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Author Manuscript Published OnlineFirst on March 31, 2017; DOI: 10.1158/0008-5472.CAN-17-0084
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited.
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Downloaded from cancerres.aacrjournals.org on July 28, 2017. © 2017 American Association for Cancer Research.
Author Manuscript Published OnlineFirst on March 31, 2017; DOI: 10.1158/0008-5472.CAN-17-0084
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited.
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Downloaded from cancerres.aacrjournals.org on July 28, 2017. © 2017 American Association for Cancer Research.
Author Manuscript Published OnlineFirst on March 31, 2017; DOI: 10.1158/0008-5472.CAN-17-0084
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited.
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Downloaded from cancerres.aacrjournals.org on July 28, 2017. © 2017 American Association for Cancer Research.
Author Manuscript Published OnlineFirst on March 31, 2017; DOI: 10.1158/0008-5472.CAN-17-0084
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited.
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Downloaded from cancerres.aacrjournals.org on July 28, 2017. © 2017 American Association for Cancer Research.
Author Manuscript Published OnlineFirst on March 31, 2017; DOI: 10.1158/0008-5472.CAN-17-0084
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited.
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Downloaded from cancerres.aacrjournals.org on July 28, 2017. © 2017 American Association for Cancer Research.
Author Manuscript Published OnlineFirst on March 31, 2017; DOI: 10.1158/0008-5472.CAN-17-0084
