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https://www.readbyqxmd.com/read/28324831/primary-and-acquired-resistance-to-pd-1-pd-l1-blockade-in-cancer-treatment
#1
REVIEW
Qiaohong Wang, Xia Wu
PD-1/PD-L1 blockade appears to be a very promising immunotherapy with significant clinical benefits and durable responses in multiple tumor types. However, the effectual clinical benefits of PD-1/PD-L1 blockade are hampered by a high rate of primary resistance, where patients do not respond to PD-1/PD-L1 blockade initially. And more distressingly, most patients eventually develop acquired resistance after an initial response to PD-1/PD-L1 blockade. The mechanisms underlying primary and acquired resistance to PD-1/PD-L1 blockade have remained ambiguous...
March 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28323900/long-term-exposure-to-estrogen-enhances-chemotherapeutic-efficacy-potentially-through-epigenetic-mechanism-in-human-breast-cancer-cells
#2
Yu-Wei Chang, Kamaleshwar P Singh
Chemotherapy is the most common clinical option for treatment of breast cancer. However, the efficacy of chemotherapy depends on the age of breast cancer patients. Breast tissues are estrogen responsive and the levels of ovarian estrogen vary among the breast cancer patients primarily between pre- and post-menopausal age. Whether this age-dependent variation in estrogen levels influences the chemotherapeutic efficacy in breast cancer patients is not known. Therefore, the objective of this study was to evaluate the effects of natural estrogen 17 beta-estradiol (E2) on the efficacy of chemotherapeutic drugs in breast cancer cells...
2017: PloS One
https://www.readbyqxmd.com/read/28319413/aberrant-promoter-hypermethylation-of-p16-survivin-and-retinoblastoma-in-gastric-cancer
#3
L Guo, C Huang, Q J Ji
BACKGROUND: Gastric cancer is common and can be found throughout the world. Notoriously like other cancers, gastric cancer is a consequence of cellular regulation disorder. Epigenetics, including many oncogenes or tumour suppressor genes, can provide some clues for this kind of disorder. DNA methylation, especially promoter methylation, which causes the silence/decrease of tumour related genes, has become a focus in various tumour types. The aim of this study was to investigate promoter methylation of certain genes: p16, survivin, retinoblastoma (Rb), all of which have been regarded as genes related to gastric cancer...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/28319045/akt-mediated-stabilization-of-histone-methyltransferase-whsc1-promotes-prostate-cancer-metastasis
#4
Ni Li, Wei Xue, Huairui Yuan, Baijun Dong, Yufeng Ding, Yongfeng Liu, Min Jiang, Shan Kan, Tongyu Sun, Jiale Ren, Qiang Pan, Xiang Li, Peiyuan Zhang, Guohong Hu, Yan Wang, Xiaoming Wang, Qintong Li, Jun Qin
Loss of phosphatase and tensin homolog (PTEN) and activation of the PI3K/AKT signaling pathway are hallmarks of prostate cancer (PCa). However, these alterations alone are insufficient for cells to acquire metastatic traits. Here, we have shown that the histone dimethyl transferase WHSC1 critically drives indolent PTEN-null tumors to become metastatic PCa. In a PTEN-null murine PCa model, WHSC1 overexpression in prostate epithelium cooperated with Pten deletion to produce a metastasis-prone tumor. Conversely, genetic ablation of Whsc1 prevented tumor progression in PTEN-null mice...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28318385/arsenic-induced-sumoylation-of-mus81-is-involved-in-regulating-genomic-stability
#5
Liyan Hu, Feikun Yang, Lou Lu, Wei Dai
Chronic environmental exposure to metal toxicants such as chromium and arsenic is closely related to the development of several types of common cancers. Genetic and epigenetic studies in the past decade reveal that post-translational modifications of histones play a role in metal carcinogenesis. However, exact molecular mechanisms of metal carcinogenesis remain to be elucidated. In this study we found that As2O3, an environmental metal toxicant, up-regulated overall modifications of many cellular proteins by SUMO2/3...
