8 results on '"Schramek P"'
Search Results
2. Exosomal mitochondrial tRNAs and miRNAs as potential predictors of inflammation in renal proximal tubular epithelial cells
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Glory Ranches, Maximilian Zeidler, Roman Kessler, Martina Hoelzl, Michael W. Hess, Jonathan Vosper, Paul Perco, Herbert Schramek, Kai K. Kummer, Michaela Kress, Anne Krogsdam, Michael Rudnicki, Gert Mayer, and Alexander Huettenhofer
- Subjects
MT: Oligonucleotides: Diagnostics and Biosensors ,ncRNAs ,mtRNAs ,miRNAs ,exosomes ,renal proximal tubular epithelial cells ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Exosomes have emerged as a valuable repository of novel biomarkers for human diseases such as chronic kidney disease (CKD). From a healthy control group, we performed microRNA (miRNA) profiling of urinary exosomes and compared it with a cell culture model of renal proximal tubular epithelial cells (RPTECs). Thereby, a large fraction of abundant urinary exosomal miRNAs could also be detected in exosomes derived from RPTECs, indicating them as a suitable model system for investigation of CKD. We subsequently analyzed exosomes from RPTECs in pro-inflammatory and pro-fibrotic states, mimicking some aspects of CKD. Following cytokine treatment, we observed a significant increase in exosome release and identified 30 dysregulated exosomal miRNAs, predominantly associated with the regulation of pro-inflammatory and pro-fibrotic-related pathways. In addition to miRNAs, we also identified 16 dysregulated exosomal mitochondrial RNAs, highlighting a pivotal role of mitochondria in sensing renal inflammation. Inhibitors of exosome biogenesis and release significantly altered the abundance of selected candidate miRNAs and mitochondrial RNAs, thus suggesting distinct sorting mechanisms of different non-coding RNA (ncRNA) species into exosomes. Hence, these two exosomal ncRNA species might be employed as potential indicators for predicting the pathogenesis of CKD and also might enable effective monitoring of the efficacy of CKD treatment.
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- 2022
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3. Pan-cancer analysis of non-coding transcripts reveals the prognostic onco-lncRNA HOXA10-AS in gliomas
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Keren Isaev, Lingyan Jiang, Shuai Wu, Christian A. Lee, Valérie Watters, Victoire Fort, Ricky Tsai, Fiona J. Coutinho, Samer M.I. Hussein, Jie Zhang, Jinsong Wu, Peter B. Dirks, Daniel Schramek, and Jüri Reimand
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long non-coding RNAs ,lncRNAs ,cancer ,prognostic biomarkers ,machine learning ,glioma ,Biology (General) ,QH301-705.5 - Abstract
Summary: Long non-coding RNAs (lncRNAs) are increasingly recognized as functional units in cancer and powerful biomarkers; however, most remain uncharacterized. Here, we analyze 5,592 prognostic lncRNAs in 9,446 cancers of 30 types using machine learning. We identify 166 lncRNAs whose expression correlates with survival and improves the accuracy of common clinical variables, molecular features, and cancer subtypes. Prognostic lncRNAs are often characterized by switch-like expression patterns. In low-grade gliomas, HOXA10-AS activation is a robust marker of poor prognosis that complements IDH1/2 mutations, as validated in another retrospective cohort, and correlates with developmental pathways in tumor transcriptomes. Loss- and gain-of-function studies in patient-derived glioma cells, organoids, and xenograft models identify HOXA10-AS as a potent onco-lncRNA that regulates cell proliferation, contact inhibition, invasion, Hippo signaling, and mitotic and neuro-developmental pathways. Our study underscores the pan-cancer potential of the non-coding transcriptome for identifying biomarkers and regulators of cancer progression.
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- 2021
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4. In Vitro Selection of Cell-Internalizing DNA Aptamers in a Model System of Inflammatory Kidney Disease
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Glory Ranches, Melanie Lukasser, Herbert Schramek, Andreas Ploner, Taras Stasyk, Gert Mayer, Günter Mayer, and Alexander Hüttenhofer
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Therapeutics. Pharmacology ,RM1-950 - Abstract
Chronic kidney disease (CKD) is a progressive pathological condition marked by a gradual loss of kidney function. Treatment of CKD is most effective when diagnosed at an early stage and patients are still asymptomatic. However, current diagnostic biomarkers (e.g., serum creatinine and urine albumin) are insufficient for prediction of the pathogenesis of the disease. To address this need, we applied a cell-SELEX (systematic evolution of ligands by exponential enrichment) approach and identified a series of DNA aptamers, which exhibit high affinity and selectivity for cytokine-stimulated cells, resembling some aspects of a CKD phenotype. The cell-SELEX approach was driven toward the enrichment of aptamers that internalize via the endosomal pathway by isolating the endosomal fractions in each selection cycle. Indeed, we demonstrated co-localization of selected aptamers with lysosomal-associated membrane protein 1 (LAMP-1), a late endosomal and lysosomal marker protein, by fluorescence in situ hybridization. These findings are consistent with binding and subsequent internalization of the aptamers into cytokine-stimulated cells. Thus, our study sets the stage for applying selected DNA aptamers as theragnostic reagents for the development of targeted therapies to combat CKD. Keywords: cell-SELEX, DNA aptamers, chronic kidney disease, inflammatory kidney disease, cytokines
- Published
- 2017
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5. The Use of Neoadjuvant Chemotherapy in Patients With Urothelial Carcinoma of the Bladder: Current Practice Among Clinicians.
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Martini T, Gilfrich C, Mayr R, Burger M, Pycha A, Aziz A, Gierth M, Stief CG, Müller SC, Wagenlehner F, Roigas J, Hakenberg OW, Roghmann F, Nuhn P, Wirth M, Novotny V, Hadaschik B, Grimm MO, Schramek P, Haferkamp A, Colleselli D, Kloss B, Herrmann E, Fisch M, May M, and Bolenz C
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- Age Factors, Aged, Carcinoma, Transitional Cell pathology, Carcinoma, Transitional Cell surgery, Cystectomy, Female, Humans, Male, Middle Aged, Neoplasm Staging, Prospective Studies, Sex Factors, Surveys and Questionnaires, Urinary Bladder Neoplasms pathology, Urinary Bladder Neoplasms surgery, Carcinoma, Transitional Cell drug therapy, Chemotherapy, Adjuvant methods, Practice Patterns, Physicians', Urinary Bladder Neoplasms drug therapy
- Abstract
Introduction: Guidelines recommend neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) in patients with urothelial carcinoma of the bladder in clinical stages T2-T4a, cN0M0. We examined the frequency and current practice of NAC and sought to identify predictors for the use of NAC in a prospective contemporary cohort., Materials and Methods: We analyzed prospective data from 679 patients in the PROMETRICS (PROspective MulticEnTer RadIcal Cystectomy Series 2011) database. All patients underwent RC in 2011. Uni- and multivariable regression analyses identified predictors of NAC application. Furthermore, a questionnaire was used to evaluate the practice patterns of NAC at the PROMETRICS centers., Results: A total of 235 patients (35%) were included in the analysis. Only 15 patients (2.2%) received NAC before RC. Younger age (< 70 years; P = .035), lower case volume of the center (< 30 RC/year; P < .001), and advanced tumor stage (≥ cT3; P = .038) were identified as predictors for NAC. Of the 200 urologists who replied to the questionnaire, 69% (n = 125) declared tumor stage cT3-4 a/o N1M0 to be the best indication for NAC application, although 45% of the urologists stated that they would not perform NAC despite recommendations. The decision for NAC was made by the individual urologist in 69% of cases, and only 29% reported that all cases were discussed in an interdisciplinary tumor board., Conclusion: NAC was rarely applied in the present cohort. We observed a discrepancy between guideline recommendations and practice patterns, despite medical indication and pre-therapeutic interdisciplinary discussion. The potential benefit of NAC within a multimodal approach seems to be neglected by many urologists., (Copyright © 2016 Elsevier Inc. All rights reserved.)
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- 2017
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6. Does increasing the nodal yield improve outcomes in contemporary patients without nodal metastasis undergoing radical prostatectomy?
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Kluth LA, Xylinas E, Rieken M, Chun FK, Fajkovic H, Becker A, Karakiewicz PI, Passoni N, Herman M, Lotan Y, Seitz C, Schramek P, Remzi M, Loidl W, Guillonneau B, Rouprêt M, Briganti A, Scherr DS, Graefen M, Tewari AK, and Shariat SF
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- Aged, Disease-Free Survival, Follow-Up Studies, Humans, Lymph Node Excision, Lymphatic Metastasis, Male, Middle Aged, Neoplasm Grading, Neoplasm Recurrence, Local, Neoplasm Staging, Prognosis, Prostate-Specific Antigen blood, Prostatic Neoplasms blood, Retrospective Studies, Treatment Outcome, Lymph Nodes pathology, Prostatectomy methods, Prostatic Neoplasms pathology, Prostatic Neoplasms surgery
- Abstract
Objectives: To determine if the number of lymph nodes (LNs) removed is an independent predictor of biochemical recurrence (BCR) in patients without LN metastases undergoing radical prostatectomy (RP)., Material and Methods: Retrospective analysis of 7,310 patients treated at 7 centers with RP and pelvic LN dissection for clinically localized prostate cancer between 2000 and 2011. Patients with LN metastases (n = 398) and other reasons (stated later in the article) (n = 372) were excluded, which left 6,540 patients for the final analyses., Results: Overall, median biopsy and RP Gleason score were both 7; median prostate specific antigen level was 6 ng/ml (interquartile range [IQR]: 5); and median number of LNs removed was 6 (IQR: 8). A total of 3,698 (57%), 2,064 (32%), and 508 (8%) patients had ≥ 6, ≥ 10, and ≥ 20 LNs removed, respectively. Patients with more LNs removed were older, had a higher prostate specific antigen level, had higher clinical and pathologic T stage, and had higher RP Gleason score (all P<0.002). Within a median follow-up of 21 (IQR: 16) months, more LNs removed was associated with an increased risk of BCR (continuous: P = 0.021; categorical: P = 0.014). In multivariable analyses that adjusted for the effects of standard clinicopathologic factors, none of the nodal stratifications predicted BCR., Conclusions: The number of LNs did not have any prognostic significance in our contemporary cohort of patients with LN-negative prostate cancer. This suggests that the risk of missed clinically significant micrometastasis may be minimal in patients currently treated with RP and having a lower LN yield., (Copyright © 2014 Elsevier Inc. All rights reserved.)
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- 2014
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7. In vitro generation of dysmorphic erythrocytes.
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Schramek P, Moritsch A, Haschkowitz H, Binder BR, and Maier M
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- Adult, Blood Physiological Phenomena, Erythrocytes, Abnormal ultrastructure, Hematuria blood, Hemoglobinuria urine, Hemolysis physiology, Humans, In Vitro Techniques, Kallikreins urine, Microscopy, Electron, Scanning, Nephrons physiology, Osmolar Concentration, Pepsin A metabolism, Urokinase-Type Plasminogen Activator metabolism, Erythrocytes, Abnormal pathology
- Abstract
In hematuria, dysmorphic red blood cells found in the urine sediment are known to indicate glomerular origin of bleeding. To better understand the mechanisms which might cause the typical membrane changes in dysmorphic erythrocytes in vivo, we have exposed normal human erythrocytes in vitro to an osmotic and enzymatic environment similar to that of the nephron. In addition, treated or untreated erythrocytes were exposed to a hemolytic environment. The morphology of the cells was evaluated by light and electron microscopy in comparison of that of dysmorphic erythrocytes obtained in vivo. Neither the passage of erythrocytes in sequence through various solutions each simulating the tubule fluid in a different part of the nephron, nor exposure to urinary or renal enzymes or to serum per se causes the typical membrane alterations. Upon exposure of passaged erythrocytes to a hemolytic environment, however, 50 to 90% of the cells become dysmorphic in a time and dose dependent fashion. By light and electron microscopy these dysmorphic erythrocytes obtained in vitro are indistinguishable from those obtained in vivo. In contrast, non-passaged red blood cells are not affected by the same hemolytic environment. We conclude that osmotically challenged erythrocytes exposed to a hemolytic environment develop dysmorphic membrane alterations.
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- 1989
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8. Value of urinary erythrocyte morphology in assessment of symptomless microhaematuria.
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Schramek P, Schuster FX, Georgopoulos M, Porpaczy P, and Maier M
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- Adolescent, Adult, Aged, Aged, 80 and over, Child, Erythrocyte Count, Female, Follow-Up Studies, Hematuria etiology, Humans, Kidney Diseases complications, Male, Microscopy, Interference, Middle Aged, Prospective Studies, Erythrocytes pathology, Erythrocytes, Abnormal pathology, Hematuria urine
- Abstract
To assess the value of microscopic analysis of urinary erythrocyte morphology as the initial step in the investigation of patients with isolated symptomless microhaematuria, 316 consecutive patients were grouped according to whether they excreted eumorphic or mixed forms of erythrocytes or only dysmorphic forms. The former group was investigated fully, and urological disease was found in 85% of 123 patients. The 192 patients with exclusively dysmorphic erythrocytes in their urine and normal renal function (benign renal microhaematuria) were assigned to annual follow-up examinations of urinary red cell morphology and renal function, and subjected to invasive diagnostic procedures when a change was noted. In only 2 of the 132 patients followed up for at least 2 years did a new disease develop; this was easily identified at one of the annual examinations. Microscopic analysis of urinary erythrocyte morphology is therefore an effective method for identifying patients with symptomless microhaematuria needing specific diagnostic investigation.
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- 1989
- Full Text
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