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Endocrine-related Cancer

Sara G Creemers, P M van Koetsveld, Wouter W de Herder, Fadime Dogan, Gaston J H Franssen, R A Feelders, Leo Hofland
Chemotherapy for adrenocortical carcinoma (ACC) has limited efficacy and is accompanied by severe toxicity. This lack of effectiveness has been associated with high tumoral levels of the multidrug resistance (MDR) pump P-glycoprotein (P-gp), encoded by the MDR1 gene. In this study, effects of P-gp inhibition on sensitivity of ACC cells to cytotoxic drugs were evaluated. MDR1 mRNA and P-gp expression were determined in human adrenal tissues and cell lines. H295R, HAC15, and SW13 cells were treated with mitotane, doxorubicin, etoposide, cisplatin, and streptozotocin, with or without the P-glycoprotein inhibitors verapamil and tariquidar...
January 1, 2019: Endocrine-related Cancer
Gabriela Carreno, Jessica K R Boult, John R Apps, Jose Mario Gonzalez-Meljem, Scott Haston, Romain Guiho, Christina Stache, Laura S Danielson, Alexander Koers, Laura S Smith, Alex Virasami, Leonidas Panousopoulos, Michael Buchfelder, Thomas S Jacques, Louis Chesler, Simon Robinson, Juan Pedro Martinez-Barbera
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 up. We have previously demonstrated overactivation of the SHH pathway in both human and mouse ACP. Here, we show that this activation is ligand dependent and induced by the expression of SHH protein in a small proportion of tumour cells...
January 1, 2019: Endocrine-related Cancer
Vanessa Michel López-Ozuna, Ibrahim Yaseen Hachim, Mahmood Yaseen Hachim, Jean-Jacques Lebrun, Suhad Ali
Triple negative breast cancer (TNBC) accounts for ~20% of all breast cancer cases. The management of TNBC represents a challenge due to its aggressive phenotype, heterogeneity and lack of targeted therapy. Loss of cell differentiation and enrichment with breast cancer stem-like cells (BCSC) are features of TNBC contributing to its aggressive nature. Here, we found that PRL treatment of TNBC cells to significantly depletes the highly tumorigenic BCSC subpopulations CD44+/CD24- and ALDH+ and differentiate them to the least tumorigenic CD44-/CD24- and ALDH- phenotype with limited tumorsphere formation and self-renewal capacities...
January 1, 2019: Endocrine-related Cancer
Fabia O Andrade, Wei Yu, Xiyuan Zhang, Elissa Carney, Rong Hu, Robert Clarke, Kevin FitzGerald, Leena Hilakivi-Clarke
Resistance to endocrine therapy remains a clinical challenge in the treatment of estrogen receptor positive (ER+) breast cancer. We investigated if adding a traditional Asian herbal mixture consisting of 12 herbs, called Jaeumkanghwa-tang (JEKHT), to tamoxifen (TAM) therapy might prevent resistance and recurrence in the ER+ breast cancer model of 7,12-dimethylbenz[a]anthracene (DMBA)-exposed Sprague Dawley rats. Rats were divided into four groups treated as follows: 15 mg/kg TAM administered via diet as TAM citrate (TAM only); 500 mg/kg JEKHT administered via drinking water (JEKHT only group); TAM + JEKHT; and no treatment control group...
January 1, 2019: Endocrine-related Cancer
Aura D Herrera Martínez, Leo Hofland, María Ángeles Gálvez Moreno, Justo P Castaño, Wouter W de Herder, R A Feelders
Some biomarkers for functioning and non-functioning neuroendocrine neoplasms (NENs) are currently available. Despite their application in clinical practice, results should be interpreted cautiously. Considering the variable sensitivity and specificity of these parameters there is an unmet need for novel biomarkers to improve diagnosis and predict patient outcome. Nowadays, several new biomarkers are being evaluated and may become future tools for the management of NENs. These biomarkers include: (1) peptides and growth factors; (2) DNA and RNA markers based on genomics analysis, e...
