A5083069711- Endometriosis Research and Treatment
- Reproductive System and Pregnancy
- Estrogen and related hormone effects
- HER2/EGFR in Cancer Research
- Uterine Myomas and Treatments
- Endometrial and Cervical Cancer Treatments
- Monoclonal and Polyclonal Antibodies Research
- Liver physiology and pathology
- Cancer therapeutics and mechanisms
- Cancer, Hypoxia, and Metabolism
- Computational Drug Discovery Methods
- Genetic factors in colorectal cancer
- Reproductive Physiology in Livestock
- Cholinesterase and Neurodegenerative Diseases
- Intestinal and Peritoneal Adhesions
- Cancer Research and Treatments
- bioluminescence and chemiluminescence research
- Gynecological conditions and treatments
- Cancer Cells and Metastasis
- Multiple Myeloma Research and Treatments
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Cytokine Signaling Pathways and Interactions
- PI3K/AKT/mTOR signaling in cancer
- Angiogenesis and VEGF in Cancer
- Pregnancy and preeclampsia studies
Synthon (Netherlands)
2014-2023
Merck (Netherlands)
2017
Merck & Co., Inc., Rahway, NJ, USA (United States)
2014
MSD (Netherlands)
2011-2013
Maastricht University Medical Centre
1999-2011
Maastricht University
1922-2011
Universitat de València
2007
University of Oxford
2007
Human Fertilisation and Embryology Authority
2007
Foundation for Growth Science
2000-2006
It is known that angiogenesis of pivotal importance for the development endometriosis. However, in treatment endometriosis patients, prevention lesion only will not be sufficient as a therapy. Treatment options, aimed at interfering with established lesions, have to developed. In this study we evaluated whether inhibition by angiostatic therapy also effective antagonizing sustentation We effect compounds antihuman vascular endothelial growth factor, TNP-470, endostatin, and anginex on...
SYD985 is a HER2-targeting antibody-drug conjugate (ADC) based on trastuzumab and vc-seco-DUBA, cleavable linker-duocarmycin payload. To evaluate the therapeutic potential of this new ADC, mechanistic in vitro studies vivo patient-derived xenograft (PDX) were conducted to compare head-to-head with T-DM1 (Kadcyla), another trastuzumab-based ADC. had similar binding affinities HER2 showed internalization. In cytotoxicity assays potencies efficacies 3+ cell lines, but lines low expression, was...
A linker-drug platform was built on the basis of a cleavable linker-duocarmycin payload for development new-generation antibody-drug conjugates (ADC). leading ADC originating from that is SYD983, HER2-targeting based trastuzumab. HER2-binding, antibody-dependent cell-mediated cytotoxicity and HER2-mediated internalization are similar SYD983 as compared with HER2-expressing cells in vitro very potently killed by but inactive do not express HER2. dose dependently reduces tumor growth BT-474...
Significance The age-adjusted incidence of colonic adenomas and colorectal cancer is higher in men than women. In a careful analysis two established animal models, we found that castration reduced, testosterone supplementation restored, the number male rat mouse colon, whereas ovariectomy replacement female hormones had no measureable effect on adenomagenesis. Min mice, which most tumors arise small intestine, this testosterone-dependent sexual dimorphism mice was specific to colon. Our...
Estradiol (E(2)) is an important promoter of the growth both eutopic and ectopic endometrium. The findings with regard to expression activity steroidogenic enzymes in endometrium controls, endometriosis patients endometriotic lesions are not consistent.In this study, we have looked at mRNA protein levels a range [aromatase, 17beta-hydroxysteroid dehydrogenases (17beta-HSD) type 1, 2 4, estrogen sulfotransferase (EST) steroid sulfatase (STS)] (n = 14) deep-infiltrative as well disease-free...
Context: substantial evidence suggests that the expression of steroid metabolizing enzymes in endometriosis is altered, turning ectopic endometrium into a source 17β-estradiol. However, whether these differences result net increase local 17β-estradiol production/activity has not been shown. Subjects and Methods: The activities most important steroidogenic synthesizing inactivating were determined by HPLC matched eutopic tissue from patients with (n = 14) controls 20). Results: Aromatase...
The human progesterone receptor (PR) is a ligand-dependent transcription factor and two isoforms, (PRA PRB), can be distinguished. PROGINS, PR polymorphic variant, affects PRA PRB acts as risk-modulating in several gynaecological disorders. Little known about the functional consequences of this variant. Here, we characterise properties PROGINS with respect to transcription, mRNA maturation, protein activity proliferation. characterised by 320 bp PV/HS-1 Alu insertion intron G point...
