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https://www.readbyqxmd.com/read/28430521/perinatal-light-imprinting-of-circadian-clocks-and-systems-pliccs-a-signature-of-photoperiod-around-birth-on-circadian-system-stability-and-association-with-cancer
#1
Philip Lewis, Thomas C Erren
Recent findings from animal models suggest that plasticity of human circadian clocks and systems may be differentially affected by different paradigms of perinatal photoperiod exposure to the detriment of health in later life, including cancer development. Focusing on the example of cancer, we carry out a series of systematic literature reviews concerning perinatal light imprinting of circadian clocks and systems (PLICCS) in animal models, and concerning the risk of cancer development with the primary determinants of the perinatal photoperiod, namely season of birth or latitude of birth...
April 21, 2017: Chronobiology International
https://www.readbyqxmd.com/read/28430399/targeting-conformational-activation-of-cdk2-kinase
#2
Morgan Pellerano, Sergey Tcherniuk, Corine Perals, Thi Nhu Ngoc Van, Elsa Garcin, Florence Mahuteau-Betzer, Marie-Paule Teulade-Fichou, May C Morris
Cyclin-dependent kinases constitute attractive pharmacological targets for cancer therapeutics, yet inhibitors in clinical trials target the ATP-binding pocket of the CDK and therefore suffer from limited selectivity and emergence of resistance. The more recent development of allosteric inhibitors targeting conformational plasticity of protein kinases offers promising perspectives for therapeutics. In particular tampering with T-loop dynamics of CDK2 kinase would provide a selective means of inhibiting this kinase, by preventing its conformational activation...
April 21, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28428965/natural-killer-cells-in-the-orchestration-of-chronic-inflammatory-diseases
#3
REVIEW
Luca Parisi, Barbara Bassani, Marco Tremolati, Elisabetta Gini, Giampietro Farronato, Antonino Bruno
Inflammation, altered immune cell phenotype, and functions are key features shared by diverse chronic diseases, including cardiovascular, neurodegenerative diseases, diabetes, metabolic syndrome, and cancer. Natural killer cells are innate lymphoid cells primarily involved in the immune system response to non-self-components but their plasticity is largely influenced by the pathological microenvironment. Altered NK phenotype and function have been reported in several pathological conditions, basically related to impaired or enhanced toxicity...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28426879/acute-exposure-to-dehp-metabolite-mehp-cause-genotoxicity-mutagenesis-and-carcinogenicity-in-mammalian-chinese-hamster-ovary-cells
#4
Yu-Jung Chang, Chia-Yi Tseng, Pei-Ying Lin, Yu-Chen Chuang, Ming-Wei Chao
Di-(2-ethylhexyl) phthalate (DEHP), the common plasticizer used in the production of polyvinyl chloride, can be converted to the more potent metabolite mono-ethylhexyl phthalate (MEHP). Epidemiological studies have shown an association with elevated induction of rat hepatic cancer and reproductive toxicity in response to MEHP exposure. However, the mechanism of genotoxicity and carcinogenicity induced by MEHP treatment remains unclear. As a means to elucidate the mechanisms of action, lethality and mutagenicity in the adenine phosphoribosyltransferase (aprt+/-) gene induced in several CHO cell types by MEHP were assessed...
March 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28425453/aptamer-mediated-impairment-of-egfr-integrin-%C3%AE-v%C3%AE-3-complex-inhibits-vasculogenic-mimicry-and-growth-of-triple-negative-breast-cancers
#5
Simona Camorani, Elvira Crescenzi, Matteo Gramanzini, Monica Fedele, Antonella Zannetti, Laura Cerchia
Current treatment options for triple-negative breast cancers (TNBCs) is limited by the absence of well-defined biomarkers, excluding a targeted therapy. Notably, epidermal growth factor receptor (EGFR) is overexpressed in a great proportion of TNBCs and is a negative prognostic factor. In clinical trials, however, existing EGFR inhibitors showed disappointing outcome. Oligonucleotide aptamers are a valid alternative to antibodies for diagnostic and therapeutic uses. Here, we prove that, when applied to aggressive TNBC cell lines with unique stem-like plasticity, the anti-EGFR CL4 aptamer, but not erlotinib or cetuximab, prevents the vasculogenic mimicry (VM) capability of the cells and destroys previously formed channels in three-dimensional culture...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28422972/challenges-in-enumeration-of-ctcs-in-breast-cancer-using-techniques-independent-of-cytokeratin-expression
#6
John Castle, Karen Morris, Susan Pritchard, Cliona C Kirwan
INTRODUCTION: Given the current postulated plasticity between epithelial and mesenchymal states of migratory cancer cells the detection of non-epithelial CTCs is an important scientific and clinical goal. METHODS: We used the filtration-based ISET technology to enrich circulating tumour cells (CTCs) in early breast cancer blood samples and identify them using a morphology-based immunocytochemistry (ICC) approach. RESULTS: We found greater numbers of putative CTCs by this approach than by the cytokeratin-based CellSearch technology, but a high number of CTC false positives were identified in healthy volunteer samples which were not reduced in successive blood draws...
