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Scorpion venom offers improved cancer surgery outcome

 
 
Reply Mon 16 Jul, 2007 10:45 am
Scorpion venom offers improved cancer surgery
By Sadie Gray
Published: 16 July 2007
Independent UK

A substance derived from scorpion venom could be the key to more effective treatment for a wide range of cancers, researchers say.

Turned into a "paint" which can distinguish even a small number of cancerous cells from healthy tissue, the venom would vastly improve surgeons' accuracy when removing tumours.

Scientists found that chlorotoxin, a chemical in the venom, would attach itself to cancer cells. Joined to a fluorescent marker, Cy5.5, it becomes a molecular beacon which emits light near the infra-red spectrum, illuminating whole tumours or even clusters of only a few hundred cancerous cells. When injected, it sticks to cancer cells within two minutes.

Precision is paramount in operations to remove tumours, when cancerous cells can be missed and left behind. It is especially important when dealing with the brain, where some 80 per cent of malignant cancers return at the edge of surgical sites and where surrounding neurons must not be damaged.

At the moment, surgeons use colour, texture and blood supply to tell cancerous from healthy tissue. The paint marks tumours with at least 500 times more sensitivity than a magnetic resonance imaging scan, which will only work if more than a million cancer cells are present. Lasting for two weeks, it also massively outperforms contrast agents currently used to show up cancers, which last only a few minutes.

The research team, from Seattle Children's Hospital and the Fred Hutchinson Cancer Research Centre in Washington, found in tests on mice that they could illuminate brain tumours as small as 1mm in diameter. In another case they detected 200 prostate cancer cells travelling through a mouse's lymph system.

Dr James Olson, who led the team, said: "My greatest hope is that tumour paint will fundamentally improve cancer therapy. By allowing us to see cancer that would be undetectable by other means, we can give our patients better outcomes."

Dr Richard Ellenbogen, a paediatric neurosurgeon at Seattle Children's Hospital, co-wrote the study, which was published in the journal Cancer Research. He said: "This development has the potential to save lives and make brain tumour resection safer."

The researchers are due to start clinical trials in humans and say the paint could be used in surgery in as little as 18 months.

Experts in the UK say more research is needed into why the molecule only binds to tumour cells, and to ensure it is not toxic in humans. Professor John Griffiths, head of molecular imaging at Cancer Research UK's Cambridge Research Institute, said: "The big problem with surgery for brain cancer is that tumours can infiltrate normal brain tissue, making it very hard to tell where the tumour ends and the normal tissue begins. If you could light up the tumour cells by shining an infra-red beam on them, it might be very helpful."

Chlorotoxin:Cy5.5 could be used as a non-invasive screening tool for the early detection of skin, cervical, oesophageal, colon and lung cancers, and may help identify positive lymph nodes in patients with breast, prostate and testicular cancers.
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Miller
 
  1  
Reply Mon 16 Jul, 2007 11:20 pm
Tumor Painting Revolutionizes Fight Against Cancer


SEATTLE, July 15, 2007 /PRNewswire-USNewswire via COMTEX/ -- A tumor paint developed by researchers at Seattle Children's Hospital Research Institute and Fred Hutchinson Cancer Research Center will help surgeons see where a tumor begins and ends more precisely by illuminating the cancerous cells. The study, published in the July 15, 2007 issue of Cancer Research, shows that the tumor paint can help surgeons distinguish between cancer cells and normal brain tissue in the operating room. The paint is a scorpion-derived peptide called chlorotoxin that is linked to the molecular beacon Cy5.5. Until now there has been no way to allow surgeons to see tumors "live" during surgery.

Chlorotoxin:Cy5.5 is a fluorescent molecular beacon that emits photons in the near infrared spectrum. This illumination gives surgeons a better chance of removing cancerous cells during surgery without injuring surrounding healthy tissue. This is particularly significant in the brain, where approximately 80% of malignant cancers recur at the edges of the surgical site. Current technology, such as magnetic resonance imaging (MRI) can distinguish tumors from healthy tissue only if more than 1 million cancer cells are present. But Cy5.5 can identify tumors with fewer than 2000 cancer cells, making it 500 times more sensitive than MRI under operating conditions.

"My greatest hope is that tumor paint will fundamentally improve cancer therapy," said James M. Olson, MD, PhD, of Seattle Children's Hospital and The Hutchison Center who is the senior author of the study. "By allowing surgeons to see cancer that would be undetectable by other means, we can give our patients better outcomes."

Olson led the team that included neurosurgeons, engineers and biologists. The bioconjugate, Chlorotoxin:Cy5.5 which, when injected, emits a near- infrared light, was created in his laboratory at the Hutchinson Center. In mouse models, the team demonstrated that they could light up brain tumors as small as 1 millimeter in diameter without lighting up the surrounding normal brain tissue. In a prostate cancer model, as few as 200 cancer cells traveling in a mouse lymph channel could be detected.

