TY - JOUR A1 - Götz, Lisa A1 - Rueckschloss, Uwe A1 - Balk, Gözde A1 - Pfeiffer, Verena A1 - Ergün, Süleyman A1 - Kleefeldt, Florian T1 - The role of carcinoembryonic antigen-related cell adhesion molecule 1 in cancer JF - Frontiers in Immunology N2 - The Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), also known as CD66a, is a member of the immunoglobulin superfamily. CEACAM1 was shown to be a prognostic marker in patients suffering from cancer. In this review, we summarize pre-clinical and clinical evidence linking CEACAM1 to tumorigenicity and cancer progression. Furthermore, we discuss potential CEACAM1-based mechanisms that may affect cancer biology. KW - CEACAM1 KW - CEA KW - cancer KW - tumor KW - malignancy KW - metastasis KW - signaling Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357250 VL - 14 ER - TY - JOUR A1 - Annunziata, Ida A1 - van de Vlekkert, Diantha A1 - Wolf, Elmar A1 - Finkelstein, David A1 - Neale, Geoffrey A1 - Machado, Eda A1 - Mosca, Rosario A1 - Campos, Yvan A1 - Tillman, Heather A1 - Roussel, Martine F. A1 - Weesner, Jason Andrew A1 - Fremuth, Leigh Ellen A1 - Qiu, Xiaohui A1 - Han, Min-Joon A1 - Grosveld, Gerard C. A1 - d'Azzo, Alessandra T1 - MYC competes with MiT/TFE in regulating lysosomal biogenesis and autophagy through an epigenetic rheostat JF - Nature Communications N2 - Coordinated regulation of the lysosomal and autophagic systems ensures basal catabolism and normal cell physiology, and failure of either system causes disease. Here we describe an epigenetic rheostat orchestrated by c-MYC and histone deacetylases that inhibits lysosomal and autophagic biogenesis by concomitantly repressing the expression of the transcription factors MiT/TFE and FOXH1, and that of lysosomal and autophagy genes. Inhibition of histone deacetylases abates c-MYC binding to the promoters of lysosomal and autophagy genes, granting promoter occupancy to the MiT/TFE members, TFEB and TFE3, and/or the autophagy regulator FOXH1. In pluripotent stem cells and cancer, suppression of lysosomal and autophagic function is directly downstream of c-MYC overexpression and may represent a hallmark of malignant transformation. We propose that, by determining the fate of these catabolic systems, this hierarchical switch regulates the adaptive response of cells to pathological and physiological cues that could be exploited therapeutically. KW - autophagy KW - cancer KW - cancer metabolism KW - cell biology KW - mechanisms of disease Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221189 VL - 10 ER - TY - JOUR A1 - Ascheid, David A1 - Baumann, Magdalena A1 - Funke, Caroline A1 - Volz, Julia A1 - Pinnecker, Jürgen A1 - Friedrich, Mike A1 - Höhn, Marie A1 - Nandigama, Rajender A1 - Ergün, Süleyman A1 - Nieswandt, Bernhard A1 - Heinze, Katrin G. A1 - Henke, Erik T1 - Image-based modeling of vascular organization to evaluate anti-angiogenic therapy JF - Biology Direct N2 - In tumor therapy anti-angiogenic approaches have the potential to increase the efficacy of a wide variety of subsequently or co-administered agents, possibly by improving or normalizing the defective tumor vasculature. Successful implementation of the concept of vascular normalization under anti-angiogenic therapy, however, mandates a detailed understanding of key characteristics and a respective scoring metric that defines an improved vasculature and thus a successful attempt. Here, we show that beyond commonly used parameters such as vessel patency and maturation, anti-angiogenic approaches largely benefit if the complex vascular network with its vessel interconnections is both qualitatively and quantitatively assessed. To gain such deeper insight the organization of vascular networks, we introduce a multi-parametric evaluation of high-resolution angiographic images based on light-sheet fluorescence microscopy images of tumors. We first could pinpoint key correlations between vessel length, straightness and diameter to describe the regular, functional and organized structure observed under physiological conditions. We found that vascular networks from experimental tumors diverted from those in healthy organs, demonstrating the dysfunctionality of the tumor vasculature not only on the level of the individual vessel but also in terms of inadequate organization into larger structures. These parameters proofed effective in scoring the degree of disorganization in different tumor entities, and more importantly in grading a potential