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
An oncogene is a gene that has the potential to cause cancer. In tumor cells, they are mutated or expressed at high levels. Most normal cells undergo a programmed form of rapid cell death (apoptosis) when critical functions are altered.
ONCOGENE AND PROTOONCOGENE
P53 GENE AND ITS APPLICATION IN CANCER ETIOLOGY
TUMOUR SUPPRESSOR GENE AND BCA AND BAC GENE AND ITS APPLICATION ON THE APOPTOSIS AND DEATH RECEPTORS
An oncogene is a gene that has the potential to cause cancer. In tumor cells, they are mutated or expressed at high levels. Most normal cells undergo a programmed form of rapid cell death (apoptosis) when critical functions are altered.
ONCOGENE AND PROTOONCOGENE
P53 GENE AND ITS APPLICATION IN CANCER ETIOLOGY
TUMOUR SUPPRESSOR GENE AND BCA AND BAC GENE AND ITS APPLICATION ON THE APOPTOSIS AND DEATH RECEPTORS
Cancer is mainly caused by the conversion of proto-oncogenes into oncogenes. The process is known as oncogenesis.
This slide will help to get an idea about oncogenesis and also the proto-oncogenes which get converted.
Introduction
History
Tumor suppressor gene- pRB
- RB gene
- Role of RB in regulation of cell cycle
- Tumor associated with RB gene mutation
Tumor suppressor gene- p53
- What is p53 gene?
- Function of p53 gene
- How it regulates cell cycle
- What happen if p53 gene inactivated
- Cancer associated with p53 mutation
- Conclusion
- References
Cancer is mainly caused by the conversion of proto-oncogenes into oncogenes. The process is known as oncogenesis.
This slide will help to get an idea about oncogenesis and also the proto-oncogenes which get converted.
Introduction
History
Tumor suppressor gene- pRB
- RB gene
- Role of RB in regulation of cell cycle
- Tumor associated with RB gene mutation
Tumor suppressor gene- p53
- What is p53 gene?
- Function of p53 gene
- How it regulates cell cycle
- What happen if p53 gene inactivated
- Cancer associated with p53 mutation
- Conclusion
- References
Basis of viral oncogenesis and the most common viruses causing cancer and their mechanism of causing cancer. Helpful for undergraduate and postgraduate teaching.
Carcinogenesis
Theories of carcinogenesis
Hallmarks of cancer
Important Oncogenes
RB & p53 genes
Metastasis
Aetiology and Pathogenesis of cancer
Tests for carcinogenicity
How to repair damaged DNA?
Basic DNA repair mechanism
Repair of double stranded break
Role of human papillomavirus and tumor suppressor genesishita1994
Oral cancer is synonymous to Squamous Cell Carcinoma (SCC) of oral mucosal origin that accounts for more than 90% of all malignant presentations at the aforementioned anatomical sites.
More than 300,000 new cases worldwide are being diagnosed with oral SCC (OSCC) annually.
Approximately, 30,000 (US) & 40,000(EUROPE).
Oral cancer is estimated by the WHO to be the 8th most common cancer worldwide.
In India & other Asian countries, oral & oropharyngeal carcinomas (OCs) comprise up to half of all malignancies, with this particularly high prevalence being attributed to the influence of carcinogens & region-specific epidemiological factors, especially tobacco & betel quid chewing.
This presentation explores a brief idea about the structural and functional attributes of nucleotides, the structure and function of genetic materials along with the impact of UV rays and pH upon them.
THE IMPORTANCE OF MARTIAN ATMOSPHERE SAMPLE RETURN.Sérgio Sacani
The return of a sample of near-surface atmosphere from Mars would facilitate answers to several first-order science questions surrounding the formation and evolution of the planet. One of the important aspects of terrestrial planet formation in general is the role that primary atmospheres played in influencing the chemistry and structure of the planets and their antecedents. Studies of the martian atmosphere can be used to investigate the role of a primary atmosphere in its history. Atmosphere samples would also inform our understanding of the near-surface chemistry of the planet, and ultimately the prospects for life. High-precision isotopic analyses of constituent gases are needed to address these questions, requiring that the analyses are made on returned samples rather than in situ.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Comparing Evolved Extractive Text Summary Scores of Bidirectional Encoder Rep...University of Maribor
Slides from:
11th International Conference on Electrical, Electronics and Computer Engineering (IcETRAN), Niš, 3-6 June 2024
Track: Artificial Intelligence
https://www.etran.rs/2024/en/home-english/
Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
2. HEADINGS
• INTRODUCTION
• HISTORY
• MECHANISMS OF ACTIVATION
• CLASSIFICATION OF ONCOGENE
• LIST OF ONCOGENES
• ONCOGENIC MICROBES
• DETECTION OF ONCOGENES
• CLINICAL IMPLICATIONS
4. PARTS of
CHROMOSOME
Metaphase arrest (by
colchicine)chromosom
e=,if treated with
trypsin and stained
with Giemsa shows 2
sister chromatids
joined together at the
centromere and
having light and dark
regions called bands
which itself have
several subbands.