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited.
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Author Manuscript Published OnlineFirst on March 31, 2017; DOI: 10.1158/0008-5472.CAN-17-0084
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited.
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Downloaded from cancerres.aacrjournals.org on July 28, 2017. © 2017 American Association for Cancer Research.
Author Manuscript Published OnlineFirst on March 31, 2017; DOI: 10.1158/0008-5472.CAN-17-0084
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited.
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Downloaded from cancerres.aacrjournals.org on July 28, 2017. © 2017 American Association for Cancer Research.
Author Manuscript Published OnlineFirst on March 31, 2017; DOI: 10.1158/0008-5472.CAN-17-0084
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited.
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ŚŝƐƚŽŶĞ,ϮyƉŚŽƐƉŚŽƌLJůĂƚŝŽŶŽŶƐĞƌŝŶĞϭϯϵ͘dŚĞ:ŽƵƌŶĂůŽĨďŝŽůŽŐŝĐĂůĐŚĞŵŝƐƚƌLJ
ϭϵϵϴ͖Ϯϳϯ;ϭϬͿ͗ϱϴϱϴͲϲϴ͘
ZŝŶŐĞů/͕,Žƌǁŝƚnj^͘^ƚƵĚŝĞƐǁŝƚŚZWϱϲϵϳϲ;ƚĂdžŽƚĞƌĞͿ͗ĂƐĞŵŝƐLJŶƚŚĞƚŝĐĂŶĂůŽŐƵĞŽĨƚĂdžŽů͘:ŽƵƌŶĂů
ŽĨƚŚĞEĂƚŝŽŶĂůĂŶĐĞƌ/ŶƐƚŝƚƵƚĞϭϵϵϭ͖ϴϯ;ϰͿ͗ϮϴϴͲϵϭ͘
EĂŬĂƐŽŶĞ^͕ƐŬĂƵƚƌƵĚ,͕<ĞĞƐd͕WĂƌŬ:,͕WůĂŬƐs͕ǁĂůĚ:͕ĞƚĂů͘/ŵĂŐŝŶŐƚƵŵŽƌͲƐƚƌŽŵĂ
ŝŶƚĞƌĂĐƚŝŽŶƐĚƵƌŝŶŐĐŚĞŵŽƚŚĞƌĂƉLJƌĞǀĞĂůƐĐŽŶƚƌŝďƵƚŝŽŶƐŽĨƚŚĞŵŝĐƌŽĞŶǀŝƌŽŶŵĞŶƚƚŽƌĞƐŝƐƚĂŶĐĞ͘
ĂŶĐĞƌĐĞůůϮϬϭϮ͖Ϯϭ;ϰͿ͗ϰϴϴͲϱϬϯĚŽŝϭϬ͘ϭϬϭϲͬũ͘ĐĐƌ͘ϮϬϭϮ͘ϬϮ͘Ϭϭϳ͘
<ƌŽĞŵĞƌ'͕'ĂůůƵnjnjŝ>͕<ĞƉƉK͕ŝƚǀŽŐĞů>͘/ŵŵƵŶŽŐĞŶŝĐĐĞůůĚĞĂƚŚŝŶĐĂŶĐĞƌƚŚĞƌĂƉLJ͘ŶŶƵĂů
ƌĞǀŝĞǁŽĨŝŵŵƵŶŽůŽŐLJϮϬϭϯ͖ϯϭ͗ϱϭͲϳϮĚŽŝϭϬ͘ϭϭϰϲͬĂŶŶƵƌĞǀͲŝŵŵƵŶŽůͲϬϯϮϳϭϮͲϭϬϬϬϬϴ͘
'ƌŝĨĨŝƚŚƐ'D͕dƐĐŚŽƉƉ:͘WĂƚŚǁĂLJƐĨŽƌLJƚŽůLJƐŝƐ͘^ƉƌŝŶŐĞƌĞƌůŝŶ,ĞŝĚĞůďĞƌŐ͖ϮϬϭϮ͘
