scholarly journals Magmas, a Gene Newly Identified as Overexpressed in Human and Mouse ACTH-Secreting Pituitary Adenomas, Protects Pituitary Cells from Apoptotic Stimuli

Endocrinology ◽  
2010 ◽  
Vol 151 (10) ◽  
pp. 4635-4642 ◽  
Author(s):  
Federico Tagliati ◽  
Erica Gentilin ◽  
Mattia Buratto ◽  
Daniela Molè ◽  
Ettore Ciro degli Uberti ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Pituitary Adenomas ◽  
Mitochondrial Protein ◽  
Pituitary Tumors ◽  
Pituitary Cells ◽  
Subcellular Compartment ◽  
Adenoma Cell ◽  
Macrophage Colony ◽  
Reduced Rate ◽  
Acth Secreting

Pituitary tumors are mostly benign, being locally invasive in 5–35% of cases. Deregulation of several genes has been suggested as a possible alteration underlying the development and progression of pituitary tumors. We here report the identification of a cDNA, corresponding to Magmas gene (mitochondria-associated protein involved in granulocyte-macrophage colony-stimulating factor signal transduction), which is highly expressed in two different ACTH-secreting mouse pituitary adenoma cell lines as compared with normal pituitary as well as in two thirds of 64 examined pituitary adenomas as compared with human normal pituitary. Tim 16, the mitochondrial protein encoded by Magmas, was indeed expressed in a mouse ACTH-secreting pituitary adenoma cell line, AtT-20 D16v-F2 cells, in a subcellular compartment likely corresponding to mitochondria. Magmas silencing determined a reduced rate of DNA synthesis, an accumulation in G1 phase, and a concomitant decrease in S phase in At-T20 D16v-F2 cells. Moreover, Magmas-silenced cells displayed basal caspase 3/7 activity and DNA fragmentation levels similar to control cells, which both increased under proapoptotic stimuli. Our data demonstrate that Magmas is overexpressed in mouse and human ACTH-secreting pituitary adenomas. Moreover, our results show that Magmas protects pituitary cells from apoptosis, suggesting its possible involvement in neoplastic transformation.

scholarly journals miR-26a Plays an Important Role in Cell Cycle Regulation in ACTH-Secreting Pituitary Adenomas by Modulating Protein Kinase Cδ

Endocrinology ◽  
2013 ◽  
Vol 154 (5) ◽  
pp. 1690-1700 ◽  
Author(s):  
Erica Gentilin ◽  
Federico Tagliati ◽  
Carlo Filieri ◽  
Daniela Molè ◽  
Mariella Minoia ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pituitary Adenoma ◽  
Protein Kinase ◽  
Pituitary Adenomas ◽  
Viable Cell Number ◽  
Pituitary Cells ◽  
Human Pituitary ◽  
Human Pituitary Adenoma ◽  
Acth Secreting ◽  
Protein Kinase Cδ

Abstract The functional aftermath of microRNA (miRNA) dysregulation in ACTH-secreting pituitary adenomas has not been demonstrated. miRNAs represent diagnostic and prognostic biomarkers as well as putative therapeutic targets; their investigation may shed light on the mechanisms that underpin pituitary adenoma development and progression. Drugs interacting with such pathways may help in achieving disease control also in the settings of ACTH-secreting pituitary adenomas. We investigated the expression of 10 miRNAs among those that were found as most dysregulated in human pituitary adenoma tissues in the settings of a murine ACTH-secreting pituitary adenoma cell line, AtT20/D16v-F2. The selected miRNAs to be submitted to further investigation in AtT20/D16v-F2 cells represent an expression panel including 5 up-regulated and 5 down-regulated miRNAs. Among these, we selected the most dysregulated mouse miRNA and searched for miRNA targets and their biological function. We found that AtT20/D16v-F2 cells have a specific miRNA expression profile and that miR-26a is the most dysregulated miRNA. The latter is overexpressed in human pituitary adenomas and can control viable cell number in the in vitro model without involving caspase 3/7-mediated apoptosis. We demonstrated that protein kinase Cδ (PRKCD) is a direct target of miR-26a and that miR26a inhibition delays the cell cycle in G1 phase. This effect involves down-regulation of cyclin E and cyclin A expression via PRKCD modulation. miR-26a and related pathways, such as PRKCD, play an important role in cell cycle control of ACTH pituitary cells, opening new therapeutic possibilities for the treatment of persistent/recurrent Cushing's disease.

scholarly journals Cushing Disease Due to Ectopic Pituitary Adenoma.

