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  • 1
    Keywords: CANCER ; EXPRESSION ; IN-VITRO ; VITRO ; DISEASE ; RISK ; GENE ; PROTEIN ; validation ; PATIENT ; DNA ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; BREAST ; BREAST-CANCER ; TRIAL ; CARCINOMA CELLS ; OVARIAN-CANCER ; SNP ; PCR ; PROGNOSTIC-FACTORS ; PROGNOSTIC FACTORS ; P-SELECTIN ; POOR-PROGNOSIS ; MULTIPLE-SCLEROSIS ; PATIENT SURVIVAL ; AUTOIMMUNE-DISEASES ; PROGNOSTIC MARKER ; NEOADJUVANT CHEMOTHERAPY ; AUTOREACTIVE T-CELLS ; pathologic complete response ; primary breast cancer ; LYMPHOCYTE ; ANTICANCER CHEMOTHERAPY ; Predictive marker
    Abstract: Overexpression of CD24 is an independent prognostic factor for breast cancer. Recently, two polymorphisms in the CD24 gene were linked to disease risk and progression in autoimmune diseases. Here, we evaluated the clinical relevance of these polymorphisms with respect to their potential to predict a pathologic complete response (pCR) to neoadjuvant chemotherapy (NCT) for primary breast cancer (PBC), one of the strongest prognostic factors in this setting. A total of 257 patients were randomized to either doxorubicin/cyclophosphamide (AC) or doxorubicin/pemetrexed (AP), both followed by docetaxel (Doc) as NCT for T2-4 N0-2 M0 PBC as part of an international, multicenter, randomized phase II trial. CD24 polymorphisms were analyzed on germ line DNA and correlated with clinicopathologic variables and pCR. No significant associations were found between either of the polymorphisms and any of the clinicopathologic variables. In a multivariate analysis, CD24 Val/Val genotype was the only significant predictor of pCR (OR: 4.97; P = 0.003). The predictive potential was significant in both treatment arms and in the hormone receptor-positive subgroup. There was no correlation between CD24 3'UTR (TG/Del) genotype and pCR. We did not observe any association between CD24 genotype and CD24 protein expression or in vitro chemosensitivity, but there was a significant correlation between CD24 Val/Val and intratumoral lymphocyte aggregates. In conclusion, CD24 Ala/Val SNP is a strong and independent predictor of pCR after NCT for PBC and may affect immune functions rather than tumor characteristics. Further evaluation of the CD24 function and validation of its predictive potential are clearly warranted.
    Type of Publication: Journal article published
    PubMed ID: 21960110
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  • 2
    Keywords: CANCER ; CELLS ; EXPRESSION ; tumor ; BLOOD ; CELL ; Germany ; NEW-YORK ; PROTEIN ; MICE ; RELEASE ; kidney ; MARKER ; ANTIGEN ; T-CELLS ; treatment ; CLEAVAGE ; knockout ; MEMBRANE ; WOMEN ; SURFACE ; INDIVIDUALS ; L1 ; CALCIUM ; BODY ; ADHESION MOLECULE ; membrane vesicles ; MEMBRANE-VESICLES ; CD24 ; URINE ; AGENT ; BODIES ; RE ; VESICLES ; secretion ; interaction ; KNOCKOUT MICE ; USA ; BIOGENESIS ; PODOCYTES ; exosome ; OVARIAN-CARCINOMA CELLS ; exosomes ; amniotic fluid ; INFANT
    Abstract: Exosomes are small membrane vesicles that are secreted from a variety of cell types into various body fluids including the blood and urine. These vesicles are thought to play a role in cell-cell interactions. CD24 is a small but extensively glycosylated protein linked to the cell surface by means of a glycosyl-phosphatidylinositol anchor. In this study we found that CD24 is present in membrane vesicles characterized as exosomes that were isolated from the urine of normal individuals. CD24 was expressed by both tubule cells and podocytes and treatment of the latter with a cholesterol-extracting agent, but not with a calcium ionophore, caused the release of CD24-containing exosomes. Using CD24 as a marker, we found exosomes in the urine of newborn infants and in the amniotic fluid of pregnant women with similar findings made in mice. Interestingly, studies with CD24 knockout mice showed that the exosomes are released from the fetus but not from the mother; however, exosome release was similar from both the knockout and the wild-type mice. This indicates that CD24 is not essential for exosome formation or release but may be a convenient exosome marker. Our studies suggest that exosomal secretion from the embryonic kidney could play a biological role at the fetal-maternal interphase
