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Endocrine-related Cancer

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https://www.readbyqxmd.com/read/30139768/antitumor-effects-of-anlotinib-in-thyroid-cancer
#1
Xianhui Ruan, Xianle Shi, Qiman Dong, Yang Yu, Xiukun Hou, Xinhao Song, Xi Wei, Lingyi Chen, Ming Gao
There is no effective treatment for patients with poorly differentiated papillary thyroid cancer or anaplastic thyroid cancer (ATC). Anlotinib, a multi-kinase inhibitor, has already shown antitumor effects in various types of carcinoma in a phase I clinical trial. In this study, we aimed to better understand the effect and efficacy of anlotinib against thyroid carcinoma cells in vitro and in vivo. We found that anlotinib inhibits the cell viability of papillary thyroid cancer and ATC cell lines, likely due to abnormal spindle assembly, G2/M arrest, and activation of TP53 upon anlotinib treatment...
August 23, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/30139767/non-secreting-pituitary-tumours-characterised-by-enhanced-expression-of-yap-taz
#2
Paraskevi Xekouki, Emily Jane Lodge, Jakob Matschke, Alice Santambrogio, John R Apps, Ariane Sharif, Thomas S Jacques, Simon Aylwin, Vincent Prevot, Ran Li, Jörg Flitsch, Stefan R Bornstein, Marily Theodoropoulou, Cynthia Andoniadou
Tumours of the anterior pituitary can manifest from all endocrine cell types but the mechanisms for determining their specification are not known. The Hippo kinase cascade is a crucial signalling pathway regulating growth and cell fate in numerous organs. There is mounting evidence implicating this in tumour formation, where it is emerging as an anti-cancer target. We previously demonstrated activity of the Hippo kinase cascade in the mouse pituitary and nuclear association of its effectors YAP/TAZ with SOX2-expressing pituitary stem cells...
August 23, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/30121624/ddr1-regulates-thyroid-cancer-cell-differentiation-via-igf-2-ir-a-autocrine-signaling-loop
#3
Veronica Vella, Maria Luisa Nicolosi, Patrizia Cantafio, Michele Massimino, Rosamaria Lappano, Paolo Vigneri, Roberto Ciuni, Pietro Gangemi, Andrea Morrione, Roberta Malaguarnera, Antonino Belfiore
Patients with thyroid cancers refractory to radioiodine (RAI) treatment show a limited response to various therapeutic options and a low survival rate. The recent use of multikinase inhibitors has also met limited success. An alternative approach relies on drugs that induce cell differentiation, as the ensuing increased expression of the cotransporter for sodium and iodine (NIS) may partially restore sensitivity to radioiodine. The inhibition of the ERK1/2 pathway has shown some efficacy in this context. Aggressive thyroid tumors overexpress the isoform A of the insulin receptor (IR-A) and its ligand IGF-2; this IGF-2/IR-A loop is associated with de-differentiation and stem-like phenotype, resembling RAI refractory tumors...
August 18, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/30121623/tgfb1-driven-mesenchymal-stem-cell-mediated-nis-gene-transfer
#4
Christina Schug, Sarah Urnauer, Carsten Jäckel, Kathrin Alexandra Schmohl, Mariella Tutter, Katja Steiger, Nathalie Schwenk, Markus Schwaiger, Ernst Wagner, Peter Jon Nelson, Christine Spitzweg
Based on their excellent tumor-homing capacity, genetically engineered mesenchymal stem cells (MSCs) are under investigation as tumor-selective gene delivery vehicles. Transgenic expression of the sodium iodide symporter ( NIS ) in genetically engineered MSCs allows noninvasive tracking of MSC homing by imaging of functional NIS expression as well as therapeutic application of 131 I. The use of tumor-stroma activated promoters can improve tumor-specific MSC-mediated transgene delivery. The essential role of transforming growth factor B1 (TGFB1) and the SMAD downstream target in the signaling between tumor and the surrounding stroma makes the biology of this pathway a potential option to better control NIS expression within the tumor milieu...
