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Potential Therapeutic Target Discovered For Cushing's Disease

Scientists at the Salk Institute for Biological Studies have identified a protein that drives the formation of pituitary tumors in Cushing's disease, a development that may give clinicians a therapeutic target to treat this potentially life-threatening disorder. The protein, called TR4 (testicular orphan nuclear receptor 4), is one of the human body's 48 nuclear receptors, a class of proteins found in cells that are responsible for sensing hormones and, in response, regulating the expression of specific genes...
Source: Health News from Medical News Today - Category: Consumer Health News Tags: Cancer / Oncology Source Type: news

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Rats affected by the MENX syndrome spontaneously develop multiple neuroendocrine tumors (NETs) including adrenal, pituitary and thyroid gland neoplasms. MENX was initially reported to be inherited as a recessive trait and affected rats were found to be homozygous for the predisposing Cdkn1b mutation encoding p27. We here report that heterozygous MENX-mutant rats (p27+/mut) develop the same spectrum of NETs seen in the homozygous (p27mut/mut) animals but with slower progression. Consequently, p27+/mut rats have a significantly shorter lifespan compared with their wild-type (p27+/+) littermates. In the tumors of p27+/mut rat...
Source: Endocrine-Related Cancer - Category: Endocrinology Authors: Tags: Research Source Type: research
In conclusion, our results elucidate that IL‐6/STAT3 activation can increase PTTG1 expression and consequently promote the resistance to ADT in CRPC via inducing EMT and increasing the cancer stem cell population, suggesting that PTTG1 may be a novel therapeutic target for CRPC. This article is protected by copyright. All rights reserved.
Source: Cancer Science - Category: Cancer & Oncology Authors: Tags: Original Article Source Type: research
Evidence for the presence of pituitary gland stem cells has been provided over the last decade using a combination of approaches including in vitro clonogenicity assays, flow cytometric side population analysis, immunohistochemical analysis and genetic approaches. These cells have been demonstrated to be able to self-renew and undergo multipotent differentiation to give rise to all hormonal lineages of the anterior pituitary. Furthermore, evidence exists for their contribution to regeneration of the organ and plastic responses to changing physiological demand. Recently, stem-like cells have been isolated from pituitary neo...
Source: Journal of Endocrinology - Category: Endocrinology Authors: Tags: Review Source Type: research
Abstract The pharmacological therapy of GH‐secreting pituitary tumors is based on somatostatin (SS) analogs that reduce GH secretion and cell proliferation by binding mainly SS receptors type 2 (SST2). Antimigratory effects of SS have been demonstrated in different cell models, but no data on pituitary tumors are available. Aims of this study were to evaluate SST2 effects on migration and invasion of human and rat tumoral somatotrophs, and to elucidate the molecular mechanism involved focusing on the role of cofilin and filamin A (FLNA). Our data revealed that SST2 agonist BIM23120 significantly reduced GH3 cells migrati...
Source: International Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Article Source Type: research
AbstractBackgroundAdrenocortical carcinoma (ACC) has a poor prognosis and there is an unmet clinical need for biomarkers to improve both diagnostic and prognostic assessment. Pituitary-tumor transforming gene (PTTG1) has been shown to modulate cancer invasiveness and response to therapy. The potential role of PTTG1 protein levels in ACC has not been previously addressed. We assessed whether increased nuclear protein expression of PTTG1 distinguished ACCs from adrenocortical adenomas (ACAs).MethodsPatients with ACC or ACA were identified from prospective tissue banks at two independent institutions. Two tissue microarrays (...
Source: Annals of Surgical Oncology - Category: Cancer & Oncology Source Type: research
We report a case of a 63-year-old woman with a history of bilateral breast cancer with surgery 15 years ago on the left side and 8 years ago on the right side. A pituitary macroadenoma was first suspected because of a visual disturbance for months before a magnetic resonance imaging examination. The patient underwent resection of the pituitary tumor by endoscopic transnasal trans-sphenoidal surgery. The final histopathological and immunohistochemistry analysis confirmed a pituitary metastasis of breast mucinous carcinoma. Postoperative follow-up continued for 2.5 half years, and the subsequent clinical imaging studies did ...
Source: International Journal of Gerontology - Category: Geriatrics Source Type: research
Pituitary tumor-transforming gene 1-binding factor (PTTG1IP; PBF) is a multifunctional glycoprotein, which is overexpressed in a wide range of tumours, and significantly associated with poorer oncological outcomes, such as early tumour recurrence, distant metastasis, extramural vascular invasion and decreased disease-specific survival. PBF transforms NIH 3T3 fibroblasts and induces tumours in nude mice, while mice harbouring transgenic thyroidal PBF expression show hyperplasia and macrofollicular lesions. Our assumption that PBF becomes an oncogene purely through increased expression has been challenged by the recent repor...
Source: Endocrine-Related Cancer - Category: Endocrinology Authors: Tags: Research Source Type: research
The CABLES1 cell cycle regulator participates in the adrenal–pituitary negative feedback, and its expression is reduced in corticotropinomas, pituitary tumors with a largely unexplained genetic basis. We investigated the presence of CABLES1 mutations/copy number variations (CNVs) and their associated clinical, histopathological and molecular features in patients with Cushing’s disease (CD). Samples from 146 pediatric (118 germline DNA only/28 germline and tumor DNA) and 35 adult (tumor DNA) CD patients were screened for CABLES1 mutations. CNVs were assessed in 116 pediatric CD patients (87 germline DNA only/29 ...
Source: Endocrine-Related Cancer - Category: Endocrinology Authors: Tags: Research Source Type: research
The use of PET CT for staging in cancer patients and the widespread use of MRI led to an increased incidence of incidental sellar mass detection. The imaging findings can be suggestive of a benign pituitary tumor but metastasis can never be completely ruled out with non-invasive work-up. Appropriate diagnosis of these sellar masses is critical as the treatment paradigm might change in the presence of a pituitary metastasis. Moreover, definitive tissue diagnosis might prevent unnecessary radiotherapy to the skull base or even the need for systemic treatment when benign pituitary disease is confirmed.
Source: World Neurosurgery - Category: Neurosurgery Authors: Tags: Original article Source Type: research
The use of combined positron emission tomography/computed tomography for staging in patients with cancer and the widespread use of magnetic resonance imaging has led to increased detection of incidental sellar masses. The imaging findings can be suggestive of a benign pituitary tumor, but metastasis can never be completely ruled out with noninvasive work-up. Appropriate diagnosis of sellar masses is critical, as the treatment paradigm might change in the presence of a pituitary metastasis. Definitive tissue diagnosis might prevent unnecessary radiotherapy to the skull base or the need for systemic treatment when benign pit...
Source: World Neurosurgery - Category: Neurosurgery Authors: Tags: Original Article Source Type: research
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