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Authors = Felix J. F. Herth

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14 pages, 2557 KiB  
Article
Early Assessment of Chemotherapy Response in Advanced Non-Small Cell Lung Cancer with Circulating Tumor DNA
by Stephanie J. Yaung, Corinna Woestmann, Christine Ju, Xiaoju Max Ma, Sandeep Gattam, Yiyong Zhou, Liu Xi, Subrata Pal, Aarthi Balasubramanyam, Nalin Tikoo, Claus Peter Heussel, Michael Thomas, Mark Kriegsmann, Michael Meister, Marc A. Schneider, Felix J. Herth, Birgit Wehnl, Maximilian Diehn, Ash A. Alizadeh, John F. Palma and Thomas Muleyadd Show full author list remove Hide full author list
Cancers 2022, 14(10), 2479; https://doi.org/10.3390/cancers14102479 - 18 May 2022
Cited by 4 | Viewed by 12137
Abstract
Monitoring treatment efficacy early during therapy could enable a change in treatment to improve patient outcomes. We report an early assessment of response to treatment in advanced NSCLC using a plasma-only strategy to measure changes in ctDNA levels after one cycle of chemotherapy. [...] Read more.
Monitoring treatment efficacy early during therapy could enable a change in treatment to improve patient outcomes. We report an early assessment of response to treatment in advanced NSCLC using a plasma-only strategy to measure changes in ctDNA levels after one cycle of chemotherapy. Plasma samples were collected from 92 patients with Stage IIIB-IV NSCLC treated with first-line chemo- or chemoradiation therapies in an observational, prospective study. Retrospective ctDNA analysis was performed using next-generation sequencing with a targeted 198-kb panel designed for lung cancer surveillance and monitoring. We assessed whether changes in ctDNA levels after one or two cycles of treatment were associated with clinical outcomes. Subjects with ≤50% decrease in ctDNA level after one cycle of chemotherapy had a lower 6-month progression-free survival rate (33% vs. 58%, HR 2.3, 95% CI 1.2 to 4.2, log-rank p = 0.009) and a lower 12-month overall survival rate (25% vs. 70%, HR 4.3, 95% CI 2.2 to 9.7, log-rank p < 0.001). Subjects with ≤50% decrease in ctDNA level after two cycles of chemotherapy also had shorter survival. Using non-invasive liquid biopsies to measure early changes in ctDNA levels in response to chemotherapy may help identify non-responders before standard-of-care imaging in advanced NSCLC. Full article
(This article belongs to the Special Issue Cell-Free DNA as Prognostic and Predictive Biomarker in Solid Cancers)
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10 pages, 2304 KiB  
Article
Establishment of a Tissue-Mimicking Surrogate for Pulmonary Lesions to Improve the Development of RFA Instruments and Algorithms
by Louisa Bühler, Markus D. Enderle, Nicolas Kahn, Markus Polke, Marc A. Schneider, Claus Peter Heußel, Felix J. F. Herth and Walter Linzenbold
Biomedicines 2022, 10(5), 1100; https://doi.org/10.3390/biomedicines10051100 - 10 May 2022
Cited by 2 | Viewed by 11044
Abstract
(1) Development of radiofrequency ablation (RFA) systems for pulmonary lesions is restricted by availability of human tumor specimens and limited comparability of animal tissue. We aimed to develop a new surrogate tissue overcoming these drawbacks. (2) Reference values for electrical impedance in lung [...] Read more.
