scholarly journals Evaluation of the expression of necroptosis pathway mediators and its association with tumor characteristics in functional and non-functional pituitary adenomas

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Mohammad E. Khamseh ◽  
Alireza Sheikhi ◽  
Zahra Shahsavari ◽  
Mohammad Ghorbani ◽  
Hamideh Akbari ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pituitary Adenoma ◽  
Tumor Size ◽  
Pituitary Adenomas ◽  
Molecular Mechanisms ◽  
Rna Extraction ◽  
Pituitary Tumors ◽  
Normal Tissues ◽  
Cancer Pathogenesis ◽  
Cell Death Pathway

Abstract Background Pituitary adenomas impose a burden of morbidity on patients and characterizing the molecular mechanisms underlying its pathogenesis received remarkable attention. Despite the appealing role of necroptosis as an alternative cell death pathway in cancer pathogenesis, its relevance to pituitary adenoma pathogenesis has yet to be determined that is perused in the current study. Methods The total number of 109 specimens including pituitary adenomas and cadaveric healthy pituitary tissues were enrolled in the current study. Tumor and healthy pituitary tissues were subjected to RNA extraction and gene analysis using Real-Time PCR. The expression levels of necroptosis markers (RIP1K, RIP3K and, MLKL) and their association with the patient’s demographic features were evaluated, also the protein level of MLKL was assessed using immunohistochemistry in tissues. Results Based on our data, the remarkable reduction in RIP3K and MLKL expression were detected in nonfunctional and GH-secreting pituitary tumors compared to pituitary normal tissues. Invasive tumors revealed lower expression of RIP3K and MLKL compared to non-invasive tumors, also the attenuated level of MLKL was associated with the tumor size in invasive NFPA. The simultaneous down-regulation of MLKL protein in pituitary adenoma tissues was observed which was in line with its gene expression. While, RIP1K over-expressed significantly in both types of pituitary tumors which showed no significant correlation with patient’s age, gender and tumor size in GHPPA and NFPA group. Notably, MLKL and RIP3K gene expression was significantly correlated in the GHPPA group. Conclusions According to our data, the reduced expression of necroptosis mediators (RIP3K, MLKL) in pituitary adenoma reinforces the hypothesis that the necroptosis pathway can be effective in regulating the proliferation and growth of pituitary tumor cells and tumor recurrence.

scholarly journals Incidence, demographics, and survival of patients with primary pituitary tumors: a SEER database study in 2004–2016

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Cheng Chen ◽  
Yu Hu ◽  
Liang Lyu ◽  
Senlin Yin ◽  
Yang Yu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Pituitary Adenoma ◽  
Incidence Rate ◽  
Tumor Size ◽  
Pituitary Adenomas ◽  
Pituitary Tumors ◽  
The United States ◽  
Reliable Estimate ◽  
Seer Database ◽  
Factors Associated

AbstractComprehensive investigations on the incidence and prognosis of pituitary tumors are still lacking. The present study aims to summarize the incidence, demographics, and survival outcome of pituitary adenoma on a population-based level. This study includes all pituitary adenomas reported in the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2016 in the United States. Extensive clinical and demographic characteristics were extracted and submitted to group comparisons. The standardized incidence rate was calculated and stratified by year at diagnosis, age/sex and age/treatment groups. The Kaplan–Meier analysis and multivariable regressions were performed to identify the factors associated with overall survival. A total of 47,180 pituitary tumors were identified, including 47,030 typical adenomas, 111 uncertain behavior pituitary adenomas, and 39 pituitary carcinomas. The overall standardized incidence rate was 4.8 cases per 100,000 person-years and the annual incidence rate continually trended upwards, with a peak seen in 2015. We noticed a bimodal age-related distribution in females and a unimodal distribution in males. In the multivariate regression analysis, the factors associated with prolonged survival included typical adenoma, younger age, and smaller tumor size. Whereas, black and male patients had worse overall survival. Our study provides a reliable estimate on the incidence of pituitary adenoma and confirms that the annual standardized incidence rate is increasing. Pituitary adenomas have a satisfactory long-term prognosis and age, tumor size, and tumor subtypes are related to overall survival. Though statistically significant, our inferential findings should be constrained within the limitations of SEER database.

