| 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. |
- Duffy, Stephen W., et al.
(författare)
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Beneficial effect of consecutive screening mammography examinations on mortality from breast cancer : a prospective study
- 2021
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Ingår i: Radiology. - : Radiological Society of North America (RSNA). - 0033-8419 .- 1527-1315. ; 299:3, s. 541-547
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previously, the risk of death from breast cancer was analyzed for women participating versus those not participating in the last screening examination before breast cancer diagnosis. Consecutive attendance patterns may further refine estimates.Purpose: To estimate the effect of participation in successive mammographic screening examinations on breast cancer mortality.Materials and Methods: Participation data for Swedish women eligible for screening mammography in nine counties from 1992 to 2016 were linked with data from registries and regional cancer centers for breast cancer diagnosis, cause, and date of death (Uppsala University ethics committee registration number: 2017/147). Incidence-based breast cancer mortality was calculated by whether the women had participated in the most recent screening examination prior to diagnosis only (intermittent participants), the penultimate screening examination only (lapsed participants), both examinations (serial participants), or neither examination (serial nonparticipants). Rates were analyzed with Poisson regression. We also analyzed incidence of breast cancers proving fatal within 10 years.Results: Data were available for a total average population of 549 091 women (average age, 58.9 years 6 6.7 [standard deviation]). The numbers of participants in the four groups were as follows: serial participants, 392 135; intermittent participants, 41 746; lapsed participants, 30 945; and serial nonparticipants, 84 265. Serial participants had a 49% lower risk of breast cancer mortality (relative risk [RR], 0.51; 95% CI: 0.48, 0.55; P ,.001) and a 50% lower risk of death from breast cancer within 10 years of diagnosis (RR, 0.50; 95% CI: 0.46, 0.55; P ,.001) than serial nonparticipants. Lapsed and intermittent participants had a smaller reduction. Serial participants had significantly lower risk of both outcomes than lapsed or intermittent participants. Analyses correcting for potential biases made little difference to the results.Conclusion: Women participating in the last two breast cancer screening examinations prior to breast cancer diagnosis had the largest reduction in breast cancer death. Missing either one of the last two examinations conferred a significantly higher risk.
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| 3. |
- Duffy, Stephen W., et al.
(författare)
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Mammography screening reduces rates of advanced and fatal breast cancers : Results in 549,091 women
- 2020
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Ingår i: Cancer. - : John Wiley & Sons. - 0008-543X .- 1097-0142. ; 126:13, s. 2971-2979
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is of paramount importance to evaluate the impact of participation in organized mammography service screening independently from changes in breast cancer treatment. This can be done by measuring the incidence of fatal breast cancer, which is based on the date of diagnosis and not on the date of death.Methods: Among 549,091 women, covering approximately 30% of the Swedish screening‐eligible population, the authors calculated the incidence rates of 2473 breast cancers that were fatal within 10 years after diagnosis and the incidence rates of 9737 advanced breast cancers. Data regarding each breast cancer diagnosis and the cause and date of death of each breast cancer case were gathered from national Swedish registries. Tumor characteristics were collected from regional cancer centers. Aggregated data concerning invitation and participation were provided by Sectra Medical Systems AB. Incidence rates were analyzed using Poisson regression.Results: Women who participated in mammography screening had a statistically significant 41% reduction in their risk of dying of breast cancer within 10 years (relative risk, 0.59; 95% CI, 0.51‐0.68 [P < .001]) and a 25% reduction in the rate of advanced breast cancers (relative risk, 0.75; 95% CI, 0.66‐0.84 [P < .001]).Conclusions: Substantial reductions in the incidence rate of breast cancers that were fatal within 10 years after diagnosis and in the advanced breast cancer rate were found in this contemporaneous comparison of women participating versus those not participating in screening. These benefits appeared to be independent of recent changes in treatment regimens.
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| 4. |
- Tabar, Laszlo, et al.
