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HY Oncology

Day 8 (includes anti-cancer drugs)

QuestionAnswer
What are the 2 MC cancer mutations? p53 and RAS; of the 2, RAS is the MC
Which RAS mutation is associated with colon,lung, and pancreatic tumors? K-RAS (Kolon and panKreatic)
Which RAS mutation is associated with bladder and kidney tumors? H-RAS (Hematuria)
Which RAS mutation is associated with is associated with melanomas and hematologic malignancies? N-RAS
White reflex caused by tumor outgrowing the vascular supply Retinoblastoma
How do most cases of sporadic retinoblastoma present? Always unilateral; most cases are sporadic
How do most cases of heritable retinoblastoma present? May be bilateral or unilateral; all bilateral cases are inherited point mutations
How do the 2 "hits" arise in heritable retinoblastoma? 1 hit comes from a parent, and the second hit arises sporadically
p53 is the "guardian" of which cell cycle checkpoints? G1/S and G2/M
How does p53 cause apoptosis? By inducing the transcription of pro-apoptotic genes such as BAX.
Strep bovis is associated with which malignancy? Colon cancer
H pylori is associated with which malignancy? Gastric cancer
Schistosoma hematobium is associated with which malignancy? Squamous cell carcinoma of the bladder
Clonarchis sinesis is associated with which malignancy? Biliary carcinoma
Name 3 drugs used to treat testicular cancer. Etoposide, Bleomycin, and Cisplatin (Eradicate Ball Cancer!)
Cells have increased in number Hyperplasia
Abnormal proliferation of cells with loss of size, shape, and orientation Dysplasia
Name two factors that allow neoplastic cells to invade the basement membrane. Collagenases and hydrolases. ALso metalloproteases.
What do the seed and soil of the "seed and soil" theory of metastasis stand for? Seed: tumor embolus Soil: target organ
How does increased expression of laminins help mediate metastasis? Allows for adherence to basement membrane (Let me/LAMI INto this basement membrane now!)
How do neoplastic cells mediate detachment from the surrounding cells for the purpose of metastasis? Loss of E cadherins
Very poor differentiation of a neoplastic cell Anaplasia
Name 4 features of anaplastic cells. 1. High nucleus to cytoplasmic ratio 2. Prominent nucleoli 3. Nuclear chromatin clumping 4. Many mitotic figures
Which -plasias are reversible? Hyperplasia (increase in # of cells) and Dysplasia (abnormal growth with loss of cellular orientation, shape, and size in comparison with normal tissue maturation)
What test detects dysplasia of the cervix? Pap smear
Which plasias are irreversible? Anaplasia (little or no resemblance to tissue of origin), neoplasia (clonal proliferation), and desmoplasia (fibrous tissue formation in response to neoplasm)
Which has more prognostic value-- stage or grade? Stage (how much tumor has spread)
What is the TNM staging system? T: size of Tumor N: Node involvement M: Metastases
Via which route do epithelial tumors spread? Lymph nodes
Via which route do mesenchymal tumors spread? Hematogenous
Can an adenoma progress to an adenosarcoma? Yes (note that the majority of benign tumors do not progress to their malignant counterparts; epithelial tumors are the exception)
Which teratoma is malignant in men? Both immature and mature teratomas are malignant in men. In women, the mature teratoma is benign (older, mature women will behave benignly)
Which immunohistochemical stain is used to ID sarcomas and some carcinomas? Vimentin (CT stain)
Which immunohistochemical stain is used to ID rhabdomyosarcomas or leiomyosarcomas? Desmin (muscle stain)
Which immunohistochemical stain is used to ID carcinomas and some sarcomas? Cytokeratin (epithelial cell stain)
Which immunohistochemical stain is used to stain neuroglial cells? GFAP
Which immunohistochemical stain is used to ID adrenal neuroblastoma and primitive neuroectodermal tumors (PNETs) Neurofilaments (neuron stain)
Which cancer(s) does the following condition predispose the patient to?: Down syndrome ALL (we ALL fall DOWN), AML
Which cancer(s) does the following condition predispose the patient to?: xeroderma pigmentosum, albinism Melanoma, basal cell carcinoma, and especially squamous cell carcinoma
Which cancer(s) does the following condition predispose the patient to?: chronic gastritis, pernicious anemia, postsurgical gastric remnants Gastric adenocarcinoma
Which cancer(s) does the following condition predispose the patient to?: tuberous sclerosis (facial angiofibroma/adenosebaceum, seizures, mental retardation, ash leaf spots) Astrocytoma, angiomyolipoma, and cardiac rhabdomyoma (2/3!)
