ALPL-1 is a target for chimeric antigen receptor therapy in osteosarcoma.

Osteosarcoma (OS) remains a dismal malignancy in children and young adults, with poor outcome for metastatic and recurrent disease. Immunotherapies in OS are not as promising as in some other cancer types due to intra-tumor heterogeneity and considerable off-target expression of the potentially targetable proteins. Here we show that chimeric antigen receptor (CAR) T cells could successfully target an isoform of alkaline phosphatase, ALPL-1, which is highly and specifically expressed in primary and metastatic OS.

The Impact of the COVID-19 Pandemic on the Professional Autonomy of Anesthesiological Nurses and Trust in the Therapeutic Team of Intensive Therapy Units-Polish Multicentre Study.

Introduction: The COVID-19 pandemic as well as the rate of spread of this particular pathogen around the world have caused the number of patients requiring medical attention and intensive care to exceed the capacity of even the best organized health care systems. This resulted in the need to hire employees who had not previously worked in intensive care units. Experience and knowledge have become particularly important in the context of mutual trust in the ICU team.

miR-486-5p expression is regulated by DNA methylation in osteosarcoma.

Background: Osteosarcoma is the most common primary malignant tumour of bone occurring in children and young adolescents and is characterised by complex genetic and epigenetic changes. The miRNA miR-486-5p has been shown to be downregulated in osteosarcoma and in cancer in general.

Results: To investigate if the mir-486 locus is epigenetically regulated, we integrated DNA methylation and miR-486-5p expression data using cohorts of osteosarcoma cell lines and patient samples.

Discovery of novel candidates for anti-liposarcoma therapies by medium-scale high-throughput drug screening.

Sarcomas are a heterogeneous group of mesenchymal orphan cancers and new treatment alternatives beyond traditional chemotherapeutic regimes are much needed. So far, tumor mutation analysis has not led to significant treatment advances, and we have attempted to bypass this limitation by performing direct drug testing of a library of 353 anti-cancer compounds that are either FDA-approved, in clinical trial, or in advanced stages of preclinical development on a panel of 13 liposarcoma cell lines. We identified and validated six drugs, targeting different mechanisms and with good efficiency across the cell lines: MLN2238 -a proteasome inhibitor, GSK2126458 -a PI3K/mTOR inhibitor, JNJ-26481585 -a histone deacetylase inhibitor, triptolide-a multi-target drug, YM155 -a survivin inhibitor, and APO866 (FK866)-a nicotinamide phosphoribosyl transferase inhibitor.

Preclinical Evaluation of the Pan-FGFR Inhibitor LY2874455 in FRS2-Amplified Liposarcoma.

FGFR inhibition has been proposed as treatment for dedifferentiated liposarcoma (DDLPS) with amplified , but we previously only demonstrated transient cytostatic effects when treating -amplified DDLPS cells with NVP-BGJ398. Effects of the more potent FGFR inhibitor LY2874455 were investigated in three DDLPS cell lines by measuring effects on cell growth and apoptosis and also testing efficacy . Genome, transcriptome and protein analyses were performed to characterize the signaling components in the FGFR pathway.