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158 Cards in this Set
- Front
- Back
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Neoplasia
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A process of uncontrolled growth (accumulation) of cells due to:
1. Proliferation and/or 2. Evasion of apoptosis |
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Neoplasm
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A mass of cells, which grow without control
Tumor: a neoplasm, which can be recognized as a distinct lump or lesion |
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Benign tumors
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Slow-growing, innocuous tumors, that usually are of little consequence to the host
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Malignant tumors
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More rapid growth rate, invade and destroy adjacent tissues, CAN seed and grow at distant sites (metastasize), and are fatal (if left untreated)
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Intermediate tumors
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Locally invasive (therefore not benign), but do not have tendency to metastasize
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Carcinoma in situ
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Pre-invasive proliferation of the epithelium, that has cytological features of malignancy
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Carcinoma
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A malignant tumor of epithelial origin
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Name three examples of malignant epithelial tumors
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1. Adenocarcinoma originates from glandular or ductal (small ducts) epithelium
2. Squamous cell carcinoma originates from stratified squamous or cuboidal (large duct) epithelium 3. Transitional cell (urothelial) carcinoma originates from transitional epithelium (urothelium) |
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Name two examples of benign epithelial tumors
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1. Adenoma: a benign tumor originating from glandular or ductal (small ducts) epithelium
- Polyp: any mass of tissue that bulges outward of a mucosal surface -- either neoplastic or hyperplastic 2. Papilloma: a benign tumor of either stratified squamous, or transitional, or cuboidal (large ducts) epithelium with finger-like projections seen macro- and/or microscopically |
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Two types of tumors of mesenchymal origin. Name them.
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Benign tumors: the name of tissue of origin + the suffix "-oma"
- Fibroma, rhabdo/leiomyoma hemangioma, lipoma, etc. Malignant tumors: the name of tissue of origin + the suffix "-sarcoma" - Fibrosarcoma, rhabdo/leiomyosarcoma, hemangiosarcoma, liposarcoma, etc. "Sarcoma: a malignant tumor of mesenchymal origin" |
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Differentiate between blastoma and teratoma.
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The suffix ”-blastoma" designates tumors of embryonic origin seen in infancy and early childhood
- Retino-, nephro-, and neuroblastoma Teratoma: a tumor made up of cells of more than one germ layer (usually all three) * Originates from totipotent cells * Usual location: gonads and adjacent tissues, e.g., sacrococcygeal area * Cells differentiate along various germ lines * Seen in children and adults * Can be benign or malignant (teratoblastoma) |
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Differentiate between hamartoma and choristoma.
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Hamartoma: a non-neoplastic overgrowth of tissues, which are regularly found within an affected organ
- Hemagioma: irregular accumulation of mature blood vessels - Nodule of mature cartilage within the bronchial wall Choristoma: a small area of normal mature tissue misplaced within another organ - Nodules of splenic tissue in the peritoneal cavity - Pancreatic tissue in the stomach wall |
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Cancer incidence rates in males and females.
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MALES
33% prostate 14% lungs and bronchi 11% colon and rectum FEMALES 32% breast 12% lungs and bronchi 11% colon and rectum NOTE: lungs & bronchi and colon and rectum are the same for males and females! |
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Cancer mortality rates in males and females.
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MALES
31% lungs and bronchi 10% prostate 10% colon and rectum FEMALES 25% lung and bronchi 15% breast 11% colon and rectum NOTE: lungs & bronchi cancer kills more people than the other two combined! |
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TRUE or FALSE
The frequency of cancer increases with age and if so what is the most common type? |
True
Carcinoma |
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The peak of cancer mortality is between which age range
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55 - 75 mostly due to accumulation of somatic mutations
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LIST TUMORS FOR THE FOLLOWING AGE GROUPS
* Infancy and early childhood * Young adults * Late adults |
* Infancy and early childhood:
neuroblastoma, retinoblastoma, nephroblastoma (wilms tumor), acute leukemia, rhabdomyosarcoma * Young adults leukemia lymphoma CNS and soft tissue tumors * Late adults carcinoma |
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Characteristics of neoplastic growth
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* Uncontrolled growth
* Increased growth rate * Lack of differentiation * Tissue and cellular atypia * Monoclonality * Progression |
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Factors of neoplastic uncontrolled growth
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* Evasion of host control over the cell/tissue growth
- E.g., activation of growth promoting factors or inhibition of growth-suppressing factors * Limitless replicative potential (immortalization) * Loss of contact inhibition |
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Uncontrolled growth of neoplastic cells is more expressed in ________________
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malignant tumors
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Neoplasms grow faster than normal tissues because
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* Retention of cells in the cell cycle (cell proliferation)
* Inhibition of apoptosis --> accumulation of neoplastic cells |
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Retention of cell in cell cycles means?
