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Cancer system biology

Sara Sigismund, Giorgio Scita
An explosive growth in knowledge, in the last two decades, has conferred a new dimension to the process of endocytosis. Endocytic circuitries have come into focus as a pervasive system that controls virtual all aspects of cell biology. A few years ago, we proposed the term 'endocytic matrix' to define a cellular network of signalling wiring that is at the core of the cellular blueprint. A primary role of the endocytic matrix is the delivery of space-resolved and time-resolved signals to the cell in an interpretable format, and, as such, it has profound consequences on polarized cellular and supra-cellular functions, first and foremost, cell motility...
March 12, 2018: Current Opinion in Cell Biology
Allison M Weis, Raymond Soto, June L Round
The commensal microbiota influences many aspects of immune system regulation, including T cells, but molecular details of how this occurs are largely unknown. Here we review our findings that the microbiota regulates Erdr1, a secreted apoptotic factor, to control T cell survival. Erdr1 is highly upregulated in CD4+ T cells from germfree mice and antibiotic treated animals, and our study shows that Erdr1 is suppressed by the microbiota via Toll-like receptor signaling and MyD88 dependent pathways. Erdr1 functions in an autocrine fashion and promotes apoptosis through the FAS/FASL pathway...
March 15, 2018: Gut Microbes
Jagpreet Singh Sidhu, Ashutosh Singh, Neha Garg, Navneet Kaur, Narinder Singh
Thioredoxin Reductase (TrxR) is a redox regulating enzyme which is predestined for the maintenance of redox homeostasis of mammalian cells. However, the elevated level of TrxR is associated with the progress of various types of tumors and therefore, this is a significant target for the detection of cancer cells. Herein, an easily engineered 'Turn ON' fluorescent sensor probe has been synthesized for the detection of TrxR and cell imaging using carbon dots. The emission intensity of fCDs on complexation with Cu2+ ions was drastically quenched...
March 15, 2018: Analyst
Ali Hafez Ali Mohammed El-Far, Seiichi Munesue, Ai Harashima, Akira Sato, Mika Shindo, Shingo Nakajima, Mana Inada, Mariko Tanaka, Akihiko Takeuchi, Hiroyuki Tsuchiya, Hiroshi Yamamoto, Hazem M E Shaheen, Yasser S El-Sayed, Shuhei Kawano, Sei-Ichi Tanuma, Yasuhiko Yamamoto
Receptor for advanced glycation end-products (RAGE) is a pattern recognition receptor implicated in the pathogenesis of certain types of cancer. In the present study, papaverine was identified as a RAGE inhibitor using the conversion to small molecules through optimized-peptide strategy drug design system. Papaverine significantly inhibited RAGE-dependent nuclear factor κ-B activation driven by high mobility group box-1, a RAGE ligand. Using RAGE- or dominant-negative RAGE-expressing HT1080 human fibrosarcoma cells, the present study revealed that papaverine suppressed RAGE-dependent cell proliferation and migration dose-dependently...
April 2018: Oncology Letters
Lea Ann Matura, Susan Malone, Rosario Jaime-Lara, Barbara Riegel
Fatigue, a commonly reported symptom, is defined as an overwhelming, debilitating, and sustained sense of exhaustion that decreases the ability to function and carry out daily activities. To date, cancer researchers have been in the forefront in investigating the possible biological mechanisms of fatigue, identifying inflammation, dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, and activation of the autonomic nervous system. The purpose of this systematic review is to describe fatigue and what is known about the biological mechanisms described in cancer in five chronic, noninfectious illnesses: heart failure, multiple sclerosis, chronic kidney disease, rheumatoid arthritis, and chronic obstructive pulmonary disease...
January 1, 2018: Biological Research for Nursing
Lucia Negri, Napoleone Ferrara
The mammalian prokineticins family comprises two conserved proteins, EG-VEGF/PROK1 and Bv8/PROK2, and their two highly related G protein-coupled receptors, PKR1 and PKR2. This signaling system has been linked to several important biological functions, including gastrointestinal tract motility, regulation of circadian rhythms, neurogenesis, angiogenesis and cancer progression, hematopoiesis, and nociception. Mutations in PKR2 or Bv8/PROK2 have been associated with Kallmann syndrome, a developmental disorder characterized by defective olfactory bulb neurogenesis, impaired development of gonadotropin-releasing hormone neurons, and infertility...