March 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28315775/assessment-of-histone-tail-modifications-and-transcriptional-profiling-during-colon-cancer-progression-reveals-a-global-decrease-in-h3k4me3-activity
#6
Karen Triff, Mathew W McLean, Kranti Konganti, Jiahui Pang, Evelyn Callaway, Beiyan Zhou, Ivan Ivanov, Robert S Chapkin
During colon cancer, epigenetic alterations contribute to the dysregulation of major cellular functions and signaling pathways. Modifications in chromatin signatures such as H3K4me3 and H3K9ac, which are associated with transcriptionally active genes, can lead to genomic instability and perturb the expression of gene sets associated with oncogenic processes. In order to further elucidate early pre-tumorigenic epigenetic molecular events driving CRC, we integrated diverse, genome-wide, epigenetic inputs (by high throughput sequencing of RNA, H3K4me3, and H3K9ac) and compared differentially expressed transcripts (DE) and enriched regions (DER) in an in-vivo rat colon cancer progression model...
March 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28315714/cadmium-induced-malignant-transformation-of-rat-liver-cells-potential-key-role-and-regulatory-mechanism-of-altered-apolipoprotein-e-expression-in-enhanced-invasiveness
#7
Masayo Suzuki, Shuso Takeda, Noriko Teraoka-Nishitani, Akane Yamagata, Takahiro Tanaka, Marika Sasaki, Natsuki Yasuda, Makiko Oda, Tatsuji Okano, Kazuhiro Yamahira, Yuta Nakamura, Takanobu Kobayashi, Katsuhito Kino, Hiroshi Miyazawa, Michael P Waalkes, Masufumi Takiguchi
Cadmium is a transition metal that is classified as human carcinogen by the International Agency for Research on Cancer (IARC) with multiple target sites. Many studies using various model systems provide evidence of cadmium-induced malignancy formation in vivo or malignant cell transformation in vitro. Nonetheless, further studies are needed to completely understand the mechanisms of cadmium carcinogenicity. Our prior studies have utilized a rat liver epithelial cell line (TRL 1215) as a model for cadmium-induced malignant transformation...
March 15, 2017: Toxicology
https://www.readbyqxmd.com/read/28315378/epigenetic-regulation-of-ret-receptor-tyrosine-kinase-and-non-coding-rnas-in-mtc
#8
Lauren Jin Suk Joo, Jing Ting Zhao, Matti L Gild, Anthony R Glover, Stan B Sidhu
Medullary thyroid carcinoma (MTC) is an aggressive and rare cancer with limited treatment options for metastatic disease. Due to this, there is a need for a better understanding of MTC biology in the hope of improved treatments. One area of improved understanding of cancer biology is epigenetics. Epigenetics is defined as cellular processes which alter gene expression independent of changes in the primary DNA sequence. These processes include modifications such as DNA methylation, microRNA deregulation and post-translational histone modifications, all of which have been implicated in tumorigenesis of MTC...
March 14, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28315368/the-emerging-role-of-pi3k-akt-mediated-epigenetic-regulation-in-cancer
#9
REVIEW
Jennifer M Spangle, Thomas M Roberts, Jean J Zhao
The PI3-kinase/AKT pathway integrates signals from external cellular stimuli to regulate essential cellular functions, and is frequently aberrantly activated in human cancers. Recent research demonstrates that tight regulation of the epigenome is critical in preserving and restricting transcriptional activation, which can impact cellular growth and proliferation. In this review we examine mechanisms by which the PI3K/AKT pathway regulates the epigenome to promote oncogenesis, and highlight how connections between PI3K/AKT and the epigenome may impact the future therapeutic treatment of cancers featuring a hyperactivated PI3K/AKT pathway...
March 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28315155/synchronous-triple-primary-cancers-of-the-pharynx-and-esophagus
#10
Seita Kataoka, Masami Omae, Yusuke Horiuchi, Akiyoshi Ishiyama, Toshiyuki Yoshio, Toshiaki Hirasawa, Yorimasa Yamamoto, Tomohiro Tsuchida, Junko Fujisaki, Kazuhiko Yamada, Masahiro Igarashi
A 72-year-old male with nausea and heartburn was found to have early pharyngeal squamous cell carcinoma, superficial and advanced esophageal squamous cell carcinoma and early esophageal adenocarcinoma by esophagogastroduodenoscopy. Computerized tomography demonstrated left cardiac lymph node swellings. We prioritized the treatment for esophageal squamous cell carcinoma, as this was the most advanced cancer among the triple primaries. The patient underwent neoadjuvant chemotherapy for esophageal squamous cell carcinoma followed by esophagectomy...
