BIO302 Exam 1 Study Guide PDF

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TRUE: Compared to other major diseases, cancer death rates have changed little over the past 60 years. TRUE: More and more people are getting cancer because we live longer now and cancer increases with age. TRUE: Cancer is a global problem. o More than 60% of the world’s new cancer cases occur in Africa, Asia, and Central/South America TRUE: In 2003, despite increasing population size and lifespan, the American Cancer Society announced the total number of deaths from cancer in the U.S. TRUE: Recent statistics show decreases in mortality rates for some cancers (lung, breast, colon, prostate) TRUE: Cancer death rates have fallen 25% since 1991. TRUE: A single nucleotide polymorphism (SNP) is found in more than 1% of the population, while a mutation is found in less than 1% of the population TRUE: Mutations can be repaired or cells can be prevented from mutating from replicating by mutation control. TRUE: Mutations happen all the time in human cells but are normally repaired or eliminated to maintain order and stability within the organism. TRUE: There are multiple highly evolved cellular mechanisms that exist to protect against changes in DNA (mutations) that occur as part of life. TRUE: In normal cells, if DNA damage can’t be repaired, programmed death of cells or immune destruction of cells occurs. TRUE: The development of cancer requires the loss, malfunction, or overriding of normal mutation control mechanisms. TRUE: The loss of control seen in cancer cells is itself caused by mutation in control mechanisms. TRUE: All processes involved in the development of cancer are integrally linked to fundamental mammalian biology and the evolution of biological life itself. TRUE: Elimination of cancer would require elimination of mutation. TRUE: Mutation is integral to normal biology and cannot be eliminated. TRUE: Cancer can never be eliminated as a disease process. TRUE: We are evolved to be susceptible to cancer. TRUE: Genomic “instability” is fundamental to cancer’s ability to acquire new traits and pass them on to progeny TRUE: Genomic instability leads to accumulation of key (“driver”) mutations required for cancer progression. TRUE: Genes that drive cell division are always “on” or gain function. TRUE: Not all tumors are cancer but all tumors are abnormal and require diagnosis TRUE: Most cancers come from dysplasias, not benign neoplasms TRUE: Dysplastic cells typically grow in masses and form benign tumors

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TRUE: Expansion of dysplastic cells occurs within flat surface, has ill-defined borders, and cannot be identified with the naked eye TRUE: Biopsies and cytology with microscopic examination is required for diagnosis TRUE: Carcinoma is by far the most common human malignancy TRUE: Carcinoma in situ never metastasizes TRUE: Not all carcinogens are mutagens, but all mutagens are carcinogens TRUE: Most cancer-initiating mutations are acquired, not inherited TRUE: Somatic mutations cannot be inherited, while germline mutations can be inherited. TRUE: Cancer is primarily an environmental disease. TRUE: Laboratory studies in humans that are analogous to those in non-human systems are unethical. FALSE: Some carcinogens have been found to always cause cancer, under all circumstances. TRUE: There are some substances in vegetables and fruits that may help protect against cancer, especially in cruciferous vegetables! TRUE: Viruses associated with human cancers include: Hep B/C and HIV. TRUE: Most cancer can be prevented through behavior change. TRUE: A causal factor is a determining element of a disease. TRUE: Detection by screening decreases the time to diagnosis and treatment. TRUE: Sensitivity does not take false positives into account and specificity does not take false negatives into account. TRUE: All causal factors are risk factors for cancer, but not all risk factors are causal TRUE: Cancers generally take years to develop following carcinogen exposure. TRUE: Some of the agents that are used to treat cancer also cause cancer. TRUE: The right therapy and management are dependent on the right diagnosis and assessment. TRUE: For most cancers, there are no effective screening tests. TRUE: The rarer the disease, the more likely false positives are to be. TRUE: Our most effective screening tools are the Pap smear and colonoscopy TRUE: PSA-based screening is Grade D, meaning it is highly discouraged. TRUE: Physician education is highly necessary because the large number of uninformed patients is related to the large number of uniformed clinicians. TRUE: Mortality rates are the only way to judge cancer screening accurately. TRUE: The two types of bias that mislead physicians into thinking screening saves lives are lead time bias and over-diagnosis bias TRUE: The goal of screening is to detect disease early and treat before cancer has progressed. TRUE: Effective screening is defined by a decrease mortality from the disease in the screened versus unscreened population TRUE: The benefit-to-harm ratio of screening tests depends on false negative and false positive rates. TRUE: The predictive value of a screening test depends on the prevalence of the disease.

