Virology & Mycology Infectious Diseases
 
   Publications A-Z
A
»Accounting & Marketing
» Addiction Research & Therapy
» Advanced Chemical Engineering
»Advances in Automobile Engineering
»Advances in Crop Science and Technology
»Advances in Dairy Research
»Advancements in Genetic Engineering
»Advances in Pharmacoepidemiology & Drug Safety
»Advances in Robotics & Automation
»Advanced Techniques in Biology & Medicine
»Advance Research in Meteorological Sciences
»Aeronautics & Aerospace Engineering
»Aging Science
»Agrotechnology
»AIDS & Clinical Research
»Alcoholism and Drug Dependence
»Allergy & Therapy
»Alternative & Integrative Medicine
»Air & Water borne Diseases
»Alzheimers Disease & Parkinsonism
»Analytical & Bioanalytical Techniques
»Anaplastology
»Anatomy & Physiology
»Ancient Diseases & Preventive Remedies
»Andrology-Open Access
»Anesthesia & Clinical Research
»Angiology: Open Access
»Antivirals & Antiretrovirals
»Anthropology
»Applied & Computational Mathematics
»Applied Mechanical Engineering
»Aquaculture Research & Development
» Arabian Journal Business and Management Review
»Architectural Engineering Technology
»Arthritis
»Arts and Social Sciences Journal
» Astrobiology & Outreach
»Astrophysics & Aerospace technology
»Autacoids
»Automatic Control of Physiological State and Function
»Autism-Open Access
  
B
»Bacteriology & Parasitology
»Bioanalysis & Biomedicine
»Bioceramics Development and Applications
»Biochemistry and Analytical Biochemistry
»Biochemistry & Pharmacology: Open Access
»Biochips & Tissue Chips
»Biodiversity & Endangered Species
»Bioenergetics: Open Access
»Bioengineering & Biomedical Science
»Bioequivalence & Bioavailability
»Biosafety & Health Education
»Biofertilizers & Biopesticides
»Biometrics & Biostatistics
»Biomimetics Biomaterials and Tissue Engineering
»Biomolecular Research & Therapeutics
» Biomusical Engineering
»Biochemistry & Physiology: Open Access
»Biological Systems- Open Access
»Biology and Medicine
»Bioprocessing & Biotechniques
»Bioremediation & Biodegradation
»Biosafety
»Biosensors & Bioelectronics
» Biosensors Journal
»Biotechnology & Biomaterials
»Bioterrorism & Biodefense
»Blood Disorders & Transfusion
»Blood & Lymph
»Bone Marrow Research
»Brain Disorders & Therapy
»Business and Economics Journal
»Business and Financial Affairs
  
C
»Cancer Science & Therapy
»Climatology & Weather forecasting
»Carcinogenesis & Mutagenesis
»Cardiovascular Diseases & Diagnosis
»Cardiovascular Pharmacology: Open Access
»Cell & Developmental Biology
»Cell Science & Therapy
»Chemical Engineering & Process Technology
»Chemical Sciences Journal
»Chemotherapy: Open Access
»Child and Adolescent Behavior
»Chromatography & Separation Techniques
»Civil & Environmental Engineering
»Civil & Legal Sciences
»Clinical & Cellular Immunology
»Clinical Case Reports
»Clinical & Experimental Cardiology
»Clinical & Experimental Dermatology Research
»Clinical & Experimental Ophthalmology
»Clinical & Experimental Pathology
»Clinical & Experimental Pharmacology
»Clinical Microbiology: Open Access
»Clinical Pharmacology & Biopharmaceutics
»Clinical Research & Bioethics
»Clinical Research on Foot & Ankle
»Clinical Toxicology
»Clinical Trials
»Clinics in Mother and Child Health
»Cloning & Transgenesis
»Community Medicine & Health Education
»Communication Disorders, Deaf Studies & Hearing Aids
»Computer Science & Systems Biology
» Current Synthetic & Systems Biology
»Cytology & Histology
D
»Data Mining in Genomics & Proteomics
»Defense Management
»Dentistry
»Depression and Anxiety
»Developing Drugs
»Diabetes & Metabolism
»Drug Designing
»Drug Metabolism & Toxicology
  
E
»Earth Science & Climatic Change
»Ecosystem & Ecography
»Endocrinology & Metabolic Syndrome
»Entomology, Ornithology & Herpetology
»Environmental & Analytical Toxicology
»Epidemiology: Open Access
»Emergency Medicine
»Ergonomics
»Electrical & Electronics
»Enzyme Engineering
»Entrepreneurship & Organization Management
  
F
»Family Medicine & Medical Science Research
»Fermentation Technology
»Fertilization: In Vitro - IVF-Worldwide
»Fisheries and Aquaculture Journal
»Fisheries & Livestock Production
»Food Processing & Technology
»Forensic Biomechanics
»Forensic Research
»Forest Research: Open Access
»Fundamentals of Renewable Energy and Applications
»Fungal Genomics & Biology
  
G
»Gastrointestinal & Digestive System
»Genetic Syndromes & Gene Therapy
»Gene Technology
»Generalized Lie Theory and Applications
»Glycobiology
»Glycomics & Lipidomics
»Gynecology& Obstetrics
»General Medicine
»General Practice
»Geography & Natural Disasters
»Geology & Geosciences
»Geophysics & Remote Sensing
»Gerontology & Geriatric Research
»Global Economics
»Global Journal of Technology and Optimization
  
H
»Hair : Therapy & Transplantation
»Hematology & Thromboembolic Diseases
»Health Care : Current Reviews
»Health & Medical Informatics
»Hereditary Genetics
»Homeopathy & Ayurvedic Medicine
»Horticulture
»Hotel & Business Management
»Human Genetics & Embryology
»Hydrology: Current Research
»Hypertension- Open Access
  
I
»Industrial Engineering & Management
»Irrigation and Drainage Systems Engineering
»Infectious Diseases and Therapy
»Information Technology & Software Engineering
»Intellectual Property Rights: Open Access
»Integrative Oncology
»Internal Medicine
»International Journal of Accounting Research
»International Journal of Advanced Innovations, Thoughts & Ideas
»International Journal of Biomedical Data Mining
»International Journal of Economics and Management Science
»International Journal of Sensor Networks and Data Communications
»International Journal of Swarm Intelligence and Evolutionary Computation
»International Journal of waste resources
»International Journal of Genomic Medicine
»International Journal of Physical Medicine & Rehabilitation
»Innovative Energy Policies
»Immunome Research
  
J
»JBR Journal of Interdisciplinary Medicine and Dental Science
»JBR Journal of Clinical Diagnosis and Research
»JBR Journal of Young Scientist
  
L
»Liver
» Leukemia
» Lovotics
  
M
»Marine Science: Research & Development
»Malaria Chemotherapy, Control & Elimination
»Mass Communication & Journalism
»Material Sciences & Engineering
»Medicinal Chemistry
»Medicinal & Aromatic Plants
»Medical Diagnostic Methods
»Medical Microbiology & Diagnosis
»Medical & Surgical Urology
»Membrane Science & Technology
»Metabolic Syndrome
»Metabolomics:Open Access
»Microbial & Biochemical Technology
»Modern Chemistry & Applications
»Molecular Biology
»Molecular Biomarkers & Diagnosis
»Molecular and Genetic Medicine
»Molecular Imaging & Dynamics
»Molecular Pharmaceutics & Organic Process Research
»Mycobacterial Diseases
N
»Natural Products Chemistry & Research
»Nanomedicine & Biotherapeutic Discovery
»Nanomedicine & Nanotechnology
»Neonatal Biology
»Nephrology & Therapeutics
»Neurology & Neurophysiology
»Neuroinfectious Diseases
»Neurological Disorders
»Novel Physiotherapies
»Nuclear Medicine & Radiation Therapy
»Nutrition & Food Sciences
»Nutritional Disorders & Therapy
»Nursing & Care
  
O
»Obesity & Weight Loss Therapy
»Oceanography-Open Access
»Occupational Medicine & Health Affairs
»OMICS Journal of Radiology
»Osteoporosis and Physical Activity
»Oral Health and Dental Management
»Oral Hygiene & Health
»Organic Chemistry: Current Research
»Orthopedic & Muscular System: Current Research
»Otolaryngology
  
P
»Pain & Relief
»Palliative Care & Medicine
»Pancreatic Disorders & Therapy
»Pediatrics & Therapeutics
»Petroleum & Environmental Biotechnology
»Pharmaceutica Analytica Acta
»Pharmaceutical Regulatory Affairs: Open Access
»Pharmacogenomics & Pharmacoproteomics
»Pharmacovigilance
»Physical Chemistry & Biophysics
»Physical Mathematics
»Plant Pathology & Microbiology
»Plant Biochemistry & Physiology
»Pollution Effects & Control
»political Sciences & public affairs
»Poultry, Fisheries & Wildlife Sciences
»Powder Metallurgy & Mining
»Primatology
»Primary Health Care: Open Access
»Probiotics & Health
» Phylogenetics & Evolutionary Biology
»Proteomics & Bioinformatics
»Phylogenetics & Evolutionary Biology
»Psychology & Psychotherapy
»Psychological Abnormalities in Children
»Pulmonary & Respiratory Medicine
  
R
»Reproductive System & Sexual Disorders
»Research and Development
»Review of Public Adminstration and Management
»Rheumatology: Current Research
»Rice Research: Open Access
  
