Zusammenfassung Hintergrund Das Klassifikationssystem zur Prognoseeinschätzung der International Germ Cell Cancer Cooperative Group (IGCCCG) für testikuläre Keimzelltumoren basiert auf dem histologischen Subtyp, der Lokalisation des Primärtumors und der Metastasen sowie der Serumkonzentrationen der Tumormarker vor Chemotherapie. Fragestellung Ziel der Arbeit war die Evaluation des Einflusses der Verwendung der Tumormarkerserumkonzentrationen vor Ablatio testis im Vergleich zu denen vor Chemotherapie im Hinblick auf die Eingruppierung entsprechend der IGCCCG-Klassifikation. Material und Methoden Wir führen eine retrospektive Datenanalyse an 135 Patienten mit metastasiertem testikulärem Keimzelltumor durch, die eine Primärtherapie mit einer Chemotherapie erhalten haben. Es erfolgte die Analyse von klinischen Parametern mit Fokus auf der Tumormarkerserumkonzentration vor Ablatio testis und vor Chemotherapie, die zur Eingruppierung in eine Prognosegruppe entsprechend der IGCCCG-Klassifikation führten. Ergebnisse Die Verwendung der Tumormarkerserumkonzentrationen zur Berechnung der IGCCCG-Klassifikation vor der Ablatio testis im Vergleich zu denen vor Chemotherapie führte bei 8 % (11/135) aller Patienten zu einer veränderten Prognosegruppe sowie daraus folgend nicht-leitliniengerechten Therapieschemata. Es zeigt sich ein „up-staging“ bei 8 der 11 Patienten und somit 6 % (8/135) der gesamten Patientenkohorte, d. h. die Serumkonzentrationen der Tumormarker sind nach Ablatio bis zum Beginn der Chemotherapie abgefallen. Bei 3 der 11 Patienten bzw. 2 % (3/135) der gesamten Patientenkohorte, kam es zu einem „down-staging“, d. h. die Tumormarker sind bis zum Beginn der Chemotherapie angestiegen. Diskussion Die Verwendung der Tumormarkerserumkonzentrationen vor Ablatio testis im Vergleich zu denen vor Chemotherapie kann zu einer signifikanten IGCCCG-Fehlklassifikation und somit inkorrekter Therapie führen. Für ein leitlinienkonformes „staging“ der Patienten sollten folglich die Tumormarker vor der Chemotherapie verwendet werden.
Background Recently, our group showed that Vim3 is overexpressed in tissue samples of renal oncocytomas and Mxi‐2 in clear cell renal carcinoma (ccRCC). The mechanism leading to the truncation of both proteins is known and involves with two miRs, both detectable in urine. Since the analysis of miRs is time‐consuming, our aim was to identify the truncated proteins in urine instead. Furthermore, urine samples from small renal masses (SRMs) (n = 45, <4 cm) were analyzed to get a pre‐surgical differentiation of the cancer subtypes. Methods Urines were accessed from the urological biobank (n = 350). Proteins were isolated from urine samples, and Western blots were performed. Each sample was analyzed with ELISA for the expression of Vim3 and Mxi‐2. A lateral flow assay was established. For the detection of SRMs, the miRs were isolated and qRT‐PCR was performed. Results A significant increase of Vim3 in urines from patients with oncocytoma (n = 20) was detectable with ELISA compared to all other subtypes of RCCs (chromophobe (n = 50), papillary (n = 40), ccRCC (n = 200), and controls (n = 40) (***p < 0.0001)). Mxi‐2 was predominantly overexpressed in ccRCCs (***p < 0.0001). Lateral flow assay of Vim3 and Mxi‐2 shows two bands in the case of oncocytoma and ccRCC indicating the specificity of this test. For SRMs, an overexpression of miR‐15a/Mxi2 was detectable in urine samples from ccRCC and chromoRCC patients. In contrast to that, miR‐498/Vim3 were predominantly overexpressed in oncocytoma patients. Conclusion Both proteins (Vim3 and Mxi‐2) were detectable in patients’ urines and can be used for the non‐invasive differentiation of kidney cancers.
Background/Aim: Endothelin-1 (ET-1) is overexpressed in many types of cancer, inhibiting the release of the microRNA 15a (miR-15a) and inducing the production of Mxi-2. Our aim was to identify a molecular complex regulating p53 activity in prostate cancer (PCa). Materials and Methods: DU145 cells were treated with ET-1, MAPK p38 inhibitor, Endothelin A receptor inhibitor (ETAR inhibitor) and Endothelin B receptor inhibitor (ETBR inhibitor). Extracts were analysed using Western Blot, immunoprecipitation and qRT-PCR. Furthermore, prostate cancer patient samples were analysed using qRT-PCR and ELISA. Results: The hypothesised molecular complex was identified, with miR-15a, microRNA 1285miR-15a, microRNA (miR-1285 and Mxi-2 levels up-regulated in patients in relation to increasing aggressiveness of PCa. Conclusion: A complex composed of Argonaut 2 (Ago2)/Mxi-2/miR-1285 is involved in PCa. The expression of Mxi-2 correlates with increasing PCa aggressiveness and might be used as a noninvasive marker for the diagnosis and progression of PCa.Endothelin-1 (ET-1) is a potent vasoconstrictor and multifunctional protein in cancer. It is one of the most studied proteins in the family of multifunctional proteins (1). ET-1 is able to bind to two different G-protein coupled receptors, called Endothelin A and B receptor (ETAR and ETBR). The binding to the ETAR and its subsequent activation results in cell proliferation, hault of apoptosis, angiogenesis, invasion, and metastatic spread (2) and activates a survival pathway, whereas binding to the ETBR causes clearance of ET-1 and apoptosis. In prostate cancer, ET-1 is produced in prostate epithelial cells and is associated with progression of prostate cancer (2).ET-1 is a transcriptional target gene of the tumor suppressor protein p53 (3), which plays a major role in tumor development (4). In general, p53 can respond to many stress signals, especially to DNA damage, and plays a major role in the regulation of the cell cycle (5). In addition, p53 is needed for a proper stress response to protect the cell from malignant transformations (6). In prostate cancer, a mutation in p53 is associated with tumor development and progression (7, 8). Mutant p53 functions as an oncogene, which allows tumour growth and survival advantages (9).The transcription factor activity of p53 can be activated by Protein kinase C (PKC) α (10), a member of the protein kinase family (11). PKCα is able to migrate into the nucleus via the transcription complex, composed of MAPK p38α and NFĸB p65, where it binds to the pri-miR 15a, inhibiting its maturation. This migration process is regulated by the presence of . As recently described, miR-15a binds to the intron region of MAPK p38α introducing a stop codon and resulting in a C-terminal truncated protein, called .In this article, we show that ET-1 induces a signalling pathway that influences the presence of p53. This pathway involves Mxi-2, Ago2 and miR-1285. In the literature it is known that miR-1285 binds directly to the 3' UTR of the mRNA of p53 (13), wh...
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