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Endocrine-related Cancer

Miguel A Zaballos, Adrián Acuña-Ruiz, Marta Morante, Piero Crespo, Pilar Santisteban
Thyroid cancer is mostly an ERK-driven carcinoma, as up to 70% of thyroid carcinomas are caused by mutations that activate the RAS/ERK mitogenic signaling pathway. The incidence of thyroid cancer has been steadily increasing for the last four decades, yet there is still no effective treatment for advanced thyroid carcinomas. Current research efforts are focused on impairing ERK signaling with small molecule inhibitors, mainly at the level of BRAF and MEK. However, despite initial promising results in animal models, the clinical success of these inhibitors has been limited by the emergence of tumor resistance and relapse...
April 1, 2019: Endocrine-related Cancer
Emmanuelle Fleurot, Caroline Goudin, Vincent Hanoux, Pierre-Jacques Bonnamy, Jérôme Levallet
Breast cancer (BC) is the primary cause of cancer-related mortality among women. Patients who express the estrogen receptor (ER), which mediates the tumorigenic effects of estrogens, respond to antihormonal therapy. Loss of ER expression or acquired resistance to E2 is associated with aggressive malignant phenotypes, which lead to relapse. These BC subtypes overexpress syndecan-1 (SDC1), a transmembrane heparan sulfate proteoglycan that mediates angiogenesis as well as the proliferation and invasiveness of cancer cells...
April 1, 2019: Endocrine-related Cancer
Kensey N Bergdorf, Donna C Ferguson, Mitra Mehrad, Kim Ely, Thomas Stricker, Vivian L Weiss
The prevalence of thyroid carcinoma is increasing and represents the most common endocrine malignancy, with papillary thyroid carcinoma (PTC) being the most frequent subtype. The genetic alterations identified in PTCs fail to distinguish tumors with different clinical behaviors, such as extra-thyroidal extension and lymph node metastasis. We hypothesize that the immune microenvironment may play a critical role in tumor invasion and metastasis. Computational immunogenomic analysis was performed on 568 PTC samples in The Cancer Genome Atlas using both CIBERSORT and TIMER deconvolution analytic tools for characterizing immune cell composition...
April 1, 2019: Endocrine-related Cancer
Robert Clarke, John J Tyson, Ming Tan, William T Baumann, Lu Jin, Jianhua Xuan, Yue Wang
Drawing on concepts from experimental biology, computer science, informatics, mathematics, and statistics, systems biologists integrate data across diverse platforms and scales of time and space to create computational and mathematical models of the integrative, holistic functions of living systems. Endocrine-related cancers are well suited to study from a systems perspective because of the signaling complexities arising from the roles of growth factors, hormones, and their receptors as critical regulators of cancer cell biology and from the interactions among cancer cells, normal cells, and signaling molecules in the tumor microenvironment...
April 1, 2019: Endocrine-related Cancer
Anna Angelousi, Eva Kassi, Narjes Nasiri-Ansari, Harpal S Randeva, Gregory A Kaltsas, George P Chrousos
Circadian rhythms in central and peripheral level are operated by transcriptional/translational feedback loops involving a set of genes called 'clock genes' that are implicated in the development of several diseases including malignancies. Dysregulation of Clock system can affect cancer susceptibility by regulating DNA damage and repair mechanisms as well as apoptosis. A number of oncogenic pathways can be dysregulated via clock genes' epigenetic alterations including hypermethylation of clock genes' promoters or variants of clock genes...
April 1, 2019: Endocrine-related Cancer
Aura D Herrera Martínez, Rosanna van den Dungen, Fadime Dogan, P M van Koetsveld, Michael Culler, Wouter W de Herder, Raul M Luque, R A Feelders, Leo Hofland
Control of symptoms related to hormonal hypersecretion by functioning neuroendocrine tumors (NETs) is challenging. New therapeutic options are required. Since novel in vitro tumor models seem to better mimic the tumor in vivo conditions, we aimed to study the effect of somatostatin and dopamine receptor agonists (octreotide and cabergoline, respectively) and novel somatostatin-dopamine chimeric multi-receptor drugs (BIM-065, BIM-23A760) using 2D (monolayer) and 3D (spheroids) cultures. METHODS: Dose-response studies in 2D and 3D human pancreatic NET cell cultures (BON-1 and QGP-1) were performed under serum-containing and serum-deprived conditions...
April 1, 2019: Endocrine-related Cancer
Marijn Annette Vermeulen, Carolien van Deurzen, Shusma Charlane Doebar, Wendy de Leng, John Martens, Paul J van Diest, Cathy B Moelans
Ductal carcinoma in situ (DCIS) of the male breast is very rare and has hardly been studied molecularly. In males, we compared methylation status of 25 breast cancer-related genes in pure DCIS (N=18) and invasive breast carcinoma (IBC) with adjacent DCIS (DCIS-AIC) (N=44) using methylation-specific multiplex ligation-dependent probe amplification. Results were compared to female breast cancer (BC). There were no significant differences in methylation features between male pure DCIS, DCIS-AIC and IBC after correction for multiple comparisons...