reversal under treatment with therapeutic agents. The presented vascular network analysis will support vascular normalization assessment and future optimization of anti-angiogenic therapy. KW - vascular structure KW - cancer KW - tumor microenvironment KW - optical clearing KW - light sheet fluorescence microscopy KW - 3D image analysis Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357242 VL - 18 ER - TY - JOUR A1 - Schlecht, Sina A1 - Neubert, Sven A1 - Meng, Karin A1 - Rabe, Antonia A1 - Jentschke, Elisabeth T1 - Changes of symptoms of anxiety, depression, and fatigue in cancer patients 3 months after a video-based intervention JF - International journal of environmental research and public health N2 - During the COVID-19 pandemic, social distancing restricted psycho-oncological care. Therefore, this secondary analysis examines the changes in anxiety, fear of progression, fatigue, and depression in cancer patients after a video-based eHealth intervention. We used a prospective observational design with 155 cancer patients with mixed tumor entities. Data were assessed before and after the intervention and at a three-month follow-up using self-reported questionnaires (GAD-7, FOP-Q-SF, PHQ-8, and EORTC QLQ-FA12). The eight videos included psychoeducation, Acceptance and Commitment Therapy elements, and yoga and qigong exercises. The results showed that three months after finishing the video-based intervention, participants showed significantly reduced fear of progression (d = −0.23), depression (d = −0.27), and fatigue (d = −0.24) compared to the baseline. However, there was no change in anxiety (d = −0.09). Findings indicated marginal improvements in mental distress when using video-based intervention for cancer patients for up to three months, but long-term effectiveness must be confirmed using a controlled design. KW - cancer KW - psycho-oncology KW - eHealth KW - supportive care intervention KW - psychoeducation KW - mind–body intervention KW - distress Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357294 VL - 20 IS - 20 ER - TY - JOUR A1 - Vollmer, Andreas A1 - Nagler, Simon A1 - Hörner, Marius A1 - Hartmann, Stefan A1 - Brands, Roman C. A1 - Breitenbücher, Niko A1 - Straub, Anton A1 - Kübler, Alexander A1 - Vollmer, Michael A1 - Gubik, Sebastian A1 - Lang, Gernot A1 - Wollborn, Jakob A1 - Saravi, Babak T1 - Performance of artificial intelligence-based algorithms to predict prolonged length of stay after head and neck cancer surgery JF - Heliyon N2 - Background Medical resource management can be improved by assessing the likelihood of prolonged length of stay (LOS) for head and neck cancer surgery patients. The objective of this study was to develop predictive models that could be used to determine whether a patient's LOS after cancer surgery falls within the normal range of the cohort. Methods We conducted a retrospective analysis of a dataset consisting of 300 consecutive patients who underwent head and neck cancer surgery between 2017 and 2022 at a single university medical center. Prolonged LOS was defined as LOS exceeding the 75th percentile of the cohort. Feature importance analysis was performed to evaluate the most important predictors for prolonged LOS. We then constructed 7 machine learning and deep learning algorithms for the prediction modeling of prolonged LOS. Results The algorithms reached accuracy values of 75.40 (radial basis function neural network) to 97.92 (Random Trees) for the training set and 64.90 (multilayer perceptron neural network) to 84.14 (Random Trees) for the testing set. The leading parameters predicting prolonged LOS were operation time, ischemia time, the graft used, the ASA score, the intensive care stay, and the pathological stages. The results revealed that patients who had a higher number of harvested lymph nodes (LN) had a lower probability of recurrence but also a greater LOS. However, patients with prolonged LOS were also at greater risk of recurrence, particularly when fewer (LN) were extracted. Further, LOS was more strongly correlated with the overall number of extracted lymph nodes than with the number of positive lymph nodes or the ratio of positive to overall extracted lymph nodes, indicating that particularly unnecessary lymph node extraction might be associated with prolonged LOS. Conclusions The results emphasize the need for a closer follow-up of patients who experience prolonged LOS. Prospective trials are warranted to validate the present