| 1. |
- 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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| 2. |
- Roland, Teboh, et al.
(författare)
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Tradeoffs for Assuming Rigid Target Motion in Mlc-Based Real Time Target Tracking Radiotherapy : A Dosimetric and Radiobiological Analysis
- 2010
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Ingår i: Technology in Cancer Research & Treatment. - : SAGE Publications. - 1533-0346 .- 1533-0338. ; 9:2, s. 199-210
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Tidskriftsartikel (refereegranskat)abstract
- We report on our assessment of two types of real time target tracking modalities for lung cancer radiotherapy namely (1) single phase propagation (SPP) where motion compensation assumes a rigid target and (2) multi-phase propagation (MPP) where motion compensation considers a deformable target. In a retrospective study involving 4DCT volumes from six (n=6) previously treated lung cancer patients, four-dimensional treatment plans representative of the delivery scenarios were generated per modality and the corresponding dose distributions were derived. The modalities were then evaluated (a) Dosimetrically for target coverage adequacy and normal tissue sparing by computing the mean GTV dose, relative conformity gradient index (CGI), mean lung dose (MLD) and lung V-20; (b) Radiobiologically by calculating the biological effective uniform dose ((sic)) for the target and organs at risk (OAR) and the complication free tumor control probability (P+). As a reference for the comparative study, we included a 40 Static modality, which was a conventional approach to account for organ motion and involved the use of individualized motion margins. With reference to the 4D Static modality, the average percent decrease in lung V-20 and MLD were respectively (13.1 +/- 6.9) % and (11.4 +/- 5.6) % for the MPP modality, whereas for the SPP modality they were (9.4 +/- 6.2) % and (7.2 +/- 4.7) %. On the other hand, the CGI was observed to improve by 15.3 +/- 13.2 and 9.6 +/- 10.0 points for the MPP and SPP modalities, respectively while the mean GTV dose agreed to better than 3% difference across all the modalities. A similar trend was observed in the radiobiological analysis where the P+ improved on average by (6.7 +/- 4.9) % and (4.1 +/- 3.6) % for the MPP and SPP modalities, respectively while the (sic) computed for the OAR decreased on average by (6.2 +/- 3.6) % and (3.8 +/- 3.5) % for the MPP and SPP tracking modalities, respectively. The (sic) calculated for the GTV for all the modalities was in agreement to better than 2% difference. In general, respiratory motion induces target displacement and deformation and therefore the complex MPP real time target tracking modality is the preferred. On the other hand, the SPP approach affords simplicity in implementation at the expense of failing to account for target deformation. Radiobiological and dosimetric analyses enabled us to investigate the consequences of failing to compensate for deformation and assess the impact if any on the clinical outcome. While it is not possible to draw any general conclusions on a small patient cohort, our study suggests that the two tracking modalities can lead to comparable clinical outcomes and as expected are advantageous when compared with the static conventional modality.
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| 3. |
- Stathakis, Sotirios, et al.
(författare)
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gamma(+) index : A new evaluation parameter for quantitative quality assurance
- 2014
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Ingår i: Computer Methods and Programs in Biomedicine. - : Elsevier BV. - 0169-2607 .- 1872-7565. ; 114:1
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The accuracy dose delivery and the evaluation of differences between calculated and delivered dose distributions, has been studied by several groups. The aim of this investigation is to extend the gamma index by including radiobiological information and to propose a new index that we will here forth refer to as the gamma plus (gamma(+)). Further more, to validate the robustness of this new index in performing a quality control analysis of an IMRT treatment plan using pure radiobiological measures such as the biologically effective uniform dose ((D) over bar) and complication-free tumor control probability (P+). Material and methods: A new quality assurance index, the (gamma(+)), is proposed based on the theoretical concept of gamma index presented by Low et al. (1998). In this study, the dose difference, including the radiobiological dose information (biological effective dose, BED) is used instead of just the physical dose difference when performing the gamma(+) calculation. An in-house software was developed to compare different dose distributions based on the gamma(+) concept. A test pattern for a two-dimensional dose comparison was built using the in-house software platform. The gamma(+) index was tested using planar dose distributions (exported from the treatment planning system) and delivered (film) dose distributions acquired in a solid water phantom using a test pattern and a theoretical clinical case. Furthermore, a lung cancer case for a patient treated with IMRT was also selected for the analysis. The respective planar dose distributions from the treatment plan and the film were compared based on the gamma(+) index and were evaluated using the radiobiological measures of P+ and (D) over bar. Results: The results for the test pattern analysis indicate that the gamma(+) index distributions differ from those of the gamma index since the former considers radiobiological parameters that may affect treatment outcome. For the theoretical clinical case, it is observed that the gamma(+) index varies for different treatment parameters (e.g. dose per fraction). The dose area histogram (DAH) from the plan and film dose distributions are associated with P+ values of 50.8% and 49.0%, for a (D) over bar to the target of 54.0 Gy and 53.3 Gy, respectively. Conclusion: The gamma(+) index shows advantageous properties in the quantitative evaluation of dose delivery and quality control of IMRT treatments because it includes information about the expected responses and radiobiological doses of the individual tissues.
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| 4. |
- Su, Fan-Chi, et al.
(författare)
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A graphic user interface toolkit for specification, report and comparison of dose-response relations and treatment plans using the biologically effective uniform dose
- 2010
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Ingår i: Computer Methods and Programs in Biomedicine. - : Elsevier BV. - 0169-2607 .- 1872-7565. ; 100:1, s. 69-78
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Tidskriftsartikel (refereegranskat)abstract
- A toolkit (BEUDcal) has been developed for evaluating the effectiveness and for predicting the outcome of treatment plans by calculating the biologically effective uniform dose (BEUD) and complication-free tumor control probability. The input for the BEUDcal is the differential dose-volume histograms of organs exported from the treatment planning system. A clinical database is built for the dose-response parameters of different tumors and normal tissues. Dose-response probabilities of all the examined organs are illustrated together with the corresponding BEUDs and the P+ values. Furthermore, BEUDcal is able to generate a report that simultaneously presents the radiobiological evaluation together with the physical dose indices, showing the complementary relation between the physical and radiobiological treatment plan analysis performed by BEUDcal. Comparisons between treatment plans for helical tomotherapy and multileaf collimator-based intensity modulated radiotherapy of a lung patient were demonstrated to show the versatility of BEUDcal in the assessment and report of dose-response relations.
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