Lecture | Neoplasms (part 2) Flashcards
1
Q
Cancer grading is subjective and semi-quantitative. T/F
A
True
2
Q
Is based on the degree of anaplasia and number of proliferating cells
A
Cancer grading
3
Q
Is based on the shape and regularity of cells, presence and distinct differentiated features
A
Degree of anaplasia
4
Q
Is based on evidence of rapid growth, which includes large number of mitoses, presence of atypical mitoses, nuclear pleomorphism, and tumor giant cells.
A
Number of proliferating cells
5
Q
Tumor marker that can also be used yo quantify how much of these cells are actively proloferating
A
Ki67
6
Q
Correlation of cytological grade and biological behavior is variable. T/F
A
True
7
Q
The higher the anaplasia, the poorly differentiated the tumor, and the large number of mitosis correlates with a higher grade. T/F
A
True
8
Q
Refers to the extent of tumor spread; influence choice of surgical approach or treatment modalities
A
Cancer staging
9
Q
Criteria used in cancer staging:
A
- Tumor size,
- Extent of local growth,
- Presence of lymph node metastasis,
- Presence of distant metastasis
10
Q
The bigger the tumor, the most likely it will be resectable. T/F
A
False,
… will not be resectable
11
Q
One global scheme to address cancer staging; has a specific staging for particular malignancies in the different organs of the body
A
TNM cancer staging
12
Q
What is TNM cancer staging?
A
T stands for Tumor - evaluates tumor size and the extent of its growth in relation to the structures that is located.
N stands for Nodal metastasis - pertains to the regional lymph nodes
M stands for Metastasis - refers to the distant metastasis
13
Q
Most cancers arise from a single transformed cell. T/F
A
True. (Evidence-based)
14
Q
Malignant change in the target cell is referred to as
A
Transformation
15
Q
Stage 3 usually involves
A
Nodal metastasis
16
Q
Stage 4 usually means that there is already
A
Distant metastasis
17
Q
Transformation is the last step in the natural history of a malignant tumor. T/F
A
False,
It is the initial step
18
Q
Accompanied by mutations of the DNA/genome of the cell
A
Transformation
19
Q
Diagnosis should be early when the tumor is still small, when it is still amenable for resection. T/F
A
True
20
Q
Additional treatment modalities if a tumor is very hard to manage due to late diagnosis.
A
Chemotherapy and radiation
21
Q
Literally means abnormal growth
A
Dysplasia
22
Q
Malignant transformation is a single-step process. T/F
A
False,
It is a multistep process
23
Q
Precursor lesion of cancer
A
Dysplasia
24
Q
In dysplasia, some features of malignancy are present microscopically. T/F
A
T
25
Dysplasia may develop into malignancy such as:
Uterine cervix and colon polyps
26
Dysplasia is irreversible like neoplasia. T/F
False,
It is still reversible unlike neoplasia
27
What is needed to remove in dysplasia so that the cells will go back to a normal state?
Instigating stimuli
If stimuli is not removed, dysplasia would eventually develop into malignancy
28
Dysplasia is graded as _, and what are its involvement?
Low grade - involves the lower portion of the epithelium
High grade - involves the entire layer of the epithelium
29
Dysplasia may not develop into malignancy. T/F
True.
It may not develop into malignancy if there is an early diagnosis and early treatment. If diagnosis and/or treatment is late, it may develop into malignancy.
30
When abnormality of the cells involves the entire thickness (or almost the entire layer of the epithelium), it will now become ____.
High grade dysplasia
31
If cell abnormality incorporates all the layers of the epithelium (or full thickness of the epithelium) and there’s no invasion of the basement membrane, it will now be called
Carcinoma in situ
32
Once basement membrane is breached, it will now become
Invasive carcinoma
33
The problem with a transformed cell is that it will not be under the tight regulation of the cells because once the tumor is malignant, it becomes a cancer cell and it will now have an ___
Autonomous growth
34
What lengthens as tumor grows?
Doubling time of tumor cells
35
Tumor cells actually needs ________for the cell to become space occupying lesion
10 more doublings ([1kg] lethal burden)
36
30 doublings (?) = ?
