Tuberculosis drug shows promise against latent bacteria
September 13, 2008 by Breakthrough digest
A new study has shown that an investigational drug (R207910, currently in clinical trials against multi-drug resistant tuberculosis strains) is quite effective at killing latent bacteria. This revelation suggests that R207910 may lead to improved and shortened treatments for this globally prevalent disease.
Despite numerous treatment advances, tuberculosis (TB) remains a serious disease –fueled by co-infection of HIV patients, the rise of drug-resistant strains, and the ability of Mycobacterium tuberculosis to become dormant and linger in the lungs. In fact, one third of the world population is infected, asymptomatically, with latent TB and is at risk of developing active TB disease during their life time.
Anil Koul and colleagues at Johnson & Johnson tested ? on dormant M. tuberculosis in three different laboratory models of latency. ? targets a protein (ATP synthase) essential for making cellular energy (ATP) in actively replicating TB. The researchers reasoned that even dormant bacteria, which are essentially physiologically “turned off”, still need to produce small quantities of ATP to survive. As such, a block in ATP synthesis might be an Achilles heel for killing dormant bacteria.
This reasoning proved to be correct and ? was able to kill dormant bacteria by greater than 95% whereas current drugs like isoniazid had no effect. Surprisingly, they found that ? is slightly more effective in killing dormant bacteria as compared to actively replicating ones, a unique spin as all known TB drugs are more effective on replicating bugs. Koul and colleagues hope to validate these results clinically, and note that ATP synthase should be looked at as a drug target for other persistent bacterial infections.
Sunday, September 14, 2008
Anti Tumor Therapy....
Anti-tumor therapy with endoscopic ultrasound may fight cancer more safely and effectively
September 12, 2008 by
Anti-tumor therapy guided by endoscopic ultrasound may allow doctors to fight cancer more safely and effectively
The chairman of EUS2008 today announced that investigational research on a therapeutic technique that will allow physicians to directly inject malignant tumors with cancer fighting agents from inside the body will be presented at the 16th International Symposium of
Endoscopic Ultrasonography (EUS2008) in San Francisco on September 12-13. This technique, which uses a flexible gastrointestinal endoscope with a miniature ultrasound transducer on the tip to guide a small needle directly into a tumor, could prove to be a safer and more effective approach to administering chemotherapy since it allows doctors to deliver therapy right to the tumor and avoid damaging normal surrounding tissues. Injecting drugs directly into the cancer using endoscopic ultrasound (EUS) in combination with systemic chemotherapy to kill cancer cells that have spread may prove to be a more effective approach to some cancers.
EUS combines endoscopy and ultrasound in order to obtain the most accurate, high resolution images and information about the digestive tract and the surrounding tissue and organs. A more advanced form of EUS, called curvilinear EUS, allows doctors to operate within the lumen of the gut while at the same time detect, biopsy and treat lesions and tumors that lie outside the intestinal wall. This technique is particularly useful in patients with pancreatic, esophageal and rectal cancer.
“Curvilinear endosonography will likely become the dominant technology within the field of EUS,” said co-chairman of EUS2008, Robert Hawes, M.D., Professor of Medicine and Peter Cotton Chair for Endoscopic Innovation at the Medical University of South Carolina. “The potential for accurate diagnosis using ultrasound-guided biopsy, precise staging with high resolution ultrasound images and then the enormous opportunity for new therapies with the curvilinear endoscope is why we are focusing this meeting on the use of this instrument alone.”
Used in conjunction with real time imaging, EUS can help physicians to detect blood flow in blood vessels in and around tumors as well as detect and biopsy tumors and lymph nodes as small as 3-5 mm. This allows doctors to avoid puncturing blood vessels when sampling tissue, get the most accurate view of the cancer and know exactly what stage a cancer is in for optimal therapy for treatment. This could save cancer patients with late stage disease from going through unnecessary surgery. EUS may also play a role in the future of minimally invasive surgery (MIS). A new paradigm in MIS is called natural orifice translumenal endoscopic surgery (NOTES®). This entails using the stomach as a window to the abdominal cavity rather than the skin. EUS could play an important role in helping surgeons gain safe access to the abdominal cavity as part of NOTES.
