XML Feed for RxPG News   Add RxPG News Headlines to My Yahoo!   Javascript Syndication for RxPG News

Research Health World General
 
  Home
 
 Latest Research
 Cancer
 Psychiatry
 Genetics
 Surgery
 Aging
 Ophthalmology
 Gynaecology
 Neurosciences
 Pharmacology
  Anti-Inflammatory
  Antivirals
  Antihypertensives
  Anticholesterol
  Anti-Clotting Drugs
  Anti Cancer Drugs
  Hypnotics
  PPI
  Antibiotics
   Tigecycline
   Sirolimus
  Analgesics
  Surfactants
  Fatty Acids
  Adrenergics
  Metals
  Varenicline
 Cardiology
 Obstetrics
 Infectious Diseases
 Respiratory Medicine
 Pathology
 Endocrinology
 Immunology
 Nephrology
 Gastroenterology
 Biotechnology
 Radiology
 Dermatology
 Microbiology
 Haematology
 Dental
 ENT
 Environment
 Embryology
 Orthopedics
 Metabolism
 Anaethesia
 Paediatrics
 Public Health
 Urology
 Musculoskeletal
 Clinical Trials
 Physiology
 Biochemistry
 Cytology
 Traumatology
 Rheumatology
 
 Medical News
 Health
 Opinion
 Healthcare
 Professionals
 Launch
 Awards & Prizes
 
 Careers
 Medical
 Nursing
 Dental
 
 Special Topics
 Euthanasia
 Ethics
 Evolution
 Odd Medical News
 Feature
 
 World News
 Tsunami
 Epidemics
 Climate
 Business
Search

Last Updated: Aug 19th, 2006 - 22:18:38

Antibiotics Channel
subscribe to Antibiotics newsletter

Latest Research : Pharmacology : Antibiotics

   DISCUSS   |   EMAIL   |   PRINT
Rapamycin shown to inhibit angiogenesis
Aug 15, 2006, 02:48, Reviewed by: Dr. Priya Saxena

"First, unlike healthy blood vessels which are uniform in structure, a tumor's blood vessels balloon and narrow, forming a highly irregular shape. Second, the layer of smooth muscle that you would expect to find covering the blood vessels is inadequate, often resulting in only intermittent coverage. And last, a tumor's blood vessels are overly permeable or leaky."

 
Scientists have long known that the blood vessels of tumors differ markedly from normal blood vessels. Now, a research team led by scientists at Beth Israel Deaconess Medical Center (BIDMC) has identified a signaling pathway which, when activated, transforms otherwise healthy blood vessels into the leaky, misshapen vasculature that characterizes cancerous tumors.

The findings, published in the August 2006 issue of Cancer Cell, additionally demonstrate that rapamycin, a compound used for immunosuppression in transplant patients and currently under investigation as a cancer treatment, can successfully block this signaling pathway--known as the Akt pathway-- in blood vessels. This discovery further enhances the drug's promise as a cancer therapy.

"There are three major hallmarks associated with tumor blood vessels," explains the study's senior author Laura Benjamin, PhD, an investigator in BIDMC's Department of Pathology and Associate Professor of Pathology at Harvard Medical School.

"First, unlike healthy blood vessels which are uniform in structure, a tumor's blood vessels balloon and narrow, forming a highly irregular shape. Second, the layer of smooth muscle that you would expect to find covering the blood vessels is inadequate, often resulting in only intermittent coverage. And last, a tumor's blood vessels are overly permeable or leaky."

The hypothesis that blood vessel formation in tumors is essential for the growth and spread of cancer was first proposed in the early 1970's, and in 1983, it was shown that tumors secrete a factor called VEGF (vascular endothelial growth factor) that induces the permeability associated with blood vessels in cancer.

In this new study, Benjamin and first author Thuy Phung, MD, PhD, of BIDMC's Department of Pathology, hypothesized that the Akt pathway was mediating many of the functions of VEGF in tumors, including the stimulation of blood vessels with abnormal structure and excessive leak. Using a mouse model that enabled them to activate the Akt pathway in healthy blood vessel cells – without the complicating influence of tumor cells – they observed that Akt-induced blood vessels demonstrated the very same abnormalities that are seen in tumor blood vessels. Moreover, adds Benjamin, "We discovered that simply removing the activated Akt was sufficient to reverse these vasculature changes."

The scientists then went on to treat the animals with rapamycin. As predicted, the agent blocked the Akt-induced blood vessel changes. In subsequent experiments, rapamycin reduced tumor growth and vascular leak in a mouse tumor model.

"This paper represents an impressive advance in our understanding of the mechanisms by which tumors generate the new blood vessels they need to survive and grow," says Harold Dvorak, MD, Director of the Vascular Biology Center at BIDMC and Mallinckrodt Professor of Pathology Emeritus at Harvard Medical School, in whose laboratory VEGF was first discovered 23 years ago. "This suggests an attractive new molecular target for cancer therapy."

Approved by the U.S. Food and Drug Administration (FDA) as an immunosuppressant agent, rapamycin is being tested in clinical trials as a cancer treatment.

"These new findings suggest that we should think about using rapamycin in regimens where anti-angiogenic therapy in cancer patients is desired," says Benjamin. "If human tumors respond in the same way that animal models have, rapamycin may normalize and diminish the tumor vasculature, and this is particularly exciting because these findings are clinically relevant today."

In addition to Benjamin and Phung, study coauthors include BIDMC investigators Donnette Dabydeen, BS, Godfred Eyiah-Mensah, BA, Marcela Riveros, MD, Carole Perruzzi, BA, Jingfang Sun, DVM, Rita Monahan-Earley, BA, Janice Nagy, PhD, Ann Dvorak, MD, and Harold F. Dvorak, MD; Keren Ziv, MS, and Michal Neeman, PhD, of the Weizmann Institute of Science in Israel; Ichiro Shiojima, MD, PhD, and Kenneth Walsh, PhD, of Boston University School of Medicine; Michelle Lin, PhD, and William Sessa PhD, of Yale University School of Medicine, New Haven, Connecticut; and David Briscoe, MD, of Children's Hospital, Boston.
 

- August 2006 issue of Cancer Cell
 

www.bidmc.harvard.edu

 
Subscribe to Antibiotics Newsletter
E-mail Address:

 

This study was funded, in part, by grants from the National Institutes of Health and the Israel Science Foundation.

Beth Israel Deaconess Medical Center is a patient care, research and teaching affiliate of Harvard Medical School and ranks fourth in National Institutes of Health funding among independent hospitals nationwide. BIDMC is clinically affiliated with the Joslin Diabetes Center and is a research partner of Dana-Farber/Harvard Cancer Center. BIDMC is the official hospital of the Boston Red Sox.


Related Antibiotics News

Two-component lantibiotic with therapeutic potential discovered
Antibiotic inhibits cancer gene activity
Rapamycin shown to inhibit angiogenesis
Tigecycline, world’s first glycylcycline expanded broad-spectrum antibiotic, launched in UK
FDA Warns of Liver Failure With Telithromycin
What is the optimal duration of antibiotic therapy?
Should children with suspected meningitis be given antibiotics before transfer to hospital?
Production Practices Effect Antimicrobial Resistance in Poultry
Aspirin Protects Against Aminoglycoside Induced Hearing Loss
Avelox (Moxifloxacin) is as effective as Levofloxacin combination therapy for severe community-acquired pneumonia


For any corrections of factual information, to contact the editors or to send any medical news or health news press releases, use feedback form

Top of Page

 

© Copyright 2004 onwards by RxPG Medical Solutions Private Limited
Contact Us