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https://www.readbyqxmd.com/read/29149251/parental-age-and-risk-of-lymphoid-neoplasms
#1
Gunnar Larfors, Ingrid Glimelius, Sandra Eloranta, Karin E Smedby
High parental age at childbirth has repeatedly been linked to childhood malignancies, while few studies have focused on the offspring's risk of adult cancer. In this population-based case-control study, we identified 32,000 patients with lymphoid neoplasms, diagnosed at ages 0-79 years during the period 1987-2011, and 160,000 matched controls in Sweden. Using prospectively registered data on their first-degree relatives, we evaluated the impact of parental age on the risk of lymphoid neoplasms by subtype. Overall, each 5-year increment in maternal age was associated with a 3% increase in incidence of offspring lymphoid neoplasms (hazard ratio = 1...
November 15, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/29148847/emerging-therapeutic-targets-in-myeloproliferative-neoplasms-and-peripheral-t-cell-leukemia-and-lymphomas
#2
Anna Orlova, Bettina Wingelhofer, Heidi A Neubauer, Barbara Maurer, Angelika Berger-Becvar, György Miklós Keserű, Patrick T Gunning, Peter Valent, Richard Moriggl
Hematopoietic neoplasms are often driven by gain-of-function mutations of the JAK-STAT pathway together with mutations of chromatin remodeling and DNA damage control pathways. The interconnection between the JAK-STAT pathway, epigenetic regulation or DNA damage control is still poorly understood in cancer cell biology. Areas covered: Here, we focus on a broader description of mutational insights into myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas, since sequencing efforts have identified similar combinations of driver mutations in these diseases covering different lineages...
November 17, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29148109/notch-signaling-controls-transdifferentiation-of-pulmonary-neuroendocrine-cells-in-response-to-lung-injury
#3
Erica Yao, Chuwen Lin, Qingzhe Wu, Kuan Zhang, Hai Song, Pao-Tien Chuang
Production of an appropriate number of distinct cell types in precise locations during embryonic development is critical for proper tissue function. Homeostatic renewal or repair of damaged tissues in adults also requires cell expansion and transdifferentiation to replenish lost cells. However, the responses of diverse cell types to tissue injury are not fully elucidated. Moreover, the molecular mechanisms underlying transdifferentiation remain poorly understood. This knowledge is essential for harnessing the regenerative potential of individual cell types...
November 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/29146225/response-comparison-of-multiple-myeloma-and-monoclonal-gammopathy-of-undetermined-significance-to-the-same-anti-myeloma-therapy-a-retrospective-cohort-study
#4
John P Campbell, Jennifer L J Heaney, Sankalp Pandya, Zaheer Afzal, Martin Kaiser, Roger Owen, J Anthony Child, David A Cairns, Walter Gregory, Gareth J Morgan, Graham H Jackson, Chris M Bunce, Mark T Drayson
BACKGROUND: Multiple myeloma is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS), which is usually only treated by a form of anti-multiple myeloma therapy if it is causing substantial disease through deposition of secreted M proteins. However, studies comparing how MGUS and multiple myeloma plasma cell clones respond to these therapies are scarce. Biclonal gammopathy multiple myeloma is characterised by the coexistence of an active multiple myeloma clone and a benign MGUS clone, and thus provides a unique model to assess the responses of separate clones to the same anti-multiple myeloma therapy, in the same patient, at the same time...
November 13, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/29146205/pax3-foxo1-zooming-in-on-an-undruggable-target
#5
REVIEW
Marco Wachtel, Beat W Schäfer
Driver oncogenes are prime targets for therapy in tumors many of which, including leukemias and sarcomas, express recurrent fusion transcription factors. One specific example for such a cancer type is alveolar rhabdomyosarcoma, which is associated in the majority of cases with the fusion protein PAX3-FOXO1. Since fusion transcription factors are challenging targets for development of small molecule inhibitors, indirect inhibitory strategies for this type of oncogenes represent a more promising approach. One can envision strategies at different molecular levels including upstream modifiers and activators, epigenetic and transcriptional co-regulators, and downstream effector targets...
