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Adrenocortical cancer

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https://www.readbyqxmd.com/read/28277340/update-on-adrenocortical-carcinoma-management-and-future-directions
#1
Jeena Varghese, Mouhammed Amir Habra
PURPOSE OF REVIEW: To present an update on the management of and future directions in adrenocortical carcinoma (ACC). RECENT FINDINGS: ACC is a rare malignancy with high morbidity and mortality. Surgery remains the mainstay treatment for localized disease, but it is often not feasible in more advanced cases. There is an ongoing controversy about the routine use of adjuvant treatments after surgery. Hormonal overproduction can complicate the management and worsen the prognosis of the disease...
March 8, 2017: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/28249601/a-novel-foxo1-mediated-dedifferentiation-blocking-role-for-dkk3-in-adrenocortical-carcinogenesis
#2
Joyce Y Cheng, Taylor C Brown, Timothy D Murtha, Adam Stenman, C Christofer Juhlin, Catharina Larsson, James M Healy, Manju L Prasad, Wolfram T Knoefel, Andreas Krieg, Ute I Scholl, Reju Korah, Tobias Carling
BACKGROUND: Dysregulated WNT signaling dominates adrenocortical malignancies. This study investigates whether silencing of the WNT negative regulator DKK3 (Dickkopf-related protein 3), an implicated adrenocortical differentiation marker and an established tumor suppressor in multiple cancers, allows dedifferentiation of the adrenal cortex. METHODS: We analyzed the expression and regulation of DKK3 in human adrenocortical carcinoma (ACC) by qRT-PCR, immunofluorescence, promoter methylation assay, and copy number analysis...
March 1, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28146118/jun-dimerization-protein-2-activates-mc2r-transcriptional-activity-role-of-phosphorylation-and-sumoylation
#3
Chiung-Min Wang, Raymond X Wang, Runhua Liu, Wei-Hsiung Yang
Jun dimerization protein 2 (JDP2), a basic leucine zipper transcription factor, is involved in numerous biological and cellular processes such as cancer development and regulation, cell-cycle regulation, skeletal muscle and osteoclast differentiation, progesterone receptor signaling, and antibacterial immunity. Though JDP2 is widely expressed in mammalian tissues, its function in gonads and adrenals (such as regulation of steroidogenesis and adrenal development) is largely unknown. Herein, we find that JDP2 mRNA and proteins are expressed in mouse adrenal gland tissues...
January 31, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28127763/mutational-signature-analysis-identifies-mutyh-deficiency-in-colorectal-cancers-and-adrenocortical-carcinomas
#4
Camilla Pilati, Jayendra Shinde, Ludmil B Alexandrov, Guillaume Assié, Thierry André, Zofia Hélias-Rodzewicz, Romain Doucoudray, Delphine Le Corre, Jessica Zucman-Rossi, Jean-François Emile, Jérôme Bertherat, Eric Letouzé, Pierre Laurent-Puig
Germline alterations in DNA repair genes are implicated in cancer predisposition and can result in characteristic mutational signatures. However, specific mutational signatures associated with base excision repair (BER) defects remain to be characterized. Here, by analysing a series of colorectal cancers (CRC) using exome sequencing, we identified a particular spectrum of somatic mutations characterized by an enrichment of C > A transversions in NpCpA or NpCpT contexts, in three tumours from a MUTYH-associated polyposis (MAP) patient and in two cases harbouring pathogenic germline MUTYH mutations...
January 27, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28114280/rarres2-functions-as-a-tumor-suppressor-by-promoting-%C3%AE-catenin-phosphorylation-degradation-and-inhibiting-p38-phosphorylation-in-adrenocortical-carcinoma
#5
Y Liu-Chittenden, M Jain, K Gaskins, S Wang, M J Merino, S Kotian, S Kumar Gara, S Davis, L Zhang, E Kebebew
Tumor suppressor genes and the immune system are critical players in inhibiting cancer initiation and/or progression. However, little is known about whether a tumor suppressor gene can function through both immune-dependent and -independent mechanisms. Retinoic acid receptor responder 2 (RARRES2) is transcriptionally downregulated in multiple cancer types. Previous studies suggested that it can serve as an immune-dependent tumor suppressor by acting as a chemoattractant to recruit anticancer immune cells expressing its receptor, the chemerin chemokine receptor 1 (CMKLR1), to sites of tumor...
January 23, 2017: Oncogene
https://www.readbyqxmd.com/read/28063163/immediate-versus-modified-release-hydrocortisone-in-mitotane-treated-patients-with-adrenocortical-cancer
#6
Marianne Weigel, Stefanie Hahner, Mark Sherlock, Amar Agha, Lucy Ann Behan, Paul M Stewart, Wiebke Arlt, Daniela Beier, Kathrin Frey, Kathrin Zopf, Marcus Quinkler
OBJECTIVE: Mitotane induces hepatic CYP3A4 activity, resulting in accelerated cortisol inactivation, and also increases cortisol binding globulin (CBG). Therefore, higher hydrocortisone doses are required in patients with adrenocortical cancer (ACC) on mitotane treatment. Modified release hydrocortisone has not been used in mitotane-treated ACC patients yet. AIM: Case series to compare serum cortisol, calculated free serum cortisol and ACTH levels in ACC patients on mitotane treatment with immediate and modified release hydrocortisone...
January 7, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/27988912/clinical-characteristics-of-adrenal-tumors-in-children-a-retrospective-review-of-a-15-year-single-center-experience
#7
Xiaokun Lin, Dazhou Wu, Congde Chen, Na Zheng
OBJECTIVE: Adrenal tumors are rare in children. The aim of this study is to review and analyze clinical data on the diagnosis and management of adrenal tumors in children. METHODS: Between 2001 and 2015, 48 pediatric patients (<14 years old) admitted to our institute with adrenal tumors were reviewed. Clinical features, imaging studies, surgical approaches, as well as pathological diagnoses were recorded. RESULTS: The series comprised 28 males and 20 females...
December 17, 2016: International Urology and Nephrology
https://www.readbyqxmd.com/read/27967600/dna-methylation-is-an-independent-prognostic-marker-of-survival-in-adrenocortical-cancer
#8
Anne Jouinot, Guillaume Assie, Rossella Libe, Martin Fassnacht, Thomas Papathomas, Olivia Barreau, Bruno DE LA Villeon, Simon Faillot, Nadim Hamzaoui, Mario Neou, Karine Perlemoine, Fernande Rene-Corail, Stéphanie Rodriguez, Mathilde Sibony, Frédérique Tissier, Bertrand Dousset, Silviu Sbiera, Cristina Ronchi, Matthias Kroiss, Esther Korpershoek, Ronald DE Krijger, Jens Waldmann, Detlef K Bartsch, Marcus Quinkler, Magalie Haissaguerre, Antoine Tabarin, Olivier Chabre, Nathalie Sturm, Michaela Luconi, Franco Mantero, Massimo Mannelli, Regis Cohen, Véronique Kerlan, Philippe Touraine, Gaelle Barrande, Lionel Groussin, Xavier Bertagna, Eric Baudin, Laurence Amar, Felix Beuschlein, Eric Clauser, Joel Coste, Jérôme Bertherat
CONTEXT: Adrenocortical cancer (ACC) is an aggressive tumor with heterogeneous outcome. Prognostic stratification is difficult even based on tumor stage and Ki67 index. Recently integrated genomics studies have demonstrated that CpG islands hypermethylation is correlated with poor survival. OBJECTIVE: To confirm the prognostic value of CpG islands methylation on an independent cohort with a single commonly available methylation assay. DESIGN: CpG islands methylation was measured by methylation-specific-multiplex-ligation-dependent-probe-amplification (MS-MLPA) using the ME002 kit (MRC-Holland)...
