Abstract:
:Reliable prediction of disease status is a major challenge in managing gastroenteropancreatic neuroendocrine tumors (GEP-NET). The aim of the study was to validate the NETest®, a blood molecular genomic analysis, for predicting the course of disease in individual patients compared to Chromogranin A (CgA). NETest® (normal ≤20%) and CgA (normal <100 µg/l) were measured in 152 GEP-NETs. Median follow-up was 36 [4-56] months. Progression free survival (PFS) was blindly assessed (RECIST 1.1). Optimal cutoffs (area-under-the-ROC curve (AUC)), odds ratios (OR), negative and positive predictive values (NPV/PPV) were calculated for predicting stable (SD) and progressive disease (PD). Of the 152 GEP-NETs, 86% were NETest®-positive and 52% CgA-positive. The NETest® AUC was 0.78 vs CgA 0.73 (p=NS). The optimal cut-offs for predicting SD and PD were 33% for the NETest® and 140 µg/l for CgA. Multivariate analyses identified NETest® as the strongest predictor for PD (OR: 5.7 [score: 34-79%]; 12.6 [score≥80%]) compared to CgA (OR 3.0), tumor grade (OR 3.1) or liver metastasis (OR 7.7). NETest® NPV for SD was 87% at 12 months. The PPV for PD were 47% and 64% (scores 34-79% and ≥80%, respectively). NETest® metrics were comparable in watchful waiting-, treatment- and no evidence of disease (NED) subgroups. For CgA (>140ng/ml), NPV and PPV were 83% and 52%. CgA could not predict PD in watchful waiting or NED subgroups. The NETest® reliably predicted SD and was the strongest predictor of PD. CgA had lower utility. The NETest® anticipates RECIST defined disease status up to one year before imaging alterations are apparent.
journal_name
Neuroendocrinologyjournal_title
Neuroendocrinologyauthors
van Treijen MJC,van der Zee D,Heeres BC,Staal FCR,Vriens MR,Saveur LJ,Verbeek WHM,Korse CM,Maas M,Valk GD,Tesselaar Mdoi
10.1159/000509091subject
Has Abstractpub_date
2020-06-03 00:00:00eissn
0028-3835issn
1423-0194pii
000509091pub_type
杂志文章abstract::Lewis (LEW) and Fischer 344 (F344) rats differ in responsiveness of the hypothalamo-pituitary-adrenocortical (HPA) axis as well as in their behavioral responses to drugs of abuse. The present experiments were conducted to compare hypothalamic corticotropin-releasing factor (CRF), plasma adrenocorticotropic hormone (AC...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000126940
更新日期:1996-01-01 00:00:00
abstract::The release of endogenous noradrenaline in the anterior hypothalamus was studied with microdialysis perfusion in freely moving rats that were subjected to immobilization stress. Experiments were carried out in sham-adrenalectomized and adrenalectomized rats that were first given drinking water containing corticosteron...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000126442
更新日期:1993-05-01 00:00:00
abstract::Vasopressin-containing neurosecretory cells are partly regulated by GABAergic neurons present both at the hypothalamic and the pituitary level. In the present work, we compared GABA effects on vasopressin release from posterior pituitaries of Sprague-Dawley (SPD), Wistar (W), Wistar-Kyoto (WKY) and spontaneously hyper...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000126585
更新日期:1993-11-01 00:00:00
abstract::To study the role of the hypothalamus in the regulation of growth hormone (GH) synthesis, the rate of amino acid incorporation into GH in vitro was examined in rats with anterolateral deafferentation of the medial basal hypothalamus. Amino acid incorporation into GH (GH synthesis) decreased significantly 7 days after ...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000124946
更新日期:1988-05-01 00:00:00
abstract::In vitro and in vivo perfusion techniques were used to examine the changes in the release of beta-endorphin, methionine-enkephalin (met-enkephalin), dynorphin and luteinizing hormone releasing hormone (LHRH) in response to the corticotropin releasing factor (CRF) receptor antagonist, alpha-helical CRF9-41. All four pe...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000124967
更新日期:1988-06-01 00:00:00
abstract::This study compares the processing of pro-opiomelanocortin (POMC) at two Lys-Lys cleavage sites, located in the carboxy-terminal domain of the precursor, one site marking the amino terminus of beta-melanocyte-stimulating hormone (beta-MSH) and the other in the carboxy-terminus of beta-endorphin (beta E). These compari...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000126518
更新日期:1993-07-01 00:00:00
abstract::The worldwide obesity epidemic is increasing, yet at this time, no long-acting and specific pharmaceutical therapies are available. Peripheral hormonal signals communicate metabolic status to the hypothalamus by activating their corresponding receptors in the arcuate nucleus (ARC). In this brain region, a variety of G...
