What is Cancer?

- Accounts for about 25% of deaths (1:4)

- Group of more than 200 diseases characterized by unregulated growth of cells
- Group of diseases in which cells multiply without restraint, destroy healthy tissues and endanger life
- Disease process that begins when abnormal cell is transformed by the genetic mutation of the cellular DNA

Cancer is:
- A family of complex diseases
- Affect different organs and organ systems
- Eventually harm and destroy host
- A dreaded disease

** PET vs. CT – Identify the sentinel of cancer cells

THEORIES OF CARCINOGENESIS
1. Cellular Mutation – caused by carcinogens

Steps of Carcinogenesis
- Initiation
o begins with exposure of normal cells to carcinogens that alters DNA, repair mechanisms and
programmed apoptosis;
o brief irreversible interaction between carcinogen and predisposed cells
- Promotion
o repeatedly over time on the already transformed cell;
o must be in continuous contact, if removed, effects can be reversed;
o (latent period) 1 ½ to 49 years
- Progression – the uncontrolled growth of a malignant tumor capable of metastasis

2. Role of Oncogenes
- Genes capable of triggering cancerous characteristics
- Produce proteins that accelerates cell’s rate of multiplication, increased responsiveness to growth hormones,
enable to invade other tissues

*CEA – Carcinogen Embryonic Antigen

- Proto-oncogenes
o Can transformed to a malignant state when activated
- Suppressor genes “turn off”, or regulate unneeded cellular proliferation
o Once mutated or lose their regulatory capabilities, malignant cells are allowed to reproduce

3. Immune Response Failure

- Allow expression of oncogenes
o A health immune system recognizes cancerous cells as ‘foreign’ and produce tumor-specific Ig to destroy
them
o Aberrant cells escape immune surveillance because their surface lack human leukocyte antigen (HLA)
helps identify invaders to be destroyed

4. Derangement in Cell-cycle machinery

- p53, p21, p16 – genes that produce proteins that inhibit cell growth becomes mutated or absent
o p53 -
o p21 -
 o p16 -
- Genes for cyclin are believed to be oncogenic: with excessive production
o Cyclin D1 - cause DNA synthesis without further stimulus
o Cyclin D2 and D3 - block cell differentiation
o Cyclin E – interferes contact inhibition
o Cyclin A – promotes cell growth not anchored to surface

5. Known Carcinogens
- Genotoxic or promoter
o Viruses
o Drugs
o Hormones
o Chemical
o Physical agents

Viruses
- Modify genes they invade
- Retrovirus - make DNA copies of their on RNAs by taking over DNA synthesis machinery
- Viral DNA copy, then enter gene becomes virogene (normal gene with copy of viral gene)
- Example:
o Herpes simplex type 1 and 2: Kaposi’s sarcoma, cervical carcinoma, lip carcinoma
o Human CMV: Kaposi’s sarcoma, prostate cancer
o Papilloma virus: malignant melanoma
o Hep B virus: primary hepacellular cancer

Drugs and Hormones

- Genotoxic
o Chemo. Drugs – to normal cells
o Betel nut – chewed by Pacific islander
o Hormones:
 DES (diethylstilbestrol) – cause vaginal carcinomas
 Estrogen (pills/ replacement therapy) – cause endometrial, cervical and breast cancer
 But decrease risk of ovarian Ca
- Promoter:
o Chemodrugs
 Drastic reduction of leukocytes impair immune function
 E.g. cyclophosphamide, chorambucil, busulfan
 Immunosuppressants: e.g. heroin and cocaine
 Glucocorticosteroids and anabolic steroids – alter immune response of endocrine balance

Chemical Agents
- Genotoxic:
o Polycyclic hydrocarbon - Soot, smoked foods, tobacco
o Benzopyrene - In cigarette smoke
o Arsenic – in pesticides
o Methylaminobenzine – in fabric, rubber and glue
o Chemo drugs:
 Aflatoxin – grains and peanuts
 Sodium saccharine, nitrosamines
 Use din preparation and preservation of pickled, salted foods
- Promoter:
o Wood and leather dust
 o Polymer esters – used in plastic and paints
o Asbestos – use din old rundown buildings for insulation
o Bile acid – high fat diet
o Tobacco – smoking/ chewed

