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Publisher: Elsevier   (Total: 3031 journals)

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Showing 1 - 200 of 3031 Journals sorted alphabetically
AASRI Procedia     Open Access   (Followers: 15)
Academic Pediatrics     Hybrid Journal   (Followers: 20, SJR: 1.402, h-index: 51)
Academic Radiology     Hybrid Journal   (Followers: 16, SJR: 1.008, h-index: 75)
Accident Analysis & Prevention     Partially Free   (Followers: 79, SJR: 1.109, h-index: 94)
Accounting Forum     Hybrid Journal   (Followers: 22, SJR: 0.612, h-index: 27)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 27, SJR: 2.515, h-index: 90)
Achievements in the Life Sciences     Open Access   (Followers: 4)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 5, SJR: 0.338, h-index: 19)
Acta Astronautica     Hybrid Journal   (Followers: 303, SJR: 0.726, h-index: 43)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 3)
Acta Biomaterialia     Hybrid Journal   (Followers: 25, SJR: 2.02, h-index: 104)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription  
Acta de Investigación Psicológica     Open Access   (Followers: 2)
Acta Ecologica Sinica     Open Access   (Followers: 8, SJR: 0.172, h-index: 29)
Acta Haematologica Polonica     Free   (SJR: 0.123, h-index: 8)
Acta Histochemica     Hybrid Journal   (Followers: 3, SJR: 0.604, h-index: 38)
Acta Materialia     Hybrid Journal   (Followers: 196, SJR: 3.683, h-index: 202)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 5, SJR: 0.615, h-index: 21)
Acta Mechanica Solida Sinica     Full-text available via subscription   (Followers: 9, SJR: 0.442, h-index: 21)
Acta Oecologica     Hybrid Journal   (Followers: 9, SJR: 0.915, h-index: 53)
Acta Otorrinolaringologica (English Edition)     Full-text available via subscription   (Followers: 1)
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 3, SJR: 0.311, h-index: 16)
Acta Pharmaceutica Sinica B     Open Access   (Followers: 2)
Acta Poética     Open Access   (Followers: 4)
Acta Psychologica     Hybrid Journal   (Followers: 21, SJR: 1.365, h-index: 73)
Acta Sociológica     Open Access  
Acta Tropica     Hybrid Journal   (Followers: 5, SJR: 1.059, h-index: 77)
Acta Urológica Portuguesa     Open Access  
Actas Dermo-Sifiliograficas     Full-text available via subscription   (Followers: 4)
Actas Dermo-Sifiliográficas (English Edition)     Full-text available via subscription   (Followers: 3)
Actas Urológicas Españolas     Full-text available via subscription   (Followers: 3, SJR: 0.383, h-index: 19)
Actas Urológicas Españolas (English Edition)     Full-text available via subscription   (Followers: 2)
Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 5, SJR: 0.141, h-index: 3)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 4, SJR: 0.112, h-index: 2)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 4)
Ad Hoc Networks     Hybrid Journal   (Followers: 11, SJR: 0.967, h-index: 57)
Addictive Behaviors     Hybrid Journal   (Followers: 15, SJR: 1.514, h-index: 92)
Addictive Behaviors Reports     Open Access   (Followers: 5)
Additive Manufacturing     Hybrid Journal   (Followers: 7, SJR: 1.039, h-index: 5)
Additives for Polymers     Full-text available via subscription   (Followers: 20)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 119, SJR: 5.2, h-index: 222)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 11, SJR: 1.265, h-index: 53)
Advanced Powder Technology     Hybrid Journal   (Followers: 16, SJR: 0.739, h-index: 33)
Advances in Accounting     Hybrid Journal   (Followers: 8, SJR: 0.299, h-index: 15)
Advances in Agronomy     Full-text available via subscription   (Followers: 15, SJR: 2.071, h-index: 82)
Advances in Anesthesia     Full-text available via subscription   (Followers: 24, SJR: 0.169, h-index: 4)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 3)
Advances in Applied Mathematics     Full-text available via subscription   (Followers: 6, SJR: 1.054, h-index: 35)
Advances in Applied Mechanics     Full-text available via subscription   (Followers: 10, SJR: 0.801, h-index: 26)
Advances in Applied Microbiology     Full-text available via subscription   (Followers: 21, SJR: 1.286, h-index: 49)
Advances In Atomic, Molecular, and Optical Physics     Full-text available via subscription   (Followers: 16, SJR: 3.31, h-index: 42)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4, SJR: 2.277, h-index: 43)
Advances in Botanical Research     Full-text available via subscription   (Followers: 3, SJR: 0.619, h-index: 48)
Advances in Cancer Research     Full-text available via subscription   (Followers: 26, SJR: 2.215, h-index: 78)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 9, SJR: 0.9, h-index: 30)
Advances in Catalysis     Full-text available via subscription   (Followers: 5, SJR: 2.139, h-index: 42)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 12)
Advances in Chemical Engineering     Full-text available via subscription   (Followers: 24, SJR: 0.183, h-index: 23)
Advances in Child Development and Behavior     Full-text available via subscription   (Followers: 10, SJR: 0.665, h-index: 29)
Advances in Chronic Kidney Disease     Full-text available via subscription   (Followers: 8, SJR: 1.268, h-index: 45)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 28, SJR: 0.938, h-index: 33)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 18, SJR: 2.314, h-index: 130)
Advances in Computers     Full-text available via subscription   (Followers: 16, SJR: 0.223, h-index: 22)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 11)
Advances in Digestive Medicine     Open Access   (Followers: 4)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 5)
Advances in Drug Research     Full-text available via subscription   (Followers: 22)
Advances in Ecological Research     Full-text available via subscription   (Followers: 39, SJR: 3.25, h-index: 43)
Advances in Engineering Software     Hybrid Journal   (Followers: 25, SJR: 0.486, h-index: 10)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 7)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 38, SJR: 5.465, h-index: 64)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 3)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 8)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 41, SJR: 0.674, h-index: 38)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 14)
Advances in Genetics     Full-text available via subscription   (Followers: 15, SJR: 2.558, h-index: 54)
Advances in Genome Biology     Full-text available via subscription   (Followers: 11)
Advances in Geophysics     Full-text available via subscription   (Followers: 6, SJR: 2.325, h-index: 20)
Advances in Heat Transfer     Full-text available via subscription   (Followers: 18, SJR: 0.906, h-index: 24)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 0.497, h-index: 31)
Advances in Human Factors/Ergonomics     Full-text available via subscription   (Followers: 22)
Advances in Imaging and Electron Physics     Full-text available via subscription   (Followers: 2, SJR: 0.396, h-index: 27)
Advances in Immunology     Full-text available via subscription   (Followers: 33, SJR: 4.152, h-index: 85)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 9, SJR: 1.132, h-index: 42)
Advances in Insect Physiology     Full-text available via subscription   (Followers: 3, SJR: 1.274, h-index: 27)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 4)
Advances in Intl. Accounting     Full-text available via subscription   (Followers: 4)
Advances in Life Course Research     Hybrid Journal   (Followers: 7, SJR: 0.764, h-index: 15)
Advances in Lipobiology     Full-text available via subscription   (Followers: 1)
Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 8)
Advances in Marine Biology     Full-text available via subscription   (Followers: 16, SJR: 1.645, h-index: 45)
Advances in Mathematics     Full-text available via subscription   (Followers: 10, SJR: 3.261, h-index: 65)
Advances in Medical Sciences     Hybrid Journal   (Followers: 5, SJR: 0.489, h-index: 25)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 5)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 4, SJR: 1.44, h-index: 51)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 21)
Advances in Molecular and Cellular Endocrinology     Full-text available via subscription   (Followers: 10)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 6, SJR: 0.324, h-index: 8)
Advances in Nanoporous Materials     Full-text available via subscription   (Followers: 3)
Advances in Oncobiology     Full-text available via subscription   (Followers: 3)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 15, SJR: 2.885, h-index: 45)
Advances in Parallel Computing     Full-text available via subscription   (Followers: 7, SJR: 0.148, h-index: 11)
Advances in Parasitology     Full-text available via subscription   (Followers: 7, SJR: 2.37, h-index: 73)
Advances in Pediatrics     Full-text available via subscription   (Followers: 20, SJR: 0.4, h-index: 28)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 14)
Advances in Pharmacology     Full-text available via subscription   (Followers: 13, SJR: 1.718, h-index: 58)
Advances in Physical Organic Chemistry     Full-text available via subscription   (Followers: 7, SJR: 0.384, h-index: 26)
Advances in Phytomedicine     Full-text available via subscription  
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3, SJR: 0.248, h-index: 11)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 8)
Advances in Plant Pathology     Full-text available via subscription   (Followers: 5)
Advances in Porous Media     Full-text available via subscription   (Followers: 4)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 18)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 17, SJR: 1.5, h-index: 62)
Advances in Psychology     Full-text available via subscription   (Followers: 56)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 5, SJR: 0.478, h-index: 32)
Advances in Radiation Oncology     Open Access  
Advances in Small Animal Medicine and Surgery     Hybrid Journal   (Followers: 1, SJR: 0.1, h-index: 2)
Advances in Space Research     Full-text available via subscription   (Followers: 332, SJR: 0.606, h-index: 65)
Advances in Structural Biology     Full-text available via subscription   (Followers: 7)
Advances in Surgery     Full-text available via subscription   (Followers: 6, SJR: 0.823, h-index: 27)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 28, SJR: 1.321, h-index: 56)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 14)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 12)
Advances in Virus Research     Full-text available via subscription   (Followers: 5, SJR: 1.878, h-index: 68)
Advances in Water Resources     Hybrid Journal   (Followers: 42, SJR: 2.408, h-index: 94)
Aeolian Research     Hybrid Journal   (Followers: 5, SJR: 0.973, h-index: 22)
Aerospace Science and Technology     Hybrid Journal   (Followers: 303, SJR: 0.816, h-index: 49)
AEU - Intl. J. of Electronics and Communications     Hybrid Journal   (Followers: 8, SJR: 0.318, h-index: 36)
African J. of Emergency Medicine     Open Access   (Followers: 4, SJR: 0.344, h-index: 6)
Ageing Research Reviews     Hybrid Journal   (Followers: 7, SJR: 3.289, h-index: 78)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 388, SJR: 1.385, h-index: 72)
Agri Gene     Hybrid Journal  
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 15, SJR: 2.18, h-index: 116)
Agricultural Systems     Hybrid Journal   (Followers: 29, SJR: 1.275, h-index: 74)
Agricultural Water Management     Hybrid Journal   (Followers: 36, SJR: 1.546, h-index: 79)
Agriculture and Agricultural Science Procedia     Open Access  
Agriculture and Natural Resources     Open Access   (Followers: 1)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 48, SJR: 1.879, h-index: 120)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.434, h-index: 14)
Air Medical J.     Hybrid Journal   (Followers: 3, SJR: 0.234, h-index: 18)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.285, h-index: 3)
Alcohol     Hybrid Journal   (Followers: 9, SJR: 0.922, h-index: 66)
Alcoholism and Drug Addiction     Open Access   (Followers: 5)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 1, SJR: 0.436, h-index: 12)
Alexandria J. of Medicine     Open Access  
Algal Research     Partially Free   (Followers: 7, SJR: 2.05, h-index: 20)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 3)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.46, h-index: 29)
Allergology Intl.     Open Access   (Followers: 5, SJR: 0.776, h-index: 35)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 6, SJR: 0.158, h-index: 9)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 45, SJR: 4.289, h-index: 64)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 5)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 3)
American Heart J.     Hybrid Journal   (Followers: 45, SJR: 3.157, h-index: 153)
American J. of Cardiology     Hybrid Journal   (Followers: 47, SJR: 2.063, h-index: 186)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 34, SJR: 0.574, h-index: 65)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 6, SJR: 1.091, h-index: 45)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 14, SJR: 1.653, h-index: 93)
American J. of Human Genetics     Hybrid Journal   (Followers: 32, SJR: 8.769, h-index: 256)
American J. of Infection Control     Hybrid Journal   (Followers: 25, SJR: 1.259, h-index: 81)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 31, SJR: 2.313, h-index: 172)
American J. of Medicine     Hybrid Journal   (Followers: 48, SJR: 2.023, h-index: 189)
American J. of Medicine Supplements     Full-text available via subscription   (Followers: 3)
American J. of Obstetrics and Gynecology     Hybrid Journal   (Followers: 173, SJR: 2.255, h-index: 171)
American J. of Ophthalmology     Hybrid Journal   (Followers: 51, SJR: 2.803, h-index: 148)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 2)
American J. of Orthodontics and Dentofacial Orthopedics     Full-text available via subscription   (Followers: 6, SJR: 1.249, h-index: 88)
American J. of Otolaryngology     Hybrid Journal   (Followers: 22, SJR: 0.59, h-index: 45)
American J. of Pathology     Hybrid Journal   (Followers: 23, SJR: 2.653, h-index: 228)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 21, SJR: 2.764, h-index: 154)
American J. of Surgery     Hybrid Journal   (Followers: 32, SJR: 1.286, h-index: 125)
American J. of the Medical Sciences     Hybrid Journal   (Followers: 13, SJR: 0.653, h-index: 70)
Ampersand : An Intl. J. of General and Applied Linguistics     Open Access   (Followers: 5)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.066, h-index: 51)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 52, SJR: 0.124, h-index: 9)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 3)
Anales de Cirugia Vascular     Full-text available via subscription  
Anales de Pediatría     Full-text available via subscription   (Followers: 2, SJR: 0.209, h-index: 27)
Anales de Pediatría (English Edition)     Full-text available via subscription  
Anales de Pediatría Continuada     Full-text available via subscription   (SJR: 0.104, h-index: 3)
Analytic Methods in Accident Research     Hybrid Journal   (Followers: 2, SJR: 2.577, h-index: 7)
Analytica Chimica Acta     Hybrid Journal   (Followers: 38, SJR: 1.548, h-index: 152)
Analytical Biochemistry     Hybrid Journal   (Followers: 151, SJR: 0.725, h-index: 154)
Analytical Chemistry Research     Open Access   (Followers: 7, SJR: 0.18, h-index: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 10)
Anesthésie & Réanimation     Full-text available via subscription  
Anesthesiology Clinics     Full-text available via subscription   (Followers: 21, SJR: 0.421, h-index: 40)
Angiología     Full-text available via subscription   (SJR: 0.124, h-index: 9)
Angiologia e Cirurgia Vascular     Open Access  
Animal Behaviour     Hybrid Journal   (Followers: 141, SJR: 1.907, h-index: 126)
Animal Feed Science and Technology     Hybrid Journal   (Followers: 5, SJR: 1.151, h-index: 83)
Animal Reproduction Science     Hybrid Journal   (Followers: 5, SJR: 0.711, h-index: 78)
Annales d'Endocrinologie     Full-text available via subscription   (SJR: 0.394, h-index: 30)
Annales d'Urologie     Full-text available via subscription  
Annales de Cardiologie et d'Angéiologie     Full-text available via subscription   (SJR: 0.177, h-index: 13)
Annales de Chirurgie de la Main et du Membre Supérieur     Full-text available via subscription  
Annales de Chirurgie Plastique Esthétique     Full-text available via subscription   (Followers: 2, SJR: 0.354, h-index: 22)
Annales de Chirurgie Vasculaire     Full-text available via subscription   (Followers: 1)

