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Article: Visceral Medicine: The View of GI.

Huebener, Peter / Amin, Tania / Lohse, Ansgar W

2023 Volume 39, Issue 6, Page(s) 163–165

Language	English
Publishing date	2023-09-12
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2850733-2
ISSN	2297-475X ; 2297-4725
ISSN (online)	2297-475X
ISSN	2297-4725
DOI	10.1159/000533435
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Book ; Online ; Thesis: Einfluss der Tumor-assoziierten Fibroblasten auf Differenzierung, Proliferation und Therapieansprechen in pankreatischen Neuroendokrinen Tumoren

Amin, Tania [Verfasser]

2020

Author's details	Tania Amin
Keywords	Medizin, Gesundheit ; Medicine, Health
Subject code	sg610
Language	German
Publisher	Staats- und Universitätsbibliothek Hamburg Carl von Ossietzky
Publishing place	Hamburg
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article ; Online: Does gamma-glutamyltransferase correlate with liver tumor burden in neuroendocrine tumors?

Schmidt, Benjamin Christopher / Leiderer, Miriam Theresa / Amin, Tania / Viol, Fabrice / Huber, Samuel / Henes, Frank Oliver / Schrader, Jörg

Endocrine

2023 Volume 83, Issue 2, Page(s) 511–518

Abstract: Purpose: In patients with neuroendocrine tumors (NETs) and liver metastases, increased gamma-glutamyltransferase (GGT) is commonly assumed as an indicator for progressive disease. To date, however, empirical data are lacking. This study aimed to ... ...

Abstract	Purpose: In patients with neuroendocrine tumors (NETs) and liver metastases, increased gamma-glutamyltransferase (GGT) is commonly assumed as an indicator for progressive disease. To date, however, empirical data are lacking. This study aimed to investigate associations between GGT and liver tumor burden. In longitudinal analyses, associations of GGT and radiographic responses of liver metastases under therapy were investigated. Methods: The cross-sectional sample consisted of 104 patients who were treated at the University Medical Center Hamburg-Eppendorf from 2008 to 2021 (mean age 62.3 ± 12.6 years, 58.7% male). GGT and liver imaging were identified in a time range of 3 months. Radiologic reassessments were performed to estimate liver tumor burden. In a separate longitudinal sample (n = 15), the course of GGT levels under chemotherapy was analyzed. Data were retrospectively analyzed with a univariate ANOVA, linear regression analyses, and Wilcoxon tests. Results: Of 104 cross-sectionally analyzed patients, 54 (51.9%) showed a GGT elevation. GGT levels and liver tumor burden were positively correlated (p < 0.001), independently from age, gender, primary tumor location, grading, and cholestasis. Notably, GGT increase was associated with a liver tumor burden of >50%. In the longitudinal sample, 10 of 11 patients with progressive disease showed increasing GGT, whereas 4 of 4 patients with regressive disease showed declining GGT. Conclusion: Our findings indicate that GGT is associated with liver tumor burden. Over the course of therapy, GGT appears to change in line with radiographic responses. Further longitudinal studies with larger sample sizes are required to define GGT as a reliable marker for tumor response.
MeSH term(s)	Humans ; Male ; Middle Aged ; Aged ; Female ; gamma-Glutamyltransferase ; Retrospective Studies ; Neuroendocrine Tumors ; Cross-Sectional Studies ; Liver Neoplasms
Chemical Substances	gamma-Glutamyltransferase (EC 2.3.2.2)
Language	English
Publishing date	2023-09-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	1194484-5
ISSN	1559-0100 ; 1355-008X ; 0969-711X
ISSN (online)	1559-0100
ISSN	1355-008X ; 0969-711X
DOI	10.1007/s12020-023-03545-x
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Article ; Online: Non-invasive imaging and clinical skin scores in juvenile localized scleroderma.

Pain, Clare E / Murray, Andrea / Dinsdale, Graham / Marsden, Antonia / Manning, Joanne / Riley, Phil / Leone, Valentina / Amin, Tania / Zulian, Francesco / Herrick, Ariane L

Rheumatology (Oxford, England)

2023 Volume 63, Issue 5, Page(s) 1332–1340

Abstract: Objectives: To evaluate whether in juvenile localized scleroderma (JLS), non-invasive imaging can differentiate affected from non-affected skin and whether imaging correlates with a validated skin score [Localised Scleroderma Cutaneous Assessment Tool ( ... ...

