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  • 1
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    Online Resource
    Caveolin 1 Expression Correlates with Poor Prognosis and Focal Adhesion Kinase Expression in Gastric Cancer
    S. Karger AG ; 2013
    In:  Pathobiology Vol. 80, No. 2 ( 2013), p. 87-94
    Details
    In: Pathobiology, S. Karger AG, Vol. 80, No. 2 ( 2013), p. 87-94
    Abstract: 〈 b 〉 〈 i 〉 Objective: 〈 /i 〉 〈 /b 〉 〈 i 〉 Caveolin 1 〈 /i 〉 gene is known as a tumor promoter or suppressor, depending on the tumor type and/or tumor stage. We aimed to investigate the clinical significance of caveolin 1 protein (Cav1) expression in gastric cancer (GC). 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Immunohistochemistry was performed on tissue array slides containing 405 GC specimens. The relationships between Cav1 expression and clinicopathological factors, prognosis, focal adhesion kinase expression, mucin phenotypes and p53 expression were analyzed. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 In non-neoplastic gastric mucosa, Cav1 was not expressed in the epithelial compartment. In GC, positive staining of Cav1 was shown in 22 (5.4%) of 405 cases and was significantly higher in the advanced GC group than in the early GC group (p 〈 i 〉 = 〈 /i 〉 0.037). Also, it was significantly associated with advanced pTNM stage (p 〈 i 〉 = 〈 /i 〉 0.027) and lymph node metastasis (p 〈 i 〉 = 〈 /i 〉 0.018). Moreover, survival analysis showed that Cav1 expression was an independent prognostic factor of poor survival (p = 0.028). In addition, the expression of Cav1 was positively correlated with that of focal adhesion kinase (p = 0.034). 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 These results indicate that the expression of Cav1 is significantly correlated with cancer progression and poor prognosis in GC. Thus, Cav1 could supplement its protein expression for the diagnosis and treatment of GC.
    Type of Medium: Online Resource
    ISSN: 1015-2008 , 1423-0291
    URL: Article
    DOI: 10.1159/000341685
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2013
    detail.hit.zdb_id: 1483541-1
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  • 2
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    Leptin, MUC2 and mTOR in Appendiceal Mucinous Neoplasms
    S. Karger AG ; 2012
    In:  Pathobiology Vol. 79, No. 1 ( 2012), p. 45-53
    Details
    In: Pathobiology, S. Karger AG, Vol. 79, No. 1 ( 2012), p. 45-53
    Abstract: 〈 i 〉 Objective: 〈 /i 〉 Leptin contributes to mucin production in colonic epithelium and regulates carcinogenesis via various signalling pathways. We evaluated the proteins involved in mucin-producing carcinogenesis and putative targets for molecular therapy in appendiceal mucinous neoplasms. 〈 i 〉 Methods: 〈 /i 〉 Immunohistochemistry and fluorescence in situ hybridization were performed in 22 cases of appendiceal mucinous adenoma, 20 mucinous neoplasms of uncertain malignant potential and 14 mucinous adenocarcinomas. 〈 i 〉 Results: 〈 /i 〉 Leptin, MUC2, MUC5AC, mTOR and ERK were more frequently immunopositive in mucinous adenocarcinomas compared with mucinous adenomas or mucinous neoplasms of uncertain malignant potential (p 〈 0.05). STAT3 revealed immunopositivity in 82% of tumours, regardless of tumour category. MUC2 immunopositivity was associated with pseudomyxoma peritonei (p 〈 0.05). None of the tumours exhibited c-kitimmunoexpression, amplification of 〈 i 〉 Her2 〈 /i 〉 or 〈 i 〉 EGFR, 〈 /i 〉 or translocation of 〈 i 〉 ALK 〈 /i 〉 . The mTOR-immunopositive group of patients had a lower rate of disease-free survival compared with the mTOR-immunonegative group (p 〈 0.05). 〈 i 〉 Conclusions: 〈 /i 〉 Leptin may collaborate with MUC2 and MUC5AC in mucin-producing carcinogenesis in an mTOR-, STAT3- and ERK-dependent manner. STAT3 may be activated early during tumorigenesis. 〈 i 〉 MUC2 〈 /i 〉 and 〈 i 〉 mTOR 〈 /i 〉 (but not c 〈 i 〉 -kit 〈 /i 〉 , 〈 i 〉 Her2 〈 /i 〉 , 〈 i 〉 EGFR 〈 /i 〉 and 〈 i 〉 ALK 〈 /i 〉 ) may represent targets for molecular therapy in pseudomyxoma peritonei and appendiceal mucinous adenocarcinoma, respectively.
