9 research outputs found

    Molecular and cellular mechanisms controlling integrin-mediated cell adhesion and tumor progression in ovarian cancer metastasis: a review

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    Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy in the developed world. EOC metastasis is unique since malignant cells detach directly from the primary tumor site into the abdominal fluid and form multicellular aggregates, called spheroids, that possess enhanced survival mechanisms while in suspension. As such, altered cell adhesion properties are paramount to EOC metastasis with cell detachment from the primary tumor, dissemination as spheroids, and reattachment to peritoneal surfaces for secondary tumor formation. The ability for EOC cells to establish and maintain cell–cell contacts in spheroids is critical for cell survival in suspension. Integrins are a family of cell adhesion receptors that play a crucial role in cell–cell and cell-extracellular matrix interactions. These glycoprotein receptors regulate diverse functions in tumor cells and are implicated in multiple steps of cancer progression. Altered integrin expression is detected in numerous carcinomas, where they play a role in cell migration, invasion, and anchorage-independent survival. Like that observed for other carcinomas, epithelial-mesenchymal transition (EMT) occurs during metastasis and integrins can function in this process as well. Herein, we provide a review of the evidence for integrin-mediated cell adhesion mechanisms impacting steps of EOC metastasis. Taken together, targeting integrin function may represent a potential therapeutic strategy to inhibit progression of advanced EOC

    Investigation of β5 integrin function in epithelial ovarian cancer cell adhesion and metastatic properties of spheroids

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    Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy in the developed world. EOC metastasis is unique since malignant cells detach directly from the primary tumor site into the abdominal fluid and form multicellular aggregates, called spheroids, that possess enhanced survival mechanisms while in suspension. As such, altered cell adhesion properties are paramount to EOC metastasis with cell detachment from the primary tumor, dissemination as spheroids, and reattachment to peritoneal surfaces for secondary tumor formation. These interactions play a crucial role in cell-cell and cell-extracellular matrix interactions, having implications in multiple steps of cancer progression. We previously showed that the CRISPR-ablation of Liver Kinase B1 (LKB1) or its downstream effector Nua Kinase 1 (NUAK1) resulted in spheroid disaggregation in vitro and is required for efficient EOC metastasis in mouse tumor cell xenografts. Global gene expression analysis demonstrated a coordinated reduction in b5-integrin (encoded by ITGB5 gene). Integrins are a family of cell-adhesion receptors required to mediate cellular interactions with the extracellular matrix (ECM) and promote tumorigenesis in various malignancies; however, the role of b5-integrin in EOC is unknown. Using publicly-available datasets and western blot analysis, we identified relatively high b5 integrin expression in established and patient ascites-derived EOC cell lines. siRNA-mediated knockdown of ITGB5 reduced EOC cell adhesion, impacted adherent cell and spheroid viability. We identified that b5 integrin is required for efficient spheroid reattachment and subsequent cell spreading. When evaluating the interaction of b5 integrin with ECM ligands, results indicate that b5 integrin and its association with vitronectin may play a role in spheroid reattachment

    Infant Feeding Practices: A Global Perspective

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    Infant nutrition is a primary determinant of growth and development, with long-term impacts on health. The World Health Organization (WHO) offers guidelines for infant feeding, however practices vary by geographical location, culture, and biopsychosocial factors. This chapter provides a comprehensive overview of peer-reviewed and gray literature on the current infant feeding guidelines and cultural practices across the globe. The findings draw attention to the multiple drivers and barriers to exclusive breastfeeding in various regions. This chapter can serve as a building block to inform future public health initiatives and research. By addressing these barriers, we can improve maternal and infant health and reduce the burden of malnutrition and associated health consequences for infants globally

    Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

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    Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

    Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study (Intensive Care Medicine, (2021), 47, 2, (160-169), 10.1007/s00134-020-06234-9)

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    The original version of this article unfortunately contained a mistake. The members of the ESICM Trials Group Collaborators were not shown in the article but only in the ESM. The full list of collaborators is shown below. The original article has been corrected
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