[Circulating tumor cells: a new challenge for laboratory medicine].

Circulating tumor cells (CTCs) can be detected in the blood of patients with nearly all types of locally and metastatic adenocarcinomas. CTCs are epithelial cells whose release from a primitive tumor or a metastatic localization may be mediated by an epithelial-mesenchymal transition. Their pro-metastatic potential is still under debate because their phenotypes may be very heterogeneous, even within the same patient (expression of stem-cells markers, apoptotic status.

Urinary cystatin C can improve the renal safety follow-up of tenofovir-treated patients.

A receiver operating curve analysis was performed to assess the predictive value of the urinary cystatin C to urinary creatinine ratio for the renal monitoring of tenofovir. Urinary cystatin C to urinary creatinine ratio was measured in 37 samples from patients referred for suspected tenofovir-induced Fanconi syndrome. The best threshold (14 microg/mmol) was associated with sensitivity, 90.

Population pharmacokinetics and pharmacogenetics of imatinib in children and adults.

Purpose: The aim of this study was to explore the effect of several demographic, biological, and pharmacogenetic covariates on the disposition of imatinib and its main metabolite (CGP74588) in both adults and children.

Experimental Design: Thirty-three children with solid malignancies included in a phase II exploratory study and 34 adults with gastrointestinal stromal tumors received 340 mg/m(2) and 400 mg imatinib, respectively. Plasma imatinib and CGP74588 concentrations observed on day 1 and at steady-state were analyzed by a population pharmacokinetic method (NONMEM) to evaluate the effect of age, body weight, age, sex, albuminemia, plasma alpha1-acid glycoprotein (AGP), and eight polymorphisms corresponding to ABCB1, ABCG2, CYP3A4, CYP3A5, and AGP (pharmacogenetic data available for 46 of 67 patients).

Cystatin C: current position and future prospects.

Cystatin C is a low-molecular-weight protein which has been proposed as a marker of renal function that could replace creatinine. Indeed, the concentration of cystatin C is mainly determined by glomerular filtration and is particularly of interest in clinical settings where the relationship between creatinine production and muscle mass impairs the clinical performance of creatinine. Since the last decade, numerous studies have evaluated its potential use in measuring renal function in various populations.

[Cystatin C: current step and future prospects].

Cystatin C is a low molecular weight-protein, which may replace creatinine for the evaluation of renal function, particularly in the clinical settings where the relationship between creatinine production and muscular mass impairs the clinical performance of creatinine. This paper intends to summarize the current knowledge about the physiology of cystatin C and about its use as a renal marker, alone or within formulas developed to estimate the glomerular filtration rate. Moreover, this paper reviews the recent data about potential other applications of cystatin C, especially in cardiology, in oncology and in clinical pharmacology.

[Evaluation of renal function: an update].

During the last years, GFR estimation has received substantial attention with a focus on comparing results of new formulas with GFR measurements, and standardization of creatinine assays. Calibration of creatinine should improve performances. However, frequently used equations have lower precision in high GFR populations.

[Consequences for clinical biochemists of the modifications of the creatinine-based evaluation of glomerular filtration rate between 2005 and 2008].

Since 2005, international guidelines propose a stadification for chronic renal failure based on the glomerular filtration rate (GFR) value. The performance of the creatinine-based equations allowing the estimation of GFR and the bias of the creatinine measurements is, more than ever, a crucial issue. The consequences for the clinical biologists are of importance.

Modeling the variability of creatinine measurements improves estimates of the glomerular filtration rate.

Background: The precision of the formulae used to estimate glomerular filtration rate (GFR) decreases when the serum creatinine (SCr) assay is biased compared with the assay used during the development of the formulae.

Methods: For 100 children referred for 51Cr-EDTA clearance (CLEDTA), SCr was measured with a JAFFE (classic Jaffe colorimetric creatinine assay), a compensated Jaffe (COMP), an enzymatic (ENZ) and an HPLC assay. A population pharmacokinetics approach based on a non-linear mixed effects model (NONMEM) was used to model the relationships between the CLEDTA and physiopathological/analytical variables.

[Interest of cystatin C for individual dosing of anticancer drugs cleared by the kidneys].

Cystatin C is a protein freely filtered in the renal glomerulus, then reabsorbed and completely metabolised within the tubular cells. The possibility to predict the clearance of compounds eliminated by the kidneys (and then to control their interindividual variability) was evaluated for two cytotoxic drugs (carboplatin and topotecan) in adults and EDTA (ethylene diamine tetraacetic acid), a compound used to determine the glomerular filtration rate in children. The population pharmacokinetic approach based on NONMEM program was used.

Pharmacokinetic-pharmacodynamic relationships of imatinib and its main metabolite in patients with advanced gastrointestinal stromal tumors.

Purpose: This study explored factors affecting the pharmacokinetic variability of imatinib and CGP 74588, and the pharmacokinetic-pharmacodynamic correlations in patients with advanced gastrointestinal stromal tumors.

Experimental Design: Thirty-five patients with advanced gastrointestinal stromal tumors received 400 mg of imatinib daily. Six blood samples were drawn: before intake, during 1- to 3- and 6- to 9-hour intervals after intake on day 1, and before intake on days 2, 30, and 60.

