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Adrenocortical carcinoma

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https://www.readbyqxmd.com/read/28819017/adrenocortical-carcinoma-and-succinate-dehydrogenase-gene-mutations
#1
Tobias Else, Antonio Marcondes Lerario, Jessica Everett, Lori Haymon, Deborah Wham, Michael Mullane, Tremika LeShan Wilson, Irene Rainville, Huma Rana, Andrew J Worth, Nathaniel W Snyder, Ian A Blair, Rana McKay, Kerry Kilbridge, Gary D Hammer, Justine Barletta, Anand Vaiyda
OBJECTIVE: Germline loss-of-function mutations in succinate dehydrogenase (SDHx) genes results in rare tumor syndromes that include pheochromocytoma, paraganglioma, and others. Here we report a case series of patients with adrenocortical carcinoma (ACC) that harbor SDHx germline mutations. PATIENTS AND RESULTS: We report four unrelated patients with ACC and SDHx mutations. All cases presented with Cushing syndrome and large adrenal masses that were confirmed to be ACC on pathology...
August 17, 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28814383/high-resolution-accurate-mass-hram-mass-spectrometry-urine-steroid-profiling-in-the-diagnosis-of-adrenal-disorders
#2
Jolaine M Hines, Irina Bancos, Cristian Bancos, Raman D Singh, Aditya V Avula, William F Young, Stefan K Grebe, Ravinder J Singh
BACKGROUND: Steroid profiling is a promising diagnostic tool for those with adrenal tumors, Cushing syndrome (CS), and disorders of steroidogenesis. Our objective was to develop a multiple-steroid assay using liquid-chromatography, high-resolution, accurate-mass mass spectrometry (HRAM LC-MS) and to validate the assay in patients with various adrenal disorders. METHODS: We collected 24-h urine samples from 114 controls and 71 patients with adrenal diseases. An HRAM LC-MS method was validated for quantitative analysis of 26 steroid metabolites in hydrolyzed urine samples...
August 16, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28809444/circannual-variation-of-mitotane-and-its-metabolites-plasma-levels-in-patients-with-adrenocortical-carcinoma
#3
Jessica Cusato, Silvia De Francia, Sarah Allegra, Simona Carrella, Elisa Pirro, Francesca Maria Piccione, Francesca De Martino, Anna Ferrero, Fulvia Claudia Daffara, Massimo Terzolo, Alfredo Berruti, Francesco Di Carlo, Marco Tampellini, Antonio D'Avolio
OBJECTIVES: Mitotane is the reference drug for the adrenocortical carcinoma treatment; its pharmacological activity seems to depend on drug transformation in two active metabolites: o,p'-DDE (dichlorodiphenylethene) and o,p'-DDA (dichlorodiphenylacetate). Mitotane and metabolites are lipophilic agents; thus, they tend to accumulate into adipose tissues (white and brown), which change their prevalence seasonally. Aim of the work was to evaluate mitotane and metabolites plasma levels variation over the year, in adrenocortical cancer patients treated with Lysodren(®) for at least 6 months...
August 15, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28804590/feminizing-adrenocortical-carcinoma-without-gynecomastia
#4
Farida Chentli, Fadila Chabour, Djafer Bouchibane, Nouria Nouar
Malignant feminizing adrenocortical tumors are exceedingly rare. Their main presentation is gynecomastia. In these estrogen secreting tumors (with or without other adrenocortical hormones) lack of gynecomastia is exceptional as in our case. A 44-year-old man presented with abdominal pain. Radiological assessment revealed a tumor measuring 120 × 95 mm in the retroperitoneal area with numerous metastases. Pathological examination pleaded for an adrenal origin with a Weiss's score of 5. Six months later, the tumor relapsed, and he had a second surgery and was sent for hormone assessment...
July 2017: Oman Medical Journal
https://www.readbyqxmd.com/read/28801373/metformin-and-melatonin-in-adrenocortical-carcinoma-morphoproteomics-and-biomedical-analytics-provide-proof-of-concept-in-a-case-study
#5
Robert E Brown, Jamie Buryanek, Mary F McGuire
Metformin has been proposed as a novel anti-cancer drug for adrenocortical carcinoma (ACC) based upon Poli's recent preclinical studies that 1. "in vitro" metformin modulates the ACC cell model H295R and 2. "in vivo" metformin inhibits tumor growth in a xenograft model as confirmed by a significant reduction of Ki67 [1]. Here we report on our prior clinical case study that provides proof of concept for Poli's studies. We were requested to perform morphoproteomic analysis to further define the biology of, and raise targeted therapeutic options, for a case of post-treatment and chemoresistant ACC metastatic to the liver and the lung...