March 17, 2017: Clinical Journal of Gastroenterology
https://www.readbyqxmd.com/read/28315153/effects-of-histone-deacetylase-inhibitory-prodrugs-on-epigenetic-changes-and-dna-damage-response-in-tumor-and-heart-of-glioblastoma-xenograft
#11
Nataly Tarasenko, Abraham Nudelman, Gabriela Rozic, Suzanne M Cutts, Ada Rephaeli
The histone deacetylase (HDAC) inhibitory prodrugs of butyric (AN7) and valproic (AN446) acids, which release the active acids upon metabolic degradation, were studied examining their differential effects on the viability, HDAC inhibitory activity and the DNA damage response (DDR), in glioblastoma cell and normal human astrocytes (NHAs). In xenografts of glioblastoma, AN7 or AN446 given or the combination of each of them with Dox augmented the anticancer activity of Dox and protected the heart from its toxicity...
March 17, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28314692/identification-of-an-atypical-etiological-head-and-neck-squamous-carcinoma-subtype-featuring-the-cpg-island-methylator-phenotype
#12
K Brennan, J L Koenig, A J Gentles, J B Sunwoo, O Gevaert
Head and neck squamous cell carcinoma (HNSCC) is broadly classified into HNSCC associated with human papilloma virus (HPV) infection, and HPV negative HNSCC, which is typically smoking-related. A subset of HPV negative HNSCCs occur in patients without smoking history, however, and these etiologically 'atypical' HNSCCs disproportionately occur in the oral cavity, and in female patients, suggesting a distinct etiology. To investigate the determinants of clinical and molecular heterogeneity, we performed unsupervised clustering to classify 528 HNSCC patients from The Cancer Genome Atlas (TCGA) into putative intrinsic subtypes based on their profiles of epigenetically (DNA methylation) deregulated genes...
March 1, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28314406/the-role-of-targeted-therapy-in-the-management-of-sinonasal-malignancies
#13
REVIEW
Lawrence Kashat, Christopher H Le, Alexander G Chiu
Cancers develop secondary to genetic and epigenetic changes that provide the cell with a survival advantage that promotes cellular immortality. Malignancy arises when tumors use mechanisms to evade detection and destruction by the immune system. Many malignancies seem to elicit an immune response, yet somehow manage to avoid destruction by the cells of the immune system. Cancers may evade this immune response by numerous mechanisms. Several targeted immune therapies are available that block some of these inhibitory signals and enhance the cell-mediated immune response...
April 2017: Otolaryngologic Clinics of North America
https://www.readbyqxmd.com/read/28314271/identification-of-methylation-profiles-of-cancer-related-genes-in-circulating-tumor-cells-population
#14
Anna Lyberopoulou, Michail Galanopoulos, Gerasimos Aravantinos, George E Theodoropoulos, Evangelos Marinos, Efstathios P Efstathopoulos, Maria Gazouli
BACKGROUND: We performed an epigenetic analysis of the first exon of the hVIM gene and the SFRP2 in circulating tumor cells (CTCs) and correlation with the corresponding primary colorectal cancer (CRC) tissue. PATIENTS AND METHODS: CTCs detection in 52 colorectal cancer patients was managed by a multi-marker immunomagnetic method with the use of quantum dots (QDs). To determine methylation levels we used high-resolution melting (HRM) technology. RESULTS: In the case of VIM we found 76...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28306719/chromosome-19q13-disruption-alters-expressions-of-cyp2a7-mia-and-mia-rab4b-lncrna-and-contributes-to-fap-like-phenotype-in-apc-mutation-negative-familial-colorectal-cancer-patients
#15
Lai Fun Thean, Yu Hui Wong, Michelle Lo, Carol Loi, Min Hoe Chew, Choong Leong Tang, Peh Yean Cheah
Familial adenomatous polyposis (FAP) is an autosomal-dominantly inherited form of colorectal cancer (CRC) caused by mutation in the adenomatous polyposis coli (APC) gene. Our ability to exhaustively screen for APC mutations identify microsatellite-stable and APC-mutation negative familial CRC patients, enabling us to search for novel genes. We performed genome-wide scan on two affected siblings of one family and 88 ethnicity- and gender-matched healthy controls to identify deletions shared by the siblings. Combined loss of heterozygosity, copy number and allelic-specific copy number analysis uncovered 5 shared deletions...
