Get to Know About the Molecular Cytogenetic Analysis for Acute Lymphoblastic Leukemia. This test will diagnose and monitor the treatment response of patients.
Get to Know About the Molecular Cytogenetic Analysis for Acute Lymphoblastic Leukemia. This test will diagnose and monitor the treatment response of patients.
This presentation contains all the updated information regarding ongoing treatment protocol, HSCT, Antibiotic prophylaxis, upcoming targeted therapies related to AML
Chronic myelogenous leukemia (CML) - pluripotential stem cell disease
A malignancy the treatment of which has been revolutionised over the last decade.
Here is a comprehensive discussion on the disease
onco-nephrology this missed part of our spectrum of care to very specific group of patients>>>cancer patients
this is introduction to types of chemotherapy, causes and how to manage AKI caused by these drugs
INTRODUCTION
DNA VACCINES
GENE THERAPY
TIME LINE OF DEVELOPING GENE THERAPY
GENE THERAPY STRATEGIES
TECHNOLOGY OF CLASSICAL GENE THERAPY
PRINCIPLES OF GENE TRANSFER
VECTORS
VIRAL VECTORS
NON-VIRAL VECTORS
APPLICATIONS OF GENE THERAPY
ETHICAL IMPLICATIONS
THE FUTURE
CONCLUSION
REFERENCES
This presentation contains all the updated information regarding ongoing treatment protocol, HSCT, Antibiotic prophylaxis, upcoming targeted therapies related to AML
Chronic myelogenous leukemia (CML) - pluripotential stem cell disease
A malignancy the treatment of which has been revolutionised over the last decade.
Here is a comprehensive discussion on the disease
onco-nephrology this missed part of our spectrum of care to very specific group of patients>>>cancer patients
this is introduction to types of chemotherapy, causes and how to manage AKI caused by these drugs
INTRODUCTION
DNA VACCINES
GENE THERAPY
TIME LINE OF DEVELOPING GENE THERAPY
GENE THERAPY STRATEGIES
TECHNOLOGY OF CLASSICAL GENE THERAPY
PRINCIPLES OF GENE TRANSFER
VECTORS
VIRAL VECTORS
NON-VIRAL VECTORS
APPLICATIONS OF GENE THERAPY
ETHICAL IMPLICATIONS
THE FUTURE
CONCLUSION
REFERENCES
Gene therapy involves the insertion of a functioning gene into cells to correct a cellular dysfunction
KEY WORDS : GENETICS, MUTATION , GENETIC ENGINEERING.
Gene therapy is now bringing a revolutionary treatment options to most of genetic related diseases including cancers, offering the theoretical advantage of the possibility of achieving the therapeutic goal by a single treatment.
Clustered regularly interspaced short palindromic repeat is a recent genome-editing approach have attracted significant attention among the researchers due to their potential to cure all genetic related diseases including cancer by editing the genome in a way based on RNA-guided nuclease
In the past 10 years, there has been tremendous progress made in the field of gene therapy. Effective
treatments of Leber congenital amaurosis, hemophilia, and spinal muscular atrophy have been largely based on
the efficiency and safety of adeno-associated vectors. Myocardial gene therapy has been tested in patients with
heart failure using adeno-associated vectors with no safety concerns but lacking clinical improvements. Cardiac
gene therapy is adapting to the new developments in vectors, delivery systems, targets, and clinical end points and
is poised for success in the near future
A normal cell can be transformed into a cancerous cell. Discuss the therapeutic strategies that are employed to target the cellular transformation process for cancer prevention and treatment.
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Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
2. Introduction
Cancer is still one of the most devastating diseases in the world.
According to the Centers for Disease Control and Prevention (CDC), cancer incidence in the
U.S.A. was 7,178,172 from 2006 to 2010, with mortality reaching 2,830,559.
The existing therapeutic approaches, such as surgery, thermotherapy, chemotherapy, and
radiotherapy, often have severe side effects, such as cytotoxicity to normal cells and strong host
immune responses.
Most critically, some cancers barely respond to these therapies and so alternative therapeutic
approaches are needed.
Gene therapy is one such attempt.
2
3. Gene Therapy
Gene therapy is one of the frontiers of modern medicine.
A technique for correcting defective genes that are responsible for disease development
The most common form of gene therapy involves inserting a normal gene to replace an
abnormal gene
Gene therapy consists of three basic steps:
1. Constructing a gene carrying vector
2. Transferring genes into target cancer cells with the vector
3. Expressing gene products to kill cancer cells
3
5. Gene-carrying vectors
Constructing an effective vector for carrying therapeutic genes is essential for successful gene
therapy.
