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Book ; Online ; E-Book: Moderne Chirurgie des Magen- und Kardiakarzinoms

Kreis, Martin Ernst / Seeliger, Hendrik

2017

Author's details	Martin E. Kreis, Hendrik Seeliger Hrsg
Keywords	Medicine ; Radiotherapy ; Gastroenterology ; Oncology ; Abdominal surgery ; Surgical oncology ; Palliative treatment
Subject code	617.55059
Language	German
Size	1 Online-Ressource (XIII, 211 Seiten), 104 Illustrationen, Diagramme
Publisher	Springer
Publishing place	Berlin
Publishing country	Germany
Document type	Book ; Online ; E-Book
Remark	Zugriff für angemeldete ZB MED-Nutzerinnen und -Nutzer
HBZ-ID	HT019412534
ISBN	978-3-662-53188-4 ; 9783662531877 ; 3-662-53188-7 ; 3662531879
DOI	10.1007/978-3-662-53188-4
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Book ; Thesis: Untersuchungen zur Funktion, Morphologie und Toleranzinduktion zellulärer Nebennierenrindentransplantate am Modell MHC-Klasse I-transgener Mäuse

Seeliger, Hendrik

2000

Author's details	vorgelegt von Hendrik Seeliger
Language	German
Size	116 Bl., Ill., graph. Darst., 30 cm
Publishing country	Germany
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Hannover, Med. Hochsch., Diss., 2001
HBZ-ID	HT013216780
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Article: Targeting Interleukin-6/Glycoprotein-130 Signaling by Raloxifene or SC144 Enhances Paclitaxel Efficacy in Pancreatic Cancer.

Hering, Nina A / Günzler, Emily / Arndt, Marco / Zibell, Miriam / Lauscher, Johannes C / Kreis, Martin E / Beyer, Katharina / Seeliger, Hendrik / Pozios, Ioannis

Cancers

2023 Volume 15, Issue 2

Abstract: Interleukine-6 plays a key role in the progression and poor survival in pancreatic ductal adenocarcinoma (PDAC). The present study aimed to clarify if targeting the interleukin-6/glycoprotein-130 signaling cascade using the small-molecule gp130 inhibitor ...

Abstract	Interleukine-6 plays a key role in the progression and poor survival in pancreatic ductal adenocarcinoma (PDAC). The present study aimed to clarify if targeting the interleukin-6/glycoprotein-130 signaling cascade using the small-molecule gp130 inhibitor SC144 or raloxifene, a non-steroidal selective estrogen receptor modulator, enhances paclitaxel efficacy. MTT/BrdU assays or TUNEL staining were performed to investigate cell viability, proliferation and apoptosis induction in L3.6pl and AsPC-1 human pancreatic cell lines. In vivo, effects were studied in an orthotopic PDAC mouse model. Tumor specimens were analyzed by qPCR, immunohistochemistry and ELISA. Combination of paclitaxel/raloxifene, but not paclitaxel/SC144, enhanced proliferation and viability inhibition and increased apoptosis compared to single treatment in vitro. Synergy score calculations confirmed an additive influence of raloxifene on paclitaxel. In the PDAC mouse model, both combinations of raloxifene/paclitaxel and SC144/paclitaxel reduced tumor weight and volume compared to single-agent therapy or control. Raloxifene/paclitaxel treatment decreased survivin mRNA expression and showed tendencies of increased caspase-3 staining in primary tumors. SC144/paclitaxel reduced interleukin-6 levels in mice's tumors and plasma. In conclusion, raloxifene or SC144 can enhance the anti-tumorigenic effects of paclitaxel, suggesting that paclitaxel doses might also be reduced in combined chemotherapy to lessen paclitaxel side effects.
Language	English
Publishing date	2023-01-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15020456
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Article ; Online: Gp130 is expressed in pancreatic cancer and can be targeted by the small inhibitor molecule SC144

