RESUMEN
Malignant epithelioid angiomyolipoma is a recently described rare tumor of the kidney. Its existence has been questioned, however, on the basis of incomplete evidence of malignant behavior, the absence of an associated classic angiomyolipoma component, or the absence of immunoreactivity for HMB-45 in some cases. We describe a case that was HMB-45-positive and arose in association with a classic angiomyolipoma. The patient was treated with a partial nephrectomy. Three years later, she developed rapidly enlarging liver nodules. A fine-needle aspiration of the liver confirmed the presence of pleomorphic epithelioid cells morphologically and immunohistochemically identical to those comprising the primary renal tumor. After two cycles of treatment with doxorubicin, there was a 50% reduction in the size of the tumors with marked improvement in performance status. We believe this case confirms the existence of a malignant epithelioid angiomyolipoma.
Asunto(s)
Angiomiolipoma/patología , Antígenos de Neoplasias/análisis , Antígenos de Superficie/análisis , Neoplasias Renales/patología , Proteínas de Neoplasias/análisis , Angiomiolipoma/química , Femenino , Humanos , Neoplasias Renales/química , Antígenos Específicos del Melanoma , Persona de Mediana EdadRESUMEN
We have previously reported the inhibitory effects of oncostatin M (OSM) and leukemia inhibitory factor (LIF) on the proliferation of breast cancer cell lines. In this study, we examined the action of OSM and LIF on normal, non-malignant human breast epithelial cells (HBECs). We demonstrated expression of three components of the OSM receptor; gp130, the leukemia inhibitory factor receptor (LIFRbeta) and the OSM specific receptor (OSMRbeta). Treatment of the normal HBECs with OSM and LIF resulted in inhibition of proliferation, even in the presence of the breast mitogen, epidermal growth factor (EGF), which is required for HBEC growth. The inhibition was associated with a reduction of cells in the S-phase of the cell cycle and an accumulation of cells in G0/G1. These results suggest a previously unrecognised physiological role for these growth factors in the regulation of normal breast epithelium.
Asunto(s)
Mama/metabolismo , Proteínas de Caenorhabditis elegans , Células Epiteliales/metabolismo , Inhibidores de Crecimiento/metabolismo , Proteínas del Helminto/metabolismo , Interleucina-6 , Linfocinas/metabolismo , Péptidos/metabolismo , Antígenos CD/metabolismo , Western Blotting , Ciclo Celular , División Celular , Línea Celular , Receptor gp130 de Citocinas , Citocinas/biosíntesis , Factor de Crecimiento Epidérmico/metabolismo , Femenino , Humanos , Factor Inhibidor de Leucemia , Subunidad alfa del Receptor del Factor Inhibidor de Leucemia , Glicoproteínas de Membrana/metabolismo , Oncostatina M , Receptores de Citocinas/metabolismo , Receptores OSM-LIF , Receptores de Oncostatina M , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de TiempoRESUMEN
We compared the safety, effect on plasma proteins, and contribution to hypocalcemic toxicity of 10% pentastarch vs. 5% albumin in plasma exchange. Thirty-two neurology patients underwent 161 plasma exchange procedures. Subjects were randomized to receive either 10% pentastarch (n = 17) or 5% albumin (n = 15) as the first (1/2) of colloid replacement. The second (1/2) of colloid replacement was 5% albumin in all cases. NaCl (plus small amounts of ACD-A) accounted for (1/4) of the total return fluid. Mean total exchange volume was 3,842.6 +/- 450 ml. Hemoglobin, platelet count, coagulation parameters, and plasma fibrinogen were similar between the two groups at the outset of plasma exchange and at the time of the last (4th or 5th) procedure of the series. Immunoglobulin levels were equivalent at the outset and were reduced by plasma exchange to the same extent in the two groups. Serum albumin concentration fell significantly faster in the group receiving pentastarch. On the other hand, serum calcium, corrected for the albumin concentration, fell significantly further in the control group than in the group receiving pentastarch. Mean serum ionized calcium fell approximately 25 % in procedures using only albumin but only approximately 16% when pentastarch was used (P < 0.0001). This was reflected in the occurrence of hypocalcemic toxicity in 33.3% of procedures performed using only albumin but in only 8.1% of those using pentastarch (P = 0.0002). Pentastarch may be suitable for partial colloid replacement in plasma exchange and would have saved our hospital $127,050 to $434,280 in 1998 if used in all procedures.