Gene-carrying vectors can be divided into two categories:
Non-viral vectors
Such as naked plasmids, microbubbles, nanoparticles, liposomes, and polymers, are safe, low-cost,
and offer large insert size of genes; however, in vivo gene transfection and expression is inefficient
and transient, despite low immunogenicity
Viral vectors
Such as adenoviral vectors, retroviral vectors, and lentiviral vectors, provide effective gene
transduction and expression; however, they have several disadvantages, including high
immunorejection, possible tumorigenicity, uncertain insertional mutagenesis, and limited
constructive sizes for gene insertion.
These disadvantages have prevented translation into clinical practice
5
6. Cont..
It is imperative that gene-carrying vectors have
(1) high transferring ability,
(2) low immunorejection
(3) long-term gene expression.
Adeno-associated virus (AAV) gene-carrying vectors meet these requirements.
6
7. Adeno-associated virus (AAV)-mediated gene therapy
A promising approach to treat a variety of diseases and cancers.
AAV-mediated cancer gene therapies have rapidly advanced due to their superiority to other
gene-carrying vectors, such as
the lack of pathogenicity,
the ability to transfect both dividing and non-dividing cells,
low host immune response,
long-term expression.
AAVs have been successfully used to deliver and transfer a variety of therapeutic genes to cancer
cells, including suicide genes, anti-angiogenic genes, and immune-related genes, to inhibit
tumor initiation, growth, and metastasis.
7
8. Biology of AAVs
First discovered in the 1960s
Replication-deficient and belongs to the family of Parvoviridae.
As the best known representative of all the AAVs, AAV2
Contains a single stranded DNA genome comprising inverted terminal repeats (ITRs)
Two open reading frames encoding replication and capsid proteins.
The structure of AAV2 has been determined to 3-Å resolution
8
9. Structure of the AAV-2 subunit and comparison with related structures.
(a) Experimental electron density for AAV-2
(b) Ribbon drawing of the AAV-2 subunit. The locations of the neighboring symmetry axes are shown.
(c) Comparison of the backbones of AAV-2 (red) and canine parvovirus (cyan).
9
10. Advances of AAV vectors
The AAV based gene delivery systems are more attractive compared to other vectors.
More benefits were discovered using AAV vectors such as
more safety due to the lack of pathogenicity,
more varied host and cell-type tropisms,
long-term gene expression,
ability to transfect both dividing and non-dividing cells,
absence of enormous immune response.
10
11. Development of AAV-mediated gene therapy
A variety of preclinical experiments involving AAV-based gene therapies have been carried out.
First construction of AAVs as vectors for gene transfer was repoted in 1984
By utilizing AAV vectors, scientists successfully transduced a therapeutic gene, cystic fibrosis
transmembrane regulator (CFTR), into the airways of rabbits and monkeys.
Expression of CFTR was detected for as long as 6 years in the airways. Subsequently, the first trial of
AAVmediated CF gene therapy was reported in 1995.
Since then, extensive research has been done on gene/vector delivery routes, pathophysiologic
effects, and AAV vector immune profiling.
Glybra was the first licensed gene therapy product with an AAV vector, designed and used to
supplement deficiency in lipoprotein lipase (LPL).
In recent years, gene therapies with different subtypes of AAV vectors have been reported for
treatments of a variety of diseases.
11
13. Advances in AAV-mediated cancer gene therapy
There are different types of AAV-mediated gene therapies
AAV-mediated suicide gene therapy
AAV-mediated antiangiogenesis gene therapy
AAV-mediated immune gene therapy
AAV-mediated targeting gene therapy
13
14. AAV-mediated suicide gene therapy
Suicide gene therapy, also called gene-directed enzyme prodrug therapy (GDEPT) or molecular
chemotherapy, is currently the most promising strategy for genetic treatment of different
cancers.
GDEPT relies on the intratumor delivery of a transgene encoding an enzyme, which then
activates a systemically-delivered prodrug that inhibits DNA polymerase and blocks DNA
replication in tumor cells.
The herpes simplex virus thymidine kinase gene/ganciclovir prodrug (HSV-tk/GCV) system is an
excellent example of the clinical application of GDEPT.
The AAV-mediated HSV-tk/GCV therapeutic system generates strong antitumor efficacy.