Physical Agents
- Radiation – solar (UV rays) and ionizing
- Radon – naturally formed radioactive gas found in the basement of many homes
- Areas where nuclear weapons testing are done
o Nuclear bomb in Nagasaki and Hiroshima
o Leukemia
- EMF Exposure from household appliances, electrical wiring, or living near electrical power lines
o The nearer one if to the source (within 50m), the greater the exposure
o Cellular phones are being studied

*Differences between benign and malignant neoplasms

TYPES OF NEOPLASMS
Benign Malignant
Well-differentiated Undifferentiated
Encapsulated, grow by expansion Infiltrates and destroy surrounding tissues
Slow growth More anaplastic, faster growth
Does not spread by metastasis Metastasize
No generalized effects Generalized effects
Does not usually cause tissue damage or death Extensive tissue damaged
Usually causes death unless growth is controlled

CHARACTERISTICS OF MALIGNANT CELLS

- Loss of regulation of mitotic rate
- Loss of cell specialization
- Loss of contact inhibition
- Progressive acquisition of the cancerous phenotype and immortality
- Irreversibility of cancerous phenotype to greater aggressiveness
- Altered cell structure; l diff.***

1. Have Aggressive growth

2. Not under body’s homeostatic***
3. ********
4. Can recur after removal of primary and secondary tumors and other treatments
5. Malignant neoplasms vary in differentiation
a. Highly differentiated are more like the originating tissue
b. Undifferentiated neoplasms consist of immature cells with no resemble to parent cells and have no
useful function
6. Malignant cells do not stop growing and die, as do normal cells (immortality)

Angiogenesis
- Ability of cancer cells to secrete substances that stimulate blood vessel growth (growth factors and enzymes
such as vascular endothelial growth factor – VEGF)

9. Ability to metastasize
- travel through blood or lymph circulation to other body areas
 - Common sites = bone, brain, liver, lungs, lymph nodes

Six Hallmarks of Cancer: Multiple Pathways of Carcinogenesis

1. Self-sufficiency in growth signals
2. Insensitivity to antigrowth signals
3. Evading apoptosis
4. Limitless replicative potentials
5. Sustained angiogenesis
6. Tissue invasion and metastasis

CLASSIFICIATION, GRADING AND STAGING

Most Common Tissue Types
- Fibrosarcoma – may grow anywhere but frequently form in the uterus, starts as benign
- Liposomas – in adipose tissue
- **
- Sarcoma – from mesenchymal origins (blood vessels, lymphatic, nerve tissues)
- Carcinoma – arises from epithelial tissues
- Carcinoma in situ – confined **

Grading:
- Evaluates degree of differentiation and rate of growth
- Grade 1 (least aggressive) to Grade 4 (most aggressive)
- Grade x: grade cannot be assessed
- Grade 1: well-differentiated; mild dysplasia; differ slightly from normal cell
- Grade 2: moderately well differentiated; moderate dysplasia
- Grade 3: poorly differentiated; severe dysplasia
- Grade 4: very poorly differentiated; immature and primitive (anaplasia); undifferentiated; cell origin difficult to
determine

Staging – the extent of the disease

- 0 cancer in situ
- I Tumor limited to the tissue of origin
- II limited local spread
- III extensive local and regional spread
- IV metastasis

Staging
- Determines the size of the tumor and the existence of metastasis
- TNM:
o Tumor size, depth of penetration and invasion of adjacent structures
o Nodes: regional lymph node involvement; presence, extent and location
o Metastases: presence of absence and degree of dissemination

**TNM Classification System; Anatomic classification of tumors – Lewis pg 290

Cytologic Examination
- Basic method of collecting specimens:
o Exfoliation from an epithelial surface (e.g. Pap smear)
o Aspiration from body cavities or blood
o Needle suction aspiration of solid tumors

Tumor Markers
- Biochemical substances synthesized and released by tumor cells
 - Indicators of the presence of tumors
- May be present in benign conditions
- Used to diagnose, determine response to therapy, predict or confirm relapse and assess prognosis
- Categories:
o Tumor-derived marker
o Host (immune)-response marker