results. KW - prediction KW - head and neck cancer KW - machine learning KW - deep learning KW - artificial intelligence KW - length of stay KW - cancer Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-350416 SN - 2405-8440 VL - 9 IS - 11 ER - TY - THES A1 - Peter, Leslie T1 - In-vitro-Analyse der Glutamin-Restriktion im murinen Modellsystem L929 sowie des Einflusses potentieller caloric restriction mimetics auf das Plattenepithelkarzinom HNSCC T1 - In vitro analysis of glutamine restriction in the murine model system L929 and the influence of potential caloric restriction mimetics on squamous cell carcinoma HNSCC N2 - Grundsätzlich sollte in dieser Arbeit der Einfluss der Glutamin-Restriktion als eine Form der Aminosäure-Restriktion auf das Proliferationsverhalten, den Stoffwechsel sowie die Morphologie der murinen Fibroblastenzelllinie L929 untersucht werden. Es sollte dabei auch gezeigt werden, ob sich Indizien für die Induktion eines LEM finden lassen. Weiterhin sollten die Polyamine Spermidin, Spermin, Putrescin und N-Acetylputrescin als CRMs diskutiert und ihr Einfluss auf das Proliferationsverhalten an sieben Zelllinien herausgestellt werden. Der antiproliferative Effekt der Polyamine Spermidin und Spermin auf das Wachstum der untersuchten Zelllinien konnte in dieser Arbeit bestätigt werden, wobei sich Spermin als potenter erwies als Spermidin. Eine durch Spermidin/Spermin induzierte Autophagie konnte in den Western Blots nicht signifikant nachgewiesen werden. Putrescin und N-Acetylputrescin zeigten nur leichte Wirkungen bei hoher Dosis (10 mM). Während Putrescin einen leicht antiproliferativen Effekt hatte, zeigte N-Acetylputrescin eine leicht proliferationssteigernde Wirkung. Die Autophagie-Induktion durch Methionin-Restriktion konnte durch den Nachweis Autophagie-assoziierter Proteine in den durchgeführten Western Blots bestätigt werden. Um regelmäßig von den positiven Effekten der Autophagie zu profitieren, wäre eine pflanzenbasierte Ernährungsweise sinnvoll und gut durchführbar, da Methionin hauptsächlich in tierischen Lebensmitteln und nur geringfügig in pflanzlichen Nahrungsmitteln vorkommt. Ein völliger Verzicht auf Methionin ist nicht empfehlenswert, da die Aminosäure essentiell ist und somit über die Nahrung aufgenommen werden muss. Um das Methionin-Level konstant, aber niedrig zu halten, erscheint eine Bedarfsdeckung über pflanzliche Nahrung als ideal. Die an den Zelllinien L929 und HeLa durchgeführten Proliferationsstudien zeigten, dass die Zellen selbst nach fünftägiger Glutamin- Restriktion geringfügig weiter proliferierten und keinerlei Merkmale des Zelltodes aufwiesen. Die massenspektrometrische Analyse der Modellzelllinie L929, welche über einen Zeitraum von fünf Tagen einer Glutamin-Restriktion ausgesetzt war, zeigte deutliche metabolische Veränderungen bei den über 150 untersuchten Metaboliten, die auf die Induktion eines LEM schließen lassen. Es konnte ein metabolischer Fingerabdruck nach 48 h für die Zelllinie L929 unter Glutamin-Restriktion definiert werden, der zukünftig als Referenz bei der Testung potentieller CRMs herangezogen werden kann. N2 - The basic aim of this study was to investigate the influence of glutamine restriction as a form of amino acid restriction on the proliferation behavior, metabolism and morphology of the murine fibroblast cell line L929. It should also be shown whether there is evidence for the induction of LEM. Furthermore, the polyamines spermidine, spermine, putrescine and N-acetylputrescine should be discussed as CRMs and their influence on the proliferation behavior of seven cell lines should be highlighted. The antiproliferative effect of the polyamines spermidine and spermine on the growth of the cell lines was confirmed in this study, with spermine proving to be more potent than spermidine. Autophagy induced by spermidine/spermine could not be significantly detected in the Western blots. Putrescine and N-acetylputrescine showed only slight effects at high doses (10 mM). While putrescine had a slight antiproliferative effect, N-acetylputrescine showed a slight proliferation-enhancing effect. The induction of autophagy by methionine restriction was confirmed by the detection of autophagy-associated proteins in the Western blots. In order to benefit regularly from the positive effects of autophagy, a plant-based diet would be sensible and easy to implement, as methionine is mainly found in animal foods and only slightly in plant foods. Completely