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Trends in Cancer Apr 2024Epithelial cancers have served as a paradigm to study tumor dissemination but recent data have highlighted significant differences with nonepithelial cancers. Here, we... (Review)
Review
Epithelial cancers have served as a paradigm to study tumor dissemination but recent data have highlighted significant differences with nonepithelial cancers. Here, we review the current knowledge on nonepithelial tumor dissemination, drawing examples from the latest developments in melanoma, glioma, and sarcoma research. We underscore the importance of the reactivation of developmental processes during cancer progression and describe the nongenetic mechanisms driving nonepithelial tumor spread. We also outline therapeutic opportunities and ongoing clinical approaches to fight disseminating cancers. Finally, we discuss remaining challenges and emerging questions in the field. Defining the core principles underlying nonepithelial cancer dissemination may uncover actionable vulnerabilities of metastatic tumors and help improve the prognosis of patients with cancer.
Topics: Humans; Melanoma; Glioma; Tumor Microenvironment
PubMed: 38135572
DOI: 10.1016/j.trecan.2023.11.006 -
BMB Reports Jun 2024Cancer cells metastasize to distant organs by altering their characteristics within the tumor microenvironment (TME) to effectively overcome challenges during the... (Review)
Review
Cancer cells metastasize to distant organs by altering their characteristics within the tumor microenvironment (TME) to effectively overcome challenges during the multistep tumorigenesis. Plasticity endows cancer cell with the capacity to shift between different morphological states to invade, disseminate, and seed metastasis. The epithelial-to-mesenchymal transition (EMT) is a theory derived from tissue biopsy, which explains the acquisition of EMT transcription factors (TFs) that convey mesenchymal features during cancer migration and invasion. On the other hand, adherent-to-suspension transition (AST) is an emerging theory derived from liquid biopsy, which describes the acquisition of hematopoietic features by AST-TFs that reprograms anchorage dependency during the dissemination of circulating tumor cells (CTCs). The induction and plasticity of EMT and AST dynamically reprogram cell-cell interaction and cell-matrix interaction during cancer dissemination and colonization. Here, we review the mechanisms governing cellular plasticity of AST and EMT during the metastatic cascade and discuss therapeutic challenges posed by these two morphological adaptations to provide insights for establishing new therapeutic interventions. [BMB Reports 2024; 57(6): 273-280].
Topics: Humans; Epithelial-Mesenchymal Transition; Cell Plasticity; Neoplasms; Tumor Microenvironment; Neoplastic Cells, Circulating; Neoplasm Metastasis; Transcription Factors; Animals; Neoplasm Invasiveness
PubMed: 38627950
DOI: 10.5483/BMBRep.2024-0018 -
Advances in Kidney Disease and Health Jan 2024Patient involvement in research can improve the relevance of research, consequently enhancing the recruitment, retention, and uptake of interventions and policies... (Review)
Review
Patient involvement in research can improve the relevance of research, consequently enhancing the recruitment, retention, and uptake of interventions and policies impacting patient outcomes. Despite this, patients are not often involved in the design and conduct of research. The research agenda and innovations are frequently determined by the interest of health and industry professionals rather than proactively aligning with the priorities of patients. It is now being encouraged and recommended to engage patients in research priority setting to ensure interventions and trials report outcomes valuable to patients, moving away from a history of overlooking the outcomes that reflect the feel and function of patients. Involving patients ensures constant innovative research in nephrology, as this broader depth of evidence fortifies reliability and validity through knowledge gained from lived experience. Findings from such research can enhance clinical practice and strengthen decision-making and policy to support better outcomes. We aim to outline principles and strategies for patient involvement in research, including setting research priorities, identifying and designing interventions, selecting outcomes, and disseminating and translating research. Principles and strategies including engagement, education and training, empowerment, and connection and community provide guidance in patient involvement. There are increasing efforts to involve patients across all stages of research including setting research priorities. Efforts are rising to involve patients across all stages of research including priority setting, identifying and designing interventions, selecting outcomes, and dissemination and translation. Patient involvement throughout the research cycle drives innovative investigations ensuring funding, efforts, and resources are directed toward priorities of patients, contributing to catalyst advancements in care and outcomes.