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TRUE: Cancer site implies survival differences. TRUE: The less resemblance to normal morphology, the higher the grade. TRUE: High grade tumors grow and spread more aggressively and are less responsive to therapy than low grade tumors. TRUE: Grade of cancer is based on degree of differentiation of cancer cells. TRUE: Stage of cancer is based on how far cancer has progressed at diagnosis based on extent of local tumor and spread of disease (TNM system) TRUE: The greater the spread, the higher the stage. TRUE: Survival correlates with stage (highest stage being incurable) TRUE: Stage is a more powerful predictor of outcome than grade and is more clinically useful in classifying patients. TRUE: The higher the tumor grade and stage, the lower the probability of survival

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The mortality rate is the cancer deaths per 100,000 population per year The biggest factor in improved prevention, detection, and treatment is the decline in smoking Natural evolution is the mutation and selection that favors “fitness” with respect to competition, adaptation, and survival within a physical environment Cancer evolution is the mutation and selection that favors “fitness” with respect to competition, adaptation, and survival within the body’s biological environment A permanent change in the nucleotide sequence of DNA that can be passed on to daughter cells with mitosis is called a mutation A specific type of mutation that is considered to be in the realm of normal human variation is a single nucleotide polymorphism A SNP is defined by convention according to frequency The acquired characteristics cancers have in common include: o Uncontrolled cell division o Invasion and destruction of normal tissues o Metastasize: Ability to travel to and colonize other parts of the body Hallmarks of cancer include abnormal form and function. Some examples of abnormal form include: abnormal cytology and abnormal tissue (histopathological) morphology Some examples of abnormal function include: o Resistance to cell death o Sustaining of proliferative signaling o Evasion of growth suppression o Limitless replicative potential o Ability to invade and metastasize o Induction of new blood supply (angiogenesis) “Cancer” is the term that refers to a group of diseases in which abnormal cells:  o Divide without control o Invade (and destroy) other tissues without control o Metastasize (travel to other parts of the body through the blood and lymph) The process of a normal cell turning cancerous is called carcinogenesis

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Carcinogenesis always requires mutation in the genome of the cell (initiation) AND proliferation (growth) of the genetically altered cell (promotion) Additional mutations accumulate in a multistep process with growth over time (progression) A mass of abnormal (mutated) cells is called a neoplasm Normal cell growth includes hypertrophy (increase in cell size) and hyperplasia (increase in cell number), while abnormal cell growth includes dysplasia (precancer; does not form mass/tumor) and neoplasia (benign or malignant) Dysplasia and neoplasia are irreversible Initiators cause mutation in one cell capable of dividing Promoters promote clonal expansion (proliferation) of initiated (mutated) cells, but don’t affect normal cells Progressors cause additional mutations that confer additional growth-aggressive changes Low grade dysplasia occurs when initiated cell clones gain additional proliferative advantage and begin to change their morphology High grade dysplasia (carcinoma in situ) occurs when more mutations happen within proliferative cell line lead to development of pre-invasive cancer; it is high risk for progression to cancer and must be treated!! Invasive carcinoma (malignant neoplasm) invades through basal lamina is now classified as malignant and considered capable of metastasis. This is the beginning of epithelial-mesenchymal transformation Cancer cells with migratory and invasive properties break through walls of lymphatics or blood vessels in metastasis Carcinoma is cancer arising from epithelial cells (covering/lining cells) Keratin “pearl” is a concentric collection of cornified squamous cells seen in carcinoma Sarcoma is cancer arising from connective tissue cells Lymphoma is cancer that arises from immune system cell precursors in bone marrow or lymph nodes Systemic Leukemia arises from blood forming cells in bone marrow Melanoma arise from pigment-producing cells in epithelia Acute lymphocytic leukemia happens when leukemic cells have replaced normal blood forming cells Anaplastic refers to cancers that are unclassifiable because they are so undifferentiated Neoplasias are abnormal tissue growths characterized by mutation, abnormal cell appearance, abnormal tissue architecture, and growth advantage Neoplasms are classified by their site of origin and their predominant cell type (differentiation pattern) Carcinogens are agents that cause cancer Mutagens are agents that alter DNA Empirical science includes information gained by experience, observation, or experiment  observation, induction, deduction, testing Causal factors are those that are mutation-causing risk factors

