Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation

A key aspect of cancer metastases is the tendency for specific cancer cells to home to defined subsets of secondary organs. Despite these known tendencies, the underlying mechanisms remain poorly understood. Here we develop a microfluidic 3D in vitro model to analyze organ-specific human breast cancer cell extravasation into bone- and muscle-mimicking microenvironments through a microvascular network concentrically wrapped with mural cells. Extravasation rates and microvasculature permeabilities were significantly different in the bone-mimicking microenvironment compared with unconditioned or myoblast containing matrices. Blocking breast cancer cell A[subscript 3] adenosine receptors resulted in higher extravasation rates of cancer cells into the myoblast-containing matrices compared with untreated cells, suggesting a role for adenosine in reducing extravasation. These results demonstrate the efficacy of our model as a drug screening platform and a promising tool to investigate specific molecular pathways involved in cancer biology, with potential applications to personalized medicine.National Cancer Institute (U.S.) (Grant R33 CA174550-01)National Cancer Institute (U.S.) (Grant R21 CA140096)Italian Ministry of HealthCharles Stark Draper Laboratory (Fellowship

Influenza vaccination coverage among medical residents: An Italian multicenter survey

Although influenza vaccination is recognized to be safe and effective, recent studies have confirmed that immunization coverage among health care workers remain generally low, especially among medical residents (MRs). Aim of the present multicenter study was to investigate attitudes and determinants associated with acceptance of influenza vaccination among Italian MRs. A survey was performed in 2012 on MRs attending post-graduate schools of 18 Italian Universities. Each participant was interviewed via an anonymous, self-administered, web-based questionnaire including questions on attitudes regarding influenza vaccination. A total of 2506 MRs were recruited in the survey and 299 (11.9%) of these stated they had accepted influenza vaccination in 2011-2012 season. Vaccinated MRs were older (P = 0.006), working in clinical settings (P = 0.048), and vaccinated in the 2 previous seasons (P < 0.001 in both seasons). Moreover, MRs who had recommended influenza vaccination to their patients were significantly more compliant with influenza vaccination uptake in 2011-2012 season (P < 0.001). "To avoid spreading influenza among patients" was recognized as the main reason for accepting vaccination by less than 15% of vaccinated MRs. Italian MRs seem to have a very low compliance with influenza vaccination and they seem to accept influenza vaccination as a habit that is unrelated to professional and ethical responsibility. Otherwise, residents who refuse vaccination in the previous seasons usually maintain their behaviors. Promoting correct attitudes and good practice in order to improve the influenza immunization rates of MRs could represent a decisive goal for increasing immunization coverage among health care workers of the future. © 2014 Landes Bioscience

Cogging force analysis of linear motor arrays driving the thirty meter telescope

A finite element analysis of the cogging force generated by an array of linear synchronous motors moving on a curvilinear track is presented. This system is under consideration as the driving system for the two main axes of the Thirty Meter Telescope that will be built in Mauna Kea, Hawaii. The main objective of this work is the quantification of the effects of the curvilinear track on the motors cogging force. The finite element analysis is carried out using planar cross sections, and the results found are used to find an approximate solution for the three-dimensional model. The results show that the presence of the curvilinear-configured track significantly increases the cogging force of a single motor, while the presence of several motors interacts in limiting the increase in the cogging force. Finally, in order to reduce the total cogging force, an optimization in regards to the relative positions of the motors along the tracks is carried out. \ua9 2011 IEEE.Peer reviewed: YesNRC publication: Ye

Finite element analysis of the cogging force in the linear synchronous motor array for the Thirty Meter Telescope

In this paper, a finite element analysis of the cogging force generated by an array of linear synchronous motors (LSM) moving on a curvilinear track is presented. This system is under consideration as the driving system for the two main axes of the proposed Thirty Meter Telescope that will be built in Mauna Kea, Hawaii. The main objective of this work is the quantification of the effects of the curvilinear track of LSM arrays on the cogging force. The finite element analysis is carried out using planar cross sections, and the results found are used to find an approximate solution for the three-dimensional model. The results show that the presence of the curvilinear-configured track increases the cogging force of a single LSM significantly, while the presence of the array of LSMs interacts in limiting the increase in the cogging force. A geometric optimization in regards to the relative positions of the LSMs along the curvilinear tracks is subsequently carried out in order to reduce the total cogging force. (C) 2010 Elsevier Ltd. All rights reserved.Peer reviewed: YesNRC publication: Ye

Engineering the early bone metastatic niche through human vascularized immuno bone minitissues

Bone metastases occur in 65%-80% advanced breast cancer patients. Although significant progresses have been made in understanding the biological mechanisms driving the bone metastatic cascade, traditional 2Din vitromodels and animal studies are not effectively reproducing breast cancer cells (CCs) interactions with the bone microenvironment and suffer from species-specific differences, respectively. Moreover, simplifiedin vitromodels cannot realistically estimate drug anti-tumoral properties and side effects, hence leading to pre-clinical testing frequent failures. To solve this issue, a 3D metastatic bone minitissue (MBm) is designed with embedded human osteoblasts, osteoclasts, bone-resident macrophages, endothelial cells and breast CCs. This minitissue recapitulates key features of the bone metastatic niche, including the alteration of macrophage polarization and microvascular architecture, along with the induction of CC micrometastases and osteomimicry. The minitissue reflects breast CC organ-specific metastatization to bone compared to a muscle minitissue. Finally, two FDA approved drugs, doxorubicin and rapamycin, have been tested showing that the dose required to impair CC growth is significantly higher in the MBm compared to a simpler CC monoculture minitissue. The MBm allows the investigation of metastasis key biological features and represents a reliable tool to better predict drug effects on the metastatic bone microenvironment

Correction: A microphysiological early metastatic niche on a chip reveals how heterotypic cell interactions and inhibition of integrin subunit β3 impact breast cancer cell extravasation

Correction for 'A microphysiological early metastatic niche on a chip reveals how heterotypic cell interactions and inhibition of integrin subunit β3 impact breast cancer cell extravasation' by Martina Crippa et al., Lab Chip, 2021, DOI: