BIOL 2200 Unit 3

neoplasia

when either or both cell proliferation or cell differentiation is lost

cell proliferation

process of new cells replacing old ones

tumour

uncontrolled growth of cells, or commonly known as growth of neoplasia; two types called benign and malignant

cell differentiation

cells gaining characteristics of tissue that they make up

stroma

connective tissue framework

benign tumour

tumour that have lost ability to control proliferation; growth is usually slow and may come to a stop; made of fairly well-differentiated cells and well-organized stroma; does not spread beyond their capsule; no metastasis; can still be a problem if the growth interferes with function of surrounding tissue

anaplasia

loss of cell differentiation

malignant tumour

is characterized by rapid growth rate due to anaplasia, loss of tissue organization, cells are pleomorphic; lacks a capsule; invasion of nearby blood vessels, lymphatics, and surrounding structures, and the ability to metastasize; known as “cancer”

carcinoma

cancer originating from epithelial tissue; usually malignant

sarcoma

cancer originating from from mesenchymal tissue, connective tissue, bone, or muscle; usually malignant

lymphoma

cancer from lymphatic cells; always malignant

leukemia

cancer of blood-forming cells; always malignant

two categories of malignant tumours

solid tumours and hemalogical tumours

solid tumours

cancer cells confined to specific tissue or organ

hematologic tumours

cancer cells found in the blood or lymph

carcinoma in situ

the abnormal cells in situations where they originated and haven’t invaded surrounding tissue; not yet malignant; often occurs in breast, cervical, skin, and stomach; can become malignant, stable, or regress

characteristics of cancer cells

genetic instability, independence of external growth signals, loss of contact inhibition, decrease in cell adhesion, loss of anchorage dependence, production of unusual antigens, division without limit, and altered metabolism

genetic instability

high frequency of mutations, such as deletion, insertions, and substitutions

independence of external growth signals

cancer cell is able to be independent of external growth signals, so it’s able to make its own growth signals and can be sensitive to growth factors

loss of contact inhibition

cancer cells pile on top of each other, unlike normal cells that stick together and stop growing when in contact of each other

decrease in cell adhesion

cancel cells lack the membrane structures to stick to each other, leading to increased chance of metastasis

loss of anchorage dependence

cancer cells do not die if not attached to an underlying extracellular matrix, not like normal cells

production of unusual antigens

cancer cells contain cell markers, enzymes, or hormones not made by tissue of origin

telomerase

cancer cells have an overactive enzyme that can lengthen telomeres and divide without limit

altered metabolism

cancer cells use anaerobic respiration (glycolysis) even if oxygen is present, which yields less ATP; lactic acid is produced and used to synthesize other molecules for rapid growth; more glucose is needed, causing weight loss

metastasis

defining characteristic of cancer; the spread of cancer cells from the original site to distant organs and tissues; cancer can be spread locally or distantly

local spread of cancer

spread occurs with enzymes created by cancer cells; enzymes break down cells and connective tissues; growth happens via crab-like extensions, which makes it harder to perform surgery

distant spread of cancer

cancer cells invade lymph and blood vessels into tumour, helped by lymphangiogenesis and neoangiogenesis

sentinel node

the area, if spread is through the lymph, where the tumour cells lodge first in the initial lymph node that drains

steps of metastasis

cancer cells must evolve necessary characteristics (e.g. decrease in cell adhesion, production of unusual antigens), invade interstitial spaces of local tissue, go to primary or sentinel lymph node (if carried by lymph drainage), enter venous system, avoid the immune system by mimicking normal cells, secrete proteolytic enzymes, and become “seeded” to release cytokines and growth factors

angiogenesis

cancer that is more than 1 cm requires its own blood supply and must develop this ability to create blood

local effects of tumours

compression, obstruction, hemorrhage, infarction, perforation, effusions

compression

cancer cells can cause headaches, nausea, loss of consciousness, death, loss of function or sensation

hemorhage

damage to blood vessels

Infarction

obstruction of blood vessels that causes local necrosis of tissues

effusion

inappropriate amounts of fluid in pleural, pericardial or peritoneal spaces

systematic manifestations of cancer

paraneoplastic syndrome, pain, fatigue, cachexia, loss of blood cells (anemia, leukocytopenia, thrombocytopenia), infection, gastrointestinal tract issues, hair and skin issues

paraneoplastic syndrome

symptoms are triggered by substances released by the cancer cells, but not caused by direct local effects of the tumour mass (e.g. tumours release hormones that cause Cushing syndrome)

