Lecture 2/3: Neoplasia and Cancer

Cancer

The leading cause of death

Cancer

Diseases in which abnormal cells divide without control and are able to invade other tissues

Metastasize

Cancer travels through the lymph and blood and can affect other parts of the body

2/5

How many Canadians will develop cancer in their lifetime?

Lung cancer

Leading cancer in Canada

Life expectancy is increasing

Why are prostate cancer rates increasing?

PSA test

Blood test for prostate cancer:

1. breast

2. colorectal

3. prostate

Other cancers with high rates in canada [3]

FIT test

Test for colorectal cancer where stool sample is tested for altered genes

Tumour or neoplasm (neoplastic growth)

Solid cancer

Benign

Non-cancerous neoplasm

Slow growth

Growth rate for benign tumour

Rapid growth

growth rate for malignant tumours

no.

Benign: well-defined capsule

Malignant: not encapsulated

Are malignant tumours encapsulated?

Anaplasia

Loss of cellular differentiation (ability to perform functions it previously had)

Stroma

Connective tissue of any organ

Pleomorphism

variability in size and shape of cells. No organization, happens with malignant tumours

Named according to the type of tissue. Includes the suffix “-oma”

How are benign tumours named?

Named according to the type of cell affected

How are malignant tumours named?

Lipoma

Tumour in fat.

Meningioma

Tumour in the meninges of the brain. Causes signs and symptoms if it grows and presses on surrounding structures(ex: those affecting speech, movement, vision etc.)

Carnicoma

Tumour in epithelial tissue

Adenocarcinoma

Tumour from ductal or glandular tissue

Sarcoma

Tumour from mesenchymal tissue (connective tissue, muscle, bone, blood vessels)

Lymphoma

Tumour in lymphatic tissue

Leukemia

cancer of the blood

Myeloma

Cancer in plasma cells and bone marrow

Prognosis

How long you are expected to live with this cancer treated or untreated

Carcinoma in situ (CIS)

Cancerous tumour in glands or epithelium hat has not broken through basement membrane or invaded the surrounding stroma

ductal carcinoma in situ of the breast. They will not remove it immediately, will be checked every 3/6 months

DCIS: common type mentioned in class

50%

Percentage of DCIS that becomes locally invasive

Ewing sarcoma

rare type of bone cancer, usually in young people

Leiomyosarcoma

Cancer affects smooth muscle cells that line our blood vessels, GI tract, and uterus

Lymphoma

Cancer that can affect any lymph nodes or glands. Lymphocytes grow out of control

Epstein-Barr virus

Virus that most people have been exposed to that is believed to cause lymphoma

Hodgkins Lymphoma

Lymphoma that is easier to treat, with a better prognosis

Non-Hodgkins Lymphoma

Lymphoma with a poorer prognosis. Life expectancy is five years

Hodgkins have Reed-Sternberg cells. Large white blood cells that look like owl eyes together.

To differentiate hodgkins/non-Hodgkins lymphoma under a microscope:

Myeloid leukemia

Leukemia that affects myeloid cells. Cannot fight off infection as well

Lymphoid leukemia

Leukemia that affects T and B cells. They are part of the immune response and making antibodies. When people get this cancer, they are at a higher risk of infection and cannot fight off everything else

Myeloma

Disease affecting plasma cells. WIthout plasma cells, we can’t make antibodies meaning we cannot fight off infection.

Hyperplasia

increase in the number of cells

Dysplasia

normal changes in size shape, organization of mature cells.

1. diet

2. exercise

3. sleep

4. controlling stress

How to keep immune system healthy: [4]

HPV

Main cause of cervical cancer

Colonoscopy

Checks for dysplasia of the rectum and bowel. Looks for pollup (pre-cancerous neoplasms)

Neoplasia

Growth of a neoplasm

Food is sitting in intestine. It gets stuck in the bowel, constipation happens. Mutagens are being exposed to colon epithelium

How low fiber diet increases cancer risk

1. unprotected

2. multiple partners

Sex practices that increase risk of cancer [2]

1. penile

2. anorectal

3. cervical

4. mouth

HPV is linked to which cancers: [4]

High levels of cortisol related to chronic stress increase inflammation. Chronic inflammation related to changes in DNA relates to changer

How can stress cause cancer?

Profilactric gastrectomy

Procedure where people choose to get their stomachs removed if they test positive for a certain gene linked to stomach cancer

BRCA1 (female) and BRCA2 (Male)

Gene linked to breast cancer

Prophylactic

When somebody tests positive for a certain gene that will cause a cancer, and chooses to get the procedure done to remove it before cancer develops.

AFP

altered gene expression secreted by ovaries, testicles, and liver. If these levels are high, indicates cancer in those places

CEA

altered gene expression secreted by GI tract, pancreas, lungs, breast. If these levels are high, indicates cancer in those places

If these levels are high, indicates cancer in those places

prostate specific antigen. Secreted by prostate. Men should be getting PSA levels checked

Once tumour markers are present, hopefully immune system will destroy it. But, if there becomes too many altere cells in immune system, or “normal” looking cacer cells get bipassed, you’ll get proliferation of that cell line and cancer devlopes.

