuse_intrinsic_pontine_glioma" target="_blank">new intra-arterial Hopkins DIPG trial</a>!</span></span><br />
<span style="line-height: 23.328125px;"><span style="font-family: Times, Times New Roman, serif;"><br /></span></span>
<span style="font-family: Times, Times New Roman, serif;"><span style="line-height: 23.328125px;">Other agents that were found to have a signficant effect included</span> doxorubicin, mitoxantrone and BCNU. The next level included etoposide, thiotepa and carboplatin. Carboplatin was of special note since that is what the<a href="http://dipg.blogspot.com/2013/04/uk-gives-ced-go.html" target="_blank"> UK in their CED report</a>.</span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, 'Times New Roman', serif;">What this means for DIPG is that DIPG is not necessarily resistant to chemotherapy! Effective drgus might not be the biggest hurdle for a cure for DIPG. It might be getting them to the tumor cells.</span><br />
<br />
<i><span style="font-family: Times, Times New Roman, serif;">This work was funded by<a href="http://www.kika.nl/" target="_blank"> KiKa "Stichting Kinderen Kankervrij"</a>- Dutch Children Cancer-free Foundation.</span></i><br />
<span style="font-family: Times, 'Times New Roman', serif;"><br /></span>
<span style="font-family: Times, 'Times New Roman', serif;">Tomorrow.....</span><br />
<b><u><span style="font-family: Times, Times New Roman, serif;">Part 2- Do the efflux transporters protect the glioma cells?</span></u></b><br />
<span style="font-family: Times, 'Times New Roman', serif;"><br /></span>
<span style="font-family: Times, 'Times New Roman', serif;">References:</span><br />
<span style="font-family: Times, Times New Roman, serif;">In vitro drug response and efflux transporters associated with drug resistance in pediatric high grade glioma and diffuse intrinsic pontine glioma</span><br />
<span style="font-family: Times, Times New Roman, serif;"><span role="menubar" style="background-color: white; line-height: 15.954861640930176px;"><a abstractlink="yes" alsec="jour" alterm="PLoS One." aria-expanded="false" aria-haspopup="true" href="http://www.ncbi.nlm.nih.gov/pubmed/23637844#" role="menuitem" style="border-bottom-width: 0px; color: #660066;" title="PloS one.">PLoS One.</a></span><span style="background-color: white; line-height: 15.954861640930176px;"> 2013 Apr 29;8(4):e61512. doi: 10.1371/journal.pone.0061512. Print 2013.</span></span><br />
<span style="font-family: Times, Times New Roman, serif;"><span style="background-color: white; line-height: 15.954861640930176px;">Free Full Text- </span><a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639279/">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639279/</a></span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">KiKa Stichting Kinderen Kankervrij- Dutch Children Cancer-free Foundation</span><br />
<a href="http://www.kika.nl/"><span style="font-family: Times, Times New Roman, serif;">http://www.kika.nl/</span></a>LAShttp://www.blogger.com/profile/10542398672724609734noreply@blogger.com0tag:blogger.com,1999:blog-5847488566805525031.post-3056819242705861872013-05-05T14:59:00.000-05:002013-05-05T14:59:21.304-05:00More than 2 Million- DC Race for Hope!Today was the 16th year for the DC Race for Hope. It drew over 11,000 people and raised more than 2 million dollars! The <a href="https://www.facebook.com/RFHDC" target="_blank">facebook page</a> says that the count is more than 2.3 million and counting. Check out the pictures on their page. It is heartening to see the street with people filled supporting the fight against brain tumors.<br />
<br />
One of the teams for the past several years has been David Cook. He is the Season 7 winner of American Idol. He also lost his brother to a 10 year battle with brain cancer. This week he was back on the Idol stage and specific mention was made of his passion for supporting brain tumor research. (Click <a href="http://www.youtube.com/watch?v=WIRc682FUno" target="_blank">here</a> to see the video)<br />
<br />
In it's history the DC Race for Hope has raised more than 17 million for brain tumor research. The funds go to the National Brain Tumor Society and Accelerated Brain Cancer Cure (ABC2). These foundations are fighting all brain tumors- many kinds and all ages. <br />
<br />
Perhaps at one time pediatric brain tumors seemed to be off on their own but not anymore. To me, it definitely seems that DIPG research has matured in the past few years that it has now naturally melded into other glioma research.<br />
<br />
I was taken by surprised when <a href="http://abc2.org/smarter-research/who-we-fund/dipg-preclinical-consortium" target="_blank">ABC2 </a>decided not only to provide funds for the DIPG Preclinical Consortium (initiated at the first DIPG Collaborative Symposium) but also provided strategic advice "to help the research consortium preform DNA (exon) sequencing of all DIPG cell lines, their primary tumor and paired normal DNA via the laboratory of Dr Paul Spellman at OHSU.<br />
<br />
And the National Brain Tumor Society sponsored and attended the DIPG Collaborative Symposium. Their <a href="http://www.braintumor.org/research/research-initiatives/pediatric-research.html" target="_blank">Pediatric Research Initiative</a> seems to be exactly what are top priorities for DIPG- molecular profiling and neuordevelopmental biology (gliomagenesis). The National Brain Tumor Society grants in 2010 funded the ground-breaking work DIPG genomic work of both Cynthia Hawkins in Toronto and Suzanne Baker of St. Jude which has reported some of the most exciting results for DIPG- particularly the histone/K27M findings.<br />
<br />
Times are changing. Just a few years ago there was no preclinical DIPG research. Now DIPG research has garnered the interest and inclusion from larger brain tumor organizations. DIPG does have alot in common with adult GBMs- particularly poor statistics, invasiveness and the blood brain barrier. The combined efforts with these other organizations seems to be a great thing in fighting DIPG.<br />
<br />
Reference:<br />
DC Race for Hope-<br />
<a href="http://www.braintumorcommunity.org/site/PageServer?pagename=RFH_DC_Homepage">http://www.braintumorcommunity.org/site/PageServer?pagename=RFH_DC_Homepage</a><br />
<!--EndFragment-->LAShttp://www.blogger.com/profile/10542398672724609734noreply@blogger.com0tag:blogger.com,1999:blog-5847488566805525031.post-37937684892800804172013-05-04T10:00:00.000-05:002013-05-04T10:00:24.013-05:00Dr Souweidane CED Trial on 8th PatientThe <a href="http://www.cristianriverafoundation.org/" target="_blank">Cristian Rivera Foundation</a>, a significant support of the <a href="http://clinicaltrials.gov/ct2/show/NCT01502917?term=dipg&rank=16" target="_blank">Cornell convection enhanced delivery (CED) trial for newly diagnosed children with DIPG</a>, announced in their <a href="http://mad.ly/3b05b3?pact=419779530678882037&fe=1" target="_blank">April 2013 newsletter</a> that the primary investigator, Dr. Mark Souweidane, is now up to his 8th patient in this trial that opened at the end of 2012.<br />
<br />
This is a very exciting, innovative trial for DIPG where a catheter is placed from the top of the head down in to the brainstem. A few weeks after traditional radiation, a radiolabelled antibiody is infused directly in to the pons. Thus, the blood brain barrier is no longer a problem in getting an agent into the tumor. <br />
<br />
This is different than other DIPG CED trials in that it uses a radiolabelled antibody. The antibody is<br />
8H9 which has been found in several different tumors. This is linked to 124I which is radioactive. Since radiation has been the only thing that has made a dent in survival statistics the hope seems that this targeted radiation will clean up some of the cancer cells that have thus far been radioresistant with routine radiation.<br />
<br />
This trial is the culmination of more than a decade of research utlitizing CED in the brainstem undertaken by Dr Souweidane and his team at Cornell. Below is a video illustrating how CED is performed.<br />
<br />
<br />
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<br /></div>
For more information about this trial, about the trial and contact information for Dr. Soweidane click <a href="http://cornellneurosurgery.org/pedneuro/dipg-news.html" target="_blank">here</a>.<br />
<br />
Related Blog Post:<br />
UK Gives CED a Go<br />
<a href="http://dipg.blogspot.com/2013/04/uk-gives-ced-go.html">http://dipg.blogspot.com/2013/04/uk-gives-ced-go.html</a><br />
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<!--EndFragment-->LAShttp://www.blogger.com/profile/10542398672724609734noreply@blogger.com0tag:blogger.com,1999:blog-5847488566805525031.post-69693654492395879342013-05-03T09:42:00.001-05:002013-05-03T09:42:32.829-05:00DIPG CollaborativeThe DIPG Collaborative "is an association of foundations unified with the mission of efficiently funding and inspiring DIPG research in hopes of finding a wider cure for cancer". From The Cure Starts now website it says that the Collaborative Council is to:<br />
1) provide the tools and information to families whose children face the difficult diagnosis of pediatric brain cancer.<br />
2) provide a warm and caring envirnoment to share information, discuss options and support one another.<br />
3) make available accurate and easy to understand information for families that are newly diagnosed. <br />
<br />
