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- Durno, C., et al.
(författare)
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Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance
- 2021
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 39:25
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals. PATIENTS AND METHODS Data were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium. Tumor spectrum, efficacy of the surveillance protocol, and malignant transformation of low-grade lesions were examined for the entire cohort. Survival outcomes were analyzed for patients followed prospectively from the time of surveillance implementation. RESULTS A total of 193 malignant tumors in 110 patients were identified. Median age of first cancer diagnosis was 9.2 years (range: 1.7-39.5 years). For patients undergoing surveillance, all GI and other solid tumors, and 75% of brain cancers were detected asymptomatically. By contrast, only 16% of hematologic malignancies were detected asymptomatically (P < .001). Eighty-nine patients were followed prospectively and used for survival analysis. Five-year overall survival (OS) was 90% (95% CI, 78.6 to 100) and 50% (95% CI, 39.2 to 63.7) when cancer was detected asymptomatically and symptomatically, respectively (P = .001). Patient outcome measured by adherence to the surveillance protocol revealed 4-year OS of 79% (95% CI, 54.8 to 90.9) for patients undergoing full surveillance, 55% (95% CI, 28.5 to 74.5) for partial surveillance, and 15% (95% CI, 5.2 to 28.8) for those not under surveillance (P < .0001). Of the 64 low-grade tumors detected, the cumulative likelihood of transformation from low-to high-grade was 81% for GI cancers within 8 years and 100% for gliomas in 6 years. CONCLUSION Surveillance and early cancer detection are associated with improved OS for individuals with CMMRD.
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- Pierre, M., et al.
(författare)
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The XXL survey : First results and future
- 2017
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Ingår i: Astronomical Notes - Astronomische Nachrichten. - : Wiley-VCH Verlagsgesellschaft. - 0004-6337 .- 1521-3994. ; 338:2-3, s. 334-341
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Tidskriftsartikel (refereegranskat)abstract
- The XXL survey currently covers two 25 deg(2) patches with XMM observations of similar to 10 ks. We summarize the scientific results associated with the first release of the XXL dataset, which occurred in mid-2016. We review several arguments for increasing the survey depth to 40 ks during the next decade of XMM operations. X-ray (z < 2) cluster, (z < 4) active galactic nuclei (AGN), and cosmic background survey science will then benefit from an extraordinary data reservoir. This, combined with deep multi-lambda observations, will lead to solid standalone cosmological constraints and provide a wealth of information on the formation and evolution of AGN, clusters, and the X-ray background. In particular, it will offer a unique opportunity to pinpoint the z > 1 cluster density. It will eventually constitute a reference study and an ideal calibration field for the upcoming eROSITA and Euclid missions.
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- Pierre, M., et al.
(författare)
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The XXL Survey I. Scientific motivations - XMM-Newton observing plan - Follow-up observations and simulation programme
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 592
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Tidskriftsartikel (refereegranskat)abstract
- Context. The quest for the cosmological parameters that describe our universe continues to motivate the scientific community to undertake very large survey initiatives across the electromagnetic spectrum. Over the past two decades, the Chandra and XMM-Newton observatories have supported numerous studies of X-ray-selected clusters of galaxies, active galactic nuclei (AGNs), and the X-ray background. The present paper is the first in a series reporting results of the XXL-XMM survey; it comes at a time when the Planck mission results are being finalised. Aims. We present the XXL Survey, the largest XMM programme totaling some 6.9 Ms to date and involving an international consortium of roughly 100 members. The XXL Survey covers two extragalactic areas of 25 deg(2) each at a point-source sensitivity of similar to 5 x 10(-15) erg s(-1) cm(-2) in the [0.5-2] keV band (completeness limit). The survey's main goals are to provide constraints on the dark energy equation of state from the space-time distribution of clusters of galaxies and to serve as a pathfinder for future, wide-area X-ray missions. We review science objectives, including cluster studies, AGN evolution, and large-scale structure, that are being conducted with the support of approximately 30 follow-up programmes. Methods. We describe the 542 XMM observations along with the associated multi-lambda and numerical simulation programmes. We give a detailed account of the X-ray processing steps and describe innovative tools being developed for the cosmological analysis. Results. The paper provides a thorough evaluation of the X-ray data, including quality controls, photon statistics, exposure and background maps, and sky coverage. Source catalogue construction and multi-lambda associations are briefly described. This material will be the basis for the calculation of the cluster and AGN selection functions, critical elements of the cosmological and science analyses. Conclusions. The XXL multi-lambda data set will have a unique lasting legacy value for cosmological and extragalactic studies and will serve as a calibration resource for future dark energy studies with clusters and other X-ray selected sources. With the present article, we release the XMM XXL photon and smoothed images along with the corresponding exposure maps.