Topics: Humans; Nephrology; Reproducibility of Results; Patients; Patient-Centered Care
PubMed: 38403395
DOI: 10.1053/j.akdh.2023.12.004 -
BMJ Open Sep 2023Observational studies are increasingly used to inform health decision-making when randomised trials are not feasible, ethical or timely. The target trial approach... (Observational Study)
Observational Study
BACKGROUND
Observational studies are increasingly used to inform health decision-making when randomised trials are not feasible, ethical or timely. The target trial approach provides a framework to help minimise common biases in observational studies that aim to estimate the causal effect of interventions. Incomplete reporting of studies using the target trial framework limits the ability for clinicians, researchers, patients and other decision-makers to appraise, synthesise and interpret findings to inform clinical and public health practice and policy. This paper describes the methods that we will use to develop the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) reporting guideline.
METHODS/DESIGN
The TARGET reporting guideline will be developed in five stages following recommended guidance. The first stage will identify target trial reporting practices by systematically reviewing published studies that explicitly emulated a target trial. The second stage will identify and refine items to be considered for inclusion in the TARGET guideline by consulting content experts using sequential online surveys. The third stage will prioritise and consolidate key items to be included in the TARGET guideline at an in-person consensus meeting of TARGET investigators. The fourth stage will produce and pilot-test both the TARGET guideline and explanation and elaboration document with relevant stakeholders. The fifth stage will disseminate the TARGET guideline and resources via journals, conferences and courses.
ETHICS AND DISSEMINATION
Ethical approval for the survey has been attained (HC220536). The TARGET guideline will be disseminated widely in partnership with stakeholders to maximise adoption and improve reporting of these studies.
Topics: Humans; Consensus; Policy; Referral and Consultation; Research Personnel
PubMed: 37699620
DOI: 10.1136/bmjopen-2023-074626 -
Cancer Biology & Therapy Dec 2024Metastasis accounts for the vast majority of cancer deaths; however, this complex process has yet to be fully explained. To form metastases, cancer cells must undergo a... (Review)
Review
Metastasis accounts for the vast majority of cancer deaths; however, this complex process has yet to be fully explained. To form metastases, cancer cells must undergo a series of steps, known as the "Metastatic cascade", each of which requires a specific functional transformation. Cancer stem cells (CSCs) play a vital role in tumor metastasis, but their dynamic behavior and regulatory mechanisms have not been fully elucidated. Based on the "Metastatic cascade" theory, this review summarizes the effect of liver CSCs on the metastatic biological programs that underlie the dissemination and metastatic growth of cancer cells. Liver CSCs have the capacity to initiate distant organ metastasis via EMT, and the microenvironment transformation that supports the ability of these cells to disseminate, evade immune surveillance, dormancy, and regenerate metastasis. Understanding the heterogeneity and traits of liver CSCs in these processes is critical for developing strategies to prevent and treat metastasis of advanced hepatocellular carcinoma (HCC).
