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Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine.

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Title: Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine.
Authors: Geller, Leore T., Barzily-Rokni, Michal, Danino, Tal, Jonas, Oliver H., Shental, Noam, Nejman, Deborah, Gavert, Nancy, Yaara Zwang, Cooper, Zachary A., Shee, Kevin, Thaiss, Christoph A., Reuben, Alexandre, Livny, Jonathan, Avraham, Roi, Frederick, Dennie T., Ligorio, Matteo, Chatman, Kelly, Johnston, Stephen E., Mosher, Carrie M., Brandis, Alexander
Source: Science (pre-March 2025). 9/15/2017, Vol. 357 Issue 6356, p1156-1160. 5p. 4 Diagrams.
Subjects: Colon cancer treatment, Antineoplastic agents, Drug resistance, Proteobacteria, High performance liquid chromatography
Abstract: Growing evidence suggests that microbes can influence the efficacy of cancer therapies. By studying colon cancer models, we found that bacteria can metabolize the chemotherapeutic drug gemcitabine (2′,2′-difluorodeoxycytidine) into its inactive form, 2′,2′-difluorodeoxyuridine. Metabolism was dependent on the expression of a long isoform of the bacterial enzyme cytidine deaminase (CDDL), seen primarily in Gammaproteobacteria. In a colon cancer mouse model, gemcitabine resistance was induced by intratumor Gammaproteobacteria, dependent on bacterial CDDL expression, and abrogated by cotreatment with the antibiotic ciprofloxacin. Gemcitabine is commonly used to treat pancreatic ductal adenocarcinoma (PDAC), and we hypothesized that intratumor bacteria might contribute to drug resistance of these tumors. Consistent with this possibility, we found that of the 113 human PDACs that were tested, 86 (76%) were positive for bacteria, mainly Gammaproteobacteria. [ABSTRACT FROM AUTHOR]
Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine.
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  Data: <searchLink fieldCode="AR" term="%22Geller%2C+Leore+T%2E%22">Geller, Leore T.</searchLink><br /><searchLink fieldCode="AR" term="%22Barzily-Rokni%2C+Michal%22">Barzily-Rokni, Michal</searchLink><br /><searchLink fieldCode="AR" term="%22Danino%2C+Tal%22">Danino, Tal</searchLink><br /><searchLink fieldCode="AR" term="%22Jonas%2C+Oliver+H%2E%22">Jonas, Oliver H.</searchLink><br /><searchLink fieldCode="AR" term="%22Shental%2C+Noam%22">Shental, Noam</searchLink><br /><searchLink fieldCode="AR" term="%22Nejman%2C+Deborah%22">Nejman, Deborah</searchLink><br /><searchLink fieldCode="AR" term="%22Gavert%2C+Nancy%22">Gavert, Nancy</searchLink><br /><searchLink fieldCode="AR" term="%22Yaara+Zwang%22">Yaara Zwang</searchLink><br /><searchLink fieldCode="AR" term="%22Cooper%2C+Zachary+A%2E%22">Cooper, Zachary A.</searchLink><br /><searchLink fieldCode="AR" term="%22Shee%2C+Kevin%22">Shee, Kevin</searchLink><br /><searchLink fieldCode="AR" term="%22Thaiss%2C+Christoph+A%2E%22">Thaiss, Christoph A.</searchLink><br /><searchLink fieldCode="AR" term="%22Reuben%2C+Alexandre%22">Reuben, Alexandre</searchLink><br /><searchLink fieldCode="AR" term="%22Livny%2C+Jonathan%22">Livny, Jonathan</searchLink><br /><searchLink fieldCode="AR" term="%22Avraham%2C+Roi%22">Avraham, Roi</searchLink><br /><searchLink fieldCode="AR" term="%22Frederick%2C+Dennie+T%2E%22">Frederick, Dennie T.</searchLink><br /><searchLink fieldCode="AR" term="%22Ligorio%2C+Matteo%22">Ligorio, Matteo</searchLink><br /><searchLink fieldCode="AR" term="%22Chatman%2C+Kelly%22">Chatman, Kelly</searchLink><br /><searchLink fieldCode="AR" term="%22Johnston%2C+Stephen+E%2E%22">Johnston, Stephen E.</searchLink><br /><searchLink fieldCode="AR" term="%22Mosher%2C+Carrie+M%2E%22">Mosher, Carrie M.</searchLink><br /><searchLink fieldCode="AR" term="%22Brandis%2C+Alexander%22">Brandis, Alexander</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Science+%28pre-March+2025%29%22">Science (pre-March 2025)</searchLink>. 9/15/2017, Vol. 357 Issue 6356, p1156-1160. 5p. 4 Diagrams.
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  Data: <searchLink fieldCode="DE" term="%22Colon+cancer+treatment%22">Colon cancer treatment</searchLink><br /><searchLink fieldCode="DE" term="%22Antineoplastic+agents%22">Antineoplastic agents</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+resistance%22">Drug resistance</searchLink><br /><searchLink fieldCode="DE" term="%22Proteobacteria%22">Proteobacteria</searchLink><br /><searchLink fieldCode="DE" term="%22High+performance+liquid+chromatography%22">High performance liquid chromatography</searchLink>
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  Data: Growing evidence suggests that microbes can influence the efficacy of cancer therapies. By studying colon cancer models, we found that bacteria can metabolize the chemotherapeutic drug gemcitabine (2′,2′-difluorodeoxycytidine) into its inactive form, 2′,2′-difluorodeoxyuridine. Metabolism was dependent on the expression of a long isoform of the bacterial enzyme cytidine deaminase (CDDL), seen primarily in Gammaproteobacteria. In a colon cancer mouse model, gemcitabine resistance was induced by intratumor Gammaproteobacteria, dependent on bacterial CDDL expression, and abrogated by cotreatment with the antibiotic ciprofloxacin. Gemcitabine is commonly used to treat pancreatic ductal adenocarcinoma (PDAC), and we hypothesized that intratumor bacteria might contribute to drug resistance of these tumors. Consistent with this possibility, we found that of the 113 human PDACs that were tested, 86 (76%) were positive for bacteria, mainly Gammaproteobacteria. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=125179372
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        Value: 10.1126/science.aah5043
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      – SubjectFull: Proteobacteria
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