Search results for "ADULT"
showing 10 items of 17453 documents
Direct estrogen receptor (ER) / HER family crosstalk mediating sensitivity to lumretuzumab and pertuzumab in ER+ breast cancer.
2017
Bidirectional cross talk between members of the human epidermal growth factor family of receptors (HER) and the estrogen receptor (ER) is believed to underlie resistance mechanisms that develop in response to treatment with anti-HER agents and endocrine therapy. We investigated the interaction between HER2, HER3 and the ER in vitro using human embryonic kidney cells transfected with human HER2, HER3, and ERα. We also investigated the additive efficacy of combination regimens consisting of anti-HER3 (lumretuzumab), anti-HER2 (pertuzumab), and endocrine (fulvestrant) therapy in vivo. Our data show that both HER2 and HER3 can directly complex with the ER and can mediate phosphorylation of the …
Increasing Neural Stem Cell Division Asymmetry and Quiescence Are Predicted to Contribute to the Age-Related Decline in Neurogenesis.
2018
Summary: Adult murine neural stem cells (NSCs) generate neurons in drastically declining numbers with age. How cellular dynamics sustain neurogenesis and how alterations with age may result in this decline are unresolved issues. We therefore clonally traced NSC lineages using confetti reporters in young and middle-aged adult mice. To understand the underlying mechanisms, we derived mathematical models that explain observed clonal cell type abundances. The best models consistently show self-renewal of transit-amplifying progenitors and rapid neuroblast cell cycle exit. In middle-aged mice, we identified an increased probability of asymmetric stem cell divisions at the expense of symmetric di…
Taking Advantage of Nature’s Gift: Can Endogenous Neural Stem Cells Improve Myelin Regeneration?
2016
Irreversible functional deficits in multiple sclerosis (MS) are directly correlated to axonal damage and loss. Neurodegeneration results from immune-mediated destruction of myelin sheaths and subsequent axonal demyelination. Importantly, oligodendrocytes, the myelinating glial cells of the central nervous system, can be replaced to some extent to generate new myelin sheaths. This endogenous regeneration capacity has so far mainly been attributed to the activation and recruitment of resident oligodendroglial precursor cells. As this self-repair process is limited and increasingly fails while MS progresses, much interest has evolved regarding the development of remyelination-promoting strateg…
Grey Matter Microstructural Integrity Alterations in Blepharospasm Are Partially Reversed by Botulinum Neurotoxin Therapy.
2016
OBJECTIVE Benign Essential Blepharospasm (BEB) and hemifacial spasm (HFS) are the most common hyperkinetic movement disorders of facial muscles. Although similar in clinical presentation different pathophysiological mechanisms are assumed. Botulinum Neurotoxin (BoNT) is a standard evidence-based treatment for both conditions. In this study we aimed to assess grey matter microstructural differences between these two groups of patients and compared them with healthy controls. In patients we furthermore tracked the longitudinal morphometric changes associated with BoNT therapy. We hypothesized microstructural differences between the groups at the time point of maximum symptoms representation a…
Opposing Effects of CREBBP Mutations Govern the Phenotype of Rubinstein-Taybi Syndrome and Adult SHH Medulloblastoma
2018
Recurrent mutations in chromatin modifiers are specifically prevalent in adolescent or adult patients with Sonic hedgehog-associated medulloblastoma (SHH MB). Here, we report that mutations in the acetyltransferase CREBBP have opposing effects during the development of the cerebellum, the primary site of origin of SHH MB. Our data reveal that loss of Crebbp in cerebellar granule neuron progenitors (GNPs) during embryonic development of mice compromises GNP development, in part by downregulation of brain-derived neurotrophic factor (Bdnf). Interestingly, concomitant cerebellar hypoplasia was also observed in patients with Rubinstein-Taybi syndrome, a congenital disorder caused by germline mu…
Could lymphadenectomy be avoided in locally advanced cervical cancer patients administered preoperative chemoradiation? A large-scale retrospective s…
2017
Abstract Introduction To identify a subset of cervical cancer (CC) patients administered chemoradiation (CT/RT) plus radical surgery (RS), who can be spared lymphadenectomy, and complications. Patients and methods 430 Stage IB2-IIB patients without LN involvement at imaging were accrued (March 1996–December 2015) at Gynecologic Oncology Unit of the Catholic University of Rome/Campobasso. CT/RT consisted of pelvic irradiation plus cisplatin based chemotherapy. Objective response was evaluated according to RECIST criteria; radical hysterectomy and pelvic ± aortic lymphadenectomy was attempted in patients achieving response or stable disease. Surgical morbidity was classified according to the …
Specific norovirus interaction with Lewis x and Lewis a on human intestinal inflammatory mucosa during refractory inflammatory bowel disease
2021
Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are progressive diseases affecting millions of people each year. Flare-ups during IBD result in severe mucosal alterations of the small intestine (in CD) and in the colon and rectum (in CD and UC).
Bumetanide prevents brain trauma-induced depressive-like behavior
2019
AbstractBrain trauma triggers a cascade of deleterious events leading to enhanced incidence of drug resistant epilepsies, depression and cognitive dysfunctions. The underlying mechanisms leading to these alterations are poorly understood and treatment that attenuates those sequels not available. Using controlled-cortical impact (CCI) as experimental model of brain trauma in adult mouse we found a strong suppressive effect of the sodium-potassium-chloride importer (NKCC1) specific antagonist bumetanide on appearance of depression-like behavior. We demonstrate that this alteration in behavior is associated with a block of CCI-induced decrease in parvalbumin-positive interneurons and impairmen…
Molecular surveillance of norovirus, 2005–16 : an epidemiological analysis of data collected from the NoroNet network
2018
BACKGROUND: The development of a vaccine for norovirus requires a detailed understanding of global genetic diversity of noroviruses. We analysed their epidemiology and diversity using surveillance data from the NoroNet network.METHODS: We included genetic sequences of norovirus specimens obtained from outbreak investigations and sporadic gastroenteritis cases between 2005 and 2016 in Europe, Asia, Oceania, and Africa. We genotyped norovirus sequences and analysed sequences that overlapped at open reading frame (ORF) 1 and ORF2. Additionally, we assessed the sampling date and country of origin of the first reported sequence to assess when and where novel drift variants originated.FINDINGS: W…
Longitudinal Investigation into Genetics in the Conservation of Metabolic Phenotypes in Danish and Chinese Twins
2016
Longitudinal twin studies on long term conservation of individual metabolic phenotypes can help to explore the genetic and environmental basis in maintaining metabolic homeostasis and metabolic health. We performed a longitudinal twin study on 12 metabolic phenotypes from Danish twins followed up for 12 years and Chinese twins traced for 7 years. The study covered a relatively large sample of 502 pairs of Danish adult twins with a mean age at intake of 38 years and a total of 181 Chinese adult twin pairs with a mean baseline age of 39.5 years. Bivariate twin models were fitted to the longitudinal measurements taken at two time points (at baseline and follow-up) to estimate the genetic and e…