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Melanoma DNA methylation

George Jour, Varshini Vasudevaraja, Victor G Prieto, Matija Snuderl, Carlos A Torres-Cabala, Rami Al-Rohil, Erik P Sulman, Leomar Y Ballester, Phyu P Aung
Superficial/cutaneous malignant peripheral nerve sheath tumor is a rare soft tissue neoplasm that shares morphological, immunohistochemical, and molecular features with spindle/desmoplastic melanoma. We aimed to identify a methylome signature to distinguish these two entities. We analyzed 15 cases of spindle/desmoplastic melanoma and 15 cases of cutaneous malignant peripheral nerve sheath tumor in 23 men and 7 women. DNA from formalin-fixed, paraffin-embedded tissues was extracted and processed using the Illumina Infinium Methylation EPIC array interrogating 866,562 CpG sites...
October 11, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Thomas C Chen, Nymph Chan, Radu O Minea, Hannah Hartman, Florence M Hofman, Axel H Schönthal
The chemotherapeutic agent temozolomide (TMZ) kills tumor cells preferentially via alkylation of the O6-position of guanine. However, cells that express the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT), or harbor deficient DNA mismatch repair (MMR) function, are profoundly resistant to this drug. TMZ is in clinical use for melanoma, but objective response rates are low, even when TMZ is combined with O6-benzylguanine (O6BG), a potent MGMT inhibitor. We used in vitro and in vivo models of melanoma to characterize the early events leading to cellular TMZ resistance...
September 28, 2018: Cancers
Anna-Maria Barciszewska
Brain metastases are the most common intracranial tumors in adults. They usually origin from: lung, breast, renal cell, and gastrointestinal cancers, as well as melanoma. Prognosis for brain metastases is still poor and classical treatment combining surgery and radiation therapy should be strongly supported with molecular approaches. However, their successful application depends on a deep understanding of not only genetic, but also epigenetic background of the disease. That will result in earlier and more precise diagnosis, successful treatment, as well as individualized estimation of clinical outcomes and prognosis...
September 25, 2018: Bioscience Reports
Aniruddha Chatterjee, Euan J Rodger, Antonio Ahn, Peter A Stockwell, Matthew Parry, Jyoti Motwani, Stuart J Gallagher, Elena Shklovskaya, Jessamy Tiffen, Michael R Eccles, Peter Hersey
Constitutive expression of the immune checkpoint, PD-L1, inhibits anti-tumor immune responses in cancer, although the factors involved in PD-L1 regulation are poorly understood. Here we show that loss of global DNA methylation, particularly in intergenic regions and repeat elements, is associated with constitutive (PD-L1CON ), versus inducible (PD-L1IND ), PD-L1 expression in melanoma cell lines. We further show this is accompanied by transcriptomic up-regulation. De novo epigenetic regulators (e.g., DNMT3A) are strongly correlated with PD-L1 expression and methylome status...
June 29, 2018: iScience
Ane F Santos, Isabella P Ferreira, Carlos B Pinheiro, Verlane G Santos, Miriam T P Lopes, Letícia R Teixeira, Willian R Rocha, Gabriel L S Rodrigues, Heloisa Beraldo
Complexes [Ag(H2BzPh)NO3 ] ( 1 ), [Ag(H2Bz p CH3 Ph)NO3 ] ( 2 ), [Ag(H2Bz p ClPh)NO3 ] ( 3 ), and [Ag(H2Bz p NO2 Ph)NO3 ] ( 4 ) were synthesized with 2-benzoylpyridine benzoylhydrazone (H2BzPh) and its para -methyl-benzoylhydrazone (H2Bz p CH3 Ph), para -chloro-benzoylhydrazone (H2Bz p ClPh), and para -nitro-benzoylhydrazone (H2Bz p NO2 Ph) derivatives. Experimental data indicate that the nitrate ligand binds more strongly to the silver center through one of the oxygen atoms, whereas the second oxygen atom from nitrate and the hydrazone oxygen makes much weaker interactions with the metal...
