Abstract:
:Adrenocortical cancer is a rare malignancy for which current pharmacological therapies are still insufficient. We tested the effect of a novel PI3 kinase - mammalian target of rapamycin dual inhibitor (NVP-BEZ235) on proliferation of the H295R adrenocortical cancer cell line in vitro and grown as xenografts in immunodeficient mice. NVP-BEZ235 was able to significantly inhibit phosporylation of Akt kinase and S6 ribosomal protein in H295R cells and to significantly reduce their proliferation in vitro and xenograft growth in vivo. The drug also induced activation of Erk phosphorylation, which could be inhibited by simultaneous treatment with the Erk inhibitor FR180204. This latter drug synergized with NVP-BEZ235 in the inhibition of H295R proliferation in vitro. Our data suggest that dual PI3K/mTOR inhibitors may represent a useful pharmacological tool in the therapy of advanced adrenocortical cancer and that simultaneous inhibition of both Erk and PI3K - mTOR pathways may be required to obtain a higher antiproliferative effect in this type of tumor.
journal_name
Mol Cell Endocrinoljournal_title
Molecular and cellular endocrinologyauthors
Doghman M,Lalli Edoi
10.1016/j.mce.2012.08.014subject
Has Abstractpub_date
2012-11-25 00:00:00pages
101-4issue
1-2eissn
0303-7207issn
1872-8057pii
S0303-7207(12)00409-1journal_volume
364pub_type
杂志文章abstract::We have carried out further in vitro studies on the priming effect of LH-RH and the effect of steroids on pituitary responsiveness to LH-RH. In hemipituitary glands, the priming effect could be elicited only once within an 11-h period and was found to diminish significantly with time after the first exposure to LH-RH....
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(81)90003-4
更新日期:1981-12-01 00:00:00
abstract::Aggresome formation, a cellular response to misfolded protein aggregates, is linked to cancer and neurodegenerative disorders. Previously we showed that Gag-v-ErbA (v-ErbA), a retroviral variant of the thyroid hormone receptor (TRα1), accumulates in and sequesters TRα1 into cytoplasmic foci. Here, we show that foci re...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2010.10.012
更新日期:2011-01-30 00:00:00
abstract::Corticotropin (ACTH) regulates glucocorticoid production through specific receptors on the adrenal cortex. Analysis of the ACTH receptor mRNA in human adrenal has revealed the presence of five transcripts ranging from 1.8 to 11 kilobases (kb). Characterization of the 5'-untranslated regions (UTRs) of the ACTH receptor...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(94)90194-5
更新日期:1994-12-01 00:00:00
abstract::The prostate gland is highly dependent on androgens for its development, growth and function. Consequently, the prostatic epithelium predominantly consists of androgen-dependent luminal cells, which express the androgen receptor at high levels. In contrast, androgens are not required for the survival of the androgen-r...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/j.mce.2011.07.008
更新日期:2012-09-05 00:00:00
abstract::A pair of glands (Y-organs) in crustaceans synthesize and secrete ecdysteroid hormones; the obligate precursor for synthesis is circulating cholesterol. Ecdysteroid output by the Y-organs is regulated negatively by an eyestalk neurosecretory peptide, molt-inhibiting hormone (MIH). The question was addressed, does MIH ...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(93)90035-i
更新日期:1993-09-01 00:00:00
abstract::Diabetic cardiomyopathy is characterized by an abnormal oxidative metabolism, but the underlying mechanisms remain to be defined. To uncover potential mechanisms involved in the pathophysiology of diabetic cardiomyopathy, we performed a gene expression profiling study in hearts of diabetic db/db mice. Diabetic hearts ...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2016.04.004
更新日期:2016-07-15 00:00:00
abstract::The interaction between thyroid microsomal autoantibodies and thyroid microsomal antigen/thyroid peroxidase (TPO) has been studied using both intact antigen preparations and their water-soluble trypsin fragments. In an analysis of sera from 30 patients with Graves' or Hashimoto's diseases, microsomal antibodies showed...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(87)90187-0
更新日期:1987-09-01 00:00:00
abstract::The production of glucocorticoids and aldosterone in the adrenal cortex is regulated at multiple levels. Biosynthesis of these hormones is initiated when cholesterol, the substrate, enters the inner mitochondrial membrane for conversion to pregnenolone. Unlike most metabolic pathways, the biosynthesis of adrenocortica...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/j.mce.2012.11.014