    Type of Medium: Online Resource
    ISSN: 1015-2008 , 1423-0291
    URL: Article
    DOI: 10.1159/000332739
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2012
    detail.hit.zdb_id: 1483541-1
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  • 3
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    Loss of AT-Rich Interactive Domain 1A Expression in Gastrointestinal Malignancies
    S. Karger AG ; 2015
    In:  Oncology Vol. 88, No. 4 ( 2015), p. 234-240
    Details
    In: Oncology, S. Karger AG, Vol. 88, No. 4 ( 2015), p. 234-240
    Abstract: 〈 b 〉 〈 i 〉 Objective: 〈 /i 〉 〈 /b 〉 AT-rich interactive domain 1A (ARID1A) has recently been identified as a novel tumor suppressor in various tumor types. This study was designed to explore the clinical relevance and prognostic impact of ARID1A expression loss in colorectal cancer (CRC) and gastric cancer (GC). 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Immunohistochemistry for ARID1A was performed using tissue microarray blocks containing 196 CRCs and 275 GCs, along with paired normal mucosa. Data on clinicopathologic variables and oncologic outcomes of patients were collected and analyzed. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 We identified 6.1% (12/196) CRC and 8.0% (22/275) GC cases showing loss of ARID1A expression. Expression of ARID1A in paired mucosal epithelial cells was normal in all patients. Loss of ARID1A expression was significantly correlated with negative lymphatic invasion (p = 0.003) in CRC, with large tumor size (p = 0.037) in GC, and with expanding tumor border in both tumor types (CRC, p = 0.010; GC, p = 0.031). However, no association was evident between ARID1A expression and 5-year overall survival in both tumor types. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 Loss of ARID1A expression is uncommon and not associated with oncologic outcome but may be related to less invasive clinicopathologic features in CRC and GC. Further studies with a larger number of subjects are needed to establish the possible prognostic impact of ARID1A expression loss. © 2014 S. Karger AG, Basel
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    URL: Article
    DOI: 10.1159/000369140
    RVK:
    XH 3305
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2015
    detail.hit.zdb_id: 1483096-6
    detail.hit.zdb_id: 250101-6
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  • 4
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    Expression of the ERBB Family of Ligands and Receptors in Gastric Cancer
    S. Karger AG ; 2017
    In:  Pathobiology Vol. 84, No. 4 ( 2017), p. 210-217
    Details
    In: Pathobiology, S. Karger AG, Vol. 84, No. 4 ( 2017), p. 210-217
    Abstract: 〈 b 〉 〈 i 〉 Objective: 〈 /i 〉 〈 /b 〉 Gastric cancer (GC) is the second most common cancer and the third leading cause of cancer-related death in Korea. Alterations in the ERBB (homology to the erythroblastoma viral gene product, v-erbB) receptor family and ERBB-related signaling pathways are frequently observed in GC. However, the roles of the ERBB receptors and their ligands in GC are not well established. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We evaluated the expression levels of various ERBB receptor ligands (i.e., heparin-binding epidermal growth factor-like growth factor [HBEGF], transforming growth factor-α [TGFA] , amphiregulin [AREG], epiregulin [EREG] , epidermal growth factor [EGF], and betacellulin [BTC] ) and 3 ERBB family receptors (i.e., epidermal growth factor receptor [EGFR], human EGFR2 [HER2] , and ERBB3) in 313 cases of GC using immunohistochemistry, fluorescence in situ hybridization, and mRNA in situ hybridization. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 A high expression of EGFR, HER2, and ERBB3 was observed in 30, 32, and 27 cases, respectively. A high expression of HBEGF, TGFA, AREG, EREG, EGF, and BTC was observed in 91, 97, 151, 74, 26, and 37 cases, respectively. A high expression of TGFA was associated with better survival, while a high expression of BTC was associated with worse survival. These results were confirmed using Cox proportional hazards analysis. HBEGF, TGFA, AREG, tumor-node-metastasis classification, Lauren's classification, and ERBB3 were significant survival parameters in multivariate analysis. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Among the ERBB family receptors and ligands examined, 3 ligands (i.e., TGFA, HBEGF, and AREG) and ERBB3 had a prognostic impact.
