جستجوی مقالات مرتبط با کلیدواژه "receptor tyrosine kinases" در نشریات گروه "پزشکی"

The MET receptor is a critical member of cancer-associated receptor tyrosine kinases and plays an important role in different biological activities, including differentiation, migration, and cell proliferation.

In this study, novel MET inhibitors were introduced and applied on esophageal squamous carcinoma cell line KYSE-30, and the level of proliferation and migration, as well as the activated form of MET receptor protein were assessed in the examined cells. The human KYSE-30 cell line was cultured according to ATCC recommendations. The mRNA level of the MET gene was measured in the examined cell line using the quantitative RT-PCR assay. Cytotoxicity evaluation test was performed at different concentrations of heterocyclic anti-MET compounds (i.e. D1, D2, D5, D6, D7, and D8). Finally, the capability of these compounds in MET receptor inhibition was evaluated using the migration assay and Western blot. All experiments were performed in triplicate and repeated three times with similar results.

Cell growth and proliferation were significantly inhibited (p ≤ 0.05) by all the above-mentioned compounds. Moreover, the majority of compounds significantly prevented the cell migration (p ≤ 0.05) and inhibited MET autophosphorylation. Interestingly, the level of phosphorylated MET was significantly correlated with KYSE-30 cell migration.

The obtained data introduced and confirmed the biological activities of the mentioned novel compounds in KYSE-30 cells and proposed that the therapeutic inhibition of MET with these compounds may be a powerful approach for inhibiting cancer cell migration and proliferation although some structural optimizations are needed to improve their inhibitory functions.

Depression is one of the most common mood disorders. Considering the evidence on the effect of Cinnamomum on mood disorders, this study investigatedthe effect of hydroalcoholic extract of Cinnamomum (HEC) in an animal model of depression.

Thirty-two male rats were selected and divided into four groups (n=8) including: control, depressed, and depressed treated with200 and 400 mg/kg HEC. Depression induction protocol was conducted in all groups except for the control group. Sucrose preference test (SPT) and forced swimming test (FST) were done to analyze the depression score. After four weeks, the animals brain cortex was removed and BDNF protein and tyrosine receptor kinase B (TrkB) gene expression levels were determined by ELISA and Real Time PCR, respectively.

The results of this study showed that 400 mg/kg of HEC increased the tendency to drink the sucrose solution. Furthermore, immobility time significantly increased in the depressed group compared to the control group while it was attenuated by administration of 400 mg/kg extract on the 28th day versus the depressed group. Also the extract at both doses increased swimming time compared to the depressed group. In addition, an increase in the BDNF protein and TrkB gene expression levels was observed in the prefrontal cortex of the treatment groups.

We found that HEC ameliorated depression symptoms in rats and these effects were probably due to an increase in BDNF proteins and its receptor, TrkB, gene expressions in the prefrontal cortex.

We aimed to determine the role of receptor tyrosine kinases (RTK) signaling family genes in the development of oral squamous cell carcinoma (OSCC). In the present in silico study, 40 whole genome sequences of patients with OSCC from the cBioPortal was analysed to identify the mutations in the genes of the RTK signaling pathway. Using the STRING v10.5, we further checked the gene with the highest frequency of mutations for its protein interactions. The obtained protein interaction network was used to identify the possible pathways related to disease phenotype. Epidermal growth factor receptor (EGFR) gene showed the highest frequency of mutation (5%) among the 16 genes clustered in the RTK signaling pathway as available in the cBioportal database. Missense mutations viz., G203E, R521K were identified in the EGFR gene. The other genes which returned positive results during analysis were ERBB4 (D245N, L993S), PDGFB (R100H), and PDGFRB (L667M). The in silico method of analysis can be a contemporary approach for identifying possible mutations or pathways associated with the development of OSCC. Further high throughput strategies should be applied to substantiate the role of the genes identified in the present study and draw conclusive evidence as to their association with the disease phenotype.