(1) Development of radiofrequency ablation (RFA) systems for pulmonary lesions is restricted by availability of human tumor specimens and limited comparability of animal tissue. We aimed to develop a new surrogate tissue overcoming these drawbacks. (2) Reference values for electrical impedance in lung tumor tissue were collected during routine lung tumor RFA (n = 10). Subsequently, a tissue-mimicking surrogate with comparable electrical impedance and facilitating detection of the ablation margins was developed. (3) The mean electrical impedance for all patients was 103.5 ± 14.7 Ω. In the optimized surrogate tissue model consisting of 68% agar solution, 23% egg yolk, 9% thermochromic ink, and variable amounts of sodium chloride, the mean electrical impedance was adjustable from 74.3 ± 0.4 Ω to 183.2 ± 5.6 Ω and was a function (y = 368.4x + 175.2; R2 = 0.96; p < 0.001) of sodium chloride concentration (between 0 and 0.3%). The surrogate tissue achieved sufficient dimensional stability, and sample cuts revealed clear margins of color change for temperatures higher 60 °C. (4) The tissue-mimicking surrogate can be adapted to lung tumor with respect to its electrical properties. As the surrogate tissue allows for simple and cost-effective manufacturing, it is suitable for extensive laboratory testing of RFA systems for pulmonary ablation. Full article
(This article belongs to the Special Issue Clinical Application for Tissue Engineering)
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16 pages, 292 KiB  
Article
Germline Genetic Variants of the Renin-Angiotensin System, Hypoxia and Angiogenesis in Non-Small Cell Lung Cancer Progression: Discovery and Validation Studies
by Maria Joana Catarata, Rui Medeiros, Maria José Oliveira, Alice Pêgo, João Gonçalo Frade, Maria Fátima Martins, Carlos Robalo Cordeiro, Felix J F Herth, Michael Thomas, Mark Kriegsmann, Michael Meister, Marc A Schneider, Thomas Muley and Ricardo Ribeiro
Cancers 2020, 12(12), 3834; https://doi.org/10.3390/cancers12123834 - 18 Dec 2020
Cited by 1 | Viewed by 2562
Abstract
Introduction: The renin–angiotensin system (RAS) is involved in cell proliferation, immunoinflammatory response, hypoxia and angiogenesis, which are critical biological processes in lung cancer. Our aim was to study the association of putatively functional genetic polymorphisms in genes coding for proteins involved in RAS, [...] Read more.
Introduction: The renin–angiotensin system (RAS) is involved in cell proliferation, immunoinflammatory response, hypoxia and angiogenesis, which are critical biological processes in lung cancer. Our aim was to study the association of putatively functional genetic polymorphisms in genes coding for proteins involved in RAS, hypoxia and angiogenesis with non-small cell lung cancer (NSCLC) prognosis. Methods: Genotyping of 52 germline variants from genes of the RAS and hypoxic/angiogenic factors/receptors was performed using MassARRAY iPLEX Gold in a retrospective cohort (n = 167) of advanced NSCLC patients. Validation of the resulting genetic markers was conducted in an independent group (n = 190), matched by clinicopathological characteristics. Results: Multivariate analysis on the discovery set revealed that MME rs701109 C carriers were protected from disease progression in comparison with homozygous T (hazard ratio (HR) = 0.5, 95% confidence interval (CI) = 0.2–0.8, p = 0.010). Homozygous A and T genotypes for KDR rs1870377 were at increased risk for disease progression and death compared to heterozygous (HR = 1.7, 95% CI = 1.2–2.5, p = 0.005 and HR = 2.1, 95% CI = 1.2–3.4, p = 0.006, respectively). Carriers of homozygous genotypes for ACE2 rs908004 presented increased risk for disease progression, only in the subgroup of patients without tumour actionable driver mutations (HR = 2.9, 95% CI = 1.3–6.3, p = 0.010). Importantly, the association of homozygous genotypes in MME rs701109 with risk for disease progression was confirmed after multivariate analysis in the validation set. Conclusion: This study provides evidence that MME polymorphism, which encodes neprilysin, may modulate progression-free survival in advanced NSCLC. Present genetic variation findings will foster basic, translational, and clinical research on their role in NSCLC. Full article
15 pages, 1629 KiB  
Article
Deep Learning for the Classification of Small-Cell and Non-Small-Cell Lung Cancer
by Mark Kriegsmann, Christian Haag, Cleo-Aron Weis, Georg Steinbuss, Arne Warth, Christiane Zgorzelski, Thomas Muley, Hauke Winter, Martin E. Eichhorn, Florian Eichhorn, Joerg Kriegsmann, Petros Christopoulos, Michael Thomas, Mathias Witzens-Harig, Peter Sinn, Moritz von Winterfeld, Claus Peter Heussel, Felix J. F. Herth, Frederick Klauschen, Albrecht Stenzinger and Katharina Kriegsmannadd Show full author list remove Hide full author list
Cancers 2020, 12(6), 1604; https://doi.org/10.3390/cancers12061604 - 17 Jun 2020
Cited by 94 | Viewed by 17800
Abstract
Reliable entity subtyping is paramount for therapy stratification in lung cancer. Morphological evaluation remains the basis for entity subtyping and directs the application of additional methods such as immunohistochemistry (IHC). The decision of whether to perform IHC for subtyping is subjective, and access [...] Read more.
