Analyse Prostatasekret

Réalisation des Biopsies Echoguidées de la Prostate au CHU Mondor par le Pr A de la Taille

Acinetobacter lwoffii Prostata

Hintergrund der Erfindung Background of the Invention. The invention disclosed herein was made in part with government support under NIH grants grants no.

Accordingly, the US government has certain rights in this invention. In dieser Anmeldung wird überall auf verschiedene Quellenangaben in Klammern verwiesen. In this application, reference is made anywhere to various references in brackets. Die kompletten bibliographischen Literaturstellen für diese Quellenangaben können am Ende jeder Reihe von Experimenten gefunden werden.

The complete bibliographic citations for these references may be found at the end Analyse Prostatasekret each series of experiments. Prostatakrebs zählt zu den bedeutendsten medizinischen Problemen in den Vereinigten Staaten, da die Krankheit Analyse Prostatasekret die häufigste bei amerikanischen Männern diagnostizierte Malignität darstellt. Prostate Analyse Prostatasekret is one of the most significant medical problems in the United States since the disease today Analyse Prostatasekret the most common diagnosed in American men malignancy.

In there were overnew cases of prostate cancer discovered with more than 36, deaths that are attributed to Analyse Prostatasekret disease, representing an increase of The rapid increase in the number of cases appears to result in part from increased disease awareness as well as by the widespread use of clinical markers such as the secreted proteins Analyse Prostatasekret antigen PSA and prostatic acid phosphatase PAP The prostate gland is a pathological important place that states such as benign growth BPHneoplasia prostate cancer and infection prostatitis is affected.

Prostatakrebs stellt die zweithäufigste Todesursache von Analyse Prostatasekret bei Männern dar 1. Prostate cancer is the second leading cause of cancer in men is 1. Prostatakrebs ist jedoch die am häufigsten betroffene Stelle bei der Krebsentstehung bei Männern.

However, prostate cancer is the most commonly affected area in cancer development in men. Die Abweichung zwischen diesen beiden Tatsachen hängt damit zusammen, dass Prostatakrebs mit steigender Häufigkeit auftritt, wenn Männer altern, insbesondere in einem Alter über 60, zu einer Zeit, in Analyse Prostatasekret häufig Todesfälle aus anderen Gründen dazwischenkommen.

The deviation between these two facts is related to the fact that prostate cancer occurs with increasing frequency when men age, especially over the age of 60 at Analyse Prostatasekret time, often intervene deaths from other causes in Analyse Prostatasekret. In addition, the spectrum of the biological aggressiveness of prostate cancer is very large, so that in some men the tumor after the discovery of a latent histologic tumor remains and klinsch is not significant, whereas it progresses rapidly in others, metastasizes, and the man in a relatively short period of years kill 1, 3.

Two specific proteins that are produced in prostate cancer cells in very high concentrations are prostatic acid phosphatase PAP and prostate specific antigen PSA 4, 5, 6. Diese Proteine sind charakterisiert worden und sind dazu eingesetzt worden, um das Ansprechen auf eine Therapie zu verfolgen.

These proteins have been characterized and have been used to to track the response to treatment. During the development of cancer, the normal structure of the gland, including a loss of normal structure of the channel to drain Analyse Prostatasekret secretions belongs changes, and therefore the secretions reach the serum.

In fact, the measurement of serum PSA has been proposed as a possible screening test for prostate cancer. PAP was one of the earliest serum markers for detecting metastatic spread 4.

PAP hydrolysiert Tyrosinphosphat und hat eine breite Substratspezifität. PAP hydrolyses tyrosine phosphate and has a broad substrate specificity. Tyrosinphosphorylierung ist bei oncogenen Transformationen häufig erhöht. Tyrosine phosphorylation is often increased with oncogenic transformation. Man hat die Analyse Prostatasekret aufgestellt, dass während einer neoplastischen Transformation weniger Phosphataseaktivität zur Verfügung steht Analyse Prostatasekret Proteine zu inaktivieren, welche durch Phosphorylierung auf Tyrosinresten aktiviert sind.

It has been hypothesized that during neoplastic Analyse Prostatasekret there is less phosphatase activity available to inactivate proteins that Analyse Prostatasekret activated by phosphorylation on tyrosine residues. In einigen Fällen hat die Analyse Prostatasekret von Phosphatasen, die Tyrosinphosphatase-Aktivität aufweisen, zu einer Rückentwicklung des malignen Phänotyps geführt.