cachexia

loss of body mass due to metabolic disturbances caused by a disease and cannot be reversed nutritionally; happen as a result of altered metabolism; can be compounded by side effects, such as anorexia, loss of taste, nausea

carcinogenesis

small number of changes in the genetic material of the cell that allow for less cell division inhibition; more likely to happen in later life due to lifetime accumulation of cell mutation

factors that lead to cell cancer development

DNA mutations, changes in cell metabolic pathway (e.g. loss of apoptosis, loss of DNA repair), epigenetics

types of mutations in genes

proto-oncogenes and tumour suppressor genes

proto-oncogenes

genes that code for proteins to cause the cell to divide in its normal state (e.g. growth factor, estrogen)

oncogenes

a proto-oncogene that mutates and causes cell to be more active and divide uncontrollably

tumour-suppressor genes

genes that code for proteins that slow the rate of cell division or stop when the cell is damaged; both copies of genes must be mutated (i.e. recessive genes in effect) to cause effect on cell growth

epigenetics

DNA sequence remains the same, but genes can be turned off or on; affected by acetylation of histones or methylation of DNA; impacted by lifestyle, diet, and exercise

steps in carcinogenesis

initiation (i.e. exposure to carcinogen that causes mutation), promotion (i.e. cytokines and growth factors cause cell proliferation), progression (i.e. tumour forms)

causes of cancer

inflammation, infections

inflammation

chronic inflammation is a big factor in development of cancer; induces release of factors that stimulate the growth of cells and blood vessels, and releases compounds (e.g. ROS) that promote mutations

cancer-causing infections

viral infections include chronic hepatitis (can cause liver cancer), human papilloma virus (can cause cervical cancer), Epstein Barr virus (can cause B cell lymphoma); bacterial infections include Helicobacter pylori (causes gastric carcinoma); not all people with infections develop cancer, but they increase the risk

genetics in cancer

only 10-20% of cancers linked to heritable factors; examples include BRCA1 / BRCA2 mutation can can increase likelihood of breast cancer, Wilms’ tumour can cause kidney cancer

environmental and lifestyle factors

includes cigarette smoking, excessive alcohol consumption, poor diet, obesity, lack of exercise, exposure to UV and ionizing radiation, pesticides and other chemicals; strong evidence but no direct causation

population-based cancer

differs from country to country (e.g. stomach cancer in Japan, colon cancer in USA)

immunological mechanisms

Chemical carcinogens

Low strength (solar) radiation

age factor

high strength (nuclear) radiation

diagnostic methods for cancer

tumour markers, histology, imaging

tumour markers

substances, such as hormones, enzymes, antigens, or antibodies, are produced by both benign and malignant cells that are either present on tumour cells, or found in blood, spinal fluid, or urine; can make false positives

papanicolaou test

the examination of secretions around a tumour that can reveal abnormal cells

biopsy

the removal and examination of tissue sample

immunohistochemistry

the use of antibodies specific for a particular cell product or surface marker for detection on tumour cells

computerized tomography

many x-rays taken from different angles, fed through a computer to
produce a 3D image

magnetic resonance imaging

uses a magnetic field and provides more soft tissue detail, but more
expensive and time-consuming

positron emission tomography

uses a biologically active molecule attached to a tracer to show metabolically active tissue

two methods of classifying cancer

grading and staging

grading

a portion of the tumour is obtained through a biopsy and examined; the closer the tumour cells resemble normal tissue, the lower the grade

staging

includes size and spread of the disease; stage 1 is confined to origin, stage 2 is local invasion, stage 3 is spread to lymph nodes, and stage 4 is spread to distant sites

cancer treatments

chemotherapy, radiation therapy, and surgery

chemotherapy

chemicals/drugs that target metabolic pathways to have cells more sensitive to chemicals (e.g. leukemia is sensitive to folic acid deficiency); used in combinations

induction

chemotherapy by itself

adjuvant

chemotherapy used after surgery to eliminate small metastasized tumours

neoadjuvant

chemotherapy before surgery to minimize removal of tissue

radiation therapy

targeted cells die through molecular damage, particularly to the DNA, caused by the ionizing radiation; can be done through an external beam or by placing small radioactive capsules in the affected area; most effective on rapidly renewing cells and used for hard to reach areas

surgery

used for localized masses

brachytherapy

WHO’s TNM system

cancer in children

second leading cause of death in children; more likely to develop leukemia, brain, or sarcoma (bone); hard to diagnose because it resembles other childhood illnesses; causes are largely unknown; more than 70% of children are cured; chemotherapy is best used; increased risk of developing cancer in the future