RESUMEN
Several proteins implicated in hormonogenesis of the thyroid have alternatively spliced isoforms. Alternative splicing of pre-mRNA is considered to be important to regulate the hormonal activity. Heterogeneous nuclear ribonucleoproteins (hnRNP) A2 and B1 are two of the abundant nuclear RNA-binding proteins involved in alternative splicing. We examined the expression of hnRNP A2 and B1 in the thyroid, paying particular attention to the relationship between their function and the cellular morphology. B1 was expressed more frequently in cuboidal follicular cells that are hormonally active than in flat follicular cells in normal thyroid, although A2 expression showed no significant difference in two cell types. In Graves' disease, the patients who had high serum levels of triiodothyronine and thyroxine showed significantly increased expression of B1. B1 expression did not differ significantly between normal thyroids and thyroid neoplasms, except undifferentiated (anaplastic) carcinoma. Conclusively, B1 expression varied in relation to hormonal activity in thyroid follicular cells. B1 protein is a good immunohistological marker to detect hormonal activity of follicular cells, and may provide a key to elucidate the splicing mechanisms involved in thyroid hormonogenesis.
Asunto(s)
Enfermedad de Graves/metabolismo , Ribonucleoproteína Heterogénea-Nuclear Grupo A-B/metabolismo , Glándula Tiroides/metabolismo , Neoplasias de la Tiroides/metabolismo , Empalme Alternativo , Biomarcadores de Tumor/metabolismo , Western Blotting , Enfermedad de Graves/patología , Humanos , Inmunohistoquímica , Glándula Tiroides/anatomía & histología , Glándula Tiroides/patología , Neoplasias de la Tiroides/patología , Regulación hacia ArribaRESUMEN
Several proteins implicated in hormonogenesis of the adrenal cortex have alternatively spliced isoforms, which respond differently to adrenocorticotropic hormone (ACTH). Heterogeneous nuclear ribonucleoproteins A2 and B1 are among the abundant pre-mRNA-binding proteins involved in alternative splicing. We examined the expression of A2 and B1 in normal adrenal cortex and tumors. B1 was variably expressed in the zona fasciculata-reticularis, although A2 was diffusely expressed in the three zones. B1 was more abundant in compact cells than clear cells, and B1 expression was frequent in the zona reticularis, which consists mainly of compact cells. In three kinds of cortical adenomas autonomously producing hormones, B1 was generally overexpressed and there were no significant differences among them. In cortisol-producing tumors, non-tumor parts of the cortex, which were generally atrophic due to low ACTH, had less B1 protein than normal adrenals. These results suggested a correlation between B1 expression and the hormonal activity responding to ACTH. In vitro ACTH stimulation induced a biphasic expression of B1 in an H295R cortical carcinoma cell line, and it paralleled hormonogenesis. Conclusively, B1 expression varied in relation to the hormonal activity responding to the ACTH, and it may provide a key to elucidating the splicing mechanisms involved in hormonogenesis.
Asunto(s)
Neoplasias de la Corteza Suprarrenal/metabolismo , Corteza Suprarrenal/metabolismo , Ribonucleoproteína Heterogénea-Nuclear Grupo A-B/biosíntesis , Empalme Alternativo , Línea Celular Tumoral , Electroforesis en Gel de Poliacrilamida , Ribonucleoproteína Heterogénea-Nuclear Grupo A-B/genética , Humanos , InmunohistoquímicaRESUMEN
PURPOSE: Cancer diagnostics and therapeutics are often based on clinically relevant markers that are expressed specifically in a malignant tissue at levels higher than in normal tissue. We examined potential markers for papillary thyroid carcinoma (PTC) by monitoring PTC-specific gene expression using cDNA microarray. EXPERIMENTAL DESIGN: Gene expression profiles for PTC tissue, normal thyroid tissue, and healthy peripheral blood cells were compared by use of a human 4000-gene cDNA microarray. Protein expressions of the up-regulated genes in PTC were examined in thyroid tissues by immunohistochemistry. RESULTS: Sixty-four genes were overexpressed in PTC tissue relative to normal thyroid tissue and healthy peripheral blood cells. The genes that were up-regulated in PTC were involved in cell cycle regulation, DNA damage response, angiogenesis, and oncogenesis. Among these genes, basic fibroblast growth factor and platelet-derived growth factor were identified by immunochemical methods as proteins that are specifically expressed at high levels in thyroid neoplasms. Basic fibroblast growth factor, which has been identified as a biomarker for PTC, was overexpressed in 54% of PTC cases, 67% of follicular thyroid carcinomas, and 36% of benign thyroid neoplasms. Platelet-derived growth factor was overexpressed in 81% of PTC cases and 100% of follicular carcinomas, but was immunonegative in normal thyroid tissues and benign thyroid neoplasms. CONCLUSIONS: Platelet-derived growth factor may be a potential biomarker for PTC and follicular carcinoma. Expression profile analysis using a microarray followed by immunohistochemical study can be used to facilitate the development of molecular biomarkers for cancer.
Asunto(s)
Carcinoma Papilar/genética , Perfilación de la Expresión Génica/métodos , Factor de Crecimiento Derivado de Plaquetas/genética , Neoplasias de la Tiroides/genética , Ciclo Celular/genética , Ciclo Celular/fisiología , Regulación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Marcadores Genéticos , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Valores de Referencia , Glándula Tiroides/citología , Glándula Tiroides/fisiología , Neoplasias de la Tiroides/patologíaRESUMEN
Neo-adjuvant chemotherapy has been used for locally advanced breast cancers. With special attention to the proportion of intraductal component, we pathologically studied 25 patients that underwent neo-adjuvant chemotherapy via intra-arterial infusion or intravenous injection. In general, neo-adjuvant chemotherapy had a favorable effect on tumor reduction. The effectiveness varies depending on the predominance of intraductal component. The cases with a high proportion of intraductal component had lower response to the chemotherapies. The larger number of cancer cells remained within the mammary ducts. The residual cancer cells conserved proliferative activity. Intraductal component is poorly responsive to neoadjuvant chemotherapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma Intraductal no Infiltrante/tratamiento farmacológico , Quimioterapia Adyuvante , Paclitaxel/análogos & derivados , Taxoides , Adulto , Anciano , Apoptosis , División Celular , Ciclofosfamida/administración & dosificación , Docetaxel , Doxorrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Antígeno Ki-67/biosíntesis , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Resultado del TratamientoRESUMEN
Phase-contrast x-ray imaging with x-ray interferometer can depict the minute difference within the biological object, and its sensitivity is about 1000 times higher than that of absorption-contrast method. For biomedical use of this technique, a large monolithic x-ray interferometer and 2 crystal interferometer having a field of view with 25 mm x 25 mm is being developed. Phase-contrast x-ray CT could reveal detail structures within tumor and surrounded tissue, and the vessel imaging of rat liver is also possible using physiological saline at 17.7 keV x-ray energy. Recently, human breast tissues were imaged at 35 keV and the contrast of image was much better than usual absorption contrast x-ray image obtained at 17.7 keV energy.