Project description:Mixed MCBA PBFM dosing of wild-type C57BL/6Crl mice. 80 mg/kg total bile acid dose (10 mg/kg individual MCBA). MCBAs included in the dosing included AlaCA, AspCA, GluCA, LeuCA, PheCA, SerCA, ThrCA, and TyrCA.
Project description:Mixed MCBA PBFM dosing of wild-type C57BL/6Crl mice. 80 mg/kg total bile acid dose (10 mg/kg individual MCBA). MCBAs included in the dosing included AlaCA, AspCA, GluCA, LeuCA, PheCA, SerCA, ThrCA, and TyrCA.
Project description:A clinical study evaluating the dosing of an oral HDACi panobinostat in patient infected with HIV-1. Dosing was 20 mg orally, 3 times weekly, every other week for a total of 8 weeks. Gene expression was evaluated in whole PBMCs at baseline (Visit 2), after 3 doses (Visit 4), 4 weeks after dosing (Visit 12) and 6 months after dosing (Visit 13) using the Affymetrix HTA 2.0 gene expression chip
Project description:Tamoxifen, a selective estrogen receptor modulator (SERM), is an effective treatment for breast cancers. In the CD-1 mouse model, neonatal oral dosing with tamoxifen leads to the development of adenomyosis. Both 4-hydroxyestradiol and tamoxifen can form DNA-reactive metabolites and may be involved in carcinogenesis of the uterus. After comparing the uterotrophic response of several SERMs the maximal uterotrophic doses of estradiol (100mg/kg) 4-hydroxyestradiol (385mg/kg) and tamoxifen (250mg/kg) were determined. Maximal uterotrophic doses were given orally to newborn CD-1 mice on days 1 â 4 after birth and gene and pathological changes examined in the uterus at 3 months after dosing. ERKOa knockout mice were dosed orally with tamoxifen (1mg/Kg) on days 1 â 4 after birth and uterine gene expression compared with CD-1 mice. Dosing groups: Estradiol (E2): 100mg/Kg 4-hydroxyestradiol (4OHE2): 385mg/Kg Tamoxifen : 250mg/Kg ERKO mice dosed with tamoxifen (1mg/Kg) 4 dosed animals and 4 controls for each treatment group. Uteri removed at 3 months after dosing and total RNA extracted. Controls were pooled. RNA labelling, hybridisation and analysis of fluorescence was carried out as described by Turton et al (2001). Cy3/Cy5 dye swap labelling was carried out on samples from each animal. Reference: Turton NJ et. al. (Oncogene (2001) 20, 1300-1306
Project description:The phase 2 KNOCKOUT (NCT05283135) study evaluated higher-than-approved doses of risankizumab, an interleukin-23 inhibitor, for treatment of moderate-to-severe plaque psoriasis. Patients received either 300 or 600 mg of risankizumab at Weeks 0, 4, and 16 and were monitored through Week 100 without further dosing. Efficacy and safety were tracked throughout the study and RNASeq was performed on lesional/non-lesional tissue. Nine patients per treatment group completed dosing. At Weeks 28 and 52, Psoriasis Areas and Severity Index 75/90/100 responses were achieved by 94.4%/94.4%/83.3% and 77.8%/61.1%/44.4% of all patients, respectively, with no new safety signals. At Week 52, TRM cell numbers in lesional skin were markedly reduced, with numbers similar to non-lesional resident memory T cell numbers at Week 0. High skin clearance rates with higher-than-approved initial dosing of risankizumab with prolonged maintenance of skin clearance, despite the lack of continuous dosing, represent a potential novel treatment strategy for patients with psoriasis.
Project description:C57BL/6Crl mice were fed 10 mg/kg BA or control for 13 days. Samples collected on day 14. Treatment groups included serocholate, serine + cholate, phenylalanocholate, phenylalanine + cholate, taurocholate, taurine + cholate, and a mock control.
Fecal, F; Colon, CL; Cecum, CE; Duodenum, DD; Gallbladder, GB; Ileum, IL; Liver, L