2017: PloS One
https://www.readbyqxmd.com/read/28420963/rna-seq-analysis-of-microglia-reveals-time-dependent-activation-of-specific-genetic-programs-following-spinal-cord-injury
#7
Harun N Noristani, Yannick N Gerber, Jean-Charles Sabourin, Marine Le Corre, Nicolas Lonjon, Nadine Mestre-Frances, Hélène E Hirbec, Florence E Perrin
Neurons have inherent competence to regrow following injury, although not spontaneously. Spinal cord injury (SCI) induces a pronounced neuroinflammation driven by resident microglia and infiltrating peripheral macrophages. Microglia are the first reactive glial population after SCI and participate in recruitment of monocyte-derived macrophages to the lesion site. Both positive and negative influence of microglia and macrophages on axonal regeneration had been reported after SCI, raising the issue whether their response depends on time post-lesion or different lesion severity...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28414315/the-emt-activator-zeb1-is-a-key-factor-for-cell-plasticity-and-promotes-metastasis-in-pancreatic-cancer
#8
Angela M Krebs, Julia Mitschke, María Lasierra Losada, Otto Schmalhofer, Melanie Boerries, Hauke Busch, Martin Boettcher, Dimitrios Mougiakakos, Wilfried Reichardt, Peter Bronsert, Valerie G Brunton, Christian Pilarsky, Thomas H Winkler, Simone Brabletz, Marc P Stemmler, Thomas Brabletz
Metastasis is the major cause of cancer-associated death. Partial activation of the epithelial-to-mesenchymal transition program (partial EMT) was considered a major driver of tumour progression from initiation to metastasis. However, the role of EMT in promoting metastasis has recently been challenged, in particular concerning effects of the Snail and Twist EMT transcription factors (EMT-TFs) in pancreatic cancer. In contrast, we show here that in the same pancreatic cancer model, driven by Pdx1-cre-mediated activation of mutant Kras and p53 (KPC model), the EMT-TF Zeb1 is a key factor for the formation of precursor lesions, invasion and notably metastasis...
April 17, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28412735/glucose-deprivation-elicits-phenotypic-plasticity-via-zeb1-mediated-expression-of-nnmt
#9
Justyna Kanska, Paul-Joseph P Aspuria, Barbie Taylor-Harding, Lindsay Spurka, Vincent Funari, Sandra Orsulic, Beth Y Karlan, W Ruprecht Wiedemeyer
Glucose is considered the primary energy source for all cells, and some cancers are addicted to glucose. Here, we investigated the functional consequences of chronic glucose deprivation in serous ovarian cancer cells. We found that cells resistant to glucose starvation (glucose-restricted cells) demonstrated increased metabolic plasticity that was dependent on NNMT (Nicotinamide N-methyltransferase) expression. We further show that ZEB1 induced NNMT, rendered cells resistant to glucose deprivation and recapitulated metabolic adaptations and mesenchymal gene expression observed in glucose-restricted cells...
February 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28411208/lgr5-cancer-stem-cells-drive-primary-and-metastatic-colorectal-cancer
#10
(no author information available yet)
LGR5(+) colorectal cancer CSCs are dispensable for primary tumor growth due to plasticity.