Sister chromatids
7. ORGANIZATION
OF GENE
Gene is part a part
of DNA which
codes for a
protein.It has
expressing
sequences(exons)
interspersed by
intervening
sequences(introns)
8. LOCATION OF
GENE
Each chromosome
has two
sets,likewise each
gene also has two
sets.The location of
the gene in
chromosome is
called a locus
where one allele of
the gene resides
10. INTRODUCTION
• Normally chromosome contains genes which
promote growth of the cell and cell survival.
These are called proto-oncogene.
• Proto-oncogenes are under strict control and
are activated for a short period of time on a
particular part of cell cycle.
• If this control over them is lost, the proto-
oncogene is converted to an oncogene.
• Product of the oncogene is oncoprotein.
11. HISTORY
• In 1911,Peyton
Rous prepared cell-
free filtrate from
sarcoma of chicken
• Injection of this cell
free filtrate to
healthy chicken
caused sarcoma
Nobel Prize in
1966
12. Cont.
• In 1958 Hary Rubin and
Howard Temin showed
morphological changes
in chicken embryo
fibroblast by infection
with RSV
13. Cont.
• C-src was found to
be the normal
counterpart of v-src
• Conversion of
normal
protooncogene c-
src to oncogene v-
src causes sarcoma.
• Transmission of v-
src from one host
to another is by the
process of
transduction
14. MECHANISMS OF ONCOGENE
ACTIVATIONS
• 3 mechanisms
1. Mutation:
a) It is insertion or deletion or missence
b) Affect only one allele; i.e.,heterozygous
c) Affects only one codon or clustered in
neighbouring codons
15. Cont.
2)Gene amplification:
a) Here the number of the copies of the gene
gets amplified
b) Oncoprotein is normal but present in
excessive amount.
c) Example is Her2/neu amplification in breast
cancer.
19. Growth factors
Growth
Factors
Source Function
EGF Platelets,macro
phages
Mitogenic for
keratinocytes and
fibroblast
TGF-a Macrophages,Tl
ymphocytes
Similar to EGF;stimulates
hepatocyte growth
HGF/scatter
factor
Mesenchymal
cells
Proliferation of
hepatocytes,epithelial,e
ndothelial cells
VEGF-
A,B,C,D
Many cell types Mitogenic for
endothelial cells
PDGF-
A,B,C,D
Platelets,kerati
nocytes,endoth
elial cells
MMP
production,angiogenesis
,fibroblast growth
FGF-1,2 Fibroblasts,mas
t
cells,keratinocy
tes
Keratinocytes and
fibroblast
growth,angiogenesis
KGF(FGF-7) fibroblasts Keratinocyte
migration,proliferation
They have
paracrine action.
They are
expressed only
in small part of
cell cycle. But in
cancers there is
continuous
expression.
20. Cont.
• Growth factor
receptors:
a) They have
extracellular ligand-
binding,
transmembrane and
intracellular domains
b) Intracellular domain
has intrinsic tyrosine
kinase activitity
21. Cont.
d) Dimerization causes autophosphorylation
of intrinsic domain and recruitment of
other signalling proteins
e) Growth factor receptor oncoproteins are in
constitutively dimerized condition without
binding to ligand
22. Cont.
• Cytoplasmic signal transduction molecules:
a) These are serine/threonine or tyrosine
kinases
b) examples:RAS,RAF,MEK,PI3K,AKT
23. Cont.
• Nuclear transcription factors:
a)Growth factors ultimately induce synthesis or activity
of transcription factors
b)C-fos,N-myc
24. Cont.
•Cell cycle regulators:
•They are cyclins and
cyclin dependent
kinases regulating
transition from one
phase of cell cycle to
another
•Ink family cyclin
inhibitors:p15,p16,p18
,p19
•CIP/WAF family cyclin
inhibitors:p21.p27,p57
25. PROTOTYPE ONCOGENES
• EGFR:
a) Also called erbB or HER
b) 4 types:1,2,3,4
c) HER2 does not bind to a known ligand but
acts as co-factors for other members of the
family
d) HER3 does not have tyrosine kinase domain
26. Cont.
e)Ligand binding to extracellular domain causes
conformal changes and 2 receptors come in
close alignment-this is called dimerization.
