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Radiation Treatment Generates Cancer Stem Cells from Less Aggressive Breast Cancer Cells

By MedImaging International staff writers
Posted on 01 Mar 2012
Breast cancer stem cells are believed to be the only source of tumor recurrence and are known to be resistant to radiation therapy and do not respond well to chemotherapy. Researchers now report for the first time that radiation treatment--in spite of killing half of all tumor cells during every treatment--converts other cancer cells into treatment-resistant breast cancer stem cells.

The generation of these breast cancer stem cells offsets the otherwise highly effective radiation treatment. If scientists can determine the processes and prevent this transformation from occurring, radiation treatment for breast cancer could become even more effective, according to study senior author Dr. Frank Pajonk, an associate professor of radiation oncology and UCLA department of radiation oncology at the University of California, Los Angeles’ (UCLA) Jonsson Comprehensive Cancer Center (USA). “We found that these induced breast cancer stem cells (iBCSC) were generated by radiation-induced activation of the same cellular pathways used to reprogram normal cells into induced pluripotent stem cells (iPS) in regenerative medicine,” said Dr. Pajonk, who also is a scientist with the Eli and Edythe Broad Center of Regenerative Medicine at UCLA. “It was remarkable that these breast cancers used the same reprogramming pathways to fight back against the radiation treatment.”

The study recently appeared February 10, 2012, in the early online edition of the journal Stem Cells. “Controlling the radiation resistance of breast cancer stem cells and the generation of new iBCSC during radiation treatment may ultimately improve curability and may allow for de-escalation of the total radiation doses currently given to breast cancer patients, thereby reducing acute and long-term adverse effects,” the study authors stated.
There are very few breast cancer stem cells in a larger pool of breast cancer cells. In this study, Dr. Pajonk and colleagues eliminated the smaller pool of breast cancer stem cells and then irradiated the remaining breast cancer cells and placed them into mice. Using a unique imaging system Dr. Pajonk and his team developed to visualize cancer stem cells, the researchers were able to observe their initial generation into iBCSC in response to the radiation treatment. The newly generated iBCSC were amazingly similar to breast cancer stem cells found in tumors that had not been irradiated, according to Dr. Pajonk.

The investigators also discovered that the iBCSC had a more than 30-fold increased ability to form tumors compared to the non-irradiated breast cancer cells from which they originated. Dr. Pajonk reported that the study unites the competing models of clonal evolution and the hierarchical organization of breast cancers, as it suggests that undisturbed, growing tumors maintain a small number of cancer stem cells. However, if confronted by various stressors that threaten their numbers, including ionizing radiation, the breast cancer cells generate iBCSC that may, together with the surviving cancer stem cells, repopulate the tumor. “What is really exciting about this study is that it gives us a much more complex understanding of the interaction of radiation with cancer cells that goes far beyond DNA damage and cell killing,” Dr. Pajonk said. “The study may carry enormous potential to make radiation even better.”

Dr. Pajonk stressed that breast cancer patients should not be worried by the study findings and should continue to undergo radiation if recommended by their oncologists. “Radiation is an extremely powerful tool in the fight against breast cancer,” he concluded. “If we can uncover the mechanism driving this transformation, we may be able to stop it and make the therapy even more powerful.”

Related Links:

University of California, Los Angeles’ Jonsson Comprehensive Cancer Center


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88 (32.901763916016): SELECT show_live FROM jos_com_show_setting LIMIT 1
89 (94.890594482422): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294739557 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
90 (46.014785766602): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294739557 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
91 (42.915344238281): 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`
92 (565.0520324707): SELECT show_live FROM jos_com_show_setting LIMIT 1
93 (67.949295043945): SELECT show_live FROM jos_com_show_setting LIMIT 1
94 (499.96376037598): SELECT show_live FROM jos_com_show_setting LIMIT 1
95 (59.127807617188): SELECT show_live FROM jos_com_show_setting LIMIT 1
96 (57.93571472168): SELECT show_live FROM jos_com_show_setting LIMIT 1
97 (36.954879760742): SELECT show_live FROM jos_com_show_setting LIMIT 1
98 (150.91896057129): SELECT show_live FROM jos_com_show_setting LIMIT 1
99 (157.11784362793): SELECT show_live FROM jos_com_show_setting LIMIT 1
100 (69.141387939453): SELECT show_live FROM jos_com_show_setting LIMIT 1
101 (!!!!! 7487.0586395264): SELECT show_live FROM jos_com_show_setting LIMIT 1
102 (!!!!! 7841.1102294922): SELECT show_live FROM jos_com_show_setting LIMIT 1
103 (!!!!! 8060.9321594238): SELECT show_live FROM jos_com_show_setting LIMIT 1
104 (!!!!! 7755.9947967529): SELECT show_live FROM jos_com_show_setting LIMIT 1
105 (!!!!! 5618.0953979492): SELECT show_live FROM jos_com_show_setting LIMIT 1
106 (!!!!! 5730.8673858643): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294739557 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294739557 AND published='1' LIMIT 1
107 (!!!!! 5844.8314666748): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294739557 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294739557 AND published='1' LIMIT 1
108 (654.93583679199): 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=294739557 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
109 (712.87155151367): 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=294739557 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
110 (642.06123352051): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294739557 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294739557 AND published='1' LIMIT 1
111 (!!!!! 2078.0563354492): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294739557 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294739557 AND published='1' LIMIT 1
112 (539.77966308594): 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=294739557 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
113 (!!!!! 3097.0573425293): 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=294739557 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
114 (!!!!! 6996.8700408936): 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
115 (!!!!! 6698.8468170166): 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
116 (974.89356994629): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294739557 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294739557 AND published='1' LIMIT 1
117 (298.02322387695): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294739557 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294739557 AND published='1' LIMIT 1
118 (!!!!! 1698.9707946777): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294739557 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294739557 AND published='1' LIMIT 1
119 (473.0224609375): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294739557 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294739557 AND published='1' LIMIT 1
120 (!!!!! 3513.0977630615): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294739557 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294739557 AND published='1' LIMIT 1
121 (747.2038269043): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294739557 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294739557 AND published='1' LIMIT 1
122 (!!!!! 7628.9176940918): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294739557 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294739557 AND published='1' LIMIT 1
123 (!!!!! 7979.154586792): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294739557 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294739557 AND published='1' LIMIT 1
124 (408.88786315918): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`
125 (!!!!! 72818.040847778): 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
126 (!!!!! 1296.0433959961): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294739557 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294739557 AND type='deeppockets_item' AND published='1' LIMIT 1
127 (!!!!! 24580.001831055): ( 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
128 (412.94097900391): ( 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
129 (468.01567077637): 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
130 (58.889389038086): 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
131 (602.96058654785): 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
132 (50.067901611328): 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
133 (891.92390441895): 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
134 (56.982040405273): 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
135 (742.91229248047): 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
136 (52.928924560547): 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
137 (!!!!! 2784.9674224854): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294739557 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
138 (!!!!! 4606.9622039795): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294739557 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
139 (!!!!! 9166.0022735596): SELECT name FROM jos_deeppockets WHERE id=211
140 (444.88906860352): SELECT name FROM jos_deeppockets WHERE id=211
141 (!!!!! 1088.1423950195): 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((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
142 (!!!!! 7075.0713348389): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))211((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
143 (!!!!! 1367.0921325684): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294739557 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294739557 AND published='1' LIMIT 1
144 (102.99682617188): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294739557 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294739557 AND published='1' LIMIT 1
145 (!!!!! 22231.101989746): TRUNCATE TABLE jos_trademed_module
146 (!!!!! 2530.0979614258): 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=294739557 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
147 (536.91864013672): 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=294739557 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
148 (!!!!! 2097.8450775146): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294739557 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
149 (243.9022064209): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294739557 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
150 (!!!!! 1095.0565338135): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294739557 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294739557 AND published='1' LIMIT 1
151 (201.94053649902): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294739557 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294739557 AND published='1' LIMIT 1
152 (!!!!! 8426.9046783447): 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
153 (!!!!! 12449.026107788): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294739557 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294739557 AND published='1' LIMIT 1
154 (!!!!! 4841.8045043945): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294739557 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294739557 AND published='1' LIMIT 1
155 (!!!!! 2044.9161529541): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294739557 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294739557 AND type='deeppockets_item' AND published='1' LIMIT 1
156 (!!!!! 4544.0196990967): 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)
157 (84.161758422852): 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)
158 (!!!!! 1015.9015655518): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1
159 (344.99168395996): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294739557 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294739557 AND published='1' LIMIT 1
160 (192.88063049316): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294739557 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294739557 AND published='1' LIMIT 1
161 (!!!!! 3962.0399475098): select jos_twitters.link from jos_twitters where cat=10
162 (70.095062255859): select jos_facebook.link from jos_facebook where cat=10
163 (56.028366088867): select jos_google_plus.link from jos_google_plus where cat=10
164 (197.8874206543): select jos_linkedin.link from jos_linkedin where cat=10