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miR-200b-3p accelerates progression of pituitary adenomas by negatively regulating expression of RECK

Oncology Research 2024年第5期32卷 933-941页

作者： XIAOXI WANG YANFEI JIA QIANG LI QIANG YANG YINGFENG LIU BEIFENG WEI XIANG NIU YINJIE ZHANG XIAODONG LUO ZIYU ZHAO PENG WANG Department of Neurosurgery Tianshui First People’s HospitalTianshuiChina Department of Neurosurgery The Second Affiliated Hospital of Lanzhou UniversityLanzhouChina

MicroRNA(miR)-200b-3p has been associated with many tumors,but its involvement in pituitary adenoma is unclear.This study investigated the molecular mechanism underlying miR-200b-3p regulation in pituitary adenomas to provide a theoretical basis for treatment.Bioinformatics was used to analyze pituitary adenoma-related genes and screen new targets related to RECK and miRNA.As well,the relationship between miR-200b-3p and RECK protein was verified using a double-luciferase reporter gene assay.The expression of miR-200b-3p in clinical samples was analyzed by in situ hybridization.Transfection of the miR-200b-3p inhibitor and small interfering-RECK(si-RECK)was verified by qPCR.GH3 cell viability and proliferation were detected using CCK8 and EdU assays.Apoptosis was detected by flow cytometry and western blotting.Wound healing and Transwell assays were used to detect cell migration and invasion.The effects of miR-200b-3p and RECK on GH3 cells were verified using salvage experiments.miR-200b-3p was highly expressed in pituitary tumor tissue.Inhibitors of miR-200b-3p inhibited cell proliferation promoted cell apoptosis,inhibited invasion and migration,and inhibited the expression of matrix metalloproteinases.Interestingly,miR-200b-3p negatively regulated RECK.The expression of RECK in pituitary adenoma tissues was lower than that in neighboring tissues.Si-RECK rescued the function of miR-200b-3p inhibitors in the above cellular behaviors,and miR-200b-3p accelerated the development of pituitary adenoma by negatively regulating RECK expression.In summary,this study investigated the molecular mechanism by which miR-200b-3p regulates the progression of pituitary adenoma through the negative regulation of RECK.The findings provide a new target for the treatment of pituitary adenoma.

关键词： pituitary adenomas miR-200b-3p RECK Matrix metalloproteinase

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Predictors and dynamic online nomogram for postoperative delayed hyponatremia after endoscopic transsphenoidal surgery for pituitary adenomas:a single-center,retrospective,observational cohort study with external validation

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Chinese Neurosurgical Journal 2023年第4期9卷 241-250页

作者： Xiangming Cai An Zhang Peng Zhao Zhiyuan Liu Yiliyaer Aili Xinrui Zeng Yuanming Geng Chaonan Du Feng Yuan Junhao Zhu Jin Yang Chao Tang Zixiang Cong Yuxiu Liu Chiyuan Ma Department of Neurosurgery Jinling HospitalNanjingChina School of Medicine Southeast UniversityNanjingChina Department of Molecular Cell Biology and Immunology Amsterdam UMCVrije Universiteit AmsterdamAmsterdamNetherlands Department of Neurosurgery The First Affiliated Hospital of Nanjing Medical UniversityNanjingChina Department of Neurosurgery The Affiliated Jinling Hospital of Nanjing Medical UniversityNanjingChina Department of Neurosurgery Affiliated Jinling HospitalMedical School of Nanjing UniversityNanjingChina Department of Critical Care Medicine Jinling HospitalNanjing Medical UniversityNanjingChina Department of Biostatistics School of Public HealthSouthern Medical UniversityGuangzhouChina Department of Neurosurgery Jinling Hospitalthe First School of Clinical MedicineSouthern Medical UniversityNanjingChina