MICROSURGICAL ANATOMY OF THE DIAPHRAGMA SELLAE AND ITS ROLE IN DIRECTING THE PATTERN OF GROWTH OF PITUITARY ADENOMAS

Neurosurgery ◽  
2008 ◽  
Vol 62 (3) ◽  
pp. 717-723 ◽  
Author(s):  
Alvaro Campero ◽  
Carolina Martins ◽  
Alexandre Yasuda ◽  
Albert L. Rhoton
Keyword(s):  
Pituitary Adenoma ◽  
Cavernous Sinus ◽  
Dura Mater ◽  
Pituitary Adenomas ◽  
Potential Role ◽  
Pituitary Tumors ◽  
Microsurgical Anatomy ◽  
Suprasellar Region ◽  
Lateral Distance ◽  
Diaphragma Sellae

Abstract OBJECTIVE To evaluate the anatomic aspects of the diaphragma sellae and its potential role in directing the growth of a pituitary adenoma. METHODS Twenty cadaveric heads were dissected and measurements were taken at the level of the diaphragma sellae. RESULTS The diaphragma sellae is composed of two layers of dura mater. There is a remarkable variation in the morphology of the diaphragm opening. The average anteroposterior distance of the opening was 7.26 mm (range, 3.4–10.7 mm) and the average lateral-to-lateral distance was 7.33 mm (range, 2.8–14.1 mm). CONCLUSION The variability in the diameter of the opening of the diaphragma sellae could explain the growth of pituitary tumors toward the cavernous sinus or toward the suprasellar region.

Screening of cervical cancer-related hub genes based on comprehensive bioinformatics analysis

2021 ◽  
pp. 1-13
Author(s):  
Simei Tu ◽  
Hao Zhang ◽  
Xiaocheng Yang ◽  
Wen Wen ◽  
Kangjing Song ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cervical Cancer ◽  
Molecular Mechanisms ◽  
Disease Free Survival ◽  
The Cancer Genome Atlas ◽  
Mrna Levels ◽  
Hub Genes ◽  
Normal Tissues ◽  
Significant Difference ◽  
Core Genes

BACKGROUND: Since the molecular mechanisms of cervical cancer (CC) have not been completely discovered, it is of great significance to identify the hub genes and pathways of this disease to reveal the molecular mechanisms of cervical cancer. OBJECTIVE: The study aimed to identify the biological functions and prognostic value of hub genes in cervical cancer. METHODS: The gene expression data of CC patients were downloaded from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database. The core genes were screened out by differential gene expression analysis and weighted gene co-expression network analysis (WGCNA). R software, the STRING online tool and Cytoscape software were used to screen out the hub genes. The GEPIA public database was used to further verify the expression levels of the hub genes in normal tissues and tumour tissues and determine the disease-free survival (DFS) rates of the hub genes. The protein expression of the survival-related hub genes was identified with the Human Protein Atlas (HPA) database. RESULTS: A total of 64 core genes were screened, and 10 genes, including RFC5, POLE3, RAD51, RMI1, PALB2, HDAC1, MCM4, ESR1, FOS and E2F1, were identified as hub genes. Compared with that in normal tissues, RFC5, POLE3, RAD51,RMI1, PALB2, MCM4 and E2F1 were all significantly upregulated in cervical cancer, ESR1 was significantly downregulated in cervical cancer, and high RFC5 expression in CC patients was significantly related to OS. In the DFS analysis, no significant difference was observed in the expression level of RFC5 in cervical cancer patients. Finally, RFC5 protein levels verified by the HPA database were consistently upregulated with mRNA levels in CC samples. CONCLUSIONS: RFC5 may play important roles in the occurrence and prognosis of CC. It could be further explored and validated as a potential predictor and therapeutic target for CC.

