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Cancer regulatory

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https://www.readbyqxmd.com/read/28231588/checkpoint-inhibition-in-head-and-neck-cancer-immune-therapeutic-options-limitations-and-beyond
#1
Bastian Höchst, Percy A Knolle
The immune system functions to defend the organism against infectious microorganisms but also against transformed cells. This key role of the immune system, in particular cancer-specific T cells, in eliminating cancer cells is compromised by various immune escape strategies employed by cancer cells and the cancer microenvironment. Here, we review the current knowledge about the immune escape mechanisms of cancer and the attempts to reconstitute cancer-specific immunity by using checkpoint inhibitors in head and neck squamous cell carcinoma...
February 24, 2017: ORL; Journal for Oto-rhino-laryngology and its related Specialties
https://www.readbyqxmd.com/read/28230721/the-interplay-of-lncrna-h19-and-its-binding-partners-in-physiological-process-and-gastric-carcinogenesis
#2
REVIEW
Li Zhang, Yuhang Zhou, Tingting Huang, Alfred S L Cheng, Jun Yu, Wei Kang, Ka Fai To
Long non-coding RNA (lncRNA), a novel and effective modulator in carcinogenesis, has become a study hotspot in recent years. The imprinted oncofetal lncRNA H19 is one of the first identified imprinted lncRNAs with a high expression level in embryogenesis but is barely detectable in most tissues after birth. Aberrant alterations of H19 expression have been demonstrated in various tumors, including gastric cancer (GC), implicating a crucial role of H19 in cancer progression. As one of the top malignancies in the world, GC has already become a serious concern to public health with poor prognosis...
February 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28230290/a3-adenosine-receptor-agonist-inhibited-survival-of-breast-cancer-stem-cells-via-gli-1-and-erk1-2-pathway
#3
Seyyed Mehdi Jafari, Mojtaba Panjehpour, Mahmoud Aghaei, Hamid Reza Joshaghani, Seyed Ehsan Enderami
Numerous studies have demonstrated the role of A3 adenosine receptor (A3AR) and signaling pathways in the multiple aspects of the tumor. However, there is a little study about the function of A3AR in the biological processes of cancer stem cells (CSCs). CSCs have a critical role in the maintenance and survival of breast cancer. The aim of current study was to investigate the effect of A3AR agonist on breast cancer stem cells (BCSCs). XTT assay showed antiprolierative effect of A3AR agonist (Cl-IB-MECA) on BCSCs...
February 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28230171/impact-of-genetic-variation-on-human-camkk2-regulation-by-ca-2-calmodulin-and-multisite-phosphorylation
#4
Matthew T O'Brien, Jonathan S Oakhill, Naomi X Y Ling, Christopher G Langendorf, Ashfaqul Hoque, Toby A Dite, Anthony R Means, Bruce E Kemp, John W Scott
The Ca(2+)-calmodulin dependent protein kinase kinase-2 (CaMKK2) is a key regulator of neuronal function and whole-body energy metabolism. Elevated CaMKK2 activity is strongly associated with prostate and hepatic cancers, whereas reduced CaMKK2 activity has been linked to schizophrenia and bipolar disease in humans. Here we report the functional effects of nine rare-variant point mutations that were detected in large-scale human genetic studies and cancer tissues, all of which occur close to two regulatory phosphorylation sites and the catalytic site on human CaMKK2...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28229932/csn5-jab1-suppresses-the-wnt-inhibitor-dkk1-in-colorectal-cancer-cells
#5
Sandra Jumpertz, Thomas Hennes, Yaw Asare, Anke K Schütz, Jürgen Bernhagen
The COP9 signalosome (CSN) is a multi-protein complex that is highly conserved in eukaryotes. Due to its regulatory impact on processes such as cell cycle, DNA damage response and apoptosis, the CSN is essential for mammalian cells. One of the best-studied functions of the CSN is the deNEDDylation of cullin-RING ligases (CRLs) via its catalytically active subunit CSN5/JAB1, thereby triggering the degradation of various target proteins. CSN5 was found to be overexpressed in many human cancer entities, including colon adenocarcinoma...
