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Drug Action IV > Neoplasia (Patho) - Block 4 > Flashcards

Neoplasia (Patho) - Block 4 Flashcards

1
Q

All cancer is ____ resulting from damaged DNA and RNA?

A

Genetic

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2
Q

What are the purines?

A

Adenine and Guanine

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3
Q

What are the pyrimidines?

A

Thymine
Cytosime
Uracil

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4
Q

What is redundancy?

A

Most amino acids are specified by more than one mRNA codon

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5
Q

Before the mitotic phase, the DNA must ___?

A

replicate

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6
Q

What are the check points of the cell cycle?

A
  1. Near the end of G1
  2. At the G2/M transition
  3. During metaphase
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7
Q

Describe the process of DNA replication?

A
  1. Enzymes unwinds the double helix and expose the bases
  2. Parental strand acts as a template for synthesis of new strand
  3. Two new strands (leading and lagging) are synthesized in opposite directions

This process is called semiconservative replication

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8
Q

What is mitotic recombination?

A

Type of genetic recombination that occurs in somatic cells during their prep for mitosis

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9
Q

Process of abnormal growth of cells.

A

Neoplasia

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10
Q

Abnormal growth of cells

A

Tumor (neoplasm)

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11
Q

Condition caused by genetic alterations and defective cell functions?

A

Cancer

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12
Q

Decreased cell size due to resorption and breakdown

A

Atrophy

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13
Q

Increased cell size?

A

Hypertrophy

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14
Q

Increased cell number due to increased reproduction rate

A

Hyperplasia

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15
Q

Transformation of one differentiated cell to another?

A

Metaplasia

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16
Q

Abnormal cell development?

A

Dysplasia

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17
Q

Poor cellular differentiation

A

Anaplasia

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18
Q

What are the characteristics of benign neoplasms?

A

Tumor is localized and doesn’t invade or spread to other tissues:
1. Non cancerous
2. Slow development
3. No spreading
4. Well diffentiated
5. Rarely life-threatening

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19
Q

What are the characterisitcs of malignant neoplasms?

A

Tumor that invades surrounding tissues or spreads to other parts of the body:
1. Cancerous
2. Grows quickly
3. Life-threatening
4. Loss of control of cell division
5. Poorly differentiated

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20
Q

Distinguish the types of malignant neoplasms?

A

Carcinoma: Epithelial tissue
Sarcoma: Mesenchymal tissue
Leukemias: Hematopoietic or lymphoid tissue

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21
Q

What is a cell cycle?

A

Period of time from one cell division to the next

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22
Q

What is the function of a cell cycle checkpoint?

A

To take into account the errors in DNA

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23
Q

What occurs during G1?

A

Cell growth and DNA is prepared to be copied
* Tumor suppressor stops cell progression

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24
Q

What occurs during S phase?

A

Copies all chromosomes in the cells
* Tumor suppressor stop progression of the cell cycle and activate DNA repair enzymes.

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25
Q

What occurs during G2 phase?

A

Production of mitotic spindles and proteins for cell division

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26
Q

What occurs during mitosis?

A

Division into 2 genetically identical daughter cells

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27
Q

What occurs during G0?

A

Daughter cells have a temporary or permanent rest from cell division

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28
Q

What are the proteins associated with cell cycle checkpoints?

A
  1. Kinase enzymes (catalytic)
  2. Cyclins (regulatory subunits)
  3. Proteins that inhibits the kinase enzymes
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29
Q

What activates CDKs?

A

Cyclins

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30
Q

How are CDKs affected by cancer?

A

CDK mutations lead to constitutive mitogenic signaling and hyperactivation of CDKs -> tumor formation from amplified and unregulated cell division

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31
Q

What is the overall function of CDKIs?

A

Promotes tumor suppression

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32
Q

What is differentiation?

A

Maturation of a normal cell to one with distinct morphology

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33
Q

Describe the grading of cell differntiation?

A

1-4: The lower number (low grade) is more/well differentiated

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34
Q

What factors affecting the development of cancer?

A

Genetic and environment alter gene products (proteins) or a cell or tissue

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35
Q

What is a silent point mutation?

A

A base substitution in the 3rd codon to where gene product is unaltered

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36
Q

What is missense point mutations?

