BLOCK 9 Flashcards
(135 cards)
1
Q
which genes are associated with ovarian cancer?
A
BRCA 1 and 2
2
Q
which genes are associated with lung cancer/
A
KRAS
TP53
EGFR
3
Q
which genes are associated with hereditary nonpolyposis colorectal cancer?
A
MSH2 and MLM1
4
Q
which genes are associated with familial adenomatous polyposis?
A
APC
5
Q
which genes are associated with breast cancer?
A
BRCA 1
6
Q
what are aflatoxins?
A
family of toxins produced by certain fungi that are found on agricultural crops such as maize (corn), peanuts, cottonseed, and tree nuts
e.g. aspergillus
7
Q
what cancer are aflatoxins linked to?
A
liver
8
Q
what are the 2 characteristics of neoplasia?
A
anaplasia - loss of differentiation and organisation
autonomy
9
Q
how can tumours cause angiogenesis??
A
they can secrete angiogenic factors which bind epithelial cells and cause formation of new blood vessels
10
Q
what are some angiogenic factors?
A
vascular endothelial growth factor (VEGF)
fibroblast growth factor 2 (FGF-2)
platelet derived growth factor (PDGF)
11
Q
how many chromatids are present at the end of G1?
A
46 chromosomes and 46 chromatids
12
Q
how many chromatids are present at the end of S phase?
A
46
13
Q
how many chromatids are present at the end of G2?
A
92
14
Q
when are the 3 checkpoints of cell division?
A
end of G1
end of G2
at the metaphase/anaphase transition in mitosis
15
Q
whats the specific cyclin and CDK subtype in early G1?
A
cyclin D and CDK4 and 6
16
Q
whats the specific cyclin and CDK subtype in late G1?
A
cyclin E
CDK 2
17
Q
whats the specific cyclin and CDK subtype in S phase?
A
cyclin A and CDK 2 and 1
18
Q
whats the specific cyclin and CDK subtype in G2?
A
cycln B and CDK 1
19
Q
whats the difference between protooncogenes and oncogenes?
A
proto oncogenes are healthy cells with regulate cell growth and division
oncogenes are the mutated form
20
Q
how many mutated alleles are needed for an oncogene to cause avoidance of apoptosis?
A
1
21
Q
how many mutated alleles are needed for an tumour suppressor gene to cause avoidance of apoptosis?
A
both - its recessive
22
Q
what are examples of oncogenes?
A
RAS
MYC
23
Q
what are examples of tumour suppressor genes?
A
P53
APC
BRCA 1 and 2
24
Q
whats the normal function of RAS protein?
A
they are intracellular proteins which sit below the plasma membrane and when activated turn from RAS-GDP to RAS-GTP and induce apoptosis
25
whats the normal function of MYC?
they increase expression of cyclin and CDKs
26
which gene is found is almost all pancreatic cancers?
K-ras
27
what are examples of gatekeeper genes?
p53 and Rb
28
whats the function of gatekeeper genes?
they directly regulate tymour growth
29
outline the DNA damage response pathway?
P53 is normally bound to MDM2
when ATM is released during cell damage, P53 is phosphorylated and released from MDM2
this can then upregulate P21/WAF1 which inhibits cyclinE and CDK2, preventing the transuton from G1 phase to S phase
P53 can also increase transcription of PUMA which inhibits bcl-2 leading to activation of caspases and apoptosis
30
simply outline pathophysiology behind cervical cancer?
HPV protein E6 stimulates ubiquitin attachment to P53 which causes destruction
HPV protein E7 binds to Rb and inhibits it so cell cycle isnt inhibited
31
what cancers can Rb gene cause?
retinoblastoma and osteosarcoma
32
outline the mechanism of activation of pRb?
pRB is usually bound to and inhibits E2F
when its activated by cyclin D CDK4, pRB gets phosphorylated and E2F is released
E2F can then transcribe cyclin E and CDK 2 which prevents G1 to S transition
33
whats an example of a protein which inhibits apoptosis?
