Y-box protein-1/p18 fragment identifies malignancies in patients with chronic liver disease

<p>Abstract</p> <p>Background</p> <p>Immunohistochemical detection of cold shock proteins is predictive for deleterious outcome in various malignant diseases. We recently described active secretion of a family member, denoted Y-box (YB) protein-1. We tested the clinical and diagnostic value of YB-1 protein fragment p18 (YB-1/p18) detection in blood for malignant diseases.</p> <p>Methods</p> <p>We used a novel monoclonal anti-YB-1 antibody to detect YB-1/p18 by immunoblotting in plasma samples of healthy volunteers (n = 33), patients with non-cancerous, mostly inflammatory diseases (n = 60), hepatocellular carcinoma (HCC; n = 25) and advanced solid tumors (n = 20). YB-1/p18 was then tested in 111 patients with chronic liver diseases, alongside established tumor markers and various diagnostic measures, during evaluation for potential liver transplantation.</p> <p>Results</p> <p>We developed a novel immunoblot to detect the 18 kD fragment of secreted YB-1 in human plasma (YB-1/p18) that contains the cold-shock domains (CSD) 1-3 of the full-length protein. YB-1/p18 was detected in 11/25 HCC and 16/20 advanced carcinomas compared to 0/33 healthy volunteers and 10/60 patients with non-cancerous diseases. In 111 patients with chronic liver disease, YB-1/p18 was detected in 20 samples. Its occurrence was not associated with advanced Child stages of liver cirrhosis or liver function. In this cohort, YB-1/p18 was not a good marker for HCC, but proved most powerful in detecting malignancies other than HCC (60% positive) with a lower rate of false-positive results compared to established tumor markers. Alpha-fetoprotein (AFP) was most sensitive in detecting HCC, but simultaneous assessment of AFP, CA19-9 and YB-1/p18 improved overall identification of HCC patients.</p> <p>Conclusions</p> <p>Plasma YB-1/p18 can identify patients with malignancies, independent of acute inflammation, renal impairment or liver dysfunction. The detection of YB-1/p18 in human plasma may have potential as a tumor marker for screening of high-risk populations, e.g. before organ transplantation, and should therefore be evaluated in larger prospective studies.</p

Gentamicin supplemented polyvinylidenfluoride mesh materials enhance tissue integration due to a transcriptionally reduced MMP-2 protein expression

<p>Abstract</p> <p>Background</p> <p>A beneficial effect of gentamicin supplemented mesh material on tissue integration is known. To further elucidate the interaction of collagen and MMP-2 in chronic foreign body reaction and to determine the significance of the MMP-2-specific regulatory element (RE-1) that is known to mediate 80% of the MMP-2 promoter activity, the spatial and temporal transcriptional regulation of the MMP-2 gene was analyzed at the cellular level.</p> <p>Methods</p> <p>A PVDF mesh material was surface modified by plasma-induced graft polymerization of acrylic acid (PVDF+PAAc). Three different gentamicin concentrations were bound to the provided active sites of the grafted mesh surfaces (2, 5 and 8 μg/mg). 75 male transgenic MMP-2/LacZ mice harbouring the LacZ reporter gene under control of MMP-2 regulatory sequence -1241/+423, excluding the RE-1 were randomized to five groups. Bilateral of the abdominal midline one of the five different meshes was implanted subcutaneously in each animal. MMP-2 gene transcription (anti-ß-galactosidase staining) and MMP-2 protein expression (anti-MMP-2 staining) were analyzed semiquantitatively by immunohistochemistry 7, 21 and 90 days after mesh implantation. The collagen type I/III ratio was analyzed by cross polarization microscopy to determine the quality of mesh integration.</p> <p>Results</p> <p>The perifilamentary ß-galactosidase expression as well as the collagen type I/III ratio increased up to the 90^thday for all mesh modifications, whereas no significant changes could be observed for MMP-2 protein expression between days 21 and 90. Both the 5 and 8 μg/mg gentamicin group showed significantly reduced levels of ß-galactosidase expression and MMP-2 positive stained cells when compared to the PVDF group on day 7, 21 and 90 respectively (5 μg/mg: p < 0.05 each; 8 μg/mg: p < 0.05 each). Though the type I/III collagen ratio increased over time for all mesh modifications significant differences to the PVDF mesh were only detected for the 8 μg/mg group at all 3 time points (p < 0.05 each).</p> <p>Conclusions</p> <p>Our current data indicate that lack of RE-1 is correlated with increased mesh induced MMP-2-gene expression for coated as well as for non-coated mesh materials. Gentamicin coating reduced MMP-2 transcription and protein expression. For the 8 μg/mg group this effect is associated with an increased type I/III collagen ratio. These findings suggest that gentamicin is beneficial for tissue integration after mesh implantation, which possibly is mediated via RE-1.</p

Adult clear cell sarcoma of the kidney with tumour externsion into the lower part of the inferior vena cava

