Navigation Links
Scientists define a new mechanism leading to tumor hypoxia
Date:5/9/2013

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.

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.


'/>"/>

Contact: Maria Hrynkiewicz
maria@versita.com
48-660-476-421
Versita
Source:Eurekalert

Related medicine news :

1. Scientists solving the mystery of human consciousness
2. Scientists uncover multiple faces of deadly breast cancer
3. Scientists identify major source of cells defense against oxidative stress
4. Scientists tailor cell surface targeting system to hit organelle ZIP codes
5. Scientists rewrite rulebook on breast cancer in landmark global study
6. Warwick scientists uncover how checkpoint proteins bind chromosomes
7. NIH scientists link quickly spreading gene to Asian MRSA epidemic
8. Joslin scientists identify important mechanism that affects the aging process
9. Scripps Research scientists show how memory B cells stay in class to fight different infections
10. Scientists Map Melanomas Genome
11. A*STAR scientists discover switch to boost anti-viral response to fight infectious diseases
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/22/2017)... ... February 22, 2017 , ... Bellus ... the latest innovation in the delivery of Platelet Rich Plasma (PRP). PRP systems ... pain management, to accelerate tissue synthesis and provide a faster and more efficient ...
(Date:2/22/2017)... ... February 22, 2017 , ... Forty-five percent of American respondents ... family members or friends have also commented about their poor hearing. However, only ... aids. One reason, suggested by 89 percent of American respondents, is that they ...
(Date:2/22/2017)... ... 22, 2017 , ... Pet obesity in the U.S. continued to steadily increase ... Association for Pet Obesity Prevention (APOP). During the ninth annual survey, APOP also found ... benefits of corn and grains, value of raw and organic diets, and the best ...
(Date:2/22/2017)... ... 22, 2017 , ... BrightStar Care Charleston , a home care and ... South Carolina (MUSC) Center on Aging’s Senior Expo on Thursday, March 23, 2017, ... a tremendous resource in our community. We are thrilled to participate in this event ...
(Date:2/22/2017)... ... February 22, 2017 , ... Alto-Shaam is pleased to announce ... Oven offers up to four ovens in one. Control temperature, fan speed and ... evenness in cooking. Alto-Shaam has partnered with Appliance Innovation to introduce this game-changing ...
Breaking Medicine News(10 mins):
(Date:2/22/2017)... Feb. 22, 2017 Summary Provides ... partnering deals and agreements entered into by the worlds ... http://www.reportlinker.com/p03605668-summary/view-report.html Description The Global Non-Small Cell Lung ... understanding and access to partnering deals and agreements entered ... - Trends in partnering deals - Top deals ...
(Date:2/22/2017)... Feb. 22, 2017  Corin Group announced today the ... used to treat patients with both a massive rotator ... The condition, known as cuff tear arthropathy, causes pain ... The Humelock Reversed Shoulder System, which was ... company based near Lyon, France , ...
(Date:2/22/2017)... Research and Markets has announced the ... 2016" report to their offering. ... Dermatological conditions are one ... one-third of the US population suffers from at least one ... the dermatology market has remained saturated with established and generic ...
Breaking Medicine Technology: