PBT4 - Anticancer and Cancer Etiology

-Proliferation

-Differentiation

-Programmed death (apoptosis)

Normal control mechanism that govern our cells

-Initiation

-Promotion

-Progression

Multistep Process of Tumorigenesis (Malignant Transformation)

Arises from the spread of cancer cells from the PRIMARY SITE and the formation of new tumors in DISTANT SITES

Metastases

-Structural

-Energy Use

-Blood Vessels

-Growth Factors

-Functional

Normal vs Cancer Cells - Differences

-Normal cell: Divides in orderly way

-Cancer cell: Mutations created w/o order or control

Structural Differences VS

-Normal cell: 70% of energy from the Krebs cycle, 20% of energy from Glycolysis

-Cancer cell: Defective Krebs cycle (ALMOST ALL energy from Glycolysis)

Differences in Energy Use VS

How do you diagnose Malignant tumors' high Aerobic Glycolysis?

Imaging uptake of 2-18F-2-deoxyglucose

-Normal cell: Built-in blood vessel system

-Cancer cell: DOES NOT have a built-in blood vessel system; requires chemical stimulation to build one **b/c tumor growth depends on development of new blood supply (i.e. angiogenesis)

Differences in Blood Vessels VS

-Normal cell: Produce a balanced amount of growth factors

-Cancer cell: Overproduces growth factors → cells are overactive

Differences in Growth Factors VS

-Normal cell: Produce enzymes and hormones in a balanced manner

-Cancer cell: The enzymes and hormones are either OVERactive or UNDERactive

Functional Differences VS

Carcinomas

Cancers from epithelial cells (line some organs and skin)

The cancer staging system is NOT applicable to what type of cancer? Why?

Leukemia (blood is NOT localized)

This describes how far the cancer has spread anatomically

Cancer Staging Systems

-The overall stage grouping system

-The tumor, nodes, and metastases (TNM) system

The 2 Cancer Staging Systems for SOLID Tumors

Stage 0 and 1 (of the Overall Stage Grouping System)

Small localized cancers that are usually curable

Stages 2 and 3 (of the Overall Stage Grouping System)

Locally advanced cancers and/or involvement of local lymph nodes

Stage 4 (of the Overall Stage Grouping System)

Inoperable or Metastatic cancer...

In which each tumor (T), lymph node (N), or metastases (M) is classified w/ a number

The TNM System of Solid Tumors

Tumor Grading: Gx

LEAST aggressive; grade cannot be assessed

Tumor Grading: G1

Well-differentiated

Tumor Grading: G2

Moderately differentiated

Tumor Grading: G3

Poorly differentiated

Tumor Grading: G4

Undifferentiated (MOST aggressive and fast-growing)

-Tobacco

-Alcohol

-Radiation

-Dietary habits

-Chemicals

-Viruses

Environmental Exposure - Etiology

Germline or somatic

Heredity - Etiology

This risk factor is associated w/ Upper Respiratory Tract, Lung, Esophageal, Bladder, and Pancreatic cancer

Tobacco

This risk factor CAN cause cancer in the Upper GI tract by increasing permeability of mucosa to carcinogens (tho it is not a carcinogen itself)

Alcohol

This risk factor is associated w/:

-skin cancer

-development of leukemia, and thyroid cancer

Radiation (Solar, Ionizing)

Highest risk or getting skin cancer like squamous and basal cell carcinoma and melanoma is...??

White skin

Thyroid cancer is the MOST documented cancer linked to...

Chernobyl

-High fat, high calories intake

-Alcohol

-Salt, cured, smoked, or charred foods

-Nitrates and nitrites additives in processed meats

Foods associated w/ INC'd risk of developing Colon, Prostate, and Breast cancers

-High-fiber

-High content of veggies, fruits, and whole grain cereal

Foods associated w/ DEC'd risk of developing Cancer

Aflatoxin

Highly toxic chemical associated to Hepatoma (liver cancer); produced by fungi that contaminate crops

How do we PREVENT hepatoma?

-Proper food storage

-Dietary interventions

-Regular screening for liver cancer in high-risk populations

This virus → Non-Hodgkin's lymphoma and Nasopharyngeal cancer

Epstein-Barr

This virus → Kaposi's sarcoma and lymphoma

HIV

This virus → Cutaneous T-cell lymphoma

HTLV1

This virus → Cervical cancer

Human papilomavirus

This virus → Liver cancer

Hepatitis B

-Activation of Proto-oncogenes to Oncogenes

-Inactivation of Tumor suppressor genes

Genetic changes that Lead to Cancer

Normal genes whose protein products stimulate growth and viability of cells; also includes genes that contribute to tumor growth by inhibiting cell death

Proto-oncogenes

MUTATED or DAMAGED genes that contribute to tumor growth

Oncogenes

-Mutation or Amplification (INC number of gene copies)

-INC of Protein Expression (epigenetics; changes that alter gene activity w/o changing DNA sequence)

Ways of Activating Proto-oncogenes

Genes whose protein products can directly or indirectly PREVENT cell division or lead to cell death

Tumor Suppressor Genes

-Mutation or deletion

-DEC protein expression (epigenetics)

Ways to Inactivate Tumor Suppressor Genes

P53

Example of a tumor suppressor gene