November 13, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29145976/not-only-p-glycoprotein-amplification-of-the-abcb1-containing-chromosome-region-7q21-confers-multidrug-resistance-upon-cancer-cells-by-coordinated-overexpression-of-an-assortment-of-resistance-related-proteins
#6
Ilaria Genovese, Andrea Ilari, Yehuda G Assaraf, Francesco Fazi, Gianni Colotti
The development of drug resistance continues to be a dominant hindrance toward curative cancer treatment. Overexpression of a wide-spectrum of ATP-dependent efflux pumps, and in particular of ABCB1 (P-glycoprotein or MDR1) is a well-known resistance mechanism for a plethora of cancer chemotherapeutics including for example taxenes, anthracyclines, Vinca alkaloids, and epipodopyllotoxins, demonstrated by a large array of published papers, both in tumor cell lines and in a variety of tumors, including various solid tumors and hematological malignancies...
May 2017: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/29145898/making-gametes-from-alternate-sources-of-stem-cells-past-present-and-future
#7
REVIEW
Deepa Bhartiya, Sandhya Anand, Hiren Patel, Seema Parte
Infertile couples including cancer survivors stand to benefit from gametes differentiated from embryonic or induced pluripotent stem (ES/iPS) cells. It remains challenging to convert human ES/iPS cells into primordial germ-like cells (PGCLCs) en route to obtaining gametes. Considerable success was achieved in 2016 to obtain fertile offspring starting with mouse ES/iPS cells, however the specification of human ES/iPS cells into PGCLCs in vitro is still not achieved. Human ES cells will not yield patient-specific gametes unless and until hES cells are derived by somatic cell nuclear transfer (therapeutic cloning) whereas iPS cells retain the residual epigenetic memory of the somatic cells from which they are derived and also harbor genomic and mitochondrial DNA mutations...
November 16, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/29145444/inhibition-of-the-h3k9-methyltransferase-g9a-attenuates-oncogenicity-and-activates-the-hypoxia-signaling-pathway
#8
Jolene Caifeng Ho, Lissa Nurrul Abdullah, Qing You Pang, Sudhakar Jha, Edward Kai-Hua Chow, Henry Yang, Hiroyuki Kato, Lorenz Poellinger, Jun Ueda, Kian Leong Lee
Epigenetic mechanisms play important roles in the regulation of tumorigenesis, and hypoxia-induced epigenetic changes may be critical for the adaptation of cancer cells to the hypoxic microenvironment of solid tumors. Previously, we showed that loss-of-function of the hypoxia-regulated H3K9 methyltransferase G9A attenuates tumor growth. However, the mechanisms by which blockade of G9A leads to a tumor suppressive effect remain poorly understood. We show that G9A is highly expressed in breast cancer and is associated with poor patient prognosis, where it may function as a potent oncogenic driver...
2017: PloS One
https://www.readbyqxmd.com/read/29143818/visualization-of-chemical-modifications-in-the-human-80s-ribosome-structure
#9
S Kundhavai Natchiar, Alexander G Myasnikov, Hanna Kratzat, Isabelle Hazemann, Bruno P Klaholz
Chemical modifications of human ribosomal RNA (rRNA) are introduced during biogenesis and have been implicated in the dysregulation of protein synthesis, as is found in cancer and other diseases. However, their role in this phenomenon is unknown. Here we visualize more than 130 individual rRNA modifications in the three-dimensional structure of the human ribosome, explaining their structural and functional roles. In addition to a small number of universally conserved sites, we identify many eukaryote- or human-specific modifications and unique sites that form an extended shell in comparison to bacterial ribosomes, and which stabilize the RNA...
November 15, 2017: Nature
https://www.readbyqxmd.com/read/29143608/physical-activity-in-the-prevention-of-human-diseases-role-of-epigenetic-modifications
#10
REVIEW
Elisa Grazioli, Ivan Dimauro, Neri Mercatelli, Guan Wang, Yannis Pitsiladis, Luigi Di Luigi, Daniela Caporossi
Epigenetic modification refers to heritable changes in gene function that cannot be explained by alterations in the DNA sequence. The current literature clearly demonstrates that the epigenetic response is highly dynamic and influenced by different biological and environmental factors such as aging, nutrient availability and physical exercise. As such, it is well accepted that physical activity and exercise can modulate gene expression through epigenetic alternations although the type and duration of exercise eliciting specific epigenetic effects that can result in health benefits and prevent chronic diseases remains to be determined...
