Glucocorticoid-induced cell death is mediated through reduced glucose metabolism in lymphoid leukemia cells

Malignant cells are known to have increased glucose uptake and accelerated glucose metabolism. Using liquid chromatography and mass spectrometry, we found that treatment of acute lymphoblastic leukemia (ALL) cells with the glucocorticoid (GC) dexamethasone (Dex) resulted in profound inhibition of glycolysis. We thus demonstrate that Dex reduced glucose consumption, glucose utilization and glucose uptake by leukemic cells. Furthermore, Dex treatment decreased the levels of the plasma membrane-associated glucose transporter GLUT1, thus revealing the mechanism for the inhibition of glucose uptake. Inhibition of glucose uptake correlated with induction of cell death in ALL cell lines and in leukemic blasts from ALL patients cultured ex vivo. Addition of di-methyl succinate could partially overcome cell death induced by Dex in RS4;11 cells, thereby further supporting the notion that inhibition of glycolysis contributes to the induction of apoptosis. Finally, Dex killed RS4;11 cells significantly more efficiently when cultured in lower glucose concentrations suggesting that modulation of glucose levels might influence the effectiveness of GC treatment in ALL. In summary, our data show that GC treatment blocks glucose uptake by leukemic cells leading to inhibition of glycolysis and that these effects play an important role in the induction of cell death by these drugs.     

Comparison of guideline recommendations with daily practice in patients with renal cell carcinoma

Objectives and Aims

To compare guideline recommendations with daily practice patterns in a German patient cohort with renal cell carcinoma.

Patients and methods

81 patients with T1 oder T2 renal cell carcinoma (RCC) were included in this prospective single-center study. All patients were operated in a single institution either by open radical nephrectomy (ORN) or nephron sparing surgery (NSS). Patients and doctors were evaluated using a written questionnaire with a follow-up of 12 months. Follow-up intervals, follow-up modalities (e. g. imaging modalities, laboratory controls of blood and urine) and the call on psycho-oncological support were evaluated.

Results

The majority of patients (72%) were followed up by their urologists. Follow-up examinations included abdominal ultrasound, urine and blood diagnostics, conventional chest x-rays, computed tomography (CT) of abdomen, chest or head or abdominal Magnetic Resonance Imaging (MRI). There were no significant differences between patients operated by ORN or NSS. In total, 12.5% of patients were asking for psycho-oncological support.

Conclusions

In general, patients were followed up according to existing guideline recommendations. Only a small proportion of patients asked for psycho-oncological treatment.     

不完全投影医学图像的多目标向量优化重建算法

目的解决少数据投影图像重建中分辨率差、伪影严重等问题。方法提出了一种基于多目标决策的交叉熵向量优化图像重建算法。算法中折衷考虑了图像重建中最小交叉熵、范数极小化以及最大熵3个目标,并建立了一种新的动态权系数迭代法。应用该算法对模拟的有噪声投影数据和SIEMENS SOMATOM DR3的头部实际扫描数据分别进行了重建。结果文中算法较传统的重建算法．如卷积反投影法、代数重建法以及单目标优化算法,在误差、平滑性以及分辨率方面均有显著改善。结论本算法将对采用迭代法求解少数据投影重建问题产生一定的影响。