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- Das, A., et al.
(författare)
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Genomic predictors of response to PD-1 inhibition in children with germline DNA replication repair deficiency
- 2022
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 28:1, s. 125-135
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Tidskriftsartikel (refereegranskat)abstract
- Cancers arising from germline DNA mismatch repair deficiency or polymerase proofreading deficiency (MMRD and PPD) in children harbour the highest mutational and microsatellite insertion–deletion (MS-indel) burden in humans. MMRD and PPD cancers are commonly lethal due to the inherent resistance to chemo-irradiation. Although immune checkpoint inhibitors (ICIs) have failed to benefit children in previous studies, we hypothesized that hypermutation caused by MMRD and PPD will improve outcomes following ICI treatment in these patients. Using an international consortium registry study, we report on the ICI treatment of 45 progressive or recurrent tumors from 38 patients. Durable objective responses were observed in most patients, culminating in a 3 year survival of 41.4%. High mutation burden predicted response for ultra-hypermutant cancers (>100 mutations per Mb) enriched for combined MMRD + PPD, while MS-indels predicted response in MMRD tumors with lower mutation burden (10–100 mutations per Mb). Furthermore, both mechanisms were associated with increased immune infiltration even in ‘immunologically cold’ tumors such as gliomas, contributing to the favorable response. Pseudo-progression (flare) was common and was associated with immune activation in the tumor microenvironment and systemically. Furthermore, patients with flare who continued ICI treatment achieved durable responses. This study demonstrates improved survival for patients with tumors not previously known to respond to ICI treatment, including central nervous system and synchronous cancers, and identifies the dual roles of mutation burden and MS-indels in predicting sustained response to immunotherapy. © 2022, The Author(s).
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- Smolcic, V., et al.
(författare)
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The XXL Survey: XXIX. GMRT 610 MHz continuum observations
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 620
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Tidskriftsartikel (refereegranskat)abstract
- We present the 25 square-degree GMRT-XXL-N 610 MHz radio continuum survey, conducted at 50 cm wavelength with the Giant Metrewave Radio Telescope (GMRT) towards the XXL Northern field (XXL-N). We combined previously published observations of the XMM-Large Scale Structure (XMM-LSS) field, located in the central part of XXL-N, with newly conducted observations towards the remaining XXL-N area, and imaged the combined data-set using the Source Peeling and Atmospheric Modeling (SPAM) pipeline. The final mosaic encompasses a total area of 30:4 square degrees, with rms <150 μJy beam-1 over 60% of the area. The rms achieved in the inner 9.6 square degree area, enclosing the XMM-LSS field, is about 200 μJy beam-1, while that over the outer 12.66 square degree area (which excludes the noisy edges) is about 45 μJy beam-1. The resolution of the final mosaic is 6.5 arcsec. We present a catalogue of 5434 sources detected at ≥7 × rms. We verify, and correct the reliability of, the catalog in terms of astrometry, flux, and false detection rate. Making use of the (to date) deepest radio continuum survey over a relatively large (2 square degree) field, complete at the flux levels probed by the GMRT-XXL-N survey, we also assess the survey's incompleteness as a function of flux density. The radio continuum sensitivity reached over a large field with a wealth of multi-wavelength data available makes the GMRTXXL- N 610 MHz survey an important asset for studying the physical properties, environments and cosmic evolution of radio sources, in particular radio-selected active galactic nuclei (AGN).