November 14, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29143563/mammalian-target-of-rapamycin-complex-2-mtorc2-controls-glycolytic-gene-expression-by-regulating-histone-h3-lysine-56-acetylation
#11
Raghavendra Vadla, Devyani Haldar
Metabolic reprogramming is a hallmark of cancer cells, but the mechanisms are not well understood. The mammalian target of rapamycin complex 2 (mTORC2) controls cell growth and proliferation and plays a critical role in metabolic reprogramming in glioma. mTORC2 regulates cellular processes such as cell survival, metabolism, and proliferation by phosphorylation of AGC kinases. Components of mTORC2 are shown to localize to the nucleus, but whether mTORC2 modulates epigenetic modifications to regulate gene expression is not known...
November 16, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29143365/epigenetic-down-regulation-of-sox2-is-an-independent-poor-prognostic-factor-for-hypopharyngeal-cancers
#12
Mehmet Ozgur Avincsal, Naoe Jimbo, Kohei Fujikura, Hirotaka Shinomiya, Naoki Otsuki, Koichi Morimoto, Tatsuya Furukawa, Naruhiko Morita, Ritsuko Maehara, Tomoo Itoh, Ken-Ichi Nibu, Yoh Zen
AIMS: We recently reported that a small subset (7%) of oesophageal squamous cell carcinomas completely lacking SOX2 expression had unique clinicopathological features and a dismal prognosis. The present study aimed to elucidate whether the findings obtained in oesophageal cancers are applicable to hypopharyngeal or oropharyngeal squamous cell carcinomas (HPSCCs or OPSCCs, respectively). METHODS AND RESULTS: The study cohort consisted of consecutive patients with HPSCC (n=130) and OPSCC (n=65) who underwent surgery without preoperative therapy...
November 15, 2017: Histopathology
https://www.readbyqxmd.com/read/29143120/epigenetic-silencing-of-adamts5-is-associated-with-increased-invasiveness-and-poor-survival-in-patients-with-colorectal-cancer
#13
Jizhen Li, Yi Liao, Jintuan Huang, Yi Sun, Hao Chen, Chunyu Chen, Senmao Li, Zuli Yang
A disintegrin and metalloprotease with motif 5(ADAMTS5) has been involved in colorectal cancer (CRC) with hypermethylation in the promoter. However, its role in CRC remains unclear. The aim of this study was to explore the clinical significance and biological effect of ADAMTS5 on colorectal carcinogenesis. Through MSP, qRT-PCR, WB and IHC analysis, followed by a variety of in vitro assays, we report the function of ADAMTS5 in CRC. ADAMTS5 was markedly hypermethylaed and downregulated in tumor tissues compared with non-tumor tissues (p < 0...
November 15, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29142217/fbxo32-promotes-microenvironment-underlying-epithelial-mesenchymal-transition-via-ctbp1-during-tumour-metastasis-and-brain-development
#14
Sanjeeb Kumar Sahu, Neha Tiwari, Abhijeet Pataskar, Yuan Zhuang, Marina Borisova, Mustafa Diken, Susanne Strand, Petra Beli, Vijay K Tiwari
The set of events that convert adherent epithelial cells into migratory cells are collectively known as epithelial-mesenchymal transition (EMT). EMT is involved during development, for example, in triggering neural crest migration, and in pathogenesis such as metastasis. Here we discover FBXO32, an E3 ubiquitin ligase, to be critical for hallmark gene expression and phenotypic changes underlying EMT. Interestingly, FBXO32 directly ubiquitinates CtBP1, which is required for its stability and nuclear retention...
November 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29141972/epigenetic-regulation-of-centromere-chromatin-stability-by-dietary-and-environmental-factors
#15
REVIEW
Diego Hernández-Saavedra, Rita S Strakovsky, Patricia Ostrosky-Wegman, Yuan-Xiang Pan
The centromere is a genomic locus required for the segregation of the chromosomes during cell division. This chromosomal region together with pericentromeres has been found to be susceptible to damage, and thus the perturbation of the centromere could lead to the development of aneuploidic events. Metabolic abnormalities that underlie the generation of cancer include inflammation, oxidative stress, cell cycle deregulation, and numerous others. The micronucleus assay, an early clinical marker of cancer, has been shown to provide a reliable measure of genotoxic damage that may signal cancer initiation...
