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Article ; Online: Clear cell endometrial carcinoma with high microsatellite instability in a complicated pregnancy

Fabian Weiss / Till Kaltofen / Veronika Kanitz / Lennard Schröder / Bernd Kost / Alexander König / Maria Delius / Sven Mahner / Irene Alba Alejandre

Journal of Medical Case Reports, Vol 17, Iss 1, Pp 1-

a case report

2023 Volume 6

Abstract: Abstract Background Endometrial carcinomas are the most common female genital malignancies. They are very rare in pregnancy and worldwide less than 60 cases associated with pregnancy are published. No clear cell carcinoma has been described in a ... ...

Abstract	Abstract Background Endometrial carcinomas are the most common female genital malignancies. They are very rare in pregnancy and worldwide less than 60 cases associated with pregnancy are published. No clear cell carcinoma has been described in a pregnancy with a live birth. Case presentation We present the course of a 43-year-old Uyghur female patient with the diagnosis of endometrial carcinoma with a deficiency in the DNA mismatch repair system in the pregnancy. The malignancy with clear cell histology was confirmed by biopsy following the delivery via caesarean section due to preterm birth of a fetus with sonographically suspected tetralogy of Fallot. Earlier whole exome sequencing after amniocentesis had shown a heterozygous mutation in the MSH2 gene, which was unlikely to be related to the fetal cardiac defect. The uterine mass was initially deemed an isthmocervical fibroid by ultrasound and was confirmed as stage II endometrial carcinoma. The patient was consequently treated with surgery, radiotherapy and chemotherapy. Six months after the adjuvant therapy, re-laparotomy was performed due to ileus symptoms and an ileum metastasis was found. The patient is currently undergoing immune checkpoint inhibitor therapy with pembrolizumab. Conclusion Rare endometrial carcinoma should be included in the differential diagnosis of uterine masses in pregnant women with risk factors.
Keywords	Endometrial neoplasms ; Pregnancy ; DNA mismatch repair ; Clear cell adenocarcinoma ; Amniocentesis ; Case report ; Medicine ; R
Subject code	610
Language	English
Publishing date	2023-07-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Increased risk for thromboembolic events from combination of a gynecologic malignancy with severe acute respiratory syndrome coronavirus 2 infection

Alexandra Stefan / Marija Petkovic / Alexander König / Julian Koch / Friederike Hagemann / Rachel Wuerstlein / Nadia Harbeck / Sven Mahner / Till Kaltofen

Journal of Medical Case Reports, Vol 16, Iss 1, Pp 1-

a case report

2022 Volume 7

Abstract: Abstract Purpose During the severe acute respiratory syndrome coronavirus 2 pandemic, several patient groups are at particular risk. Mortality is higher among cancer patients and may be increased further by thromboembolic events, which are more common in ...

Abstract	Abstract Purpose During the severe acute respiratory syndrome coronavirus 2 pandemic, several patient groups are at particular risk. Mortality is higher among cancer patients and may be increased further by thromboembolic events, which are more common in coronavirus 2019 patients according to recent publications. We discuss the association of gynecologic malignancies, Severe acute respiratory syndrome coronavirus 2, and thromboembolism by reporting a case study and summarizing available literature. Case report A 71-year-old Caucasian patient with ovarian cancer receiving first-line chemotherapy was diagnosed with deep vein thrombosis and pulmonary embolism. Routine screening revealed infection with severe acute respiratory syndrome coronavirus 2 in absence of specific symptoms. After uneventful recovery, oncologic treatment could be continued a few weeks later. Methods We performed a systematic review of the literature on PubMed following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. The search included articles ahead of print, published between 1 December 2019 and 1 June 2020. Cross-searches were conducted on all relevant articles. Results We identified five articles meeting the defined criteria, including two retrospective studies, a review, a position paper, as well as a letter to the editor. Conclusion Cancer patients infected with severe acute respiratory syndrome coronavirus 2 have a relatively poor outcome, which may partially be due to a higher rate of thromboembolic events. Thromboprophylaxis is recommended, and scoring systems are helpful in early detection. In cancer patients with severe acute respiratory syndrome coronavirus 2, individual risk for thromboembolic events should be taken into account when considering interruption versus continuation of antitumoral therapy. However, further data and studies are required.
Keywords	Ovarian cancer ; Gynecologic malignancies ; COVID-19 ; SARS-CoV-2 ; Thromboembolism ; Review ; Medicine ; R
Subject code	610
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Time to Deliver on Promises