2019 ◽  
pp. 1-5
Keyword(s):  
Pituitary Adenoma ◽  
Pituitary Adenomas ◽  
Adrenocorticotropic Hormone ◽  
Pituitary Tumors ◽  
Pituitary Stalk ◽  
Cushing Disease ◽  
Ectopic Acth ◽  
Common Cause ◽  
Ectopic Pituitary Adenoma ◽  
Acth Secreting

Abstract Adrenocorticotropic hormone (ACTH) - secreting pituitary adenomas are the most common cause of Cushing disease. A pituitary adenoma is rarely ectopic and suprasellar dependent (ectopic) ACTH -secreting pituitary tumors are extremely rare, with few cases described in the literature. Therefore, this study aimed to report the case of a patient with a diagnosis of Cushing disease because of a suprasellar ACTH-secreting tumor attached to the pituitary stalk, requiring a craniotomy.

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.

scholarly journals Marked Response of a Hypermutated ACTH-Secreting Pituitary Carcinoma to Ipilimumab and Nivolumab

2018 ◽  
Vol 103 (10) ◽  
pp. 3925-3930 ◽  
Author(s):  
Andrew L Lin ◽  
Philip Jonsson ◽  
Viviane Tabar ◽  
T Jonathan Yang ◽  
John Cuaron ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Liver Metastasis ◽  
Effective Treatment ◽  
Somatic Hypermutation ◽  
Treatment Options ◽  
Pituitary Tumors ◽  
Pituitary Carcinoma ◽  
Tumor Resistance ◽  
Clinical Sequencing ◽  
Acth Secreting

Abstract Context Pituitary carcinoma is a rare and aggressive malignancy with a poor prognosis and few effective treatment options. Case A 35-year-old woman presented with an aggressive ACTH-secreting pituitary adenoma that initially responded to concurrent temozolomide and capecitabine prior to metastasizing to the liver. Following treatment with ipilimumab and nivolumab, the tumor volume of the dominant liver metastasis reduced by 92%, and the recurrent intracranial disease regressed by 59%. Simultaneously, her plasma ACTH level decreased from 45,550 pg/mL to 66 pg/mL. Molecular Evaluation Both prospective clinical sequencing with Memorial Sloan Kettering–Integrated Mutation Profiling of Actionable Cancer Targets and retrospective whole-exome sequencing were performed to characterize the molecular alterations in the chemotherapy-naive pituitary adenoma and the temozolomide-resistant liver metastasis. The liver metastasis harbored a somatic mutational burden consistent with alkylator-induced hypermutation that was absent from the treatment-naive tumor. Resistance to temozolomide treatment, acquisition of new oncogenic drivers, and subsequent sensitivity to immunotherapy may be attributed to hypermutation. Conclusion Combination treatment with ipilimumab and nivolumab may be an effective treatment in pituitary carcinoma. Clinical sequencing of pituitary tumors that have relapsed following treatment with conventional chemotherapy may identify the development of therapy-induced somatic hypermutation, which may be associated with treatment response to immunotherapy.

scholarly journals Endoscopic endonasal transsphenoidal approach for pituitary adenomas: technical aspects and report of casuistic

2010 ◽  
Vol 68 (4) ◽  
pp. 608-612 ◽  
Author(s):  
Américo Rubens Leite dos Santos ◽  
Roberto Monteiro Fonseca Neto ◽  
José Carlos Esteves Veiga ◽  
José Viana Jr ◽  
Nilza Maria Scaliassi ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Pituitary Tumors ◽  
Hormonal Control ◽  
Subtotal Resection ◽  
Endoscopic Endonasal ◽  
Technical Aspects ◽  
Transphenoidal Approach ◽  
Acth Secreting ◽  
Csf Leaks

