Module 2 (2.1 and 2.2) Flashcards
1
Q
What is cancer?
A
- Begin when some of the body’s cells start to divide without stopping and spread into surrounding tissue
- In short, it is uncontrolled growth of abnormal cells
- Affects half of Canadians
- More common in older individuals
- Leading cause of death among Canadians
- Mortality rates have decreased since 1988 (peak)
- “Cancer”: latin word ‘crab’ bc it grabs on and do not let go
2
Q
what is neoplasm?
A
any abnormal tissue that forms when cells grow and divide more than they should, without dying when they are signalled to, can also refer to harmless or cancerous growths
3
Q
what is a tumour?
A
classified on the tissue where it arose. Non specific term for neoplasm. Means “mass”, any swelling or abnormal enlargement in or on the body, can be harmless or cancerous
4
Q
Begin tumour
A
- Harmless
-Cannot invade or spread
-can attain sizes of 50 kg with killing
-smooth and round
5
Q
Malignant tumour
A
- Cancerous
-Can spread to other tissues (metastasis)
-May kill before 50 g
-spiky contour
6
Q
What is metastasis?
A
(process) invade other tissues through the bloodstream and colonize distant sites, this is why cancer kills
7
Q
How do we find the origin of cancer?
A
- Full body imaging
- Gene expression can also be used to trace the origin of cancer
8
Q
Name all tumour classifications? (5)
A
Carcinoma, sarcoma, lymphoma, glioma, leukemia
9
Q
Carcinoma
A
type of cancer that affects epithelial cells (found on the surface of the body, i.e skin, blood vessels, urinary tract and organs), forms solid tumour (breast, lung, prostate and colorectal cancers)
10
Q
Sarcoma
A
begin in the tissue that supports and connect the body, develops in fat, muscle and nerves, tendons, joints, blood vessels, cartilage or bone
11
Q
Lymphoma
A
begins in lymphocytes (infection fighting cells of the immune system found in glands, nodes and other lymphoid tissues)
12
Q
Glioma
A
arises from the connective of the brain (cells that support the neurons of the brain)
13
Q
Leukemia
A
cancer of blood and bone marrow cells
14
Q
what is glioblastoma?
A
A form of glioma (brain and spinal cord cancers) arising from cells called astrocytes.
15
Q
What is prevalence?
A
measure of total cases of disease in a population
16
Q
What is incidence?
A
measure of the number of new occurrences of a disease in a population
17
Q
What the cause behind cancer?
A
genetic mutations -> chromosomal damage by a combination of mutation + envir risk factors
18
Q
Cancer in 1st nation individuals?>
A
- Higher incidence rate
- Prevalence: most cases are breast, prostate and colorectal cancer
- High rate of mortality
(1st nation males have a lower mortality rate from leukemia)
Lower survival rates
19
Q
True or false: There are tissues in the body that can almost never give rise to cancer
A
True, ex: heart, epididymis and vesicle
20
Q
Proven carcinogens that can lead to genetic mutations?
A
- Family history
- Tobacco use (cigarette smoke can lead to an accumulation of tissue damage -> development of cancer) -> causes a third and a half of all cancer cases
- Age
- HPV infection
- UV radiation (cumulative exposure to sun -> increases the risk of sustaining damage to the genome of normal cells -> when there is enough damage or mutations within a cell, the cell dies but in some cases the there is a build up of mutations that provides selective growth advantages to the cells making them more likely to thrive and to continue dividing)
21
Q
How does smoking lead to cancer?
A
Smoke contains a number of toxic chemicals -> it can kill epithelial cells that line the airway and the lungs -> injury: when the epithelial tissue dies; stem cells at the edges of the airway injury sense the damage and begin rapid asymmetrical cell division to repair it. In a normal healing process: the epithelial layer is restored and stem stop dividing and go back to their resting state. -> Persistent activation: chronic injury stem cell activation and re-injury cases mutations that permanently activate stem cell growth and cause cancer.
22
Q
True or false: cancer is not preventable?
A
false: 30-50% of cancer is preventable
Most cases it is a product of bad luck: a susceptible cell in the body experiences a number of insults to the DNA, BUT it is usually avoided through DNA repair and the immune system -> but sometime it all fails -> the build up provides selective growth advantage -> to make more of the mutated cells.
23
Q
why do some tissues have higher rates of cancer?