A major kick off of the DIPG Collaborative was the 2011symposium that brought 13 foundations together with researcher to find substantive ways to research DIPG jointly together. From that meeting several research infrastructure developments occurred which now really allows us to start to unravel DIPG. These included the DIPG Preclinical Consortium, the DIPG Resgistry and the DIPG Genomics Repository. <br />
<br />
If one hasn't looked at the <a href="http://pptiohsu.blogspot.com/2011/12/open-science-forum-dipg-preclinical.html" target="_blank">Preclinical Consortium</a>, I think it is worth the time as it is impressive. It is less than 4 years from when the first cell line was promulgated in Michelle Monje's lab (from tissue donated by <a href="http://stanmed.stanford.edu/2009summer/article7.html" target="_blank">Dylan Jewett)</a>. Through the consoritum we now have ten institutions working together on more than 30 cell lines (as well as various animal models) trying to find the best single agents or combinations in those cell lines to be a basis for rapid translation into clinical trials. Every week there is an update on the consortiums work including DNA and RNA analysis. This is fully funded byt the Foundational Leadership Partnters of the DIPG Colaborative.<br />
<br />
The <a href="http://www.dipgregistry.org/" target="_blank">DIPG Registry</a> is equally impressive. There is a section for<a href="http://www.dipgregistry.org/medical-professionals/" target="_blank"> medical professionals</a> including sections on enrollment information and consultations. There is also a section for parents where one can make contact for second opinions and also search for open clinical trials. Parents can make contact with the registry to discuss enrollment- even for children who have died. There already is some <a href="http://www.dipgregistry.org/patients-families/" target="_blank">specific research</a> in the works.<br />
<br />
The DIPG Collaborative Symposium starts today, however, the major work of the DIPG Collaborative for foundations starts tomorrow. The first session is on objectives for the next two years. It would be really interesting to see the direction this collaborative is moving.<br />
<br />
There are three levels of support:<br />
<u>Foundational Leadership Partners -</u> <a href="http://www.thecurestartsnow.org/" target="_blank">The Cure Starts Now</a>, <a href="http://chapters.thecurestartsnow.org/australia/" target="_blank">The Cure Starts Now Australia</a>, <a href="http://www.jthf.org/" target="_blank">Jeffrey Thomas Hayden Foundation</a>, <a href="http://www.hopeforcaroline.org/" target="_blank">Hope for Caroline</a>, <a href="http://soarwithgrace.org/" target="_blank">Soar with Grace</a>, <a href="http://www.reflectionsofgrace.org/" target="_blank">Reflections of Grace Foundation</a>, <a href="http://www.lylansoulifoundation.org/" target="_blank">The Lyla Nsouli Foundation</a><br />
<br />
<u>Foundation Partners</u>- <a href="http://www.smilesforsophieforever.org/" target="_blank">Smiles for Sophie Forever</a>, <a href="http://www.bennysworld.org/" target="_blank">Benny World</a>, <a href="http://www.teamjulianfoundation.com/" target="_blank">The Team Julian Foundation</a><br />
<br />
<u>Symposium Sponsors</u>- <a href="http://www.maxlacewell.org/" target="_blank">Max Lacewell Foundation</a>, <a href="https://www.facebook.com/pages/Love-Chloe-Foundation/58900648500" target="_blank">Love Chloe Foundation</a>, <a href="http://www.carolinesmiraclefoundation.org/" target="_blank">Caroline's Miracle Foundation,</a> <a href="https://www.kintera.org/AutoGen/Simple/Donor.asp?ievent=447507&en=grIHJSOCKhKLKZOJJ9KGKTMDJoLVI0NHIjLMJZONIrI5E" target="_blank">Ellie DIPG Research Fund</a>, <a href="http://www.carolinesmiraclefoundation.org/" target="_blank">American Childhood Cancer Organization,</a> <a href="http://www.prayhopebelieve.org/" target="_blank"> Pray Hope Believe Foundation,</a> <a href="http://www.braintumor.org/" target="_blank">National Brain Tumor Society</a>, Lurie Children's Hospital of Chicago, Cincinnati Children's Hospital<br />
<br />
References:<br />
CSN DIPG Collaborative Council<br />
<a href="http://www.thecurestartsnow.org/about/foundation/councils/DIPGcollaborative/">http://www.thecurestartsnow.org/about/foundation/councils/DIPGcollaborative/</a><br />
<br />
DIPG Collaborative<br />
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<a href="http://dipg.org/">http://dipg.org/</a></div>
LAShttp://www.blogger.com/profile/10542398672724609734noreply@blogger.com0tag:blogger.com,1999:blog-5847488566805525031.post-20914378158357415452013-05-02T09:26:00.000-05:002013-05-02T09:26:14.126-05:00DIPG Collaborative Symposium Begins in CincinnatiTomorrow the 2nd <a href="http://www.soc-neuro-onc.org/en/cev/95/" target="_blank"> DIPG Collaborative Symposium</a> begins in Cincinnati. This two track program brings together doctors and researchers in one track and foundations and parents in another (with a potential networking dinner Friday evening). The goal is to be able to "efficiently fund and inspire diffuse intrinsic pontine glioma cancer research in hopes of finding a wider cure for cancer". This year there is expected to be approximately 140 from 7 countries. With the <a href="https://csn.donordrive.com/assets/csn/files/$cms$/100/2097.pdf" target="_blank">diverse agenda</a> with international speakers on the forefront of DIPG research, I suspect it will be an exciting place to be for those interested in pediatric diffuse intrinsic pontine glioma.<br />
<br />
The 2011 DIPG Collaborative Symposium brought about some substantive advances in the infrastructure critical for DIPG research including the <a href="http://www.dipgregistry.org/" target="_blank">DIPG Registry</a>, <a href="http://pptiohsu.blogspot.com/2011/12/open-science-forum-dipg-preclinical.html" target="_blank"> the DIPG Preclinical Consortium</a>, and the<a href="http://www.progenetix.org/cgi-bin/projectsHome.cgi?project=DIPG" target="_blank"> DIPG Genomics Repository</a>.<br />
<br />
This meeting starts Friday morning with a Keynote Lecture from Canadian geneticist and researcher, Nada Jaboda MD PhD. Although the topic has not been release I am thinking- H3.3,K27M and epigenetics. To get a taste of the work she has been doing in unravelling pediatric vs adult astrocytomas (including DIPG) there is a NYU Grand Rounds titled "Rewiring the Epigenome in Pediatric and Young High Grade Astrocytomas" presented on December 18, 2012. (click <a href="http://grandrounds.pediatrics.med.nyu.edu/grandrounds/archive?page=2&vid=892968&gnr=538311" target="_blank">here</a> to watch the video) This work has the potential to change how we approach and treat DIPGs.<br />
<br />
The meeting continues with a <a href="http://www.thecurestartsnow.org/research/grants/" target="_blank">update of research funded</a> through the collaborative and the Cure Starts Now:<br />
<u>Preclinica/Traslantional</u><br />
* Xiao-Nan Li(Baylor)- an oncolytic picorna virus in a DIPG xenograft mouse model.<br />
* Oren Becher (Duke)- systemic and direct delivery of a PDFGR-alpha antibody.<br />
* Suzanne Baker (St Jude)- establishment and characterization of DIPG renewable tissue resources<br />
* Patricia Baxter (Texas)- Novel BMI-1 inhibitors in brainstem xenograft mouse models.<br />
* Michele Monje (Stanford)- combined targeted therapy for cellular subpopulations in DIPG.<br />
<u><br /></u>
<u>Clinical</u><br />
Mark Souweidane (Cornell)- CED trial update<br />
multiple- DIPG Registry update<br />
<br />
This will be followed by various other sessions especially revolving around biopsy, biologic understanding of DIPG and current trends in clinical trials. One of the most anticipated things for me is the Xerecept session on Friday afternoon. It has been years of waiting for this drug to see if it can decease the suffering caused by steroids in so many DIPG children (click <a href="http://www.onetruemedia.com/otm_site/view_shared?p=8d2edf5ee009313a2c54e7&skin_id=1901&large" target="_blank">here</a> for video). Hopefully something substantive will come from this session.<br />
<br />
The other track- the parents and foundation track- will meet primarily on Saturday to discuss the Collaborative objectives, structure, prior efforts and success.<br />
<br />
The event will culminate with a <a href="http://csn.donordrive.com/index.cfm?fuseaction=donorDrive.event&eventID=628" target="_blank">Once in a Lifetime Gala</a> which looks to be spectacular (sold out- 1200 seat). This year's three ring circus them features the Cincinnati Circus and Nik Walenda.<br />
<br />
Reference:<br />
DIPG Collaborative Symposium Meeting Agenda<br />
<a href="https://csn.donordrive.com/assets/csn/files/$cms$/100/2097.pdf">https://csn.donordrive.com/assets/csn/files/$cms$/100/2097.pdf</a><br />
<br />
DIPG Preclinical Consortium-<br />
<a href="http://pptiohsu.blogspot.com/2011/12/open-science-forum-dipg-preclinical.html">http://pptiohsu.blogspot.com/2011/12/open-science-forum-dipg-preclinical.html</a><br />
<br />
DIPG Registry-<br />
<a href="http://www.dipgregistry.org/">http://www.dipgregistry.org/</a>LAShttp://www.blogger.com/profile/10542398672724609734noreply@blogger.com0tag:blogger.com,1999:blog-5847488566805525031.post-34661271908155848312013-05-01T09:44:00.000-05:002013-05-02T07:44:21.834-05:00Voices on Pediatric DIPG Biopsy- Mark Kieran MD PhD<div style="text-align: center;">
</div>
<h4>
<div style="text-align: left;">
<div style="text-align: center;">