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Causal inference is the process of deriving cause-and-effect conclusions by reasoning from knowledge and factual evidence  reduction in risk with removal of exposure, consistency of association, biological plausibility Risk factors are characteristics, conditions, or behaviors that increase probability of a cancer; vary in degree of risk imposed and may/may not be a causal factor o Some can be treated: chronic inflammation, viral infections, bacterial infections, diabetes, etc o Tobacco and diet/obesity are biggest causes of cancer Obesity is associated with substantial metabolic and endocrine abnormalities and has been linked to 13 different cancers Screening for cancer involves testing people without symptoms and testing defined populations (usually those at risk) A test’s ability to correctly identify those WITH the disease is test sensitivity A test’s ability to correctly identify those WITHOUT the disease is test specificity Test performance is depicted by the RoC curve, where the area under curve (AUC) represents perfection, measuring the diagnostic accuracy across spectrum of test values The probability that an individual is affected by the disease when the test result is positive (counting false positives) is the positive predictive value    o  =     The probability that an individual is not affected by the disease when the test result is negative (counting false negative) is the negative predictive value   o  =     Diagnosis is the identification of a disease in an individual through process of evaluation and elimination Symptoms include patient’s perceptions, while signs are examiner’s observations TNM Staging System refers to tumor, nodes, and metastases progression.

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Imhotep: documents first reported case of cancer Hippocrates: uses word carcinoma to describe tumors and recognizes benign versus malignant Galen: Uses word “oncos” meaning “mass” to describe tumors Celsus: translates word crab into Latin as “cancer” Sir Percivall Pott: first demonstrated cancer can be caused by environment Rudolf Virchow: discovered cancer is made up of otherwise normal cells Theodor Boveri: suggested that cancer comes from single somatic cell with chromosomal alterations causing uncontrolled growth  Thomas Hunt Morgan: demonstrated genes are carried on chromosomes, validating Boveri’s hypothesis Paul Ehrlich: coined term “chemotherapy” and developed concept of using chemicals to treat disease  Sir Austin B. Hill and Sir Richard Doll: Linked smoking and lung cancer 

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William S. Halsted: Developed “radical mastectomy” procedure with the notion that the wider the excision, the greater the chance of preventing metastasis and curing disease Claudius Regaud: Showed normal tissue sparing effects by reducing dose rates and delivering doses at spaced intervals could stop rapidly growing cells like cancer George Papanicolaou: Developed Pap test for early detection of cervical cancer Sidney Farber: Achieved first remission of cancer using drugs; father of chemotherapy Peter Nowell and David Hungerford: reported recurrent chromosomal translocation (Philadelphia chromosome in CML cells) Henry S. Kaplan: established importance of clinical staging and used radiation therapy to successfully treat Hodgkin’s disease Vincent T. Devita: developed first combination therapy to produce a high proportion of complete remission and cure (MOPP) Bernard Fisher: lumpectomy just as effective as radical mastectomy for breast cancer Harald Zur Hauzen: Discovered causal link between HPV (Human Papilloma Virus) and cervical cancer, leading to development of a vaccine Michael Bishop and Harold Varmus: discovered viral genes with ability to cause cancer are derived from mammalian genome (cancer causation is innate)  Weinberg, Wigler, and Barbacid: simultaneously discovered first human oncogene (RAS) Webster Cavenee: first validation of presence of tumor suppressor gene in humans Brian Druker: discovered CML is caused by a single driver mutation and its oncoprotein; able to provide a cure to formerly incurable disease Dennis Slamon: identified amplified oncogene in breast cancer Gordon Freeman: discover PD-L1 is expressed by cancer cells, allowing them to evade immune destruction

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National Cancer Institute: Federal government’s primary agency for cancer research and training National Cancer Act: Amended Public Health Service Act to strength NCI The Cancer Genome Atlas: Goal to define and catalog all genomic defects in cancers International Agency for Research on Cancer: evaluates risk of carcinogenicity with Group 1 being worst and Group 4 being decent (lists those found not to be carcinogens) The Report on Carcinogens (RoC) lists two groups, those known to be human carcinogens and those reasonably anticipated to be human carcinogens U.S. Preventative Services Task Force gives evaluations and recommendations (grades) regarding cancer treatments and practices ...