Neoplasia Flashcards
(102 cards)
1
Q
neoplasia
A
- disorder of cell growth
- triggered by series of acquired mutations of single cell and its clones
- monoclonal, autonomous, irreversible
2
Q
cancer
A
-generic term for malignant neoplasm
3
Q
parenchyma
A
- neoplastic cells
- largely determines biological behavior
- source for the name of the neoplasm
- neuroectodermal, epithelial or mesenchymal in origin
4
Q
stroma
A
- CT, blood vessels, and immune system cells
- support growth and spread of neoplasm
5
Q
classification of tumor
A
- based on cell of origin
- most tumors originate from one cell (monoclonal) and of one parenchyma cell type
- some rare tumors contain cells from more than one germ layer (teratomas)
6
Q
mesenchyme cells
A
- fibrous tissue
- chondroid (cartilage)
- osteoid (bone)
- blood vessels
- smooth muscle
- skeletal muscle
- lymphoid tissue
- hematopoeitic cells
7
Q
fibrous tissue tumors
A
benign- fibroma
malignant- fibrosarcoma
8
Q
chondroid tumors
A
benign- chondroma
malignant-chondrosarcoma
9
Q
osteoid tumors
A
benign- osteoma
malignant- osteosarcoma
10
Q
blood vessels tumors
A
benign- hemangioma
malignant- angiosarcoma
11
Q
smooth muscle tumors
A
benign - leiomyoma
malignant- leimyosarcoma
12
Q
skeletal muscle tumor
A
benign - rhabdomyoma
malignant- rhabdomyosarcoma
13
Q
lymphoid tissue tumor
A
lymphoma
14
Q
hematopoietic cells tumor
A
leukemia
15
Q
stratified squamous cells tumor
A
benign- squamous papilloma
malignant- squamous cell carcinoma
16
Q
epithelial lining of glands of ducts tumor
A
benign- adenoma
malignant- adenomacarcinoma
17
Q
mixed tumors derived from 1 germ cell layer
A
- single neoplastic clone capable of divergent differentiation (more than 1 neoplastic cell type)
- ex. salivary gland and gonads
- totipotential germ cells differentiate into any cell type found in the human body
18
Q
salivary gland mixed tumor
A
- pleomorphic adenoma = benign
- derived from one germ cell layer
- has a clone capable of epithelial and myoepithelial differentiation
- neoplastic epithelial cells scattered in neoplastic myxoid stroma
- malignant mixed tumor of the salivary gland = malignant
19
Q
gonadal mixed tumor
A
- mature teratoma = benign
- immature teratoma and teratocarcinoma =malignant
- arises from totipotential germ cells
20
Q
benign tumor characteristics
A
- well-differentiated (resemble normal tissue counterpart) to dysplastic
- grows slowly
- most stay ecapsulated and stay localized
21
Q
characteristics of malignant neoplasms
A
- well differentiated to very de-differentiated (anaplastic)
- pleomorphic (variations in nuclear size and shape)
- abnormal nuclear morphology (high N/C rate, hyperchromatic, and prominent nucleoli)
- mitoses
- rate of growth is variable and unpredictable, and it usually varies with degree of differentiation
- they infiltrated and destroy locally
22
Q
dysplasia
A
- disordered growth
- considered benign but is pre-cancerous
- principally found in epithelium
- mutations leading to cytological and architectural changes of epithelial cells
- pleomorphism, hyyperchromatic nuclei, high N/C ratio, mitotic figures above basal layer, disorderly maturation, disordely architecture
- DOES NOT PENETRATE BASEMENT MB
- mild to moderate dysplasia may be reversible, especially if the inciting causes are removed but it can be a precursor to a malignant transformation
- often occurs in metaplastic epithelium
23
Q
metastasis pathways of dissemination
A
- seeding within natural body cavities (ex. ovarian carcinomas seed peritoneal cavity)
- lymphatic spread- more typical of carcinomas and will usually deposit into the closest lymph node
- hematogenous spread- more typical of sarcomas
24
Q
cancer variables
A
- geography
- environment
- age
- race
- acquired predisposing conditions
- genetic predisposition
- genetic + inherited factors
25
geography differences and cancer
different exposures to environ carcinogens and different access to preventitive care
26
environ and cancer
- tobacco- lung, upper airway, bladder, pancreas, kidney, and esophagus
- alcohol- oral cavity, pharynx, larynx, esophagus, and liver (secondary to cirrhosis)
- obesity- esophagus, pancreas, colon/rectum, breast, endometrium, kidney, thyroid, and bladder
- occupational exposure (polycyclic hydrocarbons in coal etc = lung, aromatic amines in dye and rubber = bladder, and asbestos in construction = mesothelioma, lung cancer)
- sunlight, radiation, and sexual exposures
27
proposed mechanisms of obesity and cancer link
- elevated insulin levels
- increased estrogens
- decreased adiponectin
- proinflammatory state
28
age and cancer
- most cancers in >55
- carcinomas most common
- incr mutations and decr immune competence
- in kids = >10% of deaths and mainly leukemia and CNS neoplasms
29
heredity and cancer
- autosomal dominant cancer syndromes (familial adenomatous polyps of colon, familial retinoblastoma)
- autosomal recessive syndromes of defective DNA repair (xeroderma pigmentosum)
- familial cancers of uncertain inheritance
