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https://www.readbyqxmd.com/read/28877067/diagnostic-and-prognostic-biomarkers-of-adrenal-cortical-carcinoma
#1
Ozgur Mete, Hasan Gucer, Mehmet Kefeli, Sylvia L Asa
The diagnosis of low-grade adrenal cortical carcinoma (ACC) confined to the adrenal gland can be challenging. Although there are diagnostic and prognostic molecular tests for ACC, they remain largely unutilized. We examined the diagnostic and prognostic value of altered reticulin framework and the immunoprofile of biomarkers including IGF-2, proteins involved in cell proliferation and mitotic spindle regulation (Ki67, p53, BUB1B, HURP, NEK2), DNA damage repair (PBK, γ-H2AX), telomere regulation (DAX, ATRX), wnt-signaling pathway (beta-catenin) and PI3K signaling pathway (PTEN, phospho-mTOR) in a tissue microarray of 50 adenomas and 43 carcinomas that were characterized for angioinvasion as defined by strict criteria, Weiss score, and mitotic rate-based tumor grade...
September 4, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28857256/autophagy-dependent-crosstalk-between-gilt-and-pax-3-influences-radiation-sensitivity-of-human-melanoma-cells
#2
Jessica D Hathaway-Schrader, Bently P Doonan, Azim Hossain, Faisal F Y Radwan, Lixia Zhang, Azizul Haque
Melanoma represents an ever-increasing problem in the western world as incidence rates continue to climb. Though manageable during early stages, late stage metastatic disease is highly resistant to current intervention. We have previously shown that gamma-interferon-inducible lysosomal thiol-reductase (GILT) enhances HLA class II antigen processing and immune detection of human melanoma cells. Here we report that GILT expression inhibits a potential target, paired box-3 (PAX-3) protein, in late stage human metastatic melanoma...
August 31, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28812328/prognostic-significance-of-daxx-ncr-nuclear-cytoplasmic-ratio-in-gastric-cancer
#3
Jian-Feng Xu, Zhi-Guang Zhao, Le-le Ye, Weishan Zhuge, Zheng Han, Te-Ming Zhang, Si-Si Ye, Wen-Jing Chen, Shanli Zhu, Li Shi, Jun Zhang, Ai-Zhen Guo, Xiang-Yang Xue, Xian Shen
In addition to regulating apoptosis via its interaction with the death domain of Fas receptor, death domain associated protein 6 (Daxx) is also known to be involved in transcriptional regulation, suggesting that the function of Daxx depends on its subcellular localization. In this study, we aimed to explore Daxx subcellular localization in gastric cancer (GC) cells and correlate the findings with clinical data in GC patients. Seventy pairs of tissue samples (GC and adjacent normal tissue) were analyzed immunohistochemically for Daxx expression and localization (nuclear and cytoplasmic)...
August 15, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28796347/clinicopathological-analysis-of-atrx-daxx-and-notch-receptor-expression-in-angiosarcomas
#4
Gauri Panse, John S A Chrisinger, Cheuk H Leung, Davis R Ingram, Samia Khan, Khalida Wani, Heather Lin, Alexander J Lazar, Wei-Lien Wang
AIMS: Multiple genetic alterations including alternative lengthening of telomeres (ALT) and NOTCH mutations have been described in angiosarcoma. Loss of ATRX (α-thalessemia/mental retardation syndrome X-linked) and DAXX (death domain-associated 6) expression is frequently associated with the ALT phenotype. Additionally, inhibition of NOTCH signaling induces malignant vascular tumors in mice, indicating a tumor suppressive role of the NOTCH pathway in the pathogenesis of angiosarcoma...
August 10, 2017: Histopathology
https://www.readbyqxmd.com/read/28719461/serotonin-atrx-and-daxx-expression-in-pituitary-adenomas-markers-in-the-differential-diagnosis-of-neuroendocrine-tumors-of-the-sellar-region
#5
Olivera Casar-Borota, Johan Botling, Dan Granberg, Jerker Stigare, Johan Wikström, Henning Bünsow Boldt, Bjarne Winther Kristensen, Fredrik Pontén, Jacqueline Trouillas
Differential diagnosis based on morphology and immunohistochemistry between a clinically nonfunctioning pituitary neuroendocrine tumor (NET)/pituitary adenoma and a primary or secondary NET of nonpituitary origin in the sellar region may be difficult. Serotonin, a frequently expressed marker in the NETs, has not been systematically evaluated in pituitary NETs. Although mutations in ATRX or DAXX have been reported in a significant proportion of pancreatic NETs, the mutational status of ATRX and DAXX and their possible pathogenetic role in pituitary NETs are unknown...
