Anticancer Therapies Radiation and Drugs Flashcards

(105 cards)

1
Q

Key properties of cancer cell (2)

A

They reproduce without regard to the normal restraints on cell growth and cell division
They invade and colonize areas normally reserved for other cells

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2
Q

Tumors or neoplasms are abnormal cells that (2)

A

grow (increases in mass) and proliferate (divides)

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3
Q

Tumors are considered — if the neoplastic cells do not become invasive

A

benign

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4
Q

Tumors are considered cancerous if it acquires the ability to invade surrounding tissue at which point it is has become —

A

malignant

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5
Q

Malignant tumors often, as a consequence of
their invasiveness, produce cells that break
out of their primary site and form secondary
tumors at other sites called —

A

metastases

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6
Q

is a single mutation sufficient to cause cancer?

A

no

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7
Q

inherited mutations confer increased…

A

risk of developing cancer

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8
Q

potential risk factors (5)

A
radiation exposure
UV light from the sun 
chemicals (carcinogens)
life style (smoking, certain diets)
viruses (EBV, HIV, HPV)
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9
Q

overall incidence of cancer increases with

A

age

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10
Q

During the cell-cycle the cell has scanning
mechanisms to detect DNA damage and either
(2)

A

repair the damage or result in cell-cycle arrest

or cell death (apoptosis)

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11
Q

A key mechanism in the cellular response to

DNA damage is mediated by the protein, —

A

p53

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12
Q

Improved cancer survival rates has been achieved through

A

combination therapies that are the standard of care today

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13
Q

In addition to the battery of drugs, (2) remain an effective (co-)treatment for many forms of cancer

A

surgical removal of the tumor and radiation therapy

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14
Q

The basic strategy for treating cancer with

either drugs or radiation is to

A

induce so much
damage to the tumor cells via DNA damage
(primarily) to prevent them from dividing and
induce cell death

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15
Q

The unfortunate side-effects result from the

same damage potentially occurring in

A

normal cells

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16
Q

External Beam Therapy

A

Uses a machine to send high energy beams from outside the body to the tumor area

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17
Q

Internal Radiation Therapy

A

Radioisotope given internally, radiation generally only travels a short distance depending upon the isotope and its energy

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18
Q

Radiation induces — —, which leads

to — —

A

DNA damage

cell death

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19
Q

Photon therapy (X-ray/Gamma rays): works either by (2)

A

direct ionization of atoms in the DNA chain or indirectly by ionization of water to form hydroxyl radicals that can then damage DNA

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20
Q

— — generate energies of 20-150 kV, while most X-ray energies in radiation therapy run in the range of 1-25 MV

A

Diagnostic X-rays

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21
Q

Other photon beams derived from iridium-192, cesium-137 or cobalt-60 generate — rays with an energy range of 300 keV -1.5MeV

A

gamma

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22
Q

Charged Particle or Proton therapy

A

uses a particle accelerator to beam high-energy particles (protons or carbon, boron or neon nuclei)

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23
Q

advantage of charged particle or proton therapy

A

Better ability to precisely localize the radiation dosage and less damage to surrounding, healthy tissue

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24
Q

Doxorubicin hydrochloride (adriamycin) (2)

A

Doxorubicin intercalates between base pairs in the DNA helix, thereby preventing DNA replication and ultimately inhibiting protein synthesis

Doxorubicin also forms oxygen free radicals resulting in cytotoxicity secondary to lipid peroxidation of cell membrane lipids

