Kenzo Hiroshima, Di Wu, Shinji Hamakawa, Shingo Tsuruoka, Daisuke Ozaki, Hideki Orikasa, Mizue Hasegawa, Eitetsu Koh, Yasuo Sekine, Yoko Yonemori, Kazuki Nabeshima, Shoutaro Tsuji, Yohei Miyagi, Kohzoh Imai
BACKGROUND: The specificity and sensitivity of HEG1 for malignant mesothelioma (MM) is high. The use of BAP1/MTAP immunohistochemistry (IHC) is recommended to separate benign and malignant mesothelial proliferations. We determined how ancillary techniques can be used for the cytological diagnosis of MM with effusion. METHODS: Cell blocks from effusions from cases with MM, reactive mesothelial cells (RMCs), and carcinomas were analyzed by IHC with HEG1, BAP1, and MTAP and with homozygous deletion (HD) of CDKN2A by fluorescence in situ hybridization...
May 22, 2020: Diagnostic Cytopathology
Fan Wu, Guan-Zhang Li, Han-Jie Liu, Zheng Zhao, Rui-Chao Chai, Yu-Qing Liu, Hao-Yu Jiang, You Zhai, Yue-Mei Feng, Ren-Peng Li, Wei Zhang
Isocitrate dehydrogenase (IDH) wild-type diffuse lower-grade glioma (LGG) is usually associated with poor outcome, but there have been disputes over its clinical outcome and classification. We presented here a robust gene expression-based molecular classification of IDH wild-type diffuse LGG into two subtypes with distinct biological and clinical features. A discovery cohort of 49 IDH wild-type diffuse LGGs from Chinese Glioma Genome Atlas (CGGA) was subjected to clustering and function analysis. 73 tumors from The Cancer Genome Atlas (TCGA) were used to validate our findings...
May 17, 2020: Journal of Pathology
Marcella Barbarino, Daniele Cesari, Maria Bottaro, Luca Luzzi, Asadoor Namagerdi, Franca Maria Bertolino, Cristiana Bellan, Fabrizio Proietti, Pasquale Somma, Mariacarolina Micheli, Maria Margherita de Santi, Raffaella Guazzo, Luciano Mutti, Luigi Pirtoli, Piero Paladini, Paola Indovina, Antonio Giordano
Malignant mesothelioma (MM) is an aggressive asbestos-related cancer of the serous membranes. Despite intensive treatment regimens, MM is still a fatal disease, mainly due to the intrinsic resistance to current therapies and the lack of predictive markers and new valuable molecular targets. Protein arginine methyltransferase 5 (PRMT5) inhibition has recently emerged as a potential therapy against methylthioadenosine phosphorylase (MTAP)-deficient cancers, in which the accumulation of the substrate 5'-methylthioadenosine (MTA) inhibits PRMT5 activity, thus sensitizing the cells to further PRMT5 inhibition...
April 17, 2020: Journal of Cellular and Molecular Medicine
David B Chapel, Jefree J Schulte, Aliya N Husain, Thomas Krausz
Immunohistochemistry plays an indispensable role in accurate diagnosis of malignant mesothelioma, particularly in morphologically challenging cases and in biopsy and cytology specimens, where tumor architecture is difficult or impossible to evaluate. Application of a targeted panel of mesothelial- and epithelial-specific markers permits correct identification of tumor lineage in the vast majority of cases. An immunopanel including two mesothelial markers (calretinin, CK5/6, WT-1, or D2-40) and two epithelial markers (MOC-31 and claudin-4) offers good sensitivity and specificity, with adjustments as appropriate for the differential diagnosis...
February 2020: Translational Lung Cancer Research
Weder Pereira de Menezes, Viviane Aline Oliveira Silva, Izabela Natália Faria Gomes, Marcela Nunes Rosa, Maria Luisa Corcoll Spina, Adriana Cruvinel Carloni, Ana Laura Vieira Alves, Matias Melendez, Gisele Caravina Almeida, Luciane Sussuchi da Silva, Carlos Clara, Isabela Werneck da Cunha, Glaucia Noeli Maroso Hajj, Chris Jones, Lucas Tadeu Bidinotto, Rui Manuel Reis
The 5'-methylthioadenosine phosphorylase (MTAP) gene is located in the chromosomal region 9p21. MTAP deletion is a frequent event in a wide variety of human cancers; however, its biological role in tumorigenesis remains unclear. The purpose of this study was to characterize the MTAP expression profile in a series of gliomas and to associate it with patients' clinicopathological features. Moreover, we sought to evaluate, through glioma gene-edited cell lines, the biological impact of MTAP in gliomas. MTAP expression was evaluated in 507 glioma patients by immunohistochemistry (IHC), and the expression levels were associated with patients' clinicopathological features...
