| 1. |
- Megyesfalvi, Zsolt, et al.
(författare)
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Expression patterns and prognostic relevance of subtype-specific transcription factors in surgically resected small-cell lung cancer : an international multicenter study
- 2022
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Ingår i: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 257:5, s. 674-686
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Tidskriftsartikel (refereegranskat)abstract
- The tissue distribution and prognostic relevance of subtype-specific proteins (ASCL1, NEUROD1, POU2F3, YAP1) present an evolving area of research in small-cell lung cancer (SCLC). The expression of subtype-specific transcription factors and P53 and RB1 proteins were measured by immunohistochemistry (IHC) in 386 surgically resected SCLC samples. Correlations between subtype-specific proteins and in vitro efficacy of various therapeutic agents were investigated by proteomics and cell viability assays in 26 human SCLC cell lines. Besides SCLC-A (ASCL1-dominant), SCLC-AN (combined ASCL1/NEUROD1), SCLC-N (NEUROD1-dominant), and SCLC-P (POU2F3-dominant), IHC and cluster analyses identified a quadruple-negative SCLC subtype (SCLC-QN). No unique YAP1-subtype was found. The highest overall survival rates were associated with non-neuroendocrine subtypes (SCLC-P and SCLC-QN) and the lowest with neuroendocrine subtypes (SCLC-A, SCLC-N, SCLC-AN). In univariate analyses, high ASCL1 expression was associated with poor prognosis and high POU2F3 expression with good prognosis. Notably, high ASCL1 expression influenced survival outcomes independently of other variables in a multivariate model. High POU2F3 and YAP1 protein abundances correlated with sensitivity and resistance to standard-of-care chemotherapeutics, respectively. Specific correlation patterns were also found between the efficacy of targeted agents and subtype-specific protein abundances. In conclusion, we investigated the clinicopathological relevance of SCLC molecular subtypes in a large cohort of surgically resected specimens. Differential IHC expression of ASCL1, NEUROD1, and POU2F3 defines SCLC subtypes. No YAP1-subtype can be distinguished by IHC. High POU2F3 expression is associated with improved survival in a univariate analysis, whereas elevated ASCL1 expression is an independent negative prognosticator. Proteomic and cell viability assays of human SCLC cell lines revealed distinct vulnerability profiles defined by transcription regulators.
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| 2. |
- Schreiber Compo, Nadja, et al.
(författare)
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Methods of studying eyewitness memory
- 2019
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Ingår i: Otani, H., & Schwartz, B. L. (Eds.), Handbook of Research Methods in Human Memory. - New York : Routledge. - 9781138217959
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Bokkapitel (refereegranskat)abstract
- Many reviews have focused on the variables that affect eyewitness memory (see Loftus, 2013; Wells & Olson, 2003), but few (if any) provide a detailed summary of the general methodologies employed in studies examining eyewitness memory. As such, the present chapter seeks to fill this void by describing and synthesizing the common methods employed when researching eyewitness memory for an event, along with providing recommendations for researchers and practitioners. As eyewitness memory is a broad term, our focus will be on eyewitness recall (i.e., the ability to describe a criminal event and/or perpetrator) rather than recognition (i.e., the ability to identify a perpetrator in a subsequent lineup or photo array (see Bruce and Lander, this volume). This chapter will also limit its discussion to adult eyewitness memory, as child eyewitness memory will be discussed elsewhere (see Machluf & Sellers, this volume). We will specifically focus on methods of studying memory of cooperative witnesses as opposed to suspects or non-cooperative witnesses who have a motivation to conceal information or to lie (i.e., in interrogation contexts; Bull, Valentine, & Williamson, 2009; Vallano & Schreiber Compo, 2015; Westera, Kebbell, & Milne, 2016). Finally, the present chapter will only tangentially touch upon the methodology of misinformation and suggestibility paradigms, which are covered by Otgaar (Otgaar, this volume) and focus on the study of spontaneously reported false information and the source-monitoring paradigms used to assess witnesses’ abilities to disentangle the various sources of their memories.
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| 3. |
- Yu, Hui, et al.
(författare)
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Programmed Cell Death Ligand 1 Expression in Resected Non-Small Cell Lung Cancer
- 2021
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Ingår i: Clinical Lung Cancer. - : Elsevier. - 1525-7304 .- 1938-0690. ; 22:4, s. 555-562
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recently, anti-programmed cell death 1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) immunotherapies have yielded promising outcomes for patients with advanced non-small cell lung cancer (NSCLC) and led to great interest in applying these agents to treat resectable early-stage NSCLC. The objective of our study was to evaluate PD-L1 protein expression in resectable early-stage NSCLC specimens from a large Northern European cohort, examine the relationship to clinical characteristics, and demonstrate the prognostic role in resected NSCLC.Material and Methods: A large cohort of 875 NSCLC tumors consisted of 337 patients from Sweden and 538 patients from Norway was studied. All the patients had undergone pulmonary resection, and most patients had had early-stage NSCLC. PD-L1 protein expression was assessed by immunohistochemistry using the Dako PD-L1 22C3 pharmDx kit. The tumor proportion score for PD-L1 protein expression was compared with comprehensive demographic and clinicopathologic data.Results: The overall prevalence of PD-L1 protein expression in the resectable NSCLC cohort was 9.5% at a tumor proportion score cutoff of ≥ 50%. Stage I NSCLC had lower PD-L1 expression compared with that of the other stages (P = .0012). PD-L1 expression correlated with wild-type EGFR gene expression (P = .0156) and mutated KRAS gene expression (P = .0004). No significant association was found between PD-L1 expression and mortality after multivariable adjustment for clinical characteristics, although the survival curves showed PD-L1 expression significantly correlated with a poor prognosis in the total NSCLC cohort and in the adenocarcinoma subgroup.Conclusion: PD-L1 expression in the present large cohort of resectable NSCLC was relatively low compared with data from clinical trials of advanced NSCLC. PD-L1 expression correlated positively with tumor stage, wild-type EGFR, and KRAS mutation. PD-L1 expression was not found as an independent prognostic factor in the present study. These findings could be important in the future when evaluating the role of anti-PD-1/PD-L1 immunotherapy in the setting of neoadjuvant or adjuvant trials for early-stage resectable NSCLC.
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