September 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28718916/the-genetic-landscape-of-endometrial-clear-cell-carcinomas
#6
Deborah F DeLair, Kathleen A Burke, Pier Selenica, Raymond S Lim, Sasinya N Scott, Sumit Middha, Abhinita S Mohanty, Donavan T Cheng, Michael F Berger, Robert A Soslow, Britta Weigelt
Clear cell carcinoma of the endometrium is a rare type of endometrial cancer that is generally associated with an aggressive clinical behaviour. Here, we sought to define the repertoire of somatic genetic alterations in endometrial clear cell carcinomas (ECCs), and whether ECCs could be classified into the molecular subtypes described for endometrial endometrioid and serous carcinomas. We performed a rigorous histopathological review, immunohistochemical analysis and massively parallel sequencing targeting 300 cancer-related genes of 32 pure ECCs...
July 18, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28710117/genetic-and-epigenetic-drivers-of-neuroendocrine-tumors-net
#7
Annunziata Di Domenico, Tabea Wiedmer, Ilaria Marinoni, Aurel Perren
Neuroendocrine tumors (NET) of the gastrointestinal tract and the lung are a rare and heterogeneous group of tumors. The molecular characterization and the clinical classification of these tumors have been evolving slowly and show differences according to organs of origin. Novel technologies such as next-generation sequencing revealed new molecular aspects of NET over the last years. Notably, whole exome/genome sequencing (WES/WGS) approaches underlined the very low mutation rate of well differentiated NET of all organs compared to other malignancies, while the engagement of epigenetic changes in driving NET evolution is emerging...
July 14, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28706608/the-effects-of-melilotus-officinalis-extract-on-expression-of-daxx-nfkb-and-vegf-genes-in-the-streptozotocin-induced-rat-model-of-sporadic-alzheimer-s-disease
#8
Niloofar Bazazzadegan, Marzieh Dehghan Shasaltaneh, Kioomars Saliminejad, Koorosh Kamali, Mehdi Banan, Hamid Reza Khorram Khorshid
BACKGROUND: Possible mechanisms of Alzheimer Disease (AD) such as inflammation and oxidative stresses in the brain led us to investigate potential AD therapeutics of Melilotus officinalis, an herbal extract, with possible role as an anti-inflammatory and anti-oxidant agent. Among different genes which had important role in Sporadic AD (SAD), three genes including DAXX, NFkB and VEGF have shown significant statistical diversity in the brains of Alzheimer patients. METHODS: These genes were chosen to be investigated for neuroprotective effects of the extract by comparing the expression level in the hippocampus of Sporadic AD (SAD) rat model using quantitative polymerase chain reaction (qPCR) in the treated and untreated groups...
July 2017: Avicenna Journal of Medical Biotechnology
https://www.readbyqxmd.com/read/28706137/assessment-of-pancreatic-neuroendocrine-tumor-cytologic-genotype-diversity-to-guide-personalized-medicine-using-a-custom-gastroenteropancreatic-next-generation-sequencing-panel
#9
Ferga C Gleeson, Jesse S Voss, Benjamin R Kipp, Sarah E Kerr, John S Van Arnam, John R Mills, Cherisse A Marcou, Amber R Schneider, Zheng Jin Tu, Michael R Henry, Michael J Levy
BACKGROUND: Recent genetic studies have highlighted that alterations in MEN1, chromatin remodeling genes, and mammalian target of rapamycin (mTOR) pathway genes are the most frequent molecular events identified in pancreas neuroendocrine tumors (pNETs). The prognostic or predictive impact of these biomarkers and other less frequently observed aberrations, i.e. PTEN, TSC2 and PIK3CA are relatively unknown. The aims of this targeted next generation sequencing (NGS) study were to assess tumor cytology genotype diversity, to survey for potential adverse prognostic biomarkers and the prevalence of mTOR pathway variants...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28597868/loss-of-progesterone-receptor-expression-is-an-early-tumorigenesis-event-associated-with-tumor-progression-and-shorter-survival-in-pancreatic-neuroendocrine-tumor-patients
#10
Sung Joo Kim, Soyeon An, Jae Hoon Lee, Joo Young Kim, Ki-Byung Song, Dae Wook Hwang, Song Cheol Kim, Eunsil Yu, Seung-Mo Hong
BACKGROUND: Pancreatic neuroendocrine tumors (PanNETs) are the second most common pancreatic neoplasms and there is no well-elucidated biomarker to stratify their detection and prognosis. Previous studies have reported that progesterone receptor (PR) expression status was associated with poorer survival in PanNET patients. METHODS: To validate previous studies, PR protein expression was assessed in 21 neuroendocrine microadenomas and 277 PanNETs and compared with clinicopathologic factors including patient survival...
