A unique model for SDH-deficient GIST: an endocrine-related cancer
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. It is likely tha...
Source: Endocrine-Related Cancer - August 16, 2018 Category: Endocrinology Authors: Powers, J. F., Cochran, B., Baleja, J. D., Sikes, H. D., Zhang, X., Lomakin, I., Langford, T., Stein, K. T., Tischler, A. S. Tags: Research Source Type: research
The inverse relationship between prostate specific antigen (PSA) and obesity
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. Mixed-effects regressions ...
Source: Endocrine-Related Cancer - August 16, 2018 Category: Endocrinology Authors: Aref, A. T., Vincent, A. D., OCallaghan, M. E., Martin, S. A., Sutherland, P. D., Hoy, A. J., Butler, L. M., Wittert, G. A. Tags: Research Source Type: research
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
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. In addition to pri...
Source: Endocrine-Related Cancer - August 16, 2018 Category: Endocrinology Authors: Nyce, J. W. Tags: Review Source Type: research
Quantitative analysis of the mitochondrial proteome in human ovarian carcinomas
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. A total of 5115 quantified proteins were identified from purified mitochondrial sampl...
Source: Endocrine-Related Cancer - July 31, 2018 Category: Endocrinology Authors: Li, N., Li, H., Cao, L., Zhan, X. Tags: Research Source Type: research
The role of GSK3 and its reversal with GSK3 antagonism in everolimus resistance
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 96.70% (IC50 = 5200 nM) and 92.30% (IC50 = 2500 nM), respectively. The control cell line showed ...
Source: Endocrine-Related Cancer - July 31, 2018 Category: Endocrinology Authors: Aristizabal Prada, E. T., Spottl, G., Maurer, J., Lauseker, M., Koziolek, E. J., Schrader, J., Grossman, A., Pacak, K., Beuschlein, F., Auernhammer, C. J., Nolting, S. Tags: Research Source Type: research
Proteomics study of serum exosomes from papillary thyroid cancer patients
Lymph node metastasis (LNM) in papillary thyroid cancer (PTC) is related to increased risk of recurrence and poor prognosis. Tumour 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. We identified 1569 proteins by ...
Source: Endocrine-Related Cancer - July 31, 2018 Category: Endocrinology Authors: Luo, D., Zhan, S., Xia, W., Huang, L., Ge, W., Wang, T. Tags: Research Source Type: research
The hypothalamic-pituitary-adrenal axis in childhood cancer survivors
Endocrine abnormalities are common among childhood cancer survivors. Abnormalities of the hypothalamic–pituitary–adrenal axis (HPAA) are relatively less 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. The effects of adjunct therapies also need to be con...
Source: Endocrine-Related Cancer - July 31, 2018 Category: Endocrinology Authors: Wei, C., Crowne, E. C. Tags: Review Source Type: research
Metformin and JQ1 synergistically inhibit obesity-activated thyroid cancer
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 (Thrb PV/PV Pten +/ – mice). The Thrb PV/PV Pten +/ – mouse expresses a dominantly negative thyroid hormone receptor β (denoted as PV) and a deletion of one single allele of the Pten gene. The Thrb PV/PV Pten +/ – mouse spontaneously develops follicular thyroid cancer, which a...
Source: Endocrine-Related Cancer - July 24, 2018 Category: Endocrinology Authors: Park, S., Willingham, M. C., Qi, J., Cheng, S.-Y. Tags: Research Source Type: research
Potent effects of roniciclib alone and with sorafenib against well-differentiated thyroid cancer
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. Roniciclib activated caspase-3 activity and induced ...
Source: Endocrine-Related Cancer - July 24, 2018 Category: Endocrinology Authors: Lin, S.-F., Lin, J.-D., Hsueh, C., Chou, T.-C., Wong, R. J. Tags: Research Source Type: research
Trastuzumab inhibits pituitary tumor cell growth modulating the TGFB/SMAD2/3 pathway
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. Trastuzumab decreased the p...
Source: Endocrine-Related Cancer - July 24, 2018 Category: Endocrinology Authors: Petiti, J. P., Sosa, L. d. V., Picech, F., Moyano Crespo, G. D., Arevalo Rojas, J. Z., Perez, P. A., Guido, C. B., Leimgruber, C., Sabatino, M. E., Garcia, P., Bengio, V., Papalini, F. R., Estario, P., Berhard, C., Villareal, M., Gutierrez, S., De Paul, A Tags: Research Source Type: research
Simvastatin interferes with cancer 'stem-cell plasticity reducing metastasis in ovarian cancer
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.g., spheroid formation and mig...
Source: Endocrine-Related Cancer - July 24, 2018 Category: Endocrinology Authors: Kato, S., Liberona, M. F., Cerda-Infante, J., Sanchez, M., Henriquez, J., Bizama, C., Bravo, M. L., Gonzalez, P., Gejman, R., Branes, J., Garcia, K., Ibanez, C., Owen, G. I., Roa, J. C., Montecinos, V., Cuello, M. A. Tags: Research Source Type: research
Molecular and phenotypic evaluation of a novel germline TMEM127 mutation with an uncommon clinical presentation
(Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - July 20, 2018 Category: Endocrinology Authors: Deng, Y., Flores, S. K., Cheng, Z., Qin, Y., Schwartz, R. C., Malchoff, C., Dahia, P. L. M. Tags: Erratum Source Type: research
Splicing dysregulation as a driver of breast cancer
Breast cancer is known to be a heterogeneous disease driven by a large repertoire of molecular abnormalities, which contribute to its diverse clinical behaviour. 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 has paved the way for a more complete understanding of the molecular make-up of the breast cancer genome. As such, it is becoming apparent that disruption of canonical splicing...
Source: Endocrine-Related Cancer - July 17, 2018 Category: Endocrinology Authors: Read, A., Natrajan, R. Tags: Review Source Type: research
Emerging multitarget tyrosine kinase inhibitors in the treatment of neuroendocrine neoplasms
In the last few years, the therapeutic approach for neuroendocrine neoplasms (NENs) has changed dramatically following the approval of several novel targeted treatments. The multitarget tyrosine kinase inhibitor (MTKI), sunitinib malate, has been approved by Regulatory Agencies in pancreatic NENs. The MTKI class, however, includes several other molecules (approved for other conditions), which are currently being studied in NENs. An in-depth review on the studies published on the MTKIs in neuroendocrine tumors such as axitinib, cabozantinib, famitinib, lenvatinib, nintedanib, pazopanib, sorafenib and sulfatinib was performe...
Source: Endocrine-Related Cancer - July 17, 2018 Category: Endocrinology Authors: Grillo, F., Florio, T., Ferrau, F., Kara, E., Fanciulli, G., Faggiano, A., Colao, A., NIKE Group Tags: Review Source Type: research
Intratumoral androgen levels are linked to TMPRSS2-ERG fusion in prostate cancer
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 dihydrotestosterone (DHT) concentrations were significantly higher in the cancerous tissues compared to benign prostate (P < 0.001). The tissue/seru...
Source: Endocrine-Related Cancer - July 16, 2018 Category: Endocrinology Authors: Knuuttila, M., Mehmood, A., Maki-Jouppila, J., Ryberg, H., Taimen, P., Knaapila, J., Ettala, O., Bostrom, P. J., Ohlsson, C., Venalainen, M. S., Laiho, A., Elo, L. L., Sipila, P., Makela, S. I., Poutanen, M. Tags: Research Source Type: research