December 14, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27965001/calcifying-nested-stromal-epithelial-tumor-cnset-of-the-liver-in-beckwith-wiedemann-syndrome
#9
REVIEW
Nasim Khoshnam, Haynes Robinson, Michael R Clay, Lauren R Schaffer, Scott E Gillespie, Bahig M Shehata
Calcifying nested stromal-epithelial tumor (CNSET) is a rare neoplasm. In the 31 reported cases, CNSET is predominantly found in young girls and women. Beckwith-Wiedemann syndrome (BWS) (OMIM #130650) is an overgrowth syndrome with an increased risk to develop cancer. Associations have been seen between BWS and embryonal tumors, especially Wilms tumor, hepatoblastoma, and adrenocortical carcinoma. Here we report on a female patient with BWS who presented with CNSET. Two other cases with the same association have been reported, with our case representing the third such reported in the literature...
February 2017: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/27943004/carney-complex-a-familial-lentiginosis-predisposing-to-a-variety-of-tumors
#10
REVIEW
Constantine A Stratakis
Carney complex is a familial lentiginosis syndrome; these disorders cover a wide phenotypic spectrum ranging from a benign inherited predisposition to develop cutaneous spots not associated with systemic disease to associations with several syndromes. Carney complex is caused by PRKAR1A mutations and perturbations of the cyclic AMP-dependent protein kinase (PKA) signaling pathway. In addition to the cutaneous findings, the main tumors associated with Carney complex are endocrine: 1) primary pigmented nodular adrenocortical disease, a bilateral adrenal hyperplasia leading to Cushing syndrome; 2) growth-hormone secreting pituitary adenoma or pituitary somatotropic hyperplasia leading to acromegaly; 3) thyroid and gonadal tumors, including a predisposition to thyroid cancer...
September 2016: Reviews in Endocrine & Metabolic Disorders
https://www.readbyqxmd.com/read/27940298/cell-signaling-pathways-in-the-adrenal-cortex-links-to-stem-progenitor-biology-and-neoplasia
#11
Morgan K Penny, Isabella Finco, Gary D Hammer
The adrenal cortex is a dynamic tissue responsible for the synthesis of steroid hormones, including mineralocorticoids, glucocorticoids, and androgens in humans. Advances have been made in understanding the role of adrenocortical stem/progenitor cell populations in cortex homeostasis and self-renewal. Recently, large molecular profiling studies of adrenocortical carcinoma (ACC) have given insights into proteins and signaling pathways involved in normal tissue homeostasis that become dysregulated in cancer. These data provide an impetus to examine the cellular pathways implicated in adrenocortical disease and study connections, or lack thereof, between adrenal homeostasis and tumorigenesis, with a particular focus on stem and progenitor cell pathways...
April 15, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27899191/genetic-predisposition-to-endocrine-tumors-diagnosis-surveillance-and-challenges-in-care
#12
REVIEW
Elisabeth Joye Petr, Tobias Else
Endocrine tumor syndromes, eg, multiple endocrine neoplasia types 1 and 2, were among the first recognized hereditary predisposition syndromes to tumor development. Over time, the number of endocrine tumor syndromes has significantly expanded, eg, with the recent inclusion of hereditary paraganglioma syndromes. Associations of non-endocrine tumors with hereditary endocrine tumor syndromes and endocrine tumors with non-classical endocrine tumor syndromes have emerged. These findings have certainly expanded the scope of care, necessitating a multidisciplinary approach by a team of medical professionals and researchers, integrating shared patient decision-making at every step of surveillance, diagnosis, and treatment...
