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Nature May 2024Metastasis is a multistep process by which cancer cells break away from their original location and spread to distant organs, and is responsible for the vast majority of... (Review)
Review
Metastasis is a multistep process by which cancer cells break away from their original location and spread to distant organs, and is responsible for the vast majority of cancer-related deaths. Preventing early metastatic dissemination would revolutionize the ability to fight cancer. Unfortunately, the relatively poor understanding of the molecular underpinnings of metastasis has hampered the development of effective anti-metastatic drugs. Although it is now accepted that disseminating tumour cells need to acquire multiple competencies to face the many obstacles they encounter before reaching their metastatic site(s), whether these competencies are acquired through an accumulation of metastasis-specific genetic alterations and/or non-genetic events is often debated. Here we review a growing body of literature highlighting the importance of both genetic and non-genetic reprogramming events during the metastatic cascade, and discuss how genetic and non-genetic processes act in concert to confer metastatic competencies. We also describe how recent technological advances, and in particular the advent of single-cell multi-omics and barcoding approaches, will help to better elucidate the cross-talk between genetic and non-genetic mechanisms of metastasis and ultimately inform innovative paths for the early detection and interception of this lethal process.
Topics: Animals; Humans; Neoplasm Metastasis; Neoplasms; Single-Cell Analysis; Multiomics; Molecular Typing; Cellular Reprogramming
PubMed: 38750233
DOI: 10.1038/s41586-024-07302-6 -
European Heart Journal Oct 2023Large-scale clinical trials are essential in cardiology and require rapid, accurate publication, and dissemination. Whereas conference presentations, press releases, and...
Large-scale clinical trials are essential in cardiology and require rapid, accurate publication, and dissemination. Whereas conference presentations, press releases, and social media disseminate information quickly and often receive considerable coverage by mainstream and healthcare media, they lack detail, may emphasize selected data, and can be open to misinterpretation. Preprint servers speed access to research manuscripts while awaiting acceptance for publication by a journal, but these articles are not formally peer-reviewed and sometimes overstate the findings. Publication of trial results in a major journal is very demanding but the use of existing checklists can help accelerate the process. In case of rejection, procedures such as easing formatting requirements and possibly carrying over peer-review to other journals could speed resubmission. Secondary publications can help maximize benefits from clinical trials; publications of secondary endpoints and subgroup analyses further define treatment effects and the patient populations most likely to benefit. These rely on data access, and although data sharing is becoming more common, many challenges remain. Beyond publication in medical journals, there is a need for wider knowledge dissemination to maximize impact on clinical practice. This might be facilitated through plain language summary publications. Social media, websites, mainstream news outlets, and other publications, although not peer-reviewed, are important sources of medical information for both the public and for clinicians. This underscores the importance of ensuring that the information is understandable, accessible, balanced, and trustworthy. This report is based on discussions held on December 2021, at the 18th Global Cardiovascular Clinical Trialists meeting, involving a panel of editors of some of the top medical journals, as well as members of the lay press, industry, and clinical trialists.
PubMed: 37165687
DOI: 10.1093/eurheartj/ehad279 -
Affective Science Dec 2023Studying facial expressions is a notoriously difficult endeavor. Recent advances in the field of affective computing have yielded impressive progress in automatically...
UNLABELLED
Studying facial expressions is a notoriously difficult endeavor. Recent advances in the field of affective computing have yielded impressive progress in automatically detecting facial expressions from pictures and videos. However, much of this work has yet to be widely disseminated in social science domains such as psychology. Current state-of-the-art models require considerable domain expertise that is not traditionally incorporated into social science training programs. Furthermore, there is a notable absence of user-friendly and open-source software that provides a comprehensive set of tools and functions that support facial expression research. In this paper, we introduce Py-Feat, an open-source Python toolbox that provides support for detecting, preprocessing, analyzing, and visualizing facial expression data. Py-Feat makes it easy for domain experts to disseminate and benchmark computer vision models and also for end users to quickly process, analyze, and visualize face expression data. We hope this platform will facilitate increased use of facial expression data in human behavior research.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s42761-023-00191-4.
PubMed: 38156250
DOI: 10.1007/s42761-023-00191-4 -
PLoS Pathogens Aug 2023Most humans have a lifelong imperceptible BK Polyomavirus (BKPyV) infection in epithelial cells lining the reno-urinary tract. In kidney transplant recipients,...
