*****Medical News*****
Tubulin targets in the pathobiology and therapy of glioblastoma multiforme. I. class III beta-tubulin.
J Cell Physiol. 2009 Jul 31
“This minireview focuses on microtubules and tubulin as emerging targets in potential therapy of GBM using a new class of betaIII-tubulin-targeted drugs…”
Targeting rat brainstem glioma using human neural stem cells and human mesenchymal stem cells.
Clin Cancer Res. 2009 Aug 1;15(15):4925-34. Epub 2009 Jul 28
“Genetically engineered NSCs show therapeutic efficacy against brainstem gliomas.”
Virotherapy against malignant glioma stem cells.
Cancer Lett. 2009 Jul 28
“In this review, we highlight the literature regarding the existence of glioma stem cells and their characteristics. We also discuss the potential for virotherapy, a novel therapeutic approach utilizing conditionally replicative viruses, to directly target this population of self-renewing cancer stem cells.”
Dendritic cell vaccines for cancer stem cells.
Methods Mol Biol. 2009;568:233-47
“Our results suggest that only DC vaccination against neurospheres can restrain the growth of a highly infiltrating and aggressive model of glioma and may have implications for the design of novel, more effective immunotherapy trials for malignant glioma and possibly other malignancies.”
Paediatric high and low grade glioma: the impact of tumour biology on current and future therapy.
Br J Neurosurg. 2009 Aug;23(4):351-63
“Brainstem glioma remains a tumour with a dismal prognosis but relatively little is known about the underlying biology and progress will require a concerted effort to collect tissue by biopsy and autopsy to allow appropriate analysis to identify and validate targets. A new era of molecular based therapies offers the promise of major benefits in the management of paediatric glioma but translating this promise into reality will require further understanding of the biology driving these tumours.”
Cediranib: profile of a novel anti-angiogenic agent in patients with glioblastoma.
Expert Opin Investig Drugs. 2009 Aug 12
“Cediranib is an effective drug in patients with glioblastoma, acting through inhibition of angiogenesis and normalization of tumor vasculature. Reduction of vasogenic brain edema is a key component of its treatment effect in this patient population. The primary side effects of cediranib include fatigue, diarrhea and hypertension.”
________________________________________________
September is Childhood Cancer Awareness Month
Team Unite Awareness Flyer http://teamunite.net/pdf/TeamUnite_SEPTEMBER.pdf
Team Unite Awareness Gear http://www.cafepress.com/teamunite/6830914
September 12, 2009
Tyler's Treehouse 5K & 1-Mile Fun Run/Walk
http://www.sportoften.com/events/eventDetails.cfm?pEventId=3992
"Spirit Runners" are always appreciated!
Olde Georgetowne Swim Club, Charlotte, NC
Just One More Day
http://www.justonemoreday.org/help/NewsEvents/Sept.flyer.pdf
Celebrating Childhood Cancer Awareness Day along with the life of Alicia Martin
Sonoma Park
2922 Sonoma Way, Viera, Florida
Love, Chloe Foundation
http://www.lovechloefoundation.org/sept09.html
The foundation will be at Rolling Hills Zoo all day long to sell monkeysWe have the cutest monkeys that we are selling at the zoo. We will also have shirts, hats and bracelets
September 13, 2009
Aimee’s Army
http://www.aimeesarmy.com/howtohelp.htm
The annual Aimee Dickey walk for childhood cancer/DIPG (brain tumors)
Nay Aug Park, Scranton, PA
Just One More Day
http://www.justonemoreday.org/help/NewsEvents/Brianna%20golf%20flyer.pdf
The Brianna Sharp Golf Outing
Country Lake Golf Course
Naperville, Illinois
September 19, 2009
Love, Chloe Foundation
http://www.lovechloefoundation.org/sept09.html
2nd Annual Kickball Jam. Games start at 9am. Teams must be registeredby Tuesday, September 1.
__________________________________________________
For past issues of DIPG Digest please visit
http://www.justonemoreday.org/DIPGDigest/DIPGDigest.html
Please submit information you feel will be helpful to DIPG families to
http://health.groups.yahoo.com/group/DIPGFoundationsAlliance/post?postID=zoOUdF5j-M1_moxVNW60JogjJSyo9OuzV7qSCLwN1-mg3AbdOkstpxxZn5yIcvm_pI5NEgqKTIe3JcEOf2aq2VpOIQ subject: DIPG Digest
Copyright 2008 - 2009 Just One More Day for Love, Hope & a Cure, Inc. Allrights reserved. The materials and links provided on this site have beenprepared for information purposes only and should not be construed as advice oropinions on any specific facts or circumstances. Medical research concerningdisease and treatments is an ongoing process. Readers should not act upon thisinformation, but should obtain advice from physicians, medical institutions orother professionals, as appropriate.
