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Risk Factors for Pancreatic Cancer: Underlying Mechanisms and Potential Targets

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194681 Year: Pages: 115 DOI: 10.3389/978-2-88919-468-1 Language: English
Publisher: Frontiers Media SA
Subject: Physiology --- Science (General)
Added to DOAB on : 2016-03-10 08:14:32
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Pancreatic Cancer has been and still is one of the deadliest types of human malignancies. The annual mortality rates almost equal incidence rates making this disease virtually universally fatal. The 5-year survival of patients with pancreatic cancer is a dismal 5% or less. Therapeutic strategies are extremely limited with gemcitabine extending the survival by a disappointing few weeks. The failure of several randomized clinical trials in the past decade investigating the therapeutic efficacy of different mono- and combination therapies reflects our limited knowledge of pancreatic cancer biology. In addition, biomarkers for early detection are sorely missing. Several pancreatic cancer risk factors have been identified. Unfortunately, the underlying mechanisms linking these risk factors to cancer development are poorly understood. Well known possible and probable risk factors for the development of pancreatic cancer are age, smoking, chronic pancreatitis, obesity, and type-2 diabetes mellitus. Age is certainly of the most important risk factors as most cases of pancreatic cancer occur in the elderly population. Smoking ten cigarettes a day increases the risk by 2.6 times and smoking a pack per day increases it by 5 folds. Chronic pancreatitis increases the risk of pancreatic cancer by up to 13 times. Patients with hereditary forms of chronic pancreatitis have an even higher risk. Obesity, a growing global health problem, increases the risk of pancreatic cancer by about 1.5 fold. Type-2 diabetes mellitus is also associated with an increased risk of pancreatic cancer by at least two-fold. The more recent the onset of diabetes, the stronger the correlation with pancreatic cancer is. In addition, heavy alcohol drinking, a family history of the disease, male gender and African American ethnicity are other risk factors for pancreatic cancer. Pancreatic cancer is characterized by several genetic alterations including mutations in the Kras proto-oncogene and mutations in the tumor suppressor genes p53 and p16. While Kras mutations are currently thought as early events present in a certain percentage of pancreatic intraepithelial neoplasias (PanINs), known precursor lesions of pancreatic ductal adenocarcinomas, mutations in tumor suppressor genes, e.g. p53, seem to accumulate later during progression. In addition, several intracellular signaling pathways are amplified or enhanced, including the MAPK/ERK and PI3K/AKT signaling modules. Overall, these genetic alterations lead to enhanced and sustained proliferation, resistance to cell death, invasive and metastatic potential, and angiogenesis, all hallmarks of cancers. The scope of this Research Topic is to collect data and knowledge of how risk factors increase the risk of initiation/progression of pancreatic cancer. Of particular interest are potential underlying molecular mechanisms. Understanding the molecular mechanisms and driving signaling pathways will ultimately allow the development of targeted interventions to disrupt the risk factor-induced cancer development. This Research Topic is interested in a broad range of risk factors, including genetic and environmental, and welcomes original papers, mini and full reviews, and hypothesis papers. Manuscripts that address the effect of combination of risk factors on pancreatic cancer development and progression are of great interest as well.

Self-Eating on Demand: Autophagy in Cancer and Cancer Therapy

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889454228 Year: Pages: 111 DOI: 10.3389/978-2-88945-422-8 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Oncology
Added to DOAB on : 2018-11-16 17:17:57
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Macroautophagy, the major lysosomal pathway for recycling intracellular components including whole organelles, has emerged as a key process modulating tumorigenesis, tumor–stroma interactions, and cancer therapy. An impressive number of studies over the past decade have unraveled the plastic role of autophagy during tumor development and dissemination. The discoveries that autophagy may either support or repress neoplastic growth and contextually favor or weaken resistance and impact antitumor immunity have spurred efforts from many laboratories trying to conceptualize the complex role of autophagy in cancer using cellular and preclinical models. This complexity is further accentuated by recent findings highlighting that various autophagy-related genes have roles beyond this catabolic mechanism and interface with oncogenic pathways, other trafficking and degradation mechanisms and the cell death machinery. From a therapeutic perspective, knowledge of how autophagy modulates the tumor microenvironment is crucial to devise autophagy-targeting strategies using smart combination of drugs or anticancer modalities. This eBook contains a collection of reviews by autophagy researchers and provides a background to the state-of-the-art in the field of autophagy in cancer, focusing on various aspects of autophagy regulation ranging from its molecular components to its cell autonomous role, e.g. in cell division and oncogenesis, miRNAs regulation, cross-talk with cell death pathways as well as cell non-autonomous role, e.g. in secretion, interface with tumor stroma and clinical prospects of autophagy-based biomarkers and autophagy modulators in anticancer therapy. This eBook is part of the TransAutophagy initiative to better understand the clinical implications of autophagy in cancer.

Recent advances in Pancreatology

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193332 Year: Pages: 69 DOI: 10.3389/978-2-88919-333-2 Language: English
Publisher: Frontiers Media SA
Subject: Nutrition and Food Sciences --- Medicine (General) --- Physiology --- Science (General)
Added to DOAB on : 2016-03-10 08:14:32
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Pancreatic diseases include intractable ones including acute and chronic pancreatitis, and pancreatic cancer. In recent years, great advances have been made in the field of pancreatology, including the pathogenesis, diagnostic modalities, and development of novel therapeutic interventions. It has been established that pancreatic stellate cells play a pivotal role in the development of pancreatic fibrosis in chronic pancreatitis as well as in pancreatic cancer known as desmoplastic reaction. Although it might be still controversial, accumulating evidence has shown that interaction between pancreatic stellate cells-cancer cells contribute to the progression of pancreatic cancer through the increased proliferation and migration, and production of cytokines and extracellular matrix components. In addition, pancreatic stellate cells lead to the resistance to chemotherapy and radiation therapy. Pancreatic stellate cells attract the researchers as a novel therapeutic target of pancreatic cancer. Genetic studies have shown that mutations in the trypsin-related genes such as cationic trypsinogen (PRSS1) gene and the serine protease inhibitor, Kazal type 1 (SPINK1) gene are associated with pancreatitis. In general, each of these factors appears to limit trypsin activation or enhance inactivation, and is believed to increase intrapancreatic trypsin activity and predispose to pancreatitis when the gene is mutated. These results have supported a concept that pancreatic protease/anti-protease plays pivotal roles in the pathogenesis of pancreatitis. In addition, genetic studies focusing on phenotypic variances would provide us with important information how genetic variants would affect the phenotypic variances. Autophagy is an intracellular bulk degradation system in which cytoplasmic components are directed to the lysosome/vacuole by a membrane-mediated process. Recent studies have highlighted a role of autophagy in acute pancreatitis. Using a conditional knockout mouse that lacks the autophagy-related (Atg) gene Atg5 in the pancreatic acinar cells, autophagy exerts a detrimental effect in pancreatic acinar cells by activation of trypsinogen to trypsin. A theory in which autophagy accelerates trypsinogen activation by lysosomal hydrolases under acidic conditions, thus triggering acute pancreatitis in its early stage. The epithelial-mesenchymal transition is a developmental process that allows a polarized epithelial cell to undergo multiple biochemical changes that enable it to assume a mesenchymal phenotype. The phenotype associated with epithelial-mesenchymal transition includes enhanced migratory capacity, invasiveness, elevated resistance to apoptosis, and greatly increased production of extracellular matrix components. In addition to its role in development, tissue regeneration, and fibrosis, epithelial-mesenchymal transition is now considered as a critical process in cancer progression. Induction of epithelial-mesenchymal transition in cancer cells results in the acquisition of invasive and metastatic properties. Epithelial-mesenchymal transition could be an important mechanism in the progression of pancreatic cancer and its poor prognosis. Autoimmune pancreatitis is a unique form of pancreatitis in which autoimmune mechanisms are suspected to be involved in the pathogenesis. There is accumulating study to deal with this new disease concept. In addition to these topics, we have selected several topics in pancreatology, focusing on recent studies increasingly deepening our knowledge in both basic and clinical researches.

AR Signaling in Human Malignancies: Prostate Cancer and Beyond

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ISBN: 9783038427407 9783038427391 Year: Pages: 244 DOI: 10.3390/books978-3-03842-739-1 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General)
Added to DOAB on : 2018-02-16 08:45:39
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The notion that androgens and androgen receptor (AR) signaling are the hallmarks of prostate cancer oncogenesis and disease progression is generally well accepted. What is more poorly understood is the role of AR signaling in other human malignancies. This Special Issue of Cancers initially reviews the role of AR in advanced prostate cancer, and then explores the potential importance of AR signaling in other epithelial malignancies. The first few articles focus on the use of novel AR-targeting therapies in castration-resistant prostate cancer and the mechanisms of resistance to novel antiandrogens, and they also outline the interaction between AR and other cellular pathways, including PI3 kinase signaling, transcriptional regulation, angiogenesis, stromal factors, Wnt signaling, and epigenetic regulation in prostate cancer. The next several articles review the possible role of androgens and AR signaling in breast cancer, bladder cancer, salivary gland cancer, and hepatocellular carcinoma, as well as the potential treatment implications of using antiandrogen therapies in these non-prostatic malignancies.

