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Despite important advances in human therapeutics, no specific treatment for both non-functioning gonadotroph and resistant somatotroph adenomas is available. Gene transfer by viral vectors can be considered as a promising way to achieve a specific and efficient treatment. Here we show the possibility of efficient gene transfer in human pituitary adenoma cells in vitro using a human immunodeficiency virus (HIV)-type 1-derived vector. Using enhanced green fluorescent protein (eGFP) gene as a marker placed under the phosphoglycerate kinase (PGK) promoter, gonadotroph and somatotroph adenomas were transduced even with moderate viral loads. The expression started at day 2, reached a peak at day 5, and it was still present at day 90. For targeting somatotroph and gonadotroph adenomas, human growth hormone (GH) promoter (GH -481, +54 bp) and two fragments of the human glycoprotein hormone alpha-subunit promoter (alpha-subunit 1 -520, +33 bp, and alpha-subunit 2 -907, +33 bp) were tested. In gonadotroph adenomas, the percentage of identified fluorescent cells and the fluorescence intensity analyzed by fluorescence-activated cell sorting indicated that the strength of the alpha-subunit 1 and alpha-subunit 2 promoters were comparable to that of the PGK promoter. Primary cultures of rat pituitary cells showed that alpha-subunit 1 is more selective to thyreotroph and gonadotroph phenotypes than alpha-subunit 2. GH promoter activity appeared weak in somatotroph adenomas. The human GH enhancer did not increase the GH promoter activity at all but the human prolactin promoter (-250 bp) allowed 4-fold more fluorescent cells to be obtained than the GH promoter. Several cell lines appeared too permissive to test cell-specificity of pituitary promoters. However, on human non-pituitary cell cultures, the tested pituitary promoters seemed clearly selective to target endocrine pituitary phenotypes. This study gives a starting point for a gene-therapy program using lentiviral vectors to transfer therapeutic genes in human pituitary adenomas.
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http://dx.doi.org/10.1677/joe.1.05759 | DOI Listing |
J Clin Med
December 2024
Skull Base and Pituitary Surgery Unit, "Città della Salute e della Scienza" University Hospital, 10126 Turin, Italy.
: In pituitary adenomas, examinations of surgical specimens have shown that dural invasion occurs in 42-85% of cases. No studies about dura mater invasion have been conducted specifically in acromegaly patients. The aim of the present study was to evaluate the relationship between histologically dural invasion and the main features of GH-secreting adenomas.
View Article and Find Full Text PDFJ Craniofac Surg
December 2024
Department of Neurosurgery, Binzhou Medical University Hospital, Binzhou, Shandong, China.
Background: Pituitary adenomas are common benign intracranial tumors. This study aimed to explore the relevant factors influencing the cavernous sinus medial wall invasion by Pituitary adenomas based on intraoperative evaluation. Meanwhile, the authors introduced a safe technique for the resection of the medial wall of the cavernous sinus and conducted a preliminary evaluation of the efficacy of this technique.
View Article and Find Full Text PDFJ ASEAN Fed Endocr Soc
December 2024
Faculty of Medicine, Universiti Kebangsaan Malaysia.
Managing a patient with both pituitary hypersecretory and hyposecretory manifestations may be perplexing. We report a 14-year-old female who presented with weight gain, polyuria and polydipsia. Biochemical results were consistent with Cushing disease with central diabetes insipidus.
View Article and Find Full Text PDFJ Neurooncol
November 2024
Department of Neurosurgery, Medical College of Wisconsin, Hub for Collaborative Medicine, 8701 Watertown Plank Rd., Milwaukee, Wisconsin, 53226, USA.
Purpose: Acromegaly is characterized by an insidious clinical presentation and delayed diagnosis. Longer delays are associated with more comorbidities which can persist after treatment of the growth hormone-secreting pituitary adenoma (GH-PA). Surgery is the primary therapy of GH-secreting PA, which can lead to durable remission.
View Article and Find Full Text PDFGenes (Basel)
October 2024
National Research Council (CNR)-Istituto di Analisi dei Sistemi ed Informatica "Antonio Ruberti" (IASI), 00185 Rome, Italy.
Background: This study explores the potential for hidden variations within seemingly uniform regions of growth hormone-secreting pituitary neuroendocrine tumors (GH-PitNETs). We employed archived tissue samples using Laser Capture Microdissection Sequencing (LCM-RNAseq) to probe the molecular landscape of these tumors at a deeper level.
Methods: A customized protocol was developed to extract, process, and sequence small amounts of RNA from formalin-fixed, paraffin-embedded (FFPE) tissues derived from five patients with GH-secreting PitNETs and long-term follow-up (≥10 years).
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