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Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine.
Geller, Leore T; Barzily-Rokni, Michal; Danino, Tal; Jonas, Oliver H; Shental, Noam; Nejman, Deborah; Gavert, Nancy; Zwang, Yaara; 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; Fuks, Garold; Gurbatri, Candice; Gopalakrishnan, Vancheswaran; Kim, Michael; Hurd, Mark W; Katz, Matthew; Fleming, Jason; Maitra, Anirban; Smith, David A; Skalak, Matt; Bu, Jeffrey; Michaud, Monia; Trauger, Sunia A; Barshack, Iris; Golan, Talia; Sandbank, Judith; Flaherty, Keith T; Mandinova, Anna; Garrett, Wendy S; Thayer, Sarah P; Ferrone, Cristina R; Huttenhower, Curtis; Bhatia, Sangeeta N; Gevers, Dirk; Wargo, Jennifer A; Golub, Todd R; Straussman, Ravid.
Afiliação
  • Geller LT; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
  • Barzily-Rokni M; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Danino T; Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
  • Jonas OH; Department of Radiology, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Shental N; Joint Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Nejman D; Department of Mathematics and Computer Science, Open University of Israel, Raanana, Israel.
  • Gavert N; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
  • Zwang Y; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
  • Cooper ZA; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
  • Shee K; Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Thaiss CA; Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Reuben A; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Livny J; Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
  • Avraham R; Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Frederick DT; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Ligorio M; Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
  • Chatman K; Department of Surgical Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Johnston SE; Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA.
  • Mosher CM; Small Molecule Mass Spectrometry Facility, Faculty of Arts and Sciences Division of Science, Harvard University, Cambridge, MA 02138, USA.
  • Brandis A; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Fuks G; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Gurbatri C; Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot, Israel.
  • Gopalakrishnan V; Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot, Israel.
  • Kim M; Department of Biomedical Engineering, Columbia University, New York City, NY 10027, USA.
  • Hurd MW; Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Katz M; Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Fleming J; Ahmed Center for Pancreatic Cancer Research, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Maitra A; Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Smith DA; Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Skalak M; Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Bu J; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Michaud M; Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
  • Trauger SA; Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
  • Barshack I; Harvard T. H. Chan School of Public Health, Departments of Immunology and Infectious Diseases and Genetics and Complex Diseases, Boston, MA 02115, USA.
  • Golan T; Small Molecule Mass Spectrometry Facility, Faculty of Arts and Sciences Division of Science, Harvard University, Cambridge, MA 02138, USA.
  • Sandbank J; Department of Pathology, Sheba Medical Center, Ramat Gan, Israel.
  • Flaherty KT; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Mandinova A; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Garrett WS; Department of Oncology, Sheba Medical Center, Ramat Gan, Israel.
  • Thayer SP; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Ferrone CR; Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA.
  • Huttenhower C; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Bhatia SN; Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
  • Gevers D; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Wargo JA; Harvard T. H. Chan School of Public Health, Departments of Immunology and Infectious Diseases and Genetics and Complex Diseases, Boston, MA 02115, USA.
  • Golub TR; Dana-Farber Cancer Institute, Boston, MA 02115, USA.
  • Straussman R; Department of Surgery, University of Nebraska Medical Center, Omaha, NE 68198-6345, USA.
Science ; 357(6356): 1156-1160, 2017 09 15.
Article em En | MEDLINE | ID: mdl-28912244
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Resistencia a Medicamentos Antineoplásicos / Carcinoma Ductal Pancreático / Desoxicitidina / Antimetabólitos Antineoplásicos Limite: Animals / Humans / Male Idioma: En Revista: Science Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Israel
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Resistencia a Medicamentos Antineoplásicos / Carcinoma Ductal Pancreático / Desoxicitidina / Antimetabólitos Antineoplásicos Limite: Animals / Humans / Male Idioma: En Revista: Science Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Israel