Exam 1 Flashcards
Deadliest cancer
Lung
Most common cancer
Non-melanoma skin
2nd most common cancer
Prostate in men, breast in women
3rd most common cancer
Lung
4th most common cancer
Colorectal
5th most common cancer
Bladder in men, uterine corpus in women
2nd deadliest
Prostate in men, breast in women
3rd deadliest
Colorectal
6th most common cancer
Melanoma
4th deadliest
Pancreatic
5th deadliest
Liver in men, ovarian in women
Adenoma
Benign glandular tumor
Adenocarcinoma
Malignant glandular tumor
Basal cell adenoma
Benign basal cell tumor
Basal cell carcinoma
Malignant basal cell tumor
Keratoacanthoma
Benign squamous cell tumor
Squamous cell carcinoma
Malignant squamous cell tumor
Mole
Benign pigmented cell tumor
Melanoma
Malignant pigmented cell tumor
Teratoma
Benign multipotential cell tumor
Teratocarcinoma
Malignant multipotential cell tumor
Chondroma
Benign cartilaginous tumor
Chondrosarcoma
Malignant cartilaginous tumor
Fibroma
Benign fibroblast tumor
Fibrosarcoma
Malignant fibroblast tumor
Hemangioma
Benign blood vessel tumor
Hemangiosarcoma
Malignant blood vessel tumor
Leiomyoma
Benign smooth muscle tumor
Leiomyosarcoma
Malignant smooth muscle tumor
Lipoma
Benign adipose tumor
Liposarcoma
Malignant adipose tumor
Meningioma
Benign Meninges tumor
Meningiosarcoma
Malignant meninges tumor
Myoma
Benign muscle tumor
Myosarcoma
Malignant muscle tumor
Osteoma
Benign bone tumor
Osteosarcoma
Malignant bone tumor
Rhabdomyoma
Benign striated muscle tumor
Rhabdomyosarcoma
Malignant striated muscle tumor
Lymphoma
Malignant lymphocyte tumor (lymphocytic leukemia)
Erythrocytic leukemia
Malignant erythrocyte tumor
Myeloma
Malignant bone marrow tumor (myelogenous leukemia)
Carcinoma
Malignant cancer of epithelial tissue
Sarcoma
Malignant cancer of mesoderm-derived tissue
Leukemia
Malignant cancer of blood/lymphatic origin
Which types of skin cancer are so common that they are usually counted in most data sets?
Basal cell carcinomas and squamous cell carcinomas
What percentage of estimated new cancer cases are lung cancers?
12.2%
What percentage of lung cancers are a result of tobacco use?
~80-90%
How are cancer data sets compared between different populations?
Age-adjusted incidence per 100,00 people per year
Benign tissue histology
Normal tissue organization
Malignant tumor histology
tissue is disorganized; tumor borders are irregular
Normal nucleus:cytoplasm
low; lots of cytoplasm
Cancer nucleus:cytoplasm
high, barely any cytoplasm around nucleus
Normal cell growth
slow
Cancerous cell growth
can be slow or very rapid
What is one In vitro experiment used to determine anchorage-independent growth?
If cells grow well after settling AND while being suspended, they are anchorage-independent and likely cancerous
What is an In vitro experiment used to determine contact inhibition?
Cells are allowed to grow in flask. If cells form a monolayer and stop dividing, contact inhibition occurs. If cells continue dividing, they are likely cancerous
What are nude mice?
Athymic mice lack thymus and T cells and are immunodeficient. Used to test if cells are cancerous In vivo
What is anoikis?
When cells that become unanchored from the ECM undergo apoptosis
Hypertrophy
Increase in cell size, normal tissue organization
Hyperplasia
Increase in cell number, normal tissue organization
Dysplasia
Disorganized growth
Neoplasia
Disorganized growth and net increase in number of dividing cells
Metaplasia
The replacement of differentiated somatic cells with different differentiated somatic cells
Anaplasia
Loss of specialized features of a cell or tissue
How does malignant growth affect the basement membrane?
Cells break through the basal lamina and can spread to other body regions
What are the main cause of human cancer?
Age, environmental factors, and heredity
Transdifferentiation
Transformation of cells other than stem cells into a different cell type
epithelial-mesenchymal transition (EMT)
cells lose epithelial cell traits and gaining mesenchymal cell traits
What percentage of cancer deaths are due to metastasis
> 90%
What are some examples of tumor suppressor genes?
