10/2 Flashcards

Question

Multiple Endocrine Neoplasia Type 2

Answer 1

All caused by GOF mutations of RET Cysteine-rich region: extracellular region, MEN2A/FMTC, hyperparathyroidism, tumor in adrenal gland, most common MEN2 First Tyrosine Kinase region: FMTC, tumor of calcitonin-producing C cells of thyroid, thyroidectomy at early age Second Tyrosine Kinase Region: MEN2B/FMTC, earlier age of onset, developmental abnormalities like neuromas of the mouth and increased intestinal innervation

Answer 2

Mutations that allow tumor growth involve tumor suppressor genes, proto-oncogenes, and apoptosis regulators Proto-oncogenes: GFs, GF receptors, and signal transducers like RAS Knudsen Two-Hit Hypothesis: both alleles must be knocked out of tumor suppressor genes to have tumor formation Bcl2: blocks release of cytochrome C from mitochondria and the ensuing apoptosis, tumors overexpress Bcl2 to prevent apoptosis, translocation makes Cell make Bcl2 instead of Ig heavy chain

Answer 3

1. Tumor Initiation: due to irreversible genetic damage or epigenetics, causes a genetic error in stem cells by modifying its DNA structure like with a chemical adduct 2. Tumor Promotion: selective clinal expansion of initiated cells,nude to defects in cell growth or programmed cell death Foster the proliferation or expansion of a pop. of initiated cells 3. Malignant Conversion: transformation of a pre-Neoplastic cell into one that expresses the malignant phenotype and usually requires further genetic changes Summation of effects of initiators and promoters and the downstream effects they induce 4. Tumor progression: expression of malignant phenotype and tendency of malignant cells to acquire more aggressive characteristics over time to become capable of spreading Requires genetic change

Answer 4

Direct-acting compounds: don't require chemical transformation, directly capable of reacting with DNA Indirect-acting compounds: require metabolic conversion (often made electrophilic) to generate ultimate carcinogen, initiators are often tissue specific Form DNA adducts that are covalently bound to nucleoside, not repaired and must be replicated Effect is irreversible, permanent genetic changes that daughter cells carry Linear relationship between initiator dose and quantity of tumors

Answer 5

Don't covalently bind to DNA/macromolecules, can bind to receptors on cell surface that leads to increased cell proliferation Tumor growth has threshold and maximum effects Mechanisms- 1. Epigenetic 2. Promoters induce cell proliferation, not mutagenic, like activate PKC 3. Cells responding to promoters may have reduced GF Requirements or be less responsive to Inhibitors 4. Oxidative stress: ROS, redox active metals like As/Cr/Ni, and polycyclic aromatic compounds like Dioxin

Answer 6

1. Direct-alkylating agents: chemotherapeutic drugs, can cause secondary malignancy 2. Polycyclic Hydrocarbons: cigarette smoke, broiled animal fat, smoked meat/fish Need metabolism, why 15% smokers get lung cancer Vinyl chloride exposure leads to hepatic angiosarcoma with dark red masses 3. N-Nitrosamines: occur in smoke, water, alcohol, meats Mainly cause gastric carcinomas in Japan 4. Aromatic Amines and Azo Dyes: from rubber industry, need metabolism Urothelial carcinoma 5. Aflatoxin B1: from fungus Aspegeilus flavus, needs Metabolism, binds guanine residues in the TP53 gene and causes mutations Hepatocellular carcinoma

Answer 7

Chronic inflammation like IBS can cause colorectal cancer Initiation: ROS can damage DNA Promotion: ROS, GFs, and cytokines released from inflammatory cells can foster proliferation of initiated cells Progression: angiogenic factors, ECM synthesis and degradation

Answer 8

1. UV Radiation- UVA: oxidation reactions that indirectly cause DNA damage, darkens and ages skin, penetrates deeper into epidermis so tans us UVB: DNA photoadducts, sunburns, direct DNA damage from producing pyrimidine dimers Initiator since cause DNA damage and mutations Promoter by upregulating Inflammation that makes ROS and increased COX-2 activity UVB Induced inflammation: dysregulation of apoptosis, mutations in p53, upregulation of COX-2 plays a role in squamous cell carcinoma 2. Ionizing Radiation- Creates free radicals, use radiation therapy Breast, colon, thyroid, and lung cancer

Answer 9

1. HPV: HPV Types 16 and 18 are found in most squamous carcinomas of the cervix HPV viral oncoprotein E6 causes tags P53 for proteasome degradation, HPV viral oncoprotein E7 tags Rb for proteasome degradation Squamous of vulva, vagina, anus, cervix, adenocarcinoma of cervix 2. Epstein Barr Virus: Burkitt Lymphoma, infected B cells rearrange immunoglobulin genes to acquire t(8;14) that promotes cell proliferation by regulating c-Myc Make c-Myc instead of immunoglobulin Nasopharyngeal 3. Hepatitis B Virus: Africa and Asia, liver injury and regenerative hyperplasia, Hbx protein binds to and inactivates p53 to interfere with growth suppression 4. Human Herpes Virus 8 (HHV8): Kaposi's sarcoma and certain lymphomas in HIV patients Kaposi's sarcoma: Neoplastic endothelial cells 5. Human T-Lymphotropic Virus 1 (HTLV1): RNA virus, endemic in Japan and Caribbean, tropic for CD4 T Cells Activates IL2 and IL2R resulting in polyclonal proliferation in which leukemia develops

10/2 Flashcards

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