What is an indicator of proliferation? |
Retention = neoplastic cells do not leave cell cycle and do not differentiate
Indicator: mitotic activity = number of mitotic figures - # of meta and anaphases seen in 10 high power fields (hpf) |
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TRUE or FALSE
Cells, which are within the cell cycle, are preferably susceptible for chemo- and radiotherapy |
TRUE
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Cancers with rapid growth vs. Cancers with slow growth
- What is their proliferative activity? - What is their susceptibility to therapy? |
Cancers with rapid growth: high activity -> high susceptibility
Cancers with slow growth: low activity -> low susceptibility |
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What is differentiation?
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Cells/tissues resemble their normal progenitors, both morphologically and functionally
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Are neoplastic cells, within the cell cycle, able to differentiate?
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No
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Difference between malignant and benign tumors with respect to differentiation.
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Malignant tumors: many cells are within the cell cycle, therefore, they (and tissues which they form) do not resemble to the cells/tissues of origin of neoplastic growth
Benign tumors: proliferating activity is very low, therefore their cells (and tissues) are always differentiated |
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Benign tumors are always __________________
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differentiated
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Malignant tumors vary in degree of __________________
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differentiation
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Name the four levels of differentiation among malignant tumors.
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Well differentiated
Moderately differentiated Poorly differentiated Anaplastic == totally undifferentiated |
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Why are anaplastic, malignant, tumors especially dangerous?
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* Complete lack of differentiation (structural and functional)
* Hallmark of "high malignancy" |
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What are the three characteristics of TISSUE ATYPIA?
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1. Abnormal (size & shape) formations
2. Changes in parenchymal/stroma ratio 3. Loss of orientation (loss of polarity) |
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What is significant about tissue atypia?
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It is seen in BOTH BENIGN and MALIGNANT neoplasms
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What are the characteristics of cellular atypia?
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1. Cellular pleomorphism
2. Nuclear changes - nuclear pleomorphism - dense and irregular nuclear outline - nuclear hyperchromicity - multinucleation 3. Increased nucleo/cytoplasmic ratio 4. Nucleolar pleomorphism |
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What is the significance of cellular atypia?
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It is seen ONLY IN MALIGNANT neoplasms!
Whereas tissue atypia is seen in both malignant and benign tumors. |
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monoclonality vs. polyclonality
- definition - markers |
Monoclonality: Within a neoplasm, all tumor cells originate from a SINGLE PRECURSOR CELL
Markers: G6PD, human androgen receptor gene (HUMARA), kappa / lambda chain specificity (Ig) Polyclonality: almost always non-neoplastic (hyperplasia, dysplasia) |
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Tumor progression is characterized by:
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* Accelerated growth rate
* Increased invasiveness * Higher ability to form distant metastases * Increased resistance to hypoxia * Increased resistance to antineoplactic chemo- and radiotherapy |
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Define parenchyma, stroma.
Why is the parenchyma/stroma ratio significant? |
The parenchyma of an organ consists of that tissue which conducts the specific function of the organ and which usually comprises the bulk of the organ.
Stroma is everything else -- connective tissue, blood vessels, nerves, ducts. ----- An increase in the parenchyma / stroma ratio points to TISSUE ATYPIA |
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What is expansive growth?
What is it a feature of? |
tumor expands and compresses surrounding tissue with formation of a fibrous rim (capsule)
a feature of BENIGN TUMORS |
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What is invasive growth?
What is it a feature of? |
growth into surrounding tissues
a feature of MALIGNANT TUMORS |
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Define carcinoma in terms of growth.