BCl-2
34
whats an example of a protein that promotes cell cycle progression?
myc
35
what does vinyl chloride become once its been biotransformed in the liver and what can this cause?
vinyl chloride epoxide
| liver cancer
36
what does the hallmark of cancer 'cell immortalisation' mean?
increased telomerase activity in cells which allows them to divide indefinitly
37
what is xeroderma pigmentosum?
an autosomal recessive condition
| mutation in XP genes involved in DNA repair
38
what is familial adenomatous polyposis?
an autosomal dominant condition
| APC gene mutation which usually suppresses beta-catenin proteins
39
what infection is Kaposis sarcoma associated with?
human herpesvirus 8
40
what infection is gastric cancer associated with?
H.pylori
41
what infection is Burkitts lymphoma associated with?
epstein barr virus
42
what infection is Hodgkins lymphoma associated with?
epstein barr virus
43
what infection is nasopharyngeal cancer associated with?
epstein barr virus
44
what infection is cervical and penile cancer associated with?
human papilloema 16 and 18
45
which virus is hepatocecllular carcinoma associated with?
hep B and C
46
which cancers can contraceptive pill reduce risk of?
endometrial, ovarian, and colorectal cancers
47
which cancers can contraceptive pill increase risk of?
breast and cervical
48
which cancer is most strongly linked to occupational exposure?
bladder cancer
49
whats the precursor to colorectal cancer?
adenomatous polyp formation
50
what is the most common acute lymphoid leukaemia?
B cell ALL
51
which mutation is B-ALL associated with?
t(12,21)
| t(9,22)
52
what mutation is T-ALL associated with?
NOTCH1 mutation
53
what are the risk factors for acute leukaemia?
young age
downsyndrome
radiation exposure
54
what mutation is acute promyelocytic leukaemia associated with?
t(15,17) - disruption of retinoic acid receptor so prmyelocytes accumulate
55
whats the risk factor for acute myeloid leukaemia?
```
age around 60
radiation
chemotherapy
downsyndrome
myeloproliferative disorders
```
56
what is acute leukaemia?
uncontrolled proliferation of blast cells (partially developed WBCs) hich build up in the blood
57
what is acute leukaemia?
uncontrolled proliferation of blast cells (partially developed WBCs) hich build up in the blood
58
what can haematopoeitic stem cells become?
myeloblasts or lymphblasts
59
what can myeloblasts become?
erythrcytes
thrombocyte
monocyte
granulocyte (neutrophil, basophil and eosinophil)
60
what can lymphoblasts become?
B cells
| T cells and NK cells
61
what is the Philadelphia chromosome?
t(9,22)
62
what are the types of AML?
```
AML without maturation
AML with minimal maturation
AML with maturation
acute promyelocytic leukaemia
acute myelomonocytic leukaemia
acute monocytic leukaemia
acute erythroid leukaemia
acute megakaryoblastic leukaemia
```
63
what is myelodyplastic syndrome?
defective maturation of myeloid cells and build up of blasts in the bone marrow
this is a syndrome that can lead to AML
64
outline the pathology of acute leukaemia?
blood cells lose their ability to differentiate so they get stuck in the blast stage and don't function effectively
it causes blast cells to divide uncontrollably which takes up a lot of space in the bone marrow
this makes other blood cells get crowded out - causing cytopenias
eventually blast cells spill out into the blood. Some settle into organs and tissues.
