Biology of Cancer Chapter 11 Cancer Derived from Greek word for crab, karkinoma Malignant tumor Tumor Also referred to as a neoplasm—new growth Mosby items and.
Download
Report
Transcript Biology of Cancer Chapter 11 Cancer Derived from Greek word for crab, karkinoma Malignant tumor Tumor Also referred to as a neoplasm—new growth Mosby items and.
Biology of Cancer
Chapter 11
1
Cancer
Derived from Greek word for crab, karkinoma
Malignant tumor
Tumor
Also referred to as a neoplasm—new growth
2
Mosby items and derived items © 2006 by Mosby, Inc.
Benign vs. Malignant Tumors
Benign
Grow slowly
Malignant
Grow rapidly
Well-defined capsule
Not encapsulated
Not invasive
Well differentiated
Low mitotic index
Do not metastasize
Invasive
Poorly differentiated
High mitotic index
Can spread distantly
(metastasis)
3
Mosby items and derived items © 2006 by Mosby, Inc.
Classification and Nomenclature
Benign tumors
Named according to the tissues from which they
arise, and include the suffix “–oma”
Lipoma
Glioma
Leiomyoma
Chondroma
4
Mosby items and derived items © 2006 by Mosby, Inc.
Classification and Nomenclature
Malignant tumors
Named according to the tissues from which they
arise
Malignant epithelial tumors are referred to as
carcinomas
Adenocarcinoma and basal cell carcinoma
Malignant connective tissue tumors are referred to as
sarcomas
Chondrosarcoma and osteosarcoma
5
Mosby items and derived items © 2006 by Mosby, Inc.
Classification and Nomenclature
Cancers of lymphatic tissue are lymphomas
Cancers of blood-forming cells are leukemias
Carcinoma in situ (CIS)
Pre-invasive epithelial malignant tumors of
glandular or epithelial origin that have not broken
through the basement membrane or invaded the
surrounding stroma
6
Mosby items and derived items © 2006 by Mosby, Inc.
Classification and Nomenclature
7
Mosby items and derived items © 2006 by Mosby, Inc.
Classification and Nomenclature
8
Mosby items and derived items © 2006 by Mosby, Inc.
Cancer Cells
Transformation
Cancer cell’s independence from normal cellular
controls
Anchorage independent
Immortal
Anaplasia
Pleomorphic
9
Mosby items and derived items © 2006 by Mosby, Inc.
Cancer Stem Cells
Stem cells self-renew
Cell divisions create new stem cells
Stem cells are multipotent
Ability to differentiate into multiple different
cell types
10
Mosby items and derived items © 2006 by Mosby, Inc.
Cancer Stem Cells
11
Mosby items and derived items © 2006 by Mosby, Inc.
Cancer Stem Cells
12
Mosby items and derived items © 2006 by Mosby, Inc.
Tumor Markers
Tumor cell markers (biological markers) are
substances produced by cancer cells or that
are found on plasma cell membranes, in the
blood, CSF, or urine
Hormones
Enzymes
Genes
Antigens
Antibodies
13
Mosby items and derived items © 2006 by Mosby, Inc.
Tumor Markers
Tumor markers are used to:
Screen and identify individuals at high risk for
cancer
Diagnose specific types of tumors
Observe clinical course of cancer
14
Mosby items and derived items © 2006 by Mosby, Inc.
Cancer-Causing Mutations
Cancer is predominantly a disease of aging
Clonal proliferation or expansion
Due to a mutation, a cell acquires characteristics
that allow it to have selective advantage over its
neighbors
Increased growth rate or decreased apoptosis
Multiple mutations are required before cancer
can develop
15
Mosby items and derived items © 2006 by Mosby, Inc.
Cancer-Causing Mutations
16
Mosby items and derived items © 2006 by Mosby, Inc.
Types of Mutated Genes
Secretion of growth factors (autocrine stimulation)
Increased growth factor receptors
Signal from cell-surface receptor is mutated in the
“on” position
Mutation in the ras intracellular signaling protein
Inactivation of Rb tumor suppressor
Activation of protein kinases that drive the cell cycle
Mutation in the p53 gene
17
Mosby items and derived items © 2006 by Mosby, Inc.
Types of Mutated Genes
18
Mosby items and derived items © 2006 by Mosby, Inc.
Angiogenesis
Growth of new vessels
Advanced cancers can secrete angiogenic
factors
19
Mosby items and derived items © 2006 by Mosby, Inc.
Hallmarks of Cancer
20
Mosby items and derived items © 2006 by Mosby, Inc.
Telomeres and Immorality
Body cells are not immortal and can only
divide a limited number of times
Telomeres are protective caps on each
chromosome and are held in place by
telomerase
Telomeres become smaller and smaller with
each cell division
21
Mosby items and derived items © 2006 by Mosby, Inc.
Telomeres and Immorality
22
Mosby items and derived items © 2006 by Mosby, Inc.
Oncogenes and Tumor-Suppressor
Genes
Oncogenes
Tumor-suppressor genes
Mutant genes that in their nonmutant state direct protein
synthesis and cellular growth
Encode proteins that in their normal state negatively
regulate proliferation
Also referred to as anti-oncogenes
Proto-oncogene
A normal, nonmutant gene that codes for cellular growth
23
Mosby items and derived items © 2006 by Mosby, Inc.