A
they have a higher number of stem cells division
24
Q
Silent mutation
A
change in dna that does not effect the protein product
25
Oncogenic mutation
directly contributes to the development of cancer
26
Why is cancer hard to treat?
- Various types of tissue: each tissue respond differently to treatments
- Continuous mutations: = different subclones -> each respond differently to each treatment + has different abilities to metastasize
Diversity: Thousands of different tumours may arise from a particular cell, and no two are alike
27
Steps of cancer
1- Transformation: normal cell undergoes a change in its genetic code -> tumour cell (divides more rapidly than unaffected cells)
2- Progression: tumour cells divide -> accumulation of mutation in daughter cells. Can be the same mutations as those found in the initial tumour or genetically different -> distinct clones (tumour cell variants, can be harmful or beneficial or has no effect)
3- Proliferation: rapid multiplication + more mutations of the daughter cells -> further growth advantage (eventually many subclones - cells with different mutations but all deriving from a single tumour - can form within the same tumour)
4- Tumour heterogeneity: bc each cancer cell can accumuate a different set of advantageous mutations, each subclone may offer different physiological characteristics to the tumour
28
What is a variant?
Any change in the DNA sequence of a cell, a mutation or several mutations. Variants can be harmful, beneficial, or have no effect
29
what is a clone?
a cancer cell that has a unique genetic profile. Daughter cells with new mutations that are
descended from this are called subclones.
30
What do cancerous mutations do?
Prevention from programmed cell death or apoptosis, ability to escape the immune system or capacity to enter and exist the blood vessels (required to metastasize)
31
Oncogenes
- will produce protein that have altered functions (Selective growth advantages) due to a mutation in the gene.
- Involved in growth factor receptor pathways (embryonic growth, homeostasis, injury repair).
- ONE MUTATION in one allele is problematic.
In oncogenes, cancer-causing mutations turn growth-
stimulating proteins on in a manner that makes them impossible to turn off (gain of function mutation) -> produce cancer effects as soon as they are produced
- Most common in Sporadic (present in patient with no clear family history of cancer) cancer
- Unmutated versions (normal protein that they code for): proto-oncogenes
32
Tumour suppressor genes
- Mutation disable their normal function (preventing uncontrolled growth and inducing cell death)
- Acts as a cell checkpoint
- Plays a role in the developmental process that require controlled apoptosis
- BOTH ALLELES have to be mutated
Common in family with history of cancer (inherited)
- coded by TP53 -> protein (p53)
33
True or false: CANCER EMERGES THROUGHOUT A LIFETIME, YOU CANNOT BE BORN WITH IT
true
34
True or false: TP53 is nearly mutated in all cancers?
True
35
P53
- regulate cell survival and death
- Chromosome 17
- Key role: to respond to genomic damage by activating repair and/or cell death progress
- Prevents cell with cancer causing mutation from surirving (puts the brakes so the cells don't divide too quickly)
- P53 deficient cells: can tolerate or even thrive with oncogenic mutations, providing them with a selective advantage over cells with p53 intact
- G1/S checkpoint: if DNA damage is undetected before replication, then mutations will carry forward to future generations of that cell, therefore p53 must act in the G1 phase prior to start of DNA replication
36
Mechanism of P53?
- Activation:
From DNA damage -> accumulation of normal p53
Binding p53 to specific DNA -> cell cycle arrest in G1
+ induction of DNA repair by transcriptional upregulation (process which the level transcription mRNA of a specific gene is increased) of repair genes
- DNA repair:
success: proceed with cell cycle. Fail: p53 triggers either apoptosis or senescence (state in which a cell has lost the ability to replicate)
- Inactive p53:
Cells with loss of or mutated TP53, DNA damage does not lead to p53 accumulation or binding of p53 to specific DNA sequences -> there is no cell cycle arrest and/or DNA repair -> malignant tumour
37
What is the oncogene gene and protein?
ERBB-1, protein: epidermal growth factor receptor (EGFR)
38
EGFR
- Tyrosine kinase receptor: Detects extracellular signals (induces gene expression) or ligands + forms dimers to transmit that signal into the cell
- Chromosome 7
- Cell growth and survival
- Ligand binding: the intracellular domains (components) of EGFR undergo a structural change -> activation of receptor
- Phosphorylation: attachment of a phosphate group to another molecule, secondary messengers (Messengers that trigger physiological changes, such as cell proliferation, survival, and apoptosis) are also phosphorylated by the active EGFR, and transmit the signal to the nucleus.
