摘要
Las ictiosis hereditarias son un grupo de desórdenes mendelianos, con manifestaciones clínicas y alteraciones genéticas heterogéneas caracterizadas por la presencia de escamas y/o hiperqueratosis. Las ictiosis sindrómicas son aquellas en las que el defecto genético se manifiesta en la piel y también en otros órganos. Presentamos 7 pacientes con ictiosis sindrómicas: un síndrome IFAP (ictiosis folicular, atriquia, fotofobia), un síndrome de Conradi-Hünermann-Happle (CHH), dos síndromes de Netherton (SN), dos síndromes de Sjögren-Larsson (SSL) y un síndrome KID (queratitis, ictiosis, sordera). Se analizan las características clínicas y diagnósticas de nuestros pacientes (AU)
Inherited ichthyosis are a group of clinical and genetic heterogeneous disorders characterized by the presence of scales, hyperkeratosis or both. In syndromic ichthyosis, the genetic defect involves the skin and other organs. We present 7 patients with syndromic ichthyosis: a case of IFAP syndrome (ichthyosis follicularis with alopecia and photophobia), a case of Conradi-Hünermann-Happle (CHH) syndrome, two cases of Netherton syndrome, two cases of Sjögren-Larsson syndrome and a case of KID syndrome (keratitis, ichthyosis and deafness). We analyze the diagnostic and clinical features of our patients (AU)
Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Ichthyosis/etiology , Ichthyosis/pathology , Alopecia , Ichthyosis, X-Linked , Netherton Syndrome , Photophobia , Sjogren-Larsson Syndrome摘要
We treated 4 with a diagnosis of diffuse large B cell lymphoma involving the gastrointestinal tract with rituximab combined with adjusted dose EPOCH (R-DA-EPOCH) scheme based on a comprehensive analysis of the onset process, clinical and pathological features, and prognosis of the patients, and evaluated their treatment response. Complete remission (CR) was achieved in 3 patients after the treatment and 1 patient with diabetes and hypertension died due to severe infection. R-DA-EPOCH regimen as the first-line treatment of gastrointestinal diffuse large B cell lymphoma has a good short-term efficacy, but its long-term efficacy awaits further evaluation in future studies with larger sample sizes.
摘要
This study was aimed to investigate whether the inhibition of NHE1 activity and intracellular acidification can reverse resistance of leukemia cells to the imatinib and to explore downstream signal molecule networks of BCR/ABL in the cells of chronic myelocytic leukemia (CML) patients. The mRNA and protein expression of P-glycoprotein (Pgp) and the drug accumulation were assayed after acidifying the primary leukemia cells of patients or K562/DOX and K562/G01 cells. The effects of intracellular acidification of primary leukemia cells on the phosphorylation level changes of ERK1/2 and p38 MAPK were analyzed by Western blot. The results showed that the intracellular concentration of drugs in the advanced patients increased and the sensitivity of K562/DOX and K562/G01 cells to imatinib was enhanced after intracellular acidification or treatment with NHE1 inhibitor cariporide. With downregulation of intracellular pH, the phosphorylation of p38 MAPK decreased in advanced patients and the phosphorylation of ERK1/2 increased within 3 min and then decreased after 30 min. SB203580, the specific inhibitor of p38 MAPK, displayed a synergistic effect with the inhibitor of NHE1 to downregulate the mRNA and protein expression of Pgp. It is concluded that the inhibiton of NHE1 can significantly decrease the protein expression of Pgp in K562/DOX and K562/G01 cells, increase the accumulation of Rhodamine123 and doxorubicin in the cells of advanced patients and enhance the sensitivity of cells to imatinib in which the p38 MAPK signal transduction pathways involves.
