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Book ; Thesis: NAD(P)H cytochrome b5 oxidoreductase

Gros, Stephanie J.

role of cysteines

2006

Author's details	vorgelegt von Stephanie Jennifer Gros
Language	English
Size	100 Bl. : Ill., graph. Darst.
Publishing country	Germany
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Duisburg, Essen, Univ., Diss., 2007
HBZ-ID	HT015241114
Database	Catalogue ZB MED Medicine, Health

In stock of ZB MED Cologne/Königswinter

Shelf mark	Loan status	Location
2007 E 2217	order for loan	Magazin

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Article: Increased Proliferation of Neuroblastoma Cells under Fructose Metabolism Can Be Measured by Isothermal Microcalorimetry.

Pini, Nicola / Huo, Zihe / Holland-Cunz, Stefan / Gros, Stephanie J

Children (Basel, Switzerland)

2021 Volume 8, Issue 9

Abstract: Neuroblastoma, like other cancer types, has an increased need for energy. This results in an increased thermogenic profile of the cells. How tumor cells optimize their energy efficiency has been discussed since Warburg described the fact that tumor cells ...

Abstract	Neuroblastoma, like other cancer types, has an increased need for energy. This results in an increased thermogenic profile of the cells. How tumor cells optimize their energy efficiency has been discussed since Warburg described the fact that tumor cells prefer an anaerobic to an aerobic metabolism in the 1920s. An important question is how far the energy efficiency is influenced by the substrate. The aim of this study was to investigate how the metabolic activity of neuroblastoma cells is stimulated by addition of glucose or fructose to the medium and if this can be measured accurately by using isothermal microcalorimetry. Proliferation of Kelly and SH-EP Tet-21/N cells was determined in normal medium, in fructose-enriched, in glucose-enriched and in a fructose/glucose-enriched environment. Heat development of cells was measured by isothermal microcalorimetry. The addition of fructose, glucose or both to the medium led to increases in the metabolic activity of the cells, resulting in increased proliferation under the influence of fructose. These changes were reflected in an enhanced thermogenic profile, mirroring the results of the proliferation assay. The tested neuroblastoma cells prefer fructose metabolism over glucose metabolism, a quality that provides them with a survival benefit under unfavorable low oxygen and low nutrient supply when fructose is available. This can be quantified by measuring thermogenesis.
Language	English
Publishing date	2021-09-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2732685-8
ISSN	2227-9067
ISSN	2227-9067
DOI	10.3390/children8090784
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Orthotopic models of esophageal carcinoma and their use in drug discovery.

Gros, Stephanie J

Current protocols in pharmacology

2011 Volume Chapter 14, Page(s) Unit14.20

Abstract: The protocol detailed in this unit is for the establishment of an orthotopic model of human esophageal adenocarcinoma in NMRI/nu mice. The resultant tumor has high metastatic potential, spreading readily to liver, lungs, and lymph nodes. This model is ... ...

Abstract	The protocol detailed in this unit is for the establishment of an orthotopic model of human esophageal adenocarcinoma in NMRI/nu mice. The resultant tumor has high metastatic potential, spreading readily to liver, lungs, and lymph nodes. This model is useful for studying primary esophageal carcinoma, tumor biology, pathogenesis, tumor progression, metastatic homing, and the efficacy of therapeutic approaches for treating this condition. The practical use of this preclinical model for drug discovery is illustrated with data from a study on the chemotherapeutic effects of HER2-targeted therapy.
MeSH term(s)	Adenocarcinoma/drug therapy ; Adenocarcinoma/pathology ; Animals ; Antineoplastic Agents/therapeutic use ; Cell Line, Tumor ; Drug Discovery/methods ; Esophageal Neoplasms/drug therapy ; Esophageal Neoplasms/pathology ; Humans ; Mice ; Mice, Nude ; Xenograft Model Antitumor Assays/methods
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2011-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1934-8290
ISSN (online)	1934-8290
DOI	10.1002/0471141755.ph1420s54
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Article: AQP1 Is Up-Regulated by Hypoxia and Leads to Increased Cell Water Permeability, Motility, and Migration in Neuroblastoma.

