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  1. Shintani T, Higaki M, Rosli SNZ, Okamoto T
    In Vitro Cell Dev Biol Anim, 2024 Jun;60(6):583-589.
    PMID: 38713345 DOI: 10.1007/s11626-024-00913-3
    Heparin-binding protein 17 (HBp17), first purified in 1991 from the conditioned medium of the human A431 squamous cell carcinoma (SCC) cell line, was later renamed fibroblast growth factor-binding protein 1 (FGFBP-1). HBp17/FGFBP-1 is specifically expressed and secreted by epithelial cells, and it reversibly binds to fibroblast growth factor (FGF)-1 and FGF-2, as well as FGFs-7, -10, and -22, indicating a crucial involvement in the transportation and function of these FGFs. Our laboratory has investigated and reported several studies to elucidate the function of HBp17/FGFBP-1 in SCC cells and its potential as a molecular therapeutic target. HBp17/FGFBP-1 transgene exoression in A431-4 cells, a clonal subline of A431 that lacks tumorigenicity and does not express HBp17/FGFBP-1, demonstrated a significantly enhanced proliferation in vitro compared with A431-4 cells, and it acquired tumorigenicity in the subcutis of nude mice. Knockout (KO) of the HBp17/FGFBP-1 by genome editing significantly suppressed tumor growth, cell motility, and tumorigenicity compared with control cells. A comprehensive analysis of expressed molecules in both cell types revealed that molecules that promote epithelial cell differentiation were highly expressed in HBp17/FGFBP-1 KO cells. Additionally, we reported that 1α,25(OH)2D3 or eldecalcitol (ED-71), which is an analog of 1α,25(OH)2D3, suppresses HBp17/FGFBP-1 expression and tumor growth in vitro and in vivo by inhibiting the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway. Here, we discuss the prospects of molecular targeted therapy targeting HBp17/FGFBP-1 with 1α,25(OH)2D3 or ED71 in SCC and oral SCC.
  2. Shintani T, Rosli SNZ, Takatsu F, Choon YF, Hayashido Y, Toratani S, et al.
    J Steroid Biochem Mol Biol, 2016 11;164:79-84.
    PMID: 26444325 DOI: 10.1016/j.jsbmb.2015.09.043
    We have previously reported that 1,25(OH)2D3 inhibits NF-κB activity and thus inhibits growth of OSCC cells in serum-free culture and down-regulates HBp17/FGFBP-1 expression, which is important for cancer cell growth and angiogenesis. Here, we have investigated the effects of ED-71, an analog of vitamin D3 (VD) on OSCC cell lines in serum-free culture. It is known that ED-71 has a stronger inhibitory effect on bone resorption compared to VD and other VD analogs. To the best of our knowledge, there was no report examining the potential of ED-71 as an anti-cancer agent for OSCC. We found that ED-71 is able to inhibit the growth of cancer cell lines at a concentration of hundred times lower than calcitriol. As Cyp24A1 was reportedly induced in cancer cells, we measured the expression of CYP24A1 in OSCC cell lines (NA and UE), A431 epidermoid carcinoma and normal fibroblast cell (gfi) in serum-free culture. As a result, CYP24A1 mRNA and the protein expression in the OSCC cells treated with ED-71 increased in a dose-dependent manner. However, in vivo experiment, in which the A431 cells were implanted in mice, tumor formation was reduced by the ED-71 treatment with no significant difference between Cyp24A1 expression in the tumors of ED-71-treated and control group, as analyzed by western blotting and immunohistochemistry. These results suggest that ED-71 is a potential anti-cancer agent for OSCC.
  3. Rohner K, Marlais M, Ahn YH, Ali A, Alsharief A, Novak AB, et al.
    Nephrol Dial Transplant, 2024 Jul 31;39(8):1299-1309.
    PMID: 38211969 DOI: 10.1093/ndt/gfae009
    BACKGROUND: Immunoglobulin A vasculitis with nephritis (IgAVN) is the most common vasculitis in children. Due to a lack of evidence, treatment recommendations are based on expert opinion, resulting in variation. The aim of this study was to describe the clinical presentation, treatment and outcome of an extremely large cohort of children with biopsy-proven IgAVN in order to identify prognostic risk factors and signals of treatment efficacy.

    METHODS: Retrospective data were collected on 1148 children with biopsy-proven IgAVN between 2005 and 2019 from 41 international paediatric nephrology centres across 25 countries and analysed using multivariate analysis. The primary outcome was estimated glomerular filtration rate (eGFR) and persistent proteinuria at last follow-up.

    RESULTS: The median follow-up was 3.7 years (interquartile range 2-6.2). At last follow-up, 29% of patients had an eGFR <90 mL/min/1.73 m2, 36% had proteinuria and 3% had chronic kidney disease stage 4-5. Older age, lower eGFR at onset, hypertension and histological features of tubular atrophy and segmental sclerosis were predictors of poor outcome. There was no evidence to support any specific second-line immunosuppressive regimen being superior to others, even when further analysing subgroups of children with reduced kidney function, nephrotic syndrome or hypoalbuminemia at onset. Delayed start of immunosuppressive treatment was associated with a lower eGFR at last follow-up.

    CONCLUSION: In this large retrospective cohort, key features associated with disease outcome are highlighted. Importantly, there was no evidence to support that any specific immunosuppressive treatments were superior to others. Further discovery science and well-conducted clinical trials are needed to define accurate treatment and improve outcomes of IgAVN.

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