Neoplasia Flashcards
8742 – Paraneoplastic syndromes may
1: occur in the absence of a demonstrable primary neoplasm
2: mimic metastatic disease
3: include hypercalcaemia produced by skeletal metastasis
4: be due to hormones indigenous to the tissues of origin of the primary neoplasm
TTFF
Robbins, 6th ed, Ch 8
16807 – In the following sequential developments in the ‘metastatic, cascade’ the second event to occur is
A. degradation of collagen and other matrix components
B. tumour embolisation
C. extravasation
D. carcinogenic cell transformation
E. tumour cell interaction with platelets
A
The ‘metastatic cascade’ concept is a useful one, in that it takes the whole process and itemises the steps in sequence from cancer cell ‘initiation’ through the concepts of genetic instability, selection of ‘metastatic subclones’, the necessity for acquisition of new characteristics of cells to break down extracellular matrix and so on.
16033, 16819 – In the following steps in the ‘metastatic cascade’, the second occurrence is
A. development of a ‘metastatic subclone’
B. extravasation
C. expansion, growth and diversification
D. passage through extracellular matrix
E. tumour cell embolus
A
The concept is, that before cancer cells can invade (or metastasise), there has to be: (1) initiation, (2) promotion, (3) proliferation (clonal expansion, growth) and diversification through subclone selection; via the inherent genetic instability of cancer cells, (4) selection of a ‘metastatic subclone’ (requires eg laminin and fibronectin receptor elaboration, ECM protease synthesis etc, locomotion capability and perhaps chemotaxis), before any of the possible responses (D), (E) or (B) come onto the scene (these last three are in that order of events).
16021 – In the following sequential developments in the ‘metastatic cascade’ the second event to occur is
A. degradation of collagen and other matrix components
B. tumour embolisation
C. extravasation
D. carcinogenic cell transformation
E. tumour cell interaction with platelets
A
The ‘metastatic cascade’ concept is a useful one, in that it takes the whole process and itemises the steps in sequence from cancer cell ‘initiation’ through the concepts of genetic instability, selection of ‘metastatic subclones’, the necessity for acquisition of new characteristics of cells to break down extracellular matrix and so on.
24019 – The kinetics of malignant growth include
1: dependency between the growth fraction and the degree of inbalance between cell production and cell loss
2: a progressive increase in the proportion of cells actively cycling
3: tumour cell cycling time is often longer than for corresponding non-neoplastic cells
4: constant cell doubling time
TFTF
Robbins 5th ed. Page: 273
13998 – A carcinoma 1 cm in diameter represents approximately how many cell doublings?
A. 30
B. 100
C. 300
D. 1,000
E. 10,000
A
Refer to Robbins, 6th Ed, Ch 8, page 300, Ch 7, page 273
15187, 16843 – Using a standard accepted model of theoretical growth of a cancer clone (30 doublings = 1 x 109 cells = 1 gram), this potential is never achieved because cells are lost to the proliferative pool when they
1: enter the Go phase
2: are in the G1 phase
3: enter the G2 phase
4: differentiate
TFFT
Refer to Robbins, 6th Ed, Ch 8, page 300-301. The ‘30 doublings = 109 cells = 1 gram; 10 more doublings = 1012 = 1 kg = maximum possible tumour burden’ concept is alive and well! The question asks for the reason(s) why that model is not applicable to clinical cancer. Cells in any of the G1, S, G2 or M phases of the cell cycle are considered to be in the ‘proliferative pool’ by definition; in clinical
cancer, cells are lost to the proliferative pool for many reasons and cell proliferation is not
synchronous. Much of theoretical oncology deals with ‘models’ - try ‘Gompertzian growth curve’!
16896, 22729 – Experimental studies have shown that human cancer cells, when compared with normal tissues derived from labile cell populations
1: have a higher percentage of terminally maturing cells
2: do not have a shorter cell cycle time
3: have a greater proportion of their cells in the replication cycle (growth fraction)
4: replicate at a rate in excess of most labile cell populations
FTFF
Robbins 6th ed. Chapter: 7 Pages: 300-301. This is a difficult concept - as discussed in any treatise on neoplasia with which I am familiar. The points are valid - responses 1, 3 and 4 are false and 2 is correct - the explanations for continued growth are, however, not explored in depth and the bland statement ?… there is an imbalance between cell production and cell loss ?? is meant to explain it all! Perhaps a major factor here is that in normal epithelia (for example), mitosing cells are present only in basal layers (skin or gut crypt) and the bulk of the epithelial cells are terminally maturing. In CIN, for example, mitoses are present at all layers of dysplastic epithelium - I suspect that the cells being included for defining the ‘proliferative pool’ stacks the result. Perhaps more importantly, labile cells such as granulocytes and gut epithelia have a very short life span - cancer cells may well be more robust!
16848 – There is a positive experimental and/or clinical correlation between metastatic potential of cancer cells and their
1: elaboration of plasminogen activator
2: blockade of fibronectin receptors on tumour cells
3: secretion of type IV collagenase
4: density of laminin receptors
TFTT
Responses 2 and 4 (pages 303-4) relate to the important capacity of tumour cells to bind to collagen of basement membrane (type IV - laminin) and interstitium (type I - fibronectin). Blockade of receptors will decrease metastatic potential (response 2); 1 and 3 refer to breakdown of intercellular matrix, which creates space for cancer cell invasion and probably also growth and chemotactic stimuli (for stromal and perhaps also cancer cells). Experimental fibronectin receptor blockade (using an analogue which occupies the receptor sites for laminin on tumour cells) inhibits lung metastases.