Chlorotoxin:Cy5.5 is applicable to many cancers, but is especially helpful to surgeons operating on brain tumors. Not only would it reveal whether they'd left behind any bits of tumor, it would also help them avoid removing normal tissue. Chlorotoxin:Cy5.5 begins binding to cancer cells within minutes. The Chlorotoxin:Cy5.5 signal lasts for 14 days, illuminating cancer cells. Contrast agents currently in use only last for a few minutes.

"I feel fortunate to be working with gifted scientists to bring this revolutionary imaging technique from the laboratory to the bedside," said Richard Ellenbogen, MD, pediatric neurosurgeon, Seattle Children's Hospital and co-investigator on the study. "This development has the potential to save lives and make brain tumor resection safer."

Surgery remains a primary form of cancer therapy. Despite advances in surgical tools, surgeons currently rely on color, texture or blood supply to differentiate tumor from normal tissue, a distinction that is often subtle and imperfect. The limitations of this method contribute to cancer growth or patient mortality that is potentially preventable. The tumor painting technique combines a visual guide for the surgeon with the potential for significant improvement in accuracy and safety.

Tumor painting has been successfully tested in mice and the pilot safety trials are complete. Olson and his team are preparing the necessary toxicity studies before seeking approval from the Food and Drug Administration to begin clinical trials. Chlorotoxin:Cy5.5 could be used in operating rooms in as little as 18 months. All clinical studies will have consenting adult participants.

Olson and his team believe that Chlorotoxin:Cy5.5 has the potential to be used in the future as a non-invasive screening tool for early detection of skin, cervical, esophageal, colon and lung cancers. It is also useful in identifying positive lymph nodes which could mean a significant advancement for breast, prostate and testicular cancers.

Children's and the Hutchison Center's role as leading research institutions is underscored by their membership in the Pediatric Brain Tumor Consortium (PBTC), a group of 10 medical centers selected by the National Cancer Institute (NCI). The consortium's members were chosen by the NCI based on their experience, dedication to research and quality of patient care.

Other Children's and Hutchison Center, and University of Washington researchers on the team include Mandana Veiseh, PhD; Patrik Gabikian, S-Bahram Bahrami, PhD; Omid Veiseh, Miqin Zhang, Robert C. Hackman, MD; Ali C. Ravanpay, Mark R. Stroud, PhD; Yumiko Kusuma, Stacey J. Hansen, Deborah Kwok, Nina M. Munoz, PhD; Raymond W. Sze, MD; William M. Grady, MD; and Norman M. Greenberg, PhD.

About Seattle Children's Hospital Research Institute, Seattle, Wash.

At the forefront of pediatric research, the Seattle Children's Hospital Research Institute at Children's Hospital and Regional Medical Center in Seattle conducts research under nine major centers and is internationally recognized for its discoveries in cancer, genetics, health services, immunology, pathology, infectious disease and vaccines. Consistently ranked as one of the best children's hospitals in the country by U.S. News & World Report, Children's serves as the pediatric referral center for Washington, Alaska, Montana and Idaho. Children's has been delivering superior patient care for 100 years, including advancing new discoveries and treatments in pediatric research, and serving as a primary teaching, clinical and research site for the Department of Pediatrics at the University of Washington School of Medicine. For more information about the Institute visit http://research.seattlechildrens.org/.

At Fred Hutchinson Cancer Research Center, our interdisciplinary teams of world-renowned scientists and humanitarians work together to prevent, diagnose and treat cancer, HIV/AIDS and other diseases. Our researchers, including three Nobel laureates, bring a relentless pursuit and passion for health, knowledge and hope to their work and to the world. For more information, please visit fhcrc.org.



Media Contacts:

Amy MacIver
Children's Hospital and Regional Medical Center
(206) 987-5210
(206) 469-3745 pager
[email protected]

Dean Forbes
Fred Hutchinson Cancer Research Center
(206) 667-2896
(206) 605-0311 cell
[email protected]

SOURCE Seattle Children's Hospital Research Institute

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BumbleBeeBoogie
 
  1  
Reply Tue 17 Jul, 2007 08:23 am
Miller
Thanks for the additional information, Miller. Ain't science wonderful?

BBB
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Miller
 
  1  
Reply Tue 17 Jul, 2007 09:15 am
That Seattle Center is a major cancer research center.

One point of major interest about this dye, is the fact that the surgeon, while the patient is still on the table in the OR, can determine in a short time, the extent to which the cancer had spread and thus act accordingly, if need be.

Imaging has always been one of my major interests.
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