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Intestinal Cells Protected from Radiation by Manipulation of Molecule

By MedImaging staff writers
Posted on 25 Jun 2008

A new study identifies a signaling molecule that plays a key role in radiation-induced intestinal damage. The research may lead to new strategies for protecting normal tissues from radiation during cancer therapies.

Although radiation is one of the most effective treatments for cancer, damage to the cells that line the gastrointestinal tract is a key limiting factor for patients undergoing pelvic or abdominal radiotherapy. The specific processes that underlie radiation-induced gastrointestinal toxicity, known as gastrointestinal (GI) syndrome, are not well understood. Earlier research has suggested that damage to intestinal stem cells and/or injury to intestinal blood vessel cells, called endothelial cells, are involved in the pathogenesis of GI syndrome.

The group of researchers, led by Drs. Jian Yu and Lin Zhang from the University of Pittsburgh Cancer Institute and School of Medicine (Philadelphia, PA, USA), found that the protein p53-upregulated modulator of apoptosis (PUMA) plays a major role in the radiation-induced damage of intestinal cells. PUMA is an established mechanism in the apoptosis pathway, a process by which cells undergo a type of programmed self-destruction.

Dr. Yu and colleagues, who published their findings in the June 2008 issue of the journal Cell Stem Cell, discovered that mice with a deficiency of PUMA exhibited impaired apoptosis in intestinal stem and progenitor cells, and enhanced intestinal regeneration following injury. The mutant mice therefore retained better intestinal integrity and survived longer following lethal doses of radiation. Although endothelial cells displayed a rapid induction of PUMA upon exposure to radiation, deletion of the protein did not change apoptosis in these specific cells.

These findings provide a mechanistic explanation of intestinal radiosensitivity and suggest that apoptosis of epithelial cells, and not endothelial cells, is the primary event that underlies the rapid onset of GI syndrome. "We were really excited to learn that deficiency in a single gene significantly protects against GI syndrome,” explained Dr. Yu. "Selectively curbing radiosensitivity in the normal tissues transiently by PUMA inhibitors might be particularly beneficial in cancer therapy.”

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University of Pittsburgh School of Medicine

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70 (273.9429473877): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=287560000 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

71 (272.98927307129): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=287560000 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

72 (52.213668823242): 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`

73 (44.107437133789): SELECT show_live FROM jos_com_show_setting LIMIT 1

74 (30.994415283203): SELECT show_live FROM jos_com_show_setting LIMIT 1

75 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1

76 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1

77 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1

78 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

79 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1

80 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

81 (36.954879760742): SELECT show_live FROM jos_com_show_setting LIMIT 1

82 (29.087066650391): SELECT show_live FROM jos_com_show_setting LIMIT 1

83 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

84 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1

85 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

86 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

87 (45.061111450195): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=287560000 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

88 (29.802322387695): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=287560000 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

89 (32.186508178711): 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 (47.922134399414): SELECT show_live FROM jos_com_show_setting LIMIT 1

91 (30.994415283203): SELECT show_live FROM jos_com_show_setting LIMIT 1

92 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1

93 (29.087066650391): SELECT show_live FROM jos_com_show_setting LIMIT 1

94 (32.901763916016): SELECT show_live FROM jos_com_show_setting LIMIT 1

95 (29.087066650391): SELECT show_live FROM jos_com_show_setting LIMIT 1

96 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

97 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1

98 (27.179718017578): SELECT show_live FROM jos_com_show_setting LIMIT 1

99 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1

100 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1

101 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1

102 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

103 (34.809112548828): SELECT show_live FROM jos_com_show_setting LIMIT 1

104 (73.909759521484): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=287560000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=287560000 AND published='1' LIMIT 1

105 (41.961669921875): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=287560000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=287560000 AND published='1' LIMIT 1

106 (52.928924560547): 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=287560000 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

107 (95.844268798828): 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=287560000 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

108 (85.115432739258): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=287560000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=287560000 AND published='1' LIMIT 1