Huo, Zihe / Lomora, Mihai / Kym, Urs / Palivan, Cornelia / Holland-Cunz, Stefan G / Gros, Stephanie J

Frontiers in cell and developmental biology

2021 Volume 9, Page(s) 605272

Abstract: The water channel aquaporin 1 (AQP1) has been implicated in tumor progression and metastasis. It is hypothesized that AQP1 expression can facilitate the transmembrane water transport leading to changes in cell structure that promote migration. Its impact ...

Abstract	The water channel aquaporin 1 (AQP1) has been implicated in tumor progression and metastasis. It is hypothesized that AQP1 expression can facilitate the transmembrane water transport leading to changes in cell structure that promote migration. Its impact in neuroblastoma has not been addressed so far. The objectives of this study have been to determine whether AQP1 expression in neuroblastoma is dependent on hypoxia, to demonstrate whether AQP1 is functionally relevant for migration, and to further define AQP1-dependent properties of the migrating cells. This was determined by investigating the reaction of neuroblastoma cell lines, particularly SH-SY5Y, Kelly, SH-EP Tet-21/N and SK-N-BE(2)-M17 to hypoxia, quantitating the AQP1-related water permeability by stopped-flow spectroscopy, and studying the migration-related properties of the cells in a modified transwell assay. We find that AQP1 expression in neuroblastoma cells is up-regulated by hypoxic conditions, and that increased AQP1 expression enabled the cells to form a phenotype which is associated with migratory properties and increased cell agility. This suggests that the hypoxic tumor microenvironment is the trigger for some tumor cells to transition to a migratory phenotype. We demonstrate that migrating tumor cell express elevated AQP1 levels and a hypoxic biochemical phenotype. Our experiments strongly suggest that elevated AQP1 might be a key driver in transitioning stable tumor cells to migrating tumor cells in a hypoxic microenvironment.
Language	English
Publishing date	2021-02-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2021.605272
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Article: AQP1-Driven Migration Is Independent of Other Known Adverse Factors but Requires a Hypoxic Undifferentiated Cell Profile in Neuroblastoma.

Pini, Nicola / Huo, Zihe / Kym, Urs / Holland-Cunz, Stefan / Gros, Stephanie J

Children (Basel, Switzerland)

2021 Volume 8, Issue 1

Abstract: Neuroblastoma is a biologically very heterogeneous tumor with its clinical manifestation ranging from spontaneous regression to highly aggressive metastatic disease. Several adverse factors have been linked to oncogenesis, tumor progression and ... ...

Abstract	Neuroblastoma is a biologically very heterogeneous tumor with its clinical manifestation ranging from spontaneous regression to highly aggressive metastatic disease. Several adverse factors have been linked to oncogenesis, tumor progression and metastases of neuroblastoma including NMYC amplification, the neural adhesion molecule NCAM, as well as CXCR4 as a promoter of metastases. In this study, we investigate to what extent the expression of AQP1 in neuroblastoma correlates with changing cellular factors such as the hypoxic status, differentiation, expression of known adverse factors such as NMYC and NCAM, and CXCR4-related metastatic spread. Our results show that while AQP1 expression leads to an increased migratory behavior of neuroblastoma cells under hypoxic conditions, we find that hypoxia is associated with a reduction of NMYC in the same cells. A similar effect can be observed when using the tetracycline driven mechanism of SH-EP/Tet cells. When NMYC is not expressed, the expression of AQP1 is increased together with an increased expression of HIF-1α and HIF-2α. We furthermore show that when growing cells in different cell densities, they express AQP1, HIF-1α, HIF-2α, NMYC and NCAM to different degrees. AQP1 expression correlates with a hypoxic profile of these cells with increased HIF-1α and HIF-2α expression, as well as with NMYC and NCAM expression in two out of three neuroblastoma cell lines. When investigating cell properties of the cells that actually migrate, we find that the increased APQ1 expression in the migrated cells correlates with an increased NMYC and NCAM expression again in two out of three cell lines. Expression of the tumor cell homing marker CXCR4 varies between different tumor areas and between cell lines. While some migrated tumor cells highly express CXCR4, cells of other origin do not. In the initial phase of migration, we determined a dominant role of AQP1 expression of migrating cells in the scratch assay.
Language	English
Publishing date	2021-01-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2732685-8
ISSN	2227-9067
ISSN	2227-9067
DOI	10.3390/children8010048
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Article: Testicular Torsion in the Absence of Severe Pain: Considerations for the Pediatric Surgeon.

