Mike Ori Disclaimer These represent my understanding of the subject and have not been vetted or reviewed by faculty Use at your own peril I cant type so below are common missing letters you may need to supply ID: 1009256
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1. Slackers Cancer Molecular Biology Fact StackMike Ori
2. DisclaimerThese represent my understanding of the subject and have not been vetted or reviewed by faculty. Use at your own peril.I can’t type so below are common missing letters you may need to supplye r lI didn’t use greek letters because they are a pain to cut and paste in.
3. What are the key risk factors for colon cancer
4. AgeGeneticsChronic bowel inflammationCrohnsUCDiet
5. What are the two types of intestinal polyps
6. HyperplasticSmaller (< 5mm)Better differentiationAdenomatousLarger (>5mm)Size and dysplasia correlate with disease riskIncreased malignant potential.
7. Outline the genetic steps required for the development of colon cancer
8. Epigenetic changesLoss of growth controlLoss of WNT signaling PathwayAPC is in WNT pathwayRAS mutationsIncreases MAP kinaseIncreases PI3 kinaseLoss of suppressorsTGF-BP53APC/B-cateninGenetic instability (?)APC?Loss of apoptosis (?)P53/B-catenin
9. What is the function of the WNT pathway
10. The WNT pathway controls growth of epithelial cells via the APC and B-catenin proteins.
11. Describe the interaction of APC and B-catenin
12. APC binds free B-catenin to prevent B-catenin from initiating transcription in the nucleus.B-catenin is a component of adherens junctions and may help to signal the completion of the epithelial layer. Presumably when B-catenin is present, the layer is incomplete and cell growth ensues to fill in the layer.
13. Describe the frequency of mutation of wnt and apc in sporadic cancers
14. Wnt pathway defective in 100%APC defective in 70%
15. Describe the role of RAS in tumor development
16. RAS is a g-protein that leads to activation of downstream signaling pathways that lead proliferation
17. Describe the role of TGF-B in tumorgenesis
18. TGF-B normally halts the cell cycle in G1 to prevent proliferation and to activate differentiation or apoptosis.Loss of TGF-B allows for uncontrolled growth
19. What are the two forms of hereditary colon cancer
20. Familial adenematous polyposis (FAP)Hereditary non-polyposis colorectal cancer (HNPCC)
21. Why do molecular biologists make bad football coaches
22. Because their “simplified” playbook looks like this
23. What are the two types of genetic instability found in colon cancer
24. Chromosomal instabilityMicrosatellite instability
25. What is the failure of microsatellite instability
26. MIN results from failure of the mismatch repair mechanism
27. What is the failure in chromosomal instability
28. CIN results from defects in chromosomal segregation.
29. Relate FAP and HNPCC to MIN and CIN
30. FAP CINAPC geneHNPCCMINMSH2, MLH1, PMS2 genes
31. How many mutations are likely involved in the transformation to malignancy
32. 5-6 mutations
33. Draw a sample timeline and gene pathway leading to malignancy
34.
35. List the major types of diagnostic errors
36. Differentiate retrospective vs prospective thinking
37. Retrospective thinking such that used in CPC’s and by novice examiners relies on broad spectrum data collection with analysis performed late in the process.Prospective thinking modifies the hypothesis during the data gathering process as a result of the collected data. This in turn modifies the data collection process.
38. What is a heuristic
39. Choose the correct answerA statue of a bull commonly found in Minoan cultureA small fluid filled cyst that forms as a result of falling on the coccyx. A problem solving technique that emphasizes experience
40. What are common pitfalls of heuristics
41. AvailabilityEase of recallAnchoringInitial impressionsFraming effectsHow the problem is framed affects the thinking processBlind obedienceRemember authority figures are in charge, not all knowledgeable
42. Why are mistakes by clinicians often unrecognized
43. Happen in distant pastNot recognized as mistakes by providerPT does not return to same provider
44. What is the role of follow-up in clinical practice
45. Provides space and timeAdditional data collection (tests)ResearchTrial therapy results
46. Who is responsible for test follow-up?
47. You ordered it, you own it.
48. What are the three stages of memory?
49. EncodingAttending to the eventStorageSaving it for laterRecallGetting it back out
50. Describe the ability of the mind to process conceptual vs factual information
51. The mind is good at storing the concept (gist) of a set of facts but is relatively poor at storing the facts.An interesting aside, computers in contrast are very good at storing facts but not relating them conceptually.
52. Define impression management
53. The activities we undertake to control the impressions others have of ourselves.
54. Define self-enhancement
55. Performing actions intended to bolster the positive impression others have of us. Giving money to the poor, performing pro bono work
56. Define self verification
57. Understanding the impression others have of us and relating that back to how we see ourselves. Ideally the two will match.
58. Which type of shock is dobutamine most useful and why
59. Dobutamine is a B1 agonist (weak B2) that is useful in cardiogenic shock because it increase rate and force of contraction
60. Describe the role of dopamine in shock
61. Useful in cardiogenic shock.Interacts with dopaminergic receptors to vasodilate mesenteric and renal arterioles thus increasing renal perfusion.At moderate levels it acts as a B2 and at high levels it acts as an a1 agonist
62. What is the role of phenylephrine in shock
63. Phenylephrine is a a1 agonist that is sometimes used in septic shock as a pressor.
64. What is the role of epi and NE in hypovolemic shock
65. Relatively little. The body usually has tremendous sympathetic outflow as a result of the shock state and trauma and thus has plenty of epi/ne circulating.