- gene expression: signal increases the transcription of genes involved in cell proliferation and survival, it also drives mechanisms outside the cell (migration or angiogenesis (development of new blood vessels))
- Termination: either the ligand is released or the receptor is broken down. Those cells receptors are broken down in lysosomes
39
hyperactivation of EGFR
- Hyperactivation: same amount of ligand but more secondary messengers (large amount of signal sent to the nucleus and ramps up pro-cancer process) This ultimately increases the signal being sent to the nucleus and ramps up pro- cancer processes (angiogenesis, cell proliferation, inhibition of apoptosis, and migration, adhesion, and invasion).
40
Constitutive activation of EGFR
- Constitutive activation: signal without a ligand, cannot be terminated, active at all times As a result, the pro-cancerous processes (angiogenesis, proliferation, inhibition of apoptosis, migration, adhesion, and invasion) are always on.
41
types of therapy?
- Chemotherapy: does not target EGFR directly but will kill rapidly dividing cells in the body
- Antibodies: EGFR ligand-binding domain is extracellular -> inactivation of target protein or cell death via immune system activation (Specific antibodies produced outside the body are injected into patients. These antibodies can cause inactivation and destruction of target protein, or cell death via immune system activation)
- Kinase inhibitors: both EGFR and its secondary messengers have kinase activity. Small molecule inhibitors can traverse the plasma membrane and disrupt signalling cascades
42
difference between P53 and EGFR?
localization, p53 is inside the cell, EGFR outside.
So it is hard to design drugs that enter the cell for p53,
+ EGFR are designed to reduce or eliminate oncogene activity and termination of signal is already a part of the normal function
43
When and why does drug resistance happen?
drug resistance is more likely when the cancer is reccurent bc these resistance cells will continue to proliferate -> so when a cancer returns it is often metastasized
44
Tobacco wise
The Indigenous Tobacco Program is an initiative that promotes and encourages Indigenous
communities to become Tobacco-Wise by continuing traditional tobacco practices and eliminating
commercial tobacco use
45
Iron deficiency anemia
Anemia is a condition in which the body is unable to make a sufficient number of healthy red blood cells, and thus is unable to carry enough oxygen to the tissues.
46
upper endoscopy?
A test that physicians use to visualize the upper digestive tract, by inserting a long flexible tube with a small camera on the end into the mouth, down the esophagus and into the stomach and the first part of the small intestine.
47
Colonoscopy
A test that physicians use to visualize the lower digestive tract, by inserting a long flexible tube with a small camera on the end into the anus, and up the rectum and large intestine.
48
Biopsy
A sample of tissue taken from the body for examination
49
how rare is colorectal cancer and how does it arise?
Most colorectal cancers (3rd most common type of cancer in canada, 2nd most deadly) arise from benign epithelial neoplasms called adenomas that are located somewhere in the rectum or colon
50
Hyper-proliferation:
cell has incurred one or more oncogenic mutations to hyper-proliferate -> these cells grow that a faster than normal rate
51
Adenomatous polyp
rapidly dividing mass of cells project into intestinal lumen(central space in the digestive tract which food passes) , it is known as adenoma and they are often referred to as colonic polyp
52
True or false: Precancerous polyp can be removed before it becomes malignant, takes 7-10 years before the next stage
True
53
Adenocarcinoma:
once the polyp becomes invasive. This transition is when the cells invade into adjacent tissue (most common type is colorectal cancer)
54
new people to canada and colorectal cancer
rates for colorectal cancer among long-term
Canadian residents are higher compared to new immigrants. This incidence rate increases for
colorectal cancer the longer you reside in Canada, highlighting the importance of diet as a cancer risk
factor
55
Who should get frequent screening?
Regular screening should be done on patients that have high risks (age and family history)
56
Fecal immunochemical Test (FIT)
safe and painless at home cancer screening test, examine stool for tiny amounts of blood, for people from 50 to 70 years old, every two years -> if the results are abnormal: individual is referred for a colonoscopy
57
Why do people not get tested?
- Fear: that the test is painful or difficult
- No family history
- Misconception that only those with symptoms need to be screened
Concern over the cost
58
Computed tomography (CT scan):
A technology that uses multiple x-ray images and computer software to generate images of the body at various depths, or ‘slices
59
Hemicolectomy:
Type of surgery done to remove part of the large intestine. Once the colon is partially removed, the remaining ends are joined back together
60
Histology:
The branch of biology that studies microscopic anatomy of biological tissues. Histology slides are created by cutting thin sections out of a specimen at the desired plane (the angle at which to cut). These are then dried to remove moisture, and stained to enhance visualization of the tissue under a microscope -> pathologists use histology to look for changes to the normal tissue structure and use this information to determine the extent of tumour progression.
