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Triple combination targeting PI3K,eR,and CDK4/6 inhibits growth of eR-positive breast cancer resistant to fulvestrant and CDK4/6 or PI3K inhibitor

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Cancer Communications 2023年第6期43卷 720-725页

作者： Mikkel G.Terp Martina Tuttolomondo Neil Portman Sidse ehmsen lene e.johansen Martin Bak elgene Lim Henrik J.Ditzel Department of Cancer and Inflammation Research Institute of Molecular MedicineUniversity of Southern DenmarkOdenseDenmark Garvan Institute of Medical Research DarlinghurstSydneyNew SouthWalesAustralia St.Vincent’s Clinical School Faculty of MedicineUniversity of New SouthWales SydneySydneyNew South WalesAustralia Department of Oncology Institute of Clinical ResearchOdense University HospitalOdenseDenmark Department of Pathology Sydvestjysk SygehusEsbjergDenmark Academy of Geriatric Cancer Research(AgeCare) Odense University HospitalOdenseDenmark

Dear editor,Despite the improved outcome of advanced estrogen receptor-positive(eR+)breast cancer patients treated with endocrine therapy in combination with either a cyclindependent kinase 4/6 inhibitor(CDK4/6i)or a phosphoinositide 3-kinase inhibitor(PI3Ki),the disease will eventually progress,and the optimal treatment strategy upon progression remains undefined[1-4].To address this,we developed MCF-7-and T47D-derived PIK3CAmutated breast cancer cell lines[5]resistant to combined CDK4/6i palbociclib and fulvestrant(MPF-R and TPFR)or combined PI3Ki alpelisib and fulvestrant(MAF-R and TAF-R),respectively(Supplementary Materials and Methods).Drug-sensitive isogenic cells(M-S and T-S)grown in parallel with MPF-R and TPF-R cells and the original MCF-7/S0.5 and T47D cells were analyzed for comparison.

关键词： PIK3CA breast cancer

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evaluation of a new qPCR test to identify the organisms causing high total bacterial count in bulk tank milk

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Journal of Integrative Agriculture 2018年第6期17卷 1241-1245页

作者： Jorgen Katholm lene Trier Olesen Anders Petersen Snorri Sigurdsson DNA Diagnostic A/S Risskov 8240Denmark ARLA Foods amba Viby 8260Denmark SeGeS Aarhus N 8200Denmark

Milk quality in bulk tank milk （BTM） is measured by flow cytometry technology as total bacterial count （TBC） and somatic cell count （SCC）. To investigate SCC problems, culture or PCR can be used to identify mastitis causing bacteria, e.g., Mastit 4, a commercially available qPCR test. TBC in BTM can be investigated further using culture-based methods such as standard plate count, laboratory pasteurization count, coliform count, and spore counts. To our knowledge, no qPCR addressing the bacteria involved in TBC has been commercially introduced. The aim of this study is to evaluate a recently introduced 3-h qPCR test, TBC 4. The TBC 4 qPCR detects four target groups, Pseudomonas, Streptococci, enterobacteriacea/ enterococcus, and Bacillus/Clostridia. These target groups relate to problems on the farm such as cooling, mastitis, environment, and silage. We will continue with new research to compare the TBC 4 qPCR test with traditional culture. For this study, BTM samples from different TBC intervals were selected based on BactoCount results found at routine payment investigation at eurofins laboratory （Vejen, Denmark）. These samples were analyzed using TBC 4 qPCR assay within 24 h. In total, 346 BTM samples were divided into six different intervals of colony forming units （CFU）. For all four targets in each of the different intervals of CFU, the percent of positive samples, the average Ct-value, the percent of positive samples with Ct〈30 and Ct〈25 were calculated. For Pseudomonas, Streptococci, and enterobacteriacea/enterococcus, the number of positive samples with lower Ct-values （high bacteria content） correlated with the CFU mL-1. We found enterobacteriacea/ enterococcus, Pseudomonas, and Streptococci in high number of bacteria （Ct〈25） in 25, 19 and 56％ of samples with CFU mL-1 between 50001-100000 and 53, 44, and 39％ in samples with CFU mL-1〉100000. The TBC 4 qPCR test showed to be a strong and fast tool for farmers, advisors and service technicians to address probl