Advances in Our Understanding of Pituitary Adenoma

2008 ◽  
Vol 04 (01) ◽  
pp. 88
Author(s):  
Sandra Pekic ◽  
Vera Popovic-Brkic
Keyword(s):  
Pituitary Adenoma ◽  
Pituitary Adenomas ◽  
Pituitary Tumors ◽  
Pituitary Hormones ◽  
Current Treatment ◽  
Thyroid Stimulating Hormone ◽  
Treatment Modalities ◽  
High Resolution Computed Tomography ◽  
New Therapeutic Approaches ◽  
Asymptomatic Patients

Pituitary adenomas are common benign monoclonal neoplasms— accounting for 15% of intracranial neoplasms—that may be clinically silent or secrete anterior pituitary hormones such as prolactin, growth hormone (GH), adrenocorticotrophic hormone (ACTH), or, rarely, thyroid-stimulating hormone (TSH) or gonadotrophins. Radiological studies for other reasons using high-resolution computed tomography (CT) or magnetic resonance imaging (MRI) detect incidental pituitary adenomas in approximately 20% of asymptomatic patients.1The incidence of the various types of adenoma varies;2prolactinomas are the most common pituitary adenomas. Clinically non-functioning pituitary adenomas (NFPAs), which do not secrete hormones, often cause local mass symptoms and represent one-third of pituitary adenomas. GH- and ACTH-producing adenomas each account for 10–15% of pituitary adenomas, while TSH-producing adenomas are rare. Pituitary adenomas are infrequent in childhood: fewer than 10% of pituitary adenomas are diagnosed before 20 years of age.3These adenomas can be either microor macroadenomas. The natural course of microadenomas is that a few tumors enlarge over a period of more than eight years.Although several genes and signaling pathways have been identified as important factors in the development of pituitary tumors, our understanding of pituitary tumorigenesis remains incomplete and is the focus of current research. The reason for this is that current treatment modalities fail to completely control this disorder and prevent the associated morbidity and mortality. This article reviews the advances in our understanding of pituitary adenoma, especially in the field of pathogenesis of pituitary tumors, and the possibility of new therapeutic approaches.

Prolactin gene expression in human growth hormone-secreting pituitary adenomas

1990 ◽  
Vol 72 (6) ◽  
pp. 879-882 ◽  
Author(s):  
Takashi Nagaya ◽  
Hisao Seo ◽  
Akio Kuwayama ◽  
Tsuyoshi Sakurai ◽  
Nobuhiro Tsukamoto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Pituitary Adenomas ◽  
Tumor Tissue ◽  
Pituitary Tumors ◽  
Human Growth ◽  
Content Type ◽  
Messenger Ribonucleic Acid ◽  
Prolactin Gene ◽  
Adenoma Tissue

✓ To elucidate the mechanism of hyperprolactinemia often observed in patients with growth hormone (GH)-secreting pituitary adenomas, the presence of immunoreactive prolactin (ir-PRL) and prolactin (PRL) messenger ribonucleic acid (mRNA) in the tumor tissue was examined by immunohistochemistry and cytoplasmic dot hybridization. Hyperprolactinemia was observed in three of 18 patients with GH-secreting adenoma. The tumor tissue was demonstrated to contain ir-PRL in nine patients and PRL mRNA in 13. The presence of ir-PRL in the tumor tissue was always associated with positive PRL mRNA, indicating production of PRL in GH-secreting tumors. Among the three patients with hyperprolactinemia, both ir-PRL and PRL mRNA was revealed in the tumor tissue of one, PRL mRNA but not ir-PRL was detected in the adenoma tissue of another, and neither PRL mRNA nor ir-PRL was found in the tumor tissue of the third. The association of hyperprolactinemia with the presence of both ir-PRL and PRL mRNA or PRL mRNA alone is indicative of PRL production and secretion. However, the absence of ir-PRL and PRL mRNA in the tumor tissue may indicate that hyperprolactinemia is caused by the suppression of PRL inhibitory factor due to hypothalamic dysfunction by the tumor mass. Thus, the study of PRL gene expression and immunohistochemistry in GH-secreting adenomas is valuable to understanding the pathophysiology of pituitary tumors.

scholarly journals Genomic and molecular characterization of pituitary adenoma pathogenesis: review and translational opportunities

