Immune landscape and progress in immunotherapy for pituitary neuroendocrine tumors.

Pituitary neuroendocrine tumors (pitNETs) are the second most common primary brain tumors. Despite their prevalence, the tumor immune microenvironment (TIME) and its clinical implications remain largely unexplored. This review provides a comprehensive overview of current knowledge on the immune landscape and advancements in targeted immunotherapy for pitNETs. Macrophages and T cells are principal immune infiltrates within the TIME. Different subtypes of pitNETs display distinct immune patterns, influencing tumor progressive behaviors. PD-L1, the most extensively studied immune checkpoint, is prominently expressed in hormonal pitNETs and correlates with tumor growth and invasion. Cytokines and chemokines including interleukins, CCLs, and CXCLs have complex correlations with tumor subtypes and immune cell infiltration. Crosstalk between macrophages and pitNET cells highlights bidirectional regulatory roles, suggesting potential macrophage-targeted strategies. Recent preclinical studies have demonstrated the efficacy of anti-PD-L1 therapy in a mouse model of corticotroph pitNET. Moreover, anti-PD-1 and/or anti-CTLA-4 immunotherapy has been applied globally in 28 cases of refractory pitNETs, showing more favorable responses in pituitary carcinomas than aggressive pitNETs. In conclusion, the TIME of pitNETs represents a promising avenue for targeted immunotherapy and warrants further investigation.

A machine learning-based integrated clinical model for predicting prognosis in atypical meningioma patients.

PURPOSE: Atypical meningioma (AM) recurs in up to half of patients after surgical resection and may require adjuvant therapy to improve patient prognosis. Various clinicopathological features have been shown to have prognostic implications in AM, but an integrated prediction model is lacking. Thus, in this study, we aimed to develop and validate an integrated prognostic model for AM. METHODS: A retrospective cohort of 528 adult AM patients surgically treated at our institution were randomly assigned to a training or validation group in a 7:3 ratio. Sixteen baseline demographic, clinical, and pathological parameters, progression-free survival (PFS), and overall survival (OS) were analysed. Sixty-five combinations of machine learning (ML) algorithms were used for model training and validation to predict tumour recurrence and patient mortality. RESULTS: The random survival forest (RSF) model was the best model for predicting recurrence and death. Primary or secondary tumour, Ki-67 index, extent of resection, tumour size, brain involvement, tumour necrosis, and age contributed significantly to the model. The C-index value of the RSF recurrence prediction model reached 0.8080. The AUCs for 1-, 3-, and 5-year PFS were 0.83, 0.82, and 0.86, respectively. The C-index value of the RSF death prediction model reached 0.8890. The AUCs for 3-year and 5-year OS were 0.88 and 0.89, respectively. CONCLUSION: A high-performing integrated RSF predictive model for AM recurrence and patient mortality was proposed that may guide therapeutic decision-making and long-term monitoring.

Piperlongumine attenuates angiotensin-II-induced cardiac hypertrophy and fibrosis by inhibiting Akt-FoxO1 signalling.

BACKGROUND: Cardiac hypertrophy and fibrosis are closely related to cardiac dysfunction, especially diastolic dysfunction. Limited medications can be used to simultaneously delay cardiac hypertrophy and fibrosis in clinical practice. Piperlongumine (PLG) is an amide alkaloid extracted from Piper longum and has been shown to have multiple biological effects, including anticancer and antioxidant effects. However, the role of PLG in cardiac hypertrophy and fibrosis is not clear. PURPOSE: The aim of this study was to reveal the role of PLG in cardiac hypertrophy and fibrosis and the associated mechanism. METHODS: Cardiac hypertrophy and fibrosis were induced by angiotensin II (Ang II) in vivo and in vitro. The effect of PLG in vivo, in vitro and its mechanism were investigated by proliferation and apoptosis assays, western blot, real-time PCR, immunofluorescence, histochemistry, echocardiography, flow cytometry and chromatin immunoprecipitation. RESULTS: Proliferation and apoptosis assays showed that 2.5 µM PLG slightly inhibited proliferation and did not promote apoptosis. Treatment with 5 mg/kg PLG obviously inhibited Ang II-induced cardiac hypertrophy and fibrosis in vivo. In vitro studies of neonatal rat cardiomyocytes (NRCMs) showed that the anti-hypertrophic effect of PLG was mediated by reducing the phosphorylation of Akt and thereby preserving the level of Forkhead box transcription factor O1 (FoxO1), since knockdown of FoxO1 by siRNA reversed the protective effect of PLG on NRCMs. In addition, PLG significantly decreased the Ang II-induced expression of profibrotic proteins in neonatal cardiac fibroblasts by reducing the expression of Krüppel-like factor 4 (KLF4) and the recruitment of KLF4 to the promoter regions of transforming growth factor-ß and connective tissue growth factor. CONCLUSION: We demonstrate the cardioprotective effects of PLG in both cardiac hypertrophy and fibrosis and the potential value of PLG for developing novel medications for pathological cardiac hypertrophy and heart failure.

Effect of vasopressin injection technique in laparoscopic excision of bilateral ovarian endometriomas on ovarian reserve: prospective randomized study.

STUDY OBJECTIVE: To evaluate the effects of vasopressin injection technique in laparoscopic cystectomy on ovarian reserve in patients with bilateral endometriomas. DESIGN: Randomized prospective study (Canadian Task Force classification I). SETTING: University hospital. PATIENTS: Eighty-six women with bilateral endometriomas. INTERVENTIONS: Laparoscopic cystectomy of bilateral endometriomas was performed using different techniques including laparoscopic cystectomy by stripping without injection (control group), laparoscopic cystectomy by stripping with injection of saline solution (saline group), and laparoscopic cystectomy by stripping with vasopressin injection technique (VIT group). MEASUREMENTS AND MAIN RESULTS: The number of coagulation events on the ovarian cortex for hemostasis was counted in different groups, and the thickness of ovarian tissues removed was measured. The basal follicle-stimulating hormone (FSH) level was determined before surgery and at 3-, 6-, and 12-month follow-up after laparoscopic cystectomy in the different groups. In the saline group, fewer coagulation events were required to achieve hemostasis, less ovarian tissues were removed, and lower preoperative FSH levels were detected than in the control group (p < .01). In the VIT group, even fewer coagulation events (p < .01) and lower preoperative FSH levels (p < .01) were detected than in the saline group. There was no significant difference in the thickness of ovarian tissues removed in the 2 groups (p > .05). Basal FSH levels were significantly different before and after surgery in the control and saline groups (p < .01) but not in the VIT group (p > .05). CONCLUSION: Vasopressin injection is an ideal procedure to reduce damage from usual laparoscopic cystectomy of bilateral ovarian endometriomas to protect ovarian reserve.

Vascular endothelial growth factor expression up-regulated by endometrial ischemia in secretory phase plays an important role in endometriosis.

Primary human endometrial cells were exposed to hypoxia preconditioning (HPC), HPC-hypoxia, and hypoxia conditions, and then endometrial tissue treated with ischemia preconditioning (IPC) was transplanted onto the chick embryo chorioallantoic membrane to investigate the role of slight ischemia of endometrium in the pathologic process of endometriosis. IPC up-regulated vascular endothelial growth factor expression and decreased apoptosis of endometrial cells, thus facilitating the endometrial fragments' ectopic implantation.