Int J Fertil Steril
August 2022
Previous studies have shown that embryo donation can be a successful treatment for infertile couples,
however the willingness of Dutch couples to donate or accept embryos was unknown. The aim of this article is to
describe the protocol and results for altruistic embryo donation of the only embryo bank in the Netherlands.
Materials and Methods: This is a descriptive study.
Fusarium graminearum is a fungal pathogen that causes Fusarium head blight in cereal crops. The identification of proteins secreted from pathogens to overcome plant defenses and cause disease, collectively known as effectors, can reveal the etiology of a disease process. Proximity-dependent biotin identification (BioID) was used to identify potential effector proteins secreted in planta by F.
View Article and Find Full Text PDFSomatic hotspot mutations and structural amplifications and fusions that affect fibroblast growth factor receptor 2 (encoded by FGFR2) occur in multiple types of cancer. However, clinical responses to FGFR inhibitors have remained variable, emphasizing the need to better understand which FGFR2 alterations are oncogenic and therapeutically targetable. Here we apply transposon-based screening and tumour modelling in mice, and find that the truncation of exon 18 (E18) of Fgfr2 is a potent driver mutation.
View Article and Find Full Text PDFBackground: Aliarcobacter faecis and Aliarcobacter lanthieri are recently identified as emerging human and animal pathogens. In this paper, we demonstrate the development and optimization of two direct DNA-based quantitative real-time PCR assays using species-specific oligonucleotide primer pairs derived from rpoB and gyrA genes for A. faecis and A.
View Article and Find Full Text PDFCancer-associated systemic inflammation is strongly linked to poor disease outcome in patients with cancer. For most human epithelial tumour types, high systemic neutrophil-to-lymphocyte ratios are associated with poor overall survival, and experimental studies have demonstrated a causal relationship between neutrophils and metastasis. However, the cancer-cell-intrinsic mechanisms that dictate the substantial heterogeneity in systemic neutrophilic inflammation between tumour-bearing hosts are largely unresolved.
View Article and Find Full Text PDFBRCA1-mutated breast cancer is primarily driven by DNA copy-number alterations (CNAs) containing large numbers of candidate driver genes. Validation of these candidates requires novel approaches for high-throughput in vivo perturbation of gene function. Here we develop genetically engineered mouse models (GEMMs) of BRCA1-deficient breast cancer that permit rapid introduction of putative drivers by either retargeting of GEMM-derived embryonic stem cells, lentivirus-mediated somatic overexpression or in situ CRISPR/Cas9-mediated gene disruption.
View Article and Find Full Text PDFGenetically engineered mouse models (GEMMs) have contributed significantly to the field of cancer research. In contrast to cancer cell inoculation models, GEMMs develop de novo tumors in a natural immune-proficient microenvironment. Tumors arising in advanced GEMMs closely mimic the histopathological and molecular features of their human counterparts, display genetic heterogeneity, and are able to spontaneously progress toward metastatic disease.
View Article and Find Full Text PDFThe diagnosis of infectious disease is typically carried out at the point-of-care (POC) using the lateral flow assay (LFA). While cost-effective and portable, LFAs often lack the clinical sensitivity and specificity required for accurate diagnoses. In response to this challenge, we introduce a new digital microfluidic (DMF) platform fabricated using a custom inkjet printing and roll-coating process that is scalable to mass production.
View Article and Find Full Text PDFLarge-scale sequencing studies are rapidly identifying putative oncogenic mutations in human tumors. However, discrimination between passenger and driver events in tumorigenesis remains challenging and requires in vivo validation studies in reliable animal models of human cancer. In this study, we describe a novel strategy for in vivo validation of candidate tumor suppressors implicated in invasive lobular breast carcinoma (ILC), which is hallmarked by loss of the cell-cell adhesion molecule E-cadherin.
View Article and Find Full Text PDFPreclinical in vivo validation of target genes for therapeutic intervention requires careful selection and characterization of the most suitable animal model in order to assess the role of these genes in a particular process or disease. To this end, genetically engineered mouse models (GEMMs) are typically used. However, the appropriate engineering of these models is often cumbersome and time consuming.
View Article and Find Full Text PDFBackground: Annexin A1 (ANXA1) is a protein related with the carcinogenesis process and metastasis formation in many tumors. However, little is known about the prognostic value of ANXA1 in breast cancer. The purpose of this study is to evaluate the association between ANXA1 expression, BRCA1/2 germline carriership, specific tumor subtypes and survival in breast cancer patients.
View Article and Find Full Text PDFMetaplastic breast carcinoma (MBC) is a rare histological breast cancer subtype characterized by mesenchymal elements and poor clinical outcome. A large fraction of MBCs harbor defects in breast cancer 1 (BRCA1). As BRCA1 deficiency sensitizes tumors to DNA cross-linking agents and poly(ADP-ribose) polymerase (PARP) inhibitors, we sought to investigate the response of BRCA1-deficient MBCs to the PARP inhibitor olaparib.
