Knock-out of CD73 delays the onset of HR-negative breast cancer by reprogramming lipid metabolism and is associated with increased tumor mutational burden.

Objective: CD73 (ecto-5'-nucleotidase, NT5E), a cell-surface enzyme converting 5'-AMP to adenosine, is crucial for cancer progression. However, its role in the tumorigenesis process remains mostly obscure. We aimed to demonstrate CD73's role in breast cancer (BC) tumorigenesis through metabolic rewiring of fatty acid metabolism, a process recently indicated to be regulated by BC major prognostic markers, hormone receptors (HR) for estrogen (ER), and progesterone (PR).

MnoSR removal in triggers broad transcriptional response to 1,3-propanediol and glucose as sole carbon sources.

Introduction: The two-component signal transduction systems play an essential role in the adaptation of bacteria to changing environmental conditions. One of them is the MnoSR system involved in the regulation of methylotrophic metabolism in M. smegmatis.

Improving platelet-RNA-based diagnostics: a comparative analysis of machine learning models for cancer detection and multiclass classification.

Liquid biopsy demonstrates excellent potential in patient management by providing a minimally invasive and cost-effective approach to detecting and monitoring cancer, even at its early stages. Due to the complexity of liquid biopsy data, machine-learning techniques are increasingly gaining attention in sample analysis, especially for multidimensional data such as RNA expression profiles. Yet, there is no agreement in the community on which methods are the most effective or how to process the data.

Detection of circulating tumor cells by means of machine learning using Smart-Seq2 sequencing.

Circulating tumor cells (CTCs) are tumor cells that separate from the solid tumor and enter the bloodstream, which can cause metastasis. Detection and enumeration of CTCs show promising potential as a predictor for prognosis in cancer patients. Furthermore, single-cells sequencing is a technique that provides genetic information from individual cells and allows to classify them precisely and reliably.

Isolation of Viable Epithelial and Mesenchymal Circulating Tumor Cells from Breast Cancer Patients.

Circulating tumor cells (CTCs) undergoing epithelial-mesenchymal transition (EMT) may exhibit more aggressive features than epithelial CTCs and are more frequently observed during disease progression. Therefore, detection and characterization of both epithelial and mesenchymal CTCs in cancer patients are urgently needed to allow for a better understanding of the metastatic process and more effective treatment. Here we describe a method for detection and isolation of viable epithelial and mesenchymal CTCs from peripheral blood of breast cancer patients.

Improved Characterization of Circulating Tumor Cells and Cancer-Associated Fibroblasts in One-Tube Assay in Breast Cancer Patients Using Imaging Flow Cytometry.

Circulating tumor cells (CTCs) and circulating cancer-associated fibroblasts (cCAFs) have been individually considered strong indicators of cancer progression. However, technical limitations have prevented their simultaneous analysis in the context of CTC phenotypes different from epithelial. This study aimed to analyze CTCs and cCAFs simultaneously in the peripheral blood of 210 breast cancer patients using DAPI/pan-keratin (K)/vimentin (V)/alpha-SMA/CD29/CD45/CD31 immunofluorescent staining and novel technology-imaging flow cytometry (imFC).

Platelet-Based Liquid Biopsies through the Lens of Machine Learning.

Liquid biopsies offer minimally invasive diagnosis and monitoring of cancer disease. This biosource is often analyzed using sequencing, which generates highly complex data that can be used using machine learning tools. Nevertheless, validating the clinical applications of such methods is challenging.

Skin Microbiome in Prurigo Nodularis.

Prurigo nodularis (PN) is a chronic condition characterized by the presence of nodular lesions accompanied by intense pruritus. The disease has been linked to several infectious factors, but data on the direct presence of microorganisms in the lesions of PN are scarce. The aim of this study was to evaluate the diversity and composition of the bacterial microbiome in PN lesions by targeting the region V3-V4 of 16S rRNA.

Single-Cell Enzymatic Screening for Epithelial Mesenchymal Transition with an Ultrasensitive Superwetting Droplet-Array Microchip.

The phenotypic changes of circulating tumor cells (CTCs) during the epithelial-mesenchymal transition (EMT) have been a hot topic in tumor biology and cancer therapeutic development. Here, an integrated platform of single-cell fluorescent enzymatic assays with superwetting droplet-array microchips (SDAM) for ultrasensitive functional screening of epithelial-mesenchymal sub-phenotypes of CTCs is reported. The SDAM can generate high-density, volume well-defined droplet (0.

Detection and Characterization of Circulating Tumor Cells Using Imaging Flow Cytometry-A Perspective Study.

Tumor dissemination is one of the most-investigated steps of tumor progression, which in recent decades led to the rapid development of liquid biopsy aiming to analyze circulating tumor cells (CTCs), extracellular vesicles (EVs), and circulating nucleic acids in order to precisely diagnose and monitor cancer patients. Flow cytometry was considered as a method to detect CTCs; however, due to the lack of verification of the investigated cells' identity, this method failed to reach clinical utility. Meanwhile, imaging flow cytometry combining the sensitivity and high throughput of flow cytometry and image-based detailed analysis through a high-resolution microscope might open a new avenue in CTC technologies and provide an open-platform system alternative to CellSearch, which is still the only gold standard in this field.

