Context: Pituitary adenoma (PA) is a common intracranial tumor. The evidence indicates that the tumor immune microenvironment (TIME) is associated with PA and that the intestinal flora influences other tumors' growth through interacting with the TIME. However, how the intestinal microbial flora contributes to the development of PA through the immune response is unknown. Objective and methods: Here we used high-throughput Illumina MiSeq sequencing targeting the V3−V4 region of the 16S ribosomal RNA gene to investigate the intestinal flora of patients with growth hormone-secreting pituitary adenoma (GHPA), nonfunctional pituitary adenoma (NFPA), and healthy controls. We determined their effects on tumor growth and the TIME. Fecal microbiota transplantation (FMT) was performed after adoptive transfer via peripheral blood mononuclear cells to tumor-bearing nude mice, which allowed the study of the immune response. Result: We discovered differences in the structures and quantities of intestinal flora between patients with GHPA, patients with NFPA, and healthy controls. After FMT, the intestinal flora of GHPA patients promoted the growth of tumors in mouse models. The number of programmed cell death ligand 1 (PD-L1)-positive cells increased in tumor tissues as well as the extent of infiltration of CD8⁺ cells. Increased numbers of CD3⁺CD8⁺ cells and increased levels of sPD-L1 were detected in peripheral blood. Conclusion: These findings indicated that the intestinal flora of patients with GHPA promoted tumor growth and that the immune system may mediate this change.

The aim of the present study was to investigate the role and potential regulatory mechanisms of cyclin B1 (CCNB1) in the proliferation, apoptosis and epithelial‑to‑mesenchymal transition (EMT) in pituitary adenomas. A total of 24 specimens were included in the present study. The expression levels of CCNB1 protein in two normal pituitary and 22 pituitary adenoma tissues were determined by western blotting. CCNB1 was knocked‑down by lentiviral‑mediated infection of short hairpin RNA (shRNA) in GH3 and MMQ cell lines. The proliferation, cell cycle and apoptosis of GH3 and MMQ cell lines were detected using a Cell Counting Kit‑8 and flow cytometer. Reverse transcription‑quantitative PCR was utilized to detect the expression level of CCNB1 gene and EMT markers. In the present study, resveratrol (RES) was used as an inhibitor of CCNB1. The protein expression level of CCNB1 in pituitary adenomas was higher than that in normal pituitary tissue, as assessed by western blot analysis. In addition, the expression level of CCNB1 in invasive pituitary adenomas was higher when comparing invasive pituitary adenomas and non‑invasive pituitary adenomas. Knockdown of CCNB1 resulted in significant decreases in cell viability and proliferation, arrested cell cycle at the G2/M phase and increased apoptosis. In addition, knockdown of CCNB1 significantly decreased the expression levels of the mesothelial cell marker N‑cadherin (P<0.001), but significantly increased the expression levels of the epithelial cell markers E‑cadherin (P<0.01) and p120‑catenin (P<0.001). Further analyses identified that RES inhibited the expression level of CCNB1, and RES treatment exhibited a similar effect as CCNB1 shRNA infection. The present study suggested that suppressing the expression level of CCNB1 could regulate the proliferation and apoptosis of pituitary tumor cells and alter the expression level of various EMT markers. In addition, RES treatment could be used as an inhibitor of CCNB1. The present study also identified the molecular mechanisms underlying CCNB1 role in EMT.

Background: To investigate the relationship between cyclin B1 (CCNB1) gene expression and cavernous sinus invasion in pituitary adenomas. Methods: Twenty-four pituitary adenoma tissue samples were examined by RT-qPCR and Western blot to assess the mRNA expression levels and protein levels of CCNB1, E-cadherin and N-cadherin. Correlation analyses between the expression levels of E-cadherin, N-cadherin and CCNB1 were performed. After lentivirus-mediated knockdown of CCNB1 in rat pituitary adenoma cell lines (GH3 and GT1-1), cell function changes were studied. The relationship between CCNB1 and epithelial-mesenchymal transition (EMT) was further verified by animal experiments. Results: CCNB1 and N-cadherin gene expression were significantly higher in the invasive pituitary adenomas than in the non-invasive pituitary adenomas. Conversely, E-cadherin expression in the invasive pituitary adenomas was significantly lower. CCNB1 gene expression was downregulated in the GH3 and GT1-1 pituitary adenoma cell lines; N-cadherin expression was also decreased, but E-cadherin expression was increased. These results were confirmed in vivo. After downregulation of CCNB1, cell invasion and migration was significantly reduced in Transwell experiments. Conclusion: High CCNB1 expression in pituitary adenoma affects cavernous sinus invasion through EMT.

Objective: To determine risk factors and management for the development of a postoperative cerebrospinal fluid (CSF) leak after an endoscopic endonasal surgery (EES) for pituitary adenomas.Methods: The clinical data of 400 patients who underwent EES for resection of pituitary adenomas from December 2018 to November 2019 in the Department of Neurosurgery of Beijing Tiantan Hospital were retrospectively reviewed. Age, gender, body mass index (BMI), tumor size, Knosp grade, suprasellar extension grade, sellar floor erosion grade, repeated transsphenoidal surgery, intraoperative CSF leak, use of pedicled nasoseptal flap and lumbar drain were collected and analyzed.Results: Postoperative CSF leak occurred in 14 of 400 patients (3.5%). Age, gender, BMI, tumor size, Knosp grade and repeated transsphenoidal surgery were not risk factors for CSF leak. Suprasellar extension grade (≥B 6.0% vs. <B 1.4%; p = 0.024), sellar floor erosion grade (≥III 5.7% vs. <III 0.6%; p = 0.020) and intraoperative CSF leak (Yes 7.5% vs. No 2.0%; p = 0.009) were factors associated with an increased postoperative CSF leak rate.Conclusions: Higher suprasellar extension grade, higher sellar floor erosion grade and intraoperative CSF leak were risk factors for postoperative CSF leak after endoscopic treatment of pituitary adenoma. Strict skull base reconstruction including use of a pedicled nasoseptal flap and perioperative lumbar drainage may avoid postoperative CSF leak.

There are few studies on the mechanism of pituitary adenoma (PA) destroying bone. The current study aimed to investigate the role of MEG8/miR-454-3p/TNF-α in bone-invasive pituitary adenomas (BIPAs). In this study, we report that lncRNA MEG8 and TNF-α are upregulated in BIPA tissues while miR-454-3p is downregulated, which is associated with poor progression-free survival (PFS). Functional assays revealed the role of up-regulated MEG8 and down-regulated miR-454-3p in promoting bone destruction. Mechanistically, MEG8 promotes TNF-α expression by sponging miR-454-3p, which ultimately leads to the occurrence of bone destruction. The mechanism is confirmed in vivo and in vitro. Therefore, our data illustrated a new regulatory mechanism of MEG8/miR-454-3p/TNF-α in BIPAs. It may provide a useful strategy for diagnosis and treatment for BIPA patients.