Browsing by Subject "Glutamine"

Now showing 1 - 3 of 3
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    Expression of glutamine metabolism-related proteins in Hürthle cell neoplasm of thyroid: Comparison with follicular neoplasm
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Cha, Yoon Jin; Jang, Haerin; Koo, Ja Seung
    Purpose. We evaluated the expression of glutaminolysis-related proteins in Hurthle cell neoplasms (HCN) and follicular neoplasms (FN) of the thyroid, and investigated its clinical implication. Methods. Tissue microarrays were constructed from 264 FNs (112 follicular carcinomas [FCs] and 152 follicular adenomas [FAs]) and 108 HCNs (27 Hurthle cell carcinomas [HCCs] and 81 Hurthle cell adenomas [HCAs]. The immunohistochemical staining result of 3 glutaminolysis-related proteins (Glutaminase 1 [GLS1], glutaminate dehydrogenase [GDH] and alanine- serine, cysteine-preferring transporter 2 [ASCT2]) was analyzed. Results. GLS1 and GDH showed significantly higher expression rates in HCN compared to FN (P<0.001). More HCN cases showed co-positivity of multiple glutaminolysis-related proteins than those of FN cases (P<0.001). In silico analysis, both GLUD1 and GLUD2 showed higher expression rate in HCA compared to FA (P=0.027 and P=0.018, respectively). SLC1A5 expression was highest in HCA, followed by FC and FA (HCA vs FC, P=0.023; FC vs FA, P=0.002). Conclusion. FN and HCN exhibit a different expression pattern for glutaminolysis-related proteins, and GLS1 and GDH have higher expression rates in HCN and FN.
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    Structural patterns of swine ileal mucosa following L-glutamine and nucleotide administration during the weaning period. An histochemical and histometrical study
    (Murcia : F. Hernández, 2004) Domeneghini, C.; Di Giancamillo, A.; Savoini, G.; Paratte, R.; Bontempo, V.; Dell’Orto, V.
    Dietary supplementations with L-glutamine and/or nucleotides were screened for their effects on intestinal mucosa in 16 female weaning piglets. The animals were transported to the university’s facilities 24 hours after weaning. They were grouped four to a pen in controlled environmental conditions and fed one of the following four diets for 28 days: control diet (C); C+0.5% L-glutamine (G); C+0.05% “nucleotides” (N); and C+0.5 % L-glutamine+0.05% “nucleotides” (GN). Individual body weights and feed intake per group were recorded at the beginning and the end of the study as well as weekly during it. There were no significant performance differences among the groups. After 28 days the animals were slaughtered and the distal ileum and liver were examined histologically. Antiproliferating cell nuclear antigen (PCNA) as well as antihuman macrophage immunostaining, and a modified TdT-mediated dUTP nick-end labeling technique (TUNEL) were performed, and intraepithelial lymphocyte percentage was evaluated to assess morphofunctional aspects of the ileum. Histometry was performed by assessing cell indices and counts of immuno-reactive structures. Feeding G and/or N resulted in an increase in villi (V) height, crypt (C) depth, and a decrease in V:C ratio P<0.01). In addition, feeding G and/or N resulted in an increase in mitotic mucosal cells (M), and a decrease in apoptotic mucosal cells (A), thus decreasing the A:M index (P<0.01). The percentages of mucosal macrophages were greater in G and/or N groups (P<.001) than in control piglets, and similarly among the groups the percentages of intraepithelial lymphocytes varied (P<0.01). Our data showed that the diet supplementation with G and/or N had positive effects on some morphofunctional characteristics of piglet ileal mucosa. These ameliorative effects may potentially be linked to a good responsiveness of piglets to a stressful period, like a precocious weaning is in this species.
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    Translation reprogramming is an evolutionarily conserved driver of phenotypic plasticity and therapeutic resistance in melanoma
    (Cold Spring Harbor Laboratory Press, 2017-01-17) Falletta, Paola; Effern, Maike; Kenyon, Amy; Kershaw, Christopher J.; Siddaway, Robert; Lisle, Richard; Freter, Rasmus; Daniels, Matthew J.; Lu, Xin; Tüting, Thomas; Middleton, Mark; Buffa, Francesca M.; Willis, Anne E.; Pavitt, Graham; Ronai, Ze’ev A.; Sauka Spengler, Tatjana; Hölzel, Michael; Goding, Colin R.; Sánchez del Campo Ferrer, Luis; Bioquímica y Biología Molecular A
    The intratumor microenvironment generates phenotypically distinct but interconvertible malignant cell subpopulations that fuel metastatic spread and therapeutic resistance. Whether different microenvironmental cues impose invasive or therapy-resistant phenotypes via a common mechanism is unknown. In melanoma, low expression of the lineage survival oncogene microphthalmia-associated transcription factor (MITF) correlates with invasion, senescence, and drug resistance. However, how MITF is suppressed in vivo and how MITF-low cells in tumors escape senescence are poorly understood. Here we show that microenvironmental cues, including inflammation-mediated resistance to adoptive T-cell immunotherapy, transcriptionally repress MITF via ATF4 in response to inhibition of translation initiation factor eIF2B. ATF4, a key transcription mediator of the integrated stress response, also activates AXL and suppresses senescence to impose the MITF-low/AXL-high drug-resistant phenotype observed in human tumors. However, unexpectedly, without translation reprogramming an ATF4-high/MITF-low state is insufficient to drive invasion. Importantly, translation reprogramming dramatically enhances tumorigenesis and is linked to a previously unexplained gene expression program associated with anti-PD-1 immunotherapy resistance. Since we show that inhibition of eIF2B also drives neural crest migration and yeast invasiveness, our results suggest that translation reprogramming, an evolutionarily conserved starvation response, has been hijacked by microenvironmental stress signals in melanoma to drive phenotypic plasticity and invasion and determine therapeutic outcome.