<ƌLJƐŬŽs͕'ĂƌŐ͕<ĂĐnjŵĂƌĞŬ͕<ƌLJƐŬŽK͕ŐŽƐƚŝŶŝƐW͕sĂŶĚĞŶĂďĞĞůĞW͘/ŵŵƵŶŽŐĞŶŝĐĐĞůů
ĚĞĂƚŚĂŶĚDWƐŝŶĐĂŶĐĞƌƚŚĞƌĂƉLJ͘EĂƚƵƌĞƌĞǀŝĞǁƐĂŶĐĞƌϮϬϭϮ͖ϭϮ;ϭϮͿ͗ϴϲϬͲϳϱĚŽŝ
ϭϬ͘ϭϬϯϴͬŶƌĐϯϯϴϬ͘
KďĞŝĚD͕dĞƐŶŝĞƌĞ͕'ŚŝƌŝŶŐŚĞůůŝ&͕&ŝŵŝĂ'D͕ƉĞƚŽŚ>͕WĞƌĨĞƚƚŝŶŝ:>͕ĞƚĂů͘ĂůƌĞƚŝĐƵůŝŶĞdžƉŽƐƵƌĞ
ĚŝĐƚĂƚĞƐƚŚĞŝŵŵƵŶŽŐĞŶŝĐŝƚLJŽĨĐĂŶĐĞƌĐĞůůĚĞĂƚŚ͘EĂƚƵƌĞŵĞĚŝĐŝŶĞϮϬϬϳ͖ϭϯ;ϭͿ͗ϱϰͲϲϭĚŽŝ
ϭϬ͘ϭϬϯϴͬŶŵϭϱϮϯ͘
DŝŶĐŚŝŶƚŽŶ/͕dĂŶŶŽĐŬ/&͘ƌƵŐƉĞŶĞƚƌĂƚŝŽŶŝŶƐŽůŝĚƚƵŵŽƵƌƐ͘EĂƚƵƌĞƌĞǀŝĞǁƐĂŶĐĞƌ
ϮϬϬϲ͖ϲ;ϴͿ͗ϱϴϯͲϵϮĚŽŝϭϬ͘ϭϬϯϴͬŶƌĐϭϴϵϯ͘
DĂƚŚĞǁZ͕<ĂƌĂŶƚnjĂͲtĂĚƐǁŽƌƚŚs͕tŚŝƚĞ͘ZŽůĞŽĨĂƵƚŽƉŚĂŐLJŝŶĐĂŶĐĞƌ͘EĂƚƵƌĞƌĞǀŝĞǁƐĂŶĐĞƌ
ϮϬϬϳ͖ϳ;ϭϮͿ͗ϵϲϭͲϳĚŽŝϭϬ͘ϭϬϯϴͬŶƌĐϮϮϱϰ͘
ŵĂƌĂǀĂĚŝZ<͕>ŝƉƉŝŶĐŽƚƚͲ^ĐŚǁĂƌƚnj:͕zŝŶyD͕tĞŝƐƐt͕dĂŬĞďĞE͕dŝŵŵĞƌt͕ĞƚĂů͘WƌŝŶĐŝƉůĞƐ
ĂŶĚĐƵƌƌĞŶƚƐƚƌĂƚĞŐŝĞƐĨŽƌƚĂƌŐĞƚŝŶŐĂƵƚŽƉŚĂŐLJĨŽƌĐĂŶĐĞƌƚƌĞĂƚŵĞŶƚ͘ůŝŶŝĐĂůĐĂŶĐĞƌƌĞƐĞĂƌĐŚ͗
ĂŶŽĨĨŝĐŝĂůũŽƵƌŶĂůŽĨƚŚĞŵĞƌŝĐĂŶƐƐŽĐŝĂƚŝŽŶĨŽƌĂŶĐĞƌZĞƐĞĂƌĐŚϮϬϭϭ͖ϭϳ;ϰͿ͗ϲϱϰͲϲϲĚŽŝ
ϭϬ͘ϭϭϱϴͬϭϬϳϴͲϬϰϯϮ͘ĐĐƌͲϭϬͲϮϲϯϰ͘
DĂĞƐ,͕ZƵďŝŽE͕'ĂƌŐ͕ŐŽƐƚŝŶŝƐW͘ƵƚŽƉŚĂŐLJ͗ƐŚĂƉŝŶŐƚŚĞƚƵŵŽƌŵŝĐƌŽĞŶǀŝƌŽŶŵĞŶƚĂŶĚ
ƚŚĞƌĂƉĞƵƚŝĐƌĞƐƉŽŶƐĞ͘dƌĞŶĚƐŝŶŵŽůĞĐƵůĂƌŵĞĚŝĐŝŶĞϮϬϭϯ͖ϭϵ;ϳͿ͗ϰϮϴͲϰϲĚŽŝ
ϭϬ͘ϭϬϭϲͬũ͘ŵŽůŵĞĚ͘ϮϬϭϯ͘Ϭϰ͘ϬϬϱ͘
tŚŝƚĞ͘ĞĐŽŶǀŽůƵƚŝŶŐƚŚĞĐŽŶƚĞdžƚͲĚĞƉĞŶĚĞŶƚƌŽůĞĨŽƌĂƵƚŽƉŚĂŐLJŝŶĐĂŶĐĞƌ͘EĂƚƵƌĞƌĞǀŝĞǁƐ
ĂŶĐĞƌϮϬϭϮ͖ϭϮ;ϲͿ͗ϰϬϭͲϭϬĚŽŝϭϬ͘ϭϬϯϴͬŶƌĐϯϮϲϮ͘
ŚĂŽy͕,Ğz͕ŚĞŶ,͘ƵƚŽƉŚĂŐŝĐƚƵŵŽƌƐƚƌŽŵĂ͗ŵĞĐŚĂŶŝƐŵƐĂŶĚƌŽůĞƐŝŶƚƵŵŽƌŐƌŽǁƚŚĂŶĚ
ƉƌŽŐƌĞƐƐŝŽŶ͘/ŶƚĞƌŶĂƚŝŽŶĂůũŽƵƌŶĂůŽĨĐĂŶĐĞƌϮϬϭϯ͖ϭϯϮ;ϭͿ͗ϭͲϴĚŽŝϭϬ͘ϭϬϬϮͬŝũĐ͘Ϯϳϲϲϰ͘
ŚĞŶW͕ĞƐĐŽŶD͕ŽŶĂůĚŽW͘ƵƚŽƉŚĂŐLJͲŵĞĚŝĂƚĞĚƌĞŐƵůĂƚŝŽŶŽĨŵĂĐƌŽƉŚĂŐĞƐĂŶĚŝƚƐ
ĂƉƉůŝĐĂƚŝŽŶƐĨŽƌĐĂŶĐĞƌ͘ƵƚŽƉŚĂŐLJϮϬϭϰ͖ϭϬ;ϮͿ͗ϭϵϮͲϮϬϬĚŽŝϭϬ͘ϰϭϲϭͬĂƵƚŽ͘ϮϲϵϮϳ͘
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Downloaded from cancerres.aacrjournals.org on July 28, 2017. © 2017 American Association for Cancer Research.
Author Manuscript Published OnlineFirst on March 31, 2017; DOI: 10.1158/0008-5472.CAN-17-0084
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited.