Wednesday, August 26, 2009
Tuesday, August 25, 2009
Rare Earth's Role in Fighting the Deadliest of Cancers
The following was posted on the Metal Miner blog on August 24, 2009. JOMD is excited to be communicating with Lisa Reisman regarding the role of rare earth metals in treating brain cancer.
Rare Earth's Role in Fighting the Deadliest of Cancers
And Ella Newmiller is a lucky one as she is 15 months out from diagnosis and remains in excellent health living a seemingly “normal” life as her tumor has stabilized. In my spare time, I found myself reading up on the disease, shocked to learn that the basic treatments for this disease have not changed in literally 30 years. Essentially, the patient receives steroids to reduce swelling, typically followed up with radiation. And though radiation has been found to be helpful in reducing the size of the tumor, it typically provides a 3-9 month respite before the tumor comes raging back, snatching the life of whoever has this disease.
I was shocked to learn that the treatments had not changed for 30 years. It almost seems inconceivable. But what I learned from Dr. Loice Swisher, an MD and advisor to Just One More Day an advocacy/research/support network for families facing DIPG and who also has a daughter that had a brain tumor, is that it is difficult to gather tissue samples At this time, tissue can only be obtained by autopsy donation (which is best if gathered within 6 hours of the time of death).
It’s both the imaging and treatment side of things where rare earths play a big role. Because DIPGs are inoperable and typically not biopsied because of the risk involved, they are both difficult to see and difficult to treat. The difficult to see part involves a number of imaging studies that rely upon MRI, and advanced systems and technologies, led by the NIH. The leading expert in this field is Dr. Kathy Warren whom some believe sees 20-30% of all children diagnosed with this disease. Unlike other tumors that are responsive to chemotherapies taken orally or intravenously, the blood-brain barrier limits the efficacy of these delivery methods for DIPG. The NIH, however, leads up a new area of research using rare earth metal gadolinium to aid in what is called CED (Convection Enhanced Delivery) or actual drug therapy delivered directly to the tumor.
According to Dr. Russell Lonser, who is the leading researcher at the NIH involved in CED, the gadolinium compounds with the chemotherapeutic agent. At that point, they start the infusion and use MR imaging to ensure the drug is delivered in a very precise manner. By imaging this process, researchers can closely track drug delivery, view safety implications to determine drug efficacy and perhaps most important in DIPG cases, make sure the drug is delivered to the actual tumor site. Some describe DIPG tumors as “sand in a bed of grass,” making imaging an extremely important function.
Rare Earth's Role in Fighting the Deadliest of Cancers
About 15 months ago I went on Facebook to see if a friend of mine, who lives in Raleigh, had a Facebook page. When I typed in her name, I was taken to a link to a prayer group for Ella Newmiller. Now I knew that Ella was my friend’s daughter (we do exchange holiday cards) and quite frankly, I was in shock. Ella, now 6, was diagnosed at the end of April 2008 with a DIPG (diffuse intrinsic pontine glioma), or brain-stem tumor. DIPG is a rare form of cancer (approximately 200 children per year are diagnosed with the disease), which sits in the brain stem, or pons region of the brain. Essentially every major function within the human body (with the exception of smell) must pass through the pons (e.g. consciousness, sight, the ability to swallow etc). The trouble with DIPG is that it is inoperable and for the most part, untreatable. The diagnosis remains grim. Approximately 90% of children diagnosed with the disease do not live longer than 18 months.
And Ella Newmiller is a lucky one as she is 15 months out from diagnosis and remains in excellent health living a seemingly “normal” life as her tumor has stabilized. In my spare time, I found myself reading up on the disease, shocked to learn that the basic treatments for this disease have not changed in literally 30 years. Essentially, the patient receives steroids to reduce swelling, typically followed up with radiation. And though radiation has been found to be helpful in reducing the size of the tumor, it typically provides a 3-9 month respite before the tumor comes raging back, snatching the life of whoever has this disease.