    Type of Medium: Online Resource
    ISSN: 1015-2008 , 1423-0291
    URL: Article
    DOI: 10.1159/000464250
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2017
    detail.hit.zdb_id: 1483541-1
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  • 5
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    Immunohistochemical Analysis of Cell Cycle-Related Molecules in Gastric Carcinoma: Prognostic Significance, Correlation with Clinicopathological Parameters, Proliferation and Apoptosis
    S. Karger AG ; 2008
    In:  Pathobiology Vol. 75, No. 6 ( 2008), p. 364-372
    Details
    In: Pathobiology, S. Karger AG, Vol. 75, No. 6 ( 2008), p. 364-372
    Abstract: 〈 i 〉 Objective: 〈 /i 〉 We aimed to investigate the biological significance of cell cycle regulators in gastric carcinoma. 〈 i 〉 Methods: 〈 /i 〉 Immunohistochemistry and TUNEL staining were performed on tissue array slides containing 293 gastric carcinoma specimens. The relationship between the protein expression of each of the cell cycle regulators and prognosis, clinicopathological features, proliferation, or apoptosis was evaluated. 〈 i 〉 Results: 〈 /i 〉 The nuclear immunoreactivity for cyclin D1, cyclin E, p21, and p27 was observed in 22, 14, 31 and 27% of cases, respectively. The expression of cyclin D1, p21, or p27 positively correlated with early pTNM stages, tumor cell proliferation (represented by Ki-67 labeling) and good prognosis, whereas it inversely correlated with the lymph node metastasis (p 〈 0.05). On the other hand, p27 expression inversely correlated with the apoptosis index represented by TUNEL staining (p 〈 0.001). In addition, the expression of cyclin D1 positively correlated with that of p21 or p27 (p 〈 0.05). 〈 i 〉 Conclusions: 〈 /i 〉 Our results showed that the expression of cyclin D1, p21 and p27, alone or in combination, are early events in gastric tumorigenesis and may serve as a candidate molecular marker for the early gastric carcinoma.
    Type of Medium: Online Resource
    ISSN: 1015-2008 , 1423-0291
    URL: Article
    DOI: 10.1159/000164221
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2008
    detail.hit.zdb_id: 1483541-1
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  • 6
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    DNA Damage Response-Related Proteins in Gastric Cancer: ATM, Chk2 and p53 Expression and Their Prognostic Value
    S. Karger AG ; 2014
    In:  Pathobiology Vol. 81, No. 1 ( 2014), p. 25-35
    Details
    In: Pathobiology, S. Karger AG, Vol. 81, No. 1 ( 2014), p. 25-35
    Abstract: 〈 b 〉 〈 i 〉 Objectives: 〈 /i 〉 〈 /b 〉 The aims of this study were to assess expressions of the DNA damage response (DDR)-related proteins and to investigate their clinical significances in gastric carcinoma. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Two independent cohorts, a training set (n = 524) and validation set (n = 394), of gastric cancer patients were enrolled. Ataxia telangiectasia mutated (ATM), checkpoint kinase 2 (Chk2), and p53 expressions were examined by immunohistochemistry using tissue microarray. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 ATM loss, Chk2 loss, and p53 positivity were observed in 21.8, 14.1, and 36.1% of the training set, and in 17.3, 12.2, and 35.8% of the validation set, respectively. In the training set, the aberrant expressions of ATM, Chk2, or p53 were significantly associated with an advanced TNM stage and poor disease-specific survival. This association was verified in the validation set. Chk2 positivity and p53 negativity were significantly related to a prolonged disease-specific survival. Also, patients with nonaberrant expressional levels of all 3 DDR-related proteins had a more favorable outcome than others. Multivariate analyses showed that Chk2 loss and at least 1 aberrant DDR-related protein remained as independent prognostic factors of poor disease-specific survival. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 This study elucidated the prognostic implications of DDR-related proteins, and suggests that their aberrant expressions play critical roles in the development and progression of gastric cancer.