EUS 2008 will be devoted to teaching current applications of curvilinear endoscopic ultrasonography in order to encourage endosonographers and gastroenterologists to become proficient in these procedures, enhance their techniques and increase collaboration with oncology surgeons. This meeting has a rich tradition dating back to the first meeting held in Stockholm, Sweden in 1982. The meeting has evolved as technology has changed and improved along with the exponential growth of endosonographers around the world.
September 12, 2008 by
Anti-tumor therapy guided by endoscopic ultrasound may allow doctors to fight cancer more safely and effectively
The chairman of EUS2008 today announced that investigational research on a therapeutic technique that will allow physicians to directly inject malignant tumors with cancer fighting agents from inside the body will be presented at the 16th International Symposium of
Endoscopic Ultrasonography (EUS2008) in San Francisco on September 12-13. This technique, which uses a flexible gastrointestinal endoscope with a miniature ultrasound transducer on the tip to guide a small needle directly into a tumor, could prove to be a safer and more effective approach to administering chemotherapy since it allows doctors to deliver therapy right to the tumor and avoid damaging normal surrounding tissues. Injecting drugs directly into the cancer using endoscopic ultrasound (EUS) in combination with systemic chemotherapy to kill cancer cells that have spread may prove to be a more effective approach to some cancers.
EUS combines endoscopy and ultrasound in order to obtain the most accurate, high resolution images and information about the digestive tract and the surrounding tissue and organs. A more advanced form of EUS, called curvilinear EUS, allows doctors to operate within the lumen of the gut while at the same time detect, biopsy and treat lesions and tumors that lie outside the intestinal wall. This technique is particularly useful in patients with pancreatic, esophageal and rectal cancer.
“Curvilinear endosonography will likely become the dominant technology within the field of EUS,” said co-chairman of EUS2008, Robert Hawes, M.D., Professor of Medicine and Peter Cotton Chair for Endoscopic Innovation at the Medical University of South Carolina. “The potential for accurate diagnosis using ultrasound-guided biopsy, precise staging with high resolution ultrasound images and then the enormous opportunity for new therapies with the curvilinear endoscope is why we are focusing this meeting on the use of this instrument alone.”
Used in conjunction with real time imaging, EUS can help physicians to detect blood flow in blood vessels in and around tumors as well as detect and biopsy tumors and lymph nodes as small as 3-5 mm. This allows doctors to avoid puncturing blood vessels when sampling tissue, get the most accurate view of the cancer and know exactly what stage a cancer is in for optimal therapy for treatment. This could save cancer patients with late stage disease from going through unnecessary surgery. EUS may also play a role in the future of minimally invasive surgery (MIS). A new paradigm in MIS is called natural orifice translumenal endoscopic surgery (NOTES®). This entails using the stomach as a window to the abdominal cavity rather than the skin. EUS could play an important role in helping surgeons gain safe access to the abdominal cavity as part of NOTES.
EUS 2008 will be devoted to teaching current applications of curvilinear endoscopic ultrasonography in order to encourage endosonographers and gastroenterologists to become proficient in these procedures, enhance their techniques and increase collaboration with oncology surgeons. This meeting has a rich tradition dating back to the first meeting held in Stockholm, Sweden in 1982. The meeting has evolved as technology has changed and improved along with the exponential growth of endosonographers around the world.
Saturday, August 16, 2008
Arthritis, Gout and Joint Disease
One injection ‘vaccine’ cure for arthritis within five years
A single injection that could cure rheumatoid arthritis is being developed by British scientists. The treatment works like a vaccine and could be available within five years. Cells would be taken from the body, altered, and injected back into the affected joint.
A team at Newcastle University will now test the vaccine on volunteers with the disease.
Scientists in the field are extremely excited about the development.
There are 350,000 people in the UK with rheumatoid arthritis, which is a condition where the body’s immune system attacks the joints, unlike oestoarthritis which is more like wear and tear of the joints.
Rheumatoid arthritis is difficult to treat because it is caused by a malfunctioning immune system, causing inflammation in the wrong places.
Prof Alan Silman, medical director of the charity Arthritis Research Campaign, which funded the research, said: “This is an important potential cure. It is possible one injection could switch off the abnormal immune response.
“If it works it could reverse the disease and stop further episodes.”