What is 'carcinoma in situ'? |
Carcinoma = classical invasive growth with crab-like sprouts; STARTS FROM PENETRATION OF BASEMENT MEMBRANE
Carcinoma in situ = neoplasm WITHOUT BM PENETRATION |
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Define exophytic growth.
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A malignant neoplasm projects out from an epithelial surface while at the same time grows downward with penetration of underlying BM
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List and define the two types of malignant tumor spread.
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1. Direct spread: local invasive growth in to adjacent tissue
2. Distant spread |
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What is important about the direct spread of malignant tumors.
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Direct spread = direct invasion of tissue is an IMPORTANT SIGN OF MALIGNANCY
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Where do "locally malignant tumors spread" into?
NOTE: They are different from direct and distant spread |
Adjacent tissue only
e.g. basal cell carcinoma of the skin |
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How do locally invasive growth transform into distant spreads?
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Via proteases and other enzymes to breakdown tissues
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Define direct and distant spread.
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Direct spread = infiltration of blood and lymph vessel wall, peripheral nerve sheath and serosal surfaces
Distant spread = the spreading of tumor cells with blood and lymph to other sites |
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List four metastatic routes.
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1. Lymphatogenous spread
2. Hematogenous spread 3. Perineural spread 4. Seeding of body cavities, surfaces, and spaces |
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Lymphatogenous spread is typical for ________________
Hematogenous spread is typical for ________________ |
Carcinomas
Sarcomas |
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Which lymph nodes are first affected by carcinomas?
What is the name of the first lymph node to receive lymph from the site of primary tumor? |
Regional lymph nodes
Sentinel node |
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Which is more permeable to the invasion of neoplastic cells, venous or arterial wall?
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Venous wall
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Which initial stage carcinomas also metastasize via hematogenous spread?
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Lung, liver, thryoid, renal, and choriocarcinoma
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The first wave of blood borne metastases is directed at which organs?
The second wave at which organs? |
First wave: lung (systemic circulation), liver (portal circulation)
Second wave: bones and bone marrow, brain, and adrenals |
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Define perineural spread.
Which cancers spread via perineural spread? |
Tumors metastasize along peripheral nerves to the spinal cord
Prostate and pancreas cancers take advantage! |
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Seeding of the body cavities, surfaces, and spaces can be best observed where?
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* SEROSAL CAVITIES = peritoneal and pleural
* CSF SPACES * NATURAL PASSAGES = renal pelvis, ureter, urinary bladder |
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What is a krukenberg tumor?
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an ovary-located metastases of gastric and colon mucus-producing adenocarcinoma
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An appearance of tumor at the previous site after treatment is called ____________
It is a feature of __________ |
Recurrence
Malignant tumors |
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What are some shared effects of BOTH benign and malignant tumors on the host?
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1. Occupation of confined space
e.g. constrained subarachnoid space due to brain tumor = dysfunctional brain 2. Obstruction of lumen e.g. renal artery = renal necrosis 3. Hormone production e.g. pituitary adenoma, pheochromocytoma 4. Bleeding e.g. gastric & colon cancer 5. Ulceration e.g. gastric & colon cancer 6. Secondary infection e.g. lung cancer with pneuomina |
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List two effects of cancers on the host
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1. Cachexia
2. Paraneoplastic syndromes = pathological conditions NOT RELATED DIRECTLY to the neoplasms or metastases |
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List some of the paraneoplastic syndromes.
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1. Hypercalcemia = PTH-like peptide
2. Inappropriate antidiuretic hormone secretion 3. Polycytemia 4. Cushing syndrome = ACTH production 5. Acantosis nigricans = grey-black hyperkeratosis 6. DIC 7. Coagulapathy = non-bacterial thrombotic endocarditis OR migrating thromboplebitis |
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Define cachexia.
Which cancer(s) cause this? Is it associated with food intake? |
Anrexia, loss of body fat, loss of skeletal muscle tissue; profound muscle weakness, anemia
Advanced lung or GI carcinoma have been shown to cause this condition NOT ASSOCIATED WITH FOOD INTAKE |
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TRUE or FALSE
There is an increased frequency of cancer in immunocompromised hosts |
TRUE
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TRUE or FALSE
There is evidence of immunosurveillance in the anti-neoplasms immune response |
TRUE
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Which tumor antigens are used in immunodiagnosis?
