cancer Flashcards
1
Q
what is cancer
A
another name for malignant tumour
- disease in which abnormal cells divide without control and are able to invade other tissues
- Is an abnormal growth resulting from uncontrolled proliferation; it serves no physiologic function
- also referred to a neoplasm–> “new growth”
2
Q
what is a benign tumour?
A
not cancer
- usually encapsulated w/ connective tissue and contain fairly well-differentiated cells and well-organized stroma
- they retain normal tissue structure
- they do not invade beyond their capsule, nor do they spread to lymph nodes or distant locations
3
Q
when do benign tumors become harmful?
A
when they become extremely large and, depending on their location in the body, cause cause morbidity or be life-threatening by compressing normal tissues, preventing blood flow to the region (ischemia) or causing necrotic death of normal tissue
4
Q
what is anaplasia?
A
loss of cellular differentiation
5
Q
malignant cells are…?
A
- pleomorphic (variability of size/shape)
- often have large dark stained nuclei
- mitotic cells are common
- they have substantial amount of stroma but it is disorganized
- loss of normal tissue structure
- lack a capsule
- grow to invade nearby blood vessels, lymphatics, and surrounding structures
6
Q
what is the most important/ deadliest characteristic of malignant tumors?
A
ability to spread far beyond the tissue or origin, process known as metastasis
7
Q
what is the first hallmark of cancer?
A
uncontrolled cellular response to growth factors that bind to specific receptors on the cell surface
8
Q
what impacts the development of cancer?
A
- genetics
- age
- epigenetics and tissue
- in utero (before birth) and early life conditions
- environment
- lifestyle (smoking, nutrition, obesity, alcohol, physical inactivity)
9
Q
how does genetics, epigenetic and tissue affect cancer?
A
- cancer is driven by genetic alternation and changes in epigenetic regulation
- cancer development and progression involve tissue microenvironment or stroma
- Infiltrating immune cells cause chronic inflammation, creating a permissive tumour-progressing environment.
- epigenetic influxes cancer initiation, progression, and treatment
10
Q
factors that influence cancer risk?
A
- detoxifying enzymes
- DNA repair genes
- immune/inflammatory system
- cell’s immediate environment
- metabolic/hormonal factors
11
Q
why is age and cancer correlated?
A
bc the older u get the more your cells divide= causing cancer
12
Q
what is the leading cause of death with cancer patients?
A
sepsis due to the treatment
13
Q
what are the incident trends r/t cancer?
A
- cancer rates are higher for men than women
- highest cancer rates are found in Denmark
- decline in lung cancer correlates to decreased tabacco use
- cancer rates have increased for ages 0-19
14
Q
what are the mortality trends r/t cancer?
A
- cancer deaths have decreased in men, women, children
- liver cancer is most predominant cancer
- mortality rates for men with liver cancer are more than double the rate for women
15
Q
how does in utero affect cancer development?
A
- conditions that increase susceptibility to cancer include:
- prenatal and early life exposure
- parental exposures before conception
- nutrition and DES ( it an estrogen hormone) exposure
- gene and environment interactions
16
Q
what is developmental plasticity?
A
Degree to which development is contingent on its environment
17
Q
how to reduce the risk of cancer?
A
must start early in life
- avoiding sun exposure during peak hours
- covering your skin
- increasing physical activity
- avoiding high-risk sexual partners/practices
18
Q
tabacoo and risk to cancer
A
- smoking is is carcinogenic and the most important risk factor for cancer
- Is linked to cancers of the lung, mouth, lips, nasal cavity and sinuses, larynx, pharynx, esophagus, pancreas, kidney, uterus, cervix, colon and rectum, liver, and acute leukemia
- second hand smoking + environmental tobacco smoke increases the risk for lung cancer
19
Q
what is nutrigenomics?
A
Is the study of nutrition on the phenotypic variability of individuals, based on genomic differences.
20
Q
what are the primary dietary donors of DNA methylation include?
A
- folate
- choline
- b vitamins
21
Q
what kind of foods improve DNA repair and decreases the risk of cancer?
A
-eating kiwi fruits, cooked carrots, or supplemental coenzyme q10 improves DNA repair
22
Q
dietary factors?
A
- Altered micro-ribonucleic acid (miRNA): Predisposes an individual to cancer
- Suppress cancer stem cell renewal: Decreases the risk of cancer.
23
Q
what is Glutathione-S-transferases (GSTs)?
A
Enzyme housekeepers that metabolize environmental carcinogens and reactive oxygen species (ROS)
-If GSTs are lacking, then the risk for cancer is higher
24
Q
diets high in red meats and processed meats, pt is at risk for?
