Researchers have developed an experimental therapy that can kill human blood cancer cells in the laboratory and eradicate the disease in mice

Main Category: Lymphoma / Leukemia / Myeloma
Article Date: 15 Aug 2013 - 0:00 PDT Current ratings for:
Researchers have developed an experimental therapy that can kill human blood cancer cells in the laboratory and eradicate the disease in mice

Ottawa researchers have developed unique virus-derived particles that can kill human blood cancer cells in the laboratory and eradicate the disease in mice with few side effects. The study is published in Blood Cancer Journal by co-senior authors Drs. David Conrad and John Bell of the Ottawa Hospital Research Institute (OHRI) and the University of Ottawa (uOttawa).

While Dr. Bell and his colleagues have been investigating replicating viruses for the treatment of solid cancers for many years, with very promising results, this is the first major success they have had treating blood cancer (leukemia). It is also the first success they have had using a non-replicating virus-derived particle as opposed to a replicating virus.

"Our research indicated that a replicating virus might not be the safest or most effective approach for treating leukemia, so we decided to investigate whether we could make virus-derived particles that no longer replicate but still kill cancer," said Dr. Conrad, a hematologist conducting research in the Blood and Marrow Transplant Program at The Ottawa Hospital, and currently completing his PhD at OHRI and uOttawa in the Department of Cellular and Molecular Medicine. "We were delighted to see that this novel therapy was very safe at high doses, and worked extremely well in our laboratory leukemia models. We hope to test this in patients in the near future."

The researchers used a specific method and dose of UV light to transform regular replicating viruses into unique particles that could no longer replicate and spread, but could still enter cancer cells efficiently, kill them and stimulate a strong immune response against the cancer. These particles were able to kill multiple forms of leukemia in the laboratory, including samples taken from local patients who had failed all other therapies. Normal blood cells were not affected. This novel treatment was also successful in mouse models of leukemia. In fact, 80 per cent of the mice that received the therapy had markedly prolonged survival and 60 per cent were eventually cured, while all of the untreated mice died of their leukemia within 20 days.

"Leukemia is a devastating disease that can be very difficult to treat, and new therapies are urgently needed," said Dr. Conrad. "While we're still at the early stages of this research, I think this therapy holds a lot of promise because it appears to have a potent, long-lasting effect on leukemia without the debilitating side effects of many cancer therapies used in the clinic right now. We will likely see even better results once we optimize the dose in our preparations to advance this research into human clinical trials."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our lymphoma / leukemia / myeloma section for the latest news on this subject.

This research was funded by the Ontario Institute for Cancer Research, the Terry Fox Foundation, the Natural Sciences and Engineering Research Council of Canada, the Canadian Institutes of Health Research, Ottawa's Department of Medicine and The Ottawa Hospital Foundation.

Non-replicating rhabdovirus-derived particles (NRRPs) eradicate acute leukemia by direct cytolysis and induction of antitumor immunity. Batenchuk C, Le Boeuf F, Stubbert L, Falls T, Atkins HL, Bell JC, and Conrad DP. Blood Cancer J. 2013 Jul 12;3:e123. doi: 10.1038/bcj.2013.23.

Ottawa Hospital Research Institute

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'Molecular flashlight' developed that illuminates brain tumors in mice

Main Category: Neurology / Neuroscience
Also Included In: Cancer / Oncology;  Pediatrics / Children's Health
Article Date: 14 Aug 2013 - 0:00 PDT Current ratings for:
'Molecular flashlight' developed that illuminates brain tumors in mice

In a breakthrough that could have wide-ranging applications in molecular medicine, Stanford University researchers have created a bioengineered peptide that enables imaging of medulloblastomas, among the most devastating of malignant childhood brain tumors, in lab mice.

The researchers altered the amino acid sequence of a cystine knot peptide - or knottin - derived from the seeds of the squirting cucumber, a plant native to Europe, North Africa and parts of Asia. Peptides are short chains of amino acids that are integral to cellular processes; knottin peptides are notable for their stability and resistance to breakdown.

The team used their invention as a "molecular flashlight" to distinguish tumors from surrounding healthy tissue. After injecting their bioengineered knottin into the bloodstreams of mice with medulloblastomas, the researchers found that the peptide stuck tightly to the tumors and could be detected using a high-sensitivity digital camera.

The findings are described in a study published online in the Proceedings of the National Academy of Sciences.