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Neoplastic Stem Cells; Tumor Microenvironment
PubMed: 38393655
DOI: 10.1080/15384047.2024.2321768 -
Frontiers in Microbiology 2023Antibiotic resistance development and pathogen cross-dissemination are both considered essential risks to human health on a worldwide scale. Antimicrobial resistance... (Review)
Review
Antibiotic resistance development and pathogen cross-dissemination are both considered essential risks to human health on a worldwide scale. Antimicrobial resistance genes (AMRs) are acquired, expressed, disseminated, and traded mainly through integrons, the key players capable of transferring genes from bacterial chromosomes to plasmids and their integration by integrase to the target pathogenic host. Moreover, integrons play a central role in disseminating and assembling genes connected with antibiotic resistance in pathogenic and commensal bacterial species. They exhibit a large and concealed diversity in the natural environment, raising concerns about their potential for comprehensive application in bacterial adaptation. They should be viewed as a dangerous pool of resistance determinants from the "One Health approach." Among the three documented classes of integrons reported viz., class-1, 2, and 3, class 1 has been found frequently associated with AMRs in humans and is a critical genetic element to serve as a target for therapeutics to AMRs through gene silencing or combinatorial therapies. The direct method of screening gene cassettes linked to pathogenesis and resistance harbored by integrons is a novel way to assess human health. In the last decade, they have witnessed surveying the integron-associated gene cassettes associated with increased drug tolerance and rising pathogenicity of human pathogenic microbes. Consequently, we aimed to unravel the structure and functions of integrons and their integration mechanism by understanding horizontal gene transfer from one trophic group to another. Many updates for the gene cassettes harbored by integrons related to resistance and pathogenicity are extensively explored. Additionally, an updated account of the assessment of AMRs and prevailing antibiotic resistance by integrons in humans is grossly detailed-lastly, the estimation of AMR dissemination by employing integrons as potential biomarkers are also highlighted. The current review on integrons will pave the way to clinical understanding for devising a roadmap solution to AMR and pathogenicity. Graphical AbstractThe graphical abstract displays how integron-aided AMRs to humans: Transposons capture integron gene cassettes to yield high mobility integrons that target res sites of plasmids. These plasmids, in turn, promote the mobility of acquired integrons into diverse bacterial species. The acquisitions of resistant genes are transferred to humans through horizontal gene transfer.
PubMed: 37720149
DOI: 10.3389/fmicb.2023.1231938 -
Cell Reports Dec 2023The expression of pro-lymphangiogenic VEGF-C in primary tumors is associated with sentinel lymph node metastasis in most solid cancer types. However, the impact of...
The expression of pro-lymphangiogenic VEGF-C in primary tumors is associated with sentinel lymph node metastasis in most solid cancer types. However, the impact of VEGF-C on distant organ metastasis remains unclear. Perivascular tumor-associated macrophages (TAMs) play a crucial role in guiding hematogenous spread of cancer cells by establishing metastatic pathways within the tumor microenvironment. This process supports breast cancer cell intravasation and metastatic dissemination. We show here that VEGF-C-expressing TAMs reduce the dissemination of mammary cancer cells to the lungs while concurrently increasing lymph node metastasis. These TAMs express podoplanin and interact with normalized tumor blood vessels expressing VEGFR3. Moreover, clinical data suggest inverse association between VEGF-C-expressing TAMs and breast cancer malignancy. Thus, our study elucidates the paradoxical role of VEGF-C-expressing TAMs in redirecting cancer cells to preferentially disseminate to lymph nodes rather than to lungs, partially achieved by normalizing tumor blood vessels and promoting lymphangiogenesis.
Topics: Humans; Female; Lymphatic Metastasis; Breast Neoplasms; Tumor-Associated Macrophages; Vascular Endothelial Growth Factor C; Lymphangiogenesis; Tumor Microenvironment
PubMed: 38041815
DOI: 10.1016/j.celrep.2023.113507 -
The Journal of Infectious Diseases Nov 2023Ebola virus (EBOV) disease is marked by rapid virus replication and spread. EBOV enters the cell by macropinocytosis and replicates in the cytoplasm, and nascent virions...
Ebola virus (EBOV) disease is marked by rapid virus replication and spread. EBOV enters the cell by macropinocytosis and replicates in the cytoplasm, and nascent virions egress from the cell surface to infect neighboring cells. Here, we show that EBOV uses an alternate route to disseminate: tunneling nanotubes (TNTs). TNTs, an actin-based long-range intercellular communication system, allows for direct exchange of cytosolic constituents between cells. Using live, scanning electron, and high-resolution quantitative 3-dimensional microscopy, we show that EBOV infection of primary human cells results in the enhanced formation of TNTs containing viral nucleocapsids. TNTs promote the intercellular transfer of nucleocapsids in the absence of live virus, and virus could replicate in cells devoid of entry factors after initial stall. Our studies suggest an alternate model of EBOV dissemination within the host, laying the groundwork for further investigations into the pathogenesis of filoviruses and, importantly, stimulating new areas of antiviral design.
