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      Control of inducible chemoresistance: enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-kappaB.

      1 , , ,
      Nature medicine
      Springer Science and Business Media LLC

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          Abstract

          Programmed cell death (apoptosis) seems to be the principal mechanism whereby anti-oncogenic therapies such as chemotherapy and radiation effect their responses. Resistance to apoptosis, therefore, is probably a principal mechanism whereby tumors are able to overcome these cancer therapies. The transcription factor NF-kappaB is activated by chemotherapy and by irradiation in some cancer cell lines. Furthermore, inhibition of NF-kappaB in vitro leads to enhanced apoptosis in response to a variety of different stimuli. We show here that inhibition of NF-kappaB through the adenoviral delivery of a modified form of IkappaBalpha, the inhibitor of NF-kappaB, sensitizes chemoresistant tumors to the apoptotic potential of TNFalpha and of the chemotherapeutic compound CPT-11, resulting in tumor regression. These results demonstrate that the activation of NF-kappaB in response to chemotherapy is a principal mechanism of inducible tumor chemoresistance, and establish the inhibition of NF-kappaB as a new approach to adjuvant therapy in cancer treatment.

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          Author and article information

          Journal
          Nat Med
          Nature medicine
          Springer Science and Business Media LLC
          1078-8956
          1078-8956
          Apr 1999
          : 5
          : 4
          Affiliations
          [1 ] Lineberger Comprehensive Cancer Center, Department of Endodontics, School of Dentistry, University of North Carolina at Chapel Hill, 27599-7295, USA.
          Article
          10.1038/7410
          10202930
          b599d7fe-1022-428f-a9cd-7a34bc80595a
          History

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