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1.
Bioorg Med Chem Lett ; 19(9): 2404-8, 2009 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-19356928

RESUMEN

The C-cyclopropylalkylamide scaffold was previously identified as a new structural framework for antiestrogens. A second generation library provided three compounds that bind estrogen receptor (ER)alpha. Further screening of this library identified an ERbeta hit and inspired another round of SAR. A new focused library was tested for binding to the ERs, and for effects on the growth of breast cancer cell lines and protein levels of common cell cycle regulators.


Asunto(s)
Amidas/síntesis química , Antineoplásicos/síntesis química , Química Farmacéutica/métodos , Receptor beta de Estrógeno/química , Amidas/química , Antineoplásicos/farmacología , Unión Competitiva , Ciclo Celular , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Concentración 50 Inhibidora , Ligandos , Modelos Químicos , Unión Proteica , Isoformas de Proteínas , Relación Estructura-Actividad
2.
Mol Cancer Res ; 3(2): 71-7, 2005 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-15755873

RESUMEN

Axillary lymph node status is the most important prognostic factor in predicting disease outcome in women with breast cancer. A number of chromosomal aberrations in primary breast tumors have been correlated with lymph node status and clinical outcome, but chromosomal changes particular to metastatic lymph node tumors have not been well studied. DNA samples isolated from laser-microdissected primary breast and metastatic axillary lymph node tumors from 25 women with invasive breast cancer were amplified using 52 microsatellite markers defining 26 chromosomal regions commonly deleted in breast cancer. Levels and patterns of allelic imbalance (AI) within and between breast and lymph node tumors were assessed to identify chromosomal alterations unique to primary or metastatic tumors and to examine the timing of metastatic potential. The overall frequency of AI in primary breast tumors (0.24) was significantly greater (P < 0.001) than that in lymph node tumors (0.10), and congruent AI events were observed for < 20% of informative markers. AI at chromosomes 11q23.3 and 17p13.3 occurred significantly more frequently (P < 0.05) in primary breast tumors alone; no chromosomal regions showed a significantly higher AI frequency in lymph nodes. Higher rates of AI in primary versus metastatic lymph node tumors suggest that acquisition of metastatic potential may be an early event in carcinogenesis, occurring before significant levels of AI accumulate in the primary tumor. In addition, patterns of AI were highly discordant between tumor types, suggesting that additional genetic alterations accumulated independently in the two cell populations.


Asunto(s)
Desequilibrio Alélico/genética , Neoplasias de la Mama/genética , Carcinoma/genética , Axila , Femenino , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática , Repeticiones de Microsatélite/genética , Estadificación de Neoplasias
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