OBJECTIVE: Analyse technical aspects, effectiveness and morbidity of the endoscopic endonasal transphenoidal approach for pituitary adenomas. METHOD: From January 2005 to September 2008, 30 consecutive patients underwent endoscopic endonasal resection of pituitary adenomas with a follow up from 3 to 36 months. Their medical charts were retrospectively analysed. RESULTS: There were 18 women and 12 men, mean age 44 years (range 17-65 yr). Among the 30 patients, 23 had macroadenomas and 7 microadenomas. Twelve patients had non-functioning tumors, 9 had ACTH-secreting tumors, 8 had GH-secreting tumors and 1 prolactinoma. Complete resection and hormonal control was achieved in all microadenomas. Macroadenomas were completely removed in 6 patients, subtotal resection in 6 and partial resection in 11. Three patients had diabetes insipidus and 5 had CSF leaks treated with lumbar drainage. CONCLUSION: The endonasal endoscopic approach for pituitary tumors is effective and has low morbidity.

Bevacizumab in Aggressive Pituitary Adenomas – Experience with 3 Patients

2020 ◽  
Author(s):  
Katharina Osterhage ◽  
Roman Rotermund ◽  
Michael Droste ◽  
Judith Dierlamm ◽  
Wolfgang Saeger ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Transsphenoidal Surgery ◽  
Pituitary Tumors ◽  
Considerable Effect ◽  
General Statement ◽  
Patient Deterioration ◽  
Short Period ◽  
Acth Secreting ◽  
Design And Methods ◽  
Current Stage

Abstract Objective To investigate bevacizumab as alternative treatment of aggressive pituitary adenomas after exhaustion of standard therapies. Design and Methods Retrospectively, 3 patients undergoing microscopic transsphenoidal surgery of aggressive pituitary adenomas from 2008 till 2018 that were treated with bevacizumab were identified. Development of disease and treatment were evaluated. Results Two patients suffered from ACTH-secreting adenomas, one from a non-functioning adenoma. All patients underwent multiple surgical, chemo- and radiotherapeutical approaches including temozolomide, showing favorable results in one patient. Deterioration of clinical condition in all patients led to an individual, palliative attempt of bevacizumab. Patients 1 and 2 showed a decrease of ACTH after first administrations, but therapy had to be ended shortly after due to a further deterioration of their condition. Patient 3 showed a stabilization of the disease for 18 months. Patients died 8, 15 and 7 years after initial diagnosis, respectively, and 2, 4, and 24 months after initiation of bevacizumab therapy, respectively. Conclusion The demonstrated results suggest a considerable effect of bevacizumab in aggressive pituitary adenomas. The advanced stage of disease in all three patients, the overall short period of administration and just one patient showing a clinical benefit do not allow a general statement on the effectiveness. At the current stage of clinical experience, an approach with bevacizumab can be considered as an individual palliative attempt of treatment, when standard treatments are exhausted. Our results underline the need for further studies to evaluate this drug as potential player in therapy resistant aggressive pituitary tumors.

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.

Immunochistochemical characteristics of blood vessels in non-visualized and visualized on MRI pituitary adenoma in patients with Cushing’s disease

2016 ◽  
Vol 62 (5) ◽  
pp. 65-66
Author(s):  
Patimat M. Khandaeva ◽  
Iya A. Voronkova ◽  
Zhanna E. Belaya ◽  
Lyudmila Y. Rozhinskaya ◽  
Aleksandr V. Vorontsov ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Blood Vessels ◽  
Cushing’S Disease ◽  
Pituitary Tumor ◽  
Pituitary Tumors ◽  
Average Diameter ◽  
Cushing's Disease ◽  
Retrospective Evaluation ◽  
Acth Secreting ◽  
Microvessels Density