S
» Single Cell Biology
»Sleep Disorders & Therapy
»Socialomics
»Sociology and Criminology-Open Access
»Sports Medicine & Doping Studies
»Spine
»Stem Cell Research & Therapy
»Steroids & Hormonal Science
»Stock & Forex Trading
»Surgery: Current Research
  
T
»Telecommunications System & Management
»Textile Science & Engineering
»Theoretical and Computational Chemistry:Open Access
»Thermodynamics & Catalysis
»Thyroid Disorders & Therapy
»Tissue Science & Engineering
»Translational Medicine
»Transplantation Technologies & Research
»Transcriptomics: Open Access
»Trauma & Treatment
»Tropical Diseases
»Tropical Medicine and Surgery
»Tourism & Hospitality
  
V
»Vaccines & Vaccination
»Vascular Medicine & surgery
»Veterinary Science & Technology
»Virology & Mycology
»Vitamins & Minerals
»Vortex Science and Technology
  
W
»Women's Health Care
  
Y
»Yoga & Physical Therapy
 
   Browse by Subjects
Clinical
» AIDS & Clinical Research
» Anesthesia & Clinical Research
» Angiology
» Cancer Science & Therapy
» Carcinogenesis & Mutagenesis
» Cell Science & Therapy
» Chemotherapy
» Child & Adolescent Behavior
» Clinical & Cellular Immunology
» Clinical Case Reports
» Clinical & Experimental Cardiology
» Clinical & Experimental Dermatology Research
» Clinical & Experimental Ophthalmology
» Clinical & Experimental Pharmacology
» Clinical & Experimental Pathology
» Clinical Microbiology: Open Access
» Clinical Research & Bioethics
» Clinical Research on Foot & Ankle
» Clinical Toxicology
» Clinical Trials
»Clinics in Mother and Child Health
» Communication Disorders, Deaf Studies & Hearing Aids
» Cytology & Histology
» Forensic Research
»Forensic Biomechanics
» Integrative Oncology
»Immunome Research
»JBR Journal of Clinical Diagnosis and Research
» Neurology & Neurophysiology
» Pulmonary & Respiratory Medicine
» Stem Cell Research & Therapy
» Transplantation Technologies & Research
   
Pharmaceutical Sciences
» Advances in Pharmacoepidemiology & Drug Safety
» Alcoholism and Drug Dependence
» Bioanalysis & Biomedicine
» Biochemical Pharmacology
» Bioequivalence & Bioavailability
» Cardiovascular Pharmacology: Open Access
» Clinical Pharmacology & Biopharmaceutics
» Developing Drugs
» Drug Designing
» Drug Metabolism & Toxicology
» Medicinal & Aromatic Plants
» Molecular Pharmaceutics & Organic Process Research
» Pharmaceutica Analytica Acta
» Pharmaceutical Regulatory Affairs
» Pharmacovigilance
» Vaccines & Vaccination
   
Chemistry
» Advanced Chemical Engineering
» Analytical & Bioanalytical Techniques
» Chemical Sciences Journal
» Chromatography & Separation Techniques
» Medicinal Chemistry
» Modern Chemistry & Applications
» Natural Products Chemistry & Research
» Organic Chemistry
» Physical Chemistry & Biophysics
» Plant Biochemistry & Physiology
» Thermodynamics & Catalysis
» Theoretical and Computational Chemistry:Open Access
   
Environmental
» Anthropology
» Aquaculture Research & Development
» Astrobiology & Outreach
» Biodiversity & Endangered Species
» Earth Science & Climatic Change
» Ecosystem & Ecography
» Environmental & Analytical Toxicology
» Fisheries & Livestock Production
»Fundamentals of Renewable Energy and Applications
» Geography & Natural Disasters
» Hydrology: Current Research
»Innovative Energy Policies
»International Journal of waste resources
» Oceanography-Open Access
» Petroleum & Environmental Biotechnology
» Pollution Effects & Control
» Poultry, Fisheries & Wildlife Sciences
   
Omics
» Data Mining in Genomics & Proteomics
»Ergonomics
» Glycomics & Lipidomics
» Health & Medical Informatics
»JBR Journal of Young Scientist
» Metabolomics:Open Access
» OMICS Journal of Radiology
» Pharmacogenomics & Pharmacoproteomics
» Phylogenetics & Evolutionary Biology
» Proteomics & Bioinformatics
» Transcriptomics
   
Life Sciences
» Advanced Techniques in Biology & Medicine
»Advancements in Genetic Engineering
»Advances in Crop Science and Technology
»Advances in Dairy Research
» Aging Science
» Agrotechnology
» Air & Water Borne Diseases
» Antivirals & Antiretrovirals
» Autism-Open Access
» Bacteriology & Parasitology
» Biochemistry & Physiology
» Biochemistry and Analytical Biochemistry
» Bioenergetics
» Bioengineering & Biomedical Science
» Biofertilizers & Biopesticides
» Biological Systems
» Biometrics & Biostatistics
»Biomimetics Biomaterials and Tissue Engineering
» Biomolecular Research & Therapeutics
» Bioremediation & Biodegradation
» Biosafety
» Biosafety & Health Education
» Biosensors & Bioelectronics
» Biosensors Journal
» Biotechnology & Biomaterials
» Bioterrorism & Biodefense
» Cell & Developmental Biology
» Current Synthetic & Systems Biology
» Entomology, Ornithology & Herpetology
» Enzyme Engineering
» Fermentation Technology
» Fertilization: In Vitro - IVF-Worldwide
» Fisheries and Aquaculture Journal
» Forest Research
» Fungal Genomics & Biology
» Gene Technology
» Glycobiology
» Horticulture
» Homeopathy & Ayurvedic Medicine
»International Journal of Swarm Intelligence and Evolutionary Computation
» Marine Science: Research & Development
» Membrane Science & Technology
» Microbial & Biochemical Technology
» Molecular Biology
» Molecular Imaging & Dynamics
» Nanomedicine & Biotherapeutic Discovery
» Nanomedicine & Nanotechnology
» Nutrition & Food Sciences
» Plant Pathology & Microbiology
» Primatology
» Probiotics & Health
» Rice Research: Open Access
» Single Cell Biology
» Sociology and Criminology-Open Access
» Tissue Science & Engineering
» Tropical Diseases
» Veterinary Science & Technology
» Vitamins & Minerals
»Virology & Mycology
   
Engineering
» Advances in Automobile Engineering
» Advances in Robotics & Automation
» Aeronautics & Aerospace Engineering
» Applied & Computational Mathematics
» Applied Mechanical Engineering
» Architectural Engineering Technology
» Astrophysics & Aerospace technology
» Biochips & Tissue Chips
» Bioprocessing & Biotechniques
» Chemical Engineering & Process Technology
» Civil & Environmental Engineering
» Computer Science & Systems Biology
» Electrical & Electronics
» Food Processing & Technology
» Geology and Geosciences
» Geophysics & Remote sensing
»Global Journal of Technology and Optimization
» Industrial Engineering & Management
» Information Technology & Software Engineering
» International Journal of Advance Innovations, Thoughts & Ideas
»International Journal of Sensor Networks and Data Communications
» Irrigation and Drainage Systems Engineering
»Generalized Lie Theory and Applications
» Lovotics
» Material Sciences & Engineering
»Physical Mathematics
» Powder Metallurgy & Mining
» Telecommunications System & Management
» Textile Science & Engineering
»Vortex Science and Technology
   
Medical Sciences
» Addiction Research & Therapy
» Allergy & Therapy
» Alternative & Integrative Medicine
» Alzheimers Disease & Parkinsonism
» Anaplastology
» Anatomy & Physiology
» Ancient Diseases & Preventive Remedies
» Andrology
» Arthritis
» Autacoids
»Automatic Control of Physiological State and Function
» Bioceramics Development and Applications
» Biology and Medicine
» Biomusical Engineering
» Blood & Lymph
» Blood Disorders & Transfusion
» Bone Marrow Research
» Brain Disorders & Therapy
» Cardiovascular Diseases & Diagnosis
» Cloning & Transgenesis
» Community Medicine & Health Education
» Dentistry
» Depression and Anxiety
» Diabetes & Metabolism
» Emergency Medicine
» Endocrinology & Metabolic Syndrome
» Epidemiology: Open Access
» Family Medicine & Medical Science Research
» Gastrointestinal & Digestive System
» General Medicine
» General Practice
» Genetic Syndromes & Gene Therapy
» Gynecology& Obstetrics
» Gerontology & Geriatrics Research
» Hematology & Thromboembolic Diseases
» Hair: Therapy & Transplantation
» Health Care : Current Reviews
» Hereditary Genetics
» Human Genetics & Embryology
» Hypertension-Open Access
» Infectious Diseases & Therapy
» International Journal of Genomic Medicine
» Internal Medicine
»International Journal of Biomedical Data Mining
» International Journal of Physical Medicine & Rehabilitation
»JBR Journal of Interdisciplinary Medicine and Dental Science
» Leukemia
» Liver
»Malaria Chemotherapy, Control & Elimination
» Medical & Surgical Urology
» Medical Diagnostic Methods
» Medical Microbiology & Diagnosis
» Metabolic Syndrome
» Molecular Biomarkers & Diagnosis
» Molecular and Genetic Medicine
» Mycobacterial Diseases
» Neonatal Biology
» Nephrology & Therapeutics
»Neuroinfectious Diseases
» Neurological Disorders
» Novel Physiotherapies
» Nuclear Medicine & Radiation Therapy
» Nursing & Care
» Nutritional Disorders & Therapy
» Obesity & Weight Loss Therapy
» Occupational Medicine & Health Affairs
» Oral Health and Dental Management
» Oral Hygiene & Health
» Orthopedic & Muscular System
» Osteoporosis & Physical Activity
» Otolaryngology
» Pain & Relief
» Palliative Care & Medicine
» Pancreatic Disorders & Therapy
» Pediatrics & Therapeutics
» Primary Health Care
» Psychological Abnormalities in Children
» Psychology & Psychotherapy
» Reproductive System & Sexual Disorders
»Research and Development
» Rheumatology: Current Research
» Sleep Disorders & Therapy
» Spine
» Sports Medicine & Doping Studies
» Steroids & Hormonal Science
» Surgery: Current Research
» Thyroid Disorders & Therapy
» Translational Medicine
» Trauma & Treatment
» Tropical Medicine and Surgery
» Vascular Medicine & surgery
» Women's Health Care
» Yoga & Physical Therapy
 
