8 research outputs found
Molecular alterations of monophasic synovial sarcoma: loss of chromosome 3p does not alter RASSF1 and MLH1 transcriptional activity
Differential diagnosis of monophasic
synovial sarcoma requires the detection of specific
biological markers. In this study we evaluated the
presence of molecular alterations in 15 monophasic
synovial sarcomas. Multiple changes affecting
chromosome arms were detected by CGH-array in all
microdissected cases available, and an association
between gain or loss of specific regions harbouring
cancer progression-associated genes and aneuploid
status was found. The most frequent alteration was loss
of 3p including 3p21.3-p23 region that, however, did not
involve the promoter regions of the corresponding genes,
RASSF1 and MLH1. Using Real-Time PCR, mRNA
levels of both resulted moderately high compared to
normal tissue; however, the weak to absent protein
expression suggests RASSF1 and MLH1 posttranscription
deregulation. Moreover, immunohistochemical
analysis revealed that both mesenchymal
and epithelial antigens were present in diploid tumours.
These findings confirm the genetic complexity of
monophasic synovial sarcoma and underline the need to
integrate different analyses for a better knowledge of this
tumour, essential to investigate new diagnostic and
prognostic markers
Targeting glutathione-S transferase enzymes in musculoskeletal sarcomas: a promising therapeutic strategy.
Recent studies have indicated that targeting glutathione-S-transferase (GST) isoenzymes may be a promising novel strategy to improve the efficacy of conventional chemotherapy in the three most common musculoskeletal tumours: osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma. By using a panel of 15 drug-sensitive and drug-resistant human osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma cell lines, the efficay of the GST-targeting agent 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) has been assessed and related to GST isoenzymes expression (namely GSTP1, GSTA1, GSTM1, and MGST). NBDHEX showed a relevant in vitro activity on all cell lines, including the drug-resistant ones and those with higher GSTs levels. The in vitro activity of NBDHEX was mostly related to cytostatic effects, with a less evident apoptotic induction. NBDHEX positively interacted with doxorubicin, vincristine, cisplatin but showed antagonistic effects with methotrexate. In vivo studies confirmed the cytostatic efficay of NBDHEX and its positive interaction with vincristine in Ewing's sarcoma cells, and also indicated a positive effect against the metastatisation of osteosarcoma cells. The whole body of evidence found in this study indicated that targeting GSTs in osteosarcoma, Ewing's sarcoma and rhabdomyosarcoma may be an interesting new therapeutic option, which can be considered for patients who are scarcely responsive to conventional regimens