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Journal Cover Advances in Cancer Research
  [SJR: 2.215]   [H-I: 78]   [26 followers]  Follow
    
   Full-text available via subscription Subscription journal  (Not entitled to full-text)
   ISSN (Print) 0065-230X
   Published by Elsevier Homepage  [3031 journals]
  • MALDI IMS and Cancer Tissue Microarrays
    • Authors: R. Casadonte; R. Longuespée; J. Kriegsmann; M. Kriegsmann
      Abstract: Publication date: Available online 12 January 2017
      Source:Advances in Cancer Research
      Author(s): R. Casadonte, R. Longuespée, J. Kriegsmann, M. Kriegsmann
      Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) technology creates a link between the molecular assessment of numerous molecules and the morphological information about their special distribution. The application of MALDI IMS on formalin-fixed paraffin-embedded (FFPE) tissue microarrays (TMAs) is suitable for large-scale discovery analyses. Data acquired from FFPE TMA cancer samples in current research are very promising, and applications for routine diagnostics are under development. With the current rapid advances in both technology and applications, MALDI IMS technology is expected to enter into routine diagnostics soon. This chapter is intended to be comprehensive with respect to all aspects and considerations for the application of MALDI IMS on FFPE cancer TMAs with in-depth notes on technical aspects.

      PubDate: 2017-01-15T20:13:59Z
      DOI: 10.1016/bs.acr.2016.11.007
       
  • Mass Spectrometry Imaging in Oncology Drug Discovery
    • Authors: R.J.A. Goodwin; J. Bunch; D.F. McGinnity
      Abstract: Publication date: Available online 10 January 2017
      Source:Advances in Cancer Research
      Author(s): R.J.A. Goodwin, J. Bunch, D.F. McGinnity
      Over the last decade mass spectrometry imaging (MSI) has been integrated in to many areas of drug discovery and development. It can have significant impact in oncology drug discovery as it allows efficacy and safety of compounds to be assessed against the backdrop of the complex tumour microenvironment. We will discuss the roles of MSI in investigating compound and metabolite biodistribution and defining pharmacokinetic -pharmacodynamic relationships, analysis that is applicable to all drug discovery projects. We will then look more specifically at how MSI can be used to understand tumour metabolism and other applications specific to oncology research. This will all be described alongside the challenges of applying MSI to industry research with increased use of metrology for MSI.

