Clinical and Humanistic Burden of IgAN in Adult Patients: A Global Real-World Survey.

Background: Immunoglobulin A nephropathy (IgAN) is a chronic, progressive kidney disease in which proteinuria, reduced estimated glomerular filtration rate (eGFR), pain and fatigue are common. How symptoms interact and impact patient quality of life (QoL) in real-world practice is poorly studied. This study investigated how patient and physician symptom perceptions differ and how proteinuria and eGFR correlate with pain, fatigue, and QoL in adult IgAN patients.

Predicting Clinical Remission of Chronic Urticaria Using Random Survival Forests: Machine Learning Applied to Real-World Data.

Introduction: The time required to reach clinical remission varies in patients with chronic urticaria (CU). The objective of this study is to develop a predictive model using a machine learning methodology to predict time to clinical remission for patients with CU.

Methods: Adults with ≥ 2 ICD-9/10 relevant CU diagnosis codes/CU-related treatment > 6 weeks apart were identified in the Optum deidentified electronic health record dataset (January 2007 to June 2019).

Canakinumab improves patient-reported outcomes in children and adults with autoinflammatory recurrent fever syndromes: results from the CLUSTER trial.

Objectives: To evaluate the effect of canakinumab on health-related quality of life (HRQoL), work/school and social life of patients with autoinflammatory recurrent fever syndromes, including colchicine-resistant familial Mediterranean fever, mevalonate kinase deficiency, and tumour necrosis factor receptor-associated periodic syndrome, in the CLUSTER trial.

Methods: HRQoL of patients who received canakinumab 150 mg or 300 mg every four weeks in the CLUSTER trial (n=173) was assessed at baseline and Weeks 17 and 41. For children we used the Child Health Questionnaire - Parent Form 50 (CHQ-PF50), including psychosocial (PsS) and physical (PhS) component summary scores.

Application of systems biology-based in silico tools to optimize treatment strategy identification in Still's disease.

Background: Systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD) are manifestations of an autoinflammatory disorder with complex pathophysiology and significant morbidity, together also termed Still's disease. The objective of the current study is to set in silico models based on systems biology and investigate the optimal treat-to-target strategy for Still's disease as a proof-of-concept of the modeling approach.

Methods: Molecular characteristics of Still's disease and data on biological inhibitors of interleukin (IL)-1 (anakinra, canakinumab), IL-6 (tocilizumab, sarilumab), and glucocorticoids as well as conventional disease-modifying anti-rheumatic drugs (DMARDs, methotrexate) were used to construct in silico mechanisms of action (MoA) models by means of Therapeutic Performance Mapping System (TPMS) technology.

Exocytosis of polyubiquitinated proteins in bortezomib-resistant leukemia cells: a role for MARCKS in acquired resistance to proteasome inhibitors.

PSMB5 mutations and upregulation of the β5 subunit of the proteasome represent key determinants of acquired resistance to the proteasome inhibitor bortezomib (BTZ) in leukemic cells in vitro. We here undertook a multi-modality (DNA, mRNA, miRNA) array-based analysis of human CCRF-CEM leukemia cells and BTZ-resistant subclones to determine whether or not complementary mechanisms contribute to BTZ resistance. These studies revealed signatures of markedly reduced expression of proteolytic stress related genes in drug resistant cells over a broad range of BTZ concentrations along with a high upregulation of myristoylated alanine-rich C-kinase substrate (MARCKS) gene expression.

CGH arrays compared for DNA isolated from formalin-fixed, paraffin-embedded material.

Formalin-fixed, paraffin-embedded (FFPE) archival tissue is an important source of DNA material. The most commonly used technique to identify copy number aberrations from chromosomal DNA in tumorigenesis is array comparative genomic hybridization (aCGH). Although copy number analysis using DNA from FFPE archival tissue is challenging, several research groups have reported high quality and reproducible DNA copy number results using aCGH.

To DNA or not to DNA? That is the question, when it comes to molecular subtyping for the clinic!

Genome-wide RNA expression profiling has yielded tumor subtypes with strong predictive or prognostic value for a wide variety of cancers. Recently, for breast cancer two RNA expression classifiers have been adopted by the World Health Organization (WHO) and approved by the Food and Drug Administration (FDA). Also on the basis of DNA copy number profiles, tumor subtypes with different prognosis have been described, but have not yet led to clinical implementation.

Immortalization of oral keratinocytes by functional inactivation of the p53 and pRb pathways.

A subgroup of head and neck squamous cell carcinomas (HNSCCs) contains high-risk human papillomavirus-type 16 (HPV16). The viral E6 and E7 oncoproteins inactivate the p53 and pRb proteins, respectively. We examined the causative effect of HPV16 E6 and E7 expression on the immortalization of normal oral keratinocytes (OKCs) and compared the resulting phenotype with alternative ways of p53- and pRb-pathway abrogation frequently found in HNSCCs without HPV.

Intensity-based analysis of dual-color gene expression data as an alternative to ratio-based analysis to enhance reproducibility.

Background: Ratio-based analysis is the current standard for the analysis of dual-color microarray data. Indeed, this method provides a powerful means to account for potential technical variations such as differences in background signal, spot size and spot concentration. However, current high density dual-color array platforms are of very high quality, and inter-array variance has become much less pronounced.

