Neoplasia Flashcards
What is a cancer called contained within a basement membrane?
Carcinoma in situ
What is a cancer called when a cancer breaks through the basement membrane?
Invasive cancer.
What are the different classifications of invasive cancer?
Micro-invasive cancer. (Small amount of cancer cells released)
Invasive cancer. (Large amount of cancer cells released)
How does the cancer get out of the basement membrane?
Uses proteases.
Needs cell motility.
What proteases does a cancer use to get out of the basement membrane?
Collagenase
Cathepsin D
Urokinase-type plasminogen activator
What do cancers have to do to metastasise?
Grow.
Invade basement membrane.
Move.
Lymphatic vessels or blood vessel.
Travel without getting eaten.
Find another site to live.
Invade.
Growth.
Blood supply.
How could you treat some cancers?
Inhibit some enzymes a tumour needs to eat threw the basement membrane.
Stop them travelling around.
How can cancers evade the lymphocytes in the blood?
Aggregation with platelets.
Shredding of surface antigens.
Adhesion of other tumour cells.
What do cancers need for tumour cell motiltiy?
Tumour cell derived motility factors
Breakdown products of extracellular matrix
What do cancers need to enter the blood?
Collagenases
Cell motility
What do cancers need to exit the blood?
Adhesion receptors.
Collagenases.
Cell motility.
What do cancers need after they exit the blood?
growth factors.
Angiogenesis.
What are some angiogenesis promoters?
Vascular endothelial growth factor.
Basic fibroblast growth factor.
What are some angiogenesis inhibitors?
Vasculostatin.
Endostatin.
Angiostatin.
Give an example of an inhibitor of angiogenesis?
Avastin.
Where is an easy place for a tumour to get stuck in the body?
The lung capillaries.
Is a vein or artery easy for a tumour to metastasise to?
Vein.
Which tumours commonly metastasises to the lung?
Sarcomas or any common cancers.
Where is the first place a cancer cell will spread to in colon cancer?
Liver.
What are common cancers which metastasise to the liver?
Colon, stomach, pancreas, carcinoid tumours of intestine.
What are the tumours which commonly metastasise to bone?
Prostate, breast, thyroid, lung and kidney.
What happens when a tumour invades bone?
Either eat the bone or lay new bone down.
What is chewing up bone called in cancer?
Osteolytic metastasise.
What is laying new bone down called in cancer?
Osteosclerotic metastasise.
What does Vinblastine do?
Binds to mitotic spindels and stops them contracting.
What drug inhibits topoisomerase 2?
Etoposide.
What does ifasemide and cisplatin do?
Cross links DNA so can’t divide.
What are the side effects of conventional chemotherapy?
Not selective for tumour cells.
-Except that they might be dividing faster.
Usually hits normal cells which are dividing
- Myelosuppresion.
- Hair loss.
- Diarrhoea.
What is Myelosuppresion?
A condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets.
What do cancer cells need to do to increase in size?
Cell division.
Lack of cell death (apoptosis).
What are the pros and cons of conventional chemotherapy? Give some examples of types of cancers?
-Good for fast dividing tumours
germ cell tumours of testis
acute leukaemias
lymphomas
embryonal paediatric tumours
choriocarcinoma
-Not so good for slower dividing tumours
most other tumours.
What are the benefits of targeted chemotherapy?
Exploits some difference between cancer cells and normal cells to target drugs to the cancer cells
- more effective
- less side effects.
What can you do to work out if different diseases are present?
Gene arrays.
Proteomics.
Tissue Microarrays.
What is an example of a cancer cell proliferation?
over expression of a receptor or the receptor is always on despite no growth factor being bound to it.
How can you block a receptor which is being overexpressed?
Produce monoclonal antibodies against the receptor to block anything binding.
How can you block a receptor which is constantly on?
A small molecular inhibitor of the receptor. CAN also block over expression.
What is an example of a monoclonal antibody which blocks a receptor?
Cetuximab - blocks epidermal growth factor receptor.
What is an example of a drug which combats breast cancer?
Herceptin.
What does Herceptin bind to?
Her-2.
How does Herceptin work?
Binds to Her-2 receptors on the cell surface and make them become endocytosed, therefore there is less Her-2 on the surface to bump into each other and produce a reaction. Also cause lymphocytes to come along and destroy the cell.
What is Her-2 associated with?
large size
high grade
aneuploidy
negative oestrogen receptor status
independent adverse prognostic factor.
What can Her-2 not do?
Cross the blood brain barrier.
What is Gleevac?
inhibitor of c-kit tyrosine kinase originally developed as inhibitor of BCR-ABL protein to treat CML also found to inhibit c-kit protein.
