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Cell Reports. Medicine Mar 2023Although breast cancer mortality is largely caused by metastasis, clinical decisions are based on analysis of the primary tumor and on lymph node involvement but not on...
Although breast cancer mortality is largely caused by metastasis, clinical decisions are based on analysis of the primary tumor and on lymph node involvement but not on the phenotype of disseminated cells. Here, we use multiplex imaging mass cytometry to compare single-cell phenotypes of primary breast tumors and matched lymph node metastases in 205 patients. We observe extensive phenotypic variability between primary and metastatic sites and that disseminated cell phenotypes frequently deviate from the clinical disease subtype. We identify single-cell phenotypes and spatial organizations of disseminated tumor cells that are associated with patient survival and a weaker survival association for high-risk phenotypes in the primary tumor. We show that p53 and GATA3 in lymph node metastases provide prognostic information beyond clinical classifiers and can be measured with standard methods. Molecular characterization of disseminated tumor cells is an untapped source of clinically applicable prognostic information for breast cancer.
Topics: Humans; Lymphatic Metastasis; Prognosis; Lymph Nodes
PubMed: 36921599
DOI: 10.1016/j.xcrm.2023.100977 -
Nature Communications Feb 2022Metastases are initiated by disseminated tumor cells (DTCs) that colonize distant organs. Growing evidence suggests that the microenvironment of the primary tumor primes...
Metastases are initiated by disseminated tumor cells (DTCs) that colonize distant organs. Growing evidence suggests that the microenvironment of the primary tumor primes DTCs for dormant or proliferative fates. However, the manner in which this occurs remains poorly understood. Here, using the Window for High-Resolution Intravital Imaging of the Lung (WHRIL), we study the live lung longitudinally and follow the fate of individual DTCs that spontaneously disseminate from orthotopic breast tumors. We find that spontaneously DTCs have increased levels of retention, increased speed of extravasation, and greater survival after extravasation, compared to experimentally metastasized tumor cells. Detailed analysis reveals that a subset of macrophages within the primary tumor induces a pro-dissemination and pro-dormancy DTC phenotype. Our work provides insight into how specific primary tumor microenvironments prime a subpopulation of cells for expression of proteins associated with dissemination and dormancy.
Topics: Animals; Breast Neoplasms; Cell Line, Tumor; Female; Humans; Mice; Mice, Inbred C57BL; Neoplasms, Experimental; Neoplastic Stem Cells; Phenotype; Tumor Microenvironment; Tumor-Associated Macrophages
PubMed: 35110548
DOI: 10.1038/s41467-022-28076-3 -
Nature Cancer Oct 2022Increasing evidence shows that cancer cells can disseminate from early evolved primary lesions much earlier than the classical metastasis models predicted. Here, we...
Increasing evidence shows that cancer cells can disseminate from early evolved primary lesions much earlier than the classical metastasis models predicted. Here, we reveal at a single-cell resolution that mesenchymal-like (M-like) and pluripotency-like programs coordinate dissemination and a long-lived dormancy program of early disseminated cancer cells (DCCs). The transcription factor ZFP281 induces a permissive state for heterogeneous M-like transcriptional programs, which associate with a dormancy signature and phenotype in vivo. Downregulation of ZFP281 leads to a loss of an invasive, M-like dormancy phenotype and a switch to lung metastatic outgrowth. We also show that FGF2 and TWIST1 induce ZFP281 expression to induce the M-like state, which is linked to CDH1 downregulation and upregulation of CDH11. We found that ZFP281 not only controls the early dissemination of cancer cells but also locks early DCCs in a dormant state by preventing the acquisition of an epithelial-like proliferative program and consequent metastases outgrowth.
Topics: Humans; Fibroblast Growth Factor 2; Neoplasms; Transcription Factors; Lung
PubMed: 36050483
DOI: 10.1038/s43018-022-00424-8 -
Annals of Vascular Surgery Oct 2020The use of social media for academic or research purposes is still in infancy. However, the potential of dissemination of medical knowledge through these electronic... (Review)
Review
The use of social media for academic or research purposes is still in infancy. However, the potential of dissemination of medical knowledge through these electronic platforms is dynamically increasing. We performed a search on Twitter® collecting tweets containing the keywords "peripheral arterial disease" and "abdominal aortic aneurysm" separately and including 3 types of emitters. Our aim was to assess the dissemination of these 2 major vascular entities across the social networking and their effect on the medical and general population. The results show that people talk about their experiences of hospitals and care quality on Twitter® more than health care providers or commercial industries in critical diseases that arise more concern. Twitter® could become a successful channel through which physicians, patients, and health care providers interact, engage, and disseminate medical knowledge.
Topics: Aortic Aneurysm, Abdominal; Evidence-Based Medicine; Humans; Information Dissemination; Patient Satisfaction; Peripheral Arterial Disease; Quality Indicators, Health Care; Scholarly Communication; Social Media; Vascular Surgical Procedures
PubMed: 32562831
DOI: 10.1016/j.avsg.2020.06.024 -
BMJ Open Aug 2021Endometriosis is a debilitating chronic inflammatory condition highly burdensome to the healthcare system. The present trial will establish the efficacy of (1) yoga and... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Endometriosis is a debilitating chronic inflammatory condition highly burdensome to the healthcare system. The present trial will establish the efficacy of (1) yoga and (2) cognitive-behavioural therapy (CBT), above (3) education, on quality of life, biopsychosocial outcomes and cost-effectiveness.