30 doublings (10^9 cells) = 1g
37
Fraction of tumor cells in replicative pool
- May be only 20% even in rapidly growing tumors
- Tumor stem cells
38
Rate / cellular processes at which tumor cells
are shed or lost
- Apoptosis (when cells signal the arrest/suicide of these tumor cells)
- Maturation (cancer cells are unable to grow further)
39
The rate of the tumor growth may be loss or it will stabilize, otherwise the tumor cells will cease to grow. T/F
False,
… tumor cells will continue to grow until it becomes very very big
40
The bigger the tumor, the chances of invasion and metastasis will be increased. T/F
True
41
Transformed cell will divide forming this genetically abnormal cells; these are ?
Clone cells
42
In sun exposure, what causes injury to the DNA of the cell?
Ultraviolet radiation (basis for skin cancer)
43
___ tend to be prone to develop skin cancer compared to ___
Caucasians ; blacks / heavily pigmented people
44
Blacks have low incidence of melanoma, so do normally pigmented areas like ___ on white people
Areola
45
Geographic and environmental factors that may promote tumor growth
- Sun exposure
- Smoking and alcohol abuse
- Body mass
- Environmental vs. Racial factors
- Viral exposure
46
Overweight = __% increase in cancer
50%
47
For females, there’s an increased risk of ____, while for males, there’s an increased risk of ___
Breast cancer; prostate cancer
48
What plays a role in breast carcinoma
Testosterone and estrogen
49
What plays a role for the growth of prostatic carcinoma
Testosterone
50
There are also viruses that are ___, example pf this viruses include ___ which causes a cancer of uterine cervix
Oncogenic; Human Papillomavirus (HPV)
51
Hepatitis B virus (HBV) causes ?
________ causes burkitt’s lymphoma and nasopharyngeal carcinoma
Human Herpesvirus-8 causes ?
Liver cancer
Epstein-Barr virus (EBV)
Kaposi’s sarcoma
52
Diet high in nitrates can be converted to ___ which is a risk factor for ? cancer
Nitrosamines ; colon cancer
53
Japanese immigrants now in japan has a diet that is heavily composed of _____. Thus most of the cancers associated with the japanese are ____, followed by liver, colon, and prostate
Fish; stomach
54
Americans has a diet heavily composed of ____. Thus, Japanese immigrants that now live in USA will show a decrease in ____ and an increase in ___.
Meat; decrease in stomach cancer; increase in colon cancer
55
Most cancers occur in the elderly aging ___, however there are also childhood malignancies like ____ and ___
> (and equal to) 55 years ; leukemias & CNS neoplasms ; and bone tumors
56
There’s a familial transmission of these genetic abnormalities
Genetic predisposition
57
What explains the differences in the genetic constituencies among closely related individuals?
Ex: 2 brothers who smoke heavily, one developed cancer later on but the other one did not. What explains this phenomenon?
Genetic polymorphism
- since they’re brothers, they have difference in their genes that will encode certain enzymes. These enzymes may convert a potential carcinogen to a non-carcinogenic substance. Thus, the other brother may have this gene (which encodes the enzyme) while the one brother that developed cancer may lack this gene.
58
Hydrocarbons from smoke can be converted to ___ which can cause lung cancer
Epoxides
59
Early age at onset; two or more primary relatives with the cancer; multiple or bilateral tumors
Familial cancer syndromes
60
Nonhereditary predisposing conditions
- Chronic inflammation (causes the growth of malignancies)
- Precancerous conditions
61
Precancerous conditions in nonhereditary predisposing conditions
- Chronic ulcerative conditions / Crohn’s disease (causes colonic cacinoma)
- Atrophic gastritis of pernicious anemia
- Leukoplakia of mucous embranes
62
Hepatitis B can cause liver cirrhosis which can be a harbinger for
Hepatocellular carcinoma
63
Tumor cells do not necessarily proliferate at a faster rate than their normal counterparts. T/F
True
64
Major determinant of tumor growth is ?
More cells produced than die in a given time
65
Time taken for number of cells in mass to double
Doubling time
66
Detectable size for mass to be palpable?
30 doubling time
- 1.0 cm^3 (1.0 g) = 10^8 to 10^9 cells = doubles 30x
67
Tumor is palpable around ?
When is it not palpable?
2cm = palpable
<2cm = not palpable
68
___ can be employed to detect mass lesion
Imaging studies like CT scan, X-ray, MRI
69
Sprouting of new capillaries from pre-existing blood vessels; requirement for continued growth of cancers
Tumor angiogenesis
70
Absence of blood vessels indicate
Tumors grows no larger than 1-2 mm in diameter
71
Tumor will not grow unless they are fed by new blood vessels because these tumors needs nutrients. T/F
True
72
Tumors will secrete _____ particularly _____ which enhances the formation of small blood vessels.