Abstract	Objectives: To evaluate whether in juvenile localized scleroderma (JLS), non-invasive imaging can differentiate affected from non-affected skin and whether imaging correlates with a validated skin score [Localised Scleroderma Cutaneous Assessment Tool (LoSCAT)]. Methods: A total of 25 children with JLS were recruited into a prospective study and a single 'target' lesion was selected. High-frequency ultrasound (HFUS, measuring skin thickness), infrared thermography (IRT, skin temperature), laser Doppler imaging (LDI, skin blood flow) and multispectral imaging (MSI, oxygenation) were performed at four sites: two of affected skin (centre and inner edge of lesion) and two of non-affected skin (1 cm from the edge of the lesion 'outer' and contralateral non-affected side) at four visits at 3 month intervals. Results: Differences between affected and non-affected skin were detected with all four techniques. Compared with non-affected skin, affected skin was thinner (P < 0.001), with higher temperature (P < 0.001-0.006), perfusion (P < 0.001-0.039) and oxygenation (P < 0.001-0.028). Lesion skin activity (LoSCAT) was positively correlated with centre HFUS [r = 0.32 (95% CI 0.02, 0.61), P = 0.036] and negatively correlated with centre LDI [r = -0.26 (95% CI -0.49, -0.04), P = 0.022]. Lesion skin damage was positively correlated with centre and inner IRT [r = 0.43 (95% CI 0.19, 0.67), P < 0.001 and r = 0.36 (95% CI 0.12, 0.59), P = 0.003, respectively] and with centre and inner LDI [r = 0.37 (95% CI 0.05, 0.69), P = 0.024 and r = 0.41 (95% CI 0.08, 0.74), P = 0.015, respectively]. Conclusion: Non-invasive imaging can detect differences between affected and non-affected skin in JLS and may help to differentiate between activity (thicker, less well-perfused skin) and damage (thinner, highly perfused skin).
MeSH term(s)	Humans ; Scleroderma, Localized/diagnostic imaging ; Female ; Male ; Child ; Skin/diagnostic imaging ; Skin/pathology ; Prospective Studies ; Thermography/methods ; Adolescent ; Skin Temperature ; Ultrasonography/methods ; Severity of Illness Index ; Laser-Doppler Flowmetry ; Child, Preschool ; Scleroderma, Systemic
Language	English
Publishing date	2023-08-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/kead380
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Article ; Online: Perioperative management of pancreatic exocrine insufficiency-evidence-based proposal for a paradigm shift in pancreatic surgery.

Stern, Louisa / Schuette, Miriam / Goetz, Mara R / Nitschke, Christine / Bardenhagen, Jan / Scognamiglio, Pasquale / Stüben, Björn-Ole / Calavrezos, Lenika / Amin, Tania / Heumann, Asmus / Lohse, Ansgar W / de Heer, Geraldine / Izbicki, Jakob R / Uzunoglu, Faik G

HPB : the official journal of the International Hepato Pancreato Biliary Association

2023 Volume 26, Issue 1, Page(s) 117–124

Abstract: Background: Despite exocrine pancreatic insufficiency (EPI) being a significant consequence of pancreatic surgery, there is still no consensus on its perioperative management. This study aimed to evaluate unselective pancreatic enzyme replacement ... ...

