27 Mar 2014
School
Department
Course
Professor
LECTURE 1: NEOPLASIA
-Biology: normal response of cell to the env
-Pathology: abnormal response of cell to env OR normal response of cell to abnormal env
-Both predictable
-Pathobiology: a cells response (in the context of organ and individual) to changes in the env (env is
exogenous or endogenous)
-Central theme: change in env->adaptive response->cell death, cell injury AND disease
-Changes in env:
-chemicals
-radiation
-biological
-immunological
Neoplasia
-mass of proliferating cells
-acquired immunity
-growth is not coordinated with normal cells/tissue
-2 types
-Benign tumour (oma) : Local expansion
-Malignant tumour (CANCER) (sarcoma, carcinoma): Expansion and invasion [if shortage of blood
supply=cell death, necrosis] and metastasis
Classification of Cancers
1) Simple: one neoplastic cell type
Mesenchymal in origin (sarcoma)
a) CT tissue and derivatives
•Fibroma, Fribrosarcoma (fibrous tissue)
•Lipoma, Liposarcoma (adipose tissue)
•Chondroma, Chondrosarcoma (cartilage)
•Osteoma, Osteosarcoma (bone)
b) Endothelial tissue
•Hemangioma, Hemangiosarcoma (BV)
•Lymphangioma, Lymphangiosarcoma (LV)
•Mesothelioma, Mesotheliosarcoma (Mesothelium)
c) Lymph Tissiue and Bone Marrow
•Lymphoma, Leukemia
d) Muscle
•Leiomyoma, Leiomyosarcoma (SMC) -uterus
•Rhabdomyoma, Rhabdomyosarcoma (striated) –eyelid
Epithelial in Origin
a) Epithelium
•Papilloma/Adenoma (glandular), Carcinoma
b) Placental Epithelium
•Hydatid Mole, Choriocarcinoma
c) Testes
•Seminoma, Embryonal carcinoma
2) Mixed: Multiple neoplastic cell types but from ONE germ layer
a) Salivary gland -Benign mixed tumour, malignant mixed tumour
b) Kidney -Wilms tumour (*)
3) Compound: Multiple neoplastic cell types from more then one germ layer
-sometimes contain hair, teeth, etc
a) Ovary -Dermoid cyst, Teratoma
b) Testes -Teratoma
Cancer Incidence By Sex
-Breast cancer: men have mammillary glands but they are just underdeveloped. They can get cancer
through
a)familiar history-inherited gene BRA1 BRA2
b)Hormone exposure (ex.estrogen)
c)Chromosomal makeup is diff (if they have an extra chromosome or something)
-Women
-Highest: Breast cancer
-Low lung cancer
-Trends: Breast & lung increase, Colorectal decrease
-Men
-Highest: Skin cancer
-Lung is second highest
-Trends: lung decrease, colorectal same, prostate increase [[had HUGE jump when PSA (prostate
specific antigen test) was invented, good early diagnosis but lot’s of overdiagnosis since some
benign don’t become malignant]]
Etiology: Study of the CAUSE of cancer
Genetic
Clonal Expansion
•A normal cell undergoes a mutation in a gene that’s important for cell survival/growth/maintenance
•Mutated cell has a competitive and proliferative survival advantage over other cells
•Will undergo rapid cell proliferation into a mutant clone colony (evolution survival advantage)
•A cell in this colony may get another mutation, which can give it an advantage again
•Increases the probability of multiple mutations= increase genetic instability=ultimately cancer
Different Onset Examples
•Early childhood cancers- Retinoblastoma (RB gene)
•Adult onset cancers- Multiple polyps of colon (FAP gene)
Environment
Carcinogens: cancer causing AGENTS
•Chemicals
•Radiation
•Viruses
Carcinogen exposure
•Workplace
•Lifestyle choices
Etiological studies: ways to test if the carcinogen will cause cancer
•Testing carcinogens in animal models (mice, rats, monkeys)
•Epidemiological studies in humans (following people and monitoring their exposure, looking for
link/association)
•Ex. of epidemiological studies
oSmokeless tabacco – oral cavity, esophagus, pancreas cancer
oChimney sweep boys- skin cancer (coal exposure)
oSmoking and alcohol intake – lung and others
oMiners- lung cancer (copper, uranium exposure)
oConstruction workers- mesothelium (asbestos exposure)
•Ames Test: biological assay assessing mutagenic potential of chemical compounds (screen for
carcinogens)
oChemical + Rat/human liver extract/bacteria/yeast
oScreens for enzymatic activation of carcinogen and measures:
mutation frequency
DNA adducts
Chromosome damage (breakage)
o+ve result means chemical is mutagenic and can be carcinogenic but we need further
testing
LECTURE 2: NEOPLASIA
Mechanism Of Carcinogenesis (MEMORIZE THE SCHEMATIC)- aka cancer development
•Multi-step and multi-factorial process
•Spans over a long period of time
•Some steps are reversible (through DNA level or lifestyle choices)
•Opportunity to PREVENT and/or DELAY the cancer development
•Cancer is cell oriented and organ oriented
•Initiation, Promotion, Progression
Types of Carcinogens
•Genotoxic Carcinogens- causing direct DNA damage (directly alters genetic material)
oEx. Radiation, Aromatic amines (chemical)
•Non-Genotoxic- produce cancer based on 2ndary mechanism not related to direct DNA damage
oEx. DDT, Arsenic, Phenobarbitol
•(Co-carcinogens/promotors)- not carcinogenic on their own. Promote the effect of the carcinogen
oEx. Saccharine, Phorbol esters
o
CHEMICAL CARCINOGENS
-Active carcinogens
-Chemotherapeutic agents
•Chemo treatment of pediatric cancers- can kill cancer cells but also affect other cells, which will
stay dormant, but exposure to a new carcinogen/agent= risk of secondary cancers in later life
Produce many types of cancers-aka diverse:
Nitrosamines (nitrite + amines)
•Source: tobacco, diet, produced internally in stomach
Polycyclic Aromatic Hydrocarbons (PAHs)
•Source: cooking, cigarette smoke, car exhaust
Produce specific types of cancers:
Aromatic Amines
•Cancer types: liver, bladder
Aflatoxin B1
•Cancer type: liver
•Naturally occurring chemicals
•Produced in fungi, dermal exposure causes cancer risk
•One of the most carcinogenic substances known
Cancer Incidence- Two peaks
•1-5 years –pediatric (exposure in womb or postnatal)