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Adrenocortical carcinoma

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https://www.readbyqxmd.com/read/29035537/discovery-of-a-novel-piperidine-based-inhibitor-of-cholesteryl-ester-transfer-protein-cetp-that-retains-activity-in-hypertriglyceridemic-plasma
#1
Ken Yamada, Margaret Brousseau, Wataru Honma, Akiko Iimura, Hidetomo Imase, Yuki Iwaki, Toshio Kawanami, Daniel LaSala, Guiqing Liang, Hironobu Mitani, Kazuhiko Nonomura, Osamu Ohmori, Meihui Pan, Dean F Rigel, Ichiro Umemura, Kayo Yasoshima, Guoming Zhu, Muneto Mogi
Herein we describe the discovery and characterization of a novel, piperidine-based inhibitor of cholesteryl ester transfer protein (CETP) with a core structure distinct from other reported CETP inhibitors. A versatile synthesis starting from 4-methoxypyridine enabled an efficient exploration of the SAR, giving a lead molecule with potent CETP inhibition in human plasma. The subsequent optimization focused on improvement of pharmacokinetics and mitigation of off-target liabilities, such as CYP inhibition, whose improvement correlated with increased lipophilic efficiency...
October 16, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29028646/advances-in-understanding-the-molecular-underpinnings-of-adrenocortical-tumors
#2
Norman G Nicolson, Jianling Man, Tobias Carling
PURPOSE OF REVIEW: Adrenocortical tumors are divided into benign adenomas and malignant carcinomas. The former is relatively common and carries a favorable prognosis, whereas the latter is rare and frequently presents at an advanced stage, with poor outcomes. Advances in next-generation sequencing, genome analysis, and bioinformatics have allowed for high-throughput molecular characterization of adrenal tumorigenesis. RECENT FINDINGS: Although recent genomic, epigenomic, and transcriptomic studies in large tumor cohorts have confirmed the central roles of aberrant Wnt/ß-catenin signaling, constitutive protein kinase A pathway activation, cell cycle dysregulation, and ion channelopathies in adrenal tumorigenesis, these studies also revealed novel signature events underlying malignant differentiation of adrenocortical carcinomas...
October 11, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/29022106/minimally-invasive-adrenalectomy-for-adrenocortical-carcinoma-five-year-trends-and-predictors-of-conversion
#3
Natalie A Calcatera, Chi Hsiung-Wang, Nicholas R Suss, David J Winchester, Tricia A Moo-Young, Richard A Prinz
BACKGROUND: Adrenocortical carcinoma (ACC) is rare but often fatal. Surgery offers the only chance of cure. As minimally invasive (MI) procedures for cancer become common, their role for ACC is still debated. We reviewed usage of MI approaches for ACC over time and risk factors for conversion using a large national database. METHODS: ACC patients with localized disease were identified in the National Cancer Data Base from 2010 to 2014. A retrospective review examined trends in the surgical approach over time...
October 11, 2017: World Journal of Surgery
https://www.readbyqxmd.com/read/28989884/diagnosis-of-adrenocortical-tumors-by-reticulin-algorithm
#4
Daphne Fonseca, Sudha S Murthy, K Ravindranath Tagore, B Vishal Rao, Subramanyeshwar Rao Thamminedi, K V V N Raju, Rakesh Sharma, Sundaram Challa
AIMS: To apply reticulin algorithm (RA) to the diagnosis of adrenocortical tumors on adrenalectomy specimens and compare its efficacy to the modified Weiss criteria or Lin-Weiss-Bisceglia (LWB) criteria for oncocytic variant. MATERIALS AND METHODS: Adrenocortical tumors (ACTs) diagnosed on resected specimens including the variants during January 2010-June 2016 were retrieved from the pathology records. The demographic and clinical data were obtained from medical records...
September 2017: Indian Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28973495/identification-of-mutations-in-cell-free-circulating-tumor-dna-in-adrenocortical-carcinoma-a-case-series
#5
Sara G Creemers, Esther Korpershoek, Peggy N Atmodimedjo, Winand N M Dinjens, Peter M van Koetsveld, Richard A Feelders, Leo J Hofland
Context: The disease course of adrenocortical carcinoma (ACC) patients is heterogeneous. A marker for prognosis and treatment response would facilitate choices on diagnosis and therapy. In other cancer types, circulating cell-free tumor DNA (ctDNA) predicted tumor dynamics. Case descriptions: This pilot study included six patients. Next-generation sequencing (NGS) showed mutations in 3 ACCs. From these patients, blood was drawn before (1-2 weeks) and after surgery, from which cell-free circulating DNA (cfDNA) was isolated...
