Retinol dehydrogenase 10 promotes metastasis of glioma cells via the transforming growth factor-β/SMAD signaling pathway / 中华医学杂志(英文版)

Background@#Glioma is the most common primary malignant tumor in the central nervous system. Because of the resistance of glioma to chemoradiotherapy and its aggressive growth, the survival rate of patients with glioma has not improved. This study aimed to disclose the effect of retinol dehydrogenase 10 (RDH10) on the migration and invasion of glioma cells, and to explore the potential mechanism.@*Methods@#Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the expression levels of RDH10 in healthy glial cells and glioma cells. Human glioma cell strains, U87 and U251, were infected with negative control or RDH10-interfering lentiviruses. RT-PCR and Western blotting were performed to determine the knockdown efficiency. Scratch and transwell assays were used to assess cell migration and invasion after RDH10 knockdown. Finally, changes in transforming growth factor-β (TGF-β)/SMAD signaling pathway-related expression were examined by Western blotting. Differences between groups were analyzed by one-way analysis of variance.@*Results@#RDH10 was highly expressed in glioma cells. Compared with the control group, RDH10 knockdown significantly reduced RDH10 messenger RNA and protein expression levels in U87 and U251 glioma cells (U87: 1.00 ± 0.08 vs. 0.22 ± 0.02, t= 16.55, P < 0.001; U251: 1.00 ± 0.17 vs. 0.39 ± 0.01, t= 6.30, P < 0.001). The scratch assay indicated that compared with the control group, RDH10 knockdown significantly inhibited the migration of glioma cells (U87: 1.00% ± 0.04% vs. 2.00% ± 0.25%, t= 6.08, P < 0.01; U251: 1.00% ± 0.11% vs. 2.48% ± 0.31%, t= 5.79, P < 0.01). Furthermore, RDH10 knockdown significantly inhibited the invasive capacity of glioma cells (U87: 97.30 ± 7.01 vs. 13.70 ± 0.58, t = 20.36, P < 0.001; U251: 96.20 ± 7.10 vs. 18.30 ± 2.08, t = 18.51, P < 0.001). Finally, Western blotting demonstrated that compared with the control group, downregulation of RDH10 significantly inhibited TGF-β expression, phosphorylated SMAD2, and phosphorylated SMAD3 (TGF-β: 1.00 ± 0.10 vs. 0.53 ± 0.06, t= 7.05, P < 0.01; phosphorylated SMAD2: 1.00 ± 0.20 vs. 0.42 ± 0.17, t= 4.01, P < 0.01; phosphorylated SMAD3: 1.00 ± 0.18 vs. 0.41 ± 0.12, t= 4.12, P < 0.01).@*Conclusion@#RDH10 knockdown might inhibit metastasis of glioma cells via the TGF-β/SMAD signaling pathway.

Retinol dehydrogenase 10 promotes metastasis of glioma cells via the transforming growth factor-β/SMAD signaling pathway / 中华医学杂志(英文版)

BACKGROUND@#Glioma is the most common primary malignant tumor in the central nervous system. Because of the resistance of glioma to chemoradiotherapy and its aggressive growth, the survival rate of patients with glioma has not improved. This study aimed to disclose the effect of retinol dehydrogenase 10 (RDH10) on the migration and invasion of glioma cells, and to explore the potential mechanism.@*METHODS@#Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the expression levels of RDH10 in healthy glial cells and glioma cells. Human glioma cell strains, U87 and U251, were infected with negative control or RDH10-interfering lentiviruses. RT-PCR and Western blotting were performed to determine the knockdown efficiency. Scratch and transwell assays were used to assess cell migration and invasion after RDH10 knockdown. Finally, changes in transforming growth factor-β (TGF-β)/SMAD signaling pathway-related expression were examined by Western blotting. Differences between groups were analyzed by one-way analysis of variance.@*RESULTS@#RDH10 was highly expressed in glioma cells. Compared with the control group, RDH10 knockdown significantly reduced RDH10 messenger RNA and protein expression levels in U87 and U251 glioma cells (U87: 1.00 ± 0.08 vs. 0.22 ± 0.02, t = 16.55, P < 0.001; U251: 1.00 ± 0.17 vs. 0.39 ± 0.01, t = 6.30, P < 0.001). The scratch assay indicated that compared with the control group, RDH10 knockdown significantly inhibited the migration of glioma cells (U87: 1.00% ± 0.04% vs. 2.00% ± 0.25%, t = 6.08, P < 0.01; U251: 1.00% ± 0.11% vs. 2.48% ± 0.31%, t = 5.79, P < 0.01). Furthermore, RDH10 knockdown significantly inhibited the invasive capacity of glioma cells (U87: 97.30 ± 7.01 vs. 13.70 ± 0.58, t = 20.36, P < 0.001; U251: 96.20 ± 7.10 vs. 18.30 ± 2.08, t = 18.51, P < 0.001). Finally, Western blotting demonstrated that compared with the control group, downregulation of RDH10 significantly inhibited TGF-β expression, phosphorylated SMAD2, and phosphorylated SMAD3 (TGF-β: 1.00 ± 0.10 vs. 0.53 ± 0.06, t = 7.05, P < 0.01; phosphorylated SMAD2: 1.00 ± 0.20 vs. 0.42 ± 0.17, t = 4.01, P < 0.01; phosphorylated SMAD3: 1.00 ± 0.18 vs. 0.41 ± 0.12, t = 4.12, P < 0.01).@*CONCLUSION@#RDH10 knockdown might inhibit metastasis of glioma cells via the TGF-β/SMAD signaling pathway.

