neoplastic disruptions alterations in cell function & differentiation pp
1. Alterations in Cell
Function and
Differentiation
Management of Neoplastic Disruptions
2. I. Epidemiology of cancer
Uncontrolled and unregulated growth of cells
Can occur in any age and ethnicity
2nd most common cause of death in US
1/5 deaths from cancer
Over 50% under age 65
3. A. Cancer incidence and
prevalence by site and sex
Men Women
Prostate Breast
Lung/Bronchus Lung /Bronchus
Colon/Rectum Colon/Rectum
Urinary Tract Uterus
Melanoma Ovary
5. Estimated mortality
Men Women
Lung/Bronchus Lung/Bronchus
Prostate Breast
Colon/rectum Colon/rectum
Pancreas Pancreas
Non-Hodgkin’s Ovary
lymphoma
6. II. Host defense mechanisms in
control of cancer/neoplasia
A. Tumor antigens
- Tumor-associated antigens (TAAs)
result of malignant transformations
- Oncofetal antigen: found on surface & inside of
cells as well as fetal cells.
- CEA: carcinogen embryonic antigen
found in cancer cells of GI tract
- AFP: alpha-fetoprotein found in hepatocytes
7. B. Immunological defense
against CA
1. Immune surveillance mechanisms
Cytoxic T cells - kill tumor cells
Natural Killer cells - directly lyse tumor cells
Monocytes/Macrophages - important in
detection of CA cells. Secret cytokines
B cells – produce antibodies that bind to and kill
tumor cells
9. 2. How cancerous cells evade
immune system
Depends on ability of immune system to
recognize cancer cells as being different from
self cells
Closely resemble cells they originate from
Process where cancer cells evade immune
system is called immunologic escape
12. III. Normal vs. abnormal cell
growth and reproduction
A. Review of normal cell cycle
Reproduction of both healthy and malignant
cells follow cell cycle pattern
Time required for one tissue cell to divide and
reproduce into 2 identical cells
13. Phases of normal cell cycle
G1 phase – post mitotic phase. Relatively
dormant - some RNA & protein synthesis
S phase - DNA synthesis occurs
G 2 phase – pre mitotic phase. Some RNA &
protein synthesis
M Phase - cell division occurs
G o Phase - resting phase
15. B. Cell proliferation
Cells divide and reproduce
Regulated so number of cells dividing = to
number dying or being shed
Cell types fit into 3 large groups:
Well differentiated neurons, skeletal and cardiac
muscle cells
Parent or progenitor cells
Undifferentiated stem cells
16. C. Cell differentiation
Cells transformed into different and more
specialized cell types
Adult cell achieves specific set of structural,
functional, and life expectancy characteristics
Orderly process
18. IV. Characteristics of Benign and
Malignant Neoplasms
A. Terminology
1. Tumor
2. Neoplasia
19. B. Benign Neoplasms
Well differentiated cells that cluster together in
single mass
Resemble cells of tissue of origin
Slow, progressive rate of growth
Expands, but unable to metastasize
Usually enclosed in fibrous capsule
20. C. Malignant Neoplasms
Less well differentiated cells
Able to break loose, enter circulation or lymph
system, and form secondary malignant tumors
at other sites
Grow rapidly, spread widely
Potential to kill regardless of original location
22. 1. Cancer cell characteristics
Cells fail to undergo normal cell proliferation
and differentiation
Anaplasia – term used to describe lack of cell
differentiation in cancerous tissue
Cancer cells do not function properly and do
not die according to time frame of normal cells
24. 2. Invasion and metastasis
Cancer spreads by:
Direct invasion and extension
Seeding of cancer cells in body cavities
Metastatic spread through blood or lymph
pathways
31. 3. Tumor growth
Rate of tissue growth in normal and cancerous
cells depends on:
Number of cells actively dividing or moving
through cell cycle
Duration of cell cycle
Number of cells being lost compared with number
of cells being produced
In blood cancers ex. leukemia, the cancer is rapidly dividing as it mimics
normal life-cycle of surrounding cells EXCEPT scheduled death.
The cancer cells persist.
