Featured Research

from universities, journals, and other organizations

New mechanism leading to tumor hypoxia defined

Date:
May 9, 2013
Source:
Versita
Summary:
Hypoxia is a negative prognostic indicator for radiotherapy, chemotherapy or surgery that predicts for an aggressive and metastatic phenotype. So far, there have been two recognized forms of tumor hypoxia: Diffusion or perfusion limited. Now, scientists have attributed temporal and spatial distribution to tumor hypoxia.

An article published recently in Tumor Microenvironment and Therapy -- an open access journal by Versita, defines a novel mechanism of tumor hypoxia induced by the longitudinal gradient of residual oxygen along tumor vessels as they transverse the tumor.

Related Articles


Growing evidence from experimental studies and clinical trials suggests a fundamental role of hypoxia in solid tumors. The mechanisms leading to hypoxia include the rapid rate of tumor growth, poor tumor perfusion or transiently disrupted tumor blood flow. Now, scientists from the University of Pennsylvania, led by Professor Cameron J. Koch, have discovered a previously uncharacterized mechanism that contributes to -- and may influence -- the temporal and spatial distribution of tumor hypoxia.

Hypoxic cancer cells represent the most aggressive type of a tumor. In case of malignant tumors they tend to be resistant to radio therapy, and low oxygen concentration can actually enhance metastasis. Thus, hypoxia -- labeled accordingly as a poor prognostic factor -- is emerging as an important, high-priority target for cancer therapy.

So far, there have been two recognized forms of tumor hypoxia: Diffusion limited hypoxia occurs as a result of distance from vessels; it is a stable factor and it occurs at a scale of hundreds of microns. Perfusion limited hypoxia, in contrast, results from perturbations in tumor blood flow, which can be both transient and recurring, but it also generally occurs on a smaller scale. The current report demonstrates that in addition to these two mechanisms, there is a stable gradient of oxygen that can occur over multi-millimeter distances along the length of a tumor vessel leading to hypoxia at the more distal portions of the vessel. This finding leads to a more complete understanding of the factors that have an influence on tumor oxygenation -- adding a third mechanism that contributes to tumor hypoxia and would be expected to scale with tumor size.

The researchers used a 9L glioma model with defined and ordered vascular flow originating from the rat epigastric artery and vein pair to study hypoxia distribution using both immuno-histochemical and MRI methodologies. They further developed a gamma-H2AX labeling technique for defining hypoxia impact on DNA damage. Macroscopic regions of hypoxia occurred in every fourth of examined tumors. The researchers found large (mm) regions of moderate (0.3%) hypoxia that were not easily explained by the existing concepts of diffusion or perfusion-limited hypoxia. Due to its stability and the fact that it occurs over a large scale, this mechanism for the distribution of oxygen and other nutrients and drugs has substantial implications for hypoxia imaging, hypoxic cell targeting and for therapy effectiveness.

Hypoxia has historically been seen as occurring as the result of events at a microscopic scale. Diffusion-limited hypoxia, described in the 1950s by Thomlinson and Gray is stable and occurs as a gradient at distances of 100-200uM from vessels. Transient or perfusion limited hypoxia was described more recently and added to the complexity of detecting and targeting hypoxic cells, as well as having biological implications for tumor cell resistance to therapy. The current report superimposes a larger scale, presumably stable hypoxic gradient over these two mechanisms and could impact the interpretation of studies on hypoxia biology, approaches to hypoxia detection and targeting.

Hypoxia is a negative prognostic indicator for radiotherapy, chemotherapy and surgery and also predicts for an aggressive and metastatic phenotype. Understanding its causes can aid in detection and intervention of cancer.


Story Source:

The above story is based on materials provided by Versita. Note: Materials may be edited for content and length.


Journal Reference:

  1. Cameron J. Koch, W. Timothy Jenkins, Kevin W. Jenkins, Xiang Yang Yang, A. Lee Shuman, Stephen Pickup, Caitlyn R. Riehl, Ramesh Paudyal, Harish Poptani, Sydney M. Evans. Mechanisms of blood flow and hypoxia production in rat 9L-epigastric tumors. Tumor Microenvironment and Therapy, 2012; 1: 1 DOI: 10.2478/tumor-2012-0001

Cite This Page:

Versita. "New mechanism leading to tumor hypoxia defined." ScienceDaily. ScienceDaily, 9 May 2013. <www.sciencedaily.com/releases/2013/05/130509142138.htm>.
Versita. (2013, May 9). New mechanism leading to tumor hypoxia defined. ScienceDaily. Retrieved December 22, 2014 from www.sciencedaily.com/releases/2013/05/130509142138.htm
Versita. "New mechanism leading to tumor hypoxia defined." ScienceDaily. www.sciencedaily.com/releases/2013/05/130509142138.htm (accessed December 22, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Monday, December 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Christmas Kissing Good for Health

Christmas Kissing Good for Health

Reuters - Innovations Video Online (Dec. 22, 2014) Scientists in Amsterdam say couples transfer tens of millions of microbes when they kiss, encouraging healthy exposure to bacteria. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com
Brain-Dwelling Tapeworm Reveals Genetic Secrets

Brain-Dwelling Tapeworm Reveals Genetic Secrets

Reuters - Innovations Video Online (Dec. 22, 2014) Cambridge scientists have unravelled the genetic code of a rare tapeworm that lived inside a patient's brain for at least four year. Researchers hope it will present new opportunities to diagnose and treat this invasive parasite. Matthew Stock reports. Video provided by Reuters
Powered by NewsLook.com
Touch-Free Smart Phone Empowers Mobility-Impaired

Touch-Free Smart Phone Empowers Mobility-Impaired

Reuters - Innovations Video Online (Dec. 21, 2014) A touch-free phone developed in Israel enables the mobility-impaired to operate smart phones with just a movement of the head. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com
Earthworms Provide Cancer-Fighting Bacteria

Earthworms Provide Cancer-Fighting Bacteria

Reuters - Innovations Video Online (Dec. 21, 2014) Polish scientists isolate bacteria from earthworm intestines which they say may be used in antibiotics and cancer treatments. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins