Axl as a potential therapeutic target for adamantinomatous craniopharyngiomas: Based on single nucleus RNA-seq and spatial transcriptome profiling.

Craniopharyngiomas (CPs), particularly Adamantinomatous Craniopharyngiomas (ACPs), often exhibit a heightened risk of postoperative recurrence and severe complications of the endocrine and hypothalamic function. The primary objective of this study is to investigate potential novel targeted therapies within the microenvironment of ACP tumors. Cancer-Associated Fibroblasts (CAFs) were identified in the craniopharyngioma microenvironment, notably in regions characterized by cholesterol clefts, wet keratin, ghost cells, and fibrous stroma in ACPs. CAFs, alongside ghost cells, basaloid-like epithelium cells and calcifications, were found to secrete PROS1 and GAS6, which can activate AXL receptors on the surface of tumor epithelium cells, promoting immune suppression and tumor progression in ACPs. Additionally, the AXL inhibitor Bemcentinib effectively inhibited the proliferation organoids and enhanced the immunotherapeutic efficacy of Atezolizumab. Furthermore, neural crest-like cells were observed in the glial reactive tissue surrounding finger-like protrusions. Overall, our results revealed that the AXL might be a potentially effective therapeutic target for ACPs.

[Compensated hypothyroidism and statin administration: the symptoms of muscle damage and muscle metabolism disorders].

BACKGROUND: There is no unequivocal opinion regarding the safety of statin in patients with hypothyroidism. However, based on some new data, it can be assumed that hypothyroidism, even in a stage of compensation, may cause muscle damage in patients receiving statins. As part of this study, this hypothesis was tested, and was confirmed. AIMS: To study the possibility of muscle damage and the nature of muscle metabolism in patients with compensated hypothyroidism who takes statin. MATERIALS AND METHODS: The study is transverse and observational with the inclusion of 120 women, subdivided on three groups (n=40). The main group of patients with hypothyroidism who took statins (group 1) was compared with two control groups, including those who took statins without hypothyroidism (group 2), and who did not take statins with hypothyroidism (group 3). RESULTS: Patients taking statins and have compensated hypothyroidism are more likely to develop complaints of muscle pain, which are often associated with the elevation of muscle lesion markers, as well as the presence of the C allele in the SLCO1B1*5 gene (c.521T>C). In patients with compensated hypothyroidism, relative frequency of occurance of muscle pain syndrome associated with CPK elevation increases with TSH levels above 2.86 mU/L. Compensated hypothyroidism increases the possibility of development of SPM-ATP by 2.7 times. CONCLUSIONS: Compensated hypothyroidism is not a contraindication for statin therapy. However, the presence of even compensated hypothyroidism in patients taking statins increases the possibility of the development of muscle symptoms associated with taking statins, and requires additional monitoring of the clinical and biochemical parameters of muscle metabolism (especially the level of CPK).

miR-203 suppresses the proliferation and metastasis of hepatocellular carcinoma by targeting oncogene ADAM9 and oncogenic long non-coding RNA HULC.

MicroRNAs (miRNAs) have been integrated into tumorigenic programs by regulating genes at post-transcriptional level. Long non-coding RNAs (lncRNAs) are novel targets for miRNAs. Here, we reported that miR-203 down-regulation was closely linked to advanced clinical features and poor overall survival (OS) of patients with hepatocellular carcinoma. We also confirmed that miR-203 and oncogene ADAM9 (a disintegrin and metalloproteinase 9)/oncogenic long non-coding RNA HULC (highly up-regulated in liver cancer) were inversely expressed in hepatocellular carcinoma (HCC) tissues or cell lines. More intriguingly, up-regulation of miR-203 diminished the expression of ADAM9 and HULC in HCC cancer cells. Over-expression of miR-203 could markedly inhibit cell proliferation, invasion and induce cell apoptosis. Furthermore, we identified that miR-203 modulated ADAM9 and HULC in a novel post-transcriptional regulatory mechanism. Over-expression of HULC partly rescued the miR-203-mediated antitumor effects. These results suggested that miR-203 played tumor suppressive roles by downregulating ADAM9 and HULC and indicated its potential application in cancer treatment.