Normal cells have a defined lifespan – they grow, divide, and die in an orderly fashion. A critical balance is maintained between cell growth, proliferation, differentiation, and apoptosis.
2. Cancer
• Derived from Greek word for crab,
karkinoma
• Malignant tumor
• Tumor
– Also referred to as a neoplasm—
new growth
3. Benign vs. Malignant Tumors
Benign Malignant
Grow slowly Grow rapidly
Well-defined capsule Not encapsulated
Not invasive Invasive
Well differentiated Poorly differentiated
Low mitotic index High mitotic index
Do not metastasize Can spread distantly
(metastasis)
Mitotic index = rate of growth
4. Classification and Nomenclature
• Benign tumors
– Named according to the tissues from which they
arise, and include the suffix “-oma”
• Lipoma
• Hemangioma
• Leiomyoma
• Chondroma
5. Classification and Nomenclature
• Malignant tumors
– Named according to the tissues from which they arise
• Malignant epithelial tumors are referred to as
carcinomas
– Adenocarcinoma (from glandular epithelium)
• Malignant CT tumors are referred to as sarcomas
– Rhabdomyosarcomas (from skeletal muscle)
6. Classification and Nomenclature
• Cancers of lymphatic tissue are lymphomas
• Cancers of blood-forming cells are leukemias
• Carcinoma in situ (CIS)
– Epithelial malignant tumors that have not broken
through BM or invaded the surrounding stroma
8. Stages of Cancer Spread
• Stage 1: Confined to organ of origin
• Stage 2: Locally invasive
• Stage 3: Spread to lymph nodes
• Stage 4: Spread to distant sites
• CIS special case
10. Tumor Markers
• Tumor cell markers (biologic markers) are
substances produced by cancer cells or that
are found on plasma cell membranes, in the
blood, CSF, or urine
– Hormones (Epi – in blood, adrenal medullary
tumor)
– Enzymes
– Genes
– Antigens (PSA – in blood, prostate cancer)
– Antibodies
12. Viruses and Cancer
• Implicated
– Hepatitis B and C viruses
– Epstein-Barr virus (EBV)
– Kaposi’s sarcoma herpesvirus (KSHV)
– Human papillomavirus (HPV)
– Human T cell leukemia–lymphoma virus (HTLV)
13. Bacterial Cause of Cancer
• Helicobacter pylori
– Chronic infections are associated with:
• Peptic ulcer disease
• Stomach carcinoma
• Mucosa-associated lymphoid tissue
lymphomas
14. Inflammation and Cancer
• Chronic inflammation is an important
factor in development of cancer
– Cytokine release from inflammatory cells
– Free radicals
– Mutation promotion
– Decreased response to DNA damage
15. Tumor Spread
• Direct invasion of contiguous organs
– Known as local spread
• Metastases to distant organs
– Lymphatics and blood
• Metastases by way of implantation
16. Local Spread
• Invasion
– Cellular multiplication
• Mitotic rate vs. cellular death rate
– Mechanical pressure
– Release of lytic enzymes
– Decreased cell-to-cell adhesion
– Increased motility
• Intravasation
• Extravasation
17. Three-Step Theory of Invasion
• Tumor cell attachment
– Fibronectin and laminin
• Degradation or dissolution of the matrix
– Enzymes
• Locomotion into the matrix
– Invadopodia (pseudopodia)
18. HeLa cell
• a cell type in an immortal cell line used in research
• one of the oldest, most commonly used human cell lines
• derived from cervical cancer cells taken from Henrietta Lacks
• patient eventually died of her cancer on October 4, 1951
• cell line was found to be remarkably durable
• cells propagated by George Otto Gey
• first human cell line to prove successful in vitro, which was a
scientific achievement for the benefit of science
• neither Lacks nor her family gave Gey permission
– (at that time, permission was neither required nor sought)
• HeLa cells were used by Jonas Salk to test the first
polio vaccine in the 1950’s
19. Concept Check
• 1. Neoplasia a. abnormal proliferating cells w/ higher
degree of autonomy
• 2. Anaplasia b. lack of differentiation, primitive cells
• 3. Autonomy c. cancer cells’ independence from normal
cell controls
• 4. Tumor markers d. substances produced by cancer cells
20. • 5. Which characterizes cancer cells?
– A. Poorly differentiated
– B. Metastasis
– C. Infiltrative growth
– D. Poor cell cohesiveness
– E. All of the above
• 6. Which is/are not malignant?
