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Cancer biology

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https://www.readbyqxmd.com/read/29149589/bond-with-me-if-you-can-natural-product-covalent-ligand-and-reactivity-based-probe-compete-for-cysteine-in-pp2a-complex
#1
Douglas S Johnson, Jaimeen D Majmudar
In this issue of Cell Chemical Biology, Grossman et al. (2017) disclose a chemoproteomics-enabled strategy to identify the cysteine-reactive target(s) of the anti-cancer natural product withaferin A and then screen a cysteine-reactive fragment library to discover a covalent ligand for the same target.
November 16, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/29149414/role-of-tctp-for-cellular-differentiation-and-cancer-therapy
#2
Ean-Jeong Seo, Nicolas Fischer, Thomas Efferth
The translationally controlled tumor protein (TCTP) is a highly conserved protein that is regulated due to a high number of extracellular stimuli. TCTP has an important role for cell cycle and normal development. On the other side, tumor reversion and malignant transformation have been associated with TCTP. TCTP has been found among the 12 genes that are differentially expressed during mouse oocyte maturation, and an overexpression of this gene was reported in a wide variety of different cancer types. Its antiapoptotic effect is indicated by the interaction with several proapoptotic proteins of the Bcl-2 family and the p53 tumor suppressor protein...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29149410/tctp-in-neuronal-circuitry-assembly
#3
Cláudio Gouveia Roque, Christine E Holt
Although tctp expression in many areas of the human brain was reported more than 15 years ago, little was known about how it functions in neurons. The early notion that Tctp is primarily expressed in mitotic cells, together with reports suggesting a relative low abundance in the brain, has perhaps potentiated this almost complete disregard for the study of Tctp in the context of neuron biology. However, recent evidence has challenged this view, as a number of independent genome-wide profiling studies identified tctp mRNA among the most enriched in the axonal compartment across diverse neuronal populations, including embryonic retinal ganglion cells...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29149405/current-understanding-of-the-tctp-interactome
#4
Siting Li, Feng Ge
Evolutionarily conserved and pleiotropic, the translationally controlled tumor protein (TCTP) is a housekeeping protein present in eukaryotic organisms. It plays an important role in regulating many fundamental processes, such as cell proliferation, cell death, immune responses, and apoptosis. As a result of the pioneer work by Adam Telerman and Robert Amson, the critical role of TCTP in tumor reversion was revealed. Moreover, TCTP has emerged as a regulator of cell fate determination and a promising therapeutic target for cancers...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29149404/the-translational-controlled-tumour-protein-tctp-biological-functions-and-regulation
#5
Ulrich-Axel Bommer
The Translational Controlled Tumour Protein TCTP (gene symbol TPT1, also called P21, P23, Q23, fortilin or histamine-releasing factor, HRF) is a highly conserved protein present in essentially all eukaryotic organisms and involved in many fundamental cell biological and disease processes. It was first discovered about 35 years ago, and it took an extended period of time for its multiple functions to be revealed, and even today we do not yet fully understand all the details. Having witnessed most of this history, in this chapter, I give a brief overview and review the current knowledge on the structure, biological functions, disease involvements and cellular regulation of this protein...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29149299/twj-screen-an-isothermal-screening-assay-to-assess-ligand-dna-junction-interactions-in-vitro
#6
Ludivine Guyon, Marc Pirrotta, Katerina Duskova, Anton Granzhan, Marie-Paule Teulade-Fichou, David Monchaud
The quest for chemicals able to operate at selected genomic loci in a spatiotemporally controlled manner is desirable to create manageable DNA damages. Mounting evidence now shows that alternative DNA structures, including G-quadruplexes and branched DNA (or DNA junctions), might hamper proper progression of replication fork, thus triggering DNA damages and genomic instability. Therefore, small molecules that stabilize these DNA structures are currently scrutinized as a promising way to create genomic defects that cannot be dealt with properly by cancer cells...
November 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29148847/emerging-therapeutic-targets-in-myeloproliferative-neoplasms-and-peripheral-t-cell-leukemia-and-lymphomas
#7
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/29148176/differential-proteomic-analysis-reveals-protein-networks-and-pathways-that-may-contribute-to-helicobacter-pylori-fkbp-type-ppiase-associated-gastric-diseases
#8
Yanmei Zhu, Yuehua Gong, Aodi Li, Moye Chen, Dan Kang, Jun Liu, Yuan Yuan
PURPOSE: Though Helicobacter pylori (H. pylori) has been classified as class I carcinogen, key virulence factor generated by H. pylori that causes gastric cancer remains to be fully determined. Recently, we identified a gastric cancer-associated H. pylori gene, peptidylprolyl isomerase-FK506 binding protein (PPIase-FKBP), and showed that PPIase-FKBP was capable of inducing oncogenic transformation of gastric epithelial cells. But its mechanism was unclear. EXPERIMENTAL DESIGN: We carried out a comparative proteomic analysis of human gastric epithelial cells that either express PPIase-FKBP or green fluorescent protein (GFP) using two-dimensional (2-D) gel electrophoresis and then matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS/MS)...