Background Postoperative delayed hyponatremia(PDH)is a major cause of readmission after endoscopic transsphenoidal surgery(eTSS)for pituitary adenomas(PAs).However,the risk factors associated with PDH have not been well established,and the development of a dynamic online nomogram for predicting PDH is yet to be realized.We aimed to investigate the predictive factors for PDH and construct a dynamic online nomogram to aid in its prediction.Methods We analyzed the data of 226 consecutive patients who underwent eTSS for PAs at the Department of Neurosurgery in Jinling Hospital between January 2018 and October 2020.An additional 97 external patients were included for external validation.PDH was defined as a serum sodium level below 137 mmol/L,occurring on the third postoperative day(POD)or later.Results Hyponatremia on POD 1-2(OR=2.64,P=0.033),prothrombin time(PT)(OR=1.78,P=0.008),and percentage of monocytes(OR=1.22,P=0.047)were identified as predictive factors for PDH via multivariable logistic regression analysis.Based on these predictors,a nomogram was constructed with great discrimination in internal validation(adjusted AUC:0.613-0.688)and external validation(AUC:0.594-0.617).Furthermore,the nomogram demonstrated good performance in calibration plot,Brier Score,and decision curve analysis.Subgroup analysis revealed robust predictive performance in patients with various clinical subtypes and mild to moderate PDH.Conclusions Preoperative PT and the percentage of monocytes were,for the first time,identified as predictive factors for PDH.The dynamic nomogram proved to be a valuable tool for predicting PDH after eTSS for PAs and demonstrated good generalizability.Patients could benefit from early identification of PDH and optimized treatment decisions.

关键词： Endoscopic transsphenoidal surgery Nomogram pituitary adenomas Postoperative delayed hyponatremia Predictors

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Expression for peroxisome proliferator-activated receptor gamma in pituitary adenomas 38 cases for semi-quantitative immunohistochemical analysis

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Neural Regeneration Research 2008年第7期3卷 756-759页

作者： Xiaojie Lu Kailai Chen Weiyang Ji Qing Wang Bing Li Jiang＇an Li Jiyong Sun Department of Neurosurgery Wuxi Second Hospital Affiliated to Nanjing Medical University Wuxi 214002 Jiangsu Province China

BACKGROUND： It has been reported that peroxisome proliferator-activated receptor γ （PPAR γ ） is highly expressed in lung cancer, colon cancer, and gastric cancer, as well as other tumors.OBJECTIVE： To study expression of PPAR γ in pituitary adenomas and analyze the role of PPAR γ in hormonal typing of pituitary adenomas. DESIGN, TIME AND SETTING： Semi-quantitative immunohistochemistry of pathological specimens. The experiment was conducted at the Department of Neurosurgery, Wuxi Second Hospital Affiliated to Nanjing Medical University between January 2002 and May 2005. MATERIALS： Surgical resection samples of pituitary adenomas from 38 cases （18 male and 20 female） were analyzed. Eight cases were determined to be invasive pituitary adenomas and 30 cases were non-invasive pituitary adenomas. Hormonal classification of the types of pituitary adenomas revealed somatotrophic adenomas in six cases, corticotrophic adenoma in five cases, prolactinomas in 13 cases, multi-hormone secreting adenomas in six cases, and eight cases of adenoma without altered endocrine function. Five autopsy specimens were collected during the same period from patients of matching age that died from unrelated diseases and were included as normal anterior pituitar3, controls. METHODS： Cell counts for positive immunohistochemical signals were recorded from histopathological sections. The percentage of positive cells was reported as a semi-quantitative analysis. MAIN OUTCOME MEASURES： The rate of PPAR γ positive cells in different types of adenoma was based on hormonal levels and invasiveness of pituitary tumor cells. RESULTS： All tumor biopsies were determined to express PPAR γ. The rate of PPAR γ -positive cells ranged between 8%-65% in the pituitary adenomas. According to hormonal type, PPAR γ expression did not vary between the groups. In addition, there was no significant difference in PPAR γ expression between the non-invasive and invasive pituitary adenomas. CONCLUSIONS： Human pituitary adenomas express PPAR γ, and this expre

关键词： Peroxisome proliferator-activated receptor γ pituitary adenomas immunohistochemistry

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Comparative Study between Microscopic and Endoscopic Trans-Sphenoidal Surgery for Growth Hormone-Secreting pituitary adenomas with Super-Sellar Extension

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Open Journal of Modern Neurosurgery 2020年第4期10卷 393-402页