66. What are the expected values for cardiac output, left ventricular end diastolic volume, and mixed venous O2 in hypovolemic, cardiogenic, and septic shock
67. OutputLVEDV/wedgeMVO2SVRHypovolemicLowLowLowHighCardiogenicLowHighLowHighSepticHighNormal?HighLow
68. What physical findings are present in metabolic syndrome
69. Impaired glucose toleranceObesityHyperlipidemiaHypertension
70. How does metabolic susceptibility relate to metabolic syndrome
71. Metabolic susceptibility is believed to be a necessary component in the development of metabolic syndrome. Its presence is inferred because some similar individuals do not progress to metabolic syndrome.
72. What role do fatty acids play in the development of insulin resistance
73. Chronically elevated fatty acids induce insulin resistance by increasing the availability of substrates that alter down-stream signaling.Specifically, excess NADH and acetyl-CoA disrupt pyruvate dehydrogenase to effectively cutoff the use of glucose as a fuel.
74. What is the role of adiponectin in metabolic syndrome?
75. Adiponectin is an anti-inflammatory cytokine that decreases in obesity. One of its roles is to decrease lipogenesis. Thus obese individuals have an increased tendency to lipogenesis.
76. What is the role of resistin in metabolic syndrome
77. Resistin is an autocrine factor that protects full adipocytes. In metabolic syndrome the large number of full adipocytes causes resistin to take on a more systemic effect wherein it begins to affect muscle cells.
78. Describe the role of insulin, TNF-a, and IL-6 in VLDL synthesis
79. VLDL is synthesized in the liver. Both TNF-a and IL-6 increase its synthesis and both are increased in obesity. Normally, insulin would activate lipoprotein lipase in the periphery to encourage the uptake of the fatty acids in the VLDL but in insulin resistance, this action is diminished. Thus, the body creates more VLDL’s than usual but they are not degraded. As the levels of VLDL increase some will be broken down; resulting in increased LDL.
80. Describe the role of insulin in liver of metabolic syndrome
81. Insulin normally promotes the mobilization of glucose transporters to the membrane, the conversion of glucose to glycogen, and the conversion of acetyl-coa to fatty acids. With insulin resistance, glucose uptake and glycogenolysis are both impaired.
82. Explain the origin of the prothrombotic state associated with diabetic patients
83. Excess production of TNF-a and IL-6 coupled with a decrease in adiponectin leads to an inflammatory state. This in turn causes the liver to synthesize more fibrinogen and plasminogen activator inhibitor 1.
84. List the management goals for diabetic patients
85. A1C < 7%LDL < 100Systolic BP < 130
86. List the macronutrient proportions for patients with diabetes
87. CHO = 50%Fat = 30%Protein = 20%
88. What are the common receptors used in the prognosis and treatment of breast cancer
89. Estrogen receptorProgesterone receptorHer2/Neu/ErbB2
90. What is a gatekeeper
91.
92. Seriously, what is a gatekeeper
93. A gene that acts by directly suppressing cell proliferation
94. What is a caretaker
95. A gene that functions to maintain genenome stability
96. Is BRCA1/2 a gatekeeper or caretaker
97. Caretaker
98. What is the function of BRCA1/2
99. They are involved in homology directed repair of DS DNA breaks
100. What attributes are beneficial for screening and diagnostic tests
101. Screening tests need to be cheap, quick, easy, and sensitive. They do not have to be very specific.The ideal diagnostic tests need to be sensitive and specific. If they aren’t sensitive then they at least need to be specific.Is a home pregnancy test a screening or a diagnostic test?
102. What are the common viruses associated with cancer.
103. HIV actionHTLV1Adult T-cell leukemiaNone listedHPVSquamous cell carcinomasViral escape via immune suppressionEBVLymphomasCo factorHBVHepatocellular carcinomaNone listedHCVHepatocellular carcinomaNone listedKSVKaposi sarcomaCofactor via cytokinesHIVLymphoma, SCC, Body cavity lymphoma, primary CNS lymphoma, kaposi
104. What are the molecular events leading to cancer from viruses
105. HTLV1TAX gene drives replication. /\ cyclin D, /\ NF-kappa-BHPVViral E6 and E7 interfere with P53 and P21EBVViral LMP1 acts like CD40 ligand to drive proliferation, viral EBNA2 /\ cyclin D, Viral IL10 prevents macrophage activation of T-cellsHBVNo oncogenes. Chronic inflammationHCVNo oncogenes. Chronic inflammationKSVViral VEGF. P53 suppression. Viral cyclin D analogueHIV
106. Differentiate descriptive and inferential statistics
107. DescriptiveDescribe qualities about the data but cannot be used to inferInferentialCan be used to draw conclusions
108. Define nominal and ordinal data
109. NominalData described by labels of no numerical significance. Numerical operations are not possible even if the data appear to be numeric. For instance, the subtraction of two zip codes has no meaning.Only mode has meaningOrdinalA rank ordered category such as least to most, worst to best, pain levels, satisfaction, etcThere is intrinsic order but the value between each item is variable. For instance, what is the quantitative difference between somewhat satisfied and satisfied.Some numerical operations are allowedMode and median have meaning
110. Describe the types of metric data
111. Physical measurement or countingAll numerical operations are allowedModeMedianMeanVariable has equal intervals between values.IntervalMetric data with an arbitrary zeroRatioMetric data with a meaningful 0
112. What is the worst statistical error type, type I or type II
113. Type I is worstReject the null hypothesis (H0) even though its true. So we found something that isn’t there. In other words, we’ll treat with snake oil.Note that type II accepts the null hypothesis even though its false. Thus we will withhold a useful treatment because we fail to recognize that it is useful.