What happens when tumour markers are present?

•Sustained proliferative signalling

•Evading growth suppressors

•Genomic instability

•Enabling replicative immortality

•Inducing angiogenesis

•Reprogramming energy metabolism

•Resisting apoptotic cell death

•Tumour-promoting inflammation

•Evading immune destruction

•Activating invasion and metastasis

How is cancer allowed to grow? [10]

Sustained proiferative signalling

Uncontrolled cellular proliferation

Proto-oncogenes

Normal genes that direct protein synthesis and cellular growth (regualtes)

Tumour suppressor genes

Genes that encode proteins that regulate proliferation. basically saying “don’t allow cancer to grow”

Oncogenes (mutated genes. EX: BRCA 1 and BRCA2)

In cancer, when proto-oncogenes and tumour-suppressor genes don’t work, they become:

1. Secrete their own growth factor (autocrine stimulation_

2. Rearrange chromosomes to change DNA (Chromosomal translocatino)

3. Express themselves more powefully than the cells around them (Gene amplification)

How do oncogenes get activated: (3)

Anti-oncogenes

Tumour suppressor genes that get mutated (inactivated) to allow unregulated growth of cancer cells

Caretaker genes

These maintain our genome (all genes in the body). They have proteins that repair damaged DNA

Familial polyposis

The entire bowel fills with polups. A genetic abnormality.

Gene silencing

When a message is sent to genes saying “you’re useless, we don’t need you”

Telomeres

protective caps on each chromosome and are held in place by telomerase

Telomeres rebuild and cells become immortal. Normally, with each cell division, they become smaller and smaller. Unlimited proliferation is related to telmeres and telomerase that are not able to stop continuous division

What happens to telomeres and telomerase in cancer?

Angiogenesis

Growth f new blood vessels to supply tumour with oxygen and nutrients

1mm

A tumour can only grow how much without its own blood supply?

Increase in lipids, amino acids, and other building blocks for cells which allow rapid cell growth

aerobic glycolisis of cancer cells causes an increase in what?

They have defects that can provide resistance so cells don’t die

How can cancer resist apoptotic cell death?

1. peptic ulcer disease (stomach carcinoma)

2. Ulcerative colitis (colorectal cancer)

3. Hepatitis (hepatocellular caner)

Chronic inflammation is associated with what? these can all lead to cancers.

H. pylori

Bacteria that causes peptic ulcer disease:

Tumour-associated macrophages

These cells develop thecapacity to block cytotoxic t-cell and natural killer cell functions. Produces cytokines that are advantageous for tumour growth and spread.

Immunosuppresion

When immune system suppressed. Allows cancers to grow

Immunosuppressive factors

Tumour secretes these into the tumour microenvironment that incraeses resistance of the tumour to chemo and radiatino

Liver

Hepatits B and C can lead to what cancer?

Lymphoma

Epstein-Barr virus can lead to what cancer?

SKin

Kaopsi sarcoma herpes virus (KSHV) can lead to what cancer?

Cervical, anogenital, penile, oropharyngeal

HPV can lead to what cancers?

Metastasis

spread of cancer from a primary site of origin to a distant site

Local spread

When cancer directly invades contiguous organs (touching, very close together)

Paraneoplastic syndromes

These can be the earliest symptoms of cancer. Influenced by hormones and cytoknes released from the tumour or the IR in response to the tumour

1. fear

2. anxiety

3. sleep loss

4. fatigue

5. overall physical deterioration

Pain is influenced by the cancer, but also by: [5]

Fatigue

Most frequently reported symptom of cancer. Is a subjective clinical manifestatino that may be from sleep distrurbances, biochemical changes, psychosocial factors, environmental factors, or physical factors

Cachexia

Most severe form of malnutrtion. “Wasting away”

Anorexia

Abnormal loss of appetite for food, not eating

Anemia

Decrease in hemoglobin/RBCs in the blood.

1. chronic bleeding resulting in iron deficiency

2. Severe malnutrition

3. Cytotoxic chemo or other treatments

4. Malignancy in bone marrow

5. Surgery to remove stomach (b12 deficiency)

Mechanisms for anemia: (5)

Leukopenia

When cancer directly invades the bone marrow. causes low white blood cells

Thrombocytopenia

Cancer directly invades bone marrow, causing low platelets.

Infection (immune system for cellular and humoral) and bleeding (platelets and coagulation)

Leukopenia and thrombocytopenia increase risk of what?

When neutrophils and lymphocytes (WBC) count falls due to cancer or chemo

When does risk for infection increase?

Phagocytose pathogens

Role of neutrophils in immune response

Mounts an immune response to pathogens

Role of lymphocytes in immunity

all caused by decreased cell turnover from chemo and radiation:

1. oral ulcers

2. stomatitis

3. mucousitis

malabsorption

Diarrhea

Therapy-induced nausea

GI symptoms of cancer [6]

1. biopsy

2. Microscopic examination for cell hallmarks of cancer and for grading

How is cancer diagnosed? [2]