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- Vanhees, L, et al.
(författare)
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Importance of characteristics and modalities of physical activity and exercise in the management of cardiovascular health in individuals with cardiovascular risk factors : recommendations from the EACPR. Part II.
- 2012
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Ingår i: European journal of preventive cardiology. - : Oxford University Press (OUP). - 2047-4881 .- 2047-4873. ; 19:5, s. 1005-33
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Tidskriftsartikel (refereegranskat)abstract
- In a previous paper, as the first of a series of three on the importance of characteristics and modalities of physical activity (PA) and exercise in the management of cardiovascular health within the general population, we concluded that, in the population at large, PA and aerobic exercise capacity clearly are inversely associated with increased cardiovascular disease risk and all-cause and cardiovascular mortality and that a dose–response curve on cardiovascular outcome has been demonstrated in most studies. More and more evidence is accumulated that engaging in regular PA and exercise interventions are essential components for reducing the severity of cardiovascular risk factors, such as obesity and abdominal fat, high BP, metabolic risk factors, and systemic inflammation. However, it is less clear whether and which type of PA and exercise intervention (aerobic exercise, dynamic resistive exercise, or both) or characteristic of exercise (frequency, intensity, time or duration, and volume) would yield more benefit for each separate risk factor. The present paper, therefore, will review and make recommendations for PA and exercise training in the management of cardiovascular health in individuals with cardiovascular risk factors. The guidance offered in this series of papers is aimed at medical doctors, health practitioners, kinesiologists, physiotherapists and exercise physiologists, politicians, public health policy makers, and individual members of the public. Based on previous and the current literature overviews, recommendations from the European Association on Cardiovascular Prevention and Rehabilitation are formulated regarding type, volume, and intensity of PA and regarding appropriate risk evaluation during exercise in individuals with cardiovascular risk factors.
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| 10. |
- Brennan, D. J., et al.
(författare)
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The cocaine- and amphetamine-regulated transcript mediates ligand-independent activation of ER alpha, and is an independent prognostic factor in node-negative breast cancer
- 2012
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 31:30, s. 3483-3494
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Tidskriftsartikel (refereegranskat)abstract
- Personalized medicine requires the identification of unambiguous prognostic and predictive biomarkers to inform therapeutic decisions. Within this context, the management of lymph node-negative breast cancer is the subject of much debate with particular emphasis on the requirement for adjuvant chemotherapy. The identification of prognostic and predictive biomarkers in this group of patients is crucial. Here, we demonstrate by tissue microarray and automated image analysis that the cocaine- and amphetamine-regulated transcript (CART) is expressed in primary and metastatic breast cancer and is an independent poor prognostic factor in estrogen receptor (ER)-positive, lymph node-negative tumors in two separate breast cancer cohorts (n = 690; P = 0.002, 0.013). We also show that CART increases the transcriptional activity of ER alpha in a ligand-independent manner via the mitogen-activated protein kinase pathway and that CART stimulates an autocrine/paracrine loop within tumor cells to amplify the CART signal. Additionally, we demonstrate that CART expression in ER-positive breast cancer cell lines protects against tamoxifen-mediated cell death and that high CART expression predicts disease outcome in tamoxifen-treated patients in vivo in three independent breast cancer cohorts. We believe that CART profiling will help facilitate stratification of lymph node-negative breast cancer patients into high- and low-risk categories and allow for the personalization of therapy. Oncogene (2012) 31, 3483-3494; doi:10.1038/onc.2011.519; published online 5 December 2011
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