Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Botox could help target resistant tumors for treatment

15.02.2006


The cosmetic treatment Botox may have a new use as an adjuvant to cancer therapy, providing an open door for chemotherapy and radiation treatments, according to a study published in the Feb. 15 issue of Clinical Cancer Research.



The study in mice, led by Bernard Gallez, Ph.D., professor of pharmacy at the Université de Louvain in Brussels, Belgium, found that by injecting Botulinum neurotoxin type A into two types of mouse tumors, the tumors’ cellular vasculature opened, allowing for more effective destruction of previously resistant cancer cells. The study is the first to test the idea of using Botox against cancer and explores the possibility of its use as an adjuvant, assisting the effective delivery of chemotherapies and radiation.

The findings mark a relatively new area of cancer research, which focuses on briefly opening blood vessels that feed tumor cells in order to better deliver therapeutic agents. Until recently, much cancer research has focused on the opposite: reduction of blood vessel growth, which starves tumor cells of nutrients.


"Tumor vasculature is targeted by several advanced anti-cancer approaches that may appear contradictory," said Gallez. "Anti-angiogenesis and anti-vascular targeting are methods aimed at destroying the vessels that feed tumors, thereby depriving them of oxygen and nutrients.

"In contrast, pro-vascular approaches increase tumor perfusion and oxygenation temporarily."

While chemotherapy and radiation treatments have remained the standard of care, tumor cells of most cancer types have shown increasing resistance to therapies. This phenomenon has resulted in more toxic dosages of chemotherapy and radiation, and increased efforts to develop more drugs to which tumors don’t show resistance. To increase the efficacy of anti-cancer treatments, the new study examined strategies that transiently opened the tumor vascular bed to alleviate tumor hypoxia.

"Hypoxia is a source of resistance to radiotherapy, and is a determining factor in the poor prognosis of tumors to cytotoxic treatments," said Gallez. "Botulinum toxin could lead to inhibition of contractions of tumor vessels, improve tumor perfusion and oxygenation, and enhance the response of tumors to radio- and chemotherapy."

Botulinum toxin is a naturally occurring molecule, and historically has been implicated with intestinal poisonings. It has been developed for several clinical applications, including facial spasms, strabismus (a disease of the eye muscles), and other muscle hyperactivity. It also has become popularly known as Botox for its cosmetic uses on the face.

The toxin acts on the nervous system by blocking the release of neurotransmitters, particularly acetylcholine and norepinephrine. Gallez and his colleagues hypothesized that since Botulinum toxin impeded neurotransmitter release in the sympathetic nervous system, it could prevent neuromuscular contractions of vessels in tumors. The inhibition of this contraction could literally open the gate to improved tumor perfusion by chemotherapeutic drugs and oxygenation that enhances radiotherapy.

The scientists used two tumor models, one for fibrosarcoma and the other for mouse liver tumor. Botox was injected into the tumor once it had grown to about 6 mm. The tumors were then examined for three days, for vascular and perfusion changes as well as responses to anti-cancer therapies. In tests on oxygenation, cellular oxygen pressure was shown to significantly increase after treatment by Botox in both types of tumors. In tests on perfusion, magnetic resonance imaging results (MRI) showed significantly greater perfusion in treated mice after three days.

In addition, Botox "pre-treatment" led to significantly greater delays in tumor growth as well as stimulation of apoptosis (programmed cellular death) when compared by irradiation without Botox. The combination of Botox and the chemotherapeutic agent cyclophosphamide showed significantly stunted tumor growth after three days, as well.

Since Botox is used in clinics without serious toxicity, the study indicates the possibility for human trials. In addition, dosages used in the mouse study were within the range used with humans in clinical settings. The toxin is administered inside the tumor with very limited diffusion into normal tissues, which may limit the amount of damage to normal cells in proximity to the tumor.

"This is the first experimental model demonstrating how Botox can affect the reaction of blood vessels that feed tumors," said Gallez. "Tumor microvessels are formed hastily, and lack smooth muscle layers, but one can find mature blood vessels, with smooth muscle layers that respond to toxins like Botulinun, inside tumors. Several laboratories, including ours, are working on new strategies to alleviate tumor hypoxia, which sensitizes the tumor to treatment. Botox appears to offer the advantage of selectivity, absence of toxicity and persistence for a longer time than other agents that act on tumor vasculature. Further research may help us determine whether this approach would be useful to treating cancer in humans."

The Gallez study was conducted by Réginald Ansiaux, Christine Baudelet, Greg Cron, Jérôme Segers, Chantal Dessy, Philippe Martinive, Julie De Wever, Julien Verrax, Valérie Wauthier, Nelson Beghein, Vincent Grégoire, Pedro Buc Calderon, and Olivier Feron, all of the Université de Louvain.

Russell Vanderboom, PhD | EurekAlert!
Further information:
http://www.aacr.org

More articles from Health and Medicine:

nachricht One gene closer to regenerative therapy for muscular disorders
01.06.2017 | Cincinnati Children's Hospital Medical Center

nachricht The gut microbiota plays a key role in treatment with classic diabetes medication
01.06.2017 | University of Gothenburg

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: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>