Neoplasia (Patho) - Block 4 Flashcards
1
Q
All cancer is ____ resulting from damaged DNA and RNA?
A
Genetic
2
Q
What are the purines?
A
Adenine and Guanine
3
Q
What are the pyrimidines?
A
Thymine
Cytosime
Uracil
4
Q
What is redundancy?
A
Most amino acids are specified by more than one mRNA codon
5
Q
Before the mitotic phase, the DNA must ___?
A
replicate
6
Q
What are the check points of the cell cycle?
A
- Near the end of G1
- At the G2/M transition
- During metaphase
7
Q
Describe the process of DNA replication?
A
- Enzymes unwinds the double helix and expose the bases
- Parental strand acts as a template for synthesis of new strand
- Two new strands (leading and lagging) are synthesized in opposite directions
This process is called semiconservative replication
8
Q
What is mitotic recombination?
A
Type of genetic recombination that occurs in somatic cells during their prep for mitosis
9
Q
Process of abnormal growth of cells.
A
Neoplasia
10
Q
Abnormal growth of cells
A
Tumor (neoplasm)
11
Q
Condition caused by genetic alterations and defective cell functions?
A
Cancer
12
Q
Decreased cell size due to resorption and breakdown
A
Atrophy
13
Q
Increased cell size?
A
Hypertrophy
14
Q
Increased cell number due to increased reproduction rate
A
Hyperplasia
15
Q
Transformation of one differentiated cell to another?
A
Metaplasia
16
Q
Abnormal cell development?
A
Dysplasia
17
Q
Poor cellular differentiation
A
Anaplasia
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
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
20
Q
Distinguish the types of malignant neoplasms?
A
Carcinoma: Epithelial tissue
Sarcoma: Mesenchymal tissue
Leukemias: Hematopoietic or lymphoid tissue
21
Q
What is a cell cycle?
A
Period of time from one cell division to the next
22
Q
What is the function of a cell cycle checkpoint?
A
To take into account the errors in DNA
23
Q
What occurs during G1?
A
Cell growth and DNA is prepared to be copied
* Tumor suppressor stops cell progression
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.
25
What occurs during G2 phase?
Production of mitotic spindles and proteins for cell division
26
What occurs during mitosis?
Division into 2 genetically identical daughter cells
27
What occurs during G0?
Daughter cells have a temporary or permanent rest from cell division
28
What are the proteins associated with cell cycle checkpoints?
1. Kinase enzymes (catalytic)
2. Cyclins (regulatory subunits)
3. Proteins that inhibits the kinase enzymes
29
What activates CDKs?
Cyclins
30
How are CDKs affected by cancer?
CDK mutations lead to constitutive mitogenic signaling and hyperactivation of CDKs -> tumor formation from amplified and unregulated cell division
31
What is the overall function of CDKIs?
Promotes tumor suppression
32
What is differentiation?
Maturation of a normal cell to one with distinct morphology
33
Describe the grading of cell differntiation?
1-4: The lower number (low grade) is more/well differentiated
34
What factors affecting the development of cancer?
Genetic and environment alter gene products (proteins) or a cell or tissue
35
What is a silent point mutation?
A base substitution in the 3rd codon to where gene product is unaltered
36
What is missense point mutations?
Occur when an ammino acid in the sequence is replaced
37
What is nonsense point mutation?
Base substitution results in a stop codon -> gene product is truncated and nonfunctional
38
What is the difference between deletion and isertion?
**Deletion:** at least one base pair is lost from a sequnce of DNA
**Insertion:** additional base pairs lead to a frameshift mutation
39
What is the function of a tumor suppressor gene
Responsible for inhibiting cell replication or braking cell growth
40
That is considered the guardian of the genome?
TP53
41
Normal genes responsible for regulation of proliferation of cells.
Proto-oncogenes
42
Mutated form of a gene that, when upregulated, can allow continuous and ongoing cell growth
Oncogene
43
When a piece of one chromosome breaks off and fuses to another chromosome
Chromosome translocation
44
What is the hallmark of leukemias and lymphomas?
Philadelphia chromosome
45
Suppression of what gene leads to the regression of all tumors when doxycycline is administered?
Myc oncogene
46
What is the mutator gene?
Increases the rate of mutation of one or more genes
47
What is microsatellile instability?
Genetic hypermutability -> impaired DNA mismatch repair
48
What method has the highest frequency of mutations in malignant cells?
Mutator phenotyped
49
What is clonal expansion?
A cell that acquires a mutation that increases its fitness -> generating more daughter cells than competitor cells that lack that mutation
50
Specific genes that are responsible for chromosomal instability?
Drivers
51
Chromosomal deletions are associated most often with what type of tumors?
Solid
52
An abnormal chromosome number and can involve a loss or gain of chromosomes.
Aneuploidy
53
An increase in the number of gene copies that results in elevations of the protein without modification of the gene itself.
Gene amplification
54
What is the function of microRNA?
