Limits...
Comprehensive establishment and characterization of orthoxenograft mouse models of malignant peripheral nerve sheath tumors for personalized medicine.

Castellsagué J, Gel B, Fernández-Rodríguez J, Llatjós R, Blanco I, Benavente Y, Pérez-Sidelnikova D, García-Del Muro J, Viñals JM, Vidal A, Valdés-Mas R, Terribas E, López-Doriga A, Pujana MA, Capellá G, Puente XS, Serra E, Villanueva A, Lázaro C - EMBO Mol Med (2015)

Bottom Line: These aggressive malignancies confer poor survival, with no effective therapy available.Our work points to differences in the engraftment process of primary tumors compared with the engraftment of established cell lines.Sorafenib (a BRAF inhibitor), in combination with doxorubicin or rapamycin, was found to be the most effective treatment for reducing MPNST growth.

View Article: PubMed Central - PubMed

Affiliation: Hereditary Cancer Program, Catalan Institute of Oncology (ICO-IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain Translational Research Laboratory ICO-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.

No MeSH data available.


Related in: MedlinePlus

Preclinical orthoxenograft MPNST models to test drug treatment regimensTumor growth effects of treatment with doxorubicin, sorafenib, rapamycin and combinations thereof in the five MPNST xenograft models. Results are plotted as an average of the log2 ratio of tumor volume at different days relative to the initial value. Statistically significant differences are shown as *P < 0.05 and **P < 0.001 versus control group by the Bonferroni test.For long-term studies, a subgroup of treated mice (n = 3–5 mice/group) was kept alive for a maximum period of 4 months and sacrificed over time when relapsed tumor masses grew as large solid masses (usually 1,500–2,000 mm3). The graph illustrates differences in the time delay (in days) of relapsed tumor masses for the different treatments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4492820&req=5

fig07: Preclinical orthoxenograft MPNST models to test drug treatment regimensTumor growth effects of treatment with doxorubicin, sorafenib, rapamycin and combinations thereof in the five MPNST xenograft models. Results are plotted as an average of the log2 ratio of tumor volume at different days relative to the initial value. Statistically significant differences are shown as *P < 0.05 and **P < 0.001 versus control group by the Bonferroni test.For long-term studies, a subgroup of treated mice (n = 3–5 mice/group) was kept alive for a maximum period of 4 months and sacrificed over time when relapsed tumor masses grew as large solid masses (usually 1,500–2,000 mm3). The graph illustrates differences in the time delay (in days) of relapsed tumor masses for the different treatments.

Mentions: As the orthoxenografts tumor models were found to closely recapitulate the human disease at the histopathological, genomic, and transcriptomic levels, they were used to test clinically relevant therapeutic approaches. The four PDTX plus the orthoxenograft derived from the NF1-cell line S462 were treated in monotherapy with: (i) doxorubicin, the standard clinical chemotherapeutic agent, (ii) oral and (iii) intraperitoneal rapamycin, an allosteric mTOR inhibitor, and (iv) sorafenib, a BRAF inhibitor, or with combined drug regimens (v) doxorubicin + rapamycin, (vi) doxorubicin + sorafenib, and (vii) rapamycin + sorafenib. Both short- and long-term responses were evaluated (Fig7A and B, respectively).


Comprehensive establishment and characterization of orthoxenograft mouse models of malignant peripheral nerve sheath tumors for personalized medicine.

Castellsagué J, Gel B, Fernández-Rodríguez J, Llatjós R, Blanco I, Benavente Y, Pérez-Sidelnikova D, García-Del Muro J, Viñals JM, Vidal A, Valdés-Mas R, Terribas E, López-Doriga A, Pujana MA, Capellá G, Puente XS, Serra E, Villanueva A, Lázaro C - EMBO Mol Med (2015)

Preclinical orthoxenograft MPNST models to test drug treatment regimensTumor growth effects of treatment with doxorubicin, sorafenib, rapamycin and combinations thereof in the five MPNST xenograft models. Results are plotted as an average of the log2 ratio of tumor volume at different days relative to the initial value. Statistically significant differences are shown as *P < 0.05 and **P < 0.001 versus control group by the Bonferroni test.For long-term studies, a subgroup of treated mice (n = 3–5 mice/group) was kept alive for a maximum period of 4 months and sacrificed over time when relapsed tumor masses grew as large solid masses (usually 1,500–2,000 mm3). The graph illustrates differences in the time delay (in days) of relapsed tumor masses for the different treatments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492820&req=5

fig07: Preclinical orthoxenograft MPNST models to test drug treatment regimensTumor growth effects of treatment with doxorubicin, sorafenib, rapamycin and combinations thereof in the five MPNST xenograft models. Results are plotted as an average of the log2 ratio of tumor volume at different days relative to the initial value. Statistically significant differences are shown as *P < 0.05 and **P < 0.001 versus control group by the Bonferroni test.For long-term studies, a subgroup of treated mice (n = 3–5 mice/group) was kept alive for a maximum period of 4 months and sacrificed over time when relapsed tumor masses grew as large solid masses (usually 1,500–2,000 mm3). The graph illustrates differences in the time delay (in days) of relapsed tumor masses for the different treatments.
Mentions: As the orthoxenografts tumor models were found to closely recapitulate the human disease at the histopathological, genomic, and transcriptomic levels, they were used to test clinically relevant therapeutic approaches. The four PDTX plus the orthoxenograft derived from the NF1-cell line S462 were treated in monotherapy with: (i) doxorubicin, the standard clinical chemotherapeutic agent, (ii) oral and (iii) intraperitoneal rapamycin, an allosteric mTOR inhibitor, and (iv) sorafenib, a BRAF inhibitor, or with combined drug regimens (v) doxorubicin + rapamycin, (vi) doxorubicin + sorafenib, and (vii) rapamycin + sorafenib. Both short- and long-term responses were evaluated (Fig7A and B, respectively).

Bottom Line: These aggressive malignancies confer poor survival, with no effective therapy available.Our work points to differences in the engraftment process of primary tumors compared with the engraftment of established cell lines.Sorafenib (a BRAF inhibitor), in combination with doxorubicin or rapamycin, was found to be the most effective treatment for reducing MPNST growth.

View Article: PubMed Central - PubMed

Affiliation: Hereditary Cancer Program, Catalan Institute of Oncology (ICO-IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain Translational Research Laboratory ICO-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.

No MeSH data available.


Related in: MedlinePlus