    Type of Publication: Journal article published
    PubMed ID: 17700640
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  • 3
    Abstract: OBJECTIVE: Cancer cells in the body release soluble and membranous factors that manipulate the tumor environment to facilitate growth and survival. Recent years have provided evidence that small microvesicles that are termed exosomes may play a pivotal role in this process. Exosomes are membrane vesicles with a size of 40-100nm that are released by both tumor and normal cells and can be found in various body fluids. Tumor-derived exosomes carry functional proteins, mRNAs, and miRNAs and could serve as novel platform for tumor diagnosis and prognosis. However, marker proteins that allow enrichment of tumor-derived exosomes over normal exosomes are less well defined. METHODS: We used Western blot analysis and antibody coupled magnetic beads to characterize CD24 and EpCAM as markers for exosomes. We investigated ovarian carcinoma ascites, pleural effusions and serum of breast carcinoma patients. As non-tumor derived control we used exosomes from ascites of liver cirrhosis patients. RESULTS: Exosomes could be isolated from all body fluids and contained marker proteins as well as miRNAs. We observed that CD24 and EpCAM were selectively present on ascites exosomes of tumor patients and copurified together on anti-EpCAM or anti-CD24 magnetic beads. In breast cancer patients CD24 was present but EpCAM was absent from serum exosomes. Instead, the intact EpCAM ectodomain was recovered in a soluble form. We provide evidence that EpCAM can be cleaved from exosomes via serum metalloproteinase(s). CONCLUSION: Loss of EpCAM on serum exosomes may hamper enrichment by immune-affinity isolation. We suggest that CD24 could be an additional marker for the enrichment of tumor-derived exosomes from blood.
    Type of Publication: Journal article published
    PubMed ID: 21601258
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  • 4
  • 5
    Keywords: CELLS ; EXPRESSION ; INVASION ; tumor ; TUMOR-CELLS ; carcinoma ; CELL ; Germany ; DENSITY ; ENZYMES ; PROTEIN ; PROTEINS ; cell line ; TISSUE ; LINES ; PATIENT ; MARKER ; prognosis ; CELL-LINES ; MOLECULE ; BREAST-CANCER ; NO ; PROGRESSION ; TUMOR PROGRESSION ; CELL-LINE ; LINE ; ADHESION ; CELL-ADHESION ; CARCINOMAS ; P-SELECTIN ; ADHESION MOLECULE ; POOR-PROGNOSIS ; cell lines ; TUMOR CELLS ; CD24 ; ORIGIN ; ONCOLOGY ; RE ; VESICLES ; secretion ; INDEPENDENT PROGNOSTIC MARKER ; cell adhesion ; TUMOR TISSUE ; ENZYME ; analysis ; methods ; TUMOR-CELL ; OVARIAN CARCINOMAS ; USA ; correlation ; EpCAM ; B-LYMPHOCYTES ; OVARIAN ; exosome ; exosomes ; FRACTIONATION ; OVARIAN-CARCINOMA ; ovarian carcinoma cells ; malignant ascites ; PRE-B
    Abstract: Objective. CD24 is an established marker for poor prognosis in ovarian and other carci nomas. Acquisition of cytoplasmic CD24, as opposed to membranous expression, has been correlated with a higher invasiveness of tumor cells. Exosomes are small vesicles of endosomal origin that are often secreted by tumor cells. Given the emerging role of exosomes in tumor progression, we investigated whether cytoplasmic CD24 expression is correlated with the secretion of CD24 in exosomes. Methods. We used CD24 transfected carcinoma cell lines, ovarian carcinoma cell lines and malignant ascites fluid of ovarian carcinoma patients. Exosomes were isolated via ultracentrifugation and sucrose density fractionation and subsequently examined by Western blot analysis and gelatine zymography. In tissue sections CD24 was detected by immunohistochemical staining. Results. We show that CD24 is released by transfected as well as endogenously expressing cells in vesicles that represent exosomes. CD24 was also identified in exosomes isolated from ascites fluid of ovarian carcinoma patients. In 16 ovarian carcinomas analyzed no correlation between CD24 in tumor tissue sections and the appearance of CD24 in exosomes was detected. Furthermore, we provide evidence that the epithelial cell adhesion molecule (EpCAM), known to be overexpressed in ovarian carcinomas, is secreted in exosomes. The ascites exosomes contain gelatinolytic enzymes. Conclusions. Our study identifies CD24 and EpCAM as cargo proteins of exosomes of cultured cell lines and malignant ascites. The exosome-associated proteolytic activity in the tumor vicinity might augment tumor invasion into the stroma. (c) 2007 Elsevier Inc. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 17900673