avoiding methionine is not recommended, as the amino acid is essential and must therefore be obtained from food. In order to keep the methionine level constant but low, it seems ideal to cover the requirement via plant food. The proliferation studies carried out on the cell lines L929 and HeLa showed that the cells continued to proliferate slightly even after five days of glutamine restriction and did not exhibit any signs of cell death. The mass spectrometric analysis of the model cell line L929, which was exposed to glutamine restriction over a period of five days, showed clear metabolic changes in the more than 150 metabolites examined, suggesting the induction of LEM. A metabolic fingerprint could be defined after 48 h for the cell line L929 under glutamine restriction, which can be used as a reference for testing potential CRMs in the future. KW - Plattenepithelcarcinom KW - Massenspektrometrie KW - Glutamin KW - Spermidine KW - HNSCC KW - glutamine KW - methionine KW - LC-MS KW - Glutamin-Restriktion KW - Autophagy KW - restriction KW - cancer Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-349627 ER - TY - JOUR A1 - Cerezo-Echevarria, Argiñe A1 - Kehl, Alexandra A1 - Beitzinger, Christoph A1 - Müller, Tobias A1 - Klopfleisch, Robert A1 - Aupperle-Lellbach, Heike T1 - Evaluating the histologic grade of digital squamous cell carcinomas in dogs and copy number variation of KIT Ligand — a correlation study JF - Veterinary Sciences N2 - Dark-haired dogs are predisposed to the development of digital squamous cell carcinoma (DSCC). This may potentially suggest an underlying genetic predisposition not yet completely elucidated. Some authors have suggested a potential correlation between the number of copies KIT Ligand (KITLG) and the predisposition of dogs to DSCC, containing a higher number of copies in those affected by the neoplasm. In this study, the aim was to evaluate a potential correlation between the number of copies of the KITLG and the histological grade of malignancy in dogs with DSCC. For this, 72 paraffin-embedded DSCCs with paired whole blood samples of 70 different dogs were included and grouped according to their haircoat color as follow: Group 0/unknown haircoat color (n = 11); Group 1.a/black non-Schnauzers (n = 15); group 1.b/black Schnauzers (n = 33); group 1.c/black and tan dogs (n = 7); group 2/tan animals (n = 4). The DSCCs were histologically graded. Additionally, KITLG Copy Number Variation (CNV) was determined by ddPCR. A significant correlation was observed between KITLG copy number and the histological grade and score value. This finding may suggest a possible factor for the development of canine DSCC, thus potentially having an impact on personalized veterinary oncological strategies and breeding programs. KW - canine KW - cancer KW - toe KW - grading KW - haircoat KW - color KW - genetics KW - gene Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304824 SN - 2306-7381 VL - 10 IS - 2 ER - TY - JOUR A1 - Solimando, Antonio G. A1 - Bittrich, Max A1 - Shahini, Endrit A1 - Albanese, Federica A1 - Fritz, Georg A1 - Krebs, Markus T1 - Determinants of COVID-19 disease severity – lessons from primary and secondary immune disorders including cancer JF - International Journal of Molecular Sciences N2 - At the beginning of the COVID-19 pandemic, patients with primary and secondary immune disorders — including patients suffering from cancer — were generally regarded as a high-risk population in terms of COVID-19 disease severity and mortality. By now, scientific evidence indicates that there is substantial heterogeneity regarding the vulnerability towards COVID-19 in patients with immune disorders. In this review, we aimed to summarize the current knowledge about the effect of coexistent immune disorders on COVID-19 disease severity and vaccination response. In this context, we also regarded cancer as a secondary immune disorder. While patients with hematological malignancies displayed lower seroconversion rates after vaccination in some studies, a majority of cancer patients’ risk factors for severe COVID-19 disease were either inherent (such as metastatic or progressive disease) or comparable to the general population (age, male gender and comorbidities such as kidney or liver disease). A deeper understanding is needed to better define patient subgroups at a higher risk for severe COVID-19 disease courses. At the same time, immune disorders as functional disease models offer further