August 18, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/30121622/chi3l1-results-in-poor-outcome-of-ovarian-cancer-by-promoting-properties-of-stem-like-cells
#5
Han-Wei Lin, Ying-Cheng Chiang, Nai-Yun Sun, Yu-Li Chen, Chi-Fang Chang, Yi-Jou Tai, Chi-An Chen, Wen-Fang Cheng
The role of chitinase-3-like protein 1 (CHI3L1) in ovarian cancer and the possible mechanisms were elucidated. CHI3L1 is a secreted glycoprotein and associated with inflammation, fibrosis, asthma, extracellular tissue remodeling and solid tumors. Our previous study showed CHI3L1 could be a potential prognostic biomarker for epithelial ovarian cancer and protect cancer cells from apoptosis. Therefore, clinical data and quantitation of CHI3L1 of ovarian cancer patients, tumor spheroid formation, side-population assays, Aldefluor and apoptotic assays, ELISA, RT-PCR, immunoblotting, and animal experiments were performed in two ovarian cancer cells lines, OVCAR3 and CA5171, and their CHI3L1-overexpressing and knockdown transfectants...
August 18, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/30121621/molecular-basis-of-distinct-oestrogen-responses-in-endometrial-and-breast-cancer
#6
Eva Baxter, Karolina Windloch, Greg Kelly, Jason S Lee, Frank Gannon, Donal Brennan
Up to 80% of endometrial and breast cancers express oestrogen receptor alpha (ERα). Unlike breast cancer, anti-oestrogen therapy has had limited success in endometrial cancer, raising the possibility that oestrogen has different effects in both cancers. We investigated the role of oestrogen in endometrial and breast cancers using data from The Cancer Genome Atlas (TCGA) in conjunction with cell line studies. Using phosphorylation of ERα (ERα-pSer118) as a marker of transcriptional activation of ERα in TCGA datasets, we found that genes associated with ERα-pSer118 were predominantly unique between tumour types and have distinct regulators...
August 18, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/30121620/inhibition-of-notch-signaling-attenuates-pituitary-adenoma-growth-in-nude-mice
#7
Lautaro Zubeldia-Brenner, Catalina De Winne, Sofia Perrone, Santiago Andres Rodriguez-Segui, Christophe Willems, Ana Maria Ornstein, Isabel Maria Lacau-Mengido, Hugo Vankelecom, Carolina Cristina, Damasia Becú-Villalobos
Preclinical and clinical studies support that Notch signaling may play an important oncogenic role in cancer, but there is scarce information for pituitary tumors. We therefore undertook a functional study to evaluate Notch participation in pituitary adenoma growth. Tumors generated in nude mice by subcutaneous GH3 somatolactotrope cell injection were treated in vivo with DAPT, a γ-secretase inhibitor, thus inactivating Notch signaling. This treatment led to pituitary tumor reduction, lower prolactin and GH tumor content, and a decrease in angiogenesis...
August 18, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/30093601/an-update-of-wnt-signalling-in-endometrial-cancer-and-its-potential-as-a-therapeutic-target
#8
Amy Coopes, Claire E Henry, Estelle Llamosas, Caroline Elizabeth Ford
Endometrial cancer is the most common gynaecological malignancy in developed nations, and its prevalence is rising as women defer or decide not to have children and as obesity rises, both key risk factors. Despite this, treatment options remain limited, particularly for advanced or refractory disease. New genomic analyses have revealed distinct mutational profiles with therapeutic and prognostic potential. Wnt signalling, which is pivotal in embryogenesis, healing and homeostasis, is of importance in the endometrium and has been linked to carcinogenesis...
August 9, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/30072486/tumor-cells-may-circulate-in-medullary-thyroid-cancer-patients-independently-of-serum-calcitonin
#9
Sathya Neelature Sriramareddy, Etienne Hamoir, Marcela Chavez, Renaud Louis, Albert Beckers, Luc Willems
Early detection of tumor relapse is a major issue in patients with medullary thyroid carcinoma. Calcitonin has been reported as a sensitive and accurate marker for recurrence of medullary thyroid carcinoma after thyroidectomy. Recent evidence nevertheless reveals pitfalls in calcitonin immunoassays due to the presence of heterophilic antibodies or macroaggregates. Calcitonin can also remain undetectable despite metastasis of rare tumor cells in thyroidectomized patients. In this context, we designed a sensitive and specific technique to identify calcitonin-positive circulating tumor cells (CTC) in medullary thyroid carcinoma...