Reliable entity subtyping is paramount for therapy stratification in lung cancer. Morphological evaluation remains the basis for entity subtyping and directs the application of additional methods such as immunohistochemistry (IHC). The decision of whether to perform IHC for subtyping is subjective, and access to IHC is not available worldwide. Thus, the application of additional methods to support morphological entity subtyping is desirable. Therefore, the ability of convolutional neuronal networks (CNNs) to classify the most common lung cancer subtypes, pulmonary adenocarcinoma (ADC), pulmonary squamous cell carcinoma (SqCC), and small-cell lung cancer (SCLC), was evaluated. A cohort of 80 ADC, 80 SqCC, 80 SCLC, and 30 skeletal muscle specimens was assembled; slides were scanned; tumor areas were annotated; image patches were extracted; and cases were randomly assigned to a training, validation or test set. Multiple CNN architectures (VGG16, InceptionV3, and InceptionResNetV2) were trained and optimized to classify the four entities. A quality control (QC) metric was established. An optimized InceptionV3 CNN architecture yielded the highest classification accuracy and was used for the classification of the test set. Image patch and patient-based CNN classification results were 95% and 100% in the test set after the application of strict QC. Misclassified cases mainly included ADC and SqCC. The QC metric identified cases that needed further IHC for definite entity subtyping. The study highlights the potential and limitations of CNN image classification models for tumor differentiation. Full article
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16 pages, 2398 KiB  
Article
FAM83A and FAM83B as Prognostic Biomarkers and Potential New Therapeutic Targets in NSCLC
by Sarah Richtmann, Dennis Wilkens, Arne Warth, Felix Lasitschka, Hauke Winter, Petros Christopoulos, Felix J. F. Herth, Thomas Muley, Michael Meister and Marc A. Schneider
Cancers 2019, 11(5), 652; https://doi.org/10.3390/cancers11050652 - 11 May 2019
Cited by 46 | Viewed by 13493
Abstract
Although targeted therapy has improved the survival rates in the last decade, non-small-cell lung cancer (NSCLC) is still the most common cause of cancer-related death. The challenge of identifying new targets for further effective therapies still remains. The FAMily with sequence similarity 83 [...] Read more.
Although targeted therapy has improved the survival rates in the last decade, non-small-cell lung cancer (NSCLC) is still the most common cause of cancer-related death. The challenge of identifying new targets for further effective therapies still remains. The FAMily with sequence similarity 83 (FAM83) members have recently been described as novel oncogenes in numerous human cancer specimens and shown to be involved in epidermal growth factor receptor (EGFR) signaling. Here, gene expression of FAM83A and B was analyzed in a cohort of 362 NSCLC patients using qPCR. We further investigated relations in expression and their prognostic value. Functional assays in NSCLC cell lines were performed to evaluate FAM83A and B involvement in proliferation, anchorage-independent growth, migration, and the EGFR pathway. We observed a highly increased gene expression level of FAM83A (ø = 68-fold) and FAM83B (ø = 20-fold) which resulted in poor survival prognosis (p < 0.0001 and p = 0.002). Their expression was influenced by EGFR levels, pathway signaling, and mutation status. Both genes affected cell proliferation, and FAM83A depletion resulted in reduced migration and anchorage-independent growth. The results support the hypothesis that FAM83A and B have different functions in different histological subtypes of NSCLC and might be new therapeutic targets. Full article
(This article belongs to the Special Issue Molecular Profiling of Lung Cancer)
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12 pages, 4687 KiB  
Article
Glycodelin as a Serum and Tissue Biomarker for Metastatic and Advanced NSCLC
by Marc A. Schneider, Thomas Muley, Rebecca Weber, Sabine Wessels, Michael Thomas, Felix J. F. Herth, Nicolas C. Kahn, Ralf Eberhardt, Hauke Winter, Gudula Heussel, Arne Warth, Christel Herold-Mende and Michael Meister
Cancers 2018, 10(12), 486; https://doi.org/10.3390/cancers10120486 - 4 Dec 2018
Cited by 10 | Viewed by 3515
Abstract
A major part of non-small cell lung cancer (NSCLC) patients treated with mono- or multimodal concept develop therapy resistance. Despite the abundance of biomarkers investigated in the past, there is still a need for valid NSCLC biomarkers. Glycodelin, an immunosuppressive endometrial protein, has [...] Read more.