February 13, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28228643/a-chemical-probe-toolbox-for-dissecting-the-cancer-epigenome
#6
REVIEW
Jake Shortt, Christopher J Ott, Ricky W Johnstone, James E Bradner
Cancer cell hallmarks are underpinned by transcriptional programmes operating in the context of a dynamic and complicit epigenomic environment. Somatic alterations of chromatin modifiers are among the most prevalent cancer perturbations. There is a pressing need for targeted chemical probes to dissect these complex, interconnected gene regulatory circuits. Validated chemical probes empower mechanistic research while providing the pharmacological proof of concept that is required to translate drug-like derivatives into therapy for cancer patients...
February 23, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28228558/the-ribosomal-protein-s19-suppresses-antitumor-immune-responses-via-the-complement-c5a-receptor-1
#7
Maciej M Markiewski, Surya Kumari Vadrevu, Sharad K Sharma, Navin Kumar Chintala, Shanawaz Ghouse, Jun-Hung Cho, David P Fairlie, Yvonne Paterson, Aristotelis Astrinidis, Magdalena Karbowniczek
Relatively little is known about factors that initiate immunosuppression in tumors and act at the interface between tumor cells and host cells. In this article, we report novel immunosuppressive properties of the ribosomal protein S19 (RPS19), which is upregulated in human breast and ovarian cancer cells and released from apoptotic tumor cells, whereupon it interacts with the complement C5a receptor 1 expressed on tumor infiltrating myeloid-derived suppressor cells. This interaction promotes tumor growth by facilitating recruitment of these cells to tumors...
February 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28228083/oncolytic-virus-regulatory-aspects-from-quality-control-to-clinical-studies
#8
Teruhide Yamaguchi, Eriko Uchida
Oncolytic viruses, which include both naturally occurring wild-type viruses/attenuated viruses and genetically modified viruses, have recently been developed for use in innovative cancer therapies. Genetically modified oncolytic viruses possess the unique ability to replicate conditionally as a unique gene therapy product. Since oncolytic viruses exhibit prolonged persistence in patients, viral shedding and transmission to third parties should be major concerns for clinical trials, along with the clinical safety and efficacy...
February 22, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28227912/a-hybrid-discrete-continuous-model-of-in-vitro-spheroid-tumor-growth-and-drug-response
#9
Giorgos Tzedakis, Evangelos Liapis, Eleftheria Tzamali, Giannis Zacharakis, Vangelis Sakkalis, Giorgos Tzedakis, Evangelos Liapis, Eleftheria Tzamali, Giannis Zacharakis, Vangelis Sakkalis, Giannis Zacharakis, Vangelis Sakkalis, Evangelos Liapis, Giorgos Tzedakis, Eleftheria Tzamali
Anti-cancer therapy efficacy in solid tumors mainly depends on drug transportation through the vasculature system and the extracellular matrix, on diffusion gradients and clonal heterogeneity within the tumor mass, as well as on the responses of the individual tumor cells to drugs and their interactions with each other and their local microenvironment. In this work, we develop a mathematical predictive model for tumor growth and drug response based on 3D spheroids experiments that possess several in vivo features of tumors and are considered better for drug screening...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28227870/identifying-disease-network-perturbations-through-regression-on-gene-expression-and-pathway-topology-analysis
#10
Georgios N Dimitrakopoulos, Panos Balomenos, Aristidis G Vrahatis, Kyriakos Sgarbas, Anastasios Bezerianos, Georgios N Dimitrakopoulos, Panos Balomenos, Aristidis G Vrahatis, Kyriakos Sgarbas, Anastasios Bezerianos, Kyriakos Sgarbas, Panos Balomenos, Georgios N Dimitrakopoulos, Anastasios Bezerianos, Aristidis G Vrahatis