June 30, 2018: ACS Omega
Feng Su, Xiaoli Guo, Yanchao Wang, Yuding Wang, Guiling Cao, Yunliang Jiang
The Jining Gray goat is famous for its sexual precocity; however, the exact regulatory mechanism is still unknown. The hypothalamus is the key centrum in the process of animal reproduction, especially in signal transduction, and the initiation of puberty. The identification of potential genes and pathways in the hypothalamus of Jining Gray goat is critical to understanding the regulatory mechanism of sexual precocity in these goats. In this study, mRNA transcriptome analysis of the hypothalamus of juvenile and pubertal goats revealed eight genes ( NTS, ADORA1, CRH, UCN3, E2F2, PDGFRB, GNRH1 , and CACNA1C ) and three pathways [neuroactive ligand-receptor interaction; gonadotropin-releasing hormone (GnRH) signal; melanoma] that are involved in this regulation...
2018: Frontiers in Endocrinology
SneŽana Radisavljević, Ioannis Bratsos, Andreas Scheurer, Jana Korzekwa, Romana Masnikosa, Aleksandar Tot, Nevenka Gligorijević, Siniša Radulović, Ana Rilak Simović
With the aim of assessing whether Au(iii) compounds with pincer type ligands might be utilized as potential antitumor agents, three new monofunctional Au(iii) complexes of the general formula [Au(N-N'-N)Cl]Cl2, where N-N'-N = 2,6-bis(5-tert-butyl-1H-pyrazol-3-yl)pyridine (H2LtBu, 1), 2,6-bis(5-tert-butyl-1-methyl-1H-pyrazol-3-yl)pyridine (Me2LtBu, 2) or 2,6-bis((4S,7R)-1,7,8,8-tetramethyl-4,5,6,7-tetrahydro-1H-4,7-methanoindazol-3-yl)pyridine (Me2*L, 3) were synthesized. All complexes were characterized by elemental analysis, spectroscopic techniques (IR, UV-Vis, 1D and 2D NMR) and mass spectrometry (MALDI TOF MS)...
October 2, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
Yishui Lian, Lingjiao Meng, Pingan Ding, Meixiang Sang
The melanoma antigen gene (MAGE) proteins are a group of highly conserved family members that contain a common MAGE homology domain. Type I MAGEs are relevant cancer-testis antigens (CTAs), and originally considered as attractive targets for cancer immunotherapy due to their typically high expression in tumor tissues but restricted expression in normal adult tissues. Here, we reviewed the recent discoveries and ideas that illustrate the biological functions of MAGE family in cancer progression. Furthermore, we also highlighted the current understanding of the epigenetic mechanism of MAGE family expression in human cancers...
September 5, 2018: Clinical Epigenetics
Alok Mishra, Mukesh Verma
Utilizing biology of PD-1: PD-L1 interaction related pathways for cancer immunotherapy is an emerging concept in cancer research. However, there is limited literature on epigenetic regulation of PD1 gene (PDCD1). Promising data from clinical trials of PD/PDl-1 immunotherapy in melanoma, renal cancers, colorectal and lung cancers has generated a lot of hope for successful treatment of patients. Immunotherapy in cancers has a significant role in strategizing NCI's Cancer Moonshot Program of US NIH and FDA policies...
2018: Methods in Molecular Biology
Sougata Datta, Santosh K Misra, Manik Lal Saha, Nabajit Lahiri, Janis Louie, Dipanjan Pan, Peter J Stang
Curcumin (Cur) is a naturally occurring anticancer drug isolated from the Curcuma longa plant. It is known to exhibit anticancer properties via inhibiting the STAT3 phosphorylation process. However, its poor water solubility and low bioavailability impede its clinical application. Herein, we used organoplatinum(II) ← pyridyl coordination-driven self-assembly and a cucurbit[8]uril (CB[8])-mediated heteroternary host-guest complex formation in concert to produce an effective delivery system that transports Cur into the cancer cells...