Management
» Accounting & Marketing
» Arabian Journal Business and Management Review
» Arts and Social Sciences Journal
» Business and Economics Journal
» Business and Financial Affairs
» Civil & Legal Sciences
» Defense Management
» Entrepreneurship & Organization Management
» Global Economics
» Hotel & Business Management
» Intellectual Property Rights: Open Access
»International Journal of Accounting Research
» International Journal of Economics & Management Sciences
» Mass Communication & Journalism
» political Sciences & public affairs
»Review of Public Adminstration and Management
» Socialomics
» Stock & Forex Trading
» Tourism & Hospitality
 
   Conferences
Upcoming Conferences
»4th International Conference on Clinical & Experimental Cardiology April 14-16, 2014 San Antonio, USA
»4th International Conference on Clinical & Experimental Dermatology April 14-16, 2014 San Antonio, USA
»3rd International Conference and Exhibition on Pathology April 14-16, 2014 San Antonio, USA
»5th International Conference on Biomarkers and Clinical Research April 15-17, 2014 University of Oxford, UK
»2nd International Conference on Business Economics and Management April 21-23, 2014 Dubai, UAE
»2nd International Conference on Dental and Oral Health April 21-23, 2014 Dubai, UAE
»4th World Congress on Cell Science & Stem Cell Research June 24-26, 2014 Valencia, Spain
»3rd International Conference on Biodiversity & Sustainable Energy Development June 24-26, 2014 Valencia, Spain
»3rd International Conference and Exhibition on Occupational Health & Safety June 24-25, 2014 Valencia, Spain
»5th World congress on Biotechnology June 25-27, 2014 Valencia, Spain
»3rd International Conference on Nephrology & Therapeutics June 26-27, 2014 Valencia, Spain
»2nd International Conference on Bioprocess and Engineering June 26-27, 2014 Valencia, Spain
»International Conference on Geriatrics & Gerentology July 08-10, 2014 Chicago , USA
»International Conference on Women's Health, Gynecology & Obstetrics July 08-10, 2014 Chicago, USA
»International Conference on Computer Graphics and Media Design July 08-10, 2014 Chicago, USA
»4th International Conference on Clinical & Experimental Ophthalmology July 14-16, 2014 Baltimore, USA
»3rd International Conference & Exhibition on Biometrics & Biostatistics July 14-16, 2014 Baltimore, USA
»2nd International Conference and Exhibition on Physical Medicine & Rehabilitation July 14-16, 2014 Baltimore, USA
»3rd International Conference and Exhibition on Cosmetology & Trichology July 21-23, 2014 Las Vegas, USA
»3rd International Conference and Exhibition on Food Processing & Technology July 21-23, 2014 Las Vegas, USA
»2nd International Conference on Oceanography July 21-23 , 2014 Las Vegas USA
»Health Informatics & Technology Conference July 28-29, 2014 Baltimore, USA
»3rd International Conference on Gastroenterology & Urology July 28-30, 2014 San Francisco, USA
»3rd International Conference on Earth Science & Climate Change July 28-30, 2014 San Francisco, USA
»3rd International Conference and Exhibition on Orthopedics & Rheumatology July 28-30, 2014 San Francisco, USA
»International Conference on Business Economics of Broadcasting Media & Film Industry July 28-30, 2014, Baltimore, USA
»4th International Conference on Proteomics & Bioinformatics August 04-06, 2014 Chicago, USA
»3rd International Conference and Exhibition on Addiction Research & Therapy August 04-06, 2014 Chicago, USA
»2nd International Conference on Integrative Biology Summit August 04-05, 2014 Chicago, USA
»3rd International Conference and Exhibition on Biosensors & Bioelectronics August 11-13, 2014 San Antonio, USA
»2nd World Associations Congress August 11-13, 2014 San Antonio, USA
»International Meeting on Space- Open Debate August 12-13, 2014 San Antonio, USA
»5th International Conference and Exhibition on Analytical & Bioanalytical Techniques August 18-20, 2014 Beijing, China
»2nd International Conference on Epidemiology and Evolutionary Genetics August 18-19, 2014 Beijing, China
»2nd International Conference and Exhibition on Pharmacognosy, Phytochemistry & Natural Products August 25-27, 2014 Beijing, China
»2nd International Conference and Exhibition on Traditional & Alternative Medicine August 25-26, 2014 Beijing, China
»2nd International Conference and Exhibition on Mechanical & Aerospace Engineering September 08-10, 2014 Philadelphia, USA
»2nd International Conference and Exhibition on Lasers, Optics & Photonics September 08-10, 2014 Philadelphia, USA
»3rd International Conference and Exhibition on Neurology & Therapeutics September 08-10, 2014 Philadelphia, USA
»4th International Conference on Pharmaceutical Regulatory Affairs September 08-10, 2014 Raleigh, USA
»2nd International Conference on Radiology and Imaging September 08-09, 2014 Raleigh, USA
»2nd International Conference on Genomics & PharmacogenomicsSeptember 08-09, 2014 Raleigh, USA
»2nd International Conference on Alzheimer's Disease and Dementia September 23-25, 2014 Valencia Convention Centre, Valencia, Spain
»3rd International Conference and Exhibition on Nutrition & Food Sciences September 23-25, 2014 Valencia, Spain
»3rd International Conference on Clinical Microbiology & Microbial Genomics September 24-26, 2014 Valencia, Spain
»3rd International Conference on Tissue Science & Regenerative Medicine September 24-26, 2014 Valencia, Spain
»4th International Conference on Vaccines & Vaccination September 24-26, 2014 Valencia, Spain
»3rd International Summit on GMP, GCP & Quality Control September 25-26, 2014 Valencia, Spain
»5th World Congress on Bioequivalence and Bioavailability: Pharmaceutical R&D Summit September 29-October 01, 2014 Baltimore, USA
»2nd International Conference on Hematology & Blood Disorders September 29-October 01, 2014 Baltimore, USA
»3rd International Conference and Exhibition on Clinical & Cellular Immunology September 29-October 01, 2014 Baltimore, USA
»3rd International Conference and Exhibition on Materials Science & Engineering October 06-08, 2014 San Antonio, USA
»3rd International Conference on Forensic Research and Technology October 06-08, 2014 San Antonio, USA
»4th World Congress on Virology October 06-08, 2014 San Antonio, USA
»2nd International Conference on Endocrinology October 20-22, 2014 Chicago, USA
»3rd 3rd International Summit on Toxicology & Applied Pharmacology October 20-22, 2014 Chicago, USA
»3rd 4th World Congress on Cancer Science and Therapy October 20-22, 2014 Chicago, USA
»3rd 3rd International Conference and Exhibition on Cell & Gene Therapy October 27-29, 2014 Las Vegas, USA
»2nd International Conference on HIV/AIDS, STDs & STIs October 27-29, 2014 Chicago, USA
»2nd World Congress on Petrochemistry and Chemical Engineering October 27-29, 2014 Las Vegas, USA
»3rd International Conference and Exhibition on Pharmacovigilance & Clinical Trials October 27-29, 2014 Hyderabad, India
»3rd International Conference and Exhibition on Biowaivers and Biosimilars October 27-29, 2014 Hyderabad, India
»3rd International Conference on Translational Medicine November 03-05, 2014 Las Vegas, USA
»2nd International Conference on Predictive, Preventive and Personalized Medicine & Molecular Diagnostics November 03-05, 2014 Las Vegas, USA
»5th International Conference on Diabetes & Metabolism November 03-05, 2014 Las Vegas, USA
»2nd International Congress on Bacteriology and Infectious Diseases November 17-19, 2014 Chicago, USA
»2nd International Conference on Nursing & Healthcare November 17-19, 2014 Chicago, USA
»3rd International Conference on Surgery and Anesthesia November 17-19, 2014 Chicago, USA
»4th International Conference on Nanotek & Expo December 01-03, 2014 San Francisco, USA
»3rd International Conference and Exhibition on Obesity & Weight Management December 01-03, 2014 San Francisco, USA
»2nd International Summit on Clinical PharmacyDecember 02-03, 2014 San Francisco, USA
»3rd International Conference on Medicinal Chemistry & Computer Aided Drug Designing December 08-10, 2014 San Francisco, USA
»3rd International Conference and Exhibition on Probiotics & Functional Foods December 08-10, 2014 San Francisco, USA
Previous Conferences Organized/Co-organized
»4th International Conference and Exhibition on Pharmaceutics & Novel Drug Delivery Systems March 24-26, 2014 San Antonio, USA
»3rd International Conference and Exhibition on Metabolomics & Systems Biology March 24-26, 2014 San Antonio, USA
»2nd International Conference on Agricultural & Horticultural Sciences, February 03-05, 2014 Hyderabad, India