Growth factors ; Angiogenic factors
73
Small blood vessels will nourish the growing tumor. T/F
True
74
Angiogenic factors (7)
1. FGF (Fibroblasts Growth Factor)
2. TNF-a (Tumor Necrosis Factor alpha)
3. EGF (Epidermal Growth Factor)
4. VEGF (Vascular Endothelial Growth Factor)
5. TGF (Transforming Growth Factor)
6. PDGF (Platelet-derived Growth Factor)
7. Angiogenin
75
Cell proliferation is balanced by apoptosis in the absence of tumor angiogenesis; or may be due to cell cycle arrest
Tumor dormancy
76
Unregulated growth of cancer cells results from sequential acquisition of somatic mutations in genes that control and differentiation or that maintains the integrity of the genome. T/F
True
77
Hereditary predisposition
Concept of cancer gene
78
In cancer gene, there is a presence of chromosomal abnormalities in neoplastic cells. T/F
True
79
In cancer gene, there is a correlation of _ and _
Impaired DNA repair and occurrence of cancer
80
In the concept of cancer gene, there is a close association between _ and _
Carcinogenesis and mutagenesis
81
Most common mechanism of mutagenesis relates to
Spontaneous errors in DNA replication and repair
82
Genes involved in the pathogenesis of cancer:
- Oncogenes
-Tumor surpressor genes
- Mutator genes
83
These are positive effectors of neoplastic phenotype
Oncogenes
84
Genes wherein there is loss of function will permit unregulated cell growth
Tumor suppressor genes
85
The inactivation of this genes will allow further mutations
Mutator genes
86
Alteration in structure of protooncogene results in
Abnormal gene product
- change in nucleic acids sequence by point mutation, deletion, chromosomal translocation which leads to the synthesis of mutant protein that functions abnormally
87
Increase in expression of protooncogenes causes
Overproduction of normal gene product
- increased transcription occurs insertional, mutagenesis, chromosomal translocation, and gene amplification
88
Example of activation by mutation wherein there is a point mutation in codon __ resulting in substitution of _
C-RAS in bladder cancer : point mutation in codon 12 = valine to glycine
- because of the point mutation, C-RAS is activated resulting in urinary bladder cancer
89
Example of Activation by Chromosomal Translocation wherein it is found in 95% of Chronic Myelogenous Leukemia.
Philadelphia chromosome
90
In Philadelphia chromosome, ____ on chromosome 9 translocated to chromosome 22 where it is placed in juxtaposition to a site known as ___, wherein an aberrant protein with very high kinase activity is coded
C-ABL Protooncogene; Breakpoint Cluster Region (BCR)
91
This BCR will ultimately code for an enzyme with a very high kinase activity which will now result or manifested as
Granulocytic hyperplasia (increase in the number of WBCs), a manifestation of Chronic Myelogenous Leukemia
92
Increase number of gene copies
Activation by gene amplification
93
____ found in neuroblastoma (a common childhood tumor) or _____ is found in the breast and ovarian cancer.
N-myc protooncogene ; erb protooncogene
94
Mechanisms of actions of oncogenes (6)
1. Extracellular growth factors
- synthesis of PDGF-like factors by neoplastic cells
2. Cell surface receptors
- generation of mitogenic signals that override normal control of signaling pathways
3. Intracellular signal trandpsduction pathways
- activation of growth factor receptors
4. DNA-binding nuclear proteins (transcription factors)
- C-myc activation render cells competent to receive signals for mitosis
5. Cell cycle proteins (cycling and cyclin-dependent protein kinases)
6. Inhibitors of apoptosis (bcl-2)
95
Loss of heterozygosity by deletion or somatic mutation predispose to tumor development
Tumor suppressor genes
96
What happened if the tumor suppressor gene will be subject to mutation?