I was shocked to learn that the treatments had not changed for 30 years. It almost seems inconceivable. But what I learned from Dr. Loice Swisher, an MD and advisor to Just One More Day an advocacy/research/support network for families facing DIPG and who also has a daughter that had a brain tumor, is that it is difficult to gather tissue samples At this time, tissue can only be obtained by autopsy donation (which is best if gathered within 6 hours of the time of death).
It’s both the imaging and treatment side of things where rare earths play a big role. Because DIPGs are inoperable and typically not biopsied because of the risk involved, they are both difficult to see and difficult to treat. The difficult to see part involves a number of imaging studies that rely upon MRI, and advanced systems and technologies, led by the NIH. The leading expert in this field is Dr. Kathy Warren whom some believe sees 20-30% of all children diagnosed with this disease. Unlike other tumors that are responsive to chemotherapies taken orally or intravenously, the blood-brain barrier limits the efficacy of these delivery methods for DIPG. The NIH, however, leads up a new area of research using rare earth metal gadolinium to aid in what is called CED (Convection Enhanced Delivery) or actual drug therapy delivered directly to the tumor.
According to Dr. Russell Lonser, who is the leading researcher at the NIH involved in CED, the gadolinium compounds with the chemotherapeutic agent. At that point, they start the infusion and use MR imaging to ensure the drug is delivered in a very precise manner. By imaging this process, researchers can closely track drug delivery, view safety implications to determine drug efficacy and perhaps most important in DIPG cases, make sure the drug is delivered to the actual tumor site. Some describe DIPG tumors as “sand in a bed of grass,” making imaging an extremely important function.
In a follow-up post we’ll discuss this particular research in greater detail and the role of rare earth metals in other medical research studies.
–Lisa Reisman
Friday, August 21, 2009
Tyrosine Kinase Inhibitors
Kinases are cellular enzymes that have specific jobs. One group of kinases is the tyrosine kinases, and their job is to phosphorylate proteins. In other words, these enzymes take a phosphate group from a chemical molecule called ATP and transfer it to a tyrosine of one of the cell’s proteins. This placing of the phosphate molecule on the protein then becomes a signal for the cell to do something. In the case of tyrosine kinases, it seems that the signal affects the cell’s normal growth, metabolism, adhesion, and motility. If not properly controlled, however, these tyrosine kinases can cause uncontrolled cellular growth and thus be a factor in the development of cancer.
The approximately 90 different tyrosine kinases known today can be divided into two groups: those associated with receptors on the cell surface (also called transmembrane receptor-linked kinases), and those within the cytoplasm of the cell. There are 58 receptor tyrosine kinases (RTKs) which have been grouped into 20 families. Of the 20 families several names recurrently come up in the literature with DIPGs. Examples are VEGF, EGFR and PDGFR. (See http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase)
Tyrosine kinases have been a focus for anticancer drug development because over-active RTKs have led to the uncontrolled growth of tumors. Many of these RTKs are affected by genetic mutation or over-expression, leading to cancerous growth. Two different classes of drugs are currently being developed to target different RTKs: small molecule inhibitors and monoclonal antibodies. The web references below provide information on investigations for each class of drugs.
Small Molecule Inhibitors. These tend to be orally administered and have been used in several different trials which included children with DIPGs. Here are some examples of small molecule references:
1. Gefitinib and Radiation Therapy in Treating Children With Newly Diagnosed Gliomas (www.clinicaltrial.gov/ct2/show/NCT00042991?term=iressa+children+St+Jude&rank=5
2. Erlotinib Alone or in Combination With Radiation Therapy in Treating Young Patients With Refractory or Relapsed Malignant Brain Tumors or Newly Diagnosed Brain Stem Glioma (http://www.clinicaltrial.gov/ct2/show/NCT00360854?term=Tarceva+brainstem&rank=2)
3. Vandetanib and Radiation Therapy in Treating Young Patients With Newly Diagnosed Diffuse Brainstem Glioma (http://www.clinicaltrial.gov/ct2/show/NCT00472017?term=vandetanib+St+Jude&rank=1)
4. A recently opened multi-TKI trial: Pazopanib Hydrochloride in Treating Young Patients With Solid Tumors That Have Not Responded to Treatment (www.clinicaltrial.gov/ct2/show/NCT00929903?term=pazopanib+brain+tumor&rank=2)
5. Targeting cancer with small molecule kinase inhibitors. Nat Rev Cancer. 2009 Jan;9(1):28-39 (http://www.ncbi.nlm.nih.gov/pubmed/19104514?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pub med.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=1&log$=relatedreviews&logdbfrom=pubmed)
Monoclonal Antibodies. Intravenous monoclonal antibodies, such as Avastin and Cetuximab, are currently being investigated in the treatment of DIPG both on and off trial.
