Feasibility of flattening filter free beams for hippocampal avoidance whole-brain radiotherapy: a dosimetric and radiobiological analysis

ObjectivesThe purpose of this study is to evaluate the potential of the flattening filter free (FFF) mode of a linear accelerator for patients with hippocampal avoidance whole-brain radiotherapy (HA-WBRT) by comparison with flattened beams (FF) technique in the application of volumetric modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT) using dosimetric and radiobiological indexes based on the volume of hippocampus and target.Methods2 VMAT- and 2 IMRT- plans were optimized in Eclipse planning system with 2 different delivery modes (6 MV standard vs. 6 MV FFF) for each of 25 patients. Dose distributions of the target and organs at risk (OARs), normal tissue complication probability (NTCP) of the hippocampus, monitor units, treatment time and quality assurance results were evaluated to compare the normal and FFF beam characteristics by Wilcoxon matched-pair signed-rank test with a significance level of 0.05.ResultsVMAT-FFF provided the significantly best homogeneity and conformity of the target, delivered the lowest dose to hippocampus and the other OARs, and led to the lowest NTCP of the hippocampus among all modalities, which has the potential to alleviate neurocognitive decline after WBRT. IMRT-FFF reduced the dose to the lens with similar dose distributions of the target compared with IMRT-FF, whereas the lower dose to the hippocampus was achieved using the conventional beams. The monitor units were obviously increased by 19.2% for VMAT and 33.8% for IMRT, when FFF beams w ere used. The removal of flattening filter for IMRT resulted in a 26% reduction in treatment time, but VMAT had the similar treatment time for the two modes owing to the limitation of gantry rotation speed. Gamma analysis showed an excellent agreement for all plans at 3%/2 mm, and no statistical differences were found between FF and FFF.ConclusionIn conclusion, this study suggests that FFF mode is feasible and advantageous in HA-WBRT and VMAT-FFF is the optimal solution in terms of dose distribution of the target, OARs sparing, NTCP of the hippocampus and delivery efficiency compared to the other three techniques. Additionally, the advantages of the FFF technique for VMAT are more prominent in cases with small hippocampal volumes

Spontaneously immortalised bovine mammary epithelial cells exhibit a distinct gene expression pattern from the breast cancer cells

<p>Abstract</p> <p>Background</p> <p>Spontaneous immortalisation of cultured mammary epithelial cells (MECs) is an extremely rare event, and the molecular mechanism behind spontaneous immortalisation of MECs is unclear. Here, we report the establishment of a spontaneously immortalised bovine mammary epithelial cell line (BME65Cs) and the changes in gene expression associated with BME65Cs cells.</p> <p>Results</p> <p>BME65Cs cells maintain the general characteristics of normal mammary epithelial cells in morphology, karyotype and immunohistochemistry, and are accompanied by the activation of endogenous <it>bTERT </it>(bovine Telomerase Reverse Transcriptase) and stabilisation of the telomere. Currently, BME65Cs cells have been passed for more than 220 generations, and these cells exhibit non-malignant transformation. The expression of multiple genes was investigated in BME65Cs cells, senescent BMECs (bovine MECs) cells, early passage BMECs cells and MCF-7 cells (a human breast cancer cell line). In comparison with early passage BMECs cells, the expression of senescence-relevant apoptosis-related gene were significantly changed in BME65Cs cells. P16^INK4awas downregulated, p53 was low expressed and Bax/Bcl-2 ratio was reversed. Moreover, a slight upregulation of the oncogene <it>c-Myc</it>, along with an undetectable level of breast tumor-related gene <it>Bag-1 </it>and <it>TRPS-1</it>, was observed in BME65Cs cells while these genes are all highly expressed in MCF-7. In addition, <it>DNMT1 </it>is upregulated in BME65Cs. These results suggest that the inhibition of both senescence and mitochondrial apoptosis signalling pathways contribute to the immortality of BME65Cs cells. The expression of <it>p53 </it>and <it>p16</it>^{<it>INK4a </it>}in BME65Cs was altered in the pattern of down-regulation but not "loss", suggesting that this spontaneous immortalization is possibly initiated by other mechanism rather than gene mutation of <it>p53 </it>or <it>p16</it>^{<it>INK4a</it>}.</p> <p>Conclusions</p> <p>Spontaneously immortalised BME65Cs cells maintain many characteristics of normal BMEC cells and exhibit non-malignant transformation. Although this cell line displays altered patterns of gene expression, it is clearly distinct from malignant breast cancer cell line. It showed that co-inhibition of cellular senescence and mitochondrial apoptosis pathways coordinates BME65Cs cells immortalisation. Additionally, mechanisms other than gene mutation are likely to be involved in regulation of cellular functions. This study provides an insight into the relationship between cell senescence and immortalisation. BME65Cs cells will be useful in future studies of cellular senescence and tumorigenesis.</p

Efficacy and safety of the compound Chinese medicine SaiLuoTong in vascular dementia: A randomized clinical trial

Introduction: No licensed medications are available to treat vascular dementia (VaD). Methods: Patients were randomly assigned to experimental groups (SaiLuoTong [SLT] 360 or 240 mg for groups A and B for 52 weeks, respectively) or placebo group (SLT 360 mg and 240 mg for group C only from weeks 27 to 52, respectively). Results: Three hundred twenty-five patients were included in final analysis. At week 26, the difference in VaD Assessment Scale-cognitive subscale scores was 2.67 (95% confidence interval, 1.54 to 3.81) for groups A versus C, and 2.48 (1.34 to 3.62) for groups B versus C (both Discussion: This study suggests that SLT is effective for treatment of VaD, and this compound Chinese medicine may represent a better choice to treat VaD

The pooled sensitivity and specificity of unstimulated CSF IFN-γ for diagnosing tuberculous meningitis.

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Hierarchical summary receiver operating characteristic (HSROC) plot to summarize diagnostic accuracy for CSF IGRA in diagnosing tuberculous meningitis.

Hierarchical summary receiver operating characteristic (HSROC) plot to summarize diagnostic accuracy for CSF IGRA in diagnosing tuberculous meningitis.</p

The pooled sensitivity and specificity of CSF IGRA for diagnosing tuberculous meningitis.

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Diagnostic performance of IFN-γ in the individual studies.

Diagnostic performance of IFN-γ in the individual studies.</p