      PubDate: 2017-01-15T20:13:59Z
      DOI: 10.1016/bs.acr.2016.11.005
       
  • Applications of Mass Spectrometry Imaging to Cancer
    • Authors: G. Arentz; P. Mittal; C. Zhang; Y.-Y. Ho; M. Briggs; L. Winderbaum; M.K. Hoffmann; P. Hoffmann
      Abstract: Publication date: Available online 9 January 2017
      Source:Advances in Cancer Research
      Author(s): G. Arentz, P. Mittal, C. Zhang, Y.-Y. Ho, M. Briggs, L. Winderbaum, M.K. Hoffmann, P. Hoffmann
      Pathologists play an essential role in the diagnosis and prognosis of benign and cancerous tumors. Clinicians provide tissue samples, for example, from a biopsy, which are then processed and thin sections are placed onto glass slides, followed by staining of the tissue with visible dyes. Upon processing and microscopic examination, a pathology report is provided, which relies on the pathologist's interpretation of the phenotypical presentation of the tissue. Targeted analysis of single proteins provide further insight and together with clinical data these results influence clinical decision making. Recent developments in mass spectrometry facilitate the collection of molecular information about such tissue specimens. These relatively new techniques generate label-free mass spectra across tissue sections providing nonbiased, nontargeted molecular information. At each pixel with spatial coordinates (x/y) a mass spectrum is acquired. The acquired mass spectrums can be visualized as intensity maps displaying the distribution of single m/z values of interest. Based on the sample preparation, proteins, peptides, lipids, small molecules, or glycans can be analyzed. The generated intensity maps/images allow new insights into tumor tissues. The technique has the ability to detect and characterize tumor cells and their environment in a spatial context and combined with histological staining, can be used to aid pathologists and clinicians in the diagnosis and management of cancer. Moreover, such data may help classify patients to aid therapy decisions and predict outcomes. The novel complementary mass spectrometry-based methods described in this chapter will contribute to the transformation of pathology services around the world.

      PubDate: 2017-01-15T20:13:59Z
      DOI: 10.1016/bs.acr.2016.11.002
       
  • About the Editors
    • Abstract: Publication date: 2017
      Source:Advances in Cancer Research, Volume 133


      PubDate: 2017-01-15T20:13:59Z
       
  • Mass Spectrometry Imaging in Cancer Research: Future Perspectives
    • Authors: L.A. McDonnell; P.M. Angel; S. Lou; R.R. Drake
      Abstract: Publication date: Available online 30 December 2016
      Source:Advances in Cancer Research
      Author(s): L.A. McDonnell, P.M. Angel, S. Lou, R.R. Drake
      In the last decade mass spectrometry imaging has developed rapidly, in terms of multiple new instrumentation innovations, expansion of target molecules, and areas of application. Mass spectrometry imaging has already had a substantial impact in cancer research, uncovering biomolecular changes associated with disease progression, diagnosis, and prognosis. Many new approaches are incorporating the use of readily available formalin-fixed paraffin-embedded cancer tissues from pathology centers, including tissue blocks, biopsy specimens, and tumor microarrays. It is also increasingly used in drug formulation development as an inexpensive method to determine the distributions of drugs and their metabolites. In this chapter, we offer a perspective in the current and future methodological developments and how these may open up new vistas for cancer research.

      PubDate: 2017-01-15T20:13:59Z
      DOI: 10.1016/bs.acr.2016.11.010
       
  • Ambient Mass Spectrometry in Cancer Research
    • Authors: Z. Takats; N. Strittmatter; J.S. McKenzie
      Abstract: Publication date: Available online 29 December 2016
      Source:Advances in Cancer Research
      Author(s): Z. Takats, N. Strittmatter, J.S. McKenzie
      Ambient ionization mass spectrometry was developed as a sample preparation-free alternative to traditional MS-based workflows. Desorption electrospray ionization (DESI)-MS methods were demonstrated to allow the direct analysis of a broad range of samples including unaltered biological tissue specimens. In contrast to this advantageous feature, nowadays DESI-MS is almost exclusively used for sample preparation intensive mass spectrometric imaging (MSI) in the area of cancer research. As an alternative to MALDI, DESI-MSI offers matrix deposition-free experiment with improved signal in the lower (<500 m/z) range. DESI-MSI enables the spatial mapping of tumor metabolism and has been broadly demonstrated to offer an alternative to frozen section histology for intraoperative tissue identification and surgical margin assessment. Rapid evaporative ionization mass spectrometry (REIMS) was developed exclusively for the latter purpose by the direct combination of electrosurgical devices and mass spectrometry. In case of the REIMS technology, aerosol particles produced by electrosurgical dissection are subjected to MS analysis, providing spectral information on the structural lipid composition of tissues. REIMS technology was demonstrated to give real-time information on the histological nature of tissues being dissected, deeming it an ideal tool for intraoperative tissue identification including surgical margin control. More recently, the method has also been used for the rapid lipidomic phenotyping of cancer cell lines as it was demonstrated in case of the NCI-60 cell line collection.

      PubDate: 2017-01-15T20:13:59Z
      DOI: 10.1016/bs.acr.2016.11.011
       
  • Chapter Two The Relationship Between Dormant Cancer Cells and Their
           Microenvironment
    • Authors: N. Linde; G. Fluegen; J.A. Aguirre-Ghiso
      Pages: 45 - 71
      Abstract: Publication date: 2016
      Source:Advances in Cancer Research, Volume 132
      Author(s): N. Linde, G. Fluegen, J.A. Aguirre-Ghiso
      The majority of cancer deaths are due to metastases that can occur years or decades after primary tumor diagnosis and treatment. Disseminated tumor cells (DTCs) surviving in a dormant state in target organs appear to explain the timing of this phenomenon. Knowledge on this process is important as it might provide a window of opportunity to prevent recurrences by eradicating dormant DTCs and/or by maintaining DTCs in a dormant state. Importantly, this research might offer markers of dormancy for early monitoring of metastatic relapse. However, our understanding of the mechanisms underlying the regulation of entry into and exit from dormancy is still limited and crippling any therapeutic opportunity. While cancer cell-intrinsic signaling pathways have been linked to dormancy regulation, it is likely that these pathways and the switch controlling reactivation from dormancy are regulated by microenvironmental cues. Here we review and discuss recent findings on how the microenvironment regulates cancer dormancy and raise new questions that may help advance the field.

      PubDate: 2016-10-13T14:09:00Z
      DOI: 10.1016/bs.acr.2016.07.002
      Issue No: Vol. 132 (2016)
       
  • Chapter One The Dual Role of Senescence in Pancreatic Ductal
           Adenocarcinoma
    • Authors: A. Porciuncula; C. Hajdu; G. David
      Pages: 1 - 20
      Abstract: Publication date: 2016
      Source:Advances in Cancer Research, Volume 131
      Author(s): A. Porciuncula, C. Hajdu, G. David
      The role of senescence as a tumor suppressor is well established; however, recent evidence has revealed novel paracrine functions for senescent cells in relation to their microenvironment, most notably protumorigenic roles in certain contexts. Senescent cells are capable of altering the inflammatory microenvironment through the senescence-associated secretory phenotype, which could have important consequences for tumorigenesis. The role of senescent cells in a highly inflammatory cancer like pancreatic cancer is still largely undefined, apart from the fact that senescence abrogation increases tumorigenesis in vivo. This review will summarize our current knowledge of the phenomenon of cellular senescence in pancreatic ductal adenocarcinoma, its overlapping link with inflammation, and some urgent unanswered questions in the field.

      PubDate: 2016-10-13T14:09:00Z
      DOI: 10.1016/bs.acr.2016.05.006
      Issue No: Vol. 131 (2016)
       
  • Chapter One The Evolving, Multifaceted Roles of Autophagy in Cancer
    • Authors: J. Liu; J. Debnath
      Pages: 1 - 53
      Abstract: Publication date: 2016
      Source:Advances in Cancer Research, Volume 130
      Author(s): J. Liu, J. Debnath
      Autophagy is a lysosomal degradation process crucial for adaptation to stress and cellular homeostasis. In cancer, autophagy has been demonstrated to serve multifaceted roles in tumor initiation and progression. Although genetic evidence corroborates a role for autophagy as a tumor suppressor mechanism during tumor initiation, autophagy also sustains metabolic pathways in cancer cells and promotes survival within the harsh tumor microenvironment and in response to diverse anticancer therapies. Moreover, though traditionally viewed as an autodigestive process, more recent work demonstrates that autophagy also facilitates cellular secretion; the importance of these new functions of the autophagy pathway is being increasingly appreciated during cancer progression and treatment. In this review, we discuss how these evolving and diverse roles for autophagy both impede and promote tumorigenesis.

      PubDate: 2016-04-27T02:25:53Z
      DOI: 10.1016/bs.acr.2016.01.005
      Issue No: Vol. 130 (2016)
       
  • Chapter Two Inhibitors of DNA Methylation, Histone Deacetylation, and
           Histone Demethylation
    • Authors: C.A. Zahnow; M. Topper; M. Stone; T. Murray-Stewart; H. Li; S.B. Baylin; R.A. Casero
      Pages: 55 - 111
      Abstract: Publication date: 2016
      Source:Advances in Cancer Research, Volume 130
      Author(s): C.A. Zahnow, M. Topper, M. Stone, T. Murray-Stewart, H. Li, S.B. Baylin, R.A. Casero
      Epigenetic silencing and inappropriate activation of gene expression are frequent events during the initiation and progression of cancer. These events involve a complex interplay between the hypermethylation of CpG dinucleotides within gene promoter and enhancer regions, the recruitment of transcriptional corepressors and the deacetylation and/or methylation of histone tails. These epigenetic regulators act in concert to block transcription or interfere with the maintenance of chromatin boundary regions. However, DNA/histone methylation and histone acetylation states are reversible, enzyme-mediated processes and as such, have emerged as promising targets for cancer therapy. This review will focus on the potential benefits and synergistic/additive effects of combining DNA-demethylating agents and histone deacetylase inhibitors or lysine-specific demethylase inhibitors together in epigenetic therapy for solid tumors and will highlight what is known regarding the mechanisms of action that contribute to the antitumor response.