更新日期:2013-05-22 00:00:00
abstract::The beneficial effects of empagliflozin (EMPA) on cardiac functions during ischemia and reperfusion were characterized. The contractile functions of isolated cardiomyocytes from adult C57BL/6J mice were determined with IonOptix SoftEdgeMyoCam system. The mitochondrial superoxide production was measured by MitoSOX fluo...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2019.110642
更新日期:2020-02-05 00:00:00
abstract::We reported previously that stem Leydig cells (SLC) on the surfaces of rat testicular seminiferous tubules are able to differentiate into Leydig cells. The proliferation and differentiation of SLCs seem likely to be regulated by niche cells, including nearby germ and Sertoli cells. Due to the cyclical nature of sperma...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2018.11.007
更新日期:2019-02-05 00:00:00
abstract::The status of the neuroendocrine reproductive axis differs dramatically during various stages of development, and also differs in several critical ways between the sexes, including its earlier pubertal activation in females than males and the presence of neural circuitry that generates preovulatory hormone surges in f...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/j.mce.2010.01.017
更新日期:2010-08-05 00:00:00
abstract::The present study examines the involvement of cAMP in the transduction of the short-term effect of gonadotropin-releasing hormone (GnRH) on gonadotropin release in the teleost fish, tilapia. A 5 min pulse of dibutyryl cyclic AMP (dbcAMP; 0.03-3 mM) or forskolin (0.1-10 microM) resulted in dose-dependent surges in tila...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(92)90256-6
更新日期:1992-06-01 00:00:00
abstract::Under physiological conditions substantial amounts of hormone may be degraded within endocrine cells by a crinophagic process comprising fusions of secretory granules with lysosomes. Glucocorticoids may stabilise and progesterone destabilise lysosomal membranes. The effects of corticosterone and progesterone on intrac...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2007.07.007
更新日期:2007-10-15 00:00:00
abstract::The Nile tilapia, Oreochromis niloticus, is a gonochoristic teleost fish with an XX/XY genetic system and is an excellent model for gonadal sex differentiation. In the present study, we screened novel genes that were expressed predominantly in either XY or XX undifferentiated gonads during the critical period for diff...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2015.08.008
更新日期:2015-11-05 00:00:00
abstract::Vitamin D is a key factor for calcium and bone homeostasis, but signalling through the vitamin D receptor (VDR) seems also to be important for testicular function. To test the functional role of vitamin D signalling we examined the male reproductive system of the Leuven Vdr-ablated (Vdr(-/-)) mice, previously establis...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2013.06.036
更新日期:2013-09-05 00:00:00
abstract::During development, the insulin-like growth factor I (IGF-I) gene is expressed in a tissue specific manner; however, the molecular mechanisms governing its developmental regulation remain poorly defined. To examine the hypothesis that expression of the growth hormone (GH) receptor accounts, in part, for the tissue spe...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(99)00045-3
更新日期:1999-06-25 00:00:00
abstract::Apolipoprotein E (APOE) deficient mice exhibit unexplained hypercorticosteronemia. Given that APOE is also produced locally within the adrenals, we evaluated the effect of adrenal-specific APOE deficiency on the glucocorticoid function. Hereto, one adrenal containing or lacking APOE was transplanted into adrenalectomi...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2019.04.001
更新日期:2019-06-15 00:00:00
abstract::Tumor necrosis factor-alpha (TNF-alpha) was found to induce type-1 plasminogen activator inhibitor (PAI-1) antigen in the human fibrosarcoma cell line HT-1080, and PAI-1 and urokinase-type plasminogen activator (u-PA) antigens in the human carcinoma cell line T-CAR1; tissue-type plasminogen activator (t-PA) antigen wa...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(89)90192-5
更新日期:1989-01-01 00:00:00
abstract::Calbindin-D9k (CaBP-9k) is a high affinity calcium binding protein that is highly expressed in the duodenum, kidney, uterus, and pituitary glands. Previous studies have shown that CaBP-9k expression is regulated by several steroid hormones, such as 1,25-dihydroxyvitamin D3, glucocorticoids, 17beta-estradiol (E2), and ...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2007.07.009
