SDA BPH-2 zur Behandlung von

UroLift procedure with fast recovery. BPH be gone!

Behandlung von Prostata-Adenom urorekom

Die vorliegende Erfindung betrifft Prostatakrebs. The present invention relates to prostate cancer. Specifically, the present invention relates to an in vitro method for diagnosing the presence of prostate cancer or predisposition to develop prostate cancer in a patient, the SDA BPH-2 zur Behandlung von comprising: a determining the amount of differentially expressed PCA3 mRNA in one of taken from the patient sample, and b diagnosing the presence of prostate cancer or predisposition to develop prostate cancer in the patient, wherein the presence of a long PCA3 mRNA having a sequence between exon 3 and exon 4a, resulting in a PCA3- mRNA having a sequence which is longer than that in SEQ ID nO: 2 is shown, leads, indicating a non-malignant state of the prostate, and the presence of a short PCA3 mRNA having a sequence as shown in SEQ ID nO: 2, the presence of prostate cancer or to develop prostate cancer predisposition, that displays.

Des weiteren wird ein Verfahren zur Feststellung des Stadiums von Prostatakrebs zur Verfügung gestellt. Furthermore, a method to determine the stage of prostate cancer is provided. Additionally, the present invention relates to the use of probes or primers specific to the additional sequence as shown in SEQ ID NO: 1 in comparison to SEQ ID NO: 2, hybridize SDA BPH-2 zur Behandlung von for the preparation of a diagnostic composition for diagnosing the presence of prostate cancer or predisposition to develop prostate cancer.

Über die letzte Dekade wurde der Prostatakrebs zu der am häufigsten diagnostizierten, bösartigen Erkrankung beim Menschen und nach Lungenkrebs die zweithäufigste Ursache für Todesfälle bei Männern mit einer Krebserkrankung in der westlichen Bevölkerung Landis et al.

Clin 48 1 Over the last decade of prostate cancer was the second leading cause of death in men with cancer in Western populations for the most commonly diagnosed malignant disease in humans and, after lung cancer Landis et al. Von allen Krebsarten steigt die Verbreitung von Prostatakrebs am schnellsten in Korrelation zum Alter. Of all cancers, the spread of prostate cancer increases most rapidly in correlation with age. Die Mortalität stieg mit einer niedrigeren Rate, hat sich aber in den letzten 50 Jahren verdoppelt.

Mortality increased at a lower rate, but has doubled in the last 50 years. Obwohl diese Erkrankung typischerweise bei Männern mit einem Alter von über 65 Jahren diagnostiziert wird, ist die Auswirkung jedoch insofern bedeutsam, dass die durchschnittliche Lebenserwartung eines Mannes, der an Prostatakrebs stirbt, um 9—10 Jahre vermindert ist.

Although this disease is typically diagnosed in men over the age of 65 years, the effect is significant in that the average life expectancy of a man who dies SDA BPH-2 zur Behandlung von prostate cancer is reduced by years. Unfortunately, the disease is fatal in a slow way, when the tumor has spread outside of the gland area and forms distant metastases.

SDA BPH-2 zur Behandlung von früher Nachweis der Erkrankung, während sie noch auf die Prostatadrüse beschränkt ist, und ein genaues Feststellen des Stadiums für die Auswahl einer geeigneten Therapie sollte die Mortalitätsraten verbessern.

An early detection of the disease while it is still confined to the prostate gland, and a precise determination of the stage for the selection of appropriate therapy should improve mortality rates. Trotz vieler Fortschritte in den letzten Jahren ist die Präzision, mit der das Stadium eines Individuums, das unter Prostatakrebs leidet, festgestellt werden kann, suboptimal. Despite many advances in recent years, the precision with which the state of a subject suffering from prostate cancer can be found, suboptimal.

The main reason for this is that the tumor has spread outside the prostate, generally is more microscopically than macroscopic. A digital rectal examination of the prostate was the basis for determining the local stage of prostate cancer for many decades, but the extent of the disease was often underestimated.

An exclusive transrectal ultrasound as a means to determine the stage of prostate cancer is of limited value. Computertomographie und magnetische Resonanzabbildung waren im Allgemeinen enttäuschend für das Feststellen des Stadiums von Prostatakrebs Kirby,Prostata Cancer and Prostatic Diseases Computed tomography and magnetic resonance imaging have generally been disappointing for determining the stage of prostate cancer Kirby, SDA BPH-2 zur Behandlung von, Prostate Cancer and Prostatic Diseases 1: Lippincott-Raven Publisher, K.

