Compositions and methods for treating sarcoma
A composition and sarcoma technology, applied in the field of compositions and methods for treating sarcoma, capable of solving problems such as poor prognosis of patients
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
example 1
[0128] Example 1. IGF-1, IGF-2 and IGF-1R levels and IR-A:IR-B ratios in sarcoma xenografts and cells
[0129] Insulin-like growth factor 1 (IGF-1), insulin-like growth factor 2 (IGF-2), and Insulin-like growth factor 1 receptor (IGF-1R) mRNA levels. exist Figure 1A to Figure 1D The results of these analyzes are shown in . Such as Figure 1A As shown, the mRNA level of IGF-1 was found to be significantly higher in Ewing's sarcoma compared to osteosarcoma (p=0.029) and rhabdomyosarcoma (p=0.0024). In contrast, if Figure 1B As shown, mRNA levels of IGF-2 were found to be significantly higher in rhabdomyosarcoma compared to Ewing's sarcoma (p=0.0005) and osteosarcoma (p=0.0066). Such as Figure 1C As shown, all three subtypes of sarcomas express high mRNA levels of IGF-1R. Most of the sarcoma xenograft samples assayed had a high cycle threshold (ΔCt) differential (ΔCt Figure 1D ).
[0130] IGF ligand and receptor mRNA levels were also measured in various sarcoma cell li...
example 2
[0135] Example 2. MEDI-573 Inhibits Sarcoma Cell Growth and Proliferation Driven by Autocrine or Paracrine IGF Ligands
[0136] To determine the effect of treatment with the MEDI-573 antibody on tumor cell growth, three rhabdomyosarcoma cell lines were treated with MEDI-573, an anti-IGF antibody, in the absence of exogenous IGF-1 or IGF-2 (RD, SJCRH30, and Hs729); three Ewing sarcoma cell lines (RD-ES, TC-71, and SK-ES-1); and four osteosarcoma cell lines (SJSA-1, KHOS, MG-63 , and SAOS2).
[0137] In the absence of exogenous IGF-1 or IGF-2, all three Ewing sarcoma cell lines (RD-ES, TC-71, and SK-ES-1) and one rhabdomyosarcoma cell line (SJCRH30) Growth was inhibited by MEDI-573 antibody. Without being bound by a particular theory, this result suggests that these cell lines secrete endogenous IGF-1 or IGF-2 to drive their growth (autocrine drive). There was modest growth inhibition (-30% at the highest dose tested) in RD and SJSA-1 cells. These results are depicted in Tab...
example 3
[0147] Example 3. MEDI-573 inhibits tumor growth in a sarcoma xenograft model
[0148] Twice-weekly treatment of mice bearing RD-ES (Ewing's sarcoma) xenografts with MEDI-573 resulted in 25% inhibition of tumor growth at 10 mg / kg, 44% at 30 mg / kg, and 52% at 60 mg / kg ( Figure 7A ). Similar effects were seen when mice bearing TC-71 xenografts, another Ewing sarcoma model, were treated in the same manner. Comparable results were obtained when MEDI-573 was used to treat mice bearing SJSA-1 (an osteosarcoma model) xenograft ( Figure 7B ). Although the proliferation of SK-ES-1 and SJCRH30 cells was inhibited by MEDI-573 in vitro in the absence of exogenous IGF, the in vivo growth of these two models was not affected by MEDI-573 treatment. Consistent with this in vitro finding, KHOS cells also did not respond to MEDI-573 in vivo ( Figure 7C ). MEDI-573 treatment was well tolerated in mice as no weight loss was observed.
[0149] Free IGF ligand was measured in xenograft tu...
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More