Many of the recent posts have been highly scientific. It the spring season of new abstracts so I guess it isn't to be unexpected. However, sometimes I feel that I just need to sit back and look at pictures to gain perspective on more than molecular pathways. Today I did just that. I looked at pictures of a little boy I got to know only from the internet.
Caleb loved hockey and jokes but his life was completely derailed at age 8 when he was diagnosed with DIPG. Due to the persistence of his parents got a second round of radiation at progression that gave them another 9 months. This was something that simply wasn't done before and was only happened due to the valiant fight of this family.
Caleb still inspires fighting for change through the A Cure From Caleb Society which specifically fund s DIPG research. This past Friday, the foundation hosted a Spring Dance to create awareness and fund research.
The research A Cure From Caleb Society is supporting is that of Cynthia Hawkins, MD PhD of Sick Kids. Dr. Hawkins has been on the leading edge of many recent advances in DIPG research-from creating an post-mortem tissue collection program at Sick Kids to the first publication of DIPG molecular analysis. She was also instrumental in the Toronto DIPG Think Tank in 2010 and is a participant in the DIPG Preclinical Consortium. I am sure there is going to be much more research coming from this lab as in addition to yesterday's abstract there another one that will be presented at the same conference.
And for Caleb- we are not chicken and will continue to work on crossing the road to a cure.
Sunday, April 14, 2013
Saturday, April 13, 2013
Genetic and histopathological spectrum of paediatric diffuse intrinsic pontine gliomas
Sick Kids instituted an brainstem glioma project back in 2003 in hopes of trying to understand diffuse intrinsic pontine glioma. To do this the researchers reached out to families with an autopsy-based protocol asking for consideration of post-mortem tissue donation. This decade commitment and collaborative effort against DIPG has lead to another DIPG abstract for the upcoming SNO/CBTF supported 2013 Pediatric Neuro-Oncology Basic and Translational Research Conference. This one comes from Sick Kids in conjunction with Oren Becher from Duke.
The researchers examined 71diffuse intrinsic pontine tumors:
Reference:
Genetic and histopathological spectrum of paediatric diffuse intrinsic pontine gliomas
https://soc-neuro-onc.conference-services.net/reports/template/onetextabstract.xml?xsl=template/onetextabstract.xsl&conferenceID=3467&abstractID=73797
The researchers examined 71diffuse intrinsic pontine tumors:
- 65 were high grade gliomas, 8 were low grade and 3 were PNETs.
- survival was not related to grade.
- leptomeningeal spread was present in one third of cases.
- 68% had K27M-H3.
- these tumors were histologically heterogenous, however increased homogeneity was found of the histone mutation.
- the histone mutations were also present in low grade tumors that had worse outcomes.
The authors conclude with a call for "incorporation of histological and molecular data"- specifically stating "histone mutational status at biopsy"- in designing new therapies for DIPG.
There has been a rash of publication regarding K27M mutations recently. Several of the other abstracts for this meeting feature this histone mutation in DIPG. I am sure more will be coming in the future.
Reference:
Genetic and histopathological spectrum of paediatric diffuse intrinsic pontine gliomas
https://soc-neuro-onc.conference-services.net/reports/template/onetextabstract.xml?xsl=template/onetextabstract.xsl&conferenceID=3467&abstractID=73797
Inhibition of PRC2 Activity by a Gain-of-Function H3 Mutation Found in Pediatric Glioblastoma
Friday, April 12, 2013
St Jude Looks at Long Term DIPG Survivors
At a poster session for the 3rd biennial Pediatric Neuro-Oncology Basic and Translational Research Conference next month, physicians from St Jude Research Hospital will be presenting a retrospective review of their patients who had prolonged survival despite being given a diagnosis of diffuse intrinsic pontine glioma.
These physicians reviewed the records of DIPG patients at St Jude from October 1, 192 to May 31, 2011. Of the 191 patients there were 5 long time survivors with a median time from diagnosis being 9.3 years! It seems 4 out of 5 of these patients had some atypical clinical or imaging features that put them on the side of potentially better outcomes than the average.
All these survivors underwent neurocognitive testing. Interestingly, and unfortunately like so many other children who undergo brain radiation, cognitive function was impacted in 4 of 5 patients- two falling in the range of borderline/mild mental retardation. These findings will become increasingly important when there is better survival statistics for DIPG.
The researcher point out that prolonged survival does not equal cure. Two of the patients had progression years after their initial treatment with radiation.
It will be interesting to see what comes of this. Certainly the DIPG Registy could become very important to bring the information on all long term survivors together at one place.
Reference:
Clinico-radiologic characteristics and neurocognitive assessment of long-term survivors of diffuse intrinsic pontine glioma
https://soc-neuro-onc.conference-services.net/reports/template/onetextabstract.xml?xsl=template/onetextabstract.xsl&conferenceID=3467&abstractID=738281
These physicians reviewed the records of DIPG patients at St Jude from October 1, 192 to May 31, 2011. Of the 191 patients there were 5 long time survivors with a median time from diagnosis being 9.3 years! It seems 4 out of 5 of these patients had some atypical clinical or imaging features that put them on the side of potentially better outcomes than the average.
All these survivors underwent neurocognitive testing. Interestingly, and unfortunately like so many other children who undergo brain radiation, cognitive function was impacted in 4 of 5 patients- two falling in the range of borderline/mild mental retardation. These findings will become increasingly important when there is better survival statistics for DIPG.
The researcher point out that prolonged survival does not equal cure. Two of the patients had progression years after their initial treatment with radiation.