November 16, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/29147712/a-biocompatible-betaine-functionalized-polycation-for-coacervation
#9
Mintai P Hwang, Xiaochu Ding, Jin Gao, Abhinav P Acharya, Steven R Little, Yadong Wang
The aqueous nature of complex coacervates provides a biologically-relevant context for various therapeutic applications. In this sense, biological applications demand a corresponding level of biocompatibility from the polyelectrolytes that participate in complex coacervation. Continued development with naturally-occurring polyelectrolytes such as heparin and chitosan underscore such aims. Herein, we design a synthetic polycation, in which betaine is conjugated to a biodegradable polyester backbone. Betaine is a naturally-occurring methylated amino acid that is ubiquitously present in human plasma...
November 17, 2017: Soft Matter
https://www.readbyqxmd.com/read/29147648/molecular-crosstalking-among-noncoding-rnas-a-new-network-layer-of-genome-regulation-in-cancer
#10
REVIEW
Marco Ragusa, Cristina Barbagallo, Duilia Brex, Angela Caponnetto, Matilde Cirnigliaro, Rosalia Battaglia, Davide Barbagallo, Cinzia Di Pietro, Michele Purrello
Over the past few years, noncoding RNAs (ncRNAs) have been extensively studied because of the significant biological roles that they play in regulation of cellular mechanisms. ncRNAs are associated to higher eukaryotes complexity; accordingly, their dysfunction results in pathological phenotypes, including cancer. To date, most research efforts have been mainly focused on how ncRNAs could modulate the expression of protein-coding genes in pathological phenotypes. However, recent evidence has shown the existence of an unexpected interplay among ncRNAs that strongly influences cancer development and progression...
2017: International Journal of Genomics
https://www.readbyqxmd.com/read/29147618/programmed-cell-death-ligands-expression-in-phaeochromocytomas-and-paragangliomas-relationship-with-the-hypoxic-response-immune-evasion-and-malignant-behavior
#11
David J Pinato, James R Black, Sebastian Trousil, Roberto E Dina, Pritesh Trivedi, Francesco A Mauri, Rohini Sharma
The hypoxic response underlies the pathogenesis and malignant behavior of PCC/PGL. Regulation of PD-1 receptor-ligand signaling, a therapeutically actionable driver of the anti-tumor immune response, is a hypoxic-driven trait across malignancies. We evaluated the prognostic role of PD ligands in association with biomarkers of hypoxia and angiogenesis in patients with PCC/PGL. Tissue microarrays sections including consecutive cases diagnosed between 1983-2011 were stained for PD-L1 and 2, hypoxia inducible factor 1a (Hif-1a), Carbonic Anhydrase IX (CaIX), Vascular Endothelial Growth Factor-A (VEGF-A)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147558/discovery-and-design-of-self-assembling-peptides
#12
REVIEW
Shuguang Zhang
Peptides are ubiquitous in nature and useful in many fields, from agriculture as pesticides, in medicine as antibacterial and antifungal drugs founded in the innate immune systems, to medicinal chemistry as hormones. However, the concept of peptides as materials was not recognized until 1990 when a self-assembling peptide as a repeating segment in a yeast protein was serendipitously discovered. Peptide materials are so called because they have bona fide materials property and are made from simple amino acids with well-ordered nanostructures under physiological conditions...
December 6, 2017: Interface Focus
https://www.readbyqxmd.com/read/29146996/the-role-of-cxcr3-lrp1-cross-talk-in-the-invasion-of-primary-brain-tumors
#13
Kevin Boyé, Nadège Pujol, Isabel D Alves, Ya-Ping Chen, Thomas Daubon, Yi-Zong Lee, Stephane Dedieu, Marion Constantin, Lorenzo Bello, Marco Rossi, Rolf Bjerkvig, Shih-Che Sue, Andreas Bikfalvi, Clotilde Billottet
CXCR3 plays important roles in angiogenesis, inflammation, and cancer. However, the precise mechanism of regulation and activity in tumors is not well known. We focused on CXCR3-A conformation and on the mechanisms controlling its activity and trafficking and investigated the role of CXCR3/LRP1 cross talk in tumor cell invasion. Here we report that agonist stimulation induces an anisotropic response with conformational changes of CXCR3-A along its longitudinal axis. CXCR3-A is internalized via clathrin-coated vesicles and recycled by retrograde trafficking...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29146897/gwas-for-male-pattern-baldness-identifies-71-susceptibility-loci-explaining-38-of-the-risk
#14
Nicola Pirastu, Peter K Joshi, Paul S de Vries, Marilyn C Cornelis, Paul M McKeigue, NaNa Keum, Nora Franceschini, Marco Colombo, Edward L Giovannucci, Athina Spiliopoulou, Lude Franke, Kari E North, Peter Kraft, Alanna C Morrison, Tõnu Esko, James F Wilson
Male pattern baldness (MPB) or androgenetic alopecia is one of the most common conditions affecting men, reaching a prevalence of ~50% by the age of 50; however, the known genes explain little of the heritability. Here, we present the results of a genome-wide association study including more than 70,000 men, identifying 71 independently replicated loci, of which 30 are novel. These loci explain 38% of the risk, suggesting that MPB is less genetically complex than other complex traits. We show that many of these loci contain genes that are relevant to the pathology and highlight pathways and functions underlying baldness...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29146569/found-in-translation-how-preclinical-research-is-guiding-the-clinical-development-of-the-bcl2-selective-inhibitor-venetoclax
#15
REVIEW
Joel D Leverson, Deepak Sampath, Andrew J Souers, Saul H Rosenberg, Wayne J Fairbrother, Martine Amiot, Marina Konopleva, Anthony Letai
Since the discovery of apoptosis as a form of programmed cell death, targeting the apoptosis pathway to induce cancer cell death has been a high-priority goal for cancer therapy. After decades of effort, drug-discovery scientists have succeeded in generating small-molecule inhibitors of antiapoptotic BCL2 family proteins. Innovative medicinal chemistry and structure-based drug design, coupled with a strong fundamental understanding of BCL2 biology, were essential to the development of BH3 mimetics such as the BCL2-selective inhibitor venetoclax...
