Genetics plays a key role in cancer development. Cancer results from mutations in proto-oncogenes, tumor suppressor genes, miRNA genes, and mutator genes. Proto-oncogenes promote cell growth but become oncogenes when mutated. Tumor suppressor genes normally inhibit cell growth but are inactivated by mutations in cancer. The cell cycle is tightly regulated by checkpoints but deregulation can lead to uncontrolled cell division in cancer. Cancers can be caused by inherited genetic mutations or environmental exposures like radiation and carcinogens. The development of cancer typically involves multiple genetic alterations accumulating over time.
Audio and slides for this presentation are available on YouTube: http://youtu.be/e_KVYJX2GTs
Have you ever wondered about your genetic predisposition to cancer? How cancer evolves in families? Or how cancer cells differ from normal cells in your body? Join Judy Garber, MD, MPH, director of the Center for Cancer Genetics and Prevention at Dana-Farber Cancer Institute, as she explores the basics of cancer genetics, DNA mutations, genetic screening, management, and more.
Audio and slides for this presentation are available on YouTube: http://youtu.be/e_KVYJX2GTs
Have you ever wondered about your genetic predisposition to cancer? How cancer evolves in families? Or how cancer cells differ from normal cells in your body? Join Judy Garber, MD, MPH, director of the Center for Cancer Genetics and Prevention at Dana-Farber Cancer Institute, as she explores the basics of cancer genetics, DNA mutations, genetic screening, management, and more.
This presentation on Epigenetics is most advanced and evidence based one. Its Very helpful for Genetics students and research fellows, Reproductive Medicine specialist, Reproductive Biologist, Infertility practitioners
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
The epigenetic regulation of DNA-templated processes has been intensely studied over the last 15
years. DNA methylation, histone modification, nucleosome remodeling, and RNA-mediated targeting regulate many biological processes that are fundamental to the genesis of cancer. Here, we
present the basic principles behind these epigenetic pathways and highlight the evidence suggesting that their misregulation can culminate in cancer. This information, along with the promising clinical and preclinical results seen with epigenetic drugs against chromatin regulators, signifies that it
is time to embrace the central role of epigenetics in cancer.
This presentation on Epigenetics is most advanced and evidence based one. Its Very helpful for Genetics students and research fellows, Reproductive Medicine specialist, Reproductive Biologist, Infertility practitioners
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
The epigenetic regulation of DNA-templated processes has been intensely studied over the last 15
years. DNA methylation, histone modification, nucleosome remodeling, and RNA-mediated targeting regulate many biological processes that are fundamental to the genesis of cancer. Here, we
present the basic principles behind these epigenetic pathways and highlight the evidence suggesting that their misregulation can culminate in cancer. This information, along with the promising clinical and preclinical results seen with epigenetic drugs against chromatin regulators, signifies that it
is time to embrace the central role of epigenetics in cancer.
Cancer (Concept of oncogenes and tumor suppressor genes with special referenc...RubinSahu5
Cancer (Concept of oncogenes and tumor suppressor genes with special referencetop53, Retinoblastoma and Ras and APC)
Cancer is a non-infectious disease. It starts at the molecular level of the cell and, ultimately affects the cellular behavior.
It can be defined as uncontrolled proliferation of cells without any differentiation.
Cancer is a genetic disease because it can be traced to alterations within specific genes.
Most cancer cells experience a breakdown in all of these regulatory influences that protect the body from chaos and self‐destruction.
Cancer cells proliferate uncontrollably, producing Malignant tumors that invade surrounding healthy tissue.
Malignant tumors tend to metastasize, that is, to spawn renegade cells that break away from the parent mass, enter the lymphatic or vascular circulation, and spread to distant sites in the body where they establish lethal secondary tumors that are no longer amenable to surgical removal.
All types of cancer can result from uncontrolled Cell Growth And Division of any of the different kinds of cells in the body.
The uncontrolled cell growth produces a mass of cells which are called tumors or neoplasm tumors may be Benign or Malignant.
Oncogenes encode proteins that promote the loss of growth control and the conversion of a cell to a malignant state and Cell Proliferation.
Oncogenes may lead to genetic instability, prevent a cell from becoming a victim of apoptosis, or promote metastasis.
Tumor‐suppressor genes act as a cell’s brakes; they encode proteins that restrain cell growth and prevent cells from becoming malignant.
The first tumor suppressor gene to be studied and eventually cloned is associated with a rare childhood cancer of the retina of the eye, called Retinoblastoma.
The gene responsible for this disorder is named RB .
RAS refers to a family of genes that encode proteins involved in cell signaling pathways regulating cell growth and differentiation.
