Search

Cell lineage plasticity is one of the major causes for the failure of targeted therapies in various cancers. However, the driver and actionable drug targets in promoting cancer cell lineage plasticity are scarcely identified. Here, we found that a G protein-coupled receptor, ADORA2A, is specifically upregulated during neuroendocrine differentiation, a common form of lineage plasticity in prostate cancer and lung cancer following targeted therapies. Activation of the ADORA2A signaling rewires the proline metabolism via an ERK/MYC/PYCR cascade. Increased proline synthesis promotes deacetylases SIRT6/7-mediated deacetylation of histone H3 at lysine 27 (H3K27), and thereby biases a global transcriptional output toward a neuroendocrine lineage profile. Ablation of Adora2a in genetically engineered mouse models inhibits the development and progression of neuroendocrine prostate and lung cancers, and, intriguingly, prevents the adenocarcinoma-to-neuroendocrine phenotypic transition. Importantly, pharmacological blockade of ADORA2A profoundly represses neuroendocrine prostate and lung cancer growth in vivo. Therefore, we believe that ADORA2A can be used as a promising therapeutic target to govern the epigenetic reprogramming in neuroendocrine malignancies., Introduction Lineage plasticity is often exploited by cancer cells to acquire therapeutic resistance (1). Lineage transition from adenocarcinoma (AD) to aggressive neuroendocrine (NE) derivatives is a common type of cancer [...]

Background: Intestinal metaplasia of the bladder is an uncommon glandular proliferation. We examined a large series of intestinal metaplasia for the clinicopathological features and discuss the significance of this lesion.Methods: All cases of intestinal metaplasia diagnosed in our institution between 1990 and 2014 were retrospectively reviewed. Patients with a history of urothelial carcinoma or concurrent adenocarcinoma were excluded. Patient characteristics, pathological features, and follow-up outcomes were obtained.Results: We identified 89 patients with intestinal metaplasia during this period. Sixty seven were men and 22 were women. Mean age at diagnosis was 57 years (range 23-81). Common presenting complaints included haematuria (73 cases), mucosuria (13 cases), and irritative voiding symptoms (seven cases). The majority of intestinal metaplasias located on or near the trigone (67 cases). Eighty-two patients underwent transurethral resection of their lesions. Partial cystectomy was performed in the remaining seven patients. The mean follow-up of 78 patients was 105 months (range 6-255). One case of bladder adenocarcinoma was indentified 6 months later. The initial histologic findings had revealed intestinal metaplasia with severe dysplasia. Four patients presented recurrence during the follow-up, and this occurred 9, 13, 17 and 24 months after the surgery.Conclusions: Although intestinal metaplasia can be treated effectively by transurethral resection in most cases, its potential malignancy need to be taken into consideration after the evidence of recurrences and its association with bladder adenocarcinoma. Therefore, it is necessary to perform close surveillance following the surgery, particularly in patients with dysplastic changes. [ABSTRACT FROM AUTHOR]

Purpose: To detect the expression of VEGF and EGFR in peripheral blood and cancer tissues of patients with renal cell carcinoma (RCC), and to explore the correlations with clinical stage, pathological grade and prognosis of disease., Methods: A total of 64 patients with RCC who were diagnosed and treated from June 2016 to August 2017 in our hospital were enrolled. Patients were divided into different clinical stages and pathological grades, and ELISA and immunohistochemistry were used to detect the expression of VEGF and EGFR in peripheral blood. Peripheral blood was also taken from 24 healthy individuals to serve as control group. Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect the expression of VEGF and EGFR in RCC tissues and paracancer tissues. All patients were followed up after discharge to record their survival., Results: Significant differences in the expression levels of VEGF and EGFR were found between stage III and IV (p<0.05), but not between stage I and II. Expressions level of VEGF and EGFR in serum of well-differentiated, moderatelydifferentiated, and poorly-differentiated RCC were all higher than those in the healthy control group, and significant differences were found between different pathological grades (p<0.05). Patients with higher expression levels of VEGF and EGFR showed shorter survival compared to patients with lower expression levels (p<0.05)., Conclusion: VEGF and EGFR in peripheral blood can be used as one of the effective indicators of prognosis of RCC. Our study provided reference for clinical treatment and prediction of prognosis of RCC.

Primary aldosteronism (PA) is the most common form of endocrine hypertension. This study was to investigate the gene expression profile in PA adrenal glands and normal controls using RNA-Sequencing. By performing transcriptome analyses for 3 PA adrenal glands and 3 controls on Illumina platform, we identified 1,093 transcripts as significantly differently expressed genes (DEGs), which provided clues for further study of these transcript changes during PA pathogenesis. Further, Gene Set Enrichment Analysis (GSEA) identified 35 significant Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathways, including 'ribosome', 'oxidative phosphorylation', 'histidine metabolism', 'xenobiotics metabolism by Cytochrome P450', 'drug metabolism by Cytochrome P450', 'tyrosine metabolism' and 'glutathione metabolism'. In summary, we identified novel genes that are associated with PA phenotype, as well as differently regulated biological pathways relating to protein synthesis, energy acquisition and metabolism. Our study provides new candidates for further elucidation of the molecular mechanisms underlying PA pathogenesis., Competing Interests: None., (IJCEP Copyright © 2017.)