»International Conference and Exhibition on Traditional & Alternative Medicine, December 09-11, 2013 Hyderabad, India
»2nd International Conference and Exhibition on Obesity & Weight Management, December 02-04, 2013 Las Vegas, USA
»International Conference on Nursing & Emergency Medicine, December 02-04, 2013 Las Vegas, USA
»3rd International Conference on Nanotek & Expo, December 02-04, 2013 Las Vegas, USA
»3rd World Congress on Virology, November, 20-22, 2013 Baltimore, USA
»International Congress on Bacteriology and Infectious diseases, November 20-22, 2013 Baltimore, USA
»3rd World Congress on Cell Science & Stem Cell Research, November 20-22, 2013 San Antonio, USA
»2nd International Conference and Exhibition on Pharmacovigilance & Clinical Trials, November 18-19, 2013 San Antonio, USA
»International Summit on Clinical Pharmacy & Dispensing, November 18-20, 2013 San Antonio, USA
»World Congress on Petrochemistry and Chemical Engineering, November 18-20, 2013 San Antonio, USA
»International Conference on Functional and Comparative Genomics & Pharmacogenomics, November 12-14, 2013 Chicago, USA
»2nd International Conference and Exhibition on Cosmetology & Trichology, November 12-14, 2013 Chicago, USA
»2nd International Summit on GMP, QA & QC, November 12-14, 2013 Chicago, USA
»2nd International Summit on GLP, GCP & Clinical Pharmacology, November 12-14, 2013 Chicago, USA
» International Conference on Fermentation Technology, Bioprocess and Cell Culture, October 28-30, 2013 Kansas City, USA
»2nd International Conference and Exhibition on Food Processing & Technology, October 28-30, 2013 Kansas City, USA
»International Conference on HIV/AIDS, STDs, & STIs, October 24-25, 2013 Orlando-FL, USA
»2nd International Conference and Exhibition on Cell & Gene Therapy, October 23-25, 2013 Orlando, USA
»2nd International Conference and Exhibition on Probiotics & Functional Foods, October 23-25, 2013 Orlando, USA
»International Conference and Exhibition on Pharmacognosy, Phytochemistry and Natural Products, October 21-23, 2013 Hyderabad, India
» 3rd World Congress on Cancer Science & Therapy, October 21-23, 2013 California, USA
»3rd International Conference on Pharmaceutical Regulatory Affairs, October 21-23, 2013 California, USA
»2nd International Conference on Clinical & Cellular Immunology, October 15-17, 2013 Las Vegas, USA
»2nd International Conference on Medicinal Chemistry & Computer Aided Drug Designing, October 15-17, 2013 Las Vegas, USA
»4th International Conference and Exhibition on Analytical & Bioanalytical Techniques, October 15-17, 2013 Las Vegas, USA
»2nd International Summit on Toxicology, October 07-09, 2013 Las Vegas, USA
»International Conference and Exhibition on Lasers, Optics & Photonics, October 7-9, 2013 San Antonio, USA
»2nd International Conference and Exhibition on Materials Science & Engineering, October 07-09, 2013 Las Vegas, USA
»2nd International Conference on Forensic Research & Technology, October 07-09, 2013 Las Vegas, USA
»International Conference and Exhibition on Biochemical & Molecular Engineering, October 07-08, 2013 San Antonio, USA
»International Conference on Psychology, Autism and Alzheimer's Disease, September 30-October 01, 2013 San Antonio, USA
»International Conference and Exhibition on Mechanical & Aerospace Engineering, September 30-October 02, 2013 San Antonio, USA
»2nd International Conference and Exhibition on Biowaivers & Biosimilars, September 23-25, 2013 Raleigh, USA
»4th World Congress on Biotechnology, September 23-25, 2013 Raliegh, USA
»International Conference on Hematology & Blood Disorders, September 23-25, 2013 Raliegh, USA
»2nd International Conference on Surgery and Anesthesia, September 16-18, 2013 Las Vegas, USA
»2nd International Conference on Clinical Microbiology & Microbial Genomics, September 16-18, 2013 Las Vegas, USA
» International Conference on Omics Studies, September 04-06, 2013 Orlando-FL, USA
»International Symposia on Entomology, September 04-06, 2013 Miami, USA
» World Congress on Endocrinology, August 26-28, 2013 Raleigh, USA
»2nd International Conference on Hydrology and Groundwater Expo, August 26-27, 2013 Raleigh, USA
» 2nd International Conference on Tissue Science & Regenerative Medicine, August 26-28, 2013 Raleigh, USA
»International Conference on Molecular Epidemiology and Evolutionary Genetics, August 21-23, 2013 Miami, USA
»International Conference on Oceanography, August 21-23, 2013 Orlando, USA
»International Conference on Biodefense & Natural Disasters, August 21-23, 2013 Miami, USA
»2nd International Conference and Exhibition on Orthopedics & Rheumatology, August 19-21, 2013 Las Vegas, USA
»International Conference on Dental & Oral Health, August 19-21, 2013 Las Vegas, USA
»International Conference and Exhibition on Physical Medicine & Rehabilitation, August 19-21, 2013 Las Vegas, USA
» 4th World Congress on Diabetes & Metabolism, August 14-16, 2013 Chicago, USA
»International Conference on Radiology and Imaging, August 14-16, 2013 Chicago, USA
» 2nd International Conference on Biodiversity & Sustainable Energy Development, August 12-14, 2013 Raleigh, USA
» International Conference on Genetic Engineering & Genetically Modified Organisms, August 12-14, 2013 Raleigh, USA
»2nd International Conference and Exhibition on Pathology, August 05-07, 2013 Las Vegas, USA
»International Conference on Integrative Biology Summit, August 05-07, 2013 Las Vegas, USA
»2nd International Conference on Translational Medicine, August 05-07, 2013 Chicago, USA
»International Conference on Predictive, Preventive and Predictive, Preventive and Personalized Medicine & Molecular Diagnostics, August 05-07, 2013 Chicago, USA
»2nd International Conference on Nephrology & Therapeutics, July 29-31, 2013 Las Vegas, USA
»3rd International Conference on Vaccines & Vaccination, July 29-31, 2013 Las Vegas, USA
»2nd International Conference on Earth Science & Climate Change, July 22-24, 2013 Las Vegas, USA
»2nd International Conference and Exhibition on Addiction Research & Therapy, July 22-24, 2013 Las Vegas, USA
»International Conference on Animal & Dairy Sciences, July 23-24, 2013 Las Vegas, USA
»3rd International Conference on Proteomics & Bioinformatics, July 15-17, 2013 Philadelphia, USA
»2nd International Conference and Exhibition on Nutritional Science & Therapy, July 15-17, 2013 Philadelphia, USA
»4th International Conference on Biomarkers & Clinical Research, July 15-17, 2013 Philadelphia, USA
»2nd International Conference and Exhibition on Biosensors & Bioelectronics, June 17-19, 2013 Chicago, USA
»2nd International Conference and Exhibition on Neurology & Therapeutics, June 17-19, 2013 Chicago, USA
»2nd International Conference on Gastroenterology & Urology, June 10-12, 2013 Chicago, USA
»2nd International Conference and Exhibition on Biometrics & Biostatistics, June 10-12, 2013 Chicago, USA
»2nd International Conference and Exhibition on Occupational Health & Safety, May 21-22, 2013 Beijing, China
»4th World Congress on Bioavailability & Bioequivalence, May 20-22, 2013 Beijing, China
»3rd International Conference on Clinical & Experimental Ophthalmology, April 15-17, 2013 Chicago, USA
»3rd International Conference on Clinical & Experimental Cardiology, April 15-17, 2013 Chicago, USA
»3rd International Conference on Clinical & Experimental Dermatology, April 15-17, 2013 Chicago, USA
»2ndInternational Conference and Exhibition on Metabolomics & Systems Biology, April 08-10, 2013 Chicago, USA
»3rd International Conference and Exhibition on Pharmaceutics & Novel Drug Delivery Systems, April 08-10, 2013 Chicago, USA
»International Exhibition and Conference on Water Technologies, Environmental Technologies & Renewable Energy, February 13-14, 2013 Mumbai, India
»International Summit on GMP & GCP: USA, Europe, Japan, Asia Pacific December 03-05, 2012 DoubleTree by Hilton Philadelphia Center City, USA
»International Conference on QA, QC and Validation, December 03-05, 2012 DoubleTree by Hilton Philadelphia Center City, USA
»2nd International Conference on Nanotek and Expo, December 03-05, 2012 DoubleTree by Hilton Philadelphia Center City, USA
»International Conference and Exhibition on Obesity and Weight Management, December 03-05, 2012 at DoubleTree by Hilton Philadelphia, USA.
»International conference on Hair Transplantation and Trichology November 26-28, 2012 San Antonio, USA.
»International Conference on Anesthesia & Perioperative Care during November 26-28, 2012 San Antonio, USA.
»International Toxicology Summit & Expo November 26-28, 2012 Hilton San Antonio Airport, USA
