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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 -
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 -
MBio Apr 2018Journal clubs are important mechanisms for teaching how to approach the scientific literature critically and for disseminating findings. Papers from high-impact journals...
Journal clubs are important mechanisms for teaching how to approach the scientific literature critically and for disseminating findings. Papers from high-impact journals often dominate journal club selections, a practice that reinforces the unscientific emphasis of placing high value on publishing venue rather than scientific content and critical analysis of the publications. We suggest improving journal clubs by including preprints rather than focusing completely on published papers. This change in practice might benefit the scientific enterprise in numerous ways, including by providing direct criticisms to preprint authors before publication, deemphasizing publishing venue, teaching students the art of reviewing papers, and making journal clubs more current by discussing unpublished data.
Topics: Humans; Information Dissemination; Preprints as Topic
PubMed: 29615505
DOI: 10.1128/mBio.00516-18 -
Cancers Nov 2020Cancer immunotherapy has shifted the paradigm in cancer therapy by revitalizing immune responses against tumor cells. Specifically, in primary tumors cancer cells evolve... (Review)
Review
Cancer immunotherapy has shifted the paradigm in cancer therapy by revitalizing immune responses against tumor cells. Specifically, in primary tumors cancer cells evolve in an immunosuppressive microenvironment, which protects them from immune attack. However, during tumor progression, some cancer cells leave the protective tumor mass, disseminating and seeding secondary organs. These initial disseminated tumor cells (DTCs) should potentially be susceptible to recognition by the immune system in the new host tissues. Although Natural Killer or T cells eliminate some of these DTCs, a fraction escape anti-tumor immunity and survive, thus giving rise to metastatic colonization. How DTCs interact with immune cells and the underpinnings that regulate imperfect immune responses during tumor dissemination remain poorly understood. Uncovering such mechanisms of immune evasion may contribute to the development of immunotherapy specifically targeting DTCs. Here we review current knowledge about systemic and site-specific immune-cancer crosstalk in the early steps of metastasis formation. Moreover, we highlight how conventional cancer therapies can shape the pre-metastatic niche enabling immune escape of newly arrived DTCs.
PubMed: 33207601
DOI: 10.3390/cancers12113385 -
The British Journal of Surgery Jan 2019Effective dissemination of technology in global surgery is vital to realize universal health coverage by 2030. Challenges include a lack of human resource,... (Review)
Review
BACKGROUND
Effective dissemination of technology in global surgery is vital to realize universal health coverage by 2030. Challenges include a lack of human resource, infrastructure and finance. Understanding these challenges, and exploring opportunities and solutions to overcome them, are essential to improve global surgical care.
METHODS
This review focuses on technologies and medical devices aimed at improving surgical care and training in low- and middle-income countries. The key considerations in the development of new technologies are described, along with strategies for evaluation and wider dissemination. Notable examples of where the dissemination of a new surgical technology has achieved impact are included.
RESULTS
Employing the principles of frugal and responsible innovation, and aligning evaluation and development to high scientific standards help overcome some of the challenges in disseminating technology in global surgery. Exemplars of effective dissemination include low-cost laparoscopes, gasless laparoscopic techniques and innovative training programmes for laparoscopic surgery; low-cost and versatile external fixation devices for fractures; the LifeBox pulse oximeter project; and the use of immersive technologies in simulation, training and surgical care delivery.
CONCLUSION
Core strategies to facilitate technology dissemination in global surgery include leveraging international funding, interdisciplinary collaboration involving all key stakeholders, and frugal scientific design, development and evaluation.
Topics: Biomedical Technology; Delivery of Health Care; Developing Countries; Diffusion of Innovation; General Surgery; Global Health; Humans
PubMed: 30620068
DOI: 10.1002/bjs.11036 -
Asian Journal of Neurosurgery 2021The objective of this study was to provide an overview of acute disseminating encephalomyelitis, a potential and serious complication of COVID-19. (Review)
Review
OBJECTIVE
The objective of this study was to provide an overview of acute disseminating encephalomyelitis, a potential and serious complication of COVID-19.
METHODS
Three primary databases were used, PubMed, LitCovid, and WHO. The final review articles reported acute disseminated encephalomyelitis (ADEM) in COVID-19-positive patients and were full-text, peer-reviewed articles. Articles which did not have patient data such as studies and articles with unclear inference were excluded.
RESULTS
Out of 21 cases of ADEM, the diagnosis of severe acute respiratory syndrome-coronavirus 2 was confirmed in 18 and suspected in 3. Among the neurological symptoms, altered consciousness was most common (7/21), followed by anosmia (3), paraplegia (3/21), brain stem involvement (3/21), sphincter involvement (2/21), and quadriplegia (1/21). Raised inflammatory markers were most commonly seen in 9/17. Central nervous system imaging was abnormal in 19 cases and unavailable in 2 cases. Fifteen patients were treated with corticosteroids, 11 patients received intravenous immunoglobulin, while 3 patients received convalescent plasma. Two patients needed surgical intervention. Complications included seizures (1), acute kidney injury and septicemic shock (1), raised intracranial pressure (1), and supraventricular tachycardia secondary to hydroxychloroquine (1). One patient recovered completely and one had good recovery with mild deficits. Thirteen patients had incomplete recovery with residual neurological deficit while three patients died as the consequence of the disease.
CONCLUSION
The physicians and neurosurgeons should be diligent while treating the COVID-19 patients with neurological manifestations and include ADEM as a differential diagnosis and stress on early diagnosis and treatment to reduce mortality and achieve satisfactory clinical outcome.
PubMed: 34660355
DOI: 10.4103/ajns.AJNS_406_20