    Type of Medium: Online Resource
    ISSN: 1015-2008 , 1423-0291
    URL: Article
    DOI: 10.1159/000351072
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2014
    detail.hit.zdb_id: 1483541-1
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  • 7
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    Evaluation of Fibroblast Growth Factor Receptor 2 Expression, Heterogeneity and Clinical Significance in Gastric Cancer
    S. Karger AG ; 2015
    In:  Pathobiology Vol. 82, No. 6 ( 2015), p. 269-279
    Details
    In: Pathobiology, S. Karger AG, Vol. 82, No. 6 ( 2015), p. 269-279
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 We aimed to evaluate the protein and mRNA expression of fibroblast growth factor receptor 2 (FGFR2) by immunohistochemistry (IHC) and mRNA in situ hybridization (ISH), respectively, and to assess the heterogeneity of FGFR2 expression in gastric cancer (GC). 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 A tissue microarray containing 362 surgically resected GC tissues and 135 matched metastatic lymph nodes was evaluated using FGFR2b IHC and 〈 i 〉 FGFR2 〈 /i 〉 ISH. 〈 i 〉 FGFR2 〈 /i 〉 fluorescence ISH was also performed in 188 cases. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 All 〈 i 〉 FGFR2 〈 /i 〉 -amplified cases (5 of 188) showed FGFR2b protein and 〈 i 〉 FGFR2 〈 /i 〉 mRNA overexpression (p 〈 0.001), and 〈 i 〉 FGFR2 〈 /i 〉 amplification was not identified in FGFR2b IHC- and 〈 i 〉 FGFR2 〈 /i 〉 mRNA ISH-negative cases. Kaplan-Meier survival analysis revealed that FGFR2b protein and 〈 i 〉 FGFR2 〈 /i 〉 mRNA overexpression was significantly associated with a poor overall survival (p 〈 0.001 and p = 0.012, respectively), and multivariate analyses showed that 〈 i 〉 FGFR2 〈 /i 〉 mRNA overexpression was an independent biomarker of a poor overall survival. Intratumoral heterogeneity of FGFR2b protein and 〈 i 〉 FGFR2 〈 /i 〉 mRNA overexpression was observed in 5 of 9 (55.5%) and 18 of 21 (85.7%) cases, respectively. Discordant FGFR2b and 〈 i 〉 FGFR2 〈 /i 〉 expression results between primary and matched metastatic lymph nodes were observed in 5 of 9 (55.5%) and 4 of 14 (28.6%) cases, respectively. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 Intratumoral heterogeneity and discordant FGFR2b expression in primary tumors and metastatic lymph nodes are common in GC.
    Type of Medium: Online Resource
    ISSN: 1015-2008 , 1423-0291
    URL: Article
    DOI: 10.1159/000441149
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2015
    detail.hit.zdb_id: 1483541-1
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  • 8
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    Fibroblast Growth Factor Receptor 1 Gene Copy Number and mRNA Expression in Primary Colorectal Cancer and Its Clinicopathologic Correlation
    S. Karger AG ; 2015
    In:  Pathobiology Vol. 82, No. 2 ( 2015), p. 76-83
    Details
    In: Pathobiology, S. Karger AG, Vol. 82, No. 2 ( 2015), p. 76-83
    Abstract: 〈 b 〉 〈 i 〉 Objectives: 〈 /i 〉 〈 /b 〉 Fibroblast growth factor receptor 1 (FGFR1) has been reported to be overexpressed in colorectal cancer (CRC) and suggested to be a therapeutic target. In this study, we investigated FGFR1 expression and amplification in CRC and its correlation with clinicopathologic parameters. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 〈 i 〉 FGFR1 〈 /i 〉 dual-color fluorescence in situ hybridization and mRNA in situ hybridization were performed on tissue array blocks composed of 291 consecutive primary CRCs. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Of the 291 CRC cases, 〈 i 〉 FGFR1 〈 /i 〉 gene amplification was found in 11 (3.8%) cases, high 〈 i 〉 FGFR1 〈 /i 〉 polysomy in 4 (1.4%) cases, and 〈 i 〉 FGFR1 〈 /i 〉 gene copy number (GCN) gain (GCN 〉 2) in 77 (26.5%) cases. 〈 i 〉 FGFR1 〈 /i 〉 GCN gain was significantly associated with left-sided location, lymph node metastasis, distant metastasis, and higher TNM stage (p 〈 0.05). 〈 i 〉 FGFR1 〈 /i 〉 GCN gain also correlated with poor patient survival (p = 0.015). 〈 i 〉 FGFR1 〈 /i 〉 mRNA overexpression (score 3-4) was present in 11.7% (34/291) of the patients and was significantly associated with 〈 i 〉 FGFR1 〈 /i 〉 GCN alteration (Pearson correlation coefficient, r = 0.463; p 〈 0.001). 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 〈 i 〉 FGFR1 〈 /i 〉 GCN gain was more frequently found (26.5%) than gene amplification (3.8%) and correlated with aggressive clinical behavior in consecutive CRC patients. 〈 i 〉 FGFR1 〈 /i 〉 GCN alteration was associated with a high 〈 i 〉 FGFR1 〈 /i 〉 mRNA level.
