Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Getting through the matrix

19.05.2003


MGH research suggests strategies for improving drug delivery to cancer cells



The best cancer drugs in the world are not much good if they cannot get to tumor cells. That problem has been challenging cancer physicians and researchers for years because the physical structure of many tumors can prevent anticancer agents from reaching their targets. In a study appearing in the June issue of Nature Medicine, researchers from Massachusetts General Hospital (MGH) describe a new technique for assessing the permeability of tumors and a promising new way of improving tumors’ accessibility to drugs. The report is receiving advance online publication on the journal’s website at http://www.nature.com/nm/.

"We’ve known for a long time that many cancer drugs work very well on cells, but not so well in patients," says Rakesh Jain, PhD, director of the Steele Laboratory for Tumor Biology at MGH, senior author of the study. "As we have improved the understanding of tumor physiology, we have found that a significant portion of a tumor is made up of an extracellular matrix that acts as a barrier, keeping drugs away from tumor cells."


This matrix is largely made up of the connective tissue collagen. To determine the structure and content of collagen in different tumor types and to assess its effect on a tumor’s permeability, Jain’s team used a new imaging technique called second-harmonic generation (SHG), a non-invasive way of measuring an optical signal released by certain molecular structures. The researchers first showed that SHG can distinguish among types of connective tissue molecules and can specifically image the structure and density of collagen fibers.

By imaging tumors that had been implanted in mice, Jain’s team was able to produce high-definition 3-D images that revealed the amount and form of collagen. Studying three types of tumors known to have different relative collagen contents, they showed that SHG could accurately measure collagen levels that correlated with measurements of tumor permeability. This result suggests that SHG could allow analysis of the structure and content of a tumor’s collagen to help with treatment planning.

To test whether SHG could measure collagen modification, the researchers first applied the enzyme collagenase, which breaks down collagen, directly to mouse tumors. Images taken after collagenase application showed significant changes in the SHG images. However, because collagen is an important part of the body’s overall structure, collagenase would not be a useful treatment adjunct since its effect could spread far beyond the tumor itself.

In their search for an agent to selectively break down tumor-matrix collagen, the research team turned to a hormone called relaxin. Naturally produced in pregnant females, relaxin increases production of enzymes associated with dilation of the cervix and other processes needed for birth preparation. Clinical trials for other potential uses of relaxin have found only minor side effects in humans.

The researchers used intravenous pumps to deliver relaxin into the bloodstream of mice with implanted human tumors and then used SHG to image the tumors over a 12-day period. They also imaged the tumors of a control group that did not receive relaxin. While the amount of collagen in the relaxin-treated tumors was similar to that seen in the control group at the end of the study period, in the relaxin-treated mice the collagen fibers had broken down and were measurably shorter. When the researchers used probe molecules to measure the tumors’ permeability, the results indicated that the relaxin-treated matrix tissue was looser and less of an obstacle to penetration.

"We have already started animal studies to measure whether relaxin can improve actual response to chemotherapy drugs," says Jain, who is A.W. Cook Professor of Tumor Biology at Harvard Medical School. "If those results are positive, the fact that relaxin is so safe means we could move relatively quickly into human clinical trials."

A key collaborator in this research is Brian Seed, PhD, of the MGH Department of Molecular Biology. Other authors of the report are Edward Brown, PhD, of MGH and Trevor McKee, BSc, of Massachusetts Institute of Technology, co-first authors; Emmanuelle diTomaso, PhD, and Yves Boucher, PhD, also of MGH; and Alain Pluen, PhD, of the University of Manchester in the United Kingdom. The research was supported by grants from the National Cancer Institute.


###
Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $350 million and major research centers in AIDS, cardiovascular research, cancer, cutaneous biology, neurodegenerative disorders, transplantation biology and photomedicine. In 1994, MGH and Brigham and Women’s Hospital formed Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups, and nonacute and home health services.


Sue McGreevey | EurekAlert!
Further information:
http://www.mgh.harvard.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: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

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...

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

Rare find from the deep sea

20.02.2018 | Life Sciences

In living color: Brightly-colored bacteria could be used to 'grow' paints and coatings

20.02.2018 | Life Sciences

Observing and controlling ultrafast processes with attosecond resolution

20.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>