Unit 5 Flashcards
What is the tumor structure of a which determines the biological nature (aggressiveness) of the tumor,are clonal, and basically are transformed cells or neoplastic?
Parenchyma
What is the tumor structure that is non- neoplastic, utilizes vessels and ecm as support and has a long term tumor survival?
Stroma (the more vascular a tissue is the more chances of stroma there are)
Which type of tumor exhibit “relatively innocent” features, is localized and reselectable, and posesses a favorable prognosis? Could cause : vascular compression and hormone production
Benign tumors
what is the name for a benign epithelial neoplasms producing or derived from glandular tissue?
adenoma
What is the name for a benign epithelial neoplasms that has Finger-like fronds?
Papilloma
what is the name for benign tumor of capillary endothelial cells?
hemangioma
what is the name for a benign tumor of adipose tissue?
Lipoma
What is the name for a benign smooth muscle tumors • “fibroid”?
leiomyoma
Malignant neoplasms that are composed of undiffer- entiated cells are said to be _______
anaplastic
These types of tumors are associated with cancer, they tend to be invasive and destructive, they have a tendency to metastasize, has parenchyma determining aggressiveness?
Malignant tumors
Malignant tumors are typically classified by
Embryonic tissue of origin
These tumors are typically derived from mesenchyme, associated with connective tissue and can develop at nearly any age?
Sarcomas
What is the 2nd most common cause of death in the US?
Cancer
This type of cancer has a higher incidence of cancer in males
Prostate
Most common type of cancer in females is
Breast cancer
This cancer is the cause of most death related to cancer
Lung and bronchus cancer
Cancer is basically a type of _____ growth
disregulated
What is neoplasia ?
new growth
Cancer is known to be a _____ ______ in which some sort of genetic material has been altered via mutations or epigenetics and is _____ to daughter cells
Genetic disorder; heritable
These characteristics Autonomous growth, independent of growth-inhibition, evasion of cell death & immune system, limitless replication, angiogenesis, invade/spread, abnormal metabolism are common with what?
neoplasia
It is important to note that neoplastic cells are _____ which means they are creating exact copies of themselves
clonal
What are the risks associated with cancer?
excessive alcohol, obesity, Toxins, irradiation, age, genetics
What is a parenchyma?
a cell that has undergone neoplasmic transformation, typically clonal and determine the aggressiveness of the tumor
What is a stroma?
Cells that support parenchyma, they are non neoplastic cells, necessary for long term tumor survival
What is a synonym to cancer?
Malignancy
Secondary site is a synonym for
metastasis
What is the rule of thumb for naming tumors?
Cell type + OMA
Where do carcinomas originate from?
Epithelial cells it is the MOST COMMON type of cancer 90%
What age range are carcinomas typically found in?
Mid to late adulthood
What is dysplasia?
Disorderly proliferation which means irregular growth but not neoplastic
In early neoplasia the carcinoma is _____ ___
in situ which means they have not penetrated the basement membrane
Invasive carcinoma are _____ and _____ aggressive
infiltrative and more aggressive which entails local destruction
multiple germ cell layers
• (Usually, described as 3)
• Bone, teeth, epithelia, muscle,
fat, & neurons
Are characteristics of which tumor?
Teratoma
MC benign tumor of the female breast • 2 tissue types
• Mixed tumor
• Only fibrous neoplasia
Are characteristics of which tumor?
Fibroadenoma
what is a benign tumor of tissue native to a particular site, well-differentiated
Hamartoma
What is a mass that projects from a mucosal surface (e.g. colon polyp)?
Polyp
What the criteria for Neoplasia?
Differentiation/anaplasia
Rate of growth
Local Invasiveness
Metastasis
Utilizing the criteria for neoplasia we are able to establish a _____
prognosis
What is differentiation?
How closely cells resemble their precursors
Normal: Well differentiated, slow mitosis
Benign: more well differentiated
What is anaplasia?
Loss of parenchymal differentiation
Cells that are poorly differentiated, are pleomorphic and have a high a rate of mitosis are said to be
Anaplastic
What is the difference in rate of growth between malignant and benign tumors?
