Exam 3: Section 5 Remaining Material Flashcards
What is Mets
Metastasis
Which form of cancer is most likely to travel via lymphatics
Carcinoma
Tumors with anaplasia are most likely to be
Invasive malignant tumor
Tumors with fairly well differentiated cells are more likely to be
Slowly growing benign tumors
Most cancer related deaths occur between
55-70 years old
Most common cause of cancer related deaths in males
Prostate CA
____ correlation between rate of growth and differentiation in cancer cells
Inverse
____ tumors are less likely to be encapsulated
Malignant
MC breast cancer
Invasive ductal carcinoma
MC breast tumor
Fibroadenoma
Osteosarcomas travel ____ primarily
Lungs
Colorectal CA travels to ____ primarily
Liver
Most reliable indicator for malignancy
Metastasis
Most people from cancer die from ____ as a result of Mets
Organ failure
3 types of Mets
- Seeding
- Lymphatic
- Hematogenous
Seeding Mets
Invasion of natural body cavities
2 types of body cavities primary associated with seeding Mets
Ovaries
CNS
Lymphatic Mets are MC form of Mets for
Carcinomas
Lymphatic Mets are determined by
Site and tumor parenchyma
Lymphatic Mets usually involved a ___ node
Sentinel lymph node
Hematogenous Mets is MC Mets for
Sarcoma
Type of Mets that is very rapid
Hematogenous
Hematogenous Mets are most likely to spread to
First capillary bed
GI cancer using hematogenous Mets go to
Liver
Systemic circulation cancers using hematogenous Mets go to
Lungs
Ultimate cause of CA is
Genetic alterations
Common CA in US
Breast
Colorectal
Esophageal
Common CA in Africa
Liver
Common CA in Japan
Stomach
Cancer diagnosis is ___, but cancer related deaths are ___
Increasing
Decreasing
CA deaths in men is decreasing by
20%
CA deaths in women is decreasing by
10%
Cancer related deaths are decreasing due to
- Reduced tobacco
- Improved treatment
- Improved screening
Pediatric CA results in ___ of childhood deaths
10%
2 reasons CA affects older adults
- Acquired more somatic mutations
2. Less active immune system
Sporadic CA develops in the absence of
Family history
Sporadic CA is primary result of
Harmful environmental exposures and damage to genetic material
Examples of preneoplastic lesions
Metaplasia
Dysplasia
Proto-oncogene
Normal gene that promotes cellular growth by encoding for transcription factors
Oncogene
Altered proto-oncogene that now promotes excessive cellular growth
Only ___ allele is needed to be mutated to change a proto-oncogene to an oncogene
1
Tumor suppressor gene
Normal genes that slow down cellular growth
If TSGs are altered, they can contribute to
Uncontrolled/ dysregulated cell growth
___ alleles must be altered for a TSG to contribute to carcinogenesis
Both
Apoptosis Genes normally ___ cells that have genetic alterations
Kill
CA cells ____ pathways that enact apoptosis for altered cells
Deactivate
DNA repair genes
Gene abnormalities go uncorrected and may contribute to carcinogenesis
Karyotype
Number and appearance of chromosomes
Aneuploidy
Abnormal number of chromosomes
Balanced translocation
Large genetic change on chromosome level
Balanced translocations can result in
Overexpression of proto-oncogenes
Deletions can deactivate
TSGs by losing genes
Gene amplifications can overexpress
Proto-oncogenes
Structural abnormalities
- Balanced translocations
- Deletions
- Gene amplifications
Example of gene amplification
Breast CA over expressing HER2
Indications of gene amplification
Homogeneously stained region
Double minutes
Epigenetic modifications are ____ changes in gene expression
Heritable
Epigenetics impacts function, but not
Genotype
Epigenetic modifications are
Reversible
Epigenetic modifications silences genes via
DNA methylation
Histone modification
Epigenetics impacts carcinogenesis when ___ are silenced
TSGs or DNS repair genes
Sub clones ____ malignant potential
Increase
8 hallmarks of cancer
- Evade apoptosis
- Self sufficiency in growth signals
- Insensitivity to anti-growth signals
- Tissue invasion and metastasis
- Limitless replicative potential
- Sustained angiogenesis
- Evasion of immune system
- Altered cellular metabolism
Driver mutations
Directly contribute to development and progression of CA
Passenger mutations
Produce genetic variants that may give tumor selective advantage
Mutations inherited via the germline affect
Entire body
Mutation in RB gene
Retinoblastoma
TP53 gene mutation
LI-Fraumeni Syndrome
APC gene mutations
Colorectal CA
NF1 gene mutations
Neurofibromatosis
BRCA 1 and BRCA 2 gene mutations
Breast and ovarian CA
Philadelphia chromosome
Abnormality in chromosome 22 in which part of chromosome 9 is transferred to it
Bone marrow cells that contain Philadelphia chromosome are often found in
Chronic myelogenous leukemia
Burkitt Lymphoma involved balance translocation between chromosome __ and __
8
14
Warburg Effect
Change in CA cell metabolism
Aerobic glycolysis
Governor of cell cycle
RB gene
RB plays role at ___ checkpoint
G1 to S
This infection may inactivate Rb
HPV
Guardian of genome
TP53 gene
MC mutated gene in all CA
TP53 gene
>70%
P53 monitors for cellular stressors such as
Anoxia
Activation of oncogenes
Genetic alterations
3 controls mechanisms involving TP53 gene
- Quiescence
- Senescence
- Apoptosis
Quiescence causes ___ cell cycle arrest in response to ___
Reversible
Minor DNA damage
Senescence results in ___ cell cycle arrest in response to ___
Permanent
Major DNA damage
Apoptosis results in ____ in response to irreversible genetic damage
Programmed cell death
4 most common cancers associated with Li-Fraumeni Syndrome
SBLA
- Sarcomas
- Breast
- Leukemia / lymphomas
- Adrenal gland
Hay flick limit
40-70 divisions
Why is there a hay flick limit?
Telomeres shorten —activates TSGs—senescence
Limitless replication in CA results from non-homologous end-joining between haphazard chromosomes, which can rarely cause
Telomerase re-activation
Telomerase
Repairs and maintains telomeres
The normal result from non-homologous end-joining
Mitotic catastrophe
Reactivation of telomerase is observed in ___ of all cancers
90%
Pro-angiogenic Factors can be from
Tumor cells
Macrophages
Stromal cells
Angiogenesis is in response to
Tissue hypoxia
The new vessels from angiogenesis are dilated, ___, and ____, and can be a route for
Tortuous, leaky
Metastasis
Invasion occurs on a ___ level
Local
Metastasis occurs on a __ level
Distant
Invasion metastasis cascade
- Invasion of ECM
- Vascular spread
- Micrometastases grow and invade
Intravasation
Process of tumor cells metastasizing and entering the blood vessels
Sites of blood stasis
Lungs
Bone marrow
Once in blood vessels, tumor cells can be vulnerable to attach from these lymphocytes
NK
CD8+ T cells
___ can aggregate and provide some protection to CA cells from an immune attack
Platelets
Genomic instability
High frequency of mutations within an individual’s genome
Types of DNA repair
- Mismatch repair
- Nucleotide excision repair (NER)
- Homologous recombination
Pathology caused by dysfunction in DNA mismatch repair
Hereditary Nonpolyposis Colorectal CA (HNPCC)
Aka lynch syndrome
Pathology caused by dysfunction in NER
Xeroderma Pigmentosum
Pathology caused by dysfunction in homologous recombination
Breast cancer
Xeroderma pigmentosum is a ____ defect in NER
Congenital
TP53 gene can by deactivated by __ or ___
HPV or Hep B
CA cells loosen surrounding intercellular connections by deactivation
E-Cadherin genes
CA degrade ECM via
Proteolytic enzymes
Once a CA cells invades the basement membrane, it is no longer considered “____”, but rather ____
In situ
Stage 1 “invasive” CA
3 features of inflammation that increase CA risk
- Release of growth factors
- Angiogenesis
- Local invasion
Acute radiation syndrome can cause these cancers
Leukemia Thyroid Breast Colon Lung
Most common cancer, that exceeds breast, prostate, lung and colorectal ca combined
Skin
MC skin cancer
Basal cell carcinoma
Most lethal and rare skin cancer
Melanoma
Melanoma is due to
Intense UV exposure
3 types of skin cancer
- Basal cell carcinoma
- Squamous cell carcinoma
- Melanoma
H. Pylori is associated with 90% of
Peptic ulcer disease
H. Pylori can cause these 2 cancers
Gastric adenocarcinoma
MALT lymphoma
Only ___ of H.pylori transitions to CA
3%
Retroviruses are ___ viruses that use ____
RNA viruses
Reverse transcriptase
Human T cell Lymphotropic virus-1 (HTLV-1) infects
CD4+ T cells
HTLV-1 uses the ___ gene
TAX
TAX gene activates ____ and suppresses ____
Cyclins (cyclin D)
TP53
HTLV-1 is more common in
Japan
Africa
S. America
How is HTLV-1 transmitted
Sexual contact
Infected blood
Breastfeeding
Strains of HPV making genital warts
HPV-6
HPV-11
Strains of HPV responsible for squamous cell carcinoma
HPV-16
HPV-18
HPV promotes cellular growth by activating ____ and deactivating ____
Cyclins
TSGs
HPV gene ___ deactivates p53
E6
HPV gene ___ inactivates Rb
E7
Epstein-Barr virus is responsible for __ and infects ___
Mono
B cells and epithelial cells
EBV predisposes you for risk of
Burkitt lymphoma
Lymphomas
Hodgkin lymphoma
Nasopharyngeal CA
Responsible for 80% liver CA
Hep b and c
Hep B and C are MC in
Africa
SE Asia
Cancer cachexia is associated with ___ cancer
Advanced
Cachexia
Wasting away of body fat and lean muscles due to widespread CA causing hypermetabolic state on body
Anorexia can be observed in cachexia due to
Cytokine TNF
Not due to local destruction of tumor or tumor putting pressure on surrounding tissues
Paraneoplastic syndromes
Paraneoplastic syndromes can be due to
Immune activation or hormone production
Paraneoplastic syndromes occur in
15% of all CA
Hypercalcemia is an example of
Paraneoplastic syndromes
Hypercalcemia can be caused by
Breast CA stimulates PTH levels, increasing osteoclasts activity
Cushing syndrome is an ____ disorder
Endocrine
Cushing syndrome aka
Hypercorticoid
Cushing syndrome can be due to
- Exogenous corticosteroid therapy
- Pituitary adenoma (Cushing disease)
- Adrenal adenoma
Characteristics of Cushing syndrome
- Weight gain
- Hirsutism
- Purple striae
- Hypertension
- Muscle atrophy and weakness
- Menstrual abnormalities
Suspected antigen Cushing syndrome
ACTH
Suspected antigen hypercalcemia
PTH
Suspected antigen polycythemia
EPO
Suspected antigen anemia
Immune activation
Suspected antigen thrombotic endocarditis
Inflammation
Hypercoagulability
Suspected antigen acanthosis nigricans
Epidermal GFs
Type of CA with Cushing syndrome
Lung
Pancreas
Neuronal
Type of CA with hypercalcemia
Lung Breast Kidney Leukemia Lymphoma
Type of CA with polycythemia
Liver
Kidney
Cerebellar
Hemangioma
Type of CA with anemia
Thymus gland
Type of CA with hypertrophic osteoarthropathy
Lung
Type of CA with thrombotic endocarditis
Any advanced CA
Type of CA with acanthosis nigricans
Gastric
Lung
Uterine
Grading
Degree of cellular differentiation
Staging measures
Extent of spread
Staging uses
Multiple sources
Excision
Partial removal of organ or tissue from body
Biopsy
Removal of smaller sample of cell
Colposcopy
Imaging procedure to view magnified image of cervix
Colposcopy is an example of a
Biopsy
Fine needle aspiration
Removal of cells via aspiration with a needle
Fine needle aspiration is used with
Superficial tumor that is easily palpated
Examples of tissues that can have fine needle aspiration
Breast
Thyroid
Lymph nodes
Salivary glands
Cytological smear aka
Papanicolaou smear
Pap smear
Sampling sheet cells off the surface of an organ
Organs that can have a Pap smear
Cervix Endometrium Meninges Bronchi Bladder Prostate Stomach
___ may be sample for biochemical abnormalities or irregular enzyme levels
Body fluids
Tumor makers are _____ for presence of cancer
Non-diagnostic
Prostate specific antigen (PSA) elevated levels can be due to
Benign prostatic hyperplasia
Recent ejaculation
Prostate cancer