insights into the role of specific immune cells and cytokines when orchestrating the immune response towards SARS-CoV-2 infection. Longitudinal serological studies are urgently needed to determine the extent and the duration of SARS-CoV-2 immunity in the general population, as well as immune-compromised and oncological patients. KW - COVID-19 KW - SARS-CoV-2 KW - disorder of immunity KW - cancer Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-319412 SN - 1422-0067 VL - 24 IS - 10 ER - TY - JOUR A1 - Henriksson, Sofia A1 - Calderón-Montaño, José Manuel A1 - Solvie, Daniel A1 - Warpman Berglund, Ulrika A1 - Helleday, Thomas T1 - Overexpressed c-Myc sensitizes cells to TH1579, a mitotic arrest and oxidative DNA damage inducer JF - Biomolecules N2 - Previously, we reported that MTH1 inhibitors TH588 and TH1579 selectively induce oxidative damage and kill Ras-expressing or -transforming cancer cells, as compared to non-transforming immortalized or primary cells. While this explains the impressive anti-cancer properties of the compounds, the molecular mechanism remains elusive. Several oncogenes induce replication stress, resulting in under replicated DNA and replication continuing into mitosis, where TH588 and TH1579 treatment causes toxicity and incorporation of oxidative damage. Hence, we hypothesized that oncogene-induced replication stress explains the cancer selectivity. To test this, we overexpressed c-Myc in human epithelial kidney cells (HA1EB), resulting in increased proliferation, polyploidy and replication stress. TH588 and TH1579 selectively kill c-Myc overexpressing clones, enforcing the cancer cell selective killing of these compounds. Moreover, the toxicity of TH588 and TH1579 in c-Myc overexpressing cells is rescued by transcription, proteasome or CDK1 inhibitors, but not by nucleoside supplementation. We conclude that the molecular toxicological mechanisms of how TH588 and TH1579 kill c-Myc overexpressing cells have several components and involve MTH1-independent proteasomal degradation of c-Myc itself, c-Myc-driven transcription and CDK activation. KW - MTH1 KW - TH588 KW - TH1579 KW - c-Myc KW - replication stress KW - DNA damage KW - cell death KW - cancer Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-297547 SN - 2218-273X VL - 12 IS - 12 ER - TY - JOUR A1 - Haussmann, Alexander A1 - Schmidt, Martina E. A1 - Illmann, Mona L. A1 - Schröter, Marleen A1 - Hielscher, Thomas A1 - Cramer, Holger A1 - Maatouk, Imad A1 - Horneber, Markus A1 - Steindorf, Karen T1 - Meta-analysis of randomized controlled trials on yoga, psychosocial, and mindfulness-based interventions for cancer-related fatigue: What intervention characteristics are related to higher efficacy? JF - Cancers N2 - Cancer-related fatigue (CRF) is a burdensome sequela of cancer treatments. Besides exercise, recommended therapies for CRF include yoga, psychosocial, and mindfulness-based interventions. However, interventions conducted vary widely, and not all show a significant effect. This meta-analysis aimed to explore intervention characteristics related to greater reductions in CRF. We included randomized controlled trials published before October 2021. Standardized mean differences were used to assess intervention efficacy for CRF and multimodel inference to explore intervention characteristics associated with higher efficacy. For the meta-analysis, we included 70 interventions (24 yoga interventions, 31 psychosocial interventions, and 15 mindfulness-based interventions) with 6387 participants. The results showed a significant effect of yoga, psychosocial, and mindfulness-based interventions on CRF but with high heterogeneity between studies. For yoga and mindfulness-based interventions, no particular intervention characteristic was identified to be advantageous for reducing CRF. Regarding psychosocial interventions, a group setting and work on cognition were related to higher intervention effects on CRF. The results of this meta-analysis suggest options to maximize the intervention effects of psychosocial interventions for CRF. The effects of yoga and mindfulness-based interventions for CRF appear to be independent of their design, although the limited number of studies points to the need for further research. KW - fatigue KW - cancer KW - psychosocial KW - mindfulness KW - yoga KW - quality of life KW - patient-reported outcomes Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-270753 SN - 2072-6694 VL - 14 IS - 8 ER -