January 1, 2019: Endocrine-related Cancer
Rabii Ameziane-El-Hassani, Camille Buffet, Sophie Leboulleux, Corinne Dupuy
At physiological concentrations, reactive oxygen species (ROS), including superoxide anions and H2O2, are considered as second messengers that play key roles in cellular functions, such as proliferation, gene expression, host defence and hormone synthesis. However, when they are at supraphysiological levels, ROS are considered potent DNA damaging agents. Their increase induces oxidative stress, which can initiate and maintain genomic instability. The thyroid gland represents a good model for studying the impact of oxidative stress on genomic instability...
January 1, 2019: Endocrine-related Cancer
Florian Bösch, Katharina Brüwer, Annelore Altendorf-Hofmann, Christoph J Auernhammer, Christine Spitzweg, C Benedikt Westphalen, Stefan Boeck, Gabriele Schubert-Fritschle, Jens Werner, Volker Heinemann, Thomas Kirchner, Martin Angele, Thomas Knösel
Cancer immunotherapy has evolved major breakthroughs in the last years. The cell surface receptor programmed death-1 (PD-1) and its ligand, programmed death ligand-1 (PD-L1) have been detected in various cancer types. However the analysis in gastroenteropancreatic neoplasia (GEP-NENs) is limited. Therefore, the aim of this study was to characterize GEP-NENs with regard to PD-1/PD-L1 pathway and tumor infiltrating lymphocytes (TILs). On protein level we examined TILs, PD-1 and PD-L1 expression in tumor tissue of 244 GEP-NENs using immunohistochemistry...
January 1, 2019: Endocrine-related Cancer
Johannes Hofland, Aura D Herrera Martínez, Wouter T Zandee, Wouter W de Herder
Carcinoid syndrome (CS) is a debilitating disease caused by functional neuroendocrine tumors. Several treatment options are available to alleviate the hormonal symptoms, but their relative efficacy is unknown. Online databases were searched for publications on the treatment of CS symptoms. Independent reviewers assessed relevant publications for study quality and outcome. Meta-analysis of the outcomes of the intervention on CS-related symptoms was stratified by type of treatment. We found 3682 therapeutic interventions on CS-specific outcomes collected from 93 studies...
January 1, 2019: Endocrine-related Cancer
Fei Han, Wen-Bin Liu, Jian-Jun Li, Ming-Qian Zhang, Jun-Tang Yang, Xi Zhang, Xiang-Lin Hao, Li Yin, Cheng-Yi Mao, Xiao Jiang, Jia Cao, Jin-Yi Liu
New potential biomarkers and therapeutic targets for ovarian cancer should be identified. The amplification in chromosomal region 5q31-5q35.3 exhibits the strongest correlation with overall survival (OS) of ovarian cancer. SOX30 coincidentally located at this chromosomal region has been determined as a new important tumor-suppressor. However, the prognostic value, role and mechanism of SOX30 in ovarian cancer are unexplored. Here, we revea1 that SOX30 is frequently over-expressed in ovarian cancer tissues, and is associated with clinical-stage and metastasis of ovarian cancer patients...
January 1, 2019: Endocrine-related Cancer
Willem Corver, Hans Morreau
In their back-to-back published articles "Integrated Genomic Analysis of Hürthle Cell Cancer Reveals Oncogenic Drivers, Recurrent Mitochondrial Mutations, and Unique Chromosomal Landscapes" and "Widespread Chromosomal Losses and Mitochondrial DNA Alterations as Genetic Drivers in Hürthle Cell Carcinoma" Ganly and co-workers (Ganly, et al. 2018) and Gopal and co-workers (Gopal, et al. 2018), respectively, defined alterations in oncogenic drivers and mitochondrial DNA mutations complex I (mtDNA), including the widespread whole-chromosome losses in oncocytic or Hürthle cell thyroid carcinoma (HCC)...
