Abstract:
:Pancreatic endocrine tumors (PET) represent a heterogenous group of neoplasms. Although surgical resection is considered a safe and effective treatment for many PET, therapeutic options for inoperable and progressive PET are limited. The expression of heat-shock protein (HSP) 90 was investigated in 120 clinically and pathomorphologically well-characterized PET from 84 patients using immunohistochemistry. In addition, in 19 snap-frozen PET and in three healthy pancreatic tissues, we performed immunoblot analyses, and in 15 snap-frozen PET and in three healthy pancreatic tissues, we investigated the expression of HSP90 isoforms by means of semiquantitative RT-PCR. Functional tests were conducted using the human pancreas carcinoid cell line BON and the mouse insulinoma cell line β-TC-3. HSP90 was expressed in 95% of the PET patients. The transcript levels of the HSP90 isoforms HSP90α, HSP90β, glucose-related protein 94, and TNF receptor-associated protein 1 were significantly increased in PET compared with non-neoplastic pancreatic tissues. The treatment of the cell lines BON and β-TC-3 with the HSP90 inhibitors 17-allylamino-17-demethoxygeldanamycin and 17-dimethylaminoethylamino-17-demethoxy-geldanamycin resulted in significant, dose-dependent reduction of cell viability, cell cycle arrest, and increased apoptosis. Furthermore, HSP90 inhibition induced the degradation and inactivation of several oncogenetic HSP90 client proteins in a time- and dose-dependent manner. HSP90 inhibitors increased the therapeutic effects of doxorubicin and 5-fluorucacil in BON and β-TC-3 cells. HSP90 is expressed in the vast majority of PET and its inhibition reveals significant treatment effects in vitro. Thus, HSP90 qualifies as a promising new target.
journal_name
Endocr Relat Cancerjournal_title
Endocrine-related cancerauthors
Mayer P,Harjung A,Breinig M,Fischer L,Ehemann V,Malz M,Scherübl H,Britsch S,Werner J,Kern MA,Bläker H,Schirmacher P,Bergmann Fdoi
10.1530/ERC-11-0227subject
Has Abstractpub_date
2012-05-03 00:00:00pages
217-32issue
3eissn
1351-0088issn
1479-6821pii
ERC-11-0227journal_volume
19pub_type
杂志文章abstract::Thirty percent of medullary thyroid carcinomas (MTCs) are related to dominant germline pathogenic variants in the RET proto-oncogene. According to their aggressiveness, these pathogenic variants are classified in three risk levels: 'moderate', 'high' and 'highest'. The present study compares the metabolomics profiles ...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-18-0314
更新日期:2019-03-01 00:00:00
abstract::Metastatic duodenopancreatic neuro-endocrine tumors (dpNETs) are the most important disease-related cause of death in patients with multiple endocrine neoplasia type 1 (MEN1). Nonfunctioning pNETs (NF-pNETs) are highly prevalent in MEN1 and clinically heterogeneous. Therefore, management is controversial. Data on prog...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-19-0372
更新日期:2020-06-01 00:00:00
abstract::The central involvement of estrogen in the development of the mammary gland and in the genesis of breast cancer has lent impetus to studies of the links between estrogen action and the cell cycle machinery. Recent studies of the estrogenic regulation of molecules with known roles in the control of G1/S phase progressi...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1677/erc.0.0100179
更新日期:2003-06-01 00:00:00
abstract::The prognosis remains ill-defined in patients with liver metastases of well-differentiated (WD) digestive endocrine carcinomas (DEC) with high Ki-67 index. The objectives of this study were to determine whether Ki-67 index, tumor differentiation, and extent of liver involvement are independent prognostic factors in pa...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/ERC-09-0319
更新日期:2010-12-13 00:00:00
abstract::Epidemiologic and experimental evidence suggest that a subset of breast cancer is insulin responsive, but it is unclear whether safe and effective therapies that target the insulin receptor (IR), which is homologous to oncogenes of the tyrosine kinase class, can be developed. We demonstrate that both pharmacologic inh...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-11-0136
更新日期:2011-11-14 00:00:00
abstract::Thyroid cancers are usually surrounded by a significant number of immune-reactive cells. Tumor-associated lymphocytes as well as background lymphocytic thyroiditis are frequently mentioned in pathology reports of patients who have undergone surgery for thyroid cancer. The nature of this lymphocytic reaction is not wel...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-13-0436
