Gestational trophoblastic diseases: 1. Pathophysiology of hyperglycosylated hCG

Cole, Laurence A.; Dai, Donghai; Butler, Stephen A.; Leslie, Kimberly K.; Kohorn, Ernest I.

doi:10.1016/j.ygyno.2005.12.047

Cited by 81 publications

(105 citation statements)

References 26 publications

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“…The specificity of this antibody is for hyperglycosylated hCG [7,8]. As published, this antibody detects an O-linked oligosaccharide on hCG at Ser 132 and segments of ß-subunit and a-subunit peptide [21].…”

Section: Resultsmentioning

confidence: 99%

“…The assay was tested here with the only pure hCG and hyperglycosylated hCG preparations (Sigma, St Louis, recombinant hCG) and pure hyperglycosylated hCG preparations (C5 hCG and cytotrophoblast cell hCG). As published [7,8,22], the hormone hCG is produced exclusively by syncytiotrophoblast cells and the autocrine hyperglycosylated hCG by cytotrophoblast cells.…”

Section: Resultsmentioning

confidence: 99%

“…All reports show structure of a invariable mixture of the hormone hCG and a completely independent molecule, the autocrine hyperglycosylated hCG. Yes, it is only in recent years, after most of these carbohydrate structure projects were completed [1][2][3][4][5], that the presence of two separate molecules in pregnancy, a hormone and an autocrine, has been demonstrated [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

“…It is just in the last 8 years that separate research has shown that two molecules both sharing a common a-and ß-subunit amino acid sequence, are produced in pregnancy [7,8]. hCG the hormone promotes hemochorial placentation, promotes maternal ovarian progesterone production, suppresses macrophage destruction of the feto-placenta unit, and suppresses myometrial contractions during pregnancy.…”

Section: Introductionmentioning

confidence: 99%

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hCG and Hyperglycosylated hCG Carbohydrate Structure Corrected

Cole¹

2015

J Glycobiol

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Multiple articles have been published describing the N-linked and O-linked oligosaccharide structures of hCG. All, however, have used purified preparation from pregnancy urine and from choriocarcinoma patient urine. This has told the scientific community that pregnancy and choriocarcinoma hCG-related molecules contain Type 1 and Type 2 O-linked oligosaccharides and biantennary and triantennary N-linked oligosaccharide. Recent years have seen the demonstration of two completely independent hCG molecules, hCG and hyperglycosylated hCG. hCG is a pregnancy hormone made by syncytiotrophoblast cell. Hyperglycosylated hCG is a TGFß receptor binding autocrine produced by cytotrophoblast cells. The two independent share a common amino acid sequence and just vary in carbohydrate structure. Unfortunately, all the carbohydrate structure reports are on a mixture of hCG and hyperglycosylated hCG, as present in pregnancy and choriocarcinoma. This does not all anyone to clearly see the carbohydrate structural differences between the two molecules. Here we carefully examine the carbohydrate structural differences between hCG and hyperglycosylated hCG using the B152 hyperglycosylated hCG-specific immunoassay. It is shown that hCG has only Type 1 O-linked oligosaccharides, while hyperglycosylated hCG only has Type 2 O-linked oligosaccharides. Type of O-linked oligosaccharide structure completely distinguishes hCG and hyperglycosylated hCG.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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hCG and Hyperglycosylated hCG Carbohydrate Structure Corrected

Cole¹

2015

J Glycobiol

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“…Regular HCG is produced only by differentiated syncytiotrophoblast cells. [10][11][12] it is also expressed as particular glycoforms by certain malignancies. These glycoforms, which are called "hyperglycosylated" HCG (hCGh), have been reported to contain more complex glycan moieties.…”

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confidence: 99%

Elevated Human Chorionic Gonadotropin HCG Serum Level in Germ Cell Testicular Tumor

Elnour¹

2018

MOJPB

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Submit Manuscript | http://medcraveonline.com cancer diagnosis, determining prognosis, surveillance following curative surgery for cancer, Tumor markers are playing an increasingly important role in cancer detection and management.In case of testicular cancer diagnosis/case finding, staging, prognosis determination, alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), and lactate dehydrogenase (LDH) are recommended, they play an important role as serum tumor markers for in the staging and monitoring of germ cell tumors. 2But what the relationship between HCG serum levels and germ cell testicular tumors? Human chorionic gonadotropin (HCG)HCG is a glycoprotein hormone composed of two dissimilar subunits, α and β, joined noncovalently. It is produced by trophoblast tissue in pregnancy and trophoblast disease and in small amounts by certain poorly differentiated cancers. The α-subunit of HCG is similar to that of the pituitary glycoprotein hormones. It is produced principally by the trophoblastic cells of the placenta but may also be produced by nontrophoblastic tissues including normal pituitary and neoplastic cells.3 It is normal for non-pregnant women and men to make very small amounts of HCG, with blood levels less than 5mIU/ mL. If HCG is high in non-pregnant women or men, it may indicate cancer. 4 Where used in malignant causes as tumor marker which is secreted by some cancers including choriocarcinoma, endometrium, and ovarian carcinoma. HCG is elevated in most type of testicular cancer seminomas and non-seminoma germ cell testicular tumors.It has been found that HCG possesses a role in the angiogenic process in vivo and in vitro by increasing capillary formation and endothelial cell migration, also, hCG-induced neovascularization. HCG may regulate vascular neoformation through vascular endothelial growth factor (VEGF). 5HCG contains five acidic asparagines-linked sugar chains. These five sugar chains are derived by sialylation from three neutral oligosaccharides: two biantennary (N-1 and N-2) and one monoantennary (N-3) complex-type oligosaccharides. The malignant transformational change of the sugar moiety of HCG can be explained by an increase of a fucosyltransferas. 6 Which indicate that N-acetylglucosaminyltransferase IV (GnT-IV) is abnormally expressed in the malignant cells. There are independent variants of HCG, each produced by different cells with separate biological functions. Multiple molecular variants of HCG include intact HCG, nicked HCG (hCGn), free β-subunit HCG (hCGβ), nicked free β-subunit HCG (hCGβn), free α-subunit hCG (hCGα), and the β-core fragment hCG (hCGβcf). In addition, HCG is differentially glycosylated in various tissues, resulting in a range of molecular forms from hypoglycosylated to hyperglycosylated. So-called hyperglycosylated HCG (hCG-h) is probably the best known of these glycosylated variants, 8 each one of them sharing the common amino acid sequence but each differing in meric structure and carbohydrate side chain structure.Hcg that produced by trophoblast cells...

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