Evaluation of the efficacy of a self-cleaning automated compounding system for the decontamination of cytotoxic drugs.

INTRODUCTION: Low surface contamination levels of hazardous drugs in compounding areas can be used as indicators of exposure and efficacy of cleaning procedures. We report the efficacy results of the KIRO® Oncology self-cleaning automated compounding system for decontamination of cytotoxic drugs, assessed in an oncology health center using a sanitizing method and an alkaline method. METHODS: The study was conducted for six-days over a three-week period. A mixture with known levels of 5-fluorouracil, ifosfamide, cyclophosphamide, gemcitabine, etoposide, methotrexate, paclitaxel, docetaxel and carboplatin was added to the KIRO® Oncology's compounding area surface before each self-cleaning method was used. Contamination levels were determined, with a surface wipe sampling kit, at the end of the self-cleaning process. RESULTS: Background surface contamination for quantified levels of cytotoxic drugs during routine use of KIRO® Oncology was below limit of quantification (99.8% for all cytotoxic drugs analyzed. CONCLUSION: This study provides evidence on the efficacy of the KIRO® Oncology automatic self-cleaning system for surface area decontamination during the preparation of cytotoxic drugs.

seqCNA: an R package for DNA copy number analysis in cancer using high-throughput sequencing.

BACKGROUND: Deviations in the amount of genomic content that arise during tumorigenesis, called copy number alterations, are structural rearrangements that can critically affect gene expression patterns. Additionally, copy number alteration profiles allow insight into cancer discrimination, progression and complexity. On data obtained from high-throughput sequencing, improving quality through GC bias correction and keeping false positives to a minimum help build reliable copy number alteration profiles. RESULTS: We introduce seqCNA, a parallelized R package for an integral copy number analysis of high-throughput sequencing cancer data. The package includes novel methodology on (i) filtering, reducing false positives, and (ii) GC content correction, improving copy number profile quality, especially under great read coverage and high correlation between GC content and copy number. Adequate analysis steps are automatically chosen based on availability of paired-end mapping, matched normal samples and genome annotation. CONCLUSIONS: seqCNA, available through Bioconductor, provides accurate copy number predictions in tumoural data, thanks to the extensive filtering and better GC bias correction, while providing an integrated and parallelized workflow.

Clinical and experimental approaches to the pathophysiology of interleukin-18 in cancer progression.

Interleukin-18 (IL-18, interferon [IFN]-gamma-inducing factor) is a proinflammatory cytokine converted to a biologically active molecule by interleukin (IL)-1beta converting enzyme (caspase-1). A wide range of normal and cancer cell types can produce and respond to IL-18 through a specific receptor (IL-18R) belonging to the toll-like receptor family. The activity of IL-18 is regulated by IL-18-binding protein (IL-18bp), a secreted protein possessing the ability to neutralize IL-18 and whose blood level is affected by renal function and is induced by IFNgamma. IL-18 plays a central role in inflammation and immune response, contributing to the pathogenesis and pathophysiology of infectious and inflammatory diseases. Because immune-stimulating effects of IL-18 have antineoplastic properties, IL-18 has been proposed as a novel adjuvant therapy against cancer. However, IL-18 increases in the blood of the majority of cancer patients and has been associated with disease progression and, in some cancer types, with metastatic recurrence risk and poor clinical outcome and survival. Under experimental conditions, cancer cells can also escape immune recognition, increase their adherence to the microvascular wall and even induce production of angiogenic and tumor growth-stimulating factors via IL-18-dependent mechanism. This is particularly visible in melanoma cells. Thus, the role of IL-18 in cancer progression and metastasis remains controversial. This review examines the clinical correlations and biological effects of IL-18 during cancer development and highlights recent experimental insights into prometastatic and proangiogenic effects of IL-18 and the use of IL-18bp against cancer progression.

Gene expression profiling of renal dysfunction in rats with experimental cirrhosis.

BACKGROUND/AIMS: Renal dysfunction is a frequent complication in advanced cirrhosis. The mechanisms underlying this complication have classically been addressed through conventional methods of study of candidate genes, but never on a genome-wide scale. In this investigation, we used microarrays to monitor global gene expression changes in the kidney of cirrhotic rats. METHODS: Renal samples were obtained from control and carbon tetrachloride-induced cirrhotic rats. RNA samples were reverse-transcribed into Cy5-labeled cDNA, combined with a Cy3-labeled reference and hybridized to oligonucleotide microarrays. Microarrays were scanned in a Genepix 4000B and data analyzed by Luminator v2.0 software. RESULTS: A total of 620 genes were differentially regulated (354 up and 266 down) in the cirrhotic kidney, accounting for approximately 11% of all analyzed transcripts. Functional grouping of these genes revealed that 47 were related to the category of vascular tone and 85 to transporters/channels. Among these, we identified genes and pathways already associated with renal dysfunction as well as a new subset of genes previously unknown to participate in this complication, including a G protein-coupled receptor that binds apelin, a protein phosphatase (calcineurin B) and a number of neuropeptide receptors and growth factors. CONCLUSIONS: These findings furnish new data for mechanistic investigation into renal dysfunction in cirrhosis.

Interleukin-18 binding protein reduces b16 melanoma hepatic metastasis by neutralizing adhesiveness and growth factors of sinusoidal endothelium.

We studied the role of endogenous interleukin (IL)-18 in hepatic metastasis by blocking this cytokine using the naturally occurring IL-18 binding protein (IL-18BP). A single i.p. dose of IL-18BP given 30 min before intrasplenic injection of murine B16 melanoma (B16M) cells reduced the number of hepatic metastatic foci by 75% and metastatic volume by 80%. Same treatment reduced the intrahepatic retention of luciferase-transfected B16M by 50% and abolished VCAM-1 up-regulation in the hepatic microvasculature, as assessed by reverse transcription-PCR, Western blot, and immunohistochemistry. Twelve hours after IL-18BP, hepatic sinusoidal endothelium (HSE) cells were isolated, and adhesion of B16M cells to these cultured HSE cells was reduced to the level of vehicle-treated mice. IL-18BP treatment of mice with established micrometastases resulted in a 25% decrease in metastasis number and 40% decrease in metastasis volume, suggesting inhibition of endogenous growth factors. Indeed, the addition of IL-18BP to normal HSE abolished the release of melanoma cell growth factor(s) induced by B16M. IL-18 promoted the in vitro growth of B16M and human melanoma cells, which was IL-1 dependent. These data demonstrate a significant role of endogenous IL-18 on hepatic metastasis by up-regulating melanoma cell adhesion to HSE cells and tumor growth, implicating a possible antimetastatic benefit of neutralizing IL-18.