Patho Unit 1

well-differentiated cells that resemble normal counterpart in structure & function but lost ability to control proliferation

• less differentiated
• lost ability to control cell proliferation & differention

• transformed or neoplastic cells
• determines behavior of cells

connective tissue, ECM & blood vessels around neoplasm

-oma

-sarcoma

• characteristic of cells- benign resemble origin cells; malignant less differentiated
• rate of growth- benign slow
• local invasion- benign fibrous capsule

localized preinvasive lesion

poorly differentiated cells

undifferentiated cells that vary in size and shape

malignant cells w/ abnormal # chromosomes

• growth factor independence- make own growth factor
• lack of cell density-dependent inhibition- cells should stop dividing when close together
• impaired cohesiveness & adhesion
• loss of anchorage dependence- grow w/out attach to ECM
• faulty cell-to-cell communication-
• indefinite cell life span

• immunologically distinct from original tissue
• produce fetal antigens

abnormal production of substances that affect body function

ratio of dividing cells to resting

initial growth rate of tumor exponential then tends to decrease with time due to limitations in blood supply & nutrients

initial lymph node to which primary tumor drains

chemoattractant cytokines regulate leukocytes play role in invasion & metastisis

• silence genes
• may be factor in pathogenesis of cancer

normal genes that become cancer causing if mutated

when less active create environment where cancer promoted

• point mutation- single nucleotide base change
• RAS oncogene: signal-relaying proteins transmit growth signals to cell nucleus
• chromosomal translocations- gene sites change from one chromosome to another displacing other genes (philadelphia +)
• multiple copies of certain genes overexpress higher # proteins (HER human epidermal growth factor in breast cancer)

• recessive- cells behave normally until both genes are effected
• suppressor gene p53- prevents propogation of defective cells stopping G1 for repair; loss of activity promotes angiogenesis & removes antiangiogenesis switch
• retinoblastoma gene (suppressor gene)- both alleles inactivated

• one genetic change is inheredited (1st hit)
• second mutation occurs to express the cancer (2nd hit)

• defect in DNA repair mechanism- chemical, free radical
• disorders in growth factor signaling pathways- couple growth factor receptors to nuclear target
• evasion of apoptosis
• development of sustained angiogenesis
• evasion of metastasis

• changes in gene expression w/out change in DNA
• may silence genes like tumor suppressor
• may be hit in 2 hit hypothesis

proteins involved in signalingpathways; factors that control growth factors

• can be tumor suppressor if critical target is oncogene
• can be oncogene if target is tumor suppressor gene

• altered cell survival signaling
• down-regulation of death receptors
• stabilization of mitochrondia
• inactivation of apoptotic proteins

• key regulator of invasive growth
• expressed in both stem & cancer cells

• exposure of cells to appropriate doses og carcinogenic agent that makes them susceptable to malignancy
• chemical, physical, biologic
• cells most vulnerable are actively synthesizing DNA

• induction of unregulated accelerated growth in already initiated cells by various chemicals and growth factors
• reversible of promotor substance removed

can initiate & promote neoplasm

process where tumor cells get malignant phenotype changes that promote invasiveness, metastatic competence, autonomous growth tendicies, increased karyotypic instability

• point mutation in single allele to tumor-suppressor gene
• one normal & one mutant gene
• for cancer to develop, mutation must occur in normal gene

• action unknown
• may drive cell division in malignant phenotype

• increased sex hormones (androgens & estrogens)
• insulin resistance & increased production of pancreatic insulin
• insulin-like growth factor stimulates cell proliferation & inhibit apoptosis
• inflammation w/ production of cytokines

molecular configurations that can be recognized by immune T cells or antibodies

• important host responses for controlling growth of antigenic cells & activation of immune system
• T-cell immunity of cancer cells reflects action of CD4 helper T cells & CD8 cytotoxic T cells

• direct-reacting; do not need activation to become carcinogenic
• indirect-reacting (procarcinogens or initiators); active only after metabolic conversion

• enhance carcinogenicity of other agents
• change expression of genetic material
• increase DNA synthesis
• alter intercellular communication

causes chromosomal breakage, translocations, point mutations

• low energy rays; sallow penetration
• effects additive
• long delay from exposure & cancer

• HPV-cervical
• EBV-burkitts, NP cancer, lymphoma
• hepBV- liver
• HHV-8 (herpes)
• HTLV-1 (human T-cell leukemia virus)

• persistent inflammatory response in conjunction w/ production of cytokines & catabolic factors from tumor
• people w/ cachexia poorer outcomes
• TNF & IL 1&2 produce wasting syndrome

• peripheral- inability of neuromuscular apparatus to do task in response to central stimulation;lack of ATP
• build up of metabolic products (lactic acid)
• central- difficulty initiating voluntary activities; poor regulation of 5-HT (serotonin)

manifestations in sites not affected in cancer

• peptic hormones (ADH)- SIADH
• adrenocorticotropic (ACTH)- Cushings
• parathyroid hormone (PTH)- hypercalcemia

• procoagulation factors that cause thromboembolism
• mucin-producing adenocarcinoma release thromboplastin

• small lung cell cancer
• muscle weakness in limbs
• immune mediated

• expressed from tumor cells
• screening, establishing prognosis, monitoring tx, detect recurrent disease

• AFP-liver
• CEA (carcinoembryonic antigen)-colorectal, pancreas, lung

• hCG- gestational trophoblastic, germ cell
• calcitonin- thyroid
• catecholamines- pheochromocytoma

• monoclonal immunoglobin- multiple myeloma
• PSA- prostate

• CA-125: ovarian
• CA-19-9: pancreas, colon

• cancer cells lack cohesive intercellular junctions
• cnacer cells exfoliate & mix w/ secretions

• use monoclonal antibodies to ID cell products or surface markers
• ID site of origin

gene chips that can simultaneously perform miniature assays to detect and quantify expression of large numbers of genes at the same time

• microscopic exam of tissue to determine level of differentiation & # of mitoses
• the close the cells resemble the normal cells the lower the grade

• size of primary tumor
• extent of local growth
• lymph node involvement
• presence of distant metastisis

• T 1-4 increasing size of primary tumor
• N 0-3 advancing node involvement
• M0-1 ansence or presence of distant mets

• indirect ionization- cellular damage when x-rays absorbed into tissue & give up fast moving electrons which are absorbed & produce free radicals
• immediately kill cells, delay cell cycle progression, nuclear damage
• rapidly dividing & poorly differentated

number of survivingcells proportionate to drug dose & # cells at risk porporitonate to destructive action of drug

exert action during specific phase on cell cycle

deprive cancer cell of hormonal signals that stimulate them to survive

pharmocologic suppression of hormones at level of hypothalmus

• inhibit tumor protein synthesis
• prolong cell cycle
• increase % cells in G0
• stimulate NK & T-cells
• types alpha, beta, gamma

cytokines that bind to reseptor sites on surface membrane of target cells