Is the Morphological Subtype of Extra-Pulmonary Neuroendocrine Carcinoma Clinically Relevant?
AuthorsFrizziero, Melissa; email: email@example.com
Durand, Alice; orcid: 0000-0002-0193-9058; email: firstname.lastname@example.org
Taboada, Rodrigo G.; orcid: 0000-0001-5674-2669; email: email@example.com
Zaninotto, Elisa; email: firstname.lastname@example.org
Luchini, Claudio; orcid: 0000-0003-4901-4908; email: email@example.com
Chakrabarty, Bipasha; email: firstname.lastname@example.org
Hervieu, Valérie; email: email@example.com
Claro, Laura C. L.; email: firstname.lastname@example.org
Zhou, Cong; orcid: 0000-0002-6938-4685; email: email@example.com
Cingarlini, Sara; email: firstname.lastname@example.org
Milella, Michele; email: email@example.com
Walter, Thomas; orcid: 0000-0002-4199-4561; email: firstname.lastname@example.org
Riechelmann, Rachel S.; orcid: 0000-0002-0107-9617; email: email@example.com
Lamarca, Angela; email: firstname.lastname@example.org
Hubner, Richard A.; email: email@example.com
Mansoor, Wasat; email: firstname.lastname@example.org
Valle, Juan W.; email: email@example.com
McNamara, Mairéad G.; orcid: 0000-0002-2272-3678; email: firstname.lastname@example.org
MetadataShow full item record
AbstractExtra-pulmonary neuroendocrine carcinomas (EP-NECs) are lethal cancers with limited treatment options. Identification of contributing factors to the observed heterogeneity of clinical outcomes within the EP-NEC family is warranted, to enable identification of effective treatments. A multicentre retrospective study investigated potential differences in “real-world” treatment/survival outcomes between small-cell (SC) versus (vs.) non-SC EP-NECs. One-hundred and seventy patients were included: 77 (45.3%) had SC EP-NECs and 93 (54.7%) had non-SC EP-NECs. Compared to the SC subgroup, the non-SC subgroup had the following features: (1) a lower mean Ki-67 index (69.3% vs. 78.7%; p = 0.002); (2) a lower proportion of cases with a Ki-67 index of ≥55% (73.9% vs. 88.7%; p = 0.025); (3) reduced sensitivity to first-line platinum/etoposide (objective response rate: 31.6% vs. 55.1%, p = 0.015; and disease control rate; 59.7% vs. 79.6%, p = 0.027); (4) worse progression-free survival (PFS) (adjusted-HR = 1.615, p = 0.016) and overall survival (OS) (adjusted-HR = 1.640, p = 0.015) in the advanced setting. Within the advanced EP-NEC cohort, subgroups according to morphological subtype and Ki-67 index (55% vs. ≥55%) had significantly different PFS (adjusted-p = 0.021) and OS (adjusted-p = 0.051), with the non-SC subgroup with a Ki-67 index of 55% and non-SC subgroup with a Ki-67 index of ≥55% showing the best and worst outcomes, respectively. To conclude, the morphological subtype of EP-NEC provides complementary information to the Ki-67 index and may aid identification of patients who could benefit from alternative first-line treatment strategies to platinum/etoposide.
CitationCancers, volume 13, issue 16, page e4152
DescriptionFrom MDPI via Jisc Publications Router
History: accepted 2021-08-13, pub-electronic 2021-08-18
Publication status: Published
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Peptide Location Fingerprinting Reveals Tissue Region-Specific Differences in Protein Structures in an Ageing Human OrganEckersley, Alexander; orcid: 0000-0003-1602-4851; email: email@example.com; Ozols, Matiss; orcid: 0000-0001-5663-1053; email: firstname.lastname@example.org; Chen, Peikai; orcid: 0000-0003-1880-0893; email: email@example.com; Tam, Vivian; email: firstname.lastname@example.org; Hoyland, Judith A.; orcid: 0000-0003-4876-5208; email: email@example.com; Trafford, Andrew; orcid: 0000-0002-2770-445X; email: Andrew.W.Trafford@manchester.ac.uk; Chan, Danny; orcid: 0000-0003-3824-5778; email: firstname.lastname@example.org; Sherratt, Michael J.; orcid: 0000-0003-4759-6617; email: email@example.com (MDPI, 2021-09-27)In ageing tissues, long-lived extracellular matrix (ECM) proteins are susceptible to the accumulation of structural damage due to diverse mechanisms including glycation, oxidation and protease cleavage. Peptide location fingerprinting (PLF) is a new mass spectrometry (MS) analysis technique capable of identifying proteins exhibiting structural differences in complex proteomes. PLF applied to published young and aged intervertebral disc (IVD) MS datasets (posterior, lateral and anterior regions of the annulus fibrosus) identified 268 proteins with age-associated structural differences. For several ECM assemblies (collagens I, II and V and aggrecan), these differences were markedly conserved between degeneration-prone (posterior and lateral) and -resistant (anterior) regions. Significant differences in peptide yields, observed within collagen I α2, collagen II α1 and collagen V α1, were located within their triple-helical regions and/or cleaved C-terminal propeptides, indicating potential accumulation of damage and impaired maintenance. Several proteins (collagen V α1, collagen II α1 and aggrecan) also exhibited tissue region (lateral)-specific differences in structure between aged and young samples, suggesting that some ageing mechanisms may act locally within tissues. This study not only reveals possible age-associated differences in ECM protein structures which are tissue-region specific, but also highlights the ability of PLF as a proteomic tool to aid in biomarker discovery.