更新日期:2007-10-15 00:00:00
abstract::Although earlier studies focused on the hormonal regulation of antral and preovulatory follicles, recent studies indicate the importance of the hormonal control mechanism for preantral follicles. The endocrine hormone FSH is not only a survival factor for early antral follicles but also a potent growth and differentia...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/s0303-7207(99)00245-2
更新日期:2000-05-25 00:00:00
abstract::Recent evidence suggests that lymphocytes produce prolactin (PRL). Here, we report the cDNA cloning and expression of PRL from normal human thymocytes. Sequence analysis showed that the thymocyte cDNA encodes a 23 kDa protein which is identical to pituitary PRL. RNA blot analysis showed that the thymocyte PRL mRNA is ...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(92)90251-z
更新日期:1992-09-01 00:00:00
abstract::The aim of our study was to investigate the direct effects of atypical antipsychotics on muscle cell functions in order to ascertain the diabetic liability of these drugs. We investigated the effects of olanzapine, clozapine and alpha-methyl-5-hydroxytryptamine on basal glucose uptake and glucose uptake in response to...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2008.04.010
更新日期:2008-09-24 00:00:00
abstract::Human estrogen receptor alpha (ER) mRNA is a mixture of wild type and alternatively spliced variants. Many studies have examined the potential of ER mRNA profiles to serve as diagnostic/prognostic cancer biomarkers, but only a few have attempted to correlate ER mRNA profiles with protein expression. Representative ER ...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(00)00194-5
更新日期:2000-04-25 00:00:00
abstract::Several common KCNQ1 gene polymorphisms have been associated with the risk of type 2 diabetes (T2DM) and diabetic nephropathy. This effect is explained by the role of the kcnq1 protein as a potassium channel that in the pancreatic beta-cells drives an electrical signal that facilitates glucose-stimulated insulin secre...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2016.03.007
更新日期:2016-05-15 00:00:00
abstract::The aims of the study were to characterize leptin and it is receptor (LEPR) proteins immunoexpression in ovine ovaries and to evaluate the effects of leptin on development of secondary follicles cultured in vitro. The ovaries were collected and fixed for immunohistochemical analysis. Additional pairs of ovaries were c...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2019.110506
更新日期:2019-09-15 00:00:00
abstract::Mutations in Thyroglobulin (TG) are common genetic causes of congenital hypothyroidism (CH). But the TG mutation spectrum and its frequency in Chinese CH patients have not been investigated. Here we conducted a genetic screening of TG gene in a cohort of 382 Chinese CH patients. We identified 22 rare non-polymorphic v...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2016.01.007
更新日期:2016-03-05 00:00:00
abstract::The molecular cloning and nucleotide sequencing of the gonadotropin-releasing hormone (GnRH) receptor represented an enhanced step in the experimental effort to understand this key molecule in the reproductive process at a cell and molecular level. A subsequent step in this broad effort is heterologous expression of t...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(96)04003-8
更新日期:1997-03-28 00:00:00
abstract::Men have had a substantially higher risk of developing bladder cancer than women. This has prompted research on androgen-mediated androgen receptor (AR) signaling in urothelial cancer. Indeed, increasing preclinical evidence indicates that AR activation correlates with the promotion of urothelial carcinogenesis and tu...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/j.mce.2017.06.021
更新日期:2018-04-15 00:00:00
abstract::In cultured human lymphocytes (IM-9) and in isolated rat adipocytes human growth hormone is substrate for a receptor-mediated degradation. When the cells are incubated with monoiodinated human growth hormone half of the radioactivity dissociating from the cells is in the form of [125I]monoiodotyrosine. Since IM-9 lymp...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(85)90145-5
更新日期:1985-06-01 00:00:00
abstract::In the 40 years of transferrin research, no previous role for apotransferrin has been recognized other than to serve as a plasma carrier for dietary and storage iron. Our studies have revealed a new 'autocrine' growth role for this molecule as well as a possible new cell-cell bridge/CAM function. Certainly, these obse...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/0303-7207(91)90053-u
更新日期:1991-05-01 00:00:00