Recent promising approaches to determine the stage of prostate cancer include the use of biochemical and molecular techniques, focusing on proteins or their corresponding nucleic acids which are preferentially expressed in prostate cells concentrate Lange,in "Principles and Practice of Genitourinary Oncology ", ed. Lippincott-Raven publishers, K. Es wird unter Androgenkontrolle von den glandulären Epithelzellen der Prostata exprimiert und in das Samenplasma sezerniert.

It is expressed under Androgenkontrolle by glandular epithelial cells of the prostate and secreted into the seminal plasma. The PSA protein is normally confined to the prostate but in the case of prostatic disease such as cancer or BPH benign prostate hyperplasia delivers PSA in the blood, where it is present in different forms, including one that is bound to protein complexes, and one that is not bound to protein complexes EL-Shirbiny,Adv Clin Chem Measuring the total concentrations of PSA in serum is one of the biochemical tests for the screening of SDA BPH-2 zur Behandlung von most commonly used and approved by the FDA and the treatment of patients with prostate cancer.

Bisherige Studien deuten darauf hin, dass das Absuchen mit PSA zusammen mit einer digitalen rektalen Untersuchung und einem transrektalen Ultraschall den Nachweis von frühen Prostatakrebsen erhöht, häufig während er SDA BPH-2 zur Behandlung von in der Drüse selbst lokalisiert ist Brawer et al. Previous studies suggest SDA BPH-2 zur Behandlung von screening with PSA increased along with a digital rectal examination and transrectal ultrasound detection of early prostate cancers often while still localized to the gland itself Brawer et al,J Urol th: PSA in serum is also useful for monitoring of patients after therapy, especially after surgical removal of the prostate.

However, measuring the total PSA also identified a large number of patients with abnormally elevated levels, which then no prostate cancer is found. The PSM gene encodes a transmembrane glycoprotein of the epithelial cells of normal prostate, benign hyperplasia of the prostate, and expressed to a greater extent of malignant prostate tissue. This very sensitive nucleic acid amplification technology is used to identify cells based on the expression of specific messenger RNAs.

It includes the preparation of RNA samples from tissues or body fluids, its reverse transcription into cDNA and amplifying specific cDNAs by the use of primers that target the particular gene of interest.

Der klinische Nutzen von molekularen Tests muss jedoch noch bestätigt werden Verkaik et al. However, the clinical utility of molecular tests to be confirmed Verkaik et al,Urol Res. Daher bleibt eine Notwendigkeit, einen sensitiveren Test für das Diagnostizieren von Prostatakrebs zur Verfügung zu stellen, bestehen. Therefore, there remains a need to provide a more sensitive test for diagnosing prostate cancer are available, there are. Es bleibt ebenfalls einen Notwendigkeit, einen besseren Test für das Feststellen des Stadiums von Prostatakrebs bestehen.

There also remains a need to pass a better test for determining the stage of prostate cancer. Ebenfalls bleibt eine Notwendigkeit bestehen, einen Prostatakrebsmarker, SDA BPH-2 zur Behandlung von spezifischer und verlässlicher für den Nachweis, das Feststellen des Stadiums und die Behandlungsverfahren von Prostatakrebs ist, zur Verfügung zu stellen. Also remains a need to provide a prostate cancer marker specific and reliable for the detection, determining the stage and the method of treating prostate cancer available.

Die vorliegende Erfindung versucht, diese und andere Erfordernisse zu erfüllen. The present invention seeks to meet these and other needs. A new prostate cancer marker, PCA3, was discovered a few years ago by differential display analysis intended to genes that are associated with the development of prostate cancer, highlight PCT Application No. PCA3 ist auf Chromosom 9 lokalisiert und ist aus vier Exons zusammengesetzt. PCA3 is located on chromosome 9 and composed of four exons.

It encodes at least four different transcripts produced by alternative splicing and polyadenylation. By RT-PCR analysis, it was found that the expression is restricted to the prostate of PCA3 and that it is absent in all other tissues, including testis, ovary, breast and bladder.

The Northern blot analysis shows that PCA3 is 50 47 is highly expressed in the vast majority of untersuchtem prostate cancer, whereas no or only a very low level expression is found in benign prostate hyperplasia or normal prostate cells from the same patients. PCA3 expression seems to increase with tumor grade and is detected in metastatic lesions. In summary, determining the stage of prostate cancer based on specific markers such as PSA and PSM is a very promising avenue for the treatment of the disease.