What is a tumour?
Any abnormal swelling.
What is a neoplasm?
A lesion resulting from the AUTONOMOUS or relatively autonomous ABNORMAL growth of cells which persists after the initiating stimulus has been removed.
Which is worse malignant or benign?
Malignant.
What is the structure of a neoplasm?
Neoplastic cells and Stroma.
What are neoplastic cells of a neoplasm?
Derive from nucleated cells.
Usually monoclonal.
Growth pattern related to parent cell.
Synthetic activity related to parent cell:
Collagen, mucin, keratin, hormones.
What is the stroma of a neoplasm?
Mattress.
Connective tissue framework.
Mechanical support.
Nutrition. Stroma grows by growth factors from neoplastic cells.
What cell and tissue types would you therefore expect to find within a neoplasm’s stroma?
Fibrous connective tissue.
Unorganised.
Blood vessels.
What is essential to tumour growth?
Angiogenesis. 2mm small takes oxygen by diffusion.
How do you classify a neoplasm?
Behavioural: benign/malignant
Histogenetic: cell of origin.
Why do we classify a neoplasm?
To determine appropriate treatment
To provide prognostic information.
How may a neoplasm be classified?
benign
borderline
malignant.
What do borderline tumours do?
defy precise classification.
What are the features of benign neoplasms at low magnification?
Localised, non-invasive
Slow growth rate
Low mitotic activity
Close resemblance to normal tissue
Circumscribed or encapsulated.
What are the features of benign neoplasms at high magnification?
Nuclear morphometry often normal
Necrosis rare
Ulceration rare
Growth on mucosal surfaces
often exophytic
Why should we worry about benign neoplasm?
Pressure on adjacent structures
Obstruct flow
Production of hormones
Transformation to malignant neoplasm
Anxiety.
What are the features of malignant neoplasms at low magnification?
Invasive
Metastases (Not always)
Rapid growth rate
Variable resemblance to normal tissue
Poorly defined or irregular border
What are the features of malignant neoplasms at high magnification?
Hyperchromatic nuclei (lots)
Pleomorphic nuclei (Different shaped)
Increased mitotic activity
Necrosis common
Ulceration common
Growth on mucosal surfaces and skin often endophytic
What are the key features of a malignant neoplasm?
Encroach upon and destroy surrounding tissue
Are poorly circumscribed
Have a ‘crab-like’ cut surface (Latin: cancer)
Metastasise
Why do we need to worry about malignant neoplasms?
Destruction of adjacent tissue
Metastases
Blood loss from ulcers
Obstruction of flow
Hormone production
Paraneoplastic effects
Anxiety and pain.
What is histogenesis?
The specific cell of origin of a tumour.
Where can neoplasms arise from?
Epithelial cells
Connective tissues
Lymphoid/haemopoietic organs.
What do neoplasms end in?
OMA.
What is a papilloma?
Benign tumour of non-glandular, non-secretory epithelium
Prefix with cell type of origin
e.g. squamous cell papilloma.
What is an adenoma?
Benign tumour of glandular or secretory epithelium
Prefix with cell type of origin
e.g. colonic adenoma, thyroid adenoma.
What is a Carcinoma?
Malignant epithelial neoplasm.
Malignant tumour of epithelial cells
Prefixed by name of epithelial cell type
e.g. transitional cell Ca.
What is a adenocarcinoma?
Malignant tumour of epithelial cells,
Carcinomas of glandular epithelium.
What is a: Lipoma Chondroma Osteoma Angioma?
adipocytes cartilage bone vascular
What is a rhabdomyoma?
Benign neoplasm of striated muscle.
What is a leiomyoma?
Benign neoplasm of smooth muscle.
What is a neoplasm of nerves called?
Neuroma.
What do you call connective tissue malignant neoplasms?
Sarcoma.
How can you further classify carcinomas and sarcomas?
Degree of differentiation.
What is it called when the cell-type is unknown?
Anaplastic.
What words have Oma but are not neoplasms?
Granuloma, mycetoma and tuberculoma.
What are some exceptions to malignant tumours being carcinomas or sarcomas?
melanoma: malignant neoplasm of melanocytes
Mesothelioma: malignant tumour of mesothelial cells
lymphoma: malignant neoplasm of lymphoid cells
What is carcinogenesis?
The transformation of normal cells to neoplastic cells though permanent genetic alterations or mutations.
What does carcinogenesis apply to?
Malignant neoplasms.
What is oncogenesis?
Benign and malignant tumours.
What are carcinogens?
Agents known or suspected to cause tumours.
What is carcinogenic?
Cancer causing.
What is oncogenic?
Tumour causing.
How much of cancer risk is environmental?
85%.