»International Conference and Exhibition on Surgery & Transplantation November 26-28, 2012 Hilton San Antonio Airport, USA.
»International Conference and Exhibition on Food Processing and Technology November 22-24, 2012 Hyderabad, India.
»3rd International Conference and Exhibition on Analytical & Bioanalytical Techniques November 22-24, 2012 Hyderabad International Convention Center, India
»2ndInternational Conference and Exhibition on Pharmaceutical Regulatory Affairs November 23-24, 2012 HICC Hyderabad, India
»International Conference and Exhibition on Cosmetology & Cosmetics November 23-24, 2012 HICC Hyderabad, India.
»International Conference on Genetic Syndromes & GeneTherapy November 19-21, 2012 Hilton San Antonio Airport, USA
»Global Biofuels and Bioproducts Summit November 19-21, 2012 San Antonio, USA.
»International Conference and Exhibition on Probiotics-2012, November 1921, 2012, Hilton San Antonio Airport, USA.
»2nd World Congress on Cell Science and Stem Cell Research, November 12-14, 2012 Hilton San Antonio Airport, USA.
»International Conference on Regenerative and Functional Medicine, November 12-14, 2012 at San Antonio, Texas, USA.
»International Conference on Clinical Microbiology & Microbial Genomics November 12-14, 2012 San Antonio, USA.
» International Confeernce on Pulmonary & Respiratory Medicine October 29 - 31, 2012 Chicago, USA
»International Conference and Exhibition on Computer Aided Drug Design & QSAR October 29-31, 2012, Chicago, USA.
»International Conference on Clinical and Cellular Immunology October 22-24, 2012 Las Vegas, USA.
»International Conference and Expo on Material science and Engineering October 22-24, 2012 DoubleTree by Hilton Chicago-North Shore, USA.
» International Expo and Conference on Analytrix & HPLC October 22-24, 2012 Hilton Northbrook, Chicago, USA.
»International Conference on Forensic Research & Technology October 15 - 17, 2012 DoubleTree by Hilton Chicago - Northshore, USA.
»International Conference and Exhibition on Otolaryngology October 15 - 17, 2012 DoubleTree by Hilton Chicago - Northshore, USA.
»International conference on Biothreats and Biodefense October 15 - 17, 2012 DoubleTree by Hilton Chicago - Northshore, USA.
»International Conference on Tissue Science and Engineering October 1-3, 2012 DoubleTree by Hilton Chicago-North Shore, USA.
»International conference and Exhibition on Pharmacovigilance and Clinical Trials October 1-3, 2012 DoubleTree by Hilton Chicago-North Shore, USA.
»International Conference on Emerging Cell Therapies October 1-3, 2012 DoubleTree by Hilton Chicago-North Shore, USA.
»3rd World Congress on Diabetes & Metabolism which is to be held on September 24-26, 2012 Marriott Convention Center, Hyderabad, India.
»2nd International Conference on Pediatrics & Gynecology September 24-26, 2012, Hyderabad Marriott Hotel & Convention Centre , Hyderabad, India.
»International Conference on Translational medicine-2012, September 17-19, 2012 Holiday Inn San Antonio, Texas, USA.
»3rd World Congress on Biotechnology September 13-15, 2012 HICC, Hyderabad, India
»International Conference on Biodiversity & Sustainable Energy Development September 14-15, 2012 Hyderabad, India.
» International Conference on Agricultural & Horticultural Sciences September 14-15, 2012 Hyderabad International Convention Center, India
» International Conference on Hotel and Business Management September 14-15, 2012 Hyderabad International Convention Center, India
»International Conference on Hydrology and Groundwater Expo September 10-12, 2012 Hilton San Antonio Airport, USA.
»2nd World Congress on Cancer Science & Therapy September 10-12, 2012 San Antonio, USA.
»International Conference and Exhibition on Biowaivers and Biosimilars September 10-12, 2012 San Antonio, TX, USA.
»International Conference on Central Nervous System September 5-7, 2012 Double by Hilton Philadephia, USA.
»International Conference on Occupational Health and Safety Summit September 5-7, 2012 Philadelphia, USA.
»International Conference and Exhibition on pathology August 27-29, 2012 Philadelphia, USA.
»International Conference and Exhibition on Nutritional Science & Therapy-2012 August 27-29, 2012 Philadelphia, USA.
»International Conference and Exhibition on Addiction Research & Therapy August 20-22, 2012 Las Vegas, USA.
»International Conference and Exhibition on Nephrology and Therapeutics August 20-22, 2012 Chicago Chicago, USA.
»2nd International Conference on Vaccines & Vaccination August 20-22, 2012 at Chicago, USA.
»2nd World Congress on Virology August 20-22, 2012 Las Vegas, USA.
»World Congress on Earth Science & Climate Change August 21-22, 2012 Chicago, USA.
»International Conference and Exhibition on Orthopedics August 13-15, 2012 Chicago, USA.
»International Conference and Exhibition on Rheumatology & Therapeutics August 1415, 2012 at Chicago, USA
»3rd International Conference on Biomarkers & Clinical Research July 2-4, 2012 Las Vegas, USA.
»2nd International Conference on Proteomics & Bioinformatics July 2-4, 2012 Las Vegas, USA.
» International Conference and Exhibition on Neurology &Therapeutics May 14-16, 2012 Las Vegas, USA.
»International Conference and Exhibition on Biosensors & Bioelectronics May 14-16, 2012 Las Vegas, USA.
»3rd World Congress on Bioavailability & Bioequivalence: Pharmaceutical R & D Summit March 26-28, 2012 Marriott Hotel, Hyderabad, India.
»International Conference & Exhibition on Nanotechnology and Nanomedicine March 12-14, 2012 Omaha, USA.
»World Congress on Gastroenterology and Urology March 12-14, 2012 Omaha, USA
»International Conference and Exhibition on Biometrics & Biostatistics March 5-7, 2012 Omaha, USA.
»2nd World Congress on Clinical & Experimental Dermatology March 5-7, 2012 Omaha, USA
»2nd World Congress on Clinical & Experimental Cardiology March 5-7, 2012 Omaha, USA.
» 2nd World Congress on Clinical & Experimental Ophthalmology March 5-7, 2012 Omaha, USA.
»International Conference and Exhibition on Metabolomics & Systems Biology February 20-22, 2012 San Francisco, USA.
»2nd World Congress on Pharmaceutics & Novel Drug Delivery Systems February 20-22, 2012 San Francisco, USA.
»2nd world Congress on Analytical and Bioanalytical Techniques December 16-17, 2011 San franscico, USA.
»2nd World Congress on Diabetes & Metabolism December 6-8, 2011 Philadelphia, USA.
»World Congress on Pediatrics & Gynecology December 6-8, 2011 Philadelphia, USA.
»International Conference and Exhibition on Cell Science & Stem Cell Research Nov 29-Dec 1, 2011 Philadelphia, USA.
»2nd World Congress on Biotechnology Nov 29 -Dec 1, 2011 Philadelphia, USA.
»International Conference and Exhibition on Vaccines & Vaccination November 22-24, 2011 Philadelphia, USA.
»2nd World Congress on Biomarkers & Clinical Research September 12-14, 2011 Baltimore, USA.
»International Conference and Exhibition on Virology September 5-7, 2011 Baltimore, USA.
»International Conference and Exhibition on Pharmaceutical Regulatory Affairs September 6-7, 2011 Baltimore, USA.
»International Conference and Exhibition on Cancer Science & Therapy August 15-17, 2011 Las Vegas, USA.
»International Conference on Clinical Research: Dermatology, Ophthalmology and Cardiology July 5-6, 2011 San Francisco, USA.
»International Conference & Exhibition on Proteomics & Bioinformatics June 6-8, 2011 HICC, Hyderabad, India.
»International Conference & Exhibition on Pharmaceutical Biotechnology June 6-8, 2011 HICC, Hyderabad, India.
»2nd World Congress on Bioavailability & Bioequivalence: Pharmaceutical R & D Summit June 6-8, 2011 Las Vegas, USA.
»International Conference on Pharmaceutics & Novel Drug Delivery Systems June 7-8, Las Vegas, USA.
»World Congress on Biotechnology March 21-23, 2011 Hyderabad, India.
»International Conference on Diabetes and Metabolism December 13-14, 2010 Santa Clara, USA.
»International Conference on Biomarkers & Clinical Research November 22-23, 2010 Santa Clara, USA
»International Conference and Exhibition on Analytical and Bioanalytical Techniques: Pharmaceutical R & D Summit November 01-03, 2010 Hyderabad, India
»International Conference & Exhibition on Bioequivalence & Bioavailability 2010, Pharmaceutical R & D Summit March 01-03, 2010.
»Integrating Glycomics with other Omics in Cancer Detection and Diagnosis, January 19-20, 2010, Stanford University School of Medicine.
»3rd World Congress of Gene-2009, December 1-7, 2009.
»7th Annual World Congress of International Drug Discovery Science & Technology, October 22-25.
»2nd WSA-2009, July 18-20, 2009
»1st CCSB-2009, February 16-17, 2009
»2nd PRICPS-4th AOHUPO, June 22-26, 2008
»95th ISCA, January 5-8, 2008