Which cancer(s) does the following condition predispose the patient to?: actinic keratosis SCC of skin
What is the treatment for actinic keratosis? 5-fluorouracil cream
Which cancer(s) does the following condition predispose the patient to?: Barret's esophagus Esophageal adenocarcinoma
Which cancer(s) does the following condition predispose the patient to?: Plummer-Vinson syndrome (atrophic glossitis, esophageal webs, anemia; all due to iron deficiency) SCC of esophagus
Which cancer(s) does the following condition predispose the patient to?: Cirrohsis (alcoholic, HepB, HepC) Hepatocellular carcinoma
Which cancer(s) does the following condition predispose the patient to?: Ulcerative colitis (UC) Colonic adenocarcinoma (UC U have Colon cancer now)
Which cancer(s) does the following condition predispose the patient to?: Paget's disease of bone secondary osteosarcoma adn fibrosarcoma
Which cancer(s) does the following condition predispose the patient to?: immunodeficiency states Malignant lymphoma
Which cancer(s) does the following condition predispose the patient to?: AIDS aggressive malignant lymphoma (non-Hodgkin's or primary CNS lymphoma) and Kaposi sarcoma
Which cancer(s) does the following condition predispose the patient to?: Autoimmune diseases (e.g., Hashimoto's thyroiditis, Myasthenia Gravis) Lymphoma
Which cancer(s) does the following condition predispose the patient to?: Acanthosis nigricans (hyperpigmentation and epidermal thickening) Visceral malignancy (sotmach, lung, breast, uterus), esp in a patient with new onset acanthosis nigricans who is >40yo
What non-malignant condition can acanthosis nigricans be seen in? Diabetes
Which cancer(s) does the following condition predispose the patient to?: Dysplastic nevus (mole) Malignant melanoma
Which cancer(s) does the following condition predispose the patient to?: Radiation exposure Sarcoma, papillary thyroid cancer
Which cancer(s) does the following condition predispose the patient to?: achalasia (narrowing of the LES) SCC of esophagus
Which cancer(s) does the following condition predispose the patient to?: Sjogren's B cell lymphoma
Which cancer(s) does the following condition predispose the patient to?: Ataxia telangiectasia Lymphomas and acute leukemias
What is the associated gene and gene product for the following tumor?: CML abl gene; tyrosine kinase product
What is the treatment for CML? What translocation is CML associated with? Treatment is imatinib (anti-bcr abl antibody); t(9;22) translocation
What is the associated gene and gene product for the following tumor?: Burkitt's lymphoma c-myc gene; transcription factor product
What is the translocation associated with Burkitt's lymphoma? With what virus is it associated? t(8;14); EBV
What is the associated gene and gene product for the following tumor?: Follicular and undifferentiated lymphomas bcl-2 gene (inhibits apoptosis); anti-apoptotic molecule product
What is the associated gene and gene product for the following tumor?: Breast, ovarian, and gastric carcinomas erb-B2 gene; tyrosine kinase product
What is the associated gene and gene product for the following tumor?: Colon carcinoma ras (K-ras specifically) gene; GTPase product; Ras is also assoc'd with follicular thyroid carcinoma
What is the associated gene and gene product for the following tumor?: Lung tumor (specifically small cell) L-myc gene; transcription factor product
What is the associated gene and gene product for the following tumor?: neuroblastoma (adrenal tumor with Homer Wright rosettes) N-myc gene; transcription factor product