In some cases, the introduction of phosphatases that have tyrosine phosphatase activity, led to a regression of the malignant phenotype. PSA ist eine Protease und es ist nicht einfach zu verstehen, wie ein Verlust ihrer Aktivität mit der Krebsentwicklung in Beziehung steht 5, Analyse Prostatasekret.

PSA is a protease and it is not easy to understand how a loss of their activity is related to cancer development 5, 6. The proteolytic activity of PSA is inhibited Analyse Prostatasekret zinc. Die Zinkkonzentrationen sind in der normalen Prostata hoch und bei Prostatakrebs erniedrigt. The zinc Analyse Prostatasekret are reduced and high in prostate Analyse Prostatasekret in normal prostate. Possibly the loss of zinc Analyse Prostatasekret for increased proteolytic activity by PSA.

Da Proteasen an der Metastasierung beteiligt sind und einige Proteasen die mitotische Aktivität stimulieren, könnte man die Hypothese aufstellen, dass die möglicherweise erhöhte Aktivität von PSA eine Rolle bei der Metastasierung und Ausbreitung des Tumors spielt 7. As proteases are involved in metastasis and some proteases stimulate mitotic activity, one could Analyse Prostatasekret that the potentially increased activity of PSA plays a role in metastasis and spread of the tumor 7.

Die Produktion von beiden scheint davon abhängig zu sein, dass Androgene vorhanden sind, und diese sind nach einem Androgenentzug deutlich vermindert. The production of the two seems to be dependent on androgens are present, and these are significantly reduced after androgen withdrawal.

Das Prostata-spezifische Membranantigen PSMdas anscheinend in der Prostatamembran vorliegt, ist identifiziert Analyse Prostatasekret.

The prostate-specific membrane antigen PSM which is present Analyse Prostatasekret in the prostate membrane has been identified. This antigen was identified as the result of the preparation of monoclonal antibodies against a prostate cancer cell, LNCaP 8. Horoszewicz etablierte eine als Analyse Prostatasekret bezeichnete Zelllinie aus dem Lymphknoten eines auf Hormonbehandlung nicht ansprechenden, stark vorbehandelten Patienten 9.

Horoszewicz established a called LNCaP cell line from the lymph node of a hormone treatment unresponsive, heavily pretreated patient 9. Man stellte fest, dass diese Analyse Prostatasekret einen aneuploiden Analyse Prostatasekret männlichen Karyotyp aufwies. It was noted that this line had an aneuploid human male karyotype. She possessed an androgen receptor high affinity and specificity. Ein monoclonaler Antikörper wurde daraus abgeleitet und als 7EC5 bezeichnet 8. A monoclonal antibody was derived from it and designated 7EC5 8.

The antibody staining was consistent with a membrane location and isolated fractions of LNCaP Analyse Prostatasekret membranes exhibited a strongly positive reaction with immunoblotting and ELISA techniques. Neither of these antibodies increased still inhibited the growth of LNCaP cells in vitro or in vivo. Der Antikörper gegen dieses Analyse Prostatasekret war bemerkenswert spezifisch für Prostataepithelzellen, da man keinerlei Reaktivität bei irgendeinem anderen Bestandteil beobachtete.

The antibody to this antigen was remarkably specific to prostatic epithelial cells, as was observed no reactivity with any other ingredient. Die immunhistochemische Färbung von krebsartigen Epithelzellen war stärker als die von normalen oder benignen Zellen. Immunohistochemical staining of cancerous epithelial cells was stronger than that of normal or benign cells.

Horoszewicz also Analyse Prostatasekret detection of immunoreactive material using 7EC5 in serum of patients with prostate cancer 8.

The immunoreactivity was detectable with a disease stage D2 and in a slightly lower percentage of patients with a disease at an earlier stage, but the numbers of patients in the latter group were low. Patients with benign prostatic hyperplasia BPH were negative.

Patienten mit anderen als Prostatatumoren zeigten keine Immunreaktivität mit 7EC5. Patients with other than prostate tumors showed no immunoreactivity with 7EC5. The monoclonal antibody 7EC5 is currently undergoing clinical trials. Der so erhaltene Antikörper wurde als CYT bezeichnet. The immunohistochemical staining were similar except that the CYT modified antibody skeletal muscle to stain.