作者： Ahmed Sabry Abdelkader Ibrahim Abdel Fattah Abou Alfotoh Shehab Mohammad Fathy Eissa Neurosurgery Department Nasr City Hospital of Health Insurance Cairo Egypt Neurosurgery Department Faculty of Medicine Al-Azhar University Cairo Egypt

Background: Advances in the era of modern micro-neurosurgery enabled a reduction of surgical invasiveness and brain retraction which has been defined as minimally invasive or keyhole surgery. Sinonasal endoscopy has brought radical changes in the concepts of pathophysiology and treatment of sinonasal aliments as well as surgical techniques. Aim of the Study: To compare between the use of endoscopic and microscopic trans-sphenoidal approach in resection of growth hormone-secreting pituitary adenomas with Suprasellar Extension. Patients and Methods: This is a prospective study. It had been conducted upon 20 patients having growth hormone secreting pituitary adenoma admitted to Neurosurgery department in Alzar University hospitals and Nasr City Insurance hospital from 2015 to 2018, divided into 2 groups;group A (10 cases) underwent endoscopic endonasal trans-sphenoidal pituitary adenoma resection, while group B (10 cases) operated upon using the standard microscopic trans-sphenoidal pituitary adenoma resection. The inclusion criteria were included: All patients with growth hormone secreting pituitary adenomas showing manifestations of acromegaly, mass effect or hormonal disturbance. Results: This study showed that improvement in outcome was higher in endoscopic group opposed to microscopic group (100% vs. 71% improved headache, 80% vs. 60% visual improvement, 75% vs. 20% fundus improvement and 60% vs. 30% field improvement). Conclusion: We concluded that fully endoscopic procedure result in improved rates of complete tumor removal and a reduced incidence of complications, when compared to the microscopic approach.

关键词： Acromegaly pituitary adenomas Endoscopic Trans-Sphenoidal Surgery Microscopic Trans-Sphenoidal Surgery

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TPA Enhances Growth Horm one (GH) Secretion Effect ofGH-Releasing Horm one (GHRH) by Hum an gsp-PositivePi-tuitary Som atotrophinom as

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Journal of Huazhong University of Science and Technology(Medical Sciences) 1999年第3期19卷 237-239,248页

作者： LEI Ting , BAI Xiangjun , HU Wenan , XUE Delin , JIANG Xianhui Department of Neurosurgery, Tongji Hospital, Tongji Medical University, Wuhan 430030 Department of Neurosurgery Tongji Hospital Tongji Medical University Wuhan

In recent years, one of the most exciting advances in the researches of pituitary adenomas is the discovery that 30 %-40 % of human pituitary somatotrophinomas carry somatic mutations of the gene for the α subunit of the stimulatory GTP binding protein, G s (G sα). These mutations, termed gsp oncogenes, may play an important role in the tumorigenesis of pituitary adenomas. Of 10 somatotrophinomas examined, 3 (30 %) were proved to be gsp positive, as determined by sequence analysis of DNA generated by the polymerase chain reaction (PCR). GHRH exerted a significant stimulatory effect on GH secretion in 2 of 3 gsp positive and 4 of 7 gsp negative tumors. Moreover, phorbol ester, 1, 2 tetradecanoylphorbol 13 acetate (TPA), enhanced stimulation of lated the GH secretion effect exerted by GHRH in gsp positive somatotrophinomas, whereas this effect was not observed in gsp negative tumors. This result suggests that the protein kinase C signal system as well as adenylyl cyclase cAMP protein kinase A intracellular signal transduction system plays a pivotal role in GH secretory control of GHRH, which may work together via a cross talk mechanism.

