PRIN401 WEEK 5
CANCER
CANCER
peripheral crescents of compacted chromatin, and others that are uniformly dense or fragmented. These cells are undergoing:
apoptosis
_______ are synthesized and degraded at specific points in the cell cycle, which allows them to control various parts of the cell cycle.
cyclins
Malignancy of a tumor includes its uncontrollable ________, ________ and ______
growth, invasion, and metastasis
Intravasation of a cancer and subsequent extravasation of that cancer is known as:
(Intravasation is where cancer cells invade through the basement membrane of blood vessels, ending up in the lumen of blood vessels. The cancer cells can then travel through the bloodstream and undergo extravasation, which is where the cancer cells invade through the basement membrane of another portion of blood vessel)
metastasis
Only ___ copy of an oncogene needs to be mutated for it to become oncogenic. This is why oncogenic mutations can be inherited in a _____ fashion. Tumour suppressor genes usually require mutations in ___ copies in order for them to cause cancer. Remember that more than one gene usually needs to be mutated for cancers to form, but oncogenic transformation is a big step in that direction.
one , dominant
both
Many neoplastic cells have lost ________ ________ gene function
tumor suppressor
The vast majority of hereditary cancers are due to inheritance of _________ _______genes
tumor suppressor
Mismatch repair genes such as the MMR genes are usually ______ ______genes. _____ copies of an MMR gene need to be mutated in order for cancer growth to be promoted.
tumor suppressor
Both
gene _____ are not typical oncogenic mutations.
deletions.
because deletions are typical of tumor suppresor gene mutations
t(9;22) translocation is likely the bcr-abl translocation, which is known as the Philadelphia chromosome, which is associated with which cancer?
cml (chronic myelogenous leukemia)
the cellular target of taxane is _____, while the cellular target of vinka alkaloids is ______. taxane prevents microtubule ______ , while vinca alkaloids target microtubule _______.
taxane targets microtubules, while vinca alkaloids target tubulin.
taxane prevents disassembly, while vinca alkaloids prevent asasembly of microtubule.
high grade dysplasia of the breast may be called ________ carcinoma or ______ carcinoma in situ
intraductal carcinoma
ducttal carcinoma in situ
the cells of a tumor derive from one _____ cell, and the progeny evolves and becomes _____
progenitor,
heterogenous
which of the following are considered types of adjuvant therapy?
explain these terms:
carcinoma
adenoma
adenocarcinoma
papilloma
sarcoma
carcinoma is a malignant tumor of epithelial cells
adenoma is a benign tumor of glandular cells
adenocarcinoma is a malignant tumor that of glandular cells.
papilloma is a benign tumor of epithelial cells
sarcoma is a malignant tumor of connective tissue cells (or simply mesechymal origin)
The left vagus gives rise to the ____ esophageal plexus, while the right vagus gives rise to the ________ esophageal plexus
Left vagus --> Anterior E. plexus
Right Vagus --> Posterior E. plexus
(mnemonic: LA RP)
CASE OBJECTIVE: risk factors for colon cancer?
Dietary: low fiber, high refined carb, red meat
Genetic: family history
Pre-exisitng disease: polypms , IBD (inflammatory Bowel disease) increase risk
CASE OBJECTIVE: explain the significance of MMR gene mutations and describe the process by which cancer occurs in these.
- MMR gene mutations mean that mismatches in DNA are less repaired, thus mutations accumulate (esp. severe if mutation occurs in tumor suppressor or oncogenes)
- inherited individuals will likely develop cancer in 40s-50s (80% penetrance)
- higher risk for a lot of cancers of the viscera: endometrial, ovarian, colon, small bowel, pancreas, stomach
oncogenes code for which types of proteins normally?
- Growth factor and receptors
- Signal transduction
- Nuclear regulator
- Cell cycle regulators
what is the class name of doxorubicin and what is the moa?
class name is anthracyclin.