– A. Glioma
– B. Adenocarcinoma
– C. Rhabdomyoma
– D. Leukemia
– E. A and C
21. • 7. Metastasis is:
– A. Alteration in normal cell growth
– B. Growth of benign or or malignant cells
– C. Mutational
– D. Ability to establish a secondary neoplasm at a new site
• 8. CIS is:
– A. Preinvasive
– B. Glandular or epithelial lesion
– C. Teratoma
– D. Carcinoma that has broken through BM
– E. Both a and b are correct
24. Environmental Risk Factors
• Tobacco
– Multipotent carcinogenic mixture
– Linked to cancers of the lung, lower urinary tract,
aerodigestive tract, liver, kidney, pancreas, cervix
– Linked to myeloid leukemia
25. Environmental Risk Factors
• Ionizing radiation
– Emission from x-rays, radioisotopes, and other
radioactive sources
– Exposure causes cell death, gene mutations, and
chromosome aberrations
– Bystander effects
– Poor gene repair
– Changes in gap junction intercellular
communication
26. Environmental Risk Factors
• 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 and release of
free radicals
27. Environmental Risk Factors
• Alcohol consumption
– Risk factor for oral cavity, pharynx,
hypopharynx, larynx, esophagus, and
liver cancers
– Cigarette/alcohol combination increases
a person’s risk
28. Environmental Risk Factors
• Sexual reproductive behavior
–Carcinogenic types of human papilloma virus
–High-risk HPV
29. Environmental Risk Factors
• Physical activity
– Reduces cancer risk
• Decreases insulin and insulin-like growth factors
• Decreases obesity
• Decreases inflammatory mediators and free
radicals
• Increased gut motility
30. Environmental Risk Factors
• Occupational hazards
– Substantial number of occupational carcinogenic
agents
• Asbestos
• Dyes, rubber, paint, explosives, rubber cement,
heavy metals, air pollution, etc.
• Radon
32. Environmental Risk Factors
• Diet
–Xenobiotics
• Toxic, mutagenic, and carcinogenic chemicals in
food
• Activated by phase I activation enzymes
• Defense mechanisms
– Phase II detoxification enzymes
• Examples
– Compounds produced in the cooking of fat, meat, or
proteins
– Alkaloids or mold by-products
33. Environmental Risk Factors
• Obesity
– Correlates with the body mass index (BMI)
– Adipose tissue is active endocrine and
metabolic tissue
34. Environmental Risk Factors
• Obesity
– In response to endocrine and metabolic signaling,
adipose tissue releases free fatty acids
• Increased free fatty acids gives rise to insulin
resistance and causes chronic hyperinsulinemia
• Correlates with colon, breast, pancreatic, and
endometrial cancers
35. Clinical Manifestations of Cancer
• Pain
– Little or no pain is associated with early
stages of malignancy
– Influenced by fear, anxiety, sleep loss,
fatigue, and overall physical deterioration
– Mechanisms
• Pressure, obstruction, invasion of sensitive
structures, stretching of visceral surfaces, tissue
destruction, and inflammation
36. Clinical Manifestations of Cancer
• Fatigue
– Subjective clinical manifestation
– Tiredness, weakness, lack of energy, exhaustion,
lethargy, inability to concentrate, depression,
sleepiness, boredom, and lack of motivation
– Suggested causes
• Sleep disturbance, biochemical changes (cytokines),
secondary to disease and treatment, psychosocial
factors, level of activity, nutritional status, and
environmental factors
37. Clinical Manifestations of Cancer
• Syndrome of cachexia (Gr. “bad condition”)
– Most severe form of malnutrition
– Present in 80% of cancer patients at death
– Includes:
• Anorexia, early satiety, weight loss, anemia,
asthenia, taste alterations, and altered protein,
lipid, and CHO metabolism
39. Clinical Manifestations of Cancer
• Anemia
– A decrease of hemoglobin in the blood
– Mechanisms
• Chronic bleeding resulting in iron
deficiency, severe malnutrition, medical
therapies, or malignancy in blood-
forming organs
40. Clinical Manifestations of Cancer
• Leukopenia and thrombocytopenia
– Direct tumor invasion to the bone marrow
causes leukopenia and thrombocytopenia
– Chemotherapy drugs are toxic to the bone
marrow
• Infection
– Risk increases when the absolute neutrophil
and lymphocyte counts fall
41. Cancer Treatment
• Chemotherapy
– Use of nonselective cytotoxic drugs that
target vital cellular machinery or metabolic
pathways critical to both malignant and
normal cell growth and replication
– Goal
• Eliminate enough tumor cells so body’s
defense can eradicate any remaining cells
42. Cancer Treatment
• Chemotherapy
– Compartments