METHODS AND ANALYSIS
This study is a parallel randomised controlled trial. Participants will be randomly allocated to yoga, CBT or education. Participants will be English-speaking adults, have a diagnosis of endometriosis by a qualified physician, with pain for at least 6 months, and access to internet. Participants will attend 8 weekly group CBT sessions of 120 min; or 8 weekly group yoga sessions of 60 min; or receive weekly educational handouts on endometriosis. The primary outcome measure is quality of life. The analysis will include mixed-effects analysis of variance and linear models, cost-utility analysis from a societal and health system perspective and qualitative thematic analysis.
ETHICS AND DISSEMINATION
Enrolment in the study is voluntary and participants can withdraw at any time. Participants will be given the option to discuss the study with their next of kin/treating physician. Findings will be disseminated via publications, conferences and briefs to professional organisations. The University's media team will also be used to further disseminate via lay person articles and media releases.
TRIAL REGISTRATION NUMBER
ACTRN12620000756921p; Pre-results.
Topics: Adult; Cognitive Behavioral Therapy; Cost-Benefit Analysis; Endometriosis; Female; Health Care Costs; Humans; Quality of Life; Treatment Outcome; Yoga
PubMed: 34373298
DOI: 10.1136/bmjopen-2020-046603 -
Cells Nov 2022Pancreatic cancer is a disease notorious for its high frequency of recurrence and low survival rate. Surgery is the most effective treatment for localized pancreatic... (Review)
Review
Pancreatic cancer is a disease notorious for its high frequency of recurrence and low survival rate. Surgery is the most effective treatment for localized pancreatic cancer, but most cancer recurs after surgery, and patients die within ten years of diagnosis. The question persists: what makes pancreatic cancer recur and metastasize with such a high frequency? Herein, we review evidence that subclinical dormant pancreatic cancer cells disseminate before developing metastatic or recurring cancer. We then discuss several routes by which pancreatic cancer migrates and the mechanisms by which pancreatic cancer cells adapt. Lastly, we discuss unanswered questions in pancreatic cancer cell migration and our perspectives.
Topics: Humans; Pancreatic Neoplasms; Pancreas; Cell Movement
PubMed: 36429111
DOI: 10.3390/cells11223683 -
Environmental Health : a Global Access... Dec 2022Environmental health sciences have identified and characterized a range of environmental exposures and their associated risk for disease, as well as informed the... (Review)
Review
BACKGROUND
Environmental health sciences have identified and characterized a range of environmental exposures and their associated risk for disease, as well as informed the development of interventions, including recommendations, guidelines, and policies for mitigating exposure. However, these interventions only serve to mitigate exposures and prevent disease if they are effectively disseminated, adopted, implemented, and sustained.
MAIN BODY
Numerous studies have documented the enormous time lag between research and practice, noting that dissemination and implementation are not passive processes but rely on active and intentional strategies. Implementation science seeks to build the knowledge base for understanding strategies to effectively disseminate and implement evidence and evidence-based interventions, and thus, bridge the research-to-practice gap.
CONCLUSION
Environmental health researchers are well positioned to advance health promotion and disease prevention by incorporating implementation science into their work. This article describes the rationale for and key components of implementation science and articulates opportunities to build upon existing efforts to advance environmental health supported by the National Institute of Environmental Health Sciences and National Institutes of Health broadly.
Topics: United States; Humans; Implementation Science; Environmental Health; Environmental Exposure; National Institute of Environmental Health Sciences (U.S.)
PubMed: 36564832
DOI: 10.1186/s12940-022-00933-0 -
Revista de La Facultad de Ciencias... Sep 2023When we recognize the importance of disseminating scientific knowledge, we recognize not only the potential it can have in the hands of the scientific community, but...
When we recognize the importance of disseminating scientific knowledge, we recognize not only the potential it can have in the hands of the scientific community, but also in the hands of society as a whole. From this premise, we first reflect, hoping that such reflection will lead us to commit ourselves to make dissemination actions accessible and non-discriminatory. "Equal access to science is not only a social and ethical requirement for human development, but also a necessity to fully exploit the potential of scientific communities around the world and to guide scientific progress in a way that meets the needs of humanity".
PubMed: 37773336
DOI: 10.31053/1853.0605.v80.n3.42305 -
Cellular Microbiology Nov 2019Toxoplasma gondii (T. gondii) is a parasitic protist that can infect nearly all nucleated cell types and tissues of warm-blooded vertebrate hosts. T. gondii utilises a... (Review)
Review
Toxoplasma gondii (T. gondii) is a parasitic protist that can infect nearly all nucleated cell types and tissues of warm-blooded vertebrate hosts. T. gondii utilises a unique form of gliding motility to cross cellular barriers, enter tissues, and penetrate host cells, thus enhancing spread within an infected host. However, T. gondii also disseminates by hijacking the migratory abilities of infected leukocytes. Traditionally, this process has been viewed as a route to cross biological barriers such as the blood-brain barrier. Here, we review recent findings that challenge this view by showing that infection of monocytes downregulates the program of transendothelial migration. Instead, infection by T. gondii enhances Rho-dependent interstitial migration of monocytes and macrophages, which enhances dissemination within tissues. Collectively, the available evidence indicates that T. gondii parasites use multiple means to disseminate within the host, including enhanced motility in tissues and translocation across biological barriers.
Topics: Animals; Blood-Brain Barrier; Cell Movement; Central Nervous System Infections; Host-Pathogen Interactions; Humans; Integrins; Leukocytes; Macrophages; Monocytes; Toxoplasma; Toxoplasmosis; Transendothelial and Transepithelial Migration
PubMed: 31219666
DOI: 10.1111/cmi.13070