The Newcastle team will test the effectiveness of the new vaccine in eight volunteers with rheumatoid arthritis from the Freeman Hospital as part of a pilot study, which could then lead to larger trials.
The vaccine works by reprogramming the body’s own immune cells.
Using chemicals, steroids and Vitamin D, the team has devised a way to manipulate a patient’s white blood cells so they surpress, rather than activate, the immune system.
It is thought the cells will then act as a brake on the over-reacting immune system and stop it attacking its own joints.
Although a similar technique has been used in cancer research, this is the first time it has been adapted to rheumatoid arthritis.
John Isaacs, Professor of Clinical Rheumatology at Newcastle University’s Musculoskeletal Research Group, who is leading the team, said that although the work was in a very early, experimental stage it was “hugely exciting”.
“Based on previous laboratory research we would expect that this will specifically suppress or down regulate the auto-immune response,” he said.
Samples will be taken two weeks after the injection to establish whether it has induced the expected response.
The team also hope to find out if the vaccine is effective only in the joints it is injected into, or whether the new cells spread throughout the body.
Prof Silman said the treatment may prove expensive as each patient would have to have their own cells taken and manipulated rather than a drug which can be made in bulk and prescribed to all people with a condition.
He said it would be unlikely that the vaccine could be offered in normal local hospitals because of the expertise necessary to manipulate the cells in the laboratory.
It raises fears the vaccine would have to go through the National Institute for health and Clinical Excellence cost effectiveness tests.
But if the vaccine did work with a one off injection and completely stop the disease it is likely to offer such a huge benefit to the patient that even a relatively large price may be deemed acceptable. Prof Silman said he expected the jab to cost less than £25,000.
The research is being funded by medical research charity the Arthritis Research Campaign, which is providing £216,000 over 18 months.
A single injection that could cure rheumatoid arthritis is being developed by British scientists. The treatment works like a vaccine and could be available within five years. Cells would be taken from the body, altered, and injected back into the affected joint.
A team at Newcastle University will now test the vaccine on volunteers with the disease.
Scientists in the field are extremely excited about the development.
There are 350,000 people in the UK with rheumatoid arthritis, which is a condition where the body’s immune system attacks the joints, unlike oestoarthritis which is more like wear and tear of the joints.
Rheumatoid arthritis is difficult to treat because it is caused by a malfunctioning immune system, causing inflammation in the wrong places.
Prof Alan Silman, medical director of the charity Arthritis Research Campaign, which funded the research, said: “This is an important potential cure. It is possible one injection could switch off the abnormal immune response.
“If it works it could reverse the disease and stop further episodes.”
The Newcastle team will test the effectiveness of the new vaccine in eight volunteers with rheumatoid arthritis from the Freeman Hospital as part of a pilot study, which could then lead to larger trials.
The vaccine works by reprogramming the body’s own immune cells.
Using chemicals, steroids and Vitamin D, the team has devised a way to manipulate a patient’s white blood cells so they surpress, rather than activate, the immune system.
It is thought the cells will then act as a brake on the over-reacting immune system and stop it attacking its own joints.
Although a similar technique has been used in cancer research, this is the first time it has been adapted to rheumatoid arthritis.
John Isaacs, Professor of Clinical Rheumatology at Newcastle University’s Musculoskeletal Research Group, who is leading the team, said that although the work was in a very early, experimental stage it was “hugely exciting”.
“Based on previous laboratory research we would expect that this will specifically suppress or down regulate the auto-immune response,” he said.
Samples will be taken two weeks after the injection to establish whether it has induced the expected response.
The team also hope to find out if the vaccine is effective only in the joints it is injected into, or whether the new cells spread throughout the body.
Prof Silman said the treatment may prove expensive as each patient would have to have their own cells taken and manipulated rather than a drug which can be made in bulk and prescribed to all people with a condition.
He said it would be unlikely that the vaccine could be offered in normal local hospitals because of the expertise necessary to manipulate the cells in the laboratory.
It raises fears the vaccine would have to go through the National Institute for health and Clinical Excellence cost effectiveness tests.
But if the vaccine did work with a one off injection and completely stop the disease it is likely to offer such a huge benefit to the patient that even a relatively large price may be deemed acceptable. Prof Silman said he expected the jab to cost less than £25,000.
