Search results for "plastic"
showing 10 items of 7296 documents
Phase I Study of the Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Navoximod (GDC-0919) Administered with PD-L1 Inhibitor (Atezolizumab) in Advanced…
2019
Abstract Purpose: IDO1 induces immune suppression in T cells through l-tryptophan (Trp) depletion and kynurenine (Kyn) accumulation in the local tumor microenvironment, suppressing effector T cells and hyperactivating regulatory T cells (Treg). Navoximod is an investigational small-molecule inhibitor of IDO1. This phase I study evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of navoximod in combination with atezolizumab, a PD-L1 inhibitor, in patients with advanced cancer. Patients and Methods: The study consisted of a 3+3 dose-escalation stage (n = 66) and a tumor-specific expansion stage (n = 92). Navoximod was given orally every 12 hours continuously for 21 consecu…
Dynamic clonal remodelling in breast cancer metastases is associated with subtype conversion
2019
Background: Changes in the clinical subtype (CS) and intrinsic subtype (IS) between breast cancer (BC) metastases and corresponding primary tumours have been reported. However, their relationship with tumour genomic changes remains poorly characterised. Here, we analysed the association between genomic remodelling and subtype conversion in paired primary and metastatic BC samples. Methods: A total of 57 paired primary and metastatic tumours from GEICAM/2009-03 (ConvertHER, NCT01377363) study participants with centrally assessed CS (n = 57) and IS (n = 46) were analysed. Targeted capture and next-generation sequencing of 202 genes on formalin-fixed paraffin-embedded samples was performed. Th…
Epithelial-mesenchymal transition: a new target in anticancer drug discovery
2016
The conversion of cells with an epithelial phenotype into cells with a mesenchymal phenotype, referred to as epithelial-mesenchymal transition, is a critical process for embryonic development that also occurs in adult life, particularly during tumour progression. Tumour cells undergoing epithelial-mesenchymal transition acquire the capacity to disarm the body's antitumour defences, resist apoptosis and anticancer drugs, disseminate throughout the organism, and act as a reservoir that replenishes and expands the tumour cell population. Epithelial-mesenchymal transition is therefore becoming a target of prime interest for anticancer therapy. Here, we discuss the screening and classification o…
Genome-wide DNA methylation differences according to oestrogen receptor beta status in colorectal cancer.
2019
Involvement of sex hormones in colorectal cancer (CRC) development has been linked to oestrogen receptor β (ERβ). Expression of ERβ is found reduced in tumour tissue and inversely related to mortality. However, mechanisms are not well understood. Our study aimed to detect differentially methylated genes associated with ERβ expression, which could point to mechanisms by which ERβ could influence risk and prognosis of CRC. Epigenome-wide DNA methylation profiling was performed using Illumina HumanMethylation450k BeadChip arrays in two independent tumour sample sets of CRC patients recruited in 2003–2010 by the German DACHS study (discovery cohort n = 917, replication cohort n = 907). ERβ expr…
Adjuvant chemotherapy and relative survival of patients with stage II colon cancer - A EURECCA international comparison between the Netherlands, Denm…
2016
BACKGROUND: The aim of the present EURECCA international comparison is to compare adjuvant chemotherapy and relative survival of patients with stage II colon cancer between European countries.METHODS: Population-based national cohort data (2004-2009) from the Netherlands (NL), Denmark (DK), Sweden (SE), England (ENG), Ireland (IE), and Belgium (BE) were obtained, as well as single-centre data from Lithuania. All surgically treated patients with stage II colon cancer were included. The proportion of patients receiving adjuvant chemotherapy was calculated and compared between countries. Besides, relative survival was calculated and compared between countries.RESULTS: Overall, 59,154 patients …
Therapeutic drug monitoring as a tool to optimize 5-FU-based chemotherapy in gastrointestinal cancer patients older than 75 years.
2019
Abstract Aims Most clinical trials exclude elderly people, leading to a limited understanding of the benefit-to-risk ratio in this population. Despite existing data regarding the oncological management of elderly receiving fluorouracil (5-FU)-based regimen, our objective was to investigate 5-FU exposure/toxicity relationship in patients ≥75 years and compare the effectiveness of 5-FU therapeutic drug monitoring between elderly and younger patients. Methods Hundred fifty-four patients (31 of whom are older than 75 years) with gastrointestinal cancers, who were to receive 5-FU–based regimens, were included in our study. At cycle 1 (C1), the 5-FU dose was calculated using patient's body surfac…
The Amount of Melanin Influences p16 Loss in Spitzoid Melanocytic Lesions: Correlation With CDKN2A Status by FISH and MLPA.
2019
AIMS The risk assessment of spitzoid lesions is one of the most difficult challenges in dermatopathology practice. In this regard, the loss of p16 expression and the homozygous deletion of CDKN2A, have been pointed in the literature as reliable indicators of high risk. However, these findings are poorly reproducible, and the molecular bases underlying the loss of p16 expression remain unclear. We aimed to identify the underlying events causing loss of CDKN2A/p16 in spitzoid tumors. MATERIALS AND METHODS We evaluated the immunohistochemical expression of p16, and the presence of CDKN2A genetic alterations detected through fluorescence in situ hybridization (FISH) and multiplex ligation-depen…
Primary prophylaxis of invasive fungal infections with posaconazole or itraconazole in patients with acute myeloid leukaemia or high-risk myelodyspla…
2017
This is an observational-retrospective study comparing the real-world outcomes associated with posaconazole vs. itraconazole as prophylaxis treatments. Two hundred and ninety-three patient admissions attributable to 174 patients were included in the study. Patients were treated with itraconazole (n = 114 admissions; 39%) or posaconazole (n = 179; 61%). Antifungal prophylaxis failure (APF) due to treatment-related adverse events (in 34 out of 293 patient admissions; 11.6%) was more frequent in the posaconazole group (6.1% vs. 15.1%; P = 0.024). There were 9 patient admissions for episodes of APF due to probable/proven breakthrough fungal infection (primary endpoint): 6 and 3 in the itraconaz…
Impact of somatic mutations in myelodysplastic patients with isolated partial or total loss of chromosome 7
2020
Monosomy 7 [-7] and/or partial loss of chromosome 7 [del(7q)] are associated with poor and intermediate prognosis, respectively, in myelodysplastic syndromes (MDS), but somatic mutations may also play a key complementary role. We analyzed the impact on the outcomes of deep targeted mutational screening in 280 MDS patients with -7/del(7q) as isolated cytogenetic abnormality (86 with del(7q) and 194 with -7). Patients with del(7q) or -7 had similar demographic and disease-related characteristics. Somatic mutations were detected in 79% (93/117) of patients (82% in -7 and 73% in del(7q) group). Median number of mutations per patient was 2 (range 0-8). There was no difference in mutation frequen…