Most humans have a lifelong imperceptible BK Polyomavirus (BKPyV) infection in epithelial cells lining the reno-urinary tract. In kidney transplant recipients, unrestricted high-level replication of donor-derived BKPyV in the allograft underlies polyomavirus-associated nephropathy, a condition with massive epithelial cell loss and inflammation causing premature allograft failure. There is limited understanding on how BKPyV disseminates throughout the reno-urinary tract and sometimes causes kidney damage. Tubule epithelial cells are tightly connected and have unique apical and basolateral membrane domains with highly specialized functions but all in vitro BKPyV studies have been performed in non-polarized cells. We therefore generated a polarized cell model of primary renal proximal tubule epithelial cells (RPTECs) and characterized BKPyV entry and release. After 8 days on permeable inserts, RPTECs demonstrated apico-basal polarity. BKPyV entry was most efficient via the apical membrane, that in vivo faces the tubular lumen, and depended on sialic acids. Progeny release started between 48 and 58 hours post-infection (hpi), and was exclusively detected in the apical compartment. From 72 hpi, cell lysis and detachment gradually increased but cells were mainly shed by extrusion and the barrier function was therefore maintained. The decoy-like cells were BKPyV infected and could transmit BKPyV to uninfected cells. By 120 hpi, the epithelial barrier was disrupted by severe cytopathic effects, and BKPyV entered the basolateral compartment mimicking the interstitial space. Addition of BKPyV-specific neutralizing antibodies to this compartment inhibited new infections. Taken together, we propose that during in vivo low-level BKPyV replication, BKPyV disseminates inside the tubular system, thereby causing minimal damage and delaying immune detection. However, in kidney transplant recipients lacking a well-functioning immune system, replication in the allograft will progress and eventually cause denudation of the basement membrane, leading to an increased number of decoy cells, high-level BKPyV-DNAuria and DNAemia, the latter a marker of allograft damage.
Topics: Humans; Cytology; BK Virus; Polyomavirus; Kidney; Epithelial Cells; Polyomavirus Infections
PubMed: 37639485
DOI: 10.1371/journal.ppat.1011622 -
Frontiers in Bioscience (Landmark... Apr 2024Metastasis remains a leading cause of mortality for patients with solid tumors. An expanding body of literature suggests interplay between the host, gut, and tumoral... (Review)
Review
Metastasis remains a leading cause of mortality for patients with solid tumors. An expanding body of literature suggests interplay between the host, gut, and tumoral microbiomes may play a role in cancer initiation and distant dissemination. These associations have been particularly well-studied in colorectal cancer, where gut dysbiosis and an endotoxin-induced inflammatory milieu foster premalignant polyp formation, setting the stage for carcinogenesis. Subsequent violation of the gut vascular barrier enables dissemination of bacterial agents to sites such as the liver, where they contribute to establishment of pre-metastatic niches, which promote tumor cell extravasation and metastatic outgrowth. Intriguingly, breakdown of this vascular barrier has been shown to be aided by the presence of tumoral bacteria. The presence of similar species, including and , in both primary and metastatic colorectal tumors, supports this hypothesis and their presence is associated with chemotherapy resistance and an overall poor prognosis. Specific gut microbial populations are also associated with differential response to immunotherapy, which has a growing role in microsatellite unstable colorectal cancers. Recent work suggests that modulation of gut microbiome using dietary modification, targeted antibiotics, or fecal microbiota transplantation may improve response to immunotherapy and oncologic outcomes. Elucidation of the precise mechanistic links between the microbiome and cancer dissemination will open the doors to additional therapeutic possibilities.
Topics: Humans; Colorectal Neoplasms; Gastrointestinal Microbiome; Neoplasm Metastasis; Dysbiosis; Bacteria; Fecal Microbiota Transplantation
PubMed: 38682201
DOI: 10.31083/j.fbl2904152 -
Journal of Korean Medical Science Feb 2024
Topics: Humans; Social Media; Video Recording; Information Dissemination
PubMed: 38412615
DOI: 10.3346/jkms.2024.39.e93 -
Clinical & Experimental Metastasis Mar 2024Cancer cells can leave their primary sites and travel through the circulation to distant sites, where they lodge as disseminated cancer cells (DCCs), even during the... (Review)
Review
Cancer cells can leave their primary sites and travel through the circulation to distant sites, where they lodge as disseminated cancer cells (DCCs), even during the early and asymptomatic stages of tumor progression. In experimental models and clinical samples, DCCs can be detected in a non-proliferative state, defined as cellular dormancy. This state can persist for extended periods until DCCs reawaken, usually in response to niche-derived reactivation signals. Therefore, their clinical detection in sites like lymph nodes and bone marrow is linked to poor survival. Current cancer therapy designs are based on the biology of the primary tumor and do not target the biology of the dormant DCC population and thus fail to eradicate the initial or subsequent waves of metastasis. In this brief review, we discuss the current methods for detecting DCCs and highlight new strategies that aim to target DCCs that constitute minimal residual disease to reduce or prevent metastasis formation. Furthermore, we present current evidence on the relevance of DCCs derived from early stages of tumor progression in metastatic disease and describe the animal models available for their study. We also discuss our current understanding of the dissemination mechanisms utilized by genetically less- and more-advanced cancer cells, which include the functional analysis of intermediate or hybrid states of epithelial-mesenchymal transition (EMT). Finally, we raise some intriguing questions regarding the clinical impact of studying the crosstalk between evolutionary waves of DCCs and the initiation of metastatic disease.
