RESUMO
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.
Assuntos
Crescimento Excessivo da Gengiva/metabolismo , Proteoglicanas de Heparan Sulfato/biossíntese , Adulto , Estudos de Casos e Controles , Ciclosporina/efeitos adversos , Feminino , Expressão Gênica , Crescimento Excessivo da Gengiva/induzido quimicamente , Humanos , Imunossupressores/efeitos adversos , Transplante de Rim , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Proteoglicanas/biossíntese , RNA Mensageiro/análise , Receptores de Fatores de Crescimento Transformadores beta/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estatísticas não Paramétricas , Sindecana-2/biossíntese , Sindecana-4/biossínteseRESUMO
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.
Assuntos
Antibióticos Antineoplásicos/farmacologia , Daunorrubicina/farmacologia , Leucemia Mieloide Aguda/tratamento farmacológico , Lipoproteínas LDL/farmacologia , Adolescente , Adulto , Antibióticos Antineoplásicos/farmacocinética , Criança , Daunorrubicina/farmacocinética , Combinação de Medicamentos , Emulsões , Feminino , Humanos , Células K562/efeitos dos fármacos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Lipoproteínas LDL/farmacocinética , Masculino , Receptores de LDL/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ensaio Tumoral de Célula-TroncoRESUMO
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
Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto , Antibióticos Antineoplásicos , Daunorrubicina , Leucemia Mieloide Aguda , Lipoproteínas LDL , Células-Tronco Neoplásicas , Células da Medula Óssea , Morte Celular , Ésteres do Colesterol , Células K562 , Leucemia Mieloide Aguda , Fosfolipídeos , Receptores de LDL , Reação em Cadeia da Polimerase Via Transcriptase Reversa , RNA MensageiroRESUMO
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.
