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Endocrine-related Cancer

Na Li, Huanni Li, Lanqing Cao, Xianquan Zhan
Mitochondria play important roles in growth, signal transduction, division, tumorigenesis and energy metabolism in epithelial ovarian carcinomas (EOCs) without an effective biomarker. To investigate the proteomic profile of EOC mitochondrial proteins, a 6-plex isobaric tag for relative and absolute quantification (iTRAQ) proteomics was used to identify mitochondrial expressed proteins (mtEPs) in EOCs relative to controls, followed by an integrative analysis of the identified mtEPs and the Cancer Genome Atlas (TCGA) data from 419 patients...
July 11, 2018: Endocrine-related Cancer
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
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
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
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
James F Powers, Brent Cochran, James D Baleja, Hadley D Sikes, Xue Zhang, Inna Lomakin, Troy F 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...
July 2, 2018: Endocrine-related Cancer
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
Jonathan Wesley 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 dehydroepiandrosterone sulfate (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...
June 25, 2018: Endocrine-related Cancer
Adel Aref, Andrew D Vincent, Michael O'Callaghan, Sean Martin, Peter Sutherland, Andrew Hoy, Lisa M Butler, Gary 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 (body mass index (BMI), waist circumference (WC)) and serum hormone (serum testosterone (T), estradiol (E2)), PSA and hematology assessments obtained over two waves was assessed...
June 25, 2018: Endocrine-related Cancer
Sunmi Park, Mark Willingham, Jun Qi, Sheue-Yann Cheng
Compelling epidemiological evidence shows a strong positive correlation of obesity with thyroid cancer. In vivo studies have provided molecular evidence that high-fat-diet-induced obesity promotes thyroid cancer progression by aberrantly activating leptin-JAK2-STAT3 signaling in a mouse model of thyroid cancer (ThrbPV/PVPten+/- mice). The ThrbPV/PVPten+/- mouse expresses a dominantly negative thyroid hormone receptor β (denoted as PV) and a deletion of one single allele of the Pten gene. The ThrbPV/PVPten+/- mouse spontaneously develops follicular thyroid cancer, which allows its use as a preclinical mouse model to test potential therapeutics...
June 18, 2018: Endocrine-related Cancer
Dan Luo, Shaohua Zhan, Wenchao Xia, Liang Huang, Wei Ge, Tianxiao Wang
Lymph node metastasis (LNM) in papillary thyroid cancer (PTC) is related to increased risk of recurrence and poor prognosis. Tumor exosomes have been shown to be associated with metastasis of cancer cells. Therefore, we aim to identify the characteristics and biological functions of serum exosomes in lymph node metastases of PTC. We compared proteome profiles of serum-purified exosomes (SPEs) from PTC patients with LNM, PTC patients without LNM, and healthy donors, using a combination of liquid chromatography-tandem mass spectroscopy analyses and Tandem Mass Tag label quantitation analysis...
June 12, 2018: Endocrine-related Cancer
Elke Tatjana Aristizabal Prada, Gerald Spoettl, Julian Maurer, Michael Lauseker, Eva Koziolek, Jörg Schrader, Ashley B Grossman, Karel Pacak, Felix Beuschlein, Christoph J Auernhammer, Svenja Nölting
Pancreatic neuroendocrine tumors (panNETs) are often inoperable at diagnosis. The mTORC1 inhibitor everolimus has been approved for the treatment of advanced NETs. However, the regular development of resistance to everolimus limits its clinical efficacy. We established two independent everolimus-resistant panNET (BON1) cell lines (BON1 RR1, BON1 RR2) to find potential mechanisms of resistance. After 24 weeks of permanent exposure to 10 nM everolimus, BON1 RR1 and BON1 RR2 showed stable resistance with cellular survival rates of 96...
June 12, 2018: Endocrine-related Cancer
Shu-Fu Lin, Jen-Der Lin, Chuen Hsueh, Ting-Chao Chou, Richard J Wong
Activation of cyclin-dependent kinase activity is frequently observed in many human cancers; therefore, cyclin-dependent kinases that promote cell cycle transition and cell proliferation may be potential targets in the treatment of malignancy. The therapeutic effects of roniciclib, a cyclin-dependent kinase inhibitor for papillary and follicular thyroid cancer (designated as well-differentiated thyroid cancer), were investigated in this study. Roniciclib inhibited cell proliferation in two papillary and two follicular thyroid cancer cell lines in a dose-dependent manner...
June 12, 2018: Endocrine-related Cancer
Christina Wei, Elizabeth Crowne
Endocrine abnormalities are common among childhood cancer survivors. Abnormalities of the hypothalamic-pituitary-adrenal axis (HPAA) are the least common, but the consequences are severe if missed. Patients with tumours located and /or had surgery performed near the hypothalamic-pituitary region and those treated with an accumulative cranial radiotherapy dose of over 30 Gy are most at risk of adrenocorticotrophic hormone (ACTH) deficiency. Primary adrenal insufficiency may occur in patients with tumours located in or involving one or both adrenals...