      PubDate: 2016-04-27T02:25:53Z
      DOI: 10.1016/bs.acr.2016.01.007
      Issue No: Vol. 130 (2016)
       
  • Chapter Three Emerging Roles of Epigenetic Regulator Sin3 in Cancer
    • Authors: N. Bansal; G. David; E. Farias; S. Waxman
      Pages: 113 - 135
      Abstract: Publication date: 2016
      Source:Advances in Cancer Research, Volume 130
      Author(s): N. Bansal, G. David, E. Farias, S. Waxman
      Revolutionizing treatment strategies is an urgent clinical need in the fight against cancer. Recently the scientific community has recognized chromatin-associated proteins as promising therapeutic candidates. However, there is a need to develop more targeted epigenetic inhibitors with less toxicity. Sin3 family is one such target which consists of evolutionary conserved proteins with two paralogues Sin3A and Sin3B. Sin3A/B are global transcription regulators that provide a versatile platform for diverse chromatin-modifying activities. Sin3 proteins regulate key cellular functions that include cell cycle, proliferation, and differentiation, and have recently been implicated in cancer pathogenesis. In this chapter, we summarize the key concepts of Sin3 biology and elaborate the recent advancements in the role of Sin3 proteins in cancer with specific examples in multiple endocrine neoplasia type 2, pancreatic ductal adenocarcinoma, and triple negative breast cancer. Finally, a program to create an integrative approach for screening antitumor agents that target chromatin-associated factors like Sin3 is presented.

      PubDate: 2016-04-27T02:25:53Z
      DOI: 10.1016/bs.acr.2016.01.006
      Issue No: Vol. 130 (2016)
       
  • Rapid Mass Spectrometry Imaging to Assess the Biochemical Profile of
           Pituitary Tissue for Potential Intraoperative Usage
    • Authors: K.T. Huang; S. Ludy; D. Calligaris; I.F. Dunn; E. Laws; S. Santagata; N.Y.R. Agar
      Abstract: Publication date: Available online 28 December 2016
      Source:Advances in Cancer Research
      Author(s): K.T. Huang, S. Ludy, D. Calligaris, I.F. Dunn, E. Laws, S. Santagata, N.Y.R. Agar
      Pituitary adenomas are relatively common intracranial neoplasms that are frequently treated with surgical resection. Rapid visualization of pituitary tissue remains a challenge as current techniques either produce little to no information on hormone-secreting function or are too slow to practically aid in intraoperative or even perioperative decision-making. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) represents a powerful method by which molecular maps of tissue samples can be created, yielding a two-dimensional representation of the expression patterns of small molecules and proteins from biologic samples. In this chapter, we review the use of MALDI MSI, its application to the characterization of the pituitary gland, and its potential applications for guiding the management of pituitary adenomas.

      PubDate: 2016-12-29T18:12:48Z
      DOI: 10.1016/bs.acr.2016.11.006
       
  • Assessing the Potential of Metal-Assisted Imaging Mass Spectrometry in
           Cancer Research
    • Authors: M. Dufresne; N.H. Patterson; N. Lauzon; P. Chaurand
      Abstract: Publication date: Available online 27 December 2016
      Source:Advances in Cancer Research
      Author(s): M. Dufresne, N.H. Patterson, N. Lauzon, P. Chaurand
      In the last decade, imaging mass spectrometry (IMS) has been the primary tool for biomolecular imaging. While it is possible to map a wide range of biomolecules using matrix-assisted laser desorption/ionization IMS ranging from high-molecular-weight proteins to small metabolites, more often than not only the most abundant easily ionisable species are detected. To better understand complex diseases such as cancer more specific and sensitive methods need to be developed to enable the detection of lower abundance molecules but also molecules that have yet to be imaged by IMS. In recent years, a big shift has occurred in the imaging community from developing wide reaching methods to developing targeted ones which increases sensitivity through the use of more specific sample preparations. This has been primarily marked by the advent of solvent-free matrix deposition methods for polar lipids, chemical derivatization for hormones and metabolites, and the use of alternative ionization agents for neutral lipids. In this chapter, we discuss two of the latest sample preparations which exploit the use of alternative ionization agents to enable the detection of certain classes of neutral lipids along with free fatty acids by high-sensitivity IMS as demonstrated within our lab.

      PubDate: 2016-12-29T18:12:48Z
      DOI: 10.1016/bs.acr.2016.11.003
       
  • The Importance of Histology and Pathology in Mass Spectrometry Imaging
    • Authors: K. Schwamborn
      Abstract: Publication date: Available online 21 December 2016
      Source:Advances in Cancer Research
      Author(s): K. Schwamborn
      Mass spectrometry imaging (MSI) has become a valuable tool in cancer research. Even more, due to its capability to directly link molecular changes with histology, it holds the prospect to revolutionize tissue-based diagnostics. In order to learn to walk before running, however, information obtained through classical histology should not be neglected but rather used to its full capacity and integrated with mass spectrometry data to lead to a superior molecular histology synthesis. In order to achieve this, pathomorphological analyses have to be integrated into MSI analyses right from the beginning to avoid errors and pitfalls of MSI application possibly leading to incorrect or imprecise study outcomes. Such errors can be caused by different sample or tissue inherent factors or through factors in sample preparation. Future studies should, therefore, aim for a comprehensive incorporation of histology and pathology characteristics to ensure the generation of high-quality data in MSI to exploit its full capacity in tissue-based basic and translational research.

      PubDate: 2016-12-22T16:20:49Z
      DOI: 10.1016/bs.acr.2016.11.001
       
  • The Importance of Histology and Pathology in Mass Spectrometry Imaging
    • Authors: K. Schwamborn
      Abstract: Publication date: Available online 21 December 2016
      Source:Advances in Cancer Research
      Author(s): K. Schwamborn
      Mass spectrometry imaging (MSI) has become a valuable tool in cancer research. Even more, due to its capability to directly link molecular changes with histology, it holds the prospect to revolutionize tissue-based diagnostics. In order to learn to walk before running, however, information obtained through classical histology should not be neglected but rather used to its full capacity and integrated with mass spectrometry data to lead to a superior molecular histology synthesis. In order to achieve this, pathomorphological analyses have to be integrated into MSI analyses right from the beginning to avoid errors and pitfalls of MSI application possibly leading to incorrect or imprecise study outcomes. Such errors can be caused by different sample or tissue inherent factors or through factors in sample preparation. Future studies should, therefore, aim for a comprehensive incorporation of histology and pathology characteristics to ensure the generation of high-quality data in MSI to exploit its full capacity in tissue-based basic and translational research.

      PubDate: 2016-12-22T16:20:49Z
      DOI: 10.1016/bs.acr.2016.11.001
       
  • MALDI Mass Spectrometry Imaging of N-Linked Glycans in Cancer Tissues
    • Authors: R.R. Drake; T.W. Powers; E.E. Jones; E. Bruner; A.S. Mehta; P.M. Angel
      Abstract: Publication date: Available online 20 December 2016
      Source:Advances in Cancer Research
      Author(s): R.R. Drake, T.W. Powers, E.E. Jones, E. Bruner, A.S. Mehta, P.M. Angel
      Glycosylated proteins account for a majority of the posttranslation modifications of cell surface, secreted, and circulating proteins. Within the tumor microenvironment, the presence of immune cells, extracellular matrix proteins, cell surface receptors, and interactions between stroma and tumor cells are all processes mediated by glycan binding and recognition reactions. Changes in glycosylation during tumorigenesis are well documented to occur and affect all of these associated adhesion and regulatory functions. A MALDI imaging mass spectrometry (MALDI-IMS) workflow for profiling N-linked glycan distributions in fresh/frozen tissues and formalin-fixed paraffin-embedded tissues has recently been developed. The key to the approach is the application of a molecular coating of peptide-N-glycosidase to tissues, an enzyme that cleaves asparagine-linked glycans from their protein carrier. The released N-linked glycans can then be analyzed by MALDI-IMS directly on tissue. Generally 40 or more individual glycan structures are routinely detected, and when combined with histopathology localizations, tumor-specific glycans are readily grouped relative to nontumor regions and other structural features. This technique is a recent development and new approach in glycobiology and mass spectrometry imaging research methodology; thus, potential uses such as tumor-specific glycan biomarker panels and other applications are discussed.