Search :     Advanced Search 

HomeHome   |   Join Join   |   Contact Contact     

Journal of Cancer Science & Therapy Video  Journal of Cancer Science & Therapy  LinkedIn - Journal of Cancer Science & Therapy Twitter - Journal of Cancer Science & Therapy Facebook - Journal of Cancer Science & Therapy Journal of Cancer Science & Therapy Blog
Journal Details
 
 
Research Article Open Access
Are all Glioma Cells Cancer Stem Cells?
1Department of Clinical Neuroscience R54, Karolinska Institute, Stockholm, Sweden
2Department of Neurology, Karolinska University Hospital, Stockholm, Sweden
3Universidad Nacional de San Martín Buenos Aires, Argentina
*Corresponding author: Dr. Yakisich J. Sebastian, Ph.D.,
Department of Clinical Neuroscience,
Karolinska University Hospital,
Stockholm, Sweden,
Tel: +46 8 585 89 533,
Fax: +46 8 585 83810,
E-mail: Sebastian.Yakisich@ki.se
 
Received May 06, 2010; Accepted June 16, 2010; Published June 16, 2010
 
Citation: Cruz M, Siden , Tasat DR, Yakisich JS (2010) Are all Glioma Cells Cancer Stem Cells? J Cancer Sci Ther 2: 100-106. doi:10.4172/1948-5956.1000032
 
Copyright: 2010 Cruz M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
 
Abstract
 
The cancer stem cell theory proposes that there is a small but constant subpopulation of cancer cells with stem cell properties responsible for the self renewal capacity and unlimited proliferation of tumor as well as increased resistance to antineoplastic drugs. Targeting these cells might constitute an effective way to cure cancer. Regarding gliomas, by analysing proliferation kinetics of cultures containing mixed subpopulations and experimental data from literature on glioma cell lines, we propose a model (Stemness Phenotype Model) in which all glioma cells have stem cells properties but their phenotype varies depending on the environmental conditions. This model provides an alternative explanation to different and sometimes controversial experimental findings and might be a useful guide for future research in the field of gliomas and stem cell biology.
 
Keywords
 
Cancer; Glioma; Stem cells; Proliferation; Stem cell theory; Stemness
 
Introduction
 
Limitless replicative potential is one of the hallmarks of cancer cells and normal stem cells: while normal cells have limited replication capacity, stem cells and cancer cells can be propagated indefinitely (Hanahan and Weinberg, 2000; Rubin, 2002). Stem cells have also long-term self-renewal ability and capacity to give rise to one or more types of differentiated progeny (Nicolis, 2007). The existence of cancer stem cells was reported in several cancer cell lines (Setoguchi et al., 2004) suggesting that cancers are maintained by cancer stem cells making them an important therapeutic target. Increasing data support the existence of cancer stem cells in gliomas and several publications reported the existence of glioma stem cells (GSCs) in available glioma cell lines as well as in patient derived cell lines (Fukaya et al., 2010; Kondo et al., 2004; McCord et al., 2009; Qiang et al., 2009; Ropolo et al., 2009; Singh et al., 2004; Zheng et al., 2007; Zhou et al., 2009). In general, resistance of gliomas and other brain tumors to therapy and relapse after standard treatments is attributed to the presence of stem-like cells (Charles and Holland, 2010). Criteria for defining GSCs include properties such as multipotentiality, self-renewal, indefinite proliferation in vitro (Limitless Replicative Potential), and tumorigenicity in vivo. Regarding the percentage of glioma stem cells in cell lines, the data have been controversial. The best studied cell line is the glioma C6 cell line where authors reported values from 0.4 to 100% (Table 1). These marked differences can be attributed to technical procedures such as among others, isolation methods, cell culture conditions, stem cell markers (Table 1). Probably, the best experimental approach to define the percentage of GSCs in the C6 glioma cell line was the work published by Zheng et al. (2007) (Zheng et al., 2007), where isolated single cells were expanded as clonal lines and representative subclones evaluated for their ability to sustain tumor growth in mouse. In that study 67 out of 67 subclones were able to form a new tumor in mouse indicating that most (probably 100%) of cells were cancer stem cells. The authors also proposed a model where stem cells always divided symmetrically (Figure 4 in Zheng et al. (2007)). Shen et al. (2008) found by means of a tumor sphere culture system and a single-cell subsphere generation assay that the majority C6 cells (>80%) have stem cell properties (Shen et al., 2008) while analysis of stem cells markers and the “side population” showed that a small percentage of C6 cells has stem cell properties (Kondo et al., 2004; Zhou et al., 2009). The current dogma in the cancer field is that cell lines contain at least two subpopulations of cells: cancer stem cells and non-cancer stem cells. Elucidating the real percentage of each subpopulation in cell lines and cancers in vivo is not only of academic interest but has also important implications for the development of new therapeutic modalities for cancer treatment.
 
Table 1: Detection of GSCs in established glioma cell lines.
 
Are all glioma cells in cell lines stem cells?
 
It is widely accepted that GSCs proliferate slower than non-GSCs and experimental data support this statement. A recent study showed that the average population doubling time (PDT) for non GSCs and GSCs is approximately 28-30h and 55-60h respectively (Ropolo et al., 2009). In order to bring together experimental data and the stem cell concept we analysed the theoretical possibility of coexistence of two different subpopulations in a same cell line. A simple mathematical analysis predicts that existing cells lines containing at least two subpopulations with different cell cycle length, when propagated for a high number of passages, should be enriched for the fastest dividing subpopulation initially present at the moment of isolation. Even small differences in the cell cycle length will produce a cell line enriched for the fastest subpopulation (Yakisich, 2009) . Since the C6 glioma cell line has been propagated thousands of times (Kondo et al., 2004) it is expected that the slowly proliferating stem cells subpopulations might have disappeared at some point. However, the C6 glioma cell line was apparently isolated and expanded from a single cell (Benda et al., 1968). Then, to explain the presence of GSCs and non-GSC in this cell line, the primordial C6 cell must have been a GSC that, by definition of SC, was able to originate non-GSCs (this assumption does not explain Zheng’s experiment, see below). Other cell lines and patient derived cell lines were obtained by propagating mixed cell populations instead of single cells. Frequently cell biologists isolate cell lines from tumoral tissue. Therefore, in these cases, the primary cell culture might contain different cell subpopulations with different proliferative kinetics. After continuous passages, the expected progressive enrichment of the fastest growing subpopulation opens, in the stem cells field, some controversial questions. It is likely that glioma cells lines after extensive passages should contain either pure non-GSCs (that proliferate fast) or pure GSCs (that proliferate slowly) but not both. Since several cell lines, as mentioned above, were isolated from expanding mixed tumors, it is expected that most of the cell lines should contain only non-GSCs (if they outgrow GSCs). The second possibility is that the expansion of the culture selected for stem cells because non-GSCs did not survive the procedure or they spontaneously stop dividing after they reach the Hayflick limit.
 
This theoretical analysis raises the following question: how can glioma cell lines maintain a constant but rare subpopulation of GSCs? The model proposed by Zheng et al. (2007) (Figure 4 therein) concludes that “a cell line cannot maintain a rare but constant fraction of stem cells unless the stem cells divide symmetrically”(Zheng et al., 2007). The model shows that when starting a culture containing 99 non-GSCs and 1 GSC (1%), after four cell divisions the culture would contain 1564 non-GSC and 16 GSCs (1%). This might be true only for non-GSCs and GSCs dividing at the same rate. Zheng’s model assumes that stem and non stem cells have similar proliferation rates. When the slower PDT of GSCs is considered, this scenario changes completely and fails to reconciliate experimental data. Table 2 shows the expected outcome for the percentage of two different GSCs with PDTs (24h and 36h) present in a cell culture when starting at a ratio non-GSCs: GSC= 99:1 and compares it to non-GSC (PDT= 24h). It clearly shows that the slower proliferating cell subpopulation (PDT 36h) will gradually decrease and eventually disappear when co-incubated with a subpopulation of shorter PDT (24h). Using the same type of analysis showed in Table 2, a faster subpopulation (PDT = 18h) will undergo 8 divisions within 144h and its percentage will increase up to 4%. Undoubtedly, unless GSCs and nonGSCs have the same PDT, one cell subpopulation will sooner or later outgrow the other. Thus, it is unlikely that mixed non-GSCs and GSCs cultures will keep a constant but rare fraction of stem cells as the model based in independent cell subpopulations proposes.
 
Table 2: Percentage of GSCs in a mixed culture compared to non-GSCs of similar (Blue) or longer PDT (Red) than the GSC subpopulation.
 
The symmetrical and asymmetrical cell division models
 
Can the symmetrical or asymmetrical nature of cell division explain the experimental findings?
 
In symmetrically dividing cells (GSCs producing only GSCs and non-GSCs producing only non-GSCs), isolation of single cells will produce only pure GSCs clones and subclones or pure non-GSCs clones and subclones (Figure 1A-B). To account for a small population of non-GSCs, one can assume that a fraction of GSCs “differentiate” producing non-GSCs (Figure 1B, box). In this case, it becomes a type of asymmetrical division after all. Once a non-GSC (that divides faster than the GSCs) is generated it will outgrow the GSC population and at the end the culture will become a pure non-GSC cell line. More important, this assumption does not explain Zheng’s experiment where 100% of isolated cells had stem cell properties.
 