View Article and Find Full Text PDFBackground: Elevated expression of focal adhesion kinase (FAK) occurs in numerous human cancers including colon-, cervix- and breast cancer. Although several studies have implicated FAK in mammary tumour formation induced by ectopic oncogene expression, evidence supporting a role for FAK in spontaneous mammary tumour development caused by loss of tumour suppressor genes such as p53 is lacking. Alterations in the tumour suppressor gene p53 have been implicated in over 50% of human breast cancers.
View Article and Find Full Text PDFThe cell surface is made electrochemically active by interfacing with graphene sheets. The electrical and thermal properties of graphene allow the control of cell surface potential for electrochemical synthesis. Using this approach radially projecting ZnO nanorods are templated on the surface of single cells.
View Article and Find Full Text PDFEnhanced epidermal growth factor receptor (EGFR) activity has been strongly linked to breast cancer progression and mediators of EGFR endocytosis may well be involved. We developed a semi-automated high-content fluorescence microscopy-based EGFR endocytosis screen to identify proteins that mediate EGFR endocytosis in human HBL100 breast cancer cells. Knockdown of 172 individual endocytosis and actin-regulatory genes with small interfering RNAs led to the identification of 14 genes of which the contribution to EGFR endocytosis in breast cancer is until now poorly defined, including DNAJC6, GDI2, FGD6, HAX1, NECAP2 and AnxA2.
View Article and Find Full Text PDFCancer develops through a multistep process in which normal cells progress to malignant tumors via the evolution of their genomes as a result of the acquisition of mutations in cancer driver genes. The number, identity and mode of action of cancer driver genes, and how they contribute to tumor evolution is largely unknown. This study deployed the Mouse Mammary Tumor Virus (MMTV) as an insertional mutagen to find both the driver genes and the networks in which they function.
View Article and Find Full Text PDFBreast cancer is the most common type of cancer in women. A substantial fraction of breast cancers have acquired mutations that lead to activation of the phosphoinositide 3-kinase (PI3K) signaling pathway, which plays a central role in cellular processes that are essential in cancer, such as cell survival, growth, division and motility. Oncogenic mutations in the PI3K pathway generally involve either activating mutation of the gene encoding PI3K (PIK3CA) or AKT (AKT1), or loss or reduced expression of PTEN.
View Article and Find Full Text PDFGenetically engineered mouse models (GEMMs) have contributed greatly to the field of cancer research. In contrast to tumor cell transplantation models, GEMMs have the potential to capture both the cell-intrinsic and cell-extrinsic factors that drive de novo formation of autochthonous tumors and their progression toward metastatic disease. In addition, GEMMs provide experimentally tractable in vivo platforms for validating candidate cancer genes, determining therapy efficacy, and defining mechanisms of drug resistance.
View Article and Find Full Text PDFAnnexin A1 (AnxA1) is a candidate regulator of the epithelial- to mesenchymal (EMT)-like phenotypic switch, a pivotal event in breast cancer progression. We show here that AnxA1 expression is associated with a highly invasive basal-like breast cancer subtype both in a panel of human breast cancer cell lines as in breast cancer patients and that AnxA1 is functionally related to breast cancer progression. AnxA1 knockdown in invasive basal-like breast cancer cells reduced the number of spontaneous lung metastasis, whereas additional expression of AnxA1 enhanced metastatic spread.
View Article and Find Full Text PDFThe adult, virgin mammary gland is a highly organized branched ductal network comprising two major cell types: myoepithelial and luminal epithelial cells. To study the role and mechanism of focal adhesion kinase (FAK)-mediated signaling in mammary gland development and differentiation, we used a conditional Fak-knockout mammary epithelial cell (MEC) transplantation model. Conditional Cre recombinase (Cre)-mediated Fak deletion in primary cultured MECs isolated from FAK(lox/lox)/Rosa26Cre-ERT2 donor mice caused loss of FAK in all mammary cells.
View Article and Find Full Text PDFBackground: Morphology discrimination (MD) in implantable cardioverter-defibrillators (ICDs) is based on the comparison of the ventricular electrogram during tachycardia with a stored reference template obtained during baseline rhythm. However, the effect of heart rate on the template match percentage during supraventricular tachyarrhythmias (SVT) is not known. The purpose of this study was to evaluate the performance of the template match percentage during SVT at different heart rates.
View Article and Find Full Text PDFObjectives: To compare the acute success and short-term follow-up of ablation of atrial flutter using 8 mm tip radiofrequency (RF) and cryocatheters.
Methods: Sixty-two patients with atrial flutter were randomized to RF or cryocatheter (cryo) ablation. Right atrial angiography was performed to assess the isthmus.
Background: Glucocorticoids (GCs) are commonly used in the treatment of (chronic) inflammatory diseases and cancer, but inherent or acquired resistance to these drugs limits their optimal efficacy. The availability of drugs that could modulate GC resistance is therefore of potential clinical interest.
Objective: To explore the molecular basis of GC sensitisation of GC resistant monocytic/macrophage cells after chronic exposure to sulfasalazine.