A comparison of CYT with the monoclonal antibody 7EC5 suggested that both showed binding to muscle fiber type. It was alleged Analyse Prostatasekret the reason for the discrepancy with the earlier study, which reported that skeletal muscle would be negative, was due to differences in tissue fixation techniques.

Dennoch wurde die stärkste und klarste Reaktion bei Prostataepithelzellen, insbesondere bei krebsartigen Zellen beobachtet. However, the strongest and clearest response in prostate epithelial cells, particularly in the cancerous cells was observed. Eine Reaktivität mit Skelettmuskelzellen der Maus wurde mittels Immunhistochemie, aber nicht in bildgebenden Untersuchungen nachgewiesen.

Reactivity with skeletal muscle cells of the mouse was detected by immunohistochemistry but not in imaging tests. In vivo, no selective retention of the antibody in antigen negative tumors such as PC-3 and DU or in skeletal muscle was observed. Über das PSM-Antigen war sehr wenig bekannt. An attempt by the purification and characterization is at meetings by Dr.

George Wright und Kollegen beschrieben worden 11, George Wright and colleagues have been described 11, These investigators have shown that the PSM antigen by electrophoresis on acrylamide gels and Western blotting has a molecular weight of kilodaltons kD retains.

Eine chemische und enzymatische Behandlung zeigte, dass sowohl die Peptid- als auch die Kohlenhydrateinheiten des PSM-Antigens für die Erkennung durch den monoclonalen Antikörper 7EC5 erforderlich sind. Chemical and enzymatic treatment showed that both the peptide and the carbohydrate moieties of the PSM antigen for recognition by the monoclonal antibody 7EC5 are required.

Kompetitive Bindungsstudien mit spezifischen Lectinen wiesen darauf hin, dass galNAc das vorherrschende Kohlenhydrat des antigenen Epitops darstellt. Competitive binding studies with specific Analyse Prostatasekret pointed out that GalNAc represents the dominant carbohydrate of the antigenic epitope. The specific for prostate cells and -fabric kDa glycoprotein has been purified and characterized. Das Protein wurde proteolytisch mit Trypsin verdaut und neun Peptidfragmente wurden sequenziert.

The protein was proteolytically digested with trypsin and nine peptide fragments were sequenced. Preliminary results have shown Analyse Prostatasekret this antigen is expressed in prostate cancer tissue in large amounts, including in bone and lymph node metastases Further characterization of the PSM Analyse Prostatasekret is Analyse Prostatasekret done in the laboratory of the applicant, this includes: an investigation of the gene expression of PSM in a variety of tissues, transfection of the PSM gene into cells not expressing the antigen, the localization of the PSM gene on the chromosome, cloning of the genomic PSM gene with analysis of the PSM promoter and the production of polyclonal Analyse Prostatasekret monoclonal antibodies against highly antigenic peptide domains of the PSM antigen, and identification of any endogenous PSM Analyse Prostatasekret molecules ligands.

Die Zellen besitzen einen aneuploiden männlichen Karyotyp mit Analyse Prostatasekret Y-Chromosom, exprimieren einen Androgenrezeptor von hoher Affinität und reagieren hormonell sowohl auf Analyse Prostatasekret als auch auf DHT. The cells possess an aneuploid male karyotype with a Y chromosome, express an androgen receptor of high affinity and hormonally responsive to both testosterone and DHT. Da PSM ein Transmembran- Glycoprotein zu sein scheint, betrachtet man es als attraktives Zielmolekül für sowohl Antikörper-gesteuerte Bildgebung als auch für das Zielen auf Prostatatumorablagerungen Because PSM appears to be a transmembrane glycoprotein, you look at it as an attractive target for both antibody-directed imaging and for the targeting of prostate tumor deposits Incubation with rabbit anti-mouse antibody alone served as the negative control and is shown in lane third.

The lower two panels show invasive prostate carcinoma human sections of showing positive staining for the expression of PSM antigen. The arrow points to sample IN, which is a 1. The 1. Samples have been cut with the restriction enzymes Not I and Sal Analyse Prostatasekret to release the insert.

The size is approximately 2. Die Spuren sind von links nach Analyse Prostatasekret nummeriert.