Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Existe grande interesse na determinação das bases genéticas do carcinoma basocelular (CBC) que expliquem seu fenótipo pouco agressivo e comportamento metastático infreqüente. Investigamos a instabilidade de microssatélites (MSI) e perda de heterozigosidade (LOH) nos microssatélites D6S251 (6q14) e D6S252 (6q16) de CBCs esporádicos de alto e baixo risco histológico através da análise de bandas obtidas pelo gel de poliacrilamida após PCR em comparação com o tecido normal. Não houve alteração do microssatélite D6S252 nas 15 amostras estudadas. Para o microssatélite D6S251, houve alterações em 6 das 26 amostras estudadas (23,07%). MSI e LOH ocorreram em 46,15% das amostras de alto risco (respectivamente 15,38% e 30,76), o que sugere o provável envolvimento da região 6q14 na diferenciação histológica do CBC / A lot of interest lies in determining the genetic basis of basal cell carcinoma (BCC) to explain the lack of aggressive phenotype and infrequent metastatic behavior. We have analyzed the microsatellite instability (MSI) and loss of instability (LOH) in the D6S251 (6q14) and D6S252 (6q16) microsatellites patterns of histological low- high-risk sporadic BCC tumor samples using PCR-based assay in comparison with normal tissue. We have not found any alteration in D6S252 microsatellite 15 samples studied. We have encountered D6S251 alterations in 6 of 26 BCC samples (23.07%).MSI and LOH occurred in 46.15% of high-risk samples (15.38% and 30.76%), These results probably suggests participation of 6q14 region in histological differentiation of BCC

Background. Both basal-like subtype and BRCA1-related breast cancers tend to have a poor overall prognosis and lack of effective treatments. Given that the lung cancer drug gefitinib and the leukemia drug dasatinib inhibit proteins also belonging to the molecular signature of this subtype, we and others hypothesized that they might be useful therapies for those two breast cancer subgroups. / Methods. Eight breast cancer cell lines were characterized by immunohistochemistry and western blotting and were treated with both drugs. Response was measured by using the sulphorhodamine B (SRB) assay. / Results. Two out of six basal-like cell lines were sensitive to gefitinib and five of six to dasatinib. BRCA1-related breast cancers were also responsive to dasatinib (three out of four). Moreover, EGFR and caveolin-1 act as markers for dasatinib sensitivity, but do not appear to be the primary targets of this drug. The presence of SRC but not ABL is necessary to achieve a response to dasatinib. / Conclusion. Dasatinib is more effective in the treatment of basal-like breast cancers than gefitinib and acts by inhibiting SRC and other molecules that are yet to be determined.

Existe grande interesse na determinação das bases genéticas do carcinoma basocelular (CBC) que expliquem seu fenótipo pouco agressivo e comportamento metastático infreqüente. Investigamos a instabilidade de microssatélites (MSI) e perda de heterozigosidade (LOH) nos microssatélites D6S251 (6q14) e D6S252 (6q16) de CBCs esporádicos de alto e baixo risco histológico através da análise de bandas obtidas pelo gel de poliacrilamida após PCR em comparação com o tecido normal. Não houve alteração do microssatélite D6S252 nas 15 amostras estudadas. Para o microssatélite D6S251, houve alterações em 6 das 26 amostras estudadas (23,07%). MSI e LOH ocorreram em 46,15% das amostras de alto risco (respectivamente 15,38% e 30,76), o que sugere o provável envolvimento da região 6q14 na diferenciação histológica do CBC / A lot of interest lies in determining the genetic basis of basal cell carcinoma (BCC) to explain the lack of aggressive phenotype and infrequent metastatic behavior. We have analyzed the microsatellite instability (MSI) and loss of instability (LOH) in the D6S251 (6q14) and D6S252 (6q16) microsatellites patterns of histological low- high-risk sporadic BCC tumor samples using PCR-based assay in comparison with normal tissue. We have not found any alteration in D6S252 microsatellite 15 samples studied. We have encountered D6S251 alterations in 6 of 26 BCC samples (23.07%).MSI and LOH occurred in 46.15% of high-risk samples (15.38% and 30.76%), These results probably suggests participation of 6q14 region in histological differentiation of BCC

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