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New Technology Doubles Effectiveness of Radiotherapy

By MedImaging International staff writers
Posted on 09 Jan 2012
Scientists may have found a way to double the effectiveness and reduce the side effects of radiation therapy.

Georgia Health Sciences University (GHSU; Augusta, USA) scientists have formulated a way to reduce lung cancer cells’ ability to repair the lethal double-strand DNA breaks caused by radiation therapy. “Radiation is a great therapy--the problem is the side effects,” said Dr. William S. Dynan, biochemist and associate director of research and chief, nanomedicine and gene regulation at the GHSU Institute of Molecular Medicine and Genetics. “We think this is a way to get the same amount of cancer cell death with less radiation or use the same amount and maybe cure a patient that could not be cured before.”

Radiation therapy exploits radiation’s ability to kill cells by causing double-strand breaks in DNA. However, because varying levels of radiation are basically everywhere (i.e., food, air, and the ground) means all cells, including cancer cells, have internal mechanisms to inhibit the lethal breakage.

GHSU scientists are targeting the natural defense mechanisms by packaging a piece of an antibody against one of them with folate, which has easy access to most cells, particularly cancer cells. Many cancers, including the lung cancer cells they examined, have large numbers of folate receptors so that cancer cells get an unequal portion of the cargo.

Earlier efforts to destroy cancer cells’ ability to avoid radiation damage have concentrated on receptors on their surface, according to Dr. Shuyi Li, a molecular biologist, pediatrician, and corresponding author on the study published December 5, 2011, in the International Journal of Radiation Oncology.

To acquire a more direct hit, the scientists took advantage of folate receptors as a point of entry by chemically binding folate with the small piece of their antibody, ScFv 18-2. The package heads straight for the cell nucleus where a different chemical environment breaks the bond, freeing ScFv 18-2 to attack the regulatory region of DNA-dependent protein kinase, an enzyme essential to DNA repair. “We are joining a targeting molecule with a cargo,” said Dr. Dynan.

“This strategy targets one of the key enzymes so it’s harder to repair,” Dr. Li said. This makes cancer cells more vulnerable to radiation. Drs. Dynan and Li reported that the approach could be used to deliver any number of drugs directly inside cancer cells. Future research includes studying other cell entry points as well as other targets to ensure they have the most effective payload. Studies to date have been in human lung cancer cells in culture, therefore the next steps also need to include animal studies.
This approach mimics a natural process called endocytosis in which cells engulf proteins and other substances they want to let inside but cannot fit through normal doorways.

Folate receptors already are being used as direct entry points for chemotherapeutic drugs, including clinical studies of a new strategy for ovarian cancer. GHSU is participating in clinical trials of a therapy that combines an agent too toxic to be delivered through the bloodstream with folate to better target one of the most deadly cancers.