A major part of non-small cell lung cancer (NSCLC) patients treated with mono- or multimodal concept develop therapy resistance. Despite the abundance of biomarkers investigated in the past, there is still a need for valid NSCLC biomarkers. Glycodelin, an immunosuppressive endometrial protein, has been shown to be also expressed in NSCLC. Here, we investigated its potential as a biomarker in metastatic and advanced stage NSCLC. Glycodelin gene and protein expression were measured in 28 therapy-naïve resected tumors as well as in corresponding brain (n = 16) and adrenal gland (n = 12) metastasis by qPCR and IHC. Moreover, we correlated glycodelin gene expression of cryoconserved therapy-naïve biopsies (n = 55) of advanced stage patients with glycodelin serum concentrations and patient survival. Using follow-up samples of the patients, we monitored glycodelin serum concentrations during therapy. Glycodelin expression correlated between primary tumor and distant metastases within the same patients. The gene expression of glycodelin in therapy-naïve biopsies also correlated with the serum concentrations of the patients (r = 0.60). Patients with elevated serum concentrations showed a tendency in lower overall survival (p = 0.088) and measuring of glycodelin indicated a progression of the disease earlier compared to clinical diagnostic. Taken together, we demonstrate that glycodelin is a promising prognostic and follow-up biomarker for metastatic and advanced NSCLC. Full article
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15 pages, 2058 KiB  
Article
A Face-Aging Smoking Prevention/Cessation Intervention for Nursery School Students in Germany: An Appearance-Focused Interventional Study
by Titus J. Brinker, Jonas Alfitian, Werner Seeger, David A. Groneberg, Christof Von Kalle, Alexander H. Enk, Felix J. F. Herth, Michael Kreuter, Claudia M. Bauer, Martina Gatzka and Janina L. Suhre
Int. J. Environ. Res. Public Health 2018, 15(8), 1656; https://doi.org/10.3390/ijerph15081656 - 4 Aug 2018
Cited by 7 | Viewed by 6877
Abstract
The Education Against Tobacco (EAT) network delivers smoking prevention advice in secondary schools, typically using the mirroring approach (i.e., a “selfie” altered with a face-aging app and shared with a class). In November 2017, however, the German assembly of EAT opted to expand [...] Read more.
The Education Against Tobacco (EAT) network delivers smoking prevention advice in secondary schools, typically using the mirroring approach (i.e., a “selfie” altered with a face-aging app and shared with a class). In November 2017, however, the German assembly of EAT opted to expand its remit to include nursing students. To assess the transferability of the existing approach, we implemented it with the self-developed face-aging app “Smokerface” (=mixed − methods approach) in six nursing schools. Anonymous questionnaires were used to assess the perceptions of 197 students (age 18–40 years; 83.8% female; 26.4% smokers; 23.3% daily smokers) collecting qualitative and quantitative data for our cross-sectional study. Most students perceived the intervention to be fun (73.3%), but a minority disagreed that their own animated selfie (25.9%) or the reaction of their peers (29.5%) had motivated them to stop smoking. The impact on motivation not to smoke was considerably lower than experienced with seventh graders (63.2% vs. 42.0%; notably, more smokers also disagreed (45.1%) than agreed (23.5%) with this statement. Agreement rates on the motivation not to smoke item were higher in females than in males and in year 2–3 than in year 1 students. Potential improvements included greater focus on pathology (29%) and discussing external factors (26%). Overall, the intervention seemed to be appealing for nursing students. Full article
(This article belongs to the Section Health Behavior, Chronic Disease and Health Promotion)
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