What is the associated gene and gene product for the following tumor?: multiple endocrine neoplasia (MEN types 2A and 2B) ret gene; tyrosine kinase gene product; ret mutation is also assoc'd with papillary carcinoma of the thyroid
What is the associated gene and gene product for the following tumor?: gastrointestinal stromal tumor (GIST) c-kit gene; cytokine receptor product
Which gene is mutated in retinoblastoma, osteosarcoma? Rb
Which gene is mutated in Li-Fraumenni syndrome? p53
Which BRCA mutation is associated with breast cancer only? BRCA 2 (you only have 2 breasts-- i hope!); BRCA 1 is both breast and ovarian
Which gene is mutated in melanoma? p16
Which gene is mutated in colorectal cancer associated with Familial Adenomatous Polyposis (FAP)? APC
Which gene is mutated in Wilm's tumor? WT1
Which gene is mutated in neurofibromatosis type 1? NF1 (neurofibromatosis type 2 is just NF2 mutation)
Which gene is mutated in pancreatic cancer? DPC (Deleted in Pancreatic Cancer)
Which gene is mutated in colon cancer? DCC (Deleted in Colon Cancer)
What is the proper usage of a tumor marker? To confirm a diagnosis, to monitor for tumor recurrence, and to monitor response to therapy. Tumor markers should NEVER be used as the primary tool for making a cancer diagnosis.
Name that tumor marker: elevated in BPH and prostatitis PSA
Name that tumor marker: elevated in prostate carcinoma Prostatic acid phosphatase
Name that tumor marker: GI tumors, breast, and thyroid medullary carcinomas CEA (carcinoembryonic antigen)
Name that tumor marker: HCC, nonseminomatous germ cell tumors of the testis (e.g., yolk sac tumor aka endodermal sinus tumor) AFP (America's Favorite Pancakes go great with eggs=yolk)
Name that tumor marker: Hyaditiform moles, Choriocarcinomas, and Gestational trophoblastic tumors beta-HCG (HCG for Hyatidiform, Choriocarcinoma, and Gestational trophoblastic)
Name that tumor marker: Ovarian, malignant epithelial tumors CA-125 (caused by peritoneal irritation, so not a good screening tool for ovarian cancer)
Name that tumor marker: melanoma, neural tumors, astrocytomas S100
Name that tumor marker: metastases to bone, obstructive biliary disease, Paget's disease of bone Alkaline phosphatase
Name that tumor marker: Adrenal neuroblastoma, lung and gastric cancer Bambesin (little bambinos get adrenal neuroblastoma)
Name that tumor marker: Hairy cell leukemia (a mature B cell tumor in the elderly) TRAP (tartrate resistant acid phosphatase); TRAP the hairy animal
Name that tumor marker: Pancreatic adenocarcinoma CA-19-9
Name that tumor marker: Thyroid medullary carcinoma Calcitonin
Which oncogenic microbe causes adult T cell leukemia/lymphoma? HTLV-1
Which oncogenic microbe causes Burkitt's lymphoma, nasopharyngeal carcionma, Hodgkin's, and oral hairy leukoplakia? EBV
Which oncogenic microbe is asociated with papillary thyroid carcinoma? HepC
Which oncogenic microbe causes primary CNS lymphoma? HIV
Aflatoxins cause which type of cancer? HCC (liver)
Vinyl chloride causes which type of cancer? Angiosarcoma of the liver
CCl4 causes which type of liver damage? Centrilobular necrosis and fatty change
Nitrosamines cause cancer in which two organs? Esophagus and stomach
What is the carcinogen found in cigarette smoke? PAH (polycyclic aromatic hydrocarbons)
What cancers are caused by asbestos? Mesothelioma and bronchogenic carcinoma
What cancers are caused by arsenic? Skin (SCC) and angiosarcoma of the liver
Naphthalene (aniline) dyes found in mothballs cause which cancer? Transitional cell cancer of the bladder