65
why can thymus and lymph nodes enlarge in T cell ALL?
because pe-T cells can migrate to these areas, settle down here an cause these structures to enlarge
66
which type of acute leukaemia can cause disseminated intravascular coagulation and why?
acute promyelocytic leukaemia
| as it can activate the clotting process (along with already low platelets)
67
which type of acute leukaemia can cause swelling of gums and why?
acute myelomonocytic leukaemia because we get monocytic infiltration
68
what would you expect the percentage of blast cells to be in acute leukaemia?
from 1-2% to >20%
69
how can you differentiate AML from ALL?
blood smear:
myeloblasts are larger than lymphoblasts
myeloblasts have finer chromatin and auer rods
lymphoblasts have coarse chromatin and glycogen granules
immunophenotying
TdT - lymphocytes
CD10- pre-B cells
70
how is acute leukaemia treated?
chemo
biological therapy
stem cell transplants and bone marrow transplants
acute promyelocytic leukaemia can be treated with all-trans-retinoic acid
71
what mutation is 30% of AML associated with?
FLt3
72
whats the cause of chronic myeloblastic leukaemia?
translocation of 9;22 to form BCR-ABL gene (Philadelphia chromosome)
This codes for the BCR-ABL protein which is a tyrosine kinase that is always on. This causes myeloid cells to divide faster, increasing mutation risk
73
whats the cause of chronic lymphoblastic leukaemia?
not entirely known specifically but known that B cells constantly interact with their B cell receptors, activating tyrosine kinases constantly which prevents the maturation of cells and cell death
74
which is chronic lymphoid leukaemia also known as?
small lymphocytic lymphoma
75
what would you see on a blood smear in chronic myeloid leukaemia?
increased granulocytes and monocytes
76
what would you see on a blood smear in chronic lymphoid leukaemia?
smudge cells - immature B cells broken during the smear
77
what are receptor tyrosine kinases?
plasma membrane receptors with enzymatic activity that catalyses the transfer of phosphate groups
78
whats an example of a tyrosine kinase inhibitors?
imatinib
79
what is imatinibs moa?
targets the BCR-ABL tyrosine kinase to inhibit the cell proliferation driven by this as well as inducing apoptosis
80
what is tretinoin? what is it used to treat?
a naturally occuring derivative of vitamin A
| acute promyelocytic leukaemia
81
what is tretinoins moa?
binds to alpha beta and gamma retinoid acid receptors which are associated with the development of acute promyelocytic leukaemia
82
what is cefuroxime and what is its moa?
a transpeptidase inhibitor
| similar to penicillin - inhibits cell wall synthesis
83
what type of drug is vancomycin? whats its moa? whats it used for?
a peptidoglycan inhibitor (antibiotic)
used for gram negative, mycobacteria and fungi
incorporates NAM and NAG peptide subunits Into the peptidoglycan matrix forming the major structural component of cell walls
84
what type of drug is fusidic acid? whats its moa?
a translocation inhibitor (antibiotic)
| inhibits translocation of EF_G from the ribosome, leading to inhibition of protein synthesis
85
what type of drug is amprenavir?
protease inhibitor
86
what type of drug is zidovudine?
a nucleoside reverse transcriptase inhibitor used to treat HIV-1 - its a structural analog of thymidine so competes for incorporation into viral DNA
87
what type of drug is pyrimethamine?
folate antagonist - anti parasitic
88
what type of drug is artemether?
a peroxide antimalarial
89
what type of drug is griseofulvin?
a fungal mitosis inhibitor
90
what type of drug is clobetasone?
a glucocorticoid nuclear hormone receptor agonist
91
what type of drug is dacarbazine?
an alkylating agent
92
what type of drug is cyclophosphamide?
an alkylating agent
93
what type of drug is rituximab?
B cell CD20 antibody (monoclonal)
94
what type of drug is doxorubicin?
a DNA/RNA synthesis inhibitor (cytotoxic Anthracyclines antibiotic)
95
what type of drug is paclitaxal??
a microtubule stabilisation agent (taxed antineoplastic)
96
what type of drug is 5-fluorouracil?
a pyridine analogue
97
what type of drug is etoposide?
a DNA topoisomerase 2 inhibitor
98
what type of drug is vinblastine?
a tubulin polymerase inhibitor (vinca alkaloid)
99
can viruses contain both DNA and RNA?
no they only contain 1 type
100
whats the function of reverse transcriptase?