Backgraund. Regardless of improvements in MRI, up to 20% of ACTH-secreting pituitary tumors are only identified at surgical exploration.Aim: to estimate whether there is any difference in blood vessels and the subsequent ability to uptake contrast agent in visualized microadenoma as compared to non-visualized on MRI ACTH-secreting pituitary tumors.Materials and methods. retrospective evaluation of ACTH-positive pituitary tumors from patients with Cushing’s disease (n=39) with either non-visualized pituitary tumor on MRI (n=17) or pituitary tumor less then 25 mm (n=22). MRI was performed using Siemens Magnetom Harmony 1.0T with gadolinium. Selected tumors were stained with anty-СD34 antibody (clone QBEnd/10, RTU, Leica) and anty-D2-40 antibody (clone D2-40, RTU, Dako). We evaluated the microvessels density and measured the diameter of larger and smaller vessel.Results. The microvessels density were not different in subject with visualized (123 [77;136]) and non-visualized (112 [110,0;126,5]) pituitary adenomas as well as number of slit-shaped vessels (32 [5;50] in visualized vs 25 [5;50] in non-visualized pituitary adenoma). The diameter of these vessels also did not differ: the diameter of the largest vessels in patients without visualization 53 µm [32,5;63,5] vs 33 µm [30,0;51,5], the average diameter of the blood vessels 15 µm [14,5-26,0] against 13 µm [12;14].Conclusions. The diameter and microvessels density in ACTH-producing pituitary adenoma does not affect the visualization of adenoma on MRI in patients with Cushing 's disease.

scholarly journals A Rare Corticotroph-Secreting Tumor with Coexisting Prolactin and Growth Hormone Staining Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Subramanian Kannan ◽  
Susan M. Staugaitis ◽  
Robert J. Weil ◽  
Betul Hatipoglu
Keyword(s):  
Growth Hormone ◽  
Transcription Factors ◽  
Pituitary Adenoma ◽  
Pituitary Adenomas ◽  
Rare Case ◽  
Pituitary Hormones ◽  
Review Literature ◽  
Pituitary Cells ◽  
Biological Mechanisms

Pituitary adenomas can express and secrete different hormones. Expression of pituitary hormones in nonneoplastic pituitary cells is regulated by different transcription factors. Some pituitary adenomas show plurihormonal expression. The most commonly reported plurihormonal adenomas are composed of somatotrophs, lactotrophs, thyrotrophs and gonadotrophs. Pituitary adenomas composed of both corticotroph and somatolactotroph secreting cells are not common because transcription factors regulating the expression of these hormones are different. We report a rare case of pituitary adenoma with concomitant corticotroph, prolactin, and growth hormone staining cells, review literature on similar cases, and discuss possible biological mechanisms underlying these plurihormonal tumors.

scholarly journals Functional in vitro studies on the role and regulation of interleukin-6 in human somatotroph pituitary adenomas

2003 ◽  
Vol 149 (5) ◽  
pp. 455-461 ◽  
Author(s):  
JO Thiele ◽  
P Lohrer ◽  
L Schaaf ◽  
M Feirer ◽  
W Stummer ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Cultures ◽  
Interleukin 6 ◽  
Pituitary Adenomas ◽  
Transforming Growth Factor ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Pituitary Cells ◽  
Stimulatory Action ◽  
Adenoma Cell

OBJECTIVE: Interleukin-6 (IL-6), a member of the gp130 cytokine family, is considered to be an important modulator of function and growth in endocrine anterior pituitary cells. In pituitary adenomas, where IL-6 is often produced by the tumour cells, it is thought to be involved in pituitary adenoma pathophysiology via autocrine/paracrine mechanisms. METHODS: We have studied in primary cell cultures of human somatotroph adenomas whether IL-6 stimulates growth hormone secretion and whether intratumoral IL-6 is affected by various IL-6-regulating factors. RESULTS: Interleukin-6 stimulated GH secretion in 10 out of 11 somatotroph adenoma cultures (1.4- to 6.5-fold above basal levels). In comparative studies the GH-stimulatory potency of IL-6 was identical, or even stronger, than that of GHRH. In eight out of 11 adenoma cell cultures, IL-6 production was observed. This suggests that GH production might be stimulated by IL-6 in an autocrine/paracrine manner in these tumours. Dexamethasone strongly inhibited basal IL-6 secretion in all IL-6-producing adenoma cell cultures, whereas the IL-6 inhibitory or stimulatory action of other factors (octreotide, transforming growth factor-beta1, insulin-like growth factor-I, pituitary adenylate cyclase-activating peptide and oestradiol) were heterogeneous in the different adenomas. Only transforming growth factor-alpha consistently stimulated IL-6 secretion in all of the adenomas studied. CONCLUSIONS: Intratumoral IL-6, which is differently regulated by various factors, might contribute to excessive GH production in the majority of somatotroph adenomas.

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