Soeren M. Buchholz / Nelia Nause / Ute König / Johanna Reinecke / Benjamin Steuber / Christoph Ammer-Herrmenau / Kirsten Reuter-Jessen / Hanibal Bohnenberger / Lorenz Biggemann / Friederike Braulke / Albrecht Neesse / Volker Ellenrieder / Philipp Ströbel / Marius Adler / Alexander König

Journal of Personalized Medicine, Vol 13, Iss 12, p

The Role of ERBB2 Alterations as Treatment Options for Colorectal Cancer Patients in the Era of Precision Oncology

2023 Volume 1701

Abstract: Receptor tyrosine kinase erythroblastic oncogene B2 ( ERBB2 ), also known as human epidermal growth factor receptor 2 ( HER2 ), represents an oncogenic driver and has been effectively targeted in breast and gastric cancer. Recently, next-generation ... ...

Abstract	Receptor tyrosine kinase erythroblastic oncogene B2 ( ERBB2 ), also known as human epidermal growth factor receptor 2 ( HER2 ), represents an oncogenic driver and has been effectively targeted in breast and gastric cancer. Recently, next-generation sequencing (NGS) discovered ERBB2 as a promising therapeutic target in metastatic colorectal cancer (mCRC), where it is altered in 3–5% of patients, but no therapies are currently approved for this use. Herein, we present the experience of a single center in diagnosing actionable genetic ERBB2 alterations using NGS and utilizing the latest therapeutic options. Between October 2019 and December 2022, a total of 107 patients with advanced CRC underwent molecular analysis, revealing actionable ERBB2 mutations in two patients and ERBB2 amplifications in two other patients. These findings correlated with immunohistochemical (IHC) staining. Of these four patients, two were treated with trastuzumab-deruxtecan (T-DXd). We present two exemplary cases of patients with actionable ERBB2 alterations to demonstrate the effectiveness of T-DXd in heavily pretreated ERBB2 -positive mCRC patients and the need for early molecular profiling. To fully exploit the potential of this promising treatment, earlier molecular profiling and the initiation of targeted therapies are essential.
Keywords	HER2 ; ERBB2 ; colorectal cancer ; molecular tumor board ; genomic profiling ; targeted therapy ; Medicine ; R
Subject code	616
Language	English
Publishing date	2023-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Robot-Driven Locomotor Perturbations Reveal Synergy-Mediated, Context-Dependent Feedforward and Feedback Mechanisms of Adaptation

Giacomo Severini / Alexander Koenig / Catherine Adans-Dester / Iahn Cajigas / Vincent C. K. Cheung / Paolo Bonato

Scientific Reports, Vol 10, Iss 1, Pp 1-

2020 Volume 16

Abstract: Abstract Humans respond to mechanical perturbations that affect their gait by changing their motor control strategy. Previous work indicates that adaptation during gait is context dependent, and perturbations altering long-term stability are compensated ... ...

Abstract	Abstract Humans respond to mechanical perturbations that affect their gait by changing their motor control strategy. Previous work indicates that adaptation during gait is context dependent, and perturbations altering long-term stability are compensated for even at the cost of higher energy expenditure. However, it is unclear if gait adaptation is driven by unilateral or bilateral mechanisms, and what the roles of feedback and feedforward control are in the generation of compensatory responses. Here, we used a robot-based adaptation paradigm to investigate if feedback/feedforward and unilateral/bilateral contributions to locomotor adaptation are also context dependent in healthy adults. A robot was used to induce two opposite unilateral mechanical perturbations affecting the step length over multiple gait cycles. Electromyographic signals were collected and analyzed to determine how muscle synergies change in response to perturbations. The results unraveled different unilateral modulation dynamics of the muscle-synergy activations during adaptation, characterized by the combination of a slow-progressive feedforward process and a fast-reactive feedback-driven process. The relative unilateral contributions of the two processes to motor-output adjustments, however, depended on which perturbation was delivered. Overall, these observations provide evidence that, in humans, both descending and afferent drives project onto the same spinal interneuronal networks that encode locomotor muscle synergies.
Keywords	Medicine ; R ; Science ; Q
Subject code	629
Language	English
Publishing date	2020-03-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: CA19-9 for detecting recurrence of pancreatic cancer

Azadeh Azizian / Felix Rühlmann / Tanja Krause / Markus Bernhardt / Peter Jo / Alexander König / Mathias Kleiß / Andreas Leha / Michael Ghadimi / Jochen Gaedcke

Scientific Reports, Vol 10, Iss 1, Pp 1-

2020 Volume 10

Abstract: Abstract CA19-9 values are regularly measured in patients with pancreatic cancer. Certainly, its potential as a biomarker has been compromised by false negative results in CA19-9 negative patients and false positive results in benign pancreatico-biliary ... ...

