Abstract:
BACKGROUND/AIM:Somatostatin (SST) analogs are mainstay for controlling tumor proliferation and hormone secretion in carcinoid patients. Recent data suggest that extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation may potentiate the anti-tumor effects of SST analogs in carcinoids. Additionally, ERK1/2 phosphorylating agents have been shown to suppress biomarker expression in carcinoids. Thus, Raf-1/MEK/ERK1/2 pathway activating drugs may be synergistic with SST analogs such as pasireotide (SOM230), which may be more effective than others in its class given its elevated receptor affinity and broader binding spectrum. Here, we investigate the effects of SOM230 in combination with teriflunomide (TFN), a Raf-1 activator, in a human carcinoid cell line. METHODS:Human pancreatic carcinoid cells (BON) were incubated in TFN, SOM230 or a combination. Cell proliferation was measured using a rapid colorimetric assay. Western analysis was performed to analyze expression levels of achaete-scute complex-like 1 (ASCL1), chromogranin A (CgA), phosphorylated and total ERK1/2, and markers for apoptosis. RESULTS:Combination treatment with SOM230 and TFN reduced cell growth beyond the additive effect of either drug alone. Combination indices (CI) fell below 1, thus quantifiably verifying synergy between both drugs as per the Chou-Talalay CI scale. Combined treatment also reduced ASCL1 and CgA expression beyond the additive effect of either drug alone. Furthermore, it increased levels of phosphorylated ERK1/2, cleaved poly(ADP)-ribose polymerase and caspase-3, and reduced levels of anti-apoptotic biomarkers. Elevated phosphorylated ERK1/2 expression following combination therapy may underlie the synergistic interaction between the two drugs. CONCLUSION:Since efficacy is achieved at lower doses, combination therapy may palliate symptoms at low toxicity levels. Because each drug has already been evaluated in clinical trials, combinatorial drug trials are warranted.
journal_name
Neuroendocrinologyjournal_title
Neuroendocrinologyauthors
Somnay Y,Chen H,Kunnimalaiyaan Mdoi
10.1159/000341810subject
Has Abstractpub_date
2013-01-01 00:00:00pages
183-92issue
2eissn
0028-3835issn
1423-0194pii
000341810journal_volume
97pub_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 effect of stress- or lipopolysaccharide (LPS) endotoxin-induced release of ACTH, beta-endorphin (beta-END) and prolactin (PRL) was investigated in two groups of conscious male rats: (1) Rats pretreated with different H3 receptor agonists, which inhibit neuronal histamine (HA) synthesis and release, and (2) rats wi...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000054402
更新日期:1999-01-01 00:00:00
abstract:BACKGROUND/AIMS:A mammalian circannual pacemaker responsible for regulating the seasonal pattern of prolactin has been recently described in sheep. This pacemaker resides within the pars tuberalis, an area of the pituitary gland that densely expresses melatonin receptors. However, the chemical identity of the cell type...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000350790
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Prolactin-raising antipsychotics, risperidone (antidopaminergic activity), may be associated with low bone mass. On the other hand, risperidone may cause an increase in body weight thought to be favorable for bone. OBJECTIVES:(1) To determine bone remodeling parameters and bone mass in patients with schizop...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000329391
更新日期:2011-01-01 00:00:00
abstract::In the paraventricular nucleus of normal or adrenalectomized colchicine-treated guinea pigs and rats, corticotropin-releasing factor (CRF), vasopressin (VP) and oxytocin (OX) immunoreactivities were compared. In the control animals, respective stainings for these three peptides are distinct. Adrenalectomy resulted in ...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000123595
更新日期:1983-12-01 00:00:00
abstract::Lactotrophs, gonadotrophs, thyrotrophs and somatotrophs of the rat anterior pituitary (AP) express 68-kDa neurofilaments (NF68) and other neuronal markers. NF68 expression in the AP appears to be estrogen-dependent, but its significance is unknown. The aims of this work were: (1) to establish the expression pattern of...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000095548
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:We previously presented data of this multicentric, phase II study showing that everolimus plus octreotide long-acting repeatable (LAR) for advanced neuroendocrine neoplasms (NENs), in the first line setting, is an active and safe treatment. We now present updated data at 5 years. METHODS:Patients with advan...
