cancer-cause – Flashcards
Unlock all answers in this set
Unlock answersquestion
does not have contact inhibition can grow and divide without restraint
answer
what are some heritable properties of cancer cell?
question
tumor mass
answer
what grow and divide without restraint lead to?
question
when tumor mass grow with angiogenesis but without invasion
answer
what is benign growth?
question
when cancer cells acquire ability to invade surrounding tissue and can metastasize
answer
what is malignant cancer?
question
VGEF=vascular endothelial growth factor
answer
what is the important factor that contributes to angiogenesis?
question
benign cartilage tumor
answer
chondroma
question
benign epithelial tumor with a glandular organization
answer
adenoma
question
malignant cancer arise from epithelial cell
answer
carcinoma
question
malignant cancer arise from connective tissue or muscle cell
answer
scarcomas
question
malignant cancer arise from white blood cells and hematopoietic cells (WBC precursor)
answer
leukemia and lymphoma
question
using a CT scan overlaid with PET scan with fluorodeoxyglucose (FDG) to show areas with high glucose uptake and metabolic activity tumor cells tend to have higher metabolism rate
answer
how are metastases of malignant cancer revealed?
question
benign tumor: remains inside the basal lamina that marks the boundary of a normal structure malignant tumor: can develop from benign tumor cell and destroy the integrity of the tissue to spread
answer
benign VS malignant tumor
question
tumors arise from a single primary tumor (a single cell that experience heritable changes) then additional changes accumulate that allow tumor cell to outgrow the other normal cells
answer
how does tumor originate?
question
molecular analysis
answer
what are methods to detect clonal origin or tumor cell?
question
chronic myelogenous leukemia can distinguish the leukemic WBC from the patient's normal cells by a specific chromosomal abnormality: (Philadelphia chromosome) translocation of chromosome 9 and 22 somatic mutation
answer
what is CML?
question
the novel gene created as a result of translocation of chromosome 9 and 22 in patient with CML chromosome 22 --> chromosome 22q- gene that encodes a protein that promotes cell proliferation
answer
what is a Philadelphia chromosome?
question
when tumor has 10^8 cells detectable by X-ray
answer
when is a tumor first visible?
question
when tumor has 10^9 cells
answer
when is a tumor first palpable?
question
when tumor is 10^12 cells large
answer
when does a tumor cause death of a patient?
question
heritable changes in gene expression that results from modification of chromatin structure without alteration of the cell's DNA sequence
answer
what are epigenetic changes?
question
abnormal changes need to pass from parent cell to progeny
answer
what does clonal origin suggest?
question
could be either genetic- altered DNA sequence Epigenetic - altered gene expression
answer
is cancer due to epigenetic changes or genetic changes?
question
chemical carcinogens and radiation
answer
where are the causes of genetic changes?
question
simple local changes in the nucleotide sequence
answer
what does chemical carcinogens lead to?
question
cause chromosome breaks and translocation
answer
what does X-ray lead to?
question
causes specific DNA base alteration
answer
what does UV light lead to?
question
people who have inherited genetic defect in one of several DNA repair mechanisms causing their cells to accumulate mutations at an elevated rate
answer
what kind of people would have high risk of cancer?
question
10^16 cell divisions/ human life
answer
how many cell divisions occur in human life with mutagen ?
question
10^12 divisions / mous life
answer
how many cell divisions occur in mouse life with mutagens?
question
10^10 occasions lead to a mutation in a human gene
answer
what is the mutation occurrence in human that happens without mutagens?
question
10^6 occasions lead to a mutation in a mouse gene
answer
what is the mutation occurrence in mouse that happens without mutagens?
question
development of a cancer require a substantial number of independent, rare genetic and epigenetic accidents in a single cell
answer
why does cancer occur so infrequently even with high mutation rate?
question
We can see that the incidence rate of cancer is age dependent. More occurrence of cancer are seen in older people The delayed cancer onset indicates successive DNA alteration
answer
how can we shown that tumor phenotype require multiple mutations ?
question
a gradual accumulation of mutation successive DNA alteration
answer
what is required for tumor progression?
question
in 5 years
answer
when did leukemia become detectable after the hiroshima-nagasaki radiation exposure ?
question
in the basal layer
answer
where does the proliferation of cervical cancer occur?
question
in normal epithelial cell, the basal cells differentiate then move to the surface. in a tumor cell that is not yet malignant, undifferentiated proliferating cells moves from the basal layer to cell surface
answer
how does the normal epithelial cell migration compare to the tumor?
question
when the undifferentiated, proliferating cells move through or destroy the basal lamina that underlies the basal layer of epithelium and invade the underlying connective tissue
answer
what make a epithelial cell a invasive carcinoma?
question
tumorigenesis
answer
what is the term for the beginning of true malignancy?
question
aka pap smear in a invasive carcinoma pap, the cells have alternative levels of differentiation as well as enlarged nucleus
answer
what is papanicolaou? what can you see in it?
question
cancer progress through cycles of random inherited changes (random mutation) and natural selection different sub-clones may gain an advantage and come to predominate but then gets overtaken or outgrown by their own sub-clones (very large genetic diversity)
answer
what occurs during tumor progression that makes cure so difficult ?