A
colorectal cancer
25
humans are constantly exposure to a variety of compounds termed xenobiotics
xenobiotics include toxic, mutagenic, and carcinogenic chemicals
- many of these chemicals are found in the human diet
- most xenobiotics are transported in the blood by lipoproteins and penetrate lipid membranes
- these chemicals can react w/ cellular macromolecules like proteins and DNA or can react directly w/ cell structure to cause cell damage
26
the body has 2 main defense system for counteracting xenobiotics effects
1. detoxification enzymes
| 2. antioxidant systems
27
phase 1
enzymes that activate xenobiotics are called phase 1 activation enzymes and are represented by the mutligene cytochrome p-450 family
28
phase II
phase II detoxification enzymes then protect against further against a large array of reactive intermediates and nonactivated semiotics
-enzymes are mainly in the liver and provide clearance of compounds through the portal circulation that prevents the carcinogenic agents from entering the body through the GI tract or portal circulation
29
obesity
- is associated w/ endometrial, colorectal, kidney, esophageal, breast (postmenopausal), pancreatic, and several other cancers.
- Energy expenditure involves resting metabolic rate, thermic food effects, and physical activity.
- causes poorer outcomes for some cancers
- increases insulin resistance-producing hyperinsulinemia/ hyperglycemia
- insulin promotes insulin-like growth factor 1
- adipose tissues secretes adiokine
- circadian disruptions may affect cancer growth
30
alcohol
is classified as a human carcinogen
- a combo of cigarette smoking and alcohol consumption increases a person's risk for malignant tumors
- increases the risk for oral cavity, pharynx, larynx, esophageal, liver, colorectal, and breast cancers
31
physical activity
-decreases the risk for cancer
-decreases insulin and insulin-like growth factors
-decreases obesity
-decreases inflammatory mediators
-decreases circulating sex/metabolic hormones
and improves immune function
-Reduces the risk for breast, colon, and endometrial cancers, independent of weight changes
-After a cancer diagnosis, physical activity is associated with improved cancer-specific and overall survival with early-stage breast, prostate, and colorectal cancers
32
air pollution
-is linked to lung cancer
-outdoor pollution- smog and particle pollution
smog- increases daily mortality
-particle pollution- causes pulmonary inflammation, oxidative stress and oxidation of DNA, nonfatal heart attacks, irregular heartbeat, and decreases lung function
-indoor pollution- is worse than outdoor pollution --> cigarette smoking
radon: lung cancer
33
how does radiation impact the development of cancer?
- Enters cells and randomly deposits energy in tissues
- Oncogene activation
- tumour-suppressor genes deactivation
- Chromosomal aberrations and DNA damage
- Cell transformation
- Nontargeted/bystander effects
34
UV radiation (ultraviolet A & ultraviolet B) impact on cancer
principal source is sunlight
| -causes basal cell carcinoma, squamous cell carcinoma (more severe), and melanoma
35
how does (EMR) electromagnetic radiation development of cancer
energy in the form of transverse magnetic and electric waves
-microwaves, radar, mobile and cellular telephones, mobile telephone stations, appliances, power frequency radiation associated with electricity and radio waves, fluorescent lights, computers, and other electric equipment
36
human papillomavirus (HPV) causes
cervical cancer
37
Hepatitis B and C together
causes liver cancer
38
Helicobacter pylori
causes stomach cancers
39
Epstein-Barr virus (EBV)
Cancers of the nasopharynx and stomach, Hodgkin disease, and non-Hodgkin lymphoma
40
human herpes virus type 8
cause Kaposi sarcoma
41
human T-cell lymphotropic virus type 1 causes
causes Leukemia and lymphoma
42
HPV and cancer
- HPV is the most common sexually transmitted virus
- HPV types 16 and 18 cause the majority of cancers.
- are associated with cervical and anal cancers.
- cause almost one-half of vaginal, vulvar, and penile cancers.
- are recently associated with cancers of the oropharynx (soft palate, base of the tongue, tonsils).
- HPV infects epithelial cells.
- mutations lead to cancer.