No Abstract

Cancer Primitif de l\'Urètre

Objectif: Dans la présente nous rapportons six cas de cancer primitif de l\'urètre colligés en 12 ans sur 1109 cas de cancers urologiques hospitalisés pendant la même période. Patients and Méthodes: De 1990 à 2001 six patients (quatre hommes, deux femmes) ont été hospitalisés pour la prise en charge d\'un cancer de l\'urètre. Les tumeurs ont été analysées selon la classification de Grabstald. Tous les patients ont été explorés par une urethrocystographie rétrograde montrant une image irrégulière de l\'urètre et opacifiant parfois les trajets fistuleux. L\'urethrocystoscopie a permis de montrer le siège de la tumeur, son aspect et surtout de faire des biopsies à visée diagnostique. Il s\'agissait dans 5 cas d\'une tumeur épidermoïde et dans un cas d\'un adénocarcinome. Les traitements utilisés dépendent du stade de la maladie et de l\'état général des patients. Deux patientes on bénéficié d\'une pelvectomie antérieure sans aucun traitement adjuvant. Deux patients porteurs d\'une maladie disséminée ont été traités d\'une manière palliative par radiothérapie àvisée antalgique. Les deux derniers ayant refusé le traitement chirurgical ont également été traités par radiothérapie seule. Résultats: Globalement, le taux de survie moyen est 17,5 mois (extrêmes allant de 3 à 60 mois). Les meilleurs résultats ont été obtenus chez les patients traités chirurgicalement. Deux des patients confiés aux oncologues pour une radiothérapie palliative sont décédés à 3 et à 6 mois. Un patient traité par radiothérapie exclusive après avoir refusé le traitement chirurgical a été revu 6 mois plus tard pour sténose longue post-radique de l\'urètre. Le patient refusant toujours le traitement chirurgical a été traité par cystostomie définitive. Le dernier patient traité également par radiothérapie exclusive est suivi par les radiothérapeutes. Conclusion: Le cancer primitif de l\'urètre est rare. La sémiologie est peu spécifique ce qui explique le retard fréquent au diagnostic. C\'est l\'examen minutieux de l\'urètre qui permet le diagnostic. Le traitement repose sur la chirurgie et / ou la radiothérapie. Primitive Cancer of the Urethra Objective: We report six cases of primitive cancer of the urethra out of a total of 1109 cases of urologic cancers hospitalized during a period of 12 years. Patients and Methods: From 1990 to 2001 six patients (four males, two females) were hospitalized for cancer of the urethra. The tumors were analyzed according to the classification of Grabstald. All the patients were explored by retrograde urethrocystography showing an irregular image of the urethra and at times opacifying the sinus ways. Urethrocystoscopy showed the site of the tumor and its aspect and allowed for diagnostic biopsies. In five cases it revealed an epidermoid cancer and an adenocarcinoma in one case. The treatment used depended on the stage of the disease and the general condition of the patients. Two patients underwent radical pelvectomy without any adjuvant treatment. Two patients with disseminated disease received palliative treatment by radiotherapy. The two remaining patients having refused surgical treatment were also treated by radiotherapy alone. Results: Overall, the average rate of survival was 17.5 months (3 to 60 months). The best results were achieved with surgical treatment. Two of the patients referred to the oncologist for palliative radiotherapy died within 3 and 6 months, respectively. One patient treated by radiotherapy alone after having refused surgical treatment presented 6 months later with a long post-radiation stenosis of the urethra. Since the patient still refused surgical treatment, he was treated by final cystostomy. The last patient also treated by exclusive radiotherapy is being followed up by the radiologists. Conclusion: Primitive cancer of the urethra is rare. Its semiology is not very specific which explains the frequently delayed diagnosis. It is the meticulous examination of the urethra which allows the diagnosis. The treatment of choice is surgery and/or radiotherapy. African Journal of Urology Vol.10(4) 2004: 252-25

Y-box protein-1 controls transforming growth factor-beta1 translation in proximal tubular cells

Transforming growth factor-1 (TGF-1) mRNA has low basal translational efficiency in proximal tubule cells; however, its translation is stimulated by profibrotic cytokines. We studied the role of the multifunctional Y-box protein-1 (YB-1) in regulating proximal tubule cell TGF-1 translation. Using RNA-electrophoretic mobility shift assays and ultraviolet crosslinking, we found two protein complexes of 50 and 100 kDa, which bound to the TGF-1 mRNA 5'-untranslated region. Supershift studies using antibodies to YB-1 showed that both sites contained YB-1 as did studies with recombinant YB-1, which demonstrated that it was sufficient to form both complexes. RNA competition experiments confirmed YB-1 binding to the two predicted binding sites; one with high affinity and the other with lower affinity. Strong basal YB-1 association with TGF-1 mRNA was found in proximal tubule cells, which decreased when platelet-derived growth factor was used to activate TGF-1 translation. In contrast, knockdown of proximal tubule cell YB-1 expression abrogated TGF-1 synthesis. Our results suggest that TGF-1 translation in proximal tubule cells requires YB-1 binding to a high-affinity site in the 5'-untranslated region of its mRNA; however, binding to a low-affinity site inhibits basal translation