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1. Oncofetal proteins
- carcinoembrionic antigen - alpha-fetoprotein 2. Altered cell surface glycolipids and glycoproteins - Mucin CA-19-9 = colon, pancreas - Mucin CA-125 = ovarian 3. Cell type-specific differentiation antigens - CDs |
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TRUE or FALSE
The aggresiveness of malignancy is useful for (1)prognosis and (2)determination of the type of treatment |
TRUE
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Level of malignancy is evaluated in two ways. List them.
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* Grading
* Staging |
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List the criteria for grading a malignant tumor
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1. Degree of differentiation
2. Growth rate 3. Cellular atypia |
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What are the criteria for differentiation?
How is it graded? |
Grade 1 - well differentiated -> produces keratin pearls and intercellular bridges
Grade 2 - intermediately differentiated Grade 3 - poorly differentiated -> NO keratin or intercellular bridges Grade 4 - anaplastic carcinoma |
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What is growth rate?
How is it graded? |
Estimate of rapidity of growth = number of mitoses per unit of tissue (HPF)
Low grade : 3-5 mitoses/10 HPF Intermediate grade : 5-15 mitoses/10 HPF High grade: >15 mitoses/10 HPF |
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What is the criteria for cellular atypia?
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Low grade: moderate cellular and nuclear pleomorphism
Intermediate grade: prominent cellular and nuclear pleomorphism High grade: prominent cellular and nuclear pleomorphism, multinucleation, atypical mitosis |
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Low grade tumors vs. High grade tumors
* growth * penetration * metastasis |
Low grade
- grow more slowly - penetrate adjacent tissue less actively - metastasize more rarely High grade tumors - grow more rapidly - more often invade adjacent tissue - metastasize more rapidly |
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TRUE or FALSE
well-differentiated cancers often transform into poorly differentiated |
TRUE
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TRUE or FALSE
rarely, a tumor becomes more differentiated and of lower grade |
TRUE
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The stage of a cancer is an evaluation of:
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1. size of primary lesion
2. extension to adjacent organs/tissues 3. spread to regional lymph nodes 4. presence/absence of distant metastases |
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Which has a GREATER CLINICAL VALUE, staging or grading?
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staging
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What are two important staging systems?
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TNM (tumor, lymph node, distant metastases)
AJC (dividing cancers into stages 0 - IV) |
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Describe the TNM staging system
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Increasing primary lesion:
T1, T2, T3, T4 Progressively advancing node involvement: N0, N1, N2, N3 Presence of distant metastases: M0, M1 |
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Which of the TNM stages correspond the STAGE IV of AJC?
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T1N0M1
T3N0M1 Note: M1 is the marker for stage IV |
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Describe the AJC staging system.
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Stage 0 - carcinoma in situ
Stage 1 - small invasive carcinoma w/o lymph node metastases Stage 2 - large invasive carcinoma w/ or w/o lymph node metastases Stage 3 - large carcinoma invading surrounding tissue Stage 4 - any carcinoma with distant metastases |
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List some of the acquired predispositions.
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* Chronic inflammation
* Hyperplasia * Atrophy and hypoplasia * Metaplasia * Benign tumors * Dysplasia |
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What components make up dysplasia?
Dysplasia has been identified in _______________ |
Dysplasia = cellular atypia + loss of polarity
Dysplasia has been primarily linked to "uterine cervix" |
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Among all of the preneoplastic disorders, only ____________ has a real risk of cancer
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Dysplasia
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TRUE or FALSE
Carcinoma in situ is the most severe form of dysplasia |
TRUE
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What are the most common autosomal dominant cancers associated with a single mutant gene?
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* Retinoblastoma
* Familial adenomatous polyposis (FAP) * Hereditary non-polyposis colon cancer (HNPCC) * Neurofibromatosis * Multiple endocrine neoplasia (MEN) * Li Fraumeni syndrome |
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TRUE or FALSE
Familial cancers are seen in first and second degree relatives |
TRUE
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What are the most common familial cancers?
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* Breast cancer
- BRCA1 and BRCA2 gene mutation * Ovarian cancer - only ovarian cancer associated with BRCA1 * Familial melanoma - p16INK4a gene mutation |
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What are some of the defective DNA repair syndromes?