April 1, 2018: Physiological Reviews
Kumar Parijat Tripathi, Marina Piccirillo, Mario Rosario Guarracino
BACKGROUND: The endomembrane system, known as secretory pathway, is responsible for the synthesis and transport of protein molecules in cells. Therefore, genes involved in the secretory pathway are essential for the cellular development and function. Recent scientific investigations show that ER and Golgi apparatus may provide a convenient drug target for cancer therapy. On the other hand, it is known that abundantly expressed genes in different cellular organelles share interconnected pathways and co-regulate each other activities...
March 8, 2018: BMC Bioinformatics
Niloofar Yousefi Moteghaed, Keivan Maghooli, Masoud Garshasbi
Background: Gene expression data are characteristically high dimensional with a small sample size in contrast to the feature size and variability inherent in biological processes that contribute to difficulties in analysis. Selection of highly discriminative features decreases the computational cost and complexity of the classifier and improves its reliability for prediction of a new class of samples. Methods: The present study used hybrid particle swarm optimization and genetic algorithms for gene selection and a fuzzy support vector machine (SVM) as the classifier...
January 2018: Journal of Medical Signals and Sensors
Sinead A Noonan, Maria E Morrissey, Petra Martin, Monika Biniecka, Shane Ó'Meachair, Aoife Maguire, Miriam Tosetto, Blathnaid Nolan, John Hyland, Kieran Sheahan, Diarmuid O'Donoghue, Hugh Mulcahy, David Fennelly, Jacintha O'Sullivan
Despite treatment of patients with metastatic colorectal cancer (mCRC) with bevacizumab plus chemotherapy, response rates are modest and there are no biomarkers available that will predict response. The aim of this study was to assess if markers associated with three interconnected cancer-associated biological processes, specifically angiogenesis, inflammation and oxidative damage, could stratify the survival outcome of this cohort. Levels of angiogenesis, inflammation and oxidative damage markers were assessed in pre-bevacizumab resected tumour and serum samples of mCRC patients by dual immunofluorescence, immunohistochemistry and ELISA...
February 13, 2018: Oncotarget
Gwendolyn N Y van Gorkom, Roel G J Klein Wolterink, Catharina H M J Van Elssen, Lotte Wieten, Wilfred T V Germeraad, Gerard M J Bos
Vitamin C or ascorbic acid (AA) is implicated in many biological processes and has been proposed as a supplement for various conditions, including cancer. In this review, we discuss the effects of AA on the development and function of lymphocytes. This is important in the light of cancer treatment, as the immune system needs to regenerate following chemotherapy or stem cell transplantation, while cancer patients are often AA-deficient. We focus on lymphocytes, as these white blood cells are the slowest to restore, rendering patients susceptible to often lethal infections...
March 10, 2018: Antioxidants (Basel, Switzerland)
Azam Peyvandipour, Nafiseh Saberian, Adib Shafi, Michele Donato, Sorin Draghici
Motivation: Identification of novel therapeutic effects for existing U.S. Food and Drug Administration (FDA)-approved drugs, drug repurposing, is an approach aimed to dramatically shorten the drug discovery process, which is costly, slow and risky. Several computational approaches use transcriptional data to find potential repurposing candidates. The main hypothesis of such approaches is that if gene expression signature of a particular drug is opposite to the gene expression signature of a disease, that drug may have a potential therapeutic effect on the disease...
March 9, 2018: Bioinformatics
V Vongsutilers, P M Gannett
Base modifications are known to affect the structure and function of DNA. C8-guanine adducts from various carcinogenic compounds have been shown to be potent Z-DNA inducers. Hence, it has been hypothesized that Z-DNA plays a role in cancer and other genetic diseases. In this comprehensive review, Z-DNA and the effect of prevalent C8-guanine adducts on the B-Z transition are addressed. The discoveries of Z-DNA binding proteins including ADAR1, E3L, DLM1, and PKZ have suggested the relevance of Z-DNA in living systems...
March 13, 2018: Organic & Biomolecular Chemistry
Caroline C Swift, Meryle J Eklund, Jacqueline M Kraveka, Adina L Alazraki
Neuroblastoma is an embryonic tumor of the peripheral sympathetic nervous system. It is the most common extracranial solid tumor of childhood and accounts for up to 15% of all pediatric cancer fatalities. The manifestation of neuroblastoma is variable depending on the location of the tumor and on the presence or absence of paraneoplastic syndromes. The prognosis of neuroblastoma is also highly variable, ranging from spontaneous regression to widespread metastatic disease that is unresponsive to treatment. The age of the patient, stage of disease, histopathologic results, and multiple biologic factors contribute to the presurgical and pretreatment risk stratification of a patient with neuroblastoma...