Pozios, Ioannis / Hering, Nina A. / Guenzler, Emily / Arndt, Marco / Elezkurtaj, Sefer / Knösel, Thomas / Bruns, Christiane J. / Margonis, Georgios A. / Beyer, Katharina / Seeliger, Hendrik

J Cancer Res Clin Oncol. 2023 Jan., v. 149, no. 1, p. 271-280

2023 , Page(s) 271–280

Abstract: PURPOSE: Interleukin 6 (IL-6), Oncostatin M (OSM), and downstream effector STAT3 are pro-tumorigenic agents in pancreatic ductal adenocarcinoma (PDAC). Glycoprotein 130 (gp130) is a compound of the IL-6 and OSM receptor complex that triggers STAT3 ... ...

Abstract	PURPOSE: Interleukin 6 (IL-6), Oncostatin M (OSM), and downstream effector STAT3 are pro-tumorigenic agents in pancreatic ductal adenocarcinoma (PDAC). Glycoprotein 130 (gp130) is a compound of the IL-6 and OSM receptor complex that triggers STAT3 signaling. SC144 is a small molecule gp130 inhibitor with anticancer activity. This study examines the gp130 expression in human PDAC specimens and the in vitro effects of SC144 in PDAC cell lines. METHODS: Tissue micro-arrays were constructed from 175 resected human PDAC. The gp130 expression in tumor epithelium and stroma was determined by immunohistochemistry, and survival analysis was performed. Growth inhibition by SC144 was assessed in vitro using BrdU and MTT assays. Western blotting was performed to evaluate the SC144 effect on IL-6 and OSM signaling. RESULTS: Gp130 was expressed in the epithelium of 78.8% and the stroma of 9.4% of the tumor samples. The median overall survival for patients with or without epithelial gp130 expression was 16.7 months and 15.9 months, respectively (p = 0.830). Patients with no stromal gp130 expression showed poorer survival than patients with stromal gp130 expression (median 16.2 and 22.9 months, respectively), but this difference did not reach significance (p = 0.144). SC144 inhibited cell proliferation and viability and suppressed IL-6- and OSM-stimulated STAT3Y⁷⁰⁵ phosphorylation in PDAC cells. CONCLUSION: Gp130 is expressed in the epithelium of most human PDAC, but stromal expression is rare. The small molecule gp130 inhibitor SC144 potently inhibits PDAC progression in vitro and may abrogate IL-6 or OSM/gp130/STAT3 signaling. These results suggest gp130 as a novel drug target for pancreatic cancer therapy.
Keywords	adenocarcinoma ; antineoplastic activity ; cancer therapy ; cell proliferation ; drugs ; epithelium ; glycoproteins ; growth retardation ; humans ; immunohistochemistry ; interleukin-6 ; pancreatic neoplasms ; phosphorylation ; viability
Language	English
Dates of publication	2023-01
Size	p. 271-280
Publishing place	Springer Berlin Heidelberg
Document type	Article ; Online
ZDB-ID	134792-5
ISSN	1432-1335 ; 0171-5216 ; 0084-5353 ; 0943-9382
ISSN (online)	1432-1335
ISSN	0171-5216 ; 0084-5353 ; 0943-9382
DOI	10.1007/s00432-022-04518-9
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Near-infrared Fluorescence Imaging for Detecting Pancreatic Liver Metastasis in an Orthotopic Athymic Mouse Model.

Lee, Lucas D / Hering, Nina A / Zibell, Miriam / Lobbes, Leonard A / Kamphues, Carsten / Lauscher, Johannes C / Margonis, Georgios A / Seeliger, Hendrik / Beyer, Katharina / Weixler, Benjamin / Pozios, Ioannis

In vivo (Athens, Greece)

2023 Volume 37, Issue 2, Page(s) 519–523

Abstract: Background/aim: Evidence of metastatic disease precludes oncological resection of pancreatic cancer. Near-infrared (NIR) fluorescent labels, such as indocyanine green (ICG), assist in the intraoperative detection of occult and micrometastatic liver ... ...