The drawback of using PSA or PSM for determining the stage of prostate cancer is that they are expressed in both SDA BPH-2 zur Behandlung von cells and cancer cells.

Zusätzlich können nur schwach differenzierte Tumore der Diagnose entkommen, da sie dazu tendieren, deutlich weniger PSA-Protein als weniger aggressive Tumore herzustellen. In addition, poorly differentiated tumors diagnosed escape, because they tend to produce significantly less PSA protein than SDA BPH-2 zur Behandlung von aggressive tumors.

Auf der anderen Seite wird PCA3 in Krebszellen und in normalen Zellen der Prostata differentiell exprimiert und seine Expression sinkt nicht mit einem erhöhten Tumorgrad. On the other hand, is differentially expressed PCA3 in cancer cells and in normal cells of the prostate and its expression does not decrease with an increased tumor grade.

PCA3 could therefore be a useful tool that overcomes the drawbacks of PSA and PSM in the diagnosis, the detection of the stage and the treatment of patients with prostate cancer.

The disclosure also relates to the finding that a balance between the level of these PCA3 mRNAs with the non-malignant or the malignant status of the prostate correlated. The RNA lacking the additional sequence is associated with prostate cancer whereas the RNA comprising same is associated with a non-malignant state of the prostate. Based on the differential expression of these two PCA3 RNA species protocols for the diagnosis SDA BPH-2 zur Behandlung von prostate disease are provided.

Die vorstehend beschriebenen Ergebnisse können ebenfalls zu einem SDA BPH-2 zur Behandlung von Ansatz gegen den Prostatakrebs führen. The results described above may also lead to a therapeutic approach to prostate cancer. The disclosure further concerns reagents and methods to determine the stage of the prostate gland in an animal, comprising a quantitative determination of SEQ ID NO: 2 or fragments or variants thereof: 1 or fragments or variants thereof with respect to SEQ ID NO.

The present invention therefore relates to the discovery and characterization of a SDA BPH-2 zur Behandlung von sequence expressed in PCA3 mRNA and which enables a determination of the condition of the prostate gland in an animal, which is based on a determination of the relative amount of two differentially expressed PCA3 mRNAs.

The disclosure generally believe isolated nucleic acid molecules are available encoding differentially expressed PCA3 mRNAs and variants or units that retain their ability to enable a determination of the condition of the prostate. The invention further provides purified polypeptides are available which are encoded by the differentially expressed PCA3 mRNAs of the present invention or an epitope binding portion thereof. The disclosure also provides nucleic acids for the specific detection of the presence of differentially expressed PCA3 mRNAs associated with prostate cancer or proteins or polypeptides encoded by such mRNAs in a sample.

The invention provides an in vitro method of detecting nucleic acid encoding differentially expressed PCA3 mRNAs are available. There is also disclosed a kit for detecting the presence of nucleic acid encoding SDA BPH-2 zur Behandlung von expressed PCA3 mRNAs in a sample. The disclosure further relates SDA BPH-2 zur Behandlung von a diagnostic kit comprising a first container containing nucleic acid molecules specific for a differentially expressed PCA3 mRNA and a second container containing a probe which is specific for differentially expressed PCA3 mRNAs.

Die Erfindung betrifft des weiteren diagnostische Verfahren für menschliche Erkrankungen, insbesondere Prostatakrebs. The invention further relates to diagnostic methods for human disease, in particular prostate cancer.

Vorzugsweise wird hierin ein Verfahren zum Diagnostizieren des Vorliegens von Prostatakrebs oder der Prädisposition, Prostatakrebs zu entwickeln, in einem Patienten zur Verfügung gestellt. Preferably, a method of diagnosing the presence of prostate cancer or SDA BPH-2 zur Behandlung von to develop prostate cancer is herein provided in a patient.

