1,720,988 research outputs found
The anti-vegf(R) drug discovery legacy: Improving attrition rates by breaking the vicious cycle of angiogenesis in cancer
Full text linkResistance to anti-vascular endothelial growth factor (VEGF) molecules causes lack of response and disease recurrence. Acquired resistance develops as a result of genetic/epigenetic changes conferring to the cancer cells a drug resistant phenotype. In addition to tumor cells, tumor endothelial cells also undergo epigenetic modifications involved in resistance to anti-angiogenic therapies. The association of multiple anti-angiogenic molecules or a combination of anti-angiogenic drugs with other treatment regimens have been indicated as alternative therapeutic strategies to overcome resistance to anti-angiogenic therapies. Alternative mechanisms of tumor vasculature, including intussusceptive microvascular growth (IMG), vasculogenic mimicry, and vascular co-option, are involved in resistance to anti-angiogenic therapies. The crosstalk between angiogenesis and immune cells explains the efficacy of combining anti-angiogenic drugs with immune check-point inhibitors. Collectively, in order to increase clinical benefits and overcome resistance to anti-angiogenesis therapies, pan-omics profiling is key
A comprehensive biological and clinical perspective can drive a patient-tailored approach to multiple myeloma: Bridging the gaps between the plasma cell and the neoplastic niche
Full text linkThere is a broad spectrum of diseases labeled as multiple myeloma (MM). This is due not only to the composite prognostic risk factors leading to different clinical outcomes and responses to treatments but also to the composite tumor microenvironment that is involved in a vicious cycle with the MM plasma cells. New therapeutic strategies have improved MM patients' chances of survival. Nevertheless, certain patients' subgroups have a particularly unfavorable prognosis. Biological stratification can be subdivided into patient, disease, or therapy-related factors. Alternatively, the biological signature of aggressive disease and dismal therapeutic response can promote a dynamic, comprehensive strategic approach, better tailoring the clinical management of highrisk profiles and refractoriness to therapy and taking into account the role played by the MM milieu. By means of an extensive literature search, we have reviewed the state-of-the-art pathophysiological insights obtained from translational investigations of the MM-bone marrow microenvironment. A good knowledge of the MM niche pathophysiological dissection is crucial to tailor personalized approaches in a bench-bedside fashion. The discussion in this review pinpoints two main aspects that appear fundamental in order to gain novel and definitive results from the biology of MM. A systematic knowledge of the plasma cell disorder, along with greater efforts to face the unmet needs present in MM evolution, promises to open a new therapeutic window looking out onto the plethora of scientific evidence about the myeloma and the bystander cells
SARS-CoV-2 and Endothelial Cells: Vascular Changes, Intussusceptive Microvascular Growth and Novel Therapeutic Windows
Full text linkEndothelial activation in infectious diseases plays a crucial role in understanding and predicting the outcomes and future treatments of several clinical conditions. COVID-19 is no exception. Moving from basic principles to novel approaches, an evolving view of endothelial activation provides insights into a better knowledge of the upstream actors in COVID-19 as a crucial future direction for managing SARS-CoV-2 and other infections. Assessing the function of resting and damaged endothelial cells in infection, particularly in COVID-19, five critical processes emerged controlling thrombo-resistance: vascular integrity, blood flow regulation, immune cell trafficking, angiogenesis and intussusceptive microvascular growth. Endothelial cell injury is associated with thrombosis, increased vessel contraction and a crucial phenomenon identified as intussusceptive microvascular growth, an unprecedented event of vessel splitting into two lumens through the integration of circulating pro-angiogenic cells. An essential awareness of endothelial cells and their phenotypic changes in COVID-19 inflammation is pivotal to understanding the vascular biology of infections and may offer crucial new therapeutic windows
Epigenetic regulation of angiogenesis in tumor progression
No full textEpigenetic is the study of those alterations regulating gene expression without altering DNA sequence and inherited by transmission through cell division. DNA hypomethylation, hypermethylation of tumor suppressor genes, aberrant histone modifications and/or specific microRNAs expression profiles contribute to tumor initiation and progression. In this review, we will discuss the role of epigenetic changes in the regulation of tumor angiogenesis
Can vitamin D status influence seroconversion to SARS-COV2 vaccines?
Full text link: Existing data indicate an association between vitamin D deficiency and increased severity of respiratory distress due to COVID-19 infection, especially in high-risk populations. To date, the effect of vitamin D on immunogenicity to SARS-CoV-2 vaccines has been investigated solely in young healthcare workers in a few studies, yielding conflicting findings, yet highlighting that the response to immunization is inversely related to age. Vitamin D status can potentially influence the antibody titers in people with a previous (or naïve) SARS-CoV-2 infection and vaccination, given its role in immune regulatory functions. From this standpoint, vitamin D supplementation can help reduce the risk of SARS-CoV-2 infection, COVID-19 severity/mortality and rebalance immunological function, particularly in subjects with vigorous T lymphocyte responses to COVID-19. However, more research is needed to establish a correlation between vitamin D status and the generation of protective serological responses to SARS-CoV-2 vaccination
The Urgent Need for Precision Medicine in Cancer and Its Microenvironment: The Paradigmatic Case of Multiple Myeloma
Full text linkPrecision medicine is particularly relevant for cancer and microenvironment deconvolution for therapeutic purposes in hematological and non-hematological malignancies [...]
Visual Clustering of Transcriptomic Data from Primary and Metastatic Tumors—Dependencies and Novel Pitfalls
Full text linkPersonalized oncology is a rapidly evolving area and offers cancer patients therapy options that are more specific than ever. However, there is still a lack of understanding regarding transcriptomic similarities or differences of metastases and corresponding primary sites. Applying two unsupervised dimension reduction methods (t-Distributed Stochastic Neighbor Embedding (t-SNE) and Uniform Manifold Approximation and Projection (UMAP)) on three datasets of metastases (n = 682 samples) with three different data transformations (unprocessed, log10 as well as log10 + 1 transformed values), we visualized potential underlying clusters. Additionally, we analyzed two datasets (n = 616 samples) containing metastases and primary tumors of one entity, to point out potential familiarities. Using these methods, no tight link between the site of resection and cluster formation outcome could be demonstrated, or for datasets consisting of solely metastasis or mixed datasets. Instead, dimension reduction methods and data transformation significantly impacted visual clustering results. Our findings strongly suggest data transformation to be considered as another key element in the interpretation of visual clustering approaches along with initialization and different parameters. Furthermore, the results highlight the need for a more thorough examination of parameters used in the analysis of clusters
Bone metastasis as primary presentation of pancreatic ductal adenocarcinoma: A case report and literature review
Full text linkPDAC bone metastases represent a clinical challenge characterized by multifaceted biological entity
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
- …