July 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28596481/mislocalization-of-centromeric-histone-h3-variant-cenp-a-contributes-to-chromosomal-instability-cin-in-human-cells
#11
Roshan L Shrestha, Grace S Ahn, Mae I Staples, Kizhakke M Sathyan, Tatiana S Karpova, Daniel R Foltz, Munira A Basrai
Chromosomal instability (CIN) is a hallmark of many cancers and a major contributor to tumorigenesis. Centromere and kinetochore associated proteins such as the evolutionarily conserved centromeric histone H3 variant CENP-A, associate with centromeric DNA for centromere function and chromosomal stability. Stringent regulation of cellular CENP-A levels prevents its mislocalization in yeast and flies to maintain genome stability. CENP-A overexpression and mislocalization are observed in several cancers and reported to be associated with increased invasiveness and poor prognosis...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28591701/daxx-atrx-and-men1-genes-are-strong-prognostic-markers-in-pancreatic-neuroendocrine-tumors
#12
Joo Kyung Park, Woo Hyun Paik, Kyoungbun Lee, Ji Kon Ryu, Sang Hyub Lee, Yong-Tae Kim
BACKGROUND: PanNETs shows heterogeneous biological behaviors. The aim was to investigate prognostic markers based on most frequently mutated genes in PanNETs. RESULTS: There was a total of 76 patients (M: 39, F: 37) with pathologically proven PanNETs. ATRX/DAXX and MEN1 protein expression was detected in 16 (21%) and 31 (41%) patients, respectively. The mean OS of the total study patients was 16 years, and DFS was 17 years among the 68 patients with curative resections...
July 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28535583/molecular-testing-of-brain-tumor
#13
REVIEW
Sung-Hye Park, Jaekyung Won, Seong-Ik Kim, Yujin Lee, Chul-Kee Park, Seung-Ki Kim, Seung-Hong Choi
The World Health Organization (WHO) classification of central nervous system (CNS) tumors was revised in 2016 with a basis on the integrated diagnosis of molecular genetics. We herein provide the guidelines for using molecular genetic tests in routine pathological practice for an accurate diagnosis and appropriate management. While astrocytomas and IDH-mutant (secondary) glioblastomas are characterized by the mutational status of IDH, TP53 , and ATRX , oligodendrogliomas have a 1p/19q codeletion and mutations in IDH, CIC , FUBP1 , and the promoter region of telomerase reverse transcriptase ( TERTp )...
May 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28510731/letter-retention-of-atrx-and-daxx-expression-in-meningiomas
#14
Gina Fürtjes, Katharina Heß, Andrea Wagner, Volker Senner, Caroline Brokinkel, Walter Stummer, Benjamin Brokinkel
No abstract text is available yet for this article.
August 1, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28501693/necrostatin-1-protects-hippocampal-neurons-against-ischemia-reperfusion-injury-via-the-rip3-daxx-signaling-pathway-in-rats
#15
Rongli Yang, Kun Hu, Jieyun Chen, Shiguang Zhu, Lei Li, Hailong Lu, Pingjing Li, Ruiguo Dong
Global cerebral ischemia/reperfusion (I/R) induces selective neuronal injury in CA1 region of hippocampus, leading to severe impairment in behavior, learning and memory functions. However, the molecular mechanism underlying the processes was not elucidated clearly. RIP3 is a key molecular switch connecting apoptosis, necrosis and necroptosis. DAXX, as a novel substrate of RIP3, plays a vital role in ischemia-induced neuronal death. The aim of this study is to investigate the role and mechanism of RIP3/DAXX signaling pathway on neurons in CA1 region of the rat hippocampus after cerebral I/R...