- Rare diseases with autosomal recessive type of inheritance |
* Hereditary non-polyposis colon cancer (HNPCC)
* Xeroderma pigmentosum - predisposition to sunlight-induced skin melanomas * Ataxia-teleangiectasia - predisposition to radiation-induced lymphoid malignancies |
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What is the function of the G1/S checkpoint?
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Prevent a cell with damaged DNA from entry to S phase
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Which phase is the point of no return?
G1, S, G2, M |
S phase
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What is important about the G2/M checkpoint?
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Important in radiation-induced DNA damage (double-stranded breaks)
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List the cyclins and cyclin dependent kinases (CDKs) in order of appearance.
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Cyclins: D, E, A, B
CDKs: CDK4, CDK2, CDK1 |
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What are the cell cycle activators?
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* Cyclins
* CDKs * Retinoblastoma protein (Rb) * Transcription factor E2F * Activator complexes: - Cyclin D / CDK4 - G1/S before E2F - Cyclin B / CDK1 - G2/M |
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Name the steps in the stepwise activator interaction between Cyclin D and CDK4.
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1. Cyclin D phosphorylates CDK4
2. CDK4 phosphorylates Rb (at G1/S) 3. Retinoblastoma protein (Rb), if phosphorylated by Cyclin D/CDK4, dissociates from the complex with transcription factor E2F -------> E2F activation 4. E2F activates genes essential for progression through S phase |
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What is important about the Cyclin B/CDK1 complex?
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* Active at G2/M
* Sensitive to radiation-induced double strand DNA breaks |
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What are some examples of cell cycle inhibitors?
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* TP53
* Cyclin D / CDK4 inhibitors - p27 - p21 - p16INK4a * p14ARF * ATM |
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What is the function of p14ARF?
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prevents TP53 degradation
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What is the function of ATM?
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phosphorylates TP53, inhibits Cyclin B / CDK1 complex
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What is the function of TP53?
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1. cell cycle arrests at G1 / S
2. activation of DNA repair 3. apoptosis (if DNA repair was unsuccessful) |
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What is the ATM (ataxia teleangiectasia mutated) protein?
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* A nuclear phosphoprotein
* Activated by double-stranded DNA breaks |
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What are the steps and mechanisms of carcinogenicity?
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Step 1. Formation of a neoplastic cell
- activation of oncogenes - insufficiency of anti-oncogenes - evasion of apoptosis - insufficiency in DNA repair Step 2. Formation of a neoplastic mass (tumor) - limitless replication potential - sustained angiogenesis - invade and metastasize |
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List steps in growth regulation of a normal cell.
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1. GF binds receptor
2. Activation of signal-transducing proteins 3. Transmission of signal across cytosol to nucleus 4. Induction of nuclear regulatory factors -> initiate transcription 5. Entry and progression of cell through cell cycle |
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Give an example of a mutation of EGF receptors in breast and ovarian cancer.
What treatment is used to block this receptor? |
HER2/NEU (ERB-B2): amplification
Herceptin or Trastuzumab |
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List the steps for RAS activation.
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1. Receptor activation
2. RAS-GDP -> RAS-GTP (activation) 3. Activation of RAD (BRAF) 4. Activation of MAP-kinase cascade ... ... |
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How is RAS inactivated in a normal cell?
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RAS-GTP -> RAS-GAP -> RAS-GDP
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What happens to a mutated RAS in a normal cell?
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The mutated RAS is trapped by GAP in its activated form (RAS-GTP) and the cell cannot leave the cell cycle
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A mutation in which GAP is associated with NF-1?
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Neurofibromin-1
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What is the ABL protein?
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An intranuclear tyrosine kinase
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A mutation in t(9;22) leads to a fusion of which receptors?
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ABL with BCR
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Why does the ABL-BCR hybrid found only in the cytoplasm?
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ABL-BCR is too large to enter the nucleus -> activates cytosolic pathways (phosphorylation)
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What is the treatment of CML (chronic myelogenous leukemia)?
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STI517 (imatinib mesylate) inhibits ABL-BCR
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What is an important "nuclear transcription factor" in the activation of oncogenes?
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MYC
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List two MYC mutations.