It becomes defective
97
Deletion or mutation of tumor suppressor genes enables the damaged DNA to progress through the cell cycle. T/F
True
98
Most common genetic change in human cancer (deleted or mutated in 80% of cases of colon cancer, frequently in breast cancer, small sell carcinoma of lung, hepatocellular carcinoma, astrocytoma)
Also give its location
P53 gene
Location: small arm of chromosome 17
- protein product of this gene is present in all normal tissues
99
In P53 gene, mutations allow cells with damage DNA to progress through the cycle. T/F
True
100
Other tumor suppressor genes:
- _______ - implicated in familial adenomatous polyposis coli and colorectal cancers
- ______ - hereditary Wilm’s tumor
- ______ - neurofibromatosis type 1
- ______ - 90% of pancreatic cancers
- ______ - breast and some ovarian cancers
- APC gene
- WT-1 gene
- NF-1 gene
- DPC-4 gene
-BRCA-1 and BRCA-2 genes
101
_____ are called _____ which exercise surveillance over the integrity of genetic information by participating in cellular response to DNA damage
Mutator genes ; caretaker genes
102
Loss of these gene functions renders the DNA susceptible to the progressive accumulations of mutation; when these affect protooncogenes or tumor suppressor genes, cancer will result
Mutator genes
103
It is estimated that ____ are responsible for 15% of all human cancers
Viral infections
104
The strongest association of viruses and human cancer includes:
- HTLV-1 virus = T-cell leukemia and Lymphoma
- HPV = squamous cell carcinoma of the cervix
- HBV = hepatocellular carcinoma
- EBV = Burkitt’s lymphoma and Nasopharyngeal carcinoma
- HHV-8 = Kaposi’s sarcoma
105
Hepatitis B virus > chronic hepatitis > ________ > _______
Liver cirrhosis > liver cancer
106
______ are proven by epidemiological studies and animal studies
Chemical carcinogen as mutagens
107
An agent that can permanently alter the genetic constitution of a cell
Mutagen
108
About 90% of known carcinogens are mutagenic, and all mutagens are carcinogenic. T/F
False,
Most (not all) mutagens are carcinogenic
109
Many compounds known to be potent carcinogens are relatively _____ in terms of chemical reactivity; most require _______ before they can react with cell constituents
Inert ; metabolic activation
110
Is a short-term laboratory test done on _______ wherein you will expose this bacteria to these particular chemicals and look for mutations in the genetic material of the bacteria.
It is a test for potential mutagenic capacity of these chemicals
AMES test ; Salmonella typhimurium
111
4 stages of chemical carcinogenesis
1. Initiation - mutations in a single cell
2. Promotion - characterized by clonal expansion of the initiated cell
3. Progression - growth becomes autonomous; cancer is independent of the carcinogen or promoter; instability of the genome with the end result of further clonal expansion
4. Cancer - result when cells acquire the capacity to invade and metastasize
112
Are inherently reactive to bind covalently to cellular macromolecules. E.g., ______
Direct acting carcinogens ; benzyl chloride
113
________ through enzymatic reactions effected by cellular systems
- ex: __________ to epoxides (cigarette smoke -> lung cancer)
- aromatic amines and azo dyes converted to _____ (aniline dyes -> _____)
Conversion to a more reactive compound
- polycyclic aromatic hydrocarbons
- hydroxyl derivatives ; bladder cancer
114
Bronchogenic carcinoma is a relatively common phenomenon because of
Increased smoking cigarettes
115
Cancers attributed to sun exposure, due to ____, namely:
1. Basal cell carcinoma
2. Squamous cell carcinoma
3. Melanoma
116
______ are not prone to skin cancer but _____ show increased cases of skin cancer
Blacks / heavily pigmented people with more melanin content ; Caucasians
117
Carcinogenic effects of UV radiation occurs at wavelength of
290nm to 320nm
118
Effects of uv radiation in cells include
Enzyme inactivation, inhibition of cell division, mutagenesis, cell death, and cancer
119
Most important biochemical effect of UV radiation is the _______________ which distorts the backbone of the DNA helix (unless repaired, this genomic injury is mutagenic and carcinogenic)
Formation of pyramidine dimers on DNA
120
Material widely used in construction, insulation, and manufacturing
Asbestos
121
Characteristic tumor associates with asbestos is
Malignant mesothelioma of the pleura and peritoneal cavities
122
These small fibers can cause changes in the cells lining the lung cavity
- ‘Serpentine’ - chrysotile
- ‘Amphiboles’ - crocidolite and amosite
123
In the ____, asbestos has been banned as a construction material but there is a long latent period of about _____ between exposure and appearance of tumor
1970s ; 20years
124
Most common cause of death associated with malignancy
Lung cancer
Followed by prostate / breast, colon, stomach, liver, and leukemia
125
What are usually detected late in the clinical course
Lungs, prostate, and colon
126
Cause of cancer in males and females:
M: Lungs, prostate, and then colon
F: Lungs, breast, and then colon