October 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/27886397/telomerase-and-n-cadherin-differential-importance-in-adrenocortical-cancers-and-adenomas
#13
Sofia S Pereira, Valdemar Máximo, Ricardo Coelho, Rui Batista, Paula Soares, Susana G Guerreiro, Manuel Sobrinho-Simões, Mariana P Monteiro, Duarte Pignatelli
Adrenocortical carcinomas (ACC) are most frequently highly aggressive tumors. We assessed the telomerase reverse transcriptase (TERT) and N-cadherin role in the biology of ACC and their potential utility as molecular biomarkers, in different types of tumoral adrenocortical tissue. A total of 48 adrenal cortex samples (39 tumoral and 9 normal adrenal glands) were studied. TERT promoter mutations were searched by PCR and Sanger sequencing in two hotspots positions (-124 and -146). Also, telomerase and N-cadherin expression were evaluated by immunohistochemistry...
November 25, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27819856/investigating-the-chemokine-receptor-4-as-potential-theranostic-target-in-adrenocortical-cancer-patients
#14
Christina Bluemel, Stefanie Hahner, Britta Heinze, Martin Fassnacht, Matthias Kroiss, Thorsten A Bley, Hans-Juergen Wester, Saskia Kropf, Constantin Lapa, Andreas Schirbel, Andreas K Buck, Ken Herrmann
PURPOSE: Adrenocortical carcinoma (ACC) is a rare but aggressive endocrine tumor with limited treatment options. Preclinical studies confirmed overexpression of the chemokine receptor 4 (CXCR4) in this cancer type. This study aimed to analyze the role of CXCR4 imaging using Ga-pentixafor for ACC staging and selection of patients for CXCR4-directed endoradiotherapy. METHODS: Thirty patients with histologically proven advanced, metastasized ACC underwent F-FDG PET/CT and Ga-pentixafor PET/CT within a time interval of 3 ± 4 days to evaluate suitability for CXCR4-directed endoradiotherapy...
January 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/27819669/a-cdk2-activity-signature-predicts-outcome-in-cdk2-low-cancers
#15
S R McCurdy, M Pacal, M Ahmad, R Bremner
The role of cyclin-dependent kinase 2 (CDK2) in cancer is controversial. A major hurdle is the availability of tools to easily assess its activity across many samples. Here, we introduce a transcriptional signature to specifically track CDK2 activity. It responds to genetic and chemical perturbations in the CDK-RB-E2F axis, correlates with mitotic rate in vitro and in vivo and reacts rapidly to changes in CDK2 activity during cell cycle progression. We find that CDK2 activity is specifically elevated in human testes, mirroring its critical function in mice, and report very distinct profiles across human cancers...
November 7, 2016: Oncogene
https://www.readbyqxmd.com/read/27771624/non-androgen-secreting-adrenocortical-carcinoma-in-preadolescence-a-case-report-and-literature-review
#16
Hiroko Narumi, Shunji Hasegawa, Kazuyuki Waki, Ken Fukuda, Yuji Ohnishi, Takuya Ichimura, Yousuke Fujimoto, Shunsaku Katsura, Hiroo Kawano, Eiji Ikeda, Satoshi Okada, Shouichi Ohga
Adrenocortical carcinoma (ACC) is a rare malignancy in childhood. Affected children with ACC mostly present with virilization, but not the pure form of Cushing's syndrome. A 9-year-old Japanese girl was hospitalized, because of the unstable emotions and excessive weight gain. She was diagnosed as having Cushing's syndrome and a left adrenal tumor. The adrenalectomy led to the pathological diagnosis of ACC without metastasis. There was no mutation of PRKACA in the tumor-derived DNA, or p53 in peripheral blood-derived DNA...