December 1, 2018: Endocrine-related Cancer
Zhe Wang, Ke Ma, Steffie Pitts, Yulan Cheng, Xi Liu, Xiquan Ke, Samuel Kovaka, Hassan Ashktorab, Duane T Smoot, Michael Schatz, Zhirong Wang, Stephen Meltzer
Circular RNAs (circRNAs) are a new class of RNA involved in multiple human malignancies. However, limited information exists regarding the involvement of circRNAs in gastric carcinoma (GC). Therefore, we sought to identify novel circRNAs, their functions and mechanisms in gastric carcinogenesis. We analyzed next-generation RNA sequencing data from GC tissues and cell lines, identifying 75,201 candidate circRNAs. Among these, we focused on one novel circRNA, circNF1, that was upregulated in GC tissues and cell lines...
December 1, 2018: Endocrine-related Cancer
Isobel C Mouat, Kei Omata, Andrew S McDaniel, Namita Hattangady, Debnita Talapatra, Andi K Cani, Daniel H Hovelson, Scott A Tomlins, William Rainey, Gary Hammer, Thomas J Giordano, Tobias Else
Several somatic mutations specific to aldosterone-producing adenomas (APA) have been described. A small proportion of adrenocortical carcinomas (ACC) are associated with hyperaldosteronism, either primary aldosteronism or hyperreninemic hyperaldosteronism. However, it is unknown, whether they harbor mutations of the same spectrum as APAs. The objective of this study is to describe the clinical phenotype and molecular genotype of ACCs with hyperaldosteronism, particularly the analysis for common APA-associated genetic changes...
November 1, 2018: Endocrine-related Cancer
Priscilla A Furth
Peroxisome proliferator-activated receptor gamma agonists have been proposed as breast cancer preventives. Individuals who carry a mutated copy of BRCA1, DNA Repair Associated gene are at increased risk for development of breast cancer. Published data in the field suggests there could be interactions between peroxisome proliferator-activated receptor gamma and BRCA1 that could influence the activity of peroxisome proliferator-activated receptor gamma agonists for prevention. This review explores these possible interactions between peroxisome proliferator-activated receptor gamma, peroxisome proliferator-activated receptor gamma agonists and BRCA1 and discusses feasible experimental directions to provide more definitive information on the potential connections...
November 1, 2018: Endocrine-related Cancer
Charline Dubois, Natacha Rocks, Silvia Blacher, Irina Primac, Anne Gallez, Melissa García-Caballero, Céline Gérard, Laurent Brouchet, Agnes Noel, Francoise Lenfant, Didier Cataldo, Christel Péqueux
Estrogen signalling pathways are emerging targets for lung cancer therapy. Unravelling the contribution of estrogens in lung cancer development is a pre-requisite to support the development of sex-based treatments and to identify patients who could potentially benefit from anti-estrogen treatments. In this study, we highlight the contribution of lymphatic and blood endothelia in the sex-dependent modulation of lung cancer. The orthotopic graft of syngeneic lung cancer cells into immunocompetent mice showed that lung tumours grew faster in female mice than in males...
November 1, 2018: Endocrine-related Cancer
Dawei Wu, Dongwei Lv, Ting Zhang, Lianying Guo, Fangli Ma, Caihua Zhang, Guofeng Lv, Lin Huang
Ewing sarcoma family tumors (ESFTs) are a group of aggressive and highly metastatic tumors lacking efficient therapies. Insulin-like growth factor 1 receptor (IGF1R) blockade is one of the most efficient targeting therapy for ESFTs. However, the appliance is obstructed by drug resistance and disease recurrence due to the activation of insulin receptor (IR) signaling induced by IGF1R blockade. Herein β-elemene, a compound derived from natural plants, exhibited a remarkable proliferation repression on ESFT cells, which was weakened by a caspase inhibitor Z-VAD...