      PubDate: 2016-12-22T16:20:49Z
      DOI: 10.1016/bs.acr.2016.11.009
       
  • MALDI Mass Spectrometry Imaging of N-Linked Glycans in Cancer Tissues
    • Authors: R.R. Drake; T.W. Powers; E.E. Jones; E. Bruner; A.S. Mehta; P.M. Angel
      Abstract: Publication date: Available online 20 December 2016
      Source:Advances in Cancer Research
      Author(s): R.R. Drake, T.W. Powers, E.E. Jones, E. Bruner, A.S. Mehta, P.M. Angel
      Glycosylated proteins account for a majority of the posttranslation modifications of cell surface, secreted, and circulating proteins. Within the tumor microenvironment, the presence of immune cells, extracellular matrix proteins, cell surface receptors, and interactions between stroma and tumor cells are all processes mediated by glycan binding and recognition reactions. Changes in glycosylation during tumorigenesis are well documented to occur and affect all of these associated adhesion and regulatory functions. A MALDI imaging mass spectrometry (MALDI-IMS) workflow for profiling N-linked glycan distributions in fresh/frozen tissues and formalin-fixed paraffin-embedded tissues has recently been developed. The key to the approach is the application of a molecular coating of peptide-N-glycosidase to tissues, an enzyme that cleaves asparagine-linked glycans from their protein carrier. The released N-linked glycans can then be analyzed by MALDI-IMS directly on tissue. Generally 40 or more individual glycan structures are routinely detected, and when combined with histopathology localizations, tumor-specific glycans are readily grouped relative to nontumor regions and other structural features. This technique is a recent development and new approach in glycobiology and mass spectrometry imaging research methodology; thus, potential uses such as tumor-specific glycan biomarker panels and other applications are discussed.

      PubDate: 2016-12-22T16:20:49Z
      DOI: 10.1016/bs.acr.2016.11.009
       
  • Mass Spectrometry Imaging for the Investigation of Intratumor
           Heterogeneity
    • Authors: B. Balluff; M. Hanselmann; R.M.A. Heeren
      Abstract: Publication date: Available online 20 December 2016
      Source:Advances in Cancer Research
      Author(s): B. Balluff, M. Hanselmann, R.M.A. Heeren
      One of the big clinical challenges in the treatment of cancer is the different behavior of cancer patients under guideline therapy. An important determinant for this phenomenon has been identified as inter- and intratumor heterogeneity. While intertumor heterogeneity refers to the differences in cancer characteristics between patients, intratumor heterogeneity refers to the clonal and nongenetic molecular diversity within a patient. The deciphering of intratumor heterogeneity is recognized as key to the development of novel therapeutics or treatment regimens. The investigation of intratumor heterogeneity is challenging since it requires an untargeted molecular analysis technique that accounts for the spatial and temporal dynamics of the tumor. So far, next-generation sequencing has contributed most to the understanding of clonal evolution within a cancer patient. However, it falls short in accounting for the spatial dimension. Mass spectrometry imaging (MSI) is a powerful tool for the untargeted but spatially resolved molecular analysis of biological tissues such as solid tumors. As it provides multidimensional datasets by the parallel acquisition of hundreds of mass channels, multivariate data analysis methods can be applied for the automated annotation of tissues. Moreover, it integrates the histology of the sample, which enables studying the molecular information in a histopathological context. This chapter will illustrate how MSI in combination with statistical methods and histology has been used for the description and discovery of intratumor heterogeneity in different cancers. This will give evidence that MSI constitutes a unique tool for the investigation of intratumor heterogeneity, and could hence become a key technology in cancer research.

      PubDate: 2016-12-22T16:20:49Z
      DOI: 10.1016/bs.acr.2016.11.008
       
  • Mass Spectrometry Imaging for the Investigation of Intratumor
           Heterogeneity
    • Authors: B. Balluff; M. Hanselmann; R.M.A. Heeren
      Abstract: Publication date: Available online 20 December 2016
      Source:Advances in Cancer Research
      Author(s): B. Balluff, M. Hanselmann, R.M.A. Heeren
      One of the big clinical challenges in the treatment of cancer is the different behavior of cancer patients under guideline therapy. An important determinant for this phenomenon has been identified as inter- and intratumor heterogeneity. While intertumor heterogeneity refers to the differences in cancer characteristics between patients, intratumor heterogeneity refers to the clonal and nongenetic molecular diversity within a patient. The deciphering of intratumor heterogeneity is recognized as key to the development of novel therapeutics or treatment regimens. The investigation of intratumor heterogeneity is challenging since it requires an untargeted molecular analysis technique that accounts for the spatial and temporal dynamics of the tumor. So far, next-generation sequencing has contributed most to the understanding of clonal evolution within a cancer patient. However, it falls short in accounting for the spatial dimension. Mass spectrometry imaging (MSI) is a powerful tool for the untargeted but spatially resolved molecular analysis of biological tissues such as solid tumors. As it provides multidimensional datasets by the parallel acquisition of hundreds of mass channels, multivariate data analysis methods can be applied for the automated annotation of tissues. Moreover, it integrates the histology of the sample, which enables studying the molecular information in a histopathological context. This chapter will illustrate how MSI in combination with statistical methods and histology has been used for the description and discovery of intratumor heterogeneity in different cancers. This will give evidence that MSI constitutes a unique tool for the investigation of intratumor heterogeneity, and could hence become a key technology in cancer research.

      PubDate: 2016-12-22T16:20:49Z
      DOI: 10.1016/bs.acr.2016.11.008
       
  • In Situ Metabolomics in Cancer by Mass Spectrometry Imaging
    • Authors: A. Buck; M. Aichler; K. Huber; A. Walch
      Abstract: Publication date: Available online 20 December 2016
      Source:Advances in Cancer Research
      Author(s): A. Buck, M. Aichler, K. Huber, A. Walch
      Metabolomics is a rapidly evolving and a promising research field with the expectation to improve diagnosis, therapeutic treatment prediction, and prognosis of particular diseases. Among all techniques used to assess the metabolome in biological systems, mass spectrometry imaging is the method of choice to qualitatively and quantitatively analyze metabolite distribution in tissues with a high spatial resolution, thus providing molecular data in relation to cancer histopathology. The technique is ideally suited to study tissues molecular content and is able to provide molecular biomarkers or specific mass signatures which can be used in classification or the prognostic evaluation of tumors. Recently, it was shown that FFPE tissue samples are also suitable for metabolic analyses. This progress in methodology allows access to a highly valuable resource of tissues believed to widen and strengthen metabolic discovery-driven studies.

      PubDate: 2016-12-22T16:20:49Z
      DOI: 10.1016/bs.acr.2016.11.004
       
  • In Situ Metabolomics in Cancer by Mass Spectrometry Imaging
    • Authors: A. Buck; M. Aichler; K. Huber; A. Walch
      Abstract: Publication date: Available online 20 December 2016
      Source:Advances in Cancer Research
      Author(s): A. Buck, M. Aichler, K. Huber, A. Walch
      Metabolomics is a rapidly evolving and a promising research field with the expectation to improve diagnosis, therapeutic treatment prediction, and prognosis of particular diseases. Among all techniques used to assess the metabolome in biological systems, mass spectrometry imaging is the method of choice to qualitatively and quantitatively analyze metabolite distribution in tissues with a high spatial resolution, thus providing molecular data in relation to cancer histopathology. The technique is ideally suited to study tissues molecular content and is able to provide molecular biomarkers or specific mass signatures which can be used in classification or the prognostic evaluation of tumors. Recently, it was shown that FFPE tissue samples are also suitable for metabolic analyses. This progress in methodology allows access to a highly valuable resource of tissues believed to widen and strengthen metabolic discovery-driven studies.

      PubDate: 2016-12-22T16:20:49Z
      DOI: 10.1016/bs.acr.2016.11.004
       
  • Social Networks Across Common Cancer Types: The Evidence, Gaps, and Areas
           of Potential Impact
    • Authors: L.J. Rice; C.H. Halbert
      Abstract: Publication date: Available online 29 November 2016
      Source:Advances in Cancer Research
      Author(s): L.J. Rice, C.H. Halbert
      Although the association between social context and health has been demonstrated previously, much less is known about network interactions by gender, race/ethnicity, and sociodemographic characteristics. Given the variability in cancer outcomes among groups, research on these relationships may have important implications for addressing cancer health disparities. We examined the literature on social networks and cancer across the cancer continuum among adults. Relevant studies (N =16) were identified using two common databases: PubMed and Google Scholar. Most studies used a prospective cohort study design (n =9), included women only (n =11), and were located in the United States (n =14). Seventy-five percent of the studies reviewed used a validated scale or validated items to measure social networks (n =12). Only one study examined social network differences by race, 57.1% (n =8) focused on breast cancer alone, 14.3% (n =2) explored colorectal cancer or multiple cancers simultaneously, and 7.1% (n =1) only prostate cancer. More than half of the studies included multiple ethnicities in the sample, while one study included only low-income subjects. Despite findings of associations between social networks and cancer survival, risk, and screening, none of the studies utilized social networks as a mechanism for reducing health disparities; however, such an approach has been utilized for infectious disease control. Social networks and the support provided within these networks have important implications for health behaviors and ultimately cancer disparities. This review serves as the first step toward dialog on social networks as a missing component in the social determinants of cancer disparities literature that could move the needle upstream to target adverse cancer outcomes among vulnerable populations.

      PubDate: 2016-11-30T08:51:24Z
      DOI: 10.1016/bs.acr.2016.09.002
       
  • Disparities in Cervical Cancer Incidence and Mortality: Can Epigenetics
           Contribute to Eliminating Disparities
    • Authors: R.L. Maguire; A.C. Vidal; S.K. Murphy; C. Hoyo
      Abstract: Publication date: Available online 9 November 2016
      Source:Advances in Cancer Research
      Author(s): R.L. Maguire, A.C. Vidal, S.K. Murphy, C. Hoyo
      Screening for uterine cervical intraepithelial neoplasia (CIN) followed by aggressive treatment has reduced invasive cervical cancer (ICC) incidence and mortality. However, ICC cases and carcinoma in situ (CIS) continue to be diagnosed annually in the United States, with minorities bearing the brunt of this burden. Because ICC peak incidence and mortality are 10–15 years earlier than other solid cancers, the number of potential years of life lost to this cancer is substantial. Screening for early signs of CIN is still the mainstay of many cervical cancer control programs. However, the accuracy of existing screening tests remains suboptimal. Changes in epigenetic patterns that occur as a result of human papillomavirus infection contribute to CIN progression to cancer, and can be harnessed to improve existing screening tests. However, this requires a concerted effort to identify the epigenomic landscape that is reliably altered by HPV infection specific to ICC, distinct from transient changes.

