Physiology Flashcards
What is angiogenisis?
The delivery of nutrients and oxygen through vascular supply to a tumour to aid its growth
What is cancer?
Abnormal cell growth through which cells acquire the potential to metastasise from the site of origin to other sites in the body
What is a benign tumour?
The cells are well differentiated, slow growing and encapsulated in one area
That is a malignant tumour?
Cells that are poorly differentiated, fast growing and capable of intravastation arrest at distant site and meatsasis
What is a carcinoma?
This is the most common type of cancer arising from cells of the embryonic endoderm or ectoderm
What is a sarcoma?
From the cells of the embryonic mesoderm bone cartilage muscle ect.
What is a lymphoma?
In the lymph nodes and the tissues of the bodies immune system
what is leukaemia?
Cancer of the immature white blood cells that grow in the bone marrow and accumulate in large numbers in the blood stream.
What are common symptoms of lung cancer?
Cough haemoptysis, chest pain, breathlessness and tiredness
What are the symptoms of pancreatic cancer?
Weight loss jaundice, back pain and development of diabetes
What are the symptoms of breast cancer?
Lump, change in breast size, discharge, bleeding and weightloss
What makes a metastatic cell?
Mutagenic initiation, point mutations, chromosomal alterations and epigenetic alterations
What are the properties of metastatic cells?
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.
For a metastasised cancer, why is vessel formation so important
Gas exchange, nutrient delivery, disposal of metabolic waste
What is angiogenesis?
Formation of new blood vessels from pre-existing vasculature enabling vascularisation in an avascular region.
Why is it harder to target a tumour with chemo than normal cells?
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
How does normal angiogenisis occur?
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.
What are the three different goals of cancer treatment?
Curative, Maintenance and palliative
What are the general problems with anticancer drugs?
Selectivity and specificity, off target side effects, tumour cell heterogeneity, drug resistance, dose intensity and patient specific factors.
How can surgery treat cancer?
Preventative- moles, remove isolated tumours. debulking
How can radiotherapy be used in cancer treatment?
external beam radiotherapy can also target good cells and internal brachytherapy from small radioactive seeds
What are the two stages of the cell cycle that are most commonly targeted with chemo?
S stage-DNA REPLICATION
M stage- MITOSIS division of two daughter cells
How does Bevacizumab work?
Acts on VEGF to inhibit the interaction of growth factor with its receptor
How does Trastuzumab work?
Acs on HER-2 receptor to inhibit signalling via receptor
How does tamoxifen work?
On the oestrogen receptor and targets hormone signalling by blocking dimerisation so can’t transcribe
What are the common adverse effects associated with chemo?
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
How does cisplatin work?
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
Adverse effects associated with alkylting agents
Nephrotoxicity, neurotoxicity and peripheral neuropathy
Give 4 examples of Alkylating like agents
Cisplatin, Cyclophosphamide, Carboplatin, Oxaliplatin
Give examples of 4 Antimetabolites
Methotrexate, 5-Fluoruracil, Gemcitabine, Mercaptopurine
How do antimetabolites work?
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’
What can antimetabolites treat?
solid tumours and leukaemias
What are the adverse effects associated with antimetabolites?
Nephrotoxicicty, hepatic and pulmonary and neurotoxicity
Give an example of a topoisomerase I inhibitor and its mechanism of action
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
Give an example of a topoisomerase II inhibitor and its mechanism of action
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
What are the adverse effects associated with doxorubicin?
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.
Name a microtubule poison and its mechanism of action
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
What are the adverse effects of vincristine?
Cardiovascular, peripheral neuropathy and gastrointestinal
What is Bevacizumab and how does it work?
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
What are the cardiovascular side effects of Bevacizumab therapy?
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
How does sunitinib work?
Multi target kinase inhibitor that blocks PDGFR c-KIT FLT-3R VEGR signalling
used to treat advanced renal cell carcinoma and gastrointestinal stromal tumours
What are the side effects of tamoxifen?
Sweating weight gain due to water retention may increase incidence of endometrial cancer