Previous clinical studies revealed that cabergoline and bromocriptine can normalize serum PRL levels in more than 80% of prolactinomas patients [15,16] and have a good effect in somatotropinoma patients [17], which consistent with our data from immunostaining analysis. Our data also showed 83.8%
of FSH-secreting PAs and 66.7% of ACTH-secreting PAs are high expression of D2R, which is supported by several other reported studies, although clinical studies showed a long-term cure of 48% in cabergoline treated ACTH-secreting PAs [18-20]. Only 37.1% of non-functioning (NF) PAs highly expressed D2R according to our data, consistenting with the report by Colao et al. that the cumulative evidence for NF PAs shrinkage after DA therapy is 27.6% [21]. MGMT is a DNA repair protein that counteracts the effect of TMZ which is used for malignant glioma standard treatment. Recently, #Repotrectinib ic50 randurls[1|1|,|CHEM1|]# more SB525334 and more studies revealed the therapeutic effect of TMZ on PAs, especially on aggressive PAs and pituitary carcinomas. MGMT expression as assessed by immunohistochemistry may predict response to temozolomide therapy in patients with
aggressive pituitary tumors [7,22]. McCormack group demonstrated that low MGMT expression and MGMT promoter methylation were found in the pituitary tumor of the patient who responded to TMZ, high MGMT expression was seen in the patient demonstrating a poor response to TMZ [23]. They reported the results that eleven out of 88 PA samples (13%) had low MGMT expression, and that prolactinomas
were more likely to have low MGMT expression compared with other pituitary tumor subtypes. Herein, in this study we detected 170 out of 197 PAs (86.3%) existing MGMT expression lower than 50% (<50%) G protein-coupled receptor kinase which was considered to be low MGMT expression. This data was higher than that form reported clinical studies in TMZ treated functioning PA, non-functioning PA and pituitary carcinoma with the remission rate of 75%, 55% and 72% respectively, which can be explained by Bush’s study that not all MGMT low expression PA respond to TMZ although medical therapy with TMZ can be helpful in the management of life-threatening PAs that have failed to respond to conventional treatments [24]. Our results showed low MGMT expression (<50%) in 85.7% of PRL-secreting PAs, 90% of GH-secreting PAs, 81.5% of ACTH-secreting PAs, 93.3% of TSH-secreting PAs, 70.3% of FSH-secreting PAs and 94.3% of non-functioning PAs, predicting almost all subtypes of PAs are suitable for TMZ therapy, although only fewer curative cases were separately reported [25,26]. Further large scale clinical trials are necessary. VEGF is a key mediator of endothelial cell proliferation, angiogenesis and vascular permeability. It plays a pivotal role in the genesis and progression of solid tumors. Onofri et al.