Physiology

Question 1

What is angiogenisis?

Answer 1

The delivery of nutrients and oxygen through vascular supply to a tumour to aid its growth

Question 2

What is cancer?

Answer 2

Abnormal cell growth through which cells acquire the potential to metastasise from the site of origin to other sites in the body

Question 3

What is a benign tumour?

Answer 3

The cells are well differentiated, slow growing and encapsulated in one area

Question 4

That is a malignant tumour?

Answer 4

Cells that are poorly differentiated, fast growing and capable of intravastation arrest at distant site and meatsasis

Question 5

What is a carcinoma?

Answer 5

This is the most common type of cancer arising from cells of the embryonic endoderm or ectoderm

Question 6

What is a sarcoma?

Answer 6

From the cells of the embryonic mesoderm bone cartilage muscle ect.

Question 7

What is a lymphoma?

Answer 7

In the lymph nodes and the tissues of the bodies immune system

Question 8

what is leukaemia?

Answer 8

Cancer of the immature white blood cells that grow in the bone marrow and accumulate in large numbers in the blood stream.

Question 9

What are common symptoms of lung cancer?

Answer 9

Cough haemoptysis, chest pain, breathlessness and tiredness

Question 10

What are the symptoms of pancreatic cancer?

Answer 10

Weight loss jaundice, back pain and development of diabetes

Question 11

What are the symptoms of breast cancer?

Answer 11

Lump, change in breast size, discharge, bleeding and weightloss

Question 12

What makes a metastatic cell?

Answer 12

Mutagenic initiation, point mutations, chromosomal alterations and epigenetic alterations

Question 13

What are the properties of metastatic cells?

Answer 13

Local invasion into vasculature (loss of cadherins and gain of integrins), Survival in vessel (Selectins platelet enhanced metastatic spread), arrest at distant site, extravasation, growth o secondary tumour and angiogenisis.

Question 14

For a metastasised cancer, why is vessel formation so important

Answer 14

Gas exchange, nutrient delivery, disposal of metabolic waste

Question 15

What is angiogenesis?

Answer 15

Formation of new blood vessels from pre-existing vasculature enabling vascularisation in an avascular region.

Question 16

Why is it harder to target a tumour with chemo than normal cells?

Answer 16

There is high interstitial pressure- meaning there is high pressure outside the vessel so chemo is going against gradient so cancer not treated as well

Question 17

How does normal angiogenisis occur?

Answer 17

A stimulus causes vascular endothelial growth factor to stimulate the growth of a sprout. One cell starts to change and becomes tip cell and supporting cells move away. The matrix becomes chewed up by matrix metalloproteinases, stalk cells follow tip cell so orderly and efficient.

Question 18

What are the three different goals of cancer treatment?

Answer 18

Curative, Maintenance and palliative

Question 19

What are the general problems with anticancer drugs?

Answer 19

Selectivity and specificity, off target side effects, tumour cell heterogeneity, drug resistance, dose intensity and patient specific factors.

Question 20

How can surgery treat cancer?

Answer 20

Preventative- moles, remove isolated tumours. debulking

Question 21

How can radiotherapy be used in cancer treatment?

Answer 21

external beam radiotherapy can also target good cells and internal brachytherapy from small radioactive seeds

Question 22

What are the two stages of the cell cycle that are most commonly targeted with chemo?

Answer 22

S stage-DNA REPLICATION

M stage- MITOSIS division of two daughter cells

Question 23

How does Bevacizumab work?

Answer 23

Acts on VEGF to inhibit the interaction of growth factor with its receptor

Question 24

How does Trastuzumab work?

Answer 24

Acs on HER-2 receptor to inhibit signalling via receptor

Question 25

How does tamoxifen work?

Answer 25

On the oestrogen receptor and targets hormone signalling by blocking dimerisation so can't transcribe

Question 26

What are the common adverse effects associated with chemo?