March 1, 2019: Endocrine-related Cancer
Joakim Crona, Angela Lamarca, Suman Ghosal, Staffan Welin, Britt Skogseid, Karel Pacak
Pheochromocytoma and paraganglioma (PPGL) can be divided into at least four molecular subgroups. Whether such categorizations are independent factors for prognosis or metastatic disease is unknown. We performed a systematic review and individual patient meta-analysis aiming to estimate if driver mutation status can predict metastatic disease and survival. Driver mutations were used to categorize patients accordingly to three different molecular systems: two subgroups (SDHB mutated or wild type), three subgroups (pseudohypoxia, kinase signaling or Wnt/unknown) and four subgroups (tricarboxylic acid cycle, VHL/EPAS1, kinase signaling or Wnt/unknown)...
March 1, 2019: Endocrine-related Cancer
Soeren Latteyer, Sandra Christoph, Sarah Theurer, Georg Sebastian Hönes, Kurt Werner Schmid, Dagmar Fuehrer, Lars C Moeller
Thyroid hormones are important for physiology and homeostasis. In addition to nuclear thyroid hormone receptors, the plasma membrane protein integrin αvβ3 has been recognized as a receptor for both thyroxine (T4) and triiodothyronine (T3). Here, we studied whether thyroid hormone promotes growth of murine lung cancer via αvβ3 in vivo. Murine Lewis lung carcinoma cells (3LL), stably transfected with luciferase, were injected into mouse lungs. Tumor growth in untreated mice was compared to hypothyroid mice and hypothyroid mice treated with T3 or T4 with or without the αvβ3 inhibitor 3,5,3',5'-tetraiodothyroacetic acid (Tetrac)...
March 1, 2019: Endocrine-related Cancer
Feng Wu, Fuxingzi Li, Xiao Lin, Feng Xu, Rongrong Cui, Jiayu Zhong, Ting Zhu, Su-Kang Shan, Xiao-Bo Liao, Lingqing Yuan, Zhaohui Mo
Tumour-derived exosomes under hypoxic conditions contain informative microRNAs involved in the interaction of cancer and para-carcinoma cells, thus contributing to tissue remodelling of the tumour microenvironment (TME). Exosomes isolated from hypoxic papillary thyroid cancer cells, BCPAP cells and KTC-1 cells, enhanced the angiogenesis of human umbilical vein endothelial cells (HUVECs) compared with exosomes isolated from normal thyroid follicular cell line (Nthy-ori-3-1), normoxic BCPAP cells or KTC-1 cells both in vitro and vivo...
March 1, 2019: Endocrine-related Cancer
Suzan Stelloo, Andries M Bergman, Wilbert Zwart
The androgen receptor (AR) is commonly known as a key transcription factor in prostate cancer development, progression and therapy resistance. Genome-wide chromatin association studies revealed that transcriptional regulation by AR mainly depends on binding to distal regulatory enhancer elements that control gene expression through chromatin looping to gene promoters. Changes in the chromatin epigenetic landscape and DNA sequence can locally alter AR DNA binding capacity and consequently impact transcriptional output and disease outcome...
March 1, 2019: Endocrine-related Cancer
Raquel Santana da Cruz, Johan Clarke, Ana Cristina Curi, Aseel Al-Yawar, Lu Jin, Ali Baird, Idalia Cruz, Bhaskar V Kallakury, Sonia de Assis
Epidemiological studies suggest that timing of obesity onset (and underlying metabolic dysfunction) is important in determining pancreatic cancer rates: Early and young adult abdominal overweight/obesity is more strongly associated with this cancer than obesity that develops later in life. Parental obesity and overweight is associated with metabolic dysfunction and obesity in their children. Here, we evaluated the impact of parental overweight on offspring's susceptibility of pancreatic cancer using the P48Cre/+ /KrasG120/+ mouse model...
March 1, 2019: Endocrine-related Cancer
Grant Foglesong, Nicholas Queen, Wei Huang, Kyle Widstrom, Lei Cao
Obesity is becoming a global epidemic and is a risk factor for breast cancer. Environmental enrichment (EE), a model recapitulating an active lifestyle, leads to leanness, resistance to diet-induced obesity (DIO) and cancer. One mechanism is the activation of the hypothalamic-sympathoneural-adipocyte (HSA) axis. This results in the release of norepinephrine onto adipose tissue inducing a drop of leptin. This study aimed to test the effects of EE on breast cancer onset and progression while considering the effect of leptin by utilizing the transgenic MMTV-PyMT model as well as several models of varied leptin signaling...
March 1, 2019: Endocrine-related Cancer
María Andrea Camilletti, Alejandra Inés Abeledo Machado, Pablo Aníbal Pérez, Erika Yanil Faraoni, Fernanda De Fino, Susana B Rulli, Jimena Ferraris, Daniel Pisera, Silvina Gutiérrez, Peter Thomas, Graciela Diaz-Torga
Membrane progesterone receptors are known to mediate rapid nongenomic progesterone effects in different cell types. Recent evidence revealed that mPRα is highly expressed in the rat pituitary, being primarily localized in lactotrophs, acting as an intermediary of P4-inhibitory actions on prolactin secretion. The role of mPRs in prolactinoma development remains unclear. We hypothesize that mPR agonists represent a novel tool for hyperprolactinemia treatment. To this end, pituitary expression of mPRs was studied in three animal models of prolactinoma...