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25
Bleomycin sulfate (1)
forms complexes with iron that reduce molecular oxygen to superoxide and hydroxyl radicals which cause single- and double-stranded breaks in DNA
26
Cisplatin (1)
forms highly reactive, charged, platinum complexes which bind to nucleophilic groups such as GC- rich sites in DNA, inducing intrastrand and interstrand DNA cross-links, as well as DNA-protein cross-links
27
Methotrexate (1)
inhibits the enzyme dihydrofolate reductase, resulting in inhibition of purine nucleotide and thymidylate synthesis
28
Vinblastine (1)
Vinblastine binds to tubulin and inhibits microtubule formation, resulting in disruption of mitotic spindle assembly and arrest of tumor cells in the M phase of the cell cycle.
29
Vincristine (1)
Vincristine binds irreversibly to microtubules and spindle proteins in S phase of the cell cycle and interferes with the formation of the mitotic spindle, thereby arresting tumor cells in metaphase.
30
Prednisolone (2)
binds to and activates specific nuclear receptors, resulting in an altered gene expression and inhibition of proinflammatory cytokine production stimulates apoptosis in sensitive tumor cells populations.
31
Immunotherapy is a treatment designed to (3)
induce, enhance or suppress the immune response
32
Most applications are designed to stimulate a
person’s own immune response to destroy cancer cells that have escaped normal immune surveillance
33
Opdivo and Keytruda target
PD-1 on T-cells (also highly expressed on some type of tumors)
34
Opdivo and Keytruda target PD-1 on T-cells (also highly expressed on some type of tumors). It has been shown to help shrink or slow growth of tumors such as (3)
melanoma, non-small cell lung cancer, Hodgkin lymphoma, others
35
Opdivo and Keytruda target PD-1 on T-cells (also highly expressed on some type of tumors). It has been shown to help shrink or slow growth of tumors such as (3)
melanoma, non-small cell lung cancer, Hodgkin lymphoma, others
36
PD-1 is part of an immune checkpoint control system that keeps immune cells from
attacking “self”
37
CML
Chronic Myelogenous Leukemia
38
Leukemia characterized by
increased production/growth of myeloid cells in the bone marrow that then circulate in the blood
39
what is CML. caused by
a chromosomal translocation called the Philadelphia chromosome
40
the translocation creases a
fusion gene/protein between the BCR and ABL gene
41
fusion protein is a
tyrosine kinase
42
long term survival rates of CML
>95%
43
what is the parent drug used to treat CML?
Gleevec (imatinib)
44
treatment phases for leukemia (3)
induction therapy consolidation/intensification therapy maintenance therapy
45
Induction therapy
this is the first phase of treatment. The goal is to kill the leukemia cells in the blood and bone marrow. This puts the leukemia into remission. This is also called the remission induction phase.
46
Consolidation/intensification therapy
This is the second phase of therapy. It begins once the leukemia is in remission. The goal of consolidation/intensification therapy is to kill any remaining leukemia cells that may not be active but could begin to regrow and cause a relapse
47
Maintenance therapy
This is the third phase of treatment. The goal is to kill any remaining leukemia cells that may regrow and cause a relapse. Often the cancer treatments are given in lower doses than those used for induction and consolidation/intensification therapy. This is also called the continuation therapy phase.
48
AML
acute myeloid leukemia
49
how many subtypes of AML?
8 (M0-M7)
50
what are the 8 subtypes of AML based upon?
the cell that the leukemia develops from and many have chromosomal translocations that create fusion proteins
51
AML M3
acute promyelocytic leukemia
52
patients with AML M3 can develop
blood clotting and bleeding problems
53
AML M3: --- --- of the retinoic acid receptor-alpha gene (RARA) on Cs17 with the PML gene on Cs15. Other translocations have also been described with RARA.
Chromosomal tranlocation
54
treatment of AML M3 (3)
– Induction: all-trans-retinoic acid (ATRA, tretinoin), often combined with daunorubicin or idarubicin, sometimes with ara-C – Consolidation: anthracycline with ATRA (few cycles), anthracycline plus ara-C (2 cycles), arsenic trioxide (2 cycles then ATRA + anthracycline for 2 cyles, ATRA + arsenic trioxide for several cycles. – Maintenance: mainly ATRA for at least a year.
55
Fusion protein has --- function
altered
56
It binds with high affinity to sites on the DNA important for --- differentiation.
granulocyte
57
the blocking of differentiation involves enhanced interactions of (2)
the nuclear co-repressor (NCOR) and histone deacetylase (HDAC)
58
ATRA does not kill the immature leukemic promyelocytes, but induces
their terminal differentiation and then these differentiated malignant cells undergo apoptosis
59
ATRA induces the dissociation of NCOR and HDAC allowing for
differentiation to proceed
60
ALL
acute lymphoblastic leukemia
61
ALL
bone marrow produces too many immature lymphocytes (at the expense of other blood cell types)
62
ALL risk factors (5)
• Being exposed to x-rays before birth. • Being exposed to radiation. • Past treatment with chemotherapy. • Having certain changes in the genes. • Having certain genetic conditions that include the following: – Down syndrome, Ataxia telangiectasia, Bloom syndrome, Neurofibramatosis, Schwachman Syndrome.
