Chances of cancer increase or decrease with age?-increase

4 types of cancer derevied as hereditary?-retinoblastoma-adenomatous polypsosis coli-xeroderma pigmentosum-familial dispositions

Heredity cancers with autosomal dominate pattern?-retonoblastoma-adenomatous polyposis coli-xeroderma pigmentosum

Hereditive cancer, which homozygotes may develop?-xeroderma pigmentosum

Sun induced skin cancer (name for)?-xeroderma pigmentosum

Persistent regenerative cell replications- acquired preneoplastic or post neoplastic?-acquired preneoplastic disorder

Hyperplastic and dysplastic proliferations- acquired pre or post neoplastic?-acquired preneoplastic disorder

HPV associated cancer?-cervical cancer

Cancers (3) derived from environmental influences?-stomach cancer-hepatocellular cancer-cervical cancer

Carcinogenesis is genetic damage or non- lethal mutation. What is the cause of this?-virus-radiation-chemical-inherited-cumulative replication errors

What does cancer mass develop from?-single progenitor (monoclonal expansion)

What results from damaged genes?-promotion of cancer

What is tumor progression?-excessive growth local invasion metastases

How are genes damaged, which promote cancer?1. growth promoting protooncogens2. Cancer suppressor genes (antioncogens)3. Apoptosis regulating genes4. Genes encoding DNA repair proteins

Normal cell DNA damage (acquired environmental factors) mutations in genome of somatic cells mutations in genome of somatic cells (genetic factors- inherited mutations in genes affecting cell growth or DNA repair) 1. Activating of growth promoting oncongenes- alterations of genes that regulate apoptosis- inactivation of cancer suppressor genes expression of altered gene products and loss of regulatory gene products (clonal expansion additional mutations (progression) heterogeneity) malignant neoplasm

In a genome, what to proto oncongenes result in?-regulation of cell proliferation or apoptosis

In a genome, what do non oncogenic genes result in?-do not regulate cell proliferation

What encodes oncoproteins?-oncogenes

What do oncoproteins resemble?-normal products of proto- oncogenes

Oncoproteins make up consists of?-growth factors-growth factor receptors-signal transducing proteins critical for mitogenesis

What is a result of mutations of genes encoding growth factors?-renders them oncogenic by causing their over expression

What is generated in mutant oncogenic receptor proteins of growth factor receptors?-continued mitotic signal

What is an example of a mutation of oncogenic growth factor receptor proteins generating a continued mitotic signal?

-EGF gene c-erb B1

What is an example of a signal transducing protein?

-c- ras gene

Where are signal transducing proteins located?-inner leaflet of membrane

What do signal transducing proteins encode?-GTP

What does encoding of GTP binding protein of a signal transducing protein activate?-other cellular protein kinases

What does the encoding of GTP binding of signal transucing proteins, activating other cellular protein kinases result in?

-mitosis

What is GTPase activity enhanced by?-GAP (GTPase activating protein)

When are ras family of proteins inactive?-when intrinsic GTPase activity cleaves GTP-> GDP

Mutations in the gene sequence that reduces or abolishes GTPase activity activates what?-RAS protein

What does activating the RAS protein result in?-unregulated mitosis

What may be activated when mutations of GAP gene, which reduce GTPase activity?-RAS

What is an example of a point mutation?-ras protein

What activates oncogenes?-point mutations-chromosomal translocations-gene amplification.

How do point mutations cause intrinsic GTPase activity to decline?-constitutively activates protein

What do chromosolam translocations result in?-over expression

In gene amplification, what does over expression result from?-increased copies of gene in genome

What is an example of gene amplification?-N-myc protein in neuroblastoma

What do cancer suppressor genes inhibit?-cell proliferation

What are proteins that normally bind to external receptors and inhibit growth?-growth inhibitory factors

What type of cancer suppressor gene molecule regulates cell proliferation?-molecules that regulate cell adhesion

What is an example of a molecule that regulate cell adhesion?-E- cadherin

What type of cancer suppressor gene molecules attenuate growth promoting signals?-molecules that regulate signal transduction

What is an example of a molecule that regulate signal transduction?-NF-1 gene

What does a molecule that regulates signal transduction encode (NF-1fene?-encodes GAP protein

What is an example of a molecule that regulates nuclear transcription and cell cycle?-retinoblastoma gene

What do molecules that regulate nuclear transcription and cell cycle encode?-encodes transcription factor binding protein

What does an unphosphorylated state of transcription factor binding protein do?-actively binds transcription factors and prevents cell division

What does a phosphorylated state of transcription factor binding protein do?-releases transcription factors

What does HPV bind to (transcription)?-HPV binds to hypophosphorylated protein, thereby displacing transctiption

factors

What does this result in?-cancer of cervix

What gene example inhibits apoptosis?-bcl-2

What gene opposes bcl- 2 gene?-bax gene

What do relative levels of expression regulate?-cell death

What is repair DNA damage caused by?-extrinsic agents-errors in replications

Can a single oncogene transform cells?-no

What does multistep carcinogenesis require?-multiple genetic alterations

Can a tumor outgrow blood supply?-no

What are angiogeneic factors in tumor angiogenesis produced by?-tumor

What is tumor progression caused by?-subpopulation of cells

What type of cells is most chemotherapy only effective on-cycling cells

What are the most susceptible tumors for chemo?-tumors with higher growth fraction

What is an example of a cancer, which chemotherapy is most effective on?-high- grade lymphoma

How is the extracellular matrix invaded?-detachment of tumor cells attachment of cells to ECM degradation of ECM migration of tumor cells

What are in circulation tumor cells subject to?-immunodestruction

How do tumor cells aggregate?-attaching to each other-attachment to platelets

-attachment to leykocytes

Do tumor cells migrate individually or with a friend?-individually

What is the mtastatic site preticted by-primary site

What is organ tropism known as?-homing

Why is the metastatic site predicted by primary site?-due to drainage

Are chemicals direct acting, cancer causing?-yes

What are procarcinogens?-a chemical substance that becomes a carcinogen only after it is altered by metabolic processes.