March 1, 2019: Endocrine-related Cancer
Marie Colombe Agahozo, Anieta M Sieuwerts, Shusma Charlane Doebar, Esther Verhoef, Corine M Beaufort, Kirsten Ruigrok-Ritstier, Vanja de Weerd, Hein F B M Sleddens, Winand Nm Dinjens, John Martens, Carolien van Deurzen
PIK3CA is one of the most frequently mutated genes in invasive breast cancer (IBC). These mutations are generally associated with hyper-activation of the phosphatidylinositol 3-kinase signaling pathway, which is negatively regulated by the tumor suppressor PTEN. Data is limited regarding the variant allele frequency (VAF) of PIK3CA and PTEN expression during various stages of breast carcinogenesis. Therefore, the aim of this study was to gain insight into PIK3CA VAF and associated PTEN expression during the progression from ductal carcinoma in situ (DCIS) to IBC...
March 1, 2019: Endocrine-related Cancer
Rayzel Fernandes, Theresa Hickey, Wayne D Tilley, Luke A Selth
The androgen receptor (AR) is a ligand activated transcription factor that drives prostate cancer. Since therapies that target the AR are the mainstay treatment for men with metastatic disease, it is essential to understand the molecular mechanisms underlying oncogenic AR signaling in the prostate. MicroRNAs (miRNAs) are small, non-coding regulators of gene expression that play a key role in prostate cancer, and are increasingly recognized as targets or modulators of the AR signaling axis. In this review, we examine the regulation of AR signalling by miRNAs and vice versa, and discuss how this interplay influences prostate cancer growth, metastasis and resistance to therapy...
February 1, 2019: Endocrine-related Cancer
Peder Rustøen Braadland, Alfonso Urbanucci
Tumor evolution is based on the ability to constantly mutate and activate different pathways under the selective pressure of targeted therapies. Epigenetic alterations including those of the chromatin structure are associated with tumor initiation, progression, and drug resistance. Many cancers, including prostate cancer, present enlarged nuclei and chromatin appears altered and irregular. These phenotypic changes are likely to result from epigenetic dysregulation. High-throughput sequencing applied to bulk samples and now to single cells has made it possible to study these processes in unprecedented detail...
February 1, 2019: Endocrine-related Cancer
Antonio Marcondes Lerario, Kazutaka Nanba, Amy R Blinder, Sachiko Suematsu, Masao Omura, Tetsuo Nishikawa, Thomas J Giordano, William Rainey, Tobias Else
Somatic variants in genes that regulate intracellular ion homeostasis have been identified in aldosterone-producing adenomas (APA). Although the mechanisms leading to an increased aldosterone production in APA cells has been well studied, the molecular events that cause cell proliferation and tumor formation are poorly understood. In the present study, we have performed whole exome sequencing (WES) to characterize the landscape of somatic alterations in a homogeneous series of APA with pathogenic KCNJ5 variants...
February 1, 2019: Endocrine-related Cancer
Ornella Affinito, Paolo Salerno, Alfonso Manuel D'Alessio, Mariella Cuomo, Ermanno Florio, Francesca Carlomagno, Agnese Proietti, Riccardo Giannini, Fulvio Basolo, Lorenzo Chiariotti, Sergio Cocozza, Massimo Santoro
Molecular differentiation between benign (follicular thyroid adenoma, FTA) and malignant (follicular thyroid carcinoma, FTC) thyroid neoplasms is challenging. Here, we explored the genome-wide DNA methylation profile of FTA (n.10) and FTC (n.11) compared to normal thyroid (NT) (n.7) tissues. FTC featured 3,564 differentially-methylated CpGs (DMCpG), most (84%) of them hypermethylated, with respect to normal controls. At the principal component analysis (PCA), the methylation profile of FTA occupied an intermediate position between FTC and normal tissue...
February 1, 2019: Endocrine-related Cancer
Tobias Hofving, Viktor Sandblom, Yvonne Arvidsson, Emman Shubbar, Gülay Altiparmak, John Swanpalmer, Bilal Almobarak, Anna-Karin Elf, Viktor Johanson, Erik Elias, Erik Kristiansson, Eva Forssell-Aronsson, Ola Nilsson
177Lu-octreotate is an FDA-approved radionuclide therapy for patients with gastroenteropancreatic neuroendocrine tumours (NETs) expressing somatostatin receptors. The 177Lu-octreotate therapy has shown promising results in clinical trials by prolonging progression-free survival, but complete responses are still uncommon. The aim of this study was to improve the 177Lu-octreotate therapy by means of combination therapy. To identify radiosensitising inhibitors, two cell lines, GOT1 and P-STS, derived from small intestinal neuroendocrine tumours (SINETs), were screened with 1,224 inhibitors alone or in combination with external radiation...
February 1, 2019: Endocrine-related Cancer
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