June 12, 2018: Endocrine-related Cancer
Juan Pablo Petiti, Liliana Del Valle Sosa, Florencia Picech, Gabriela Deisi Moyano Crespo, Jean Zander Arevalo Rojas, Pablo Anibal Pérez, Carolina Beatriz Guido, Carolina Leimgruber, María Eugenia Sabatino, Pedro Emilio García, Verónica Bengió, Francisco Roque Papalini, Paula Estario, Maria Celina Bernhardt, Marcos Villarreal, Silvina Gutiérrez, Ana Lucía De Paul, Jorge Humberto Mukdsi, Alicia I Torres
In pituitary adenomas, early recurrences and resistance to conventional pharmacotherapies are common, but the mechanisms involved are still not understood. The high expression of epidermal growth factor receptor 2 (HER2)/extracellular signal-regulated kinase (ERK1/2) signal observed in human pituitary adenomas, together with the low levels of the antimitogenic transforming growth factor beta receptor 2 (TBR2), encouraged us to evaluate the effect of the specific HER2 inhibition with trastuzumab on experimental pituitary tumor cell growth and its effect on the antiproliferative response to TGFB1...
June 6, 2018: Endocrine-related Cancer
Sumie Kato, María Francisca Liberona, Javier Cerda-Infante, Marianela Sanchez, Jenny F Henriquez, Carolina Bizama, Maria Loreto Bravo, Pamela Gonzalez, Roger Gejman, Jorge Branes, Karen García, Carolina Ibañez, Gareth Ivor Owen, Juan Carlos Roa, Viviana Montecinos, Mauricio Arturo Cuello
Cell plasticity of 'stem-like' cancer-initiating cells (CICs) is a hallmark of cancer, allowing metastasis and cancer progression. Here, we studied whether simvastatin, a lipophilic statin, could impair the metastatic potential of CICs in high-grade serous ovarian cancer (HGS-ovC), the most lethal among the gynecologic malignancies. qPCR, immunoblotting, and immunohistochemistry were used to assess simvastatin effects on proteins involved in stemness and epithelial-mesenchymal cell plasticity (EMT). Its effects on tumor growth and metastasis were evaluated using different models (e...
May 30, 2018: Endocrine-related Cancer
Abigail Read, Rachael Natrajan
Breast cancer is known to be a heterogeneous disease driven by a large repertoire of molecular abnormalities, which contribute to its diverse clinical behavior. Despite the success of targeted therapy approaches for breast cancer patient management, there is still a lack of the molecular understanding of aggressive forms of the disease and clinical management of these patients remains difficult. The advent of high throughput sequencing technologies, have paved the way for a more complete understanding of the molecular make-up of the breast cancer genome...
May 30, 2018: Endocrine-related Cancer
Hartmut P H Neumann, William Young, Tobias Krauss, Jean-Pierre Bayley, Francesca Schiavi, Giuseppe Opocher, Carsten Boedeker, Amit Tirosh, Frederic Castinetti, Juri Ruf, Dmitry Beltsevich, Martin K Walz, Harald Groeben, Ernst Von Dobschuetz, Oliver Gimm, Nelson Wohllk, Marija Pfeifer, Delmar Muniz Lourenço, Mariola Peczkowska, Attila Patocs, Joanne Ngeow, Ozer Makay, Nalini Shah, Arthur S Tischler, Helena Leijon, Gianmaria Pennelli, Karina Villar Gómez de Las Heras, Thera P Links, Birke Bausch, Charis Eng
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 field of molecular genetics, the well-established axiom that familial (genetic) pheochromocytoma represents 10% of all cases has been overturned, with >35% of cases now attributable to germline disease-causing mutations...
May 24, 2018: Endocrine-related Cancer
Lamis Yehia, Charis Eng
An average of 10% of all cancers (range 1-40%) are caused by heritable mutations and over the years, have become powerful models for precision medicine practice. Furthermore, such cancer predisposition genes for seemingly rare syndromes have turned out to help explain mechanisms of sporadic carcinogenesis and often inform normal development. The tumor suppressor PTEN encodes a ubiquitously expressed phosphatase that counteracts the PI3K/AKT/mTOR cascade - one of the most critical growth-promoting signaling pathways...
May 23, 2018: Endocrine-related Cancer
Matias Knuuttila, Arfa Mehmood, Jenni Mäki-Jouppila, Henrik Ryberg, Pekka Taimen, Juha Knaapila, Otto Ettala, Peter J Bostrom, Claes Ohlsson, Mikko S Venäläinen, Asta Laiho, Laura L Elo, Petra Sipilä, Sari Makela, Matti Poutanen
Intratumoral androgen biosynthesis is one of the mechanisms involved in the progression of prostate cancer, and an important target for novel prostate cancer therapies. Using gas chromatography-tandem mass spectrometry and genome-wide RNA sequencing, we have analyzed androgen concentrations and androgen-regulated gene expression in cancerous and morphologically benign prostate tissue specimens and serum samples obtained from 48 primary prostate cancer patients. Intratumoral DHT concentrations were significantly higher in the cancerous tissues compared to benign prostate (p<0...
May 17, 2018: Endocrine-related Cancer
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