更新日期:2014-06-01 00:00:00
abstract::Type 3 deiodinase (DIO3, D3) is reactivated in human neoplasias. Increased D3 levels in papillary thyroid carcinoma (PTC) have been associated with tumor size and metastatic disease. The objective of this study is to investigate the signaling pathways involved in DIO3 upregulation in PTC. Experiments were performed in...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-15-0162
更新日期:2016-03-01 00:00:00
abstract::Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a heat shock protein 90 (HSP90) molecular chaperone upregulated in several human malignancies and involved in protection from apoptosis and drug resistance, cell cycle progression, cell metabolism and quality control of specific client proteins. TRAP1 role...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-16-0063
更新日期:2016-09-01 00:00:00
abstract::The Hippo signaling pathway has been implicated as a conserved regulator of organ size in both Drosophila and mammals. Yes-associated protein (YAP), the central component of the Hippo signaling cascade, functions as an oncogene in several malignancies. Ovarian granulosa cell tumors (GCT) are characterized by enlargeme...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-13-0339
更新日期:2014-03-04 00:00:00
abstract::Along with breast and endometrial cancers, thyroid cancer is a major component cancer in Cowden syndrome (CS). Germline variants in SDHB/C/D (SDHx) genes account for subsets of CS/CS-like cases, conferring a higher risk of breast and thyroid cancers over those with only germline PTEN mutations. To investigate whether ...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-14-0537
更新日期:2015-04-01 00:00:00
abstract::Pharmacological inhibition of the sonic hedgehog (SHH) pathway can be beneficial against certain cancers but detrimental in others. Adamantinomatous craniopharyngioma (ACP) is a relevant pituitary tumour, affecting children and adults, that is associated with high morbidity and increased mortality in long-term follow-...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-18-0538
更新日期:2019-03-01 00:00:00
abstract::Although the authors of the present review have contributed to genetic discoveries in the field of pheochromocytoma research, we can legitimately ask whether these advances have led to improvements in the diagnosis and management of patients with pheochromocytoma. The answer to this question is an emphatic Yes! In the...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-18-0085
更新日期:2018-08-01 00:00:00
abstract::Long-term culture of MCF-7 wild-type (wt) cells in steroid-depleted medium (LTED) results in hypersensitivity to oestradiol (E2) coinciding with elevated levels of ERalpha and enhanced growth factor signalling. In this study, we aimed to compare the effects of the pure anti-oestrogen ICI 182,780 (ICI) with the competi...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/erc.1.00905
更新日期:2005-12-01 00:00:00
abstract::Male breast cancer (MBC) is extremely rare and accounts for less than 1% of all breast malignancies. Therefore, clinical management of MBC is currently guided by research on the disease in females. In this study, DNA obtained from 45 formalin-fixed paraffin-embedded (FFPE) MBCs with and 90 MBCs (52 FFPE and 38 fresh-f...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-19-0278
更新日期:2019-10-01 00:00:00
abstract::The high degree of conservation in microRNA from Caenorhabditiselegans to humans has enabled relatively rapid implementation of findings in model systems to the clinic. The convergence of the capacity for genomic screening being implemented in the prevailing precision medicine initiative and the capabilities of microR...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-16-0525
更新日期:2017-05-01 00:00:00
abstract::The aim of this randomized multicenter phase III trial was to compare chemotherapy and interferon (IFN) in patients with metastatic carcinoid tumors. Patients with documented progressive, unresectable, metastatic carcinoid tumors were randomized between 5-fluorouracil plus streptozotocin (day 1-5) and recombinant IFN-...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1677/ERC-09-0104
更新日期:2009-12-01 00:00:00
abstract::It has been proposed that knowledge of estrogen receptor beta (ER-beta) expression may refine estrogen receptor alpha (ER-alpha) predictivity of response to endocrine therapy. We challenged this hypothesis in ER-alpha-positive breast cancers subjected to preoperative antiestrogen treatment. Forty-seven elderly (> or =...