Abstract	Background: Despite exocrine pancreatic insufficiency (EPI) being a significant consequence of pancreatic surgery, there is still no consensus on its perioperative management. This study aimed to evaluate unselective pancreatic enzyme replacement therapy (PERT). Methods: A prospective, observational study of patients undergoing partial pancreatectomy was conducted. EPI status was assessed pre- and postoperatively, based on three fecal-elastase measurements each. Characteristic symptoms were evaluated by questionnaire. In 85 post-surgical patients, the subjective burden of PERT was measured. Results: 101 patients were followed prospectively. Preoperative EPI screening was available for 83 patients, of which 48% were diagnosed with preexisting EPI. Of those patients with regular exocrine function, 54% developed EPI de novo; this rate being higher following pancreatic head resections (72%) compared to left-sided pancreatectomies (LP) (20%) (p = 0.016). Overall postoperative EPI prevalence was significantly greater following pancreatic head resections (86%) than LP (33%) (p < 0.001). Only young and female patients described a significant burden related to PERT. Conclusion: For all patients undergoing pancreatic head resection PERT should be considered beginning prior to surgery, due to the subgroup's high EPI rate and the comparatively low burden of PERT. Patients with LP are at lower risk and should be pre- and postoperatively screened and supplemented accordingly.
MeSH term(s)	Humans ; Female ; Prospective Studies ; Exocrine Pancreatic Insufficiency/diagnosis ; Exocrine Pancreatic Insufficiency/etiology ; Exocrine Pancreatic Insufficiency/drug therapy ; Pancreas ; Digestive System Surgical Procedures ; Pancreatectomy/adverse effects ; Enzyme Replacement Therapy/adverse effects
Language	English
Publishing date	2023-09-09
Publishing country	England
Document type	Observational Study ; Journal Article
ZDB-ID	2131251-5
ISSN	1477-2574 ; 1365-182X
ISSN (online)	1477-2574
ISSN	1365-182X
DOI	10.1016/j.hpb.2023.09.003
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Article: The Patient's Point of View: COVID-19 and Neuroendocrine Tumor Disease.

Krug, Sebastian / Khosravian, Maryam / Weissbach, Julia / George, Katharina / Damm, Marko / Garbe, Jakob / Walldorf, Jens / Reuken, Philipp A / Amin, Tania / Siebenhüner, Alexander / Rosendahl, Jonas / Gress, Thomas M / Michl, Patrick / Schrader, Jörg / Rinke, Anja

Cancers

2022 Volume 14, Issue 3

Abstract: The assessment of cancer patient care during the COVID-19 pandemic has been mainly reported from a physician's perspective. Patients with rare tumor entities such as neuroendocrine tumors (NET), which require a complex and specialized care infrastructure, ...

Abstract	The assessment of cancer patient care during the COVID-19 pandemic has been mainly reported from a physician's perspective. Patients with rare tumor entities such as neuroendocrine tumors (NET), which require a complex and specialized care infrastructure, were highly affected by the COVID-19 crisis. Using a structured questionnaire consisting of a general section on the disease and a special COVID-19 section to record medical care, vaccination behavior as well as social and psycho-emotional parameters were collected from NET patients. The survey was distributed via direct medical contact and via the patient organization NETZWERK NeT. A total of 684 patients participated in the survey and 79.2% (
Language	English
Publishing date	2022-01-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14030613
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Article ; Online: Novel preclinical gastroenteropancreatic neuroendocrine neoplasia models demonstrate the feasibility of mutation-based targeted therapy.

Viol, Fabrice / Sipos, Bence / Fahl, Martina / Clauditz, Till S / Amin, Tania / Kriegs, Malte / Nieser, Maike / Izbicki, Jakob R / Huber, Samuel / Lohse, Ansgar W / Schrader, Jörg

Cellular oncology (Dordrecht)

2022

Abstract: Purpose: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) form a rare and remarkably heterogeneous group of tumors. Therefore, establishing personalized therapies is eminently challenging. To achieve progress in preclinical drug development, ... ...