The research is being funded by medical research charity the Arthritis Research Campaign, which is providing £216,000 over 18 months.
FDA : Some cholesterol and heart drugs dont mix
FDA: Some cholesterol and heart drugs don’t mix
Patients taking some common medications for high cholesterol and irregular heart beats can suffer severe muscle damage because of a problem in the way the drugs interact, the government warned on Friday.
The Food and Drug Administration said doctors should use extra care when prescribing Zocor, generic Zocor, or Vytorin to patients who are also taking amiodarone, a heart rhythm drug marketed as Cordarone or Pacerone. The danger is higher for patients taking more than 20 milligrams a day of the cholesterol drugs, the agency said.
The generic name for the cholesterol medications is simvastatin.
Muscle injury is a risk with any of the cholesterol drugs known as statins, including Lipitor, particularly for the elderly. Although the risk of such injuries is low overall, they can be serious because they can lead to kidney failure and even death.
The FDA urged doctors to consider switching patients who are taking the heart rhythm drug to other statins for controlling cholesterol. The heart medication is mainly used to treat irregular rhythms in the ventricles, the heart chambers that pump blood to the lungs and body.
A previous warning dating back to 2002 about the drug interaction apparently has not put an end to the problem. The FDA said since that time it has received 52 reports of serious muscle injury to patients taking the combination of medications, and almost all the patients had to be hospitalized.
Patients taking some common medications for high cholesterol and irregular heart beats can suffer severe muscle damage because of a problem in the way the drugs interact, the government warned on Friday.
The Food and Drug Administration said doctors should use extra care when prescribing Zocor, generic Zocor, or Vytorin to patients who are also taking amiodarone, a heart rhythm drug marketed as Cordarone or Pacerone. The danger is higher for patients taking more than 20 milligrams a day of the cholesterol drugs, the agency said.
The generic name for the cholesterol medications is simvastatin.
Muscle injury is a risk with any of the cholesterol drugs known as statins, including Lipitor, particularly for the elderly. Although the risk of such injuries is low overall, they can be serious because they can lead to kidney failure and even death.
The FDA urged doctors to consider switching patients who are taking the heart rhythm drug to other statins for controlling cholesterol. The heart medication is mainly used to treat irregular rhythms in the ventricles, the heart chambers that pump blood to the lungs and body.
A previous warning dating back to 2002 about the drug interaction apparently has not put an end to the problem. The FDA said since that time it has received 52 reports of serious muscle injury to patients taking the combination of medications, and almost all the patients had to be hospitalized.
Tuesday, June 10, 2008
Solid Tumor Cells....
As published on 11th june 2008 in Breakthrough digest.
Solid tumor cells not killed by radiation and chemotherapy become stronger
Because of the way solid tumors adapt the body’s machinery to bring themselves more oxygen, chemotherapy and radiation may actually make these tumors stronger.
“In a sense, these therapies can make the tumor healthier,” said Mark W. Dewhirst, D.V.M., Ph.D., professor of radiation oncology at Duke University Medical Center. “Unless the treatment is very effective in killing many if not most tumor cells, you are shooting yourself in the foot.”
Dewhirst and colleagues Yiting Cao, M.D., Ph.D., of Duke Pathology, and Benjamin Moeller, M.D., Ph.D. have introduced this counter-intuitive idea at recent conferences and in a review article featured in the June issue of Nature Reviews Cancer.
Radiation and chemotherapy do kill most solid tumor cells, but in the cells that survive, the therapies drive an increase in a regulatory factor called HIF1 (hypoxia-inducible factor 1), which cells use to get the oxygen they need by increasing blood vessel growth into the tumor. Solid tumors generally have low supplies of oxygen, Dewhirst explained and HIF1 helps them get the oxygen they need.
The review article concludes that blocking HIF1 would provide a clear mechanism for killing solid-tumor cells, particularly cells that are proving resistant to radiation or chemotherapy treatments.
As a part of this work, Dewhirst’s team has been studying the phenomenon of rising and falling oxygen levels in tumors, called cycling hypoxia. Oxygen levels have been found to naturally cycle up and down in individual blood vessels as well as large tumor regions. This instability in the tumor’s oxygen levels can increase HIF-1 production and cause radiation therapy to fail, Dewhirst said.
