{"120171":{"#nid":"120171","#data":{"type":"news","title":"Novel Compound Halts Tumor Spread, Improves Brain Cancer Treatment in Animal Studies","body":[{"value":"\u003Cp\u003ETreating invasive brain tumors with a combination of chemotherapy and radiation has improved clinical outcomes, but few patients survive longer than two years after diagnosis. The effectiveness of the treatment is limited by the tumor\u2019s aggressive invasion of healthy brain tissue, which restricts chemotherapy access to the cancer cells and complicates surgical removal of the tumor.\u003C\/p\u003E\u003Cp\u003ETo address this challenge, researchers from the Georgia Institute of Technology and Emory University have designed a new treatment approach that appears to halt the spread of cancer cells into normal brain tissue in animal models. The researchers treated animals possessing an invasive tumor with a vesicle carrying a molecule called imipramine blue, followed by conventional doxorubicin chemotherapy. The tumors ceased their invasion of healthy tissue and the animals survived longer than animals treated with chemotherapy alone.\u003C\/p\u003E\u003Cp\u003E\u201cOur results show that imipramine blue stops tumor invasion into healthy tissue and enhances the efficacy of chemotherapy, which suggests that chemotherapy may be more effective when the target is stationary,\u201d said \u003Ca href=\u0022http:\/\/www.bme.gatech.edu\/facultystaff\/faculty_record.php?id=59\u0022 target=\u0022_blank\u0022\u003ERavi Bellamkonda\u003C\/a\u003E, a professor in the \u003Ca href=\u0022http:\/\/www.bme.gatech.edu\u0022 target=\u0022_blank\u0022\u003EWallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University\u003C\/a\u003E. \u201cThese results reveal a new strategy for treating brain cancer that could improve clinical outcomes.\u201d\u003C\/p\u003E\u003Cp\u003EThe results of this work were published on March 28, 2012 in the journal \u003Ca href=\u0022http:\/\/stm.sciencemag.org\/content\/4\/127\/127ra36\u0022 target=\u0022_blank\u0022\u003E\u003Cem\u003EScience Translational Medicine\u003C\/em\u003E\u003C\/a\u003E. The research was supported primarily by the Ian\u2019s Friends Foundation and partially by the Georgia Cancer Coalition, the Wallace H. Coulter Foundation and a National Science Foundation graduate research fellowship.\u003C\/p\u003E\u003Cp\u003EIn addition to Bellamkonda, collaborators on the project include Jack Arbiser, a professor in the Emory University Department of Dermatology; Daniel Brat, a professor in the Emory University Department of Pathology and Laboratory Medicine; and the paper\u2019s lead author, Jennifer Munson, a former Fulbright Scholar who was a bioengineering graduate student in the \u003Ca href=\u0022http:\/\/www.chbe.gatech.edu\u0022 target=\u0022_blank\u0022\u003EGeorgia Tech School of Chemical \u0026amp; Biomolecular Engineering\u003C\/a\u003E when the research was conducted.\u003C\/p\u003E\u003Cp\u003EArbiser designed the novel imipramine blue compound, which is an organic triphenylmethane dye. After \u003Cem\u003Ein vitro\u003C\/em\u003E experiments showed that imipramine blue effectively inhibited movement of several cancer cell lines, the researchers tested the compound in an animal model of aggressive cancer that exhibited attributes similar to a human brain tumor called glioblastoma.\u003C\/p\u003E\u003Cp\u003E\u201cThere were many reasons why we chose to use the RT2 astrocytoma rat model for these experiments,\u201d said Brat. \u201cThe tumor exhibited properties of aggressive growth, invasiveness, angiogenesis and necrosis that are similar to human glioblastoma; the model utilized an intact immune system, which is seen in the human disease; and the model enabled increased visualization by MRI because it was a rat model, rather than a mouse.\u201d\u003C\/p\u003E\u003Cp\u003EBecause imipramine blue is hydrophobic and doxorubicin is cytotoxic, the researchers encapsulated each compound in an artificially-prepared vesicle called a liposome so that the drugs would reach the brain. The liposomal drug delivery vehicle also ensured that the drugs would not be released into tissue until they passed through leaky blood vessel walls, which are only present where a tumor is growing.