      PubDate: 2016-11-10T02:05:55Z
      DOI: 10.1016/bs.acr.2016.09.001
       
  • Disparities in Obesity, Physical Activity Rates, and Breast Cancer
           Survival
    • Authors: M.E. Ford; G. Magwood; E.T. Brown; K. Cannady; M. Gregoski; K.D. Knight; L.L. Peterson; R. Kramer; A. Evans-Knowell; D.P. Turner
      Abstract: Publication date: Available online 31 October 2016
      Source:Advances in Cancer Research
      Author(s): M.E. Ford, G. Magwood, E.T. Brown, K. Cannady, M. Gregoski, K.D. Knight, L.L. Peterson, R. Kramer, A. Evans-Knowell, D.P. Turner
      The significantly higher breast cancer (BCa) mortality rates of African-American (AA) women compared to non-Hispanic (NHW) white women constitute a major US health disparity. Investigations have primarily focused on biological differences in tumors to explain more aggressive forms of BCa in AA women. The biology of tumors cannot be modified, yet lifestyle changes can mitigate their progression and recurrence. AA communities have higher percentages of obesity than NHWs and exhibit inefficient access to care, low socioeconomic status, and reduced education levels. Such factors are associated with limited healthy food options and sedentary activity. AA women have the highest prevalence of obesity than any other racial/ethnic/gender group in the United States. The social ecological model (SEM) is a conceptual framework on which interventions could be developed to reduce obesity. The SEM includes intrapersonal factors, interpersonal factors, organizational relationships, and community/institutional policies that are more effective in behavior modification than isolation from the participants’ environmental context. Implementation of SEM-based interventions in AA communities could positively modify lifestyle behaviors, which could also serve as a powerful tool in reducing risk of BCa, BCa progression, and BCa recurrence in populations of AA women.

      PubDate: 2016-11-03T00:57:53Z
      DOI: 10.1016/bs.acr.2016.08.002
       
  • The Role of Advanced Glycation End-Products in Cancer Disparity
    • Authors: D.P. Turner
      Abstract: Publication date: Available online 12 October 2016
      Source:Advances in Cancer Research
      Author(s): D.P. Turner
      While the socioeconomic and environmental factors associated with cancer disparity have been well documented, the contribution of biological factors is an emerging field of research. Established disparity factors such as low income, poor diet, drinking alcohol, smoking, and a sedentary lifestyle may have molecular effects on the inherent biological makeup of the tumor itself, possibly altering cell signaling events and gene expression profiles to profoundly alter tumor development and progression. Our understanding of the molecular and biological consequences of poor lifestyle is lacking, but such information may significantly change how we approach goals to reduce cancer incidence and mortality rates within minority populations. In this review, we will summarize the biological, socioeconomic, and environmental associations between a group of reactive metabolites known as advanced glycation end-products (AGEs) and cancer health disparity. Due to their links with lifestyle and the activation of disease-associated pathways, AGEs may represent both a biological consequence and a bio-behavioral indicator of poor lifestyle which may be targeted within specific populations to reduce disparities in cancer incidence and mortality.

      PubDate: 2016-10-13T14:09:00Z
      DOI: 10.1016/bs.acr.2016.08.001
       
  • Applying a Conceptual Framework to Maximize the Participation of Diverse
           Populations in Cancer Clinical Trials
    • Authors: A. Napoles; E. Cook; T. Ginossar; K.D. Knight; M.E. Ford
      Abstract: Publication date: Available online 5 October 2016
      Source:Advances in Cancer Research
      Author(s): A. Napoles, E. Cook, T. Ginossar, K.D. Knight, M.E. Ford
      The underrepresentation of ethnically diverse populations in cancer clinical trials results in the inequitable distribution of the risks and benefits of this research. Using a case study approach, we apply a conceptual framework of factors associated with the participation of diverse population groups in cancer clinical trials developed by Dr. Jean Ford and colleagues to increase understanding of the specific strategies, and barriers and promoters addressed by these strategies, that resulted in marked success in accrual of racially and ethnically diverse populations in cancer clinical research. Results indicate that the studies presented were able to successfully engage minority participants due to the creation and implementation of multilevel, multifaceted strategies that included: culturally and linguistically appropriate outreach, education, and research studies that were accessible in local communities; infrastructure to support engagement of key stakeholders, clinicians, and organizations serving minority communities; testimonials by ethnically diverse cancer survivors; availability of medical interpretation services; and providing infrastructure that facilitated the engagement in clinical research of clinicians who care for minority patient populations. These strategic efforts were effective in addressing limited awareness of trials, lack of opportunities to participate, and acceptance of engagement in cancer clinical trials. Careful attention to the context and population characteristics in which cancer clinical trials are conducted will be necessary to address disparities in research participation and cancer outcomes. These studies illustrate that progress on minority accrual into clinical research requires intentional efforts to overcome barriers at all three stages of the accrual process: awareness, opportunity, and acceptance of participation.

      PubDate: 2016-10-13T14:09:00Z
      DOI: 10.1016/bs.acr.2016.08.004
       
  • MicroRNAs and Their Impact on Breast Cancer, the Tumor Microenvironment,
           and Disparities
    • Authors: A. Evans-Knowell; A.C. LaRue; V.J. Findlay
      Abstract: Publication date: Available online 26 September 2016
      Source:Advances in Cancer Research
      Author(s): A. Evans-Knowell, A.C. LaRue, V.J. Findlay
      Breast cancer is a worldwide health issue as it represents the leading cause of cancer in women and the second-leading cause of cancer-related mortality in women, with an increasing incidence. Nothing speaks more clearly to the shocking breast cancer health disparities than the fact that African American (AA) women are as likely to get breast cancer as Caucasian American (CA) women, yet have a higher breast cancer death rate. It is becoming increasingly apparent that racial disparity in cancer exists due to molecular differences in tumor biology as well as, or in addition to, socioeconomic and standard of care issues (Albain, Unger, Crowley, Coltman, & Hershman, 2009). A greater understanding of the risk factors and biological links associated with breast cancer, will significantly impact AA communities due to the higher deaths associated with this disease in this population. microRNAs are small noncoding RNA molecules that were recently discovered as major players in the regulation of many diseases including cancer. Although, there are many studies that have investigated the role of miRNAs in breast cancer, few have investigated their role if any in breast cancer disparities. This review serves to summarize the current published literature that is involved in the study of microRNAs and their impact on breast cancer disparities.

      PubDate: 2016-10-13T14:09:00Z
      DOI: 10.1016/bs.acr.2016.08.003
       
  • Chapter One Detecting Tumor Metastases
    • Authors: M.E. Menezes; S.K. Das Minn Emdad X.-Y. Wang Sarkar M.G.
      Abstract: Publication date: 2016
      Source:Advances in Cancer Research, Volume 132
      Author(s): M.E. Menezes, S.K. Das, I. Minn, L. Emdad, X.-Y. Wang, D. Sarkar, M.G. Pomper, P.B. Fisher
      Metastasis is the complex process by which primary tumor cells migrate and establish secondary tumors in an adjacent or distant location in the body. Early detection of metastatic disease and effective therapeutic options for targeting these detected metastases remain impediments to effectively treating patients with advanced cancers. If metastatic lesions are identified early, patients might maximally benefit from effective early therapeutic interventions. Further, monitoring patients whose primary tumors are effectively treated for potential metastatic disease onset is also highly valuable. Finally, patients with metastatic disease can be monitored for efficacy of specific therapeutic interventions through effective metastatic detection techniques. Thus, being able to detect and visualize metastatic lesions is key and provides potential to greatly improve overall patient outcomes. In order to achieve these objectives, researchers have endeavored to mechanistically define the steps involved in the metastatic process as well as ways to effectively detect metastatic progression. We presently overview various preclinical and clinical in vitro and in vivo assays developed to more efficiently detect tumor metastases, which provides the foundation for developing more effective therapies for this invariably fatal component of the cancerous process.

