Telomerase-pulsed dendritic cells: preclinical results and outcome of a clinical phase I/II trial in patients with metastatic renal cell carcinoma

Objective: Therapeutic vaccination with dendritic cells (DC) showed promising results in first clinical trials in cases of metastatic renal cell carcinoma (RCC). Human telomerase reverse transcriptase (hTERT) could be a potential target because it is detectable in more than 85% of human tumors including RCC

MicroRNAs in Renal Cell Carcinoma: Diagnostic Implications of Serum miR-1233 Levels

BACKGROUND: MicroRNA expression is altered in cancer cells, and microRNAs could serve as diagnostic/prognostic biomarker for cancer patients. Our study was designed to analyze circulating serum microRNAs in patients with renal cell carcinoma (RCC). METHODOLOGY/PRINCIPAL FINDINGS: We first explored microrna expression profiles in tissue and serum using taqman low density arrays in each six malignant and benign samples: Although 109 microRNAs were circulating at higher levels in cancer patients' serum, we identified only 36 microRNAs with up-regulation in RCC tissue and serum of RCC patients. Seven candidate microRNAs were selected for verification based on the finding of up-regulation in serum and tissue of RCC patients: miR-7-1*, miR-93, miR-106b*, miR-210, miR-320b, miR-1233 and miR-1290 levels in serum of healthy controls (n = 30) and RCC (n = 33) patients were determined using quantitative real-time PCR (TaqMan MicroRNA Assays). miR-1233 was increased in RCC patients, and thus validated in a multicentre cohort of 84 RCC patients and 93 healthy controls using quantitative real-time PCR (sensitivity 77.4%, specificity 37.6%, AUC 0.588). We also studied 13 samples of patients with angiomyolipoma or oncocytoma, whose serum miR-1233 levels were similar to RCC patients. Circulating microRNAs were not correlated with clinical-pathological parameters. CONCLUSIONS/SIGNIFICANCE: MicroRNA levels are distinctly increased in cancer patients, although only a small subset of circulating microRNAs has a tumor-specific origin. We identify circulating miR-1233 as a potential biomarker for RCC patients. Larger-scaled studies are warranted to fully explore the role of circulating microRNAs in RCC

A potential role of karyopherin a2 in the impaired maturation of dendritic cells observed in glioblastoma patients

Aim: Patients with glioblastomas demonstrate well-documented immunological impairments including decreased numbers of mature dendritic cells (DCs). Recent data identified karyopherin a2 (KPNA2), a nucleocytoplasmic shuttling receptor, as diagnostic and prognostic biomarker for gliomas. The aim of this ongoing study is to correlate parameters of immunity and nucleocytoplasmic transport in glioblastoma patients.Methods: We preoperatively collected serum from 17 patients with glioblastomas and determined DC subsets (HLA DR+ Lin-, CD34-, CD45+, CD123+, CD11+ were analyzed) using a 6-color flow cytometry panel. Expression levels of KPNA2 and nuclear accumulation of p53 were evaluated semi-quantitatively by immunohistochemistry. O6-methylguanine DNA methyltransferase (MGMT) and isocitrate dehydrogenase-1 (IDH-1) status were assessed by pyrosequencing and immunohistochemistry, respectively.Results: Median expression levels for both KPNA2 and p53 were 5-10%. IDH-1-R132H mutation and MGMT promoter hypermethylation was detected in 3/16 and 1/9 patients, respectively. Mean counts of total mature DCs, myeloid DCs and plasmacytoid DCs were 9.6, 2.1, 3.4 cells/μL. A preliminary analysis suggests an association between low KPNA2 nuclear expression and increased numbers of mature DCs. However, this correlation did not reach statistical significance so far (P = 0.077).Conclusion: Our preliminary data may indicate a role of KPNA2 in the impaired maturation of DCs observed in glioblastoma patients

Western Star, 1903-04-22

The Western Star began publication on Newfoundland's west coast on 4 April 1900, appearing weekly with brief semiweekly periods up to 1952, when it became a daily. As of 17 April 2019 it continues as a free weekly community paper

The effects of sodium bicarbonate supplementation at individual time-to-peak blood bicarbonate on 4-km cycling time trial performance in the heat

The purpose of this study was to explore the effect of individualised sodium bicarbonate (NaHCO3) supplementation according to a pre-established individual time-to-peak (TTP) blood bicarbonate (HCO3−) on 4-km cycling time trial (TT) performance in the heat. Eleven recreationally trained male cyclists (age: 28 ± 6 years, height: 180 ± 6 cm, body mass: 80.5 ± 8.4 kg) volunteered for this study in a randomised, crossover, triple-blind, placebo-controlled design. An initial visit was conducted to determine TTP HCO3− following 0.2 g.kg−1 body mass (BM) NaHCO3 ingestion. Subsequently, on three separate occasions, participants completed a 4-km cycling TT in the heat (30 degrees centigrade; °C) (relative humidity ∼40%) following ingestion of either NaHCO3 (0.2 g.kg−1 body mass), a sodium chloride placebo (0.2 g.kg−1 BM; PLA) at the predetermined individual TTP HCO3−, or no supplementation (control; CON) . Absolute peak [HCO3−] prior to the 4-km cycling TT's was elevated for NaHCO3 compared to PLA (+2.8 mmol.l−1; p = 0.002; g = 2.2) and CON (+2.5 mmol.l−1; p < 0.001; g = 2.1). Completion time following NaHCO3 was 5.6 ± 3.2 s faster than PLA (1.6%; CI: 2.8, 8.3; p = 0.001; g = 0.2) and 4.7 ± 2.8 s faster than CON (1.3%; CI: 2.3, 7.1; p = 0.001; g = 0.2). These results demonstrate that NaHCO3 ingestion at a pre-established individual TTP HCO3− improves 4-km cycling TT performance in the heat, likely through enhancing buffering capacity