<span style="font-family: Times, Times New Roman, serif;"><span style="font-weight: normal;"><a href="http://meetinglibrary.asco.org/content/66592" target="_blank">Identification of Novel Biologic Targets in the Treatment of </a></span></span></div>
<div style="text-align: center;">
<span style="font-family: Times, Times New Roman, serif;"><span style="font-weight: normal;"><a href="http://meetinglibrary.asco.org/content/66592" target="_blank">Newly Diagnosed Diffuse Intrinsic Pontine Glioma</a></span></span></div>
<div style="text-align: center;">
<span style="font-family: Times, 'Times New Roman', serif; font-weight: normal; text-align: left;">ASCO 2012 Education Session Presentation</span></div>
<div style="text-align: center;">
<br /></div>
<span style="font-family: Times, Times New Roman, serif; font-weight: normal;">The third speaker on the 2012 ASCO session was Mark Kieran from Boston presenting "<a href="http://meetinglibrary.asco.org/content/66592" target="_blank">Identification of Novel Biologic T</a><a href="http://meetinglibrary.asco.org/content/66592" target="_blank">argets in the Treatment of Newly Diagnosed Diffuse Intrinsic Pontine Glioma"</a>. Certainly Dr Kieran has been enduring in his passionate belief that non-treated tissue is going to be critical to the understanding and hopefully cure of DIPG. He has worked much of the past decade to bring the standard of care for typical pediatric DIPG in line with advancements in neurosurgical techniques and cancer molecular biology research. The video announcing that DIPG biopsy would be an educational session at 2012 ASCO much have provided a sense of satisfaction that this issue had reached prominence enough to be discussed at a significant cancer meeting. (click<a href="http://video.chemotherapyadvisor.com/video/Dr-Mark-Kieran-talks-about-pedi" target="_blank"> here</a> to watch announcement video)</span><br />
<span style="font-family: Times, Times New Roman, serif; font-weight: normal;"><br /></span></div>
<span style="font-weight: normal;"><span style="font-family: Times, Times New Roman, serif;"><div style="text-align: left;">
The first video I saw of Dr Kieran discussing this advancements in neurosurgery and cancer molecular biology research that makes DIPG biopsy possible and critical in understanding pediatric DIPGs was back in 2009. The first international DIPG conference in Barcelona, Spain sponsored by the Alicia Pueyo Foundation included a presentation on this issue. (click <a href="http://justonemoreday.org/DIPGConference/MolecularMedicineforDIPG.html" target="_blank">here</a> for video) The 2012 video shows how far we have come in the DIPG community as well as with cancer molecular biology.</div>
<div style="text-align: left;">
<br /></div>
</span><span style="font-family: Times, Times New Roman, serif;"><div style="text-align: left;">
Dr Kieran points out that the understanding DIPG biology is in it's infancy. Few existing publications are on non-treated (biopsy specimens). Treatment has the potential of significantly altering the genomics of a tumor. However, there have been some consistencies:</div>
</span><span style="font-family: Times, Times New Roman, serif;"><div style="text-align: left;">
* P53 loss/mutation is present in a significant number of tumors.</div>
</span><span style="font-family: Times, Times New Roman, serif;"><div style="text-align: left;">
* The RTK-Ras-PI3K-Akt pathway is altered in a number of tumors. </div>
</span><span style="font-family: Times, Times New Roman, serif;"><div style="text-align: left;">
* PTEN loss might mean that mTOR might be a target.</div>
</span><span style="font-family: Times, Times New Roman, serif;"><div style="text-align: left;">
* Hedgehog-dependent cancer stem cells might be a target.</div>
<div style="text-align: left;">
<br /></div>
</span><span style="font-family: Times, Times New Roman, serif;"><div style="text-align: left;">
Regardless of the ultimate biology of DIPG, we can definitely say that DIPG is different from both adult and pediatric high grade gliomas. Treatment for kids with DIPG can not be based on these other tumors.</div>
<div style="text-align: left;">
<br /></div>
</span><span style="font-family: Times, Times New Roman, serif;"><div style="text-align: left;">
There is a caveat- just finding drugable targets might not alter the outcome with DIPG. So for this approach has not changed the prognosis in adult GBMs despite a huge amount of available tissue. We are at the beginning. We don't know yet. There is hope and optimism that this is a start. </div>
</span><span style="font-family: Times, Times New Roman, serif;"><div style="text-align: left;">
<br /></div>
<div style="text-align: left;">
References:</div>
<div style="text-align: left;">
<span style="background-color: white; color: #111111; line-height: 1.364em;">From boos to hope: Challenging the dogma about deadly brain stem gliomas</span></div>
</span></span><div style="text-align: left;">
<span style="font-family: Times, Times New Roman, serif; font-weight: normal;"><a href="http://childrenshospitalblog.org/from-boos-to-hope-challenging-the-dogma-about-deadly-brain-stem-gliomas">http://childrenshospitalblog.org/from-boos-to-hope-challenging-the-dogma-about-deadly-brain-stem-gliomas</a> </span><br />
<span style="font-family: Times, Times New Roman, serif; font-weight: normal;"><br /></span>
<span style="font-family: Times, Times New Roman, serif; font-weight: normal;">Critical oncogenic mutations in newly diagnosed pediatric diffuse intrinsic pontine glioma</span><br />
<a href="http://www.ncbi.nlm.nih.gov/pubmed/22190243"><span style="font-family: Times, Times New Roman, serif; font-weight: normal;">http://www.ncbi.nlm.nih.gov/pubmed/22190243</span></a><br />
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</h4>
LAShttp://www.blogger.com/profile/10542398672724609734noreply@blogger.com0tag:blogger.com,1999:blog-5847488566805525031.post-76298363684780327372013-04-30T13:01:00.000-05:002013-04-30T13:01:07.281-05:00Voices on Pediatric DIPG Biopsy- Nicholas Foreman MD ChB<br />
<div style="text-align: center;">
<a href="http://meetinglibrary.asco.org/content/68404" target="_blank">The Ethics of Biopsy in Children with Newly Diagnosed Diffuse Intrinsic Pontine Glioma</a></div>
<div style="text-align: center;">
<span style="background-color: white; color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.545454025268555px; line-height: 1.4;">ASCO 2012 Educational Session Presentation</span></div>
<div style="text-align: center;">
<span style="background-color: white; color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.545454025268555px; line-height: 1.4;"><br /></span></div>
<div style="text-align: center;">
<span style="color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif;"><span style="font-size: 15px; line-height: 20px;">"If the the definition of insanity is doing the same useless thing with the same outcome, this is it."</span></span></div>
<div style="text-align: center;">
<span style="color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif;"><span style="font-size: 15px; line-height: 20px;">....Dr Nick Foreman speaking on the negative results on dozens of trials in DIPGs with no biologic knowledge of the tumor</span></span></div>
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<div class="post-body entry-content" id="post-body-5493814896937546386" itemprop="description articleBody" style="background-color: white; position: relative; width: 528.1818237304688px;">
<div style="color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.545454025268555px; line-height: 1.4; text-align: left;">
<br /></div>
<div style="color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.545454025268555px; line-height: 1.4; text-align: left;">
<a href="http://www.ucdenver.edu/academics/colleges/medicalschool/departments/pediatrics/people/bios/Pages/foremanbio.aspx" target="_blank">Dr Nick Foreman</a>, director of the pediatric neuro-oncology program at Denver Children's, presented the second lecture at the 2012 ASCO educational meeting <span style="font-size: 14.545454025268555px; line-height: 1.4; text-align: center;"> "Pontine Gliomas in Children:To Biopsy or Not to Biopsy". Dr Foreman along with his colleague, <a href="http://www.ucdenver.edu/academics/colleges/medicalschool/departments/Neurosurgery/faculty/clinicalfaculty/Pages/Handler.aspx" target="_blank">neurosurgeon Dr Michael Handler</a>, actively and aggressively challenged medicine's standard practice of not preforming biopsies in 10% of children with brain tumors when that tumor (DIPG) has been almost always fatal and no trial has shown any benefit for the tumor. They argued that it was really unethical to continue to subject these patients to phase 1 trials to obtain toxicity and dosage data when one could not show any benefit from the dozens of trials previously. These two physicians worked to have the American Society of Neurosurgery reverse the standard practice of not preforming biopsies for DIPG children. </span></div>
<div style="color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.545454025268555px; line-height: 1.4; text-align: left;">
<span style="font-size: 14.545454025268555px; line-height: 1.4; text-align: center;"><br /></span></div>
<div style="color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.545454025268555px; line-height: 1.4; text-align: left;">
