Lect 16 Oncology

Neoplasia

tumor, new growth

Oncology

study of tumors

Malignant

cancer; lesions can invade and destroy adjacent structures and spread to distant sites to cause death

Benign

localized, microscopic, relatively innocent, localized lumps

Basic component of all tumors

parenchyma and stroma

Parenchyma (blue cells)

transformed or neoplastic cells; largely determines biologic behavior

Stroma

connective tissue, blood vessels and host-derived inflammatory cells; crucial to neoplastic growth

Why is stroma crucial to neoplastic growth

carries blood supply and provides support

Naming Benign tumors

cell type-oma; also epithelial tumors named based on macro- or microscopic patterns

Well-differentiated cancer cells

look more like normal cells of their tissue of origin and tend to grow and spread more slowly than poorly differentiated or undifferentiated cancer cells

Degree of differentiation: Benign

often resemble tissue of origin

Degree of differentiation: Malignant

often poorly or completely undifferentiated

Rate of growth: Benign

slow growing

Rate of growth: Malignant

generally grow faster

Local invasiveness: Benign

well-circumscribed, have a capsule

Local invasiveness: Malignant

poorly circumscribed, invade surrounding tissues

Distant spread: benign

localized to site of origin

distant spread: malignant

locally invasive and metastasize distantly

Autosomal dominant cancerous diseases

Linked to inheritance of germ-line mutation of cancer suppressor gene ("loss of function" mutation)

Autosomal recessive

Typically assoc. with inherited defects in DNA repair

Carcinogenesis

Mutation in no single gene is sufficient to cause cancer

7 Fundamental Changes in Cell Physiology that Dictate Malignant Phenotype

1. Self-sufficiency in growth signals

2. Insensitivity to growth-inhibitory signals

3. Evasion of apoptosis

4. Limitless replicative potential

5. Development of sustained angiogenesis

6. Ability to invade and metastasize

7. Genomic instability resulting from defects in DNA

repair

1. Self-sufficiency in growth signals

Mutations in genes encoding signaling molecules; Overproduction or unregulated activity of transcription factors

2. Insensitivity to growth-inhibitory signals

Tumor suppressor genes (TSGs)

Tumor suppressor genes (TSGs)

Encode proteins that inhibit cellular proliferation by regulating cell cycle

3. Evasion of apoptosis

Apoptosis can be initiated through the Death Receptor (extrinsic) or Mitochondrial (intrinsic) pathways; balance between pro-apoptotic and anti-apoptotic molecules

4. Limitless replicative potential

-Telomere maintenance is usually accomplished by activating the gene encoding telomerase

-Cancer cells maintain telomere length above a critical threshold

-Thus, they are able to divide indefinitely

Hayflick limit

the maximum number of times a cell can divide before dying

5. Development of sustained angiogenesis

Vascularization of tumor stroma is essential for growth

6. Ability to invade and metastasize

Ability to invade occurs in 4 steps: Loosening of cell-cell contacts, Degradation of ECM, Attachment to novel ECM components, Migration of tumor cells

7. Genomic instability resulting from defects in DNA repair

Individuals with inherited mutations of genes involved in DNA repair systems have higher risk of developing cancer

Carcinogens

Chemicals, Radiation, RNA Viruses, DNA Viruses

Chemical carcinogens

Highly reactive electrophile groups, directly damaging DNA

Chemical carcinogens: Direct-acting agents

do not require metabolic conversion

Chemical carcinogens: indirect-acting agents

not active until converted, require

endogenous enzymes

radiation carcinogens

onizing radiation (gamma, X-, and higher part of the UV spectrum) causes chromosome breakage,

translocations, point mutations

Tumor Grading

Determined by cytologic appearance; Based on idea that behavior and differentiation

are related

Tumor Staging

Determined surgically or on imaging, TNM system; Greater clinical value than "grading"

TNM system

Size (T), Local and regional lymph node spread (N), Distant metastases (M)