RESUMEN
BACKGROUND AND OBJECTIVE: Cyclosporin A-induced gingival overgrowth comprises a variety of signaling pathways (including growth factors and proteoglycans) that are still not completely understood. In the present study, gingival overgrowth was investigated in transplant patients receiving cyclosporin A (cyclosporin A group) and compared with gingival tissues never exposed to the drug (control group) by analyzing the gene expression of the cell-surface heparan sulfate proteoglycans syndecan-2, syndecan-4 and betaglycan. MATERIAL AND METHODS: mRNA analysis was carried out by reverse transcription-polymerase chain reaction amplification of pooled samples from nine patients of the cyclosporin A group and six control subjects. The groups were compared by the Student's t-test. RESULTS: The expression of heparan sulfate proteoglycans was increased in the cyclosporin A group (165% for syndecan-2, 308% for syndecan-4, and 42% for betaglycan) compared with the control group. CONCLUSION: Our findings agree with the current concept of cyclosporin A-induced gingival overgrowth and provide new evidence that its noncollagenous extracellular matrix is overexpressed.
Asunto(s)
Sobrecrecimiento Gingival/metabolismo , Proteoglicanos de Heparán Sulfato/biosíntesis , Adulto , Estudios de Casos y Controles , Ciclosporina/efectos adversos , Femenino , Expresión Génica , Sobrecrecimiento Gingival/inducido químicamente , Humanos , Inmunosupresores/efectos adversos , Trasplante de Riñón , Trasplante de Hígado , Masculino , Persona de Mediana Edad , Proteoglicanos/biosíntesis , ARN Mensajero/análisis , Receptores de Factores de Crecimiento Transformadores beta/biosíntesis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Estadísticas no Paramétricas , Sindecano-2/biosíntesis , Sindecano-4/biosíntesisRESUMEN
Acute myelogenous leukemia (AML) blast cells show high-affinity degradation of low-density lipoprotein (LDL), suggesting an increased expression of cellular LDL receptors. LDE is a lipid microemulsion easily synthesized in vitro which is known to mimic the metabolic pathway of LDL. We used LDE as a carrier for daunorubicin and assayed the cytotoxicity of the complex using AML blast cells since RT-PCR analysis showed that AML cells express LDL receptor mRNA. The LDE:daunorubicin complex killed 46.7% of blast cells and 20.2% of normal bone marrow cells (P<0.001; Student t-test). Moreover, this complex destroyed AML blast cells as efficiently as free daunorubicin. Thus, LDE might be a suitable carrier of chemotherapeutic agents targeting these drugs to neoplastic cells and protecting normal tissues.
Asunto(s)
Antibióticos Antineoplásicos/farmacología , Daunorrubicina/farmacología , Leucemia Mieloide Aguda/tratamiento farmacológico , Lipoproteínas LDL/farmacología , Adolescente , Adulto , Antibióticos Antineoplásicos/farmacocinética , Niño , Daunorrubicina/farmacocinética , Combinación de Medicamentos , Emulsiones , Femenino , Humanos , Células K562/efectos de los fármacos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Lipoproteínas LDL/farmacocinética , Masculino , Receptores de LDL/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Ensayo de Tumor de Célula MadreRESUMEN
Acute myelogenous leukemia (AML) blast cells show high-affinity degradation of low-density lipoprotein (LDL), suggesting an increased expression of cellular LDL receptors. LDE is a lipid microemulsion easily synthesized in vitro which is known to mimic the metabolic pathway of LDL. We used LDE as a carrier for daunorubicin and assayed the cytotoxicity of the complex using AML blast cells since RT-PCR analysis showed that AML cells express LDL receptor mRNA. The LDE:daunorubicin complex killed 46.7 percent of blast cells and 20.2 percent of normal bone marrow cells (P<0.001; Student t-test). Moreover, this complex destroyed AML blast cells as efficiently as free daunorubicin. Thus, LDE might be a suitable carrier of chemotherapeutic agents targeting these drugs to neoplastic cells and protecting normal tissues
Asunto(s)
Humanos , Masculino , Femenino , Niño , Adolescente , Adulto , Antibióticos Antineoplásicos , Daunorrubicina , Leucemia Mieloide Aguda , Lipoproteínas LDL , Células Madre Neoplásicas , Células de la Médula Ósea , Muerte Celular , Ésteres del Colesterol , Células K562 , Leucemia Mieloide Aguda , Fosfolípidos , Receptores de LDL , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , ARN MensajeroRESUMEN
Glycosaminoglycan composition of normal saphenous veins and atherosclerotic saphenous vein grafts is reported. Dermatan sulfate is the main glycosaminoglycan present in both normal saphenous veins and saphenous vein grafts. These tissues also contain chondroitin sulfate and heparan sulfate. Although the total amount of glycosaminoglycans decreased in the grafts (compared with normal saphenous veins), the grafts showed an increase in the relative amounts of dermatan sulfate and chondroitin sulfate. Heparan sulfate was decreased, compared with normal controls. These findings suggest the involvement of blood vessel glycosaminoglycans (not only the arterial glycosaminoglycans) in the process of atherosclerosis.