Disease relevance of Adrenocortical Carcinoma

• The cyclase of an ACTH-unresponsive adrenocortical carcinoma ws activated only by PGE1 and not by other hormones including ACTH, whereas that of an ACTH-responsive adrenocortical nodular hyperplasia was stimulated by ACTH and glucagon but not by other hormones including PGE1 [1].
• CONCLUSION: The regimen of CDDP and o,p'DDD has activity in patients with adrenocortical carcinoma; however, the toxicity of this treatment was moderate to severe [2].
• Two adrenocortical carcinomas and three adenomas manifested cytokeratin positivity after trypsin digestion [3].
• Bisulfite genomic sequencing revealed a significantly higher mean degree of methylation at each of 12 CpG sites of the H19 promoter in adrenocortical carcinomas than in normal adrenals (P < 0.01 for all sites) or adrenocortical adenomas (P < 0.01, except P < 0.05 for site 12 and P > 0.05 for site 11) [4].
• IGF-II mRNA levels were more than 10-fold higher in hormonally active adrenocortical carcinomas than in normal adult adrenals, and increased IGF-II-like immunoreactivity was detectable in these carcinomas [5].

High impact information on Adrenocortical Carcinoma

• Mitotane therapy of adrenocortical carcinoma [6].
• It may be reasonable for children with adrenocortical carcinoma to be candidates for germline TP53 analysis [7].
• PCR amplification was also carried out using total RNA from adrenocortical carcinoma samples of the proband in family 1 [8].
• One patient with adrenocortical carcinoma had a somatic mutation in the HRAS1 gene in the normal adrenal gland [9].
• The molecular basis for the aberrant catecholamine responsiveness of the adenylate cyclase of adrenocortical carcinoma 494 was explored [10].

Chemical compound and disease context of Adrenocortical Carcinoma

• Suramin for treatment of adrenocortical carcinoma [11].
• Transplacental carcinogenesis (adrenocortical carcinoma) associated with hydroxyprogesterone hexanoate [12].
• Aldosterone-producing adrenocortical carcinoma. Preoperative recognition and course in three cases [13].
• Autophosphorylating protein kinase 500 (AUT-PK 500) is a unique serine protein kinase that was originally purified and characterized from the rat adrenocortical carcinoma [14].
• We show that a phosphorothioate-modified, antisense oligodeoxynucleotide directed against the DNA MeTase mRNA reduces the level of DNA MeTase mRNA, inhibits DNA MeTase activity, and inhibits anchorage independent growth of Y1 adrenocortical carcinoma cells ex vivo in a dose-dependent manner [15].

Biological context of Adrenocortical Carcinoma

• We detected heterozygous germline mutations (exon 7, Val 281Leu) in two patients, one with a cortisol-producing adenoma and the other with an androgen-secreting adrenocortical carcinoma [16].
• Prevalence of HLA-DRB1 genotype and altered Fas/Fas ligand expression in adrenocortical carcinoma [17].
• Our results suggest that altered DNA methylation of the H19 promoter is involved in the abnormal expression of both H19 and IGF-II genes in human adrenocortical carcinomas [4].
• High local levels of IGF-II in combination with elevated IGF-I receptor concentrations would represent a significant growth advantage of the adrenocortical carcinoma cell and could contribute to a highly malignant phenotype [18].
• The cause was not aldosterone excess, but there was an adrenal cortical carcinoma producing 11-deoxycorticosterone (DOC) in extremely large quantities, with ineffective 11 beta-steroid hydroxylation [19].

Anatomical context of Adrenocortical Carcinoma

• Establishment and characterization of a human adrenocortical carcinoma cell line that expresses multiple pathways of steroid biosynthesis [20].
• Most non-neuroendocrine cells and tumors did not express N-CAM, although uterine smooth muscle and an adrenal cortical carcinoma were both positive [21].
• A sixth patient had recurrent right adrenal cortical carcinoma with tumor invasion of the vena cava and occlusion to the right atrium [22].
• The adenylate cyclase of an adrenocortical carcinoma of the rat is activated not only by ACTH but also by beta-adrenergic agonists, which bind to ectopic beta-adrenergic receptors not present in normal rat adrenal cortex [23].
• Angiotensin II promotes selective uptake of high density lipoprotein cholesterol esters in bovine adrenal glomerulosa and human adrenocortical carcinoma cells through induction of scavenger receptor class B type I [24].

Gene context of Adrenocortical Carcinoma

• In contrast, relative abundance of AKR1B1 mRNA was decreased in adrenocortical carcinomas (n = 5; mean +/- sem, 0.95 +/- 0.2) when compared with adenomas (n = 12; 9.29 +/- 3.05; P < 0.001) [25].
• Both TGF-alpha and EGFR expression were markedly elevated in adrenocortical carcinomas [26].
• Evaluation of the effects of ghrelin on GHS-R expression and proliferation of human adrenocortical carcinoma (ACC) cell lines [27].
• CONCLUSIONS: Mutations in the TP53 gene are frequent in adrenocortical carcinomas and might be used as a marker of malignancy [28].
• Two of three adrenocortical carcinomas expressed ACTH-R mRNA [29].

Analytical, diagnostic and therapeutic context of Adrenocortical Carcinoma

• Furthermore, the human adrenocortical carcinoma cell line, NCI-H295, expresses LPL mRNA and protein, which is localized to the outer cellular membrane as demonstrated by immunofluorescence confocal microscopy and can be released in the medium by heparin addition [30].
• Abdominal scintigraphy using a new 131I-labeled steroid agent was performed on a 40-year-old women proven by surgery to have adrenocortical carcinoma [31].
• The H295R xenograft model is a good model of human adrenocortical carcinoma, as it mimics dysregulation of the IGF system usually found in these tumors [32].
• Overlapping expression of immunohistochemical markers and synaptophysin mRNA in pheochromocytomas and adrenocortical carcinomas. Implications for the differential diagnosis of adrenal gland tumors [33].
• Recovery of adrenal function after treatment of adrenocortical carcinoma with o,p'-DDD [34].

References