Topics: Humans; Ebolavirus; Hemorrhagic Fever, Ebola; Nanotubes; Cell Communication
PubMed: 37723997
DOI: 10.1093/infdis/jiad400 -
Clinics in Dermatology 2024HIV infection alters the skin microbiome and predisposes to a wide range of cutaneous infections, from atypical presentations of common skin infections to severe...
HIV infection alters the skin microbiome and predisposes to a wide range of cutaneous infections, from atypical presentations of common skin infections to severe disseminated infections involving the skin that are AIDS-defining illnesses. Bacterial infection of the skin, most commonly caused by Staphylococcus aureus, occurs frequently and can result in bacteremia. Nontuberculous mycobacterial infections that are usually localized to the skin may disseminate, and guidance on the treatment of these infections is limited. Herpes simplex can be severe, and less common presentations such as herpetic sycosis and herpes vegetans have been reported. Severe herpes zoster, including disseminated infection, requires intravenous antiviral treatment. Viral warts can be particularly difficult to treat, and in atypical or treatment-resistant cases a biopsy should be considered. Superficial candidosis occurs very commonly in people living with HIV, and antifungal resistance is an increasing problem in non-albicans Candida species. Systemic infections carry a poor prognosis. In tropical settings the endemic mycoses including histoplasmosis are a problem for people living with HIV, and opportunistic infections can affect those with advanced HIV in all parts of the world. Most cutaneous infections can develop or worsen as a result of immune reconstitution in the weeks to months after starting antiretroviral therapy. Direct microscopic examination of clinical material can facilitate rapid diagnosis and treatment initiation, although culture is important to provide microbiological confirmation and guide treatment.
Topics: Humans; HIV Infections; AIDS-Related Opportunistic Infections; Skin Diseases, Infectious; Mycoses; Bacterial Infections; Dermatitis
PubMed: 38142787
DOI: 10.1016/j.clindermatol.2023.12.005 -
Frontiers in Immunology 2024Melanoma is one of the most lethal neoplasms of the skin. Despite the revolutionary introduction of immune checkpoint inhibitors, metastatic spread, and recurrence... (Review)
Review
Melanoma is one of the most lethal neoplasms of the skin. Despite the revolutionary introduction of immune checkpoint inhibitors, metastatic spread, and recurrence remain critical problems in resistant cases. Melanoma employs a multitude of mechanisms to subvert the immune system and successfully metastasize to distant organs. Concerningly, recent research also shows that tumor cells can disseminate early during melanoma progression and enter dormant states, eventually leading to metastases at a future time. Immune escape and metastasis have previously been viewed as separate phenomena; however, accumulating evidence is breaking down this dichotomy. Recent research into the progressive mechanisms of melanoma provides evidence that dedifferentiation similar to classical epithelial to mesenchymal transition (EMT), genes involved in neural crest stem cell maintenance, and hypoxia/acidosis, are important factors simultaneously involved in immune escape and metastasis. The likeness between EMT and early dissemination, and differences, also become apparent in these contexts. Detailed knowledge of the mechanisms behind "dual drivers" simultaneously promoting metastatically inclined and immunosuppressive environments can yield novel strategies effective in disabling multiple facets of melanoma progression. Furthermore, understanding progression through these drivers may provide insight towards novel treatments capable of preventing recurrence arising from dormant dissemination or improving immunotherapy outcomes.
Topics: Humans; Melanoma; Epithelial-Mesenchymal Transition; Immunotherapy
PubMed: 38426087
DOI: 10.3389/fimmu.2024.1336023