Basis of viral oncogenesis and the most common viruses causing cancer and their mechanism of causing cancer. Helpful for undergraduate and postgraduate teaching.
An oncovirus is a virus that can cause cancer. This term originated from studies of acutely transforming retroviruses in the 1950–60s, often called oncornaviruses to denote their RNA virus origin. It now refers to any virus with a DNA or RNA genome causing cancer and is synonymous with "tumor virus" or "cancer virus".
An oncovirus is a virus that can cause cancer. This term originated from studies of acutely transforming retroviruses in the 1950–60s, often called oncornaviruses to denote their RNA virus origin. It now refers to any virus with a DNA or RNA genome causing cancer and is synonymous with "tumor virus" or "cancer virus".
The Epstein–Barr virus (EBV), also called human herpesvirus 4 (HHV-4), is one of eight known human herpesvirus types in the herpes family, and is one of the most common viruses in humans.
Viruses and Cancer: Introduction to OncovirusesAparna Dubey
The presentation describes about Oncoviruses or the cancer causing viruses with emphasis on HPV ( Human papillomavirus ) responsible for Cervical Cancer.
The Epstein–Barr virus (EBV), also called human herpesvirus 4 (HHV-4), is one of eight known human herpesvirus types in the herpes family, and is one of the most common viruses in humans.
Viruses and Cancer: Introduction to OncovirusesAparna Dubey
The presentation describes about Oncoviruses or the cancer causing viruses with emphasis on HPV ( Human papillomavirus ) responsible for Cervical Cancer.
A brief exploration of the way some modern viruses act and ancient viruses have acted to benefit their hosts - particularly humans - today and through evolutionary history, by various means (such as targeted destruction of pathogenic bacteria and introduction of new genetic material).
It contains introduction on basic molecular biology followed by detailed description on discovery , mechanism of oncogene activation, their effect on tumerogenesis , name of important oncogenes , their detection and targeted therapies against oncogenes in treating cancer
here i discussed some human oncogenic viruses , their epidemeology, life cycle, treatment, prevention and control. . oncogenic viruses are cancer causing viruses.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
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.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
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.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
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
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
2. Virus family Human cancer
Papovaviridae
Human papilloma virus • Cervical ca
• Other genital tract ca
• Esophageal ca
• Laryngeal ca
• Oropharyngeal ca
Merkel cell virus Merkel cell ca of skin
Herpesviridae
Epstein Barr virus • Burkitt’s lymphoma
• Hodgkins’s disease
• Nasopharyngeal ca
Human Herpesvirus -8 • Kaposi’s sarcoma
• Primary effusion lymphoma
Hepadnaviride
Hepatitis B virus Hepatocellular carcinoma
Retroviridae
HTLV -1 Adult T-cell leukemia/lymphoma
HIV AIDS related malignancies
Flaviviridae
Hepatitis C Hepatocellular carcinoma
DNAVirusesRNAViruses
3. Basic concepts
• Proto-oncogenes –
• Oncogenes –
• Tumour suppressor genes – supress any abnormal proliferation of cells(eg. p53, Retinoblastoma)
• Apoptosis regulatory genes – eg. bcl-2 (anti-apoptotic) and bax (pro-apoptotic genes)
• DNA repair genes
• Normal cellular genes whose products promote cell proliferation.
• Over-activation can lead to transformation of host cells
• Mutant or overexpressed versions of proto-oncogenes that function autonomously
without a requirement for normal growth-promoting signals
• When present in viral genome they are designated as V-onc
• Oncoproteins cause continuous stimulation of nuclear transcription factors that
cause increased expression of growth-promoting genes.
4. • Cell cycle is controlled by checkpoints at
different stages
• Any stress or damaged DNA is detected
at any checkpoint results in increased
protein p53 production.
• p53 is a tumour suppressor gene that
stops the progression of the cell cycle
(G1 arrest) and starts repair
mechanisms for the damaged DNA by inducing the expression of DNA repair genes
• If this DNA cannot be repaired, then it ensures the cell undergoes apoptosis and can
no longer replicate.
