Jill Trendel - Academia.edu (original) (raw)

Papers by Jill Trendel

Expert opinion on drug discovery, 2013

Prostate cancer is the second most common cancer death in men after lung cancer, due to distant m... more Prostate cancer is the second most common cancer death in men after lung cancer, due to distant metastases. While distant prostate cancer is typically castrate resistant, it is not necessarily androgen independent. For this reason, a review of the literature regarding the pathways involved in androgen signaling and therapeutic regimens to treat distant metastases is beneficial to increasing the survival rate of prostate cancer patients. In this article, the author reviews the literature from the past decade covering metastatic hormone refractory prostate cancer with the aim to examine and identify pathways, therapeutic targets and current therapies for treating castrate-resistant disease. As this area is lacking, the author aims to provide the reader with knowledge of the molecular consequences of castrate resistant prostate cancer, the current treatment paradigms and future directions. While there have been advances in the treatment of castrate resistant prostate cancer, only minim...

Journal of Biological Chemistry

Burger's Medicinal Chemistry and Drug Discovery, 2003

... Step 6 generally involves in vivo testing and utilizes a pharmacodynamic (observable pharmaco... more ... Step 6 generally involves in vivo testing and utilizes a pharmacodynamic (observable pharmacologic effect) approach toward assessing compound availability and duration of ... The FDA's fast-track review of this information is said to have been reduced to an average of about ...

Journal of Medicinal Chemistry, 2011

i) Historical structural assignment.

Journal of Chromatography B, 2008

A sensitive high performance liquid chromatography tandem mass spectrometry (LC-MS/MS) method has... more A sensitive high performance liquid chromatography tandem mass spectrometry (LC-MS/MS) method has been developed for simultaneous determination of procaine and its metabolite p-aminobenzoic acid (PABA). N-Acetylprocainamide (NAPA) was used as an internal standard for procaine and PABA analysis. This assay method has also been validated in terms of linearity, lower limit of detection, lower limit of quantitation, accuracy and precision as per ICH guidelines. Chromatography was carried out on an XTerra TM MS C 18 column and mass spectrometric analysis was performed using a Quattro Micro TM mass spectrometer working with electro-spray ionization (ESI) source in the positive ion mode. Enhanced selectivity was achieved using multiple reaction monitoring (MRM) functions, m/z 237 → 100, m/z 138 → 120, and m/z 278 → 205 for procaine, PABA and NAPA, respectively. Retention times for PABA, procaine and NAPA were 4.0, 4.7 and 5.8 min, respectively. Linearity for each calibration curve was observed across a range from 100 nM to 5000 nM for PABA, and from 10 nM to 5000 nM for procaine. The intra-and inter-day relative standard deviations (RSD) were <5%.

Journal of Chromatography B, 2007

Journal of Chromatography A, 2007

A rapid high-performance liquid chromatography method has been developed for simultaneous determi... more A rapid high-performance liquid chromatography method has been developed for simultaneous determination of capecitabine and its metabolites: 5 -deoxy-5-fluorocytidine (5 -DFCR), 5 -deoxy-5-fluorouridine (5 -DFUR) and 5-fluorouracil (5-FU). 5 -DFCR was synthesized by hydrolyzing capecitabine using commercially available carboxyl esterase (CES) and characterized by NMR, mass spectrometry and elemental analysis. Baseline separations between capecitabine, 5 -DFCR, 5 -DFUR and 5-FU were found with symmetrical peak shapes on a Discovery RP-amide C 16 column using 10 mM ammonium acetate at pH 4.0 and methanol as the mobile phase. The retention times of capecitabine, 5 -DFCR, 5 -DFUR and 5-FU were 8.9, 5.0, 5.3 and 3.0 min, respectively. Linear calibration curves were obtained for each compound across a range from 1 to 500 g ml −1 . The intra-and inter-day relative standard deviations (%RSD) were <5%. A single-step protein precipitation method was employed for separation of the analytes from bio-matrices. Greater than 85% recoveries were obtained for capecitabine, 5 -DFCR, 5 -DFUR and 5-FU from bio-fluids including mouse plasma, mouse serum and rabbit bile.

Journal of Cellular Biochemistry, 2000

Phenotypic changes resembling an epithelial-to-mesenchymal transition often occur as epithelial c... more Phenotypic changes resembling an epithelial-to-mesenchymal transition often occur as epithelial cells become tumorigenic. Two proteins that have been implicated in this process are vimentin and N-cadherin. In this study, we sought to establish a link between expression of vimentin and N-cadherin as oral squamous epithelial cells undergo a morphologic change resembling an epithelial-to-mesenchymal transition. We found that N-cadherin and vimentin did not influence the expression of one another.