August 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
Xiao Chen, Wei Li, Chengchao Xu, Jie Wang, Bo Zhu, Qilai Huang, Dianhua Chen, Jianfei Sheng, Yong Zou, Yew Mun Lee, Renxiang Tan, Pingping Shen, Yin Kwan Wong, Qingsong Lin, Jigang Wang, Zichun Hua
Many plant-specialized metabolites have remedial properties and provide an endless chemical resource for drug discovery. However, most of these metabolites have promiscuous binding targets in mammalian cells and elicit a series of responses that collectively change the physiology of the cells. To explore the potential of these multi-functional and multi-targeted drugs, it is critical to understand the direct relationships between their key chemical features, the corresponding binding targets and the relevant biological effects, which is a prerequisite for future drug modification and optimization...
2018: Theranostics
Sirinun Pisamai, Sittiruk Roytrakul, Narumon Phaonakrop, Janthima Jaresitthikunchai, Gunnaporn Suriyaphol
Oral tumors, including highly invasive and metastatic oral melanoma (OM), non-tonsillar oral squamous cell carcinoma (OSCC) and benign tumors (BN), are common neoplasms in dogs. Although these tumors behave differently, limited data of their protein expression profiles have been exhibited, particularly at the proteome level. The present study aimed to i.) characterize peptide-mass fingerprints (PMFs) and identify potential protein candidates of OM, OSCC, BN and normal control subjects, using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and liquid chromatography tandem mass spectrometry (LC-MS/MS), ii...
2018: PloS One
Diane Goltz, Heidrun Gevensleben, Timo J Vogt, Joern Dietrich, Carsten Golletz, Friedrich Bootz, Glen Kristiansen, Jennifer Landsberg, Dimo Dietrich
Recent years have witnessed the groundbreaking success of immune checkpoint blockage (ICB) in metastasized malignant melanoma. However, biomarkers predicting the response to ICB are still urgently needed. In the present study, we investigated CTLA4 promoter methylation (mCTLA4) in 470 malignant melanoma patients from The Cancer Genome Atlas (non-ICB cohort) and in 50 individuals with metastasized malignant melanomas under PD-1/CTLA-4-targeted immunotherapy (ICB cohort). mCTLA4 levels were quantified using the Infinium HumanMethylation450 BeadChip (non-ICB cohort) and methylation-specific quantitative real-time PCR in DNA formalin-fixed and paraffin-embedded tissues (ICB cohort)...
July 12, 2018: JCI Insight
J Huang, S-G Sun, S Hou
OBJECTIVE: Never in Mitosis (NIMA) Related Kinase 2 (Nek2) is a serine/threonine-protein kinase encoded by the NEK2 gene and is an essential enzyme in cell cycle progression. In this study, we investigated NEK2 expression profile, its independent prognostic value in terms of recurrence-free survival (RFS)/overall survival (OS), and the potential mechanisms of its dysregulation in melanoma. PATIENTS AND METHODS: A retrospective study was conducted using data from Gene Expression Omnibus (GEO) datasets and the Cancer Genome Atlas (TCGA)-skin cutaneous melanoma (SKCM)...
June 2018: European Review for Medical and Pharmacological Sciences
Brian T Joyce, Yinan Zheng, Drew Nannini, Zhou Zhang, Lei Liu, Tao Gao, Masha Kocherginsky, Robert Murphy, Hushan Yang, Chad J Achenbach, Lewis R Roberts, Mirjam Hoxha, Jincheng Shen, Pantel Vokonas, Joel Schwartz, Andrea Baccarelli, Lifang Hou
Researchers hypothesized that telomere shortening facilitates carcinogenesis. Previous studies found inconsistent associations between blood leukocyte telomere length (LTL) and cancer. Epigenetic reprogramming of telomere maintenance mechanisms may help explain this inconsistency. We examined associations between DNA methylation in telomere-related genes (TRG) and cancer. We analyzed 475 participants providing 889 samples 1 to 3 times (median follow-up, 10.1 years) from 1999 to 2013 in the Normative Aging Study...