A

Occur when an ammino acid in the sequence is replaced

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37
Q

What is nonsense point mutation?

A

Base substitution results in a stop codon -> gene product is truncated and nonfunctional

38
Q

What is the difference between deletion and isertion?

A

Deletion: at least one base pair is lost from a sequnce of DNA
Insertion: additional base pairs lead to a frameshift mutation

39
Q

What is the function of a tumor suppressor gene

A

Responsible for inhibiting cell replication or braking cell growth

40
Q

That is considered the guardian of the genome?

A

TP53

41
Q

Normal genes responsible for regulation of proliferation of cells.

A

Proto-oncogenes

42
Q

Mutated form of a gene that, when upregulated, can allow continuous and ongoing cell growth

A

Oncogene

43
Q

When a piece of one chromosome breaks off and fuses to another chromosome

A

Chromosome translocation

44
Q

What is the hallmark of leukemias and lymphomas?

A

Philadelphia chromosome

45
Q

Suppression of what gene leads to the regression of all tumors when doxycycline is administered?

A

Myc oncogene

46
Q

What is the mutator gene?

A

Increases the rate of mutation of one or more genes

47
Q

What is microsatellile instability?

A

Genetic hypermutability -> impaired DNA mismatch repair

48
Q

What method has the highest frequency of mutations in malignant cells?

A

Mutator phenotyped

49
Q

What is clonal expansion?

A

A cell that acquires a mutation that increases its fitness -> generating more daughter cells than competitor cells that lack that mutation

50
Q

Specific genes that are responsible for chromosomal instability?

A

Drivers

51
Q

Chromosomal deletions are associated most often with what type of tumors?

A

Solid

52
Q

An abnormal chromosome number and can involve a loss or gain of chromosomes.

A

Aneuploidy

53
Q

An increase in the number of gene copies that results in elevations of the protein without modification of the gene itself.

A

Gene amplification

54
Q

What is the function of microRNA?

A

Noncoding RNA that control gene expression and regulates mRNA exprssion post-transciption

55
Q

What are the downstreem effects caused by dysregulated microRNA?

A
  1. Sustain proliferative signaling
  2. Evade growth suppressors
  3. Resist cell death
  4. Activate invasion and metastasis (angiogenesis)
56
Q

What are growth facotrs?

A

Proteins that act outside the cell as chemical signals to regulate cellular behavior

57
Q

What pathways mediated signal transduction from growth factors?

A

Ras/Raf/MEK/ERK

58
Q

What is the function of G proteins?

A

Singal transducers (on-off switches)

59
Q

What superfamily is often times mutated to form malignant transformation?

A

RAS proto-oncogne

60
Q

What is Loss of heterozygosity?

A

Mutation that confines genes with recessive status from the loss of one normal copy of a gene or group of genes

61
Q

The process where normal cells become cancer cells?

A

Carcinogenesis

62
Q

Describe the stochastic model

A

Each cancer cell has the ability to proliferate and form a variety of new tumors from the same tissue of origin

63
Q

What is the cancer stem cell model?

A

Suggest that most cells have limited ability to proliferate while the stem cells are responsible for forming sites for growth of new tumors
* Cancer stems don’t rapidly divide making them insensitive to chemo and radiation

64
Q

What factors stimulate angiogenesis?

A
  1. Hypoxia
  2. Glucose uptake and glycolysis to generate energy
  3. Lactate is produced -> decreased ATP (Warburg effect)
65
Q

What is angiogenesis?

A

VEGF causes the growth of new vessels -> formation of microcirculatory system for the tumor

66
Q

What GF are overexpressed in cancer?

A
  1. EGFR
  2. HER2
  3. TGF-b

Changes in proliferative signals

67
Q

Describe the steps of carcinogenesis?

A

Initiation: Cancer-causing agent damages DNA
Promotion: Carcinogen introduced to cell -> clonal expansion and acquire mutation (benign)
Progression: Accumulation of mutations -> malignancy

68
Q

The patterns of spread of cancer cells may depend on what factor?

A

Host’s immune status

69
Q

What are the cellular functions of malignant cells?

A
  1. Altered cyctoskeletal control
  2. Prevents normal function of the microtubules
  3. Modification of external cytoskeleton
  4. HLA is lost -> cancer cell becomes unidentifiable (Malignant cells are able to masquerade as normal cells)
  5. Loss of fibronectin
  6. Alterations in lectin binding
70
Q

In normal cells, dysregulated glycosylation triggers cell apoptosis through what pathway? How does that compare to tumor cells?