Abstract	Purpose: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) form a rare and remarkably heterogeneous group of tumors. Therefore, establishing personalized therapies is eminently challenging. To achieve progress in preclinical drug development, there is an urgent need for relevant tumor models. Methods: We successfully established three gastroenteropancreatic neuroendocrine tumor (GEP-NET) cell lines (NT-18P, NT-18LM, NT-36) and two gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) cell lines (NT-32 and NT-38). We performed a comprehensive characterization of morphology, NET differentiation, proliferation and intracellular signaling pathways of these five cell lines and, in addition, of the NT-3 GEP-NET cell line. Additionally, we conducted panel sequencing to identify genomic alterations suitable for mutation-based targeted therapy. Results: We found that the GEP-NEN cell lines exhibit a stable neuroendocrine phenotype. Functional kinome profiling revealed a higher activity of serine/threonine kinases (STK) as well as protein tyrosine kinases (PTK) in the GEP-NET cell lines NT-3 and NT-18LM compared to the GEP-NEC cell lines NT-32 and NT-38. Panel sequencing revealed a mutation in Death Domain Associated Protein (DAXX), sensitizing NT-18LM to the Ataxia telangiectasia and Rad3 related (ATR) inhibitor Berzosertib, and a mutation in AT-Rich Interaction Domain 1A (ARID1A), sensitizing NT-38 to the Aurora kinase A inhibitor Alisertib. Small interfering RNA-mediated knock down of DAXX in the DAXX wild type cell line NT-3 sensitized these cells to Berzosertib. Conclusions: The newly established GEP-NET and GEP-NEC cell lines represent comprehensive preclinical in vitro models suitable to decipher GEP-NEN biology and pathogenesis. Additionally, we present the first results of a GEP-NEN-specific mutation-based targeted therapy. These findings open up new potentialities for personalized therapies in GEP-NEN.
Language	English
Publishing date	2022-10-21
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2595109-9
ISSN	2211-3436 ; 1875-8606 ; 2211-3428
ISSN (online)	2211-3436
ISSN	1875-8606 ; 2211-3428
DOI	10.1007/s13402-022-00727-z
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Article ; Online: Metabolic Syndrome Is Associated with Impaired Survival after Surgery for Pancreatic Neuroendocrine Tumors.

Awwad, Fayez / Ozga, Ann-Kathrin / Amin, Tania / Schlueter, Catarina / Kailani, Sajeda / Perez, Daniel / Wolter, Stefan / Sauter, Guido / Izbicki, Jakob / Lohse, Ansgar Wilhelm / Schrader, Joerg

Neuroendocrinology

2022 Volume 112, Issue 12, Page(s) 1225–1236

Abstract: Introduction: Pancreatic neuroendocrine tumors (pNETs) are a heterogeneous group of neoplasms. Surgery is the only curative treatment option. However, our understanding of predictors of survival after surgery remains incomplete. The aim of the study was ...

Abstract	Introduction: Pancreatic neuroendocrine tumors (pNETs) are a heterogeneous group of neoplasms. Surgery is the only curative treatment option. However, our understanding of predictors of survival after surgery remains incomplete. The aim of the study was to evaluate metabolic syndrome (MetS) as a prognostic factor in pNET. Methods: In a retrospective single-center cohort study, we examined the influence of MetS in 120 patients with curative intended resection of pNETs on overall survival (OS), recurrence-free survival, and outcome after recurrence. Results: MetS was present in 32 patients (26.6%). Patients with MetS had an impaired OS after curative intended surgery compared to patients without MetS (median OS 72 months [95% CI 13.3-130.7] vs. not reached, p < 0.001). The shortest survival was observed in patients with MetS in the presence of oligometastatic disease at time of surgery. In a multivariable Cox regression analysis, MetS was identified as an independent risk factor for mortality (hazard ratio [HR] = 4.54, 95% CI [1.88-11.00], p = 0.01). In our dataset, MetS was not associated with tumor recurrence or recurrence-free survival. Nevertheless, in patients with recurrence, MetS was associated with shorter time to recurrence (median 3.4 months, 95% CI [2.48-4.24], vs. 20.1 months, 95% CI [10.8-29.49], p < 0.001), and poor outcome (HR = 5.03, 95% CI [1.25-20.20], p = 0.01). Conclusions: We identified MetS as a negative prognostic factor after curative intended surgery for pNET. In particular, patients with oligometastatic disease might not benefit from extensive surgery in the presence of MetS. Furthermore, MetS had a strong impact on survival after recurrence.
MeSH term(s)	Humans ; Neuroendocrine Tumors/complications ; Neuroendocrine Tumors/surgery ; Pancreatic Neoplasms/complications ; Pancreatic Neoplasms/surgery ; Retrospective Studies ; Metabolic Syndrome/complications ; Metabolic Syndrome/surgery ; Cohort Studies ; Neuroectodermal Tumors, Primitive ; Prognosis
Language	English
Publishing date	2022-03-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	123303-8
ISSN	1423-0194 ; 0028-3835
ISSN (online)	1423-0194
ISSN	0028-3835
DOI	10.1159/000524366
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Article ; Online: Cancer-Associated Fibroblasts Induce Proliferation and Therapeutic Resistance to Everolimus in Neuroendocrine Tumors through STAT3 Activation.