Growth inhibitors and DNA repair proteins (p53)
What is an example of an oncogene?
Mutated growth inducer
What is the main restriction point in the cell cycle?
The border between G1 and S
What are the categories of chemical carcinogens
Polycyclic aromatic hydrocarbons, heterocyclic aromatic amines, nitrosamines and nitrosamides, alkylating agents, fibrous minerals: asbestos and erionite
How does DMBA act as a carcinogen?
Forms adduct with DNA bases, causing mutation. Functions as initiator to promotion of tumor formation from croton oil
What is the Multistep Theory of Chemical Carcinogenesis?
Initiation: exposure to chemical, DNA mutation, precancerous cells; Promotion: proliferation of cells; Progression: cells accumulate mutations selected for more aggressive traits
Depurination
Purine base is hydrolyzed from DNA
Deamination
Amine group is removed from Cytosine, forming Uracil
Pyrimidine dimer
Pyrimidine bases on the same strand dimerize
Which forms of radiation cause DNA damage
UV (mainly UVB and UVC) and Ionizing radiation (X-rays, gamma rays, alpha particles, and beta particles)
Alpha particles
Positively charged, 2 neutrons and 2 protons, can’t penetrate paper
Beta particles
Negatively charged electrons, can’t penetrate metal or wood
gamma rays
EM radiation emitted by alpha and beta particles, can penetrate deep into concrete
UVA
Causes skin aging and cell proliferation
UVB
Causes sunburn, skin aging, and pyrimidine dimers
UVC
Causes severe burns; filtered out by ozone layer
Types of DNA damage caused by ionizing radiation
Base alteration, base removal, single- and double-stranded breaks
Electron volt (eV)
expresses total energy
Gray (Gy)
expresses the energy absorbed when radiation acts on biological tissue
Relative Biological effectiveness (RBE)
expresses damage caused by radiation and is measures in sieverts (Sv)
Background Equivalent Radiation Time (BERT)
Compares standard daily radiation with what will be experienced in other scenarios
Ames test procedure
Bacteria requiring histidine is grown on media without histidine supplemented with the substance being tested mixed with liver homogenate
Why are some animal carcinogens not detected by the Ames test?
Some carcinogens require other substances to exert their mutagenic effect
Genetic effects of chemical carcinogens
Direct mutagenesis on DNA
Epigenetic effects of chemical carcinogens
Carcinogenic effects without mutating effects (affects cell signaling, RNAi, etc.)
Most lethal commercial product
Tobacco causes lung cancer
2nd most lethal commercial product
Asbestos causes mesothelioma
2-naphthylamine
Similar to aniline (purple dye) causes bladder cancer
Butadiene
From ship channel; causes leukemia
Acrylamide
Used in cooking, industry, and labs; binds to DNA and causes damage
How is mesothelioma different from lung cancer?
Lung cancer is cancer of lung interior; mesothelioma is cancer of pleural tissue on exterior of lung
Linear model of cancer development
As carcinogen dose increases, cancer rate increases linearly
Threshold model of cancer development
Cancer rate increases linearly once carcinogen dose reaches a certain threshold
Hormetic model of cancer development
At low doses, carcinogen may actually prevent cancer
Iatrogenic causes
Prescription drugs that cause cancer
Maximum Tolerated Dose (MTD)
Maximum dose of carcinogen that does not present immediate life-threatening toxicity or significant weight loss
Dose effect
Longer exposure to carcinogen increases risk
Delayed Effect
cancer occurs long after initial exposure to carcinogen
How was the Rous sarcoma virus studied?
Sarcoma was removed form one chicken, ground into fine particles, and injected into a second chicken. The second chicken then presented the same sarcoma.
What type of virus is the Rous sarcoma virus?
Retrovirus
Provirus
virus that inserts its genome into the host’s genome
What gene is key to the Rous sarcoma virus transformation process?
v-src (codes for constitutively active tyrosine receptor)
What is the proposed origin of viral oncogenes?
Proviral DNA is replicated from host genome along with an adjacent proto-oncogene. Proto-oncogene eventually mutates into oncogene with subsequent viral replications
Which country has highest rate of stomach cancer?
Japan
Which bacteria is linked to stomach cancers?
