Publications by authors named "Mogler C"

The labyrinthian fetoplacental capillary network is vital for proper nourishment of the developing embryo. Dysfunction of the maternal-fetal circulation is a primary cause of placental insufficiency. Here, we show that the spatial zonation of the murine placental labyrinth vasculature is controlled by flow-regulated epigenetic mechanisms.

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  • SARS-CoV-2 can infect liver cells (hepatocytes), leading to elevated liver enzymes and more severe disease in those with pre-existing liver conditions.
  • The study shows that the virus replicates and spreads in hepatocytes, with infection being dependent on two specific proteins, ACE2 and TMPRSS2, which are found on the liver cells.
  • Infection causes rapid liver cell death, with the Omicron variant causing quicker but less extensive damage compared to other strains, as seen in both human liver cells and infected mice.
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  • - Pancreatic ductal adenocarcinoma (PC) is a highly aggressive cancer with a low survival rate, projected to become the second leading cause of cancer deaths in the coming decades due to its resistance to treatment.
  • - Recent advancements in clinical trials have improved patient survival, with new therapeutic strategies emerging, including adjuvant, neoadjuvant, and palliative treatments aimed at extending life expectancy.
  • - The role of molecular tumor boards and genetic profiling is highlighted as vital for enhancing treatment options and customizing therapies, especially with the introduction of targeted therapies like KRAS inhibitors, steering future research directions.
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Background: We aimed to validate the prognostic significance of tumor budding (TB) in p16-positive oropharyngeal squamous cell carcinomas (OPSCC).

Methods: We analyzed digitized H&E-stained slides from a multicenter cohort of five large university centers consisting of n = 275 cases of p16-positive OPSCC. We evaluated TB along with other histological parameters (morphology, tumor-stroma-ratio, lymphovascular invasion (LVI), perineural invasion) and calculated survival outcomes using both univariate and multivariate analyses.

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Background/objectives: One of the most important diagnostic tools in bone tumors is X-rays. Preliminary and, in the case of some benign lesions, definitive diagnoses are formed using this basic tool. Part of the decision making in this stage is based on statistical probability using the patient's age, as well as the incidence and predilection sites of different entities.

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  • The study analyzed 1,220 tumors from six different cancer types over three years, highlighting the need for better normalization methods to ensure consistent sample loading in proteome profiling.
  • Researchers found that they could profile over 4,000 proteins on average from tumor samples, but current analysis software struggles with the large datasets generated.
  • The study created a pan-cancer proteome expression resource containing 11,000 proteins from FFPE specimens, which allows for detailed comparisons and exploration of protein characteristics related to different cancer types.
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Purpose: Rapidly expanding medical literature challenges oncologists seeking targeted cancer therapies. General-purpose large language models (LLMs) lack domain-specific knowledge, limiting their clinical utility. This study introduces the LLM system Medical Evidence Retrieval and Data Integration for Tailored Healthcare (MEREDITH), designed to support treatment recommendations in precision oncology.

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A lack of advanced preclinical mouse tumor models impedes the progress in urothelial carcinoma research. We present here a novel fast, robust, reliable, and highly reproducible model for the genetic induction of bladder cancer in immunocompetent mice. Different sets of oncogenic transposons (Cmyc, Kras) and Cre drivers were transfected into the murine bladder wall of two different genetic backgrounds (Trp53 and Braf, Pten, Ctnnb1).

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Background: Chondrosarcomas (CS) are a rare and heterogenic group of primary malignant bone tumors. In the literature, data on prognostic factors in chondrosarcomas are scarce, and most studies are limited by a short follow-up. The aim of this retrospective study was therefore to determine factors associated with the survival and local recurrence of chondrosarcomas and to compare the results with previous studies.

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Background: The primary goal of surgery in HNSCC is the complete resection of tumor cells with maximum preservation of normal tissue. The membrane Hsp70-targeting fluorescence labelled peptide TPP-IRDye800 represents a promising tool for real-time intraoperative tumor visualization, enabling the detection of true tumor margins, critical isles of high-grade dysplasia and LN metastases.

Methods: Membrane Hsp70 (mHsp70) expression on HNSCC cell lines and primary HNSCC was determined by flow cytometry and fluorescence microscopy using FITC-conjugated mAb cmHsp70.

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  • Cutaneous leiomyosarcoma (cLMS) is a rare skin tumor with smooth muscle differentiation, showing key genetic mutations in TP53 and RB1, along with copy number changes in other genes like MYCOD and IGF1R.
  • This study aimed to thoroughly investigate the genetics of cLMS by analyzing a larger sample size (38 cases) using whole-exome and RNA sequencing, revealing significant recurrent mutations and potential environmental factors like UV exposure.
  • Findings indicated critical genetic alterations, including various deletions and amplifications, highlighting the complexity of cLMS and emphasizing the need for extensive genetic analysis in rare tumors for better understanding and potential treatment options.
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Background: Local ablative therapies (LAT) are increasingly used in patients with metastatic soft tissue sarcoma (STS), yet evidence-based standards are lacking. This study aimed to assess the impact of LAT on survival of metastatic STS patients and to identify prognostic factors.