Nachdem die differentielle Expression von mRNAs als ein Marker für den Zustand der Prostata eines Tieres identifiziert wurde und insbesondere nachdem gezeigt wurde, dass das Vorliegen einer zusätzlichen Sequenz, welche die codierende Sequenz des codierten PCA3-Proteins unterbricht, mit einem nicht bösartigen Stadium korreliert, während das Fehlen der zusätzlichen Sequenz und die fehlende Unterbrechung des dadurch codierten Proteins mit einem bösartigen Krebs korreliert, stellt die vorliegende Offenbarung daher die Mittel zur Verfügung, die codierende Sequenz des PCA3-Proteins zu unterbrechen, wobei jedes Mittel der Gentechnik verwendet werden kann, das einem Fachmann bekannt ist, und bewertet, ob eine solche Unterbrechung den bösartigen Phänotyp umkehren kann.

After the differential expression of mRNAs has been identified as a marker for the condition of the prostate of an animal and has been particularly shown after that the presence of an additional sequence, which interrupts the coding sequence of the encoded PCA3 protein, correlates with a non-malignant state, while the absence of the additional sequence and the lack of interruption of the thereby encoded protein with a malignant cancer correlated, therefore, the present disclosure, the resources available to interrupt the coding SDA BPH-2 zur Behandlung von of the PCA3 protein, any means of genetic engineering can be used, the one skilled in the art, and assesses whether such an interruption can reverse the malignant phenotype.

Um ein klares und SDA BPH-2 zur Behandlung von Verstehen SDA BPH-2 zur Behandlung von Begriffe, die in der vorliegenden Beschreibung verwendet werden, zur Verfügung zu stellen, wird nachfolgend eine SDA BPH-2 zur Behandlung von von Definitionen zur Verfügung gestellt.

In order to provide a clear and matching understanding of the terms used in this specification, available, a number of definitions is provided below. Die Terminologie "nichtbösartige Prostata oder nichtbösartiger Zustand", wie sie hierin verwendet wird, soll einen nicht kanzerösen Zustand der Prostata umfassen.

Therefore, such terminologies are to a normal state as well as a benign condition of the prostate such as BPH include. Weil die differenzierenden Marker zwischen dem bösartigen und dem nicht bösartigen Zustand der Prostata im mRNA-Spiegel und Proteinspiegel liegen dh ein exprimierter Markerist einer der Vorteile der vorliegenden Erfindung, dass eine Bestimmung des Prostatazustandes in einem Tier unter Verwendung einer Anzahl von Mitteln, die dem Fachmann zur Verfügung stehen, ermöglicht wird.

Since the differentiating markers between the malignant and non-malignant state of the prostate in mRNA levels and protein levels are ie an expressed markerone of the advantages of the present invention that a determination of the prostate status in an animal using a number SDA BPH-2 zur Behandlung von means available to the skilled person available, is made possible.

Examples of such agents, which are not to be limiting, include nucleic acid probes, antibodies, ligands and PNAs in readily available cells that express these differentiating markers one. Ein Beispiel, das nicht einschränkend sein soll, beinhaltet Lymphocyten, wodurch eine Bestimmung von einer einfachen Blutprobe ermöglicht SDA BPH-2 zur Behandlung von. An example that is not limiting, including lymphocytes, whereby a determination SDA BPH-2 zur Behandlung von made possible by a simple blood test.

Examples thereof which are not to be limiting, include biopsies, blood, fine needle biopsies, urine and bone marrow. Nucleotide sequences are presented herein by single strand in the 5 SDA BPH-2 zur Behandlung von 3' direction, from left to right, the one letter nucleotide, which are generally used in the art and according to the recommendations of the IUPAC-IUB Biochemical Nomenclature Commission is used.

Wenn sie nicht anders definiert sind, haben die hierin verwendeten wissenschaftlichen und technologischen Begriffe und die hierein verwendete SDA BPH-2 zur Behandlung von und technologische Nomenklatur die gleiche Bedeutung, wie im Allgemeinen von einem Fachmann, auf den sich die Erfindung bezieht, verstanden wird.

If they SDA BPH-2 zur Behandlung von not otherwise defined herein used scientific and technological concepts and scientific and technological nomenclature used herein have the same meaning as in general by an expert, to which the invention relates, is understood. Im Allgemeinen sind die Verfahren für die Zellkultur, Infektion, Verfahren der Molekularbiologie und dergleichen auf dem Fachgebiet allgemein verwendete Verfahren. In general, the procedures for cell culture, infection, molecular biology methods and the like methods commonly used in the art are.

Solche Standardtechniken können in Handbüchern, auf die Bezug genommen wird, wie zum Beispiel Sambrook et al. Such standard techniques can in manuals, reference is made to the reference, such as Sambrook et al.