Abstract	Abstract CA19-9 values are regularly measured in patients with pancreatic cancer. Certainly, its potential as a biomarker has been compromised by false negative results in CA19-9 negative patients and false positive results in benign pancreatico-biliary diseases. For detection of PDAC recurrence, however, CA19-9 might play an important role. The aim of this study is to analyze the accuracy of CA19-9 for detecting recurrence of pancreatic cancer. All included patients were treated either at the University Medical Center Goettingen, or at the Department of Interdisciplinary Oncology and Pneumonology, DRK-Kliniken Nordhessen, Kassel. We analyzed data of 93 patients with pancreatic cancer in the training set and 41 in the validation set, both retrospectively. Pre- and postoperative CA19-9 values and results of imaging techniques were compared. We performed ROC-analysis. The association between longitudinally measured CA19-9 values and relapse was studied with a joint model between a random effects model for the longitudinal CA19-9 measurements and a Cox proportional hazards models for the survival data. In the test set (n = 93 patients) the median follow-up time was 644 days (22 months). Overall, 71 patients (76.3%) developed recurrence during follow-up. Patients with CA19-9 values of <10kU/l were considered as CA19-9 negative patients (n = 11) and excluded from further analysis. Among the rest, approximately 60% of the patients showed significantly elevated CA19-9 prior to detection of recurrence by imaging techniques. Recurrence was shown by 2.45 times elevated CA19-9 values with 90% positive predictive value. In the validation set, 2.45 times elevated CA19-9 values showed recurrence with 90% sensitivity and 83,33% specificity, with an area under the curve of 95%. Based on measured CA19-9 values during follow-up care, the joint model estimates in recurrence-free patients the probability of recurrence-free survival. CA19-9 elevation is an early and reliable sign for PDAC recurrence. On the strength of a very high accuracy in CA19-9 positive patients, it should be considered to use CA19-9 for therapy decision even without a correlate of imaging technics. Using the joint model, follow-up care of PDAC patients after curative therapy can be stratified.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Characterisation of the hepatitis B virus cross-species transmission pattern via Na+/taurocholate co-transporting polypeptides from 11 New World and Old World primate species.

Simon F Müller / Alexander König / Barbara Döring / Dieter Glebe / Joachim Geyer

PLoS ONE, Vol 13, Iss 6, p e

2018 Volume 0199200

Abstract: The hepatic Na+/taurocholate co-transporting polypeptide (NTCP in man, Ntcp in animals) is the high-affinity receptor for the hepatitis B (HBV) and hepatitis D (HDV) viruses. Species barriers for human HBV/HDV within the order Primates were previously ... ...

Abstract	The hepatic Na+/taurocholate co-transporting polypeptide (NTCP in man, Ntcp in animals) is the high-affinity receptor for the hepatitis B (HBV) and hepatitis D (HDV) viruses. Species barriers for human HBV/HDV within the order Primates were previously attributed to Ntcp sequence variations that disable virus-receptor interaction. However, only a limited number of primate Ntcps have been analysed so far. In the present study, a total of 11 Ntcps from apes, Old and New World monkeys were cloned and expressed in vitro to characterise their interaction with HBV and HDV. All Ntcps showed intact bile salt transport. Human NTCP as well as the Ntcps from the great apes chimpanzee and orangutan showed transport-competing binding of HBV derived myr-preS1-peptides. In contrast, all six Ntcps from the group of Old World monkeys were insensitive to HBV myr-preS1-peptide binding and HBV/HDV infection. This is basically predetermined by the amino acid arginine at position 158 of all studied Old World monkey Ntcps. An exchange from arginine to glycine (as present in humans and great apes) at this position (R158G) alone was sufficient to achieve full transport-competing HBV myr-preS1-peptide binding and susceptibility for HBV/HDV infection. New World monkey Ntcps showed higher sequence heterogeneity, but in two cases with 158G showed transport-competing HBV myr-preS1-peptide binding, and in one case (Saimiri sciureus) even susceptibility for HBV/HDV infection. In conclusion, amino acid position 158 of NTCP/Ntcp is sufficient to discriminate between the HBV/HDV susceptible group of humans and great apes (158G) and the non-susceptible group of Old World monkeys (158R). In the case of the phylogenetically more distant New World monkey Ntcps amino acid 158 plays a significant, but not exclusive role.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Molecular basis of the interaction of the human tyrosine phosphatase PTPN3 with the hepatitis B virus core protein

