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Pembrolizumab-Induced Nasal Polyposis: The First Reported Case
Hintze Justin M.,Jones Holly,Lacy Peter 대한비과학회 2023 Journal of rhinology Vol.30 No.2
The last decade has seen the emergence of immune checkpoint inhibitors for the treatment of a wide variety of cancer types. While these medications are generally speaking well tolerated, the full long-term side effect profiles of these medications have not been fully elucidated. We describe a case of chronic rhinosinusitis with nasal polyposis induced treatment with pembrolizumab, the first reported case. We present the case of a 48-year-old man with a background history of stage IV non-small cell lung cancer with bone metastases. He was commenced on pembrolizumab and over the course of the subsequent 5 years he developed significant nasal polyps bilaterally, and was commenced on medical therapy. Sinus CT scan demonstrated bilateral total opacification of all his sinuses and nasal cavity. He subsequently underwent bilateral functional endoscopic sinus surgery. He remains symptom-free and at his last clinical follow-up visit 1 year later. There are limited case reports of nasal polyposis occurring in patients receiving immune checkpoint inhibitors, with only one case requiring surgery. We describe the first case of severe nasal polyps due to pembrolizumab and successfully treated with polypectomy. From our review, there were no cases that required a cessation of therapy.
Luzia Jaeger Hintze,Ana Claudia Pelissari Kravchychyn,Yasmin Alaby Martins Ferreira,Raquel Munhoz da Silveira Campos,Alexandre D. Aguilera Dantas,Deborah Cristina Landi Masquio,Danielle Arisa Caranti 대한비만학회 2021 The Korean journal of obesity Vol.30 No.4
Background: The purpose of the present study was to compare the impact of semi-intensive and intensive interdisciplinary weight-loss therapies on the treatment of metabolic syndrome (MS) and selected inflammatory markers in adolescents with obesity. Methods: The study included 166 adolescents enrolled in two groups for 22 weeks: the intensive group (in-person aerobic and resistance exercise three times a week, and psychological and nutritional counselling once a week), or the semi-intensive group (six in-person exercise orientation meetings and six in-person psychological support sessions with an online nutritional and exercise program). Anthropometric parameters, blood pressure, fasting glucose, insulin, lipid profile, triglycerides (TG), leptin and adiponectin were assessed before and after the interventions. Results: Body weight and waist circumference decreased in both groups (P<0.001) and large effect sizes (η2=0.586 and η2=0.465, respectively) were noted. Significant time and group interactions were found (P=0.001) with medium effect sizes (η2=0.095 and η2=0.105, respectively). The prevalence of MS decreased from 27.9% to 13.1% (P=0.012) and 29.4% to 5.9% (P=0.004) in the semi-intensive and intensive groups, respectively. All MS risk factors decreased significantly over time (P<0.001) and a significant time*group interaction was observed (P<0.05), except for fasting TG (P=0.832) and glucose (P=0.128, η2=0.021). Conclusion: The results suggested that both approaches promoted significant clinical improvement in the condition of adolescents with MS and reduced associated risk factors. Studies that consider the cost effectiveness of both treatments are still needed to determine whether semi-intensive care, with its lower financial costs, may be a suitable option to treat obesity and MS in adolescents with obesity.
Eades, C.Joshua,Hintz, William E. The Korean Society for Biotechnology and Bioengine 2000 Biotechnology and Bioprocess Engineering Vol.5 No.4
Although filamentous fungi are used extensively for protein expression, their use for the production of heterologous glycoproteins is constrained by the types of N-glycan structures produced by filamentous fungi as compared to those naturally found on the glycoproteins. Attempts are underway to engineer the N-glycan synthetic pathways in filamentous fungi in order to produce fungal expression strains which can produce heterologous glycoproteins carrying specific N-glycan structures. To fully realize this goal, a detailed understanding of the genetic components of this pathway in filamentous fungi is required. In this review, we discuss the characterization of the $\alpha$-mannosidase gene family in filamentous fungi and its implications for the elucidation of the N-glycan synthetic pathway.