Tumor-induced osteomalacia with elevated fibroblast growth factor 23: a case of phosphaturic mesenchymal tumor mixed with connective tissue variants and review of the literature / 癌症

Tumor-induced osteomalacia (TIO), or oncogenic osteomalacia (OOM), is a rare acquired paraneoplastic disease characterized by renal phosphate wasting and hypophosphatemia. Recent evidence shows that tumor-overexpressed fibroblast growth factor 23 (FGF23) is responsible for the hypophosphatemia and osteomalacia. The tumors associated with TIO are usually phosphaturic mesenchymal tumor mixed connective tissue variants (PMTMCT). Surgical removal of the responsible tumors is clinically essential for the treatment of TIO. However, identifying the responsible tumors is often difficult. Here, we report a case of a TIO patient with elevated serum FGF23 levels suffering from bone pain and hypophosphatemia for more than three years. A tumor was finally located in first metacarpal bone by octreotide scintigraphy and she was cured by surgery. After complete excision of the tumor, serum FGF23 levels rapidly decreased, dropping to 54.7% of the preoperative level one hour after surgery and eventually to a little below normal. The patient's serum phosphate level rapidly improved and returned to normal level in four days. Accordingly, her clinical symptoms were greatly improved within one month after surgery. There was no sign of tumor recurrence during an 18-month period of follow-up. According to pathology, the tumor was originally diagnosed as "lomangioma" based upon a biopsy sample, "proliferative giant cell tumor of tendon sheath" based upon sections of tumor, and finally diagnosed as PMTMCT by consultation one year after surgery. In conclusion, although an extremely rare disease, clinicians and pathologists should be aware of the existence of TIO and PMTMCT, respectively.

Measurement of serum free light chains and its clinical significance in 20 newly diagnosed patients of multiple myeloma / 中国实验血液学杂志

The objective of this study was to explore the clinical significance of measuring serum free light chains (sFLC) and to compare with serum total light chains (free and binded) in multiple myeloma (MM). sFLC in 20 newly diagnosed MM patients and 20 cases of healthy people as control were measured by immuno-nephelometric assays; the serum light chains and kappa/lambda ratio were measured in all patients, while immunofixation electrophoresis (IFE) tests were carried out at the same time in 18 out of 20 patients. The results showed that the abnormality of serum free light chains and kappa/lambda ratio were found in all of the 20 newly diagnosed MM patients (p < 0.01). The measurement of sFLC showed higher sensitivity than the total serum chains (p < 0.01). It is concluded that the method testing sFLC by immuno-nephelometric assay combined with kappa/lambda ratio is valuable for MM diagnosis, and the measurement of sFLC can be used as one of indicators for MM diagnosis.

Efficacy Observation of Telmisartan Combined with Metoprolol in the Treatment of Chronic Heart Failure / 中国药房

OBJECTIVE:To observe the efficacy of telmisartan combined with metoprolol in the treatment of chronic heart failure.METHODS:102 patients with chronic heart failure admitted in hospital from Jan.2008 to Feb.2010 were given therapy of cardiotonic,diuresis,vasodilator,anti-infection,blood sugar control.Then patients were additionally treated with telmisartan and metoprolol.The parameters before treatment and after 2 weeks of treatment were determined such as heart function,24 h dynamic electrocardiogram,Bultrasound of heart,blood pressure,heart rate,6 min walking distance,liver and kidney function,electrolytes,blood sugar,urine routine,myocardial enzyme.RESULTS:After treatment,cardiac function,heart rate and 6 min walking distance,left ventricular ejection fraction(LVEF),the number of premature beats were significantly reduced(P