“It is my opinion that the whole tumor grows more aggressively because of this pulsation of oxygen at low levels,” Dewhirst said. “Most people thought cycling hypoxia was caused by temporary stoppage of blood flow in single blood vessel in tumors. In fact, however, oxygen levels cycle up and down virtually everywhere in the tumor, which is caused by fluctuations in blood flow rate. It has been a challenge to convince people of this.”
Dewhirst and colleagues have made movies of oxygen transport in a tumor of a living animal that show the oxygen levels cycle up and down significantly, pulsing in waves seen as color changes in the movies. (View these movies at the Nature Reviews Cancer site: http://www.nature.com/nrc/journal/v8/n6/suppinfo/nrc2397.html )
The Duke team argues that blocking HIF1 is the consistent answer to tumor growth problems. Blocking HIF1 activity interferes with the tumor’s ability to undergo glycolysis (energy production) in low-oxygen conditions, which blocks tumor growth, the authors wrote. Exactly how to accomplish chemotherapy or radiation treatment in the safest, most effective ways, in combination with HIF1 blockade, is still open for exploration, Dewhirst said.
For example, targeting HIF1 in the early stages of tumor growth, especially in very early cancer spread, may help, Dewhirst said. “For a woman who has had a primary breast tumor removed, and who is at high risk for cancer spread, this might be a situation in which you’d target HIF1,” he explained. “Blocking HIF1 makes sense during the early stages of angiogenesis, which is the accelerated phase of blood vessel formation. In this way, you could keep the early metastasis sites inactive and prevent them from growing.”
The Duke team has completed a phase I trial with a HIF1 inhibitor. “We are actively pursuing this clinically and will be moving this study into Phase 2,” Dewhirst said. “We are interested in other applications of HIF-1 inhibition in combination with radiation and chemotherapy for different diseases.”
Solid tumor cells not killed by radiation and chemotherapy become stronger
Because of the way solid tumors adapt the body’s machinery to bring themselves more oxygen, chemotherapy and radiation may actually make these tumors stronger.
“In a sense, these therapies can make the tumor healthier,” said Mark W. Dewhirst, D.V.M., Ph.D., professor of radiation oncology at Duke University Medical Center. “Unless the treatment is very effective in killing many if not most tumor cells, you are shooting yourself in the foot.”
Dewhirst and colleagues Yiting Cao, M.D., Ph.D., of Duke Pathology, and Benjamin Moeller, M.D., Ph.D. have introduced this counter-intuitive idea at recent conferences and in a review article featured in the June issue of Nature Reviews Cancer.
Radiation and chemotherapy do kill most solid tumor cells, but in the cells that survive, the therapies drive an increase in a regulatory factor called HIF1 (hypoxia-inducible factor 1), which cells use to get the oxygen they need by increasing blood vessel growth into the tumor. Solid tumors generally have low supplies of oxygen, Dewhirst explained and HIF1 helps them get the oxygen they need.
The review article concludes that blocking HIF1 would provide a clear mechanism for killing solid-tumor cells, particularly cells that are proving resistant to radiation or chemotherapy treatments.
As a part of this work, Dewhirst’s team has been studying the phenomenon of rising and falling oxygen levels in tumors, called cycling hypoxia. Oxygen levels have been found to naturally cycle up and down in individual blood vessels as well as large tumor regions. This instability in the tumor’s oxygen levels can increase HIF-1 production and cause radiation therapy to fail, Dewhirst said.
“It is my opinion that the whole tumor grows more aggressively because of this pulsation of oxygen at low levels,” Dewhirst said. “Most people thought cycling hypoxia was caused by temporary stoppage of blood flow in single blood vessel in tumors. In fact, however, oxygen levels cycle up and down virtually everywhere in the tumor, which is caused by fluctuations in blood flow rate. It has been a challenge to convince people of this.”
Dewhirst and colleagues have made movies of oxygen transport in a tumor of a living animal that show the oxygen levels cycle up and down significantly, pulsing in waves seen as color changes in the movies. (View these movies at the Nature Reviews Cancer site: http://www.nature.com/nrc/journal/v8/n6/suppinfo/nrc2397.html )
The Duke team argues that blocking HIF1 is the consistent answer to tumor growth problems. Blocking HIF1 activity interferes with the tumor’s ability to undergo glycolysis (energy production) in low-oxygen conditions, which blocks tumor growth, the authors wrote. Exactly how to accomplish chemotherapy or radiation treatment in the safest, most effective ways, in combination with HIF1 blockade, is still open for exploration, Dewhirst said.