APC stands for Adenomatous Polyposis Coli.
It's a tumor suppressor gene that plays a critical role in regulating cell proliferation and maintaining the integrity of the epithelial lining of the colon and rectum.
Mutations in the APC gene are associated with familial adenomatous polyposis (FAP), an inherited condition characterized by the development of numerous polyps in the colon and rectum, leading to a significantly increased risk of colorectal cancer.
The cells of patients with this condition were found to contain a deletion of a small portion of chromosome 5, which was subsequently identified as the site of a tumor‐suppressor gene called Adenomatous Polyposis Coli, or APC .
APC is known to suppress the Wnt pathway, which activates the transcription of genes, that promote cell proliferation.
Loss of APC function could therefore lead directly to abnormal chromosome segregation and aneuploidy.
Introduction to Cancer
Stem cells and cancer cells
major pathways that lead to formation of tumors.
Tumor Supressors
Colon cancer to prove Knudson hypothesis.
The modern treatments available to treat cancer.
Answer:
Cellular oncogene formation: Carcinogenesis, tumorogenesis or oncogenesis are developed from
normal cells into a lethal cancer due to the following mechanisms inside the cell.
1. Point mutation: This mutation induces alteration in cellular DNA sequence through
synonymous nucleotide substitution result in normal gene becomes protooncogene finally
become oncogene due to chromosomal DNA replication. For example normal Ras protein
synthesizing gene become mutant Ras oncogene due to point mutation.
2. Gene amplification: This is the process of abnormal amplification of DNA in chromosomes
and generates protooncogenes into oncogenes due to numerous replications of chromosomal
DNA in succession. Example is presence of MYC gene family in lung and breast cancer cells
due to amplied DNA homogeneously.
3. Chromosomal translocation: BCR-ABL leukemia is the due to chromosomal translocation and
meticulous translocation of chromosmomal regions leading to coding of a fusion protein from an
oncogene. Ex. Philadelphia chromosome
4. DNA rearrangement: Insertions, deletions, transposition & inversion of nitrogen bases of
nucleotide sequences in DNA rearrangement generates cellular oncogenes. These rearrangements
are due to exposure of cells to carcinogenic agent
5. Insertional mutagenesis: This type of oncogene development is mainly due to retrovirus as
explained
below
For example:
The genetic changes are expected to alter the activity of the gene product --> loss of
heterozygosity ---> abnormal phenotype
Mutations result in genetic drift, which in turn results in the loss of heterozygosity. This loss of
one parental copy of nucleotide gene bases may lead to the lethal and dangerous consequences of
the living being in the following of life. This loss or drift may result in the occurrence of cancer
(breast cancer) hereditary retinoblastoma, because there may be nonexistence of the functional
tumor suppressor gene in the lost region. One parental copy only can be noticed at that lost
region there by hemizygosity.
But however there is one more functional gene copy inside the genome copy thereby offspring
can get resistance proteins synthesis against the mutation induced cancer.
If both copies are bad or one copy is become badly due to mutation the remaining gene copy
responsible for the tumor growth (the tumor suppressor gene example p53) can be denaturated by
another point mutation, result in complete suppression of gene to protect the body.
A lot of catastrophic events and consequences may occur with loss of heterozygosity (LOH).
Genetic drift results in loss of heterozygosity which may reduce and limit longevity of asexual
organisms in a population there by low population size.
During intermittent cancer development, usually inactivation of the TSG induced due to the two
somatic mutations acting on respective 2 alleles. In contrast, during the familial cancer
development merely one somatic mutation is considerably enough to generate inactivation of
TSG (p.
describe the tumor suppressor genes and examples for downloading the presentation, more presentations , infographics and blogs visit :
studyscienceblog.wordpress.com
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
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.
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.
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
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
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
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
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.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
- 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
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. Genetics controls cell division and tissue
differentiation
Proliferation is tightly controlled
Cell transformation results in unregulated
growth (oncogenesis)
Benign growth is restricted to one site
and is readily managed.
Malignant growth is metastatic – it
spreads throughout the body.
3. Relationship of the Cell Cycle to Cancer
Cell differentiation occurs as cells proliferate to form
specialized tissues. Differentiated cells lose the ability to
proliferate and have a finite life span
Cell proliferation is executed by the cell cycle, which is
divided into 4 phases
G1 (gap 1), S (synthesis), G2 (gap 2), M (mitosis)
The cell cycle is controlled by gene-activity driven
checkpoints, which arise due to DNA damage***
The G1-to-S checkpoint monitors cell size
The G2-to-M checkpoint monitors the cellular environment and
the status of DNA duplication
Checkpoints use cyclins and cyclin-dependent kinases
Kinase phosphorylation of the cyclin can activate or cancel cell
cycle progression
4.
