(E3) Cancer Powerpoint

Cancer

uncontrolled proliferation of abnormal cells that can cause a mass of tissue

CA cells proliferate faster than normal cells

Since cancer cells proliferate (grow and spread) faster than normal cells, this perpetuates what..?

Mutations

Causes of Cancer

-Genes (hereditary)

-Defective tumor suppressor gene (loss of protection against CA formation)

-Mutated proto-oncogenes (which normally control cell growth / proliferation)

-Faulty apoptosis mechanisms

Problems that occur with CA

Disorganized, nonuniform, misshapen

-cancer cells compete with normal cells for space, nutrients, oxygen, and blood supply

-travels to other sites in the body

Epidemiology of Cancer

-2nd leading cause of death behind heart disease

-among ALL people, lung CA is the higher

-among MEN, prostate CA is the highest

-among WOMEN, breast CA is the highest

-men are at higher risk of developing cancer than women

-cancer rates are overall down by 27%

-most common in those 65+ years old

-rural america has the highest incidence and mortality

-African American men have the highest incident and mortality

The Cell Cycle

Sequence of growth stages → Stages; G0, G1, G2, S, M

Check points within the cell cycle

Repair, Recycling, and/or Apoptosis if needed

*Cancer cells DO NOT stop at checkpoints

How do Cancer Cells disregard growth inhibition signals?

-Grow on top, around, and beside other cells

-Cancer cells may break free

How does a Cancer Cell Cycle differ from a Normal Cell Cycle?

-Cell proliferate without control (G2 to M)

-Mutations inactivate DNA repair gene

-Cells do not undergo G0 to rest and cease division

Immune Survelliance

-Our immune sys constantly surverys the body for foreign substances aka. “non-self” antigens

How does our immune system respond to a “non-self” antigen discovered in our body?

The immune system initiates an attack to destroy the invading system

How does our immune system change with aging?

The strength of the immune system diminishes, and tumor development becomes easier

Differentiation

the extent that neoplastic cells resemble normal cells of origin

Anasplasia

total cellular disorganization, appearance, and dysfunction

Benign tumors differentiation

Benign tumors are well differentiated and localized = GOOD!

The poorer/less differentiated that cancer cells are…

…the WORSE the prognosis is

Malignant tumors differentiation

Malignant tumors are poorly differentiated (Anaplasia) = INVASIVE, DESTRUCTIVE, BAD!!

How do Malignant tumors metastasize? (spread)

via. the lymphatic system or bloodstream

Do benign tumors resemble their tissue of origin?

Yes

Do malignant tumors resemble their tissue of origin?

No

Benign tumors rate of growth

Progressive, slow

Malignant tumors rate of growth

Erratic, slow to rapidly proliferative

Life span of benign tumors

Variable

Life span of malignant tumors

cells have unlimited life span

Genetics of Benign Tumors

genetic stability

Genetics of Malignant Tumors

genetic instability w/ mutations

Local Invasion of Benign Tumors

Cohesive cells, well demarcated tumor (distinct from normal tissue)

Local Invasion of Malignant Tumors

invasive and infiltrative of the surrounding normal tissue using enzymatic destruction

Do benign tumors metastasize

No

Do malignant tumors metastasize

Yes frequently

Classification of Benign Tumors

Well-differentiated, remain localized, cohesive, and well-demarcated (separated) from surrounding tissue

Classification of Malignant Tumors

Invasive and destructive to surrounding tissue

Cells easily metastasize (spread)

Differentiation of extent neoplastic cells vs. anaplasia

Extent neoplastic cells = resemble normal cells but are ACTUALLY ABNORMAL

Anaplasia = lack of differentiation

Grading Tumors

Based on level of differentiation

I, II, III

lower is well differentiated → higher is poorly differentiated

Staging Tumors

use of TNM system

T = tumor size

N = lymph node involvement

M = metastasis to distant organs (liver, bone, lungs)

What are common sites for a tumor to metastasize to different organs

Liver, bone, lungs

Tx (TNM system)

means the primary tumor cannot be evaluated

To (in TNM system)

means there is no evidence of a primary tumor

Tis (in TNM system)

means there is a carcinoma in situ (original place)

T1, T2, T3, T4 (in TNM system)

represent increasing size or extent of the primary tumor, with T1 being small and T4 indicating a larger or more invasive tumor.

Nx (in TNM system)

regional lymph nodes cannot be evaluated

No (in TNM system)

means no regional lymph node involvement

N1, N2, N3 (in TNM system)

indicate varying degrees of regional lymph node involvement, with N1 representing the smallest involvement and N3 indicating extensive lymph node metastasis.