Matrix metalloproteinases (MMPs) are essential for extracellular matrix remodelling and may contribute to the development of endometriosis. Transplantation endometrium onto chicken chorioallantoic membrane (CAM) results in endometriosis-like lesion formation, a process that requires extensive tissue remodelling. We investigated expression wide range MMPs menstrual endometrium, lesions CAMs, peritoneal endometriosis rectovaginal space, as well function early formation CAM model.Expression was...
Using cDNA microarray analysis, we identified SGK1 (serum- and glucocorticoid-regulated kinase 1) as a gene aberrantly expressed in midsecretory endometrium of women with unexplained infertility. is serine/threonine involved primarily epithelial ion transport cell survival responses. Real-time quantitative PCR analysis larger, independent sample set timed to coincide the period uterine receptivity confirmed increased expression transcripts infertile compared fertile controls. We further...
In this study, we characterized the fibromuscular (FM) tissue, typical of deeply infiltrating endometriosis, investigated which cells are responsible for FM reaction and evaluated whether transforming growth factor-beta (TGF-beta) signaling is involved in process.FM differentiation TGF-beta were assessed endometriosis lesions (n = 20) a nude mouse model 1, 2, 3 4 weeks post-transplantation. The was by immunohistochemistry using different markers smooth muscle cell (vimentin, desmin,...
Carboxylesterase 1c (CES1c) is responsible for linker-drug instability and poor pharmacokinetics (PK) of several antibody-drug conjugates (ADC) in mice, but not monkeys or humans. Preclinical development these ADCs could be improved if the PK mice would more closely resemble that humans affected by an enzyme irrelevant SYD985, a HER2-targeting ADC based on trastuzumab vc-seco-DUBA, also sensitive to CES1c. In present studies, we first focused interaction between CES1c SYD985 size- exclusion...
ObjectiveTo identify metabolites that are associated with and predict the presence of endometriosis.DesignMetabolomics study using state-of-the-art mass spectrometry approaches.SettingUniversity hospital universities.Patient(s)Twenty-five women laparoscopically confirmed endometriosis (cases) 19 documented absence (controls). None included in this had received oral contraception or GnRH agonists for a minimum 1 month before blood collection.Intervention(s)Plasma collection.Main Outcome...
Engineering cysteines at specific sites in antibodies to create well-defined ADCs for the treatment of cancer is a promising approach increase therapeutic index and helps streamline manufacturing process. Here, we report development an silico screening procedure select optimal antibody which hydrophobic linker–drug can be conjugated. Sites were identified inside cavity that naturally present Fab part antibody. Conjugating these demonstrated ability shield character while resulting maintained...
The general concept that haemoglobin is only a carrier protein for oxygen and carbon dioxide challenged since recent studies have shown expression in non-erythroid cells the protection of against oxidative nitrosative stress. Using microarrays, we previously showed haemoglobins alpha, beta, delta gamma haeme metabolizing enzyme, oxygenase (HO)-1 human endometrium.Using real-time quantitative PCR, gamma, HO-1 mRNA levels were assessed throughout menstrual cycle (n = 30 women). Haemoglobin...
<h3>Background</h3> Hormone replacement therapy increases the risk of developing ulcerative colitis in postmenopausal women. Chronic intestinal inflammation predisposes to colon cancer development, but effects female hormones on colitis-associated development have not been examined. <h3>Aim</h3> To investigate role dextran sodium sulfate (DSS)-azoxymethane (AOM) mouse model for cancer. <h3>Design</h3> We performed ovariectomies, or sham operations, mice, and supplemented these animals with...
Lone Hummelshoj1†, Andrew Prentice2 & Patrick Groothuis3 †Author for correspondence 1Endometriosis.ORG, 89 Southgate Road, London, N1 3JS, UK. Tel.: +44 (0)7710 065 164; Fax: (0)20 7354 4708; E-mail: lone@endometriosis.org 2University Department of Obstetrics and Gynaecology, The Rosie Hospital, Robinson Way, Cambridge, CB2 2SW, (0)1223 336 876; 215 327; ap128@cam.ac.uk 3Research Institute Growth Development, University Hospital Maastricht, Peter Debyelaan 25, 6229 HX Netherlands. +31 (0)43...