关键词： pituitary adenomas gsp oncogenes growth hormone releasing hormone TPA

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Prolactin adenomas in Senegal: Epidemiological, Diagnostic and Therapeutic Aspects of 89 Cases

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Open Journal of Internal Medicine 2023年第3期13卷 209-217页

作者： Michel Assane Ndour Demba Diédhiou Djiby Sow Boundia Djiba Mouhamed Dieng Ibrahima Mané Diallo Fatou Kiné Gadji Julie Borges Muriel Diembou Fama Mody Ndiaye El Hadj Mouhamadou Moustapha Thioye Charles Halim Philippe Moreira Anna Sarr Maïmouna Ndour Mbaye Medical Clinic II Abass Ndao Hospital Center Cheikh Anta Diop University Dakar Senegal

Introduction: In Senegal, there is very little data on prolactinomas despite their negative impact on couples fertility. Patients and methods: This was a multicentre, retrospective, descriptive, analytical study conducted from 1 January 2008 to 31 December 2022 in the neurosurgery departments of the Fann and Principal hospitals and the endocrinology department of the Abass Ndao Hospital. Results: We included 89 patients, representing a prevalence of 36.7% among all cases of pituitary adenoma. The mean age was 35.6 ± 10 years and the sex ratio was 0.34. The mean time to consultation was 27.1 ± 29 months. Clinical symptoms were dominated by gonadotropic disorders represented by galactorrhoea (71 cases, 79.8%), amenorrhoea (61 cases, 68.5%), and infertility in the couple (31 cases, 34.8%). Fifty-seven (58) patients presented with a tumour syndrome (65.2%, including 57 cases of headache (64%), 34 cases of visual disorders (38.2%) and 8 patients with a dysmorphic syndrome (8.9%). Imaging revealed a macroadenoma in 68.5% (61 cases) and extension of the adenoma in 11 patients (12.4%). The hormonal profile was isolated lactotropic hypersecretion (80 cases, 89.9%) and mixed in 9 cases (including concomitant secretion of GH in 8 cases and ACTH in 1 case). All patients had initially benefited? from dopaminergic agonist-based medical treatment. pituitary surgery was effective in 45 patients (50.6%), including 44 cases by transsphenoidal approach. Postoperative incidents included transient diabetes insipidus (77.7%) and cerebrospinal fluid leakage (20%). We noted 7 cases (7.9%) of death presenting with a tumour syndrome (100%), a macro-adenoma (85.7%), having undergone pituitary surgery (42.9%). The factors significantly associated with prolactinoma were young age (p Conclusion: This series also demonstrates the impact of prolactin adenomas on reproductive function. Delayed diagnosis explains the predominance of macroadenomas, which are a source of pre- and post-operative complications.

关键词： Prolactinoma Fertility Disorders Tumour Syndrome pituitary adenomas

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Identification of Potential Key Genes,miRNAs,and Pathways Involved in pituitary Tumor Sphenoid Sinus Invasion:Bioinformatic Analysis and Machine Learning

Identification of Potential Key Genes,miRNAs,and Pathways In...

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第十六届中国医师协会神经外科医师年会

作者： Xiang-Ming Cai Feng Yuan Jun-Hao Zhu Jin Yang Chao Tang Zi-Xiang Cong Chi-Yuan Ma School of Medicine Southeast University Department of Neurosurgery Affiliated Jinling HospitalSchool of MedicineNanjing University School of Medicine Nanjing Medical University

Background:The molecular basis of pituitary adenomas(PA) invading sphenoid sinus is largely unknown.The study aims to identify key genes,miRNAs,and pathways and explore PA sphenoid sinus invasion’s molecular mechanisms.Methods:E-MTAB-7768 and E-MTAB-7969,involving sphenoid sinus-invasive pituitary adenomas and nonsphenoid sinus-invasive pituitary adenomas,were extracted from ArrayExpress.After the differential expression analysis of m RNAs and miRNAs using the EdgeR package,we performed functional enrichment analyses for differentially expressed genes(DEGs).We used protein-protein interaction network and correlation analysis to evaluate the relationship between enriched terms and pathways.miRNA-target regulatory network construction was performed using the multiMiR package and visualized by Cytoscape.Finally,we developed predictive models for sphenoid sinus invasion according to the key genes identified.Model performance was mainly evaluated based on the area under the receiver operating characteristic curve(AUC).Results:A total of 396 DEGs and 24 differentially expressed miRNAs were identified.Enrichment analyses revealed that DEGs were mainly enriched in 8 pathways,including osteoclast differentiation and PI3K-Akt pathway,and 266 biological process terms like negative regulation of biomineral tissue development and negative regulation of cell adhesion.CCL3,SRGN,and CCR1 from negative regulation of biomineral tissue development and PTPN22,LILRB2,and IL1RN from negative regulation of cell adhesion were analyzed by PPI and correlation analysis.Negative regulation of biomineral tissue development was found to have tight relationship with osteoclast differentiation.Furthermore,negative regulation of cell adhesion correlated with the PI3K-Akt pathway.Also,miR-1-3p regulates the highest number of DEGs in the miRNA-target regulation network.Lasso regression model yielded the best predictive performance(AUC=0.83).Conclusions:Osteoclast differentiation and negative regulation of cell adhesion are potential mechanisms und

