Renal cell carcinoma (RCC) incidence is highest in highly developed countries and it is the seventh most common neoplasm diagnosed. RCC management include nephrectomy and targeted therapies. Type 1 insulin-like growth factor (IGF-1) pathway plays an important role in cell proliferation and apoptosis resistance. IGF-1 and insulin share overlapping downstream signaling pathways in normal and cancer cells. IGF-1 receptor (IGF1R) stimulation may promote malignant transformation promoting cell proliferation, dedifferentiation and inhibiting apoptosis. Clear cell renal cell carcinoma (ccRCC) patients with IGF1R overexpression have 70 % increased risk of death compared to patients who had tumors without IGF1R expression. IGF1R signaling deregulation may results in p53, WT, BRCA1, VHL loss of function. RCC cells with high expression of IGF1R are more resistant to chemotherapy than cells with low expression. Silencing of IGF1R increase the chemosensitivity of ccRCC cells and the effect is greater in VHL mutated cells. Understanding the role of IGF-1 signaling pathway in RCC may result in development of new targeted therapeutic interventions. First preclinical attempts with anti-IGF-1R monoclonal antibodies or fragment antigen-binding (Fab) fragments alone or in combination with an mTOR inhibitor were shown to inhibit in vitro growth and reduced the number of colonies formed by of RCC cells.

Aims/hypothesisWe aimed to identify microRNAs (miRNAs) under transcriptional control of the HNF1β transcription factor, and investigate whether its effect manifests in serum.MethodsThe Polish cohort (N = 60) consisted of 11 patients with HNF1B-MODY, 17 with HNF1A-MODY, 13 with GCK-MODY, an HbA1c-matched type 1 diabetic group (n = 9) and ten healthy controls. Replication was performed in 61 clinically-matched British patients mirroring the groups in the Polish cohort. The Polish cohort underwent miRNA serum level profiling with quantitative real-time PCR (qPCR) arrays to identify differentially expressed miRNAs. Validation was performed using qPCR. To determine whether serum content reflects alterations at a cellular level, we quantified miRNA levels in a human hepatocyte cell line (HepG2) with small interfering RNA knockdowns of HNF1α or HNF1β.ResultsSignificant differences (adjusted p < 0.05) were noted for 11 miRNAs. Five of them differed between HNF1A-MODY and HNF1B-MODY, and, amongst those, four (miR-24, miR-27b, miR-223 and miR-199a) showed HNF1B-MODY-specific expression levels in the replication group. In all four cases the miRNA expression level was lower in HNF1B-MODY than in all other tested groups. Areas under the receiver operating characteristic curves ranged from 0.79 to 0.86, with sensitivity and specificity reaching 91.7% (miR-24) and 82.1% (miR-199a), respectively. The cellular expression pattern of miRNA was consistent with serum levels, as all were significantly higher in HNF1α- than in HNF1β-deficient HepG2 cells.Conclusions/interpretationWe have shown that expression of specific miRNAs depends on HNF1β function. The impact of HNF1β deficiency was evidenced at serum level, making HNF1β-dependent miRNAs potentially applicable in the diagnosis of HNF1B-MODY.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-016-3945-0) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Abstract.The clinical outcome of children with high-risk relapsed B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is poor. The present study assessed the utility and prognostic value of selected microRNA (miRNA/miR) in BCP-ALL. The changes in the expression levels of these miRNAs regarding known gene lesions affecting lymphoid development [early B-cell factor 1 (EBF1), ETS variant 6 (ETV6), IKAROS family zinc finger 1 (IKZF1), paired box 5 (PA X5), cyclin dependent kinase inhibitor (CDKN) 2A/CDKN2B, retinoblastoma 1 (RB1), pseudoautosomal region 1 (PAR1), B-cell translocation gene 1 protein (BTG1)] were analyzed. The following miRNAs were analyzed: miR-24, miR-31, miR-128, miR-542, and miR-708. The present study focused on patients with deletions of the IKAROS transcriptional factor gene IKZF1, which is currently considered to be an independent negative prognostic factor for ALL outcome. It was demonstrated that the expression level of miR-128 was significantly lower in patients with IKZF1 deletion compared with patients without IKZF1 deletion. Additionally, low expression of miR-542 was associated with CDKN2A/B and miR-31deletions, and low expression of miR-24 was associated with miR-31 deletion. Low expression of miR-31, miR-24, miR-708 and miR-128 was associated with PAX5 deletion, high expression of miR-24 and miR-542 was associated with PAR1 deletion and high expression of miR-708 was associated with ETV6 deletion. The expression of the selected miRNAs was not associated with deletions of BTG1, EBF1 and RB1. These data, by emphasizing the association of miRNAs expression level with microdeletions, may assist to elucidate ALL biology and contribute to future studies on the possible applications of the miRNA profile for diagnosis.

Solid organ transplant recipients are vulnerable to severe course of infectious diseases. Our study indicates that kidney transplant recipients are at high risk for severe COVID-19 illness and death, providing a rationale for prioritizing COVID-19 vaccination and aggressive management in this group. Kidney transplant recipients with lower baseline estimated glomerular filtration rate, a higher respiratory rate on admission and diabetes mellitus had increased risk of COVID-19 in-hospital mortality.

Individuals who are homozygous TT at rs1260326 of the GCKR gene have higher triglyceride, total and LDL cholesterol levels regardless of the presence of GCK mutations.