February 20, 2020: Cells
Sara Alsubait, Norah Alsaad, Sumayyah Alahmari, Fatimah Alfaraj, Hussam Alfawaz, Abdullah Alqedairi
BACKGROUND: Intracanal medicaments can be used in various endodontic conditions including multiple visit endodontics after trauma or in regenerative endodontics. These medicaments should be removed from the root canal before the placement of the filling or repair material. The aim of the present study was to evaluate the effect of prior calcium hydroxide (Ca(OH)2 ) and modified triple antibiotic paste (mTAP) placement on the push-out bond strength of TotalFill BC fast set putty (BC fast set putty) to root dentin when compared to mineral trioxide aggregate (MTA)...
February 18, 2020: BMC Oral Health
Wei Li, Jianling Liu, Bin Zhang, Qingli Bie, Hui Qian, Wenrong Xu
Background: Metastasis is the major cause of death in breast cancer patients. Although the strategies targeting metastasis have promoted survival, the underlying mechanisms still remain unclear. In this study, we used microarray data of primary breast tumor, tumor derived from bone and liver, and skin metastatic tissue, to identify the key genes and pathways that are involved in metastasis in breast cancer. Methods: We first calculated the differentially expressed genes (DEGs) between three metastatic tissues and primary tumor tissue, and then used it to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis...
2020: OncoTargets and Therapy
Wang Jing, Hui Zhu, Wenjuan Liu, Xiaoyang Zhai, Hairong Tian, Jinming Yu
To investigate the predictive value of methylthioadenosine phosphorylase (MTAP) on treatment response and survival in advanced lung adenocarcinoma. MTAP expression was detected by immunohistochemistry. Treatment response and survival were compared according to MTAP expression level. The results indicated MTAP-low expression was observed in 61.2% (101/165) of all patients. The objective response rate and disease control rate improved in the MTAP-low group (64.4% vs 46.9%, p = 0.035; 92.1% vs. 79.7%, p = 0...
January 21, 2020: Scientific Reports
Hayley C Affronti, Aryn M Rowsam, Anthony J Pellerite, Spencer R Rosario, Mark D Long, Justine J Jacobi, Anna Bianchi-Smiraglia, Christoph S Boerlin, Bryan M Gillard, Ellen Karasik, Barbara A Foster, Michael Moser, John H Wilton, Kristopher Attwood, Mikhail A Nikiforov, Gissou Azabdaftari, Roberto Pili, James G Phillips, Robert A Casero, Dominic J Smiraglia
Prostatic luminal epithelial cells secrete high levels of acetylated polyamines into the prostatic lumen, sensitizing them to perturbations of connected metabolic pathways. Enhanced flux is driven by spermidine/spermine N1-acetyltransferase (SSAT) activity, which acetylates polyamines leading to their secretion and drives biosynthetic demand. The methionine salvage pathway recycles one-carbon units lost to polyamine biosynthesis to the methionine cycle to overcome stress. Prostate cancer (CaP) relies on methylthioadenosine phosphorylase (MTAP), the rate-limiting enzyme, to relieve strain...
January 7, 2020: Nature Communications
Elisa Majounie, Kathleen Wee, Laura M Williamson, Martin R Jones, Erin Pleasance, Howard J Lim, Cheryl Ho, Daniel J Renouf, Stephen Yip, Steven J M Jones, Marco A Marra, Janessa Laskin
Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide and represents a heterogeneous group of tumours, the majority of which are treated with a combination of surgery, radiation and chemotherapy. Fluoropyrimidine (5-FU) and its oral pro-drug, capecitabine, are commonly prescribed treatments for several solid tumour types including HNSCC. 5-FU-associated toxicity is observed in approximately 30% of treated patients and is largely caused by germline polymorphisms in DPYD which encodes dihydropyrimidine dehydrogenase (DPD), a key enzyme of 5-FU catabolism and deactivation...