\u003C\/p\u003E\u003Cp\u003EAnimals received one of the following four treatments: liposomes filled with saline, liposomes filled with imipramine blue, liposomes filled with doxorubicin chemotherapy, or liposomes filled with imipramine blue followed by liposomes filled with doxorubicin chemotherapy.\u003C\/p\u003E\u003Cp\u003EAll of the animals that received the sequential treatment of imipramine blue followed by doxorubicin chemotherapy survived for 200 days -- more than 6 months -- with no observable tumor mass. Of the animals treated with doxorubicin chemotherapy alone, 33 percent were alive after 200 days with a median survival time of 44 days. Animals that received capsules filled with saline or imipramine blue \u2013 but no chemotherapy -- did not survive more than 19 days.\u003C\/p\u003E\u003Cp\u003E\u201cOur results show that the increased effectiveness of the chemotherapy treatment is not because of a synergistic toxicity between imipramine blue and doxorubicin. Imipramine blue is not making the doxorubicin more toxic, it\u2019s simply stopping the movement of the cancer cells and containing the cancer so that the chemotherapy can do a better job,\u201d explained Bellamkonda, who is also the Carol Ann and David D. Flanagan Chair in Biomedical Engineering and a Georgia Cancer Coalition Distinguished Cancer Scholar.\u003C\/p\u003E\u003Cp\u003EMRI results showed a reduction and compaction of the tumor in animals treated with imipramine blue followed by doxorubicin chemotherapy, while animals treated with chemotherapy alone presented with abnormal tissue and glioma cells. MRI also indicated that the blood-brain barrier breach often seen during tumor growth was present in the animals treated with chemotherapy alone, but not the group treated with chemotherapy and imipramine blue.\u003C\/p\u003E\u003Cp\u003EAccording to the researchers, imipramine blue appears to improve the outcome of brain cancer treatment by altering the regulation of actin, a protein found in all eukaryotic cells. Actin mediates a variety of essential biological functions, including the production of reactive oxygen species. Most cancer cells exhibit overproduction of reactive oxygen species, which are thought to stimulate cancer cells to invade healthy tissue. The dye\u2019s reorganization of the actin cytoskeleton is thought to inhibit production of enzymes that produce reactive oxygen species.\u003C\/p\u003E\u003Cp\u003E\u201cI formulated the imipramine blue compound as a triphenylmethane dye because I knew that another triphenylmethane dye, gentian violet, exhibited anti-cancer properties, and I decided to use imipramine -- a drug used to treat depression -- as the starting material because I knew it could get into the brain,\u201d said Arbiser.\u003C\/p\u003E\u003Cp\u003EFor future studies, the researchers are planning to test imipramine blue\u2019s effect on animal models with invasive brain tumors, metastatic tumors, and other types of cancer such as prostate and breast.\u003C\/p\u003E\u003Cp\u003E\u201cWhile we need to conduct future studies to determine if the effect of imipramine blue is the same for different types of cancer diagnosed at different stages, this initial study shows the possibility that imipramine blue may be useful as soon as any tumor is diagnosed, before anti-cancer treatment begins, to create a more treatable tumor and enhance clinical outcome,\u201d noted Bellamkonda.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EResearch News \u0026amp; Publications Office\u003Cbr \/\u003E Georgia Institute of Technology\u003Cbr \/\u003E 75 Fifth Street, N.W., Suite 314\u003Cbr \/\u003E Atlanta, Georgia 30308 USA\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EMedia Relations Contacts:\u003C\/strong\u003E Abby Robinson (abby@innovate.gatech.edu; 404-385-3364) or John Toon (jtoon@gatech.edu; 404-894-6986)\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EWriter: \u003C\/strong\u003EAbby Robinson\u003C\/p\u003E","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003EBy stopping the spread of cancer cells into normal brain tissue in animal models, researchers from Georgia Tech and Emory University have developed a new strategy for treating brain cancer that could improve clinical outcomes. The researchers treated animals possessing an invasive tumor with a novel molecule called imipramine blue, followed by conventional doxorubicin chemotherapy. The tumors ceased their invasion of healthy tissue and the animals survived longer than animals treated with chemotherapy alone.