• The p53-encoding tumor suppressor gene is the most commonly mutated gene in
human cancer.
5. • Cell cycle is also closely regulated by Cyclins
which by activating cyclin-dependent kinase (CDK)
enzymes control cell progression
• Rb restricts the ability of a cell to progress from G1
to S phase in the cell cycle. CDK phosphorylates
Rb to pRb, making it unable to restrict cell
proliferation. This allows cells to divide normally in
the cell cycle.
• p16-INK4A a cell-cycle regulatory protein that
interacts with CDK4 and CDK6, inhibiting their
ability to interact with cyclins D.
6. Telomere and Telomerase
• Eukaryotic telomeres are usually identified as the
“capping function”
• They protect chromosome ends from DNA degradation
and fusion with other chromosomal ends
• Their length serves as an intrinsic biological clock that regulates the life span of the cell, i.e.
they provide limits on the number of replications a cell can go through.
• Telomere repeats are lost with each round of cell replication.
• Enzyme “Telomerase” causes elongation of telomeres, but not completely
• It is a ribonucleoprotein with reverse transcriptase activity, is composed of two main parts –
a telomere RNA component and a telomere reverse transcriptase
• Most somatic cells express insufficient telomerase, reactivation in malignant conditions
7. • Selective tropism for epithelium of skin (squamous epithelium) and mucus membrane
• Benign warts to malignant condition
• Non-enveloped, Icosahedral symmetry, ds-circular DNA
Papillomavirus
• Viral genome
• Early region (E1 –E7) Non-structural proteins
• E6 protein degrades p53 gene product
• E7 protein binds to RB gene product
• Late region (L1, L2) structural proteins
• L1 – Major capsid proteins
• L2 – Minor capsid proteins
8. Human papillomaviruses • Cervical carcinoma
• Other genital tract carcinoma
-- Anal, Vulval/Vaginal, Penile
• Esophageal carcinoma
• Laryngeal carcinoma
• Oropharyngeal carcinoma
• Types 1, 2, 4, and 7 cause benign squamous papillomas (warts) in humans
• Genital warts → low malignant potential and are a/w low-risk HPVs (HPV type-6 & -11).
• Squamous cell carcinoma of the cervix and anogenital region are a/w high-risk HPVs
(types-16 & -18)
9. E6
E7
p53 Bax
p21
Apoptosis
RB-E2F
CyclinD/
CDK4
Growth
arrest
Increased
telomerase
activity
• E6 enhances p53 degradation
• E6 also stimulates the expression of
TERT, the catalytic subunit of
telomerase
• E6 from high-risk HPV types has a
higher affinity for p53
• p21 tumour suppressor gene stop
signal for mitosis in mutated cell
• E7 inhibits the tumor suppression gene
– RB gene (retinoblastoma gene)
• Displaces the E2F transcription factor
that are normally sequestered by RB
10. • In benign warts, the HPV genome is maintained in a non-integrated
episomal form
• In cancers, the HPV genome is randomly integrated into the host genome,
which interrupts a negative regulatory region in the viral DNA, resulting in
overexpression of the E6 and E7 oncoproteins.
• Cells in which the viral genome has integrated show significantly more
genomic instability → pro-oncogenic mutations in host genome.
11. Vaccines
Sub-unit vaccine composed of HPV L1 proteins (viral capsid)
produced in vectors by DNA recombinant technology
• Cervarix – L1 proteins of HPV 16, 18 expressed in Baculovirus.
Schedule – 0, 2 and 6 months
• Gardasil – L1 proteins of HPV 6, 11, 16, 18 expressed in Saccharomyces cerevisiae.
Schedule – 0, 1 and 6 months
• 9–26 yrs of females and males recommended in US
• Gardasil 9 (2014) – against HPV 6, 11, 16, 18, 31, 33, 45, 52, 58.
12. • Non-enveloped ds-DNA virus causing subclinical infection in childhood
• JCV infects 40% to 86% of the general population worldwide.
• BK virus has more prevalence than JC virus and affects children <10yrs of age
• Possible route of transmission – respiratory route
• 5HT2A receptor (glial cells, astrocytes, B lymphocytes, platelets & kidney epithelial cells)
• Viral genome gets integrated to host genome and persists for life (kidney, BM & brain).