16027 – Each of the following is true of carcinogenic initiation, except
A. effects are rapid
B. effects are reversible
C. induces DNA alteration
D. has ‘memory’
E. can be active when given in divided doses
B
This deals with oncogenic initiation and promotion. It relates to chemical carcinogenesis but is applicable, with modification, to radiation and viral oncogenesis. Rigid classification as ‘complete’ carcinogens (oncogens, but not oncogenes), initiators and promoters is conceptually useful, but not always easy. The concept is that initiators damage DNA in a fashion which is not susceptible to repair (either widely, or in individuals with genetic defect in DNA repair capability). Promoters then apparently ‘push’ the cell the extra step(s) to uncontrolled growth. This is central to understanding oncogenesis.
23289 – Chemical carcinogens
1: are intrinsically electrophilic
2: usually produce characteristic molecular fingerprints
3: metabolism may be correlated with genetically determined enzyme levels
4: cause more cell necrosis than proliferation
TTTT
Robbins 6th ed. Pages: 305-9
17817 – S: Acquisition of the characteristics of ability to metastasise by cancer cells is presumed to be dependent on multiple different mutations in the cells because R: no single gene has thus far been discovered which appears to code for metastasising behaviour by neoplastic cells.
S is true, R is true and a valid explanation of S
At present, no single ‘metastasis gene’ has been discovered. It is thought that such a ‘master gene’ influencing metastatic (or, indeed, invasive) behaviour is unlikely, because each of these activities involves multiple, apparently individual, processes (eg adhesion, secretion of extracellular matrixdigesting enzymes, locomotion etc). However, some experimental evidence does exist that some genes act to specifically suppress one or more properties which are essential for metastasis. There is some tantalising evidence that one such gene may operate in modulating metastasis behaviour in
human breast cancer.
16952, 22734 – Proto-oncogenes
1: are rendered incapable of transcribing growth-related proteins following chromosomal translocation
2: are, in the normal cell, inactive DNA sequences without physiological action
3: may be activated into functional oncogenes (c-onco-genes) by mutation of a specific gene site
4: may be activated by destruction of adjacent controller genes, which normally suppress their action
FFTT
Robbins 5th ed. Chapter: 7 Pages: 259 et seq. Response 1 is false; gene sequences may be
activated (removed from a ‘suppressor’ or inserted near an ‘activator’) by translocation. For response 2, proto-oncogenes are, in the normal cell, the activators and switches (‘on’ and ‘off’) for normal growth. Responses 3 and 4 outline two of the ways in which normal proto-oncogenes may be influenced to become oncogenes (also referred to as c-oncogenes). [Cellular] oncogenes are perverted proto-oncogenes (growth genes).
16795, 16968 – S: DNA damage by chemicals is not necessarily carcinogenic because R: DNA damage can be repaired by cellular enzyme systems.
S is true, R is true and a valid explanation of S
Whether they act as complete, direct or indirect initiators, the action of carcinogenic initiators is presumed to be because they cause permanent alteration to the DNA, by an action which is rapid and irreversible. It also has ‘memory’, in that a threshold dose is effective when given either in a single dose or as divided doses. The written evidence for this statement and reason is, perhaps, not as direct as I would like. The evidence for repair of DNA following radiation injury is very strong. Single strand breaks are rapidly repaired (within minutes) and double strand breaks may also be repaired, usually less promptly. Some are irreparable - these may lead to cell death or become the initial steps of oncogenesis. By implication, the same should be true for chemicals, but a direct and definitive statement to this effect cannot be found in Robbins.
22739 – DNA viral carcinogenesis
1: is usually a single step (single hit) process
2: may act by neutralising the influence of growth-inhibiting gene(s)
3: may involve incorporation of viral oncogene into host DNA
4: may activate growth-promoting gene(s)
FTTT
Robbins 6th ed. Pages: 311
17799 – S: Genes controlling apoptosis such as p53 are believed to be important in controlling/preventing growth of potential cancer cells because R: apoptosis genes arrest the mitotic process of cells with DNA damaged by mutagenic agents which allows time for DNA repair or, if repair does not occur, induces cell autodestruction.
S is true, R is true and a valid explanation of S.
There is no evidence that p53 gene expression is necessary for normal cell division. Once cells are exposed to mutagenic agents such as chemicals or radiation, the p53 protein (normally with very short half-life) is stabilised and accumulates in the nucleus, where it binds to DNA, causing cells to arrest in the G1 phase. This allows time for DNA repair mechanisms to work. If this does not occur, the cell undergoes apoptotic death. p53 is widely active and has been dubbed ‘guardian of the genome’.
10362 – What is the most common genetic change underlying the development of tumours?
A. Somatic activation of the ras proto-oncogene
B. Activation of the c-myc gene by chromosomal rearrangement
C. Inherited inactivation of the p53 gene
D. Loss of the p53 gene by somatic mutation
E. Point mutation of the Rb gene
D
25390 – Tumour necrosis factor
1: is synthesized by macrophages
2: is present in lower than normal amounts in HIV infected individuals
3: may induce acute phase protein synthesis in vascular endothelial cells
4: may be an important mediator in endotoxic shock
TFFT
Roitt 9th ed. CHAPTER: 7 PAGE: 181 Robbins 5th ed. Page: 226
19761 – Tumour suppressor genes
A. are commonly found to be mutated in the germ cells of cancer patients
B. have no known physiologic function
C. are present in increased copy numbers in tumour cells
D. include p53 and the retinoblastoma gene
E. are each related to a specific type of tumour
D
Robbins 6th ed. Pages: 291