30
acquired predisposing conditions to cancer
- chronic inflammation- activated immune cells produce reactive oxygen species that leads to metaplasia
- precursor lesions - barret esophagus, squamous metaplasia of bronchus, and endometrial hyperplasia
- immunodeficieny states- especially T-cell deficiences
31
T/F
| cancer arises from the clonal expansion of a single progenitor cell that has incurred damage
Tru
32
four classes of target regulatory genes which have mutations in cancer
- growth promoting proto-oncogenes
- growth inhibiting tumor suppressor genes
- genes that regulate apoptosis
- genes involved in DNA repair
33
proto-oncogenes
normal cellular genes whose products promote cell proliferation
34
oncogenes
- mutant or overexpressed versions of normal proto-oncogenes
- function autonomously
- encode transcription factors, growth regulating proteins, cell survival proteins
- lost dependence on normal growth promoting signals
- potent carcinogenic factors
- dominant- mutation of a single allele can lead to cellular transformation
35
ABL
- oncogene
- gene product =tyrosine kinase (signal transduction)
- chronic myelogenous leukemia (CML)
36
C-MYC
- oncogene
- gene product- transcription factor (nuclear regulatory protein)
- burkitt lymphoma
37
ERB-2
- Tyrosine Kinase gene product
- breast, ovarian, gastric carcinoma
- oncogene
38
RAS
- oncogene
- gene product = GTPase
- colon, pancreatic carcinoma
- most commonly mutated proto-oncogene in human tumors
- member of a family of small G proteins that bind GTP and GDP (inactive = bound to GDP and active = bound to GTP)
- active RAS stimulates downstream regulators of proliferation so that the cell is forced into a continuously proliferating state
39
L-MYC
- oncogene
- gene product- transcription factor
- lung cancer
40
RET
- oncogene
- gene product = tyrosine kinase
- multiple endocrine neoplasia
41
C-KIT
- oncogene
- gene product= cytokine (growth factor) receptor
- GI stromal tumor
42
Active RAS signal transduction pathway
- RAS ---- PI3K ---- AKT ----- mTOR -----activation of transcription with D-cyclins ---- MYC protein
- RAS ---- RAF ---- MAPK ---- activation of transcription with D-cyclins ---- MYC protein
43
tumor suppressor genes
- normally prevent uncontrolled growth
- mutation or loss leads to transformed cell
- usually both normal alleles must be damaged
44
RB
- tumor suppressor gene
- Rb gene product blocks G1--S phase of cell cycle
- retinoblastoma and osteosarcoma
- "governor of the cell cycle"
- retinoblastoma gene (RB) = first tumor suppressor gene discovered and the basis for Knudson's two-hit hypothesis
- active RB shuts off E2F which blocks its transcription which would normally activate transcription
- mutated RB is hyperp-lated and inactive so E2F is free to activate transcription
45
p53
- tumor suppressor gene
- p53 gene product blocks G1--S phase of cell cycle
- most human cancers and Li-Fraumeni syndrome
- "Guardian of the Genome"
- most commonly mutated gene in cancers
- in the face of stress, it activates temporary cell cycle arrest (quiescence), induces permanent cell cycle arrest (senescence), and triggers programmed cell death (apoptosis)
- activates p21 (CDK inhibitor) for G1 arrest and GADD45 for DNA repair. If the repair fails, it activates BAX to apoptose the cell
46
-BRCA1
- tumor suppressor gene
- gene product: DNA repair protein
- breast and ovarian cancer
47
BRCA2
- tumor suppressor gene
- gene product: DNA repair protein
- Breast cancer
48
retinoblastoma
- intra-ocular neoplasms of children
- median age at presentation =2 yr
- poor vision, strabismus, whiteish hue to pupil
- neuronal origin
- occurs when kids are born heterozygous for the RB gene and then get a mutation to become KO early in life. When it occurs in adulthood it is caused by multiple mutations
49
Li-Fraumeni syndrome
- patients inherit one defective copy of p53 in the germline
- one additional hit = 25x greater risk of developing cancer by age 5 (sarcomas, breast cancer, leukemia, brain tumors, adrenal cortex carcinomas, and multiple primary tumors)
50
anti-apoptotic gene examples
BCL-2 and BCL-XL
51
pro-apoptotic gene examples
BAX and BAK
-antagonize BCL and activate Bax/Bak channels in mitochondria to cause leakage of cytochrome c and other proteins to activate caspases which cause apoptosis
52
Fas
-death receptor
53
caspases 8-9
-initiates other caspase executioners
54
extrinsic death receptor pathway
1) FasL activates the Fas death receptor
2) the Fas receptor activates the procaspase-8 death induced signaling complex to caspase 8
3) caspase 9 activates BID which activates BAX/BAK at the mitochondria
4) stress, radiation, and chemicals induce DNA damage which causes p53 to respond and activate BAX/BAK as well
5) BAX/BAK cause cytochrome c and APAF-1 to leak out and activate Caspase-9
6) If IAP is present, it will inhibit Caspase 9
7) Caspase 9 activates caspase 3 which causes apoptosis
55
What happens if BCL-2 is activated by translocation?