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  • 6
    Abstract: CD24 is a small, highly glycosylated cell surface protein that is linked to the membrane through a glycosyl-phosphatidylinositol anchor. It is overexpressed in many human carcinomas and its expression is linked to bad prognosis. Lately, lack or low expression of CD24 was used to identify tumor stem cells resulting in conflicting data on the usefulness of this marker. In many immunohistochemical studies, the mAb SN3b was used but the epitope and specificity of this antibody have never been thoroughly investigated. In other studies based mainly on cytofluorographic analysis, the mAb ML-5 was applied. In this study, we compared the epitope of mAb SN3b to the CD24 mAbs SWA-11 and ML-5 that both bind to the core protein of CD24. Using tissue microarrays and affinity-purified CD24 glycoforms, we observed only a partial overlap of SN3b and SWA11 reactivity. The mAb SN3b recognizes sialic acid most likely on O-linked glycans that can occur independently of the CD24 protein backbone. The SN3b epitope was not related to common sialylated cancer-associated glycan structures. Both SN3b epitope positive or negative CD24 glycoforms supported the binding of P-selectin and Siglec-5. In breast cancer, the SN3b reactivity was associated with bad prognosis, whereas SWA11 was not. In renal cell cancer, the SN3b epitope was completely absent but SWA11 reactivity was a prognostic factor. Our results shed new light on the tumorbiological role of CD24 and resolve discrepancies in the literature related to the use of different CD24 mAbs.
    Type of Publication: Journal article published
    PubMed ID: 20351695
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  • 7
    Keywords: CANCER ; EXPRESSION ; GROWTH ; DIFFERENTIATION ; MECHANISM ; immunosuppression ; BIOGENESIS ; TUMOR-DERIVED EXOSOMES ; DIAGNOSTIC BIOMARKERS ; RELEASED MICROVESICLES
    Abstract: Tumor-derived exosomes have been shown to induce various immune modulatory effects. However, the underlying signaling pathways are poorly understood. Here we analyzed the effects of ex vivo-derived exosomes on monocytic cell differentiation/activation using THP-1 cells as model. We isolated exosomes from various body fluids such as amniotic fluid, liver cirrhosis ascites and malignant ascites of ovarian cancer patients. We observed that exosomes were internalized by THP-1 cells and induced the production of IL-1beta, TNF-alpha and IL-6. Analysis of the signaling pathways revealed a fast triggering of NFkappaB and a delayed activation of STAT3. Pharmacologic and antibody blocking experiments showed that the initial production of IL-6 was instrumental for subsequent activation of STAT3. Importantly, triggering of cell signaling was not a unique property of tumor exosomes but was also observed with exosomes of non-cancerous origin. Exosomal signaling was TLR dependent as the knock down of TLR2 and TLR4 blocked NFkappaB and STAT3 activation. Similar results were obtained with TLR neutralizing antibodies. Exosomes also triggered the release of cytokines from mouse bone marrow-derived dendritic cells or macrophages. This process was MyD88 dependent, further supporting a role of TLR signaling. Our results suggest that exosomes trigger TLR-dependent signaling pathways in monocytic precursor cells but possibly also in other immune cells. This process could be important for the induction of immunosuppressive mechanisms during cancer progression and inflammatory diseases.