For example, targeting HIF1 in the early stages of tumor growth, especially in very early cancer spread, may help, Dewhirst said. “For a woman who has had a primary breast tumor removed, and who is at high risk for cancer spread, this might be a situation in which you’d target HIF1,” he explained. “Blocking HIF1 makes sense during the early stages of angiogenesis, which is the accelerated phase of blood vessel formation. In this way, you could keep the early metastasis sites inactive and prevent them from growing.”
The Duke team has completed a phase I trial with a HIF1 inhibitor. “We are actively pursuing this clinically and will be moving this study into Phase 2,” Dewhirst said. “We are interested in other applications of HIF-1 inhibition in combination with radiation and chemotherapy for different diseases.”
Saturday, June 7, 2008
Cord Blood Stem Cells in Bone Marrow Transplants
New Technology Enhances and Expands “Homing”and Therapeutic Potential of Cord Blood Stem Cells in Bone Marrow Transplants
A CD26 Inhibitor increases the efficiency and responsiveness of umbilical cord blood for bone marrow transplants and may improve care for blood cancer patients according to research from Rush University Medical Center being presented at the 6th Annual International Umbilical Cord Blood
Transplantation Symposium, June 6-7 in Los Angeles.
Kent W. Christopherson II, PhD, assistant professor of medicine and researcher in the Sections of Hematology and Stem Cell Transplantation at Rush, is researching a CD26 Inhibitor, a small molecule enzyme inhibitor that enhances directional homing of stem cells to the bone marrow by increasing the responsiveness of donor stem cells to a natural homing signal. Homing is the process by which the donor stem cells find their way to the bone marrow. It is the first and essential step in stem cell transplantation.
Cord blood is increasingly being used by transplant centers as an alternative source of stem cells for the treatment of blood cancers, including myeloma, lymphoma and leukemia. The cells, which are collected from the umbilical cord after the baby is delivered and separated from the cord, are most commonly used for bone marrow transplantation when a donor from a patient’s family or an unrelated donor does not produce an appropriate bone marrow match.
The current drawback to the usage of cord blood cells is that due to the limited volume and cell number, there are generally only enough cells available from a single cord blood collection for children or very small adults. Cord blood cells also usually take longer to engraft, leaving the patient at a high risk
for infection longer than donor matched transplanted marrow or peripheral blood stem cells. The goal of Christopherson’s research is to increase the transplant efficiency of umbilical cord blood and ultimately make transplant safer and available to all patients who require this treatment.
In his discussion on “Strategies to Improve Homing,” Christopherson states that results from his and other laboratories suggest “the beneficial effects of the CD26 Inhibitor usage and the potential of this technology to change hematopoietic stem cell transplantation.”
Christopherson will co-chair the session and review some of his Leukemia & Lymphoma Society funded work at the symposium in a session entitled “Basic Science and Clinical Studies Addressing Obstacles to Successful Umbilical Cord Blood Transplants (UCBT)”. He will be joined by Dr. Patrick Zweidler-McKay of the University if Texas MD Anderson Cancer Center. Zweidler-McKay will discuss his team’s work in the same session on Engraftin™, a human recombinant enzyme technology that increases the efficiency of engraftment and reduces graft failure in transplantation of cord blood derived stem cells.
Research results in animal models by Christopherson and Zweider-McKay show that both Engraftin and CD26 Inhibitor can enhance homing and rate of engraftment, which will result in reduced patient morbidity and mortality in bone marrow transplants. American Stem Cell, Inc., the developer of both technologies, plans to begin human trials in the next few months.
There are over 250,000 new cancer patients per year who require or would benefit from stem cell transplantation and as many as 20% are unable to find a blood or marrow match.
A CD26 Inhibitor increases the efficiency and responsiveness of umbilical cord blood for bone marrow transplants and may improve care for blood cancer patients according to research from Rush University Medical Center being presented at the 6th Annual International Umbilical Cord Blood
Transplantation Symposium, June 6-7 in Los Angeles.