Subject(s)
Humans , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Metabolism , Benzamides , Pharmacology , Cation Transport Proteins , Metabolism , Drug Resistance, Neoplasm , Enzyme Inhibitors , Pharmacology , Gene Expression Regulation, Leukemic , Imatinib Mesylate , Imidazoles , Pharmacology , K562 Cells , MAP Kinase Signaling System , Piperazines , Pharmacology , Pyridines , Pharmacology , Pyrimidines , Pharmacology , Sodium-Hydrogen Exchanger 1 , Sodium-Hydrogen Exchangers , Metabolism , p38 Mitogen-Activated Protein Kinases , Metabolism摘要
This study was aimed to investigate the role of Na(+)/H(+) exchanger 1 (NHE1) in apoptosis of HL-60 cells induced by etoposide. Real-time quantitative PCR (RQ-PCR) and Western blot methods were used to determine the expression of NHE1 in HL-60 cells after the treatment with etoposide. Meanwhile, laser scanning confocal microscopy was used to test the intracellular pH (pHi) of HL-60 cells. Cell apoptosis was measured by DNA fragmentation and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. The results showed that etoposide induced cell apoptosis after treatment for 24 hours. The expression level of NHE1 mRNA increased by 2.848 +/- 0.886 times after treatment with etoposide for 12 hours (p < 0.01), and the expression of NHE1 protein was also up-regulated (p < 0.01). The pHi of HL-60 cells increased from 7.11 to 7.46 after treatment with etoposide for 24 hours. Treatment with cariporide could block etoposide-induced alkalinisation and enhance the apoptosis HL-60 cells. It is concluded that the expression of NHE1 is up-regulated in process of apoptosis of HL-60 cells induced by etoposide and the apoptosis depends on the pH increase caused by NHE1 higher expression.
Subject(s)
Humans , Apoptosis , Cation Transport Proteins , Genetics , Metabolism , DNA Fragmentation , Etoposide , Pharmacology , Gene Expression Regulation, Leukemic , HL-60 Cells , RNA, Messenger , Genetics , Sodium-Hydrogen Exchanger 1 , Sodium-Hydrogen Exchangers , Genetics , Metabolism摘要
This study was aimed to investigate the expression of midkine gene in childhood acute lymphoblastic leukemia patients (ALL) and to explore the possible effects of midkine gene on the chemotherapeutic drug efflux. Real-time quantitative PCR (RQ-PCR) method was used to determine the expression of midkine at mRNA level in 153 ALL patients and 20 normal children. Meanwhile, laser scanning confocal microscope was used to observe the rhodamine 123 efflux from the mononuclear cells in 30 de novo B-ALL patients and 20 healthy individuals (as control). Flow cytometry was used to detect intracellular mean fluorescence intensity (MFI) which can reflect the degree of drug accumulation. The results showed that the significant statistical difference of midkine gene expression was found among the normal controls, the B-ALL patients in complete remission (CR) and progress with the expression level increasing in turns 0.795 (0.697 - 1.570), 3.012 (0.932 - 5.076) and 12.909 (2.385 - 26.347) respectively (p < 0.01). Expression level of midkine gene in progressing B-ALL group was higher than that in progressing T-ALL (p < 0.01). The rhodamine 123 efflux test revealed that MFI in the leukemia cells was obviously lower than that in normal cells (p < 0.01), furthermore, there was an evident negative correlation between the MFI and MK mRNA expression (r = -0.869, p < 0.001). It is concluded that there is powerful drug efflux ability in lymphoblastic leukemia cells with high midkine gene expression. The midkine may take part in multidrug resistance.
Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Male , Case-Control Studies , Drug Resistance, Multiple , Genetics , Drug Resistance, Neoplasm , Genetics , Nerve Growth Factors , Genetics , Metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Drug Therapy , Genetics , Metabolism , RNA, Messenger , Genetics摘要
<p><b>OBJECTIVE</b>To investigate the impact of intracellular acidification (IA) on drug resistance of leukemia cells with high P-glycoprotein (P-gp) expression, and to provide a new method for the reversing of multidrug resistance (MDR).</p><p><b>METHODS</b>Real-time PCR was used to determine the expression level of mdr1 gene, and the leukemia cells with high P-gp expression were selected. The specific inhibitor of Na+/H+ exchanger 1 and the "high K+" buffer were used to acidify the cells, and the confocal laser microscopy was used to determine the intracellular pH (pHi) and effect of IA on the accumulation of doxorubicin. The MTT method was used to determine the effect of IA on the cell viability. The flow cytometry was used to detect the effect of IA on the P-gp function, and Western blotting was used to determine the effect of IA on the expression of P-gp.</p><p><b>RESULTS</b>The pHi was decreased to 7.0, and compared with that of control the mdr1 mRNA expression was decreased to (53.2+/-11.0)% after 1 h, and to (16.6+/-7.0)% after 3 h treatment. The P-gp expression was decreased to (56.0+/-9.0)% of the control after 3 h treatment. The accumulation of Rh123 was 71.03+/-0.47 at pHi 7.0, which was increased obviously as compared to the control group 20.07+/-0.39. The increased accumulation of doxorubicin was also observed by confocal laser microscopy.</p><p><b>CONCLUSION</b>The expression and function of P-gp on the patients cells are inhibited by IA.</p>