Abstract	Background/aim: Evidence of metastatic disease precludes oncological resection of pancreatic cancer. Near-infrared (NIR) fluorescent labels, such as indocyanine green (ICG), assist in the intraoperative detection of occult and micrometastatic liver disease. The present study aimed to analyse the role of NIR fluorescence imaging using ICG for pancreatic liver disease as proof of concept in an orthotopic athymic mouse model. Materials and methods: Pancreatic ductal adenocarcinoma was induced by injecting L3.6pl human pancreatic tumour cells into the pancreatic tail of seven athymic mice. After four weeks of tumour growth, ICG was injected into the tail vein and NIR fluorescence imaging was performed at harvest to determine tumour-to-liver ratios (TLR) using Quest Spectrum Results: Pancreatic tumour growth and liver metastasis could be visually confirmed for all seven animals. None of the hepatic metastases showed any detectable ICG-uptake. ICG-staining failed to visualize the liver metastases or to increase fluorescence intensity of the rim around the hepatic lesions. Conclusion: ICG-staining fails to visualize liver metastases induced by L3.6pl pancreatic tumour cells in athymic nude mice by NIR fluorescence imaging. Further studies are necessary to delineate the underlying mechanism for insufficient ICG uptake in these pancreatic liver metastases and for the lack of a fluorescent rim around the liver lesions.
MeSH term(s)	Animals ; Mice ; Humans ; Mice, Nude ; Pancreatic Neoplasms/diagnostic imaging ; Liver Neoplasms/diagnostic imaging ; Pancreatic Diseases ; Optical Imaging ; Indocyanine Green ; Pancreatic Neoplasms
Chemical Substances	Indocyanine Green (IX6J1063HV)
Language	English
Publishing date	2023-03-07
Publishing country	Greece
Document type	Journal Article
ZDB-ID	807031-3
ISSN	1791-7549 ; 0258-851X
ISSN (online)	1791-7549
ISSN	0258-851X
DOI	10.21873/invivo.13109
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Article: Frequency of Positive Familial Criteria in Patients with Adenocarcinoma of the Esophageal-Gastric Junction and Stomach: First Prospective Data in a Caucasian Cohort.

Schölzchen, Jan / Treese, Christoph / Thuss-Patience, Peter / Mrózek, Alicja / Rau, Beate / Seeliger, Hendrik / Hartmann, Dirk / Estevéz-Schwarz, Lope / Siegmund, Britta / Horn, Denise / Nassir, Mani / Daum, Severin

Cancers

2022 Volume 14, Issue 15

Abstract: Objectives: Current prospective studies investigating the frequency of hereditary criteria in a Caucasian population for adenocarcinoma of the esophagogastric junction (AEG) and stomach (GC) are missing. Genetic testing criteria (screening criteria) for ...

Abstract	Objectives: Current prospective studies investigating the frequency of hereditary criteria in a Caucasian population for adenocarcinoma of the esophagogastric junction (AEG) and stomach (GC) are missing. Genetic testing criteria (screening criteria) for hereditary diffuse gastric cancer (HDGC) were updated in 2020, but do not address patients with intestinal histology (familial intestinal gastric cancer FIGC). Thus, we prospectively screened patients residing in Berlin newly diagnosed with AEG or GC for hereditary criteria to gain insights into the frequency of HDGC. Methods: Prospective documentation of familial/clinical parameters in patients residing in Berlin with AEG or GC over three years was conducted. Besides HDGC criteria from 2015 and revised 2020, we also documented patients fulfilling these criteria but with intestinal type gastric cancer (FIGC). Statistical analysis was performed using X2-test. Results: One hundred fifty-three patients were finally included (92 GC; male: 50 (n.s.); 61 AEG; male: 47; Conclusions: HDGC criteria were found in 15.2% of GC patients according to the 2020 criteria. Percentage increased to 29.3% including patients with intestinal histology among the GC group, and was 13.1% in cases with AEG. These data indicate that family history seems to be of utmost importance in GC to further detect potential hereditary genetic risks. This equally applies for patients with intestinal subtype GC.
Language	English
Publishing date	2022-07-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14153590
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Article: Is Laterality Prognostic in Resected KRAS-Mutated Colorectal Liver Metastases? A Systematic Review and Meta-Analysis.