Kapp, Alexander / Troxler, David / Prüfer, Friederike / Holland-Cunz, Stefan / Frech, Martina / Gros, Stephanie J

Children (Basel, Switzerland)

2021 Volume 8, Issue 6

Abstract: Testicular torsion is a surgical emergency. Early diagnosis and surgical treatment are vital in order to preserve the affected gonad. Current surgical teaching emphasizes sudden, severe, persistent, unilateral scrotal pain as a cardinal symptom of ... ...

Abstract	Testicular torsion is a surgical emergency. Early diagnosis and surgical treatment are vital in order to preserve the affected gonad. Current surgical teaching emphasizes sudden, severe, persistent, unilateral scrotal pain as a cardinal symptom of testicular torsion. We present the case of unilateral testicular torsion in a 14-year-old patient who presented with the absence of severe pain. Despite a delayed presentation to the emergency department, the gonad could be salvaged successfully. Literature on the topic of testicular torsion presenting with minimal pain is limited. Nevertheless, pediatric surgeons might be faced with cases similar to the one we describe. Underestimating this phenomenon might lead to a delay of treatment. In such cases, ultrasound can be a beneficial addition in the diagnosis and accelerate definitive operative treatment. The presented case clearly demonstrates that, although we do not include testicular torsion without severe pain in our surgical teaching algorithms, we might encounter it in our clinical practice.
Language	English
Publishing date	2021-05-21
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2732685-8
ISSN	2227-9067
ISSN	2227-9067
DOI	10.3390/children8060429
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Article ; Online: Dysfunctional Voiding and Incontinence Scoring System for Children and Adolescents: A Tool to Predict Clinical Course and Outcome.

Sommer-Joergensen, Vivienne / Sarcevic, Jelena / Haecker, Frank-Martin / Holland-Cunz, Stefan / Gros, Stephanie J / Frech-Dörfler, Martina

European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift fur Kinderchirurgie

2022 Volume 32, Issue 5, Page(s) 429–434

Abstract: Introduction: Lower urinary tract symptoms (LUTS) in children are common. In 2005, Akbal et al published the dysfunctional voiding and incontinence scoring system (DVAISS) to assess patient's symptoms. Our study aimed to determine the value of this ... ...

