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Characteristics of human Ewing/PNET sarcoma models.

Teicher BA, Bagley RG, Rouleau C, Kruger A, Ren Y, Kurtzberg L - Ann Saudi Med (2011 Mar-Apr)

Bottom Line: Cell lines that express this genetic profile are confirmed to be those of Ewing sarcoma.Many Ewing sarcoma clinical specimens express the cell surface protein endosialin.With the advent of tools that allow characterization of clinical disease to facilitate optimal treatment, it becomes imperative, especially for rare tumors, to develop preclinical models reflecting disease subsets.

View Article: PubMed Central - PubMed

Affiliation: Genzyme Corporation, 49 New York Avenue, Framingham, MA 01701, USA. beverlyteicher@aol.com

ABSTRACT
Ewing/PNET (peripheral neuroepithelioma) tumors are rare aggressive bone sarcomas occurring in young people. Rare-disease clinical trials can require global collaborations and many years. In vivo models that as accurately as possible reflect the clinical disease are helpful in selecting therapeutics with the most promise of positive clinical impact. Human Ewing/PNET sarcoma cell lines developed over the past 45 years are described. Several of these have undergone genetic analysis and have been confirmed to be those of Ewing/PNET sarcoma. The A673 Ewing sarcoma line has proven to be particularly useful in understanding the biology of this disease in the mouse. The chromosomal translocation producing the EWS/FLI1 fusion transcript characterizes clinical Ewing sarcoma. Cell lines that express this genetic profile are confirmed to be those of Ewing sarcoma. The A673 Ewing sarcoma line grows in culture and as a xenograft in immunodeficient mice. The A673 model has been used to study Ewing sarcoma angiogenesis and response to antiangiogenic agents. Many Ewing sarcoma clinical specimens express the cell surface protein endosialin. Several Ewing sarcoma cell lines, including the A673 line, also express cell surface endosialin when grown as subcutaneous tumor nodules and as disseminated disease; thus the A673 is a useful model for the study of endosialin biology and endosialin-directed therapies. With the advent of tools that allow characterization of clinical disease to facilitate optimal treatment, it becomes imperative, especially for rare tumors, to develop preclinical models reflecting disease subsets. Ewing PNET sarcomas are a rare disease where models are available.

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Immunohistochemical staining of human A673 human tumor xenografts after treatment with bevacizumab or control buffer is shown. The staining for CD31 to visualize endothelial cells is green, and the staining for NG2 to visualize pericytes is red.
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Figure 4: Immunohistochemical staining of human A673 human tumor xenografts after treatment with bevacizumab or control buffer is shown. The staining for CD31 to visualize endothelial cells is green, and the staining for NG2 to visualize pericytes is red.

Mentions: The response of human A673 Ewing sarcoma xenografts grown subcutaneously in immunodeficient mice to treatment with varied doses of bevacizumab is shown in Figure 3. Three doses of bevacizumab were tested: 10, 18.6 and 37.2 mg/kg. Bevacizumab was administered by intraperitoneal injection twice weekly. In the group receiving 37.2 mg/kg, the initiation of treatment was delayed until the tumors reached 300 mm3 . Immunohistochemical analysis of the tumors showed that the vehicle-treated control tumors had well-formed vessels with endothelial cell-lined lumens surrounded by pericytes, while the bevacizumab treatment groups had poorly formed vessels that were often collapsed and missing endothelial cells and scattered endothelial cells with an absence of lumens (Figure 4). Combining bevacizumab/A4.6.1 with doxorubicin, topotecan, paclitaxel, docetaxel or radiotherapy resulted in additive or synergistic tumor growth inhibition. Changes in vascular functions were frequently reported in response to treatment. In some studies, these improvements resulted in an increase in intratumoral uptake of chemotherapy.2223 Bevacizumab/A4.6.1 treatment in combination with radiation therapy increased tumor oxygenation and tumor growth delay.