November 16, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29146477/a-review-of-s100-protein-family-in-lung-cancer
#16
REVIEW
Ting Wang, Xiaoying Huo, Zhaoyang Chong, Hamadhaider Khan, Rui Liu, Ting Wang
S100 protein family, representing 25 relatively small calcium binding proteins, has been reported to be involved in multiple stages of tumorigenesis and progression. These proteins are considered having potential value to be adopted as novel biomarkers in the detection and accurate prediction of many kinds of tumors, including lung cancer. As the one having the highest morbidity and mortality among all cancers, lung carcinoma is still occult for detection, especially at early stage. S100 proteins take participation in the lung neoplasia through playing intracellular and/or extracellular functions, therefore getting involved in a variety of biological processes such as differentiation, proliferation, and migration...
November 13, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29146452/design-synthesis-and-biological-evaluation-of-thieno-2-3-d-pyrimidine-derivatives-as-novel-dual-c-met-and-vegfr-2-kinase-inhibitors
#17
Jieming Li, Weijie Gu, Xinzhou Bi, Huilan Li, Chen Liao, Chunxia Liu, Wenlong Huang, Hai Qian
Both c-Met and VEGFR-2 are important targets for cancer therapies. Here we report a series of potent dual c-Met and VEGFR-2 inhibitors bearing thieno[2,3-d]pyrimidine scaffold. The cell proliferation assay in vitro demonstrated that most target compounds had inhibition potency both on c-Met and VEGFR-2 with IC50 values in nanomolar range, especially compound 12j and 12m. Based on the further enzyme assay in vitro, compound 12j was considered as the most potent one, the IC50 values of which were 25 nM and 48 nM for c-Met and VEGFR-2, respectively...
November 4, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29146102/outcomes-by-molecular-subtype-after-accelerated-partial-breast-irradiation-using-single-entry-catheters
#18
Aman Saini, Robert Kuske, Coral Quiet, Cheri Pantoja, Daniel Reed, Victor Zannis
PURPOSE: Tumor biology is being recognized as an important indicator of prognosis and risk of locoregional recurrence. Here, we determine actuarial recurrence rates by approximated molecular subtype for women treated with single-entry catheter accelerated partial breast irradiation (sAPBI). METHODS AND MATERIALS: One thousand four hundred eighty-six women with invasive cancer having known ER, PR, and Her2 status and at least 1-year of followup were treated using MammoSite, Contura, or SAVI sAPBI from 2002 to 2014 at our institution...
November 13, 2017: Brachytherapy
https://www.readbyqxmd.com/read/29146051/beta-catenin-and-p53-expression-in-topographic-compartments-of-colorectal-cancer-and-its-prognostic-value-following-surgery
#19
Juan Daniel Prieto, Martina Álvarez, María Isabel Hierro, Isabel García, Luis Vicioso
Colorectal cancer (CRC) is the third most prevalent neoplasm worldwide and the fourth cause of cancer-related death. From Vogelstein's initial model, new molecular knowledge has been incorporated which includes an elevated number of genetic mutations, many of them located in the Wnt pathway, which affect its principle effector: β-catenin. Additionally, it is necessary to keep the heterogeneity of CRCs in mind, both in terms of morphology and biology. The aim of this work is to study the interaction between the Wnt molecular pathway, by means of immunoexpression of β-catenin, in CRC and other molecular mechanisms, such as the p53 pathway, in order to determine the pattern - if one exists - of different immunohistochemical expression of β-catenin and p53 in the superficial and deep tumor components, and lastly, to determine the impact of these markers on prognosis...
December 2017: Annals of Diagnostic Pathology
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
#20
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
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