Answer 26

targets cells that are rapidly dividing e.g. bone marrow, gastrointestinal tract and hair follicles. So: myelosuppression, increased risk of infection, nausea and vomiting, diarrhea, infertility, hair loss

Question 27

How does cisplatin work?

Answer 27

binds to DNA via a platinum ion and causes intra strand cross linking causes a conformational change making DNA repair difficult. Works on S stage leading to G2 arrest

Question 28

Adverse effects associated with alkylting agents

Answer 28

Nephrotoxicity, neurotoxicity and peripheral neuropathy

Question 29

Give 4 examples of Alkylating like agents

Answer 29

Cisplatin, Cyclophosphamide, Carboplatin, Oxaliplatin

Question 30

Give examples of 4 Antimetabolites

Answer 30

Methotrexate, 5-Fluoruracil, Gemcitabine, Mercaptopurine

Question 31

How do antimetabolites work?

Answer 31

Methotrexate is a structural analogue of folic acid and acts as an inhibitor of folic acid in the S stage by binding to dihydrofolate reductase and preventing production of thyamidine. Impairs nucleic acid synthesis and therefore inhibits DNA, RNA and protein production in rapidly proliferating cells Fluoruracil is an analogue of uracil and results in generation of a 'nonsense nucleotide'

Question 32

What can antimetabolites treat?

Answer 32

solid tumours and leukaemias

Question 33

What are the adverse effects associated with antimetabolites?

Answer 33

Nephrotoxicicty, hepatic and pulmonary and neurotoxicity

Question 34

Give an example of a topoisomerase I inhibitor and its mechanism of action

Answer 34

Topotecan These are enzymes that regulate DNA supercoiling causing SINGLE strand breaks and re-ligation, interferes directly with DNA bases and impairs replication and synthesis leading to cell death

Question 35

Give an example of a topoisomerase II inhibitor and its mechanism of action

Answer 35

Doxorubicin Enzymes that regulate super coiling causing cleavage of BOTH strands of DNA helix in a process involving hydrolysis of ATP Binds strongly at C-G sequences to block synthesis of DNA and RNA Generate free radicals Bind to cell membranes to alter fluidity and ion transport leading to cell death In S phase Works on solid tumours and lymphoma and leukaemia

Question 36

What are the adverse effects associated with doxorubicin?

Answer 36

Cardiotoxicity is the main one, after 1 year of treatment, Dilative cardiomyopathy and congestive heard failure may appear after 1 year due to disruption in the sarcomere structure due to mitochondrial dysfunction, oxidation of cellular components and activation of protein degradation.

Question 37

Name a microtubule poison and its mechanism of action

Answer 37

Vincristine and viblastine binds to tubulin structures to prevent polymerisation into microtubules and inhibits the critical step in cell division in the m phase. used for lymphoblastic leukaemia multiple myeloma and hodgkin's lymphoma

Question 38

What are the adverse effects of vincristine?

Answer 38

Cardiovascular, peripheral neuropathy and gastrointestinal

Question 39

What is Bevacizumab and how does it work?

Answer 39

Humanised version of anti VEGF monoclonal antibody binding it and preventing its interaction with VEGFR1 and 2. colorectal cancer and lung and glioblastoma May play a role in normalising vascular structure making vessels more susceptible to chemo, with reduced vasculature could possibly surgically remove tumour There is also barriers to metastasis as no leaky vesslels

Question 40

What are the cardiovascular side effects of Bevacizumab therapy?

Answer 40

Hypertension vasoconstriction as VEGFR2 generates NO and PGI2 which induce vasodilatation Arterial thromboembolic events mediated by platelets Hemmorrhage Congestive heart failure Renal adverse events wound complications

Question 41

How does sunitinib work?

Answer 41

Multi target kinase inhibitor that blocks PDGFR c-KIT FLT-3R VEGR signalling used to treat advanced renal cell carcinoma and gastrointestinal stromal tumours

Question 42

What are the side effects of tamoxifen?

Answer 42

Sweating weight gain due to water retention may increase incidence of endometrial cancer