\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"Researchers have designed a new treatment approach that appears to halt the spread of cancer cells into normal brain tissue in animal models."}],"uid":"27206","created_gmt":"2012-03-28 15:18:40","changed_gmt":"2016-10-08 03:11:56","author":"Abby Vogel Robinson","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2012-03-28T00:00:00-04:00","iso_date":"2012-03-28T00:00:00-04:00","tz":"America\/New_York"},"extras":[],"hg_media":{"120181":{"id":"120181","type":"image","title":"Imipramine blue","body":null,"created":"1449178268","gmt_created":"2015-12-03 21:31:08","changed":"1475894741","gmt_changed":"2016-10-08 02:45:41","alt":"Imipramine blue","file":{"fid":"194355","name":"imipramine_blue_hires.jpg","image_path":"\/sites\/default\/files\/images\/imipramine_blue_hires_0.jpg","image_full_path":"http:\/\/www.tlwarc.hg.gatech.edu\/\/sites\/default\/files\/images\/imipramine_blue_hires_0.jpg","mime":"image\/jpeg","size":90121,"path_740":"http:\/\/www.tlwarc.hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/imipramine_blue_hires_0.jpg?itok=x00IaSfV"}},"120191":{"id":"120191","type":"image","title":"Imipramine blue inhibits glioblastoma cells","body":null,"created":"1449178268","gmt_created":"2015-12-03 21:31:08","changed":"1475894741","gmt_changed":"2016-10-08 02:45:41","alt":"Imipramine blue inhibits glioblastoma cells","file":{"fid":"194356","name":"ib-effect-glioblastoma-cells-hires.jpg","image_path":"\/sites\/default\/files\/images\/ib-effect-glioblastoma-cells-hires_0.jpg","image_full_path":"http:\/\/www.tlwarc.hg.gatech.edu\/\/sites\/default\/files\/images\/ib-effect-glioblastoma-cells-hires_0.jpg","mime":"image\/jpeg","size":226151,"path_740":"http:\/\/www.tlwarc.hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/ib-effect-glioblastoma-cells-hires_0.jpg?itok=iL84lBXA"}},"120201":{"id":"120201","type":"image","title":"Imipramine blue tumor invasion","body":null,"created":"1449178268","gmt_created":"2015-12-03 21:31:08","changed":"1475894741","gmt_changed":"2016-10-08 02:45:41","alt":"Imipramine blue tumor invasion","file":{"fid":"194357","name":"ib-effect-tumor_invasion-hires.jpg","image_path":"\/sites\/default\/files\/images\/ib-effect-tumor_invasion-hires_0.jpg","image_full_path":"http:\/\/www.tlwarc.hg.gatech.edu\/\/sites\/default\/files\/images\/ib-effect-tumor_invasion-hires_0.jpg","mime":"image\/jpeg","size":1511508,"path_740":"http:\/\/www.tlwarc.hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/ib-effect-tumor_invasion-hires_0.jpg?itok=3k96CjPZ"}}},"media_ids":["120181","120191","120201"],"groups":[{"id":"1188","name":"Research Horizons"}],"categories":[{"id":"140","name":"Cancer Research"},{"id":"145","name":"Engineering"},{"id":"146","name":"Life Sciences and Biology"},{"id":"135","name":"Research"}],"keywords":[{"id":"28591","name":"Actin"},{"id":"28521","name":"Brain Cancer"},{"id":"10365","name":"Brain Tumor"},{"id":"8084","name":"Cancer treatment"},{"id":"1439","name":"chemotherapy"},{"id":"594","name":"college of engineering"},{"id":"11533","name":"Department of Biomedical Engineering"},{"id":"1445","name":"doxorubicin"},{"id":"28561","name":"Glioblastoma"},{"id":"28581","name":"Glioma"},{"id":"28571","name":"Liposome"},{"id":"2471","name":"Ravi Bellamkonda"},{"id":"28601","name":"triphenylmethane dye"},{"id":"1442","name":"tumor"}],"core_research_areas":[],"news_room_topics":[],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003EAbby Robinson\u003Cbr \/\u003E Research News and Publications\u003Cbr \/\u003E \u003Ca href=\u0022mailto:abby@innovate.gatech.edu\u0022\u003Eabby@innovate.gatech.edu\u003C\/a\u003E\u003Cbr \/\u003E 404-385-3364\u003C\/p\u003E","format":"limited_html"}],"email":[],"slides":[],"orientation":[],"userdata":""}}}