Synthesis and Biological Evaluation of Water-Soluble Progesterone-Conjugated Probes for Magnetic Resonance Imaging of Hormone Related Cancers

Sukerkar, Preeti A.; MacRenaris, Keith W.; Townsend, Taryn R.; Ahmed, Roshan A.; Burdette, Joanna E.; Meade, Thomas J.

doi:10.1021/bc2003555

Cited by 36 publications

(37 citation statements)

References 43 publications

(132 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cells were seeded in 96-well plates at 7.5 × 10 3 cells/well and incubated with drugs (10 μM) for 10 hours at 37°C in a 5% CO 2 incubator. Luciferase readout was measured as described previously(53). Secondary assay : MOE cells were treated with 10 μM of “hits”.…”

Section: Methodsmentioning

confidence: 99%

PAX2 function, regulation and targeting in fallopian tube-derived high-grade serous ovarian cancer

et al. 2016

View full text Add to dashboard Cite

The fallopian tube epithelium (FTE) is one of the progenitor populations for high-grade serous ovarian cancer (HGSC). Loss of PAX2 is the earliest known molecular aberration in the FTE occurring in serous carcinogenesis followed by a mutation in p53. Pathological studies report consistent loss of PAX2 in benign lesions as well as serous tumors. In the current study, the combined loss of PAX2 and expression of the R273H p53 mutant protein in murine oviductal epithelial (MOE) cells enhanced proliferation and growth in soft agar in vitro but was insufficient to drive tumorigenesis in vivo. A serially passaged model was generated to investigate the role of aging, but was also insufficient to drive tumorigenesis. These models recapitulate early benign lesions and suggest that a latency period exists between loss of PAX2, p53 mutation, and tumor formation. Stathmin and fut8 were identified as downstream targets regulated by loss of PAX2 and mutation of p53 in MOE cells. Re-expression of PAX2 in PAX2-null human HGSC cells reduced cell survival via apoptosis. PTENshRNA negatively regulated PAX2 expression and stable re-expression of PAX2 in MOE:PTENshRNA cells significantly reduced proliferation and peritoneal tumor formation in athymic nude mice. PAX2 was determined to be a direct transcriptional target that was activated by wild-type p53, whereas mutant p53 inhibited PAX2 transcription in MOE cells. A small molecule screen using the proximal PAX2 promoter driving luciferase identified four small molecules that were able to enhance PAX2 mRNA expression in MOE cells. PAX2 re-expression in HGSC cells and PTEN-deficient oviductal tumors may have the potential to induce apoptosis. In summary, mutant p53 and PTEN loss negatively regulated PAX2 and PAX2 re-expression in HGSC cells induced cell death.

show abstract

Section: Methodsmentioning

confidence: 99%

PAX2 function, regulation and targeting in fallopian tube-derived high-grade serous ovarian cancer

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Eu-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) (Eu-DOTA) [34], Eu-(1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid) (Eu-DO3A) [35] and Tb-(1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid) (Tb-DO3A) [36] were prepared by following the literature procedures. All the solvents used were of analytical grade.…”

Section: Methodsmentioning

confidence: 99%

Detection of Ciprofloxacin in Urine through Sensitized Lanthanide Luminescence

Singha

Ahn

2016

Sensors

View full text Add to dashboard Cite

Ciprofloxacin, a fluoroquinolone antibiotic, is widely used for the treatment of bacterial infection in humans due to its broad antibacterial spectrum. An excessive use or overdose of ciprofloxacin on the other hand can cause several adverse effects not only to humans but also to microorganisms. Unabsorbed ciprofloxacin in the body is mostly excreted through urine and finally goes to the environment, providing a drug resistance pressure on bacteria. Hence a simple and efficient detection method of ciprofloxacin is necessary, which, for example, can be used to analyze ciprofloxacin content in urine. Although ciprofloxacin itself shows inherent fluorescence, direct fluorescent detection of ciprofloxacin in raw urine sample is difficult due to autofluorescence of urine by other components. Herein we report that a Tb(III) complex of DO3A (1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid) can be efficiently sensitized by ciprofloxacin to emit luminescence separately from the urine autofluorescence wavelength region. Tb-DO3A shows excellent sensitivity with a detection limit of three parts per billion in aqueous buffer solution. Further, Tb-DO3A is used to detect ciprofloxacin with high sensitivity and selectivity in a raw urine sample without any purification or separation procedures in the concentrations ranging from 1 µg·mL−1 to 50 µg·mL−1. The direct measurement of ciprofloxacin excreted in urine may be used to control overdose of the drug.

show abstract

“…Plasmid containing progesterone responsive element (PRE) fused to firefly luciferase obtained from Dr. Ken Korach, (NIEHS, NIH, Research Triangle, NC) [17] was transfected into T47D cells (0.1 μg/well) and HSEC (0.5 μg/well) using Lipofectamine 2000 (Life Technologies, Inc. Carlsbad, CA) in Opti-MEM according to the manufacturer’s protocol (Life Technologies, Inc. Carlsbad, CA). PRE-luciferase transfection efficiencies were normalized to an independent control plasmid expressing beta-galactosidase (β-gal) or renilla luciferase (0.1 μg or 0.5 μg), a kind gift of Dr. William T. Beck, (University of Illinois, Chicago, IL), cotransfected simultaneously.…”

Section: Methodsmentioning

confidence: 99%

Biological characterization of non-steroidal progestins from botanicals used for women’s health

et al. 2012

View full text Add to dashboard Cite

Progesterone plays a central role in women’s reproductive health. Synthetic progestins, such as medroxyprogesterone acetate (MPA) are often used in hormone replacement therapy (HRT), oral contraceptives, and for the treatment of endometriosis and infertility. Although MPA is clinically effective, it also promiscuously binds to androgen and glucocorticoid receptors (AR/GR) leading to many undesirable side effects including cardiovascular diseases and breast cancers. Therefore, identifying alternative progestins is clinically significant. The purpose of this study was to biologically characterize non-steroidal progestins from botanicals by investigating their interaction and activation of progesterone receptor (PR). Eight botanicals commonly used to alleviate menopausal symptoms were investigated to determine if they contain progestins using a progesterone responsive element (PRE) luciferase reporter assay and a PR polarization competitive binding assay. Red clover extract stimulated PRE-luciferase and bound to PR. A library of purified compounds previously isolated from red clover was screened using the luciferase reporter assay. Kaempferol identified in red clover and a structurally similar flavonoid, apigenin, bound to PR and induced progestegenic activity and P4 regulated genes in breast epithelial cells and human endometrial stromal cells (HESC). Kaempferol and apigenin demonstrated higher progestegenic potency in the HESC compared to breast epithelial cells. Furthermore, phytoprogestins were able to activate P4 signaling in breast epithelial cells without downregulating PR expression. These data suggest that botanical extracts used for women’s health may contain compounds capable of activating progesterone receptor signaling.

show abstract

Synthesis and Biological Evaluation of Water-Soluble Progesterone-Conjugated Probes for Magnetic Resonance Imaging of Hormone Related Cancers

Cited by 36 publications

References 43 publications

PAX2 function, regulation and targeting in fallopian tube-derived high-grade serous ovarian cancer

PAX2 function, regulation and targeting in fallopian tube-derived high-grade serous ovarian cancer

Detection of Ciprofloxacin in Urine through Sensitized Lanthanide Luminescence

Biological characterization of non-steroidal progestins from botanicals used for women’s health

Contact Info

Product

Resources

About