December 23, 2019: Cold Spring Harbor Molecular Case Studies
Kyra B Berg, Andrew M Churg, Simon Cheung, Sanja Dacic
BACKGROUND: The separation of benign from malignant mesothelial proliferations on effusion cytology can be difficult. Loss of methylthioadenosine phosphorylase (MTAP) by immunohistochemistry is an established marker of malignancy in mesothelial proliferations, but to the authors' knowledge largely has been applied only to biopsies. The current study was conducted to determine the usefulness of MTAP immunohistochemistry in the diagnosis of malignant mesothelioma in effusion cytology specimens...
December 10, 2019: Cancer Cytopathology
Loredana Urso, Ilaria Cavallari, Evgeniya Sharova, Francesco Ciccarese, Giulia Pasello, Vincenzo Ciminale
Malignant pleural mesothelioma (MPM) is a rare malignancy of mesothelial cells with increasing incidence, and in many cases, dismal prognosis due to its aggressiveness and lack of effective therapies. Environmental and occupational exposure to asbestos is considered the main aetiological factor for MPM. Inhaled asbestos fibres accumulate in the lungs and induce the generation of reactive oxygen species (ROS) due to the presence of iron associated with the fibrous silicates and to the activation of macrophages and inflammation...
December 10, 2019: British Journal of Cancer
Else Driehuis, Arne van Hoeck, Kat Moore, Sigrid Kolders, Hayley E Francies, M Can Gulersonmez, Edwin C A Stigter, Boudewijn Burgering, Veerle Geurts, Ana Gracanin, Gergana Bounova, Folkert H Morsink, Robert Vries, Sylvia Boj, Johan van Es, G Johan A Offerhaus, Onno Kranenburg, Mathew J Garnett, Lodewyk Wessels, Edwin Cuppen, Lodewijk A A Brosens, Hans Clevers
We report the derivation of 30 patient-derived organoid lines (PDOs) from tumors arising in the pancreas and distal bile duct. PDOs recapitulate tumor histology and contain genetic alterations typical of pancreatic cancer. In vitro testing of a panel of 76 therapeutic agents revealed sensitivities currently not exploited in the clinic, and underscores the importance of personalized approaches for effective cancer treatment. The PRMT5 inhibitor EZP015556, shown to target MTAP (a gene commonly lost in pancreatic cancer)-negative tumors, was validated as such, but also appeared to constitute an effective therapy for a subset of MTAP-positive tumors...
December 9, 2019: Proceedings of the National Academy of Sciences of the United States of America
E K McMeniman, D L Duffy, K Jagirdar, K J Lee, E Peach, A M McInerney-Leo, B De'Ambrosis, J E Rayner, B M Smithers, H P Soyer, R A Sturm
BACKGROUND: Skin phenotype, host genotype and UV damage play a role in development of melanoma. OBJECTIVE: To ascertain whether the level of UV damage at the site of melanomas was associated with genetic polymorphisms. METHODS: Deep phenotyping was performed on 1244 individuals: 281 with multiple primary melanomas (MPM), 304 with single primary melanoma (SPM) and 659 convenience controls. Genotype data was generated using the Illumina CoreExome microarray platform assaying over 500,000 SNPs...
December 3, 2019: British Journal of Dermatology
Maira C Conte, Cleonice da Silveira Teixeira, Eduardo A Bortoluzzi, Wilson T Felippe, Luciane G P Dos Santos, Mariana T Pandolfo, Patrícia da Agostim Cancelier, Lucas da Fonseca Roberti Garcia
The purpose of this study was to evaluate the effect of different combinations of irrigating solutions and intracanal dressings in the pretreatment of bovine radicular dentin, using an experimental immature tooth model. Eighty healthy bovine teeth, simulated with incomplete rhizogenesis, were randomly distributed according to the protocols of root canal dentin pretreatment for a regenerative endodontic procedure (n = 10): Control (irrigation with distilled water); SH (irrigation with 1.5% Sodium Hypochlorite); EDTA (irrigation with 17% EDTA); SH/EDTA (irrigation with 1...