<span style="font-size: 14.545454025268555px; line-height: 1.4; text-align: center;">This 16 1/2 minute presentation is a personal account of the resistance encountered when developing DIPG research that stemmed from work done in 2004 in biopsies of pediatric supratentorial GBMs. The 2004 work lead to a 2007 IRB proposal in which 10 children with DIPGs were to be biopsied (with parental consent) without treatment based on those biopsies. This was pretty much exactly what France had already done and published results with no mortality and transient morbidity. However, the local IRB could not make a decision resulting in an <a href="http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/PediatricAdvisoryCommittee/UCM171523.pdf" target="_blank">FDA hearing </a>on the topic. The results of the FDA panel was mixed so the initial proposal of 10 children being biopsied was rejected in favor of the <a href="http://clinicaltrials.gov/ct2/show/NCT01182350?term=dipg&rank=5" target="_blank">current upfront biopsy trial</a> that is underway.</span></div>
<div style="color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.545454025268555px; line-height: 1.4; text-align: left;">
<span style="font-size: 14.545454025268555px; line-height: 1.4; text-align: center;"><br /></span></div>
<div style="color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.545454025268555px; line-height: 1.4; text-align: left;">
Now that we have the biopsy trial open in the US and <a href="http://dipg.blogspot.com/2013/03/biopsy-consensus-statements-on-dipgs.html" target="_blank">2011 Consensus Conference on Pediatric Neurosurgery </a>specifically stated a standard regarding biopsy of typical pediatric DIPGs within clinical trials<span style="font-size: 14.545454025268555px; line-height: 1.4;">, we may now be past much of the controversy of the past decade. Still, I think it is important to know the traumatic, tragic history of how this stagnated DIPG research. </span></div>
<div style="color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.545454025268555px; line-height: 1.4; text-align: left;">
<br /></div>
<div style="color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.545454025268555px; line-height: 1.4; text-align: left;">
Dr. Foreman ends pondering a question on whether we "missed the boat" for DIPG children by failing to openly recognize that in experienced hands DIPG biopsy is not more dangerous than in other areas of the brain. </div>
<div style="color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.545454025268555px; line-height: 1.4; text-align: left;">
<br /></div>
<div style="color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.545454025268555px; line-height: 1.4; text-align: left;">
If the majority understood that the <a href="http://www.ncbi.nlm.nih.gov/pubmed/8133987" target="_blank">1993 paper</a> recommending "routine biopsies be relegated to history" was referring to MRI's accuracy of diagnosis and not on DIPGs surgical risk/safety, could we have moved faster in the current age of cancer molecular biology to have known about such abnormalities as the histone mutation much earlier. Perhaps we could have been further along on a cure.</div>
<div style="color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.545454025268555px; line-height: 1.4; text-align: left;">
<span style="font-size: 14.545454025268555px; line-height: 1.4; text-align: center;"><br /></span></div>
<div style="color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.545454025268555px; line-height: 1.4; text-align: left;">
<span style="font-size: 14.545454025268555px; line-height: 1.4; text-align: center;">References:</span></div>
<div style="color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.545454025268555px; line-height: 1.4; text-align: left;">
<span style="font-size: 14.545454025268555px; line-height: 1.4; text-align: center;">Nicholas Foreman, Pediatric Neuro-Oncologist</span></div>
<div style="color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.545454025268555px; line-height: 1.4; text-align: left;">
<a href="http://www.coloradocancerblogs.org/conversation-dr-nicholas-foreman/">http://www.coloradocancerblogs.org/conversation-dr-nicholas-foreman/</a></div>
<div style="color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.545454025268555px; line-height: 1.4; text-align: left;">
<br /></div>
<div style="color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.545454025268555px; line-height: 1.4; text-align: left;">
Interpretation of magnetic resonance images in diffuse intrinsic pontine glioma: a survey of pediatric neurosurgeons</div>
<div style="color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.545454025268555px; line-height: 1.4; text-align: left;">
<a href="http://www.ncbi.nlm.nih.gov/pubmed/21721895">http://www.ncbi.nlm.nih.gov/pubmed/21721895</a></div>
<div style="color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.545454025268555px; line-height: 1.4; text-align: left;">
<br /></div>
<div style="color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.545454025268555px; line-height: 1.4; text-align: left;">
Slides of Dr Foreman's presentation in 2009 to the FDA</div>
<div style="color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.545454025268555px; line-height: 1.4; text-align: left;">
<a href="http://www.fda.gov/downloads/AdvisoryCommittees/.../UCM150193.pdf">http://www.fda.gov/downloads/AdvisoryCommittees/.../UCM150193.pdf</a></div>
<div style="color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.545454025268555px; line-height: 1.4; text-align: left;">
<br /></div>
<div style="color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.545454025268555px; line-height: 1.4; text-align: left;">
Magnetic resonance scans should replace biopsies for the diagnosis of diffuse brainstem gliomas: a report from the Children's Cancer Group</div>
<div style="color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.545454025268555px; line-height: 1.4; text-align: left;">
<a href="http://www.ncbi.nlm.nih.gov/pubmed/8133987">http://www.ncbi.nlm.nih.gov/pubmed/8133987</a></div>
</div>
LAShttp://www.blogger.com/profile/10542398672724609734noreply@blogger.com0tag:blogger.com,1999:blog-5847488566805525031.post-54938148969375463862013-04-29T10:23:00.001-05:002013-04-29T10:23:44.806-05:00Voices on Pediatric DIPG Biopsy - Stephanie Puget MD PhD<div style="text-align: center;">
<a href="http://meetinglibrary.asco.org/content/66763" target="_blank">Is Biopsy Safe in Children with Newly Diagnosed Diffuse Intrinsic Pontine Glioma?</a></div>
<div style="text-align: center;">
ASCO 2012 Educational Session Presentation</div>
<br />
One of the most controversial subjects in pediatric DIPGs over the last decade has been the biopsy issue. This has been the topic of discussion in private, <a href="http://www.ncbi.nlm.nih.gov/pubmed/22331797" target="_blank">editorials</a> and even an <a href="http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/PediatricAdvisoryCommittee/UCM171523.pdf" target="_blank">FDA open hearing</a>. At the 2012 ASCO meeting in Chicago there was an educational meeting chaired by Mark Kieran MD PhD entitled "Pontine Gliomas in Children:To Biopsy or Not to Biopsy". To me the greatest thing about this session is that it was taped and made available on the internet. This allows for those who were not in Chicago last year for ASCO to have a better understanding directly from some of the key international figures regarding this extremely important matter.<br />
<br />
Stephanie Puget MD PhD, a French neurosurgeon, started the session with a 20 minutes presentation on "<a href="http://meetinglibrary.asco.org/content/66763" target="_blank">Is Biopsy Safe in Children with Newly Diagnosed Diffuse Intrinsic Pontine Glioma</a>?" Dr Puget is a central figure in the landmark French DIPG clinical trial with upfront biopsy. Since the 2007 <a href="http://www.ncbi.nlm.nih.gov/pubmed/17647306" target="_blank">publication</a> it seems that Dr Puget has had speaking engagements on both sides of the Atlantic to discuss DIPG biopsy. This was the first time though that I was able to actually hear her speak.<br />
<br />
Dr. Puget started her talk with five questions.<br />
1) Is biopsy needed for a DIPG diagnosis?<br />
2) If not, why do biopsy for DIPG?<br />
3) Can DIPG biopsy be safely preformed?<br />
4) Can DIPG biopsy be preformed by everyone?<br />
5) What can be done with the biopsy specimens?<br />
<br />
The short answers-<br />
1) No, it is made by MRI in conjunction with clinical symptoms.<br />
2) Analysis of the tumors may lead to relevant biomakers and hopefully better treatment.<br />
3) Yes.<br />
4) No.<br />
5) Allows for molecular studies (including whole genome sequencing and mutational analysis) and cell lines (of which they had 5 stem cell lines a the time).<br />
<br />
During the presentation she reviewed the results of the French Biopsy experience. From 2002 to 2012, 92 biopsies were preformed with no mortality and only 5 patients experience morbidity. Four of these patients had transient problems including cranial nerve palsies or weakness. One child had a permanent hemiparesis but also was found to have disease progression. She said "it could be considered as safe as a stereotactic biopsy in the supra-tentorial space in a well-trained neurosurgical team".<br />
<br />
She also addressed a few technical considerations: frame versus frameless surgery, choosing a route and choosing a biopsy site. Please note at approximately 14:30 minutes there are real videos of biopsy in children. At 18:30 minutes the size of the biopsy samples is shown as well as pre and post procedure MRIs.<br />