November 1, 2016: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/27770290/minimally-invasive-resection-of-adrenocortical-carcinoma-a-multi-institutional-study-of-201-patients
#17
Christina W Lee, Ahmed I Salem, David F Schneider, Glen E Leverson, Thuy B Tran, George A Poultsides, Lauren M Postlewait, Shishir K Maithel, Tracy S Wang, Ioannis Hatzaras, Rivfka Shenoy, John E Phay, Lawrence Shirley, Ryan C Fields, Linda X Jin, Timothy M Pawlik, Jason D Prescott, 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, Sharon M Weber
BACKGROUND AND OBJECTIVES: Minimally invasive surgery for adrenocortical carcinoma (ACC) is controversial. We sought to evaluate the perioperative and long-term outcomes following minimally invasive (MIS) and open resection (OA) of ACC in patients treated with curative intent surgery. METHODS: Retrospective data from patients who underwent adrenalectomy for primary ACC at 13 tertiary care cancer centers were analyzed, including demographics, clinicopathological, and operative outcomes...
February 2017: Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract
https://www.readbyqxmd.com/read/27750238/us-us-fusion-imaging-in-radiofrequency-ablation-for-liver-metastases
#18
Yasunori Minami, Tomohiro Minami, Hirokazu Chishina, Masashi Kono, Tadaaki Arizumi, Masahiro Takita, Norihisa Yada, Satoru Hagiwara, Hiroshi Ida, Kazuomi Ueshima, Naoshi Nishida, Masatoshi Kudo
OBJECTIVE: Radiofrequency ablation (RFA) induces gas bubbles in ablation zones, and the ablative margin cannot be evaluated accurately on ultrasound (US) during and immediately after RFA. This study assessed the usefulness of US-US fusion imaging to visualize the ablative margin of RFA for liver metastasis. METHODS: RFA guided by US-US fusion imaging was performed on 12 targeted tumors in 10 patients. Secondary hepatic malignancies included patients with colorectal cancer (n = 4), breast cancer (n = 2), lung cancer (n = 1), gastrointestinal stromal tumor (n = 1), pancreatic neuroendocrine tumor (n = 1), and adrenocortical carcinoma (n = 1)...
2016: Digestive Diseases
https://www.readbyqxmd.com/read/27742785/adrenocortical-cancer-a-molecularly-complex-disease-where-surgery-matters
#19
Eden C Payabyab, Sanjeeve Balasubramaniam, Maureen Edgerly, Margarita Velarde, Maria J Merino, Aradhana M Venkatesan, Harshraj Leuva, Thomas Litman, Susan E Bates, Tito Fojo
The development of new therapies has lagged behind for rare cancers without defined therapeutic targets. Adrenocortical cancer is no exception. Mitotane, an older agent considered "adrenolytic," is used both to control symptoms in advanced disease and as adjuvant therapy after surgical resection. Molecular characterization of adrenocortical cancer has deepened our understanding of this genetically complex disease while identifying subgroups whose importance remains to be determined. Unfortunately, such studies have yet to demonstrate a therapeutic target for drug development, and to date, no targeted therapy has achieved meaningful outcomes...
October 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27725909/cell-cycle-dependent-rrm2-may-serve-as-proliferation-marker-and-pharmaceutical-target-in-adrenocortical-cancer
#20
Vince Kornél Grolmusz, Katalin Karászi, Tamás Micsik, Eszter Angéla Tóth, Katalin Mészáros, Gellért Karvaly, Gábor Barna, Péter Márton Szabó, Kornélia Baghy, János Matkó, Ilona Kovalszky, Miklós Tóth, Károly Rácz, Péter Igaz, Attila Patócs
Adrenocortical cancer (ACC) is a rare, but agressive malignancy with poor prognosis. Histopathological diagnosis is challenging and pharmacological options for treatment are limited. By the comparative reanalysis of the transcriptional malignancy signature with the cell cycle dependent transcriptional program of ACC, we aimed to identify novel biomarkers which may be used in the histopathological diagnosis and for the prediction of therapeutical response of ACC. Comparative reanalysis of publicly available microarray datasets included three earlier studies comparing transcriptional differences between ACC and benign adrenocortical adenoma (ACA) and one study presenting the cell cycle dependent gene expressional program of human ACC cell line NCI-H295R...
2016: American Journal of Cancer Research
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