August 2018: Cancer Prevention Research
Klaus G Griewank, Christian Koelsche, Johannes A P van de Nes, Daniel Schrimpf, Marco Gessi, Inga Möller, Antje Sucker, Richard A Scolyer, Michael E Buckland, Rajmohan Murali, Torsten Pietsch, Andreas von Deimling, Dirk Schadendorf
Purpose: In the central nervous system, distinguishing primary leptomeningeal melanocytic tumors from melanoma metastases and predicting their biological behavior solely using histopathologic criteria may be challenging. We aimed to assess the diagnostic and prognostic value of integrated molecular analysis. Experimental Design: Targeted next-generation sequencing, array-based genome-wide methylation analysis, and BAP1 IHC were performed on the largest cohort of central nervous system melanocytic tumors analyzed to date, including 47 primary tumors of the central nervous system, 16 uveal melanomas, 13 cutaneous melanoma metastases, and 2 blue nevus-like melanomas...
June 11, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Melina Mitsiogianni, Tom Amery, Rodrigo Franco, Vasilis Zoumpourlis, Aglaia Pappa, Mihalis I Panayiotidis
Skin cancer incidence is rapidly growing over the last decades and is generally divided into malignant melanoma and non-melanoma (NMSC) with the latter being subdivided into squamous (SCC) and basal cell carcinoma (BCC). Among them, melanoma is the most aggressive type with high mortality rates. On the other hand, aberrant gene expression is a critical step towards malignant transformation. To this end, epigenetic modifications like changes in DNA methylation patterns and miRNA expression profile as well as histone modifications are all capable of inducing an altered gene expression profile involved in various cellular cascades including cell cycle, proliferation and apoptosis...
October 2018: Pharmacology & Therapeutics
Garam Kim, Jin-Young Kim, Sung-Chul Lim, Kwang Youl Lee, Okyun Kim, Hong Seok Choi
Melanoma is among the most aggressive and treatment-resistant human cancers. Aberrant histone H3 methylation at Lys 9 (H3K9) correlates with carcinogenic gene silencing, but the significance of suppressor of variegation 3-9 homolog 1 (SUV39H1), an H3K9-specific methyltransferase, in melanoma initiation and progression remains unclear. Here, we show that SUV39H1-mediated H3K9 trimethylation facilitates retinoblastoma ( RB) 1 promoter CpG island methylation by interacting with DNA methyltransferase 3A and decreasing RB mRNA and protein in melanoma cells...
October 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Michele Guida, Stefania Tommasi, Sabino Strippoli, Maria Iole Natalicchio, Simona De Summa, Rosamaria Pinto, Antonio Cramarossa, Anna Albano, Salvatore Pisconti, Michele Aieta, Ruggiero Ridolfi, Amalia Azzariti, Gabriella Guida, Vito Lorusso, Giusepe Colucci
BACKGROUND: It is frequently asked whether chemotherapy can still play a role in metastatic melanoma considering the effectiveness of the available drugs today, including antiCTLA4/antiPD1 immunotherapy and antiBRAF/antiMEK inhibitors. However, only approximately half of patients respond to these drugs, and the majority progress after 6-11 months. Therefore, a need for other therapeutic options is still very much apparent. We report the first large trial of a sequential full dose of fotemustine (FM) preceded by a low dose of temozolomide (TMZ) as a chemo-modulator in order to inactivate the DNA repair action of O(6)-methylguanine DNA-methyltransferase (MGMT)...
May 10, 2018: BMC Cancer
Joshua S Mervis, Jean S McGee
The epigenetic regulation of gene expression is accomplished primarily through DNA methylation, histone modification, and gene silencing via the action of microRNAs. While previously very difficult to study, the field of epigenetics has been greatly facilitated by recent technological innovations. Alterations in the epigenome and epigenetic machinery are now known to be present in a variety of diseases, most notably cancers. Moreover, evidence has emerged that epigenetic dysregulation plays a causative role in disease pathogenesis...
May 22, 2018: Journal of Dermatological Treatment
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