March 2018: Radiographics: a Review Publication of the Radiological Society of North America, Inc
Yili Hu, Xiaoyang Zhu, Ruifang Zhao, Jin Wang, Yipeng Song, Guangjun Nie, Huiru Tang, Yulan Wang
AIM: To evaluate the advantages of nanomaterial methoxy poly(ethylene glycol)-poly(lactide-co-glycolide) (mPEG-PLGA) encapsulated doxorubicin (D/DOX) and paclitaxel (T/TAX; mPEG-PLGA-DT) over free form of DOX and TAX (DOX/TAX). MATERIALS & METHODS: Metabonomics was conducted to characterize the systemic metabolic response of allograft breast cancer model mice to mPEG-PLGA-DT and DOX/TAX treatments. RESULTS: Breast tumor growth induced metabolic reprogram in serum and multiple organs...
March 12, 2018: Nanomedicine
Therese W Herling, Aviad Levin, Kadi L Saar, Christopher M Dobson, Tuomas P J Knowles
The self-assembly of proteins into supramolecular structures and machinery underpins biological activity in living systems. Misassembled, misfolded and aggregated protein structures can, by contrast, have deleterious activity and such species are at the origin of a number of disease states ranging from cancer to neurodegenerative disorders. In particular, the formation of highly ordered protein aggregates, amyloid fibrils, from normally soluble peptides and proteins, is the common pathological hallmark of a range a group of over fifty protein misfolding disorders...
March 12, 2018: Lab on a Chip
Kelley M Swanberg, Hetty Prinsen, Daniel Coman, Robin A de Graaf, Christoph Juchem
Glutathione (GSH) is an endogenous antioxidant implicated in numerous biological processes, including those associated with multiple sclerosis, aging, and cancer. Spectral editing techniques have greatly facilitated the acquisition of glutathione signal in living humans via proton magnetic resonance spectroscopy, but signal quantification at 7 Tesla is still hampered by uncertainty about the glutathione transverse decay rate T2 relative to those of commonly employed quantitative references like N-acetyl aspartate (NAA), total creatine, or water...
March 1, 2018: Journal of Magnetic Resonance
Clarissa S Craft, Thomas J Broekelmann, Robert P Mecham
Microfibril-associated glycoproteins 1 and 2 (MAGP-1, MAGP-2) are protein components of extracellular matrix microfibrils. These proteins interact with fibrillin, the core component of microfibrils, and impart unique biological properties that influence microfibril function in vertebrates. MAGPs bind active forms of TGFβ and BMPs and are capable of modulating Notch signaling. Mutations in MAGP-1 or MAGP-2 have been linked to thoracic aneurysms and metabolic disease in humans. MAGP-2 has also been shown to be an important biomarker in several human cancers...
March 7, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
Sumiyo Morita, Takuro Horii, Izuho Hatada
DNA methylation, one of the most studied epigenetic modifications, regulates many biological processes. Dysregulation of DNA methylation is implicated in the etiology of several diseases, such as cancer and imprinting diseases. Accordingly, technologies designed to manipulate DNA methylation at specific loci are very important, and many epigenome editing technologies have been developed, based on zinc finger proteins, TALEs, and CRISPR/dCas9 targeting. We describe a protocol to induce and assess DNA demethylation on a target gene...
2018: Methods in Molecular Biology
Fangxu Sun, Alexander A Choi, Ronghu Wu
Fatty acids (FAs) are essential components in cells and are involved in many cellular activities. Abnormal FA metabolism has been reported to be related to human diseases such as cancer and cardiovascular diseases. Identification and quantification of FAs provide insights into their functions in biological systems, but it is very challenging to analyze them due to their structures and properties. In this work, we developed a novel method by integrating tagging FAs with stable isotope labeled aminoxy tandem mass tags (aminoxyTMTs) and mass spectrometric analysis with the positive mode...
March 9, 2018: Journal of Proteome Research
Arun V Everest-Dass, Edward S X Moh, Christopher Ashwood, Abdulrahman M M Shathili, Nicolle H Packer
The changes in glycan structures have been attributed to disease states for several decades. The surface glycosylation pattern is a signature of physiological state of a cell. In this review we provide a link between observed substructural glycan changes and a range of diseases. Areas covered: We highlight biologically relevant glycan substructure expression in cancer, inflammation, neuronal diseases and diabetes. Furthermore, the alterations in antibody glycosylation in a disease context are described. Expert commentary: Advances in technologies, as described in Part 1 of this review have now enabled the characterization of specific glycan structural markers of a range of disease states...
March 9, 2018: Expert Review of Proteomics
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