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DĂŶƚŽǀĂŶŝ͕^ŝĐĂ͕^ŽnjnjĂŶŝ^͕ůůĂǀĞŶĂW͕sĞĐĐŚŝ͕>ŽĐĂƚŝD͘dŚĞĐŚĞŵŽŬŝŶĞƐLJƐƚĞŵŝŶĚŝǀĞƌƐĞ
ĨŽƌŵƐŽĨŵĂĐƌŽƉŚĂŐĞĂĐƚŝǀĂƚŝŽŶĂŶĚƉŽůĂƌŝnjĂƚŝŽŶ͘dƌĞŶĚƐŝŶŝŵŵƵŶŽůŽŐLJϮϬϬϰ͖Ϯϱ;ϭϮͿ͗ϲϳϳͲϴϲĚŽŝ
ϭϬ͘ϭϬϭϲͬũ͘ŝƚ͘ϮϬϬϰ͘Ϭϵ͘Ϭϭϱ͘
DĂŶƚŽǀĂŶŝ͕^ŝĐĂ͘DĂĐƌŽƉŚĂŐĞƐ͕ŝŶŶĂƚĞŝŵŵƵŶŝƚLJĂŶĚĐĂŶĐĞƌ͗ďĂůĂŶĐĞ͕ƚŽůĞƌĂŶĐĞ͕ĂŶĚ
ĚŝǀĞƌƐŝƚLJ͘ƵƌƌĞŶƚŽƉŝŶŝŽŶŝŶŝŵŵƵŶŽůŽŐLJϮϬϭϬ͖ϮϮ;ϮͿ͗ϮϯϭͲϳĚŽŝϭϬ͘ϭϬϭϲͬũ͘ĐŽŝ͘ϮϬϭϬ͘Ϭϭ͘ϬϬϵ͘
ĂƌƌŽƐD,͕,ĂƵĐŬ&͕ƌĞLJĞƌ:,͕<ĞŵƉŬĞƐ͕EŝĞĚŽďŝƚĞŬ'͘DĂĐƌŽƉŚĂŐĞƉŽůĂƌŝƐĂƚŝŽŶ͗ĂŶ
ŝŵŵƵŶŽŚŝƐƚŽĐŚĞŵŝĐĂůĂƉƉƌŽĂĐŚĨŽƌŝĚĞŶƚŝĨLJŝŶŐDϭĂŶĚDϮŵĂĐƌŽƉŚĂŐĞƐ͘WůŽ^ŽŶĞ
ϮϬϭϯ͖ϴ;ϭϭͿ͗ĞϴϬϵϬϴĚŽŝϭϬ͘ϭϯϳϭͬũŽƵƌŶĂů͘ƉŽŶĞ͘ϬϬϴϬϵϬϴ͘
DƵƌƌĂLJW:͕ůůĞŶ:͕ŝƐǁĂƐ^<͕&ŝƐŚĞƌ͕'ŝůƌŽLJt͕'ŽĞƌĚƚ^͕ĞƚĂů͘DĂĐƌŽƉŚĂŐĞĂĐƚŝǀĂƚŝŽŶĂŶĚ
ƉŽůĂƌŝnjĂƚŝŽŶ͗ŶŽŵĞŶĐůĂƚƵƌĞĂŶĚĞdžƉĞƌŝŵĞŶƚĂůŐƵŝĚĞůŝŶĞƐ͘/ŵŵƵŶŝƚLJϮϬϭϰ͖ϰϭ;ϭͿ͗ϭϰͲϮϬĚŽŝ
ϭϬ͘ϭϬϭϲͬũ͘ŝŵŵƵŶŝ͘ϮϬϭϰ͘Ϭϲ͘ϬϬϴ͘
ƌĂŶŐŽƵƋƵĞ'͕ĞƐĐŽƚĞĂƵdž͘DĂĐƌŽƉŚĂŐĞLJƚŽŬŝŶĞƐ͗/ŶǀŽůǀĞŵĞŶƚŝŶ/ŵŵƵŶŝƚLJĂŶĚ/ŶĨĞĐƚŝŽƵƐ
ŝƐĞĂƐĞƐ͘&ƌŽŶƚŝĞƌƐŝŶŝŵŵƵŶŽůŽŐLJϮϬϭϰ͖ϱ͗ϰϵϭĚŽŝϭϬ͘ϯϯϴϵͬĨŝŵŵƵ͘ϮϬϭϰ͘ϬϬϰϵϭ͘
WĂƵů^D͕DLJƚĞůŬĂ^͕ƵŶǁŝĚĚŝĞd͕WĞƌƐŝŶŐĞƌ͕DƵŶŽƐ,͕>ŝŶĚďŽƌŐ^Z͕ĞƚĂů͘,ŽǁƚŽ
ŝŵƉƌŽǀĞZΘƉƌŽĚƵĐƚŝǀŝƚLJ͗ƚŚĞƉŚĂƌŵĂĐĞƵƚŝĐĂůŝŶĚƵƐƚƌLJΖƐŐƌĂŶĚĐŚĂůůĞŶŐĞ͘EĂƚƵƌĞƌĞǀŝĞǁƐƌƵŐ
