RESUMEN
OBJECTIVE: To clarify the possible influence of miR-135b on CXCL12 and airway inflammation in children and experimental mice with asthma. METHODS: The expressions of miR-135b and CXCL12 were detected using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) in the serum of asthmatic children. Besides, the experimental asthmatic mice were established by aerosol inhalation of ovalbumin (OVA) followed by the treatment with agomiR-135b and antagomir-135b. Pathological changes of lung tissues were observed via HE staining and PAS staining. Besides, the airway hyperresponsiveness of mice was elevated and bronchoalveolar lavage fluid (BALF) was isolated for cell categorization and counting. The inflammatory cytokines in BALF were determined by enzyme-linked immunosorbent assay (ELISA), and the infiltration of Th17 cells in lung tissues was measured using flow cytometry. RESULTS: MiR-135b was downregulated and CXCL12 was upregulated in asthmatic children and mice. Overexpression of miR-135b may down-regulate CXCL12 expression in the lung of OVA mice, resulting in significant decreases in inflammatory infiltration, hyperplasia of goblet cell, airway hyperresponsiveness, cell quantity, as well as the quantity of eosinophilic granulocytes, neutrophils and lymphocytes in BALF. Also, the levels of inflammatory cytokines (IL-4, IL-5, IL-13 and IL-17) and the ratio of Th17 cells and IL-17 levels in lung tissues were decreased. However, miR-135b downregulation reversed these changes in OVA mice. CONCLUSION: MiR-135b may inhibit immune responses of Th17 cells to alleviate airway inflammation and hyperresponsiveness in asthma possibly by targeting CXCL12, showing the potential value in asthma treatment.
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Asma , MicroARNs , Animales , Quimiocina CXCL12/metabolismo , Niño , Modelos Animales de Enfermedad , Humanos , Inflamación/patología , Pulmón/patología , Ratones , Ratones Endogámicos BALB C , MicroARNs/genética , MicroARNs/metabolismo , OvalbúminaRESUMEN
In human immunodeficiency virus (HIV)-infected patients, tenofovir disoproxil fumarate (TDF) may cause hypophosphatemia leading to osteomalacia due to renal phosphate wasting. Fibroblast growth factor 23 (FGF23) may play a role in this setting. We present an HIV-infected patient with TDF-induced profound hypophosphatemia, Fanconi syndrome, osteomalacia, and bilateral hip fracture. Routine serum biochemistry was assessed by standard methods. The plasma FGF23 concentration was measured at Mayo Laboratories (Scottsdale, AZ, USA). Bone mineral density (BMD) was measured using a Hologic Discovery densitometer. At presentation, the patient's plasma C-terminal FGF23 was 2,760 reference units (RU)/mL (15 times upper limit of normal; reference interval [RI] ≤ 180 RU/mL), serum phosphate was 0.58 (RI 0.8-1.6 mmol/L), and TmPO4/GFR was 95%. DXA at the lumbar spine showed a Z score of -4.0. Vitamin D3 and oral phosphate were administered, and TDF was discontinued. After 4 months off TDF, lumbar spine BMD significantly increased by 12% (Z score -3.5); by 6 months the plasma C-terminal FGF23 declined to 1.8 times the upper limit of normal, and both urine and serum phosphate levels normalized. By its marked elevation and subsequent near normalization, FGF23 may be responsible for a component of the phosphate wasting syndrome in these patients. The time course of resolution was 6 months. As expected, with calcium, vitamin D, and phosphate management, BMD significantly improved with resolution of osteomalacia. Clinicians should be aware of this side effect of TDF and the time course of its resolution.