Journal of Biomolecular Screening, 2008

Peptidylglycine α-amidating monooxygenase (PAM) converts inactive terminal-glycine prohormones in... more Peptidylglycine α-amidating monooxygenase (PAM) converts inactive terminal-glycine prohormones into their activated α-amidated forms. PAM is thought to play a role in the development of antiandrogen drug resistance in prostate cancer (CaP) through PAMactivated autocrine growth. On the basis of the previous finding that many lung cancer cell lines excrete PAM into their culture media, this study investigates PAM levels in media collected from human CaP cell line cultures. Androgen-independent DU145 and PC-3 prostate cancer cell lines exhibited readily detectable levels of PAM activity in extracts and media, whereas the androgen-dependent LNCaP cell line showed little or no activity. Because of the much larger volume of media versus cell extracts, more than 90% of the total PAM activity was located in the media for both the PC-3 and DU145 cell lines, providing a readily accessible source of CaP PAM. A simple, scalable method to obtain PAM from the culture media of androgen-independent human prostate cancer cell lines is described in this article. This approach provides a much easier means of collecting CaPderived PAM than previously described cell fractionation procedures and should facilitate the investigations of the role and targeting of PAM in hormone-independent CaP. (Journal of Biomolecular Screening 2008:804-809)

Journal of Biological Chemistry, 2011

Matrix metalloproteinase-9 (MMP-9) is important in numerous normal and pathological processes, in... more Matrix metalloproteinase-9 (MMP-9) is important in numerous normal and pathological processes, including the angiogenic switch during tumor development and tumor metastasis. Whereas TNF-␣ and other cytokines up-regulate MMP-9 expression, interferons (IFNs) inhibit MMP-9 expression. We found that IFN-␥ treatment or forced expression of the IFNinduced GTPase, mGBP-2, inhibit TNF-␣-induced MMP-9 expression in NIH 3T3 fibroblasts, by inhibiting MMP-9 transcription. The NF-B transcription factor is required for full induction of MMP-9 by TNF-␣. Both IFN-␥ and mGBP-2 inhibit the transcription of a NF-B-dependent reporter construct, suggesting that mGBP-2 inhibits MMP-9 induction via inhibition of NF-B-mediated transcription. Interestingly, mGBP-2 does not inhibit TNF-␣-induced degradation of IB␣ or p65/RelA translocation into the nucleus. However, mGBP-2 inhibits p65 binding to a B oligonucleotide probe in gel shift assays and to the MMP-9 promoter in chromatin immunoprecipitation assays. In addition, TNF-␣ activation of NF-B in NIH 3T3 cells is dependent on Rac activation, as evidenced by the inhibition of TNF-␣ induction of NF-B-mediated transcription by a dominant inhibitory form of Rac1. A role for Rac in the inhibitory action of mGBP-2 on NF-B is further shown by the findings that mGBP-2 inhibits TNF-␣ activation of endogenous Rac and constitutively activate Rac can restore NF-B transcription in the presence of mGBP-2. This is a novel mechanism by which IFNs can inhibit the cytokine induction of MMP-9 expression.

Journal of Biomolecular Screening, 2012

The rise in organisms resistant to existing drugs has added urgency to the search for new antimic... more The rise in organisms resistant to existing drugs has added urgency to the search for new antimicrobial agents. Aspartate β-semialdehyde dehydrogenase (ASADH) catalyzes a critical step in an essential microbial pathway that is absent in mammals. Our laboratory is using fragment library screening to identify efficient and selective ASADH inhibitors. These preliminary agents are then tested to identify compounds with desired antimicrobial properties for further refinement. Toward this end, we have established a microplate-based, dual-assay approach using a single reagent to evaluate antibiotic activity and mammalian cell toxicity during early stage development. The bacterial assay uses nonpathogenic bacteria to allow efficacy testing without a dedicated microbial laboratory. Toxicity assays are performed with a panel of mammalian cells derived from representative susceptible tissues. These assays can be adapted to target other microbial systems, such as fungi and biofilms, and additional mammalian cell lines can be added as needed. Application of this screening approach to antibiotic standards demonstrates the ability of these assays to identify bacterial selectivity and potential toxicity issues. Tests with selected agents from the ASADH inhibitor fragment library show some compounds with antibiotic activity, but as expected, most of these early agents display higher than desired mammalian cell toxicity.