MicroRNA-10b indicates a poor prognosis of non-small cell lung cancer and targets E-cadherin

Background. MicroRNA-10b(miR-10b) has been reported to be dysregulated in some types of cancer and to play an important role in invasion and metastasis. It was previously found to be a tumor enhancer in NSCLC; however, its clinical significance in NSCLC has not been evaluated. Methods. We compared the expression levels of miR-10b in 73 pairs of NSCLC tissues and the corresponding noncancerous tissues, as well as in human lung cancer cell line A549 and NHBE cell line by qRT-PCR. Expression of E-cadherin (E-cad) was detected using RT-PCR and Western blot analysis. The disease-specific survival (DSS) was analyzed by log-rank test, and survival curves were plotted according to Kaplan–Meier. Results. MiR-10b was significantly upregulated in NSCLC tissues as well as in A549 cell line. The relative miR-10b expression levels were significantly positively correlated with TNM stage (p = 0.01) and regional lymph node involvement (p < 0.001). Kaplan–Meier analysis showed that patients with higher levels of miR-10b had significantly poorer survival than those with lower expression of this miRNA in patients, with a 5-year DSS of 29.5 and 63.8 %, respectively (p = 0.003). The E-cad mRNA and protein were overexpressed in miR-10b-suppressed cells compared with controls. Conclusion. Our results indicated that miR-10b expression was an independent prognostic factor in NSCLC patients. Furthermore, miR-10b might be necessary for driving the expression of E-cad in NSCLC (AU)

No disponible

The therapeutic potential of TRAIL receptor signalling in cancer cells

In tumour cells, activation of the apoptotic machinery by death receptor ligands of the tumour necrosis factor (TNF) receptor superfamily of cytokines represents a novel therapeutic strategy. However, systemic treatment of tumours with TNF-α and CD95 ligand may produce severe toxic effects. The tumour necrosis-related apoptosisinducing ligand (TRAIL) is a member of the TNF family capable of inducing apoptosis in a wide variety of cancer cells upon binding to pro-apoptotic receptors, while having no effect on the majority of normal human cells tested. Interestingly, preclinical studies in mice and nonhuman primates showed no systemic cytotoxicity upon injection of either recombinant TRAIL or agonistic TRAIL-receptor antibodies. Furthermore, these treatments have been shown to effectively suppress the growth of a range of tumour xenografts. Although unwanted effects of some TRAIL preparations have been reported in normal cells, the use of TRAIL receptor agonists could represent a suitable approach in cancer therapy. Here, we shall review our current understanding of apoptotic and non-apoptotic TRAIL signalling, the therapeutic potential of TRAIL-based approaches in cancer treatment, and the results of phase 1 and 2 clinical trials with recombinant TRAIL or agonistic TRAIL receptor antibodies, either as monotherapy or in combination with other chemotherapeutic agents (AU)

La transcriptómica ilustra nuevas vías letales en la nefropatía diabética / No disponible

La nefropatía diabética es la causa más común de enfermedad renal crónica terminal. La modulación terapéutica de la angiotensina II retarda, pero no evita, su progresión. La muerte celular contribuye a la pérdida de masa renal en las nefropatías crónicas. Un consorcio europeo empleó la transcriptómica en biopsias renales para identificar nuevos mediadores implicados en la muerte de la célula renal durante la nefropatía diabética. Un 25% de los genes relacionados con la muerte celular estaban expresados diferencialmente en la nefropatía diabética. TRAIL y osteoprotegerina fueron los genes más sobre expresados, y también estaba aumentado CD74. Las células tubulares y podocitos expresan TRAIL bajo la regulación de citocinas proinflamatorias(MIF vía CD74, TNF). La hiperglucemia sensibiliza a las células renales a la apoptosis inducida por TRAIL, mientras que la osteoprotegerina protege. Estos resultados sugieren que, además de la glucemia, la inflamación y TRAIL pueden ser objetivos terapéuticos en la nefropatía diabética (AU)

Diabetic nephropathy is the most common cause of end stage renal disease. Approaches targeting angiotensin II significantly delay its progression. However, many patients still need renal replacement therapy. High throughput techniques such as unbiased gene expression profiling and proteomics may identify new therapeutic targets. Cell death is thought to contribute to progressive renal cell depletion in chronic nephropathies. A European collaborative effort recently applied renal biopsy transcriptomics to identify novel mediators of renal cell death in diabetic nephropathy. Twenty-five percent of cell death regulatory genes were up or down regulated in diabetic kidneys. TNF-related apoptosis inducing ligand (TRAIL) and osteoprotegerin had the highest-level of expression. In diabetic nephropathy, tubular cells and podocytes express TRAIL. Inflammatory cytokines, including MIF via CD74, up regulate TRAIL. A high glucose environment sensitized renal cells to the lethal effect of TRAIL, while osteoprotegerin is protective. These results suggest that, in addition to glucose levels, inflammation and TRAIL are therapeutic targets in diabetic nephropathy (AU)