Heliobacter pylori
How does prolonged inflammation cause cancer?
By promoting mutation and proliferation
Mutator phenotype
DNA repair genes are mutated, so mutations accumulate more easily
One-step DNA repair
One enzyme makes simple repair. Ex: alkyltransferase removes alkyl group added to base
Base Excision Repair (BER)
Corrects oxidation, deamination, and alkylation of base. DNA glycosylase removes the base, then endonuclease cuts backbone, then DNA pol and ligase replace base and seal strand
Nucleotide Excision Repair (NER)
Repair proteins scan DNA and identify site. Endonuclease removes several nucleotides from one strand. DNA repaired by DNA pol and ligase. Carried out by XP proteins
Mismatch repair
MutS recognizes mismatch. MutL is recruited and excises flanking DNA on one strand (endonuclease). DNA pol and ligase repair
Homologous Recombination
Repairs double-strand breaks. Broken ends of DNA are paired with unwound sister chromatid. Strands are repaired, disengaged, and paired. Done by BRCA1 and BRCA2
Non-homologous end-joining
Repairs double-strand breaks. Broken ends of DNA are brought together, and strands are filled in. Some base pairs originally present are missing.
Endogenous mutation
spontaneous (like from replication errors)
Exogenous mutation
from environmental factors
Xeroderma Pigmentosa
Arises from mutations in XP proteins responsible for NER. Unable to repair damage caused by UV
Which mutated DNA repair proteins are associated with inherited breast cancer
BRCA1 and BRCA2
Which genomic location has the highest percentage of associated SNPs in most cancers
Intergenic sequences between genes
Super-enhancers
large clusters of enhancer elements with high levels of TF binding; central to stimulating oncologic transcription
Heterochromatin
densely packed
Euchromatin
loosely packed
Histone
protein associated with DNA
Nucleosome
Complex of DNA wrapped around histone octamer
Histone acetyltransferase (HAT)
Acetylation promotes transcription
Histone deacetylase (HDAC)
Deacetylation inhibits transcription
DNA methyltransferase (DMNT)
Methylation of cytosine recruits methyl-binding proteins to interact with HDACs and inhibit transcription. Methyl cytosine spontaneously deaminates to thymine.
How to find methylated DNA
Treat with sodium bisulfite; causes unmethylated cytosine to convert to uracil
Oncomir
miRNA that acts as an oncogene
How does miRNA regulate mRNA expression?
miRNA is transcribed and modified, eventually becoming mature ds miRNA after Dicer. The strands separate and form the RISC (RNA-induced silencing complex) with Ago (argonaut; endonuclease). RISC complex binds to mRNA at the 3’ UTR and either degrades it or prevents ribosomes from binding
What is an example of a point mutation activating an oncogene?
RAS gene has point mutation, causing an amino acid change and disabling the protein
What is an example of gene amplification activating an oncogene?
ERBB2 is amplified in 25% of breast and ovarian cancers
Double minutes (DM)
small independent chromosome-like bodies
Homogenously Staining Regions (HSR)
Amplified gene stains homogenously instead of normal light and dark bands
Example of translocation activation of oncogene
Philadelphia chromosome resulting from fusion of BCL-ABR
Local gene rearrangements
Deletions, insertions, transpositions, and Inversions
Example of gene rearrangements activating an oncogene
NTRK1 (growth factor receptor) and TPM3 (tropomyosin) become fused, locking NTRK1 in active dimerized state
Example of insertional mutagenesis
Avian leukosis virus inserts near myc oncogene, causing it to be expressed
Inhibition of miRNA
Results in the protein being overexpressed
What are the three mechanisms known to activate myc?
Gene amplification, insertional mutagenesis, and chromosome translocation
How is Ras usually activated?
point mutation
Why can’t all oncogenes be identified with the transfection method?
Sometimes single oncogenes are not enough to transform cells (multi-hit hypothesis)
What may oncogenes behave like?
Growth factors, GF receptors, Intracellular signal transducers, Transcription factors
Why is ecDNA more transcribed than chromosomal DNA?
ecDNA exhibits lower-order contraction
Molecular target of Iressa
epidermal growth factor receptor (EGFR)
Molecular target of Gleevec
Abl gene (Philadelphia chromosome)
Which amino acids can be phosphorylated?
Serine, Threonine, and Tyrosine