GFR is better estimated by considering both serum cystatin C and creatinine levels.

Serum cystatin C (cysC) is a potential marker of the glomerular filtration rate (GFR) that has generated conflicting reports in children. A prospective study was conducted to assess the benefit of considering cysC together with serum creatinine (SCr) and demographic and morphologic characteristics to better estimate the 51Cr-ethylenediaminetetraacetate (EDTA) clearance (CL), i.e.

Contribution of the MDRD equation and of cystatin C for renal function estimates in cancer patients.

Background: Serum creatinine (SCr) and Cockcroft-Gault creatinine clearance (CG CrCL) are used to estimate glomerular filtration rate (GFR). Other markers have been proposed including serum cystatin C (cysC) and the Modification of Diet in Renal Disease (MDRD) study equation.

Patients And Methods: We have compared the diagnostic performances of SCr, cysC, CG CrCL, and the MDRD equation in 144 cancer patients.

Zoledronic acid treatment impairs protein geranyl-geranylation for biological effects in prostatic cells.

Background: Nitrogen-containing bisphosphonates (N-BPs) have been designed to inhibit osteoclast-mediated bone resorption. However, it is now accepted that part of their anti-tumor activities is related to interference with the mevalonate pathway.

Methods: We investigated the effects of zoledronic acid (ZOL), on cell proliferation and protein isoprenylation in two tumoral (LnCAP, PC-3,), and one normal established (PNT1-A) prostatic cell line.

Cystatin C as a new covariate to predict renal elimination of drugs: application to carboplatin.

Background And Objective: The individual dosing of drugs that are mainly eliminated unchanged in the urine is made possible by assessing renal function. Most of the methods used are based on serum creatinine (SCr) levels. Cystatin C (CysC) has been proposed as an alternative endogenous marker of the glomerular filtration rate (GFR).

Serum cystatin C is a better marker of topotecan clearance than serum creatinine.

Purpose: To evaluate plasma cystatin level as a covariate to predict topotecan pharmacokinetics. Cystatin C, a member of the cystatin superfamily of cysteine proteinase inhibitors, has been recently proposed as an alternative endogenous marker of glomerular filtration. Renal function is known as a key factor of topotecan clearance.

A recombinant cell bioassay for measurement of overall estrogenic activity of serum: preliminary results in women with breast cancer.

The estrogenic status of patients with breast cancer may influence the prognosis and the response to treatment and is currently assessed by immunological measurement of serum estradiol. This does not account for estrogenic or anti-estrogenic activity related to growth factors able to activate the estrogen receptor, to anti-estrogenic drugs or to exogenous supply of estrogen-like compounds. We developed a recombinant bioassay based on a mammary cell line expressing luciferase in an estrogen receptor-dependent way.

[Improving the interlaboratory variation for creatinine serum assay].

Purpose: To assess inter-assay variation and accuracy of blood creatinine measurements as well as the effect of the standardization of the calibration procedures on inter-assay variation.

Methods: Inter-assay variation and accuracy were assessed using 30 frozen human sera and 3 certified reference materials, which were analysed by 17 creatinine assays (colorimetric: 12, enzymatic: 4, HPLC: 1). Usual calibration procedure was compared with two common calibration procedures using either a reference material (404.

Epoetin alfa and intravenous iron sucrose to treat severe anemia in a patient with chronic radiation enteropathy: a case report.

We report the case of a patient with a severe chronic radiation enteropathy. She had been dependent on red cell transfusions for many years. On admission, she displayed anemia (8.

Impact of the biochemical assay for serum creatinine measurement on the individual carboplatin dosing: a prospective study.

We previously developed a formula to estimate the individual carboplatin clearance (CL) based on serum creatinine (Scr) determined by an enzymatic assay using creatinine amidohydrolase. An analytical comparison had shown systematic differences between this method and the commonly used Jaffé method (with Jaffé Scr (in microM)=1.08 x enzymatic Scr+1.

Carcinocythemia as the single extension of breast cancer: report of a case and review of the literature.

Carcinocythemia (carcinoma cell leukemia) has been previously described as a rare, late and dramatic event occurring in widespread tumoral disease. We report a case of carcinocythemia occurring in a patient with a particularly indolent breast cancer. When a large amount of circulating tumor cells (CTC) appeared in the blood smears, neither visceral macrometastases nor massive bone marrow infiltration could be detected.

Reversion of transformed phenotype of human adenocarcinoma A549 cells by expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase complementary DNA.

3-Hydroxy-3-methylglutaryl CoA reductase (HMG-CoA reductase) plays a rate-limiting role in isoprenoid biosynthesis and is associated with cell proliferation and transformation. Although an elevated level of HMG-CoA reductase activity is consistently detected in cancer cell lines and tumors, the question remains whether HMG-CoA reductase activity may have a causative role in cell transformation. We have stably transfected the A549 human adenocarcinoma cells with both bicistronic and retroviral expression vectors, including the whole cDNA of human HMG-CoA reductase.