43
benign tumour characteristics
- slow growth
- well-defined capsule
- not invasive
- well differentiated
- low mitotic index
- dose not metastasize
44
malignant tumour characteristics
- rapid growth
- not encapsulated
- invasive
- poorly differentiated anaplasia
- high mitotic index
- can spread distantly (metastasis)
45
what are the characteristics of cancer cells
- anaplastic -loss of cell differentiation in cancerous tissue- variations in size and shape
- Pleomorphic
- Substantial amount of stroma, disorganized, with loss of normal tissue structure
- lacks a capsule
- capable of invading nearby vessels, lymphatics, surrounding structures and metastasize
46
lipoma
is a fatty tumour
47
what is a leiomyoma
-benign tumour and are composed of smooth muscles
48
carcinomas are
malignant epithelial tumours
49
what are adenocarcinomas
cancer of the duct or glands
50
what are sarcomas
malignant cognitive tissue tumours
51
what are lymphomas
cancers of the lymphatic tissue
52
leukaemia is
cancer of blood forming cells
53
Classification and Nomenclature: Carcinoma in situ
- are preinvasive epithelial malignant tumours of glandular or squamous origin
- have not broken through the basement membrane or invaded the surrounding stroma
- are not malignant
- three prognoses:
- can remain stable for a long time
- can progress to invasive and metastatic cancers
- can regress and disappear
54
what is a stroma
tumour microenvironment, surrounds and infiltrates the tumour
55
what is the process of cancer development?
- initial proliferation of cancer cells and enlargement of the tumour elicit the synthesis of pro inflammatory mediators--> recruit inflammatory/immune cells and cells normally associated w/ tissue repair --> stroma
- stroma promotes cancer progression and metastatic potential
- **many of the hallmarks of cancer are consequences of cancer-stomal interactions
56
biology of cancer cells
- clonal proliferation or expansion occurs
- d/t mutations that is, cell acquires characteristics that allow it to have selective advantage over its neighbours
- increased growth rate or decreased apoptosis
- multiple mutations have to be present before cancer can develop
57
cancer and aging
cancer is predominantly a disease of aging
- the older u get the higher the risk of cancer- they go together
why? bc so many things trigger our cells to go awire
-as we get older our class proliferate more
58
genomic hallmarks (oncogenes)
sustained proliferative signalling (e.g protocol-oncogenes referred to as oncogenes-genes that are in cells that promote growth - think of a gas petal
when we have variations they become oncogenes- abnormal
oncogenes must be activated for cancer to occur
-a single genetic event can activate an oncogene b/c it can act in a dominant manner in the cell
59
genomic hallmarks (tumor-supressors genes)
evading growth suppressors (e.g. tumour-suppressors genes)
-must be inactivated to allow cancer to occur
-normally when regulated the cell cycle, inhibits proliferation resulting from growth signals, stop, cell division when cells are damaged and prevent mutations
(also referred to as anti-oncogenes)
-each person has 2 copies of tumor-supressors genes- one from each parent, both copies must be inactivated =two mutations are necessary for cancer to develop
60
oncogenes and tumour suppressor genes what are the 3 genetic mechanism have a role in human carcinogenesis?
1. activation of protocol-oncogenes of growth related gene products (called oncogenes)
2. mutations of genes, resulting in the loss of inactivity of gene products that would normally inhibit growth (called tumour suppressor genes)
3. mutations of genes, resulting in an overexpression of products that prevent normal cell death or apoptosis, = allowing continued growth of tumours
61
what are proto-oncogenes?
are normal nonmutant genes that code for cellular growth
62
what are oncogenes?
are mutant genes that, in their nonmnutant state, direct protein synthesis and cellular growth
63
what are tumour-suppressor genes
encode proteins that, in their normal state, negatively regulate proliferation
-are also referred to as anti-oncogenes
64
retinoblastoma (RB) gene
a prototypical tumor-suprresor gene
- normal cells receive diverse "antigrowth" signals from their normal environment
- contact w/ other cells, with basement membranes, and with some soluble factoid normally signal cells to stop proliferating
- RB, monitor antigrowth cellular signals and block activation of the growth/division phase in the cell cycle, when it mutates RB leads to persistent cell growth =cancer
65
p53 tumor-suppressor gene (TP53) "guardian of the genome" pt 1
-TP53 monitors intracellular signals related to stress and activates caretake genes--> gees that are responsible for the maintenance of genomic integrity
-many types of cellular stress produces intracellular signals detectable by p53
usually p53 is inactive
-stress actives kinases that phosphorylate p53 into an active suppressor of cell division and activator of caretaker genes
-caretake genes encode proteins that are involved in preparing damaged DNA, such as w/ errors in DNA replication, mutations caused by ultraviolet or ionizing radiation, and mutations caused by chemicals/drugs
66
p53 tumor-suppressor gene (TP53) "guardian of the genome" pt 2
p53 also controls initiation of cellular senescent or apoptosis and suppresses cell division until DNA repair is complete or other effects of stress are corrected
- if not correct, the cell enters senescent or apoptosis = further preventing DNA damage and mutations
- loss of function of tp53 or caretaker genes leads to increased mutation rates and cancer
67
what are genomic instability?
refers to an increased tendency of alterations -mutability- in the genome during the life cycle of cells
-inherited and acquired mutations in caretaker genes that protect the integrity of the genome and DNA repair increase the level of genomic instability and risk for developing cancer
68
telomeres and immortality
-body cells are not immortal and can divide only a limited number of times (Hayflick limit)
telemores- are protective caps on each chromosome that are held in place by a telomerase
-telomeres become small and small with each cell division
-cancer calls can activate telomeres, leading to continued division
-"Protective tip that comes at the end of our genes- they should be short- but what happens in cancer, over activate telomeres are found in many cancer cells, causing cancer cells to divide w/out limit= taking over the healthy cells" - what charene said
69
angiogenesis
-the growth of new vessels
-is also called neovascularization.