关键词： TBC bulk tank milk qPCR milk quality

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Increasing Incidence of extended-Spectrum Beta-Lactamase-Producing enterobacteriaceae (eSBL) and the Relation to Consumption of Broad-Spectrum Antimicrobial Agents 2003-2011 in a Large Area of Copenhagen, Denmark

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Open Journal of Medical Microbiology 2015年第1期5卷 28-42页

作者： lene Nielsen Anne Kjerulf Magnus Arpi Department of Clinical Microbiology Copenhagen University Hospital Herlev Denmark Department of Microbiology and Infection Control at Statens Serum Institut Copenhagen Denmark

Purpose: To investigate 1) the development in the incidence of eSBL-producing bacteria in hospitals and primary health care, 2) the contribution of primary health care to the incidence of eSBL-producing bacteria, and 3) the development in resistance patterns for all escherichia coli and Klebsiella pneumoniae isolates in relation to antimicrobial consumption in hospitals and primary health care. Methods: eSBL-data were retrospectively collected from bacterial isolates from all specimens received at the Department of Clinical Microbiology from 2003 to 2011 together with the corresponding patient data. eSBL-production was detected in isolates from 1067 of 59,373 patients (1.8%) with an e. coli infection and in 263 of 8660 patients (3.0%) with a K. pneumoniae infection. Results: From 2003 to 2009, an increase in patients with an eSBL-producing isolate occurred in both hospitals and primary health care at the same time as an increased consumption of broad-spectrum antimicrobial agents was seen. Interventions to reduce prescription of cephalosporins and ciprofloxacin at the hospitals from 2010 resulted in a remarkable decrease in patients with eSBL-producing K. pneumoniae whereas a continuing increase was seen in patients with eSBL-producing e. coli both at hospitals and in primary health care. The proportion of patients with community-acquired eSBL-producing e. coli was stable with an increase of only 1.4% from 2007 to 2011. Conclusions: Reduction in prescription of broad-spectrum antimicrobial agents at the hospital level had an important impact on the incidence of eSBL-producing K. pneumoniae, but not on eSBL-producing e. coli.

关键词： Incidence of eSBL-Producing e. coli and K. pneumoniae Hospital Care Primary Health Care Antimicrobial Consumption Broad-Spectrum Antimicrobial Agents

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Single Molecule Applications of Quantum Dots

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Journal of Modern Physics 2013年第11期4卷 27-42页

作者： Thomas e. Rasmussen Liselotte Jauffred Jonathan Brewer Stefan Vogel esben R. Torbensen B. Christoffer Lagerholm lene Oddershede eva C. Arnspang 1Departments of Physics Chemistry Pharmacy Biochemistry and Molecular Biology University of Southern Denmark Odense Denmark 2National Institutes of Health Bethesda USA 3Department of Molecular Biology and Genetics and Interdisciplinary Nanoscience Center Aarhus University Aarhus Denmark 1Departments of Physics Chemistry Pharmacy Biochemistry and Molecular Biology University of Southern Denmark Odense Denmark 2Weatherall Institute of Molecular Medicine University of Oxford Oxford UK Departments of Physics Chemistry Pharmacy Biochemistry and Molecular Biology University of Southern Denmark Odense Denmark Niels Bohr Institute University of Copenhagen Copenhagen Denmark

Fluorescent nanocrystals composed of semiconductor materials were first introduced for biological applications in the late 1990s. The focus of this review is to give a brief survey of biological applications of quantum dots (QDs) at the single QD sensitivity level. These are described as follows: 1) QD blinking and bleaching statistics, 2) the use of QDs in high speed single particle tracking with a special focus on how to design the biofunctional coatings of QDs which enable specific targeting to single proteins or lipids of interest, 3) a hybrid lipid-DNA analogue binding QDs which allows for tracking single lipids in lipid bilayers, 4) two-photon fluorescence correlation spectroscopy of QDs and 5) optical trapping and excitation of single QDs. In all of these applications, the focus is on the single particle sensitivity level of QDs. The high applicability of QDs in live cell imaging experiments held together with the prospects in localization microscopy and single molecule manipulation experiments gave QDs a promising future in single molecule research.

关键词： Quantum Dots Single Particle Tracking Fluorescence Correlation Spectroscopy Optical Tweezers

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