32. V. Carcinogenesis and major
risk factors
A. Carcinogenesis
1. Terms important in carcinogenesis
Two mutational routes that result in
uncontrolled cell proliferation are
characteristic of cancer:
stimulation of gene causing hyperactivity
inhibition of gene causing inactivity
33. a. Oncogene
Cancer causing gene – altered gene
Gene that promotes autonomous cell growth in
cancer cells
Mutations of normal growth-regulating genes
Oncogenesis: mechanism by which normal cells mutate into cancer cells
Only one single altered gene copy can cause an overgrowth
34. b. Proto-oncogene
Normal growth-promoting gene thought to be
active when appropriate growth-promoting
signals reach cell
“On switch” for cellular growth
If there’s a mutation in the proto-oncogene, then the cell is released from…?
35. c. Anti-oncogene/Suppressor gene
Gene that inhibits proliferation of cells
Genetic signal that normally inhibits
proliferation is removed – causes unregulated
growth
“Turns off” or regulates unneeded cellular
proliferation
37. 2. Cancer cell transformation
a. Initiation – 1st Step
Exposure of cells to appropriate doses of
carcinogenic agent - makes them susceptible to
malignant transformation
Irreversible alteration in cell’s genetic structure
Not usually significant to cells until 2 nd step of
carcinogenesis
Physical/chemical/biological agents, ex. virus, can cause cancer
38. 2. Cancer cell transformation
b. Promotion – 2nd step
Unregulated accelerated growth in already
initiated cells by various chemical and growth
factors
Characterized by reversible proliferation of
altered cell if promoter substance removed
39. 2. Cancer cell transformation
c. Progression – 3rd step
Cellular changes formed during initiation and
promotion assume increased malignant behavior
Cells divide in uncoordinated fashion, invade
and destroy neighboring tissue
42. B. Risk factors
1. Heredity
Predisposition to approx. 50 types of cancer
has been observed in families
10% of cancers have strong genetic link
43. 2. Hormones
Thought to drive cell division
Women – breast, ovary, endometrium
Men – prostate, testis
44. 3. Immunologic mechanisms
Cancer associated with impairment or decline
in immune system. See increase in:
People with immunodeficiency disease
Organ transplant pts taking immunosuppressant
drugs
Elderly
47. 6. Oncogenic viruses
Incorporate themselves into genetic structure
of cell
Alter future generations of cell
Human papillomavirus (HPV)
Epstein-Barr virus (EBV)
48. VI. Prevention and early
detection of cancer
Primary Prevention
Secondary Prevention
Tertiary Prevention
49. A. Preventive measures
Important role for RN
Must have knowledge and skills to educate
community about:
health-related behaviors
risk factors
screening and detection methods
50. 1. Patient education
Numerous factors influence degree of
knowledge people have about CA risk factors
and health promoting behaviors:
race
cultural influences
level of education
income
age
51. Seven Warning Signs of Cancer
C
A
U
T
I
O
N – nagging cough/hoarseness
See Lewis Table 16-8
52. B. Screening procedures for
different types of cancer sites
SBE for breast cancer
Rectal exams for prostate cancer
Sigmoidoscopy/colonoscopy
Occult blood for colon cancer
53. VII. Ways of classifying cancer
Tumors are classified on basis of:
cell type
tissue of origin
benign or malignant
degree of differentiation
anatomic site
function
54. A. By anatomic site
Epithelial tissue - carcinomas
Connective tissue - sarcomas
Lymphatic tissue - lymphomas
Glial cells of the CNS - gliomas
Blood forming organs (mainly bone marrow)-
leukemias
55. B. Histological Analysis
(“Grading”)
Grade I: cells differ slightly from normal cells and
are well differentiated
Grade II: cells are more abnormal and moderately
differentiated
Grade III: cells are very abnormal (severe
hyperplasia) and poorly differentiated
Grade IV: cells are immature and primitive and
undifferentiated, no resemblance to tissue of
origin
57. C. Extent of disease (“Staging”)
Describes location and pattern of spread of tumor
TNM most common:
Tumor (primary)
Node
Metastasis
58. Clinical Staging
0 - CA in situ
I - tumor limited to tissue or organ
II - limited local spread
III - extensive local and regional spread
IV - metastasis
59. VIII. Major treatment options in
cancer treatment
Goals - Cure, Control, Palliation
Used to be considered cured if no cancer
recurrence for 5 years after treatment
Widespread invasions associated with poor
prognosis
Choice of Rx depends on staging - more
metastasis = more aggressive approach
61. A. Surgery
Approx 90% treated surgically
Main benefit - removal of tumor with minimal
damage to other body cells
Surgery involves risk
Usually followed by radiation or
chemotherapy
63. B. Radiation
Used to interrupt cellular growth. Can:
immediately kill cells
delay or halt cell cycle progression
cause damage in nucleus that causes cell death
after replication
64. Types of Radiation
1. External radiation - source placed outside the
body
“Lethal tumor dose”: will eradicate 95% of tumor while
preserving normal tissue
2. Internal radiation/Brachytherapy - source placed
close to or directly in the tumor site
Seeds, beads, needle, catheter, etc.