PubMed: 38520475
DOI: 10.1007/s10585-023-10248-0 -
Journal of Community Psychology Sep 2023This community-engaged study aimed to understand effective strategies for disseminating online parenting resources (OPRs) in schools. OPRs were disseminated through...
This community-engaged study aimed to understand effective strategies for disseminating online parenting resources (OPRs) in schools. OPRs were disseminated through seven E-Parenting tips and eight Facebook posts. Facebook posts were viewed a total of 12,404 times, and each post reached an average of 505 people each month. Average engagement rate was 2.41% per post. E-Parenting tips yielded 1514 total clicks, and the average clicks per message was 216.29. E-Parenting tips related to internalizing problems (e.g., anxiety, depression) had a higher click rate than E-Parenting tips related to externalizing problems (e.g., oppositional behavior). OPRs disseminated through Facebook posts, and E-Parenting tips resulted in wide reach and engagement. Different media channels should be utilized to disseminate different OPRs to as many parents as possible.
Topics: Humans; Parenting; Social Media; Parents; Schools
PubMed: 37329566
DOI: 10.1002/jcop.23068 -
Research Square Dec 2023Uveal melanoma is the most common non-cutaneous melanoma and is an intraocular malignancy affecting nearly 7,000 individuals per year worldwide. Of these, approximately...
BACKGROUND
Uveal melanoma is the most common non-cutaneous melanoma and is an intraocular malignancy affecting nearly 7,000 individuals per year worldwide. Of these, approximately 50% will progress to metastatic disease for which there are currently no effective therapies. Despite advances in molecular profiling and metastatic stratification of uveal melanoma tumors, little is known regarding their underlying biology of metastasis. Our group has identified a disseminated neoplastic cell population characterized by co-expression of immune and melanoma proteins, circulating hybrid cells (hybrids), in patients with uveal melanoma. Compared to circulating tumor cells, which lack expression of immune proteins, hybrids are detected at an increased prevalence in peripheral blood and can be used as a non-invasive biomarker to predict metastatic progression.
METHODS
To ascertain mechanisms underlying enhanced hybrid cell dissemination we identified hybrid cells within primary uveal melanoma tumors using single cell RNA sequencing and evaluated their gene expression and predicted ligand-receptor interactions in relation to other melanoma and immune cells within the primary tumor. We then verified expression of upregulated hybrid pathways within patient-matched tumor and peripheral blood hybrids using cyclic immunofluorescence and quantified their protein expression relative to other non-hybrid tumor and disseminated tumor cells.
RESULTS
Among the top upregulated genes and pathways in hybrid cells were those involved in enhanced cell motility and cytoskeletal rearrangement, immune evasion, and altered cellular metabolism. In patient-matched tumor and peripheral blood, we verified gene expression by examining concordant protein expression for each pathway category: TMSB10 (cell motility), CD74 (immune evasion) and GPX1 (metabolism). Both TMSB10 and GPX1 were expressed on significantly higher numbers of disseminated hybrid cells compared to circulating tumor cells, and CD74 and GPX1 were expressed on more disseminated hybrids than tumor-resident hybrids. Lastly, we identified that hybrid cells express ligand-receptor signaling pathways implicated in promoting metastasis including GAS6-AXL, CXCL12-CXCR4, LGALS9-P4HB and IGF1-IGFR1.
CONCLUSION
These findings highlight the importance of TMSB10, GPX1 and CD74 for successful hybrid cell dissemination and survival in circulation. Our results contribute to the understanding of uveal melanoma tumor progression and interactions between tumor cells and immune cells in the tumor microenvironment that may promote metastasis.
PubMed: 38106024
DOI: 10.21203/rs.3.rs-3694879/v1 -
Journal of Pediatric Health Care :... Jun 2024Research methods papers are a valuable resource to researchers and clinicians that highlight novel yet effective methodologies and approaches to conducting research....
Research methods papers are a valuable resource to researchers and clinicians that highlight novel yet effective methodologies and approaches to conducting research. Clinicians can use the knowledge generated from unique research methods to conduct quality, evidence-based practice, and quality improvement projects, and nurse researchers can benefit from the lessons learned by others to improve the rigor of future studies. This paper defines research methods papers, provides an overview of their importance, including examples from the literature, and highlights important considerations when writing and disseminating the findings of research methods.
PubMed: 38842963
DOI: 10.1016/j.pedhc.2024.05.001