Targeting abundant survivin expression in liposarcoma: subtype dependent therapy responses to YM155 treatment.
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
/ pharmacology
Doxorubicin
/ administration & dosage
Etoposide
/ administration & dosage
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Imidazoles
/ administration & dosage
Liposarcoma
/ classification
Male
Middle Aged
Naphthoquinones
/ administration & dosage
Prognosis
Retrospective Studies
Survival Rate
Survivin
/ antagonists & inhibitors
Tumor Cells, Cultured
Apoptosis
Inhibitor of apoptosis protein
Liposarcoma
Survivin
Targeted therapy
Journal
Journal of cancer research and clinical oncology
ISSN: 1432-1335
Titre abrégé: J Cancer Res Clin Oncol
Pays: Germany
ID NLM: 7902060
Informations de publication
Date de publication:
Mar 2022
Mar 2022
Historique:
received:
11
08
2021
accepted:
25
11
2021
pubmed:
4
12
2021
medline:
8
3
2022
entrez:
3
12
2021
Statut:
ppublish
Résumé
Liposarcoma (LPS) represent the largest group of malignant soft tissue tumours comprising a heterogeneous group of subtypes in which the degrees of chemoresistance and radiosensitivity strongly vary. Consequently, it is of utmost interest to establish novel therapeutic regimens based on molecular targets. Immunohistochemical staining of survivin was performed in tissue microarrays comprising 49 primary LPS specimens. LPS cell lines were treated with survivin antagonist YM155 and doxorubicin or etoposide alone as well as in combination. Changes in cell viability were investigated and the synergistic effect of a combined therapy analysed. Immunohistochemistry revealed an abundant expression of survivin in LPS that significantly concurred with less-differentiated tumour subtypes and grading. In vitro, we demonstrated the impact of the survivin inhibitor YM155 on dedifferentiated LPS (DDLPS) and, even more imposing, pleomorphic LPS (PLS) tumour cell viability with a strong induction of apoptosis. A combined treatment of doxorubicin or etoposide with YM155 augmented the cytotoxic effects on DDLPS and PLS cells. These findings support the significant role of survivin in the oncogenesis and progression of LPS subtypes providing a rationale to target survivin in eligible in-vivo models and to pioneer clinical applications of survivin-specific substances unfolding their therapeutic potential in LPS patients prospectively.
Identifiants
pubmed: 34860309
doi: 10.1007/s00432-021-03871-5
pii: 10.1007/s00432-021-03871-5
pmc: PMC8881260
doi:
Substances chimiques
BIRC5 protein, human
0
Imidazoles
0
Naphthoquinones
0
Survivin
0
Etoposide
6PLQ3CP4P3
Doxorubicin
80168379AG
sepantronium
UZ77T1VFBM
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
633-645Informations de copyright
© 2021. The Author(s).
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