10,181 research outputs found

    Converging organoids and extracellular matrix::New insights into liver cancer biology

    Get PDF

    The role of cancer-associated fibroblasts in breast cancer metastasis

    Get PDF
    Breast cancer deaths are primarily caused by metastasis. There are several treatment options that can be used to treat breast cancer. There are, however, a limited number of treatments that can either prevent or inhibit the spread of breast tumor metastases. Thus, novel therapeutic strategies are needed. Studies have increasingly focused on the importance of the tumor microenvironment (TME) in metastasis of breast cancer. As the most abundant cells in the TME, cancer-associated fibroblasts (CAFs) play important roles in cancer pathogenesis. They can remodel the structure of the extracellular matrix (ECM) and engage in crosstalk with cancer cells or other stroma cells by secreting growth factors, cytokines, and chemokines, as well as components of the ECM, which assist the tumor cells to invade through the TME and cause distant metastasis. Clinically, CAFs not only foster the initiation, growth, angiogenesis, invasion, and metastasis of breast cancer but also serve as biomarkers for diagnosis, therapy, and prediction of prognosis. In this review, we summarize the biological characteristics and subtypes of CAFs and their functions in breast cancer metastasis, focusing on their important roles in the diagnosis, prognosis, and treatment of breast cancer. Recent studies suggest that CAFs are vital partners of breast cancer cells that assist metastasis and may represent ideal targets for prevention and treatment of breast cancer metastasis

    Beam scanning by liquid-crystal biasing in a modified SIW structure

    Get PDF
    A fixed-frequency beam-scanning 1D antenna based on Liquid Crystals (LCs) is designed for application in 2D scanning with lateral alignment. The 2D array environment imposes full decoupling of adjacent 1D antennas, which often conflicts with the LC requirement of DC biasing: the proposed design accommodates both. The LC medium is placed inside a Substrate Integrated Waveguide (SIW) modified to work as a Groove Gap Waveguide, with radiating slots etched on the upper broad wall, that radiates as a Leaky-Wave Antenna (LWA). This allows effective application of the DC bias voltage needed for tuning the LCs. At the same time, the RF field remains laterally confined, enabling the possibility to lay several antennas in parallel and achieve 2D beam scanning. The design is validated by simulation employing the actual properties of a commercial LC medium

    Evaluation of different segmentation-based approaches for skin disorders from dermoscopic images

    Full text link
    Treballs Finals de Grau d'Enginyeria Biomèdica. Facultat de Medicina i Ciències de la Salut. Universitat de Barcelona. Curs: 2022-2023. Tutor/Director: Sala Llonch, Roser, Mata Miquel, Christian, Munuera, JosepSkin disorders are the most common type of cancer in the world and the incident has been lately increasing over the past decades. Even with the most complex and advanced technologies, current image acquisition systems do not permit a reliable identification of the skin lesion by visual examination due to the challenging structure of the malignancy. This promotes the need for the implementation of automatic skin lesion segmentation methods in order to assist in physicians’ diagnostic when determining the lesion's region and to serve as a preliminary step for the classification of the skin lesion. Accurate and precise segmentation is crucial for a rigorous screening and monitoring of the disease's progression. For the purpose of the commented concern, the present project aims to accomplish a state-of-the-art review about the most predominant conventional segmentation models for skin lesion segmentation, alongside with a market analysis examination. With the rise of automatic segmentation tools, a wide number of algorithms are currently being used, but many are the drawbacks when employing them for dermatological disorders due to the high-level presence of artefacts in the image acquired. In light of the above, three segmentation techniques have been selected for the completion of the work: level set method, an algorithm combining GrabCut and k-means methods and an intensity automatic algorithm developed by Hospital Sant Joan de Déu de Barcelona research group. In addition, a validation of their performance is conducted for a further implementation of them in clinical training. The proposals, together with the got outcomes, have been accomplished by means of a publicly available skin lesion image database

    Living with erythropoietic protoporphyria:Bridging the gap between research and clinical practice

    Get PDF

    Overcoming drug resistance: targeting the BCL-2 family and the long non-coding RNA HCP5 in medulloblastoma and colorectal cancer