Brachytherapy: limits radiation to duration of treatment?
Time, Distance, Shielding
66. Wet desquamation
from RT
Dry desquamation
from RT
67. C. Chemotherapy
Systemic administration of anticancer
chemicals
Most agents are cytotoxic - interfere with
some aspect of cell division
More rapidly dividing cells more susceptible
Normal cells die too
69. 1. Classifications
a. Cell cycle specific
Destroys cells in specific phases of cell cycle
b. Cell cycle non-specific
Act independently of cell cycle phases
Often combine with cell-cycle specific to
increase number of cells killed
74. 3. Routes of administration
Topical, Oral, IM, IV, SQ, Arterial,
Intercavity, Intrathecal routes
Depends on type of drug, required dose, and
type, location, and extent of tumor
Patients frequently have central lines placed
for chemotherapy due to the frequency of
treatment and vesicant (caustic) nature of the
medications
78. 4. Extravasations
“Escape of fluids into the surrounding tissue”
Such as in IV infiltration. Apply ice to slow
circulation.
Can cause tissue necrosis and damage to
underlying tendons, nerves, and blood vessels
Treatment - stop drug immediately and apply
ice. Notify MD
79. 5. Toxicity and side effects
Can be acute or chronic
Cells with rapid growth rates are very
susceptible to damage
Various body systems may be affected
80. 5. Toxicity and side effects (cont.)
GI system - N & V most common; stomatitis
Hematopoietic system - depressed bone marrow function
anemia, thrombocytopenia, etc.
Renal system - damage by direct effects during excretion or
accumulation of end products after cell lysis
Hair loss (alopecia) - hair cells are rapidly dividing
Cardiopulmonary system - can cause cumulative cardiac
toxicities. Toxic effects on lung function.
Sometimes necessitates transplant.
Reproductive system - affects testicular & ovarian function
Some choose to bank their gametes.
81. 6. Nursing consideration for
patients on chemotherapy
Fluid and electrolytes
Infection and bleeding
thrombocytopenia, leukopenia
Skin Problems
Hair Loss
Nutritional Concerns
d/t stomatitis, anorexia, N/V
Chemotherapy administration
Self protection
82. D. Hormonal therapy
Used for cancers that are responsive to or
dependent on hormones for growth:
breast
prostate
adrenal glands
endometrium
83. E. Biotherapy
Active Immunotherapy – acts as nonspecific
stimulant of immune system
Passive Immunotherapy – transfer of cultured
immune cells into person with cancer
Sensitized NK cell
T lymphocytes
Cytokines
84. Biologic Response Modifiers
Changes person’s biologic response to cancer
Cytokines: IFNs, ILs that bind
Monoclonal antibodies: produced by B-cells
Hematopoietic growth factors: epogen?
85. F. Targeted therapy
Drugs that target processes of cancer cells
specifically
Leave normal cells unharmed
86. G. Bone marrow and peripheral
blood stem cell transplantation
High dose chemo and radiation therapy used to
ablate or suppress bone marrow
Self or donor stem cells transplanted
Reappearance of oncofetal Ags thought to be result of…
Immunocompromised individuals are at higher risk for cancer development
TS: cannot find tumor NX: regional lymph nodes unable to be assessed
Cure, control, or palliation
Rapidly dividing cells are more susceptible to radiation damage because there’s less time to repair DNA mutations. Daughter cells inherit mutated DNA. The downside is that radiation isn’t limited to targeting cancer cells, but also normal cells.
Limiting! Ex. Only targets cancer cells in M-phase (only a 1 hour window) multiple drugs used at once
Created by Unregisterd version of Xtreme Compressor
Vesicant solutions can be administered this way
The closer the entry point to the heart, the higher the risk of infection
Huber needle: the only type of needle that can be used because it won’t core out a portion of the diaphragm
Fatigue alone accounts for 80% of symptoms
A premenopausal woman might receive androgens with chemo whereas a postmenopausal woman may receive estrogen.