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Micronutrients in the Prevention and Improvement of the Standard Therapy for Alzheimer’s Disease
Published in Kedar N. Prasad, Micronutrients in Health and Disease, 2019
Supplementation with vitamin D3 upregulated miR-498, reduced the levels of its target protein human telomerase reverse transcriptase, and inhibited the growth of human ovarian cancer cells.130 Expression of miR-22 was lower in most human colon cancer. Treatment of cancer with vitamin D3 upregulated miR-22 and downregulated its multiple protein targets, such as NELL2 (neural epidermal growth factor-like 2), RERE (arginine-glutamic acid dipeptide repeats) and OGN (osteoglycin), and reduced the growth of colon cancer cells.131
Liquid biopsy in the clinical management of bladder cancer: current status and future developments
Published in Expert Review of Molecular Diagnostics, 2020
Erik Kouba, Antonio Lopez-Beltran, Rodolfo Montironi, Francesco Massari, Kun Huang, Matteo Santoni, Michal Chovanec, Michael Cheng, Marina Scarpelli, Jie Zhang, Alessia Cimadamore, Liang Cheng
While earlier studies of CTC in patients with UCB have focused on prognostic indications, emphasis toward the molecular characterization of these cells has been explored [46]. More detailed molecular and functional characterization has evolved in conjunction with RT-PCR for the detection of CTC transcripts or gene expression. Such studies have shown prognostic relevance of EGFR, KRT19, UPKII, and TNC (tenascin C) transcripts detected on CTC. Detection of EGFR and TNC mRNAs was associated with reduced disease-free survival [47,48]. Other studies have shown that characterization of EMT specific transcripts, KIT, and differential expression of UPKII, BRC5, IGFBP7, SNX16, CSPG6, CTSD, CHD2, NELL2, TRFRSF7 may be associated with early detection of metastases and provide prognostic value [4,49,50]. Detection of HER2 discordance between CTC and that of the primary tumor suggests a role in the treatment failure of HER2 targeted therapies [40]. Table 1 summarizes key clinical studies of CTCs and UCB as discussed in the aforementioned text.
In vitro OP9-DL1 co-culture and subsequent maturation in the presence of IL-21 generates tumor antigen-specific T cells with a favorable less-differentiated phenotype and enhanced functionality
Published in OncoImmunology, 2021
Sarah Bonte, Stijn de Munter, Lore Billiet, Glenn Goetgeluk, Joline Ingels, Hanne Jansen, Melissa Pille, Laurenz de Cock, Karin Weening, Tom Taghon, Georges Leclercq, Bart Vandekerckhove, Tessa Kerre
In their report, Vizcardo et al. state that CD8+ SP T cells generated in OP9-DL1 co-cultures are ‘abnormal’, with high expression of NK cell markers, indicating innate-like features, and upregulation of PTCRA, RAG1, RAG2 and RORC, indicating an immature phenotype.41 However, we demonstrated that addition of the agonist peptide to induce maturation from DP to CD8+ SP T cells in OP9-DL1 co-cultured cells results in downregulation of RAG1, RAG2, RORC and PTCRA. Furthermore, no NK cell markers are observed.7 On the other hand, and in line with the observations by Vizcardo et al., CD8αα T cells emerged in our cultures (as also described by Snauwaert et al).7 However, expression of CD8β was only lost after polyclonal feeder expansion, not after agonist selection. We do acknowledge that, as our cells are agonist selected cells, they might not fit into one of the conventional T cell differentiation states (TN, TSCM, TCM, TEM or TEFF) but rather represent an unconventional T cell subset. At the mRNA level, expression of conventional T cell markers (e.g. NELL2 and LRRN3) are absent in both the in vivo and in vitro agonist selected cells.7,42 At the protein level, unconventional agonist selected T cells, both in human thymus and CB, express high levels of CD95 and CXCR3, similar to our in vitro generated agonist selected T cells. Human unconventional agonist selected T cells are characterized by PD-1 expression in thymus, which is gradually lost in the corresponding population in CB, and also after IL-15-induced proliferation.34,42 PD-1 expression on our CB-derived in vitro generated T cells was, however, low (when IL-21 alone or in combination with IL-15 was added) or absent (with the other cytokine mixes). On the other hand, the previously described unconventional T cells express only low levels of CD62L that are even more downregulated after IL-15-induced proliferation,34,42 which we also observed after feeder expansion when IL-15 was added, but not with IL-21. These distinct phenotypes mark differences between in vitro agonist selected T cells and unconventional agonist selected T cells isolated directly from human thymus or CB. Furthermore, the cytokine(s) added during in vitro agonist selection also impact(s) the phenotype and functionality of the resulting in vitro generated agonist selected T cells.