Asunto(s)
Proteínas Sanguíneas/metabolismo , Calcio/sangre , Derivados de Hidroxietil Almidón/uso terapéutico , Intercambio Plasmático/métodos , Sustitutos del Plasma/uso terapéutico , Adulto , Anciano , Femenino , Humanos , Derivados de Hidroxietil Almidón/efectos adversos , Masculino , Persona de Mediana Edad , Intercambio Plasmático/efectos adversos , Sustitutos del Plasma/efectos adversosRESUMEN
We have recently described the action of Oncostatin M (OSM) to inhibit the proliferation of breast cancer cells. In this study we examined the action of OSM on 2 breast cancer cell lines to further characterize the nature of OSM inhibition of cellular proliferation. Treatment with OSM for 6 days resulted in an approximately 2- to 5-fold decrease in cell number, which was independent of estrogen receptor status. Consistent with this, colony formation was reduced to approximately 50% when cells were exposed to OSM in primary agar cultures. Clonogenicity was further inhibited following 7 days treatment with OSM in monolayer cultures: the total number of clonogenic cells was suppressed approximately 10-fold. Analysis of cell cycle status in OSM-treated cells demonstrated a 40% reduction in the proportion of cells in S phase within 12 hr, with an increase in cells in G0/G1. After 6 days, there was a 10-fold reduction in the absolute number of cells in S phase in OSM-treated cultures. These changes were associated with striking changes in cellular morphology, including disruption of intercellular junctions and the production of lipid droplets. There was a 5-fold increase of c-fos and c-myc mRNA within 30 min of commencing treatment with OSM. In addition, in the ER positive cells there was a decrease in ER mRNA (evident within approximately 2 hr) and ER protein expression following treatment with OSM. Conversely, there was a 5-fold increase in epidermal growth factor receptor (EGFR) mRNA within 4 hr, and a 2.5-fold rise in mRNA for transforming growth factor alpha (TGF alpha). Thus, the inhibition of breast cancer cells by OSM was associated with decreased clonogenicity, a decrease in S phase cells and a variety of phenotypic changes, all consistent with the induction of differentiation.
Asunto(s)
Antineoplásicos/farmacología , Neoplasias de la Mama/patología , Diferenciación Celular/efectos de los fármacos , Inhibidores de Crecimiento/farmacología , Péptidos/farmacología , Transactivadores , Recuento de Células/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Ciclinas/efectos de los fármacos , Ciclinas/genética , Proteínas de Unión al ADN/metabolismo , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Genes fos/efectos de los fármacos , Genes myc/efectos de los fármacos , Sustancias de Crecimiento/metabolismo , Humanos , Oncostatina M , ARN Mensajero/metabolismo , Receptores de Factores de Crecimiento/efectos de los fármacos , Receptores de Factores de Crecimiento/metabolismo , Factor de Transcripción STAT3 , Células Tumorales Cultivadas/efectos de los fármacos , Ensayo de Tumor de Célula MadreRESUMEN
Receptors for the cytokines leukemia inhibitory factor (LIF), interleukin-6 (IL-6), oncostatin M (OSM), ciliary neurotrophic factor (CNTF) and interleukin-11 (IL-11) are members of the structurally conserved hemopoietin receptor superfamily. In addition, they all share the transmembrane signalling protein gp130. In this paper the expression and function of this family of receptors in breast cancer cells was examined. RT-PCR analyses demonstrated that gp130 was expressed in 12/12 breast cell lines and the specific receptor alpha-chains for IL-6, LIF, IL-11 and CNTF were expressed in the majority of these cell lines. This was in contrast to other hemopoietin receptors. Examination of 50 clinical samples of malignant breast tissue by RT-PCR showed a similar pattern of expression of gp130 associated receptors. Treatment of breast cancer cell lines with OSM resulted in changes in cellular morphology. Cellular proliferation was inhibited following exposure to OSM (3/4 cell lines), IL-11 (2/4 cell lines), and by IL-6 and LIF (1/4 cell lines). Cell surface binding of LIF and OSM was also documented. The expression of these receptors in 12/12 cell lines and greater than 95% of clinical samples suggests that these molecules may be important in regulating the growth of breast cells.