August 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/28801349/c-myc-expression-in-adrenocortical-tumours
#6
Mirkka Pennanen, Jaana Hagström, Ilkka Heiskanen, Timo Sane, Harri Mustonen, Johanna Arola, Caj Haglund
AIMS: Widespread use of high-resolution imaging techniques and thus increased prevalence of adrenal lesions has made diagnostics of adrenocortical tumours an increasingly important clinical issue. In non-metastatic tumours, diagnosis is based on histology. New or enhanced information for clinicopathological diagnosis, revealing the malignant potential of the tumour, could emerge by means of biomarkers. The connection of proto-oncogene c-myc to adrenocortical neoplasias is poorly known, although the Wnt/beta-catenin pathway, one of the signalling pathways leading to induction of c-myc expression, has been connected to development of adrenocortical neoplasias...
August 11, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28780517/mitotane-effects-on-the-hypothalamic-pituitary-adrenal-axis-in-patients-with-adrenocortical-carcinoma
#7
Giuseppe Reimondo, Soraya Puglisi, Barbara Zaggia, Vittoria Basile, Laura Saba, Paola Perotti, Silvia De Francia, Marco Volante, Maria Chiara Zatelli, Salvatore Cannavò, M Terzolo
OBJECTIVE: Mitotane, a drug used to treat adrenocortical cancer (ACC), inhibits multiple enzymatic steps of adrenocortical steroid biosynthesis, potentially causing adrenal insufficiency. Recent studies in vitro have also documented a direct inhibitory effect of mitotane at the pituitary level. The present study was aimed to assess the hypothalamic pituitary adrenal axis in ACC patients receiving mitotane. DESIGN AND METHODS: We prospectively enrolled 16 patients on adjuvant treatment with mitotane after radical surgical resection of ACC, who underwent standard hormone evaluation and h-CRH stimulation...
August 5, 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28756477/p53-signaling-pathway-polymorphisms-cancer-risk-and-tumor-phenotype-in-tp53-r337h-mutation-carriers
#8
Gabriel S Macedo, Igor Araujo Vieira, Fernanda Salles Luiz Vianna, Barbara Alemar, Juliana Giacomazzi, Ana Paula Carneiro Brandalize, Maira Caleffi, Sahlua Miguel Volc, Henrique de Campos Reis Galvão, Edenir Inez Palmero, Maria Isabel Achatz, Patricia Ashton-Prolla
Li-Fraumeni and Li-Fraumeni-like syndrome (LFS/LFL) are clinically heterogeneous cancer predisposition syndromes characterized by diagnosis of early-onset and often multiple cancers with variable tumor patterns and incomplete penetrance. To date, the genetic modifiers described in LFS/LFL have been shown to map to either TP53 or its main negative regulator, MDM2. Additionally, all studies were focused on families with different TP53 germline mutations. Hence, in this study we explored the effect of the most studied polymorphisms of p53 pathway genes on clinical manifestations of individuals carrying the founder TP53 mutation R337H (n = 136) and controls (n = 186)...
July 29, 2017: Familial Cancer
https://www.readbyqxmd.com/read/28754418/surgical-treatment-of-adrenal-carcinoma
#9
S Gaujoux, M Weinandt, S Bonnet, V Reslinger, J Bertherat, B Dousset
Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis. The presence of a mass syndrome or signs of hormonal hypersecretion often lead to its discovery, but more and more frequently, adrenocortical malignancy is fortuitously discovered as an incidentaloma. Cross-sectional imaging (CT and MRI) often points to the malignant character of the adrenal mass. Needle biopsy is contraindicated. Laboratory testing showing combined hypersecretion of cortisol, androgens or inactive corticosteroid precursors is highly suggestive of ACC...
July 25, 2017: Journal of Visceral Surgery
https://www.readbyqxmd.com/read/28753846/the-landscape-of-whole-genome-alterations-and-pathologic-features-in-genitourinary-malignancies-an-analysis-of-the-cancer-genome-atlas
#10
Mark W Ball, Michael A Gorin, Charles G Drake, Hans J Hammers, Mohamad E Allaf
BACKGROUND: The accumulation of somatic genetic alterations drives carcinogenesis. Little is known, however, about how the level of genetic alteration across an entire cancer genome affects tumor grade, stage or survival. OBJECTIVE: To investigate the influence of somatic mutation count (MC) and copy number variation (CNV) on pathologic and oncologic outcomes in patients with genitourinary malignancies in The Cancer Genome Atlas (TCGA). DESIGN, SETTING, AND PARTICIPANTS: TCGA data sets for adrenocortical carcinoma (ACC), bladder urothelial carcinoma (BLCA), chromophobe renal cell carcinoma (RCC; KICH), clear cell RCC (KIRC), papillary RCC (KIRP), pheochromocytoma and paraganglioma (PCPG), prostate adenocarcinoma (PRAD), and testis germ cell tumor (TGCT) were accessed via cBioportal...
