1. Biology, Clinical Manifestations, and Treatment of Cancer
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Cell Proliferation: Cancer
Biology, Clinical Manifestations, and Treatment of Cancer
The hallmarks of Cancer

2. Cancer Derived from Greek word for crab, karkinoma Malignant tumor
Also referred to as a neoplasm— new growth

3. Benign vs. Malignant Tumors
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
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Classification and Nomenclature
Benign tumors
Named according to the tissues from which they arise, and include the suffix “-oma”
Lipoma
Hemangioma
Leiomyoma
Chondroma
Fats, glial cells, uterine SMC, cartilage

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

7. Classification and Nomenclature

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

9. Tumor Staging by TNM System
NODES
METASTASIS

10. Bio217 F12
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
Adrenal medulla tumor - pheochromocytoma

11. Hallmarks of Cancer Bio217 F12
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

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
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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 Mechanical pressure
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
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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
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

19. Bio217 F12
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
1. A 2.B 3.C 4.D

20. 5. Which characterizes cancer cells?
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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
5. E E (a and c)

21. 7. Metastasis is: 8. CIS is: A. Alteration in normal cell growth
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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
7. D new growth at new site 8. e

22. Cancer Epidemiology
Chapter 10

23. Environmental Risk Factors
Increased Decreased
Tobacco * Exercise
Radiation * Proper Diet
Ionizing UV
Alcohol
Sexual Behavior
Diet
Obesity
Occupational Hazards
Electromagnetic Fields ?

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

31. Environmental Risk Factors
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Environmental Risk Factors
Electromagnetic fields
Carcinogenic?
Are they, or aren’t they?
EMR or EMF

32. Environmental Risk Factors
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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
Xeno = foreigner, stranger; bios = life

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

38. Cachexia

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

43. Chemotherapy

44. Cancer Treatment Ionizing radiation Surgery Hormone therapy
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:
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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
1. D 2. D