Characteristics of human Ewing/PNET sarcoma models.

Teicher BA, Bagley RG, Rouleau C, Kruger A, Ren Y, Kurtzberg L - Ann Saudi Med (2011 Mar-Apr)

Immunohistochemical staining of human A673 human tumor xenografts after treatment with bevacizumab or control buffer is shown. The staining for CD31 to visualize endothelial cells is green, and the staining for NG2 to visualize pericytes is red.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3102479&req=5

Figure 4: Immunohistochemical staining of human A673 human tumor xenografts after treatment with bevacizumab or control buffer is shown. The staining for CD31 to visualize endothelial cells is green, and the staining for NG2 to visualize pericytes is red.
Mentions: The response of human A673 Ewing sarcoma xenografts grown subcutaneously in immunodeficient mice to treatment with varied doses of bevacizumab is shown in Figure 3. Three doses of bevacizumab were tested: 10, 18.6 and 37.2 mg/kg. Bevacizumab was administered by intraperitoneal injection twice weekly. In the group receiving 37.2 mg/kg, the initiation of treatment was delayed until the tumors reached 300 mm3 . Immunohistochemical analysis of the tumors showed that the vehicle-treated control tumors had well-formed vessels with endothelial cell-lined lumens surrounded by pericytes, while the bevacizumab treatment groups had poorly formed vessels that were often collapsed and missing endothelial cells and scattered endothelial cells with an absence of lumens (Figure 4). Combining bevacizumab/A4.6.1 with doxorubicin, topotecan, paclitaxel, docetaxel or radiotherapy resulted in additive or synergistic tumor growth inhibition. Changes in vascular functions were frequently reported in response to treatment. In some studies, these improvements resulted in an increase in intratumoral uptake of chemotherapy.2223 Bevacizumab/A4.6.1 treatment in combination with radiation therapy increased tumor oxygenation and tumor growth delay.

Bottom Line: Cell lines that express this genetic profile are confirmed to be those of Ewing sarcoma.Many Ewing sarcoma clinical specimens express the cell surface protein endosialin.With the advent of tools that allow characterization of clinical disease to facilitate optimal treatment, it becomes imperative, especially for rare tumors, to develop preclinical models reflecting disease subsets.

View Article: PubMed Central - PubMed

Affiliation: Genzyme Corporation, 49 New York Avenue, Framingham, MA 01701, USA. beverlyteicher@aol.com

ABSTRACT
Ewing/PNET (peripheral neuroepithelioma) tumors are rare aggressive bone sarcomas occurring in young people. Rare-disease clinical trials can require global collaborations and many years. In vivo models that as accurately as possible reflect the clinical disease are helpful in selecting therapeutics with the most promise of positive clinical impact. Human Ewing/PNET sarcoma cell lines developed over the past 45 years are described. Several of these have undergone genetic analysis and have been confirmed to be those of Ewing/PNET sarcoma. The A673 Ewing sarcoma line has proven to be particularly useful in understanding the biology of this disease in the mouse. The chromosomal translocation producing the EWS/FLI1 fusion transcript characterizes clinical Ewing sarcoma. Cell lines that express this genetic profile are confirmed to be those of Ewing sarcoma. The A673 Ewing sarcoma line grows in culture and as a xenograft in immunodeficient mice. The A673 model has been used to study Ewing sarcoma angiogenesis and response to antiangiogenic agents. Many Ewing sarcoma clinical specimens express the cell surface protein endosialin. Several Ewing sarcoma cell lines, including the A673 line, also express cell surface endosialin when grown as subcutaneous tumor nodules and as disseminated disease; thus the A673 is a useful model for the study of endosialin biology and endosialin-directed therapies. With the advent of tools that allow characterization of clinical disease to facilitate optimal treatment, it becomes imperative, especially for rare tumors, to develop preclinical models reflecting disease subsets. Ewing PNET sarcomas are a rare disease where models are available.

Show MeSH
Related in: MedlinePlus