A

Lectin signaling

In tumor cells the lectin pathway is impaired (TME-mediated alterations in endothelial cell glycosylation)

71
Q

What are primary tumors?

A

Tumors that metastasize to organ sites (lung and liver commonly) -> secretion of lytic enzymes to spread cancer

72
Q

What is the function of ADAMs family protease?

A

Causes shedding of extracellular domains of GF, cytokines, and adhesion proteins, so they can’t bind along the outside of the plasma membrane -> released by the cancer cells

73
Q

Examples of inappropriate hormones produced by tumors?

A
  1. ObGFs (prostate and breast cancer)
  2. OcAFs (breast cancer)
  3. ACTH (neuroendocrine tumors)
74
Q

What is the most common type of cancer in women? Men? Children?

A

Breast; prostate; Leukemia (brain or spinal cord are second most common in children)

75
Q

What are clinical presentations of cancer?

A

Change in bowel habits
A sore that doesn’t heal
Unusual bleeding or discharge
Thickening or lump in the breat or any part of the body
Indigestion or difficulty swallowing
Obvious change in a mole
Nagging cough or hourseness

76
Q

What are the clinical manifestations of childhood cancer?

A

Continued weight loss
Headaches
Increased pain
Lumps
Development of bruising, bleeding, or rash
Hard time sleeping
Obvious paleness
Occur suddenly and persist
Diseases that are uncommon
Constatn infection
A whitish color behind pupil
Nausea
Constant tiredness
Eye changes
Recurring fever of unknown origin

77
Q

What are the local effects of cancer?

A
  1. occlusion
  2. Destruction of critical structures
  3. Ulceration
  4. Tumor infarction
  5. Abscess formation
78
Q

Differentiate the cytokines released by tumors in order to produce systemic effects?

A

TNF: produces cachexia and muscle wasting
IL-6: Secreted during inflammation
PIF: Proteolysis inducing factor

79
Q

What is cachexia?

A

Wasting disorder that causes extreme weight loss and muscle wasting, may include loss of body fat

80
Q

What is the first inidcation that a patient has cancer?

A

Paraneoplastic syndromes:
1. Endocrine: ectopic hormones
2. Hematologic: anemia
3. Dermatologic: pruritis
4. Neurologic: eripheral neuropathies, cerebellar, and other central neurological paraneoplastic syndromes -> changes in sensations

81
Q

What are tumor markers?

A

Molecules in blood, urine, other fluids that indicate a change in tumor growth status

82
Q

What diagnosis method is used to provide a histology grade of a tumor?

A

Biopsy: extraction of tissue
1. Fine needle aspiration
2. Core needle
3. Incisional
4. Excisional

83
Q

What is the difference between the radiographic tests used to identify cancer?

A

PET: used to identify increased metabolism
CT: Uses a computer to construct a series of cross-sectional scans obtained by examining body organs with X-ray

84
Q

What is the cancer staging system used globally?

A

TNM: Tumor, node, meastasis

85
Q

What are the classifcations of for tumor sites?

A

Clincal staging: completed at initial workup
Pathologic staging: completed from information identified by the pathologist
Posttherapy staging: Based on info after tx
Retreatment staging: Based on info obtained after exacerbation or disease progression
Autopsy staging: completed upon death of the patient by the med examiner

86
Q

What is the oldest, most researches, and most sucessful therapy for cancer?

A

Surger

87
Q

What are the usual targets of chemotherapy?

A

Target the cell cycle or specific phases in the cycle

88
Q

What is radiation therapy?

A

Used to treat localized cancers through ionized particles

89
Q

What is the function of biologic therapies to combat cancer?

A

Enhance the ability of the body to use its natural defenses to fight cancer

89
Q

Another name for targeted therpaies?

A

Personalized medicine: targets the hallmarks of cancer growth with less toxicity than conventional chemo

90
Q

Indications for stem cell transplant?

A

Uses multiple types of cancer tx: leukemia, lymphoma, myelomas, neuroblastoma, germ cell tumors, ewing sarcoma

Drug Action IV (28 decks)

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