question
using appearance of cell nucleus
answer
what is a method of classification of tumor?
question
epigenetic refers to accidental heterochromatin packing and methylation of nucleotide, result in inactivation of genes that could potentially block tumor progression
answer
how does epigenetic change cause cancer?
question
altered chromatin modifying enzyme in cancer cell
answer
what causes epigenetic changes in cancer ?
question
rapid accumulation of genetic abnormalities
answer
what is genetic instability ?
question
inability for DNA repair or inability to correct replication errors independently occurring epigenetic changes
answer
what causes genetic instability ?
question
changes in DNA sequence or produce rearrangements unable to maintain number or integrity of chromosome ex: DNA translocations, Duplications ==> over all change in karyotype
answer
what is the result of genetic instability?
question
when the DNA changes alter epigenetic control mechanism that least to production of extra heterochromatin and DNA methylation
answer
How are the genetic instability amplified?
question
involved in propagating DNA or chromosome
answer
what is a DNA maintenance gene?
question
have raised incidence of cancer because of loss in genetic stability
answer
what is the significance of people with mutation in DNA maintenance gene?
question
no, there is a optimum level of genetic instability making the cell mutable enough to evolve rapidly but not so mutable that it accumulates too many harmful changes and dies
answer
is genetic instability uncontrolled in cancer cell?
question
more cells available for proliferation and greater rate of proliferation leads to high mutation rate
answer
how does defects in cell differentiation and cell death lead to cancer?
question
increase cell division + normal apoptosis = tumor normal cell division + decreased apoptosis = tumor
answer
how do we get increased number of cell for proliferation?
question
cell-division-counting mechanism that depends on the progressive shortening of the telomeres at the ends of chromosomes make sure cell stop dividing after a certain number of population doubling
answer
what is replicative senescence?
question
it sets a physiological limit to cell proliferation for most of the types of cells in the body
answer
what is the importance of replicative senescence?
question
acquire epigenetic changes that disable check point control inactivate the P53 pathway maintain active telomerase alternative ways of extending telomeres
answer
how does tumor cells avoid replicative senescence?
question
stem cell maintain their lineage by producing some daughter cells that can remain stem cells
answer
what is self-renewal?
question
make transit amplifying cell (= slow dividing stem cells that proliferate extensively and eventually differentiate into specialized cell ) produce stem cells that maintains stem cell lineage
answer
what does a normal stem cell do?
question
it maintains the population of cells in a tumor
answer
why is cancer stem cell important?
question
they are capable of indefinite self-renewal but also give rise to rapidly dividing transit amplifying cells that have limited capacity for self-renewal
answer
what can cancer stem cells do?
question
only a small subset of cancer cells have the special property needed for tumor propagation
answer
what does it mean that cancer cells are heterogeneous?
question
mutations in normal tissue stem cell change in a proliferating cell that is more differentiated (aka transit amplifying cell)
answer
what are the origins of cancer stem cell?
question
with FACS stem cells are weakly fluorescent because they have ABC transporter that actively pumps dye out of the cell
answer
how are cancer stem cells sorted?
question
invasion and colonization of distant organ 1. cell crosses the basal lamina and endothelial lining of blood vessel or lymph vessel to travel 2. cell exit vessel to grow on a new site 3. growth on new site forms micrometastasis 4. micrometastases much colonize by producing cells that survive and proliferate in the new environment
answer
what are the steps to metastasis?
question
cancer cells are more resistant to apoptosis and more readily survive after escaping form their proper home cancer cells are less dependent on signals from other cells to grow and divide
answer
why are cancer cells more capable of metastasis than compare to normal cells?
question
formation of new blood vessels
answer
what is angiogenesis ?
question
1. hypoxia (deficient oxygen level) in a enlarge tumor activates angiogenic switch 2. "on" of angiogenic switch increase Hypoxia inducible factor (HIF-1a) 3. HIF-1a activates transcription of VEGF 4. VEGF attracts endothelial cells, stimulate blood vessel growth 5. irregular blood flow stimulates even more hypoxia..cycle continues
answer
what is steps of angiogenesis in tumor cell?
question
cells in the tumor that supports connective tissue
answer
what are stroma?
question
fibroblast myofibroblast inflammatory white blood cells endothelial cell of blood and lymph vessel pericytes smooth muscles cells
answer
what are examples of stroma?
question
development of a tumor relies on cross-talk between the tumor cell and the tumor stroma cancer cell induced changes in the stroma and the stroma acts back to stimulate cancer cell growth and division
answer
what is stroma significant in tumor development ?
question
more self-sufficient for growth and proliferation insensitive to anti-proliferative extracellular signal less prone to undergo apoptosis defective in control mechanism that normally stops cell division induce help from nornal stroma cells in the environment induce angiogenesis can escape from home tissue and survive in foreign site genetic instability can produce telomerase or acquire way of stabilizing telomeres
answer
what are properties that contribute to cancer growth
question
mutation causing agents that leads to cancer
answer
what are carcinogens?
