human bio iii oncology i

11/3/2000 Human Biology III Oncology I

Human Biology IIIOncology I

Ken Bauer

[email protected]


Objectives

• Following the lecture the student should be able to:

1. Differentiate between the characteristics of benign and malignant tumors.

2. List the 5 broad categories of cancer etiology

3. Describe the effect cigarette smoking has had on cancer incidence and death rates from 1930 to present.


Objectives

4. Explain the roles of oncogenes proro-oncogenes, and tumor suppressor genes in the malignant transformation .

5. List the 3 most common tumor types in men and women by gender


Cancer Terminology

• Cancer is a disorder that occurs at a cellular level

• Cancer occurs when genetic alterations result in the unregulated proliferation of cells


Cancer Terminology

• Cancer - A group of diseases

• Anaplasia - Lack of differentiation

• Dysplasia - Abnormal size, shape

• Hyperplasia - Increase in number of cells


Benign Tumor

• Characteristics typical of tissue of origin

• Slow rate of growth

• Slowly progressive; Not fatal if untreated

• Encapsulated growth

• No tissue destruction

• Rare recurrence

• Poor prognosis only if unable to remove


Malignant Tumor

• Characteristics atypical of tissue of origin

• Slow or rapid rate of growth

• Usually progressive; Fatal if untreated

• Growth by infiltration or metastasis

• Tissue destruction is common

• Recurrence is common

• Fatal prognosis if uncontrolled


2000 Estimated Cancer Statistics

• 1,220,100 : Estimated number of new cancer cases.– Over 100 types of cancer most common ->– Women: Breast, Lung, Colon– Men: Prostate, Lung , Colon

• 552,200 : Estimated number of cancer deaths.– Lung cancer is leading cause of cancer deaths.

» Source: American Cancer Society, www.cancer.org


Cancer Statistics

• From 1930 until 1989 there was a steady overall rise in the age-adjusted death rate due to cancer

• Since 1989 the mortality trend is downward

• Major cause of increase over 60 years was increasing tobacco use and lung cancer

• The current trend down is due at least in part to decreased tobacco use


Leading Sites of New Cancer Cases and Deaths—2000 Estimates


Age-Adjusted Cancer Death Rates,* Females by Site, US, 1930-1996


Age-Adjusted Cancer Death Rates,* Males by Site, US, 1930-1996


Etiology of Cancer

• The most common way of treating cancer today is to treat after detection

• Ideal strategy is prevention:– eliminate/reduce controllable risk factors

• smoking, diet, alcohol

– chemoprevention• tamoxifen {breast}• finasteride {prostate} -investigational• retinoids {head and neck} -investigational


Etiology of Cancer

• Environmental factors

• Viruses

• Lifestyle factors

• Medical - Drugs and Hormones

• Hereditary


Environmental Factors• Industrial/Occupational

– Coal miners, factory workers, asbestos

• Ultraviolet Light risk of skin cancers

• Ionizing Radiation (Lifestyle Factor?)

– X-rays, nuclear weapons or accidents• evidence from Japan & Chernobyl

risk of breast cancer and leukemias

• Thyroid irradiation (for hyperthyroid) risk thyroid cancer


Viruses

• Epstein-Barr virus - Hodgkin’s lymphoma

• Human Immuno-deficiency virus - NHL and Kaposi’s sarcoma

• Human Papilloma virus - Cervical cancer

• Hepatitis A, B - Hepatocellular cancer

• HTLV-1 - T-cell leukemia


Lifestyle Factors

• Tobacco - Cigarette Smoking – lung, oropharygeal, and bladder cancers– “If cigarettes did not exist lung cancer would be

an rarity”

• Radon– lung cancer

• Electromagnetic fields– cell phones and high tension power lines– causal relationship ?


Lifestyle Factors

• Alcohol– associated with several cancers including

esophogeal, liver, oropharynx, breast and larynx

– usually associated with another carcinogen

• Diet– implicated in colorectal cancer– Decrease Fat, Increase Fruits and Vegetables


Drugs and Hormones

• Alkylating Agents

– Cyclophosphamide - bladder

– melphalan - leukemia

• Antimetabolites

– Azathioprine - NHL, skin

• Corticosteroids

– Prednisone - NHL


Drugs and Hormones

• Estrogens

– Diethylstilbestrol - vaginal Ca in offspring

• Combined Modalities

– Chemo + Radiation - leukemia

• Others – Phenacetin - renal – Phenytoin - liver (rats)– Chloramphenicol - leukemia


Hereditary/Genetic• Cancer as Primary Manifestation

– Retinoblastoma, neuroblastoma, pheochromocytoma

• Inherited Condition– Familial polyposis, Fanconi’s anemia,

xeroderma pigmentosum

• Inherited Disease of Immune System– Wiskott-Aldrich Syndrome

• Chromosomal Aberrations– Down’s Syndrome, Fanconi’s anemia


Hereditary/Genetic

• Breast cancer– If first degree relative has(d) breast cancer

greatly increases the risk – BRCA1 mutation

• Retinoblastoma– Rb


Genetic Regulation

• Oncogenes/Proto-Oncogenes– normal exons which when mutated promote

oncogenesis• wt = proto-oncogene (no tumor promoting effect)

• mutant = oncogene

• Tumor Suppressor Genes– Genes which regulate cell proliferation and

prevent cell from dividing ‘out of control’• wt = ‘prevent’ cell from becoming a tumor

• mutant = unable to prevent tumor-genesis


Proto-Oncogenes and Malignant Transformation

• N-myc {transcription factor}– Neuroblastoma

• Erb-B(her2neu) {cell surface receptor}– Breast cancer

• RAS {intracellular messenger}– Acute Myeloid Leukemia

• BCL {transcription factor/apoptosis}– Chronic Myeloid Leukemia


Tumor Supressor Genes

• Rb (cell cycle)– retinoblastoma, osteosarcoma

• p53 (growth arrest/apoptosis)– sarcomas, breast, and brain tumors

• BRCA1 and BRCA2 (DNA repair)– breast and ovarian tumors

• E-Cadherin (cell adhesion regulator)– breast, colon, skin, and lung


Cell Cycle Entry to Death: Regulation

Growth Factor

Receptor Activation

Intracellular Kinase Cascade

Early Nuclear Proteins (myc, fos, jun etc.)

Cell Cycle Activators (cyclins)

Regulators (Rb)

Genome Checkers (p53)

Apoptosis: Cell Cycle Balancers (bcl-2 family)


Malignant Transformation

• Genetic alterations transform normal cells into malignant cells

• Two (multiple) hit hypothesis– predisposition + external factor– multiple external factors


Questions?

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