    Type of Medium: Online Resource
    ISSN: 1015-2008 , 1423-0291
    URL: Article
    DOI: 10.1159/000398807
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2015
    detail.hit.zdb_id: 1483541-1
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  • 9
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    Cytologic Evaluation of Low Grade Transitional Cell Carcinoma and Instrument Artifact in Bladder Washings
    S. Karger AG ; 2002
    In:  Acta Cytologica Vol. 46, No. 2 ( 2002), p. 341-348
    Details
    In: Acta Cytologica, S. Karger AG, Vol. 46, No. 2 ( 2002), p. 341-348
    Type of Medium: Online Resource
    ISSN: 1938-2650 , 0001-5547
    URL: Article
    DOI: 10.1159/000326732
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2002
    detail.hit.zdb_id: 2256676-4
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  • 10
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    Impact of BMI on Complications of Gastric Endoscopic Submucosal Dissection
    S. Karger AG ; 2021
    In:  Digestive Diseases Vol. 39, No. 4 ( 2021), p. 301-309
    Details
    In: Digestive Diseases, S. Karger AG, Vol. 39, No. 4 ( 2021), p. 301-309
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Gastric endoscopic submucosal dissection (ESD) has a high rate of complications. However, it is unclear whether BMI affects ESD complications. We aimed to investigate the impact of BMI on ESD complications. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 A total of 7,263 patients who underwent gastric ESD were classified into 3 groups according to the Asia-Pacific classification of BMI: normal (BMI & #x3c;23 kg/m 〈 sup 〉 2 〈 /sup 〉 , 〈 i 〉 n 〈 /i 〉 = 2,466), overweight (BMI 23–24.9 kg/m 〈 sup 〉 2 〈 /sup 〉 , 〈 i 〉 n 〈 /i 〉 = 2,117), and obese (BMI ≥25 kg/m 〈 sup 〉 2 〈 /sup 〉 , 〈 i 〉 n 〈 /i 〉 = 2,680). Adjusted logistic regression analyses were conducted to assess the association between BMI and ESD complications. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Compared to the normal group, a lower incidence of perforation and a higher incidence of pneumonia and leukocytosis were found in the overweight and obese groups, and intra-ESD desaturation and hypertension were more frequent in the obese group. After adjustment for confounders, the risk of perforation significantly decreased in the overweight (odds ratio [OR] = 0.24, 95% confidence interval [CI] : 0.17–0.33) and obese (OR = 0.12, 95% CI: 0.08–0.18) groups compared to that in the normal group. Meanwhile, the risk of pneumonia significantly increased in the overweight (OR = 11.04, 95% CI: 6.31–19.31) and obese (OR = 10.71, 95% CI: 6.14–18.66) groups compared to the normal group. During sedation, the obese group had a significantly increased risk of desaturation (OR = 2.81, 95% CI: 1.18–6.69) and hypertension (OR = 1.35, 95% CI: 1.11–1.63) compared to the normal group. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 High BMI was significantly associated with ESD complications. More caution is needed in cases of obese patients undergoing ESD.
    Type of Medium: Online Resource
    ISSN: 0257-2753 , 1421-9875
    URL: Article
    DOI: 10.1159/000512899
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2021
    detail.hit.zdb_id: 1482221-0
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