Smart Nanovesicles for Drug Targeting and Delivery

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ISBN: 9783038978947 9783038978954 Year: Pages: 198 DOI: 10.3390/books978-3-03897-895-4 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General) --- Therapeutics
Added to DOAB on : 2019-06-26 08:44:06
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Nanovesicles are highly-promising systems for the delivery and/or targeting of drugs, biomolecules and contrast agents. Despite the fact that initial studies in this area were performed on phospholipid vesicles, there is an ever-increasing interest in the use of other molecules to obtain smart vesicular carriers focusing on strategies for targeted delivery. These systems can be obtained using newly synthesized smart molecules, or by intelligent design of opportune carriers to achieve specific delivery to the site of action.

Isolation and Structure Elucidation of Bioactive Compounds (Dedicated to the memory of the late Professor Charles D. Hufford)

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ISBN: 9783038977803 9783038977810 Year: Pages: 276 DOI: 10.3390/books978-3-03897-781-0 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Chemistry (General)
Added to DOAB on : 2019-04-25 16:37:17
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We are very pleased to introduce the Book Version of our Special Issue in Molecules dedicated to the memory of the late Professor Dr. Charles D. Hufford. The issue has been a huge success, with 22 full-length peer-reviewed papers and a tribute by Professor Alice M.Clark. Authors, reviewers, and collaborators from many countries across the worldhave contributed to this endeavour, and we are truly grateful to all. This Special Issue isrepresentative of the broad impact that “Charlie” had on the field of bioactive naturalproducts. This Special Issue comprises papers from Professor Hufford’s former students,colleagues, and collaborators throughout the world who have utilized a wide array ofstate-of-the-art techniques to examine diverse natural sources to isolate and identify avariety of natural products with a wide spectrum of biological activities, including somenew microbial transformations and insights into bioactive molecules. Many new bioactive compounds are described and reported here for the first time. Bioactivities reportedinclude cytotoxicity, antimicrobial activity, anti-inflammatory activity, antileishmanialactivity, antitrypanosomal activity, antimalarial activity, analgesic activity, and beneficialliver activities, just to name a few. This Special Issue will undoubtedly have a lasting impact on the field of bioactive natural products, as exemplified by the career of Dr. Hufford.Lastly, without the timely and outstanding contributions from all of you, this Special Issue would not have been possible. We thank you all very much for your contributions and your time devoted to this Special Issue in memory of a special person. Finally, we express ourgratitude and thanks to the journal Molecules and their excellent team of expert reviewers for giving us the support and opportunity to make this Special Issue a huge success!

Keywords

fusidic acid --- Cunninghamella echinulata --- C-26-oxidation --- C-27-oxidation --- Morus alba L. --- aldose reductase inhibitor --- neuroprotective agent --- natural products --- Mitracarpus scaber Zucc. --- pentalogin --- anti-inflammatory --- MS/MS --- Il-8 --- Crinum amabile --- augustine N-oxide --- buphanisine N-oxide --- biological activities --- Cryptococcus neoformans --- cryptococcosis --- HepG2 --- Prosopis glandulosa --- prosopilosidine --- amphotericin B --- fluconazole --- resveratrol --- dietary supplement --- gastro-resistant --- microparticles --- obesity --- HPLC --- Jatropha pelargoniifolia --- alkaloids --- flavonoids --- coumarinolignans --- diterpenes --- anti-inflammatory --- analgesic --- antipyretic --- Cochlospermum vitifolium --- Cochlospermaceae --- flavonoids --- lignans --- aromatic compounds --- carotenoids --- sterols --- liver activity --- Arthrinium sp. --- chromone --- polyketide --- antioxidant activity --- Rubiaceae --- jenipapo --- HPLC-ESI-IT-MS/MS --- flavonoids glycosides --- Baccharis --- antimalarial activity --- antitrypanosomal activity --- insecticidal activity --- GC/MS --- DNA barcoding --- microscopy --- antibacterial --- channel catfish --- columnaris disease --- Flavobacterium columnare --- stilbenes --- muscadine --- pyranoanthocyanin --- anti-leishmanial activity --- Leishmania donovani --- maleimides --- cytotoxicity --- SAR --- phlorogluciniol --- acylphloroglucinol --- anti-inflammatory --- iNOS --- NF-?B --- endophytic fungi --- sesterterpene --- cytotoxic activity --- pancreatic cancer --- Stevia rebaudiana --- diterpene glycosides --- rebaudioside A isomers --- 13(S)-hydroxyatisenoic acid derivative --- iso-stevioside X-ray structure --- Litsea cubeba --- cytotoxicity --- isolation and elucidation --- lignans --- antimicrobial resistance --- multi-drug resistant (MDR) --- methicillin resistant Staphylococcus aureus (MRSA) --- Zingiber monatnum --- terpenes --- (E)-8(17),12-labdadiene-15,16-dial --- zerumbol --- microbial transformation --- hop prenylflavanone --- isoxanthohumol --- cardiomyogenesis --- factor VII --- factor X --- inflammation --- thrombosis --- vasculogenesis --- herbal medicine --- n/a --- Nemania --- Xylariaceae --- Torreya taxifolia --- plant pathogenic and endophytic fungi --- cytochalasins --- malaria --- cytotoxicity --- phytotoxicity --- acacetin 7-methyl ether --- acacetin --- monoamine oxidase-A --- monoamine oxidase-B --- molecular docking --- molecular dynamics --- neurological disorder --- Turnera diffusa