Belias, Michail / Sasaki, Kazunari / Wang, Jane / Andreatos, Nikolaos / Kamphues, Carsten / Kyriakos, Georgios / Seeliger, Hendrik / Beyer, Katharina / Kreis, Martin E / Margonis, Georgios Antonios

Cancers

2022 Volume 14, Issue 3

Abstract: Background: It is debated whether primary tumor laterality (PTL) is prognostic in all patients with colorectal liver metastases (CRLM) or only those with KRAS wild-type or KRAS-mutated tumors; Methods: We systematically reviewed PubMed for studies ... ...

Abstract	Background: It is debated whether primary tumor laterality (PTL) is prognostic in all patients with colorectal liver metastases (CRLM) or only those with KRAS wild-type or KRAS-mutated tumors; Methods: We systematically reviewed PubMed for studies reporting on resected CRLM originating from left-sided (LS) versus right-sided (RS) colon cancer stratified by KRAS status. Individual participant data (IPD) were used if available. Given that there are two definitions of PTL, we performed two meta-analyses for KRAS-mutated and two for wild-type patients. To assess if an interaction underlies the possible difference between the effects of PTL in KRAS-mutated vs. wild-type CRLM, we similarly performed two meta-analyses of interaction terms; Results: The meta-analyses included eight studies and 7475 patients. PTL had a prognostic association with OS in patients with wild-type tumors (HR for LS: 0.71 [0.60-0.84]), but not in those with KRAS-mutated tumors (HR: 0.99 [0.82-1.19]). This difference stemmed from a truly variable effect of PTL for each KRAS status (mutated vs. wild-type) as the meta-analysis of interaction terms showed a significant interaction between them (HR:1.38 [1.24-1.53]). Similar results were obtained when the second definition of PTL (LS to not include the rectum) was used; Conclusions: KRAS status modifies the association of tumor site with survival. Right-sided tumors are associated with worse OS only in patients with wild-type CRLM.
Language	English
Publishing date	2022-02-04
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14030799
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Article ; Online: Gp130 is expressed in pancreatic cancer and can be targeted by the small inhibitor molecule SC144.

Pozios, Ioannis / Hering, Nina A / Guenzler, Emily / Arndt, Marco / Elezkurtaj, Sefer / Knösel, Thomas / Bruns, Christiane J / Margonis, Georgios A / Beyer, Katharina / Seeliger, Hendrik

Journal of cancer research and clinical oncology

2022 Volume 149, Issue 1, Page(s) 271–280

Abstract: Purpose: Interleukin 6 (IL-6), Oncostatin M (OSM), and downstream effector STAT3 are pro-tumorigenic agents in pancreatic ductal adenocarcinoma (PDAC). Glycoprotein 130 (gp130) is a compound of the IL-6 and OSM receptor complex that triggers STAT3 ... ...