ĚŝƐĐŽǀĞƌLJϮϬϭϬ͖ϵ;ϯͿ͗ϮϬϯͲϭϰĚŽŝ
ŚƚƚƉ͗ͬͬǁǁǁ͘ŶĂƚƵƌĞ͘ĐŽŵͬŶƌĚͬũŽƵƌŶĂůͬǀϵͬŶϯͬƐƵƉƉŝŶĨŽͬŶƌĚϯϬϳϴͺ^ϭ͘Śƚŵů͘
'ĂŽ,͕<ŽƌŶ:D͕&ĞƌƌĞƚƚŝ^͕DŽŶĂŚĂŶ:͕tĂŶŐz͕^ŝŶŐŚD͕ĞƚĂů͘,ŝŐŚͲƚŚƌŽƵŐŚƉƵƚƐĐƌĞĞŶŝŶŐ
ƵƐŝŶŐƉĂƚŝĞŶƚͲĚĞƌŝǀĞĚƚƵŵŽƌdžĞŶŽŐƌĂĨƚƐƚŽƉƌĞĚŝĐƚĐůŝŶŝĐĂůƚƌŝĂůĚƌƵŐƌĞƐƉŽŶƐĞ͘EĂƚƵƌĞŵĞĚŝĐŝŶĞ
ϮϬϭϱ͖ĂĚǀĂŶĐĞŽŶůŝŶĞƉƵďůŝĐĂƚŝŽŶĚŽŝϭϬ͘ϭϬϯϴͬŶŵ͘ϯϵϱϰ
ŚƚƚƉ͗ͬͬǁǁǁ͘ŶĂƚƵƌĞ͘ĐŽŵͬŶŵͬũŽƵƌŶĂůͬǀĂŽƉͬŶĐƵƌƌĞŶƚͬĂďƐͬŶŵ͘ϯϵϱϰ͘ŚƚŵůηƐƵƉƉůĞŵĞŶƚĂƌLJͲŝŶĨŽƌŵĂƚŝŽŶ͘
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,ŽĞůĚĞƌ^͕ůĂƌŬĞW͕tŽƌŬŵĂŶW͘ŝƐĐŽǀĞƌLJŽĨƐŵĂůůŵŽůĞĐƵůĞĐĂŶĐĞƌĚƌƵŐƐ͗ƐƵĐĐĞƐƐĞƐ͕
ĐŚĂůůĞŶŐĞƐĂŶĚŽƉƉŽƌƚƵŶŝƚŝĞƐ͘DŽůĞĐƵůĂƌŽŶĐŽůŽŐLJϮϬϭϮ͖ϲ;ϮͿ͗ϭϱϱͲϳϲĚŽŝ
ϭϬ͘ϭϬϭϲͬũ͘ŵŽůŽŶĐ͘ϮϬϭϮ͘ϬϮ͘ϬϬϰ͘
KƌůŽĨĨ:͕ŽƵŐůĂƐ&͕WŝŶŚĞŝƌŽ:͕>ĞǀŝŶƐŽŶ^͕ƌĂŶƐŽŶD͕ŚĂƚƵƌǀĞĚŝW͕ĞƚĂů͘dŚĞĨƵƚƵƌĞŽĨĚƌƵŐ
ĚĞǀĞůŽƉŵĞŶƚ͗ĂĚǀĂŶĐŝŶŐĐůŝŶŝĐĂůƚƌŝĂůĚĞƐŝŐŶ͘EĂƚƵƌĞƌĞǀŝĞǁƐƌƵŐĚŝƐĐŽǀĞƌLJϮϬϬϵ͖ϴ;ϭϮͿ͗ϵϰϵͲϱϳ
ĚŽŝϭϬ͘ϭϬϯϴͬŶƌĚϯϬϮϱ͘
DĞĂĚƐD͕'ĂƚĞŶďLJZ͕ĂůƚŽŶt^͘ŶǀŝƌŽŶŵĞŶƚͲŵĞĚŝĂƚĞĚĚƌƵŐƌĞƐŝƐƚĂŶĐĞ͗ĂŵĂũŽƌĐŽŶƚƌŝďƵƚŽƌ
ƚŽŵŝŶŝŵĂůƌĞƐŝĚƵĂůĚŝƐĞĂƐĞ͘EĂƚƵƌĞƌĞǀŝĞǁƐĂŶĐĞƌϮϬϬϵ͖ϵ;ϵͿ͗ϲϲϱͲϳϰ͘
KůŝǀĞ<W͕:ĂĐŽďĞƚnjD͕ĂǀŝĚƐŽŶ:͕'ŽƉŝŶĂƚŚĂŶ͕DĐ/ŶƚLJƌĞ͕,ŽŶĞƐƐ͕ĞƚĂů͘/ŶŚŝďŝƚŝŽŶŽĨ
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Figure 1.