2017: PloS One
https://www.readbyqxmd.com/read/28304185/modulation-of-transcription-factor-binding-and-epigenetic-regulation-of-the-mlh1-cpg-island-and-shore-by-polymorphism-rs1800734-in-colorectal-cancer
#16
Andrea J Savio, Bharati Bapat
The MLH1 promoter polymorphism rs1800734 is associated with MLH1 CpG island hypermethylation and expression loss in colorectal cancer (CRC). Conversely, variant rs1800734 is associated with MLH1 shore, but not island, hypomethylation in peripheral blood mononuclear cell DNA. To explore these distinct patterns, MLH1 CpG island and shore methylation was assessed in CRC cell lines stratified by rs1800734 genotype. Cell lines containing the variant A allele demonstrated MLH1 shore hypomethylation compared to wild type (GG)...
March 17, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28303350/immunohistochemical-evaluation-of-klotho-and-dna-methyltransferase-3a-in-oral-squamous-cell-carcinomas
#17
Bhoj Raj Adhikari, Osamu Uehara, Hirofumi Matsuoka, Rie Takai, Fumiya Harada, Masafumi Utsunomiya, Takatoshi Chujo, Tetsuro Morikawa, Mamata Shakya, Koki Yoshida, Jun Sato, Toshiya Arakawa, Michiko Nishimura, Hiroki Nagayasu, Itsuo Chiba, Yoshihiro Abiko
Carcinoma follows a course of multiple changes that are affected by several important factors, with epigenetic silencing of the promoter gene being one of them. A series of studies have suggested that epigenetic changes in the anti-aging gene Klotho may be one of the emerging areas of concern in the study of carcinogenesis. We hypothesized that epigenetic silencing of Klotho due to hypermethylation of DNMT3a may be one of the causes of carcinoma in the oral and maxillofacial region. In this study, we analyzed the immunohistochemical expressions of Klotho and DNMT3a in tissues obtained from oral dysplasia and oral squamous cell carcinoma...
March 16, 2017: Medical Molecular Morphology
https://www.readbyqxmd.com/read/28302822/the-cancer-epigenome-concepts-challenges-and-therapeutic-opportunities
#18
REVIEW
Mark A Dawson
Cancer biology is profoundly influenced by changes in the epigenome. Because the dynamic plasticity of the epigenome lends itself well to therapeutic manipulation, the past few years have witnessed an unprecedented investment in the development, characterization, and translation of targeted epigenetic therapies. In this review, I provide a broad context for recent developments that offer a greater understanding of how epigenetic regulators facilitate the initiation, maintenance, and evolution of cancer. I discuss newly developed epigenetic therapies and the cellular and molecular mechanisms that may govern sensitivity and resistance to these agents...
March 17, 2017: Science
https://www.readbyqxmd.com/read/28302680/genomic-and-epigenomic-heterogeneity-of-hepatocellular-carcinoma
#19
De-Chen Lin, Anand Mayakonda, Huy Q Dinh, Pinbo Huang, Lehang Lin, Xiaoping Liu, Ling-Wen Ding, Jie Wang, Benjamin Berman, Erwei Song, Dong Yin, H Phillip Koeffler
Understanding the intratumoral heterogeneity of hepatocellular carcinoma (HCC) is instructive for developing personalized therapy and identifying molecular biomarkers. Here we applied whole-exome sequencing to 69 samples from 11 patients to resolve the genetic architecture of subclonal diversification. Spatial genomic diversity was found in all 11 HCC cases, with 29% of driver mutations being heterogeneous, including TERT, ARID1A, NOTCH2, and STAG2. Similar with other cancer types, TP53 mutations were always shared between all tumor regions i...
February 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28302417/muc1-c-oncoprotein-integrates-a-program-of-emt-epigenetic-reprogramming-and-immune-evasion-in-human-carcinomas
#20
REVIEW
Hasan Rajabi, Donald Kufe
The MUC1 gene evolved in mammalian species to provide protection of epithelia. The transmembrane MUC1 C-terminal subunit (MUC1-C) signals stress to the interior of the epithelial cell and, when overexpressed as in most carcinomas, functions as an oncoprotein. MUC1-C induces the epithelial-mesenchymal transition (EMT) by activating the inflammatory NF-κB p65 pathway and, in turn, the EMT-transcriptional repressor ZEB1. Emerging evidence has indicated that MUC1-C drives a program integrating the induction of EMT with activation of stem cell traits, epigenetic reprogramming and immune evasion...
March 14, 2017: Biochimica et Biophysica Acta
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