Pharmacological characterization of chemokine receptor 7 (CCR7) as a potential therapeutic target in cancer

The expression of CCR7 was evaluated in different cancer cell lines by using flow cytometry, western blot, Immunofluorescence and immunohistochemistry. We showed for the selected cell lines that the expression is maintained in cells grown as spheroids, and xenoplanted in mice. Furthermore, we showed the expression of CCR7 correlates with stage of the disease in patient derived head and neck cancer tissue. We also showed that expression of CCR7 in cancer cell lines correlates with migratory aptitude towards CCL21 in a scratch assay, Boyden chamber assay and spheroid invasion assay. We then showed that the expression of CCR7 is elevated under serum starvation and under hypoxia in cancer cell lines grown as monolayers and as spheroids; and that there is a correlation between hypoxia and CCR7 expression in spheroids, xenografted cells and clinical cancer tissue. However, we found that in cell line OSC-19, the increase in the expression of CCR7 did not correlate to increased migration. Our investigations following this observation showed that whilst hypoxia increases the expression of CCR7, it concurrently causes a decrease in reactive oxygen species (ROS) which strongly abrogates migratory aptitude in OSC-19, resulting in an overall loss of migration in OSC-19 cells. In addition, we characterised OSC-19 as a suitable model to evaluate small molecule CCR7 antagonists using a number of different assays. In particular, we showed that ICT13069 antagonised response of this cell line across a number of drivers of malignancy such as migration, invasion in 2D and 3D models.Zarqa UniversityThe full text was made available at the end of the embargo, 3rd December 201

Targeting GSK-3β enzyme by diazepino-quinolone derivatives

Purpose: To synthesize a heterocyclic system containing quinolone and diazepine scaffolds as GSK-3β inhibitor. Methods: The diazepino-quinoline derivatives were synthesized starting from quinolone nucleus in a simple chemical reaction. The in vitro GSK-3β enzyme assay and MTT assay against cancer cell lines were carried out followed by Z´ı-LYTE GSK-3β assay. Anticancer activity was determined using U-87 glioma cell line. Results: Diazepino-quinoline derivatives were obtained in a good yield, and compound 102 exhibited significant activity against in vitro GSK-3β (IC50: 0.114 μM), and anticancer activity (IC50: 37 μM) against U-87 glioma cell line. Conclusion: The GSK-3β enzyme is a potential target to treat different diseases, and diazepines derivatives are a successful template for inhibitors design against GSK-3β enzyme with IC50 in a micromolar range

Study of the chemotactic response of multicellular spheroids in a microfluidic device

YesWe report the first application of a microfluidic device to observe chemotactic migration in multicellular spheroids. A microfluidic device was designed comprising a central microchamber and two lateral channels through which reagents can be introduced. Multicellular spheroids were embedded in collagen and introduced to the microchamber. A gradient of fetal bovine serum (FBS) was established across the central chamber by addition of growth media containing serum into one of the lateral channels. We observe that spheroids of oral squamous carcinoma cells OSC–19 invade collectively in the direction of the gradient of FBS. This invasion is more directional and aggressive than that observed for individual cells in the same experimental setup. In contrast to spheroids of OSC–19, U87-MG multicellular spheroids migrate as individual cells. A study of the exposure of spheroids to the chemoattractant shows that the rate of diffusion into the spheroid is slow and thus, the chemoattractant wave engulfs the spheroid before diffusing through it.This work has been supported by National Research Program of Spain (DPI2011-28262-c04-01) and by the project "MICROANGIOTHECAN" (CIBERBBN, IMIBIC and SEOM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

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Association between physician’s visits and socio-demographic factors.

Association between physician’s visits and socio-demographic factors.</p

Level of knowledge among the participants about routes of transmission (those who answered by choosing “yes”).

Level of knowledge among the participants about routes of transmission (those who answered by choosing “yes”).</p

Attitude and knowledge about protection measures from COVID-19 (those who answered by choosing “yes”).

Attitude and knowledge about protection measures from COVID-19 (those who answered by choosing “yes”).</p

Knowledge about high-risk groups of COVID-19 infection.

Knowledge about high-risk groups of COVID-19 infection.</p

Knowledge about why COVID-19 is dangerous? (N = 328).

RT, No: Rapid transmission rate with no mortality risk, RT, High: Rapid transmission rate with high mortality risk, RT, Low: Rapid transmission rate with low mortality risk, LT, High: Low transmission rate with high mortality risk, LT, Low: Low transmission rate with low mortality risk and DK: don’t know.</p

Socio-demographic characteristics (N = 328).

Socio-demographic characteristics (N = 328).</p