关键词： bioinformatic analysis cell adhesion MiRNAs osteoclast differentiation pituitary adenomas sphenoid sinus invasion

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The Use of Neuronavigation with Vasular Microdoppler in Transsphenoidal pituitary Surgery

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Open Journal of Modern Neurosurgery 2016年第1期6卷 45-50页

作者： Mehmet Hakan Seyithanoglu Serkan Kitis Meliha Gundag Papaker Fatih Calis Tolga Turan Dundar Serdar Cevik Department of Neurosurgery Bezmialem Vakif University Faculty of Medicine Istanbul Turkey Department of Neurosurgery Agri State Hospital Agri Turkey

Object: To evaluate the use of neuronavigation with vascular micro-doppler in transsphenoidal pituitary surgery. Methods: 141 cases having done transsphenoidal pituitary surgery are evaluated from 2005 to 2014. Fluoroscopy was used in 69 cases and vascular micro-doppler with neuronavigation were used in 72 cases. Results: Transsphenoidal surgery has a lot of risks due to sella’s deep location, and position of the carotid artery and the optic nerve. Clasically the fluoroscopy and microscopic anatomical markers were used in order to minimize the risk of carotid artery and optic nerve damage. Additional devices such as neuronavigation and vascular micro-doppler are needed to decrease the morbidity and mortality arising from these injuries. Conclusion: Neurovascular complications such as carotid artery and optic nerve injuries owing to disorientation in transsphenoidal surgery will reduce the use of neuronavigation with vascular micro-doppler.

关键词： Transsphenoidal Surgery Vascular Micro-Doppler Neuronavigation pituitary adenomas

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Evaluation of Surgical Freedom for One-and-a-half Nostril, Mononostril and Binostril Endoscopic Endonasal Transsphenoidal Approaches

Evaluation of Surgical Freedom for One-and-a-half Nostril, M...

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第十四届中国医师协会神经外科医师年会

作者：杨进乔梁马驰原南京医科大学解放军南京总医院东莞市东华医院神经外科

Objective: To determine which of the one-and-a-half nostril, mononostril and binostril endoscopic endonasal transsphenodial approach provide a superior manipulation during surgery. Methods: The three approaches were orderly performed on 10 silicon-injected cadaveric heads to quantitatively assess surgical freedom and attack angle for sella. Measurements were determined with a standardized method under neuronavigation system using data of computed tomography. Results: The one-and-a-half nostril endoscopic trans-sphenoidal approach(OETA) offered superior exposed area than that of the of the mononostril approach(META), and similar to that of the binostril approach(BETA). For surgical freedom at anatomic targets, the OETA showed greater surgical flexibility at pituitary center, the right medial optic carotid recess(R-mOCR), the left mOCR, the medial intersection of the right cavernous internal carotid artery and extension line of upper margin of the clivus(R-mICC) than those of the META, and similar to those of the BETA. For sagittal angle of attack to the R-mOCR, R-mICC, and L-mOCR, the OETA can provide better angular freedom for surgeon than that of the META, and similar to that of the BETA. The OETA had the same axial attack to the pituitary center with the BETA. The OETA and the META had limited surgical freedom at L-m ICC, and both inferior to the BETA. Conclusion: The OETA has similar exposed area, surgical freedom and attack angle for most anatomic targets to the BETA without resecting contralateral nasal septal mucosa, and obviously superior to the META.

关键词： One-and-a-half-nostril endoscopic surgery endonasal trans-sphenoidal approach cadaver study pituitary adenomas manipulation space surgical freedom

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