Amide Bond Activation

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ISBN: 9783039212033 9783039212040 Year: Pages: 466 DOI: 10.3390/books978-3-03921-204-0 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Chemistry (General)
Added to DOAB on : 2019-08-28 11:21:27
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The amide bond represents a privileged motif in chemistry. The recent years have witnessed an explosion of interest in the development of new chemical transformations of amides. These developments cover an impressive range of catalytic N–C bond activation in electrophilic, Lewis acid, radical, and nucleophilic reaction pathways, among other transformations. Equally relevant are structural and theoretical studies that provide the basis for chemoselective manipulation of amidic resonance. This monograph on amide bonds offers a broad survey of recent advances in activation of amides and addresses various approaches in the field.

Keywords

fumardiamide --- primaquine --- succindiamide --- Michael acceptor --- biofilm eradication --- antibacterial screening --- antiviral activity --- cytostatic activity --- N,N-dimethylformamide --- DMF --- N,N-dimethylacetamide --- DMAc --- amination --- amidation --- thioamidation --- formylation --- carbonylation --- cyanation --- insertion --- cyclization --- amide --- arynes --- insertion --- activation --- heterocycles --- organic synthesis --- multi-component coupling reaction --- aryl thioamides --- thiourea --- C-H/C-N activation --- C-S formation --- transition-metal-free --- rotational barrier energy --- amide bond --- nuclear magnetic resonance --- kinetic --- density functional theory --- non planar amide --- base-catalyed hydrolysis --- water solvation --- entropy --- transamidation --- amide --- amine --- catalyst --- catalysis --- acylative cross-coupling --- trialkylborane --- amide activation --- palladium --- N-heterocyclic carbene --- ruthenium (Ru) --- N-heterocyclic carbenes (NHCs) --- homogeneous catalysis --- in situ --- amide bonds --- synthesis --- density functional theory --- cis/trans isomerization --- secondary amides --- dipeptides --- steric effects --- tert-butyl --- additivity principle --- amino acid transporters --- amide bond --- gemcitabine prodrug --- metabolic stability --- pancreatic cancer cells --- pharmacokinetics --- peptide bond cleavage --- amide bond resonance --- twisted amides --- enzymes --- metal complexes --- catalysts --- amide C–N bond activation --- nickel catalysis --- amidation --- DFT study --- reaction thermodynamics --- amide resonance --- anomeric effect --- HERON reaction --- pyramidal amides --- physical organic chemistry --- reaction mechanism --- amide --- activation --- amidicity --- carbonylicity --- transamidation --- acyl transfer --- excited state --- Suzuki-Miyaura --- cross-coupling --- aryl esters --- C–O activation --- Pd-catalysis --- amides --- carbanions --- C–H acidity --- nitro-aci tautomerism --- molecular dynamics --- density-functional theory --- alkynes --- C–H bond cleavage --- C–N bond cleavage --- cyclopentadienyl complexes --- N-(1-naphthyl)acetamide --- rhodium --- [2+2+2] annulation --- amide bond --- sulfonamide bond --- alkynes --- addition reaction --- aminoacylation --- aminosulfonylation --- pre-catalysts --- palladium catalysis --- amide bond activation --- ester bond activation --- cross-coupling --- amide bond --- bridged lactams --- twisted amides --- amides --- Winkler-Dunitz parameters --- N–C activation --- hypersensitivity --- nitrogen heterocycles --- distortion --- bridged sultams --- amides --- C-N ? bond cleavage --- sodium --- crown ether --- amide hydrolysis --- model compound --- intramolecular catalysis --- twisted amide --- protease --- intein --- C-H functionalization --- directing groups --- amides --- transition metals --- catalysis

