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Adrenocortical cancer

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https://www.readbyqxmd.com/read/28604387/macrolides-selectively-inhibit-mutant-kcnj5-potassium-channels-that-cause-aldosterone-producing-adenoma
#1
Ute I Scholl, Laura Abriola, Chengbiao Zhang, Esther N Reimer, Mark Plummer, Barbara I Kazmierczak, Junhui Zhang, Denton Hoyer, Jane S Merkel, Wenhui Wang, Richard P Lifton
Aldosterone-producing adenomas (APAs) are benign tumors of the adrenal gland that constitutively produce the salt-retaining steroid hormone aldosterone and cause millions of cases of severe hypertension worldwide. Either of 2 somatic mutations in the potassium channel KCNJ5 (G151R and L168R, hereafter referred to as KCNJ5MUT) in adrenocortical cells account for half of APAs worldwide. These mutations alter channel selectivity to allow abnormal Na+ conductance, resulting in membrane depolarization, calcium influx, aldosterone production, and cell proliferation...
June 12, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28601306/disparities-in-access-to-care-and-outcomes-in-patients-with-adrenocortical-carcinoma
#2
Abdulrahman Y Hammad, Tina W F Yen, Azadeh A Carr, Douglas B Evans, Tracy S Wang
BACKGROUND: Surgical resection remains the mainstay of treatment for patients with adrenocortical carcinoma (ACC). The aim of the present study is to examine disparities in access to surgical resection and identify factors associated with overall survival following surgical resection. METHODS: The National Cancer Database was queried for patients with ACC (2004-2013). Patient characteristics and disease details were abstracted. Logistic regression analysis was performed to examine the factors associated with surgical resection, and a multivariate Cox proportional hazards model was used to identify predictors of survival in the surgical cohort...
June 1, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28583923/triple-synchronous-primary-malignancies-a-rare-occurrence
#3
Heather Katz, Hassaan Jafri, Linda Brown, Toni Pacioles
Triple synchronous primary malignant neoplasms are rare. The exact aetiology is unknown; however, risk factors include older age, family history, genetic aberrations, prolonged exposure to carcinogens and smoking. We describe a previously healthy 48-year-old woman who presented with abdominal pain and a palpable abdominal mass. Imaging revealed a complex cystic, solid pelvic mass and another mass in the right upper quadrant. She received an extensive abdominal surgery including exploratory laparotomy, pelvic mass resection, total abdominal hysterectomy, bilateral salpingo-oophorectomy, bilateral pelvic lymphadenectomy, omentectomy and right adrenalectomy...
June 5, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28559412/complete-responses-to-mitotane-in-metastatic-adrenocortical-carcinoma-a-new-look-at-an-old-drug
#4
Diane L Reidy-Lagunes, Betty Lung, Brian R Untch, Nitya Raj, Anastasia Hrabovsky, Ciara Kelly, Scott Gerst, Seth Katz, Lewis Kampel, Joanne Chou, Anu Gopalan, Leonard B Saltz
PURPOSE: Based largely on reports that predate modern reporting standards, mitotane has been considered a systemic treatment option for both hormone control and antitumor control of metastatic adrenocortical cancer (ACC), although the therapeutic window is narrow. METHODS: We searched electronic medical records to identify patients with metastatic ACC treated and prescribed single agent mitotane at Memorial Sloan Kettering Cancer Center from March 15, 1989-September 18, 2015...
May 30, 2017: Oncologist
https://www.readbyqxmd.com/read/28554744/analysis-of-histological-and-immunohistochemical-patterns-of-benign-and-malignant-adrenocortical-tumors-by-computerized-morphometry
#5
Paolo Dalino Ciaramella, Maurizio Vertemati, Duccio Petrella, Edgardo Bonacina, Erika Grossrubatscher, Eleonora Duregon, Marco Volante, Mauro Papotti, Paola Loli
Diagnosis of benign and purely localized malignant adrenocortical lesions is still a complex issue. Moreover, histology-based diagnosis may suffer of a moment of subjectivity due to inter- and intra-individual variations. The aim of the present study was to assess, by computerized morphometry, the morphological features in benign and malignant adrenocortical neoplasms. Eleven adrenocortical adenomas (ACA) were compared with 18 adrenocortical cancers (ACC). All specimens were stained with H&E, cellular proliferation marker Ki-67 and reticulin...
