Jennifer Cochran and Matthew Scott have created a bioengineered peptide that has been shown in mice to provide better imaging of a type of brain tumour known as medulloblastoma.
\nIn 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 tumours, in lab mice.
\nThe researchers altered the amino acid sequence of a cystine knot peptide \u2014 or knottin \u2014 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.
\nThe team used their invention as a ‘molecular flashlight’ to distinguish tumours 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 tumours and could be detected using a high-sensitivity digital camera.
\n‘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\u2019re extremely stable. For example, you can boil some of these peptides or expose them to harsh chemicals, and they\u2019ll remain intact.’
\nThat 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 tumours.
\nFor treatment purposes, it\u2019s critical to obtain accurate images of medulloblastomas. In conjunction with chemotherapy and radiation therapy, the tumours 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.
\n‘With brain tumours, you really need to get the entire tumour and leave as much unaffected tissue as possible,’ Cochran said. ‘These tumours can come back very aggressively if not completely removed, and their location makes cognitive impairment a possibility if healthy tissue is taken.’
\nThe researchers\u2019 molecular flashlight works by recognising a biomarker on human tumours. The bioengineered knottin is conjugated to a near-infrared imaging dye. When injected into the bloodstreams of a strain of mice that develop tumours similar to human medullublastomas, the peptide attaches to the brain tumours\u2019 integrin receptors \u2014 sticky molecules that aid in adhesion to other cells.
\nBut while the knottins stuck like glue to tumours, 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.’
\nThe new peptide represents a major advance in tumour-imaging technology, said Melanie Hayden Gephart, MD, neurosurgery chief resident at the Stanford Brain Tumor Center and a lead author of the paper.
\n‘The most common technique to identify brain tumours relies on preoperative, intravenous injection of a contrast agent, enabling most tumours to be visualised on a magnetic resonance imaging scan,’ Gephart said. These MRI scans are used like in a computer program much like an intraoperative GPS system to locate and resect the tumors.
\n‘But that has limitations,’ she added. ‘When you’re using the contrast in an MRI scan to define the tumour margins, you’re basically working off a preoperative snapshot. The brain can sometimes shift during an operation, so there’s always the possibility you may not be as precise or accurate as you want to be. The great potential advantage of this new approach would be to illuminate the tumour in real time \u2014 you could see it directly under your microscope instead of relying on an image that was taken before surgery.’
\nThough the team\u2019s research focused on medulloblastomas, Gephart said it\u2019s likely the new knottins could prove useful in addressing other cancers.\nStanford University<\/link>\n","protected":false},"excerpt":{"rendered":"
Jennifer Cochran and Matthew Scott have created a bioengineered peptide that has been shown in mice to provide better imaging of a type of brain tumour known as medulloblastoma. 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 […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"footnotes":""},"categories":[35],"tags":[],"_links":{"self":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts\/1805"}],"collection":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/comments?post=1805"}],"version-history":[{"count":0,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts\/1805\/revisions"}],"wp:attachment":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/media?parent=1805"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/categories?post=1805"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/tags?post=1805"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}