The nine identified human homologues of E. coli AlkB 2-oxoglutarate (2OG) and Fe(II)-dependent dioxygenase, ALKBH1-8 and FTO, display different substrate specificities and diverse biological functions. Here we discovered the combined overexpression of members of the ALKBH family in head and neck squamous cell carcinomas (HNSCC). We found direct correlation of ALKBH3 and FTO expression with primary HNSCC tumor size. We observed unidentified thus far cytoplasmic localization of ALKBH2 and 5 in HNSCC, suggesting abnormal role(s) of ALKBH proteins in cancer. Further, high expression of ALKBHs was observed not only in HNSCC, but also in several cancerous cell lines and silencing ALKBH expression in HeLa cancer cells resulted in dramatically decreased survival. Considering the discovered impact of high expression of ALKBH proteins on HNSCC development, we screened for ALKBH blockers among newly synthetized anthraquinone derivatives and demonstrated their potential to support standard anticancer therapy.
Introduction: M2 macrophages are predominant in the immune infiltrates of resected tumours, but little is known about macrophage phenotype in the local lung cancer environment, which may be evaluated by bronchoalveolar lavage fluid (BALF). Aim of the study: To find differences between BALF from lung affected by cancer (clBALF) and hlBALF from the opposite, healthy lung, as a control, from the same patient, regarding their individual macrophage polarization and their correlation with IL-10 and TGF-β. Material and methods: Eighteen patients with confirmed lung cancer were investigated. Macrophage subtyping was performed by immunofluorescence with antibodies anti-CCR7 and CD163 (M1 and M2, respectively). Results: We found five populations of macrophages: cells with a single reaction: only for CCR7+ or CD163+, a double reaction (CCR7+CD163+), cells with a stronger CD163 (CCR7 low CD163+), and cells with a stronger CCR7 (CCR7+CD163 low). The main population in the clBALF was composed of cells with a phenotype similar to M2 (CCR7 low CD163+), while in the hlBALF the predominating phenotype was the one similar to M1 (CCR7+CD163 low). The median proportion of TGF-β1 concentration was higher in the clBALF and hlBALF supernatant than in the serum. Conclusions: In this study we confirmed the usefulness of the immunofluorescence method with CCR7 and CD163 in the evaluation of BALF macrophage polarization in lung cancer.
In vitro SSTR2A cytoplasm expression was found to be high in all tumor specimens. However, the uptake of (68)Ga-DOTATATE was weak in the PET/CT studies. We postulate that the intracellular localization of the SSTR2A in JA may cause this discrepancy.
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