December 2, 2019: Microscopy Research and Technique
Jinyuan Xu, Xiaobo Hou, Lin Pang, Shangqin Sun, Shengyuan He, Yiran Yang, Kun Liu, Linfu Xu, Wenkang Yin, Chaohan Xu, Yun Xiao
Gliomas represent 80% of malignant brain tumors. Because of the high heterogeneity, the oncogenic mechanisms in gliomas are still unclear. In this study, we developed a new approach to identify dysregulated competitive endogenous RNA (ceRNA) interactions driven by copy number variation (CNV) in both lower-grade glioma (LGG) and glioblastoma multiforme (GBM). By analyzing genome and transcriptome data from The Cancer Genome Atlas (TCGA), we first found out the protein coding genes and long non-coding RNAs (lncRNAs) significantly affected by CNVs and further determined CNV-driven dysregulated ceRNA interactions by a customized pipeline...
2019: Frontiers in Genetics
Carolin Dorothea Strobl, Stefanie Schaffer, Tabea Haug, Simon Völkl, Katrin Peter, Katrin Singer, Martin Böttcher, Dimitrios Mougiakakos, Andreas Mackensen, Michael Aigner
Genetic alterations in tumor cells provide promising targets for anti-tumor therapy. Recently, loss of methylthioadenosine phosphorylase (MTAP), a deletion frequently occurring in cancer, has been shown to create vulnerability to the inhibition of the protein arginine methyltransferase 5 (PRMT5). MTAP deficiency leads to accumulation of methylthioadenosine (MTA), which reduces PRMT5 activity, and thus, sensitizes the tumor cells to selective PRMT5 inhibitors (PRMT5i). PRMT5i are investigated as a new strategy to selectively kill MTAP-deficient tumor cells by blocking residual PRMT5 activity, but also to treat PRMT5-overexpressing tumors...
November 11, 2019: Molecular Cancer Therapeutics
Michiel Simons, Femke Simmer, Johan Bulten, Marjolijn J Ligtenberg, Harry Hollema, Shannon van Vliet, Richarda M de Voer, Eveline J Kamping, Dirk F van Essen, Bauke Ylstra, Lauren E Schwartz, Yihong Wang, Leon F Massuger, Iris D Nagtegaal, Robert J Kurman
The origin of primary mucinous ovarian tumors is unknown. We explore the hypothesis that they originate from either Brenner tumors or teratomas and examine differences between the tumors that arise in these settings. A total of 104 Brenner tumor-associated mucinous tumors and 58 teratoma-associated mucinous tumors were analyzed. Immunohistochemistry for 21 antigens and fluorescence in situ hybridization for ERBB2 and MYC were performed. Genome-wide copy number analysis and mutation analysis for 56 cancer-related genes was carried out on a subset of mucinous ovarian tumors and their complementary Brenner tumor or teratoma...
November 6, 2019: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Jennifer Pors, Julia Naso, Kyra Berg, Andrew Churg
The separation of benign from malignant mesothelial proliferations is a morphologically difficult problem. Mutations/deletions of components of the Hippo pathway are frequent in malignant mesotheliomas, and one downstream effect of aberrant Hippo signaling is increased production of cyclin D1. We examined expression of cyclin D1 nuclear staining in two tissue microarrays containing 52 reactive epithelial mesothelial proliferations, 51 reactive spindle cell mesothelial proliferations, 54 epithelial mesotheliomas, and 22 sarcomatous/desmoplastic mesotheliomas...
February 2020: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Kazuhiro Minami, Naoe Jimbo, Yugo Tanaka, Daisuke Hokka, Yoshifumi Miyamoto, Tomoo Itoh, Yoshimasa Maniwa
Malignant pleural mesothelioma (MPM), associated with unfavorable outcomes, is closely associated with asbestos exposure. Early detection and treatment are critical to prolong survival of patients with MPM because of the rapid progression and resistance to treatment. The recently defined malignant mesothelioma in situ (MIS) has been gaining increasing attention with advances in genome-based methods including fluorescence in situ hybridization (FISH) as well as immunohistochemistry. We herein report the case of a MIS in a 73-year-old male with a history of asbestos exposure presenting with massive pleural effusion in the right thoracic cavity...
October 30, 2019: Virchows Archiv: An International Journal of Pathology
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