Abstract	Purpose: Interleukin 6 (IL-6), Oncostatin M (OSM), and downstream effector STAT3 are pro-tumorigenic agents in pancreatic ductal adenocarcinoma (PDAC). Glycoprotein 130 (gp130) is a compound of the IL-6 and OSM receptor complex that triggers STAT3 signaling. SC144 is a small molecule gp130 inhibitor with anticancer activity. This study examines the gp130 expression in human PDAC specimens and the in vitro effects of SC144 in PDAC cell lines. Methods: Tissue micro-arrays were constructed from 175 resected human PDAC. The gp130 expression in tumor epithelium and stroma was determined by immunohistochemistry, and survival analysis was performed. Growth inhibition by SC144 was assessed in vitro using BrdU and MTT assays. Western blotting was performed to evaluate the SC144 effect on IL-6 and OSM signaling. Results: Gp130 was expressed in the epithelium of 78.8% and the stroma of 9.4% of the tumor samples. The median overall survival for patients with or without epithelial gp130 expression was 16.7 months and 15.9 months, respectively (p = 0.830). Patients with no stromal gp130 expression showed poorer survival than patients with stromal gp130 expression (median 16.2 and 22.9 months, respectively), but this difference did not reach significance (p = 0.144). SC144 inhibited cell proliferation and viability and suppressed IL-6- and OSM-stimulated STAT3 Conclusion: Gp130 is expressed in the epithelium of most human PDAC, but stromal expression is rare. The small molecule gp130 inhibitor SC144 potently inhibits PDAC progression in vitro and may abrogate IL-6 or OSM/gp130/STAT3 signaling. These results suggest gp130 as a novel drug target for pancreatic cancer therapy.
MeSH term(s)	Humans ; Carcinoma, Pancreatic Ductal/drug therapy ; Cytokine Receptor gp130/metabolism ; Cytokine Receptor gp130/therapeutic use ; Glycoproteins ; Interleukin-6/metabolism ; Pancreatic Neoplasms/pathology ; STAT3 Transcription Factor/metabolism ; Pancreatic Neoplasms
Chemical Substances	Cytokine Receptor gp130 (133483-10-0) ; Glycoproteins ; Interleukin-6 ; STAT3 Transcription Factor ; N'-(7-fluoroH-pyrrolo(1,2-a)quinoxalin-4-yl)pyrazine-2-carbohydrazide
Language	English
Publishing date	2022-12-10
Publishing country	Germany
Document type	Journal Article
ZDB-ID	134792-5
ISSN	1432-1335 ; 0171-5216 ; 0084-5353 ; 0943-9382
ISSN (online)	1432-1335
ISSN	0171-5216 ; 0084-5353 ; 0943-9382
DOI	10.1007/s00432-022-04518-9
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Article ; Online: Impact of myopenia and myosteatosis on postoperative outcome and recurrence in Crohn's disease.

Pozios, Ioannis / Kaufmann, David / Boubaris, Katharina / Seeliger, Hendrik / Weixler, Benjamin / Stroux, Andrea / Kamphues, Carsten / Margonis, Georgios Antonios / Kreis, Martin E / Beyer, Katharina / Seifarth, Claudia / Lauscher, Johannes C

International journal of colorectal disease

2022 Volume 37, Issue 4, Page(s) 791–804

Abstract: Purpose: Myopenia and myosteatosis have been proposed to be prognostic factors of surgical outcomes for various diseases, but their exact role in Crohn's disease (CD) is unknown. The aim of this study is to evaluate their impact on anastomotic leakage, ... ...

Abstract	Purpose: Myopenia and myosteatosis have been proposed to be prognostic factors of surgical outcomes for various diseases, but their exact role in Crohn's disease (CD) is unknown. The aim of this study is to evaluate their impact on anastomotic leakage, CD recurrence, and postoperative complications after ileocecal resection in patients with CD. Methods: A retrospective analysis of CD patients undergoing ileocecal resection at our tertiary referral center was performed. To assess myopenia, skeletal muscle index (skeletal muscle area normalized for body height) was measured using an established image analysis method at third lumbar vertebra level on MRI cross-sectional images. Muscle signal intensity was measured to assess myosteatosis index. Results: A total of 347 patients were retrospectively analyzed. An adequate abdominal MRI scan within 12 months prior to surgery was available for 223 patients with median follow-up time of 48.8 months (IQR: 20.0-82.9). Anastomotic leakage rate was not associated with myopenia (SMI: p = 0.363) or myosteatosis index (p = 0.821). Patients with Crohn's recurrence had a significantly lower SMI (p = 0.047) in univariable analysis, but SMI was not an independent factor for recurrent anastomotic stenosis in multivariable analysis (OR 0.951, 95% CI 0.840-1.078; p = 0.434). Postoperative complications were not associated with myopenia or myosteatosis. Conclusion: Based on the largest cohort of its kind with a long follow-up time, we could provide some data that MRI parameters for myopenia and myosteatosis may not be reliable predictors of postoperative outcome or recurrence in patients with Crohn's disease undergoing ileocecal resection.
MeSH term(s)	Anastomosis, Surgical/adverse effects ; Anastomotic Leak ; Crohn Disease/complications ; Crohn Disease/diagnostic imaging ; Crohn Disease/surgery ; Humans ; Muscle, Skeletal/surgery ; Postoperative Complications/etiology ; Recurrence ; Retrospective Studies
Language	English
Publishing date	2022-02-14
Publishing country	Germany
Document type	Journal Article
ZDB-ID	84975-3
ISSN	1432-1262 ; 0179-1958
ISSN (online)	1432-1262
ISSN	0179-1958
DOI	10.1007/s00384-022-04104-y
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Thymidine phosphorylase induction by ionizing radiation antagonizes 5-fluorouracil resistance in human ductal pancreatic adenocarcinoma.