journal_title:Neuroendocrinology
pub_type: 杂志文章,多中心研究
doi:10.1159/000479587
更新日期:2018-01-01 00:00:00
abstract::We studied the effects of selected leukotrienes and hydroxyeicosatetraenoic acids (HETEs) on prolactin release from primary cultures of female rats anterior pituitary cells. Leukotrienes B4, C4, and D4 had no effect on basal prolactin release; however, they did enhance prolactin release that was stimulated by 1 or 5 n...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000125042
更新日期:1988-10-01 00:00:00
abstract::Secretion of the growth hormone (GH) in spontaneously hypertensive (SH) male rats has been determined and compared with that of normotensive Wistar-Kyoto (WKY) controls. In a first set of experiments, plasma GH concentration and pituitary GH content were measured in SH rats 30, 60 and 90 days old. 30-day rats showed r...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000125617
更新日期:1990-10-01 00:00:00
abstract::In vivo single-unit extracellular recording was used to assess neuronal membrane sensitivity at the level of the midbrain central gray (MCG) to the iontophoresis of luteinizing hormone releasing hormone (LHRH) and beta-endorphin (beta-END). The percentage of change in firing rate was evaluated to determine the effect ...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000124792
更新日期:1987-06-01 00:00:00
abstract::To assess whether gonadotropin-releasing hormone (GnRH) release from the hypothalamus might be altered by hyperprolactinemia in the male rat, we measured in chronically hyperprolactinemic rats the pituitary GnRH receptor content and described the pattern of luteinizing hormone (LH) release during the postcastration ri...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000124844
更新日期:1987-10-01 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::The relationship between the growth hormone/insulin-like growth factor (GH-IGF)-I status and memory performance is studied in 24 elderly males and females, aged 75-85 years. Positron emission tomography (PET) was used to measure differences in regional cerebral blood flow during the performance of a delayed-non-match-...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000084872
更新日期:2005-01-01 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::These studies investigated the effect of aging on thyroid hormone regulation of beta-endorphin in rat corpus striatum and hypothalamus. In both brain areas, basal levels of beta-endorphin declined with age. In addition, age modified the response of beta-endorphin to thyroid hormone status. Hypothyroid rats aged 6 mont...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000123141
更新日期:1981-02-01 00:00:00
abstract:AIM:To extensively explore microRNA expression profiles in lung carcinoids in correlation with clinical and pathological features. METHODS:A PCR-based array was employed in the screening phase to analyze 752 microRNAs in a discovery set of 12 lung carcinoids, including 6 typical (3 with lymph node metastasis) and 6 at...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000381454
更新日期:2015-01-01 00:00:00
abstract::The relationship between concentrations of vasopressin in plasma and cerebrospinal fluid (CSF) was examined under basal and hypoxic conditions in unanesthetized and unrestrained adult female sheep. Under basal conditions mean (+/- SE) concentration of vasopressin (4.1 +/- 0.3 pg/ml) in CSF was significantly (p less th...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000123933
更新日期:1984-06-01 00:00:00
abstract::The purpose of this study was to determine the effect of rendering newborn male Sprague-Dawley rats hypothyroid with 131I on development of the hypothalamic-pituitary axis. Hormonal responses to thyrotropin-releasing hormone (TRH), haloperidol (H), and luteinizing hormone-releasing hormone (LHRH) were determined at 9,...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000123011
更新日期:1980-05-01 00:00:00
abstract::The hypophysial portal vessels and anterior pituitary glands of adult male rats were surgically exposed, cannulated and infused for 1 min with saline, growth hormone-releasing factor (GH-RF), and dbcAMP. After cessation of infusion, anterior pituitary glands were collected at 1, 5, 15, 30 or 60 min for electron micros...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000122421
更新日期:1975-01-01 00:00:00
abstract::Phase relation between plasma corticosterone and locomotor activity rhythms was analyzed in individual rats with selective lesions of suprachiasmatic nuclei (SCN). SCN in Wistar male rats were selectively coagulated electrically and the extent of SCN destruction was examined histologically. Spontaneous locomotor activ...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000123200
更新日期:1981-07-01 00:00:00
abstract::We have suggested that gamma-aminobutyric acid (GABA) in the hypothalamus plays a tonic inhibitory role in the control of the luteinizing hormone (LH) release in intact male rats. To assess whether feedback from the testis alters the inhibitory GABAergic tone in the medial preoptic area (MPO) of male rats, an in vivo ...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000066625
更新日期:2002-11-01 00:00:00
abstract::Over the last 10 years, kisspeptins--peptide products of varying lengths encoded by the KISS1 gene--have been found to be key regulators of normal reproductive function throughout life in animals and humans. By activating the kisspeptin receptor [previously known as orphan G protein-coupled receptor 54 (GPR54)], they ...