Application of Bioinformatics in Cancers

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ISBN: 9783039217885 9783039217892 Year: Pages: 418 DOI: 10.3390/books978-3-03921-789-2 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Technology (General) --- Biotechnology
Added to DOAB on : 2019-12-09 11:49:16
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This collection of 25 research papers comprised of 22 original articles and 3 reviews is brought together from international leaders in bioinformatics and biostatistics. The collection highlights recent computational advances that improve the ability to analyze highly complex data sets to identify factors critical to cancer biology. Novel deep learning algorithms represent an emerging and highly valuable approach for collecting, characterizing and predicting clinical outcomes data. The collection highlights several of these approaches that are likely to become the foundation of research and clinical practice in the future. In fact, many of these technologies reveal new insights about basic cancer mechanisms by integrating data sets and structures that were previously immiscible.

Keywords

comorbidity score --- mortality --- locoregionally advanced --- HNSCC --- curative surgery --- traditional Chinese medicine --- health strengthening herb --- cancer treatment --- network pharmacology --- network target --- high-throughput analysis --- brain metastases --- colorectal cancer --- KRAS mutation --- PD-L1 --- tumor infiltrating lymphocytes --- drug resistance --- gefitinib --- erlotinib --- biostatistics --- bioinformatics --- Bufadienolide-like chemicals --- molecular mechanism --- anti-cancer --- bioinformatics --- cancer --- brain --- pathophysiology --- imaging --- machine learning --- extreme learning --- deep learning --- neurological disorders --- pancreatic cancer --- TCGA --- curation --- DNA --- RNA --- protein --- single-biomarkers --- multiple-biomarkers --- cancer-related pathways --- colorectal cancer --- DNA sequence profile --- Monte Carlo --- mixture of normal distributions --- somatic mutation --- tumor --- mutable motif --- activation induced deaminase --- AID/APOBEC --- transcriptional signatures --- copy number variation --- copy number aberration --- TCGA mining --- cancer CRISPR --- firehose --- gene signature extraction --- gene loss biomarkers --- gene inactivation biomarkers --- biomarker discovery --- chemotherapy --- microarray --- ovarian cancer --- predictive model --- machine learning --- overall survival --- observed survival interval --- skin cutaneous melanoma --- The Cancer Genome Atlas --- omics --- breast cancer prognosis --- artificial intelligence --- machine learning --- decision support systems --- cancer prognosis --- independent prognostic power --- omics profiles --- histopathological imaging features --- cancer --- intratumor heterogeneity --- genomic instability --- epigenetics --- mitochondrial metabolism --- miRNAs --- cancer biomarkers --- breast cancer detection --- machine learning --- feature selection --- classification --- denoising autoencoders --- breast cancer --- feature extraction and interpretation --- concatenated deep feature --- cancer modeling --- interaction --- histopathological imaging --- clinical/environmental factors --- oral cancer --- miRNA --- bioinformatics --- datasets --- biomarkers --- TCGA --- GEO DataSets --- hormone sensitive cancers --- breast cancer --- StAR --- estrogen --- steroidogenic enzymes --- hTERT --- telomerase --- telomeres --- alternative splicing --- network analysis --- hierarchical clustering analysis --- differential gene expression analysis --- cancer biomarker --- diseases genes --- variable selection --- false discovery rate --- knockoffs --- bioinformatics --- copy number variation --- cell-free DNA --- methylation --- mutation --- next generation sequencing --- self-organizing map --- head and neck cancer --- treatment de-escalation --- HP --- molecular subtypes --- tumor microenvironment --- Bioinformatics tool --- R package --- machine learning --- meta-analysis --- biomarker signature --- gene expression analysis --- survival analysis --- functional analysis --- bioinformatics --- machine learning --- artificial intelligence --- Network Analysis --- single-cell sequencing --- circulating tumor DNA (ctDNA) --- Neoantigen Prediction --- precision medicine --- Computational Immunology

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