"Researchers have been interested in this class of peptides for some time," said Jennifer Cochran, PhD, an associate professor of bioengineering and a senior author of the study. "They're extremely stable. For example, you can boil some of these peptides or expose them to harsh chemicals, and they'll remain intact."

That makes them potentially valuable in molecular medicine. Knottins could be used to deliver drugs to specific sites in the body or, as Cochran and her colleagues have demonstrated, as a means of illuminating tumors.

For treatment purposes, it's critical to obtain accurate images of medulloblastomas. In conjunction with chemotherapy and radiation therapy, the tumors are often treated by surgical resection, and it can be difficult to remove them while leaving healthy tissue intact because their margins are often indistinct.

"With brain tumors, you really need to get the entire tumor and leave as much unaffected tissue as possible," Cochran said. "These tumors can come back very aggressively if not completely removed, and their location makes cognitive impairment a possibility if healthy tissue is taken."

The researchers' molecular flashlight works by recognizing a biomarker on human tumors. The bioengineered knottin is conjugated to a near-infrared imaging dye. When injected into the bloodstreams of a strain of mice that develop tumors similar to human medullublastomas, the peptide attaches to the brain tumors' integrin receptors - sticky molecules that aid in adhesion to other cells.

But while the knottins stuck like glue to tumors, they were rapidly expelled from healthy tissue. "So the mouse brain tumors are readily apparent," Cochran said. "They differentiate beautifully from the surrounding brain tissue."

The new peptide represents a major advance in tumor-imaging technology, said Melanie Hayden, MD, a neurosurgeon at the Stanford Brain Tumor Center and a lead author of the paper. The most common extant technique employs a high-contrast dye that is injected intravenously shortly before or during an operation. Tumors absorb some of the dye, and can be identified on a magnetic resonance imaging scan.

"But that has limitations," Hayden said. "When you're using dye and an MRI scan, you're basically working off a snapshot. And the brain can sometimes shift during an operation, so there's always the possibility you may not be precisely where you want to be. The great advantage of this new approach is that you're illuminating the tumor in real time - you're seeing it directly under your scope instead of relying on an image that was taken earlier." An important next step will be to translate these results from mice to human patients.

Though the team's research focused on medulloblastomas, Hayden said it's likely the new knottins could prove useful in addressing other cancers.

"We know that integrins exist on many types of tumors," she said. "The blood vessels that tumors develop to sustain themselves also contain integrins. So this has the potential for providing very detailed, real-time imaging for a wide variety of tumors."

And imaging may not be the only application for the team's engineered peptide.

"We're very interested in related opportunities," Cochran said. "We envision options we didn't have before for getting molecules into the brain." In other words, by substituting drugs for dye, the knottins might allow the delivery of therapeutic compounds directly to cranial tumors - something that has proved extremely difficult to date because of the blood/brain barrier, the mechanism that makes it difficult for pathogens, as well as medicines, to traverse from the bloodstream to the brain.

"We're looking into it now," Cochran said.

A little serendipity was involved in the peptide's development, said Sarah Moore, a recently graduated bioengineering PhD student and another lead author of the study. Indeed, the propinquity of Cochran's laboratory to co-author Matthew Scott's lab at Stanford's James H. Clark Center catalyzed the project. "Our labs are next to each other," Moore said. "We had the peptide, and Matt had ideal models of pediatric brain tumors - mice that develop tumors in a similar manner to human medulloblastomas. Our partnership grew out of that."

Scott, PhD, professor of bioengineering and of developmental biology, credits the design of the Clark Center as a contributor to the project. The building is home to Stanford's Bioengineering Department, a collaboration between the School of Engineering and the School of Medicine, and Stanford Bio-X, an initiative that encourages communication among researchers in diverse scientific disciplines.

"So in a very real sense, our project wasn't an accident," Scott said. "In fact, it's exactly the kind of work the Clark Center was meant to foster. The lab spaces are wide and open, with very few walls and lots of glass. We have a restaurant that only has large tables - no tables for two, so people have to sit together. Everything is designed to increase the odds that people will meet and talk. It's a form of social engineering that really works."

Scott said he is gratified by the collaboration that led to the team's breakthrough, and observed that the peptide has proved a direct boon to his own work. About 15 percent of Scott's mice develop the tumors requisite for medulloblastoma research. The problem, he said, is that the cancers are cryptic in their early stages.

"By the time you know the mice have them, many of the things you want to study - the genesis and development of the tumors - are past," Scott said. "We needed ways to detect these tumors early, and we needed methods for following the steps of tumor genesis."