April 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28407379/epithelial-mesenchymal-plasticity-and-circulating-tumor-cells-travel-companions-to-metastases
#11
REVIEW
Marie-Emilie Francart, Justine Lambert, Aline M Vanwynsberghe, Erik W Thompson, Morgane Bourcy, Myriam Polette, Christine Gilles
Epithelial-Mesenchymal Transitions (EMT) associated with metastatic progression may contribute to the generation of hybrid phenotypes capable of plasticity. This cellular plasticity would provide tumor cells with an increased potential to adapt to the different microenvironments encountered during metastatic spread. Understanding how EMT may functionally equip Circulating Tumor Cells (CTCs) with an enhanced competence to survive in the blood stream and niche in the colonized organs has thus become a major cancer research axis...
April 13, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28405328/photodynamic-therapy-with-polyhematoporphyrin-for-malignant-biliary-obstruction-a-nationwide-retrospective-study-of-150-consecutive-applications
#12
Werner Dolak, Hubert Schwaighofer, Brigitte Hellmich, Bernhard Stadler, Georg Spaun, Wolfgang Plieschnegger, Arnold Hebenstreit, Jutta Weber-Eibel, Franz Siebert, Klaus Emmanuel, Peter Knoflach, Michael Gschwantler, Wolfgang Vogel, Michael Trauner, Andreas Püspök
BACKGROUND: Photodynamic therapy (PDT) is a palliative treatment for malignant biliary obstruction. OBJECTIVE: The objective of this article is to assess the feasibility and safety of this technique. METHODS: In this nationwide, retrospective study of prospectively collected clinical data, all patients treated with PDT using polyhematoporphyrin in Austria from March 2004 to May 2013 were included. Feasibility, adverse events, stent patency and mortality rates were investigated...
February 2017: United European Gastroenterology Journal
https://www.readbyqxmd.com/read/28402937/breaking-the-crosstalk-of-the-cellular-tumorigenic-network-hypothesis-for-addressing-resistances-to-targeted-therapies-in-advanced-nsclc
#13
REVIEW
Stefan Langhammer, Joachim Scheerer
In the light of current treatment developments for non-small cell lung cancer (NSCLC), the idea of a plastic cellular tumorigenic network bound by key paracrine signaling pathways mediating resistances to targeted therapies is brought forward. Based on a review of available preclinical and clinical data in NSCLC combinational approaches to address drivers of this network with marketed drugs are discussed. Five criteria for selecting drug combination regimens aiming at its disruption and thereby overcoming resistances are postulated...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28401192/evasion-of-targeted-cancer-therapy-through-stem-cell-like-reprogramming
#14
Kristine M Wadosky, Leigh Ellis, David W Goodrich
Prostate cancer variants expressing alternative lineage markers appear at relapse from antiandrogen therapy. We show that loss of the retinoblastoma (RB1) and tumor protein 53 (TP53) genes drives expression of stem cell reprogramming factors, lineage plasticity, and antiandrogen resistance. Epigenetic manipulation restores antiandrogen sensitivity-suggesting an approach for treating lethal prostate cancers.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28398227/miniaturized-real-time-pcr-on-a-q3-system-for-rapid-kras-genotyping
#15
Maria Guarnaccia, Rosario Iemmolo, Salvatore Petralia, Sabrina Conoci, Sebastiano Cavallaro
Colorectal cancer (CRC) is an aggressive human malignancy with a complex genomic landscape harboring KRAS mutations. In 40%-60% of patients with CRC, constantly active KRAS proteins affect the prognosis, surgical strategy, and clinical benefit from therapy with anti-epidermal growth factor receptor (EGFR) agents. For this reason, there is a greater demand for minimally-invasive diagnostic devices to characterize the genetic pattern and prevent the acquired mechanism to drug resistance. The rapid developments in cutting-edge diagnostic techniques are expected to play a growing role in medicine and represent an attractive promise to identify potential responders to personalized medicine...
April 11, 2017: Sensors
https://www.readbyqxmd.com/read/28396317/4pd-functionalized-dendrimers-a-flexible-tool-for-in-vivo-gene-silencing-of-tumor-educated-myeloid-cells
#16
Serena Zilio, Jennifer L Vella, Adriana C De la Fuente, Pirouz M Daftarian, Donald T Weed, Angel Kaifer, Ilaria Marigo, Kevin Leone, Vincenzo Bronte, Paolo Serafini
Myeloid cells play a key role in tumor progression and metastasis by providing nourishment and immune protection, as well as facilitating cancer invasion and seeding to distal sites. Although advances have been made in understanding the biology of these tumor-educated myeloid cells (TEMCs), their intrinsic plasticity challenges our further understanding of their biology. Indeed, in vitro experiments only mimic the in vivo setting, and current gene-knockout technologies do not allow the simultaneous, temporally controlled, and cell-specific silencing of multiple genes or pathways...
