Background: Pseudomonas fluorescens lectin (PFL) belongs to a recently discovered anti-HIV lectin family and induces anoikis-like cell death of MKN28 gastric cancer cells by causing α2 integrin internalization through recognition of high mannose glycans; however, the detailed anti-cancer mechanism is not fully elucidated.
Methods: Cell adherence potency of MKN28 upon PFL treatment was assessed using a colorimetric assay. Cell surface molecules to which PFL bound were identified by peptide mass finger printing with Matrix Assisted Laser Desorption/Ionization-time of flight mass spectrometry and their cellular localization determined by immunofluorescence microscopy. Gene and protein expression in PFL-treated MKN28 cells were evaluated by microarray analysis and western blot, and the function of these genes was evaluated by siRNA knock-down. A proliferation assay measured the sensitivity of PFL-treated cancer cells to anti-cancer drugs. The effect of PFL on subcutaneous MKN28 tumor growth and hepatic tumor formation in BALB/c nude mice was evaluated.
Results: The strength of MKN28 cell adherence in vitro to the extracellular matrix was impaired by PFL treatment, consistent with the observation that PFL induces rapid downregulation of surface integrins. PFL also was found to bind to cell surface epidermal growth factor receptor (EGFR). Surface EGFR molecules were endocytosed following PFL binding, and were degraded in a time-dependent fashion. This degradation process was largely the result of autophagy, as revealed by the increased expression of autophagic proteins. PFL-induced EGFR degradation was partly inhibited by RAB7 siRNA as well as LC3 siRNA, and internalized EGFR colocalized with ATG9 at 48 h post-PFL treatment, suggesting that these proteins contribute to dynamic degradation induced by PFL. PFL-induced decrease in surface EGFR rendered MKN28 cells susceptible to gefitinib, a selective inhibitor of EGFR tyrosine kinase. In vivo experiments showed that PFL-treated MKN28-EGFP cells injected in the portal vein of BALB/c nude mice failed to form tumor colonies on the liver, and intratumoral injection of PFL significantly inhibited tumor growth.
Conclusion: PFL-mediated downregulation of integrin and EGFR contributes to the inhibition of tumor growth in vitro and in vivo. This novel anti-cancer mechanism of PFL suggests that this lectin would be useful as an anti-cancer drug or an adjuvant for other drugs.
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http://dx.doi.org/10.1186/s12885-016-2099-2 | DOI Listing |
J Vis
December 2024
Department of Psychological and Brain Science, University of California, Santa Barbara, CA, USA.
Humans consistently land their first saccade to a face at a preferred fixation location (PFL). Humans also typically process faces as wholes, as evidenced by perceptual effects such as the composite face effect (CFE). However, not known is whether an individual's tendency to process faces as wholes varies with their gaze patterns on the face.
View Article and Find Full Text PDFJBJS Essent Surg Tech
December 2024
Department of Orthopaedics and Rehabilitation, Yale School of Medicine, New Haven, Connecticut.
Background: For complete disruption of the posterolateral corner (PLC) structures, operative treatment is most commonly advocated, as nonoperative treatment has higher rates of persistent lateral laxity and posttraumatic arthritis. Some studies have shown that acute direct repair results in revision rates upwards of 37% to 40% compared with 6% to 9% for initial reconstruction. In a recent study assessing the outcomes of acute repair of PLC avulsion injuries with 2 to 7 years of follow-up, patients with adequate tissue were shown to have a much lower failure rate than previously documented.
View Article and Find Full Text PDFFront Public Health
December 2024
Institute for Human-Animal Connection, Graduate School of Social Work, University of Denver, Denver, CO, United States.
Integrating community perceptions into One Health assessments is critical to understanding the structural barriers that create disproportionate health outcomes for community members, their pets, and the ecosystems that encompass them, particularly in historically marginalized and under-resourced communities. The validated One Health Community Assessment (OHCA) survey instrument was used to evaluate the associated impacts of The Humane Society of the United States' Pets for Life (PFL) programming on communities' perceptions of One Health. This evaluation took place across two phases, totaling four years.
View Article and Find Full Text PDFJ Zoo Wildl Med
December 2024
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
American alligators () are an important apex predator of semiaquatic habitats of the southern United States. Commercial alligator farming has grown in the last several decades, leading to a need to understand the health conditions that affect this species to ensure appropriate management and welfare. The aims of this study were 1) to establish and describe normative data including results of common ophthalmic diagnostic tests and conjunctival flora, 2) document ocular pathology in this population, and 3) assess the effect of topical rocuronium bromide and 10% phenylephrine for facilitating pharmacologic mydriasis.
View Article and Find Full Text PDFRev Sci Instrum
December 2024
School of Nuclear Engineering, Purdue University, West Lafayette, Indiana 47907, USA.
The need to optimize size, weight, and power of high-power microwave (HPM) systems has motivated the development of solid-state HPM sources, such as nonlinear transmission lines (NLTLs), which utilize gyromagnetic precession or dispersion to generate RF. One recent development implemented the NLTL as a pulse forming line (PFL) to form a nonlinear pulse forming line (NPFL) system that substantially reduced the system's size by eliminating the need for a separate PFL; however, matching standard loads can be challenging. This paper describes the development of a tapered NPFL using an exponentially tapered composite based ferrite core containing 60% nickel zinc ferrite (by volume) encased in polydimethylsiloxane (PDMS) and encapsulated in a 5% barium strontium titanate shell.
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