37 research outputs found

    Paraoxonase 2 overexpression inhibits tumor development in a mouse model of ovarian cancer.

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    Ovarian cancer (OC) is most lethal malignancy among all gynecological cancer. Large bodies of evidences suggest that mitochondrial-derived ROS play a critical role in the development and progression of OC. Paraoxonase 2 (PON2) is a membrane-associated lactonase with anti-oxidant properties. PON2 deficiency aggravates mitochondrial ROS formation, systemic inflammation, and atherosclerosis. The role of PON2 in cancer development remains unknown. In this report, in human, we identified that PON2 expression is higher in early stages (but not in late stages) of OC when compared to normal tissue. Using a mouse xenograft model of OC, we demonstrate that overexpression of PON2 prevents tumor formation. Mechanistically, PON2 decreases OC cell proliferation by inhibiting insulin like growth factor-1 (IGF-1) expression and signaling. Intriguingly, PON2 reduces c-Jun-mediated transcriptional activation of IGF-1 gene by decreasing mitochondrial superoxide generation. In addition, PON2 impairs insulin like growth factor-1 receptor (IGF-1R) signaling in OC cells by altering cholesterol homeostasis, which resulted in reduced caveolin-1/IGF-1R interaction and IGF-1R phosphorylation. Taken together, we report for the first time that PON2 acts as a tumor suppressor in the early stage of OC by reducing IGF-1 production and its signaling, indicating PON2 activation might be a fruitful strategy to inhibit early stage ovarian tumor

    Photoluminescence spectroscopy of YVO4_{4}:Eu3+^{3+} nanoparticles with aromatic linker molecules: a precursor to biomedical functionalization

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    Photoluminescence spectra of YVO4_{4}:Eu3+^{3+} nanoparticles are presented,with and without the attachment of of organic linker molecules that are proposed for linking to biomolecules. YVO4_{4}:Eu3+^{3+} nanoparticles with 5% dopant concentration were synthesized by wet chemical synthesis. X-ray diffraction and transmission electron microscopy show the expected wakefieldite structure of tetragonal particles with an average size of 17 nm. Fourier-transform infrared spectroscopy determines that metal-carboxylate coordination is successful in replacing the native metal-hydroxyl bonds with three organic linkers, namely benzoic acid, 3-nitro 4-chloro-benzoic acid and 3,4-dihydroxybenzoic acid, in separate treatments. UV-excitation photoluminescence spectra show that the position and intensity of dominant 5D07F2^{5}D_{0}-^{7}F_{2} electric-dipole transition at 619 nm is unaffected by the benzoic acid and 3-nitro 4-chloro-benzoic acid treatments. Attachment of the 3,4-dihydroxybenzoic acid produces an order-of-magnitude quenching of the photoluminescence, due to the presence of high-frequency modes in the linker. Ratios of the dominant electric- and magnetic-dipole transitions confirm infrared measurements, which indicate that the bulk crystal of the nanoparticle is unchanged by all three treatments.Comment: 9 pages, 5 figures, journal articl

    Cranial nerve outcomes in regionally recurrent head & neck melanoma after sentinel lymph node biopsy

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/156007/1/lary28243.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156007/2/lary28243_am.pd

    Facilitating Automated Data Analytics Through Structured Head and Neck Oncology Tumor Board Documentation

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    http://deepblue.lib.umich.edu/bitstream/2027.42/191978/2/2022_JCO_Tumor Board Automated Data Analytics.pdfPublished versionDescription of 2022_JCO_Tumor Board Automated Data Analytics.pdf : Published versio

    Investigation of gender‐based needs in academic otolaryngology

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    Abstract Objective Gaps in gender‐based equity persist in academic otolaryngology. Here we present a needs‐based assessment of otolaryngology faculty and trainees regarding facilitators and barriers to professional satisfaction and career development in academic medicine. Methods A qualitative study of otolaryngology faculty, trainees, and administrators who identify as women at an academic tertiary care center was performed from 2020 to 2021 using focus groups and semi‐structured interviews. Five confidential, virtual focus group sessions moderated by a third‐party executive coach were audio‐taped, transcribed, and reviewed for thematic content. Results Of 48 women invited, 77% participated (18 faculty/administrative leaders, 10 residents/fellows, 4 audiologists). Participants noted direct patient care, support from colleagues who identify as women, and the transition to virtual meetings as facilitators of current professional satisfaction. Five themes emerged as barriers to workplace satisfaction and career development including (1) limited professional schedule flexibility, (2) competing commitments such as childcare exacerbated by pandemic, (3) lack of visible departmental leadership who identify as women, (4) perceived lack of organic sponsorship within subspecialty divisions, and (5) frequent identity‐associated microaggressions from patients and staff outside the department. Strategies identified for improving gender‐based equity included (1) promoting department‐wide awareness of workplace gender‐based differences, (2) implicit bias training within established programming such as grand rounds conferences, and (3) novel faculty programming such as leadership development training and formal junior faculty mentorship. Conclusion Confidential needs‐based assessment of otolaryngology faculty and trainees identified both persistent gaps and strategies to enhance recruitment, support career development, and grow professional satisfaction of women within academic otolaryngology. Level of Evidence 3
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