Here is a recently completed trial for Cetuximab: Study of Erbitux™ (Cetuximab) in Pediatric Patients With Refractory Solid Tumors (www.clinicaltrial.gov/ct2/show/NCT00110357?term=Cetuximab+pediatric&rank=1)
And two more references on Tyrosine Kinase inhibitors in general:
Tyrosine kinase – Role and significance in Cancer. Int J Med Sci. 2004; 1(2): 101–115. (http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1074718)
Different drug names, targets, pharmaceutical companies and mechanism of action are given in a chart at the bottom of this Wikipedia page: http://en.wikipedia.org/wiki/Tyrosine_kinase_inhibitor
This is a rapidly evolving field. It is helpful to have some knowledge of this field in considering the options for treating DIPG.
The approximately 90 different tyrosine kinases known today can be divided into two groups: those associated with receptors on the cell surface (also called transmembrane receptor-linked kinases), and those within the cytoplasm of the cell. There are 58 receptor tyrosine kinases (RTKs) which have been grouped into 20 families. Of the 20 families several names recurrently come up in the literature with DIPGs. Examples are VEGF, EGFR and PDGFR. (See http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase)
Tyrosine kinases have been a focus for anticancer drug development because over-active RTKs have led to the uncontrolled growth of tumors. Many of these RTKs are affected by genetic mutation or over-expression, leading to cancerous growth. Two different classes of drugs are currently being developed to target different RTKs: small molecule inhibitors and monoclonal antibodies. The web references below provide information on investigations for each class of drugs.
Small Molecule Inhibitors. These tend to be orally administered and have been used in several different trials which included children with DIPGs. Here are some examples of small molecule references:
1. Gefitinib and Radiation Therapy in Treating Children With Newly Diagnosed Gliomas (www.clinicaltrial.gov/ct2/show/NCT00042991?term=iressa+children+St+Jude&rank=5
2. Erlotinib Alone or in Combination With Radiation Therapy in Treating Young Patients With Refractory or Relapsed Malignant Brain Tumors or Newly Diagnosed Brain Stem Glioma (http://www.clinicaltrial.gov/ct2/show/NCT00360854?term=Tarceva+brainstem&rank=2)
3. Vandetanib and Radiation Therapy in Treating Young Patients With Newly Diagnosed Diffuse Brainstem Glioma (http://www.clinicaltrial.gov/ct2/show/NCT00472017?term=vandetanib+St+Jude&rank=1)
4. A recently opened multi-TKI trial: Pazopanib Hydrochloride in Treating Young Patients With Solid Tumors That Have Not Responded to Treatment (www.clinicaltrial.gov/ct2/show/NCT00929903?term=pazopanib+brain+tumor&rank=2)
5. Targeting cancer with small molecule kinase inhibitors. Nat Rev Cancer. 2009 Jan;9(1):28-39 (http://www.ncbi.nlm.nih.gov/pubmed/19104514?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pub med.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=1&log$=relatedreviews&logdbfrom=pubmed)
Monoclonal Antibodies. Intravenous monoclonal antibodies, such as Avastin and Cetuximab, are currently being investigated in the treatment of DIPG both on and off trial.
Here is a recently completed trial for Cetuximab: Study of Erbitux™ (Cetuximab) in Pediatric Patients With Refractory Solid Tumors (www.clinicaltrial.gov/ct2/show/NCT00110357?term=Cetuximab+pediatric&rank=1)
And two more references on Tyrosine Kinase inhibitors in general:
Tyrosine kinase – Role and significance in Cancer. Int J Med Sci. 2004; 1(2): 101–115. (http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1074718)
Different drug names, targets, pharmaceutical companies and mechanism of action are given in a chart at the bottom of this Wikipedia page: http://en.wikipedia.org/wiki/Tyrosine_kinase_inhibitor
This is a rapidly evolving field. It is helpful to have some knowledge of this field in considering the options for treating DIPG.
