ironjustice
2011-06-03 12:33:14 UTC
Taking Advantage Of The High Iron Requirements Of Brain Cancer Cells
To Improve Treatment
03 Jun 2011
Brain cancer therapy may be more effective if the expression of an
iron-storing protein is decreased to enhance the action of therapeutic
drugs on brain cancer cells, according to Penn State College of
Medicine researchers.
Malignant glioblastoma multiforme is a deadly brain tumor for which no
long-term effective cure exists. Because drugs in the blood do not
pass from the blood vessels to the brain, effective amounts of
chemotherapy drugs do not reach the tumor. Increasing dosages damage
normal brain tissue and cause significant neurological damage. These
dosages also would likely be harmful to other organs in the body.
However, by increasing the sensitivity of the cancer cells to drugs,
the effectiveness of treatment can be increased.
"About half of all brain tumors are resistant to chemotherapy and new
therapeutic strategies are urgently needed to treat this cancer," said
James Connor, Ph.D., Distinguished Professor and vice-chairman of
neurosurgery.
Connor and his graduate student Xiaoli Liu took advantage of the high
iron requirements of the brain cancer cells to target ferritin, a
protein that stores iron in all cells.
"High levels of iron are required in cancer cells to meet the energy
requirements associated with their rapid growth," Connor said. "In
addition, iron is essential for general cell health."
Working with Achuthamangalam Madhankumar, Ph.D., assistant professor
of neurosurgery, the researchers used liposomes - tiny lipid
containers - to deliver a fragment of RNA called interference or
siRNA, to tumor cells. The siRNA targets the molecular machinery of
the cell so that the protein cannot be made - a process known as
downregulation. By targeting and turning off ferritin in cancer cells,
the protective function of H-ferritin disappears and the sensitivity
to chemotherapy increases.
Using ferritin siRNA, the protein level decreases by 80 percent within
48 hours providing a window of opportunity for enhanced sensitivity to
the chemotherapeutic agent. The researchers studied whether silencing
ferritin would lower the effective dosage of BCNU, a chemotherapy drug
used in brain tumor treatment and one of the few approved for brain
cancer. While BCNU is effective, it has serious side effects limiting
its use.
The use of siRNA reduces the amount of BCNU needed for tumor
suppression by more than half in mice, according to the researchers,
who published their findings in the journal Cancer Research.
"Our results further indicate that a nanoliposomal delivery mechanism
can increase the efficacy of siRNA and optimize the amount of siRNA
delivered," Connor said. "By silencing the ferritin gene, tumor
sensitivity to chemotoxins was increased. The results from this
project are a promising initial step toward the development of siRNA
gene therapy involving ferritin for the treatment of multiple tumor
types."
Notes:
Other researchers contributing to this project were Becky Slagle-Webb,
research assistant, and Jonas M. Sheehan, M.D., associate professor of
neurosurgery, Penn State College of Medicine and Nodar Surguladze,
Ph.D., deputy director, Institute of Molecular Biology and Biological
Physics, Republic of Georgia.
The Tara Leah Witmer Foundation partially supported this research.
Source:
Matthew Solovey
Penn State
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Tom
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http://tinyurl.com/2r2nkh
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DEAD PEOPLE WALKING
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To Improve Treatment
03 Jun 2011
Brain cancer therapy may be more effective if the expression of an
iron-storing protein is decreased to enhance the action of therapeutic
drugs on brain cancer cells, according to Penn State College of
Medicine researchers.
Malignant glioblastoma multiforme is a deadly brain tumor for which no
long-term effective cure exists. Because drugs in the blood do not
pass from the blood vessels to the brain, effective amounts of
chemotherapy drugs do not reach the tumor. Increasing dosages damage
normal brain tissue and cause significant neurological damage. These
dosages also would likely be harmful to other organs in the body.
However, by increasing the sensitivity of the cancer cells to drugs,
the effectiveness of treatment can be increased.
"About half of all brain tumors are resistant to chemotherapy and new
therapeutic strategies are urgently needed to treat this cancer," said
James Connor, Ph.D., Distinguished Professor and vice-chairman of
neurosurgery.
Connor and his graduate student Xiaoli Liu took advantage of the high
iron requirements of the brain cancer cells to target ferritin, a
protein that stores iron in all cells.
"High levels of iron are required in cancer cells to meet the energy
requirements associated with their rapid growth," Connor said. "In
addition, iron is essential for general cell health."
Working with Achuthamangalam Madhankumar, Ph.D., assistant professor
of neurosurgery, the researchers used liposomes - tiny lipid
containers - to deliver a fragment of RNA called interference or
siRNA, to tumor cells. The siRNA targets the molecular machinery of
the cell so that the protein cannot be made - a process known as
downregulation. By targeting and turning off ferritin in cancer cells,
the protective function of H-ferritin disappears and the sensitivity
to chemotherapy increases.
Using ferritin siRNA, the protein level decreases by 80 percent within
48 hours providing a window of opportunity for enhanced sensitivity to
the chemotherapeutic agent. The researchers studied whether silencing
ferritin would lower the effective dosage of BCNU, a chemotherapy drug
used in brain tumor treatment and one of the few approved for brain
cancer. While BCNU is effective, it has serious side effects limiting
its use.
The use of siRNA reduces the amount of BCNU needed for tumor
suppression by more than half in mice, according to the researchers,
who published their findings in the journal Cancer Research.
"Our results further indicate that a nanoliposomal delivery mechanism
can increase the efficacy of siRNA and optimize the amount of siRNA
delivered," Connor said. "By silencing the ferritin gene, tumor
sensitivity to chemotoxins was increased. The results from this
project are a promising initial step toward the development of siRNA
gene therapy involving ferritin for the treatment of multiple tumor
types."
Notes:
Other researchers contributing to this project were Becky Slagle-Webb,
research assistant, and Jonas M. Sheehan, M.D., associate professor of
neurosurgery, Penn State College of Medicine and Nodar Surguladze,
Ph.D., deputy director, Institute of Molecular Biology and Biological
Physics, Republic of Georgia.
The Tara Leah Witmer Foundation partially supported this research.
Source:
Matthew Solovey
Penn State
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh
Man Is A Herbivore!
http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk