Uwe J Roblick

Karolinska Institutet, Solna, Stockholm, Sweden

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Publications (209)407.84 Total impact

  • 19th Surgical Research Days; 10/2015
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    ABSTRACT: Cancer proteomics provide a powerful approach to identify biomarkers for personalized medicine. Particularly, biomarkers for early detection, prognosis and therapeutic intervention of bone cancers, especially osteosarcomas, are missing. Initially, we compared two-dimensional gel electrophoresis (2-DE)-based protein expression pattern between cell lines of fetal osteoblasts, osteosarcoma and pulmonary metastasis derived from osteosarcoma. Two independent statistical analyses by means of PDQuest® and SameSpot® software revealed a common set of 34 differentially expressed protein spots (p < 0.05). 17 Proteins were identified by mass spectrometry and subjected to Ingenuity Pathway Analysis resulting in one high-ranked network associated with Gene Expression, Cell Death and Cell-To-Cell Signaling and Interaction. Ran/TC4-binding protein (RANBP1) and Cathepsin D (CTSD) were further validated by Western Blot in cell lines while the latter one showed higher expression differences also in cytospins and in clinical samples using tissue microarrays comprising osteosarcomas, metastases, other bone malignancies, and control tissues. The results show that protein expression patterns distinguish fetal osteoblasts from osteosarcomas, pulmonary metastases, and other bone diseases with relevant sensitivities between 55.56% and 100% at ≥87.50% specificity. Particularly, CTSD was validated in clinical material and could thus serve as a new biomarker for bone malignancies and potentially guide individualized treatment regimes.
    Oncotarget 06/2015; 6(18):16517-26. DOI:10.18632/oncotarget.4140 · 6.36 Impact Factor

  • 132nd Congress of the German Society of Surgery (DGCH); 04/2015
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  • Moderne Chirurgie des Rektumkarzinoms, Edited by Martin E. Kreis, Joachim Straßburg, 03/2015: pages pp 99-109; Springer Verlag.
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    ABSTRACT: Chromosomal aneuploidy has been identified as a prognostic factor in the majority of sporadic carcinomas. However, it is not known how chromosomal aneuploidy affects chromosome-specific protein expression in particular, and the cellular proteome equilibrium in general. The aim was to detect chromosomal aneuploidy-associated expression changes in cell clones carrying trisomies found in colorectal cancer. We used microcell-mediated chromosomal transfer to generate three artificial trisomic cell clones of the karyotypically stable, diploid, yet mismatch-deficient, colorectal cancer cell line DLD1 - each of them harboring one extra copy of either chromosome 3, 7 or 13. Protein expression differences were assessed by two-dimensional gel electrophoresis and mass spectrometry, compared to whole-genome gene expression data, and evaluated by PANTHER classification system and Ingenuity Pathway Analysis (IPA). In total, 79 differentially expressed proteins were identified between the trisomic clones and the parental cell line. Up-regulation of PCNA and HMGB1 as well as down-regulation of IDH3A and PSMB3 were revealed as trisomy-associated alterations involved in regulating genome stability. These results show that trisomies affect the expression of genes and proteins that are not necessarily located on the trisomic chromosome, but reflect a pathway-related alteration of the cellular equilibrium.
    Analytical cellular pathology (Amsterdam) 01/2014; 36(5-6). DOI:10.3233/ACP-140088 · 0.85 Impact Factor
  • Ralf Czymek · Uwe Roblick · Hans-Peter Bruch ·

    Allgemein- und Viszeralchirurgie up2date 08/2013; 7(04):239-265. DOI:10.1055/s-0032-1325066
  • M Hoffmann · R Meyer · M Kleemann · UJ Roblick · M Zimmermann · T Keck ·

    Zeitschrift für Gastroenterologie 08/2013; 51(08). DOI:10.1055/s-0033-1353011 · 1.05 Impact Factor
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    ABSTRACT: Abstract Context: Biological material reflecting the in vivo composition of markers provides a high potential for biomarker discovery. Objective: We compared the serum proteome following heat- and nitrogen-preservation, with and without subsequent storage at room temperature. Materials and methods: Serum samples were collected, treated and analysed by two-dimensional gel electrophoresis. Protein spots were identified and confirmed by two mass spectrometry approaches (MALDI & ESI) and subjected to Ingenuity Pathway Analysis. Results: We revealed 24 differentially expressed proteins (p ≤ 0.05) between nitrogen and heat preservation, and 87 between nitrogen and heat preservation with subsequent storage for 120 h at room-temperature. Mass spectrometry identified 25 polypeptides. Pathway analysis resulted in networks maintaining Cellular Assembly and Organization, Movement and Maintenance. Conclusion: Heat-stabilization does not substantially change the short-term proteome composition of serum compared with nitrogen treatment. However, heat-stabilization alone seems insufficient for long-term sample preservation for serum samples. We identified transthyretin and apolipoprotein A-IV as sample quality markers.
    Archives of Physiology and Biochemistry 07/2013; 119(3). DOI:10.3109/13813455.2013.806556 · 1.76 Impact Factor
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    ABSTRACT: Introduction: Aneuploidy has been suggested as independent prognostic marker in ulcerative colitis (UC) patients for developing UC-associated colorectal carcinomas (UCCs). UCCs are associated with a poorer prognosis and more frequently present with synchronous carcinomas when compared with sporadic colorectal carcinomas (SCCs). The authors therefore investigated if the adjacent non-malignant mucosa of aneuploid UCCs and aneuploid SCCs shows differences regarding the frequency of aneuploidy and if this aneuploidy is associated with histomorphological alterations. Methods: Primary tumors of 25 UCCs and 20 SCCs were selected showing exclusively aneuploid DNA patterns and matching DNA stemlines. The UCCs' (n = 82) and SCCs' (n = 40) adjacent non-malignant mucosa were evaluated for histopathology and assessed for DNA ploidy status by image cytometry. Results: UCCs' non-malignant mucosa showed dysplasia in 31.7% and aneuploidy in 89%. In contrast, SCCs' non-malignant mucosa revealed no dysplasia and aneuploidy in only 5%. Irrespective of dysplastic lesions, aneuploidy was observed more frequently in adjacent non-malignant mucosa of UCCs than of SCCs (p < 0.001). Neither a correlation between aneuploidy and inflammation (p = 0.916) nor between aneuploidy and dysplastic lesions (p = 0.159) could be observed. Conclusion: Aneuploidy is more frequent in adjacent non-malignant mucosa of aneuploid UCCs than in adjacent non-malignant mucosa of aneuploid SCCs. Furthermore, aneuploidy seems to be irrespective of inflammation or dysplasia. The results therefore emphasize the importance of aneuploidy for UC-associated carcinogenesis and its potential as new diagnostic target.
    Scandinavian Journal of Gastroenterology 04/2013; 48(6). DOI:10.3109/00365521.2013.783103 · 2.36 Impact Factor
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    ABSTRACT: Background: Malignant transformation in ulcerative colitis (UC) is associated with pronounced chromosomal instability, reflected by aneuploidy. Although aneuploidy can precede primary cancer diagnosis in UC for more than a decade, little is known of its cellular consequences. Methods: Whole-genome gene expression analysis was applied to noninflamed colon mucosa, mucosal biopsies of patients with UC, and UC-associated carcinomas (UCCs). DNA image cytometry was used to stratify samples into ploidy types. Differentially expressed genes (DEGs) were analyzed by Ingenuity Pathway Analysis and validated by real-time quantitative PCR. Results: Gene expression changes were more pronounced between normal mucosa and UC (2587 DEGs) than between UC and UCC (827 DEGs). Cytometry identified colitis patients with euploid or aneuploid mucosa biopsies, whereas all UCCs were aneuploid. However, 1749 DEGs distinguished euploid UC and UCCs, whereas only 15 DEGs differentiated aneuploid UC and UCCs. A total of 16 genes were differentially expressed throughout the whole sequence from normal controls to UCCs. Particularly, genes pivotal for chromosome segregation (e.g., SMC3 and NUF2) were differentially regulated along aneuploidy development. Conclusions: The high number of DEGs between normal mucosa and colitis is dominated by inflammatory-associated genes. Subsequent acquisition of aneuploidy leads to subtle but distinct transcriptional alterations, revealing novel target genes that drive genomic instability and thus carcinogenesis. The gene expression signature of malignant phenotypes in aneuploid UC suggests that these lesions might need to be considered as severe as high-grade dysplasia.
    Inflammatory Bowel Diseases 02/2013; 19(4). DOI:10.1097/MIB.0b013e31827eeaa4 · 4.46 Impact Factor
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    ABSTRACT: Purpose: Research projects and clinical trials strongly rely on high-quality biospecimens which are provided by biobanks. Since differences in sample processing and storage can strongly affect the outcome of such studies, standardization between biobanks is necessary to guarantee reliable results of large, multicenter studies. The German Cancer Aid Foundation (Deutsche Krebshilfe e.V.) has therefore initiated the priority program "tumor tissue banks" in 2010 by funding four biobank networks focusing on central nervous system tumors, melanomas, breast carcinomas, and colorectal carcinomas. The latter one, the North German Tumor Bank of Colorectal Cancer (ColoNet) is managed by surgeons, pathologists, gastroenterologists, oncologists, scientists, and medical computer scientists. Methods and results: The ColoNet consortium has developed and harmonized standard operating procedures concerning all biobanking aspects. Crucial steps for quality assurance have been implemented and resulted in certification according to DIN EN ISO 9001. A further achievement is the construction of a web-based database for exploring available samples. In addition, common scientific projects have been initiated. Thus, ColoNet's repository will be used for research projects in order to improve early diagnosis, therapy, follow-up, and prognosis of colorectal cancer patients. Apart from the routine sample storage at -170 °C, the tumor banks' unique characteristic is the participation of outpatient clinics and private practices to further expand the sample and clinical data collection. Conclusion: The first 2 years of funding by the German Cancer Aid Foundation have already led to a closer scientific connection between the participating institutions and to a substantial collection of biospecimens obtained under highly standardized conditions.
    Langenbeck s Archives of Surgery 01/2013; 398(2). DOI:10.1007/s00423-012-1043-4 · 2.19 Impact Factor
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    ABSTRACT: Purpose: Presently, no markers exist to predict metachronous metastasis at the time a primary colorectal cancer is diagnosed. While aneuploidy indicates poor survival prognosis and elevated carcinoembryonic antigen (CEA) levels the presence of recurrent disease, the predictive value of both markers regarding imminent metachronous metastases is unclear. Methods: Sixty patients with distant recurrence throughout a 5-year follow-up (TM+) were randomly chosen and 60 patients without metastasis matched to this cohort (TM-). In addition, an enlarged collective (n = 217; n TM+ = 85, n TM- = 132) with median follow-up of 79.2 months was assessed by logistic regression regarding metachronous metastases. Univariate and stepwise regression analyses included clinicopathological characteristics, preoperative CEA levels and aneuploidy assessed by DNA image cytometry. Results: The matched-pair collective showed aneuploidy in 71.1 % (TM-) and 85.0 % (TM+; p = 0.076), and elevated CEA in 24.5 % (TM-) and 52.2 % [TM+; odds ratio (OR), 3.414; p = 0.007]. The enlarged collective presented aneuploidy in 71.2 % (TM-) and 83.5 % (TM+; OR 2.050, p = 0.038), and elevated CEA in 28.6 % (TM-) and 48.9 % (TM+; OR 2.391, p = 0.020). Elevated CEA and aneuploidy did not show any association (p = 0.919). In contrast, logistic regression analyses demonstrated that besides increased T category (OR 1.745, p = 0.019), both elevated CEA level (OR 2.633, p = 0.015) and aneuploidy (OR 1.929, p = 0.058) were independent predictive markers for metachronous metastasis. Conclusions: Our data show that aneuploidy and elevated CEA levels besides increased T category could serve for individual risk assessment to predict metachronous metastases. The fact that still aneuploidy missed the significance level by a small margin emphasizes the need for larger validation studies.
    International Journal of Colorectal Disease 01/2013; 28(6). DOI:10.1007/s00384-012-1625-1 · 2.45 Impact Factor
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    ABSTRACT: Background: In obstructive defecation syndrome (ODS) combinations of morphologic alterations of the pelvic floor and the colorectum are nearly always evident. Laparoscopic resection rectopexy (LRR) aims at restoring physiological function. We present the results of 19 years of experience with this procedure in patients with ODS. Methods: Between 1993 and 2012, 264 patients underwent LRR for ODS at our department. Perioperative and follow-up data were analyzed. Results: The female/male ratio was 25.4:1, mean age was 61.3 years (±14.3 years), and mean body mass index (BMI) was 25.2 kg/m(2) (±4.2 kg/m(2)). The pathological conditions most frequently found in combination were a sigmoidocele plus a rectocele (n = 79) and a sigmoidocele plus a rectal prolapse or intussusception (n = 69). The conversion rate was 2.3 % (n = 6). The mortality rate was 0.75 % (n = 2), the rate of complications requiring surgical re-intervention was 4.3 % (n = 11), and the rate of minor complications was 19.8 % (n = 51). Follow-up data were available for 161 patients with a mean follow-up of 58.2 months (±47.1 months). Long-term results showed that 79.5 % of patients (n = 128) reported at least an improvement of symptoms. In cases of a sigmoidocele (n = 63 available for follow-up) or a rectal prolapse II°/III° (n = 72 available for follow-up), the improvement rates were 79.4 % (n = 50) and 81.9 % (n = 59), respectively. Conclusions: LRR is a safe and effective procedure. Our perioperative results and long-term functional outcome strengthen the evidence regarding benefits of LRR in patients with an outlet obstruction. However, careful patient selection is essential.
    Techniques in Coloproctology 11/2012; 17(3). DOI:10.1007/s10151-012-0925-3 · 2.04 Impact Factor
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    ABSTRACT: The increasing experience within the area of laparoscopic procedures has paved the way for technically-complex procedures, such as distal pancreatectomy. In order to avoid complications associated with concomitant splenectomy, these procedures are increasingly performed with spleen preservation. A drawback is the low number of cases, which does not allow for an evidence-based comparison between laparoscopic and open procedures, and spleen-preserving and concomitant splenectomy procedures. Between 2006 and 2010, all data for patients who underwent a laparoscopic distal pancreatectomy (LDP) at the Department of Surgery, University of Schleswig-Holstein, Luebeck, Germany, were collected are stored in a prospectively-maintained database. Patients with tumours in the pancreatic tail and body that did not exceed the level of the portal vein were included in this database. A total of 22 patients who underwent LDP could be included in the evaluation. Ten of those patients underwent a laparoscopic spleen-preserving distal pancreatectomy (LSPDP), while the remaining 12 received an LDP with splenectomy (LDPwS). The median operation time was 155 min (range: 98–253) for the LSPDP group, and 201 min (range: 60–310) for the LDPwS group (P = 0.06). The median hospital stay was 8.5 days (range: 5–23) in the LSPDP group compared to 11 days (range: 4–41) in the LDPwS group (P = 0.06). Pancreatic fistula occurred in two patients from each group. It caused an intraabdominal haemorrhage in one patient of the LSPDP group, which required re-laparoscopy. Two patients experienced subphrenic abscesses in the LDPwS group and were treated interventionally. Histological examination revealed six cystadenomas and five pseudocysts (maximum diameter: 7 cm) in the LDPwS group, and six neuroendocrine tumours (maximum diameter: 2 cm) in the LSPDP group. LDP can be performed safely. The optic magnification provided by laparoscopy facilitates LSPDP, as dissection of the splenic vessels can be avoided. Although not significant, there was a trend towards reduced hospital stay and operating time for LSPDP. Oncologic outcomes and morbidity seem to not be inferior to open procedures. The size of the tumours and the peripancreatic, as well as paraneoplastic, tissue alterations determine the indication for splenectomy.
    Surgical Practice 11/2012; 16(4):142-149. DOI:10.1111/j.1744-1633.2012.00620.x · 0.17 Impact Factor
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    ABSTRACT: Background More than 1.2 million new cases of colorectal cancer are reported each year worldwide. Despite actual screening programs, about 50% of the patients are diagnosed at advanced tumor stages presenting poor prognosis. Innovative screening tools could aid the detection at early stages and allow curative treatment interventions. Methods A nine target multiplex serum protein biochip was generated and evaluated using a training- and validation-set of 317 highly standardized, liquid nitrogen preserved serum samples comprising controls, adenomas, and colon cancers. Results Serum levels of CEA, IL-8, VEGF, S100A11, MCSF, C3adesArg, CD26, and CRP showed significant differences between cases and controls. The largest areas under the receiver operating characteristics curve were observed for CEA, IL-8, and CRP. At threshold levels yielding 90% specificity, sensitivities for CEA, IL-8 and CRP were 26%, 22%, and 17%, respectively. The most promising marker combinations were CEA + IL-8 reaching 37% sensitivity at 83% specificity and CEA + CRP with 35% sensitivity at 81% specificity. In an independent validation set CEA + IL-8 reached 47% sensitivity at 86% specificity while CEA + CRP obtained 39% sensitivity at 86% specificity. Early carcinomas were detected with 33% sensitivity for CEA + IL-8 and 28% for CEA + CRP. Conclusions Apart from CEA, IL-8, and CRP, the screening value of additional blood markers and the potential advantage of combining serum biochip testing with fecal occult blood testing needs to be studied. Multiplex biochip array technology utilizing serum samples offers an innovative approach to colorectal cancer screening.