Mariano Genera / Barbara Quioc-Salomon / Antonin Nourisson / Baptiste Colcombet-Cazenave / Ahmed Haouz / Ariel Mechaly / Mariette Matondo / Magalie Duchateau / Alexander König / Marc P. Windisch / Christine Neuveut / Nicolas Wolff / Célia Caillet-Saguy

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 17

Abstract: Abstract Interactions between the hepatitis B virus core protein (HBc) and host cell proteins are poorly understood, although they may be essential for the propagation of the virus and its pathogenicity. HBc has a C-terminal PDZ (PSD-95, Dlg1, ZO-1)- ... ...

Abstract	Abstract Interactions between the hepatitis B virus core protein (HBc) and host cell proteins are poorly understood, although they may be essential for the propagation of the virus and its pathogenicity. HBc has a C-terminal PDZ (PSD-95, Dlg1, ZO-1)-binding motif (PBM) that is responsible for interactions with host PDZ domain-containing proteins. In this work, we focused on the human protein tyrosine phosphatase non-receptor type 3 (PTPN3) and its interaction with HBc. We solved the crystal structure of the PDZ domain of PTPN3 in complex with the PBM of HBc, revealing a network of interactions specific to class I PDZ domains despite the presence of a C-terminal cysteine in this atypical PBM. We further showed that PTPN3 binds the HBc protein within capsids or as a homodimer. We demonstrate that overexpression of PTPN3 significantly affects HBV infection in HepG2 NTCP cells. Finally, we performed proteomics studies on both sides by pull-down assays and screening of a human PDZ domain library. We identified a pool of human PBM-containing proteins that might interact with PTPN3 in cells and that could be in competition with the HBc PBM during infection, and we also identified potential cellular partners of HBc through PDZ-PBM interactions. This study opens up many avenues of future investigations into the pathophysiology of HBV.
Keywords	Medicine ; R ; Science ; Q
Subject code	572
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: KRAS mutation status concordance between the primary tumor and the corresponding metastasis in patients with rectal cancer

Peter Jo / Markus Bernhardt / Manuel Nietert / Alexander König / Azadeh Azizian / Markus A. Schirmer / Marian Grade / Julia Kitz / Kirsten Reuter-Jessen / Michael Ghadimi / Philipp Ströbel / Hans-Ulrich Schildhaus / Jochen Gaedcke / Sumitra Deb

PLoS ONE, Vol 15, Iss

2020 Volume 10

Abstract: Introduction Oncogenic mutation within the KRAS gene represents a negative predictor for treatment response to anti-epidermal growth factor receptor (EGFR) in patients with colorectal cancer. Recently, we have shown no relevant heterogeneity for KRAS ... ...

Abstract	Introduction Oncogenic mutation within the KRAS gene represents a negative predictor for treatment response to anti-epidermal growth factor receptor (EGFR) in patients with colorectal cancer. Recently, we have shown no relevant heterogeneity for KRAS mutation status within and between pre- and posttherapeutic samples from the primary tumor in patients with locally advanced rectal cancer. The aim of this study was to evaluate the intertumoral heterogeneity of KRAS mutation status between the primary tumor and the corresponding metastasis or local recurrence in the similar cohort and to evaluate the ideal representative tissue for KRAS mutation testing. Materials and methods KRAS mutation status was analyzed from 47 patients with locally advanced rectal cancer, which were enrolled in the CAO/ARO/AIO-94 or CAO/ARO/AIO-04 trial. Mutations in KRAS codons 12, 13, and 61 were analyzed by using the KRAS RGQ PCR Kit (therascreen® KRAS test). Six patients needed to be excluded due to incomplete follow up data. 11 patients showed a relapse of the disease during the follow up presented by distant metastases or local recurrence. DNA from representative areas of metastatic tissue was obtained from formalin-fixed paraffin-embedded specimens. Results The mean patient age was 64.13 ± 10.64 years. In total, 19 patients showed a KRAS mutation (46.34%) in the primary tumor. Of the eleven patients with a metastatic disease or local recurrence, five patients showed a KRAS mutation whereas six patients had a KRAS wildtype status. Metastatic localizations included the liver (n = 2), lung (n = 4), local recurrence (n = 1), liver + lung (n = 3), lung + local recurrence (n = 1). For these eleven patients with paired data available for the primary tumor and metastatic tissue, a significant KRAS mutation status concordance was detected in 81.18% (9/11) of the patients (p = 0.03271). Only two patients showed intertumoral heterogeneity, which harbored in one patient a KRAS G12C mutation status in the primary tumor, but a G12V KRAS mutation ...
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: KRAS mutation status concordance between the primary tumor and the corresponding metastasis in patients with rectal cancer.