What are most chemicals that are carcinogenic? What are they?-electrophiles

-A chemical compound or group that is attracted to electrons and tends to accept electrons.

What are the two DNA ocogenic viruses?-HPV-HBV

How many serotypes does HPV have?-over 50

What is the cause of HPV?-benign squamous papillomas (warts) and/or cervical CA

What proteins is HPV due to?-E7-E6

What is the function of E7?-E7 interferes with Rb binding of transcription factors

What is the function of E6?-E6 inactivates p53

What does EBV cause?-Can cause no symptoms – mono – burkitts lymphoma (b-cell proliferation) – nasopharengeal CA

What problems can both malignant and benign tumors create (symptoms)?-Impingement on adjacent structures - Hemorrhage - Infections secondary to necrosis - Hormonal activity

What is cancer cachexia?-Cachexia (wasting) syndrome common in PTs with CA

What do cancer neoplastic syndromes exclud?-cachexia

What percentage of pts have pareneoplastic syndromes?-10-15%

What are the most common paraneoplastic syndromes and what are they?-hypercalcemia

-elaboration of PTH

-cushings syndrome-ectopic production of ACTH

-hypercoaguability

What is grading and staging necessary for?-to predict outcome

What does grading establish?-estimate of aggressiveness

What is grading based upon?-cytologic features-mitotic activity

What is staging based on?-based on size of primary, extent of lymph node involvement and presence or

absence of mets

What is the TNM system?

-TO-4-size of primary

-NO-3-involvement of nodes

-MO1-presence or absence of mets

What are the tumor markers?-PSA-CEA (carcinoembryotic antigen)-Alpha- fetoprotein

When is PSA elevated?-prostatic CA-benign conditions

How often are CEA levels elevated in colorectal CA?-60% - 90%

How often are CEA levels elevated in pancreatic cancer?-50% - 80%

When is CEA elevated in malignant conditions??-colorectal cancer-pancreatic cancer

When is CEA elevated in benign conditions?-ETHOH cirrhosis-hepatitis-IBD

What does CEA lack, which is required for screening test?-lacks sensitivity and specificity

What is screening tests with CEA useful for?-detection of CA recurrences

What does alpha- fetoprotein cancer arise from?-liver and yolk sac remnants in gonads

What are benign conditions of alpha- fetoprotein?-chirrhosis-hepatitis-pregnancy with fetal distress

What does alpha- fetoprotein lack in screening tests?-sensitivity and specificity

When is there a presumptive diagnosis for alpha- fetoprotein?-levels of alpha- fetoprotein are too high

Terminology:

Benign v Malignant

Metastasis-benign- do not do-malignant- requently present

Differentiation-benign-

-well differentiated (look like normal counterparts) (myolyoma)-malignant-

-lack differentiation with anaplasia (atypical structure)

Rate of growth (mitotic index)-benign

- progressive and slow- mitotic figures are rate and normal-malignant

-erratic and may be slow to rapid- mitotic figures may be numerous and normal

Local invation-benign

- usually cohesive and expansile- well demarcated masses that do not invade or infiltrate the surrounding normal tissues

-malignant- locally invasive- infiltrating the surrounding normal tissues- sometimes may be seen coherent

Oncogenes

EGF receptor family (growth factor receptors)-erb

GTP binding-ras

tyrosine kinase-abl

RBG gene encodes for?-transcription factor binding protein

RBG gene classification?-cancer suppressor (inhibits cell proliferation)

Retino blastoma is a defect in which protein?-transcription factor protein

bax and bcl-2 determines?-if a cell lives or dies

bax? -optosis

bcl-2?-inhibits apoptosis

b53 limits (cancer suppressor gene)?-bax

Rh gene?-encodes for transcription factor binding gene-cancer suppressor- inhibits cell proliferation

pathogenesis of myostenia gravis?-abs directed against cholinergic receptors

myostenia gravis presents with?-flaciddity-ptosis of eyes-worse in afternoon

What cancer does myostenia gravis usually present with?-thymonoma (cancer of thymus)

Which of the following mutations would result in oncogenesis?-upregulation of bax gene- no-down regulation of growth factor expression- no-upregulation of bcl-2 gene –yes

ras gene is mutated such that it causes cells to be out of control. Which of the following mutations result in this oncogenic process?

-Pt. mutation which decreases gta-pt mutation which increases ATP

Which of the following genes phosphorylates tyrosine residues?-assist-erb-bc-2-abl- YES

Which of the following mechanisms of activation is responsible for the cancer, chronic myologenous leukemia?

-pt mutation-gene amplification-chromosomal translocation- YES

nf-1 gene encodes for which of the following?-ras proteins-epidermal growth factor -gap (GTPase activating protein)- YES

A clinically advanced tumor is sampled. Which of the following features would tumor cells have in common?

-antigenic-increased requirements for growth factors-increased metastatic potential- YES