Ultimately, Scott concluded, the development of the new peptide can be attributed to Stanford's long-established traditions of openness and relentless inquiry.

"You find not just a willingness, but an eagerness to exchange ideas and information here," Scott said. "It transcends any competitive instinct, any impulse toward proprietary thinking. It is what makes Stanford - well, Stanford."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our neurology / neuroscience section for the latest news on this subject.

Other Stanford co-authors were postdoctoral scholar Jamie Bergen, PhD; medical student Yourong Sophie Su; and life science research assistant Helen Rayburn.

Stanford University Medical Center

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''Molecular flashlight' developed that illuminates brain tumors in mice'

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'Molecular flashlight' developed that illuminates brain tumors in mice

Main Category: Neurology / Neuroscience
Also Included In: Cancer / Oncology;  Pediatrics / Children's Health
Article Date: 14 Aug 2013 - 0:00 PDT Current ratings for:
'Molecular flashlight' developed that illuminates brain tumors in mice

In a breakthrough that could have wide-ranging applications in molecular medicine, Stanford University researchers have created a bioengineered peptide that enables imaging of medulloblastomas, among the most devastating of malignant childhood brain tumors, in lab mice.

The researchers altered the amino acid sequence of a cystine knot peptide - or knottin - derived from the seeds of the squirting cucumber, a plant native to Europe, North Africa and parts of Asia. Peptides are short chains of amino acids that are integral to cellular processes; knottin peptides are notable for their stability and resistance to breakdown.

The team used their invention as a "molecular flashlight" to distinguish tumors from surrounding healthy tissue. After injecting their bioengineered knottin into the bloodstreams of mice with medulloblastomas, the researchers found that the peptide stuck tightly to the tumors and could be detected using a high-sensitivity digital camera.

The findings are described in a study published online in the Proceedings of the National Academy of Sciences.

"Researchers have been interested in this class of peptides for some time," said Jennifer Cochran, PhD, an associate professor of bioengineering and a senior author of the study. "They're extremely stable. For example, you can boil some of these peptides or expose them to harsh chemicals, and they'll remain intact."

That makes them potentially valuable in molecular medicine. Knottins could be used to deliver drugs to specific sites in the body or, as Cochran and her colleagues have demonstrated, as a means of illuminating tumors.

For treatment purposes, it's critical to obtain accurate images of medulloblastomas. In conjunction with chemotherapy and radiation therapy, the tumors are often treated by surgical resection, and it can be difficult to remove them while leaving healthy tissue intact because their margins are often indistinct.

"With brain tumors, you really need to get the entire tumor and leave as much unaffected tissue as possible," Cochran said. "These tumors can come back very aggressively if not completely removed, and their location makes cognitive impairment a possibility if healthy tissue is taken."

The researchers' molecular flashlight works by recognizing a biomarker on human tumors. The bioengineered knottin is conjugated to a near-infrared imaging dye. When injected into the bloodstreams of a strain of mice that develop tumors similar to human medullublastomas, the peptide attaches to the brain tumors' integrin receptors - sticky molecules that aid in adhesion to other cells.

But while the knottins stuck like glue to tumors, they were rapidly expelled from healthy tissue. "So the mouse brain tumors are readily apparent," Cochran said. "They differentiate beautifully from the surrounding brain tissue."

The new peptide represents a major advance in tumor-imaging technology, said Melanie Hayden, MD, a neurosurgeon at the Stanford Brain Tumor Center and a lead author of the paper. The most common extant technique employs a high-contrast dye that is injected intravenously shortly before or during an operation. Tumors absorb some of the dye, and can be identified on a magnetic resonance imaging scan.

"But that has limitations," Hayden said. "When you're using dye and an MRI scan, you're basically working off a snapshot. And the brain can sometimes shift during an operation, so there's always the possibility you may not be precisely where you want to be. The great advantage of this new approach is that you're illuminating the tumor in real time - you're seeing it directly under your scope instead of relying on an image that was taken earlier." An important next step will be to translate these results from mice to human patients.

Though the team's research focused on medulloblastomas, Hayden said it's likely the new knottins could prove useful in addressing other cancers.

"We know that integrins exist on many types of tumors," she said. "The blood vessels that tumors develop to sustain themselves also contain integrins. So this has the potential for providing very detailed, real-time imaging for a wide variety of tumors."

And imaging may not be the only application for the team's engineered peptide.

