Background: Endometrial cancer (EC) has robust molecular diagnostic evidence that correlates well with prognosis. In various types of cancers, FcRn has been identified as an early marker for prognosis. This study aims to assess FcRn expression and its association with clinicopathological features in endometrial cancer.
Materials And Methods: We employed a tissue microarray (TMA) from a retrospective cohort of 41 patients diagnosed with endometrioid endometrial cancer post hysterectomy between January 2002 and December 2009 at Gyeongsang National University Hospital. Relevant clinical data collection for the cohort involved reviewing patients' electronic medical charts. FcRn expression in microarrays of patient EC tissue was examined in conjunction with clinicopathologic data. Experiments, including siRNA knock-down, PCR mRNA semiquantification, Western blot, and confluence change tests, were conducted on the Ishikawa cell line.
Results: The overall FcRn expression rate in EC patients was 41.8%. FIGO stage showed a statistically significant relationship with FcRn expression, while age, lymphovascular invasion, myometrial invasion, and tumor size had no effect. In endometrioid cancer cells of FIGO stage IA, FcRn was less frequently expressed than in other high-staged EC patients ( = 0.021). In experiments on the Ishikawa cell line, the siRNA knock-down group exhibited quantitatively lower FCGRT mRNA expression and lower FcRn protein signal compared to the scrambled RNA control group. The change in confluence over time measured at three hotspots did not show a significant difference between groups.
Conclusions: To the best of our knowledge, this study represents the initial assessment of FcRn expression in endometrioid EC samples. FcRn expression was significantly associated with the FIGO stage. Ishikawa cell line proliferation did not significantly change in response to decreased FcRn expression. Further studies are needed to elucidate FcRn expression in EC as a potential molecular parameter.
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http://dx.doi.org/10.3390/diagnostics13243660 | DOI Listing |
Discov Oncol
December 2024
Department of Central Laboratory, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China.
Background: Non-small cell lung cancer (NSCLC) represents one of the most prevalent forms of lung cancer, with a five-year survival rate of 21.7%. There is an urgent need to identify pertinent biomarkers to inform the diagnosis and prognosis of tumors, particularly those that can be applied to different age groups.
View Article and Find Full Text PDFACS Nano
December 2024
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
The development of effective oral drug delivery systems for targeted gut-to-liver transport remains a significant challenge due to the multiple biological barriers including the harsh gastrointestinal tract (GIT) environment and the complex protein corona (PC) formation. In this study, we developed ligand-modified nanoparticles (NPs) that enable gut-to-liver drug delivery by crossing the GIT and attenuating PC formation. Specifically, mesoporous silica nanoparticles (MSNs) were functionalized with peptides targeting the neonatal Fc receptor (FcRn), capitalizing on FcRn expression in the small intestine and liver for targeted drug delivery.
View Article and Find Full Text PDFFront Pharmacol
October 2024
Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH and Co. KG, Ingelheim, Germany.
Introduction: Animal models play a vital role in pharmaceutical research and development by supporting the planning and design of later clinical studies. To improve confidence and reliability of first in human dose estimates it is essential to assess the comparability of animal studies with the human situation. In the context of large molecules, it is particularly important to evaluate the cross-species-translatability of parameters related to neonatal fragment crystallizable receptor (FcRn) binding and target mediated drug disposition (TMDD), as they greatly influence distribution and disposition of proteins in the body of an organism.
View Article and Find Full Text PDFACS Nano
October 2024
Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Rua Alfredo Allen 208, Porto 4200-135, Portugal.
The oral administration of the glucagon-like peptide-1 analogue, semaglutide, remains a hurdle due to its limited bioavailability. Herein, neonatal Fc receptor (FcRn)-targeted nanoparticles (NPs) were designed to enhance the oral delivery of semaglutide. The nanocarriers were covalently linked to the FcRn-binding peptide FcBP or the affibody molecule Z that specifically binds to the human FcRn (hFcRn) in a pH-dependent manner.
View Article and Find Full Text PDFFront Immunol
October 2024
Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Effective treatment and immunoprophylaxis of viral respiratory infections with neutralizing monoclonal antibodies (mAbs) require maintaining inhibitory concentrations of mAbs at the airway surface. While engineered mAbs with increased affinity to the neonatal Fc receptor (FcRn) are increasingly employed, little is known how increased affinity of Fc to FcRn influences basal-to-apical transepithelial transport (transcytosis) of mAbs across the airway epithelium. To investigate this, we utilized a model of well-differentiated human airway epithelium (WD-HAE) that exhibited robust FcRn expression, and measured the transepithelial transport of a mAb against SARS-CoV-2 Spike protein (CR3022) with either wildtype IgG-Fc or Fc modified with YTE or LS mutations known to increase affinity for FcRn.
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