Genetic classification of oral and oropharyngeal carcinomas identifies subgroups with a different prognosis.

The common risk factors for oral and oropharyngeal cancer are tobacco smoking and alcohol consumption, and recently the human papillomavirus (HPV) was shown to be involved in a subgroup. HPV-positive and -negative carcinomas can be distinguished on basis of their genetic profiles. Aim of this study was to investigate patterns of chromosomal aberrations of HPV-negative oral and oropharyngeal squamous cell carcinomas (OOSCC) in order to improve stratification of patients regarding outcome.

Genomic profiling identifies common HPV-associated chromosomal alterations in squamous cell carcinomas of cervix and head and neck.

Background: It is well known that a persistent infection with high-risk human papillomavirus (hrHPV) is causally involved in the development of squamous cell carcinomas of the uterine cervix (CxSCCs) and a subset of SCCs of the head and neck (HNSCCs). The latter differ from hrHPV-negative HNSCCs at the clinical and molecular level.

Methods: To determine whether hrHPV-associated SCCs arising from different organs have specific chromosomal alterations in common, we compared genome-wide chromosomal profiles of 10 CxSCCs (all hrHPV-positive) with 12 hrHPV-positive HNSCCs and 30 hrHPV-negative HNSCCs.

Comparative proteome analysis to explore p53 pathway disruption in head and neck carcinogenesis.

The 5-year-survival rate of head and neck squamous cell carcinoma (HNSCC) has been only moderately improved over the last few decades. HNSCC develops in precursor fields of genetically altered mucosal cells, typically characterized by p53 pathway disruption, that mostly do not give any clinical symptoms. Patients present therefore often with invasive carcinomas in an advanced stage.

Identification of genes putatively involved in the pathogenesis of diffuse large B-cell lymphomas by integrative genomics.

Diffuse large B-cell lymphomas (DLBCL) are highly heterogeneous with regard to clinical presentation and outcome. DLBCL copy number aberrations have been identified previously, of which the deletion at 6q21-24 was significantly associated with a highly favorable clinical response to chemotherapy. In this study, we aimed to identify genes implicated in this and other genomic regions with recurrent losses and/or gains.

Genome-wide microarray gene expression, array-CGH analysis, and telomerase activity in advanced ovarian endometriosis: a high degree of differentiation rather than malignant potential.

The aim of the present study was to investigate whether endometriosis and cancer share common molecular characteristics. Tissue samples were collected prospectively during diagnostic laparoscopy of patients with primary infertility. Using high-density oligonucleotide microarrays, (Affymetrix Gene Chip HG-U133 Set) the genome-wide gene expression profile of advanced ovarian endometriosis was analyzed compared with matched normal endometrium.

A novel algorithm for reliable detection of human papillomavirus in paraffin embedded head and neck cancer specimen.

Human papillomavirus type 16 (HPV16) plays a role in the development of a subgroup of head and neck squamous cell carcinomas (HNSCC). However, uncertainty exists about the true impact of HPV in this tumor type as conflicting reports have been published with prevalence rates from 0 to 100%. We aimed to find a detection algorithm of a biologically and thus clinically meaningful infection, applicable for high-throughput screening of frozen and formalin-fixed paraffin embedded (FFPE) specimens.

DNA quality assessment for array CGH by isothermal whole genome amplification.

Background: Array Comparative Genomic Hybridization (array CGH) is increasingly applied on DNA obtained from formalin-fixed paraffin-embedded (FFPE) tissue, but in a proportion of cases this type of DNA is unsuitable. Due to the high experimental costs of array CGH and unreliable methods for DNA quality testing, better prediction methods are needed. The aim of this study was to accurately determine the quality of FFPE DNA input in order to predict quality of array CGH outcome.

CGHMultiArray: exact P-values for multi-array comparative genomic hybridization data.

We compute P-values, based on the Wilcoxon test with ties, to compare two conditions with array comparative genomic hybridization data, and we provide a simple interface to export and plot these P-values.

Characterization of the human Ly-6 antigens, the newly annotated member Ly-6K included, as molecular markers for head-and-neck squamous cell carcinoma.

The E48 antigen is a successfully explored molecular marker for the diagnosis and therapy of HNSCC. The applicability of E48 as an HNSCC-associated antigen, however, is restricted due to its heterogeneous expression in 30% of tumors; and identification of additional target antigens is therefore desired. E48 belongs to the Ly-6 antigen family, comprising a group of highly homologous, low m.

Nonmalignant oral keratinocytes from patients with head and neck squamous cell carcinoma show enhanced metabolism of retinoic acid.

Background And Objective: Retinoids show promise in the treatment of various (pre)malignancies, including head and neck squamous cell carcinoma (HNSCC). It has been shown that metabolic pathways of retinoids are important in their anticancer effect and that these pathways may change during HNSCC carcinogenesis. We have previously reported that HNSCC cells have a 17-fold greater turnover rate of retinoic acid (RA) than normal oral keratinocytes from noncancer controls, and that the formation of polar metabolites such as 4-oxo-RA and 4-hydroxy-RA is only seen in HNSCC cell lines.