5. The regulation of cell division is controlled by extracellular and
intracellular means (signal transduction pathways) that stimulate or
inhibit growth (obviously, these pathways are altered in cancer)
Animation: CellAnimation: Cell
Division RegulationDivision Regulation
6. Cancers are Genetic Diseases
There is strong evidence supporting the notion that
cancer is a genetic disorder:
Some cancers are familial (hereditary), while others
are sporadic (nonhereditary)
In general, cancer is not inherited (mutations are in
somatic, not germ line cells)
Some viruses can induce cancer, indicating the action
of viral genes
Descendants of cancerous cells are all cancerous
Cancer risk rises with exposure to mutagenic agents
Specific chromosomal mutations are associated with
certain kinds of cancer
7. Four classes of genes are mutated in cancer:
Proto-oncogenes, whose products normally
stimulate cell proliferation (c-onc, v-onc)
Tumor suppressor genes, whose products
normally inhibit proliferation
Micro RNA (miRNA) genes, which produce
small RNAs that silence the expression of
other genes
Mutator genes, whose products ensure
accurate replication and maintenance of the
genome
Genes and Cancer
8. Oncogenes
Tumor viruses induce infected cells to
proliferate and produce a tumor
There are two types based on the viral
genome:
RNA tumor viruses transform cells by
inducing viral oncogenes (genes
causing unregulated proliferation)
DNA tumor viruses do not carry
oncogenes and use other mechanisms
to transform the cell
9. Retroviruses and Oncogenes
RNA tumor viruses are all retroviruses, and their
oncogenes are altered forms of normal host
genes(Not all retroviruses are oncogenic)
Structurally, retroviruses have two copies of a
10-kb ssRNA genome, encoding genes for:
The gag group antigen, which encodes the
viral protein core (capsid)
The pol gene, which produces reverse
transcriptase and integrase
The env gene, which encodes the infectious
surface glycoprotein
10.
11. Upon infection, the ssRNA
genome is released from
the virus and reverse
transcribed to ds DNA
(proviral DNA) by reverse
transcriptase (RNA-
dependent DNA pol)
Proviral DNA integrates
into the host chromosome,
controlled by viral
elements encoded in their
LTR’s
Host RNA polymerase II
transcribes the proviral
DNA and viral mRNAs are
produced by alternative
splicing
12. Viral Oncogenes
Oncogenic retroviruses carry an oncogene that is not
involved in the viral life cycle (different retroviruses
carry different oncogenes and thus, different cancer)
Retroviruses that carry an oncogene are transducing
and are formed by the random integration of the
provirus into the host chromosome
13. Cellular Proto-Oncogenes
Cellular proto-oncogenes with close homology to v-
onc have been characterized, showing that:
Oncogenes are present in human tumor cells and
cause transformation when introduced into normal
cultured cells
Human cells have intron-containing genes that are
very similar to viral genes (no introns***), but do
not cause cancer (proto-oncogenes)
These genes regulate cell division and
differentiation, and can be mutated to cause
cellular transformation (dominant mutation)
15. Normal Transformed
PDGF driven transformation in fibroblasts
No contact inhibition produces
altered histology (round shape)
16. Changing Proto-Oncogenes into Oncogenes
Conversion of proto-oncogenes to oncogenes
relaxes cell control, allowing unregulated
proliferation
Point mutations in coding or controlling
sequences changes the gene product or alters
its expression (i.e. Ras)
Deletions of coding or controlling sequences
changes the amount of activity of growth
stimulatory proteins (i.e. Myc)
Gene amplification, caused by random
overreplication of regions of genomic DNA,
increases the amount of stimulatory proteins
17. DNA Tumor Viruses
Oncogenic DNA viruses do not carry oncogenes
but may transform cells using viral gene
products
DNA viruses induce the production of cellular
DNA replication enzymes, which are used in
viral replication
Very rarely, viral DNA integrates into the host
genome, producing proteins that stimulate the
cell to proliferate (HPV is an example)
18. Tumor Suppressor Genes
In a pioneering experiment, Henry Harris showed the fusion
of cancer cells and normal cells does not always result in a
tumor, indicating the existence of tumor suppressor genes
In certain cancers, both homologous chromosomes show
deletion of specific regions which are the sites of tumor
suppressor genes (so these mutations are recessive)
19. Retinoblastoma Tumor Suppressor, RB
Retinoblastoma is the most
common eye tumor in
children; surgery and
radiation is effective (90%)
Retinoblastoma has two
forms:
Unilateral, sporadic
retinoblastoma develops in
children with no family history
Bilateral, hereditary
retinoblastoma is the
paradigm of Alfred Knudson’s
two-hit mutation model,
stating two mutations are
required for RB development
21. Retinoblastoma is rare among cancers because a single gene
is critical for its development (most cancers result from a series
of mutations in different genes; discuss later)
pRB regulates the cell cycle at the G1-to-S checkpoint
pRB is ~P by CyclinE/Cdk2; E2F is free to transactivate DNA
Some DNA tumor viruses produce proteins sequestering pRB
22. TP53 Tumor Suppressor Gene
The tumor suppressor p53 is
found mutated in roughly 50%
of human cancers!