Methods: In this retrospective multicenter study, 246 STS patients with metastatic disease who underwent LAT on tumor board recommendation between 2017 and 2021 were analyzed.

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Many pancreatic neuroendocrine tumors (PanNETs) fall into 2 major prognostic subtypes based on DAXX/ATRX-induced alternative lengthening of telomerase phenotype and alpha- and beta-cell-like epigenomic profiles. However, these PanNETs are still flanked by other PanNETs that do not fit into either subtype. Furthermore, despite advanced genotyping, PanNETs are generally not well-characterized in terms of their histologic and hormonal phenotypes.

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Aims: Chronic hypoxia causes detrimental structural alterations in the lung, which may cause pulmonary hypertension and are partially mediated by the endothelium. While its relevance for the development of hypoxia-associated lung diseases is well known, determinants controlling the initial adaptation of the lung endothelium to hypoxia remain largely unexplored.

Methods And Results: We revealed that hypoxia activates the transcription factor nuclear factor of activated T-cells 5 (NFAT5) and studied its regulatory function in murine lung endothelial cells (MLECs).

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The liver is innervated by primary sensory nerve fibres releasing the neuropeptide calcitonin gene-related peptide (CGRP). Elevated plasma levels of CGRP have been found in patients with liver fibrosis or cirrhosis. We hypothesised that signalling of CGRP and its receptors might regulate liver fibrosis and propose a novel potential target for the treatment.

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  • - Chronic hepatitis B virus (HBV) infection affects 300 million people globally, leading to dysfunction in virus-specific CD8 T cells that struggle to eliminate HBV-infected liver cells due to mechanisms that aren't fully understood.
  • - Research indicates a liver immune rheostat inhibits the activation of these CD8 T cells, particularly the CXCR6 subtype, leading to loss of their functionality, as shown by increased activity of the transcription factor cAMP-responsive element modulator (CREM) in both experimental models and chronic HBV patients.
  • - Enhanced signaling pathways related to cAMP and protein kinase A (PKA) in these T cells contribute to their dysfunction, as they establish prolonged contacts with liver cells, impairing essential activation
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Purpose: This study compares phantom-based variability of extracted radiomics features from scans on a photon counting CT (PCCT) and an experimental animal PET/CT-scanner (Albira II) to investigate the potential of radiomics for translation from animal models to human scans. While oncological basic research in animal PET/CT has allowed an intrinsic comparison between PET and CT, but no 1:1 translation to a human CT scanner due to resolution and noise limitations, Radiomics as a statistical and thus scale-independent method can potentially close the critical gap.

Methods: Two phantoms were scanned on a PCCT and animal PET/CT-scanner with different scan parameters and then the radiomics parameters were extracted.

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  • Chondrosarcomas are unusual malignant bone tumors diagnosed through imaging and histological analysis, focusing on specific tumor features like calcification and bone invasion.
  • The study involved analyzing tissue samples from three patients with different types of chondrosarcoma, utilizing advanced techniques like hematein-based x-ray staining and 3D micro-CT for detailed examination without damaging the samples.
  • Results indicated effective visualization of tumor characteristics and differences in tumor area measurements between micro-CT and traditional histology, suggesting that combining these methods could enhance diagnostic accuracy in clinical settings.
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Purpose: To report the prospective long-term outcome data of patients whose chemotherapy decision was guided by the EndoPredict test.

Methods: Patients with hormone receptor-positive HER2-negative early breast cancer with 0-3 positive lymph nodes were enrolled. The EndoPredict test was carried out on all tumor samples.

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Introduction And Objectives: Adjuvant platinum-based chemotherapy for completely resected non-small cell lung cancer is associated with modest improvement in survival; nevertheless, no validated biomarker exists for predicting the benefit or harm of adjuvant platinum-based chemotherapy.

Materials And Methods: We simultaneously measured 27 cytokines in operative tumor specimens from a discovery cohort (n = 97) by multiplex immunoassay; half of the patients received adjuvant platinum-based chemotherapy, and the other half were observed. We tested possible prognostic and predictive factors in multivariate Cox models for overall survival (OS) and relapse-free survival (RFS), and a tree-based method was applied to detect predictive factors with respect to RFS.

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Comparative experimental pathology is a research field at the interface of human and veterinary medicine. It is focused on the comparative study of similarities and differences between spontaneous and experimentally induced diseases in animals (animal models) compared to human diseases. The use of animal models for studying human diseases is an essential component of biomedical research.

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Due to the considerable technological progress in molecular and genetic diagnostics as well as increasing insights into the molecular pathogenesis of diseases, there has been a fundamental paradigm shift in the past two decades from a "one-size-fits-all approach" to personalized, molecularly informed treatment strategies. Personalized medicine or precision medicine focuses on the genetic, physiological, molecular, and biochemical differences between individuals and considers their effects on the development, prevention, and treatment of diseases. As a pioneer of personalized medicine, the field of oncology is particularly noteworthy, where personalized diagnostics and treatment have led to lasting change in the treatment of cancer patients in recent years.

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