Abstract	Introduction: Lower urinary tract symptoms (LUTS) in children are common. In 2005, Akbal et al published the dysfunctional voiding and incontinence scoring system (DVAISS) to assess patient's symptoms. Our study aimed to determine the value of this scoring system for predicting the severity and clinical course of voiding abnormalities in children and adolescents. Material and methods: Patients' symptoms were scored using the DVAISS in children and adolescents with LUTS presenting for the first time to our pediatric urology department between January 2010 and December 2015. We correlated the calculated score with voiding volume, clinical course, and outcome. Results: A total of 168 patients (113 boys, 55 girls; age 5-18 years) with isolated LUTS were included. In 53 patients (group 1), the DVAISS score was less than or equal to 8.5 and in the other 115 patients (group 2), the score was greater than 8.5 suggestive for relevant voiding abnormalities. Patients in group 1 showed a significantly higher average voiding volume (200 vs. 110 mL, Conclusion: Based on the DVAISS, a prediction of the clinical course and approximate treatment duration is possible. Therefore, the DVAISS is useful to assess LUTS in children and is also a valuable tool in rating the severity of the disease. It is also a quite precise predictor of the time needed to resolve the symptoms.
MeSH term(s)	Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Lower Urinary Tract Symptoms/diagnosis ; Lower Urinary Tract Symptoms/etiology ; Lower Urinary Tract Symptoms/therapy ; Male ; Urinary Incontinence/diagnosis ; Urinary Incontinence/etiology ; Urinary Incontinence/therapy ; Urination ; Urination Disorders
Language	English
Publishing date	2022-02-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	1065043-x
ISSN	1439-359X ; 0939-7248 ; 0939-6764 ; 0930-7249
ISSN (online)	1439-359X
ISSN	0939-7248 ; 0939-6764 ; 0930-7249
DOI	10.1055/s-0041-1741543
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Article ; Online: AQP1 in the Gastrointestinal Tract of Mice: Expression Pattern and Impact of AQP1 Knockout on Colonic Function.

Volkart, Stefanie / Kym, Urs / Braissant, Olivier / Delgado-Eckert, Edgar / Al-Samir, Samer / Angresius, Rebecca / Huo, Zihe / Holland-Cunz, Stefan / Gros, Stephanie J

International journal of molecular sciences

2023 Volume 24, Issue 4

Abstract: Aquaporin 1 (AQP1) is one of thirteen known mammalian aquaporins. Its main function is the transport of water across cell membranes. Lately, a role of AQP has been attributed to other physiological and pathological functions including cell migration and ... ...

Abstract	Aquaporin 1 (AQP1) is one of thirteen known mammalian aquaporins. Its main function is the transport of water across cell membranes. Lately, a role of AQP has been attributed to other physiological and pathological functions including cell migration and peripheral pain perception. AQP1 has been found in several parts of the enteric nervous system, e.g., in the rat ileum and in the ovine duodenum. Its function in the intestine appears to be multifaceted and is still not completely understood. The aim of the study was to analyze the distribution and localization of AQP1 in the entire intestinal tract of mice. AQP1 expression was correlated with the hypoxic expression profile of the various intestinal segments, intestinal wall thickness and edema, as well as other aspects of colon function including the ability of mice to concentrate stools and their microbiome composition. AQP1 was found in a specific pattern in the serosa, the mucosa, and the enteric nervous system throughout the gastrointestinal tract. The highest amount of AQP1 in the gastrointestinal tract was found in the small intestine. AQP1 expression correlated with the expression profiles of hypoxia-dependent proteins such as HIF-1α and PGK1. Loss of AQP1 through knockout of AQP1 in these mice led to a reduced amount of bacteroidetes and firmicutes but an increased amount of the rest of the phyla, especially deferribacteres, proteobacteria, and verrucomicrobia. Although AQP-KO mice retained gastrointestinal function, distinct changes regarding the anatomy of the intestinal wall including intestinal wall thickness and edema were observed. Loss of AQP1 might interfere with the ability of the mice to concentrate their stool and it is associated with a significantly different composition of the of the bacterial stool microbiome.
MeSH term(s)	Animals ; Mice ; Rats ; Aquaporin 1/genetics ; Aquaporin 1/metabolism ; Aquaporins/metabolism ; Colon/metabolism ; Duodenum/metabolism ; Edema ; Hypoxia ; Mammals/metabolism ; Mice, Knockout ; Sheep ; Gastrointestinal Tract/metabolism
Chemical Substances	Aqp1 protein, rat ; Aquaporin 1 (146410-94-8) ; Aquaporins
Language	English
Publishing date	2023-02-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24043616
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Article ; Online: Metastatic Esophageal Carcinoma Cells Exhibit Reduced Adhesion Strength and Enhanced Thermogenesis.