3 mechanisms:
1. top inhibitor
2. intercalating agent
3. reacts with o2 to make free radicals to damage dna
WEEK 5 EPITHELIUM. Dr. Heather Yule. How does epithelial tissue differ from the other basic tissues? (3)
1. closely adhering cells with little ECM
2. avascular
3. high mitotic index
What are the 4 functions of epithelial tissue? (4)
Secretion
Transports materials
Absorption
Protects underlying tissues
Where do you find epithelial tissue? (3)
Barriers (eg. skin, cornea) , compartments (eg. body compartments, vessels) , glands
List the types of simple and stratified epithelia.
simple: squamous, cuboidal, columnar
stratified: keratinized squamous, non-keratinized squamous, cuboidal, columnar
Where are stratified columnar epithelia found?
They are found at points of epithelial lining transitions. eg. epiglottis (from squamous to respiratory) , recto-anal junction (from stratified columnar to stratified squamous)
Where are pseudostratified and transitional epithelia found?
pseudostratified epithelia are found in the upper respiratory tract
transitional epithelia are found only in the urinary bladder (hence they are also called urothelium)
The basement membrane is the fusion of the _____ lamina and ______ lamina, which in turn can be further divided into two lamina: lamina ______ and lamina _______. The basement membrane is composed of which 4 groups of proteins ? (mnemonic)
basement membrane
- basal lamina
-lamina lucida
-lamina densa
- reticular lamina
mnemonic: GLCP
G: glycoprotein
L: linker protein
C: collagen
P: proteglycan
*the two dark arrows are lamina lucida and lamina densa respectively. The light blue arrorw is the reticular lamina.
Explain the naming system of exocrine glands.
1. Simple / compound (if the duct branches, then it is a compound gland)
2. Acinar/ tubular (if the shape is round , then it is acinar)
Define the terms metaplasia, carcinoma, and dysplasia, and give one example for each.
Metaplasia is the reversible replacement of one type of epithelium into another type, due to a stimulus, and the substitute epithelium is also normal in appearance (although unfitting). Eg. smoking may cause the reversible replacement of psuedostratified epithelium of the lungs into stratified cuboidal.
Carcinoma: Cancer of surface epithelium.
Dysplasia: epithelium looks strange (dysmorphic), due to some stimulus. Eg. HPV may cause the human cervical epithelium to exhibit dysmorphism.
Molecular Mechanisms in cancer. Christine Simmons. Explain the basis of cell cycle control.
The cell cycle consists of G1, S, G2, mitosis. Cells need to pass these checkpoints, otherwise, apoptosis.
The cell cycle is tightly regulated by:
1. cyclins, proteins that control CDK (easy to remember: cyclin is responsible for the cell cycle)
2. CDK (Cyclin-dependent kinases, the executors)
Define oncogene. Oncogenes code for which different classes of proteins? (5) How does it lead to cancer? What kind of inheritance pattern would you observe.
Oncogenes are genes that could cause cancer.
They code for
-growth factors
-growth factor receptors
-signal transduction proteins
-nuclear regulators
-cell cycle regulators.
Mutations in these oncogenes will activate them again and cause cancer (the normal form of oncogenes are proto-oncogenes, and they are usually silenced after embryological development.
They display a dominant inheritance (need only one mutation)
Define tumor suppressor genes. What is their main role , and how are they related to the development of cancer? Give one prominent example. What is the pattern of inheritance?
Tumor suppressor genes are gatekeepers and caretakers. Normally, their role is to
-population control
-apoptotic control
-repair
If there is a mutation in these genes, tumor suppressors won't work anymore. The most common mutation is mutation in the p53 protein.
Recessive inheritance pattern (need both mutations)
Give an example of how cancer can arise from genomic instability .
HNPCC (Hereditary nonpolyposis colorectal cancer) arises from failure of MMR genes (Mismatch Repair)
CELLULAR MECHANISM IN CANCER. CHRISTINE SIMMONS. What are the 5 hallmarks of cancer (mnemonic) ?
"Doesn't Always Improve My Image" -mnemonic
Division
Angiogenesis
Invasion into BM/ECM
Metastasis
Instability (aka genomic instability)
___________ can occur in cases where cell division is greater than cell death; this is more common in certain types of tissues. What type of tissues are they?