-advanced cancers can secrete angiogenic factors to facilitate feeding of the tumour
-Vascular endothelial growth factor (VEGF)
-Basic fibroblast growth factor (bFGF)
"cancer benefits from angiogenesis (abnormal bleeding) this is new blood that begins to form in a mold that was completely fine before" -charene
70
Apoptotic pathways are dysregulated in most cancers
- Programmed cell death (apoptosis) is a mechanism by which individual cells can self-destruct under conditions of tissue remodeling or as a protection against aberrant cell growth that may lead to malignancy
- apoptotic pathways are dysregulated in most cancers
- tp53 gene superes activation of apoptosis
- the inability of apoptosis is an issue bc the cell doesn't have the ability to kill itself= it multiples and cancer proliferation grows
71
t/f
| chronic inflammation is a risk factor in the development of cancer
true-active inflammation predisposes a person to cancer
72
t/f is obesity an independent risk factor for cancer
true yes
73
ulcerative colitis
anyone w/ a chronic inflammatory issue in their bowel like UC is at risk for developing bowel cancer
74
evading immune destruction
many cancers express cell surface antigens that are not generally found on normal cells from the same tissue
-"surface antigens are not found on all cancer cells"
75
what is the immune surveillance hypothesis?
most developing malignancies are suppressed by an efficient immune response against tumour-associated antigens
-the development of cancer suggests evasion of the immune response
76
what is the immunotherapy hypothesis?
predicts that the immune system could be used to target tumour-associated antigens and destroy tumours clinically
77
what is the impact of pts w/ prolonged infection w/ HPV
their viral DNA becomes integrated into the genomic DNA of the infected basal cell of the cervix and directs the persistent production of viral oncogenes
-takes about 20-30 yrs to develop
78
what is metastasis?
the spread of cancer cells from the site of the original tumour to distant tissues and organs through the body
- it is a complex process that requires cells to have many new abilities
- including: spread, survive, proliferate in distant locations, and destination must be receptive to growth of cancer
- this is when u are in trouble. cancer from the originating cells have traveled. ex., Bob Marley had melanoma and travelled into the blood streams
79
what is the best way to treat a cancer that is in situ?
surgery- removal of the tumor
80
How do cancer cells develop the ability to invade (locally) and metastasize?
-changes in the tumour microenvironment causes stroll cell adaptation to increase tumor mass and intratumor hypoxia
-cancer cells evolve w/ new abilities that facilities facilitate metastasis: Epithelial-mesenchymal transition (EMT)
and
-Invasion by direct tumour extension and then migrate away from the primary tumor= Multistep process within EMT that includes diminished cell-to-cell adhesion, digestion of the surrounding ECM, increased motility of cancer cells
81
how do cancer cells evolve w/ new abilities that facilitate metastasis
- many epithelial-like characteristics (e.g polarity, adhesion to basement membrane) are lost
- migratory capacity increases
- resistance to apoptosis increases
- dedifferentiation to a stem cell-like state favors growth in foreign microenvironments and the establishment of metastatic disease
82
Invasion: Local spread
- is a prerequisite for metastasis and the first step in the metastatic process
- cancer often spreads first to regional lymph nodes through the lymphatic system and then to distant organs through the bloodstream
- invasion then requires that the cancer attach to specific receptors and survive in the specific environment
- cells have broken through the basement membrane and enter the lymph or blood and circulate to a different organ
- breast goes to brain
- prostate goes to liver and bone
- lungs go to liver and adrenal
83
t/f we can do chemotherapy on prostate patients?
false- no chemo works
| instead we have surveillance and hope
84
what is the process of cells metastasizing?
1. Cancer cells invade local blood and lymphatic vessels
2. After release from the extracellular matrix (ECM) and digestion of basement membranes, mobile cancer cells gain access to the circulation
3. Once in the circulation, metastatic cells must be able to withstand the physiologic stresses of travel in the blood and lymphatic circulation, including high shear rates and exposure to immune cells
4. Neovascularization of a cancer offers malignant cells direct access into the venous blood and draining lymphatic vessels
5. Once metastasized, cancer cells may establish a metastatic lesion in a new location