March 9, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28501574/androgen-production-in-pediatric-adrenocortical-tumors-may-occur-via-both-the-classic-and-or-the-alternative-backdoor-pathway
#6
Nesa Marti, Jana Malikova, José A Galván, Maude Aebischer, Marco Janner, Zdenek Sumnik, Barbora Obermannova, Genevieve Escher, Aurel Perren, Christa E Flück
Children with adrenocortical tumors (ACTs) often present with virilization due to high tumoral androgen production, with dihydrotestosterone (DHT) as most potent androgen. Recent work revealed two pathways for DHT biosynthesis, the classic and the backdoor pathway. Usage of alternate routes for DHT production has been reported in castration-resistant prostate cancer, CAH and PCOS. To assess whether the backdoor pathway may contribute to the virilization of pediatric ACTs, we investigated seven children suffering from androgen producing tumors using steroid profiling and immunohistochemical expression studies...
May 10, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28499267/a-novel-germline-tp53-mutation-p-pro190arg-detected-in-a-patient-with-lung-and-bilateral-breast-cancers
#7
Małgorzata Krześniak, Dorota Butkiewicz, Jadwiga Rachtan, Iwona Matuszczyk, Ewa Grzybowska, Marek Rusin
PURPOSE: Li-Fraumeni syndrome (LFS) is a rare genetic disease with strong predispositions to multiple early-onset neoplasms, mostly sarcomas, breast cancers, brain tumors and adrenocortical carcinomas (LFS core cancers). In most LFS families the germline mutations of TP53 tumor suppressor gene were found. Lung cancer does not belong to the core cancers of LFS, however its higher incidence is observed in families with TP53 mutations. Our aim was to search for TP53 mutations in female lung cancer patients whose clinico-demographic characteristics suggested a probable genetic predisposition to the disease...
May 9, 2017: Advances in Medical Sciences
https://www.readbyqxmd.com/read/28471969/long-term-recurrence-free-survival-of-adrenocortical-cancer-extending-into-the-inferior-vena-cava-and-right-atrium-case-report-and-literature-review
#8
REVIEW
Abdulaziz Alghulayqah, Naif Alghasab, Tarik Amin, Nora Alkahtani, Rafif Farhat, Ali S Alzahrani
CONTEXT: Adrenocortical cancer (ACC) is rare but frequently fatal malignancy. Tumor extension into the inferior vena cava signifies an advanced stage (stage III) of the disease and is frequently associated with high risk of recurrence and short-term survival. OBJECTIVE: To present the surgical and medical management of an unusual case of ACC with IVC invasion up to the right atrium. He has the longest reported tumor-free survival of such a situation. We also reviewed and summarized the literature of similar cases...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28450405/unique-and-novel-urinary-metabolomic-features-in-malignant-versus-benign-adrenal-neoplasms
#9
Dhaval Patel, Matthew D Thompson, Soumen K Manna, Kristopher W Krausz, Lisa Zhang, Naris Nilbuol, Frank J Gonzalez, Electron Kebebew
Purpose: <p>Adrenal incidentalomas must be differentiated from adrenocortical cancer (ACC). Currently, size, growth, and imaging characteristics determine the potential for malignancy but are imperfect. The aim was to evaluate whether urinary small molecules (<800 Da) are associated with ACC.</p> <p>Experimental Design:</p> <p>Preoperative fasting urine specimens from patients with ACC (n=19) and benign adrenal tumors (n=46) were analyzed by unbiased ultra performance liquid chromatography/mass spectrometry...