RNA -> DNA
101
whats the virus envelope made of?
lipid and proteins derived from the host cell membrane
102
what type of antibiotics can inhibit nucleic acid synthesis?
quinolines (inhibit topoisomerase 2 aka gyrase)
103
what is the function of gyrase?
bacterial enzyme that catalyzes the ATP-dependent negative super-coiling of double-stranded closed-circular DN
104
whats the earliest manifestation of AKI?
reduced urine output
105
what is phenylketonuria?
a rare inherited disorder that causes an amino acid called phenylalanine to build up in the body. PKU is caused by a change in the phenylalanine hydroxylase (PAH) gene
106
what does it mean if the ALT is raised markedly compared to ALP?
primarily a hepatocellular pattern of injury
107
what does it mean if ALP is raised markedly compared to ALT?
this is primarily a cholestatic pattern of injury
108
other than liver disease, when else will ALP be raised?
in bone disease
109
whats the difference between gout and pseudogout?
gout involves uric acid crystals and pseudogout involves pyrophosphate crystals
gout involves smaller joints e.g. the big toe than pseudogout
110
what nerve is responsible for gag reflex?
glossopharyngeal
111
what type of vaccine is BCG?
live attenuates
112
is GFR determines by systemic bp?
no iits usually independat of it de to autoregulatuon
113
whats the difference betwene mono and bifunctional alkylating agents?
monofunctional alkylating agents, implying reactions with only one strand of DNA, or bifunctional alkylating agents, which cross-link two strands of DNA.
114
whwhats an exampke of a monofunctional alkylating agent?
procarbazine
115
what are examples of bifunctional alkylating agents?
nitrogen mustards
platinum drugs
nitrosureas
116
what are anthravyclines moa?
topisomerase inhibitors
117
what type of drug is cimetidine?
a H2 antagonist
118
what type of drug is indomethacin?
NSAID
119
what is lipopolysaccharise?
an endoxtoxin which is weakly toxic and common to all gram negative bacteria
120
where do femoral hernias protrude?
below the inguinal ligament through the femoral canal below and lateral to the pubic tubercle
121
what are anti-mitochondrial antibodies a marker of?
primary biliary cirrhosis
122
whats antinuclear antibodies a marker of?
lupus
123
what antibodies may be present in type 1 diabetes?
GAD65
| islet cell antibodies
124
what antibodies are associated with psoriatic arthritis?
anti-LL-37 antibodies
125
what antibody is associated with graves disease?
thyrotropin receptot antibody
126
which antibody is associated with hashimotos disease?
thyroid peroxidase antibodies
127
what are some causes of microcytic anaemia?
iron deficiency
anaemia of inflamation and chronic disease
thalassemias
sideroblastic
128
what are some causes of normocytic anaemia?
```
bone marrow suppression
CKD
haemorrhage
haemolysis
sickle cell
G6PD deficiency
proxysmal noctural haemoglobinuria
```
129
what are the 2 types of macrocytic anaemia?
megaloblastic and non-megaloblastic
130
what are the main causes of megaloblastic anaemia?
vitamin B12 or folate deficiency
131
whats the difference in pathology between megaloblastic and non-megaloblastic macrocyctic anemia?
megaloblastic is caused by impaired DNA synthesis during RBC production which caues continued cell growth without division
whilst non-megaloblastic anaemia does not have DNA replication issues
132
whats the difference between graves and hashimotos disease?
graves disease - autoimmune disease causing hyperthyroidism
| hashimotos disease - autoimmune disease causing hypothyroidism
133
in which species are exotoxins found?
both gram neg and pos
134
whats more heat stable, endotoxins or exotoxins?
endotoxins
135
whats more toxic, endotoxins or exotoxins
exotoxins
