Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Discovery may help prevent chemotherapy-induced anemia

06.05.2013
Cancer chemotherapy can cause peripheral neuropathy—nerve damage often resulting in pain and muscle weakness in the arms and legs.

Now, researchers at Albert Einstein College of Medicine of Yeshiva University have discovered that chemo also induces an insidious type of nerve damage inside bone marrow that can cause delays in recovery after bone marrow transplantation.

The findings, made in mice and published online today in Nature Medicine, suggest that combining chemotherapy with nerve-protecting agents may prevent long-term bone marrow injury that causes anemia and may improve the success of bone marrow transplants.

Constantly regenerating and maturing, the hematopoietic (blood-producing) stem cells in our bone marrow produce billions of red blood cells (RBC) every day. Cancer chemotherapy is notorious for injuring the bone marrow, leading to anemia, or low RBC counts. But just how chemotherapy harms the bone marrow has not been clear.

Anemia can lead to numerous health problems including chronic fatigue, tachycardia (abnormally rapid heartbeat), cognitive impairment, shortness of breath, depression and dizziness. In addition, studies have shown that cancer patients who develop anemia have a 65 percent increased risk of death compared with cancer patients without anemia.

In an earlier study, senior author Paul Frenette, M.D., professor of medicine and of cell biology and director of the Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research at Einstein, found that sympathetic nerves within bone marrow direct the movement of hematopoietic stem cells. (The body's sympathetic nervous system helps in controlling most internal organs—increasing heart rate and dilating the pupils of the eye, for example.)

"Since many chemotherapies used in cancer treatment are neurotoxic, we wondered whether they might also damage sympathetic nerves in bone marrow itself, impairing the ability of hematopoietic cells to regenerate and to manufacture RBCs," said Dr. Frenette. "This possibility hadn't been examined before."

Dr. Frenette and his colleagues treated mice with seven cycles of cisplatin, a common chemotherapy drug with known neurotoxic effects. The cisplatin caused peripheral neuropathy problems similar to those seen in cancer patients. The mice were then given fresh bone marrow transplants to see how well their marrow would regenerate. Despite receiving fresh stem cells, the cisplatin-treated mice had delayed recovery of blood counts compared to controls—suggesting that the prior cisplatin treatments had affected the bone marrow and prevented hematopoietic stem cells from regenerating. By contrast, mice treated with carboplatin—a non-neurotoxic chemotherapy—recovered their ability to produce blood after bone marrow transplantation.

To confirm that healthy sympathetic nerves in the bone marrow are needed to regenerate hematopoietic stem cells and produce RBCs, the researchers selectively damaged sympathetic nerves in bone marrow using chemicals or genetic engineering. In both cases, the mice with the damaged sympathetic nerves were less able than control mice to recover after bone marrow transplant.

The researchers found that injury to these nerves could be reduced by giving mice nerve-protecting agents along with chemotherapy. Mice treated with seven cycles of cisplatin along with 4-methylcatechol (an experimental drug that reportedly protects sympathetic nerves) showed improved response to bone marrow transplantation, compared to controls.

Dr. Frenette and his colleagues now plan to look for compounds that can protect sympathetic nerves in the bone marrow without reducing the effectiveness of cancer chemotherapies.

The title of the paper is "Chemotherapy-induced bone marrow nerve injury impairs hematopoietic regeneration." The lead author of the paper is Daniel Lucas, Ph.D., a postdoctoral reseacher in Dr. Frenette's laboratory. Other Einstein contributors are Christoph Scheiermann, Ph.D., and Yuya Kunisaki, M.D., Ph.D. Additional co-authors are Andrew Chow, M.D./Ph.D. student, Icahn School of Medicine at Mount Sinai, New York, NY; Ingmar Bruns, M.D., Ph.D., Einstein and Heinrich Heine University, Dusseldorf, Germany; Colleen Barrick, National Cancer Institute, Frederick, MD; and Lino Tessarollo, Ph.D., National Cancer Institute.

This work was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (DK056638) and the National Heart, Lung, and Blood Institute (HL069438), both parts of the National Institutes of Health.

A patent application on this technology has been filed, which is currently available for licensing and further commercialization.

The authors declare no competing financial interests.

About Albert Einstein College of Medicine of Yeshiva University

Albert Einstein College of Medicine of Yeshiva University is one of the nation's premier centers for research, medical education and clinical investigation. During the 2012-2013 academic year, Einstein is home to 742 M.D. students, 245 Ph.D. students, 116 students in the combined M.D./Ph.D. program, and 360 postdoctoral research fellows. The College of Medicine has more than 2,000 full-time faculty members located on the main campus and at its clinical affiliates. In 2012, Einstein received over $160 million in awards from the NIH. This includes the funding of major research centers at Einstein in diabetes, cancer, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Its partnership with Montefiore Medical Center, the University Hospital and academic medical center for Einstein, advances clinical and translational research to accelerate the pace at which new discoveries become the treatments and therapies that benefit patients. Through its extensive affiliation network involving Montefiore, Jacobi Medical Center –Einstein's founding hospital, and five other hospital systems in the Bronx, Manhattan, Long Island and Brooklyn, Einstein runs one of the largest residency and fellowship training programs in the medical and dental professions in the United States. For more information, please visit http://www.einstein.yu.edu and follow us on Twitter @EinsteinMed.

Kim Newman | EurekAlert!
Further information:
http://www.einstein.yu.edu

More articles from Health and Medicine:

nachricht 'Living bandages': NUST MISIS scientists develop biocompatible anti-burn nanofibers
16.02.2018 | National University of Science and Technology MISIS

nachricht New process allows tailor-made malaria research
16.02.2018 | Eberhard Karls Universität Tübingen

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

Im Focus: Autonomous 3D scanner supports individual manufacturing processes

Let’s say the armrest is broken in your vintage car. As things stand, you would need a lot of luck and persistence to find the right spare part. But in the world of Industrie 4.0 and production with batch sizes of one, you can simply scan the armrest and print it out. This is made possible by the first ever 3D scanner capable of working autonomously and in real time. The autonomous scanning system will be on display at the Hannover Messe Preview on February 6 and at the Hannover Messe proper from April 23 to 27, 2018 (Hall 6, Booth A30).

Part of the charm of vintage cars is that they stopped making them long ago, so it is special when you do see one out on the roads. If something breaks or...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Fingerprints of quantum entanglement

16.02.2018 | Information Technology

'Living bandages': NUST MISIS scientists develop biocompatible anti-burn nanofibers

16.02.2018 | Health and Medicine

Hubble sees Neptune's mysterious shrinking storm

16.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>