F) ERBB1 is overexpressed in 80% of squamous
cell carcinomas of lung,80-100% of head and
neck malignancies and 50% glioblastomas
G) ERBB2 is overexpressed in 25% breast cancers
27. EGFR
SIGNALLING
Binding of growth
factor to the
extracellular
domain of EGFR
causes conformal
changes in
extracellular
domain so that 2
receptors come in
close alignment-
dimerization.
30. RAS ONCOGENE
• Point mutation of RAS is single most common
abnormality of human tumours.
• Multiple growth factor(EGF,PDGF) signal
transduction pathways depend on RAS
• Mutated in 15-20% cancers
• 90% cholangiocarcinima,pancreatic
adenocarcinoma;50%colon,endometrial and
thyroid cancers and 30% lung and myeloid
leukemias have RAS mutation
31. Cont.
• 3 RAS proteins are: K-RAS,H-RAS and N-RAS
• K-RAS: colon and pancreas cancer
• H-RAS: bladder and kidney cancer
• N-RAS: melanoma and haematologic
malignancies
• Inactivated RAS in GDP bound state is anchored
to inner cell membrane by farnesyl group.
32. RAS –RAF-MAP KINASE PATHWAY
Growth factor binds to its tyrosine kinase receptor
Cross phosphorylation of intracellular domain of each monomers
Activation of bridging protein (GRB2,SOS)
GDP bound RAS exchanges GDP with GTP and gets activated
34. Cont.
• Active RAS gets
inactivated by its
intrinsic GTP ase
activity which itself
is stimulated by
GTP ase-activating
proteins(GAPs)
• This step is blocked
in mutant RAS
35. MAP KINASES
• They are serine/threonine kinases
• 3 parallel MAP kinase pathways are
there:MAPK,JNK,p38 pathways
• MAPK is activated by growth factors
• JNK and p38 are activated by environmental
stress signals,like ionizing radiations and UV
rays
• MAP enters nucleus to activate transcription
factors
36. BRAF
• Serine/threonine kinase
• Mutation present in 100% hairy cell leukemia's,>60%
melanomas,80% of benign nevi, small percentage of
colon and dendritic tumours
38. ONCOGENIC MICROBES
• VIRUSES
1. HTLV-1:
a)Causes human T cell leukaemia in 3-5% of infected
persons after a latency of 4-5 decades
b)Do not contain any oncogene
c)But one gene called TAX causes increase expression
of FOS gene, genes encoding IL-2,its receptor activates
NF-Kb, inhibits ATM mediated cell cycle checkpoints
activated by DNA damage and inactivates cell cycle
inhibitor p16/INK4a
40. Cont.
2)EBV:
a)African Burkitt lymphoma,nasopharyngeal
carcinoma,subset of Hodgkin lymphoma
b)LMP-1(latent membrane protein) acts as an
oncogene and behaves like constitutively active CD40
receptor which helper cell uses to activate B cells.
c)EBNA-2 activates NOTCH receptor, cyclin D and src
protooncogene
41. 3)Hepatitis B and C :
a)Cause 70-85% of HCC
b)Chronic inflammation is the predominant etiology of
HCC which causes DNA damage.
c)NF-Kb pathway plays role
d)HBx gene of HBV activates several transcription
factors
42. Cont.
3)Hepatitis B and C :
a)Cause 70-85% of
HCC
b)Chronic
inflammation is the
predominant etiology
of HCC which causes
DNA damage.
c)NF-Kb pathway plays
role
d)HBx gene of HBV
activates several
transcription factors
Genome and transcribed component of HBV
43. Cont.
Bacteria
H.pylori:
3% of Chronically
infected patients
develop
adenocarcinoma after
decades
Pathogenic strains of
H.pylori contain
cytotoxin associated A
A(CagA) gene acting as
a growth promoting
gene
44. DETECTION OF
ONCOGENIC
ALTERATION
FISH:DNA probes
specific for a gene or
particular chromosome
region are labeled and
hybridized to denatured
metaphase
chromosomes or on
interphase nuclei on
paraffin embedded
tissue.After washing
fluorescent labeled
antibodies are added
and cells or tissues are
examined under
fluorescent microscopy
45. MICROARRAY
•Alteration of multiple genes
can be studied at one time.
• Steps:
1. Isolation and purification
of mRNA from the sample
2. Reverse transcribe the
mRNA to cDNA and
fluroscent labelling
3. Hybridization of the
labelled cDNA to
microarray chips.
4. Wash
5. Fluorescent labelled
hybridized DNA will be
excited by laser and the
signal will be expressed
digitally.