Dataset Information

Induction of Myogenic Differentiation Improves Chemosensitivity of Chemoresistant Cells in Soft-Tissue Sarcoma Cell Lines.

ABSTRACT: Rhabdomyosarcoma (RMS) and rhabdoid tumors (RT) are rare soft-tissue malignancies with the highest incidence in infants, children, and adolescents. Advanced, recurrent, and/or metastatic RMS and RT exhibit poor response to treatment. One of the main mechanisms behind resistance to treatment is believed to be intratumoral heterogeneity. In this study, we investigated the myogenic determination factor 1 (MYOD1) and Noggin (NOG) markers in an embryonal RMS (ERMS) cell line and an RT cell line and the differential response of the MYOD1 and NOG expressing subpopulations to chemotherapy. Importantly, we found that these markers together identify a subpopulation of cells (MYOD1+ NOG+ cells) with primary resistance to Vincristine and Doxorubicin, two commonly used chemotherapies for ERMS and RT. The chemoresistant MYOD1+ NOG+ cells express markers of undifferentiated cells such as myogenin and ID1. Combination of Vincristine with TPA/GSK126, a drug combination shown to induce differentiation of RMS cell lines, is able to partially overcome MYOD1/NOG cells chemoresistance.

SUBMITTER: Dawson LE

PROVIDER: S-EPMC7136814 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Induction of Myogenic Differentiation Improves Chemosensitivity of Chemoresistant Cells in Soft-Tissue Sarcoma Cell Lines.

Dawson Lucy E LE D'Agostino Luca L Hakim Abraham A AA Lackman Richard D RD Brown Spencer A SA Sensenig Richard B RB Antonello Zeus A ZA Kuzin Igor I II

Sarcoma 20200326

Rhabdomyosarcoma (RMS) and rhabdoid tumors (RT) are rare soft-tissue malignancies with the highest incidence in infants, children, and adolescents. Advanced, recurrent, and/or metastatic RMS and RT exhibit poor response to treatment. One of the main mechanisms behind resistance to treatment is believed to be intratumoral heterogeneity. In this study, we investigated the myogenic determination factor 1 (MYOD1) and Noggin (NOG) markers in an embryonal RMS (ERMS) cell line and an RT cell line and t ...[more]

PMID: 32300280

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Project description:Soft-tissue sarcoma (STS) represent a rare tumor entity, accounting for less than 1% of adult malignancies. The cornerstone of curative intent treatment is surgery with free margins, although the extent of the surgical approach has been subject to change in the last decades. Multimodal approaches usually including radiation therapy have replaced extensive surgical procedures in order to preserve functionality while maintaining adequate local control. However, the possibility to apply adequate radiation doses by external beam radiation therapy (EBRT) can be limited in some situation especially in case of directly adjacent organs at risk with low radiation tolerance. Application of at least a part of the total dose via intraoperative radiation therapy (IORT) with a single fraction during the surgical procedure may overcome those limitations, because radiosensitive structures can be moved out of the radiation field resulting in reduced toxicity while the enhanced biological effectivity of the high single dose improves local control. The current review summarizes rationale, techniques, oncological and functional outcomes including possible pitfalls and associated toxicities based on the published literature for IORT focusing on extremity and retroperitoneal STS. In extremity STS, combination of limb-sparing surgery, IORT and pre- or postoperative EBRT with moderate doses consistently achieved excellent local control rates at least comparable to approaches using EBRT alone but usually including patient cohorts with higher proportions of unfavourable prognostic factors. Further on, IORT containing approaches resulted in very high limb preservation rates and good functional outcome, probably related to the smaller high dose volume. In retroperitoneal STS, the combination of preoperative EBRT, surgery and IORT consistently achieved high local control rates which seem superior to surgery alone or surgery with EBRT at least with regard to local control and in some reports even to overall survival. Further on, preoperative EBRT in combination with IORT seems to be superior to the opposite combination with regard to local control and toxicity. No major differences in wound healing disturbances or postoperative complication rates can be observed with IORT compared to non-IORT containing approaches. Neuropathy of major nerves remains a dose limiting toxicity requiring dose restrictions or exclusion from target volume. Gastrointestinal structures and ureters should be excluded from the IORT area whenever possible and the IORT volume should be restricted to the available minimum. Nevertheless, IORT represents an ideal boosting method if combined with EBRT and properly executed by experiences users which should be further evaluated preferably in prospective randomized trials.

Dataset Information

Induction of Myogenic Differentiation Improves Chemosensitivity of Chemoresistant Cells in Soft-Tissue Sarcoma Cell Lines.

Publications

Induction of Myogenic Differentiation Improves Chemosensitivity of Chemoresistant Cells in Soft-Tissue Sarcoma Cell Lines.

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