Anti-cancer alkylating agents are linked to which type of cancer? Leukemia
Radon exposure is associated with with type of cancer? Lung cancer
Which neoplasm is associated with Cushing's syndrome? Small cell lung carcinoma (elevated ACTH or ACTH-like peptide)
Which neoplasm is associated with SIADH? Small cell lung carcinoma and intracranial neoplasms (elevated ADH)
Which neoplasm is associated with hypercalcemia? Squamous cell lung carcinoma, renal cell carcinoma, breast carcinoma, and multiple myeloma (elevated PTH related peptide, TGF-beta, TNF, and IL-1)
Which neoplasm is associated with polycythemia (an abnormal increase in the # of RBCs)? Renal cell carcinoma, hemangioblastoma, pheochromocytoma, and HCC
Which neoplasm is associated with Lamber-Eaton syndrome (m weakness that improves with use)? Thymoma, small cell lung carcinoma
Which neoplasm is associated with gout and urate nephropathy? Leukemias and lymphomas (hyperuricemia due to excess nucleic acid turnover; i.e., cytotoxic therapy; salvage pathway can't keep up)
Psammoma bodies can be seen in which neoplasms? Papillary adenocarcinoma of the thyroid, serous papillary cystadenocarcinoma of the ovary, meningioma, and malignant mesothelioma
What are the 3 most common cancers in men (in order of frequency? 1. Prostate 2. Lung 3. Colorectal
What are the 5 most common cancers in women (in order of frequency? 1. Breast 2. Lung 3. Colorectal 4. Uterine 5. Ovarian
What are the 4 most common cancers causing mortality among men (in order of frequency)? 1. Lung 2. Prostate 3. Colorectal 4. Pancreatic
What are the 4 most common cancers causing mortality among women (in order of frequency)? 1. Lung 2. Breast 3. Colorectal 4. Pancreatic
What are the top 4 causes of death in the US? 1. Heart disease 2. Cancer 3. Stroke 4. COPD
What are the most common sites of origin for tumors metastasis to the brain? Lung, Breast, Skin (melanoma), Kidney (renal cell CA), GI (Lots of Bad Stuff Kills Glia)
What percentage of brain tumors are metastases? 50%
What are the most common sites of origin for tumors metastasis to the liver? Colon, Stomach, Pancreas, Breast, Lung (Cancer Sometimes Penetrates Big Livers)
What is the MC liver tumor? Metastases
What are the most common sites of origin for tumors metastasis to the bones? Prostate, Thyroid, Testes, Breast, Lung, Kidney; breast and prostate are most common (P.T. Barnum Loves Kids)
Lytic or blastic? Lung metastasis to the bone Lytic (L for Lung and Lytic)
Lytic or blastic? Prostate metastasis to the bone Blastic (prostate builds the bone)
Lytic or blastic? Breast metastasis to the bone Both (Breast does Both)
What is the most common tumor in the bone? Metastases
Rx: Forms a complex between topoisomerase II and DNA Etoposide
Rx: Alkylates DNA, toxicity=pulmonary fibrosis Busulfan
Rx: Fragments DNA; toxicty=pulmonary fibrosis Bleomycin
Rx: Blocks purine synthesis; metabolized by xanthine oxidase 6-mercaptopurine (increased toxicity with allopurinol; activated by HGPRTase)
Rx: Crosslinks DNA, nephrotoxic, ototoxic Cisplatin and carbaplatin
Rx: Nitrogen mustard, alkylates DNA (electrophil that binds DNA) cyclophosphamide
Rx: Folic acid analog that inhibits dihydrofolate reductase MTX
Rx: Prevents tubulin disassembly Paclitaxel (-taxols); it's TAXing for microtubules to stay stuck together
Rx: Intercalates DNA, produces oxygen free radicals, cardiotoxic Doxorubicin and Daunorubicin (Dox and Daun the Double D twins will break your heart= cardiotoxicity, and your DNA strands!)