Amin, Tania / Viol, Fabrice / Krause, Jenny / Fahl, Martina / Eggers, Corinna / Awwad, Fayez / Schmidt, Benjamin / Benten, Daniel / Ungefroren, Hendrik / Fraune, Christoph / Clauditz, Till S / Sauter, Guido / Izbicki, Jakob R / Lohse, Ansgar W / Huber, Samuel / Schrader, Jörg

Neuroendocrinology

2022 Volume 113, Issue 5, Page(s) 501–518

Abstract: Introduction: Cancer-associated fibroblasts (CAF) have been identified as relevant contributors to cancer progression and drug resistance in many tumors. Although neuroendocrine tumors (NET) are often associated with a strong stromal reaction, no study ... ...

Abstract	Introduction: Cancer-associated fibroblasts (CAF) have been identified as relevant contributors to cancer progression and drug resistance in many tumors. Although neuroendocrine tumors (NET) are often associated with a strong stromal reaction, no study has addressed whether CAF are involved in progression and therapeutic resistance in NET. The aim of this study was to characterize the role of CAF in NET. Methods: We established primary CAF cultures derived from NET liver metastases to study the effect on NET cell lines NT-3 and BON. Immunohistochemistry was performed on tissue sections of primary and metastatic NET tissue. Results: Immunohistochemistry identified CAF dispersed in between tumor cells and within fibrotic bands separating tumor cell clusters in NET. Stimulating NET cells with CAF decreased expression of SSTR2 and chromogranin A and induced expression of CXCR4. CAF induced a 2.3-fold increase in proliferation and completely reversed the response to everolimus in NT-3 cells. We identified STAT3 as the main signaling pathway induced by CAF. STAT3 targeting by small interfering RNA knockdown and inhibitors prevented CAF-induced proliferation and restored everolimus responsiveness. STAT3 activation in NET tissue was associated with decreased chromogranin A expression, increased Ki-67 index, and decreased 5-year overall and progression-free survival. CAF directly influence proliferation and therapeutic response in NET cells. Conclusion: Identifying STAT3 as the contributing pathway of this so far neglected tumor-stroma interaction has the potential to become a new therapeutic target to halt tumor growth and to restore therapeutic responsiveness in NET.
MeSH term(s)	Humans ; Everolimus/pharmacology ; Cancer-Associated Fibroblasts/metabolism ; Cancer-Associated Fibroblasts/pathology ; Neuroendocrine Tumors/pathology ; Drug Resistance, Neoplasm ; Chromogranin A/metabolism ; Cell Line, Tumor ; Cell Proliferation ; STAT3 Transcription Factor/metabolism
Chemical Substances	Everolimus (9HW64Q8G6G) ; Chromogranin A ; STAT3 protein, human ; STAT3 Transcription Factor
Language	English
Publishing date	2022-12-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	123303-8
ISSN	1423-0194 ; 0028-3835
ISSN (online)	1423-0194
ISSN	0028-3835
DOI	10.1159/000528539
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Article ; Online: Primary hypertrophic osteoarthropathy: ultrasound and MRI findings.

Adams, Brook / Amin, Tania / Leone, Valentina / Wood, Mark / Kraft, Jeannette K

Pediatric radiology

2016 Volume 46, Issue 5, Page(s) 727–730

Abstract: Primary hypertrophic osteoarthropathy is a rare genetic disorder related to failures in prostaglandin metabolism. Patients present with joint pain, limb enlargement, skin thickening and finger clubbing. Radiographs show characteristic periosteal reaction ...

Abstract	Primary hypertrophic osteoarthropathy is a rare genetic disorder related to failures in prostaglandin metabolism. Patients present with joint pain, limb enlargement, skin thickening and finger clubbing. Radiographs show characteristic periosteal reaction and thickening along the long bones. We present MRI and US findings in a child with the condition. Ultrasound showed echogenic tissue surrounding the long bones, presumably reflecting oedema and inflammatory tissue. Doppler sonograms demonstrated increased vascularity on the surface of some superficial bony structures.
Language	English
Publishing date	2016-05
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	124459-0
ISSN	1432-1998 ; 0301-0449
ISSN (online)	1432-1998
ISSN	0301-0449
DOI	10.1007/s00247-016-3544-8
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