Neoplasia.
Certain types of tissues are more prone to neoplasia. Eg. proliferating tissue (skin, lung, gut) and tissues under hormonal control
______ is controlled by an angiogenic switch. Name these 'switches' (there are positive and negative regulators, 3 in total). How are MMPs (Matrix proteinases) and integrins affected by the positive switches?
Angiogenesis.
1. VEGF (+ angiogenesis)
2. bFGF (+ angiogenesis)
3. Thrombospondin (- angiogenesis)
The positve regulators activate MMP and integrins , and the net effect is that the ECM is cleared out of the way to allow angiogenesis to the cancerous cell. Think of ECM as a bushy forest, MMP clears the bush.
Invasion and metastasis can occur in one of four ways. Which four ways? How do malignant cells alter its connection to ECM and detach from it?
1. blood
2. lymph
3. neighboring cells
4. through the lining of body cavities (serosal surfaces, eg. cancer may spread across the pleura)
Malignant cells do two things:
1. secrete more proteinase than proteinase inhibitor, degrades underlying BM and ECM and invades
2. alter CAMs, which is made of integrins and cadherins, allowing them to detach from the main tumor and metastasize
What are the clinical implications of the heterogeneity of tumor cells?
1. different biological traits (ie. invasiveness, metastasizing potential)
2. resistance to drugs
Outline the Gompertzian growth pattern of cancer with a diagram, specifically outlining the limit of clinical detection. When does exponential growth occur and when is chemotherapy most effective?
Limit of clinical detection is when there are 10^9 cells, or 2^30 cells, aka 30 doublings. diameter of tumor will be 1cm.
Exponential growth occurs between 10^6 cells, aka 20 doublings to 10^9 cells. Chemotherapy is the most effective during exponential growth.
describe the stepwise progression of cancer.
1. initial mutation causes increased proliferation and dysplasia
2. additional mutation causes decreased apoptosis
3. invasion of surrounding tissues
4. additional mutation causes metastasis
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Cartes-fiches
WEEK 5 EPITHELIUM. Dr. Heather Yule. How does epithelial tissue differ from the other basic tissues? (3)
1. closely adhering cells with little ECM
2. avascular
3. high mitotic index
What are the 4 functions of epithelial tissue? (4)
Secretion
Transports materials
Absorption
Protects underlying tissues
Where do you find epithelial tissue? (3)
Barriers (eg. skin, cornea) , compartments (eg. body compartments, vessels) , glands
List the types of simple and stratified epithelia.
simple: squamous, cuboidal, columnar
stratified: keratinized squamous, non-keratinized squamous, cuboidal, columnar
Where are stratified columnar epithelia found?
They are found at points of epithelial lining transitions. eg. epiglottis (from squamous to respiratory) , recto-anal junction (from stratified columnar to stratified squamous)
Where are pseudostratified and transitional epithelia found?
pseudostratified epithelia are found in the upper respiratory tract
transitional epithelia are found only in the urinary bladder (hence they are also called urothelium)
The basement membrane is the fusion of the _____ lamina and ______ lamina, which in turn can be further divided into two lamina: lamina ______ and lamina _______. The basement membrane is composed of which 4 groups of proteins ? (mnemonic)
basement membrane
- basal lamina
-lamina lucida
-lamina densa
- reticular lamina
mnemonic: GLCP
G: glycoprotein
L: linker protein
C: collagen
P: proteglycan
*the two dark arrows are lamina lucida and lamina densa respectively. The light blue arrorw is the reticular lamina.
Explain the naming system of exocrine glands.
1. Simple / compound (if the duct branches, then it is a compound gland)
2. Acinar/ tubular (if the shape is round , then it is acinar)
Define the terms metaplasia, carcinoma, and dysplasia, and give one example for each.
Metaplasia is the reversible replacement of one type of epithelium into another type, due to a stimulus, and the substitute epithelium is also normal in appearance (although unfitting). Eg. smoking may cause the reversible replacement of psuedostratified epithelium of the lungs into stratified cuboidal.
Carcinoma: Cancer of surface epithelium.