2020 ◽  
Vol 48 (6) ◽  
pp. E11 ◽  
Author(s):  
Mazin Elsarrag ◽  
Parantap D. Patel ◽  
Ajay Chatrath ◽  
Davis Taylor ◽  
John A. Jane
Keyword(s):  
Pituitary Adenoma ◽  
Pituitary Adenomas ◽  
Basic Science ◽  
Cell Cycle Progression ◽  
Regulation Of Gene Expression ◽  
Gene Mutations ◽  
Pituitary Tumors ◽  
Rational Drug Design ◽  
Therapeutic Interventions ◽  
Neoplastic Disease

OBJECTIVEInnovations in genomics, epigenomics, and transcriptomics now lay the groundwork for therapeutic interventions against neoplastic disease. In the past 30 years, the molecular pathogenesis of pituitary adenomas has been characterized. This enhanced understanding of the biology of pituitary tumors has potential to impact current treatment paradigms, and there exists significant translational potential for these results. In this review the authors summarize the results of genomics and molecular biology investigations into pituitary adenoma pathogenesis and behavior and discuss opportunities to translate basic science findings into clinical benefit.METHODSThe authors searched the PubMed and MEDLINE databases by using combinations of the keywords “pituitary adenoma,” “genomics,” “pathogenesis,” and “epigenomics.” From the initial search, additional articles were individually evaluated and selected.RESULTSPituitary adenoma growth is primarily driven by unrestrained cell cycle progression, deregulation of growth and proliferation pathways, and abnormal epigenetic regulation of gene expression. These pathways may be amenable to therapeutic intervention. A significant number of studies have attempted to establish links between gene mutations and tumor progression, but a thorough mechanistic understanding remains elusive.CONCLUSIONSAlthough not currently a prominent aspect in the clinical management of pituitary adenomas, genomics and epigenomic studies may become essential in refining patient care and developing novel pharmacological agents. Future basic science investigations should aim at elucidating mechanistic understandings unique to each pituitary adenoma subtype, which will facilitate rational drug design.

scholarly journals Identification of significant genes with invasive promotion in non-functional pituitary adenoma via bioinformatical analysis

2021 ◽  
Author(s):  
An Shuo Wang ◽  
Hao Xu ◽  
Ming Hui Zeng ◽  
Fei Wang
Keyword(s):  
Pituitary Adenoma ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Pituitary Tumors ◽  
Receptor Interaction ◽  
Protein Protein Interaction ◽  
Normal Tissues ◽  
Non Invasive ◽  
Pathway Gene ◽  
Underlying Mechanisms

Abstract Background Non-functional pituitary adenoma (NFPA) is a disease with a high incidence, which accounts for a large part of pituitary tumors and plays a pivotal role. While invasive NFPAs which have not any endocrinology manifestations and space-occupying symptoms at early stages account for about 30 percent of NFPAs. The purpose of the present academic work was to identify significant genes with invasive promotion and their underlying mechanisms. Methods Gene expression profiles of GSE51618 was available from GEO database. There are 4 non-invasive NFPA tissues, 3 invasive NFPA tissues and 3 normal tissues in the profile datasets. Differentially expressed genes (DEGs) between non-invasive NFPA tissues and invasive NFPA tissues were picked out by GEO2R online tool. There were total of 226 up-regulated genes and 298 down-regulated genes. Next, we made use of the Database for Annotation, Visualization and Integrated Discovery (DAVID) to analyze Kyoto Encyclopedia of Gene and Genome (KEGG) pathway, gene ontology (GO) and Kaplan Meier Plotter. Then protein-protein interaction (PPI) of these DEGs was visualized by Cytoscape with Search Tool for the Retrieval of Interacting Genes (STRING). There were total of 141 up-regulated genes and 171 down-regulated genes. Of PPI network analyzed by Molecular Complex Detection (MCODE) plug-in, all 141 up-regulated genes were selected. Results After reanalysis of GO, five genes (ATP2B3, ADCYAP1R1, PTGER2, FSHβ, HTR4) were found to significantly enrich in the cAMP signaling pathway, Neuroactive ligand-receptor interaction and Renin secretion via reanalysis of DAVID. Conclusions We have identified five significant up-regulated DEGs with invasive promotion in invasive NFPAs on the basis of integrated bioinformatical methods, which could be potential therapeutic targets for invasive NFPAs patients.