April 10, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28396217/mathematical-models-of-cell-phenotype-regulation-and-reprogramming-make-cancer-cells-sensitive-again
#17
David J Wooten, Vito Quaranta
A cell's phenotype is the observable actualization of complex interactions between its genome, epigenome, and local environment. While traditional views in cancer have held that cellular and tumor phenotypes are largely functions of genomic instability, increasing attention has recently been given to epigenetic and microenvironmental influences. Such non-genetic factors allow cancer cells to experience intrinsic diversity and plasticity, and at the tumor level can result in phenotypic heterogeneity and treatment evasion...
April 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28389596/single-cell-analysis-of-circulating-tumor-cells-as-a-window-into-tumor-heterogeneity
#18
David T Miyamoto, David T Ting, Mehmet Toner, Shyamala Maheswaran, Daniel A Haber
Recent advances in microfluidic approaches have enabled the efficient isolation and detailed molecular characterization of circulating tumor cells (CTCs) in the peripheral blood of patients with cancer. Single-cell molecular analyses of CTCs reveal a tremendous degree of intracellular heterogeneity in CTC populations, reflective of heterogeneity across different patients as well as the underlying heterogeneity of tumors within each individual patient. These studies have enabled the identification of heterogeneous drug resistance mechanisms that can coexist in treatment refractory tumors...
April 7, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28387316/lkb1-inactivation-drives-lung-cancer-lineage-switching-governed-by-polycomb-repressive-complex-2
#19
Haikuo Zhang, Christine Fillmore Brainson, Shohei Koyama, Amanda J Redig, Ting Chen, Shuai Li, Manav Gupta, Carolina Garcia-de-Alba, Margherita Paschini, Grit S Herter-Sprie, Gang Lu, Xin Zhang, Bryan P Marsh, Stephanie J Tuminello, Chunxiao Xu, Zhao Chen, Xiaoen Wang, Esra A Akbay, Mei Zheng, Sangeetha Palakurthi, Lynette M Sholl, Anil K Rustgi, David J Kwiatkowski, J Alan Diehl, Adam J Bass, Norman E Sharpless, Glenn Dranoff, Peter S Hammerman, Hongbin Ji, Nabeel Bardeesy, Dieter Saur, Hideo Watanabe, Carla F Kim, Kwok-Kin Wong
Adenosquamous lung tumours, which are extremely poor prognosis, may result from cellular plasticity. Here, we demonstrate lineage switching of KRAS+ lung adenocarcinomas (ADC) to squamous cell carcinoma (SCC) through deletion of Lkb1 (Stk11) in autochthonous and transplant models. Chromatin analysis reveals loss of H3K27me3 and gain of H3K27ac and H3K4me3 at squamous lineage genes, including Sox2, ΔNp63 and Ngfr. SCC lesions have higher levels of the H3K27 methyltransferase EZH2 than the ADC lesions, but there is a clear lack of the essential Polycomb Repressive Complex 2 (PRC2) subunit EED in the SCC lesions...
April 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28382467/plasticity-of-resistance-and-sensitivity-to-anti-epidermal-growth-factor-receptor-inhibitors-in-metastatic-colorectal-cancer
#20
Andrea Sartore-Bianchi, Salvatore Siena
Colorectal cancer (CRC) is one of the most prevalent cancers and the second leading cause of cancer mortality worldwide. Survival in the metastatic setting has been gradually improved by the addition to cytotoxic chemotherapy of agents targeting the vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR). Considerable heterogeneity exists within CRC due to the varied genetic and epigenetic mechanisms involved in differing pathways of carcinogenesis. The knowledge of molecular abnormalities underlying colorectal tumourigenesis and the progression of dysplastic precursors to invasive and ultimately metastatic lesions has advanced in recent years by comprehensive sequencing studies...
April 6, 2017: Handbook of Experimental Pharmacology
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