April 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28446715/establishment-of-a-mouse-xenograft-model-of-metastatic-adrenocortical-carcinoma
#10
Aurélie Morin, Carmen Ruggiero, Estelle Robidel, Mabrouka Doghman-Bouguerra, Atze T Das, Rémy Castellano, Emmanuelle Josselin, Judith Favier, Enzo Lalli
Adrenocortical carcinoma is a rare neoplasm with a poor prognosis. Very important advances have been made in the identification of the genetic determinants of adrenocortical carcinoma pathogenesis but our understanding is still limited about the mechanisms that determine cancer spread and metastasis. One major problem hindering preclinical experimentation for new therapies for adrenocortical carcinoma is represented by the lack of suitable animal models for metastatic disease. With the aim to overcome these limitations, in this study we tested several protocols in order to establish a mouse xenograft model of metastatic adrenocortical carcinoma...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445297/the-efficacy-of-radiation-therapy-in-adrenocortical-carcinoma-a-propensity-score-analysis-of-a-population-based-study
#11
You Luo, San-San Chen, Xiang-Guang Zheng, Li Luo, Sen Wang
Adrenocortical carcinoma (ACC) is a rare and malignant tumor. The main treatment is primary surgical resection with or without mitotane therapy. The role of radiation therapy is still controversial. We aim to investigate the survival efficacy of radiotherapy in a large population-based cohort.We queried the Surveillance, Epidemiology, and End Results (SEER) database (1973-2013) to identify cases with ACC. Traditional multivariate Cox regression and propensity score analysis were used to evaluate the effect of radiotherapy on cancer survival...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28432084/topoisomerase2%C3%AE-and-thymidylate-synthase-expression-in-adrenocortical-cancer
#12
Elisa Roca, Alfredo Berruti, Silviu Sbiera, Ida Rapa, Ester Oneda, Paola Sperone, Cristina L Ronchi, Laura Ferrari, Salvatore Grisanti, Antonina Germano, Barbara Zaggia, Giorgio Scagliotti, Martin Fassnacht, Marco Volante, Massimo Terzolo, Mauro Papotti
Topoisomerase II alpha (TOP2A) and Thymidylate Synthase (TS) are known prognostic parameters in several tumors and also predictors of efficacy of anthracyclines, topoisomerase inhibitors and fluoropirimidines, respectively. Expression of TOP2A and TS mRNA was assessed in 98 patients with adrenocortical carcinoma (ACC) and protein expression was assessed by immunohistochemistry in a subset of 39 tumors. Ninety-two patients were radically resected for stage II-III disease and 38 of them received adjuvant mitotane...
April 21, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28431167/performance-of-18f-fdg-pet-ct-in-the-characterization-of-adrenal-masses-in-non-cancer-patients-a-prospective-study
#13
Carole Guerin, François Pattou, Laurent Brunaud, Jean-Christophe Lifante, Eric Mirallié, Magalie Haissaguerre, Damien Huglo, Pierre Olivier, Claire Houzard, Catherine Ansquer, Elif Hindié, Anderson Loundou, Cendrine Archange, Antoine Tabarin, Fréderic Sebag, Karine Baumstarck, David Taïeb
Context: Few prospective studies have evaluated the role of 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the characterization of adrenal masses. Objective: To assess the performance of 18F-FDG PET/CT in the malignancy diagnosis of adrenal masses in non-cancer patients. Design: Prospective multicenter study. Material and methods: The study population consisted of 87 patients (87 adrenal masses) referred to endocrine surgeons: 56 with mass diameter ≥40 mm and 31 with a diameter <40 mm and of indeterminate nature based on unenhanced and washout CT attenuation densities...