It will be interesting to see what comes of this. Certainly the DIPG Registy could become very important to bring the information on all long term survivors together at one place.
Reference:
Clinico-radiologic characteristics and neurocognitive assessment of long-term survivors of diffuse intrinsic pontine glioma
https://soc-neuro-onc.conference-services.net/reports/template/onetextabstract.xml?xsl=template/onetextabstract.xsl&conferenceID=3467&abstractID=738281
Thursday, April 11, 2013
Focus on Research- Mitochondria and DIPG (New Australian Abstract)
The 3rd biennial Pediatric Neuro-Oncology Basic and Translational Research Conference jointly sponsored by the Society of Neuro-Oncology and the Children's Brain Tumor Foundation will be held on May 16th and 17th in Fort Lauderdale Florida. Several of the already available abstracts are several on DIPG. One of the ones that caught my eye will be a poster presentation from Australian researchers entitled " Targeting mitochondria and metabolism as a novel therapeutic approach in the treatment of Diffuse Intrinsic Pontine Glioma".
The interest in cellular metabolism in cancer goes back the early 1900's with Otto Heinrich Warburg. The Warburg Hypothesis says "the prime cause of cancer is the replacement of the respiratory of oxygen in normal body cells by a fermentation of sugar." He speculated that tumor development is driven by insults to the mitochondria which affects cellular respiration. Mitochondria have become a potential target for cancer therapy. One of the key mitochondrial proteins implicated in cancer has been adenine nucleotide translocase (ANT).
In this abstract, the researchers used DIPG neurospheres to evaluate the effectiveness of an ANT inhibitor PENAO. This agent appears to have first hit the internet in 2011, when some of the authors unveiled this novel compound at AACR in an abstract " PENAO: A small molecule tumor metabolism inhibitor". In the AACR abstract PENAO led arrest of proliferation and apoptosis of tumors cells. It was well tolerated by IV and subcutaneously in mice.
In this study, the use of PENAO on DIPG neurospheres was found to be a "promising therapeutic strategy" to treat DIPG. In addition, combination with a MRP1 ( multidrug resistance-associated protein ), Reversan, increased the effect. Effectiveness of PENAO was also increased by 3-bromopyruvate.
This is interesting research with a different approach to DIPG in utilizing mitochondrial small molecule inhibitors. Now, the challenge would seem to be in the steps to translate this from bench to bedside. The great thing now compared to just a few years ago is that several institutions have been able to developed DIPG animal models to be able to preform the necessary translational research.
Reference:
Targeting mitochondria and metabolism as a novel therapeutic approach in the treatment of Diffuse Intrinsic Pontine Glioma
https://soc-neuro-onc.conference-services.net/reports/template/onetextabstract.xml?xsl=template/onetextabstract.xsl&conferenceID=3467&abstractID=740145
Mitochondria and Cancer: Past, Present, and Future
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581248/
Adenine nucleotide translocase 2 is a key mitochondrial protein in cancer
http://www.ncbi.nlm.nih.gov/pubmed/20950584
Inhibition of Glycolysis in Cancer Cells: A Novel Strategy to Overcome Drug Resistance Associated with Mitochondrial Respiratory Defect and Hypoxia
http://cancerres.aacrjournals.org/content/65/2/613.full
The interest in cellular metabolism in cancer goes back the early 1900's with Otto Heinrich Warburg. The Warburg Hypothesis says "the prime cause of cancer is the replacement of the respiratory of oxygen in normal body cells by a fermentation of sugar." He speculated that tumor development is driven by insults to the mitochondria which affects cellular respiration. Mitochondria have become a potential target for cancer therapy. One of the key mitochondrial proteins implicated in cancer has been adenine nucleotide translocase (ANT).
In this abstract, the researchers used DIPG neurospheres to evaluate the effectiveness of an ANT inhibitor PENAO. This agent appears to have first hit the internet in 2011, when some of the authors unveiled this novel compound at AACR in an abstract " PENAO: A small molecule tumor metabolism inhibitor". In the AACR abstract PENAO led arrest of proliferation and apoptosis of tumors cells. It was well tolerated by IV and subcutaneously in mice.
In this study, the use of PENAO on DIPG neurospheres was found to be a "promising therapeutic strategy" to treat DIPG. In addition, combination with a MRP1 ( multidrug resistance-associated protein ), Reversan, increased the effect. Effectiveness of PENAO was also increased by 3-bromopyruvate.
This is interesting research with a different approach to DIPG in utilizing mitochondrial small molecule inhibitors. Now, the challenge would seem to be in the steps to translate this from bench to bedside. The great thing now compared to just a few years ago is that several institutions have been able to developed DIPG animal models to be able to preform the necessary translational research.
Reference:
Targeting mitochondria and metabolism as a novel therapeutic approach in the treatment of Diffuse Intrinsic Pontine Glioma
https://soc-neuro-onc.conference-services.net/reports/template/onetextabstract.xml?xsl=template/onetextabstract.xsl&conferenceID=3467&abstractID=740145
Mitochondria and Cancer: Past, Present, and Future
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581248/
Adenine nucleotide translocase 2 is a key mitochondrial protein in cancer
http://www.ncbi.nlm.nih.gov/pubmed/20950584
Inhibition of Glycolysis in Cancer Cells: A Novel Strategy to Overcome Drug Resistance Associated with Mitochondrial Respiratory Defect and Hypoxia
http://cancerres.aacrjournals.org/content/65/2/613.full
Subscribe to:
Posts (Atom)