Phenotypical analysis, relation to malignancy and prognostic relevance of ICOS+T regulatory and dendritic cells in patients with gliomas.

We determined circulating T helper, T regulatory and ICOS+T regulatory as well as DC cell counts in 29 patients with cerebral gliomas. Samples from patients with gliomas vs. healthy controls and from patients with glioblastomas vs.

Circulating microRNAs in serum: novel biomarkers for patients with bladder cancer?

Purpose: Recent studies indicate that circulating microRNAs in serum/plasma are a novel class of non-invasive biomarkers with diagnostic and prognostic information. So far, circulating microRNAs have not been analyzed in patients with bladder cancer.

Methods: We collected serum from patients with non-muscle invasive bladder cancer (NMIBC), muscle invasive bladder cancer (MIBC) and non-malignant urological disease.

Identification of prostaglandin receptors in human ureters.

Background: Prostaglandins play an important role in ureteral obstruction, but the detailed expression profiles of the prostaglandin receptors (PTGER1, PTGER2, PTGER3, PTGER4, PTGFR) remain unknown in the different parts of the human ureter.

Methods: The expression pattern of PTGER1, PTGER2, PTGER3, PTGER4 and PTGFR was determined in human distal, mid and proximal ureter and renal pelvis samples using immunohistochemistry (protein levels) and quantitative real-time PCR (mRNA).

Results: PTGER1 was highly expressed in most samples irrespective of the ureteral localization; however, urothelial cells had higher levels of PTGER1 than smooth muscle cells.

Histone methylation defines an epigenetic entity in penile squamous cell carcinoma.

Purpose: Earlier studies indicate that epigenetics contribute to the pathogenesis of penile squamous cell carcinoma. Histone methylation patterns are frequently altered during carcinogenesis. Therefore, we investigated the methylation pattern of the histones H3K4, H3K9 and H3K27 in penile carcinoma and normal tissue.

Cell-free serum DNA in patients with bladder cancer: results of a prospective multicenter study.

Background/aim: Cell-free DNA may serve as a biomarker for patients with cancer; we designed our study to determine its potential in patients with bladder cancer (BCA).

Materials And Methods: Short β-actin (ACTB)-106 and large ACTB-384 fragments were quantified using real time PCR (RT-PCR); the ratio of ACTB-384/ACTB-106 was defined as DNA integrity. We analyzed the serum from 95 patients with and from 132 without BCA.

Evaluation of reference genes for the analysis of serum miRNA in patients with prostate cancer, bladder cancer and renal cell carcinoma.

Objectives: To identify an appropriate reference gene for the analysis of circulating micro-ribonucleic acid in patients with urological malignancies.

Methods: Serum from patients with prostate cancer (n = 24), bladder cancer (n = 24), renal cell carcinoma (n = 24) and control subjects (n = 48) was spiked with cel-miR-39, and then ribonucleic acid was isolated. Quantitative real-time polymerase chain reaction was used to determine the levels of candidate reference genes (RNU1-4, RNU6-2, SNORD43, SNORD44, SNORD48, SNORA74A, miR-let-7a-1, miR-106a).

Analysis of serum microRNAs (miR-26a-2*, miR-191, miR-337-3p and miR-378) as potential biomarkers in renal cell carcinoma.

Introduction: Emerging evidence suggest that microRNAs could serve as non-invasive biomarker for cancer patients. Our study was designed to analyze circulating serum microRNAs in patients with renal cell carcinoma (RCC).

Materials And Methods: Serum RNA was isolated from patients with clear cell RCC (ccRCC) and non-malignant disease; an artificial microRNA (cel-miR-39) was spiked-in prior the isolation procedure to control isolation efficiency.

Alterations of global histone H4K20 methylation during prostate carcinogenesis.

Background: Global histone modifications have been implicated in the progression of various tumour entities. Our study was designed to assess global methylation levels of histone 4 lysine 20 (H4K20me1-3) at different stages of prostate cancer (PCA) carcinogenesis.

Methods: Global H4K20 methylation levels were evaluated using a tissue microarray in patients with clinically localized PCA (n = 113), non-malignant prostate disease (n = 27), metastatic hormone-naive PCA (mPCA, n = 30) and castration-resistant PCA (CRPC, n = 34).

Decreased levels of histone H3K9me1 indicate poor prognosis in patients with renal cell carcinoma.

Background/aim: To determine the role of global histone H3K9 and H4K20 methylation levels as prognostic parameters in patients with renal cell cancer (RCC).

