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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

Orthoxenograft mouse MPNST models closely resemble primary tumorsOrthotopic MPNST xenografts at passages 1 (OT P1) and 4 (OT P4) were histopathologically similar to their corresponding primary MPNST (PT) in hematoxylin–eosin staining of paraffin-embedded tumor sections from patients MPNST-NF1-001 and MPNST-SP-002. Main panels show a general view of the tumors at low magnification (40×); inset pictures were taken at higher magnification (400×).Orthotopic xenograft and primary MPNSTs exhibited similar immunohistochemical features. A representative immunostained section of vimentin, CD34, S100, and Ki-67 is shown for primary tumors (PT) and orthotopic tumors (OT) from patients MPNST-NF1-001 and MPNST-SP-002. Positive antibody signals are shown in brown, and the hematoxylin counterstain in blue. Main panels show pictures at high magnification (400×); inset pictures show mitotic cells present in these tumors.
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fig02: Orthoxenograft mouse MPNST models closely resemble primary tumorsOrthotopic MPNST xenografts at passages 1 (OT P1) and 4 (OT P4) were histopathologically similar to their corresponding primary MPNST (PT) in hematoxylin–eosin staining of paraffin-embedded tumor sections from patients MPNST-NF1-001 and MPNST-SP-002. Main panels show a general view of the tumors at low magnification (40×); inset pictures were taken at higher magnification (400×).Orthotopic xenograft and primary MPNSTs exhibited similar immunohistochemical features. A representative immunostained section of vimentin, CD34, S100, and Ki-67 is shown for primary tumors (PT) and orthotopic tumors (OT) from patients MPNST-NF1-001 and MPNST-SP-002. Positive antibody signals are shown in brown, and the hematoxylin counterstain in blue. Main panels show pictures at high magnification (400×); inset pictures show mitotic cells present in these tumors.

Mentions: Hematoxylin–eosin staining showed similar histopathological patterns between primary tumors and orthoxenografts at passages 1 and 4 (Fig2A and Supplementary Fig S1A). In addition, analysis of the soft-tissue tumor marker vimentin showed positivity in all models, while three canonical non-nerve tumor markers (epithelial membrane antigen, desmin, and smooth muscle actin) were all negative (Table2, Fig2B and Supplementary Fig S1B). The endothelial marker CD34 was shown to be positive in two of the NF1 tumor models (including the corresponding primary tumors) but negative for the rest of cases. S100, a neural differentiation marker that stains all benign Schwann cell tumors but only ~50% of MPNSTs (Khalifa et al, 2000), revealed positivity in all sporadic models but was negative for the NF1 tumors. As measured by Ki-67 staining, the rate of tumor cell proliferation was similar for all cases (positivity 25–35%) with the exception of S462 cells, which showed a higher proliferation rate (~80%); similar results were observed using P53 staining (Table2, Fig2B and Supplementary Fig S1B).


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)

Orthoxenograft mouse MPNST models closely resemble primary tumorsOrthotopic MPNST xenografts at passages 1 (OT P1) and 4 (OT P4) were histopathologically similar to their corresponding primary MPNST (PT) in hematoxylin–eosin staining of paraffin-embedded tumor sections from patients MPNST-NF1-001 and MPNST-SP-002. Main panels show a general view of the tumors at low magnification (40×); inset pictures were taken at higher magnification (400×).Orthotopic xenograft and primary MPNSTs exhibited similar immunohistochemical features. A representative immunostained section of vimentin, CD34, S100, and Ki-67 is shown for primary tumors (PT) and orthotopic tumors (OT) from patients MPNST-NF1-001 and MPNST-SP-002. Positive antibody signals are shown in brown, and the hematoxylin counterstain in blue. Main panels show pictures at high magnification (400×); inset pictures show mitotic cells present in these tumors.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig02: Orthoxenograft mouse MPNST models closely resemble primary tumorsOrthotopic MPNST xenografts at passages 1 (OT P1) and 4 (OT P4) were histopathologically similar to their corresponding primary MPNST (PT) in hematoxylin–eosin staining of paraffin-embedded tumor sections from patients MPNST-NF1-001 and MPNST-SP-002. Main panels show a general view of the tumors at low magnification (40×); inset pictures were taken at higher magnification (400×).Orthotopic xenograft and primary MPNSTs exhibited similar immunohistochemical features. A representative immunostained section of vimentin, CD34, S100, and Ki-67 is shown for primary tumors (PT) and orthotopic tumors (OT) from patients MPNST-NF1-001 and MPNST-SP-002. Positive antibody signals are shown in brown, and the hematoxylin counterstain in blue. Main panels show pictures at high magnification (400×); inset pictures show mitotic cells present in these tumors.
Mentions: Hematoxylin–eosin staining showed similar histopathological patterns between primary tumors and orthoxenografts at passages 1 and 4 (Fig2A and Supplementary Fig S1A). In addition, analysis of the soft-tissue tumor marker vimentin showed positivity in all models, while three canonical non-nerve tumor markers (epithelial membrane antigen, desmin, and smooth muscle actin) were all negative (Table2, Fig2B and Supplementary Fig S1B). The endothelial marker CD34 was shown to be positive in two of the NF1 tumor models (including the corresponding primary tumors) but negative for the rest of cases. S100, a neural differentiation marker that stains all benign Schwann cell tumors but only ~50% of MPNSTs (Khalifa et al, 2000), revealed positivity in all sporadic models but was negative for the NF1 tumors. As measured by Ki-67 staining, the rate of tumor cell proliferation was similar for all cases (positivity 25–35%) with the exception of S462 cells, which showed a higher proliferation rate (~80%); similar results were observed using P53 staining (Table2, Fig2B and Supplementary Fig S1B).

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