Benign: Slow and controlled
Malignant: Fast and uncontrolled
- correlation with differentiation
+ correlation with anaplasia
Which tumors are more likely to be invasive?
Malignant tumors which progress from local to distant invasion
In terms of invasiveness, this type of tumor is well localized, isolated and non invasive and capsulated
Benign tumor
What is the most reliable indicator of Cancer?
metastasis
Usually poor prognosis in cancer is attributed to _____ which causes tissue destruction and disturbs function
Metastasis
What are the types of dissemination ?
Seeding within body cavities, lymphatic spread, and hematogenous spread
How does seeding happen?
Invasion of cancer in natural body cavities and spreads to CNS or Ovaries
Which is the most common type of carcinoma spread?
Lymphatic spread
What is the most common type of SARCOMA spread?
Hematogenous spread
What is hematogenous spread?
Very rapid spread of cancer via the circulatory system and they stop at the 1st capillary bed which is usually in the liver
Most types of cancer are _____ and encompass 70-80% of all cancer diagnosis
sporadic many due to environmental factors which cause somatic mutations
Relocation might actually change the risks of cancer (T or F)
True
10% of all childhoold deaths (>15 years) are attributed to
Cancer (Leukemia, lymphomas
When a single mutant alelle is inherited and a specific phenotype marker such as neurofibromas and cafe au lait spots it is usually due to
Autosomal dominant CA syndromes
Altered NF1 genes cause
Neurofibromas and cafe au lait spots
When there are two altered genes due to genomic instability and there are defective dna repair enzymes it is due to
Autosomal recessive syndrome of defective DNA
An example of autosomal recessive syndrome of defective DNA would be
Xeroderma pigmentosa
The most sporadic types of CA have a subtle familial association. This type of hereditary CA has no marker phenotypes
familial cancer of uncertain inheritance
Why do preneoplastic lesions have an higher risk of cancer?
the cells in the lesions usuall are dysplastic or metaplastic
An example of preneoplastic lesions in which white plaquing occurs in the buccal surface of mouth and could lead to squamous cell carcinoma?
leukoplakia
what is carcinogenesis?
Creation of cancer
The steps in the process of carcinogenesis are called
nonlethal genetic damage
Genetic mutations that are usually ______ are found in a small subset of cells within the body (somatic cells) and are due to environmental factors such as irradiation and viral infection
Acquired
Genetic mutation which involves all cells of the body and does not involve environmental factors
inherited
What are the classes of regulatory genes?
proto oncogenes (later on oncogenes), TSGs, Apoptosis genes, and DNA repair genes
All of which incresase the growth and survival within the tumor cell
Accumulation of mutations could lead to
Cancer
What is a proto oncogene?
normal gene that regulates celullar growth
What is an oncogene?
a mutated or overexpressed proto oncogen. It is anaplastic and contributes to cancer growth
In order for an ocogene to gain function how many alelles need mutations?
1
What is the karyotype?
number and appearance of chromosomes in the nucleus
Damage to the karyotype could lead to
carcinogenesis by activating oncogenes and suprresing TSGs
This type of structural abnormality is due to overexpression of proto-oncogenes and creation of a fusion gene (CML). It typically affects hematopoeitic cells
Balanced translocations
A structural abnormality which is found in solid tissue cancers and impact TSGs
Deletion
a structural abnormality in which overexpression of protooncogene leads to oncogene creation and is associated with breast cancer
overamplification
What is micro RNA?
small non coding RNA molecules
What is the function of micro RNA?
inhibiting gene expression and controlling growth and survival of cells. They also suppress translation
When micro RNA is amplified it might lead to
Inhibition of TSGs
Deletion of Micro RNA may lead to a
loss of oncogene inhibition
What is epigenetics?
heritable changes of gene expression where there is no change in dna sequence. It is associated with silence genes (dna methylation/ histone modification)
In tumor progression, when a clonal cell eventually starts unregulated production of clone cells and thus lead to production of subclonal cells because of the aggressiveness of the tumor. This could lead to ____
heterogeneity
What are the hallmarks of cancer?