February 8, 2017: European Urology Focus
https://www.readbyqxmd.com/read/28750898/the-use-of-a-unique-co-culture-model-of-fetoplacental-steroidogenesis-as-a-screening-tool-for-endocrine-disruptors-the-effects-of-neonicotinoids-on-aromatase-activity-and-hormone-production
#11
Elyse Caron-Beaudoin, Rachel Viau, Andrée-Anne Hudon-Thibeault, Cathy Vaillancourt, J Thomas Sanderson
Estrogen biosynthesis during pregnancy is dependent on the collaboration between the fetus producing the androgen precursors, and the placenta expressing the enzyme aromatase (CYP19). Disruption of estrogen production by contaminants may result in serious pregnancy outcomes. We used our recently developed in vitro co-culture model of fetoplacental steroidogenesis to screen the effects of three neonicotinoid insecticides on the catalytic activity of aromatase and the production of steroid hormones. A co-culture of H295R human adrenocortical carcinoma cells with fetal characteristics and BeWo human choriocarcinoma cells which display characteristics of the villous cytotrophoblast was exposed for 24h to various concentrations of three neonicotinoids: thiacloprid, thiamethoxam and imidacloprid...
July 24, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28739615/primary-bilateral-adrenal-nodular-disease-with-cushing-s-syndrome-varying-aetiology
#12
Kush Dev Singh Jarial, Rama Walia, Uma Nahar, Anil Bhansali
Primary adrenal disorders contribute 20%â€"30% of patients with endogenous Cushing's syndrome. Most of the primary adrenal diseases are unilateral and include adenoma and adrenocortical carcinoma, whereas bilateral adrenal lesions are uncommon and include primary pigmented nodular adrenocortical disease, primary bilateral macronodular adrenocortical hyperplasia, isolated micronodular adrenocortical disease, bilateral adenomas or carcinomas, and rarely pituitary adrenocorticotropic hormone-dependent adrenal nodular disease...
July 24, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28738949/blood-transfusion-and-survival-for-resected-adrenocortical-carcinoma-a-study-from-the-united-states-adrenocortical-carcinoma-group
#13
Caroline E Poorman, Lauren M Postlewait, Cecilia G Ethun, Thuy B Tran, Jason D Prescott, Timothy M Pawlik, Tracy S Wang, Jason Glenn, Ioannis Hatzaras, Rivfka Shenoy, John E Phay, Kara Keplinger, Ryan C Fields, Linda X Jin, Sharon M Weber, Ahmed Salem, Jason K Sicklick, Shady Gad, Adam C Yopp, John C Mansour, Quan-Yang Duh, Natalie Seiser, Carmen C Solorzano, Colleen M Kiernan, Konstantinos I Votanopoulos, Edward A Levine, Charles A Staley, George A Poultsides, Shishir K Maithel
Perioperative blood transfusion is associated with decreased survival in pancreatic, gastric, and liver cancer. The effect of transfusion in adrenocortical carcinoma (ACC) has not been studied. Patients with available transfusion data undergoing curative-intent resection of ACC from 1993 to 2014 at 13 institutions comprising the United States Adrenocortical Carcinoma Group were included. Factors associated with blood transfusion were determined. Primary and secondary end points were recurrence-free survival (RFS) and overall survival (OS), respectively...
July 1, 2017: American Surgeon
https://www.readbyqxmd.com/read/28737576/hereditary-leiomyomatosis-and-renal-cell-carcinoma-syndrome-combined-with-adrenocortical-carcinoma-on-18f-fdg-pet-ct
#14
Xiuyu Guo, Haojun Chen, Hao Fu, Hua Wu
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome is a recognized distinct phenotypic variant of multiple cutaneous and uterine leiomyomatosis. The present case reports an extremely rare case of HLRCC syndrome combined with adrenocortical carcinoma. The case suggests that HLRCC should be considered in any young patient with bulky uterine leiomyomas and renal cell cancer, and F-FDG PET/CT can help detect unexpected additional primary malignancy in a patient with known cancer.
September 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28727379/adjuvant-radiotherapy-for-the-primary-treatment-of-adrenocortical-carcinoma-are-we-offering-the-best
#15
Victor Srougi, Jose Bessa, Fabio Y Tanno, Amanda M Ferreira, Ana O Hoff, João E Bezerra, Cristiane M Almeida, Madson Q Almeida, Berenice B Mendonça, William C Nahas, Jose L Chambô, Miguel Srougi, Maria C B V Fragoso
PURPOSE: To evaluate the role of ARDT after surgical resection of ACC. MATERIALS AND METHODS: Records of patients from our institutional ACC database were retrospectively assessed. A paired comparison analysis was used to evaluate the oncological outcomes between patients treated with surgery followed by ARDT or surgery only (control). The endpoints were LRFS, RFS, and OS. A systematic review of the literature and meta-analysis was also performed to evaluate local recurrence of ACC when ARDT was used...