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87 (!!!!! 4498.9585876465): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294738778 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
88 (!!!!! 1142.0249938965): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294738778 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
89 (931.97822570801): SELECT id,name,title FROM jos_deeppockets WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id != 294743300 AND id != 294743301 AND id != 294743302 AND id != 294743303 AND id != 294743304 AND id != 294743305 AND id != 294743306 AND id != 294743307 AND id != 294743308 AND id != 294743309 AND id != 294743310 AND metakey != 'aacc' ORDER BY `ordering`
90 (!!!!! 1013.9942169189): SELECT show_live FROM jos_com_show_setting LIMIT 1
91 (52.928924560547): SELECT show_live FROM jos_com_show_setting LIMIT 1
92 (!!!!! 2315.9980773926): SELECT show_live FROM jos_com_show_setting LIMIT 1
93 (96.08268737793): SELECT show_live FROM jos_com_show_setting LIMIT 1
94 (437.97492980957): SELECT show_live FROM jos_com_show_setting LIMIT 1
95 (51.021575927734): SELECT show_live FROM jos_com_show_setting LIMIT 1
96 (38.862228393555): SELECT show_live FROM jos_com_show_setting LIMIT 1
97 (34.093856811523): SELECT show_live FROM jos_com_show_setting LIMIT 1
98 (35.04753112793): SELECT show_live FROM jos_com_show_setting LIMIT 1
99 (35.04753112793): SELECT show_live FROM jos_com_show_setting LIMIT 1
100 (247.00164794922): SELECT show_live FROM jos_com_show_setting LIMIT 1
101 (77.009201049805): SELECT show_live FROM jos_com_show_setting LIMIT 1
102 (263.92936706543): SELECT show_live FROM jos_com_show_setting LIMIT 1
103 (42.915344238281): SELECT show_live FROM jos_com_show_setting LIMIT 1
104 (!!!!! 5856.0371398926): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738778 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738778 AND published='1' LIMIT 1
105 (!!!!! 7948.1601715088): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738778 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738778 AND published='1' LIMIT 1
106 (!!!!! 7869.0052032471): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294738778 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
107 (!!!!! 7927.8945922852): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294738778 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
108 (!!!!! 6386.9953155518): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738778 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738778 AND published='1' LIMIT 1
109 (!!!!! 5661.9644165039): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738778 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738778 AND published='1' LIMIT 1
110 (!!!!! 1073.1220245361): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294738778 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
111 (952.00538635254): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294738778 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
112 (!!!!! 1406.9080352783): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1
113 (697.85118103027): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1
114 (730.03768920898): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738778 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738778 AND published='1' LIMIT 1
115 (508.06999206543): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738778 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738778 AND published='1' LIMIT 1
116 (827.07405090332): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738778 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738778 AND published='1' LIMIT 1
117 (283.00285339355): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738778 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738778 AND published='1' LIMIT 1
118 (326.87187194824): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738778 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738778 AND published='1' LIMIT 1
119 (484.94338989258): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738778 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738778 AND published='1' LIMIT 1
120 (244.8558807373): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738778 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738778 AND published='1' LIMIT 1
121 (208.85467529297): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738778 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738778 AND published='1' LIMIT 1
122 (622.03407287598): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`
123 (!!!!! 68866.968154907): SELECT * FROM jos_deeppockets WHERE jos_deeppockets.cat = 10 AND jos_deeppockets.type = 'deeppockets_item' AND jos_deeppockets.published = 1 AND jos_deeppockets.created + INTERVAL 14 DAY >= NOW() ORDER BY jos_deeppockets.hits DESC LIMIT 7
124 (!!!!! 2515.7928466797): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294738778 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294738778 AND type='deeppockets_item' AND published='1' LIMIT 1
125 (!!!!! 1066.9231414795): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3
126 (63.896179199219): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3
127 (504.0168762207): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1
128 (560.04524230957): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1
129 (!!!!! 2604.9613952637): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1
130 (424.86190795898): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1
131 (160.93254089355): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1
132 (720.97778320312): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1
133 (711.91787719727): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1
134 (422.00088500977): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1
135 (!!!!! 2414.9417877197): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738778 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
136 (!!!!! 1209.9742889404): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738778 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
137 (53.882598876953): SELECT name FROM jos_deeppockets WHERE id=211
138 (221.01402282715): SELECT name FROM jos_deeppockets WHERE id=211
139 (871.18148803711): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))211((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
140 (!!!!! 1421.9284057617): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))211((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
141 (689.98336791992): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738778 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738778 AND published='1' LIMIT 1
142 (!!!!! 1133.2035064697): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738778 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738778 AND published='1' LIMIT 1
143 (!!!!! 15241.146087646): TRUNCATE TABLE jos_trademed_module
144 (!!!!! 1394.0334320068): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294738778 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
145 (233.17337036133): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294738778 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
146 (439.88227844238): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738778 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
147 (!!!!! 1111.0305786133): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738778 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
148 (773.90670776367): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738778 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738778 AND published='1' LIMIT 1
149 (373.84033203125): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738778 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738778 AND published='1' LIMIT 1
150 (!!!!! 2016.0675048828): SELECT jos_item.* FROM jos_item INNER JOIN jos_number ON jos_item.numberID=jos_number.id WHERE 1=1 AND (jos_item.imgMini<>'') AND jos_item.type='L' AND jos_item.numberID= ( SELECT jos_number.id FROM jos_number WHERE jos_number.journalID IN (10) and jos_number.id in (select distinct jos_number.id from jos_number join jos_item on jos_item.numberid=jos_number.id where jos_item.type='P') ORDER BY (CONVERT(SUBSTRING(issue,1,2),SIGNED) + (CONVERT(SUBSTRING(issue,3,2),SIGNED)*100)) DESC LIMIT 0,1 ) ORDER BY RAND() DESC LIMIT 6
151 (179.05235290527): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738778 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738778 AND published='1' LIMIT 1
152 (61.03515625): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738778 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738778 AND published='1' LIMIT 1
153 (439.16702270508): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294738778 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294738778 AND type='deeppockets_item' AND published='1' LIMIT 1
154 (178.09867858887): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=211 or channel_id is null)
155 (!!!!! 1173.9730834961): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=211 or channel_id is null)
156 (199.0795135498): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1
157 (380.9928894043): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738778 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738778 AND published='1' LIMIT 1
158 (75.817108154297): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294738778 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294738778 AND published='1' LIMIT 1
159 (71.048736572266): select jos_twitters.link from jos_twitters where cat=10
160 (!!!!! 2386.0931396484): select jos_facebook.link from jos_facebook where cat=10
161 (126.12342834473): select jos_google_plus.link from jos_google_plus where cat=10
162 (33.140182495117): select jos_linkedin.link from jos_linkedin where cat=10