Material And Methods: Global histone methylation levels were investigated in 193 RCC (including 142 clear cell (cc), 31 papillary (p), 10 chromophobe (ch) and 10 sarcomatoid (s) RCC), 10 oncocytomas and 30 benign renal specimens.

Results: Histone modifications were mostly similar in the different histological subtypes (p>0.

Global histone H3K27 methylation levels are different in localized and metastatic prostate cancer.

Global histone modification patterns have been shown to be a predictive factor of recurrence in various cancers. We analyzed global histone-3-lysine-27 (H3K27) methylation in prostate cancer (PCA) tissues. H3K27 mono-, di-, and tri-methylation patterns were different in nonmalignant prostate tissue, localized PCA, metastatic PCA, and castration-resistant PCA.

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.

Tyrosine kinase expression profile in clear cell renal cell carcinoma.

Purpose: To profile different tyrosine kinase (TK) expression patterns in clear cell renal carcinoma (ccRCC).

Methods: We analysed mRNA expression levels of 89 receptor and non-receptor TK in corresponding cancer and normal renal tissue from 5 patients with ccRCC using the TaqMan Low-Density Array technology. In order to confirm aberrant TK expressions, a subsequent analysis of 25 ccRCC and corresponding normal renal tissues was performed, applying quantitative real-time PCR.

Glutathione-S-transferase pi 1(GSTP1) gene silencing in prostate cancer cells is reversed by the histone deacetylase inhibitor depsipeptide.

Gene silencing by epigenetic mechanisms is frequent in prostate cancer (PCA). The link between DNA hypermethylation and histone modifications is not completely understood. We chose the GSTP1 gene which is silenced by hypermethylation to analyze the effect of the histone deacetylase inhibitor depsipeptide on DNA methylation and histone modifications at the GSTP1 promoter site.

Global histone H3 lysine 27 (H3K27) methylation levels and their prognostic relevance in renal cell carcinoma.

Objective: To evaluate if histone H3 lysine 27 (H3K27) methylation plays a role in renal cell carcinoma (RCC) tissue and whether its expression is a predictor of cancer recurrence in RCC.

Materials And Methods: A tissue microarray (TMA) with 193 RCC specimens (comprising 142 clear-cell, 31 papillary, 10 chromophobe and 10 sarcomatoid RCC), 10 oncocytoma tissue specimens and a TMA with 30 benign renal tissue samples were stained with antibodies against H3K27-monomethyl (H3K27me1), H3K27-dimethyl (H3K27me2) and H3K27-trimethyl (H3K27me3). Sections were scored according to staining intensity and the proportion of epithelial cells showing nuclear staining.

Global histone H4K20 trimethylation predicts cancer-specific survival in patients with muscle-invasive bladder cancer.

Objective: •To determine the role of global histone methylation as a prognostic parameter in patients with bladder cancer.

Patients And Methods: •We used a tissue microarray with samples from patients with non-muscle-invasive bladder cancer (NMIBC; n= 161), muscle-invasive bladder cancer (MIBC, n= 127), normal urothelium (NU; n= 31) and bladder cancer metastases (METS; n= 31) to determine global histone methylation (me) levels at histone H3 lysine 4 (H3K4) and H4K20.

Results: •Global histone modification levels (H3K4me1, H3K4me3, H4K20me1, H4K20me2, and H4K20me3) were lower in bladder cancer samples than in NU tissue •Global levels of H3K4me1, H4K20me1, H4K20me2 and H4K20me3 were decreasing from NU over NMIBC and MIBC to METS.

Circulating microRNAs (miRNA) in serum of patients with prostate cancer.

Objectives: To analyze circulating microRNAs (miRNA) in serum as non-invasive biomarker in patients with localized prostate cancer (PCA), benign prostate hyperplasia (BPH) and healthy individuals (HI).

Methods: Total RNA was isolated from serum samples and the circulating levels of different RNA species (miRNA, miR-16; small nuclear RNA, RNU1A-1; messenger RNA, HPRT1), as well as of 4 oncogenic miRNAs (miR-26a, miR-32, miR-195, miR-let7i), were determined using a quantitative real-time polymerase chain reaction. We also evaluated miRNA levels in a second cohort of 10 PCA patients in cancer/nonmalignant tissue, and pre- and post-prostatectomy serum samples.

Mechanisms of improved wound healing in Murphy Roths Large (MRL) mice after skin transplantation.

Scars arise in the late phase of wound healing and are characterized by fibroplasia. Previous controversial studies have discussed the regenerative wound healing capacity of Murphy Roths Large (MRL) mice. The aim of this study was to investigate the mechanisms of improved wound healing in a skin transplantation model.

Circulating mitochondrial DNA in serum: a universal diagnostic biomarker for patients with urological malignancies.

Objective: Cell-free circulating mitochondrial DNA (mtDNA) has been proposed as universal diagnostic and prognostic biomarker in cancer patients.

Patients And Methods: Cell-free DNA was isolated from 1 ml serum from patients with bladder cancer (BCA, n = 84), renal cell carcinoma (RCC, n = 33), and prostate cancer (CaP, n = 23), and compared with healthy individuals (n = 79). Quantitative real-time PCR was used to analyze the levels of a 79 bp (mtDNA-79), and 220 bp (mtDNA-220) fragment of the mitochondrial specific 16S-RNA.

Global histone acetylation levels: prognostic relevance in patients with renal cell carcinoma.

Epigenetic alterations play an important role in carcinogenesis. Recent studies have suggested that global histone modifications are predictors of cancer recurrence in various tumor entities. Global histone acetylation levels (histone H3 lysine 9 acetylation [H3K9Ac], histone H3 lysine 18 acetylation [H3K18Ac], total histone H3 acetylation [H3Ac] and total histone H4 acetylation [H4Ac]) were determined in patients with renal cell carcinoma (RCC) using immunohistochemistry in a tissue micro array with 193 RCC and 10 oncocytoma specimens.

Cell-free circulating DNA: Diagnostic value in patients with renal cell cancer.

Objectives: To analyse the diagnostic and prognostic value of cell-free DNA in patients with renal cell carcinoma (RCC).

Patients And Methods: Cell-free DNA was measured in 35 patients with RCC and 54 healthy individuals using quantitative real-time PCR. ACTB-106 detects fragmented cell-free DNA due to apoptosis and ACTB-384 detects long DNA fragments by necrosis.

Prognostic relevance of global histone H3 lysine 4 (H3K4) methylation in renal cell carcinoma.

Epigenetic alterations play an important role in carcinogenesis. Recent studies suggested that global histone modifications are predictors of cancer recurrence in various tumor entities. Our study was performed to evaluate histone H3 lysine 4 mono-methyl (H3K4me1), -di-methyl (H3K4me2) and -trimethyl (H3K4me3) patterns in renal cell carcinoma (RCC) using a tissue microarray with 193 RCC (including 142 clear cell, 31 papillary, 10 chromophobe and 10 sarcomatoid RCC) and 10 oncocytoma specimens: H3K4me3 staining was more intense in papillary RCC, whereas H3K4me1 and H3K4me2 were similar in the diverse RCC subtypes.

Regulation of protein tyrosine kinases in tumour cells by the transcription factor Ets-1.

Tyrosine phosphorylation is one of the key covalent modifications that occurs in multicellular organisms as a result of intercellular communication. The family of tyrosine kinases (PTKs) are responsible for part of the cellular phosphorylation and are involved in a broad variety of cellular functions including differentiation, proliferation, migration, invasion, angiogenesis and survival under physiological as well as pathological conditions. Aberration in PTK signalling occurs in inflammatory diseases and diabetes, and aberrant expression can lead to benign proliferative conditions as well as to various forms of cancer.

The role of cell-free circulating DNA in the diagnosis and prognosis of prostate cancer.

The presence of small amounts of circulating DNA in plasma was demonstrated 60 years ago. Since then, cell-free DNA has been tested for quantity, fragmentation pattern, and tumor-specific sequences in patients with various malignancies. Recent studies have shown that cell-free DNA levels are distinctly increased in most patients with prostate cancer (PCA) and that the DNA fragmentation pattern is different from healthy individuals and patients with benign prostate disease.

Global levels of histone modifications predict prostate cancer recurrence.

Purpose: Epigenetic alterations such as DNA methylation and histone modifications play important roles in carcinogenesis. It was reported that global histone modification patterns are predictors of cancer recurrence in various tumor entities. Our study was performed to evaluate histone lysine (H(x)K(y)) and histone acetyl (H(x)Ac) modifications in prostate tissue.

CpG island hypermethylation of cell-free circulating serum DNA in patients with testicular cancer.

Purpose: DNA hypermethylation is a common cancer associated alteration. We analyzed methylation patterns of cell-free serum DNA in patients with testicular cancer.

Materials And Methods: Hypermethylation at APC, GSTP1, PTGS2, p14(ARF), p16(INK) and RASSF1A was analyzed using real-time polymerase chain reaction following methylation sensitive restriction endonuclease treatment in 73 patients with testicular cancer and 35 healthy individuals.