"We're very interested in related opportunities," Cochran said. "We envision options we didn't have before for getting molecules into the brain." In other words, by substituting drugs for dye, the knottins might allow the delivery of therapeutic compounds directly to cranial tumors - something that has proved extremely difficult to date because of the blood/brain barrier, the mechanism that makes it difficult for pathogens, as well as medicines, to traverse from the bloodstream to the brain.

"We're looking into it now," Cochran said.

A little serendipity was involved in the peptide's development, said Sarah Moore, a recently graduated bioengineering PhD student and another lead author of the study. Indeed, the propinquity of Cochran's laboratory to co-author Matthew Scott's lab at Stanford's James H. Clark Center catalyzed the project. "Our labs are next to each other," Moore said. "We had the peptide, and Matt had ideal models of pediatric brain tumors - mice that develop tumors in a similar manner to human medulloblastomas. Our partnership grew out of that."

Scott, PhD, professor of bioengineering and of developmental biology, credits the design of the Clark Center as a contributor to the project. The building is home to Stanford's Bioengineering Department, a collaboration between the School of Engineering and the School of Medicine, and Stanford Bio-X, an initiative that encourages communication among researchers in diverse scientific disciplines.

"So in a very real sense, our project wasn't an accident," Scott said. "In fact, it's exactly the kind of work the Clark Center was meant to foster. The lab spaces are wide and open, with very few walls and lots of glass. We have a restaurant that only has large tables - no tables for two, so people have to sit together. Everything is designed to increase the odds that people will meet and talk. It's a form of social engineering that really works."

Scott said he is gratified by the collaboration that led to the team's breakthrough, and observed that the peptide has proved a direct boon to his own work. About 15 percent of Scott's mice develop the tumors requisite for medulloblastoma research. The problem, he said, is that the cancers are cryptic in their early stages.

"By the time you know the mice have them, many of the things you want to study - the genesis and development of the tumors - are past," Scott said. "We needed ways to detect these tumors early, and we needed methods for following the steps of tumor genesis."

Ultimately, Scott concluded, the development of the new peptide can be attributed to Stanford's long-established traditions of openness and relentless inquiry.

"You find not just a willingness, but an eagerness to exchange ideas and information here," Scott said. "It transcends any competitive instinct, any impulse toward proprietary thinking. It is what makes Stanford - well, Stanford."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our neurology / neuroscience section for the latest news on this subject.

Other Stanford co-authors were postdoctoral scholar Jamie Bergen, PhD; medical student Yourong Sophie Su; and life science research assistant Helen Rayburn.

Stanford University Medical Center

Please use one of the following formats to cite this article in your essay, paper or report:

MLA

Stanford University Medical Center. "'Molecular flashlight' developed that illuminates brain tumors in mice." Medical News Today. MediLexicon, Intl., 14 Aug. 2013. Web.
14 Aug. 2013. APA

Please note: If no author information is provided, the source is cited instead.

''Molecular flashlight' developed that illuminates brain tumors in mice'

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Report describes malignant melanoma that developed on a pigmented skin lesion within a tattoo underlying laser removal

Main Category: Melanoma / Skin Cancer
Also Included In: Dermatology
Article Date: 31 Jul 2013 - 13:00 PDT Current ratings for:
Report describes malignant melanoma that developed on a pigmented skin lesion within a tattoo underlying laser removal

A case report from Germany describes a young man who developed malignant melanoma on a pre-existing nevus (skin lesion known as a mole or birthmark) within a tattoo during and between the phases of laser tattoo removal, according to a report by Laura Pohl, M.D., of Laserklinik Karlsruhe, Germany, and colleagues.

"Pigmented lesions in decorative tattoos cause diagnostic difficulties at a clinical and dermoscopic level. In cases of laser removal of tattoos, hidden suspicious nevi may be revealed gradually," the researchers stated.

In the case study, the researchers describe a malignant melanoma that developed on a preexisting nevus within a tattoo during and between the phases of laser removal. According to the authors, 16 other cases have been reported in the English literature of malignant melanoma developing in tattoos. Dermoscopic assessments on a regular basis during the period of tattoo removal are recommended.

"If any question about malignancy arises, we suggest an excision before treatment. In general, tattoos should never be placed on pigmented lesions; if they are, the tattoos should never be treated by laser," the authors conclude.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our melanoma / skin cancer section for the latest news on this subject.

JAMA Dermatol. Published July 31, 2013. doi:10.1001/jamadermatol.2013.4901.

Please see article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

JAMA Dermatology

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All opinions are moderated before being included (to stop spam). We reserve the right to amend opinions where we deem necessary.

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