- perpetuation of anti-apoptosis
| - follicular B-cell lyphoma
56
What 4 things are needed for neoplasm development?
- loss of growth restraints (and evade apoptosis)
- development of limitless replicative potential
- sustained angiogenesis
- malignant neoplasms develop the ability to evade and metastasize
57
telomeres
-short, repeat sequences of DNA
-with each somatic cell duplication, small section isn't duplicated and telomeres shorten
-DNA ends appear broken
cell cycle arrest
58
telomerase
stabilizes telomere length
59
What happens if p53 is KO and telomerase is active?
cancer
- loss of p53 activates salvage and non-homologous end joining pathway causing DNA damage
- telomerase allows the cell to live forever
60
sustained angiogenesis
- vascularization of neoplasm is necessary for growth
- get nutrients and oxygen
- new endothelial cells secrete growth factors like PDGF and insulin-like growth factor
61
angiogenesis inducer
- VEGF
- hypoxia inducible factor (HIF-1alpha) transcription factor
- Von Hippel Lindau (VHL) suppressor
62
inhibitor of angiogenesis
thrombospondin 1 (TSP-1)
63
homing of cancer
certain cancers move to certain organs for unknown reasons
-ex lung cancer often goes to the adrenals. We have a large amount of skeletal muscle in the body but we rarely see cancer there
64
Metastatic Cascade
1) Clonal expansion, growth, diversification, and angiogenesis
2) metastatic subclone
3) adhesion to and invasion of the basemement mb
4) passage through the ECM
5) intravasation
6) interaction with host lymphoid cells
7) tumor cell embolus
8) adhesion to basement mb at a new location
9) extravasation
10) metastatic deposit
11) angiogenesis
12) growth
65
sequence of events in the invasion of epithelial basement mbs by tumor cells
1) E-cadherins mediate adhesion of epithelial cells to each other, and this function is lost in some cancers which facilitates detachment from primary tumor
2) degradation of basement mb and interstitial CT
3) attachment of cells to ECM proteins
4) migration of tumor cells through degraded basement mb and zones of matrix proteolysis
66
carcinogenic agents
- inflict genetic damage
| - chemicals, radiant energy, and microbial agents
67
direct acting chemical carcinogens
- require no metabolic conversion
- ex cancer chemos (alkylating agents)
- years down the line, these patients can develop cancer unrelated to the original cancer due to chemo causing mutations
68
indirect acting carcinogens
- require metabolic conversion to become ultimate carcinogens
- polycyclic hydrocarbons (tobacco, animal fats)
- aromatic amines (dye and rubber)
- the susceptibility to cancer possibly depends on the allelic form of the enzyme inherited
69
chemical carcinogens
- react with nucleic acids (RNA, DNA) and/or proteins
- carcinogenicity may be augmented by agents called promoters
- some chemical carcinogens may act in concert with viruses or radiation to induce neoplasias
70
promoters
- compounds which are nontumorigenic which facilitate the induction of cell proliferation
- initiation-promotion sequence
- there has to be some other cancer promoting mutations present but then the promoter facilitates the development of cancer
71
vinyl chloride
- liver
| - angiosarcoma
72
nitrosamine (smoked foods)
- stomach
| - gastric
73
asbestos
- lung
| - mesotheliom, bronchogenic carcinoma
74
arsenic
- skin
| - squamous cell carcinoma
75
naphthalene dyes
- bladder
| - urothelial carcinoma
76
aflatoxin B
- liver
| - hepatocellular carcinoma
77
sources of radiation carcinogenesis
- sunlight (UV)
- x-rays
- nuclear fusion/ionizing radiation
- fission by-products
- radionucleotides
78
mechanism of action for ionizing radiation
- chromosome breakage, translocations, point mutations
- leads to genetic damage and carcinogenesis
- associated cancer = papillary carcinoma of the thyroid
79
UV light
- damages DNA by forming pyrimidine dimers
- normally repaired by nucleotide excision repair pathway