What are the problems with identification of carcinogens?
Latent interval may be decades.
Complexity of environment.
Ethical constraints.
What are the different classes of carcinogens?
Chemical.
Viral.
Ionising and non-ionising radiation.
Hormones, parasites and mycotoxins.
Miscellaneous.
What are chemical carcinogens features?
No common structural features
Some act directly
Most require metabolic conversion from pro-carcinogens to ultimate carcinogens
Enzyme required may be ubiquitous or confined to certain organs.
What are polycyclic aromatic hydrocarbons tumours and how do people obtain them?
Lung cancer and skin cancer. Smoking and mineral oils.
What are aromatic amines tumours and how do people obtain them?
Bladder cancer. Rubber/dye works.
What are Nitrosamines tumours and how do people obtain them?
Gut cancer. Proven in animals.
What are alkylating agent tumours and how do people obtain them?
Leukaemia. Small risk in humans.
What is xeroderma pigmentosum?
Repair DNA mechanism is defective
What does radiation energy cause?
UV light Increase Exposure to UVA or UVB causes Increase BCC, melanoma, SCC
What are some biological agents for causing cancer?
Hormones. Mycotoxins. Parasites.
How hormones cause cancer.
Increase Oestrogen leads to an increase mammary/endometrial cancer Anabolic steroids leads to hepatocellular carcinoma
How can mycotoxins cause cancer?
Alfatoxin B1 leads to hepatocellular carcinoma
How can parasites cause cancer?
Chlonorchis sinensis leads to cholangiocarcinoma
Shistosoma leads to bladder cancer
What are the host factors for cancer?
Race
Diet
Constitutional factors - age, gender etc
Premalignant lesions
Transplacental exposure.
What race factors are there in cancer.
Increase Oral cancer in India, SE Asia (reverse smoking, betal chewing) Decrease Skin cancer in blacks (melanin)
What are some premalignant conditions?
Colonic polyps
Cervical dysplasia (CIN)
Ulcerative colitis
Undescended testis
Where does a basal cell carcinoma spread?
Basal cell carcinoma of the skin only invades locally - it never spreads to other parts of the body.
How can you treat a basal cell carcinoma?
Cut it out
Why can’t you just cut out leukaemia?
White blood cells circulate round the body and so will any tumour of white blood cells
Where are cancer cells most likely to spread to first?
Lymph nodes.
Where does the cancer spread to in breast cancer?
Axillary lymph nodes.
Where can carcinomas spread?
To bone from the blood.
What are the common cancers that spread to bone?
breast, prostate, lung, thyroid and kidney.
What do you need to do if a cancer has spread to the axilla?
Axilla clearance is needed.
What do you need to do if a cancer has spread to the rest of the body?
Chemo therapy is needed.
What do you need to do if a cancer has not spread to the rest of the body?
surgery with or without lymph node clearance.
Once a tumour has been excised will the tumour be gone?
Even if a tumour is completely excised micro metastases could be present.
What is adjuvant therapy?
Extra treatment given after surgical excision.
What is an example of adjuvant therapy?
Radiotherapy after breast excision.
What is hypertrophy?
increase in size of a tissue caused by an increase in size of the constituent cells.
What can divide in skeletal muscle?
Myofibrils.
What is hyperplasia?
Increase in size of a tissue caused by an increase in number of the constituent cells.
What is an example of hyperplasia?
Prostate in older age.
What is an example of hypertrophy and hyperplasia?
Smooth muscle in pregnancy.
What is atrophy?
decrease in size of a tissue caused by a decrease in number of the constituent cells or a decrease in their size.
What is metaplasia?
change in differentiation of a cell from one fully-differentiated type to a different fully-differentiated type.
What is an example of metaplasia?
metaplasia in bronchi of a smoker. Ciliated columnar epithelium to squamous epithelium.
What is dysplasia?
imprecise term for the morphological changes seen in cells in the progression to becoming cancer.
What limits the number of divisions in a cell?
Telomeres.
What can telemeres be used to predict?
Lifespan.
What damage can happen at DNA replication?
Telomere shortening.
Free radical generation.
Cross-linking or mutations of DNA.
Loss of calcium influx controls.
Damage to mitochondrial DNA.
Loss of DNA repair mechanisms.
How does UV-B light affect the skin?
Cross links proteins and cause wrinkling.
What is osteoporosis?
Loss of bone matrix.
What causes osteoporosis?
increased bone resorption - lack of oestrogen.
decreased bone formation - lack of oestrogen.
What happens later in life to hormones?
decreased growth hormone.
decreased testosterone.
increased catabolic cytokines.
What can a cancer cell do?
Either undergo apoptosis and go away. Grow and multiply.