June 30, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28972963/a-phase-1-study-of-arq-087-an-oral-pan-fgfr-inhibitor-in-patients-with-advanced-solid-tumours
#6
K P Papadopoulos, B F El-Rayes, A W Tolcher, A Patnaik, D W Rasco, R D Harvey, P M LoRusso, J C Sachdev, G Abbadessa, R E Savage, T Hall, B Schwartz, Y Wang, J Kazakin, W L Shaib
BACKGROUND: ARQ 087 is an orally administered pan-FGFR inhibitor with multi-kinase activity. This Phase 1 study evaluated safety, pharmacokinetics, and pharmacodynamics of ARQ 087 and defined the recommended Phase 2 dose (RP2D). METHODS: Patients with advanced solid tumours received ARQ 087 administered initially at 25 mg every other day and dose-escalated from 25 to 425 mg daily (QD) continuous dosing. FGF19, 21, 23, and serum phosphate were assessed as potential biomarkers of target engagement...
October 3, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28968749/omics-analysis-system-for-precision-oncology-oasispro-a-web-based-omics-analysis-tool-for-clinical-phenotype-prediction
#7
Kun-Hsing Yu, Michael R Fitzpatrick, Luke Pappas, Warren Chan, Jessica Kung, Michael Snyder
Summary: Precision oncology is an approach that accounts for individual differences to guide cancer management. Omics signatures have been shown to predict clinical traits for cancer patients. However, the vast amount of omics information poses an informatics challenge in systematically identifying patterns associated with health outcomes, and no general-purpose data-mining tool exists for physicians, medical researchers, and citizen scientists without significant training in programming and bioinformatics...
September 12, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28954751/unilateral-adrenal-mass-as-the-sole-initial-manifestation-of-differentiated-thyroid-cancer
#8
Geethalakshmi Sampathkumar, Arun S Menon, Bindhu M R, Vasantha Nair
Unilateral adrenal metastases without disseminated disease has rarely been reported in differentiated thyroid carcinoma (DTC). A 72-year-old female presented with vague abdominal discomfort and loss of appetite of 2 months duration. She had undergone left hemithyroidectomy for a benign thyroid nodule 18 years ago. A contrast CT of the abdomen showed a large left adrenal mass measuring 11×9 cm, suspicious of adrenocortical carcinoma. Hormonal evaluation was in keeping with a non-functional tumour. The patient underwent left adrenalectomy, histopathology of which revealed metastatic well-differentiated thyroid carcinoma...
September 27, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28943972/small-non-coding-rna-abundance-in-adrenocortical-carcinoma-a-footprint-of-a-rare-cancer
#9
Srinivas V Koduru, Ashley N Leberfinger, Dino J Ravnic
BACKGROUND: Adrenocortical carcinoma (ACC) is a relatively rare, but aggressive type of cancer, which affects both children and adults. OBJECTIVE: Small non-coding RNAs (sncRNAs) play important roles and may serve as biomarkers for disease diagnosis, prognosis and treatment. METHODS: In our study, we sought to identify sncRNAs associated with malignant adrenal tumors. We obtained publicly available, small RNA sequencing data derived from 45 ACC and 30 benign tumors arising from the cortex of the adrenal gland, adrenocortical adenomas (ACA), and compared their sncRNA expression profiles...
2017: Journal of Genomics
https://www.readbyqxmd.com/read/28940135/ectopic-retroperitoneal-adrenocortical-carcinoma-in-the-setting-of-lynch-syndrome
#10
Jesse P Wright, Kathleen W Montgomery, Joshua Tierney, Jill Gilbert, Carmen C Solórzano, Kamran Idrees
Adrenocortical carcinoma (ACC) is rare within the adult population. Ectopic ACC proves even rarer. This variant is formed by cortical fragments arrested during embryologic migration. ACC is also known to be associated with several genetic syndromes and has recently been linked to Lynch syndrome in 3% of cases. We present the case of a 68-year-old male with a confirmed diagnosis of Lynch syndrome secondary to a germline MSH2 mismatch-repair gene-mutation who presented with 2 months history of non-specific abdominal pain...