One of the most attractive elements of the HSV-tk/GCV therapeutic system is its bystander
effect, i.e., the killing of untransduced tumor cells surrounding transduced tumor cells.
14
15. The AAV/HSV-tk and GCV suicide gene system. The AAV vector is constructed carrying an HSV-tk gene
which is then transduced into the target cells. Cell killing is achieved by inhibiting the cell cycle and
promoting cell apoptosis and GCV is converted to a GCV triphosphate.
15
16. AAV-mediated antiangiogenesis gene therapy
Angiogenesis often accompanies the growth of tumors to provide oxygen and nutrients,
causing rapid proliferation of cancer cells.
Antiangiogenic therapy was developed to starve tumor cells.
Vascular endothelial growth factor (VEGF), an important mediator of angiogenesis in both
healthy and diseased tissues, is a crucial antitumor target.
A study demonstrated that a single intravenous administration of AAV/VEGF-Trap led to long-
term efficacy and permitted not only suppression of primary tumor growth but also prevention
of pulmonary metastasis.
16
17. AAV-mediated immune gene therapy
Immune gene therapy has advanced rapidly over the past decades and is becoming an
important approach in the treatment of different cancers.
AAV-mediated immune gene therapy is based on the successful activation of the host immune
system upon transfer of therapeutic genes to targets cells, including cytokines, immuno-genic
cell surface molecules, and tumor antigens
17
19. AAV-mediated targeting gene therapy
To date, the primary weakness of systemic delivery of AAV-based therapeutic genes is low
tumor-targeting efficiency.
Specificity may be improved by adding tumor-specific promoters to AAV vectors.
To date, there are a variety of AAV-mediated therapeutic genes driven by various tumor-
specific promoters, such as human telomerase reverse transcriptase (hTERT), extracellular
domain of tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) ,tumor-targeting
motif, including RGD, and tenascin C (TnC).
This target-specific AAV-gene therapy can significantly suppress tumor growth.
19
20. Combination treatment with multiple
genes and chemotherapies
To improve antitumor efficacy, recent efforts have focused on combining AAV-mediated multi-gene therapies with
chemotherapies.
Several studies reported such combination treatment:
AAV based apoptin and IL24
HSV-tk and endostatin
TRAIL and cisplatin
P125A-endostatin, a mutant endostatin
P125-endostain and carboplatin
Type I interferon beta (IFN-beta) and trichostatin A (TSA)
The survivin mutant Thr34Ala and oxaliplatin
In addition, several studies demonstrated that combining AAV-based gene therapy with radiation therapy and
focused ultrasound therapy can significantly increase cytotoxicity to tumor cells.
20
21. Clinical trials of AAV-mediated gene therapy
Clinical applications of AAV-mediated gene therapies show great promise in the treatment of
some life-threatening diseases, including
hemophilia B,
Leber congenital amaurosis,
Parkinson’s disease, and different cancers.
21
22. Parkinson’s disease
a severe neurodegenerative disorder, clinically characterized by degeneration of dopamine neurons
Neuturin is a functional analogue of glial cell-derived neurotrophic factor (GDNF), which protects
dopamine neurons from degeneration.
The delivery of AAV-based neuturin promoted long-term motor function improvement in a phase I
clinical trial.
A double-blind, randomized, controlled trial lasting for about 2 years proved that AAV2/neuturin
gene therapy for moderately advanced Parkinson’s disease is safe and feasible.
The loss of L-dopa is one of the main causes of progressive Parkinson’s disease, a response to
declining levels of aromatic amino acid decarboxylase (AADC).
A clinical phase I study of AAV2-AADC gene therapy showed safe transgene expression over 4 years.
These AAV-based clinical trials have validated the promising potential of gene therapies in Parkinson’s
disease.
22
23. Concluding remarks
Compared to other vectors, AAV offers several advantages, including
low pathogenicity,
limited immunogenicity,
efficient gene transfer,
long-lasting gene expression.
Tremendous efforts have led to the great development of AAV-mediated gene therapy in
different cancers.
Although obstacles remain, promising preclinical and clinical results have opened new avenues
for the efficient management of malignancy using AAV-integrated gene therapy technology.
23
24. Reference
Luo, J., Y. Luo, J. Sun, Y. Zhou, Y. Zhang and X. Yang. 2015. Adeno-
associated virus-mediated cancer gene therapy: Current status.
Cancer Letters, 356: 347–356.
24