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C-MYC: overexpression due to translocation t(8;14) in Burkitt lymphoma
N-MYC: amplification in neuroblastoma |
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Name the mutation/activation of the cell cyle activators of Cyclin D and CDK4.
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Cyclin D: t(11;14) -> overexpression & amplification
CDK4: amplification |
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List the four "major growth inhibitory signals".
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* RB gene / protein
* APC / beta-catenin pathway members * TP53 * p16INK4a |
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Describe RB gene inactivation.
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* Inactivation of RB gene on both alleles (13q14)
- loss of both alleles - loss of heterozygocity (LOG) * Inherited / sporadic RB = 2/3 * "Two hits hypothesis" - inherited loss of one RB allele and acquired loss of the second |
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Describe familial vs. sporadic retinoblastoma.
In which cancers is each seen? |
Inherited retinoblastoma: one allele is inherited
- retinoblastoma & bone/soft tissue sarcoma Sporadic retinoblastoma: mutations in both alleles - retinoblastoma & osteosarcoma & breast cancer & colonic cancer & lung cancer |
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A mutation in the APC gene is seen in which cancer?
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FAP (familial adenomatous polyposis)
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If TP53 is inactivated or it gene lost, what sadly occurs?
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No cell cycle arrest
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Describe acquired vs. sporadic loss / inactivation of TP53 gene.
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* Acquired TP53 mutation
* Inherited TP53 mutation - li fraumeni syndrome - by age 50 - sarcomas, breast cancer, leukemia, brain cancer, adrenal cortex cancer |
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Inhibition of apoptosis is seen in which genes?
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* TP53
* Members of BCL-2 family |
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How does the overexpression of BCL-2 occur?
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1. t(14;18)
2. overexpression of BCL-2 3. inhibition of cytochrome c release (mito) 4. inhibition of apoptosis 5. follicular lymphoma (neoplastic growth) |
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INSUFFICIENCY IN DNA REPAIR
Given the disease, name the repair mechanism: * HNPCC * Xeroderma pigmentosum * Ataxia-teleangiectasia |
HNPCC: mismatch repair
Xeroderma pigmentosum: NER Ataxia-teleangiectasia: homologous recombination repair |
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Describe insufficiency in DNA repair for HNPCC.
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* inability to mismatch repair
* accumulation of point mutations * microsatellite instability * inactivation of TGF-beta receptor |
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Describe insufficiency in DNA repair for xeroderma pigmentosum.
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* defect in NER
* inability to repair pyrimidine cross-links induced by UVL * ultimately leads to "skin cancer" |
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Describe insufficiency in DNA repair for ataxia-teleangiectasia.
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* cerebellar ataxia
* teleangiectasia * immunodeficiency "acute sensitivity to ionizing radiation -> extremely high risk of lymphoid malignancies" |
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What are two angiogenic tumor factors?
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VEGF
FGF-2 |
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Tumor circulation is marked by:
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* vasculogenic mimicry: blood flows through clefts formed by tumor cells
* Infarctions and hemorrhages of blood vessels -> cysts |
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What are the four steps of ECM invasion?
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1. Detachment of tumor cells from each other marked by LOSS OF
- E-cadherin - Catenins 2. Attachment of tumor cells to ECM components marked by INCREASE IN - Laminin - Integrins - Ig-s (ICAM1, VCAM1) 3. Local degradation of ECM - urokinase type of plasminogen activator - matrix metalloproteinases 4. Tumor cell migration - autocrine motility factor |
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What are two site exemptions to metastasis?
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* Never in skeletal muscles
* Extremely rare in spleen or heart |
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List 5 genetic and epigenetic changes.
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1. Insertion of retroviral promoters
2. Point mutations 3. Chromosomal translocations 4. Gene amplification 5. Epigenetic changes |
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List 4 translocations.
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t(8;14): C-MYC in Burkitt lymphoma
t(11;14): Cyclin D in mantle cell lymphoma t(14;18): BCL-2 in follicular lymphoma t(9;22): CML with formation of ABL-BCR hybrid w/ tyrosine kinase activity |
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Amplification occurs in which regions?
Amplification is present in which cancers? |
Regions:
homogeneous stained regions (HSRs), abnormal banding regions, double minutes (dms) Cancers: MYC in neuroblastoma HER-2/eu (ERB-B2) in breast cancer Cyclin D in mantle cell carcinoma |
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List three epigenetic changes.
