Dopamine agonists such as bromocriptine and cabergoline are the predominant treatment drugs for prolactinoma by inhibiting prolactin secretion and shrinking tumor size. However, the pathways of either dopamine or its agonists that lead to the death of cells are incompletely understood and some are even conflicting conclusions. The main aim of this paper is to review the different pathways of dopamine and its agonists in prolactinomas to help to gain a better understanding of their functions and drug resistance mechanisms.

Patients with pituitary adenomas usually receive “stress dose” steroids in the peri-operative peroids. Though randomized controlled trials(RCT) have not been performed to assess the necessity of steroid coverage, there are several studies that explained the changes of adrenal function during peri-operative peroids. The aim of the present study is to investigate whether it is necessary to employ conventional peri-operative glucocorticoid replacement therapy to all the patients undergoing surgery. We searched studies addressing peri-operative steroids coverage for pituitary adenomas in the Web of Science, Medline and the Cochrane Library. Then we extracted studies about peri-operative morning serum cortisol(MSC) levels, morbidity of early postoperative adrenal insufficiency, postoperative diabetes insipidus, relationships between MSC levels and adrenal integrity. We used RevMan Software to combine the results for meta-analysis. We used fixed-effects models for there was no significant heterogeneity existed. There are 18 studies from 11 countries published between 1987 and 2013 including 1224 patients. The postoperative serum cortisol levels were significantly increased compared with the preoperative one in hypothalamic-pituitary-adrenal axis(HPAA) functions preserved patients(P<0.00001). The morbidity of early postoperative adrenal insufficiency ranged from 0.96% to 12.90%, with the overall morbidity of 5.55%(41/739). There was no significant differences of early postoperative diabetes insipidus between no supplementation patients and in supplementation patients(P=0.82). Conversely, there may be some disadvantages of high levels of cortisols such as high incidence of osteopenia and bone derangement and even the increased mortality rate. The patients with MSC levels of less than 60 nmol/l at 3 days after operation is considered as adrenal insufficient and more than 270 nmol/l as adrenal sufficient. To patients with MSC levels of 60–270 nmol/l, we need more clinical data to establish further cortisol supplementation criteria.

Purpose: Glioblastoma multiforme (GBM) is a common and aggressive form of brain tumor. The N⁶-methyladenosine (m⁶A) mRNA modification plays multiple roles in many biological processes and disease states. However, the relationship between m⁶A modifications and the tumor microenvironment in GBM remains unclear, especially at the single-cell level.Experimental Design: Single-cell and bulk RNA-sequencing data were acquired from the GEO and TCGA databases, respectively. We used bioinformatics and statistical tools to analyze associations between m⁶A regulators and multiple factors.Results: HNRNPA2B1 and HNRNPC were extensively expressed in the GBM microenvironment. m⁶A regulators promoted the stemness state in GBM cancer cells. Immune-related BP terms were enriched in modules of m⁶A-related genes. Cell communication analysis identified genes in the GALECTIN signaling network in GBM samples, and expression of these genes (LGALS9, CD44, CD45, and HAVCR2) correlated with that of m⁶A regulators. Validation experiments revealed that MDK in MK signaling network promoted migration and immunosuppressive polarization of macrophage. Expression of m⁶A regulators correlated with ICPs in GBM cancer cells, M2 macrophages and T/NK cells. Bulk RNA-seq analysis identified two expression patterns (low m⁶A/high ICP and high m⁶A/low ICP) with different predicted immune infiltration and responses to ICP inhibitors. A predictive nomogram model to distinguish these 2 clusters was constructed and validated with excellent performance.Conclusion: At the single-cell level, m⁶A modification facilitates the stemness state in GBM cancer cells and promotes an immunosuppressive microenvironment through ICPs and the GALECTIN signaling pathway network. And we also identified two m⁶A-ICP expression patterns. These findings could lead to novel treatment strategies for GBM patients.

The treatment of hyperprolactinemia is based on the use of dopamine agonists, mainly bromocriptine (BRC) and cabergoline (CAB). They reduce tumour size effectively and restore gonadal function. However, there is a difference in drug sensitivity between CAB and BRC in patients with prolactinoma, although the underlying mechanisms are still unknown. Thus, we investigated whether there are differences in tumour sensitivity to CAB and BRC and their possible differential mechanisms in two prolactinoma cell lines. In our study, we found that GH3 cells are more sensitive to BRC and that MMQ cells are more sensitive to CAB. Moreover, BRC and CAB elicited cell death via different pathways; BRC induced prolactinoma cell death mainly through the apoptosis pathway, and CAB induced pituitary prolactinoma cell death mainly via the autophagic cell death pathway. Using gene microarray analysis, we found that BRC induces the apoptosis of prolactinoma cells through the ERK/EGR1 signalling pathway, whereas CAB induces autophagic death by inhibiting the AKT/mTOR signalling pathway. Our study showed the difference in tumour sensitivity and differential mechanisms in BRC- and CAB-treated prolactinoma cells, which provides a theoretical basis for the accurate treatment of prolactinoma.