1: cells undergoing mitosis and cytokinesis
2: cells capable of entering the cell cycle in G1 phase
3: cells not dividing or have irreversibly left cell cycle
–Cells in compartment 3 will die a natural death
44. Cancer Treatment
• Ionizing radiation
– Eradicate cancer without excessive toxicity
• Avoid damage to normal structures
– Ionizing radiation damages the cancer cell’s DNA
• Surgery
– Biopsy and lymph node sampling
• Sentinel nodes
– Debulking surgery –remove most of tumor
– Palliative surgery – relief of symptoms
• Hormone therapy
– Receptor activation or blockage
– Interferes with cellular growth and signaling
45. Cancer Treatment
• Immunotherapy
– Theoretically, antitumor responses can selectively
eliminate cancer cells while sparing normal cells
– Immune memory is long lived
– Numerous immunologic mechanisms are capable of
rejecting different types of cancer
– Biologic response modifiers (BRMs)
46. Cancer Treatment
• Other forms of immunotherapy
– Interferon administration
– Antigens
– Effector cell lymphokines
– Monoclonal antibodies
47. Side Effects of Cancer Treatment
• Gastrointestinal tract
• Bone marrow
• Hair and skin
• Reproductive tract
48. Concept Check
• 1. Likely cause for fatigue in cancer patients:
– A. Biochemical changes due to treatment
– B. Muscle loss
– C. Pychologic factors
– D. All of the above
• 2. The pain experience with cancer:
– A. Affects the patient only in the early stages
– B. Occurs in bone metastasis
– C. Due to tissue necrosis
– D. Both b and c are correct
Editor's Notes
Fats, glial cells, uterine SMC, cartilage
Adrenal medulla tumor - pheochromocytoma
Currently accepted that – multiple mutations are nec. for cancer to dev.
A number of cell control paths must be altered:
1. cancer cells proliferate in absence of growth factors
2. antigrowth signals (contact inhibition) – inactivated in cancer
3. & 4. apoptosis = self destruction path (like excessive growth) is disabled excess growth takes place
5. Angiogenesis – new blood vessel growth
6. VEGF (vascular endothel. GF) is inactivated will fight cancer growth and spread
The cells were later commercialized, although never patented in their original form. Then, as now, there was no requirement to inform a patient, or their relatives, about such matters because discarded material, or material obtained during surgery, diagnosis or therapy, was the property of the physician and/or medical institution. This issue and Mrs. Lacks' situation was brought up in the Supreme Court of California case of Moore v. Regents of the University of California. The court ruled that a person's discarded tissue and cells are not their property and can be commercialized.(As stated in The Immortal Life of Henrietta Lacks by Rebecca Skloot)
Initially, the cell line was said to be named after a "Helen Lane" or "Helen Larson", in order to preserve Lacks' anonymity. Despite this attempt, her real name was used by the press within a few years of her death. These cells are treated as cancer cells, as they are descended from a biopsy taken from a visible lesion on the cervix as part of Mrs. Lacks' diagnosis of cancer. A debate still continues on the classification of the cells.[citation needed]
HeLa cells are termed "immortal" in that they can divide an unlimited number of times in a laboratory cell culture plate as long as fundamental cell survival conditions are met (i.e. being maintained and sustained in a suitable environment). There are many strains of HeLa cells as they continue to evolve by being grown in cell cultures, but all HeLa cells are descended from the same tumor cells removed from Mrs. Lacks. It has been estimated that the total number of HeLa cells that have been propagated in cell culture far exceeds the total number of cells that were in Henrietta Lacks' body.[5]
Since that time HeLa cells have been used for "research into cancer, AIDS, the effects of radiation and toxic substances, gene mapping, and countless other scientific pursuits".[6] According to author Rebecca Skloot, by 2009, "more than 60,000 scientific articles had been published about research done on HeLa, and that number was increasing steadily at a rate of more than 300 papers each month."[7]
Rebecca Skloot – author of The Immortal Life of Henrietta Lacks 2009
http://www.jhu.edu/jhumag/0400web/01.html
1. A 2.B 3.C 4.D
5. E 6. E (a and c)
7. D new growth at new site 8. e
EMR or EMF http://quwave.com/EMF-Pollution.html?gclid=CIyygLqm76kCFRYf3wodghjoYw