Gruner, Matthew,Nelson, Dru,Winbush, Ari,Hintz, Rebecca,Ryu, Leesun,Chung, Samuel H.,Kim, Kyuhyung,Gabel, Chrisopher V.,van der Linden, Alexander M. Public Library of Science 2014 PLoS genetics Vol.10 No.10
<P>Feeding state and food availability can dramatically alter an animals' sensory response to chemicals in its environment. Dynamic changes in the expression of chemoreceptor genes may underlie some of these food and state-dependent changes in chemosensory behavior, but the mechanisms underlying these expression changes are unknown. Here, we identified a KIN-29 (SIK)-dependent chemoreceptor, <I>srh-234</I>, in <I>C. elegans</I> whose expression in the ADL sensory neuron type is regulated by integration of sensory and internal feeding state signals. We show that in addition to KIN-29, signaling is mediated by the DAF-2 insulin-like receptor, OCR-2 TRPV channel, and NPR-1 neuropeptide receptor. Cell-specific rescue experiments suggest that DAF-2 and OCR-2 act in ADL, while NPR-1 acts in the RMG interneurons. NPR-1-mediated regulation of <I>srh-234</I> is dependent on gap-junctions, implying that circuit inputs regulate the expression of chemoreceptor genes in sensory neurons. Using physical and genetic manipulation of ADL neurons, we show that sensory inputs from food presence and ADL neural output regulate <I>srh-234</I> expression. While KIN-29 and DAF-2 act primarily via the MEF-2 (MEF2) and DAF-16 (FOXO) transcription factors to regulate <I>srh-234</I> expression in ADL neurons, OCR-2 and NPR-1 likely act via a calcium-dependent but MEF-2- and DAF-16-independent pathway. Together, our results suggest that sensory- and circuit-mediated regulation of chemoreceptor genes via multiple pathways may allow animals to precisely regulate and fine-tune their chemosensory responses as a function of internal and external conditions.</P><P><B>Author Summary</B></P><P>Animals dramatically modify their chemosensory behaviors to attractive and noxious chemical stimuli when starved. This could allow them to alter and optimize their food-search strategies to increase their survival and reproduction. Changes in the gene expression of chemoreceptors specialized in detecting environmental stimuli is observed in fish, insects and nematodes, and may be a general mechanism underlying the changes in chemosensory behaviors observed in starved animals. To elucidate this mechanism, we have developed an <I>in vivo</I> reporter assay in <I>C. elegans</I> for monitoring the expression of a candidate chemoreceptor gene in a single sensory neuron type, called ADL, as a function of feeding state. Using this reporter assay, we show that sensory inputs into ADL and neural outputs from ADL, as well as inputs from the RMG interneuron, which is electrically connected to ADL, are required to fine-tune expression of chemoreceptor genes in ADL. Sensory and circuit-mediated regulation of chemoreceptor gene expression is dependent on multiple pathways, including the neuropeptide receptor, NPR-1, and the DAF-2 insulin-like receptor. Our results reveal mechanisms underlying chemoreceptor gene expression, and provide insight into how expression changes in chemoreceptor genes may contribute to changes in chemosensory behavior as a function of feeding state.</P>
Jan Krieghoff,Ann-Kristin Picke,Juliane Salbach-Hirsch,Sandra Rother,Christiane Heinemann,Ricardo Bernhardt,Christian Kascholke,Stephanie Möller,Martina Rauner,Matthias Schnabelrauch,Vera Hintze,Diete 한국생체재료학회 2020 생체재료학회지 Vol.24 No.1
Background: Delayed bone regeneration of fractures in osteoporosis patients or of critical-size bone defects after tumor resection are a major medical and socio-economic challenge. Therefore, the development of more effective and osteoinductive biomaterials is crucial. Methods: We examined the osteogenic potential of macroporous scaffolds with varying pore sizes after biofunctionalization with a collagen/high-sulfated hyaluronan (sHA3) coating in vitro. The three-dimensional scaffolds were made up from a biodegradable three-armed lactic acid-based macromer (TriLA) by crosspolymerization. Templating with solid lipid particles that melt during fabrication generates a continuous pore network. Human mesenchymal stem cells (hMSC) cultivated on the functionalized scaffolds in vitro were investigated for cell viability, production of alkaline phosphatase (ALP) and bone matrix formation. Statistical analysis was performed using student’s t-test or two-way ANOVA. Results: We succeeded in generating scaffolds that feature a significantly higher average pore size and a broader distribution of individual pore sizes (HiPo) by modifying composition and relative amount of lipid particles, macromer concentration and temperature for cross-polymerization during scaffold fabrication. Overall porosity was retained, while the scaffolds showed a 25% decrease in compressive modulus compared to the initial TriLA scaffolds with a lower pore size (LoPo). These HiPo scaffolds were more readily coated as shown by higher amounts of immobilized collagen (+ 44%) and sHA3 (+ 25%) compared to LoPo scaffolds. In vitro, culture of hMSCs on collagen and/or sHA3-coated HiPo scaffolds demonstrated unaltered cell viability. Furthermore, the production of ALP, an early marker of osteogenesis (+ 3-fold), and formation of new bone matrix (+ 2.5-fold) was enhanced by the functionalization with sHA3 of both scaffold types. Nevertheless, effects were more pronounced on HiPo scaffolds about 112%. Conclusion: In summary, we showed that the improvement of scaffold pore sizes enhanced the coating efficiency with collagen and sHA3, which had a significant positive effect on bone formation markers, underlining the promise of using this material approach for in vivo studies.