Chapter 5 Flashcards
What is the most common type of cancer in males
Prostate 33%
What is the most common type of cancer in females
Breast Cancer 31%
What cancer is most likely to cause death in both males and females
Lung and Bronchus cancer
What is the difference between Remission and Cure
Cure = No more cancerous cells Remission = Canacer has subsided but unknown if all the cancerous cells are gone
What is Neoplasia
New Growth AKA tumor
What are the features of a Neoplasia
Autonomous growth Independent of growth inhibition Evasion of cell death Limitless replication angiogenesis Adnormal metabolis
What causes Neoplasia to arrise
Dysfunction of cellular growth regulation
What are non-modifiable risks for cancer
Age
genetics
“things you cant control”
What are modifiable risks of cancer
Anything that can be controlled Obesity Excessive alcohol+animal fat Irradiation infections
What are the two parts of a Tumor
Parenchyma
Stroma
What is the Parenchyma of a Tumor
Transformed cells (neoplastic) Clonal
What is the Stroma of a Tumor
Non-neoplastic portion
Supportive structure of tumor
What part of the Tumor determines biological nature/agressivness
Parenchyma
What are the two main types of Tumors
Benign
Malignant
What is the nomenclature for a benign tumor
Cell type + oma
Fibroma, Chondroma
what is an exception to the nomenclature for a benign tumor
Melanocytic nevus
What are the features of a benign tumor
Localized
Relatively innocent
Can possibly: Vascular compression, hormone production
what is a benign tumor of glandular tissue
Adenoma
What is a benign tumor of capillary endothelia
Hemangioma
What is a bening tumor of adipose tissue
Lipoma
What is a benign smooth muscle tumor
Leiomyoma
What is a malignant tumor also known as
Cancer
What is metastasize
Spead/invade other tissues
How are cancers named
Cell type + Sarcoma or Carcinoma
What will classify a cancer as a sarcoma
Derived from mesodermal tissue
bone, Muscle, vasculature
What will classify a cancer as carcinomas
Derived from epithelial tissue
organs
What will classify a cancer as a teratoma
Contains multiple germ cell layers
What classification of cancer develops at any age?
Sarcoma
WHat classification of cancer develops during mid-late adulthood
Carcinomas
What is the most common type of tumor classification
Carcinomas (90%)
What is Fibroadenoma
Benign tumor of the female brest
Mixed tumor
What is a Hamartoma
Benign tumor tissue is native to individual site
What is a polyp
a mass that projects from the mucosal surface
What are the levels of Carcinoma progression
Dysplasia
Carcinoma in situ
Invasive Carcinoma
What is Dysplasia in reference to carcinoma
Disorderly proliferation
What is carcinoma in situ
Earyl Neoplasia
Localized
no penetration of basement membrane
What is invasive carcinoma
Local destruction
Penetration into basement membrane
likely to metastasize
What are the 4 characteristics of a cancer
Differentiation & anaplasia
Rate of growth
local invasiveness
metastasis
What is the differentiation difference between a normal cell and benign tumor
Normal: Completely differentiated, slow mitosis
Benign: Somewhat well-differentiated, decrease function
What is anaplasia
Loss of differentiation
What is associated with anaplasia
Severe loss of function
Pleomorphism
Increase of growth speed
What is pleomorphism
Various cell sizes/shapes
Less regulation
increase growth
potentialy malignant
How do benign tumors grow
Slow/controlled
How to malignant tumors grow
Fast/uncontrolled
How are growth speed and differentiation related
There is an inverse correlation
differentiation decrease, speed increase
What type of tumor is likely to be encapsulated
Bening
Lack of capsule doesn’t mean malignancy
What is a highly reliable tumor characteristic
whether it is localized of invading other tissues
What is metastasis
secondary implantation into remote tissue
What is the most reliable indicator of malignancy
Metastasis
Metastasis is most common among what type of tumors
Aggressive
high anaplasia
large size
What part of the tumor influences metastasis
The parenchyma
What are the three types of Dissemination
Seeding within body cavities
Lymphatic spread
Hematogenous spread
What does Seeding within body cavities pertaining to dissemination
Invasion of natural body cavities
What is lymphatic spread pertaining to dissemination
Most common mode of carcinoma metastasis
What determines lymphatic spread of a cancer
Site and tumor parenchyma
What is Hematogenous spread when pertaining to dissemination
Spread through blood
Most common mode of sarcoma metastasis
What is the most common way for a carcinoma to spread
