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rapid growth, lack of differentiation, Malignant The active form of a cancer causing gene Oncogene A predisposing gene for cancer that is not yet activated by mutation Proto-oncogene cancer from epithelium Carcinoma cancer of connective tissue Sarcoma non-cancerous growth, usually encapsulated and differentiated Benign Cancer spreading beyond original site Metastasis Gene found in healthy cells that acts to block oncogenes Tumor Suppressor Gene new growth (tumor) Neoplasm process by which normal cell becomes a cancer cell Transformation not clear what is the tissue or cell type Undifferentiated localized to epithelium, has not yet broken thru basement membrane or invaded stroma Carcinoma in situ loss of differentiation, irregularities in size and shape of nucleus and loss of normal tissue structure Anaplasia cancer in ductal or glandular tissue Adenocarcinoma variable cell shape and size Pleomorphic Two characteristics: self renew and multipotent Adult stem cells normal cells stop growing when touch, cancer cells keep growing Contact inhibition a rare cancer cell that may give rise to all the rest and is not targeted by current cancer treatments Cancer stem cell substances produced by cancers that can be detected with lab tests Tumor markers 3 ways to use tumor markers screen diagnose type track progress Mutant cell has selective advantage and proliferates faster than neighboring cells clonal selection Different mutations that cancer cells have to increase growth autocrine stimulation increase growth factor receptors RAS (stimulate growth w/out growth factors) ignore antigrowth signals no apoptosis Tumor grows own blood supply angiogenesis 3 angiogenic factors VEGF PDGF bFGF Normally, this is the process by which cells stop growing via cytokines, proximity, etc. this is shut off in cancer density dependent inhibition two mutational routes for cancer (?) heredity environmental results in hundreds of copies of a mutant gene being present instead of the normal 2 gene amplification Gene silencing without mutation is called epigenetic silencing (like methylation) Why does long term inflammation often lead to cancer? increase of cytokines, growth factors, vascularization at site of injury/inflammation Local spread of cancer, first step of metastasis Invasion 4 mechanisms of cancer invasion proliferation CT digestion by proteases cancer cells become slippery (prevent adhesion of macrophages) increased motility 2 characteristics of cancer cells that metastasize beyond local can enter blood motile mutant cells of a single lineage parenchyma the surrounding connective tissue and associated cells that support a tumor stroma 4 steps of metastasis detachment spread via bloodstream escape from circulation attach at favorable site 3 factors dictating cancer stage size degree of invasion degree of metastasis describe the 4 main stages of cancer isolated to organ of origin (Stage 1 ) locally invasive (Stage 2 ) regional spread (Stage 2 , ie to nearby lymph nodes) spread to distant sites (Stage 4 ) 5 types of biopsies excisional (remove all) incisional (remove piece) core needle (remove intact tissue sample) fine needle aspiration (remove cells, tissue structure destroyed) exfoliative cytology (scrape, PAP) Antimetabolite (Antifolate) drug example methotrexate (blocking folic acid reduces leukemia) types of chemotherapy antimetabolite (cell cycle specific) DNA-damaging antibiotic alkalating agents (inhibit growth, not cycle specific) monoclonal antibodies steroids hormones purposes for chemo - 3 terms induction(shrink tumor) adjuvant(after surgery/radiation) neoadjuvant(prior to surgery) symptoms that are triggered by cancer but not a direct result of it paraneoplastic syndromes 9 common paraneoplastic syndromes pain fatigue cachemia (wasting, anorexia, etc) anemia leukopenia/thrombocytopenia (low WBC platelets) infection GI symptoms hair/skin symptoms reproductive problems common chemo effects on GI tract nausea, vomitting diarrhea, anorexia alkylating agents in chemo chemically modifying a cell's DNA steroid and hormone use in chemo Because steroid hormones are powerful drivers of gene expression in certain cancer cells, changing the levels or activity of certain hormones can cause certain cancers to cease growing, or even undergo cell death. common chemo effects on skin dermatitis, hair loss, color change common chemo effects on urinary system pain, rbcs in urine (hematuria) nephrotoxicity common chemo effects neurologic damage to ear nerve (ototoxicity) and peripheral neuropathies common chemo effects on muscles myalgia (muscle pain) common chemo effects on respiratory tract pneumonitis (lung inflammation), pulmonary fibrosis (scarring of lung, excess ct formation) Most common type of radiation therapy external beam A sealed radioactive capsule of an isotope is implanted implant therapy Radioactivity delivered internally, but not sealed. absorbed by target organ preferentially. Example : Iodine to thyroid isotope therapy increase effectiveness of radiation using heat combination heat and radiation New treatments for cancer vaccines cytokines (interferon) monoclonal antibodies gene therapy (insert gene that expresses a non self marker) antiangiogenesis Risk of breast cancer if have BRC 1 or BRC 2 67% (was 40%...environmental factors at play) Alteration or unchecked activity of this important growth and clotting factor are associated with cancer. It may play a role in attachment of cancerous cell fibronectin 3 major areas of epigenetics methylation histone mods micro RNAs Does the text consider adipose tissue to be endocrine? yes Why is obsesity associated with cancer? adipose (endocrine) tissue accumulate macrophages that secrete cytokines, inflammation The degree to which an organisms development is affected by the environment developmental plasticity What happened with DES babies the female babies had damaged repro systems Tobacco is responsible for about _____% of cancer deaths 30% Chemical that does not directly cause damage, but can interact with the biological system of the organism to cause cell damage xenobiotics why obesity may cause cancer adipose>>sex hormones>>regulate cell growth and apop Hyperinsulinemia can lead to cancer via IGF-1 (increase cellular proliferation, decrease apop) effects occurring in the offspring following irradiation of one or both parents, usually the father, prior to conception Transgenerational essentially refers to radiation- induced effects in unirradiated cells. could be due to cytokines from neighbors, gap jxns bystander effects increased tendency of genome to acquire mutations because normal factors regulating damage are dysfxnl genomic instability channels that form the gap jxns betw 2 cells connexons cause of basal and squamous cell carcinoma UV radiation UV damage produces what important carcinogen in skin? ROS Most commonly found on head and neck on light skinned people in high sun areas basal cell carcinoma most common in men that work outdoors, found all over the exposeed body areas squamous cell carcinoma Often start as a mole, associated with UVB and the BRAF protooncogene melanoma BRAF activates mitogen activated protein kinase (MAPK) Activation of melanoma via MAPK occurs in____steps 4 What is the proposed mechanism for electromagnetic carcinogenesis ? thermal changes >>protein phosphorlyation how does exercise protect against cancer? reduce insulin, IGF decrease obesity keeps gut moving