Dataset Information

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence.

ABSTRACT: The demonstration of tyrosine kinase inhibitors (TKIs) in treating chronic myeloid leukemia (CML) has heralded a new era in cancer therapeutics. However, a small population of cells does not respond to TKI treatment, resulting in minimal residual disease (MRD); even the most potent TKIs fail to eradicate these cells. These MRD cells serve as a reservoir to develop resistance to therapy. Why TKI treatment is ineffective against MRD cells is not known. Growth factor signaling is implicated in supporting the survival of MRD cells during TKI treatment, but a mechanistic understanding is lacking. Recent studies demonstrated that an elevated c-Fos and Dusp1 expression as a result of convergent oncogenic and growth factor signaling in MRD cells mediate TKI resistance. The genetic and chemical inhibition of c-Fos and Dusp1 renders CML exquisitely sensitive to TKIs and cures CML in both genetic and humanized mouse models. We identified these target genes using multiple microarrays from TKI-sensitive and -resistant cells. Here, we provide methods for target validation using in vitro and in vivo mouse models. These methods can easily be applied to any target for genetic validation and therapeutic development.

SUBMITTER: Kesarwani M

PROVIDER: S-EPMC6945823 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence.

Kesarwani Meenu M Kincaid Zachary Z Azam Mohammad M

Journal of visualized experiments : JoVE 20190107 143

The demonstration of tyrosine kinase inhibitors (TKIs) in treating chronic myeloid leukemia (CML) has heralded a new era in cancer therapeutics. However, a small population of cells does not respond to TKI treatment, resulting in minimal residual disease (MRD); even the most potent TKIs fail to eradicate these cells. These MRD cells serve as a reservoir to develop resistance to therapy. Why TKI treatment is ineffective against MRD cells is not known. Growth factor signaling is implicated in supp ...[more]

PMID: 30663656

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Project description:BACKGROUND: The current paradigm of arthroscopic training lacks objective evaluation of technical ability and its adequacy is concerning given the accelerating complexity of the field. To combat insufficiencies, emphasis is shifting towards skill acquisition outside the operating room and sophisticated assessment tools. We reviewed (1) the validity of cadaver and surgical simulation in arthroscopic training, (2) the role of psychomotor analysis and arthroscopic technical ability, (3) what validated assessment tools are available to evaluate technical competency, and (4) the quantification of arthroscopic proficiency. METHODS: The Medline and Embase databases were searched for published articles in the English literature pertaining to arthroscopic competence, arthroscopic assessment and evaluation and objective measures of arthroscopic technical skill. Abstracts were independently evaluated and exclusion criteria included articles outside the scope of knee and shoulder arthroscopy as well as original articles about specific therapies, outcomes and diagnoses leaving 52 articles cited in this review. RESULTS: Simulated arthroscopic environments exhibit high levels of internal validity and consistency for simple arthroscopic tasks, however the ability to transfer complex skills to the operating room has not yet been established. Instrument and force trajectory data can discriminate between technical ability for basic arthroscopic parameters and may serve as useful adjuncts to more comprehensive techniques. There is a need for arthroscopic assessment tools for standardized evaluation and objective feedback of technical skills, yet few comprehensive instruments exist, especially for the shoulder. Opinion on the required arthroscopic experience to obtain proficiency remains guarded and few governing bodies specify absolute quantities. CONCLUSIONS: Further validation is required to demonstrate the transfer of complex arthroscopic skills from simulated environments to the operating room and provide objective parameters to base evaluation. There is a deficiency of validated assessment tools for technical competencies and little consensus of what constitutes a sufficient case volume within the arthroscopy community.

Dataset Information

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence.

Publications

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence.

Similar Datasets

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