November 2017: Advances in Nutrition
https://www.readbyqxmd.com/read/29141353/-progress-in-research-of-thyroid-carcinoma-related-gene-mutation-and-epigenetics
#16
W H Zheng, W W Gong, F Lu, M Yu
Thyroid cancer is one of the most common endocrine malignant tumors, and its molecular pathogenesis is also a process of multiple genes involved in many steps of carcinogenesis. With the development of molecular biology technology, a variety of related gene mutations and epigenetic phenomena have been found in thyroid cancer tissues. It is helpful to understand the latest progress in the research of the gene mutation and epigenetics of thyroid cancer for its early diagnosis, prevention and the development of targeted drugs...
November 10, 2017: Zhonghua Liu Xing Bing Xue za Zhi, Zhonghua Liuxingbingxue Zazhi
https://www.readbyqxmd.com/read/29139562/lncrna-ghet1-predicts-poor-prognosis-in-hepatocellular-carcinoma-and-promotes-cell-proliferation-by-silencing-klf2
#17
Li Jin, Yangke He, Shijia Tang, Shan Huang
BACKGROUND: Hepatocellular carcinoma (HCC) has been identified as one of the leading causes of cancer-related death worldwide. Recently, long non-coding RNAs (lncRNAs) attract much attention of researchers, and they are demonstrated to be dysregulated in a variety of cancers, including HCC. LncRNA gastric carcinoma high expressed transcript 1 lncRNA GHET1 is found to be dysregulated in gastric cancer (GC). However, its clinical value and potential biological function in HCC remains unclear...
November 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29138572/current-status-of-poly-adp-ribose-polymerase-inhibitors-and-future-directions
#18
REVIEW
Akihiro Ohmoto, Shinichi Yachida
Inhibitors of poly(ADP-ribose) polymerases (PARPs), which play a key role in DNA damage/repair pathways, have been developed as antitumor agents based on the concept of synthetic lethality. Synthetic lethality is the idea that cell death would be efficiently induced by simultaneous loss of function of plural key molecules, for example, by exposing tumor cells with inactivating gene mutation of BRCA-mediated DNA repair to chemically induced inhibition of PARPs. Indeed, three PARP inhibitors, olaparib, rucaparib and niraparib have already been approved in the US or Europe, mainly for the treatment of BRCA-mutant ovarian cancer...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29138005/distinct-hypoxic-regulation-of-preadipocyte-factor-1-pref-1-in-preadipocytes-and-mature-adipocytes
#19
Yunwon Moon, Seongyeol Lee, Bongju Park, Hyunsung Park
Preadipocyte factor-1 (Pref-1) is a secretory soluble protein, which exerts pleiotropic effects on maintenance of cancer stem cell characteristics and commitment of mesenchymal stem cell lineages by inhibiting adipogenesis. Observations that obesity renders the microenvironment of adipose tissues hypoxic and that hypoxia inhibits adipogenesis lead us to investigate whether hypoxia increases the expression of anti-adipogenic Pref-1 in preadipocytes, mature adipocytes, and adipose tissues from obese mouse. In 3T3-L1 preadipocytes, hypoxia induces Pref-1 by a hypoxia-inducible factor 1 (HIF-1)-dependent mechanism accompanied by increase in the levels of the active histone mark, acetylated H3K9/14 (H3K9/14Ac)...
November 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29137437/dna-hypermethyation-and-silencing-of-pitx1-correlated-with-advanced-stage-and-poor-postoperative-prognosis-of-esophageal-squamous-cell-carcinoma
#20
Takeshi Otsubo, Kazuhiko Yamada, Teruki Hagiwara, Kenshiro Oshima, Kei Iida, Koro Nishikata, Tetsuro Toyoda, Toru Igari, Kyoko Nohara, Satoshi Yamashita, Masahira Hattori, Taeko Dohi, Yuki I Kawamura
Esophageal squamous cell carcinoma (ESCC) is associated with the accumulation of genetic and epigenetic changes in the background mucosa. Dysregulated DNA methylation is known to lead to the inactivation of tumor suppressor genes and the activation of oncogenes. To identify the genes whose expression is perturbed by abnormal DNA methylation in ESCC, integrative transcriptomics by serial analysis of gene expression (SAGE) and methylome sequencing by methyl-DNA immunoprecipitation (MeDIP) analysis were performed...
October 13, 2017: Oncotarget
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