Activation Status of Receptor Tyrosine Kinases as an Early Predictive Marker of Response to Chemotherapy in Osteosarcoma Parunya Chaiyawat, Jeerawan.

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Activation Status of Receptor Tyrosine Kinases as an Early Predictive Marker of Response to Chemotherapy in Osteosarcoma Parunya Chaiyawat, Jeerawan Klangjorhor, Jongkolnee Settakorn, Voraratt Champattanachai, Areerak Phanphaisarn, Pimpisa Teeyakasem, Jisnuson Svasti, Dumnoensun Pruksakorn Translational Oncology Volume 10, Issue 5, Pages 846-853 (October 2017) DOI: 10.1016/j.tranon.2017.08.005 Copyright © 2017 The Authors Terms and Conditions

Figure 1 Tyrosine phosphorylation of tested RTKs in osteosarcoma. (A) Number and percentage of osteosarcoma cases in which RTKs were phosphorylated at tyrosine residues. (B) Unsupervised hierarchical clustering of six RTKs based on levels of tyrosine phosphorylation (MFI) of the 32 osteosarcoma cases (GENESIS software). Osteosarcoma case numbers are shown on the right. Translational Oncology 2017 10, 846-853DOI: (10.1016/j.tranon.2017.08.005) Copyright © 2017 The Authors Terms and Conditions

Figure 2 Analysis of median survival of stage IIB osteosarcoma by activation states of Group A-RTKs (c-Kit, VEGFR2, c-Met, and HER2). (A) Active (osteosarcoma tissues with at least one RTK tyrosine phosphorylated) and inactive (none of the RTK tyrosine phosphorylated). (B) Kaplan-Meier curves of overall survival based on activation status of RTKs. (C) Kaplan-Meier curves based on percentage of tumor necrosis. (P values were calculated with the log-rank test). Translational Oncology 2017 10, 846-853DOI: (10.1016/j.tranon.2017.08.005) Copyright © 2017 The Authors Terms and Conditions

Figure 3 Boxplot of percentages of tumor necrosis of osteosarcoma tissue samples obtained after neoadjuvant treatments (doxorubicin and cisplatin) in patients with at least one active Group A-RTK and with no active Group A-RTKs. (P values were calculated with the Mann-Whitney U test). Translational Oncology 2017 10, 846-853DOI: (10.1016/j.tranon.2017.08.005) Copyright © 2017 The Authors Terms and Conditions

Figure 4 In vitro cell viability of osteosarcoma primary cells using MTT assay after treatment with (A) doxorubicin and (B) cisplatin at indicated drug concentrations. (C) IC50 averages of doxorubicin and cisplatin from three independent experiments. Graph shows an association between the number of activated Group A-RTKs and sensitivity to (D) doxorubicin and (E) cisplatin. Active Group A-RTKs: at least one positive tyrosine phosphorylation of c-Kit, VEGFR2, c-Met or HER2. Inactive Group A-RTKs: unphosphorylation of c-Kit, VEGFR2, c-Met, and HER2 (results of matched frozen tissues from multiplex immunoassay). Translational Oncology 2017 10, 846-853DOI: (10.1016/j.tranon.2017.08.005) Copyright © 2017 The Authors Terms and Conditions

Figure 5 Association of proliferation of primary osteosarcoma cells with (A) the activation of Group A RTKs, (B) sensitivity to doxorubicin, and (C) sensitivity to cisplatin. P values of the linear relationship between the two data sets were calculated using the Pearson correlation coefficient. Translational Oncology 2017 10, 846-853DOI: (10.1016/j.tranon.2017.08.005) Copyright © 2017 The Authors Terms and Conditions