<br />
For those interested in the pediatric DIPG biopsy issue, this is a very informative 20 minute presentation from someone who as been on the frontline. <br />
<br />
Reference:<br />
Is Biopsy Safe in Children with Newly Diagnosed Diffuse Intrinsic Pontine Glioma?<br />
Stephanie Puget MD PhD<br />
<a href="http://meetinglibrary.asco.org/content/66763">http://meetinglibrary.asco.org/content/66763</a>LAShttp://www.blogger.com/profile/10542398672724609734noreply@blogger.com0tag:blogger.com,1999:blog-5847488566805525031.post-23383229293422537112013-04-28T16:46:00.000-05:002013-04-28T16:50:02.072-05:00DIPG in Istanbul<span style="background-color: white; font-family: Times, 'Times New Roman', serif; line-height: 1.45em;">Recently a publication came out in the journal Child's Nervous System retrospectively reviewing patient characteristics and outcomes in children treated for DIPG over a 13 year period (February 1999 to May 2012) at Cerrahpassa Medical Faculty and Oncology Institute in Instanbul, Turkey.</span><br />
<span style="background-color: white; font-family: Times, 'Times New Roman', serif; line-height: 1.45em;"><br /></span>
<span style="background-color: white; font-family: Times, 'Times New Roman', serif; line-height: 1.45em;">In this review there were 26 girls and 24 boys with a median age of 7. The median duration of symptoms - including cranial nerve palsies, motor disability and/or cerebellar dysfunction- was 30 days. The diagnosis was made by a multidisciplinary tumor board which included a </span><span style="background-color: white; font-family: Times, 'Times New Roman', serif; line-height: 1.45em;">a pediatric oncologist, radiation </span><span style="background-color: white; font-family: Times, 'Times New Roman', serif; line-height: 19.625px;">oncologist, neurosurgeon, and radiologist in the multidisciplinary tumor board.</span><br />
<span style="background-color: white; font-family: Times, 'Times New Roman', serif; line-height: 1.45em;"><br /></span>
<span style="background-color: white; font-family: Times, 'Times New Roman', serif; line-height: 1.45em;">Radiation was part of all the children's therapy although only twelve received radiation alone. The other children also received some form of chemotherapy with radiation. In 17 patients a radiosensitizer (either vincristine or cisplatin) during radiation and followed by CCNU and vincristine after radiation. After temozolomide became available this agent was used both during and after radiation for the remaining 21 children.</span><br />
<span style="background-color: white; font-family: Times, 'Times New Roman', serif; line-height: 1.45em;"><br /></span>
<span style="background-color: white; font-family: Times, 'Times New Roman', serif; line-height: 1.45em;">These three groups were analyzed regarding outcomes: group 1-radiation alone; group 2-vincristine/ciplastin; group 3- temozolomide. In this study, children in either chemotherapy group did better than those that had radiation alone. Ten of the children in group 2 were alive at 2 years and 3 at 3 years. Three children in group 3 were also alive at 3 years. </span><br />
<span style="background-color: white; font-family: Times, 'Times New Roman', serif; line-height: 1.45em;"><br /></span>
<span style="background-color: white; font-family: Times, 'Times New Roman', serif; line-height: 1.45em;">Interestingly 3 children in the temozolomide group had biopsies and were found to have pilocytic astroctyomas!</span><br />
<span style="background-color: white; font-family: Times, 'Times New Roman', serif; line-height: 1.45em;"><br /></span>
<span style="background-color: white; font-family: Times, 'Times New Roman', serif; line-height: 1.45em;">Fo me it is hard to know exactly what caused these two chemotherapy groups had better survival. It would seem that the 3 children with pilocytic astrocytomas were included in the analysis. The authors also said that there were improvements in radiation techniques over time which could have been a factor. Thus children who had radiation alone were the earliest patients in the review. Also it seems over type palliative care, PEG tubes and shunts became more common in that institution which may have played a role in the statistics.</span><br />
<span style="font-family: Times, Times New Roman, serif; line-height: 1.45em;"><br /></span>
<span style="font-family: Times, Times New Roman, serif; line-height: 1.45em;">Positive results of temozolomide with DIPG have not been replicated in other countries. Still, this article has significance to me to show the increase interest in DIPG around the world as well as the improved treatment for children with cancer. It was also good to see the conclusion that "t</span><span style="font-family: Times, 'Times New Roman', serif; line-height: 1.45em;">he complex biology of DIPG renders an unselected </span><span style="font-family: Times, 'Times New Roman', serif; line-height: 1.45em;">single-agent approach less likely to be effective. Instead, a </span><span style="font-family: Times, 'Times New Roman', serif; line-height: 1.45em;">multi-targeted approach seems to be required to improve the prognosis". Hopefully we will see increasingly available multi-targeted options for children with DIPG.</span><br />
<span style="background-color: white; font-family: Times, 'Times New Roman', serif; line-height: 1.45em;"><br /></span>
<span style="background-color: white; font-family: Times, 'Times New Roman', serif; line-height: 1.45em;">Reference:</span><br />
<span style="background-color: white; font-family: Times, 'Times New Roman', serif; line-height: 1.45em;">Pediatric diffuse intrinsic pontine glioma patients from a single center</span><br />
<span role="menubar" style="font-family: Times, 'Times New Roman', serif; line-height: 1.45em;"><a abstractlink="yes" alsec="jour" alterm="Childs Nerv Syst." aria-expanded="false" aria-haspopup="true" href="http://www.ncbi.nlm.nih.gov/pubmed/?term=DIPG+Turkey#" role="menuitem" style="border-bottom-width: 0px; color: #660066;" title="Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery.">Childs Nerv Syst.</a></span><span style="font-family: Times, 'Times New Roman', serif; line-height: 1.45em;"> </span><span style="font-family: Times, 'Times New Roman', serif; line-height: 1.45em;">2013 Apr;29(4):583-8. doi: 10.1007/s00381-012-1986-3. Epub 2012 Dec 8.</span><br />
<span style="font-family: Times, Times New Roman, serif; line-height: 1.45em;"><a href="http://www.ncbi.nlm.nih.gov/pubmed/23224361" style="line-height: 1.45em;">http://www.ncbi.nlm.nih.gov/pubmed/23224361</a></span><br />
<br />
Radiotherapy with concurrent and adjuvant temozolomide in children with newly diagnosed diffuse intrinsic pontine glioma (France)<br />
<a href="http://www.ncbi.nlm.nih.gov/pubmed/21858607">http://www.ncbi.nlm.nih.gov/pubmed/21858607</a><br />
<span style="font-family: Times, 'Times New Roman', serif;"><br /></span>
<span style="font-family: Times, 'Times New Roman', serif;">Temozolomide in the treatment of children with newly diagnosed diffuse intrinsic pontine gliomas: a report from the Children's Oncology Group</span><br />
<a href="http://www.ncbi.nlm.nih.gov/pubmed/21345842" style="background-color: white; font-family: Times, 'Times New Roman', serif; line-height: 1.125em;">http://www.ncbi.nlm.nih.gov/pubmed/21345842</a><br />
<br />
Prospective evaluation of radiotherapy with concurrent and adjuvant temozolomide in children with newly diagnosed diffuse intrinsic pontine glioma (India)<br />
<a href="http://www.ncbi.nlm.nih.gov/pubmed/19647954">http://www.ncbi.nlm.nih.gov/pubmed/19647954</a>LAShttp://www.blogger.com/profile/10542398672724609734noreply@blogger.com0tag:blogger.com,1999:blog-5847488566805525031.post-64482578084233181512013-04-27T16:57:00.000-05:002013-04-27T16:57:21.960-05:00Building a Post Mortem Tissue Donation Program- Part 2I<span style="font-family: Times, Times New Roman, serif;">t was back in the summer of 2005 that I first became aware of any institution making a concerted effort to obtain DIPG samples for research purposes. On a visit to Memphis, I found out that researchers there were going to attempting to put a comprehensive IRB proposal (and <a href="http://clinicaltrials.gov/ct2/show/NCT00899834?term=St+Jude+brainstem+glioma&rank=2" target="_blank">place in clinicaltrials.gov</a>) together to formalize a process for post-mortem DIPG donation. At that time, France had just started the biopsy trial and to me this was an American attempt to push DIPG research also. To me it was an exciting time- the first time I had heard of anyone really trying in an organized way to look at DIPG genomics in the US.</span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">Since it was something that was not done, there were concerns on how to approach families- and if they would even donate. To try to answer some of these issues, specific sections of the research would examine parental feeling towards autopsy through a decisional regret survey and a 7 question survey. Questions included items such as reasons for participating in the study, what was good and bad about participating and do you have suggestions. In February an <a href="http://www.ncbi.nlm.nih.gov/pubmed/23433673" target="_blank">article</a> came out electronically ahead of print in the Journal of Pediatrics detailing the parent experience.</span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">Thirty three parents of 32 children answered the the survey (82% participation). Of these 18 received care at St Jude and 14 at other institutions. Those that received care at other institutions were in contact with St Jude directly- some specifically because of awareness of the autopsy program. Parents completed the in a mean time of 11 months.</span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">None of the parents expressed regret in participation. The parents indicated that they consented to autopsy to help other families in the future and to help other parents know that they are not alone.</span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">Parents also said that:</span><br />
