Publications by authors named "Torben Luders"

Article Synopsis
  • * The NEOLETRIB trial specifically assesses the effectiveness of combining letrozole (an aromatase inhibitor) and ribociclib (a CDK4/6-inhibitor) in ER-positive, HER2-negative luminal A/B breast cancer patients.
  • * The study includes comprehensive molecular biology techniques, such as single-cell RNA sequencing, to analyze tumor responses and make better treatment decisions, with the aim of enhancing patient selection for this combination therapy.
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Benign breast tumors are a nonthreatening condition defined as abnormal cell growth within the breast without the ability to invade nearby tissue. However, benign lesions hold valuable biological information that can lead us toward better understanding of tumor biology. In this study, we have used two pathway analysis algorithms, Pathifier and gene set variation analysis (GSVA), to identify biological differences between normal breast tissue, benign tumors and malignant tumors in our clinical dataset.

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Background: Recent reports have demonstrated that the entire mitochondrial genome can be secreted in extracellular vesicles (EVs), but the biological attributes of this cell-free mitochondrial DNA (mtDNA) remain insufficiently understood. We used next-generation sequencing to compare plasma EV-derived mtDNA to that of whole blood (WB), peripheral blood mononuclear cells (PBMCs), and formalin-fixed paraffin-embedded (FFPE) tumor tissue from eight rectal cancer patients and WB and fresh-frozen (FF) tumor tissue from eight colon cancer patients.

Methods: Total DNA was isolated before the mtDNA was enriched by PCR with either two primer sets generating two long products or multiple primer sets (for the FFPE tumors), prior to the sequencing.

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  • Severe COVID-19 is linked to a harmful inflammatory response, which the study aimed to better understand by analyzing gene expression patterns in patients.
  • Researchers studied blood samples from 17 severe COVID-19 patients, 15 with moderate symptoms, and 11 healthy controls, all of whom were unvaccinated.
  • Findings indicated heightened activation of immune components like neutrophils and cytokines in severe cases, with a noted shift towards a less mature neutrophil phenotype over time, while interferon signaling was more active early on but did not correlate with severe disease progression.
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  • Improved transcriptomic sequencing technologies allow for extensive longitudinal experiments, generating large datasets, but there are currently no comprehensive analysis methods for these experiments.
  • This article introduces the TimeSeries Analysis pipeline (TiSA), which uses differential gene expression, clustering, and functional enrichment analysis to analyze transcriptomic data over time.
  • TiSA is versatile, capable of analyzing various types of datasets, including those with missing data, and provides visual tools like PCA and heatmaps to help interpret results clearly.
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  • Interfering with aging mechanisms can improve healthy longevity, and targeting multiple aging hallmarks could be more effective than focusing on just one.
  • Antarctic krill oil, rich in omega-3 fatty acids and other compounds, was studied for its potential to promote healthy aging in a model of Parkinson’s disease, showing protective effects on dopamine neurons and cognitive functions.
  • The research indicates that krill oil alters gene expression to combat various aging issues like oxidative stress and mitochondrial dysfunction, suggesting its potential for further research in promoting healthy aging.
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Background: Studies of the mucosal transcriptomic landscape have given new insight into the pathogenesis of inflammatory bowel disease (IBD). Recently, the predictive biomarker potential of gene expression signatures has been explored. To further investigate the mucosal gene expression in IBD, we recruited a cohort of treatment naïve patients and compared them to both symptomatic and healthy controls.

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  • Bi-allelic pathogenic variants in the ZBTB11 gene are linked to a disorder known as MRT69, characterized by varying levels of brain atrophy and specific biochemical issues.
  • Researchers identified novel variants in five patients from three families, which led to an examination of how ZBTB11 functions at a cellular level.
  • The study finds that mutated ZBTB11 significantly reduces its ability to bind to genes related to mitochondrial function and RNA processing, resulting in the dysregulation of these processes and contributing to the neurological symptoms and metabolic disorders observed in affected individuals.
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Purpose: The aim of this study was to assess protein tyrosine kinase profiles in primary breast cancer samples in correlation with the distinct hormone and growth receptor profiles ER, PR, and HER2.

Experimental Design: Pamchip® microarrays were used to measure the phosphorylation of 144 tyrosine kinase substrates in 29 ER+ breast cancer samples and cell lines MCF7, BT474 and ZR75-1. mRNA expression data from the METABRIC cohort and publicly available PR chip-sequencing data were used for validation purposes, together with RT-PCR.

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Background: Ductal carcinoma in situ (DCIS) comprises a diverse group of preinvasive lesions in the breast and poses a considerable clinical challenge due to lack of markers of progression. Genomic alterations are to a large extent similar in DCIS and invasive carcinomas, although differences in copy number aberrations, gene expression patterns, and mutations exist. In mixed tumors with synchronous invasive breast cancer (IBC) and DCIS, it is still unclear to what extent invasive tumor cells are directly derived from the DCIS cells.

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The aromatase inhibitor letrozole (Femar/Femara) and the aromatase inactivator exemestane (Aromasin) differ in their biochemical effect on the aromatase enzyme. Letrozole is a competitive aromatase inhibitor while exemestane binds irreversibly to the aromatase enzyme. This pharmacological difference is of clinical interest since a lack of cross-resistance has been documented.

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In the preceding decades, molecular characterization has revolutionized breast cancer (BC) research and therapeutic approaches. Presented herein, an unbiased analysis of breast tumor proteomes, inclusive of 9995 proteins quantified across all tumors, for the first time recapitulates BC subtypes. Additionally, poor-prognosis basal-like and luminal B tumors are further subdivided by immune component infiltration, suggesting the current classification is incomplete.

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Cancers elicit an immune response by modifying the microenvironment. The immune system plays a pivotal role in cancer recognition and eradication. While the potential clinical value of infiltrating lymphocytes at the tumor site has been assessed in breast cancer, circulating cytokines - the molecules coordinating and fine-tuning immune response - are still poorly characterized.

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A high concentration of circulating vascular endothelial growth factor (VEGF) in cancer patients is associated with an aggressive tumor phenotype. Here, serum levels of 27 cytokines and blood cell counts were assessed in breast cancer patients receiving neoadjuvant chemotherapy with or without bevacizumab (Bev) in a randomized cohort of 132 patients with non-metastatic HER2-negative tumors. Cytokine levels were determined prior to treatment and at various time-points.

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Chronic inflammation promotes breast tumor growth and invasion by accelerating angiogenesis and tissue remodeling in the tumor microenvironment. There is a complex relationship between inflammation and estrogen, which drives the growth of 70 percent of breast tumors. While low levels of estrogen exposure stimulate macrophages and other inflammatory cell populations, very high levels are immune suppressive.

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Article Synopsis
  • Breast cancer is a diverse disease that can be classified using various molecular data types, and this study aims to identify integrated subtypes by examining these different classifications.
  • Researchers analyzed tumor samples from 425 breast cancer patients and used techniques to isolate DNA, RNA, proteins, and metabolites, leading to the discovery of multiple subtypes through various clustering methods.
  • The study ultimately identified six major tumor groups that correlate strongly with mRNA subtypes, highlighting the importance of specific microRNAs in distinguishing subtypes and their potential role in cancer cell survival.
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Robust markers of invasiveness may help reduce the overtreatment of in situ carcinomas. Breast cancer is a heterogeneous disease and biological mechanisms for carcinogenesis vary between subtypes. Stratification by subtype is therefore necessary to identify relevant and robust signatures of invasive disease.

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Tumor size, as indicated by the T-category, is known as a strong prognostic indicator for breast cancer. It is common practice to distinguish the T1 and T2 groups at a tumor size of 2.0 cm.

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Background: Copy number aberrations frequently occur during the development of many cancers. Such events affect dosage of involved genes and may cause further genomic instability and progression of cancer. In this survey, canine SNP microarrays were used to study 117 canine mammary tumours from 69 dogs.

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Alterations in glycan structures are early signs of malignancy and have recently been proposed to be in part a driving force behind malignant transformation. Here, we explore whether differences in expression of genes related to the process of glycosylation exist between breast carcinoma subtypes - and look for their association to clinical parameters. Five expression datasets of 454 invasive breast carcinomas, 31 ductal carcinomas in situ (DCIS), and 79 non-malignant breast tissue samples were analysed.

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Article Synopsis
  • Breast cancer is a complex disease with varying genomic and transcriptomic profiles, making it the second leading cause of cancer death in women.
  • This study focuses on long non-coding RNAs (lncRNAs) in breast cancer, analyzing samples from 26 tumors and 5 normal tissues to identify over 19,000 regions with significant expression differences, half of which were non-coding.
  • The research highlighted the structural characteristics of lncRNAs, revealing their presence in various genomic locations and suggesting a regulatory role in tumorigenesis and the expression of nearby protein-coding genes.
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  • - Low plasma levels of adiponectin are associated with obesity, insulin resistance, and increased cancer risk, particularly in colorectal cancer, where adiponectin receptor expression is heightened in tumors compared to normal tissue.
  • - A study involving 60 patients found that adiponectin and its signaling pathways are more active in colorectal tumors than in adjacent healthy tissue, with significant increases in related proteins and genes involved in fat processing.
  • - The research suggests that the interaction between adiponectin and AMPK in tumors may promote processes that support cancer development, indicating a complex role of adiponectin in colorectal cancer progression.
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MicroRNAs (miRNAs) are endogenous non-coding RNAs, which play an essential role in the regulation of gene expression during carcinogenesis. The role of miRNAs in breast cancer has been thoroughly investigated, and although many miRNAs are identified as cancer related, little is known about their involvement in benign tumors. In this study, we investigated miRNA expression profiles in the two most common types of human benign tumors (fibroadenoma/fibroadenomatosis) and in malignant breast tumors and explored their role as oncomirs and tumor suppressor miRNAs.

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Article Synopsis
  • Breast cancers are mainly categorized as T1 (up to 2.0 cm) or T2 (2.1 to 5.0 cm) due to better early detection methods.
  • Researchers conducted a study involving 46 samples to identify genetic differences between T1 and T2 tumors, discovering 441 genes with varying expression levels linked to tumor size.
  • Using these genetic signatures for tumor classification can help identify T1 patients needing aggressive treatment and T2 patients who may not benefit as much, potentially impacting treatment decisions significantly.
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