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1. Promoter hypermethylation (inactivation)
- AOGs or DNA repair genes 2. (Proto)oncogene hypomethylation -> loss of genetic imprinting 3. Histone acetylation and deacetylation |
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What are the steps in chemical carcinogenesis?
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1. initiation: mutation with formation of a neoplastic cell (T-IC)
2. Promotion: proliferation of neoplastic cells 3 & 4. progression -> cancer |
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Mutagenicity is observed by which test?
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Ames test
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What are two types of chemical carcinogens?
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* Direct initiators
* Indirect initiators - cytochrome p-450 depdendent monooxygenases |
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Describe direct initiators.
What are the main groups? |
* highly reactive electrophils
* react with nucleophilic sites * target DNA MAIN GROUPS: * alkylating agents -> chemotherapeutic drugs * acylating agents |
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TRUE or FALSE
chemotherapeutic drugs induce secondary cancers like leukemia |
TRUE
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Name two indirect carcinogens.
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* Polycyclic hydrocarbons
* Nitrosoamines & nitrosoamides |
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What is the mechanism of polycyclic hydrocarbons?
They induce what type of cancers? |
Production of epoxides -> forming covalent adducts with DNA
- lung, oral cavity, and laryngeal carcinoma - bladder carcinoma - esophageal carcinoma |
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Where are nitrosoamines and nitrosoamides generated?
They induce what type of cancers? |
Stomach:
- amines and amides - nitrates and nitrites Esophageal and gastric cancers are induced |
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Name an example of aromatic amines and azo dyes.
What cancer does it cause? |
2-β-naphthylamine
bladder cancer |
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Which chemicals are promoters of human cancer?
Are they mutagenic? What is their participation in carcinogenesis? |
Chemicals: hormones (estrogens), drugs (phenobarbital), bile salts
Not mutagenic Clonal expansion of previously induced cells |
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TRUE or FALSE
diethylstilbestrol-induced endometrial adenocarcinoma and offspring vaginal clear cell carcinoma |
TRUE
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Ionizing radiation is most vulnerable to cells in the phase of the cell cycle
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S / G2
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Name some examples of ionizing radiation and the cancers they cause.
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X- and gamma-rays -> myeloid leukemias
Iodine -> thyroid carcinoma Strontium -> osteosarcoma Uranium & radon -> lung carcinoma Radiotherapy -> thyroid carcinoma |
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Water radiolysis leads to what type of DNA breaks?
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double stranded DNA breaks
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UV light is implicated in the formation of _______________ and it quickly exhausts this repair mechanism.
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pyrimidine dimers, NER
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UV light results in skin cancer through the formation of these carcinomas
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- squamous cell carcinoma
- basal cell carcinoma - melanoma |
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UV light induced tumors are found in this cancer
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xeroderma pigmentosum
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HTLV-1 virus is endemic for which regions?
What is its mechanism? It induces what tumor? |
Endemic for Caribbean basin and Japan
mechanism is viral TAX protein Induces T-cell leukemia/lymphoma -> tropical spastic paraparesis |
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What are the common HPV types?
What tumors do they induce? |
HPV type 16, 18, 31
moderate to severe cervical dysplasia and invasive cervical squamous cell carcinoma |
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List 5 EBV induced diseases.
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1. infectious mononucleosis
2. burkitt's lymphoma 3. b-cell lymphoma in AIDS patients 4. hodgkin's lymphoma 5. nasopharyngeal carcinoma |
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EBV-induced carcinogenesis release what?
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* latent membrane protein-1
* epstein-barr nuclear antigen |
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HBV and HCV induce which tumor?
Where is it geographically present? Which protein does it release? |
hepatocellular carcinoma
HBV: far east & africa HCV: north america & europe viral HBx protein |
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HHV8 induces which tumor?
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Kaposi sarcoma (all types)
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How does Aflatoxin B1 work?
It induces which cancers? What is its mechanism? |
heterocyclic hydrocarbon, metabolized to epoxide, covalently binds DNA
Induces hepatocellular carcinoma in africa and far east It inactivates of TP53 |
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H. pylori is known to cause which cancers?
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* gastric adenocarcinoma
* mantle cell lymphoma |