June 14, 2017: International Braz J Urol: Official Journal of the Brazilian Society of Urology
https://www.readbyqxmd.com/read/28710789/atr-101-inhibits-cholesterol-efflux-and-cortisol-secretion-by-abc-transporters-causing-cytotoxic-cholesterol-accumulation-in-adrenocortical-carcinoma-cells
#16
Veronica Elizabeth Burns, Tom Klaus Kerppola
BACKGROUND AND PURPOSE: To further the development of new agents for the treatment of adrenocortical carcinoma (ACC), we characterized the molecular and cellular mechanisms of cytotoxicity by the adrenalytic compound ATR-101 (PD132301-02). EXPERIMENTAL APPROACH: We compared the effects of ATR-101, PD129337, and ABC transporter inhibitors, on cholesterol accumulation and efflux, on cortisol secretion, on ATP levels, and on caspase activation in ACC-derived cell lines...
July 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28706747/adrenal-rest-tumor-of-the-liver-preoperatively-diagnosed-as-hepatocellular-carcinoma
#17
Megumu Enjoji, Katsuya Sanada, Ryota Seki, Takashi Ito, Masato Maeda
BACKGROUND: Hepatic adrenal rest tumors are rare and show similar findings to hepatocellular carcinoma (HCC). It is difficult to distinguish an adrenal rest tumor from HCC due to radiological similarity. We report a case of an adrenal rest tumor in the liver that mimicked HCC radiologically. CASE PRESENTATION: A 67-year-old female was referred to our hospital due to the finding of a hepatic mass. Enhanced computed tomography revealed a 17 mm well-defined tumor that was enhanced in the arterial phase and washed out in the portal and delayed phase in the posterosuperior subsegment of the right hepatic lobe, and HCC was suspected...
2017: Case Reports in Surgery
https://www.readbyqxmd.com/read/28699986/diagnosis-and-management-of-primary-aldosteronism
#18
Leticia A P Vilela, Madson Q Almeida
Primary aldosteronism (PA) is the most common form of secondary hypertension (HTN), with an estimated prevalence of 4% of hypertensive patients in primary care and around 10% of referred patients. Patients with PA have higher cardiovascular morbidity and mortality than age- and sex-matched patients with essential HTN and the same degree of blood pressure elevation. PA is characterized by an autonomous aldosterone production causing sodium retention, plasma renin supression, HTN, cardiovascular damage, and increased potassium excretion, leading to variable degrees of hypokalemia...
May 2017: Archives of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28698403/identifying-mitotane-induced-mitochondria-associated-membranes-dysfunctions-metabolomic-and-lipidomic-approaches
#19
Ségolène Hescot, Larbi Amazit, Marie Lhomme, Simon Travers, Anais DuBow, Stéphanie Battini, Geoffrey Boulate, Izzie Jacques Namer, Anne Lombès, Anatol Kontush, Alessio Imperiale, Eric Baudin, Marc Lombès
Mitotane (o,p'DDD), the most effective drug in adrenocortical carcinoma, concentrates into the mitochondria and impacts mitochondrial functions. To address the molecular mechanisms of mitotane action and to identify its potential target, metabolomic and lipidomic approaches as well as imaging analyses were employed in human adrenocortical H295R cells allowing identification of Mitochondria-Associated Membranes dysfunction as a critical impact of mitotane. Study of intracellular energetic metabolites by NMR spectroscopy showed that mitotane significantly decreased aspartate while concomitantly increased glutamate content in a time- and concentration-dependent manner...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28695321/angiogenesis-and-lymphangiogenesis-in-the-adrenocortical-tumors
#20
Sofia S Pereira, Madalena M Costa, Susana G Guerreiro, Mariana P Monteiro, Duarte Pignatelli
Adrenocortical tumors (ACT) are common adrenal tumors. The majority of ACTs are non-functioning and benign, while adrenocortical carcinomas (ACC) are rare, usually very aggressive and often metastasized when first diagnosed. Our aim was to assess whether blood and lymph vessel density within ACTs correlate with the malignancy character or tumor functionality. For that, the microvascular distribution was evaluated by immunohistochemistry staining with D2-40 antibody, for lymph vessels and CD-31 antibody, for blood vessels, in ACCs (n = 15), adenomas with Cushing syndrome (n = 9) and non-functioning adenomas (n = 10)...
July 10, 2017: Pathology Oncology Research: POR
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