Halogens in Eclogite Facies Minerals from the Western Gneiss Region, NorwayHughes; orcid: 0000-0002-4363-8675; email: firstname.lastname@example.org; Cuthbert; orcid: 0000-0002-1029-6357; email: email@example.com; Quas-Cohen; email: firstname.lastname@example.org; Ruzié-Hamilton; orcid: 0000-0002-2802-8123; email: email@example.com; Pawley; orcid: 0000-0002-3022-3235; email: firstname.lastname@example.org; Droop; email: email@example.com; Lyon; email: Ian.Lyon@manchester.ac.uk; Tartèse; email: firstname.lastname@example.org; Burgess; orcid: 0000-0001-7674-8718; email: email@example.com (MDPI, 2021-07-14)Ultra-high-pressure (UHP) eclogites and ultramafites and associated fluid inclusions from the Western Gneiss Region, Norwegian Caledonides, have been analysed for F, Cl, Br and I using electron-probe micro-analysis, time-of-flight secondary ion mass spectrometry and neutron-irradiated noble gas mass spectrometry. Textures of multi-phase and fluid inclusions in the cores of silicate grains indicate formation during growth of the host crystal at UHP. Halogens are predominantly hosted by fluid inclusions with a minor component from mineral inclusions such as biotite, phengite, amphibole and apatite. The reconstructed fluid composition contains between 11.3 and 12.1 wt% Cl, 870 and 8900 ppm Br and 6 and 169 ppm I. F/Cl ratios indicate efficient fractionation of F from Cl by hydrous mineral crystallisation. Heavy halogen ratios are higher than modern seawater by up to two orders of magnitude for Br/Cl and up to three orders of magnitude for I/Cl. No correlation exists between Cl and Br or I, while Br and I show good correlation, suggesting that Cl behaved differently to Br and I during subduction. Evolution to higher Br/Cl ratios is similar to trends defined by eclogitic hydration reactions and seawater evaporation, indicating preferential removal of Cl from the fluid during UHP metamorphism. This study, by analogy, offers a field model for an alternative source (continental crust) and mechanism (metasomatism by partial melts or supercritical fluids) by which halogens may be transferred to and stored in the sub-continental lithospheric mantle during transient subduction of a continental margin.
Oral Ferric Maltol Does Not Adversely Affect the Intestinal Microbiome of Patients or Mice, but Ferrous Sulphate DoesMahalhal, Awad; orcid: 0000-0001-6925-5018; email: firstname.lastname@example.org; Frau, Alessandra; email: A.Frau@liverpool.ac.uk; Burkitt, Michael D.; orcid: 0000-0002-5055-6408; email: email@example.com; Ijaz, Umer Z.; orcid: 0000-0001-5780-8551; email: Umer.Ijaz@glasgow.ac.uk; Lamb, Christopher A.; email: firstname.lastname@example.org; Mansfield, John C.; orcid: 0000-0003-2490-7750; email: email@example.com; Lewis, Stephen; email: firstname.lastname@example.org; Pritchard, D. Mark; orcid: 0000-0001-7971-3561; email: email@example.com; Probert, Chris S.; email: firstname.lastname@example.org (MDPI, 2021-06-30)Background and Aims: Altering dietary ferrous sulphate (FS) consumption exacerbates a murine model of colitis and alters the intestinal microbiome. We investigated the impact of oral ferric maltol (FM) and FS on mice with dextran sodium sulphate (DSS) induced colitis, and the microbiome of patients with iron deficiency. Methods: Mice had acute colitis induced, with 2% DSS for 5 days, followed by water. During this period, groups of mice were fed standard chow (200 ppm iron, SC, n = 8), or SC with 200ppm FS supplementation (n = 16, FSS), or SC with 200 ppm FM supplementation (n = 16, FMS). Clinical, pathological and microbiome assessments were compared at days 1 and 10. Fecal bacterial gDNA was extracted and the microbiome assessed by sequencing. Statistical inferences were made using MacQIIME. Principal Coordinates Analysis were used to visualize beta-diversity cluster analysis. Ten patients with IDA were treated with FS, and six with inactive inflammatory bowel disease received FM, supplements for four weeks: pre- and mid-treatment fecal samples were collected: the microbiome was assessed (see above). Results: In mice, after DSS treatment, there was a decrease in many genera in the SC and FSS groups: Lactobacillales increased in mice that received FMS. In humans, FS treatment led to an increase in five genera, but FM was not associated with any measurable change. The severity of DSS-induced colitis was greater with FSS than FMS. Conclusions: This study demonstrates differential and unique influences of ferric maltol and ferrous sulphate supplements on intestinal microbiota. These differences might contribute to the different side effects associated with these preparations.