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
Showing posts with label Australia. Show all posts
Showing posts with label Australia. Show all posts
Thursday, April 11, 2013
Saturday, March 30, 2013
Miette- Sweet Little Crumb
She loved princesses as well as castles, faires and all magical things .
She loved animals- giraffes, elephants and kittens.
She was sweet, courageous, thoughtful, light and bright.
Miette's gorgeous blue eyes, impish smile and golden locks hid a fatal tumor.
Her parents were determined to tell her story from the beginning to the end. The beginning started on July 25th 2011, when 5-year-old Miette was diagnosed with a brainstem tumor. The next day her parents were told there "with radiation there would be a 50% chance she would be here in 1 year and a zero percent chance in two." The end came this week on Tuesday. Australia's Sweet Little Crumb left this world.
She loved animals- giraffes, elephants and kittens.
She was sweet, courageous, thoughtful, light and bright.
Miette's gorgeous blue eyes, impish smile and golden locks hid a fatal tumor.
Her parents were determined to tell her story from the beginning to the end. The beginning started on July 25th 2011, when 5-year-old Miette was diagnosed with a brainstem tumor. The next day her parents were told there "with radiation there would be a 50% chance she would be here in 1 year and a zero percent chance in two." The end came this week on Tuesday. Australia's Sweet Little Crumb left this world.
A special thing on this journey- Chicken Mick and his band of merry helpers. This "big hearted Aussie bloke"put together a Wiggly Whirlwind Weekend sending Miette to Melbourne to meet the Wiggles.
The story didn't end there though. They were met by a TV crew at the airport on the flight home and taken home in a fairy pink Hummer. Although they had agreed to a "lick of paint on her cubby" while they were away and told Chicken Mike that Miette liked animals, they were not expecting what waited at home. The front yard was transformed into a little farm and her cubby into an "area fit for a princess". Here is the story in their own words...
or better yet watch this special video.....
Because of Miette, the Wiggles are now ambassadors to raise awareness of through the Isabella and Marcus Paediatric Brainstem Tumour Fund. Both Isabelle and Marcus died from DIPG. The two families started this foundation with the mission to fund Australian research into pediatric brainstem tumors with a focus on DIPG. Miette joined in with her support making hairclips and bands, selling them online and giving 50% of the proceeds to the charity.
A vision of the foundation is "to established an Endoswed Chair at the Univeristy of Melbourne, with an affiliated research laboratory in the Victorian Comprehensive Cancer Centre that will perform research to understand the nature of these tumors, develop novel treatments and to participate in international clinical trials."
Miette you will be remembered.
Reference:
A vision of the foundation is "to established an Endoswed Chair at the Univeristy of Melbourne, with an affiliated research laboratory in the Victorian Comprehensive Cancer Centre that will perform research to understand the nature of these tumors, develop novel treatments and to participate in international clinical trials."
Miette you will be remembered.
Reference:
Miette's Journey - https://www.facebook.com/miettesjourney
Miette's Journey- http://www.miettesjourney.com/
Chicken Mick-
Isabella and Marcus Paediatric Brainstem Tumour Fund- http://www.isabellaandmarcusfund.org.au/index.html
Monday, March 18, 2013
New Trial- MGMT Cancer Gene Therapy Trial
One of the huge problems with chemotherapy is that it beats up normal cells- especially bone marrow. The toxicity limits how far the doctors can increase dosages before it is just too much for the body. One novel idea is to try to make the normal bone marrow cells more resistant to chemotherapy. This is exactly what researchers are trying to do with a gene therapy which effects MGMT. This will allow for increasing doses of temozolomide.
Dr Geoffrey McCowage at The Children's Hospital of Westmead in Sydney Australia has spent the last 15 years developing a trial which removes bone marrow stem cells, genetically modifies the NA repair protein and then reinserts them into the patient. The hope is that this modification will allow a patient to withstand escalating chemotherapy while better targeting the tumor. In fact, this is more than theory. This first of kind therapy for brain tumor kids is open in trial.
This Phase 1 intervention is open to several different types of brain tumors including brainstem glioma of diffuse pontine type and all the following recurrent tumors- medulloblastoma, ependymoma, atypical teratoid rhaboid, high and low grade glioma.
Erin is the first child enrolled. You can read at-
http://www.news.com.au/national-news/south-australia/brave-erins-inspirational-battle-against-cancer/story-fndo4dzn-122658419720
Last month she had reached a year from diagnosis- and in the picture she looks great.
The trial is being funded by the Kid's Cancer Project (formerly Oncology Children's Foundation), Sporting Chance Cancer Foundation and the Australian governmental funding agency, The Department of Innovation, Industry Science and Research.
Erin is hoping to raise $50,000 for The Cure Starts Now for DIPG research.
Note- A similar trial seems to be open in the US at the NIH for adult glioblastoma patients.
References:
Brave Erin's Inspirational Battle Against Cancer- http://www.news.com.au/national-news/south-australia/brave-erins-inspirational-battle-against-cancer/story-fndo4dzn-122658419720
MGMT Cancer Gene Therapy Project- http://www.thekidscancerproject.org.au/Research/Gene-Therapy-Trial.aspx
Cancer Gene Therapy Project (Westmead Research site)-
NIH Adult Trial with Newly Diagnosed GBM- http://www.clinicaltrials.gov/ct2/show/NCT01269424
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