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Adenina/análogos & derivados , Fármacos Anti-VIH/efectos adversos , Factores de Crecimiento de Fibroblastos/sangre , Infecciones por VIH/tratamiento farmacológico , Hipofosfatemia/inducido químicamente , Organofosfonatos/efectos adversos , Osteoporosis/sangre , Adenina/efectos adversos , Adulto , Densidad Ósea , Síndrome de Fanconi/inducido químicamente , Factor-23 de Crecimiento de Fibroblastos , Humanos , Hipofosfatemia/complicaciones , Masculino , Osteomalacia/inducido químicamente , Osteoporosis/etiología , TenofovirRESUMEN
The purpose of this article was to examine historic institutional autologous stem cell mobilization practices and evaluate factors influencing mobilization failure and kinetics. In this retrospective study we analyzed clinical records of 1834 patients who underwent stem cell mobilization for autologous transplantation from November 1995 to October 2006 at the Washington University in St. Louis. Successful mobilization was defined as collection of > or =2 x 10(6) CD34(+) cells/kg. From 1834 consecutive patients, 1040 met our inclusion criteria (502 non-Hodgkin's lymphoma [NHL], 137 Hodgkin's lymphoma, and 401 multiple myeloma [MM]). A total of 976 patients received granulocyte colony-stimulating factor (G-CSF) and 64 received G-CSF plus chemotherapy (G/C) for the initial mobilization. Although the median CD34(+) cell yield was higher in G/C group than in G-CSF alone group, the failure rates were similar: 18.8% and 18.6%, respectively. Overall, 53% of patients collected > or =2 x 10(6) CD34(+) cells/kg during the first apheresis with either mobilization regimen. Regardless of mobilization regimen used, MM patients had the highest total CD34(+) cell yield and required less aphereses to collect > or =2 x 10(6) CD34(+) cells/kg. Mobilized, preapheresis, peripheral blood CD34(+) count correlated with first day apheresis yield (r = .877, P < .001) and 20 cells/microL was the minimum threshold needed for a successful day 1 collection. For the remobilization analysis we included patients from the whole database. A total of 269 of 1834 patients underwent remobilization using G/C, G-CSF, and/or GM-CSF, and G-CSF plus plerixafor. Only 23% of remobilized patients achieved > or =2 x 10(6) CD34(+) cells/kg and 29.7% failed to pool sufficient number of stem cells from both collections. Patients receiving G-CSF plus plerixafor had lowest failure rates, P = .03. NHL patients remobilized with G-CSF who waited > or =25 days before remobilization had lower CD34(+) cell yield than those who waited < or =16 days, P = .023. Current mobilization regimens are associated with a substantial failure rate irrespective of underlying disease. Patients who fail initial mobilization are more likely to fail remobilization. These findings suggest that there is a need for more effective first-line mobilization agents.
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Fármacos Anti-VIH/administración & dosificación , Eliminación de Componentes Sanguíneos , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Movilización de Célula Madre Hematopoyética/métodos , Células Madre Hematopoyéticas , Compuestos Heterocíclicos/administración & dosificación , Trasplante de Células Madre , Antígenos CD34 , Bencilaminas , Eliminación de Componentes Sanguíneos/métodos , Ciclamas , Femenino , Neoplasias Hematológicas/terapia , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes , Estudios Retrospectivos , Trasplante AutólogoRESUMEN
PURPOSE: This descriptive study compares overall survival (OS) and locoregional control (LRC) rates between cisplatin-etoposide (EP) and carboplatin-etoposide (EC) at a population level in patients with limited disease (LD) and extensive disease (ED) small cell lung cancer (SCLC). MATERIALS AND METHODS: All patients diagnosed with SCLC from January 2004 to December 2008 were identified. Patients with LD SCLC treated with EP or EC and concurrent or sequential radiotherapy and those with ED SCLC treated with EP or EC were included for analysis. A retrospective review examining prognostic features and outcomes was performed. OS and LRC curves were calculated using the Kaplan-Meier method and compared with the log-rank test. RESULTS: A total of 249 patients with LD SCLC and 287 patients with ED SCLC were identified. Patients treated with EC were significantly older for both LD (median 62 vs. 72, P<0.001) and ED (median 62 vs. 73, P<0.001). Median follow-up times were 37 and 22 months for LD and ED SCLC, respectively. Median OS for EP and EC in LD SCLC patients were 23 and 18 months (P=0.10). LRC rates at 12 months were 81% for the EP group and 68% for the EC group (P=0.97). Median OS for the EP and EC patients with ED SCLC was 10 and 11 months, respectively, (P=0.24). CONCLUSION: Despite the preferential use of EC in an older population, median OS and LRC rates were not significantly different for patients treated with EP for both LD and ED SCLC.