evading apoptosis, self sufficiency in growth signals, insensitivity to anti growth signals, tissue invasion and metastasis, limitless replicative potential, and sustained angiogenesis
Mutations of a cell promote self sufficiency in which case it makes the cell not dependent on other cells for growth thus causing an _____ loop. CA cells can produce their own GFs and stimulate stromal GFs
autocrine
HER2 mutations (overexpression of GF receptors) are usually involved with
breast cancer
When a GF receives a signal and transmits across the cytosol to the nucleus it usually entails the use of a _____ which are also involved in the inhbition of apoptosis.
signal transducing molecule
Mutations of STMs are common in tumors and could cause as much as ____ of all tumors
30%
RAS and ABL mutations are the two most common types of mutations to _____
STMs
STMs stimulate mitosis and initiation of transcription, thus if they are continuously stimulated they could lead to ____ of the cells
unregulated proliferation
What is the restriction point in the cell cycle?
G1- S phase transition
When CDKs are mutated what typically occurs?
unregulated proliferation of cells due to speeding through the restriction point of the cell cycle. ALL CANCERS DISABLE THIS RESTRICTION POINT
TSGs encode inhibitory proteins and cause decreased proliferation, however if one is ______ to growth inhibition then cells can proliferate in an erratic manner
insensitive
What do altered TSGs mimic?
oncogene stimulation
Insensitivity of growth inhibition is typically recessive and requires ____ alleles to be inactivated
2
What was the the first tumor suppressor gene to be discovered that is also expressed in every cell type examined?
RB GENE
What is the importance of the RB Gene?
It regulates the G1/S checkpoint.
Seeing as Cancer usually entails an unregulated growth and differentiation, the RB will usually be defective in many or most forms of cancer (T or F)
True
What type of viruses might affect the RB gene?
HPV
Which of the TSGs is one of the most commonly mutated genes in human cancers (70% ie Lung, breast, and colon cancer)?
TP53
which gene thwarts neoplastic transformation by three interlocking mechanisms: activation of temporary cell cycle arrest (termed quiescence), induction of permanent cell cycle arrest (termed senescence), or triggering of pro- grammed cell death (termed apoptosis)?
TP53
What are the stressors that might activate the P53 gene?
Anoxia, activation of oncogenes, and DNA damage
When working with the P53 gene which may be considered the primor- dial response to DNA damage ?
Quiesence due to minor DNA damage
Increases the rate of dna repair
What is the name for a permanent cellcycle arrest characterized by specific changes in morphology and gene expression that differentiate it from quiescence or revers-ible cell cycle arrest?
TP53 mediated senescence
What is is the ultimate protective mechanism against neoplastic
transformation?
tp53-induced apoptosis
In most cancers, there is a bi-allelic loss of the P53 gene (t or f)
true
Less commonly, some patients inherit a mutant TP53 allele; the resulting disease is called ________
Patients with _______ have a 25-fold greater chance of developing a malignant tumor by age 50 com- pared with the general population
Li Fraumeni
Cancers not only develop from unregulated growth it may also develop from a non functioning or mutation in apoptosis which helps CA cells survive instead of killing them. This increases the probability of _____ development
tumor
It is known that both apoptotic pathways (Ext/Int) activate their respective caspases ( EXT -> 8 and INT ->9) however which caspase is stimulated by BOTH pathway?
Caspase 3 (executioner)
most normal human cells have a capacity of 60 to 70 doublings. Thereafter, the cells lose the capacity to divide and enter _______ which is linked to telomere shortening
senesence
If telomere shortening is pronounced, this might eventually lead to _______ _______ which is characterized by massive apoptosis
genomic instability
t for tumors to grow indefinitely, as they often do, loss of growth restraints is not enough. Tumor cells also must develop ways to avoid both _____ and ______ therefore if a cell manages to activate telomerase then it might avoid death
senesence and mitotic catastrophe
What is the Hayflick limit?