      PubDate: 2016-10-13T14:09:00Z
       
  • Chapter Three Defining the Influence of Germline Variation on Metastasis
           Using Systems Genetics Approaches
    • Authors: Lee N.P.S.; Crawford
      Abstract: Publication date: 2016
      Source:Advances in Cancer Research, Volume 132
      Author(s): M. Lee, N.P.S. Crawford
      Cancer is estimated to be responsible for 8 million deaths worldwide and over half a million deaths every year in the United States. The majority of cancer-related deaths in solid tumors is directly associated with the effects of metastasis. While the influence of germline factors on cancer risk and development has long been recognized, the contribution of hereditary variation to tumor progression and metastasis has only gained acceptance more recently. A variety of approaches have been used to define how hereditary variation influences tumor progression and metastasis. One approach that garnered much early attention was epidemiological studies of cohorts of cancer patients, which demonstrated that specific loci within the human genome are associated with a differential propensity for aggressive tumor development. However, a powerful, and somewhat underutilized approach has been the use of systems genetics approaches in transgenic mouse models of human cancer. Such approaches are typically multifaceted, and involve integration of multiple lines of evidence derived, for example, from genetic and transcriptomic screens of genetically diverse mouse models of cancer, coupled with bioinformatics analysis of human cancer datasets, and functional analysis of candidate genes. These methodologies have allowed for the identification of multiple hereditary metastasis susceptibility genes, with wide-ranging cellular functions including regulation of gene transcription, cell proliferation, and cell–cell adhesion. In this chapter, we review how each of these approaches have facilitated the identification of these hereditary metastasis modifiers, the molecular functions of these metastasis-associated genes, and the implications of these findings upon patient survival.

      PubDate: 2016-10-13T14:09:00Z
       
  • Chapter Six MicroRNA and Metastasis
    • Abstract: Publication date: 2016
      Source:Advances in Cancer Research, Volume 132
      Author(s): L. Ma
      Noncoding RNAs are important regulatory molecules of cellular processes. MicroRNAs (miRNAs) are small noncoding RNAs that bind to complementary sequences in the 3′ untranslated region of target mRNAs, leading to degradation of the target mRNAs and/or inhibition of their translation. Some miRNAs are essential for normal animal development; however, many other miRNAs are dispensable for development but play a critical role in pathological conditions, including tumorigenesis and metastasis. miRNA genes often reside at fragile chromosome sites and are deregulated in cancer. Some miRNAs function as oncogenes or tumor suppressors, collectively termed “oncomirs.” Specific metastasis-regulating miRNAs, collectively termed “metastamirs,” govern molecular processes and pathways in malignant progression in either a tumor cell-autonomous or a cell-nonautonomous manner. Recently, exosome-transferred miRNAs have emerged as mediators of the tumor-stroma cross talk. In this chapter, we focus on the functions, mechanisms of action, and therapeutic potential of miRNAs, particularly oncomirs and metastamirs.

      PubDate: 2016-10-13T14:09:00Z
       
  • Chapter Seven Plasticity of Cancer Cell Invasion—Mechanisms and
           Implications for Therapy
    • Authors: Boekhorst Friedl
      Abstract: Publication date: 2016
      Source:Advances in Cancer Research, Volume 132
      Author(s): V. te Boekhorst, P. Friedl
      Cancer cell migration is a plastic and adaptive process integrating cytoskeletal dynamics, cell–extracellular matrix and cell–cell adhesion, as well as tissue remodeling. In response to molecular and physical microenvironmental cues during metastatic dissemination, cancer cells exploit a versatile repertoire of invasion and dissemination strategies, including collective and single-cell migration programs. This diversity generates molecular and physical heterogeneity of migration mechanisms and metastatic routes, and provides a basis for adaptation in response to microenvironmental and therapeutic challenge. We here summarize how cytoskeletal dynamics, protease systems, cell–matrix and cell–cell adhesion pathways control cancer cell invasion programs, and how reciprocal interaction of tumor cells with the microenvironment contributes to plasticity of invasion and dissemination strategies. We discuss the potential and future implications of predicted “antimigration” therapies that target cytoskeletal dynamics, adhesion, and protease systems to interfere with metastatic dissemination, and the options for integrating antimigration therapy into the spectrum of targeted molecular therapies.

      PubDate: 2016-10-13T14:09:00Z
       
  • Chapter Eight Cytokine Regulation of Metastasis and Tumorigenicity
    • Authors: Yao Brummer; Acevedo Cheng
      Abstract: Publication date: 2016
      Source:Advances in Cancer Research, Volume 132
      Author(s): M. Yao, G. Brummer, D. Acevedo, N. Cheng
      The human body combats infection and promotes wound healing through the remarkable process of inflammation. Inflammation is characterized by the recruitment of stromal cell activity including recruitment of immune cells and induction of angiogenesis. These cellular processes are regulated by a class of soluble molecules called cytokines. Based on function, cell target, and structure, cytokines are subdivided into several classes including: interleukins, chemokines, and lymphokines. While cytokines regulate normal physiological processes, chronic deregulation of cytokine expression and activity contributes to cancer in many ways. Gene polymorphisms of all types of cytokines are associated with risk of disease development. Deregulation RNA and protein expression of interleukins, chemokines, and lymphokines have been detected in many solid tumors and hematopoetic malignancies, correlating with poor patient prognosis. The current body of literature suggests that in some tumor types, interleukins and chemokines work against the human body by signaling to cancer cells and remodeling the local microenvironment to support the growth, survival, and invasion of primary tumors and enhance metastatic colonization. Some lymphokines are downregulated to suppress tumor progression by enhancing cytotoxic T cell activity and inhibiting tumor cell survival. In this review, we will describe the structure/function of several cytokine families and review our current understanding on the roles and mechanisms of cytokines in tumor progression. In addition, we will also discuss strategies for exploiting the expression and activity of cytokines in therapeutic intervention.

      PubDate: 2016-10-13T14:09:00Z
       
  • Breast Cancer Metastasis Suppressor 1 (BRMS1): Robust Biological and
           Pathological Data, But Still Enigmatic Mechanism of Action
    • Authors: D.R. Welch; C.A. Manton D.R. Hurst
      Abstract: Publication date: Available online 17 June 2016
      Source:Advances in Cancer Research
      Author(s): D.R. Welch, C.A. Manton, D.R. Hurst
      Metastasis requires coordinated expression of multiple genetic cassettes, often via epigenetic regulation of gene transcription. BRMS1 blocks metastasis, but not orthotopic tumor growth in multiple tumor types, presumably via SIN3 chromatin remodeling complexes. Although there is an abundance of strong data supporting BRMS1 as a metastasis suppressor, the mechanistic data directly connecting molecular pathways with inhibition of particular steps in metastasis are not well defined. In this review, the data for BRMS1-mediated metastasis suppression in multiple tumor types are discussed along with the steps in metastasis that are inhibited.

      PubDate: 2016-06-18T18:39:50Z
       
  • Immune Regulation of the Metastatic Process: Implications for Therapy
    • Authors: Mingo Pulido; Ruffell
      Abstract: Publication date: Available online 17 June 2016
      Source:Advances in Cancer Research
      Author(s): A. de Mingo Pulido, B. Ruffell
      Metastatic disease is the major cause of fatalities in cancer patients, but few therapies are designed to target the metastatic process. Cancer cells must perform a number of steps to successfully establish metastatic foci, including local invasion, intravasation, survival, extravasation, and growth in ectopic tissue. Due to the nonrandom distribution of metastasis, it has long been recognized that the tissue microenvironment must be an important determinant of colonization. More recently it has been established in animal models that immune cells regulate the metastatic process, including a dominant role for monocytes and macrophages, and emerging roles for neutrophils and various lymphocyte populations. While most research has focused on the early dissemination process, patients usually present clinically with disseminated, if not macroscopic, disease. Identifying pathways by which immune cells regulate growth and therapeutic resistance within metastatic sites is therefore key to the development of pharmacological agents that will significantly extend patient survival.

      PubDate: 2016-06-18T18:39:50Z
       
  • AEG-1/MTDH/LYRIC: A Promiscuous Protein Partner Critical in Cancer,
           Obesity, and CNS Diseases
    • Authors: Emdad S.K.; Das Kegelman D.-c. Kang S.-G. Lee Sarkar P.B.
      Abstract: Publication date: Available online 17 June 2016
      Source:Advances in Cancer Research
      Author(s): L. Emdad, S.K. Das, B. Hu, T. Kegelman, D.-c. Kang, S.-G. Lee, D. Sarkar, P.B. Fisher
      Since its original discovery in 2002, AEG-1/MTDH/LYRIC has emerged as a primary regulator of several diseases including cancer, inflammatory diseases, and neurodegenerative diseases. AEG-1/MTDH/LYRIC has emerged as a key contributory molecule in almost every aspect of cancer progression, including uncontrolled cell growth, evasion of apoptosis, increased cell migration and invasion, angiogenesis, chemoresistance, and metastasis. Additionally, recent studies highlight a seminal role of AEG-1/MTDH/LYRIC in neurodegenerative diseases and obesity. By interacting with multiple protein partners, AEG-1/MTDH/LYRIC plays multifaceted roles in the pathogenesis of a wide variety of diseases. This review discusses the current state of understanding of AEG-1/MTDH/LYRIC regulation and function in cancer and other diseases with a focus on its association/interaction with several pivotal protein partners.