61
True or false: Most colorectal cancer -> carcinomes (affects epithelial cells found in the mucosa layer)
true
62
stages:
- T: depth of the tumour invasion (0-4) - size of the tumour (0- no tumour, 4- invading adjacent tissues)
- N: spread to the lymph nodes (0−4) −number of nearby lymph nodes with cancer cells
M: metastasis of the cancer to the other parts of the body (0 or 1, yes or no)
63
Grade?
- How abnormal are the cells
G1-> G4
64
Sporadic colorectal cancer
BOTH alleles of the adenomatous polyposis coli (APC) gene
65
Mismatch repair gene (MSH2)
genes that correct mismatched nucleotides arising from errors in the dna replication and recombination
66
Familial colorectal cancer
inherited mutation: ONE of the mismatch repair gene (MSH2)
67
Lynch syndrome
ka hereditary nonpolyposis colorectal cancer (HNPCC)
- Most common hereditary colorectal cancer
- Caused by a germline mutation in the repair gene (passed onto the offspring)
- BOTH have to be mutated (BUT one is already inherited from the parents) to develop cancer
- People that have this type of cancer are at risk for other types of cancer
68
Prognostic factors with colorectal cancer
- Age and general health
- Response to treatment
- Stage and grade
- Genetics, some mutations are more aggressive than others
- Access and compliance
69
Five-year survival rate:
The probability of surviving cancer 5 years after diagnosis in the absence of other causes of death
70
Prognostic Factors:
Aspects or characteristics of the patient that the health care provider will consider when making a prognosis
71
what does a blood test collect?
concentration of blood cells and clotting factors
72
Clotting factors?
Proteins involved in forming blood clots, also known as coagulation.
73
Hemoglobin
The protein in red blood cells used to carry oxygen throughout the body, measured in
grams per litre of blood.
74
White blood cells?
Immune cells circulating in the bloodstream, measured in number of cells per litre of blood.
75
Percent Blasts
The percentage of circulating blood cells that are not fully differentiated and remain in
an immature, or ‘blast’, form. In healthy individuals, 1-4% are blasts in bone marrow, and these are not found in the blood.
76
Platelet
Cells involved in blood clot formation, measured in number of cells per liter of blood.
77
True or False: blood cancer is diagnosed by imaging
False: Blood cancer is NOT diagnosed by imaging
78
What is blood cancer?
- It begins in the blood marrow (spongy tissue in the bone where the majority of hematopoiesis takes place) when rapidly growing blood cells fail to mature into the healthy, functioning blood cells needed
- Immature cells crowd out the healthy ones -> cause fatigue (low amounts of red blood cells to carry o2)
- -> immune issues due to lack of different forms of white blood cells
-> bleeding and clotting issues due to loss of platelets
79
True or false: 1st nation have a lower incidence rate but also a low survival rate for blood cancer
true
80
Progenitor cells?
are multipotent and can divided into many different cell types, replaces damaged or lost cells
81
Hematopoiesis
development of mature blood cells from hematopoietic stem cells in the bone marrow
The hematopoietic stem cells:
- Small amount in the body
- Long lifespan
- Specialized into red and white, which live only for weeks to months
- Unspecialized can differentiate into progenitor cells -> spec cells
82
What does common myeloid and lymphoid refer to?
Common myeloid (refers to the tissue of the blood marrow) and lymphoid (refers to a type of connective tissue that has immune functions)
- Multipotent
- Have potential to differentiate into only a specialized blood cell types
- Replaces lost or damaged cells
- Produce immature cells called blasts which eventually develop into fully differentiated specialized cell types
83
Specialized myeloid cells
- Common myeloid progenitor cell differentiate into myeloid cells, such as red blood cells, platelets, specific type of white blood cells
- Unlike HSCs or common myeloid progenitor cells these cells are highly specialized
84
Specialized lymphoid cells?
- Common lymphoid cell differentiate into specialized lymphoid cell such as T, B cells and natural killer cells
Highly specialized cells
85
Classical blood cancer pathways:
- Differentiation block: tumour suppressor gene involved in differentiate is lost in the HSCs or the common progenitors -> accumulation of blasts
- + enhanced proliferation: another gene is mutated -> proto-oncogene that produces growth signals -> high proliferation
=blood cancer: malignant blasts crowd out normal HSCs and produce symptoms associated with disease progression
86
Blood smear?
