Cancer

Front 1

top 5 causes of death

Back 1

1. heart disease
2. cancer
3. cerebrovascular
4. chronic lower respiratory diseease
5. accidents

Front 2

top 4 cancer killers (men and women)

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1. lung/broncus
2. colorectal
3. breast
4. prostate

Front 3

top 3 cancer killers (men)

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1. lung/bronchus
2. prostate
3. colorectal

Front 4

top 3 cancer killers (women)

Back 4

1. lung/broncus
2. breast
3. colorectal

Front 5

disease of aging

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67% of deaths occur after age 65

Front 6

cancer: definition

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mass of tissue, the growth of which is incoordinate with the surrounding normal tissues and that persists in the absence of the inciting stimulus

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labile cells

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continue to multiply throughout life (skin, nails, hair)

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stable cells

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retain latent capacity to regenerate (most glands, kidney tubules)

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permanent cells

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cannot regenerate (thought: neurons, muscle cells)

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stromal repair

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proliferation of fibroblast and capillary buds
subsequent laying down of collagen to produce a scar
results in loss of specialized parenchymal function

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hyperplasia

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increase in number of cells in tissue/organ
physiologic or pathologic
cells are essentially normal (may have changes in appearance)

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metaplasia

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addaptive substitution of one cell type for another
usually represents adaptive or protective response
usually reversible
occurs in both epithelial and connective tissue

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atypical metaplasia

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transition between metaplasia and dysplasia
judgement call

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dysplasia

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loss in uniformity of individual cells
loss in architectural organization
pleomorphism and hyperchromatic nuclei
usually reversible (if stimulus is removed)
malignant transformation sometimes associated

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anaplasia

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without form
failure of differentiation of reserve or stem cells
marked pleomorphism

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neoplasia

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abnormal mass of tissue
irreversible

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benign neoplasm

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based n judgment of tumor's behavior
considered relatively innocent
remain localized
cannot spread
tend to become enclosed within fibrous capsule
generally amenable to local surgical removal and survival of patient

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malignant neoplasm

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implies can invade and destroy adjacent structures
implies can spread to distant sites to cause death
two components:
-parenchyma
-stroma
do not develop capsules

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metastasis

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anatomically distant cancer growth
seeding throughout body cavities
distinct transplantation
lymphatic permeation
transport through blood vessels

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differentiation

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extent to which cells resemble normal forebearers and achieve fully mature, specialized, functional, morphological characteristics

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poorly differentiated cells

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no specialized characteristics
resemble embryonic primitive stem cell (anaplastic)

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well-differentiated cels

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high level of specialization
maturation

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sarcoma

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malignant neoplasm
arising from mesenchymal tissue

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carcinoma

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malignant neoplasm
arising from epithelial cells

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apoptosis

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programmed cell death
activation of p53 gene
common in embryonic development

Front 26

tumor: grade 1

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well differentiated
cells resemble those of origin
retain some specialized function

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tumor: grade 2

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moderately differentiated
shows less resemblance to tissue of origin
more variation
increased mitosis

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tumor: grade 3

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poorly differentiated
cells don't resemble tissue of origin
much variation
increased mitosis

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tumor: grade 4

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very poorly differentiated
no resemblance to tissue of origin
great variation (very anaplastic)

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TNM system of staging tumors

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T0 - T3: primary tumor size
N0 - N2: lymph node involement
M0 - M2: extent of metastasis

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S phase

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DNA synthesis

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G2 phase

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gap between end of S phase and mitosis
time required to organize nucleus for mitosis

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M phase

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mitosis
chromosomal condensation and chromosomal segregation, cell division yielding 2 daughter cells
usually requires about an hour to complete

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G1 phase

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gap between mitosis and S phase
energy directed toward synthesis of RNA and protein

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G0 phase

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outside the loop
do not respond to signals that normally prompt initiation of DNA synthesis

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total cell cycle time

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Tc
from G1 through M
normal human cells: 1 to 2 days
most malignant cells: 2 to 3 days

Front 37

critical cell population

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often largely in G0

Front 38

Gompertz curve

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mathematical model applied to tumor cell growth rates
factors influencing:
hypoxia
nutrient/hormone supply
toxic metabolites
inhibitory cell-to-cell communication

Front 39

tumor growth characteristics

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10^6 - 20 doublings - 1 mm
10^9 - 30 doublings - 1.24 cm
limit of clinical detection
10^12 - 40 doublings - 20 cm
almost all malignant tumors cause death when reach this size

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time required to reach 10^9

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<2 years

Front 41

cachexia

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wasting
TNF probably contributes to wasting in humans

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proto-oncogenes

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function in regulation of normal cell growth/differentiation

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oncogenes

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altered (mutated) proto-oncogenes
encode regulatory protein that has dominant transforming properties
can cause overexpression of growth-related gene products resulting in tumor formation

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tumor suppressor genes

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inhibit cell division
mutations may remove growth inhibition
recessive trait

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multiple cell accidents

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evidence indicates several independent accidents must occur in one cell in order for tumor development to begin
referred to as malignant transformation