    BMC Cancer 09/2012; 12(1):393. DOI:10.1186/1471-2407-12-393 · 3.36 Impact Factor
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    ABSTRACT: Background: Pancreatic cancer is one of the most deadly malignancies with insufficient therapeutic options and poor outcome. Cancer stem cells (CSCs) are thought to be responsible for progression and therapy resistance. We investigated the potential of pancreatic cell lines for CSC research by analyzing to what extent they contain CSC populations and how representative these are compared to clinical tissue. Methods: Six pancreatic cancer cell lines were analyzed by flow cytometry for CD326, CD133, CD44, CD24, CXCR4 and ABCG2. Subsequently, 70 primary pancreatic tissues were evaluated for CD326, CD133 and CD44 by immunohistochemistry. Results: All the cell lines but one showed a stable expression pattern throughout biological replicates. Marker expression in clinical tissue of CD44 distinguished normal patients from pancreatic carcinoma patients with a sensitivity of 50% at 80% specificity and metastasized from nonmetastasized carcinomas with 69% sensitivity at 100% specificity. Conclusions: Our results indicate a link between elevated CD44 expression, malignancy and metastasis of pancreatic tissue. Furthermore, individual pancreatic cell lines show a substantial amount of cells with CSC properties which is comparable with interpatient variability detected in primary tissue. These pancreatic cancer cell lines could thus serve for urgently needed pharmacological CSC in vitro research.
    European Surgical Research 08/2012; 49(2):88-98. DOI:10.1159/000341669 · 2.47 Impact Factor
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    ABSTRACT: Colorectal cancer is one of the most common forms of cancer in the Western world. A wide variety of prognostic factors for colorectal cancer have been identified. There is, however, a paucity of literature addressing the influence of multiple primary carcinomas on prognosis. We conducted the present study in order to investigate the influence of second or multiple primary tumours on the prognosis of colorectal cancer patients. From 1992 to 2005, 1500 patients underwent surgery for colorectal cancer at the University Hospital of Luebeck. Of these, 276 patients (19%) had multiple primary malignant tumours. We performed statistical analyses only on patients who underwent surgery with curative intent in order to minimise additional prognostic factors. The patients were divided into groups according to the time of multiple primary tumour occurrence. Data were analysed for various variables. We did not detect any significant differences in survival either between the various groups or between patients with and without multiple primary tumours. The presence of multiple primary carcinomas is not an independent prognostic factor in patients with an index tumour of the colorectum. Multiple primary tumours are thus not necessarily associated with a poorer outcome and patients should receive curative intent surgery and appropriate follow-up care.
    Acta chirurgica iugoslavica 08/2012; 59(1):31-8. DOI:10.2298/ACI1201031H
  • T Laubert · J Habermann · M Sommer · K Fellermann · UJ Roblick · HP Bruch · J Büning ·

    Zeitschrift für Gastroenterologie 08/2012; 50(08). DOI:10.1055/s-0032-1324275 · 1.05 Impact Factor

Publication Stats

2k Citations
407.84 Total Impact Points


  • 2001-2014
    • Karolinska Institutet
      • • Department of Medical Biochemistry and Biophysics
      • • Department of Oncology-Pathology
      • • Cancer Center Karolinska - CCK
      Solna, Stockholm, Sweden
  • 2013
    • Clinic for Minimally Invasive Surgery
      Berlín, Berlin, Germany
  • 2006-2013
    • University Medical Center Schleswig-Holstein
      • Department of Pediatrics
      Kiel, Schleswig-Holstein, Germany
  • 1998-2013
    • Universität zu Lübeck
      • • Department of Surgery
      • • Klinik für Kinderchirurgie
      • • Institut für Anatomie
      Lübeck Hansestadt, Schleswig-Holstein, Germany
  • 2008-2012
    • Universitätsklinikum Schleswig - Holstein
      • Klinik für Allgemeine Chirurgie (Kiel)
      Kiel, Schleswig-Holstein, Germany
  • 2005-2007
    • Karolinska University Hospital
      • Department of Obstetrics and Gynecology
      Tukholma, Stockholm, Sweden