Peter Jo / Markus Bernhardt / Manuel Nietert / Alexander König / Azadeh Azizian / Markus A Schirmer / Marian Grade / Julia Kitz / Kirsten Reuter-Jessen / Michael Ghadimi / Philipp Ströbel / Hans-Ulrich Schildhaus / Jochen Gaedcke

PLoS ONE, Vol 15, Iss 10, p e

2020 Volume 0239806

Abstract	Introduction Oncogenic mutation within the KRAS gene represents a negative predictor for treatment response to anti-epidermal growth factor receptor (EGFR) in patients with colorectal cancer. Recently, we have shown no relevant heterogeneity for KRAS mutation status within and between pre- and posttherapeutic samples from the primary tumor in patients with locally advanced rectal cancer. The aim of this study was to evaluate the intertumoral heterogeneity of KRAS mutation status between the primary tumor and the corresponding metastasis or local recurrence in the similar cohort and to evaluate the ideal representative tissue for KRAS mutation testing. Materials and methods KRAS mutation status was analyzed from 47 patients with locally advanced rectal cancer, which were enrolled in the CAO/ARO/AIO-94 or CAO/ARO/AIO-04 trial. Mutations in KRAS codons 12, 13, and 61 were analyzed by using the KRAS RGQ PCR Kit (therascreen® KRAS test). Six patients needed to be excluded due to incomplete follow up data. 11 patients showed a relapse of the disease during the follow up presented by distant metastases or local recurrence. DNA from representative areas of metastatic tissue was obtained from formalin-fixed paraffin-embedded specimens. Results The mean patient age was 64.13 ± 10.64 years. In total, 19 patients showed a KRAS mutation (46.34%) in the primary tumor. Of the eleven patients with a metastatic disease or local recurrence, five patients showed a KRAS mutation whereas six patients had a KRAS wildtype status. Metastatic localizations included the liver (n = 2), lung (n = 4), local recurrence (n = 1), liver + lung (n = 3), lung + local recurrence (n = 1). For these eleven patients with paired data available for the primary tumor and metastatic tissue, a significant KRAS mutation status concordance was detected in 81.18% (9/11) of the patients (p = 0.03271). Only two patients showed intertumoral heterogeneity, which harbored in one patient a KRAS G12C mutation status in the primary tumor, but a G12V KRAS mutation ...
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: The systematic position and phylogenetic relationships of Asiobaccha Violovitsh (Diptera, Syrphidae

Mengual, X., Zoologisches Forschungsmuseum Alexander Koenig, Leibniz-Institut fur Biodiversitat der Tiere, Bonn, Germany

Journal of Asia-Pacific Entomology

(Sep 2015) Volume v. 18, Issue (3), Page(s) p. 397–408

Abstract: The placement and phylogenetic relationships of Asiobaccha were explored usingmolecular evidence. The mitochondrial protein-coding gene cytochrome c oxidase subunit I (COI) and the nuclear 28S and 18S ribosomal RNA geneswere analysed using parsimony, ... ...

Abstract	The placement and phylogenetic relationships of Asiobaccha were explored usingmolecular evidence. The mitochondrial protein-coding gene cytochrome c oxidase subunit I (COI) and the nuclear 28S and 18S ribosomal RNA geneswere analysed using parsimony, Bayesian inference andMaximumLikelihood. Two alignments approaches were used for rRNA genes: a multiple sequence alignment software, MAFFT, and their secondary structure. The present results do not place Asiobaccha close to Baccha or Allobaccha, which are placed in different evolutionary lineages, but close to Episyrphus and Meliscaeva. The relationship among these three genera is not fully resolved. Morphological characters are discussed and Asiobaccha stat. rev. is proposed as a valid genus.
Keywords	SYRPHIDAE ; DIPTERA
Language	English
Document type	Article
ISSN	1226-8615
Database	AGRIS - International Information System for the Agricultural Sciences and Technology

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