A quantitative bio-imaging platform is developed for analysis of human cancer dissemination in a short-term vertebrate xenotransplantation assay. Six days after implantation of cancer cells in ...zebrafish embryos, automated imaging in 96 well plates coupled to image analysis algorithms quantifies spreading throughout the host. Findings in this model correlate with behavior in long-term rodent xenograft models for panels of poorly- versus highly malignant cell lines derived from breast, colorectal, and prostate cancer. In addition, cancer cells with scattered mesenchymal characteristics show higher dissemination capacity than cell types with epithelial appearance. Moreover, RNA interference establishes the metastasis-suppressor role for E-cadherin in this model. This automated quantitative whole animal bio-imaging assay can serve as a first-line in vivo screening step in the anti-cancer drug target discovery pipeline.
Abstract Cell spheroids (CS) embedded in 3D extracellular matrix (ECM) serve as in vitro mimics for multicellular structures in vivo . Such cultures, started either from spontaneous cell aggregates ...or single cells dispersed in a gel are time consuming, applicable to restricted cell types only, prone to high variation, and do not allow CS formation with defined spatial distribution required for high-throughput imaging. Here, we describe a method where cell-polymer suspensions are microinjected as droplets into collagen gels and CS formation occurs within hours for a broad range of cell types. We have automated this method to produce CS arrays in fixed patterns with defined x-y-z spatial coordinates in 96 well plates and applied automated imaging and image analysis algorithms. Low intra- and inter-well variation of initial CS size and CS expansion indicates excellent reproducibility. Distinct cell migration patterns, including cohesive strand-like – and individual cell migration can be visualized and manipulated. A proof-of-principle chemical screen is performed identifying compounds that affect cancer cell invasion/migration. Finally, we demonstrate applicability to freshly isolated mouse breast and human sarcoma biopsy material – indicating potential for development of personalized cancer treatment strategies.
Background: Congenital heart surgeries are associated with post-bypass renal and cardiac dysfunctions. The use of low-dose vasopressin has been found to be beneficial in adult cardiac surgeries.
...Objective: To assess the hemodynamic and renal effects of patients undergoing on-pump pediatric cardiac surgery under general anesthesia (GA) with low-dose vasopressin infusion.
Design: Prospective randomized controlled study.
Setting: Operation room and ICU, tertiary care teaching hospital.
Patients: Fifty-five pediatric cardiac patients undergoing repair for congenital heart diseases (CHD).
Interventions: Low-dose vasopressin infusion in the study group and placebo in the control group.
Measurements and Main Results: Renal near-infrared spectroscopy (NIRS), serum NGAL, and inflammatory mediators-IL6 and IL8 along with other renal and hemodynamic parameters in the perioperative period were recorded. Diastolic blood pressure (DBP) and cardiac index were significantly higher in the vasopressin group. Inflammatory markers were significantly high in the immediate postoperative period in all patients which later stabilized in the next 48 h but showed similar trends in both groups. Low-dose vasopressin infusion did not improve either renal perfusion or function. The duration of mechanical ventilation and length of hospital stay, the incidence of AKI development, and transfusion requirements were marginally lower in the vasopressin group, although not significant.
Conclusion: Low-dose vasopressin infusion improved hemodynamics and showed a decreased incidence of complications. However, it failed to show any benefit of renal function and overall outcome in pediatric cardiac surgery.
Extra Corporeal Membrane Oxygenation (ECMO) has long been used for cardiorespiratory support in the immediate post-paediatric cardiac surgery period with a 2-3% success as per the ELSO registry. ...Success in recovery depends upon the optimal delivery of critical care to paediatric patients and a comprehensive healthcare team.
The survival benefit of children placed on central veno arterial (VA) ECMO following elective cardiac surgeries for congenital heart disease (n = 672) was studied in a cohort of 29 (4.3%) cases from the period of Jan 2018 to Dec 2022 in our cardiac surgical centre. Indications for placing these patients on central VA ECMO included inability to wean from cardiopulmonary bypass (CPB), low cardiac output syndrome, severe pulmonary arterial hypertension, significant bleeding, anaphylaxis, respiratory failure and severe pulmonary edema.