Asymmetrical division of non-GSCs is not possible by definition (Figure 1C). In the case that GSCs always divide asymmetrically rendering a GSC and a non-GSC, the clonal expansion of a single GSC will give a culture containing always 1 GSC and increasing number of non-GSC (Figure 1D). Of course, one can argue that in the asymmetrical cell division model, the unique GSC present in the culture might at some point divides symmetrically. (Figure 1D box). The only “advantage” of this model is that it will explain the presence of more than 1 GSC cell in the clonal line. Due to the initial high number of non-GSCs and the slower PDT of GSCs, it is expected that the clonal expansion of a single GSC cell will produce a culture composed mostly of non-GSCs. Once again, this model does not explain why 100% of GSCs after single cell isolation have stem cell properties. In summary, both “symmetrical division” followed by differentiation of a certain fraction of GSCs into non-GSCs and “asymmetrical division” followed by symmetrical division in a fraction of GSC might explain the occurrence of a fraction of GSCs. To explain the constant percentage of GSCs, one should assume a very delicate balance between non-GSC generation (produced by symmetric division or differentiation), cell death and proliferation rate of the two subpopulations.
 
In 2007, Blagosklonny, in order to explain the constant fraction of stem cells, postulated the existence of “stemloids”, defined basically as stem cells that proliferate fast (Blagosklonny, 2007). Again, to maintain a constant fraction of stem cells, “stemloids” must proliferate at the same rate as non-GSC otherwise, “stemloids” depending whether they proliferate slower or faster than non- GSCs will eventually either disappear from the cell culture or outgrow the non-GSCs rendering either a pure “stemloids” cell line or a pure non- GSCs cell line. In spite of these assumptions, none of the models explain Zheng’s experiment because all of them predict the existence of non-GSCs that will generate clones without SC properties.
 
The “stemness phenotype” model (SPM)
 
The term “stemness” is by itself controversial (Leychkis et al., 2009). In this paper, in order to follow the criteria usually adopted to define cancer stem cells, we use the term “stemness” as the property of having the potential for limitless replication, selfrenewal, multilineage differentiation, and tumorigenicity. Any model regarding the stem cell presence in culture should explain at least 1) the variable percentage of GSCs in the C6 glioma cell line reported by several groups (Table 1, 2) Zheng’s experiment, 3) the conserved tumorigenic property of the cell line over time that might be due to the persistence of at least a rare but constant fraction of GSCs in cell lines.
 
All the models discussed above assume that there are at least two different subpopulations (2 compartment models). The stemloid hypothesis proposes the existence of three subpopulations (non- GSCs, GSCs and stemloids). We propose a “1 compartment model” that we call “Stemness Phenotype Model, SPM” where there is only one cancer cell type. These cells are cells with different stemness phenotype due to random biological variation (Figure 2I). In cultures having thousands to millions of cells, individual cells varies phenotypically (e.g. expression of stem cell markers, sensitivity to drugs, resistance to apoptosis) due to random variability giving rise to the apparent presence of different subpopulations (e.g. SP fraction, CD133+ fraction, drug resistant cells). The stemness depends on the environment where the cells grow and can range from a phenotype resembling a non-GSC to a pure GSC. A prediction of this model is that there are cells having “intermediate phenotypes” between both extremes. This seems to be the case since e.g., some CD133- -a non- GSC trait- cells have self renewal ability that is a GSC trait (Kelly et al., 2009). Thus, all cells have stem cell potential but they require a permissive environment to express specific traits. Moreover, these different phenotypes can interconvert into each other when permissive environmental changes occur (Figure 2II). In 2006, Hill suggested that “it is very possible that, in cancer cells, degrees of stemness exist and that these are variably expressed depending on the environment to which the cells are exposed” (Hill, 2006 ). In agreement with Hill’s conclusion, the SPM proposes that the culture condition modifies the stemness phenotype and dictates the apparent rate of GSCs/nonGSC phenotype. Our hypothesis expands Hill’s conclusions based in theoretical analysis of proliferation kinetics of mixed populations (see above) and new experimental data generated later in several laboratories. At a constant culture condition (e.g. routine serum containing media) the majority of cells adopt a non- GSCs phenotype. Strictly speaking, not all cells in vitro grow under the same, constant culture conditions. For instance, incubation time changes the availability of nutrients and cells should adapt to these changes. In cultures favouring the GSC phenotype (e.g. Serum free + EGF + FGF) cells having a GSCs phenotype proliferate while other cells stop dividing and eventually die due to the harsh conditions. Cells adapt to the changing environment and drastic changes from one environment to another might trigger programmed cell death and only few cells might survive. For example, shifting from serum containing media to serum free media (or similar stem cell media) might be harmful for most cells with non-GSC phenotype. Milder environmental changes might shift the percentage of cells having one phenotype to another. In support of this “adaptation process”, it was recently reported that the in vivo environment changed the selfrenewal capacity of C6 cells (Shen et al., 2008), and the expression of CD133 (Griguer et al., 2008; Qiang et al., 2009; Soeda et al., 2009).
 
Interestingly, it was reported that the human lung carcinoma cell line DLKP contains 3 distinct subpopulations. On prolonged cultures two of them can interconvert to the third one and the growth and attachment properties of the clones themselves varied under the different assay conditions (McBride et al., 1998). Due to the fact that they have different proliferation kinetics, it is likely that the three subpopulations are different phenotypes of the same cell and not true different subpopulations. Unfortunately, the presence of stem cells has not been studied in this cell line. However, the fact that in a cell line a subpopulation having a certain phenotype can interconvert to another phenotype is a strong argument favoring the interconversion among different cell phenotypes proposed by the SPM (Figure 2II).
 
Figure 2: The Stemness phenotype model. I) All cancer cells have stem cell potential and divide symmetrically. Clonal expansion of a single cancer cell generates, due to random biological variation cells having different phenotypes (“stemness”) ranging from a pure GSC phenotype (red oval) to a pure non-GSC phenotype (green oval) depending on the environment (e.g. A, B or C). Environment A represents an environment similar to stem cell media and B represents an environment similar to standard culture conditions. Environment C represents an intermediate condition. II) In this example, three different phenotypes (pure SC, red ovals; pure non-SC, green ovals and an intermediate phenotype, red-green ovals) are represented in different “niches”. All three phenotypes can potentially interconvert at variable degrees (arrows) into each phenotype when permissive changes in the microenvironment occur. III) In vivo, the percentage of each fraction depends on tumor microenvironments (A, B, C) that might promote specifi c phenotypes.
 
How does the SPM brings together experimental data in a single model? The SPM proposes that there are no true different subpopulations of GSCs and non-GSCs but a single cell type that can interconvert to each other depending on the environmental conditions. By doing so, GSCs don’t need to be constantly generated in cell lines and explains why GSCs don’t disappear even when a cell line (e.g. the C6 cell line) has been sub-cultivated thousands of times. Instead, the constant presence is explained by the ability of cancer cells to adopt different phenotypes according to the environment (e.g. different culture conditions and isolation methods used in experiments showed in (Table 1). The same argument explains the conserved tumorigenic property of the C6 glioma cell line over time. The adaptation to changing environments is also critical to interpret Zheng’s experiment where 67 out of 67 subclones obtained after isolation and expansion of single cells in serum containing media were able to induce tumors: Single cells expanded in serum free media did not form clones (but remained quiescent and viable) or formed clones with limited growth but, after shifting to serum containing media, both types of cells were able to form typical tumorigenic clones (Zheng et al., 2007). Thus, their data indicate that most C6 are “cancer stem cells” and the environment dictates the phenotype. One can assume that serum containing media favor proliferation of all cells that allows successful expansion of single cells generating phenotypic diversity in the expanded clonal culture. The phenotypic diversity we postulate is supported by the fact that a) Clones formed from CD133- single cells generate descendant having a mixture of CD133- and CD133+cells (Zheng et al., 2007). b) Both CD133- and CD133+ cells have also self renewal capacity (Chen et al., 2010; Kelly et al., 2009), c) non-SP cells can generate both SP and non-SP cells (Fong et al., 2010; Platet et al., 2007) apparently depending on the culture conditions since there are studies where non-SP cells only produce non-SP cells (Kondo et al., 2004). d) expression of CNS markers (GFAP, Nestin; and NES) vary with culture conditions (Prestegarden et al., 2010) providing strong in vitro experimental evidence that tumor microenvironment might be an important factor in determining the percentage of cells expressing certain stem cell marker and perhaps, affecting the stemness of the cell as our model suggest. Nestin has been used as a glioma stem cell marker (Table 1). Another line of evidence supporting our hypothesis comes from the existence of the “side population” (SP) in glioma cell lines. In several experiments, GSCs have been isolated from the SP cell fraction that has been found to vary between cell lines (Table 1) and it is thought that this fraction are stem cells (Fukaya et al., 2010). To persist, the SP fraction must have proliferation kinetic (e.g. PDT) equal or very similar to the rest of the cells present in the culture. Otherwise, it will either progressively disappear or outgrow the culture. The percentage of the SP fraction increased in serum free media containing both PDGF and bFGF but not in either PDGF or bFGF alone (Kondo et al., 2004). More important, both SP cells as well as non-SP cells can repopulate SP and non-SP cells (Fong et al., 2010; Platet et al., 2007). The SP fraction from the SK-MG-1 cell line has greater proliferative ability (~ 10 times) than non-SP cells when growing in neurosphere media containing EGF and FGF2 (Fukaya et al., 2010) clearly indicating that the SP phenotype is culture condition dependent. In our model, the SP population is simply a fraction of cells with higher stemness phenotype. When incubated in stem cell media (that might not be adequate for the rest of the cells) they survive and generate a cell line with stem-like properties. In conclusion the SPM explains why cell lines obtained from either single cell isolation (e.g. C6 cells) or mixed primary cultures produce cell lines with a mixture of phenotypes.
 