journal_title:Neuroendocrinology
pub_type: 杂志文章,评审
doi:10.1159/000334903
更新日期:2012-01-01 00:00:00
abstract::The recent description of infertility in humans with loss-of-function mutations in genes for neurokinin B (NKB) or its receptor (NK3R) has focused attention on the importance of this tachykinin in the control of GnRH secretion. In a number of species, NKB neurons in the arcuate nucleus also produce two other neuropept...
journal_title:Neuroendocrinology
pub_type: 杂志文章,评审
doi:10.1159/000355285
更新日期:2014-01-01 00:00:00
abstract::Studies were undertaken to investigate the nature of receptors involved in the prolactin-releasing action of histamine in male rats. The increase of plasma prolactin levels induced by third-ventricle injection of histamine was blocked by intraventricular injection of ranitidine, an H2-antagonist, but not by systemic a...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000123495
更新日期:1983-06-01 00:00:00
abstract::The purpose of the present study was to examine whether repetitive intravenous injections of L-glutamic acid (Glu), like those of N-methyl-D,L-aspartic acid (NMA), are able to elicit a sustained train of gonadotropin releasing hormone (GnRH) discharges from the hypothalamus of the prepubertal male monkey. In order to ...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000126186
更新日期:1992-06-01 00:00:00
abstract::Recent work has demonstrated that the brain has the capacity to synthesize impressive amounts of the gases nitric oxide (NO) and carbon monoxide (CO). There is growing evidence that these gaseous molecules function as novel neural messengers in the brain. This article reviews the pertinent literature concerning the pu...
journal_title:Neuroendocrinology
pub_type: 杂志文章,评审
doi:10.1159/000127201
更新日期:1997-06-01 00:00:00
abstract::In order to characterize plasma prolactin (Prl) patterns during the estrous cycle and pseudopregnancy (PSP), I collected sequential blood samples between 8.00 and 19.00 h at 1-hour, 1.5-min or 1-min intervals from conscious, unrestrained female rats. During the afternoon of proestrus and estrus a single Prl surge was ...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000123247
更新日期:1981-11-01 00:00:00
abstract::To clarify the role and site of action of gamma-aminobutyric acid (GABA) in ovine pineal glands, we have investigated the effects of aminooxyacetic acid (AOAA), an inhibitor of GABA transaminase, on endogenous GABA content and beta-adrenoceptor mediated pineal function in Merino sheep. A significant elevation of endog...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000123892
更新日期:1984-03-01 00:00:00
abstract::Leptin, the product of the obese gene, is a protein that is secreted primarily from adipocytes. Leptin can influence the function of the pituitary gland through its action on the hypothalamus, but it can also directly act at the level of the pituitary gland. The ability of leptin to induce an increase in intracellular...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000081843
更新日期:2004-01-01 00:00:00
abstract::The present study investigated the effects of short-term exposure to constant light, initiated at the time of ovariectomy, on the ability of estradiol (E2) treatment alone or in conjunction with progesterone (P) to induce afternoon surges of LH and prolactin (PRL). Adult Fischer 344 rats, which had been ovariectomized...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000127009
更新日期:1995-09-01 00:00:00
abstract::In the Djungarian hamster, short photoperiods induce regression of testes and accessory glands. There is evidence that the length of time melatonin levels are elevated is the signal conveying the photoperiodic effects to the neuroendocrine axis. When the temporal course of decompression of the pattern of pineal melato...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000124562
更新日期:1986-01-01 00:00:00
abstract::Plasma TSH responses after an i.v. injection of 100 mg of L-dopa were evaluated by radioimmunoassay in 4 normal euthyroid subjects and in 8 patients with primary hypothyroidism. In agreement with previous results, no variations to plasma TSH levels were observed in the euthyroid subjects. In contrast, in primary hypo...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000122350
更新日期:1975-01-01 00:00:00
abstract::The rise in the concentration of LH in the serum that takes place in ovariectomized, estrogen-primed rats exposed to the odors from a cage with bedding soiled by a male rat was completely prevented by bilateral lesions destroying the ventral premammillary (PMv) nuclei. These results suggest that the pheromonal stimuli...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000124164
更新日期:1985-08-01 00:00:00
