FAK inhibition alone or in combination with adjuvant therapies reduces cancer stem cell activity

From Springer Nature via Jisc Publications RouterHistory: received 2020-06-29, accepted 2021-03-15, registration 2021-04-23, pub-electronic 2021-05-28, online 2021-05-28, collection 2021-12Publication status: PublishedFunder: Royal College of Surgeons of England (RCS); doi: https://doi.org/10.13039/501100000297Abstract: Cancer stem-like cells (CSC) contribute to therapy resistance and recurrence. Focal adhesion kinase (FAK) has a role in CSC regulation. We determined the effect of FAK inhibition on breast CSC activity alone and in combination with adjuvant therapies. FAK inhibition reduced CSC activity and self-renewal across all molecular subtypes in primary human breast cancer samples. Combined FAK and paclitaxel reduced self-renewal in triple negative cell lines. An invasive breast cancer cohort confirmed high FAK expression correlated with increased risk of recurrence and reduced survival. Co-expression of FAK and CSC markers was associated with the poorest prognosis, identifying a high-risk patient population. Combined FAK and paclitaxel treatment reduced tumour size, Ki67, ex-vivo mammospheres and ALDH+ expression in two triple negative patient derived Xenograft (PDX) models. Combined treatment reduced tumour initiation in a limiting dilution re-implantation PDX model. Combined FAK inhibition with adjuvant therapy has the potential to improve breast cancer survival

Heavy Metals

Fundamental societal changes resulted from the necessity of people to get organized in mining, transporting, processing, and circulating the heavy metals and their follow-up products, which in consequence resulted in a differentiation of society into diversified professions and even societal strata. Heavy metals are highly demanded technological materials, which drive welfare and progress of the human society, and often play essential metabolic roles. However, their eminent toxicity challenges the field of chemistry, physics, engineering, cleaner production, electronics, metabolomics, botany, biotechnology, and microbiology in an interdisciplinary and cross-sectorial manner. Today, all these scientific disciplines are called to dedicate their efforts in a synergistic way to avoid exposure of heavy metals into the eco- and biosphere, to reliably monitor and quantify heavy metal contamination, and to foster the development of novel strategies to remediate damage caused by heavy metals

Selective and sensitive determination of Cd(II) ions in various samples using a novel modified carbon paste electrode

Abstract Based on the highly toxic effects of Cd(II) on the aquatic environment and the human health, identification and evaluation of such pollutants is required. Efficient and economic electrodes for sensitive and selective detection of this element are very important. In this study, carbon paste electrode (CPE) modified with lanthanum tungstate ion exchanger was assembled for potentiometric assay of Cd(II) ions. The prepared sensor exhibited a Nernstian response for Cd(II) within a wide working range of 8 × 10−8–1 × 10−1 mol L−1, with a slope of 29.4 ± 0.12 mV/decade. It has been specified by a low detection limit of 8 × 10−8 mol L−1 and a short response time of ~ 5 s and can be utilized efficiently up to 22 weeks without any significant errors in the potential determination. The standard electrode potentials, E°, and the isothermal temperature coefficient (dE°/dt) of the sensor were estimated at various temperatures. The obtained results indicated that the nominated electrode has efficient performance to estimate Cd(II) in its pure solutions and other various real samples (river water, plant foodstuff, industrial wastewater, nickel cadmium battery, and fish tissue samples)

Potentiometric determination of mercury (II) ion in various real samples using novel modified screen-printed electrode

Abstract A screen-printed electrode modified with zirconium antimonate ionophore was fabricated for the quantification of Hg(II) ion. The modified electrode revealed linear response in a wide concentration range of 5 × 10−8–1 × 10−1 mol/L at 25 °C of Hg(II) with a slope of 30.02 ± 0.75 mV/decade with detection limit of 5 × 10−8 mol/L. The electrode can be used in the pH range 2.5–8.5. Selectivity coefficients were assessed using fixed interference and matched potential techniques. The electrode stability was maintained for 16 weeks. This modified electrode was allowed to determine Hg(II) ions in different media such as water, dental amalgam and fish tissue. An inductively coupled plasma-optical emission spectrometry confirmed the efficiency and accuracy of the nominated modified electrode

FAK inhibition alone or in combination with adjuvant therapies reduces cancer stem cell activity

Cancer stem-like cells (CSC) contribute to therapy resistance and recurrence. Focal adhesion kinase (FAK) has a role in CSC regulation. We determined the effect of FAK inhibition on breast CSC activity alone and in combination with adjuvant therapies. FAK inhibition reduced CSC activity and self-renewal across all molecular subtypes in primary human breast cancer samples. Combined FAK and paclitaxel reduced self-renewal in triple negative cell lines. An invasive breast cancer cohort confirmed high FAK expression correlated with increased risk of recurrence and reduced survival. Co-expression of FAK and CSC markers was associated with the poorest prognosis, identifying a high-risk patient population. Combined FAK and paclitaxel treatment reduced tumour size, Ki67, ex-vivo mammospheres and ALDH+ expression in two triple negative patient derived Xenograft (PDX) models. Combined treatment reduced tumour initiation in a limiting dilution re-implantation PDX model. Combined FAK inhibition with adjuvant therapy has the potential to improve breast cancer survival

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