FGF7/FGFR2-JunB signalling counteracts the effect of progesterone in luminal breast cancer.

We have recently demonstrated that fibroblast growth factor receptor 2 (FGFR2)-mediated signalling alters progesterone receptor (PR) activity and response of oestrogen receptor α (ER)-positive (ER+) breast cancer (BCa) cell lines to anti-ER agents. Little is known about whether the crosstalk between ER and PR, shown to be modulated by the hormonal background, might also be affected by FGFR2. Here, PR-dependent behaviour of ER+ BCa cells was studied in the presence of oestrogen (E2) and progesterone (P4) and/or FGF7.

Alpha-smooth muscle actin-positive cancer-associated fibroblasts secreting osteopontin promote growth of luminal breast cancer.

Background: Cancer-associated fibroblasts (CAFs) have been shown to support tumor development in a variety of cancers. Different markers were applied to classify CAFs in order to elucidate their impact on tumor progression. However, the exact mechanism by which CAFs enhance cancer development and metastasis is yet unknown.

ERα36-High Cancer-Associated Fibroblasts as an Unfavorable Factor in Triple-Negative Breast Cancer.

Background: Cancer-associated fibroblasts (CAFs) are the most abundant cell type in the tumor microenvironment (TME). Estrogen receptor alpha 36 (ERα36), the alternatively spliced variant of ERα, is described as an unfavorable factor when expressed in cancer cells. ERα can be expressed also in CAFs; however, the role of ERα36 in CAFs is unknown.

Chimeric virus-like particles presenting tumour-associated MUC1 epitope result in high titers of specific IgG antibodies in the presence of squalene oil-in-water adjuvant: towards safe cancer immunotherapy.

Background: Immunotherapy is emerging as a powerful treatment approach for several types of cancers. Modulating the immune system to specifically target cancer cells while sparing healthy cells, is a very promising approach for safer therapies and increased survival of cancer patients. Tumour-associated antigens are favorable targets for cancer immunotherapy, as they are exclusively expressed by the cancer cells, minimizing the risk of an autoimmune reaction.

Breast cancer circulating tumor cells with mesenchymal features-an unreachable target?

Circulating tumor cells (CTCs) mediate dissemination of solid tumors and can be an early sign of disease progression. Moreover, they show a great potential in terms of non-invasive, longitudinal monitoring of cancer patients. CTCs have been extensively studied in breast cancer (BC) and were shown to present a significant phenotypic plasticity connected with initiation of epithelial-mesenchymal transition (EMT).

Higher platelet counts correlate to tumour progression and can be induced by intratumoural stroma in non-metastatic breast carcinomas.

Background: Platelets support tumour progression. However, their prognostic significance and relation to circulating tumour cells (CTCs) in operable breast cancer (BrCa) are still scarcely known and, thus, merit further investigation.

Methods: Preoperative platelet counts (PCs) were compared with clinical data, CTCs, 65 serum cytokines and 770 immune-related transcripts obtained using the NanoString technology.

Low Tumor-to-Stroma Ratio Reflects Protective Role of Stroma against Prostate Cancer Progression.

Tumor-to-stroma ratio (TSR) is a prognostic factor that expresses the relative amounts of tumor and intratumoral stroma. In this study, its clinical and molecular relevance was evaluated in prostate cancer (PCa). The feasibility of automated quantification was tested in digital scans of tissue microarrays containing 128 primary tumors from 72 PCa patients stained immunohistochemically for epithelial cell adhesion molecule (EpCAM), followed by validation in a cohort of 310 primary tumors from 209 PCa patients.

Diagnostic Accuracy of Liquid Biopsy in Endometrial Cancer.

Background: Liquid biopsy is a minimally invasive collection of a patient body fluid sample. In oncology, they offer several advantages compared to traditional tissue biopsies. However, the potential of this method in endometrial cancer (EC) remains poorly explored.

Activation of epithelial-mesenchymal transition process during breast cancer progression - the impact of molecular subtype and stromal composition.

Breast cancer (BC) is a heterogeneous disease with different molecular subtypes, which can be defined by oestrogen (ER), progesterone (PR) and human epidermal growth factor (HER2) receptors' status as luminal, HER2+ and triple negative (TNBC). Molecular subtypes also differ in their epithelial-mesenchymal phenotype, which might be related to their aggressiveness, as activation of the epithelial-mesenchymal transition (EMT) is linked with increased ability of cancer cells to survive and metastasize. Nevertheless, the reverse process of mesenchymal-epithelial transition was shown to be required to sustain metastatic colonization.

Transcriptomic landscape of blood platelets in healthy donors.

Blood platelet RNA-sequencing is increasingly used among the scientific community. Aberrant platelet transcriptome is common in cancer or cardiovascular disease, but reference data on platelet RNA content in healthy individuals are scarce and merit complex investigation. We sought to explore the dynamics of platelet transcriptome.

imPlatelet classifier: image-converted RNA biomarker profiles enable blood-based cancer diagnostics.

Liquid biopsies offer a minimally invasive sample collection, outperforming traditional biopsies employed for cancer evaluation. The widely used material is blood, which is the source of tumor-educated platelets. Here, we developed the imPlatelet classifier, which converts RNA-sequenced platelet data into images in which each pixel corresponds to the expression level of a certain gene.