Rx: Prevents tubulin assembly Vincristine, vinblastine (BLAST the vines=microtubules)
Rx: Inhibits thymidylate synthase--> decreased nucleotide synthesis 5-flurouracil (5-FU)
Rx: SERM; blocks estrogen binding to ER + cells Tamoxifen, raloxifene
Rx: Mechanism similar to antivirals acyclovir and foscarnet Cytarabine
Rx: Mechanism similar to fluoroquinolones Etoposide
Rx: Mechanism similar to trimethoprim MTX
Rx: Monoclonal Ab against HER-2 (erb-B2) Trastuzumab (Herceptin)
Rx: Free radical induced DNA strand breakage Bleomycin, Doxorubicin, Daunorubicin
Rx: Inhibitor of PRPP synthetase 6-mercaptopurine
Rx: Reversible with leucovorin MTX
Rx: Treatment for choriocarcinoma MTX, vincristine, vinblastine
Rx: Treatment for AML Cytarabine
Rx: Treatment for CML Imatinib, busulfan
Rx: Prevents breast cancer Tamoxifen, raloxifene
Rx: Applied topically for actinic keratosis and BCCs 5-fluorouracil
Rx: Treatment for childhood tumors (Ewing's sarcoma, Wilm's tumor, rhabdomyosarcoma) dACTinomycin (kids ACT out)
Rx: Inhibits ribonucleotide reductase Hydroxyurea
Rx: Side effect of hemorrhagic cystitis Cyclophosphamide
Rx: Antibody against Philadelphia chromosome Imatinib
What are the 10 potential side effects of prednisone use? MUST know all 10! 1. Acne 2. Cushingoid symptoms 3. Cataracts 4. HTN 5. Hyperglycemia 6. Immunosuppression 7. Insomnia 8. Osteoporosis 9. Peptic ulcer 10. Psychosis
Rx: Inhibits thymidylate synthase; pyrimidine analog 5-fluorouracil
Rx: Reversible with leukovorin (folinic acid) MTX
Rx: Not reversible with leukovorin 5-FU
Rx: Use thymidine to "rescue" from overdose 5-FU
Rx: Same mechanism as 6-mercaptopurine, but can be given with allopurinol 6-thioguanine (6-TG)
How can hemorrhagic cystitis toxicity in cyclophosphamide use be partially prevented? By using mesna (binds toxic metabolite)
Name 4 general drugs/drug classes that are both ototoxic and nephrotoxic. Vancomycin, Aminoglycosides (-mycins), Loop diuretics, and Cisplatin/Carboplatin
How can osteoporosis from prednisone therapy be prevented? Prophylax with bisphosphonates if therapy will last longer than 3 mos
Rx: Nephrotoxicity and acoustic n damage in a drug used to treat testicular cancer Cisplatin, carboplatin
The presence of which organ determines which SERM a woman should receive? Uterus
Women without a uterus can be given which SERM? Raloxifene (endometrial and breast antagonist; bone agonist) or tamoxifen (breast antagonist; endometrial and bone agonist)
Women with a uterus can be given which SERM? Raloxifene only (endometrial and breast antagonist; bone agonist); no increased risk for endometrial carcinoma via partial agonist effects
Treatment for doxorubicin cardiotoxicity Dexrazoxane (an iron chelator)
What causes hemorrhagic cystitis with cyclophosphamide use? Urinary excretion of acrolein, a toxic metabolite
Person with mass in upper lobe of lung. What will it stain + for? Neurofilaments; small cell CA of lung shows evidence of neuroendocrine differentiation
What is the main mediator of paraneoplastic cachexia? TNF-alpha (also responsible for necrosis of some tumors in vitro); acts on hypothalamus--> appetite suppression, inhibits lipoprotein lipase, and increases insulin resistance in peripheral tissues
What agent can limit the nephrotoxicity seen with cisplatin? Amifostine (also aggressive hydration); prob lower yield (not in FA)
Patient treated with MTX experiences fever, painful mouth sores, and pancytopenia. Which agent could have prevented his condition? Folinic acid (leukovorin)
Why is leukovorin (folinic acid) unaffected by MTX? B/c it doesn't req' the action of dihydrofolate reductase (which is inhibited by MTX) to be converted into tetrahydrofolate.
________ of the Rb protein results in its inactivation and allows cells with damaged DNA to proceed through the G1-->S checkpoint. Hyperphosphorylation (activated/hypOphosphorylated Rb normally stops the cell cycle from progressing when DNA is damaged)
Created by: sarah3148