Sunday, August 16, 2009
Journal Watch
“Brainstem glioma remains a tumour with a dismal prognosis but relatively little is known about the underlying biology and progress will require a concerted effort to collect tissue by biopsy and autopsy to allow appropriate analysis to identify and validate targets. A new era of molecular based therapies offers the promise of major benefits in the management of paediatric glioma but translating this promise into reality will require further understanding of the biology driving these tumours”.
So ends Dr. Darren Hargrave’s new abstract in the British Journal of Neurosurgery on the impact of tumor biology on current and future therapy for pediatric gliomas.
Dr. Hargrave points out that targeted therapeutic agents directed against specific molecular tumor targets offer promise in making a difference for pediatric glioma patients. Unfortunately, the lack of evaluable tumor tissue with diffuse intrinsic pontine tumors has hindered advancement in research and understanding with these tumors. Over the past couple years there have been increasingly visible strategies to try to obtain tissue.
A transition seems to be on the horizon for diffuse intrinsic pontine gliomas with the tissue debates. The issues are not easy but a concerted, collaborative, considered focus could make a significant difference for our kids. To do the best for our children, we call on each institution treating pediatric diffuse intrinsic pontine glioma patients to critically analyze their own approach to the ‘tissue issue’ for DIPGs.
There are several places actively undertaking tumor tissue molecular analysis of DIPGs; however, these researchers are still in need of this most precious resource.
http://www.justonemoreday.org/Research/TumorTissueAnalysis.html
Reference-
Paediatric high and low grade glioma: the impact of tumour biology on current and future therapy.
Br J Neurosurg. 2009 Aug;23(4):351-63.
http://tinyurl.com/n56wpz
So ends Dr. Darren Hargrave’s new abstract in the British Journal of Neurosurgery on the impact of tumor biology on current and future therapy for pediatric gliomas.
Dr. Hargrave points out that targeted therapeutic agents directed against specific molecular tumor targets offer promise in making a difference for pediatric glioma patients. Unfortunately, the lack of evaluable tumor tissue with diffuse intrinsic pontine tumors has hindered advancement in research and understanding with these tumors. Over the past couple years there have been increasingly visible strategies to try to obtain tissue.
A transition seems to be on the horizon for diffuse intrinsic pontine gliomas with the tissue debates. The issues are not easy but a concerted, collaborative, considered focus could make a significant difference for our kids. To do the best for our children, we call on each institution treating pediatric diffuse intrinsic pontine glioma patients to critically analyze their own approach to the ‘tissue issue’ for DIPGs.
There are several places actively undertaking tumor tissue molecular analysis of DIPGs; however, these researchers are still in need of this most precious resource.
http://www.justonemoreday.org/Research/TumorTissueAnalysis.html
Reference-
Paediatric high and low grade glioma: the impact of tumour biology on current and future therapy.
Br J Neurosurg. 2009 Aug;23(4):351-63.
http://tinyurl.com/n56wpz
Monday, August 3, 2009
Gold Ribbon for Childhood Cancer
Just One More Day has teamed up with Kids V Cancer and Candlelighters Childhood Cancer Foundation in launching a petition for Gold Ribbon Awareness with a goal of a million signatures!
Earlier this year, Candlelighters Childhood Cancer Foundation unveiled the first product to have the gold ribbon for childhood cancer awareness- Jel Sert's Fla-Vor-Ice
In addition to Candlelighters, Jel Sert, also helps brain tumor researcher at Children's Memorial Hospital in Chicago through Reid's Lemon Aid.
This petition is not only to gain awareness but also to thank/recognize the first gold ribbon product. The hope is that overwhelming support of this can be used to convince other companies to consider a gold ribbon on their products.
In addition to signing the petition, one can write or call JelSert for their support of our kids-http://www.jelsert.com/Contact-Us/
1-800-323-2592
Please feel free to pass this one to your friends.
Earlier this year, Candlelighters Childhood Cancer Foundation unveiled the first product to have the gold ribbon for childhood cancer awareness- Jel Sert's Fla-Vor-Ice
In addition to Candlelighters, Jel Sert, also helps brain tumor researcher at Children's Memorial Hospital in Chicago through Reid's Lemon Aid.
This petition is not only to gain awareness but also to thank/recognize the first gold ribbon product. The hope is that overwhelming support of this can be used to convince other companies to consider a gold ribbon on their products.
In addition to signing the petition, one can write or call JelSert for their support of our kids-http://www.jelsert.com/Contact-Us/
1-800-323-2592
Please feel free to pass this one to your friends.
Subscribe to:
Posts (Atom)