September 22, 2017: Familial Cancer
https://www.readbyqxmd.com/read/28919755/synthetic-high-density-lipoprotein-nanodisks-for-targeted-withalongolide-delivery-to-adrenocortical-carcinoma
#11
Rui Kuai, Chitra Subramanian, Peter T White, Barbara N Timmermann, James J Moon, Mark S Cohen, Anna Schwendeman
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy and has a 5-year survival rate of <35%. ACC cells require cholesterol for steroid hormone production, and this requirement is met via expression on the cell surface of a high level of SRB1, responsible for the uptake of high-density lipoproteins (HDLs), which carry and transport cholesterol in vivo. Here, we describe how this natural lipid carrier function of SRB1 can be utilized to improve the tumor-targeted delivery of a novel natural product derivative - withalongolide A 4,19,27-triacetate (WGA-TA) - which has shown potent antitumor efficacy, but poor aqueous solubility...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28919607/impact-of-adrenocortical-insufficiency-on-clinical-parameters-in-haemodynamically-stable-cirrhotic-patients-with-ascites
#12
H Ahmed, M R Karim, R K Paul, M Chowdhury, M S Alam, A Saha, F Rahman, M A Rouf
Cirrhosis has many complications regardless of the aetiology. Complications include splenomegaly, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome and hepatocellular carcinoma and also linked to abnormalities in the endocrine system, including abnormal sex hormone metabolism, thyroid disease, osteoporosis, and, most recently identified, adrenal insufficiency. This prospective cohort study was done to evaluate the impact of adrenocortical insufficiency on clinical parameters in haemodynamically stable cirrhotic patients with ascites and had been performed at the inpatient of GHPD Department, BIRDEM, Dhaka, Bangladesh from April 2011 to March 2012...
July 2017: Mymensingh Medical Journal: MMJ
https://www.readbyqxmd.com/read/28911143/assessment-of-vav2-expression-refines-prognostic-prediction-in-adrenocortical-carcinoma
#13
MULTICENTER STUDY
Silviu Sbiera, Iuliu Sbiera, Carmen Ruggiero, Mabrouka Doghman-Bouguerra, Esther Korpershoek, Ronald R de Krijger, Hester Ettaieb, Harm Haak, Marco Volante, Mauro Papotti, Giuseppe Reimondo, Massimo Terzolo, Michaela Luconi, Gabriella Nesi, Massimo Mannelli, Rossella Libé, Bruno Ragazzon, Guillaume Assié, Jérôme Bertherat, Barbara Altieri, Guido Fadda, Natalie Rogowski-Lehmann, Martin Reincke, Felix Beuschlein, Martin Fassnacht, Enzo Lalli
Context: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with overall poor prognosis. The Ki67 labeling index (LI) has a major prognostic role in localized ACC after complete resection, but its estimates may suffer from considerable intra- and interobserver variability. VAV2 overexpression induced by increased Steroidogenic Factor-1 dosage is an essential factor driving ACC tumor cell invasion. Objective: To assess the prognostic role of VAV2 expression in ACC by investigation of a large cohort of patients...
September 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28904054/a-13-steroid-serum-panel-based-on-lc-ms-ms-use-in-detection-of-adrenocortical-carcinoma
#14
David R Taylor, Lea Ghataore, Lewis Couchman, Royce P Vincent, Ben Whitelaw, Dylan Lewis, Salvador Diaz-Cano, Gabriele Galata, Klaus-Martin Schulte, Simon Aylwin, Norman F Taylor
BACKGROUND: Adrenocortical carcinoma (ACC) is a rare malignancy, with an annual incidence of 1 or 2 cases per million. Biochemical diagnosis is challenging because up to two-thirds of the carcinomas are biochemically silent, resulting from de facto enzyme deficiencies in steroid hormone biosynthesis. Urine steroid profiling by GC-MS is an effective diagnostic test for ACC because of its capacity to detect and quantify the increased metabolites of steroid pathway synthetic intermediates...
