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- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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- Lindemann, K., et al.
(författare)
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First-line treatment of advanced ovarian cancer with paclitaxel/carboplatin with or without epirubicin (TEC versus TC)-a gynecologic cancer intergroup study of the NSGO, EORTC GCG and NCIC CTG
- 2012
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Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 23:10, s. 31-2613
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Tidskriftsartikel (refereegranskat)abstract
- Background: The addition of anthracyclines to platinum-based chemotherapy may provide benefit in survival in ovarian cancer patients. We evaluated the effect on survival of adding epirubicin to standard carboplatin and paclitaxel. Patients and methods: We carried out a prospectively randomized phase III study comparing carboplatin plus paclitaxel (TC; area under the curve 5 and 175 mg/m(2)) with the same combination and epirubicin (TEC; 75 mg/m(2) i.v.). Between March 1999 and August 2001, 887 patients with epithelial ovarian, tubal or peritoneal cancer International Federation of Gynecology and Obstetrics stages IIB-IV were randomized to receive either TC (442 patients) or TEC (445 patients). Results: Median time to progression was 16.4 months in the TEC arm and 16.0 months in the TC arm (hazard ratio 0.99; 95% confidence interval [CI]: 0.9-1.2). Median overall survival time was 42.4 months for the TEC arm and 40.2 for the TC arm (hazard ratio 0.96; 95% CI: 0.8-1.1). Grade 3/4 hematologic toxic effects and most grade 3/4 non-hematologic toxic effects were more frequent in the TEC arm. Accordingly, a quality-of-life analysis showed inferiority of TEC versus TC. Conclusion: The addition of epirubicin to standard carboplatin and paclitaxel treatment did not improve survival in patients with advanced ovarian, tubal or peritoneal cancer.
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- Gilbert, R. E., et al.
(författare)
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Trends in child maltreatment reply
- 2012
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Ingår i: The Lancet. - New York, USA : Elsevier. - 0140-6736 .- 1474-547X. ; 379:9831, s. 2049-2049
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Tidskriftsartikel (refereegranskat)
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| 6. |
- Kyriazis, Angelos, et al.
(författare)
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Dynamic ventilation He-3 MRI for the quantification of disease in the rat lung
- 2012
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Ingår i: IEEE Transactions on Biomedical Engineering. - 0018-9294 .- 1558-2531. ; 59, s. 777-786
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Tidskriftsartikel (refereegranskat)abstract
- Pulmonary diseases are known to be largely inhomogeneous. To evaluate such inhomogeneities, we are testing an image-based method to measure gas flow in the lung regionally. Dynamic, spin-density-weighted hyperpolarized He MR images performed during slow inhalation of this gas were analyzed to quantify regional inflation rate. This parameter was measured in regions of interest (ROIs) that were defined by a rectangular grid that covered the entire rat lung and grew dynamically with it during its inflation. We used regional inflation rate to quantify elastase-induced emphysema and to differentiate healthy ( n8) from elastase-treated ( n9) rat lungs as well as healthy from elastase-treated areas of one rat unilaterally treated with elastase in the left lung. Emphysema was also assessed by gold standard morphological and well-established hyperpolarized He MRI diffusion measurements. Mean values of regional inflation rates were significantly different for healthy and elastase-treated animals and correlated well with the apparent diffusion coefficient of He and morphological measurements. The image-based biomarker inflation rate may be useful for the assessment of regional lung ventilation. © 2011 IEEE.
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