August 2, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/30021866/evaluating-gastroenteropancreatic-neuroendocrine-tumors-through-microrna-sequencing
#10
Nicole Panarelli, Kathrin Tyryshkin, Justin Wong, Adrianna Majewski, Xiaojing Yang, Theresa Scognamiglio, Michelle Kang Kim, Kimberley Bogardus, Thomas Tuschl, Yao-Tseng Chen, Neil Renwick
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) can be challenging to evaluate histologically. microRNAs (miRNAs) are small RNA molecules that often are excellent biomarkers due to their abundance, cell-type- and disease-stage specificity, and stability. To evaluate miRNAs as adjunct tissue markers for classifying and grading well-differentiated GEP-NETs, we generated and compared miRNA expression profiles from four pathological types of GEP-NETs. Using quantitative barcoded small RNA sequencing and state-of-the-art sequence annotation, we generated comprehensive miRNA expression profiles from archived pancreatic, ileal, appendiceal, and rectal NETs...
July 18, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/30021865/hotspot-daxx-ptch2-and-cyfip2-mutations-in-pancreatic-neuroendocrine-neoplasms
#11
Timon Vandamme, Matthias Beyens, Gitta Boons, Anne Schepers, Kimberly Kamp, Katharina Biermann, Patrick Pauwels, Wouter W de Herder, Leo Hofland, Marc Peeters, Guy Van Camp, Ken Op de Beeck
Mutations in DAXX/ATRX, MEN1, and genes involved in the phosphoinositide-3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway have been implicated in pancreatic neuroendocrine neoplasms (pNENs). However, mainly mutations present in the majority of tumor cells have been identified, while proliferation-driving mutations could be present only in small fractions of the tumor. This study aims to identify high- and low-abundance mutations in pNENs using ultra-deep targeted resequencing. Formalin-fixed paraffin-embedded matched tumor-normal tissue of 38 well-differentiated pNENs was sequenced using a HaloPlex targeted resequencing panel...
July 18, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/30021864/the-igf-pathway-is-activated-in-insulinomas-but-downregulated-in-metastatic-disease
#12
Mieke Henfling, Aurel Perren, Anja Maria Schmitt, Christiane M Saddig, Achim A Starke, Robert G Riedl, Yvonne M H Versleijen-Jonkers, Diane M Sprij-Mooij, Frans C S Ramaekers, Leo Hofland, Ernst-Jan M Speel
Clinical and molecular studies have implicated epidermal growth factor receptor (EGFR), insulin-like growth factor (IGF) and target of rapamycin (mTOR) signaling pathways in the regulation of pancreatic neuroendocrine tumor (PanNET) growth. Interpretation and comparison of these studies is complex due to clinical and molecular tumor heterogeneity. We therefore focused in this study on insulinomas, which we examined for mRNA and protein expression of EGFR, IGF and mTOR signaling pathway components by quantitative real-time PCR (n=48) and immunohistochemistry (n=86)...
July 18, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29991638/biological-and-clinical-impact-of-imbalanced-progesterone-receptor-isoform-ratios-in-breast-cancer
#13
Caroline A Lamb, Victoria T Fabris, Britta Jacobsen, Alfredo A Molinolo, Claudia Lanari
There is a consensus that progestins and thus their cognate receptor molecules, the progesterone receptors (PR), are essential in the development of the adult mammary gland and regulators of proliferation and lactation. However, a role for natural progestins in breast carcinogenesis remains poorly understood. A hint to that possible role came from studies in which the synthetic progestin medroxyprogesterone acetate was associated with an increased breast cancer risk in women under hormone replacement therapy...
July 10, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29986953/aggressive-and-malignant-pituitary-tumours-state-of-the-art
#14
Dorota Dworakowska, Ashley B Grossman
Pituitary adenomas are unique in multiple ways. They are rarely malignant in terms of metastases, yet they may be aggressive. Their cancerous potential is defined in a classic oncological way by the ability to metastasise, and therefore it has been crucial to differentiate this process from aggressive behaviour, characterised as a particularly invasive and/or recurrent behaviour and resistance to common modalities of therapy. Recently, however, important changes have been introduced to the diagnosis and management of aggressive and malignant pituitary tumours including the 4th edition of the WHO classification for endocrine tumours (2017) as well as ESE Clinical Guidelines (2018), although an attempt to establish predictive and/or prognostic markers of clinical aggressiveness remains difficult...
July 9, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29976565/molecular-underpinnings-of-enzalutamide-resistance
#15
Stefan Prekovic, Thomas Van den Broeck, Simon Linder, Martin E van Royen, Adriaan Houtsmuller, Florian Handle, Steven Joniau, Wilbert Zwart, Frank Claessens
Prostate cancer (PCa) is among the most common adult malignancies, and the second leading cause of cancer-related death in men. As PCa is hormone-dependent, blockade of the androgen receptor (AR) signaling is an effective therapeutic strategy for men with advanced metastatic disease. The discovery of enzalutamide, a compound that effectively blocks the AR axis and its clinical application has led to a significant improvement in survival time. However, the effect of enzalutamide is not permanent, and resistance to treatment ultimately leads to development of lethal disease, for which there currently is no cure...