September 13, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28895102/the-impact-of-nodal-dissection-on-staging-in-adrenocortical-carcinoma
#15
Suraj Panjwani, Maureen D Moore, Katherine D Gray, Brendan M Finnerty, Toni Beninato, Laurent Brunaud, Thomas J Fahey, Rasa Zarnegar
BACKGROUND: The role of lymphadenectomy in adrenocortical carcinoma (ACC) is controversial, and formal lymph node (LN) dissection is not routine. We sought to determine the minimum number of LNs that must be examined to accurately identify a patient as node negative. METHODS: The National Cancer Database was used to identify patients diagnosed with ACC from 2004 to 2013 who underwent surgical resection. Patients with distant metastases, multivisceral resection, or missing surgical or lymphadenectomy data were excluded...
September 11, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28893836/immunotherapy-against-endocrine-malignancies-immune-checkpoint-inhibitors-lead-the-way
#16
Lucas Leite Cunha, Marjory Alana Marcello, Vinicius Rocha-Santos, Laura Sterian Ward
Immune checkpoint inhibitors are agents that act by inhibiting the mechanisms of immune escape displayed by various cancers. The success of immune checkpoint inhibitors against several tumors has promoted a new treatment strategy in clinical oncology, and this has encouraged physicians to increase the number of patients who receive the immune checkpoint therapy. In the present article, we review the main concepts regarding immune checkpoint mechanisms and how cancer disrupts them to undergo immune escape. In addition, we describe the most essential concepts related to immune checkpoint inhibitors...
September 11, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28887601/is-there-a-role-for-epithelial-mesenchymal-transition-in-adrenocortical-tumors
#17
Daniel Bulzico, Paulo Antônio Silvestre de Faria, Camila Bravo Maia, Marcela Pessoa de Paula, Davi Coe Torres, Gerson Moura Ferreira, Bruno Ricardo Barreto Pires, Rocio Hassan, Eliana Abdelhay, Mario Vaisman, Leonardo Vieira Neto
PURPOSE: Epithelial-mesenchymal transition (EMT) is a biological dynamic process by which epithelial cells lose their epithelial phenotype and acquire mesenchymal invasive and migratory characteristics. This has been postulated as an essential step during cancer progression and metastasis. Although this is well described in other tumors, the role of EMT in adrenocortical tumors (ACT) has yet to be addressed. METHODS: The aim of this study was to evaluate the expression of EMT markers e-cadherin, vimentin, and fibronectin, along with EMT-transcription factors (EMT-TFs), TWIST1, SIP1, and SNAIL in 24 adrenocortical carcinoma (ACC), 19 adrenocortical adenomas (ACA), 27 childhood-onset adrenocortical tumors (CAT), and 12 normal adrenal glands...
September 8, 2017: Endocrine
https://www.readbyqxmd.com/read/28881628/establishment-of-a-mouse-xenograft-model-of-metastatic-adrenocortical-carcinoma
#18
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...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28880439/complete-response-in-a-patient-with-stage-iv-adrenocortical-carcinoma-treated-with-adjuvant-trans-catheter-arterial-chemo-embolization-tace
#19
Eugene Wong, Sarah Jacques, Michael Bennett, Vineet Gorolay, Adrian Lee, Stephen Clarke
Adrenocortical carcinoma is a rare cancer, with estimate population incidence of 0.7-2.0 cases per 1 million each year. It also carries poor prognosis with estimated 5-year survival of less than 15% of those with metastatic disease and has a poor response to cytotoxic treatment. A randomized controlled trial published in 2012 by Fassnacht et al. demonstrated improved progression-free survival with first-line etoposide-doxirubicin-cisplatin-mitotane (EDP-M) compared to first-line streptozocin-mitotane in patients with stage III-IV disease...
September 6, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28874901/adrenocortical-carcinoma-patterns-of-care-and-role-of-adjuvant-radiation-therapy-a-population-based-study-and-review-of-the-literature
#20
REVIEW
S Atallah, H Al-Assaf, Y Xu, S El-Sayed
PURPOSE: We reviewed the experience of a tertiary cancer centre in the management of adrenocortical carcinoma (acc) treated over 40 years. We also searched the literature for guidelines related to the treatment of acc and for evidence for adjuvant radiation therapy (rt). METHODS: In a retrospective chart review, acc patients treated between January 1974 and December 2013 were identified, and patient demographics and tumour characteristics were extracted. Outcomes data, including dates and sites of failure, vital status, and cause of death, were collected...
August 2017: Current Oncology
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