• JCV is detected in urine of one third of healthy individuals.
Polyomavirus
13. • Reactivation occurs during pregnancy – asymptomatic
shedding
• Severe immunosuppression – AIDS, Organ transplant
recipients, advanced lymphoid malignancy
demonstrable shedding in urine
• Reactivation leads to lytic productive infection of
oligodendrocytes and astrocytes leading to multiple foci
of demyelination in brain
• JC virus – Progressive Multifocal Leukoencephalopathy
• BK virus causes
Haemorrhagic cystitis in BM transplant patients
Polyoma associated nephropathy in renal transplant
recipients
Atypical
astrocytes
Intra-
nuclear
inclusion
bodies
14. • Enveloped ds-DNA virus with icosahedral
symmetry
• In the oropharynx, EBV infects epithelial cells,
where it actively replicates and cause lysis,
infected epithelial cells infect B cells.
Epstein barr virus
• It binds to CR2 or CD21 (of B cells) through gp360 on its surface
• Small number of memory B cells retain the virus in form of episome and become
latently infected (1 to 50 B cells per million)
15. • EBV nuclear antigen (EBNA) 1 protein
binds to viral DNA at oriP site and
allows the EBV genome to be
maintained in the B cell through
generations, also it blocks its own
degradation by proteasomes
• EBNA-2 up-regulates the expression
of EBV latent membrane protein
(LMP) 1 and LMP-2
• LMP-2 prevents reactivation of EBV
from latently infected cells
16. LMP-1
Acts as an
oncogene
On surface of
infected cells
as CD 40-R
Activation of
NF-ĸβ & JAK-
STAT pathway
Upregulates
Bcl-2
Pro-
angiogenic
factors like
VEGF
Survival &
Proliferation of
B-cells
Anti-apoptotic
Neo-
vascularization
B-cell growth
18. • 70% to 85% of hepatocellular carcinomas (HCC) worldwide are caused by HBV or HCV.
• Do not encode any viral oncoproteins.
• HBV DNA randomly integrates with the host genome, HCV RNA remains unintegrated
• HCC has multifactorial causation but dominant effect seems to be immunologically
mediated chronic inflammation with hepatocyte death followed by compensatory
regenerative process
• In regenerative process a plethora of growth factors, cytokines, chemokines etc are
produced by activated immune cells that promote cell survival, tissue remodeling, and
angiogenesis.
• The activated immune cells also produce reactive oxygen species → mutagenic.
Hepatitis B & C viruses
19. • Mediators also cause activation of the nuclear factor-
κB (NF-κB) pathway in hepatocytes
• The HBx gene in HBV genome hepatocellular has
been shown to cause HCC in mice.
• HBx can directly or indirectly activate a variety of
transcription factors and several signal transduction
pathways
• May interfere with p53 function
• In addition, viral integration can cause secondary rearrangements of chromosomes,
including multiple deletions → loss of unknown tumor suppressor genes.
20. • Human T-cell leukemia virus type 1 (HTLV-1), is firmly implicated in the
pathogenesis of adult T-cell leukemia/lymphoma (ATLL)
• Retrovirideae – enveloped, spherical virus with 2 identical copies of ss-RNA
• MOT – Sexual intercourse, blood products.
• Leukemia develops in 3% to 5% of the infected individuals, after a long
latent period of 40 to 60 years.
• Preferentially affects the CD4+ TH cells
HTLV-1
21. • Integration in host chromosomes is random (the viral DNA is found at
different locations in different cancers), the site of integration is identical
within all cells of a given cancer.
• Transcription activator (tax) gene essential for viral replication
• tax gene product modulates host cell function
• Affected cells express large quantity of IL2-receptors
LTR LTRgag pol env tax
22. Tax
protein
Inactivates cell cycle inhibitors
p16/INK4a
Activates cell cycle
enhancer -CyclinD
Activates NF-ĸβ, transcription factor
regulating anti-apoptotic genes
Interferes with DNA
repair pathway