journal_title:Neuroendocrinology
pub_type: 杂志文章,评审
doi:10.1159/000439133
更新日期:2015-01-01 00:00:00
abstract:OBJECTIVE:The expression of somatostatin receptors (SSTRs) and dopamine receptor 2 (DR2) in neuroendocrine tumors is of clinical importance as somatostatin analogues and dopamine agonists can be used for their localization and/or treatment. The objective of this study is to examine the expression of the five SSTR subty...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000381061
更新日期:2015-01-01 00:00:00
abstract::Brain angiotensin II (AII) receptors play a role in the regulation of luteinizing hormone release. This action is thought to involve luteinizing hormone-releasing hormone containing neurons in the preoptic-anterior hypothalamic (POAH) area of the brain. Previous studies have demonstrated a discrete locus of AII recept...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000126225
更新日期:1992-08-01 00:00:00
abstract::Vasostatin, a fragment of calreticulin, was transfected in the BON cell line to evaluate the feasibility of using it for gene therapy in neuroendocrine tumors. Vasostatin transfected cells were subcutaneously inoculated in nude mice. Burkitt lymphoma cell line, CA46, colorectal adenocarcinoma cell line, SW480, as well...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000089749
更新日期:2005-01-01 00:00:00
abstract::The effect of castration and adrenalectomy was studied on vasoactive intestinal peptide (VIP) concentrations in various brain and peripheral structures of male rats. Castration has no effect on any of the structures studied, whereas 4 weeks adrenalectomy (ADX) decreases VIP concentrations in the hippocampus and increa...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000123090
更新日期:1980-10-01 00:00:00
abstract::The effects of intracerebroventricularly (i.c.v.) injected interleukin-1 beta (IL-1 beta: 1, 2.5, 10, and 25 ng) were studied on plasma growth hormone (GH) and prolactin (PRL) concentrations in freely moving rats chronically implanted with i.c.v. cannulas and intracardial catheters. Significant changes in PRL secretio...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000126217
更新日期:1992-07-01 00:00:00
abstract::We have previously shown that the serotonergic regulation of renin secretion from the kidneys is mediated by a renin-releasing factor (RRF) that is present in both plasma and hypothalamus. The present studies were designed to determine the distribution of RRF in the brain and peripheral tissues and to test whether RRF...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000126170
更新日期:1992-05-01 00:00:00
abstract::Thymic neuroendocrine neoplasms are rare tumours, but their management can often be highly problematic. While previously assumed to be essentially variants of bronchopulmonary (lung) carcinoids, they are generally more aggressive and more difficult to treat. Some 25% are associated with multiple endocrine neoplasia-1,...
journal_title:Neuroendocrinology
pub_type: 杂志文章,评审
doi:10.1159/000472255
更新日期:2017-01-01 00:00:00
abstract::The pressor effect of intravenous angiotensin II (AII) was compared in the unrestrained rat before and after electrolytic lesions of the subfornical organ (SFO), the circumventricular organ of the dorsal third cerebral ventricle. Abdominal aortic and venal caval catheters were used to measure arterial pressure and to ...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000123107
更新日期:1980-12-01 00:00:00