B
A
2000um
7
7
6
1
6
8
5
5
E
2
F
4
4
3
3
500um
H
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D
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1
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0.2
0.1
0
200
700
1200
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Gemcitabine
Docetaxel
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0
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200
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700
1200
1700
Radial Distance (um)
Downloaded from cancerres.aacrjournals.org on July 28, 2017. © 2017 American Association for Cancer Research.
Author Manuscript Published OnlineFirst on March 31, 2017; DOI: 10.1158/0008-5472.CAN-17-0084
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited.
Figure 2.
A
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B
500um
C
500um
50um
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D
vimentin/FTM
500um
MAC387/FTM
G
CRT
E
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Author Manuscript Published OnlineFirst on March 31, 2017; DOI: 10.1158/0008-5472.CAN-17-0084
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited.
Figure 3.
A
1
Vimentin response radial distance (mm)
0.9
Doxorubicin sensitive
Poor distribution
0.8
Doxorubicin resistant
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0.6
0.5
0.4
0.3
0.2
0.1
0
0
0.5
1
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γH2AX response radial distance (mm)
B
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Doxorubicin Resistant
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500um
500um
500um
500um
500um
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Author Manuscript Published OnlineFirst on March 31, 2017; DOI: 10.1158/0008-5472.CAN-17-0084
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited.
Figure 4.
B
20um
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LC3A/B
γH2AX
vimentin
γH2AX
vimentin
1
Dox
Dox + PS-1001
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0.2
0
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2
γH2AX
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4
5
vimentin
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500um
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500um
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500um
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Doxorubicin
D
C
20um
vimentin response radius (mm)
A
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Author Manuscript Published OnlineFirst on March 31, 2017; DOI: 10.1158/0008-5472.CAN-17-0084
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited.
Figure 5.
Poor
Distribution
Doxorubicin
Resistant
Doxorubicin
Sensitive
500um
500um
500um
500um
500um
800
700
700
Doxorubicin
Doxorubicin
+ PS1001
600
500
400
300
200
100
0
200
700
1200
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800
Doxorubicin
Doxorubicin
+ PS1001
600
500
400
300
200
100
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200
700
1200
-200
Doxorubicin
Doxorubicin
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600
500
400
300
200
100
0
200
1700
700
1200
1700
-100
-100
Radial Distance (μm)
700
MAC387 density (cells/mm2)
800
MAC387 density (cells/mm2)
MAC387 density (cells/mm2)
Dox + PS1001
Doxorubicin
500um
Radial Distance (μm)
-200
Radial Distance (μm)
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Author Manuscript Published OnlineFirst on March 31, 2017; DOI: 10.1158/0008-5472.CAN-17-0084
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited.
Figure 6.
A
50um
50um
pSTAT1
MAC387
MAC387/pSTAT1
50um
50um
c-Maf
+LPS + IFNγ + PS1001
(M1)
IL-6
iNOS
Socs3
Arg1
+IL-4 + PS1001
(M2)
YM-2
Mrc1
50um
MAC387/c-Maf
C
1.2
Untreated
+ PS1001
1
0.8
OD 450nm
MAC387
B
50um
0.6
0.4
0.2
SO1
0
1
2
3
Normalized Fold Induc on
4
0
IL-2
IL-4
IL-5
IL-6
IL-10 IL-12 IL-13 IL-17A IL-23 IFNܵ TNFα TGFß
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Author Manuscript Published OnlineFirst on March 31, 2017; DOI: 10.1158/0008-5472.CAN-17-0084
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited.
Figure 7.
A
LC3A/B/FTM
500um
LC3A/B
B
MAC387/pSTAT1
500um
MAC387/pSTAT1
C
CD3
500um
CD3/pSTAT1
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Author Manuscript Published OnlineFirst on March 31, 2017; DOI: 10.1158/0008-5472.CAN-17-0084
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited.
Multi-drug analyses in patients distinguish efficacious cancer
agents based on both tumor cell killing and immunomodulation
Jason Frazier, Jessica A Bertout, William S Kerwin, et al.
Cancer Res Published OnlineFirst March 31, 2017.
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