Lymphatic spread
What is the most common way for a sarcoma to spread
Hematogenous spread
What is Epidemiology
Study of heath/disease in population
What is the purpose of Epidemiology
to discover risk factors for a disease
Sex, ethnicity, geography, lifestyle
What is the ultimate cause of cancer
Genetic alterations
mutations, epigenetics
What age group has the most cancer related morality
55-75 years
When do most childhood cancers form
Under 15 years old (10%)
What are the most common children cancers
Leukemia Lymphomas Retinoblastomas Neuroblastoma Osteosarcoma
What are the three categories of hereditary cancer
Autosomal dominant
Autosomal recessive
Familial cancer of uncertain inheritance
What is autosomal dominant cancer caused by
A single inherited mutant allele
What is autosomal recessive cancer caused by
2 altered alleles due to genomic instability
Ex. Xeroderma pigmentosa
What is Xeroderma pigmentosa
Sensitivity to UV
Highly susceptible to melanoma
What is Familial cancer
Cancer that has some familial association
2 or more close relatives
early onset
bilateral
What are some types of familial cancer
Colon Breast Prostate Brain Ovarian
what is preneoplastic lesions
“pre-cancer”
Increase cancer risk but most do not develop
What can cause preneoplastic lesions
Acquired lesions
Chronic tissue injury
Inflammation
dysplasia, metaplasia
What cancers are associated with these preneoplastic leions
1) GI adenoma
2) Leukoplakia
3) Actinic Keratosis
1) Colorectal cancer
2) squamous cell carcinoma
3) Skin Cnacer
What is Carcinogenesis
Creation of cancer
What type of cell damage promotes carcinogenesis
Nonlethal genetic damage i.e. mutations, epigenetic changes
What are the two ways we can acquire nonlethal genetic damage
Acquired: Environmental
Inherited (genetic)
What is acquired carcinogenesis limited to
Somatic cells
What cells are at risk of carcinogenesis for inherited risk
All cells
Germline alteration
What are the regulatory genes that prevent cancer. and are the number one target for genetic damage
Proto-oncogenes
Tumor suppressor genes
Apoptosis genes
DNA repair genes
Genetic alterations to regulatory genes is also known as
Carcinogenesis
What do proto-oncogenes regulate
Cell growth
What is an oncogene
Mutated proto-oncogene
What do oncogenes do
Cause anaplasia
What type of mutation causes oncogenes
Dominant (1 allele)
Gain of function
What type of mutation changes tumor suppressor genes
Recessive (2 alleles)
Loss of function
What is karyotype
Number and appearance of Chromosomes in the nucles
What can damage to karyotype cause
Activation of oncogenes
Inactivation of tumor suppressor genes
What are small changes to karyotype
Deletion
Insertion
What are large changes to karyotype
Abnormal karyotype
Aneuploidy = abnormal number of chromosomes
What are MircoRNAs
Non-coding RNA m/c
What do mircoRNAs do
inhibit gene expression
if there is an increased expression of MicroRNAs what regulatory gene is affected
Tumor supressor genes
If there is a decreased expression of MircoRNAs what regulatory genes is affected
Oncogenes
What are epigenetic modifications
Heritable changes in gene expression
What do epigenetic modifications do
Silence genes
How to epigenetic modification silence genes
DNA methylation
Histone modification
are epigenetic changes reversible
Yes
What type of genetic modification does no mutate a gene
Epigenetic changes
Will one isolated mutation cause cancer
No, multiple genes must be impacted
What happens to tumors over time
They become more aggressive (tumor progression)
Less responsive to therapy
What are the Hallmarks of Cancer
Evasion of immune system Genomic instability Tumor-promoting inflammation Change in energy metabolism Angiogenesis Self suffifency in growth signals
How are cancer cells self sufficient in growth signals
Produce own growth factors
Stimulate growth factors from stroma
Alter GF receptors
Can stimulate its own receptors
What changes occur to cancer cells response to GF
they overexpress receptors
Hyperresponsive to GFs
What GF receptor are often over expressed in cancer cells
HER2
What is signal transduction
Passing of a signal from receptor to the nucleus
What signal transduction genes are commonly mutated in Tumors, and in leukemias
RAS: 30% all tumors
ABL: mutated in leukemias
What happens when the nucleus is over-stimulated due to mutated transduction/GF receptors
Decreased cellular regulation = More mutations
What happens when there is an overstimulation of growth-promoting genes
Stimulating cell cycle
Suppression of regulatory genes
Alterations to what gene “remove brakes and slam gas”