abstract::The facilitation of sexual receptivity by oxytocin (OT) in female rats is related to the regulation of oxytocin receptors (OTR) by ovarian steroids in the ventromedial nuclei (VMN) of the hypothalamus. In a previous study, we have shown that estradiol benzoate (EB) causes a twofold increase in OTR binding in the VMN. ...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000126125
更新日期:1992-03-01 00:00:00
abstract::[125I]-neuropeptide Y receptors were characterized in the rat pituitary gland using quantitative autoradiography. Scatchard analysis of saturation isotherms showed high affinity (Kd 8.5 x 10(-11) M) and single class of binding sites (Bmax 0.22 pmol/mg of protein) in the posterior lobe of the pituitary gland, with no s...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000125608
更新日期:1990-10-01 00:00:00
abstract::Quantitative autoradiography was used to evaluate the effects of sex and either 1 or 5 daily 2-hour sessions of restraint stress on binding at 5-HT1A, 5-HT1C and 5-HT2 receptors in the rat dorsal hippocampus. Neither sex nor restraint stress were found to have effects on binding at 5-HT1C or 5-HT2 receptors. However, ...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000125951
更新日期:1991-11-01 00:00:00
abstract::Adenylate cyclase activity was studied in anterior pituitary homogenates from young adult (6 months) and old (20 and 24 months) male rats. Basal, NaF-, GTP-, 5'-guanylimidodiphosphate (Gpp(NH)p)- and forskolin-stimulated activities were similar in the three groups, implying that the stimulatory guanyl nucleotide regul...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000124682
更新日期:1986-01-01 00:00:00
abstract::Hypothalamic norepinephrine (NE) and dopamine content was studied in dogs with spontaneous and iatrogenic hypercortisolism and in untreated normal dogs. The concentration of NE in the hypothalamus was subnormal in 4 of 8 dogs with pituitary-dependent hyperadrenocorticism (PDH), whereas long-term administration of cort...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000123158
更新日期:1981-04-01 00:00:00
abstract::Infusion of 2 nmol atrial natriuretic factor (ANF) into the third cerebroventricle of conscious, orchidectomized male rats results in a significant inhibition of prolactin (PRL) secretion. This effect is prevented by prior treatment with the dopamine receptor antagonist, domperidone. Furthermore, domperidone reverses ...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000124922
更新日期:1988-03-01 00:00:00
abstract::Pituitary oxytocin (OT) secretion is inversely related to saline consumption in several experimental models of sodium appetite in rats. Because systemic OT administration does not inhibit sodium appetite, release of OT as a neurotransmitter within the brain, coincident with its secretion from the pituitary, may be rel...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000126236
更新日期:1992-08-01 00:00:00
abstract::Follicle-stimulating hormone (FSH) is involved in the regulation and maintenance of gametogenesis. It exists in multiple molecular forms with different oligosaccharide structures which in turn are influenced by the hormonal milieu. Previous studies from our laboratory demonstrated that antiandrogen administration to i...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000054484
更新日期:1999-10-01 00:00:00
abstract::Both the pituitary-adrenal axis and the pituitary-gonadal axis are under the tonic inhibitory control of endogenous opioid peptides in man. However, the precise opioid receptor involved in the modulation of these hormones remains unknown. The effect of a dose of intravenous naloxone on serum levels of luteinising horm...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000124463
更新日期:1986-01-01 00:00:00
abstract::The differences in plasma prolactin concentration between normal and estradiol-implanted male rats were compared after treatment with 3 different stimulating agents of prolactin secretion [ether anesthesia, pimozide (a "specific' dopaminergic receptor blocking agent) and TRH] using conscious, free-moving rats implante...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000123087
更新日期:1980-10-01 00:00:00
abstract::It has been well documented that interleukin-1beta (IL-1beta) is a major mediator for recruiting the hypothalamo-pituitary-adrenal (HPA) axis following infectious disease. The recent localization of IL-1beta receptors in neurons of the hippocampus provides further support for the role of IL-1beta as a neurotransmitter...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000054405
更新日期:1999-02-01 00:00:00
abstract::An experiment was performed on 21-day-old male rats to determine the combined effects of pinealectomy, constant light and darkness, and intraperitoneal (i.p.) thyrotropin-releasing hormone (TRH) on pituitary and plasma radioimmunoassayable thyrotropin (TSH), serum thyroxine (T4), and pituitary, thyroid and body weight...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000122751
更新日期:1978-01-01 00:00:00