D’YOUVILLE COLLEGE
BIOLOGY 307/607 - PATHOPHYSIOLOGY
Lecture 7 - NEOPLASMS, CANCER THERAPIES
Chapter 6
1.
Patterns of Cell Growth (fig. 6 - 4 & ppt. 1): regulated by signal
molecules (growth stimulators, growth inhibitors, or failure of signal reception)
• reversible departures from normal growth - a brief primer:
- hypertrophy: adaptive increase in cell size, e.g., enlargement of heart &
skeletal muscle in athletes, or in response to losses in tissues (compensatory
hypertrophy)
- atrophy: adaptive shrinkage in response to inactivity of tissue (disuse
atrophy), e.g., skeletal & muscle losses in bedridden patients, or in response to
pressure (from tumor or aneurysm) that disrupts nutritional/blood supply (fig. 1 - 10
& ppt. 2)
- hyperplasia: adaptive or normal increase in cell number in response to
various stimuli, e.g., continuous abrasion or compression (cause of callus formation toes of tight shoes) or proliferation of uterine endometrium (response to hormonal
fluctuations during reproductive cycle)
- hypoplasia & aplasia (reduction in cell number or lack of cell number) are
conditions of functional inadequacy or lack, usually due to developmental or genetic
causes (e.g. aplastic anemia, achondroplastic dwarfism)
• metaplasia: adaptive change in pattern of growth but of normal
character, e.g., change of respiratory mucosa in response to inhaled irritants (smoke,
industrial pollutants); formerly ciliated columnar epithelium replaced by stratified
squamous (with altered function) (fig. 6 - 1 & ppt. 3)
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• dysplasia: change in growth pattern that is abnormal in terms of function,
variations of cell size & nuclear characteristics (pleiomorphism); not always reversible;
often treated as a precancerous change (fig. 6 - 2 & ppt. 4)
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Neoplasia - irreversible departure from normal growth; afflicts over 3 in 10;
at least 1 in 4 die of it; greater numbers die with it; major health threat
• oncology: (oncos = tumor) - study of neoplasia - condition characterized by
loss of normal mitotic controls
- growth is described as autonomous - independent of normal balancing
signals (growth stimulators & growth inhibitors - fig. 6 - 5 & ppt. 5) that regulate
proliferation of cells (fig. 6 - 3 & ppt. 6)
2.
- tumor terminology: tumors classified as benign or malignant; suffix -oma
signifies tumor; benign growths named according to specific tissue of origin, e.g.,
glandular --> adenoma, bone --> osteoma, fat --> lipoma, & connective tissue --> fibroma;
malignancies include word roots carcino- for tumors originating from ectodermal
and endodermal embryonic origins (epithelial or neural tissues) or sarco- for tumors
originating from mesodermal origin (musculoskeletal tissues), e.g. adenocarcinoma,
osteosarcoma, fibrosarcoma (table 6 - 1)
• benign: usually slower growing tumors; growth consolidates surrounding
connective tissues producing capsule (encapsulated tumors); discrete and localized
character usually renders less damage to normal tissues & better prognosis for
treatment (including surgical removal) (fig. 6 - 10 & ppt. 7)
• malignant: faster growing, invasive & diffuse (fig. 6 - 15 & ppt. 8), poorly
organized abnormal cells (= pleiomorphism) or cells that are less differentiated (=
anaplasia); some overlap of features compared with benign - fig. 6 - 13 & ppt. 9),
metastasizing (table 6 - 2)
- tumor cell motility facilitates invasiveness (fig. 6 - 16 & ppt. 10); growth
follows path of least resistance (fig. 6 - 17 & ppt. 11); pattern of vascularization
altered by abnormal growth factor responses (fig. 6 - 8 & ppt. 12)
- tumor growth rate varies (seldom as fast as regeneration in healing or
embryonic growth); many cells in each generation die or stop dividing, so doubling
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time is much slower than generation time (fig. 6 - 14 & ppt. 13); anaplasia usually
corresponds with faster growth rate
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• metastasis: loosely adherent cells break free from tumor and may enter
lymphatic passages, bloodstream, or body cavities as emboli; circulate until trapped
in smaller vessel where they invade and establish secondary growth (figs. 6 - 18, 6 19, 6 - 20, 6 - 21 & ppts. 14 to 17); this pattern often leads to predictable sites for
secondary tumors
- effects of tumors: compression injuries & obstructions interfere with
normal functions of surrounding tissues (fig. 6 - 23 & ppt. 18)
- abnormal adhesions may restrict normal organ functions (fig. 6 - 22 &
ppt. 19)
- damage to basement membranes & extracellular matrix, interference
with production of normal defenses may cause an increase in infections; tumors may
disrupt normal regulation of marrow, possibly causing anemias, impaired immune
responses, etc. (figs. 6 - 25, 6 - 26 & ppts. 20 & 21)
collectively, impairments due to tumors may cause a general weakness
& loss of weight (= cachexia), pain & effects of hyperfunction or hypofunction
3.
Causes, Diagnosis, Treatment:
• oncogenes: genes normally coding for proteins that regulate cell growth and
DNA repair processes (protooncogenes) may become defective; abnormal products
of such oncogenes may result in failure of controlled cell growth (fig. 6 - 27, 6 - 28 &
ppt. 22) and may lead to carcinogenic transformation
- several steps of cell damage (actions of initiators & promoters) are
needed, in appropriate sequence, to complete transformation, (fig. 6 - 29, box fig. 6 - 1 &
ppts. 23 & 24)
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• environmental agents: solar &/or ionizing radiations, certain viruses, &
numerous chemical agents (carcinogens) can provoke transformation to neoplasia
(oncogenesis or carcinogenesis - fig. 6 - 30 & ppt. 25); whether these agents act as
initiators or promoters or render cells more vulnerable to initiators or promoters is
poorly understood
• diagnosis relies on cellular morphology exhibited in biopsies, e.g. Pap
smears, tests for tumor antigens or other tumor products in blood; morphological
characteristics of tumors are used for tumor grading (scored from I to IV); this
system has predictive value for survival prognoses (table 6 - 7)
- tumor staging is a practice based on characteristics of solid tumors; it
relies on degree of localization, invasiveness, and extent of metastasis, also scored
from I to IV; although not universally applicable, the TNM staging system is
internationally recognized (fig. 6 - 34 & ppt. 26)
• treatments: - surgery has greatest prospect for success with benign tumors
or malignant tumors that are well localized; a diffuse character may necessitate
removal of surrounding healthy tissue (with possible severe effects); likelihood of
metastasis necessitates removal of regional lymph nodes serving the tumor site
- radiation damages healthy tissue as well as destroying tumors, so
techniques to maximize tumor dosage while minimizing exposure of normal tissues
are continually being sought; tumors vary in their sensitivity to radiation treatments
as do normal tissues
- chemotherapy (fig. 6 - 32 & ppt. 27) relies on mixtures of chemicals
primarily aimed at arresting cell division in tumors and promoting removal of
damaged tumor cells; tumors and cells within tumors vary in their
sensitivity/resistance to chemotherapy (table 6 - 6) & normal tissues are also
damaged by chemotherapy, e.g., labile tissues such as hair follicles, gastrointestinal
mucosa, & bone marrow
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- immunotherapy: sensitization of immune system against tumor specific
antigens; at one time a basis for great optimism in cancer therapy, appears to have
fallen short of its anticipated promise (figs. 6 - 31, 6 - 33 & ppts. 28 & 29)