Lee, Lucas D / Pozios, Ioannis / Liu, Verena / Nachbichler, Silke B / Böhmer, Dirk / Kamphues, Carsten / Beyer, Katharina / Bruns, Christiane J / Kreis, Martin E / Seeliger, Hendrik

Radiation and environmental biophysics

2022 Volume 61, Issue 2, Page(s) 255–262

Abstract: Chemoresistance in pancreatic ductal adenocarcinoma (PDAC) frequently contributes to failure of systemic therapy. While the radiosensitizing properties of 5-fluorouracil (FU) are well known, it is unknown whether ionizing radiation (IR) sensitizes ... ...

Abstract	Chemoresistance in pancreatic ductal adenocarcinoma (PDAC) frequently contributes to failure of systemic therapy. While the radiosensitizing properties of 5-fluorouracil (FU) are well known, it is unknown whether ionizing radiation (IR) sensitizes towards FU cytotoxicity. Here, we hypothesize that upregulation of thymidine phosphorylase (TP) by IR reverses FU chemoresistance in PDAC cells. The FU resistant variant of the human PDAC cell line AsPC-1 (FU-R) was used to determine the sensitizing effects of IR. Proliferation rates of FU sensitive parental (FU-S) and FU-R cells were determined by WST-1 assays after low (0.05 Gy) and intermediate dose (2.0 Gy) IR followed by FU treatment. TP protein expression in PDAC cells before and after IR was assessed by Western blot. To analyze the specificity of the FU sensitizing effect, TP was ablated by siRNA. FU-R cells showed a 2.7-fold increase of the half maximal inhibitory concentration, compared to FU-S parental cells. Further, FU-R cells showed a concomitant IR resistance towards both doses applied. When challenging both cell lines with FU after IR, FU-R cells had lower proliferation rates than FU-S cells, suggesting a reversal of chemoresistance by IR. This FU sensitizing effect was abolished when TP was blocked by anti-TP siRNA before IR. An increase of TP protein expression was seen after both IR doses. Our results suggest a TP dependent reversal of FU-chemoresistance in PDAC cells that is triggered by IR. Thus, induction of TP expression by low dose IR may be a therapeutic approach to potentially overcome FU chemoresistance in PDAC.
MeSH term(s)	Adenocarcinoma/drug therapy ; Adenocarcinoma/radiotherapy ; Cell Line, Tumor ; Fluorouracil/metabolism ; Fluorouracil/pharmacology ; Fluorouracil/therapeutic use ; Humans ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/radiotherapy ; RNA, Small Interfering ; Radiation, Ionizing ; Thymidine Phosphorylase/genetics ; Thymidine Phosphorylase/metabolism ; Pancreatic Neoplasms
Chemical Substances	RNA, Small Interfering ; Thymidine Phosphorylase (EC 2.4.2.4) ; Fluorouracil (U3P01618RT)
Language	English
Publishing date	2022-01-27
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	124987-3
ISSN	1432-2099 ; 0301-634X
ISSN (online)	1432-2099
ISSN	0301-634X
DOI	10.1007/s00411-022-00962-w
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