Finally, if we also assume that most cancers might originate from a single cell that becomes a cancer cell (Martínez-Climent et al., 2006), then models based in 2 or 3 compartments should explain not only the origin of each cell subpopulations but also their persistence in several cell lines. The stemloid hypothesis should explain the origin of each of the three cancer cell types: non-GSCs, GSC and stemloids. It is easy to imagine that a single cell may be responsible for the initial cancer and the different phenotypes arise as the tumor grows and create microenvironments favouring one or another phenotype. It is important to notice that the original C6 glioma cell line was isolated from a clonal strain (Benda et al., 1968) providing evidence that a single original tumoral cell was indeed a stem cell able to generate the different phenotypes (and subpopulations) present in the C6 cell line. In 2009, Gupta et al proposed a “plasticity model” enabling bidirectional interconvertibility between CSCs and non-CSCs (Gupta et al., 2009). Although at a first glance it seems very similar to ours, Gupta’s model proposes a unidirectional hierarchy from stem cells to post-mitotic differentiated cells. This unidirectionality predicts that, contrary to Zhengs’s experimental findings, a fraction of isolated single cells will not have stem cell properties. In our model, cancer cells can interconvert regardless of the phenotype providing that a permissive environment allows the transition (Figure 2II). In summary, our hypothesis provides an explanation to several controversial experimental data regarding the presence of GSCs in cell lines and provides and alternative way to reconciliate the cancer stem cell hypothesis.
 
Stem cells in tumors
 
The same analysis we used for cell lines can be extrapolated to this in vivo situation. While pure symmetrical division of a primordial stem cell predicts that any glioma in vivo should have 100% of GSCs, pure asymmetrical division will generate a tumor with only 1 GSC and increasing number of non-GSCs. Contrary to the situation in cell lines, the three possible models discussed above- GSCs that divides symmetrically + differentiation; GSCs that divides asymmetrically and symmetrically, (Figure 1, Figure1B and Figure1D) and the SPM (Figure 2) may occur in vivo because tumors in situ are not subjected to routine passages. All three models support the concept that a tumor can be originated from a single cell and produce cells with different phenotypes. However, the first two models by predicting the existence of non-GSCs, can’t explain Zheng’s experiments unless we assume 1) that only GSCs are able to propagate in vitro when establishing a cell line and 2) once the culture is expanded and non-GSCs appear either by differentiation of GSCs (Figure 1B) or spontaneous symmetrical division (Figure 1D), a very delicate balance exists to prevent the outgrowth of the faster cell subpopulation and maintain a low but constant fraction of GSCs. Instead, the SPM proposes that in vivo all glioma cells have stem cell properties but different stemness phenotype (but not true non-GSCs) depending on the microenvironment (Figure 2III).
 
Figure 1: Predicted composition of a cell culture after expansion of a single cell according to the mode of cell division. (A) By symmetrical division a non-GSC (green oval) will produce a culture composed of only non-GSCs. (B) A GSC (red oval) will also produce only GSCs and, non-GSCs may arise only by differentiation of GSCs (box) resembling asymmetrical division. (C) Asymmetrical division of a non-GSC does not occur by defi nition. (D) Clonal expansion of a single GSC will produce a cell culture containing increasing number of non-GSC and only one GSC unless the GSC at some point divides symmetrically (box).
 
Are all cancer cells in vivo stem cells? A key issue that need to be addressed in order to find which of the above mentioned models better explain what occurs in vivo is whether tumors always contain stem cells (“constant presence”) or not (“variable presence”) and what is the percentage (ranging between > 0 – 100%) of stem cells in a given tumor that contains GSCs (e.g. “constant percentage” or “variable percentage”). At least six different situations can be account (A-F in Table S1). With few exceptions literature data provide evidence that cancer stem cells (CSCs) have been isolated from almost all gliomas specimens when they have searched for them (Table 3). The few negative results could be due to technical reasons (e.g. in some tumors, the cells cannot withstand the process required to generate a single-cell suspension for culturing) rather than a true lack of GSCs in the tumor. This strongly suggests that the presence of CSCs might be constant and excludes situations D-F limiting the possibilities to only three situations (A-C, Table S1). Consistent with situations B or C, early studies detecting stem cell markers and/or isolating spheres from primary cultures showed that a relatively small percentage (no more than 25%) is probably stem cells (Al-Hajj and Clarke, 2004; Yuan et al., 2004 ). The fact that CD133- cells can give origin to both CD133- and CD133+ cells (Zheng et al., 2007) and the recent finding that CD133- cells express a truncated variant of the CD133 protein not recognized by some antibodies (Osmond et al., 2010) makes this approach unreliable. The use of the SP or Nestin as specific stem cell markers for isolating/detecting GSCs in tumors are also unreliable (See above). If we consider the increasing evidence that the non-SP fraction and CD133- cells, can generate the SP fraction and CD133+ cells respectively, the natural conclusion is that not only the SP fraction or CD133+ cells but all glioma cells might have stem cell properties. Therefore, at present the growing experimental evidence favours a model where tumors have “constant presence” and “constant percentage= 100%” (situation A in Table S1) that fits the SPM. The two other models (Figure 1B and Figure 1D) do not explain this situation because they predict the existence of non-stem cells. The model in Figure 1B (without assuming that a fraction of GSCs “differentiate” producing non-GSCs (box), by predicting that all the progeny are the same, do not explain the different phenotypes (degree of stemness) found in tumors. The ideal experiment to address this key issue should be by isolating single cells from a huge numbers of fresh glioma tumors, and by determination of the percentage of the number of clones having stem cell properties. It is expected that if the tumor is a mixture of GSCs and non-GSCs a certain number of clonal lines will proliferate but they will never have stem cell properties. The main concern is that non-GSC might not survive the hard condition required to propagate single cells. The number of isolated single cells that do not proliferate in vitro might be informative to address this concern. In addition, isolated single cells can be grown in different culture media that might promote non-GSCs growth and overcome this limitation.
 
Table 3: Isolation of cancer stem cells from human brain tumors. With few exceptions, cancer stem cells has been isolated from 100% of all tumors.
 
Experimental data already provide evidence supporting the idea that a single cell with stem cell properties can originate a new tumor in vivo and rule out the need of two or more different subpopulations for tumor growth. Thus, it is also likely that tumors in vivo originate from a single cell (stem cell, stem-like cell or non- GSC that mutated and acquired stem cell properties by reactivating latent stem cell program (Nicolis, 2007) and all the descendants are indeed cells having stem cell properties but very different phenotype due to microenvironmental tumor heterogeneity such as perivascular niches that migh promote stemness (Charles et al., 2010).
 
Implications of the SP model
 
As discussed above, the original hope that killing GSCs will eradicate the tumor has been challenged by the fact that surviving non-GSC might be able to induce tumor relapse because the Hayflick limit is not a barrier for preventing symptomatic tumoral masses (Hanahan and Weinberg, 2000; Withers and Lee, 2006). All models predict that survival of a single cell might induce tumor relapse. Since models B and D in Figure 1 predict that non-GSCs are being generated constantly, these newly formed cells are at early stage of the Hayflick limit (approximately 60-70 divisions) and able to divide enough number of times to generate a tumor mass responsible for symptoms. It is estimated that the volume of 1x109 cells (the result of 30 divisions from a single cell) will produce a tumor volume of approximately 1 ml (Withers and Lee, 2006) and 60-70 divisions can in theory produce large tumoral masses (Hanahan and Weinberg, 2000). Targeting specific cell subpopulation based on stem cell markers (e.g. CD133+) is also unlikely to be successful because cells lacking a specific stem cell marker can also produce (by inter conversion) descendants with stem cell properties. From the clinical point of view, if true, the SPM will change the strategy for finding new therapeutic strategies at the preclinical level. Instead of isolating SP cells or CD133+ cells from a cell line as source of stem cells to identify vulnerabilities, it might be equally or even more informative, to analyse established glioma cell lines or patient derived cell lines growing in different culture conditions that generates different phenotypes resembling in vivo microenvironments such as hypoxic regions (Heddleston et al., 2009; Kim et al., 2009; Seidel et al., 2010) or perivascular niches (Charles et al., 2010) that contributes to the maintenance of stemness. It might also be more successful to design therapies that kill all glioma cells in such environments than to identify a potential specific stem cell killer agent that will only kill a subpopulation of cells having a particular stemness phenotype.
 
Funding
 
This work was supported by grants from the Swedish Research Council and the Karolinska Institute.
 
References
 













































 
 
 
This Article
DOWNLOAD
» XML (75 kB)
» PDF (1,828 kB)
» Citation
   
CONTRIBUTE
» Write a Response
» Read other Responses
» Publishing with OPG
   
SHARE
» E-mail This Article
» Print This Article
» Rights and Permissions
   
Share
EXPLORE
Related Article at
» Pubmed
» DOAJ
» Scholar Google
 
 
 
Untitled Document
| More
OMICS Publishing Group: An Open Access Publisher
OMICS Publishing Group is the member of/publishing partner of/source content provider to
All Published content, except where otherwise noted, is licensed under a Creative Commons Attribution License.