Tumor-derived markers (blood test)

- Oncofetal antigens
o AFP, CEA
- Hormones
o HCG, ADH, PTH
o Calcitonin, catecholamines
- Tissues-specific proteins
o PSA, Ig
- Isoenzymes
o PAP (Prostatic Acid Phosphatase)
o NSE (neuron-specific enolase)

Host-Response Markers
- Serum ferritin
- Interleukin-2
- TNF
- C-reactive protein
- Lactic dehydrogenase

Tumor markers
- Alpha fetoprotein N < 10ng/ml increased in lung, pancreatic, colon, gastric, choriocarcinoma
- ***

Oncologic Imaging:
- X-ray
- MRI
- CT
- Utz
- Radioisotope scans
- Angiography

Direct Visualization:
- Sigmoidoscopy – sigmoid
- **

Other non-specific tests

- CBC, differential
- Electrolytes
- Blood Chemistries
- Liver enzymes:
o Alanine aminotransferase (ALT); aspartate aminotransferase (AST), lactic dehydrogenase (LDH)

Blood or serum
- Acid Phosphatase (N: 0.11–0.6mU/ml)
o Increased in metastatic prostate cancer
- Alkaline phosphatase (N 20-90mU/ml)
 o Inc in bone metastasis, liver ca, lymphoma

- Calcitonin: increased in medullary thyroid Ca

- Calcium N 9-11mg/dl inc in bone Ca
- LDH (100-190mU/ml) – inc in liver ca, lymphoma, acute leukemia
- SGPT (AST) (N 5-35mU/ml) – inc in liver Ca
- SGOT (ALT) (N 7-40mU/ml)
- Uric Acid (N 1.5-8mg/dl)
o Inc. in leukemia, multiple myeloma
o Dec. in Hodgkin’s disease, lung Ca

RISK FACTORS OF CANCER

- Non-controllable
o Hereditary/race
o Age
o Gender
o Lower socio-economic status

- Heredity – 5-10% of cancers; documented with some breast and colon cancers
- Race – e.g. young white males (15-40)
- **
- Controllable
o Stress
 Keeps cortisol and epinephrine at high levels  systematic fatigue
 Alarm reaction  stage of resistance  stage of exhaustion == if remains elevated 
wear and tear, depressed immune system
 Type C people – tend to others’ needs to the exclusion of their own, rarely ask help or
support even in personal crises
o Diet
 Dietary substances assoc. w/ an increased cancer risk:
 High fat, low fiber
 Alcohol
 Salt-cured or smoked meats
 Foods containing nitrates and nitrites
 High caloric dietary intake
 Repeated use of fat to fry foods at high temp.
 Produce high levels of polycyclic
 Reduces cancer risk:
 High-fiber foods
 Carotenoid e.g. carrots, tomatoes, and dark green vegetable
 Possibly vitamins E and C, zinc, and selenium
 ****
o Occupation
o Infection
o Tobacco use/Smoking
 Lung, oral and laryngeal, esophageal, gastric, pancreatic, bladder cancer
 Smokers of 2 or more pack/day – (mortality rate 12-25 times greater than the non-smoker)
 Smoking cessation after a habit of 30 years, incidence of lung cancer decreases
 Smokers who quit before age 50 decreases death risk by 50%
o Alcohol use
 Enhances metab activity of tobacco antigens
 Destroys**
 o *
o Occupational Risk
o Radiation, high stress
o EMF exposure
o Depletion of the ozone layer
o Fertilizer, rubber
o Infections: examples
 Papillomavirus – cervical Ca
 Epstein-barr virus – Hodgkin’s and Burkitt’s tumor
 Helico**
 **
o Obesity
 Risk for hormone dependent cancers
 Sex hormones are synthesized from fats
 E.g. endometrial cancer and possibly postmenopausal breat ca
 Increase**
o Sexual Practices
 High incidence of uterine cervix carcinoma:
 First coitus at an early age
 Early first marriage
 Multiple sex partners
 Carcinomas of penis virtually unknown among circumscised men
 First child before age 20 have only 1/3 the risk of women older than 35 who deliver a first child

Prevention of Cancer