63
possible signs and symptoms of ALL
Fever; foul smelling urine; easy bruising or bleeding; petechiae (flat, pinpoint, dark-red spots under the skin caused by bleeding); bone or joint pain; painless lumps in the neck, underarm, stomach or groin; pain or feeling of fullness below the ribs; weakness, feeling tired, or looking pale; loss of appetite.
64
diagnosis of ALL
Blood CBC (complete blood count), bone marrow analysis, cytogenetic analysis
65
ALL prognosis can depend upon... (7)
* Age at diagnosis, gender, and race. * The number of white blood cells at diagnosis. * Whether the leukemia cells began from B lymphocytes or T lymphocytes. * Whether there are certain changes in the chromosomes of lymphocytes. * Whether the child has Down syndrome. * Whether the leukemia has spread to the brain, spinal cord or testicle. * How quickly and how low the leukemia cell count drops after initial treatment.
66
ALL risk groups (2)
standard (low) risk | high risk
67
Standard (low) risk
Includes children aged 1 to younger than 10 years who have a WBC count of less than 50,000/μL at diagnosis.
68
High risk
Includes children younger than 1 year or 10 years and older and children who have a white blood cell count of 50,000/μL or more at diagnosis.
69
The National Cancer Institute has identified --- plants that are active against cancer cells. --% of these plants are found in the rainforest.
3000 | 70%
70
--% of the active ingredients in today's cancer
25% -fighting drugs come from organisms found only in the rainforest
71
Our understanding of the genetics of cancer has --- exponentially in the last 20 years
increased
72
New drugs continue to be developed, | but the reality is we
still have a long way to go | in our quest to cure cancer
73
Tissues not made up only of
cells
74
Extracellular space is filled with network of large
macromolecules (ECM)
75
ECM is composed from
large repertoire of specialized ECM proteins with various properties assembled into an organized network/meshwork, often in close association with producer cells
76
connective tissues
specialized tissues in which ECM is more abundant than cells
77
ECM is critical in many oral and cranioacial tissues such as (4)
teeth/bone cartilage lamina propria beneath oral epithelium gingiva, periodontium
78
teeth/bone
specialized mineralized connective tissues
79
cartilage
proteoglycan-rich specialized connective | tissue
80
Lamina Propria beneath oral epithelium
composed of collagen fibers in a connective tissue or STROMAL matrix (similar to dermis of skin)
81
Gingiva, periodontium
have a stromal matrix | containing collagen
82
stroma
cell embedded in matrix
83
Major components of STROMAL MATRIX
collagen embedded in polysaccharide ground substance of hyaluronan + proteoglycans/glyosaminoglycans
84
stromal cells are derived from the
mesodermal lineage
85
fibroblasts secrete --- in most connective tissue
ECM
86
in specialized tissues, ECM is secreted by other fibroblast-related cells, such as (3)
osetoblasts chondrocytes odontoblasts
87
basal lamina
Specialized matrix at interface between connective tissue stroma and epithelium (separates them/anchors them)
88
Basal lamina is tethered to underlying | connective tissue by
type VII collagen anchoring fibrils (“Basement membrane” – refers to the basal lamina combined with this layer of collagen fibrils)
89
basal lamina is important in cell ---
polarity
90
major protein of the tissue
ECM
91
ECM is traditionally viewed as structurally stable material whose function is to provide
support/anchorage to cells and tissues/demarcate boundaries between cells/tissues
92
function of ECM in bone (3)
- Support and locomotion - Calcium homeostasis - Skeleton protects brain, internal organs
93
function of ECM in teeth (2)
- Provides strength/structure to tooth | - Resists shear and compression forces associated with chewing
93
function of ECM in teeth (2)
- Provides strength/structure to tooth | - Resists shear and compression forces associated with chewing
94
function of ECM in cartilage (2)
- support and locomotion | - resilient -shock absorber for compressive forces associated with locomotion, mastication, etc
95
ECM roles in addition to structural roles (4)
- Embryonic Development (cell adhesion / migration / tissue morphogenesis) - Regulation of Cell Function (signaling / growth / differentiation) - Tissue Repair/wound healing - Angiogenesis
96
Composition of ECM in each tissue is perfectly suited to --- requirements of the tissue
biomechanical/functional
97
ECM can be viewed as composite material, as in
various building materials (macromolecules) with different mechanical properties combined/organized to create a tissue with optimal mechanical properties
98
Genes encode for large repertoire of ECM components, which can be used to
assemble ideal extracellular matrix for given tissue
99
examples of diverse types of ECM (3)
bone/teeth: calcified, hard ECM cornea: optically transparent ECM tendon: rope-like organization of collagen gives tensile strength in one direction
100
property of collagen (fibrillar)
tensile strength
101
property of proteoglycans
resilience/resistance to compression
102
property of elastin (elastic fibers)
elasticity/resilience
103
property of fibrin-1 (microfibrils)
controlled elasticity
104
property of mineral (hydroxyapatite)
strength, hardness, but also brittleness