The finite number of divisions a cell can have
Tumor growth without new blood vessels requires what diameter?
> 1-2mm
What does sustained angiogenesis provide and remove?
nutrients and remove waste
What is usually stimulated in neoplasia and is poorly organized (Leaky, dilated, tortuous)?
angiogenesis
Pro angiogenic factors are usually stimulated by the tumors (t or F)
true
Which system is utilized by the tumors in order to metastasize?
vascular
What requires angiogenesis for growth support, has metabolic demands and has sequential spread?
Malignancy and metastasis
What are the steps for the invasion mestastasis cascade?
- Invasion of ECM
- Vascular spread: dissemination & homing
- Micrometastases grow & invade
Mutations develop because of __+_
genetic make up and environment
What are the three DNA repair systems?
- Mismatch repair
- Nucleotide excision repair
- Homologous recombination repair
which system of DNA repair works with genes to fix “spelling errors”?
mismatch
When “spelling errors” accumulate they form a _______ phenotype which means the way the morphology of the cell will change
mutator
The most common error which includes abnormal repeats of 1-6 nucleotides, is unstable, present in 15% of sporadic colorectal cancers, and is present in HNPCC
Microsatellite instability
Which DNA repair mechanism Recognizes a segment of damaged DNA and removes it, then repairs the “gap” via DNA polymerase?
What is an example of it?
Nucleotide Excision repair
Ultraviolet light could cause cancer (t or f)
True. excess exposure increases the chance of getting cancer dramatically
Which DNA repair system involves DNA being exchanged between two homologous chromosomes to repair breaks in DNA?
Homologous recombination
If one has Hypersensitivity to DNA-damaging agents then homologous recombination cant happen (t or F)
true
Mutations in two genes, ____ and _____, account for 50% of cases of familial breast cancer.
brca 1 and 2
inflammation, often thought of as a protective response against tumors, can paradoxically also enable malignancy (t or f)
true
What are the two ways in which inflammation could stimulate tumor growth?
Persistent chronic inflammation in response to microbial infections or as part of an autoimmune reaction and When inflammation occurs in response to tumors
Patients with GI tract infections, hepatitis B and C, and other autoimmune reactions are highly susceptible to Cancers due to the compensatory proliferation of
cells in an attempt to repair the damage. This regenera- tive process is aided and abetted by a plethora of growth factors, cytokines, chemokines, and other bioactive sub- stances produced by activated immune cells collected at the site. Persistent cell replication and reduced apoptosis under these conditions place the cells at risk of acquiring mutations in one or more of the genes involved in car- cinogenesis True or false
true
In order for carcinogenesis to occur _____ genetic alterations are required however they need not follow an orderly sequence.
multiple
Breast and colon cancers have approximately 90 mutations
Carcinogenesis results from the stepwise accumulation of several genetic alterations T or F
True
. According to the scheme of Adenoma Carcinoma formation , inactivation of the ___ tumor suppressor gene occurs first, followed by activation of ____ and, ulti- mately, loss of a tumor suppressor gene on ____and loss of ____. The precise temporal sequence of mutations may be different in different tumors.
APC, RAS, 18q, TP53
What are the 3 classes of carcinogenic agents ?
(1) chemicals, (2) radiant energy, and (3) microbial agents (mainly viruses such as HPV, EBV, Hep B, HEP C, KSHV but the one primary bacteria is Helicobacter pylori)
What is a direct acting carcinogen?
carcinogens which require no metabolic conversion to become carcinogenic. They are in general weak carcino- gens but are important because some of them are cancer chemotherapy drugs
What is an indirect acting carcinogen?
refers to chemicals that require metabolic conversion to an ultimate carcinogen. Exposure to Polycyclic Hydrocarbons can cause cancers because of these type of carcinogens but also another agent that might produce this would be Aflatoxin B1 which is produced by some strains of Aspergillus, a mold that grows on improperly stored grains and nuts
Why is Aflatoxin B1 dangerous?
It carries a signature mutation which affects TP53