April 20, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28421464/a-novel-tp53-mutation-associated-with-twist1-and-sip1-expression-in-an-aggressive-adrenocortical-carcinoma
#14
Daniel Bulzico, Davi Coe Torres, Gerson Moura Ferreira, Bruno Ricardo Barreto Pires, Paulo Antônio Silvestre de Faria, Rocio Hassan, Eliana Abdelhay, Mario Vaisman, Leonardo Vieira Neto
Adrenocortical carcinomas (ACC) are very rare tumors related to TP53 mutations mostly in childhood onset cases. Epithelial-mesenchymal transition (EMT) transcription factors TWIST1 and Smad interacting protein 1 (SIP1) are related to poorer outcomes in other malignancies, but their role in ACC is unknown. We describe a case of an advanced metastatic ACC (Weiss-score of 9) in a patient at age 76. After primary tumor resection, mitotane therapy was started as palliation to low-volume liver metastasis. After a 2-year period of stable disease, the patient died due to brain metastasis...
April 18, 2017: Endocrine Pathology
https://www.readbyqxmd.com/read/28387921/contribution-of-the-tp53-r337h-mutation-to-the-cancer-burden-in-southern-brazil-insights-from-the-study-of-55-families-of-children-with-adrenocortical-tumors
#15
Maria J Mastellaro, Ana L Seidinger, Guolian Kang, Renata Abrahão, Eliana C M Miranda, Stanley B Pounds, Izilda A Cardinalli, Simone S Aguiar, Bonald C Figueiredo, Carlos Rodriguez-Galindo, Silvia R Brandalise, José A Yunes, Antônio de A Barros-Filho, Raul C Ribeiro
BACKGROUND: The tumor protein p53 (TP53) arginine-to-histidine mutation at codon 337 (R337H) predisposes children to adrenocortical tumors (ACTs) and, rarely, to other childhood tumors, but its impact on adult cancer remains undetermined. The objective of this study was to investigate the frequency and types of cancer in relatives of children with ACT who carry the TP53 R337H mutation. METHODS: TP53 R337H testing was offered to relatives of probands with ACT. The parental lineage segregating the R337H mutation was identified in all families...
April 7, 2017: Cancer
https://www.readbyqxmd.com/read/28368424/p53-rb-inhibition-induces-metastatic-adrenocortical-carcinomas-in-a-preclinical-transgenic-model
#16
M Batisse-Lignier, I Sahut-Barnola, F Tissier, T Dumontet, M Mathieu, C Drelon, J-C Pointud, C Damon-Soubeyrand, G Marceau, J-L Kemeny, J Bertherat, I Tauveron, P Val, A Martinez, A-M Lefrançois-Martinez
Adrenocortical carcinoma (ACC) is a rare cancer with poor prognosis. Pan-genomic analyses identified p53/Rb and WNT/β-catenin signaling pathways as main contributors to the disease. However, isolated β-catenin constitutive activation failed to induce malignant progression in mouse adrenocortical tumors. Therefore, there still was a need for a relevant animal model to study ACC pathogenesis and to test new therapeutic approaches. Here, we have developed a transgenic mice model with adrenocortical specific expression of SV40 large T-antigen (AdTAg mice), to test the oncogenic potential of p53/Rb inhibition in the adrenal gland...
April 3, 2017: Oncogene
https://www.readbyqxmd.com/read/28347154/-circulating-micrornas-in-the-diagnostics-of-endocrine-neoplasms
#17
Ábel Decmann, Pál Perge, Zoltán Nagy, Henriett Butz, Attila Patócs, Péter Igaz
MicroRNAs (miRNA, miR) are short - 19-25 nucleotide long - single stranded (in their mature form), non-coding RNA molecules that regulate gene expression mostly at the posttranscriptional level. microRNAs are involved in the regulation of various physiological processes such as cell differentiation and proliferation, development, haematopoesis, cell death, while their aberrant expression is observed in numerous diseases, like autoimmune disorders, inflammations, vascular diseases or tumorigenesis. microRNAs are expressed in a tissue specific fashion...
April 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/28277340/update-on-adrenocortical-carcinoma-management-and-future-directions
#18
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...
June 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
#19
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
#20
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
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