Mx (in TNM system)

means distant metastasis cannot be evaluated

Mo (in TNM system)

no distant metastasis

M1 (in TNM system)

means distant metastasis is present

All cancers originate from changes in…

DNA

(mutations turn normal cells → cancer cells)

2 types of DNA mutations in cancer

Hereditary (genetics)

or

Sporadic (acquired during a persons lifetime)

Hereditary DNA mutations are…

genetic

Sporadic DNA mutations are…

acquired during a person’s lifetime

2 major classes of cancer genes

1) tumor suppressor genes

2) oncogenes

Tumor Suppressor Genes

genes that normally control cell growth, and when mutated, lead to uncontrolled cell division (allowing cancer formation)

TP53 gene

a tumor suppressor gene that is known as the “Guardian of the genome”

*over 50% of ALL cancers have a DEFECTIVE TP53 gene

Proto-oncogenes

genes that stimulate and regulate movement through the cell cycle

*associated with cellular growth and proliferation

When mutated, proto-oncogenes become…

Oncogenes

Oncogenes

a mutated version of proto-oncogenes that stimulate constant, unrelenting cellular proliferation and cell cycling

Viral-Induced Cancer

cancer caused from a viral infection, often involving the insertion of viral oncogenes into the host genome, disrupting normal cell regulation.

the host cell then becomes a manufacturer of the virus

What do the mechanisms of viral induced cancer involve?

Activation of growth promoting pathways

or

Inhibition of tumor suppressors in infected cells

Examples of viruses linked to viral-induced cancer

Cervical cancer is associated with HPV

Hepatocellular carcinoma is associated with HBV, HCV

Cervical cancer is virally associated with…

HPV (human papillomavirus)

Hepatocellular carcinoma (cancer) is virally associated with…

HBV (hepatitis B virus) and HCV (hepatitis C virus)

Metastasis and Tumor Angiogenesis in Malignant Cells

-Malignant cells are invasive, penetrative, and destructive to surrounding tissue

-They metastasize (spread) to other areas, then embed where there is a LOT of nutrients, blood supply, and oxygen

-They can make their own blood vessels to connect (by secreting VEGF)

Metastasis definition

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

Steps of metastasis

1) Direct / Continuous extension

2) Penetrate into lymphatics, blood vessels, or body cavities

3) Transport to secondary sites

4) Entry and growth into secondary sites

Common site(s) for LUNG cancer to metastasize

bone, brain

Common site(s) for COLON cancer to metastasize

liver

Common site(s) for BREAST cancer to metastasize

bone, brain, liver, lungs

Common site(s) for PROSTATE cancer to metastasize

vertebrae

Common site(s) for MELANOMA (skin cancer) to metastasize

brain

Angiogenesis

the process by which new blood vessels form from pre-existing ones, essential for tumor growth and metastasis.

-seen in advanced cancers w/ secretion of angiogenic factors (VEGF)

Paraneoplastic syndrome definiton

an unexpected pathological disorder provoked by the presence of cancer in the body

Paraneoplastic syndrome usually involves the secretion of what..????

endocrine hormones UNRELATED to the cancer tumor

Examples of paraneoplastic syndrome

Hypercalcemia (high Ca 2+) from stimulation of parathyroid hormone (PTH) in lung or breast cancer

& SIADH (inappropriate secretion of ADH) in small cell lung cancer

Is there a clear reason why paraneoplastic syndrome occurs?

Nope

Cachexia of Cancer

progressive loss of body fat and lean body mass (muscle)

symptoms: profound weakness, unintentional weight loss, fatigue, loss of appetite, anemia

Why does Cachexia occur with cancer

theorized to originate with cytokines and mediators released by WBC that are attack the tumor

• TNF-a & IL-1

• Break down of muscle and fat → wasted appearance

Cancer screenings

Pap smear, mammograms, digital rectal exam (DRE), FOBT (hemoccult)

Diagnostic tests for cancer

MRI, CT, bone scans

Tumor cell marker definition

substances produced by cancer cells or that are found on plasma cell membranes, in the blood, CSF, or urine

Types of tumor cell markers

Hormones, Enzymes, Genes, Antigens, Immunoglobulins

Hormones that are tumor cell markers

estrogen / progesterone receptors in breast cancer

Enzymes that are tumor cell markers

lactate dehydrogenase (LDH)

Genes that are tumor cell markers

BRCA-1, BRCA-2

Antigens that are tumor cell markers

PSA = prostate specific antigen

Immunoglobulins that are tumor cell markers

multiple myeloma

Tumor Markers are used to….

screen and identify individuals at high risk for cancer

diagnose specific types of tumors

observe clinical source of cancer → track progression of cancer

Issue that can arise with tumor markers

may cause false positives and negatives

Cancer Treatments

surgery

radiation

chemotherapy (has side effects)

immunotherapy

Immunotherapy as a cancer treatment

Marked flourescent antibodies localize cancer cells

-can be used to deliver meds to cancer sites

-ex) monoclonal antibodies

Palliative care used in cancer

Specialized medical care focused on providing relief from pain and other symptoms of serious illness, improving quality of life for patients and their families.