MCCANCE UNIT 4: CELLULAR PROLIFERATION: CANCER

Required Readings:

§ McCance & Huether, 8th edition

o Chapter 12, 13, 14

§ Lecture Material:
o Cancer Characteristics, Staging, Manifestations, Epidemiology Lecture

§ Recordings – Kaltura Course Gallery

o Cancer Basics

Media/Websites:

§ National Cancer Institute -- www.cancer.gov

§ Angiogenesis – www.angio.org
§ Article on Toxins and Breast feeding -- https://www.scientificamerican.com/article/earth-
talks-breast-feeding/
§ Cancer Staging. A video presented by CTCA is on You Tube. Go to: youtube.com and search
“What is cancer staging and how does it work?”

Chapters 12, 13, & 14 from Unit 4 will be on Exam 1

 Cancer Characteristics, Staging, Manifestations, Epidemiology Lecture
NURS 7320
Dr. Kathy Plitnick

Cancer Statistics
• U.S.
▫ 2020 – estimated 1.8 million new cases will be diagnosed
▫ 2020, over 16,850 children & adolescents 0-19 diagnosed, 1,730 died of the disease
▫ Most common – breast, lung, prostate, colon/rectum, melanoma, bladder, non-Hodgkins, renal,
endometrial, leukemia, pancreatic, thyroid, liver
▫ www.cancer.gov – National Cancer Institute, excellent source

Protective Genes in our Body!

1. Caretaker genes
▫ What are the Major Functions?
1. Maintain genomic integrity
2. Repair DNA
▫ Loss of function leads to an increase in mutation rates

2. Tumor suppressor genes

▫ Normal genes that slow down cell division, encode proteins,
halt proliferation, repair DNA
1. suppression of mutated cell
2. Activate caretaker genes
3. Prolong repair phase
4. Initiate apoptosis
▫ What happens when they lose their function?
▫ 2 Important Genes TO KNOW!
1. RB gene
2. TP 53 GENE

3. Proto-oncogene
▫ Promotes cell growth, but at a controlled rate
▫ These are actually ONCOGENES but in a non-mutant state
▫ What do they do when they mutate?
Cancer Grading

• Differentiation
▫ Extent to which cells resemble parent cells
• Well differentiated
▫ Most like the parent cell
• Undifferentiated or poorly differentiated
▫ No longer similar to parent cell
▫ Give some characteristics of these types of cells

Benign and Malignant tumors

• What are Malignant tumors?
– Lack of differentiation
– very different from parent cell
– ↑ Vascularity (angiogenesis) - explain
– ↑ Invasiveness/metastasis because of:
1. Absent contact inhibition (crowding)
2. Absent cohesiveness (wandering off)
3. No capsule
– What about growth?
– What is Anaplasia?

• What are Benign tumors?

– Well - Differentiated
– very similar to parent cell
– ↓ Vascularity
– No metastasis – Explain metastasis
– Encapsulated
– Usually does not cause death

What type of tumor is easier to resect? WHY?

Learn about Angiogenesis: www.angio.org

• Formation of new blood vessels
▫ Tumors must have blood supply to grow & enlarge 1. What is the process to
form new blood vessels?
2. It is a natural process
involved in healing and
reproduction.
3. Advanced cancers can
secrete Growth Factors
• VEGF
• PDGF
• Review these!
Let’s Look at Staging Cancer:
There are 2 different ways to Stage:

• Involves the size of the tumor, degree to which it has invaded, and extent of spread
▫ Stage 0
– In situ
▫ Stage 1
– Cancer is confined to its organ of origin
– Tumor is small but starts to invade
Surrounding tissues
▫ Stage 2
– Tumor larger -- Locally invasive
▫ Stage 3
– Regional structures involved (lymph
Nodes in that region)
– Tumor now spreading
▫ Stage 4
– Distant sites – beyond the region
involved

A Second Way to Stage Tumors: The TNM System – recent literature now has a higher grading numbered
system than shown in your text
Clinical Manifestations of Cancer
• Pain
▫ Little to no pain in early stages of malignancy
▫ Influenced by fear, anxiety, sleep loss, fatigue & overall physical deterioration
▫ Mechanisms
– Pressure, obstruction, invasion of sensitive structures, stretching of visceral surfaces,
tissue destruction, and inflammation

• Fatigue
▫ Tiredness, weakness, lack of energy, exhaustion, lethargy, inability to concentrate, depression,
sleepiness, boredom & lack of motivation
▫ Suggested Causes
– Sleep disturbance, biochemical changes from circulating cytokines, secondary to disease
& treatment, psychosocial factors, level of activity, nutritional status & environmental
factors

• Cachexia
▫ Most severe form of malnutrition
▫ Present in 80% of cancer patients at death
▫ Includes
– Anorexia, early satiety, weight loss, anemia, asthenia,
taste alterations & altered protein, lipid & Carbohydrate
metabolism
– What Cytokines are involved?

• Anemia
▫ Decreased hemoglobin – often < 9 gms
▫ Mechanisms
– Chronic bleeding resulting in iron deficiency, severe malnutrition, medical therapies, or
malignancy in blood-forming organs
– Chronic blood loss in colon and GU cancers

• Leukopenia and thrombocytopenia

▫ Direct tumor invasion to bone marrow causes leukopenia & thrombocytopenia
– What does this predispose the patient to?
▫ Chemotherapy drugs are toxic to bone marrow

• Infection
▫ Risk increases when absolute neutrophil and lymphocyte counts fall

• Paraneoplastic syndromes
▫ Symptom complexes that cannot be explained by local or distant spread of tumor
▫ Commonly due to substance (a hormone) released by the tumor – i.e., Serotonin
– What symptoms may appear from Serotonin release??
Cancer Epidemiology

• Think about what Causes Cancer??

• Environmental-lifestyle factors
▫ Cigarette smoking, excessive alcohol consumption, poor diet, lack of exercise, excessive sunlight
exposure, sexual behavior (creates exposure to viruses), radiation, hormones, drugs, viruses,
bacteria, pesticides, other environmental chemicals present in air, water, food, soil, &
workplace

• Epigenetic changes
▫ coupled with genetic changes & environmental-lifestyle factors cause development of cancer

Genetics
• Parental exposure prior to conception
• In utero exposure – where a lot of Research is focusing on…
▫ Mother’s Nutrition, toxins, stressors, lifestyle
• Exposure to toxins in breast milk after birth
▫ http://www.scientificamerican.com/article/earth-talks-breast-feeding/

Environmental Risk Factors

• Tobacco – 250 toxic, 60 carcinogenic chemicals!
▫ Multi-potent carcinogenic mixture
▫ Linked to cancers of lung, lower urinary tract, aerodigestive tract, liver, kidney, pancreas, cervix
uterus & myeloid leukemia
▫ Second-hand smoke – just as bad!
– Mainstream smoke - Exhaled smoke
– Sidestream smoke - burning cig/pipe/cigar
– Risk for lung CA, heart disease, others

• DIET
▫ In our Diet, we are exposed to compounds called Xenobiotics
▫ Xenobiotics
– Toxic, mutagenic & carcinogenic chemicals in food
– Transported in blood by lipoproteins
– Penetrate lipid membranes
– React with proteins, DNA & different cell structures
▫ How do we Counteract these Effects? We have 2 Main Defense Systems
– 1. Detox enzymes
– Xenobiotics activated by Phase I activation enzymes – Read on cytochrome P450
genes – What are they, what do they produce? Why do we need them?

– Phase II detoxification enzymes – Where are they located?

 – Carcinogens in our Diet:
– Compounds produced in cooking fat, meat, or proteins; Alkaloids or mold byproducts

– 2. Antioxidant systems

– What is an Antioxidant? Give Examples.

• Obesity
▫ Correlates with BMI
▫ Adipose tissue is an active endocrine & metabolic tissue
▫ In response to endocrine & metabolic signaling, adipose tissue releases Free fatty acids (FFA’s)
– Increased FFA’s give rise to insulin resistance & cause chronic hyperinsulinemia
– Correlates with colon, breast, pancreatic & endometrial cancers

• Alcohol consumption
▫ Risk factor for oral cavity, pharynx, hypopharynx, larynx, esophagus & liver cancers
▫ Cigarette-alcohol combination increases risk
▫ How is alcohol related to cancer??

• Ionizing radiation
▫ Emissions from x-rays, radioisotopes & other radioactive sources
▫ Exposure causes cell death, gene mutations & chromosome aberrations
▫ What is a Bystander effect?
▫ Poor gene repair – Genomic instability

• Ultraviolet radiation
▫ Causes basal cell carcinoma, squamous cell carcinoma, and melanoma
▫ Principal source is sunlight
▫ Ultraviolet A (UVA) and ultraviolet B (UVB)
▫ Promotes skin inflammation & release of free radicals

• Electromagnetic fields
▫ Carcinogenic?
▫ What are examples of EM Fields??
▫ Difficult to measure exposure – not a lot of studies done

• Sexually reproductive behavior

▫ Carcinogenic types of human papillomavirus
▫ High-risk HPV
 • Physical activity
▫ Reduces cancer risk – HOW??
– Decreases insulin and insulin-like growth factors
– Decreases obesity
– Decreases inflammatory mediators and free radicals
– Increases gut motility

• Occupational hazards
▫ Substantial number of occupational carcinogenic agents
– Asbestos
– Dyes, rubber, paint, explosives, rubber cement, heavy metals, air pollution, etc.
– Radon – Where do we find this in the environment?
– Pesticides, Toxic wastes

• Air pollution
▫ Outdoor
– Industrial emissions: arsenicals, benzene, chloroform, formaldehyde, sulfuric acid,
mustard gas, vinyl chloride & acrylonitrite
▫ Indoor
– Cigarette smoke, radon – trapped in houses
– Oil vapors from heating and cooking

Incidence and Types of Cancer in Children

• Most common childhood cancers are leukemias and brain tumors

▫ Most common: Acute lymphoblastic leukemia
▫ Most common types of solid tumors: Central nervous system tumors
– Not all brain tumors are malignant, however, the treatment can be debilitating
especially when the child’s brain is developing.

• Sarcomas and embryonic tumors

▫ Embryonic tumors originate during intrauterine life
▫ Immature embryonic tissue is unable to mature or differentiate into fully developed cells
▫ Embryonic tumors are commonly named with the suffix, -blast
– What is a blast cell?

• Most childhood cancers originate from the mesodermal germ layer

▫ This layer gives rise to connective tissue, bone, cartilage, muscle, blood, blood vessels, gonads,
kidneys & lymphatic system

• Childhood cancers often diagnosed during peak times of physical growth

• Childhood cancers usually fast growing and have metastasized before a diagnosis is made
• Boys are affected more than girls
Etiology
• Environmental factors
▫ Prenatal exposure – to drugs, pesticides linked to cancer in children
– Drugs (diethylstilbestrol [DES])
▫ Childhood exposure
– Drugs, ionizing radiation, viruses
– Drugs: Anabolic androgenic steroids, cytotoxic chemotherapy,
immunosuppressive agents
– Pesticides: Linked to leukemias
– Viruses: Epstein-Barr virus, HIV