(författare)
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Early detection of breast cancer rectifies inequality of breast cancer outcomes
- 2020
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Ingår i: Journal of Medical Screening. - : Sage Publications. - 0969-1413 .- 1475-5793. ; 28:1, s. 34-38
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To explain apparent differences among mammography screening services in Sweden using individual data on participation in screening and with breast cancer-specific survival as an outcome.Methods: We analysed breast cancer survival data from the Swedish Cancer Register on breast cancer cases from nine Swedish counties diagnosed in women eligible for screening. Data were available on 38,278 breast cancers diagnosed and 4312 breast cancer deaths. Survival to death from breast cancer was estimated using the Kaplan-Meier estimate, for all cases in each county, and separately for cases of women participating and not participating in their last invitation to screening. Formal statistical comparisons of survival were made using proportional hazards regression.Results: All counties showed a reduction in the hazard of breast cancer death with participation in screening, but the reductions for individual counties varied substantially, ranging from 51% (95% confidence interval 46-55%) to 81% (95% confidence interval 74-85%). Survival rates in nonparticipating women ranged from 53% (95% confidence interval 40-65%) to 74% (95% confidence interval 72-77%), while the corresponding survival in women participating in screening varied from 80% (95% confidence interval 77-84%) to 86% (95% confidence interval 83-88%), a considerably narrower range.Conclusions: Differences among counties in the effect of screening on breast cancer outcomes were mainly due to variation in survival in women not participating in screening. Screening conferred similarly high survival rates in all counties. This indicates that the performance of screening services was similar across counties and that detection and treatment of breast cancer in early-stage reduces inequalities in breast cancer outcome.
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| 5. |
- Tabar, Laszlo, et al.
(författare)
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The incidence of fatal breast cancer measures the increased effectiveness of therapy in women participating in mammography screening
- 2019
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Ingår i: Cancer. - : John Wiley & Sons. - 0008-543X .- 1097-0142. ; 125:4, s. 515-523
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Tidskriftsartikel (refereegranskat)abstract
- Background: Women and their health care providers need a reliable answer to this important question: If a woman chooses to participate in regular mammography screening, then how much will this choice improve her chances of avoiding a death from breast cancer compared with women who choose not to participate? Methods: To answer this question, we used comprehensive registries for population, screening history, breast cancer incidence, and disease-specific death data in a defined population in Dalarna County, Sweden. The annual incidence of breast cancer was calculated along with the annual incidence of breast cancers that were fatal within 10 and within 11 to 20 years of diagnosis among women aged 40 to 69 years who either did or did not participate in mammography screening during a 39-year period (1977-2015). For an additional comparison, corresponding data are presented from 19 years of the prescreening period (1958-1976). All patients received stage-specific therapy according to the latest national guidelines, irrespective of the mode of detection. Results: The benefit for women who chose to participate in an organized breast cancer screening program was a 60% lower risk of dying from breast cancer within 10 years after diagnosis (relative risk, 0.40; 95% confidence interval, 0.34-0.48) and a 47% lower risk of dying from breast cancer within 20 years after diagnosis (relative risk, 0.53; 95% confidence interval, 0.44-0.63) compared with the corresponding risks for nonparticipants. Conclusions: Although all patients with breast cancer stand to benefit from advances in breast cancer therapy, the current results demonstrate that women who have participated in mammography screening obtain a significantly greater benefit from the therapy available at the time of diagnosis than do those who have not participated.
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| 6. |
- Wu, Wendy Yi-Ying, et al.
(författare)
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Imaging Biomarkers as Predictors for Breast Cancer Death
- 2019
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Ingår i: Journal of Oncology. - : Hindawi Publishing Corporation. - 1687-8450 .- 1687-8469.
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Tidskriftsartikel (refereegranskat)abstract
- Background. To differentiate the risk of breast cancer death in a longitudinal cohort using imaging biomarkers of tumor extent and biology, specifically, the mammographic appearance, basal phenotype, histologic tumor distribution, and conventional tumor attributes. Methods. Using a prospective cohort study design, 498 invasive breast cancer patients diagnosed between 1996 and 1998 were used as the test cohort to assess the independent effects of the imaging biomarkers and other predictors on the risk of breast cancer death. External validation was performed with a cohort of 848 patients diagnosed between 2006 and 2010. Results. Mammographic tumor appearance was an independent predictor of risk of breast cancer death (P=0.0003) when conventional tumor attributes and treatment modalities were controlled. The casting type calcifications and architectural distortion were associated with 3.13-fold and 3.19-fold risks of breast cancer death, respectively. The basal phenotype independently conferred a 2.68-fold risk compared with nonbasal phenotype. The observed deaths did not differ significantly from expected deaths in the validation cohort. The application of imaging biomarkers together with other predictors classified twelve categories of risk for breast cancer death. Conclusion. Combining imaging biomarkers such as the mammographic appearance of the tumor with the histopathologic distribution and basal phenotype, accurately predicted long-term risk of breast cancer death. The information may be relevant for determining the need for molecular testing, planning treatment, and determining the most appropriate clinical surveillance schedule for breast cancer patients.
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