In Systems Biology, network-based approaches have been extensively used to effectively study complex diseases. An important challenge is the detection of network perturbations which disrupt regular biological functions as a result of a disease. In this regard, we introduce a network based pathway analysis method which isolates casual interactions with significant regulatory roles within diseased-perturbed pathways. Specifically, we use gene expression data with Random Forest regression models to assess the interactivity strengths of genes within disease-perturbed networks, using KEGG pathway maps as a source of prior-knowledge pertaining to pathway topology...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28226421/opening-plenary-speaker-human-genomics-precision-medicine-and-advancing-human-health
#11
Eric D Green
Starting with the launch of the Human Genome Project in 1990, the past quarter-century has brought spectacular achievements in genomics that dramatically empower the study of human biology and disease. The human genomics enterprise is now in the midst of an important transition, as the growing foundation of genomic knowledge is being used by researchers and clinicians to tackle increasingly complex problems in biomedicine. Of particular prominence is the use of revolutionary new DNA sequencing technologies for generating prodigious amounts of DNA sequence data to elucidate the complexities of genome structure, function, and evolution, as well as to unravel the genomic bases of rare and common diseases...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28225892/regulation-of-semaphorin-4d-expression-and-cell-proliferation-of-ovarian-cancer-by-eralpha-and-erbeta
#12
Y Liu, Y Hou, L Ma, C Sun, J Pan, Y Yang, H Zhou, J Zhang
Ovarian cancer is one of the most common malignancies in women. Semaphorin 4D (sema 4D) is involved in the progress of multiple cancers. In the presence of estrogen-like ligands, estrogen receptors (ERα and ERβ) participate in the progress of breast and ovarian cancers by transcriptional regulation. The aim of the study was to investigate the role of sema 4D and elucidate the regulatory pattern of ERα and ERβ on sema 4D expression in ovarian cancers. Sema 4D levels were up-regulated in ovarian cancer SKOV-3 cells...
February 20, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28225038/direct-binding-of-mek1-and-mek2-to-akt-induces-foxo1-phosphorylation-cellular-migration-and-metastasis
#13
Shiri Procaccia, Merav Ordan, Izel Cohen, Sarit Bendetz-Nezer, Rony Seger
Crosstalk between the ERK cascade and other signaling pathways is one of the means by which it acquires its signaling specificity. Here we identified a direct interaction of both MEK1 and MEK2 with AKT. The interaction is mediated by the proline rich domain of MEK1/2 and regulated by phosphorylation of Ser298 in MEK1, or Ser306 in MEK2, which we identified here as a novel regulatory site. We further developed a blocking peptide, which inhibits the interaction between MEK and AKT, and when applied to cells, affects migration and adhesion, but not proliferation...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28224495/hidden-markov-models-in-bioinformatics-snv-inference-from-next-generation-sequence
#14
Jiawen Bian, Xiaobo Zhou
The rapid development of next generation sequencing (NGS) technology provides a novel avenue for genomic exploration and research. Hidden Markov models (HMMs) have wide applications in pattern recognition as well as Bioinformatics such as transcription factor binding sites and cis-regulatory modules detection. An application of HMM is introduced in this chapter with the in-deep developing of NGS. Single nucleotide variants (SNVs) inferred from NGS are expected to reveal gene mutations in cancer. However, NGS has lower sequence coverage and poor SNV detection capability in the regulatory regions of the genome...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28224211/mechanisms-overseeing-myeloid-derived-suppressor-cell-production-in-neoplastic-disease
#15
REVIEW
Colleen S Netherby, Scott I Abrams
Perturbations in myeloid cell differentiation are common in neoplasia, culminating in immature populations known as myeloid-derived suppressor cells (MDSCs). MDSCs favor tumor progression due to their ability to suppress host immunity or promote invasion and metastasis. They are thought to originate from the bone marrow as a result of exposure to stromal- or circulating tumor-derived factors (TDFs). Although great interest has been placed on understanding how MDSCs function, less is known regarding how MDSCs develop at a transcriptional level...