Huo, Zihe / Sá Santos, Mariana / Drenckhan, Astrid / Holland-Cunz, Stefan / Izbicki, Jakob R / Nash, Michael A / Gros, Stephanie J

Cells

2021 Volume 10, Issue 5

Abstract: Despite continuous improvements in multimodal therapeutic strategies, esophageal carcinoma maintains a high mortality rate. Metastases are a major life-limiting component; however, very little is known about why some tumors have high metastatic potential ...

Abstract	Despite continuous improvements in multimodal therapeutic strategies, esophageal carcinoma maintains a high mortality rate. Metastases are a major life-limiting component; however, very little is known about why some tumors have high metastatic potential and others not. In this study, we investigated thermogenic activity and adhesion strength of primary tumor cells and corresponding metastatic cell lines derived from two patients with metastatic adenocarcinoma of the esophagus. We hypothesized that the increased metastatic potential of the metastatic cell lines correlates with higher thermogenic activity and decreased adhesion strength. Our data show that patient-derived metastatic esophageal tumor cells have a higher thermogenic profile as well as a decreased adhesion strength compared to their corresponding primary tumor cells. Using two paired esophageal carcinoma cell lines of primary tumor and lymph nodes makes the data unique. Both higher specific thermogenesis profile and decreased adhesion strength are associated with a higher metastatic potential. They are in congruence with the clinical patient presentation. Understanding these functional, biophysical properties of patient derived esophageal carcinoma cell lines will enable us to gain further insight into the mechanisms of metastatic potential of primary tumors and metastases. Microcalorimetric evaluation will furthermore allow for rapid assessment of new treatment options for primary tumor and metastases aimed at decreasing the metastatic potential.
MeSH term(s)	Adenocarcinoma/pathology ; Cell Line, Tumor ; Esophageal Neoplasms/pathology ; Humans ; Lymphatic Metastasis/pathology ; Thermogenesis
Language	English
Publishing date	2021-05-16
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10051213
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Article: MIS-C-Implications for the Pediatric Surgeon: An Algorithm for Differential Diagnostic Considerations.

Manz, Nora / Höfele-Behrendt, Claudia / Bielicki, Julia / Schmid, Hanna / Matter, Matthias S / Bielicki, Isabella / Holland-Cunz, Stefan / Gros, Stephanie J

Children (Basel, Switzerland)

2021 Volume 8, Issue 8

Abstract: Background: multisystem inflammatory syndrome in children (MIS-C) is a new disease associated with a recent infection with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). Affected children can present predominantly with abdominal ... ...

Abstract	Background: multisystem inflammatory syndrome in children (MIS-C) is a new disease associated with a recent infection with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). Affected children can present predominantly with abdominal symptoms, fever and high inflammatory parameters that might lead to a consult by the pediatric surgeon and an indication for surgery. Methods: clinical data of three patients with MIS-C that underwent surgery were collected. Histopathological analysis of the appendix was performed. Results: we present the clinical course of three children with fever, abdominal pain and vomiting for several days. Clinical examination and highly elevated inflammation markers led to indication for laparoscopy; appendectomy was performed in two patients. Because of intraoperative findings or due to lack of postoperative improvement, all patients were reevaluated and tested positive for MIS-C associated laboratory parameters and were subsequently treated with corticosteroids, intravenous immunoglobulins, acetyl salicylic acid and/or light molecular weight heparin. Conclusions: we discuss the implications of MIS-C as a new differential diagnosis and stress the importance of assessing the previous medical history, identifying patterns of symptoms and critically surveilling the clinical course. We implemented an algorithm for pediatric surgeons to consider MIS-C as a differential diagnosis for acute abdomen that can be integrated into the surgical workflow.
Language	English
Publishing date	2021-08-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2732685-8
ISSN	2227-9067
ISSN	2227-9067
DOI	10.3390/children8080712
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