Jean Andre

Urinary Prostate Cancer 3 Test: Toward the Age of Reason?

The prostate cancer 3 (PCA3) gene was discovered in 1999, on the basis of differential expression between cancer and noncancerous prostate tissue. Including the first study published in 2003, 11 clinical studies have evaluated its utility for the diagnosis of prostate cancer by measuring the number of PCA3 RNA copies in urine enriched with prostate cells. Although the sensitivity of the PCA3 test was less than that of serum prostate-specific antigen (PSA), its specificity appeared to be much better, particularly in patients with a previous negative biopsy. Recent studies also have suggested that this test could be used to predict cancer prognosis.

Androgens inhibit the proliferation of a variant of the human prostate cancer cell line LNCaP

UNLABELLEDnThe paradoxical androgen response of R2, a subline of the human prostate cancer cell line LNCaP, is described here. Two androgens (DHT and R1881) decreased, in a dose-dependent manner, R2 cell proliferation and [3H]thymidine incorporation. These ligand and cell specific effects were accompanied by an increase in the metabolism of the vital dye MTT and in cell protein content. Both androgens increased the doubling time and the percentage of G0-G1 cells. No evidence of androgen-induced apoptosis was found. Cloning allowed the selection of two cell populations on the basis of the response to 10 nM of R1881. Long term culture of uncloned R2 cells with R1881 modified reversibly the pattern of androgen response. R2 was compared to the androgen-stimulated LNCaP-FGC subline to investigate the causes of their different androgen responsiveness. The androgen receptor (number, affinity for hormones and antihormones, sedimentation constant and molecular weight) and androgen receptor genes (exon size and exon 8 sequence) were found to be identical in the two sublines. EGF stimulated LNCaP-FGC but not R2. Both cells were slightly stimulated by basic FGF but were insensitive to IGF-I and TGF beta 1.nnnIN CONCLUSIONn(1) androgens inhibit the proliferation of R2 cells possibly by introducing a G0-G1 block; (2) this inhibition is incomplete because, at least in part, the R2 cell population is heterogeneous; (3) chronic androgen treatment induces reversible cell adaptation; and (4) there is no evidence that the loss of the classical stimulatory effect of androgen on cell proliferation and the gain of inhibitory effect are due to androgen receptor alteration or to a specific action of one of the four growth factors tested.

Plasminogen Activator Inhibitor Type 1 is the Most Significant of the Usual Tissue Prognostic Factors in Node-Negative Breast Ductal Adenocarcinoma Independent of Urokinase-Type Plasminogen Activator

PURPOSEnThe aim of the present investigation was to evaluate the prognostic significance of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) tissue contents in primary breast adenocarcinoma.nnnPATIENTS AND METHODSnPatients from 3 medical centers were included between 1994 and 2001. Biologic factors in tumor extracts were all assayed in the same laboratory. PAI-1 and uPA were treated as continuous or dichotomized variables. Metastasis-free survival analyses were performed using the Cox model and the classification algorithm and regression tree (CART) in the whole population and in the subsets of node-negative (pN0) or positive (pN+) cases. Kaplan curves of metastasis-free survival were designed for different groups in relation to uPA/PAI-1 combinations. Urokinase-type plasminogen activator tumor level appears related to the anatomic degree of extension; conversely, PAI-1 tumor content is independent of tumor size and nodal extension.nnnRESULTSnIn univariate analysis, adjusted on usual prognostic factors, the metastasis risk increased with PAI-1 level in all patients (HR [hazard ratio], 3.1; P < .001), in pN0 (HR, 4.3; P < .001), and pN+ patients (HR, 2.3; P = .019). It increased also with uPA in all patients (HR, 2.6; P = 0.006). In multivariate analysis, when both variables were included, PAI-1 remained significant in all patients (HR, 2.4; P = .002) and pN0 patients (HR, 3.2; P = .003) but not uPA. CART analyses confirmed that the best partitioning factor was PAI-1.nnnCONCLUSIONnThere was no evidence for any additional impact of uPA. PAI-1 is an independent prognostic factor in particular in pN0 breast ductal carcinoma.

Intérêt des marqueurs urinaires dans le diagnostic et le suivi des tumeurs urothéliales de vessie

Urothelial bladder tumours require regular surveillance: cystoscopy associated with urine cytology are reference examinations. Several new markers currently under evaluation or already validated have recently been proposed to replace cytology and potentially reduce or even replace unnecessary cystoscopies. The biological fluid studied for all of these markers is the same as that of urine cytology, i.e. urine. The authors review the results of recent studies on these new urinary markers. The results of these markers demonstrate a better global sensitivity than urine cytology, but often a lower specificity. In the majority of cases, these tests are performed during patient follow-up (NMP22, BTA, CYFRA 21-l., etc.), but do not replace cystoscopy, due to a large number of false-positives. Other techniques, such as FISH, uCyt+ or microsatellites appear to be more promising, especially for the diagnosis of low-grade tumours. The best solution in practice may consist of a combination of several markers to further improve sensitivity and to decrease the false-positive rate responsible for unnecessary cystoscopies.Resume Les tumeurs urotheliales de vessie necessitent une surveillance reguliere : la cystoscopie associee a la cytology urinaire en sont les examens de reference. Recemment, plusieurs nouveaux marqueurs valides ou en cours d’evaluation ont ete proposes afin de remplacer la cytologie et potentiellement de reduire, voire de remplacer les cystoscopies inutiles. Le liquide biologique etudie pour tous ces marqueurs est le meme que la cytologie urinaire, c’est a dire l’urine. Dans ce travail, nous avons fait le point sur les resultats des travaux recents concernant ces nouveaux marqueurs urinaires. Les resultats de ces marqueurs montrent une meilleure sensibilite globale que la cytologie urinaire, mais souvent une specificite moins bonne. Dans la majorite des cas, ces tests sont realises lors du suivi des patients (NMP22, BTA, CYFRA 21-1 …), mais ne remplacent pas la cystoscopie, du fait d’un nombre eleve de faux-positifs. D’autres techniques, tels que la FISH, le uCyt+ ou les microsatellites semblent etre des tests plus prometteurs, notamment dans le diagnostic des tumeurs de bas grade. Dans la pratique, la solution viendra peut-etre de l’association de plusieurs marqueurs pour ameliorer encore la sensibilite, et diminuer le taux de faux-positifs responsables des cystoscopies inutiles.