mod 3 pt 2 Flashcards
In Neoplasia, what characteristics are lost?
cell profileration and differentiation
4 features of benign tumours that distinguish from malignant growth
slow growth, can stop at some point.
made of differentiated cells and well organized stroma.
does not invade beyond capsule.
does not metasisize.
Explain why cancer cells require such high levels of glucose
Energy to keep on rapidly dividing
How do we use this characteristic (cancer and glucose use) to detect cancer cells in the body?
We can see which organs are using a lot or less of glucose and where it is, compare it to normal levels.
What is metastasis? Describe the difference in local growth of benign vs malignant tumours to explain why malignant tumours metastasize.
Metastasis: spread beyond tissue of origin.
Local spread - by enzymes made by cancer cells that break down connective tissue and cells of surroundings - growth is crablike.
Benign - pushes on the surrounding connective tissue that eventually forms a capsule around the growth (easier for surgery)
Malignant tumours metastasize because of anaplasia and cells are pleomorphic, lack a capsule and invade nearby blood vessels, lymphatics and surrounding structures.
Carcinomas spread through while sarcomas spread through
carcinomas: epithelial tissue derived spread through lymph.
sarcomas: fibrous tissue derived, spread through blood.
Invasion and metastasis
Cancer cells:
1.
Must evolve characteristics needed to
metastasize (as outlined previously)
2.
Initially invade the interstitial spaces of local
tissue
3.
If carried by lymphatic drainage, go to primary
or sentinel lymph node/s
4.
Enter the venous system as lymph drains into
left and right subclavian veins
5.
Must evade the innate immune system, e.g. NK
cells, lymphocytes by mimicking normal cells,
coating with platelets
6.
secrete proteolytic enzymes in order to penetrate
tissues from blood vessels (and visa versa)
7.
once “seeded” release cytokines and growth factor
that control invaded tissue functions:
–
to stimulate their growth and proliferation
–
if cancer tissue grows more than 1 mm in
diameter, it requires its own blood supply.
Cancer must develop ability to perform
angiogenesis
Local effects of tumours
Local effects of
tumour growth often depend on
location:
Compression: e.g. brain tumor: headaches, nausea,
loss of consciousness, death. Local nerve compression
> loss of function, sensation
Obstruction : e.g. blockage to airways, gut
Infarction : Growth of mass can obstruct blood vessels,
causing local necrosis of tissues (ulceration and
bleeding) (e.g., blood in stool from colorectal cancer)
Rupture or perforation e.g. gut, ovary
Effusions (inappropriate amounts of fluid) in
pleural, pericardial or peritoneal spaces may
occur (up to 65% of women with ovarian cancer
present with ascites (excess fluid in the peritoneal
cavity)).
Effects are usually combined and relate to
symptoms : e.g. cancer of the lung may present
with chest pain, shortness of breath and cough,
wheezing, blood in sputum
Hemorrhage : damage to blood vessels, e.g., intestine,
lungs
All of these can cause pain
Systemic effects of cancer
1. Paraneoplastic syndromes • Symptoms triggered by a cancer, but not caused by direct local effects of the tumour mass. E.g., some tumours release hormones that may have systemic effects, as with small cell carcinoma of the lung releasing an ACTH like substance, which results in Cushing syndrome.
2.
Pain
•
Little or none in early stages, can be strong in later stages. Can
result from pressure, stretching, inflammation. Important to control
rapidly and completely.
3.
Fatigue
•
Not relieved by sleep or rest. Mechanism not fully understood.
May be due to sleep disturbances, various biochemical changes,
nutritional status, etc.
4.
Cachexia
•
Definition: Loss of body mass due to metabolic disturbances
caused by a disease and cannot be reversed nutritionally occurs
even with adequate caloric intake.
•
Caused by altered metabolism that leads to inefficient use of
energy
•
Compounded by side effects of the cancer: depression, anorexia,
loss of sense of taste, early satiety
5.
Anemia
•
Caused by chronic bleeding, malnutrition, chemotherapy and malignancy in blood forming organs.
6.
Leukopenia and thrombocytopenia
•
Caused by tumour invasion of bone marrow, chemotherapy, radiation
therapy.
7.
Infection
•
Most significant cause of complications and death.
•
Due to loss of immune cells due to reasons above.
•
Causes increased risk from surgery, poor tissue perfusion, indwelling
devices (catheters)
8.
GI tract
•
Relies on rapidly multiplying tissue which is the type of tissue
affected by chemotherapy and radiation therapy.
•
These treatments can cause oral ulcers, malnutrition and infection
•
Nausea also effect of therapeutic agent on nervous system
9.
Hair and skin
•
Also due to rapidly growing tissue being affected by therapeutic
agents.
multi step theory of carcinogensis
Initiation • Exposure to carcinogenic agent (promoter) • irreversible mutations to genome • may be many small doses over time • cells in mitosis or meiosis most susceptible • Promotion: Cytokines and growth factors begin to induce cell proliferation • Progression: Tumour cells eventually acquire all the characteristics needed to invade and metastasize to other tissues
The affect of age on the development with cancer
•
The changes that cause a cell to become cancerous
allow that cell to divide with less inhibition therefore
that cell and all of its progeny will divide more than
regular tissue.
•
The rate of cancer increases dramatically with age,
due to accumulation of small changes in genetic
material (“mutations”) that occur over a lifetime.
•
When enough mutations occur, cancer may develop.
Name and decscribe the 2 types of controlling genes that when altered, may cause cancer.
proto-oncogenes: Genes that in their normal non
mutant state
code for proteins that cause the cell to divide.
(e.g., a growth factor, growth factor receptor, or
a protein involved in transmitting the signal from
the receptor to the nucleus). If these do mutate
and become more active, they are called
oncogenes. (e.g., the RAS family of proteins
that transmit the growth signal from the
membrane receptor to the nucleus. Involved in
30% of breast cancers.)
Tumor suppressor genes (anti oncogenes)
Genes that code for proteins that slow the rate of cell
division or stop it when the cell is damaged.
•
If one copy of the gene is inactivated, the other copy
can still perform the function. ( Remember, we have
2 copies of each gene: one maternal, one paternal ).
Therefore, both copies of the gene must be altered
in order for this to have an effect (“recessive”).
•
These are usually the type of genes that are
involved in cancer that can be inherited (Individuals
can inherit a defective allele, but have protection of
other allele. However, if the other allele becomes
inactivated, then a tumor can develop).
•
E.g., i ) BRCA1 gene in breast cancer, ii) p53 gene
(guardian of the genome) normally stops mitosis in
abnormal cells but may be inactivated in cancer
cells
Why tumour suppressor genes are recessive in effect?
Because there are two copies, if one is affected the other one will perform normally, but if both are affected if has an effect.
Inflammation cancer factor
Inflammation
–
Chronic inflammation has been recognized for close
to 150 years as being an important factor in the
development of cancer. (e.g., chronic viral hepatitis
caused by HBV or HCV infection increases the risk of
liver cancer).
–
Inflammation and cancer both involve the migration of
neutrophils, lymphocytes and macrophages, with the
release of factors that stimulate the growth of cells
and blood vessels. Inflammatory cells also release
compounds that can promote mutations (e.g., reactive
oxygen species)
viral and bacterial infections cancer factor
viral –
A number of viruses have been associated with cancer,
through alteration of the DNA that the virus may cause, or
through inflammation caused by the viral disease:
Bacterial
–
Chronic infection with Helicobacter pylori has been linked to gastric
carcinoma, a leading cause of cancer deaths worldwide.
–
Infection is asymptomatic, but the prolonged chronic inflammation
can lead to the development of cancer.