- associated cancers = skin squamous cell, basal cell, and melanoma
80
radiation carcinogenesis
- long latent period
- radiation initiation is irreversible
- continued exposure is additive
81
xeroderma pigmentosum
- autosomal recessive syndrome of defective DNA repair
- defect in nucleotide excision repair pathway
- markedly increased predisposition to skin cancerr
82
microbial oncogenesis - RNA
- Human T-cell lymphotropic virus (HTLV-1)
| - T cell leukemia/lymphoma
83
Microbial oncogenesis - DNA
- human papillloma virus- benign warts, cervical cancer
- epstein barr virus - burkitt lymphoma, nasopharyngeal carcinoma
- hepatitis B and C virus - hepatocellular carcinoma, chronic inflammatory cells can cause injury to cells that can jumpstart carcinogenesis
84
microbial oncogenesis
| bacteria
-helicobacter pylori - gastric adenocarcinoma, MALT lymphoma
85
HTLV-1
- infects many T cells and initially causes polyclonal proliferation by autocrine and paracrine pathways triggered by the TAX gene.
- Simultaneously, TAX neutralizes growth inhibitory signals by affecting TP53 and CDKN2A/p16 genes
- ultimately, a monoclonal T cell leukemia/lymphoma results when one proliferating T cell suffers additional mutations
86
what Ags are overexpressed in melanomas
tyrosinase, gp100, and MART
87
antitumor effector mechanisms
- cytotoxic T lymphocytes
- NK cells
- macrophages
- humoral mechanism: no in-vivo evidence but monoclonal Abs can be therapeutically effective
88
Immunosuppressed patients are at ____ risk for cancer development (and examples)
- increased
| - congenital immune deficiences, transplant recipients, AIDs
89
How can cancers evade the immune system
- eliminate strongly immunogenic subclones
- fail to express HLA class I, escape CTL attack
- suppress host immune response (secrete TGF- beta, express FasL, and/or activate regulatory T cells)
- produce thicker coat of glycocalyx molecules blocking access to immune cells
90
effects of tumor on host
- can compress adjacent structures
- can ulcerate through surfaces
- can produce hormones
91
cancer cachexia
- loss of body fat, lean body mass
- weakness, anorexia, anemia
- cytokine mediated- TNF, proteolysis inducing factor
- no satisfying treatment if neoplasm can't be removed
92
paraneoplastic syndrome
- symptom complexes that can't be readily explained by local or distant spread
- hormone elaboration not indigenous to tumor parenchyma
93
cancer grading
- based on cytologic differentiation of the tumor cells, an attempt is made to estimate the aggressiveness of the tumor
1) degree of cellular differentiation
2) degree of cellular pleomorphism
3) degree of loss of normal architecture
4) mitotic index
94
cancer staging
- size of primary tumor (T1.T2, T3, OR T4)
- extent of spread to lymph nodes = (N0, N1, N2, OR N3)
- presence or absence of metastasis = (M0, or M1)
- called the TNM System
- American Joint Committe (AJC) system uses 0 to IV staging system
95
______ is of greater clinical value. (Either grading or staging)
staging
96
which cancers have grading shown particular relevance
prostate cancer and chondrosarcoma
97
how do you diagnose cancer? What evidence do you use to make the diagnosis?
- clinical data like HPI, social hx, family hx, ROS, PE
- radiologic studies contribute significantly
- tissue sampling
98
tissue sampling in cancer
- should be adequate and representative of lesion
| - large excision, small biopsy, fine-needle aspiration, and cytology smears (pap)
99
Scientific methods useful in cancer diagnosis
- histologic and cytologic examination
- immunohistochemistry
- biochem studies
- ultrastructural studies (electron microscopy)
- molecular bio studes
100
Alpha-fetoprotein (AFP)
-tumor marker for liver carcinomas, tumor of yolk sac remnants, and gonadal tumors
101
carcinoembyonic antigen (CEA)
-tumor marker for colon, pancreas, lung, stomach, and breast
102
tumor markers are generally more valuable for detecting ______ of disease
recurrence (rather than primary diagnosis)