Noncoding RNA that control gene expression and regulates mRNA exprssion post-transciption
55
What are the downstreem effects caused by dysregulated microRNA?
1. Sustain proliferative signaling
2. Evade growth suppressors
3. Resist cell death
4. Activate invasion and metastasis (angiogenesis)
56
What are growth facotrs?
Proteins that act outside the cell as chemical signals to regulate cellular behavior
57
What pathways mediated signal transduction from growth factors?
Ras/Raf/MEK/ERK
58
What is the function of G proteins?
Singal transducers (on-off switches)
59
What superfamily is often times mutated to form malignant transformation?
RAS proto-oncogne
60
What is Loss of heterozygosity?
Mutation that confines genes with recessive status from the loss of one normal copy of a gene or group of genes
61
The process where normal cells become cancer cells?
Carcinogenesis
62
Describe the stochastic model
Each cancer cell has the ability to proliferate and form a variety of new tumors from the same tissue of origin
63
What is the cancer stem cell model?
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
What factors stimulate angiogenesis?
1. Hypoxia
2. Glucose uptake and glycolysis to generate energy
3. Lactate is produced -> decreased ATP (Warburg effect)
65
What is angiogenesis?
VEGF causes the growth of new vessels -> formation of microcirculatory system for the tumor
66
What GF are overexpressed in cancer?
1. EGFR
2. HER2
3. TGF-b
Changes in proliferative signals
67
Describe the steps of carcinogenesis?
**Initiation:** Cancer-causing agent damages DNA
**Promotion:** Carcinogen introduced to cell -> clonal expansion and acquire mutation (benign)
**Progression:** Accumulation of mutations -> malignancy
68
The patterns of spread of cancer cells may depend on what factor?
Host's immune status
69
What are the cellular functions of malignant cells?
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
In normal cells, dysregulated glycosylation triggers cell apoptosis through what pathway? How does that compare to tumor cells?
Lectin signaling
In tumor cells the lectin pathway is impaired (TME-mediated alterations in endothelial cell glycosylation)
71
What are primary tumors?
Tumors that metastasize to organ sites (lung and liver commonly) -> secretion of lytic enzymes to spread cancer
72
What is the function of ADAMs family protease?
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
Examples of inappropriate hormones produced by tumors?
1. ObGFs (prostate and breast cancer)
2. OcAFs (breast cancer)
3. ACTH (neuroendocrine tumors)
74
What is the most common type of cancer in women? Men? Children?
Breast; prostate; Leukemia (brain or spinal cord are second most common in children)
75
What are clinical presentations of cancer?
**C**hange in bowel habits
**A** sore that doesn't heal
**U**nusual bleeding or discharge
**T**hickening or lump in the breat or any part of the body
**I**ndigestion or difficulty swallowing
**O**bvious change in a mole
**N**agging cough or hourseness
76
What are the clinical manifestations of childhood cancer?
**C**ontinued weight loss
**H**eadaches
**I**ncreased pain
**L**umps
**D**evelopment of bruising, bleeding, or rash
**H**ard time sleeping
**O**bvious paleness
**O**ccur suddenly and persist
**D**iseases that are uncommon
**C**onstatn infection
**A** whitish color behind pupil
**N**ausea
**C**onstant tiredness
**E**ye changes
**R**ecurring fever of unknown origin
77
What are the local effects of cancer?
1. occlusion
2. Destruction of critical structures
3. Ulceration
4. Tumor infarction
5. Abscess formation
78
Differentiate the cytokines released by tumors in order to produce systemic effects?
**TNF:** produces cachexia and muscle wasting
**IL-6:** Secreted during inflammation
**PIF:** Proteolysis inducing factor
79
What is cachexia?
Wasting disorder that causes extreme weight loss and muscle wasting, may include loss of body fat
80
What is the first inidcation that a patient has cancer?
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
What are tumor markers?
Molecules in blood, urine, other fluids that indicate a change in tumor growth status
82
What diagnosis method is used to provide a histology grade of a tumor?
Biopsy: extraction of tissue
1. Fine needle aspiration
2. Core needle
3. Incisional
4. Excisional
83
What is the difference between the radiographic tests used to identify cancer?
**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
What is the cancer staging system used globally?
**TNM:** Tumor, node, meastasis
85
What are the classifcations of for tumor sites?
**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
What is the oldest, most researches, and most sucessful therapy for cancer?
Surger
87
What are the usual targets of chemotherapy?
Target the cell cycle or specific phases in the cycle
88
What is radiation therapy?
Used to treat localized cancers through ionized particles
89
What is the function of biologic therapies to combat cancer?
Enhance the ability of the body to use its natural defenses to fight cancer
89
Another name for targeted therpaies?
Personalized medicine: targets the hallmarks of cancer growth with less toxicity than conventional chemo
90
Indications for stem cell transplant?
Uses multiple types of cancer tx: leukemia, lymphoma, myelomas, neuroblastoma, germ cell tumors, ewing sarcoma
