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- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 2. |
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| 3. |
- Alvarez, Mariano J., et al.
(författare)
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A precision oncology approach to the pharmacological targeting of mechanistic dependencies in neuroendocrine tumors
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:7, s. 979-989
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Tidskriftsartikel (refereegranskat)abstract
- We introduce and validate a new precision oncology framework for the systematic prioritization of drugs targeting mechanistic tumor dependencies in individual patients. Compounds are prioritized on the basis of their ability to invert the concerted activity of master regulator proteins that mechanistically regulate tumor cell state, as assessed from systematic drug perturbation assays. We validated the approach on a cohort of 212 gastroenteropancreatic neuroendocrine tumors (GEP-NETs), a rare malignancy originating in the pancreas and gastrointestinal tract. The analysis identified several master regulator proteins, including key regulators of neuroendocrine lineage progenitor state and immunoevasion, whose role as critical tumor dependencies was experimentally confirmed. Transcriptome analysis of GEP-NET-derived cells, perturbed with a library of 107 compounds, identified the HDAC class I inhibitor entinostat as a potent inhibitor of master regulator activity for 42% of metastatic GEP-NET patients, abrogating tumor growth in vivo. This approach may thus complement current efforts in precision oncology.
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| 5. |
- Aoki, Y, et al.
(författare)
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Corrigendum
- 2018
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Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 141:5, s. e42-
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Tidskriftsartikel (refereegranskat)
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| 6. |
- Asa, S L, et al.
(författare)
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From pituitary adenoma to pituitary neuroendocrine tumor (PitNET) : an International Pituitary Pathology Club proposal
- 2017
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Ingår i: Endocrine-Related Cancer. - 1351-0088 .- 1479-6821. ; 24:4, s. C5-C8
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Tidskriftsartikel (refereegranskat)abstract
- The classification of neoplasms of adenohypophysial cells is misleading because of the simplistic distinction between adenoma and carcinoma, based solely on metastatic spread and the poor reproducibility and predictive value of the definition of atypical adenomas based on the detection of mitoses or expression of Ki-67 or p53. In addition, the current classification of neoplasms of the anterior pituitary does not accurately reflect the clinical spectrum of behavior. Invasion and regrowth of proliferative lesions and persistence of hormone hypersecretion cause significant morbidity and mortality. We propose a new terminology, pituitary neuroendocrine tumor (PitNET), which is consistent with that used for other neuroendocrine neoplasms and which recognizes the highly variable impact of these tumors on patients.
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| 9. |
- Petridou, E., et al.
(författare)
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PO-124 Childhood Leukemia International Consortium (CLIC) Studies Report Diffrential Associations of Advanced Parental Age with Childhood Acute Lymphoblastic Leukemia
- 2018
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Ingår i: Pediatric Blood & Cancer. - : John Wiley & Sons. - 1545-5009 .- 1545-5017. ; 65:52, s. S150-S151
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background/Objectives:Advanced parental age has beenassociated with adverse health effects in the offspring includ-ing childhood (0-14 years) acute lymphoblastic leukemia(ALL), as reported in our meta-analysis of published stud-ies. Primary data from 16 studies participating in theChildhood Leukemia International Consortium provide aunique methodological opportunity to further explore thisassociation.Design/Methods:Data from 11 case-control (CC) studies(7919 cases; 12942 interviewed controls) and five nested case-control (NCC) studies (8801 cases; 29690 controls recordlinked via population-based registries) with enrollment peri-ods ranging from 1968 to 2015 were used. Adjusted oddsratios (OR) were derived from each study using five-yearpaternal and maternal age increments and introduded in twometa-analyses by CC or NCC study design.Results:Advancement of paternal age was associated withstatistically significant higher risk for ALL in the off-spring (ORCC:1.05; ORNCC:1.04) and advanced mater-nal age only in the NCC (ORNCC:1.05). By contrast, theresults were heterogeneous in CC studies (ORCC:0.99, 95%CI:0.91-1.07, heterogeneityI2=58%,p=0.002). The positive association between parental age and risk of ALL was moreevident in the age group among 1-5 years and remainedunchanged after mutual adjustment for the collinear effect ofthe paternal and maternal age variables. We further performedanalyses of the relatively small numbers of discordant pater-nal and maternal age pairs to explore the collinear effect ofparental age but the results were not fully enlightening.Conclusions:The results of this larger ever dataset of primarydata allowing for separate analysis by study design and bettercontrol of selection bias in CC studies strengthen the evidencethat advanced parental age is associated with increased child-hood ALL risk. The observational study design and ollinear-ity of maternal with paternal age complicate causal interpre-tation. Employing datasets with cytogenetic information mayfurther elucidate involvement of each parental component andclarify underlying mechanisms.
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