Kent W. Christopherson II, PhD, assistant professor of medicine and researcher in the Sections of Hematology and Stem Cell Transplantation at Rush, is researching a CD26 Inhibitor, a small molecule enzyme inhibitor that enhances directional homing of stem cells to the bone marrow by increasing the responsiveness of donor stem cells to a natural homing signal. Homing is the process by which the donor stem cells find their way to the bone marrow. It is the first and essential step in stem cell transplantation.
Cord blood is increasingly being used by transplant centers as an alternative source of stem cells for the treatment of blood cancers, including myeloma, lymphoma and leukemia. The cells, which are collected from the umbilical cord after the baby is delivered and separated from the cord, are most commonly used for bone marrow transplantation when a donor from a patient’s family or an unrelated donor does not produce an appropriate bone marrow match.
The current drawback to the usage of cord blood cells is that due to the limited volume and cell number, there are generally only enough cells available from a single cord blood collection for children or very small adults. Cord blood cells also usually take longer to engraft, leaving the patient at a high risk
for infection longer than donor matched transplanted marrow or peripheral blood stem cells. The goal of Christopherson’s research is to increase the transplant efficiency of umbilical cord blood and ultimately make transplant safer and available to all patients who require this treatment.
In his discussion on “Strategies to Improve Homing,” Christopherson states that results from his and other laboratories suggest “the beneficial effects of the CD26 Inhibitor usage and the potential of this technology to change hematopoietic stem cell transplantation.”
Christopherson will co-chair the session and review some of his Leukemia & Lymphoma Society funded work at the symposium in a session entitled “Basic Science and Clinical Studies Addressing Obstacles to Successful Umbilical Cord Blood Transplants (UCBT)”. He will be joined by Dr. Patrick Zweidler-McKay of the University if Texas MD Anderson Cancer Center. Zweidler-McKay will discuss his team’s work in the same session on Engraftin™, a human recombinant enzyme technology that increases the efficiency of engraftment and reduces graft failure in transplantation of cord blood derived stem cells.
Research results in animal models by Christopherson and Zweider-McKay show that both Engraftin and CD26 Inhibitor can enhance homing and rate of engraftment, which will result in reduced patient morbidity and mortality in bone marrow transplants. American Stem Cell, Inc., the developer of both technologies, plans to begin human trials in the next few months.
There are over 250,000 new cancer patients per year who require or would benefit from stem cell transplantation and as many as 20% are unable to find a blood or marrow match.
Brain stem cells...
Brain stem cells can be awakened?
Study findings promise to help in treatment of brain diseases
Boston, MA-Scientists at Schepens Eye Research Institute have identified specific molecules in the brain that are responsible for awakening and putting to sleep brain stem cells, which, when activated, can transform into neurons (nerve cells) and repair damaged brain tissue. Their findings are published online this week in the Proceedings of the National Academy of Science (PNAS).
An earlier paper (published in the May issue of Stem Cells) by the same scientists laid the foundation for the PNAS study findings by demonstrating that neural stem cells exist in every part of the brain, but are mostly kept silent by chemical signals from support cells known as astrocytes.
³The findings from both papers should have a far-reaching impact,² says principal investigator, Dr. Dong Feng Chen, who is an associate scientist at Schepens Eye Research Institute and an assistant professor of ophthalmology at Harvard Medical School. Chen believes that tapping the brain¹s dormant, but intrinsic, ability to regenerate itself is the best hope for people suffering from brain-ravaging diseases such as Parkinson¹s or Alzheimer¹s disease or traumatic brain or spinal cord injuries.
Until these studies, which were conducted in the adult brains of mice, scientists assumed that only two parts of the brain contained neural stem cells and could turn them on to regenerate brain tissue– the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ). The hippocampus is responsible for learning and memory, while the SVZ is a brain structure situated throughout the walls of lateral ventricles (part of the ventricular system in the brain) and is responsible for generating neurons reponsible for smell. So scientists believed that when neurons died in other areas of the brain, they were lost forever along with their functions.
In the first study, Chen¹s team learned that stem cells existed everywhere in the brain by testing tissue from different parts of adult mice brains in cultures containing support cells (known as astrocytes) from the hippocampus, where stem cells do regenerate.
In the cultures the stem cells from other brain regions came to life and turned into neurons.