109 (42.915344238281): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=287560000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=287560000 AND published='1' LIMIT 1

110 (46.014785766602): 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=287560000 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

111 (436.06758117676): 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=287560000 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

112 (549.0779876709): 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 (309.94415283203): 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 (113.01040649414): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=287560000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=287560000 AND published='1' LIMIT 1

115 (66.041946411133): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=287560000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=287560000 AND published='1' LIMIT 1

116 (57.93571472168): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=287560000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=287560000 AND published='1' LIMIT 1

117 (38.14697265625): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=287560000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=287560000 AND published='1' LIMIT 1

118 (56.982040405273): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=287560000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=287560000 AND published='1' LIMIT 1

119 (41.961669921875): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=287560000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=287560000 AND published='1' LIMIT 1

120 (99.897384643555): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=287560000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=287560000 AND published='1' LIMIT 1

121 (36.001205444336): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=287560000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=287560000 AND published='1' LIMIT 1

122 (289.2017364502): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`

123 (!!!!! 20416.975021362): 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 (498.05641174316): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=287560000 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=287560000 AND type='deeppockets_item' AND published='1' LIMIT 1

125 (!!!!! 7301.0921478271): ( 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 (86.069107055664): ( 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 (41.007995605469): 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 (30.040740966797): 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 (46.014785766602): 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 (30.994415283203): 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 (288.00964355469): 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 (58.174133300781): 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 (41.007995605469): 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 (29.087066650391): 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 (488.9965057373): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=287560000 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

136 (317.09671020508): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=287560000 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

137 (201.94053649902): SELECT name FROM jos_deeppockets WHERE id=213

138 (34.093856811523): SELECT name FROM jos_deeppockets WHERE id=213

139 (533.10394287109): 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 '((;)|(^))213((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3

140 (476.83715820312): 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 '((;)|(^))213((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3

141 (67.949295043945): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=287560000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=287560000 AND published='1' LIMIT 1

142 (50.067901611328): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=287560000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=287560000 AND published='1' LIMIT 1

143 (!!!!! 11463.88053894): TRUNCATE TABLE jos_trademed_module

144 (98.943710327148): 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=287560000 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

145 (51.975250244141): 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=287560000 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

146 (844.00177001953): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=287560000 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

147 (51.975250244141): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=287560000 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

148 (57.93571472168): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=287560000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=287560000 AND published='1' LIMIT 1

149 (46.014785766602): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=287560000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=287560000 AND published='1' LIMIT 1

150 (!!!!! 1091.0034179688): 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 (56.028366088867): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=287560000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=287560000 AND published='1' LIMIT 1

152 (41.961669921875): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=287560000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=287560000 AND published='1' LIMIT 1

153 (54.836273193359): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=287560000 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=287560000 AND type='deeppockets_item' AND published='1' LIMIT 1

154 (403.88107299805): 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=213 or channel_id is null)

155 (101.08947753906): 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=213 or channel_id is null)

156 (37.908554077148): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1

157 (57.93571472168): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=287560000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=287560000 AND published='1' LIMIT 1

158 (41.007995605469): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=287560000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=287560000 AND published='1' LIMIT 1

159 (37.908554077148): select jos_twitters.link from jos_twitters where cat=10

160 (30.994415283203): select jos_facebook.link from jos_facebook where cat=10

161 (32.186508178711): select jos_google_plus.link from jos_google_plus where cat=10

162 (30.994415283203): select jos_linkedin.link from jos_linkedin where cat=10

163 (324.96452331543): update jos_bannersmanager_banner set impmade=impmade+1 where id in(14615,14202,14203)

164 (!!!!! 1103.1627655029): insert into jos_banners_delta values (14615,'2025-08-23 01:48:40','216.73.216.171','view'),(14202,'2025-08-23 01:48:40','216.73.216.171','view'),(14203,'2025-08-23 01:48:40','216.73.216.171','view')

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