Project description:Biliary tract carcinoma (BTC) has a poor prognosis due to limited treatment options. There is therefore urgent need to identify new targets and to design innovative therapeutic approaches. Among potential candidate molecules, we evaluated the non-receptor tyrosine kinase Src, observing promising antitumor effects of its small molecule inhibitor Saracatinib in BTC preclinical models. The presence of an active Src protein was investigated by immunohistochemistry in 19 surgical samples from BTC patients. Upon Saracatinib treatment, the phosphorylation of Src and of its downstream transducers was evaluated in the BTC cell lines TFK-1, EGI-1, HuH28 and TGBC1-TKB. The effect of Saracatinib on proliferation and migration was analyzed in these same cell lines, and its antitumor activity was essayed in EGI-1 mouse xenografts. Saracatinib-modulated transcriptome was profiled in EGI-1 cells and in tumor samples of the xenograft model. Src was activated in about 80% of the human BTC samples. In cultured BTC cell lines, low-dose Saracatinib counteracted the activation of Src and of its downstream effectors, increased the fraction of cells in G0/G1 phase, and inhibited cell migration. At high concentrations (median dose from 2.26 to 6.99 µM), Saracatinib was also capable of inhibiting BTC cell proliferation. In vivo, Saracatinib treatment resulted in delayed tumor growth, associated with an impaired vascular network. We here provide a demonstration that the targeted inhibition of Src kinase by Saracatinib is of therapeutic benefit in preclinical models of BTC. We propose our results as a basis for the design of Saracatinib-based clinical applications. EGI-1 cell line treated with Saracatinib at the dose of 10 µM vs EGI-1 cell line untreated; EGI-1 xenograft treated with Saracatinib at the dose of 25 mg/Kg/die vs EGI-1 xenograft untreated Transcriptional alteration mediated by Saracatinib in vitro and in vivo

2012-08-02 | E-GEOD-36622 | biostudies-arrayexpress

Acidimicrobiia strain:EGI L10123 | isolate:EGI L10123

Project description:Acidimicrobiia strain:EGI L10123 | isolate:EGI L10123 Genome sequencing

| PRJNA1012832 | ENA

Phytoactinopolyspora

Project description:Phytoactinopolyspora sp. overview

| PRJNA476818 | ENA

Phytoactinopolyspora halophila strain:YIM 96934

Project description:Phytoactinopolyspora halophila strain:YIM 96934 Genome sequencing and assembly

| PRJNA476695 | ENA

Phytoactinopolyspora limicola strain:HAJB-30

Project description:Phytoactinopolyspora limicola strain:HAJB-30 Genome sequencing and assembly

| PRJNA610467 | ENA

Phytoactinopolyspora halophila

Project description:Phytoactinopolyspora halophila Genome sequencing

| PRJNA476680 | ENA

Transcriptional characterization of bacteria-fungi interaction between Priestia endophytica FH5 and phytopathogen Rhizoctonia solani

Project description:Priestia endophytica FH5, which was isolated from healthy tomato rhizosphere soil, had biological activity against a variety of plant diseases, including R. solani. We isolated the chemicals generated by strain FH5 to better understand the interaction between strain FH5 and R. solani. A transcriptome study of strain FH5 with and without R. solani exposure was also performed. In response to the fungal pathogen R. solani, strain FH5 changed genes linked to amino acid transport, carbohydrate transport, energy generation and conversion, and inorganic ion transport and metabolism, according to our findings.

2021-07-09 | GSE179605 | GEO

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