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1.  Clinical Studies Applying Cytokine-Induced Killer Cells for the Treatment of Renal Cell Carcinoma 
Metastatic renal cell carcinoma (RCC) seems to be resistant to conventional chemo- and radiotherapy and the general treatment regimen of cytokine therapy produces only modest responses while inducing severe side effects. Nowadays standard of care is the treatment with VEGF-inhibiting agents or mTOR inhibition; nevertheless, immunotherapy can induce complete remissions and long-term survival in selected patients. Among different adoptive lymphocyte therapies, cytokine-induced killer (CIK) cells have a particularly advantageous profile as these cells are easily available, have a high proliferative rate, and exhibit a high antitumor activity. Here, we reviewed clinical studies applying CIK cells, either alone or with standard therapies, for the treatment of RCC. The adverse events in all studies were mild, transient, and easily controllable. In vitro studies revealed an increased antitumor activity of peripheral lymphocytes of participants after CIK cell treatment and CIK cell therapy was able to induce complete clinical responses in RCC patients. The combination of CIK cell therapy and standard therapy was superior to standard therapy alone. These studies suggest that CIK cell immunotherapy is a safe and competent treatment strategy for RCC patients and further studies should investigate different treatment combinations and schedules for optimal application of CIK cells.
PMCID: PMC3501961  PMID: 23193418
2.  Phenotype severity in the bladder exstrophy-epispadias complex: analysis of genetic- and non-genetic contributing factors in 441 families from North America and Europe 
The Journal of pediatrics  2011;159(5):825-831.e1.
To identify genetic and non-genetic risk factors contributing to the severity of the bladder exstrophy-epispadias complex (BEEC).
Study design
Patients with BEEC from North America (n=167) and Europe (n=274) were included. The following data were collected: associated anomalies, parental age at conception, mode of conception, periconceptional folic acid supplementation, maternal risk factors during pregnancy, and environmental risk factors. Patients were divided into three subgroups according to phenotype severity: (i) mild - epispadias (E, n=43); (ii) intermediate - classic bladder exstrophy (CBE, n=366); and (iii) severe - cloacal exstrophy (CE, n=31). These subgroups were then compared to identify factors which contribute to phenotype severity.
Males were overrepresented in all subgroups. A relatively high prevalence of cleft lip with or without cleft palate was observed. Maternal smoking and medical radiation during the first trimester were associated with the severe CE phenotype. Compliance with periconceptional folic acid supplementation was associated with the mildest phenotype (E).
Periconceptional folic acid supplementation appears to prevent the development of the severe phenotype of BEEC.
PMCID: PMC3409088  PMID: 21679965
Bladder exstrophy-epispadias complex; BEEC; epidemiology; teratogenity
3.  Alterations of global histone H4K20 methylation during prostate carcinogenesis 
BMC Urology  2012;12:5.
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.
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). Immunohistochemistry was performed to assess global levels of H4K20 methylation levels.
Similar proportions of the normal, PCA, and mPCA prostate tissues showed strong H4K20me3 staining. CRPC tissue analysis showed the weakest immunostaining levels of H4K20me1 and H4K20me2, compared to other prostate tissues. H4K20me2 methylation levels indicated significant differences in examined tissues except for normal prostate versus PCA tissue. H4K20me1 differentiates CRPC from other prostate tissues. H4K20me1 was significantly correlated with lymph node metastases, and H4K20me2 showed a significant correlation with the Gleason score. However, H4K20 methylation levels failed to predict PSA recurrence after radical prostatectomy.
H4K20 methylation levels constitute valuable markers for the dynamic process of prostate cancer carcinogenesis.
PMCID: PMC3323457  PMID: 22413846
Histone; Methylation; H4K20; Prostate cancer; Epigenetics

Results 1-3 (3)