scholarly journals Novel somatic variants involved in biochemical activity of pure growth hormone-secreting pituitary adenoma without GNAS variant

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Cheol Ryong Ku ◽  
Hyeonseob Lim ◽  
Yang Jong Lee ◽  
Sun Ho Kim ◽  
Daham Kim ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Pituitary Adenoma ◽  
Pituitary Adenomas ◽  
Pituitary Tumors ◽  
Genetic Alterations ◽  
Biochemical Activity ◽  
Recurrent Point ◽  
Targeted Resequencing ◽  
Severance Hospital

AbstractWe aimed to identify somatic genetic alterations in pure growth hormone (GH)-secreting pituitary adenomas without GNAS variants. Patients with GH-secreting pituitary adenoma who underwent transsphenoidal adenomectomy at Severance Hospital, Yonsei University College of Medicine were recruited. Somatic genetic alterations were profiled by whole-exome sequencing (WES) and targeted resequencing. WES was performed using DNA from nine GH-secreting pituitary tumors and corresponding blood samples. Absence of GNAS variant was confirmed by Sanger sequencing. For targeted resequencing of 140 fixed tissues, 48 WES-derived candidate genes and 7 GH-secreting pituitary adenoma-associated genes were included. Forty-eight genes with 59 somatic variants were identified by WES. In targeted resequencing, variants in 26 recurrent genes, including MAST4, PRIM2, TNN, STARD9, DNAH11, DOCK4, GPR98, BCHE, DARS, CUBN, NGDN, PLXND1, UNC5B, and COL22A1, were identified, but variants in previously reported genes were not detected. BCHE, DARS, NGDN, and UNC5B variants were associated with increased GH-secreting pituitary tumor biochemical activity, which was confirmed in vitro. Although recurrent point variants were rare, several somatic variants were identified in sporadic pure GH-secreting pituitary adenomas. Several somatic variants may affect pathways involved in the tumorigenesis and biochemical activities of GH-secreting pituitary adenomas.

scholarly journals Salvage therapy with temozolomide in patients with aggressive or metastatic pituitary adenomas: experience in six cases

2010 ◽  
Vol 163 (6) ◽  
pp. 843-851 ◽  
Author(s):  
Marco Losa ◽  
Elena Mazza ◽  
Maria Rosa Terreni ◽  
Ann McCormack ◽  
Anthony J Gill ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Tumor Size ◽  
Pituitary Adenomas ◽  
Dna Methyltransferase ◽  
Response Assessment ◽  
Pituitary Carcinoma ◽  
Consecutive Series ◽  
Positive Staining ◽  
Hormone Levels ◽  
Wide Range

ObjectiveThe prognosis of either pituitary carcinoma or aggressive pituitary adenoma resistant to standard therapies is poor. We assessed the efficacy of treatment with temozolomide, an oral second-generation alkylating agent, in a consecutive series of six patients with aggressive pituitary adenomas.DesignThis was a 1-year prospective study of temozolomide therapy in six consecutive patients with pituitary carcinoma (one case) or atypical pituitary adenoma (five cases) resistant to standard therapies. There were three males and three females. Age at enrollment ranged between 52 and 64 years. Temozolomide was given orally at a dose of 150–200 mg/m2 per day for 5 days every 4 weeks for a maximum of 12 cycles.MethodsResponse assessment was based on measurable change in tumor size, as assessed on magnetic resonance imaging, and hormone levels. Response was defined as reduction of at least 50% of tumor size and hormone levels.ResultsFour patients completed the 12 cycles of temozolomide treatment, as planned. Two patients stopped the drug after 3 and 6 months respectively because of the progression of disease. Two patients responded to temozolomide, while the remaining two patients had stable disease. Immunohistochemistry for O6-methylguanine-DNA methyltransferase (MGMT) in tumor sample showed a partial association with treatment response.ConclusionsTemozolomide treatment has a wide range of efficacy in patients with pituitary carcinoma or locally aggressive pituitary adenoma. Positive staining for MGMT seems likely to predict a lower chance of response.

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