When they compared the chemical makeup of the areas known to generate new neurons in the hippocampus with other parts of the brain, the team discovered that astrocytes in the hippocampus were sending one signal to the stem cells and that those from the rest of the brain were sending a different signal to stem cells.
In the second (PNAS) study, the team went on to discover the exact nature of those different chemical signals. They learned that in the areas where stem cells were sleeping, astrocytes were producing high levels of two related molecules–ephrin-A2 and ephrin-A3. They also found that removing these molecules (with a genetic tool) activated the sleeping stem cells.
The team also found that astrocytes in the hippocampus produce not only much lower levels of ephrin-A2 and ephrin-A3, but also release a protein named sonic hedghoc that, when added in culture or injected into the brain, stimulates neural stem cells to divide and become new neurons.
³These findings identify a key pathway that controls neural stem cell growth in the adult brain and suggest that it may be possible to reactivate the dormant regenerative potential by adding sonic hedgehoc, or blocking ephrin-A2 or ephrin-A3,² says Dr. Jianwei Jiao, the first author of the two papers.
The next step for the team will be to stimulate the sleeping stem cells in animals who are models of neurodegenerative disorders, such as Parkinson’s disease, to see if the brains can repair themselves and restore their damaged functions.
Study findings promise to help in treatment of brain diseases
Boston, MA-Scientists at Schepens Eye Research Institute have identified specific molecules in the brain that are responsible for awakening and putting to sleep brain stem cells, which, when activated, can transform into neurons (nerve cells) and repair damaged brain tissue. Their findings are published online this week in the Proceedings of the National Academy of Science (PNAS).
An earlier paper (published in the May issue of Stem Cells) by the same scientists laid the foundation for the PNAS study findings by demonstrating that neural stem cells exist in every part of the brain, but are mostly kept silent by chemical signals from support cells known as astrocytes.
³The findings from both papers should have a far-reaching impact,² says principal investigator, Dr. Dong Feng Chen, who is an associate scientist at Schepens Eye Research Institute and an assistant professor of ophthalmology at Harvard Medical School. Chen believes that tapping the brain¹s dormant, but intrinsic, ability to regenerate itself is the best hope for people suffering from brain-ravaging diseases such as Parkinson¹s or Alzheimer¹s disease or traumatic brain or spinal cord injuries.
Until these studies, which were conducted in the adult brains of mice, scientists assumed that only two parts of the brain contained neural stem cells and could turn them on to regenerate brain tissue– the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ). The hippocampus is responsible for learning and memory, while the SVZ is a brain structure situated throughout the walls of lateral ventricles (part of the ventricular system in the brain) and is responsible for generating neurons reponsible for smell. So scientists believed that when neurons died in other areas of the brain, they were lost forever along with their functions.
In the first study, Chen¹s team learned that stem cells existed everywhere in the brain by testing tissue from different parts of adult mice brains in cultures containing support cells (known as astrocytes) from the hippocampus, where stem cells do regenerate.
In the cultures the stem cells from other brain regions came to life and turned into neurons.
When they compared the chemical makeup of the areas known to generate new neurons in the hippocampus with other parts of the brain, the team discovered that astrocytes in the hippocampus were sending one signal to the stem cells and that those from the rest of the brain were sending a different signal to stem cells.
In the second (PNAS) study, the team went on to discover the exact nature of those different chemical signals. They learned that in the areas where stem cells were sleeping, astrocytes were producing high levels of two related molecules–ephrin-A2 and ephrin-A3. They also found that removing these molecules (with a genetic tool) activated the sleeping stem cells.
The team also found that astrocytes in the hippocampus produce not only much lower levels of ephrin-A2 and ephrin-A3, but also release a protein named sonic hedghoc that, when added in culture or injected into the brain, stimulates neural stem cells to divide and become new neurons.
³These findings identify a key pathway that controls neural stem cell growth in the adult brain and suggest that it may be possible to reactivate the dormant regenerative potential by adding sonic hedgehoc, or blocking ephrin-A2 or ephrin-A3,² says Dr. Jianwei Jiao, the first author of the two papers.
The next step for the team will be to stimulate the sleeping stem cells in animals who are models of neurodegenerative disorders, such as Parkinson’s disease, to see if the brains can repair themselves and restore their damaged functions.
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