Mutation of Normal Genes
Point mutations
Chromosome translocation
Changes in one or a few nucleotide base pairs
A piece on one chromosome is transferred to
another
Gene amplification
Duplication of a small piece of chromosome over
and over
Results in an increased expression of an oncogene
24
Mosby items and derived items © 2006 by Mosby, Inc.
Mutation of Normal Genes
25
Mosby items and derived items © 2006 by Mosby, Inc.
Mutation of Normal Genes
26
Mosby items and derived items © 2006 by Mosby, Inc.
Mutation of Normal Genes
Mutation of tumor-suppressor genes
Loss of heterozygosity
Allows unregulated cellular growth
Both chromosome copies of a gene are
inactivated
Gene silencing
Whole regions of chromosomes are shut off while
the same regions in other cells remain active
27
Mosby items and derived items © 2006 by Mosby, Inc.
Mutation of Normal Genes
28
Mosby items and derived items © 2006 by Mosby, Inc.
Mutation of Normal Genes
Caretaker genes
Encode for proteins that are involved in repairing
damaged DNA
Chromosome instability
Increased in malignant cells
Results in chromosome loss, loss of
heterozygosity, and chromosome amplification
29
Mosby items and derived items © 2006 by Mosby, Inc.
Inflammation and Cancer
Chronic inflammation is an important factor
in the development of cancer
Cytokine release from inflammatory cells
Free radicals
Mutation promotion
Decreased response to DNA damage
30
Mosby items and derived items © 2006 by Mosby, Inc.
Genetics and Cancer
Exposure to mutagens
If the mutation occurs in somatic cells, it is not
passed to progeny
If the mutation occurs in germline cells, it can be
passed to future generations
31
Mosby items and derived items © 2006 by Mosby, Inc.
Viruses and Cancer
Implicated
Hepatitis B and C viruses
Epstein-Barr virus (EBV)
Kaposi sarcoma herpesvirus (KSHV)
Human papillomavirus (HPV)
Human T cell leukemia–lymphoma virus (HTLV)
32
Mosby items and derived items © 2006 by Mosby, Inc.
Bacterial Cause of Cancer
Helicobacter pylori
Chronic infections are associated with:
Peptic ulcer disease
Stomach carcinoma
Mucosa-associated lymphoid tissue lymphomas
33
Mosby items and derived items © 2006 by Mosby, Inc.
Environmental Risk Factors
Tobacco
Multipotent carcinogenic mixture
Linked to cancers of the lung, lower urinary tract,
aerodigestive tract, liver, kidney, pancreas, cervix
uteri, and myeloid leukemia
34
Mosby items and derived items © 2006 by Mosby, Inc.
Environmental Risk Factors
Ionizing radiation
Emission from x-rays, radioisotopes, and other
radioactive sources
Exposure causes cell death, gene mutations, and
chromosome aberrations
Bystander effects
Poor gene repair
Changes in gap junction intercellular
communication
35
Mosby items and derived items © 2006 by Mosby, Inc.
Ionizing Radiation
36
Mosby items and derived items © 2006 by Mosby, Inc.
Environmental Risk Factors
Ultraviolet radiation
Causes basal cell carcinoma, squamous cell
carcinoma, and melanoma
Principal source is sunlight
Ultraviolet A (UVA) and ultraviolet B (UVB)
Promotes skin inflammation and release of free
radicals
37
Mosby items and derived items © 2006 by Mosby, Inc.
Environmental Risk Factors
Alcohol consumption
Risk factor for oral cavity, pharynx, hypopharynx,
larynx, esophagus, and liver cancers
Cigarette/alcohol combination increases a
person’s risk
38
Mosby items and derived items © 2006 by Mosby, Inc.
Environmental Risk Factors
Sexual reproductive behavior
Carcinogenic types of human papillomavirus
High-risk HPV
Physical activity
Reduces cancer risk
Decreases insulin and insulin-like growth factors
Decreases obesity
Decreases inflammatory mediators and free radicals
Increased gut motility
39
Mosby items and derived items © 2006 by Mosby, Inc.
Environmental Risk Factors
Occupational hazards
Substantial number of occupational carcinogenic
agents
Asbestos
Dyes, rubber, paint, explosives, rubber cement, heavy
metals, air pollution, etc.
Radon
40
Mosby items and derived items © 2006 by Mosby, Inc.
Environmental Risk Factors
Electromagnetic fields
Carcinogenic?
Are they, or aren’t they?
41
Mosby items and derived items © 2006 by Mosby, Inc.
Environmental Risk Factors
Diet
Xenobiotics
Toxic, mutagenic, and carcinogenic chemicals in food
Activated by Phase I activation enzymes
Defense mechanisms
Phase II detoxification enzymes
Examples
Compounds produced in the cooking of fat, meat, or proteins
Alkaloids or mold by-products
42
Mosby items and derived items © 2006 by Mosby, Inc.
Environmental Risk Factors
Obesity
Correlates with the body mass index (BMI)
Adipose tissue is active endocrine and metabolic
tissue
In response to endocrine and metabolic signaling,
adipose tissue releases free fatty acids
Increased free fatty acids gives rise to insulin
resistance and causes chronic hyperinsulinemia
Correlates with colon, breast, pancreatic, and
endometrial cancers
43
Mosby items and derived items © 2006 by Mosby, Inc.