<span style="font-family: Times, Times New Roman, serif;">* it was better if the primary physician asked- specifically someone who "they had a relationship with and who showed concern." </span><br />
<span style="font-family: Times, Times New Roman, serif;">*there is "no right time" to initiate this discussion. Parents do recognize that this is tough for the docs as well. Most said that they would have preferred an earlier discussion. Some said that an earlier discussion was less comforting. Timing of the discussion will likely take an individual approach. (And from a personal point of view- a mother and a father might be at different places when considering this discussion.)</span><br />
<span style="font-family: Times, Times New Roman, serif;">* there was a need to have clear information about procedures. Knowing specifics helped decrease anxiety. Some of these specifics included exactly what would be done during autopsy and how the child would look afterwards.</span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">One of the specific issues addressed early was funding of transportation and autopsy. Since many of children treated at St Jude die at home and not close to the facility, the logistics of funding had to be considered before this research could even be started. It was at this point that a DIPG family was looking to make a difference. <a href="http://www.tylerstreehouse.org/page.php?pageid=research" target="_blank">Tyler's Treehouse</a> agreed to fund non-covered expenses associated with post-mortem donation in order to make this research happen.</span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">Tyler's Treehouse is named for a 5 year old boy- the 3rd of 4 sons. Tyler was diagnosed on January 30, 2006 having symptoms only for 1 week. The family went to St Jude but Tyler's tumor was too advanced to even start treatment. He died a week later on February 8, 2006.</span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">Without a foundation support like Tyler's Treehouse this type of program may not have been able to get started. Thank you to the Scott's for their actions in their time of grief.</span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">The logistics of making a DIPG Post Mortem Donation Program are not easy- but it is possible. And from such programs we are beginning to <a href="http://www.ncbi.nlm.nih.gov/pubmed/22286216" target="_blank">understand DIPG</a>. Research is possible from autopsy specimens. The effort has made a difference.</span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">References:</span><br />
<span style="font-family: Times, Times New Roman, serif;">DNA Analysis of Tumor Tissue Samples from Patients with Diffuse Brain Stem Glioma (NBTP02)</span><br />
<a href="http://clinicaltrials.gov/ct2/show/NCT00899834?term=St+Jude+brainstem+glioma&rank=2"><span style="font-family: Times, Times New Roman, serif;">http://clinicaltrials.gov/ct2/show/NCT00899834?term=St+Jude+brainstem+glioma&rank=2</span></a><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">Bereaved Parents' Intention and Suggestions about Research Autopsies in Children with Lethal Brain Tumors</span><br />
<span style="font-family: Times, Times New Roman, serif;"><span role="menubar" style="background-color: white; line-height: 15.954861640930176px;"><a abstractlink="yes" alsec="jour" alterm="J Pediatr." aria-expanded="false" aria-haspopup="true" href="http://www.ncbi.nlm.nih.gov/pubmed/23433673#" role="menuitem" style="border-bottom-width: 0px; color: #660066; outline: 0px;" title="The Journal of pediatrics.">J Pediatr.</a></span><span style="background-color: white; line-height: 15.954861640930176px;"> 2013 Feb 19. pii: S0022-3476(13)00039-5. doi: 10.1016/j.jpeds.2013.01.015. [Epub ahead of print]</span></span><br />
<a href="http://www.ncbi.nlm.nih.gov/pubmed/23433673"><span style="font-family: Times, Times New Roman, serif;">http://www.ncbi.nlm.nih.gov/pubmed/23433673</span></a><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">Somatic Histone H3 alterations in pediatric diffuse intrinsic pontine glioma and non-brainstem gliobastomas</span><br />
<a href="http://www.ncbi.nlm.nih.gov/pubmed/22286216"><span style="font-family: Times, Times New Roman, serif;">http://www.ncbi.nlm.nih.gov/pubmed/22286216</span></a>LAShttp://www.blogger.com/profile/10542398672724609734noreply@blogger.com0tag:blogger.com,1999:blog-5847488566805525031.post-38024759480541439372013-04-26T09:06:00.000-05:002013-04-26T09:06:30.548-05:00Building a Post-Mortem DIPG Tissue Research ProgamPerhaps the biggest rate limiting step in DIPG research has been the lack of tissue. Without tissue, what is there really to study in the basic science realm? However, DIPGs pose significant hurdles in getting tissue as biopsies have not been traditionally preformed and post-mortem donations have infrequently been requested.<br />
<br />
Over the years there have been many barriers to post-mortem donations. Some lacked knowledge- the medical system just didn't know that any research was actively being done. Some didn't believe that usable samples could be obtained for research. Some didn't know how to logistically make this happen especially if the child died at home and the research was being done somewhere else in the country. Some didn't know how or when to approach the parents on this delicate topic.<br />
<br />
There have been a few places that have worked to collect post-mortem DIPG samples for research. One of the most impressive total package programs is Children's National Medical Center. These researchers have taken on each obstacle and overcome them.<br />
<br />
For me the first hurdle is if there is any DIPG research being done at that institution. It doesn't do us any good to have a sample donated and then it sits in the freezer. At Children's National Medical Center there was an interested researcher, <a href="http://www.gwumc.edu/isbweb/section.cfm?section_id=2&category_id=15" target="_blank">Javad Nazarian</a>, who already had a funded grant from the <a href="http://www.childhoodbraintumor.org/funded-grants/item/134-cbtf-funded-grants" target="_blank">Childhood Brain Tumor Foundation</a> to study DIPGs. This meant there was some money and someone to do the research but there are still huge problems- how does anyone know you need the samples and how do you obtain them.<br />
<br />
A researcher-clinician partnership was lead to a multi-disciplinary team. This team included a pediatric neurosurgeon (Suresh Magee) and two pediatric neuro-oncologists (Roger Packer and Brain Rood) as well as Javad Nazarian.<br />
<br />
To address the awareness issue, three things were done. First, the researchers developed an IRB protocol and took the innovative step to have it placed in<a href="http://clinicaltrials.gov/ct2/show/NCT01106794" target="_blank"> clinicaltrials.gov</a>. In this way, interested physicians and parents might more easily find out about the research and have the contact information. Secondly, they developed a <a href="http://www.virtualtrials.com/pdf/dipg.pdf" target="_blank">brochure</a> detailing the information which parents could take away and review at a later time. By the way, it also had a 24 hour contact pager to help facilitate logistics. Thirdly, they included their information on the <a href="http://www.kidsvcancer.org/tissue-donation/information-for-clinicians/researchers/" target="_blank">Kid V Cancer site </a>on research needing tissue.<br />
<br />
The logistical problems of having a child die at home and then donating a post-mortem sample are complex; but, they are overcomeable. It is easier to overcome them with some advanced planning. Transportation is one of the recurrent hurdles as often times if the child will have to be transported to the hospital first then this is not covered by insurance. There have been foundations that have stepped up to fund these expenses so that this research will not be stopped. In this case, the Musella Foundation has supported that aspect of the program.<br />
<br />
And now to maximize research, Children's National Medical Center is part of a DIPG tissue sharing consortium called the Mid-Atlantic DIPG Consortium (MADC). The other two institutions are Johns Hopkins and the National Institute of Health- Pediatric Oncology Branch. This collaboration must be highly successful as several DIPG abstracts have come out for a series of spring meetings including <a href="http://dipg.blogspot.com/2013/04/focus-on-research-3-new-dipg-abstract.html" target="_blank">AACR</a>, <a href="http://dipg.blogspot.com/2013/03/new-nihhopkins-abstract-presented-at.html" target="_blank">USCAP</a> and the <a href="https://soc-neuro-onc.conference-services.net/programme.asp?conferenceID=3467&action=prog_list&session=26434" target="_blank">SNO/PBTF Pediatric Neuro-Oncology Basic and Translational Research Conference.</a><br />