journal_title:Endocrine-related cancer
pub_type: 临床试验,杂志文章
doi:10.1677/erc.1.00822
更新日期:2004-12-01 00:00:00
abstract::CD74, the invariant chain of major histocompatibility complex class II, is also a receptor for macrophage migration inhibitory factor (MIF). CD74 and MIF have been associated with tumor progression and metastasis in hematologic and solid tumors. In this study, we found that 60 and 65% of papillary thyroid cancers were...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-14-0269
更新日期:2015-04-01 00:00:00
abstract::The fight against cancer has seen major breakthroughs in recent years. More than a decade ago, tyrosine kinase inhibitors targeting constitutively activated signaling cascades within the tumor inaugurated a new era of oncological therapy. Recently, immunotherapy with immune checkpoint inhibitors has started to revolut...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-16-0169
更新日期:2016-10-01 00:00:00
abstract::Obestatin was identified as a gut peptide encoded by the ghrelin gene that interacts with the G protein-coupled receptor, GPR39. In this work, a sequential analysis of its transmembrane signalling pathway has been undertaken to characterize the intracellular mechanisms responsible for Akt activation. The results show ...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/ERC-08-0192
更新日期:2009-06-01 00:00:00
abstract::There is a trend of increasing prevalence of neuroendocrine tumors (NETs), and the inherited multiple endocrine neoplasia type 1 (MEN1) syndrome serves as a genetic model to investigate how NETs develop and the underlying mechanisms. Menin, encoded by the MEN1 gene, at least partly acts as a scaffold protein by intera...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-17-0298
更新日期:2017-10-01 00:00:00
abstract::Malignant growth of small-cell lung carcinoma is promoted by various neuroendocrine autocrine/paracrine loops. Therefore, to interfere with this mitogenic process, it is crucial to elucidate the mechanisms involved. It is known that the oxytocin (OT) and vasopressin (VP) genes, normally transcriptionally restricted in...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/erc.1.00803
更新日期:2004-12-01 00:00:00
abstract::Prostate cancer (PCa) and breast cancer (BCa) are both hormone-dependent cancers that require the androgen receptor (AR) and estrogen receptor (ER, ESR1) for growth and proliferation, respectively. Endocrine therapies that target these nuclear receptors (NRs) provide significant clinical benefit for metastatic patient...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-20-0272
更新日期:2020-12-01 00:00:00
abstract::Medullary thyroid carcinomas (MTC) arise from thyroid parafollicular, calcitonin-producing C-cells and can occur either as sporadic or as hereditary diseases in the context of familial syndromes, including multiple endocrine neoplasia 2A (MEN2A), multiple endocrine neoplasia 2B (MEN2B) and familial MTC (FMTC). In a la...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-17-0303
更新日期:2018-02-01 00:00:00
abstract::Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine tumors of the adrenal glands and the sympathetic and parasympathetic paraganglia. They can occur sporadically or as a part of different hereditary tumor syndromes. About 30% of PCCs and PGLs are currently believed to be caused by germline mutat...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-11-0170
更新日期:2011-12-01 00:00:00
abstract::Elevated expression of steroid receptor coactivator-3 (SRC-3), a member of the p160 family of nuclear receptor coactivators, has been implicated in tamoxifen resistance of breast tumors while the involvement of the two other members of this family, SRC-1 and SRC-2, is less well characterized. In this study, using smal...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/ERC-09-0285
更新日期:2010-12-21 00:00:00
abstract::Thyroid cancer is the most frequent endocrine tumor with a growing incidence worldwide. However, common diagnostic strategy for thyroid cancer classification is hardly to make a proper diagnosis in some cases. To assist classical approach, this study used metabolomics to screen and validate biomarkers from serum and u...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-19-0344
更新日期:2019-12-01 00:00:00
abstract::Thyroid cancer is rare, but it is the most frequent endocrine malignancy. Its prognosis is generally favorable, especially in cases of well-differentiated thyroid cancers (DTCs), such as papillary and follicular cancers, which have survival rates of approximately 95% at 40 years. However, 15-20% of cases became radioi...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-15-0555
更新日期:2016-04-01 00:00:00
abstract::Pancreatic endocrine tumours (PETs) are rare and 'indolent' neoplasms that usually develop metastatic lesions and exhibit poor response to standard medical treatments. Few studies have investigated pathways responsible for PET cell growth and invasion and no alternative therapeutic strategies have been proposed. In a ...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/erc.1.01318
更新日期:2007-03-01 00:00:00
abstract::Mutations of the aryl hydrocarbon receptor interacting protein (AIP) gene are associated with pituitary adenomas that usually occur as familial isolated pituitary adenomas (FIPA). Detailed pathological and tumor genetic data on AIP mutation-related pituitary adenomas are not sufficient. Non-identical twin females pres...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-11-0059
更新日期:2011-06-08 00:00:00