Inheritance of one mutant p53
allele results in the Li-Fraumeni
syndrome, in which a rare form
of cancer develops in several
tissues
Tumors arise when the 2nd
allele is mutated, so the trait is
inherited as autosomal
dominant
The figure tells the story
~P
Animation: TumorAnimation: Tumor
Suppression (p53)Suppression (p53)
23. P53 provides
protection from
oncogene activation
Oncogenes induce
ARF expression,
producing p14
P14 binds Mdm2,
stabilizing p53
concentration
P53 transactivates
target genes involved
in arrest, apoptosis
and repair
Note: DNA damage
by radiation or chemo
is used to study p53
25. BRCA1/2
Mutation in breast cancer
tumor suppressor genes
are similar to pRB;
hereditary forms produce
early onset, bilateral
tumors
Mutations in BRCA1 are
also involved in the
genesis of ovarian cancer
Surprise District Court Ruling
Invalidates Myriad Genetics’
BRCA Patents; sequence
data is not patent domain.
“can man patent the sun?” –
Dr. Jonas Salk (Polio
vaccine)
26.
27.
28. MicroRNA and Mutator Genes
MicroRNAS are short, noncoding ssRNAs derived from the
transcripts of nuclear genes. They silence mRNA translation by
binding to the 3’ UTR
Many miRNAs show altered expression patterns in cancer cells.
miR-155 miRNA is overexpressed in lymphoma and breast, lung, and thyroid
cancer. When expression of an miRNA is increased in cancer cells, it is
considered an oncogene
let-7 miRNA is underexpressed in breast, liver, lung, and thyroid cancer. When
expression of an miRNA is decreased in cancer cells, it is considered a tumor
suppressor
A gene that increases the spontaneous mutation rate when it is
mutated is a mutator gene (DNA replication and repair genes)
Hereditary nonpolyposis colon cancer results from an autosomal dominant allele,
causing early onset of colorectal cancer (mutations in hMSH2, hMLH1, hPMS1
and hPMS2)
29. Telomere Shortening, Telomerase & Cancer
Telomere shortening and telomerase activity are related
to the development of human cancer
Human cells undergo replicative senescence caused by
structural changes in the telomeres
Only germ-line and certain stem cells maintain telomerase
activity
Telomeres of other cells shorten with each cell cycle.
Eventually, telomeres are so small, the telomere-binding
proteins are unable to bind to the shortened telomeres. The
lack of binding results in DNA damage and cell cycle arrest
If the cell is mutated in a cell cycle arrest gene (e.g., TP53),
the cell will divide despite having short telomeres. In
addition, if the telomerase gene is reactivated, the cells can
become immortal (do you think cancer cells have mutations
in both of these genes at the same time?)
30. Multistep Nature of Cancer
Cancer induction may
require the accumulation
of many mutations over
time, involving
oncogenes and tumor
suppressors
The paradigm of the
multistep nature of
cancer is embodied in the
intestinal cancer,
adenamatous polyposis
(FAP)
31. Chemicals and Radiation as Carcinogens
Chemical carcinogens are divided into two major classes
(both types of carcinogens cause point mutations):
Direct-acting carcinogens bind DNA and act as mutagens. Alkylating
agents are an example
Procarcinogens are metabolically converted by normal cellular enzymes
to ultimate carcinogens that bind DNA and cause mutations. Most
chemical carcinogens are procarcinogens. Examples include:
Polycyclic aromatic hydrocarbons are found in smoke from wood, coal, and
cigarettes
Azo dyes, natural metabolites (e.g., aflatoxin from fungi)
Nitrosamines (from nitrites in food)
Only about 2% of cancer deaths are caused by
radiation, but the cancers are often highly aggressive
melanomas. Sources include:
Sun (U-V), X-rays, cellular telephones, Radon gas
Ionizing radiation (from X-rays, radioactive materials, and radon gas) can
cause leukemia and thyroid cancer