<br />
If asked, some families will donate their child's tumor. It will not be all, but many will and it is made so much more possible with a program in place to address the issues. Kid's V Cancer is a good place to find out more about autopsy donation- both for <a href="http://www.kidsvcancer.org/tissue-donation/information-for-families/" target="_blank">families (FAQs and others experiences)</a> as well as <a href="http://www.kidsvcancer.org/tissue-donation/information-for-clinicians/" target="_blank">physicians (how to ask and autopsy donation checklist)</a>.<br />
<br />
Thank you Children's National Medical Center for putting this program in place to advance DIPG research.<br />
<br />
<b>References:</b><br />
Molecular Analysis of Samples from Patients with Diffuse Intrinsic Pontine Glioma and Brainstem Glioma<br />
Brochure: <a href="http://www.virtualtrials.com/pdf/dipg.pdf">http://www.virtualtrials.com/pdf/dipg.pdf</a><br />
<div class="MsoNormal">
<o:p></o:p></div>
<div class="MsoNormal">
Clinicaltrials.gov <a href="http://clinicaltrials.gov/ct2/show/NCT01106794">http://clinicaltrials.gov/ct2/show/NCT01106794</a><br />
<br />
<b>Selected DIPG articles/abstracts from Javad Nazarian and group:</b><br />
Protein profiling of formalin fixed paraffin embedded tissue: Identification of potential biomarkers for pediatric brain stem glioma<br />
<a href="http://www.ncbi.nlm.nih.gov/pubmed/21136889">http://www.ncbi.nlm.nih.gov/pubmed/21136889</a><br />
<br />
Insights into pediatric diffuse intrinsic pontine glioma through proteomic analysis of spinal fluid<br />
<a href="http://www.ncbi.nlm.nih.gov/pubmed/22492959">http://www.ncbi.nlm.nih.gov/pubmed/22492959</a><br />
<br />
Targeting the Notch and mTor pathways in diffuse intrinsic pontine glioma<br />
<a href="http://www.abstractsonline.com/Plan/ViewAbstract.aspx?mID=3086&sKey=6fa486c2-2701-4a76-8431-b22144df78e4&cKey=c3e199ac-82f7-486d-9d65-bb1c13525e3b&mKey=%7b9B2D28E7-24A0-466F-A3C9-07C21F6E9BC9%7d">http://www.abstractsonline.com/Plan/ViewAbstract.aspx?mID=3086&sKey=6fa486c2-2701-4a76-8431-b22144df78e4&cKey=c3e199ac-82f7-486d-9d65-bb1c13525e3b&mKey=%7b9B2D28E7-24A0-466F-A3C9-07C21F6E9BC9%7d</a><br />
<br />
NG2 Upregulation in Pediatric Diffuse Intrinsic Pontine Glioma and Its Role in Tumorigenecity in Vivo<br />
<a href="https://soc-neuro-onc.conference-services.net/reports/template/onetextabstract.xml?xsl=template/onetextabstract.xsl&conferenceID=3467&abstractID=740466">https://soc-neuro-onc.conference-services.net/reports/template/onetextabstract.xml?xsl=template/onetextabstract.xsl&conferenceID=3467&abstractID=740466</a></div>
LAShttp://www.blogger.com/profile/10542398672724609734noreply@blogger.com0tag:blogger.com,1999:blog-5847488566805525031.post-55860271455795320212013-04-25T11:57:00.000-05:002013-04-25T11:57:26.966-05:00Maddie's MarkJust five days.... that is all they got between leaving the hospital after first hearing DIPG until their girl was gone.<br />
<br />
Just five years....to live a lifetime.<br />
<br />
Maddie had the memory of an elephant. She had a winning smile. She was "fiercely independent". She was a kindergartener. She was the big sister to two younger sisters. She loved arts and crafts. She also had DIPG.<br />
<br />
The little girl diagnosed last year on February 3rd in Albany was supposed to go on a Wish Trip to Disney. She never made it there. She did get to go to Kindergarten and make her First Communion. Those final "best days ever" were spent at a dream house in Lake Placid surrounded by family. When they arrived home, it was too much of a struggle to go back and forth to the hospital so the oncologist came to them. She died on February 8th.<br />
<br />
At one point when she was struggling her dad asked her how she was doing. Her said reply, "I can't do the things I want to do." Those were her last words to him- a truly heartbreaking part many have on the DIPG journey.<br />
<br />
The community had raised funds to help with expenses but after Maddie died money was left over. The Mustos family decided to start a foundation- <a href="http://www.maddiesmark.org/" target="_blank">Maddie's Mark Foundation</a>. The purpose of this foundation was to allow kids in New York to do things they wanted to do and have a "<a href="http://www.maddiesmark.org/best-days-ever/" target="_blank">best day ever</a>".<br />
<br />
Here are some examples of Best Days Ever":<br />
<br />
<ul>
<li>Naomi , a 6 year old with Ewing's sarcoma, was able to go to a Phillies game- in VIP style.</li>
<li>Devon, a boy with an eye tumor, was able to go camping at Old Forge and Enchanged Water Safari.</li>
<li>Myles, a 9 year old boy with pontine gliomas, "best day ever" included a reptile adventure party with a "pile of friends" which included his favorite pizza and cupcakes and a video camera. They also provided him with a recliner to be more comfortable. He died a week later in his comfy chair surrounded by family.</li>
<li>Devon, also with DIPG,wanted a day having fun with friends and family. Maddie's Mark set up a dinner . Superhero Devon pins were made for this special day.</li>
</ul>
<br />
Another thing Maddie's Mark does is make <a href="http://www.maddieselephants.com/" target="_blank">stuffed animal elephants</a>- fitting for a girl who had a memory like an elephant. Proceeds go to support the foundations.<br />
<br />
This is another wonderful foundation started by a family wounded and grieving from DIPG. <br />
<br />
<span style="font-family: Times, Times New Roman, serif;">Reference:</span><br />
<span style="font-family: Times, Times New Roman, serif;">Maddie's Mark</span><br />
<a href="http://www.maddiesmark.org/" style="font-family: Times, 'Times New Roman', serif;">http://www.maddiesmark.org/</a><br />
<span style="background-color: white; font-family: Times, 'Times New Roman', serif;"><br /></span>
<span style="background-color: white; font-family: Times, 'Times New Roman', serif;">Maddie's whole purpose 'was to care'</span><br />
<a href="http://www.timesunion.com/local/article/Maddie-s-whole-purpose-was-to-care-3258157.php" style="font-family: Times, 'Times New Roman', serif;">http://www.timesunion.com/local/article/Maddie-s-whole-purpose-was-to-care-3258157.php</a><br />
<br />
Madeline Musto's memory helping children have 'best days ever'<br />
<a href="http://www.watertowndailytimes.com/article/20130217/NEWS03/702179849" style="font-family: Times, 'Times New Roman', serif;">http://www.watertowndailytimes.com/article/20130217/NEWS03/702179849</a><br />
<!--EndFragment-->LAShttp://www.blogger.com/profile/10542398672724609734noreply@blogger.com0tag:blogger.com,1999:blog-5847488566805525031.post-81563927390773387182013-04-24T23:05:00.000-05:002013-04-25T01:16:32.336-05:00Capecitabine Phase 1 Trial Publication<span style="font-family: Times, Times New Roman, serif;">As a dose-escalating phase 1, this trial's main objective was to establish the maximum tolerated dose and toxicity of capecitabine (Xeloda) in a pediatric population (between the ages of 3 and 21). The drug was given for nine weeks in two daily doses from the start of radiation. There was then a two week break followed by another 3 cycles of capecitabine in which the drug was given twice daily for two weeks followed by a one week break.</span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">From a parent perspective, a very cool thing about capecitabine is that this flavored, film coated, rapidly disintegrating tablet did not have to be swallowed intact but could be disolved in water. There have been other studies where the younger patients were excluded because of the inability to swallow pills intact.</span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">The way capecitabine works is that it is a pro-drug and can be broken down to 5-fluorouracil (5-FU) by a cellular enzyme thymidine phosphorylase (TP). TP is found at significantly higher levels in many cancers. Only <a href="http://en.wikipedia.org/wiki/Fluorouracil" target="_blank">5-FU</a> has antiproliferative properties. The hope is that then the active metabolite 5FU will concentrate specifically in the tumor cells. In addition, radiation induces the enzyme TP. </span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">5 FU has been around as a antimetabolite chemotherapy on its own since it was patented in the late 1950's. The way it works is that 5 FU blocks an enzyme (thymidylate synthase inhibitor) which allows the cell to make a protein that is needed for DNA. Without this, cells can not make new DNA needed for cell division and thus undergo a "<a href="http://en.wikipedia.org/wiki/Thymineless_death" target="_blank">thymineless death</a>".</span><br />
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<span style="font-family: Times, 'Times New Roman', serif;">Since TP has been found in increased level in gliomas, it was thought that a combination of capecitabine and radiation could be a way to attack pediatric DIPGs and high grade gliomas. Of note, capecitabine has been effective for breast cancer brain metastases.</span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">Of the 24 enrolled kids, 15 patients had DIPG. The dose-limiting toxicity included grade 2 and 3 palmar/plantar erythroderma and grade 2 and elevation of a liver enzyme alanine aminotransferase.</span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">This trial (<a href="http://www.pbtc.org/public/PBTC021%20Protocol%20Abstract.pdf" target="_blank">PBTC-021</a>) was run from at the institutions of the Pediatric Brain Tumor Consortium. Interestingly, the phase 2 (<a href="http://www.pbtc.org/public/PBTC-030%20Protocol%20Abstract.pdf" target="_blank">PBTC-30</a>) has also finished patient accural. . Although the hope of radiosensitizers in general for DIPG have not lived up to expections, this radiosensitzer seems to have other effects which perhaps might have increased effectiveness. The phase 2 is expected to complete data collection in June 2013. Hopefully, meeting abstracts or publication will follow shortly thereafter.</span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">References:</span><br />
