Therapeutic strategies for locally recurrent and metastatic de-differentiated liposarcoma with herpes simplex virus-thymidine kinase-expressing mesenchymal stromal cells
SCIE
SCOPUS
- Title
- Therapeutic strategies for locally recurrent and metastatic de-differentiated liposarcoma with herpes simplex virus-thymidine kinase-expressing mesenchymal stromal cells
- Authors
- Lee, Hyunjoo; Jo, Eun Byeol; Kim, Su Jin; Yang, Heung Mo; Kim, You Min; Sung, Young Chul; Park, Jae Berm; Hong, Doopyo; Park, Hyojun; Choi, Yoon-La; Kim, Sung Joo
- Date Issued
- 2017-09
- Publisher
- INFORMA HEALTHCARE
- Abstract
- Background aims. Major challenges in de-differentiated liposarcoma (DDLPS) therapy are the high rate of sequential recurrence (>80%) and metastasis (20-30%) following surgical removal. However, well-defined therapeutic strategies for this rare malignancy are lacking and are critically needed. Methods. We investigated a new approach to DDLPS therapy with mesenchymal stromal cells expressing herpes simplex virus thymidine kinase (MSC-TK). In an effort to evaluate this efficacy, in vitro cytotoxicity of MSC-TK against DDLPS cells was analyzed using an apoptosis assay. For pre-clinical study, the MSC-TK induced reduction in recurrence and metastasis was validated in a recurrent DDLPS model after the macroscopic complete resection and lung metastasis DDLPS model. Results. MSC-TK induced apoptosis in DDLPS cells by bystander effects via gap junction intracellular communication (GJIC) of toxic ganciclovir (GCV). Recurrent DDLPS models following no residual tumor/microscopic tumor resection and lung metastasis DDLPS models were established, which suggested clinical relevance. MSC-TK markedly reduced locoregional recurrence rates and prolonged recurrence-free survival, thus increasing overall survival in the recurrent DDLPS model. MSC-TK followed by GCV treatment yielded a statistically significant reduction in early and advanced-stage lung metastasis. Discussion. This therapeutic strategy may serve as an alternative or additional strategy by applying MSC-TK to target residual tumors following surgical resection, thus reducing local relapse and metastasis in these patients.
- Keywords
- SOFT-TISSUE SARCOMAS; STEM-CELLS; CANCER-THERAPY; SUICIDE GENE; HSV-TK; TRAIL; CISPLATIN; PATHWAY; GLIOMA
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/92037
- DOI
- 10.1016/j.jcyt.2017.05.008
- ISSN
- 1465-3249
- Article Type
- Article
- Citation
- CYTOTHERAPY, vol. 19, no. 9, page. 1035 - 1047, 2017-09
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