MYC gene
What does the MYC gene control
CDK activation
Aerobic glycolysis
What is the restriction point in the cell cycle
G1-S phase transition
What do CDKs do at G1-S transition
Organize entry
What do CDKIs do at G1-S transition
Inhibit entry
What part of the cell cycle do all cancers need to disable
G1-S checkpont
What types of proteins to Tumor suppressor genes code for
Inhibitory growth proteins
What happens when Tumor suppressor genes become non-functional
Increased Proliferation
What is the Two-hit hypothesis
Both alleles must be inactivated in the Tumor suppressor genes to change the phenotype
What protein does the Rb gene code for
Rb protein
What was the first Tumor suppressor gene discovered
Rb gene
What check point does the Rb protein govern
G1-S phase
What viral infection can inhibit Rb protein
HPV
What protein maintains DNA integrity and is known as the guardian of the genome
p53
When a cell has DNA damage what protein will send it into Quiescence or Senescence
p53
What gene codes for the p53 protein
TP53
What is the difference between Quiescence and Senescence
Quiescence: Reversible cell cycle arrest (minor damage)
Senescence: permanent cell cycle arrest (major Damage)
What cell cycle phase does p53 check for DNA damage and remove cells with damaged DNA
G1 phase
What viral infections alter both alleles of TP53 (cause Somatic mutations)
HPV
EBV
Hep B
What is the inherited disease that has TP53 damage
Li-Fraumeni Syndrome
What protein do both Apoptosis pathways use. Known as the Executioner, common target for cancer cells to destroy to avoid apoptosis
Caspse-3
What is the Hayflick limit
Maximum amount of times a cell can divide (normally 60-70 divisions)
What is the reason why cell can only divide so many times
Telomeres shorten, TSG recognize the shortening = senescence
What protein is rarely active in normal cells but very active in cancer cells. Causes cancer cells to have limitless replicative potential
Telomerase (repairs+maintains telomeres)
How large can a cancer cell get until it needs sustained angiogenesis
1-2mm in diameter
What are the major steps in invacion-metastasis cascade
1) invasion of ECM
2) Vascular Spread
3) Micrometastases grow+invade
What are the steps cancer cells have to take in order to interact with the ECM
Lossening of tumor cell
Breakdown of ECM
changes in ECM attachment
Migration
Where is the primary tumor located
The site of metastasis
What are the three types of DNA repair discussed in class
Mismatch Repair
Nucleotide excision repair
Homologous recombination repair
What is mismatch repair
Single base errors are corrected
15% of this type of cancer is caused by errors in mismatch DNA repair
Sporadic colorectal Cancers
i.e. Herediraty nonpolyposis colorectal cancer
What type of repair is done when a segment of DNA is damaged and removed. normally damaged by UV light
Nucleotide excision repair
What type of disease is associated with defective Nucleotide excision repair
Xeroderma pigmentosum
What is homologous recombination
DNA is exchanged between two homologous chromosomes
Can be used to repair DNA
What two genes are responsible for 50% of familial breast cancer. Due to problems with recombination
BRCA1 + BRCA2
Can chronic inflammation increase cancer risk
Yes
What are the classes of carcinogenic agents
Chemical
Radiant energy
Mircobial
What type of carcinogens require no metabolic conversion
Direct-Acting
What type of carcinogens require metabolic conversion
Indirect-acting
What are some indirect-acting carcinogens
Tabacco smoke
Fossil fuel exhaust
aflatoxin B1
What gene is the target for aflatoxin B1
TP53
Other than mutating a specific gene, what other way can a chemical carcinogen affect gene expression.
Mutate the promoter sequence of a gene
How can irradiation damage cells
Mutagenic effects
Carcinogenesis
What is acute radiation syndrome
Radiation sickness caused but irradiation carcinogenesis
What does UV light cause the formation of
Pyrimidine dimers
What are the three types of skin cancer caused by UV light
Basal cell carcinoma
Squamous cell carcinoma
Melanoma
What type of skin cancer is most common
Basal cell carcinoma
Why type of skin cancer is caused by intense UV exposure
Melanoma
What is the most common metastatic cancer in the US
Skin cancer
What classification of viruses cause cancer
Oncogenic RNA viruses
What was the oncogenic RNA virus that was discussed in class
Human T cell lymphotropic virus-1 (HTLV-1)
how is HTLV-1 transmitted
Sex
blood
breast feeding
What are the 4 oncogenic DNA viruses discussed in class
HPV
EBV
Hep B and C
Kaposi sarcoma herpesvirus