      PubDate: 2016-06-18T18:39:50Z
       
  • H3K27 Methylation: A Focal Point of Epigenetic Deregulation in Cancer
    • Authors: J.N. Nichol; Ezponda J.D. Licht W.H. Miller
      Abstract: Publication date: Available online 17 June 2016
      Source:Advances in Cancer Research
      Author(s): J.N. Nichol, D. Dupéré-Richer, T. Ezponda, J.D. Licht, W.H. Miller
      Epigenetics, the modification of chromatin without changing the DNA sequence itself, determines whether a gene is expressed, and how much of a gene is expressed. Methylation of lysine 27 on histone 3 (H3K27me), a modification usually associated with gene repression, has established roles in regulating the expression of genes involved in lineage commitment and differentiation. Not surprisingly, alterations in the homeostasis of this critical mark have emerged as a recurrent theme in the pathogenesis of many cancers. Perturbations in the distribution or levels of H3K27me occur due to deregulation at all levels of the process, either by mutation in the histone itself, or changes in the activity of the writers, erasers, or readers of this mark. Additionally, as no single histone mark alone determines the overall transcriptional readiness of a chromatin region, deregulation of other chromatin marks can also have dramatic consequences. Finally, the significance of mutations altering H3K27me is highlighted by the poor clinical outcome of patients whose tumors harbor such lesions. Current therapeutic approaches targeting aberrant H3K27 methylation remain to be proven useful in the clinic. Understanding the biological consequences and gene expression pathways affected by aberrant H3K27 methylation may lead to identification of new therapeutic targets and strategies.

      PubDate: 2016-06-18T18:39:50Z
       
  • Chapter Four PAKs in Human Cancer Progression
    • Authors: Kumar D.-Q.
      Abstract: Publication date: 2016
      Source:Advances in Cancer Research, Volume 130
      Author(s): R. Kumar, D.-Q. Li
      Since the initial recognition of a mechanistic role of p21-activated kinase 1 (PAK1) in breast cancer invasion, PAK1 has emerged as one of the widely overexpressed or hyperactivated kinases in human cancer at-large, allowing the PAK family to make in-roads in cancer biology, tumorigenesis, and cancer therapeutics. Much of our current understanding of the PAK family in cancer progression relates to a central role of the PAK family in the integration of cancer-promoting signals from cell membrane receptors as well as function as a key nexus-modifier of complex, cytoplasmic signaling network. Another core aspect of PAK signaling that highlights its importance in cancer progression is through PAK's central role in the cross talk with signaling and interacting proteins, as well as PAK's position as a key player in the phosphorylation of effector substrates to engage downstream components that ultimately leads to the development cancerous phenotypes. Here we provide a comprehensive review of the recent advances in PAK cancer research and its downstream substrates in the context of invasion, nuclear signaling and localization, gene expression, and DNA damage response. We discuss how a deeper understanding of PAK1’s pathobiology over the years has widened research interest to the PAK family and human cancer, and positioning the PAK family as a promising cancer therapeutic target either alone or in combination with other therapies. With many landmark findings and leaps in the progress of PAK cancer research since the infancy of this field nearly 20 years ago, we also discuss postulated advances in the coming decade as the PAK family continues to shape the future of oncobiology.

      PubDate: 2016-04-27T02:25:53Z
       
  • Chapter Five Sirtuins and the Estrogen Receptor as Regulators of the
           Mammalian Mitochondrial UPR in Cancer and Aging
    • Authors: Germain
      Abstract: Publication date: 2016
      Source:Advances in Cancer Research, Volume 130
      Author(s): D. Germain
      By being both the source of ATP and the mediator of apoptosis, the mitochondria are key regulators of cellular life and death. Not surprisingly alterations in the biology of the mitochondria have implications in a wide array of diseases including cancer and age-related diseases such as neurodegeneration. To protect the mitochondria against damage the mitochondrial unfolded protein response (UPRmt) orchestrates several pathways, including the protein quality controls, the antioxidant machinery, oxidative phosphorylation, mitophagy, and mitochondrial biogenesis. While several reports have implicated an array of transcription factors in the UPRmt, most of the focus has been on studies of Caenorhabditis elegans, which led to the identification of ATFS-1, for which the mammalian homolog remains unknown. Meanwhile, there are studies which link the UPRmt to sirtuins and transcription factors of the Foxo family in both C. elegans and mammalian cells but those have been largely overlooked. This review aims at emphasizing the potential importance of these studies by building on the large body of literature supporting the key role of the sirtuins in the maintenance of the integrity of the mitochondria in both cancer and aging. Further, the estrogen receptor alpha (ERα) and beta (ERβ) are known to confer protection against mitochondrial stress, and at least ERα has been linked to the UPRmt. Considering the difference in gender longevity, this chapter also includes a discussion of the link between the ERα and ERβ and the mitochondria in cancer and aging.

      PubDate: 2016-04-27T02:25:53Z
       
  • Small-Molecule Targeting of BET Proteins in Cancer
    • Authors: C.A. French
      Pages: 21 - 58
      Abstract: Publication date: Available online 31 May 2016
      Source:Advances in Cancer Research
      Author(s): C.A. French
      BET proteins have recently become recognized for their role in a broad range of cancers and are defined by the presence of two acetyl-histone reading bromodomains and an ET domain. This family of proteins includes BRD2, BRD3, BRD4, and BRDT. BRD4 is the most-studied BET protein in cancer, and normally serves as an epigenetic reader that links active chromatin marks to transcriptional elongation through activation of RNA polymerase II. The role of BRD3 and BRD4 first became known in cancer as mutant oncoproteins fused to the p300-recruiting NUT protein in a rare aggressive subtype of squamous cell cancer known as NUT midline carcinoma (NMC). BET inhibitors are acetyl-histone mimetics that specifically bind BET bromodomains, competitively inhibiting its engagement with chromatin. The antineoplastic effects of BET inhibitors were first demonstrated in NMC and have since been shown to be effective at inhibiting the growth of many different cancers, particularly acute leukemia. BET inhibitors have also been instrumental as tool compounds that have demonstrated the key role of BRD4 in driving NMC and non-NMC cancer growth. Many clinical trials enrolling patients with hematologic and solid tumors are ongoing, with encouraging preliminary findings. BET proteins BRD2, BRD3, and BRD4 are expressed in nearly all cells of the body, so there are concerns of toxicity with BET inhibitors, as well as the development of resistance. Toxicity and resistance may be overcome by combining BET inhibitors with other targeted inhibitors, or through the use of novel BET inhibitor derivatives.

      PubDate: 2016-06-04T12:08:26Z
      DOI: 10.1016/bs.acr.2016.04.001
       
  • Role of the RB-Interacting Proteins in Stem Cell Biology
    • Authors: M. Mushtaq; H. Viñas Gaza; E.V. Kashuba
      Pages: 133 - 157
      Abstract: Publication date: Available online 17 June 2016
      Source:Advances in Cancer Research
      Author(s): M. Mushtaq, H. Viñas Gaza, E.V. Kashuba
      Human retinoblastoma gene RB1 is the first tumor suppressor gene (TSG) isolated by positional cloning in 1986. RB is extensively studied for its ability to regulate cell cycle by binding to E2F1 and inhibiting the transcriptional activity of the latter. In human embryonic stem cells (ESCs), only a minute trace of RB is found in complex with E2F1. Increased activity of RB triggers differentiation, cell cycle arrest, and cell death. On the other hand, inactivation of the entire RB family (RB1, RBL1, and RBL2) in human ESC induces G2/M arrest and cell death. These observations indicate that both loss and overactivity of RB could be lethal for the stemness of cells. A question arises why inactive RB is required for the survival and stemness of cells' To shed some light on this question, we analyzed the RB-binding proteins. In this review we have focused on 27 RB-binding partners that may have potential roles in different aspects of stem cell biology.

      PubDate: 2016-06-18T18:39:50Z
      DOI: 10.1016/bs.acr.2016.04.002
       
  • Evolving Strategies for Therapeutically Targeting Cancer Stem Cells
    • Authors: S. Talukdar; L. Emdad; S.K. Das; D. Sarkar; P.B. Fisher
      Pages: 159 - 191
      Abstract: Publication date: Available online 3 June 2016
      Source:Advances in Cancer Research
      Author(s): S. Talukdar, L. Emdad, S.K. Das, D. Sarkar, P.B. Fisher
      Cancer is a multifactor and multistep process that is affected intrinsically by the genetic and epigenetic makeup of tumor cells and extrinsically by the host microenvironment and immune system. A key component of cancer involves a unique subpopulation of highly malignant cancerous cells referred to as cancer stem cells (CSCs). CSCs are positioned at the apex of the tumor hierarchy with an ability to both self-renew and also generate non-CSC/differentiated progeny, which contribute to the majority of the tumor mass. CSCs undergo functional changes and show plasticity that is stimulated by specific microenvironmental cues and interactions in the tumor niche, which contribute to the complexity and heterogeneity of the CSC population. The prognostic value of CSCs in the clinic is evident since there are many examples in which CSCs serve as markers for poor patient prognosis. CSCs are innately resistant to many standard therapies and they display anoikis resistance, immune evasion, tumor dormancy, and field cancerization, which may result in metastasis and relapse. Many academic laboratories and biotechnology companies are currently focusing on strategies that target CSCs. Combination therapies, epigenetic modifiers, stemness inhibitors, CSC surface marker-based therapies, and immunotherapy-based CSC-targeting drugs are currently undergoing clinical trials. Potential new targets/strategies in CSC-targeted therapy include MDA-9/Syntenin (SDCBP), Patched (PTCH), epigenetic targets, noncoding RNAs, and differentiation induction. Defining ways of targeting and destroying CSCs holds potential to impact significantly on cancer therapy, including prevention of metastasis and cancer recurrence.

      PubDate: 2016-06-04T12:08:26Z
      DOI: 10.1016/bs.acr.2016.04.003
       
 
 
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