February 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28224210/tumor-specific-regulatory-t-cells-in-the-bone-marrow-of-breast-cancer-patients-selectively-upregulate-the-emigration-receptor-s1p1
#16
Anchana Rathinasamy, Christoph Domschke, Yingzi Ge, Hans-Henning Böhm, Steffen Dettling, David Jansen, Felix Lasitschka, Ludmila Umansky, Markus H Gräler, Jennifer Hartmann, Christel Herold-Mende, Florian Schuetz, Philipp Beckhove
Regulatory T cells (Treg) hamper anti-tumor T-cell responses resulting in reduced survival and failure of cancer immunotherapy. Among lymphoid organs, the bone marrow (BM) is a major site of Treg residence and recirculation. However, the process governing the emigration of Treg from BM into the circulation remains elusive. We here show that breast cancer patients harbour reduced Treg frequencies in the BM as compared to healthy individuals or the blood. This was particularly the case for tumor antigen-specific Treg which were quantified by MHCII tumor peptide loaded tetramers...
February 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28223815/antitumor-effects-of-oncolytic-herpes-simplex-virus-type-2-against-colorectal-cancer-in-vitro-and-in-vivo
#17
Lei Yin, Chunhong Zhao, Jixia Han, Zengjun Li, Yanan Zhen, Ruixue Xiao, Zhongfa Xu, Yanlai Sun
BACKGROUND: The incidence of colorectal cancer (CRC) is on the rise. Furthermore, late-stage diagnoses and limited efficacious treatment options make CRC a complex clinical challenge. Therefore, a new therapeutic regimen with a completely novel therapeutic mechanism is necessary for CRC. In the present study, the therapeutic efficacy of oncolytic herpes simplex virus type 2 (oHSV2) in CRC was assessed in vitro and in vivo. oHSV2 is an oncolytic agent derived from herpes simplex virus type 2 that encodes granulocyte-macrophage colony-stimulating factor...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28223316/energy-metabolism-drives-myeloid-derived-suppressor-cell-differentiation-and-functions-in-pathology
#18
REVIEW
Antonio Sica, Laura Strauss
Over the last decade, a heterogeneous population of immature myeloid cells with major regulatory functions has been described in cancer and other pathologic conditions and ultimately defined as MDSCs. Most of the early work on the origins and functions of MDSCs has been in murine and human tumor bearers in which MDSCs are known to be immunosuppressive and to result in both reduced immune surveillance and antitumor cytotoxicity. More recent studies, however, suggest that expansion of these immature myeloid cells may be linked to most, if not all, chronic and acute inflammatory processes...
February 21, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28220871/identification-of-mirna-mrna-modules-in-colorectal-cancer-using-rough-hypercuboid-based-supervised-clustering
#19
Sushmita Paul, Petra Lakatos, Arndt Hartmann, Regine Schneider-Stock, Julio Vera
Differences in the expression profiles of miRNAs and mRNAs have been reported in colorectal cancer. Nevertheless, information on important miRNA-mRNA regulatory modules in colorectal cancer is still lacking. In this regard, this study presents an application of the RH-SAC algorithm on miRNA and mRNA expression data for identification of potential miRNA-mRNA modules. First, a set of miRNA rules was generated using the RH-SAC algorithm. The mRNA targets of the selected miRNAs were identified using the miRTarBase database...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220193/hsa-mir-4485-regulates-mitochondrial-functions-and-inhibits-the-tumorigenicity-of-breast-cancer-cells
#20
Lakshmi Sripada, Kritarth Singh, Anastasiya V Lipatova, Aru Singh, Paresh Prajapati, Dhanendra Tomar, Khyati Bhatelia, Milton Roy, Rochika Singh, Madan M Godbole, Peter M Chumakov, Rajesh Singh
The modulation of mitochondrial functions is important for maintaining cellular homeostasis. Mitochondria essentially depend on the import of RNAs and proteins encoded by the nuclear genome. MicroRNAs encoded in the nucleus can translocate to mitochondria and target the genome, affecting mitochondrial function. Here, we analyzed the role of miR-4485 in the regulation of mitochondrial functions. We showed that miR-4485 translocated to mitochondria where its levels varied in response to different stress conditions...
February 20, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
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