November 1, 2018: Endocrine-related Cancer
Sung Gwe Ahn, Chang Ik Yoon, Jae Hoon Lee, Hye-Sun Lee, So Eun Park, Yoon Jin Cha, Chihwan Cha, Soong June Bae, Kyung-A Lee, Joon Jeong
On the basis of TP53 mutations and standardized uptake values (SUVs) from 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET), we sought to enhance our knowledge of the biology underlying low progesterone receptor (PR) expression in estrogen receptor (ER)-positive/human epidermal growth factor receptor-2 (HER2)-negative tumors. This study included 272 patients surgically treated for ER-positive, HER2-negative breast cancer and who had undergone TP53 gene sequencing. Of these, 229 patients also underwent 18F-FDG PET or PET/CT...
November 1, 2018: Endocrine-related Cancer
Xiang Zhang, Ya Hu, Mengyi Wang, Ronghua Zhang, PeiPei Wang, Ming Cui, Zhe Su, Xiang Gao, Quan Liao, Yupei Zhao
Parathyroid carcinoma (PCa) is a rare endocrine neoplasia that typically has unfavourable outcomes. The contribution of long non-coding RNAs (lncRNAs) to the development of malignant and benign parathyroid tumours remains largely unknown. In this study, we explored transcriptomic profiling of lncRNA and mRNA expression in 6 PCa, 6 parathyroid adenoma (PAd) and 4 normal parathyroid (PaN) tissues. In total, 2641 lncRNA transcripts and 2165 mRNA transcripts were differentially expressed between PCa and PAd. Enrichment analysis demonstrated that dysregulated transcripts were involved mainly in the extracellular matrix (ECM)-receptor interaction and energy metabolism pathways...
November 1, 2018: Endocrine-related Cancer
Giorgio Secreto, Alessandro Girombelli, Vittorio Krogh
The aim of this review is to highlight the pivotal role of androgen excess in the development of breast cancer. Available evidence suggests that testosterone controls breast epithelial growth through a balanced interaction between its two active metabolites: cell proliferation is promoted by estradiol while it is inhibited by dihydrotestosterone. A chronic overproduction of testosterone (e.g. ovarian stromal hyperplasia) results in an increased estrogen production and cell proliferation that are no longer counterbalanced by dihydrotestosterone...
November 1, 2018: Endocrine-related Cancer
G Mantovani, D Treppiedi, E Giardino, R Catalano, F Mangili, P Vercesi, M Arosio, A Spada, E Peverelli
Although generally benign, pituitary tumors are frequently locally invasive, with reduced success of neurosurgery and unresponsive to pharmacological treatment with somatostatin or dopamine analogues. The molecular basis of the different biological behavior of pituitary tumors are still poorly identified, but a body of work now suggests that the activity of specific cytoskeleton proteins is a key factor regulating both the invasiveness and drug resistance of these tumors. This review recapitulates the experimental evidence supporting a role for the actin-binding protein filamin A (FLNA) in the regulation of somatostatin and dopamine receptors expression and signaling in pituitary tumors, thus in determining the responsiveness to currently used drugs, somatostatin analogues and dopamine receptor type 2 agonists...
February 1, 2019: Endocrine-related Cancer
KeeMing Chia, Heloisa Milioli, Neil Portman, Geraldine Laven-Law, Rhiannon Coulson, Aliza Yong, Davendra Segara, Andrew Parker, Catherine E Caldon, Niantao Deng, Alexander Swarbrick, Wayne D Tilley, Theresa E Hickey, Elgene Lim
The role of androgen receptor (AR) in endocrine-resistant breast cancer is controversial and clinical trials targeting AR with an AR antagonist (e.g., enzalutamide) have been initiated. Here, we investigated the consequence of AR antagonism using in vitro and in vivo models of endocrine resistance. AR antagonism in MCF7-derived tamoxifen-resistant (TamR) and long-term estrogen-deprived breast cancer cell lines were achieved using siRNA-mediated knockdown or pharmacological inhibition with enzalutamide. The efficacy of enzalutamide was further assessed in vivo in an estrogen-independent endocrine-resistant patient-derived xenograft (PDX) model...
February 1, 2019: Endocrine-related Cancer
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