May 10, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28497778/pten-regulates-glioblastoma-oncogenesis-through-chromatin-associated-complexes-of-daxx-and-histone-h3-3
#16
Jorge A Benitez, Jianhui Ma, Matteo D'Antonio, Antonia Boyer, Maria Fernanda Camargo, Ciro Zanca, Stephen Kelly, Alireza Khodadadi-Jamayran, Nathan M Jameson, Michael Andersen, Hrvoje Miletic, Shahram Saberi, Kelly A Frazer, Webster K Cavenee, Frank B Furnari
Glioblastoma (GBM) is the most lethal type of human brain cancer, where deletions and mutations in the tumour suppressor gene PTEN (phosphatase and tensin homolog) are frequent events and are associated with therapeutic resistance. Herein, we report a novel chromatin-associated function of PTEN in complex with the histone chaperone DAXX and the histone variant H3.3. We show that PTEN interacts with DAXX and, in turn PTEN directly regulates oncogene expression by modulating DAXX-H3.3 association on the chromatin, independently of PTEN enzymatic activity...
May 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28439026/the-sp100-component-of-nd10-enhances-accumulation-of-pml-and-suppresses-replication-and-the-assembly-of-hsv-replication-compartments
#17
Pei Xu, Bernard Roizman
Nuclear domain 10 (ND10) bodies are small (0.1-1 μM) nuclear structures containing both constant [e.g., promyelocytic leukemia protein (PML), SP100, death domain-associated protein (Daxx)] and variable proteins, depending on the function of the cells or the stress to which they are exposed. In herpes simplex virus (HSV)-infected cells, ND10 bodies assemble at the sites of DNA entering the nucleus after infection. In sequence, the ND10 bodies become viral replication compartments, and ICP0, a viral E3 ligase, degrades both PML and SP100...
May 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28427227/high-dose-ascorbate-and-arsenic-trioxide-selectively-kill-acute-myeloid-leukemia-and-acute-promyelocytic-leukemia-blasts-in-vitro
#18
Nélida I Noguera, Elvira Pelosi, Daniela F Angelini, Maria Liliana Piredda, Gisella Guerrera, Eleonora Piras, Luca Battistini, Lauretta Massai, Anna Berardi, Gianfranco Catalano, Laura Cicconi, Germana Castelli, Agnese D'Angiò, Luca Pasquini, Grazia Graziani, Giuseppe Fioritoni, Maria Teresa Voso, Domenico Mastrangelo, Ugo Testa, Francesco Lo-Coco
The use of high-dose ascorbate (ASC) for the treatment of human cancer has been attempted several decades ago and has been recently revived by several in vitro and in vivo studies in solid tumors. We tested the cytotoxic effects of ASC, alone or in combination with arsenic trioxide (ATO) in acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL). Leukemic cell lines and primary blasts from AML and APL patients were treated with graded concentrations of ASC, alone or in association with standard concentration (1 μM) of ATO...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28371511/alternative-lengthening-of-telomeres-and-atrx-daxx-loss-can-be-reliably-detected-in-fnas-of-pancreatic-neuroendocrine-tumors
#19
COMPARATIVE STUDY
Christopher J VandenBussche, Derek B Allison, Mindy K Graham, Vivek Charu, Anne Marie Lennon, Christopher L Wolfgang, Ralph H Hruban, Christopher M Heaphy
BACKGROUND: Pancreatic neuroendocrine tumors (PanNETs) frequently use the alternative lengthening of telomeres (ALT) pathway for telomere maintenance. ALT is strongly correlated with α thalassemia-mental retardation, X linked (ATRX), and death domain-associated protein 6 (DAXX) alterations and a poor prognosis in patients with primary PanNET. Because fine-needle aspiration (FNA) is a noninvasive way to sample tumors, the authors evaluated whether they could accurately detect ALT and loss of ATRX/DAXX in a primary PanNET cohort of FNAs...
July 2017: Cancer
https://www.readbyqxmd.com/read/28358373/myogenic-differentiation-triggers-pml-nuclear-body-loss-and-daxx-relocalization-to-chromocentres
#20
Jayme Salsman, Lindsy M Rapkin, Nandini N Margam, Roy Duncan, David P Bazett-Jones, Graham Dellaire
The promyelocytic leukemia protein (PML) is expressed in most normal human tissues and forms nuclear bodies (NBs) that have roles in gene regulation and cellular processes such as DNA repair, cell cycle control, and cell fate decisions. Using murine C2C12 myoblasts, we demonstrate that activation of skeletal muscle differentiation results in loss of PML and PML NBs prior to myotube fusion. Myotube formation was associated with marked chromatin reorganization and the relocalization of DAXX from PML NBs to chromocentres...
March 30, 2017: Cell Death & Disease
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