July 5, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29973339/tumour-growth-and-immune-evasion-as-targets-for-a-new-strategy-in-advanced-cancer
#16
Andrea Nicolini, Paola Ferrari, Giuseppe Rossi, Angelo Carpi
It has become clearer that advanced cancer, especially advanced breast cancer, is an entirely displayed pathological system that is much more complex than previously considered. However, the direct relationship between tumour growth and immune evasion can represent a general rule governing the pathological cancer system from the initial cancer cells to when the system is entirely displayed. Accordingly, a refined pathobiological model and a novel therapeutic strategy are proposed. The novel therapeutic strategy is based on therapeutically induced conditions (undetectable tumour burden and/or a prolonged tumour 'resting state'), which enable an efficacious immune response in advanced breast and other types of solid cancers...
July 4, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29941677/hyperglycemia-decreases-anti-cancer-efficiency-of-adriamycin-via-ampk-pathway
#17
Xiaqing Xu, Meimei Si, Honggang Lou, Youyou Yan, Yunxi Liu, Hong Zhu, Xiaoe Lou, Jian Ma, Difeng Zhu, Honghai Wu, Bo Yang, Haoshu Wu, Ling Ding, Qiaojun He
Accumulating clinical evidence indicates that diabetic liver cancer patients are less sensitive to intra-arterial chemotherapy than non-diabetic cancer patients. However, the underlying mechanism remains largely uncharacterized. Here, we report that hyperglycemia inhibits AMPK pathway and subsequently reduces ADR induced DNA damage, resulting in decreased chemotherapeutic sensitivity of Adriamycin (ADR). HepG2 and Bel-7402 cells were treated with ADR in various glucose conditions and then subjected to cell proliferation assay and apoptosis...
June 25, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29967109/a-unique-model-for-sdh-deficient-gist-an-endocrine-related-cancer
#18
James F Powers, Brent Cochran, James D Baleja, Hadley D Sikes, Xue Zhang, Inna Lomakin, Troy Langford, Kassi Taylor Stein, Arthur S Tischler
We describe a unique patient-derived xenograft (PDX) and cell culture model of succinate dehydrogenase-deficient gastrointestinal stromal tumor (SDH-deficient GIST), a rare mesenchymal tumor that can occur in association with paragangliomas in hereditary and non-hereditary syndromes. This model is potentially important for what it might reveal specifically pertinent to this rare tumor type and, more broadly, to other types of SDH-deficient tumors. The primary tumor and xenografts show a very high proliferative fraction, and distinctive morphology characterized by tiny cells with marked autophagic activity...
November 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29941676/detection-of-a-novel-primate-specific-kill-switch-tumor-suppression-mechanism-that-may-fundamentally-control-cancer-risk-in-humans-an-unexpected-twist-in-the-basic-biology-of-tp53
#19
REVIEW
Jonathan W Nyce
The activation of TP53 is well known to exert tumor suppressive effects. We have detected a primate-specific adrenal androgen-mediated tumor suppression system in which circulating DHEAS is converted to DHEA specifically in cells in which TP53 has been inactivated DHEA is an uncompetitive inhibitor of glucose-6-phosphate dehydrogenase (G6PD), an enzyme indispensable for maintaining reactive oxygen species within limits survivable by the cell. Uncompetitive inhibition is otherwise unknown in natural systems because it becomes irreversible in the presence of high concentrations of substrate and inhibitor...
November 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29941675/the-inverse-relationship-between-prostate-specific-antigen-psa-and-obesity
#20
Adel T Aref, Andrew D Vincent, Michael E O'Callaghan, Sean A Martin, Peter D Sutherland, Andrew J Hoy, Lisa M Butler, Gary A Wittert
Obese men have lower serum prostate-specific antigen (PSA) than comparably aged lean men, but the underlying mechanism remains unclear. The aim of this study was to determine the effect of obesity on PSA and the potential contributing mechanisms. A cohort of 1195 men aged 35 years and over at recruitment, with demographic, anthropometric (BMI, waist circumference (WC)) and serum hormone (serum testosterone, estradiol (E2)) PSA and hematology assessments obtained over two waves was assessed. Men with a history of prostate cancer or missing PSA were excluded, leaving 970 men for the final analysis...
November 2018: Endocrine-related Cancer
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