    Type of Publication: Journal article published
    PubMed ID: 24225954
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Der Chirurg 70 (1999), S. 302-305 
    ISSN: 1433-0385
    Keywords: Key words: Malignant mesothelioma ; Tunica vaginalis ; Inguinal mass ; Paratesticular tumor ; Case report. ; Schlüsselwörter: Malignes Mesotheliom ; Tunica vaginalis ; inguinale Raumforderung ; paratesticulärer Tumor ; Kasuistik.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung. Es wird über ein malignes Mesotheliom der Tunica vaginalis testis bei einem 77 jährigen Patienten berichtet. Anamnestisch ergab sich kein Hinweis für eine Asbestexposition. Klinisch fand sich eine rezidivierende Hydrocele in Kombination mit einer knotigen Induration der rechten Leiste. Eine inguinale Orchiektomie mit En-bloc-Resektion des umliegenden Gewebes wurde durchgeführt. Die Therapiealternativen dieses seltenen, aber aggressiven Tumors und insbesondere die Bedeutung der initial radikalen chirurgischen Therapie bei enttäuschenden Ergebnissen der antineoplastischen Chemo- oder Strahlentherapie werden diskutiert.
    Notes: Summary. A case of malignant mesothelioma of the tunica vaginalis testis is reported in a 77-year-old male patient. There was no history of asbestos exposure. Recurrent right hydrocele with a papillar inguinal mass was the main clinical feature. An inguinal radical orchiectomy with en bloc resection of the surrounding tissue was performed. The therapeutic options for this rare, but aggressive neoplasm are discussed. Because of the disappointing results of antineoplastic chemotherapy or radiation therapy, the importance of initial radical surgical treatment with complete excision is emphasized.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 0167-4838
    Keywords: (Human) ; Ca^2^+ ; Fibrin polymerization ; Fragment D inhibition ; Tripeptide
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1439-0973
    Keywords: Key Words Infectious diseases ; Cost ; Reduction ; Consultation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Background: In 1997 an infectious disease service (IDS) similar to those in the US was established at a university hospital in Munich, Germany. Patients and Methods: We assessed the economic impact of the new policy by performing a cost comparison analysis. Inpatients with pneumonia, skin infections/cellulitis, urinary tract infections (UTI) and bacteremia/sepsis were assigned to two groups: patients from a 6-month period after the establishment of the IDS (post-IDS group) were compared with similar patients before the implementation of the ID-servide (pre-IDS group). Costs of microbiological investigation (MB), antibiotic treatment (AB), clinical imaging (CI), total costs and length of antibiotic therapy were analyzed. Results: Patients with UTIs in the post IDS-group had 39% fewer MBs (p 〈 0.05) than patients in the pre-IDS group, resulting in a 33% decrease in average MB costs (p 〈 0.05). In the total group, in which subgroups with pneumonia, skin infection and UTI were summarized, the post-IDS group had 37% fewer MBs (p 〈 0.05) resulting in MB cost reductions of 34% (p 〈 0.05). There were no significant differences in expenditures for AB and CI and in the average length of antibiotic therapy. Conclusion: This study shows that continuous consultation by an IDS does not increase diagnostic and treatment costs, but results in significant cost reductions.
    Type of Medium: Electronic Resource
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