<span style="font-family: Times, Times New Roman, serif;">Phase I trial of capecitabine rapidly disintegrating tablets and con concomitant radiation therapy in children with newly diagnosed brainstem glioma and high-grade gliomas</span><br />
<span style="font-family: Times, Times New Roman, serif;"><a href="http://www.ncbi.nlm.nih.gov/pubmed/23592571">http://www.ncbi.nlm.nih.gov/pubmed/</a></span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">Capecitabine therapy of central nervous system metastases from breast cancer</span><br />
<a href="http://www.ncbi.nlm.nih.gov/pubmed/17611719"><span style="font-family: Times, Times New Roman, serif;">http://www.ncbi.nlm.nih.gov/pubmed/17611719</span></a><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">Long-term clinical response in leptomeningeal metastases from breast cancer treated with capecitabine monotherapy: a case report</span><br />
<a href="http://www.ncbi.nlm.nih.gov/pubmed/16800978"><span style="font-family: Times, Times New Roman, serif;">http://www.ncbi.nlm.nih.gov/pubmed/16800978</span></a>LAShttp://www.blogger.com/profile/10542398672724609734noreply@blogger.com0tag:blogger.com,1999:blog-5847488566805525031.post-58225280143537510312013-04-23T14:23:00.000-05:002013-04-23T14:24:47.340-05:00New Trial- Imetelstat for Refractory/Recurrent Pediatric Brain Tumors<span style="font-family: Times, Times New Roman, serif;">A new <a href="http://www.pbtc.org/" target="_blank">Pediatric Brain Tumor Consortium</a> phase 2 trial using a telomerase inhibitor, Imetelstat also known as GRN163L, for recurrent or refractory DIPG (as well as three other recurrent or refractory pediatric brain tumors) just went up on clinicaltrials.gov this week. This two section component study will be both a phase 2 study as well as a molecular analysis study. DIPGs will be excluded from the molecular analysis study component of this trial and will not require tissue/histological confirmation. The protocol will include a two hour IV infusion on day 1 and 8 followed by repeat infusions every 21 days for two years.</span><br />
<span style="font-family: Times, 'Times New Roman', serif;"><br /></span>
<span style="font-family: Times, 'Times New Roman', serif;">What are telomeres? I think of them like the plastic coating at the end of shoelaces which keeps the laces from fraying out. </span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">Telomeres are thought to be an important in keeping a cell's DNA intact. They are located on the end of chromosomes and shorten with cell divisions. This shortening of telomeres protects the inner DNA as if it wasn't there the DNA could be affected. One can actually see how these telomere are at the end of chromosomes (<a href="http://www.sciencedaily.com/releases/2007/10/071004143131.htm" target="_blank">image</a>). When the telomeres in normal cells become too short the cell stops dividing and dies. However, there is an enzyme called telomerase which adds some bases to the end of telomeres to keep them from getting too short. This can be present in normal young cells; but is seems to be more prevalent in cancer cells. It is thought that telomerase might be one of the things that allows cancer cells to keep dividing and not die out. </span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">For those that are interested in getting some background on telomeres check out these two article...</span><br />
<span style="font-family: Times, Times New Roman, serif;">*<a href="http://www.sciencedaily.com/releases/2007/10/071004143131.htm" style="background-color: white;" target="_blank">New Telomere Discovery Could Help Explain Why Cancer Cells Never Stop Dividing</a></span><br />
<span style="font-family: Times, Times New Roman, serif;">*<a href="http://learn.genetics.utah.edu/content/begin/traits/telomeres/" target="_blank">Are Telomeres the Key to Aging and Cancer?</a></span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">The hope is that if one can block telemorase activity in cancer that these cells will die out. </span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">For those interested in work that has been done in pediatric brain tumors with telomeres/telomerase, check the work of Uri Tabori (Sick Kids) who published work about telomeres in <a href="http://www.ncbi.nlm.nih.gov/pubmed/16611406" target="_blank">pediatric low grade gliomas</a> back in 2006 and <a href="http://www.ncbi.nlm.nih.gov/pubmed/18797459" target="_blank">ependymomas</a> in 2008. In addition, St Jude made a study available in the end of 2012 using<a href="http://www.ncbi.nlm.nih.gov/pubmed/23232254" target="_blank"> whole-genome sequencing to look at telomere content in pediatric cancer</a>.</span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;"><span style="line-height: 1.125em;">The Pediatric Brain Tumor Consortium (PBTC) is a group of US institutions banded together first in 1999 with the goal of improving treatment/outcomes with children with primary brain tumors by "rapidly conducting novel phase 1 and 2 clinical trials of new therapeutic drugs, new biological therapies, treatment delivery technologies and radiation treatment strategies in children" and a second goal of "characterizing reliable markers and predictors of response to new therapies". At this time there are </span><a href="http://www.pbtc.org/public/inst_contact_info.htm" style="line-height: 1.125em;" target="_blank">11 full members and 4 temporary members of the PBTC</a><span style="line-height: 1.125em;">. Currently the PBTC is running </span><a href="http://www.pbtc.org/public/protocol_summaries.htm" style="line-height: 1.125em;" target="_blank">5 open trials </a><span style="line-height: 1.125em;">of which two are related to DIPG- one is this trial and the other is </span><a href="http://www.pbtc.org/public/PBTC-033_Patient%20and%20Family%20Summary.pdf" style="line-height: 1.125em;" target="_blank">ABT-888/temozolomide trial for newly diagnosed kids with DIPG</a><span style="line-height: 1.125em;">. The primary investigator for this Imetelstat trial is Maryam Fouladi (Cincinnati). Contact information is available on the references below.</span></span><br />
<span style="font-family: Times, Times New Roman, serif;"><br /></span>
<span style="font-family: Times, Times New Roman, serif;">Reference:</span><br />
<span style="font-family: Times, Times New Roman, serif;"><span style="background-color: white; line-height: 19.59375px;">A Molecular Biology and Phase II Study of Imetelstat (GRN163L) in Children With Recurrent High-Grade Glioma, Ependymoma, Medulloblastoma/Primitive Neuroectodermal Tumor and</span><span style="background-color: white; line-height: 19.59375px;"> </span><span class="hit_syn" style="background-color: white; line-height: 19.59375px;">Diffuse Intrinsic Pontine Glioma</span></span><br />
<a href="http://clinicaltrials.gov/ct2/show/NCT01836549?term=dipg&rank=24" style="background-color: white; font-family: Times, 'Times New Roman', serif; line-height: 19.59375px;">http://clinicaltrials.gov/ct2/show/NCT01836549?term=dipg&rank=24</a><br />
<span style="background-color: white; font-family: Times, 'Times New Roman', serif; line-height: 19.59375px;"><br /></span>
<span style="background-color: white; font-family: Times, 'Times New Roman', serif; line-height: 19.59375px;">Protocol Summary for Parents from PBTC</span><br />
<a href="http://www.pbtc.org/public/PBTC-036_v1_1%20Summary%20for%20patients%20and%20families.pdf" style="background-color: white; font-family: Times, 'Times New Roman', serif; line-height: 19.59375px;">http://www.pbtc.org/public/PBTC-036_v1_1%20Summary%20for%20patients%20and%20families.pdf</a><br />
<span style="background-color: white; font-family: Times, 'Times New Roman', serif; line-height: 19.59375px;"><br /></span>
<span style="background-color: white; font-family: Times, 'Times New Roman', serif; line-height: 19.59375px;">Protocol Summary for Health Care Providers from PBTC</span><br />
<a href="http://www.pbtc.org/public/PBTC-036%20Protocol%20Abstract%20and%20Schema%20for%20health%20prof_v3.pdf" style="background-color: white; font-family: Times, 'Times New Roman', serif;">http://www.pbtc.org/public/PBTC-036%20Protocol%20Abstract%20and%20Schema%20for%20health%20prof_v3.pdf</a><br />
<span style="background-color: white; font-family: Times, 'Times New Roman', serif;"><br /></span>
<span style="background-color: white; font-family: Times, 'Times New Roman', serif;">COG Phase 1 Imetelstat Trial in Young Patients (appears to still be recruiting)</span><br />
<a href="http://clinicaltrials.gov/ct2/show/NCT01273090?term=imetelstat&rank=6" style="background-color: white; font-family: Times, 'Times New Roman', serif;">http://clinicaltrials.gov/ct2/show/NCT01273090?term=imetelstat&rank=6</a>LAShttp://www.blogger.com/profile/10542398672724609734noreply@blogger.com0