    Get PDF
    Colorectal cancer (CRC) is one of the most common cancers in the UK and medulloblastoma is a common cancer found in children. While there has been a progressive improvement in treatment outcomes, success has been marred by drug resistance and severe side effects. Therefore, this project focused on two aspects of chemotherapeutic drug resistance, the first using the antimitotic agent vincristine in combination with inhibitors of the anti-apoptotic Bcl-2 family proteins, while the second investigated the role of the long non-coding RNA (lncRNA), HCP5 in the resistance of cells to genotoxic agents. In the first part, three medulloblastoma cell lines (DAOY, MB03, ONS76) were analysed for the expression of Bcl-xL and ONS76 cells found to have the highest level of this anti-apoptotic protein. Subsequent results indicated that Bcl-xL encourages mitotic slippage and stemness and that knockdown of Bcl-xL in the high expressing ONS76 cells, reduces these and sensitizes the cells to the anti-mitotic agent vincristine. Thus, pharmacological inhibition of Bcl-xL should sensitize medulloblastoma cells to low doses of vincristine. Regarding the lncRNA HCP5, results showed that HCP5 was generally more highly expressed in a panel of CRC cell lines than the three medulloblastoma cell lines, corroborating data from an in-silico analysis for the corresponding tumours. One function of HCP5 is to translocate the multifunctional YB-1 protein from the cytoplasm to the nucleus where it carries out many of its functions. Knockdown of HCP5 followed by immunofluorescence indicated a reduction in the amount of YB-1 in the nucleus, confirming this function. Subsequently, HCP5 silencing sensitized all cell lines tested to the DNA damaging agents, cisplatin, oxaliplatin and tert-butyl hydroperoxide and also resulted in an increase in double-strand breaks as determined by H2AX formation. Finally, fluorescence activated cell sorting using Annexin V and propidium iodide confirmed a decrease in cell viability in HCP5 knockdown cells following treatment with genotoxic agents and that this was mirrored by an increased apoptotic fraction. Together, these studies indicate the possibilities of using novel therapeutics to increase the functionality of existing treatments to combat acquired drug resistance in cancer patients

    Modelos celulares de infección persistente por el virus de la hepatitis C revelan alteraciones transcriptómicas no reversibles tras la eliminación de la infección mediante el tratamiento con antivirales de acción directa

    Full text link
    Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 02-07-2021Esta tesis tiene embargado el acceso al texto completo hasta el 02-01-202

    Construction and validation of a novel ferroptosis-related signature for evaluating prognosis and immune microenvironment in ovarian cancer

    Get PDF
    Ovarian cancer (OV) is the most lethal form of gynecological malignancy worldwide, with limited therapeutic options and high recurrence rates. However, research focusing on prognostic patterns of ferroptosis-related genes (FRGs) in ovarian cancer is still lacking. From the 6,406 differentially expressed genes (DEGs) between TCGA-OV (n = 376) and GTEx cohort (n = 180), we identified 63 potential ferroptosis-related genes. Through the LASSO-penalized Cox analysis, 3 prognostic genes, SLC7A11, ZFP36, and TTBK2, were finally distinguished. The time-dependent ROC curves and K-M survival analysis performed powerful prognostic ability of the 3-gene signature. Stepwise, we constructed and validated the nomogram based on the 3-gene signature and clinical features, with promising prognostic value in both TCGA (p-value < .0001) and ICGC cohort (p-value = .0064). Gene Set Enrichment Analysis elucidated several potential pathways between the groups stratified by 3-gene signature, while the m6A gene analysis implied higher m6A level in the high-risk group. We applied the CIBERSORT algorithm to distinct tumor immune microenvironment between two groups, with less activated dendritic cells (DCs) and plasma cells, more M0 macrophages infiltration, and higher expression of key immune checkpoint molecules (CD274, CTLA4, HAVCR2, and PDCD1LG2) in the high-risk group. In addition, the low-risk group exhibited more favorable immunotherapy and chemotherapy responses. Collectively, our findings provided new prospects in the role of ferroptosis-related genes, as a promising prediction tool for prognosis and immune responses, in order to assist personalized treatment decision-making among ovarian cancer patients

    TERT promoter mutation and H3K27me3 trimethylation loss as focal molecular markers in meningioma aggressiveness

    Full text link
    Biomarkers to identify high-grade meningiomas have finally been added to the recent 2021 edition of the World Health Organization (WHO) grading scheme. Among them, are the well-known telomerase reverse transcriptase promoter (TERTp) mutation and the recently emerged epigenetic marker, trimethylation of lysine 27 of histone 3 (H3K27me3). Although the presence of TERTp is now associated with WHO grade 3 meningiomas and the loss of trimethylation of H3K27me3 is implicated with potentially worse prognosis, the question remains as to their ability to predict an event rather than an observed association. Furthermore, the standards for H3K27me3 immunohistochemistry (IHC) in meningiomas have not been set and have led to inconsistencies in reporting. To address these critical clinical concerns, I set out to investigate the prevalence of TERTp mutations in a cohort of suspected high-risk meningiomas through Sanger sequencing. I also conducted a meta-analysis of all H3K27me3 publications to qualify the current assessment of H3K27me3 trimethylation loss as a predictor of tumor aggressiveness. Due to complications with the quality of purified DNA from FFPE tissue, I was unable to obtain satisfactory sequencing results to assess the prevalence of TERTp mutation in my cohort. I did, however, develop an optimized DNA purification protocol for FFPE tissues for future research purposes. The pooled data on H3K27me3 did confirm a significant association between the loss of H3K27me3 trimethylation and more aggressive tumors (p5 years old resulted in significantly higher rates of H3K27me3 loss, implying tissue age and quality had a significant effect on the staining for H3K27me3 loss in meningiomas. Although H3K27me3 is associated substantially with meningiomas of more aggressive nature and thus a higher likelihood of recurrence, several criteria must be met first to standardize the process to ensure accuracy in reporting and ease of implementation into standard clinical workups
    corecore