A blood smear, which is similar to histology, involves placing a small amount of blood on
a glass slide, then spreading, or smearing, the drop across the slide surface, and finally staining the
sample to allow easy identification of various blood cell types
87
Promyelocytes
a precursor to white blood cells of myeloid lineage
88
Types of leukemia are classified based on:
Proliferation speed: acute or chronic
Cell origin: myeloid or lymphoid
89
Chronic leukemia (CMT, CLL)
- Slow growing
- Well differentiated
May be monitored for some time before treatment is initiated
90
Acute leukemia (AML, ALL)
- Fast growing
- Poorly differentiated cells
Immediate treatment
91
True or false: Patients with acute leukemia may have been suffering from chronic form for a long time, only visiting the hospital when their symptoms worsened
True
92
Chromatin?
A combination of D N A and proteins in the nucleus. Chromatin packages D N A into a
smaller volume and protects it from damage. Denser chromatin is more condensed and looks like beads on a string.
93
Myeloid or myelogenous leukemia?
(myeloid progenitors becomes malignant):
- Allows the formation of mature cells but in a skewed fashion
- CML: grow slowly
- AML: rapid growing, lost of ability to form mature cells, less differentiated blasts
94
Lymphocytic leukemia?
it arises from a lymphoid cell origin:
- ALL: malignant undifferentiated blasts grow quickly, mostly likely a common progenitor of all or most lymphocytes that becomes malignant
- CLL: slow growing and more differentiated malignant cell leading to a specialized lymphoid cell
95
Prognostic factors for leukemia?
- Age
- Weight
- Previous blood disorder
- Genetics
96
Translocation?
Translocation between genes -> chromosomes breaking -> fusion proteins (between 2 gene sequences)-> potential for being oncogenic
97
Normal RARA
- Involved in the differentiation of HSCs to specialized myeloid cells (fusion with PML, causes the pathway to be disrupted)
RAR-a gets inactivated temporarily to allow differentiation to take place
98
PML-RARA fusion
(found in half of the AML cases):
- RAR-a no longer responds to the differentiation signals, leading to an accumulation of immature blood cells
- Between chromosome 15 and 17 at the sites of PML and RARA genes
99
ATRA treatment?
Acts on the blast cells, causing them to mature into normally-functioning specialized myeloid cells.
100
Subclones?
caused by the accumulation of mutation -> different types of subclones
- Each of which may differ in its ability to metastasize and kill + respond to treatment
101
Immune checkpoint?
drugs that block the signal keeping tumour safe from destruction
102
Immune therapies
- Medications and treatment that activate or silence a patient's immune system to fight a disease
- Initially introduced to treat melanoma
- Uses the body's function
Patients with high levels of immune checkpoint gene expression!
103
Complete remission
all test how that all signs of cancer are gone
104
Immunocompromised:
temporary or permanent state of low immune system activity
105
Biomarker:
measurable indicator of some state or condition in the body (ex: gene expression)
- Types of cancer biomarkers: small chemical products, enzymes, dna, rna, cancer cells and proteins
- They have an important implication in screening and treatment options
106
Diagnostic biomarkers:
detects or confirms the presence of the disease
107
Prognostic biomarkers?
likelihood of disease progression or recurrence
108
Predictive biomarkers
prediction to treatment response
109
Genome sequencing has advanced science in many ways over the last two decades.
Human Genome Project: The complete human genome was first sequenced in 2001, a process that took 13 years and over $1 billion US dollars!
Next-Gen Sequencing: Today, thanks to various technological advancements, genomic sequencing costs under $1000 U S D and can be completed in hours to days.
Tumour Sequencing: The ability to quickly generate genomic data from tumours has revolutionized our understanding of cancer pathways. Scientists now have access to ever-increasing databases of genomic information.
Data Analysis: These databases can be used to identify previously unknown biomarkers and common mutations in certain cancers, allowing the cancers to be characterized quickly.
Application: This research can help to characterize the complexity of an important biological process, identify a new therapeutic target, or determine new diagnostic and prognostic factors, improving patient outcomes.
Genome Sequencing: Determining the complete nucleotide sequence of an organism’s D N A known as the genome.
110
What is the best improvement to patient outcomes?
use of routine cancer screening for at-risk populations who are otherwise healthy