The mean time to initiation of ECMO was less than 5 h and the mean duration of ECMO support was 56 h with a survival rate of 58.3%. Amongst perioperative complications, sepsis and arrhythmia on ECMO were found to be negatively associated with survival. Improvements in the pH, PaO2 levels and serum lactate levels after initiation of ECMO were associated with survival benefits.
The early initiation of ECMO for paediatric cardiotomies could be a beacon of hope for families and medical teams confronting these challenging situations. Improvement in indicators of adequate perfusion and ventricular recoveries like pH and serum lactate and absence of arrhythmia and sepsis are associated with good outcomes.
Radiotherapy is one of the treatment options for locally or regionally advanced prostate cancer, but radioresistance of prostate cancer cells is a practical limitation of radiotherapy. The ...identification of molecular targets of radioresistance in prostate cancer is important to improve therapeutic intervention. The aim of this review is to give more biological insight into some well known processes involved in radioresistance of prostate cancer especially Apoptotic pathway; DNA damage response; and NF- κB(nuclear factor kappalight- chain-enhancer of activated B cells) signaling pathway. This review integrates salient, published, research findings with underlying molecular mechanisms, preclinical efficacy, and potential clinical applications of combining radiotherapy with these molecular targeted agents for the treatment of prostate cancer.
Improved targeted therapies are needed to combat metastatic prostate cancer. Here, we report the identification of the spleen kinase SYK as a mediator of metastatic dissemination in zebrafish and ...mouse xenograft models of human prostate cancer. Although SYK has not been implicated previously in this disease, we found that its expression is upregulated in human prostate cancers and associated with malignant progression. RNAi-mediated silencing prevented invasive outgrowth in vitro and bone colonization in vivo, effects that were reversed by wild-type but not kinase-dead SYK expression. In the absence of SYK expression, cell surface levels of the progression-associated adhesion receptors integrin α2β1 and CD44 were diminished. RNAi-mediated silencing of α2β1 phenocopied SYK depletion in vitro and in vivo, suggesting an effector role for α2β1 in this setting. Notably, pharmacologic inhibitors of SYK kinase currently in phase I-II trials for other indications interfered similarly with the invasive growth and dissemination of prostate cancer cells. Our findings offer a mechanistic rationale to reposition SYK kinase inhibitors for evaluation in patients with metastatic prostate cancer.
Radiographers' profession is constantly evolving, which demands adaptation of education and training programs to build up medical imaging and radiation therapy professionals (MIRTPs) that provide ...healthcare to improve patient experience and outcomes. This study aimed to map radiographers’ practices, competences, and autonomy level in Western Switzerland.
Data was collected by 2 cross-sectional online surveys targeting Alumni, radiographers, clinical placement tutors and medical imaging equipment specialists from industry, with opened and closed-end questions. Descriptive statistics and thematic analysis were used to analyse the data.
81 Alumni and 93 Chief-Radiographers, clinical tutors, practitioner-radiographers and industry answered the questionnaires. The competences considered as the most “acquired or completely acquired” by the Alumni were: adopt a reflective posture on practice (90.1 %; 73/81), adopt ethical behaviour (90.1 %; 73/81), carrying out and providing radiological services for diagnostic, therapeutic and preventive purposes (81.5 %; 68/81), adapting communication to the other surrounding persons (81.5 %; 66/81), and check compliance of procedures with standards (69.1 %; 56/81). Similar results were referred by Employers. The autonomy of the participant radiographers was considered as average, and it focuses only the preparation of the patient and the protocol optimisation. The development and integration of research is weak as well as the application of competences regarding professionalism.
A better link between educational institutions and clinical practice can help on the integration of research and evidence-based on practice, necessary to progress the radiographers' profession in Western Switzerland. The autonomy needs to be further developed and leadership courses must be integrated in the curricula to facilitate the implementation of new approaches to reinforce radiographer's profession.
Practice must be revised to integrate evidence-based; to facilitate research development, the managers need to increase support.
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