question
chemical - aromatic hydrocarbon, alkylating agents radiation - UV, gamma particle, alpha particles from radioactive decay
answer
what are some carcinogens?
question
Ames test
answer
how can mutagenicity of a chemical be tested?
question
carcinogen is mixed with an activating extract (prepared from rat liver cell) and added to a culture of specially designed test bacteria
answer
what is a ames test?
question
mutagen compound can revert a defect in cultured bacteria and allow proliferation of cell ex: mutagen reverted histidine-dependent characteristic of salmonella, allowing salmonella to grow in a histidine lacking medium (salmonella is now histidine -independent)
answer
what are the differential result between mutagen and non-mutagen in ames test?
question
no, carcinogens are more damaging after they have been changed to more reactive form by metabolic process in the liver
answer
do the carcinogens act directly on DNA?
question
cytochrome P-450 oxidase
answer
what enzyme catalyze the change of carcinogen to more reactive?
question
carcinogen from mold Aspergilus associated with liver cancer in tropics via P53 mutation activated by cytochrom P-450 active form: aflatoxin 2,3- epoxide active form binds to Guanine in DNA
answer
what is Aflatoxin?
question
C P-450 usually help convert ingested toxins into harmless and easily excreted compounds in a cancer cell case, its activity on certain chemicals generates products that are highly mutagenic
answer
what does Cytochrome P-450 normally do?
question
vinyl chloride
answer
what is the carcinogen for liver angiosarcoma
question
benzene
answer
what is the carcinogen for acute leukemia
question
arsenic
answer
what is the carcinogen for skin carcinoma and bladder cancer?
question
asbestos
answer
what is the carcinogen for mesothelioma?
question
radium
answer
what is the carcinogen for osteosarcoma?
question
a initial mutagen that alter DNA sequence to initiate tumor
answer
what is a tumor initiator?
question
one single application may lead to latent change multiple application result in overt tumor single application followed by tumor promoting agent expedite tumors
answer
what is the affect of tumor initiators?
question
a promoter is not a mutagen induce an inflammation response that cause secretion of growth factor and proteases allow mutant cell growth by lifting growth restraint on mutant initiator
answer
what is a tumor promoter?
question
tumor promoter (ex: phorbol esters, TPA) behave as artificial activators of protein kinase C and activates part of the phosphatidylinositol intracellular signaling pathway can cause cancer if applied after a treatment with tumor initiator
answer
what is TPA?
question
cancer happens if the exposure to the promoter follows exposure to the initiator and if the promoter exposure intensity meets a threshold
answer
what is required of relationship between tumor initiator and promoter to lead to cancer?
question
no, repeated exposure of initiator along can also lead to cancer
answer
are both promoter and initiator required for cancer development?
question
benign warts carcinoma of uterine cervix
answer
what is the associate cancer of Papovavirus family virus ? (papillomavirus)
question
liver cancer
answer
what is the associate cancer of hepadnavirus family virus? ( hepatitis-B and hep-C virus)
question
burkitt's lymphoma (cancer of B lymphocytes) nasopharyngeal carcinoma
answer
what is the associate cancer of herpevirus family virus? (epstein-barr virus)
question
adult T-cell leukemia/ lymphoma HTLV-1 is a RNA (retro) virus
answer
what is the associate cancer of HTLV-1 (human T-cell retrovirus) ?
question
kaposi' sarcoma HIV and AIDS are RNA virus in the retrovirus family
answer
what is the assocaite cancer of HIV, AIDS virus?
question
genes whose alteration frequently contribute to the cause of cancer
answer
what are cancer- critical genes?
question
proto-oncogene tumor supressor gene DNA maintenance gene
answer
what are the types of cancer critical gene?
question
a normal functioning gene that can become oncogene (cancer) via gain of function mutation. mutant, overactive form are called oncogenes oncogene have growth promoting effect, promote cell transformation
answer
what is a proto-oncogene?
question
loss of function mutation that can contribute to cancer Loss of function is recessive so tumor suppressor genes in both chromatids have to be silenced. when two inactivating mutation functionally eliminate tumor suppressor gene, it will promote cell transformation
answer
what is a tumor suppressor gene ?
question
they are genes whose mutation results in genomic instability
answer
how does DNA maintenance gene affect cancer development?
question
-nondisjunction causes chromosome loss -chromosome loss, then chromosome duplication -mitotic recombination -gene conversion -deletion -point mutation ...and also epigenetic changes
answer
what are the possible ways for a cell to lose its only remaining tumor suppressor gene?
question
- mutation in both gene copies of gene - heritable gene silencing (epigenetic change) in both copies of gene - heritable gene silencing (epigenetic change) in one copy and mutation in the other copy of gene
answer
what are the epigenetic and genetic changes that leads to loss-of-function in tumor suppressor gene?
question
point mutation promoter alteration gene amplification gene rearrangement
answer
what are way hyperactivate proto-oncogene to oncogene?
question
oncogene that is incorporated in a virus cell that can be incorporated into host cell and proliferated
answer
Src gene?