Dysplasia: epithelium looks strange (dysmorphic), due to some stimulus. Eg. HPV may cause the human cervical epithelium to exhibit dysmorphism.
Molecular Mechanisms in cancer. Christine Simmons. Explain the basis of cell cycle control.
The cell cycle consists of G1, S, G2, mitosis. Cells need to pass these checkpoints, otherwise, apoptosis.
The cell cycle is tightly regulated by:
1. cyclins, proteins that control CDK (easy to remember: cyclin is responsible for the cell cycle)
2. CDK (Cyclin-dependent kinases, the executors)
Define oncogene. Oncogenes code for which different classes of proteins? (5) How does it lead to cancer? What kind of inheritance pattern would you observe.
Oncogenes are genes that could cause cancer.
They code for
-growth factors
-growth factor receptors
-signal transduction proteins
-nuclear regulators
-cell cycle regulators.
Mutations in these oncogenes will activate them again and cause cancer (the normal form of oncogenes are proto-oncogenes, and they are usually silenced after embryological development.
They display a dominant inheritance (need only one mutation)
Define tumor suppressor genes. What is their main role , and how are they related to the development of cancer? Give one prominent example. What is the pattern of inheritance?
Tumor suppressor genes are gatekeepers and caretakers. Normally, their role is to
-population control
-apoptotic control
-repair
If there is a mutation in these genes, tumor suppressors won't work anymore. The most common mutation is mutation in the p53 protein.
Recessive inheritance pattern (need both mutations)
Give an example of how cancer can arise from genomic instability .
HNPCC (Hereditary nonpolyposis colorectal cancer) arises from failure of MMR genes (Mismatch Repair)
CELLULAR MECHANISM IN CANCER. CHRISTINE SIMMONS. What are the 5 hallmarks of cancer (mnemonic) ?
"Doesn't Always Improve My Image" -mnemonic
Division
Angiogenesis
Invasion into BM/ECM
Metastasis
Instability (aka genomic instability)
___________ can occur in cases where cell division is greater than cell death; this is more common in certain types of tissues. What type of tissues are they?
Neoplasia.
Certain types of tissues are more prone to neoplasia. Eg. proliferating tissue (skin, lung, gut) and tissues under hormonal control
______ is controlled by an angiogenic switch. Name these 'switches' (there are positive and negative regulators, 3 in total). How are MMPs (Matrix proteinases) and integrins affected by the positive switches?
Angiogenesis.
1. VEGF (+ angiogenesis)
2. bFGF (+ angiogenesis)
3. Thrombospondin (- angiogenesis)
The positve regulators activate MMP and integrins , and the net effect is that the ECM is cleared out of the way to allow angiogenesis to the cancerous cell. Think of ECM as a bushy forest, MMP clears the bush.
Invasion and metastasis can occur in one of four ways. Which four ways? How do malignant cells alter its connection to ECM and detach from it?
1. blood
2. lymph
3. neighboring cells
4. through the lining of body cavities (serosal surfaces, eg. cancer may spread across the pleura)
Malignant cells do two things:
1. secrete more proteinase than proteinase inhibitor, degrades underlying BM and ECM and invades
2. alter CAMs, which is made of integrins and cadherins, allowing them to detach from the main tumor and metastasize
What are the clinical implications of the heterogeneity of tumor cells?
1. different biological traits (ie. invasiveness, metastasizing potential)
2. resistance to drugs
Outline the Gompertzian growth pattern of cancer with a diagram, specifically outlining the limit of clinical detection. When does exponential growth occur and when is chemotherapy most effective?
Limit of clinical detection is when there are 10^9 cells, or 2^30 cells, aka 30 doublings. diameter of tumor will be 1cm.
Exponential growth occurs between 10^6 cells, aka 20 doublings to 10^9 cells. Chemotherapy is the most effective during exponential growth.
describe the stepwise progression of cancer.
1. initial mutation causes increased proliferation and dysplasia
2. additional mutation causes decreased apoptosis
3. invasion of surrounding tissues
4. additional mutation causes metastasis
respiratory epithelium is also known as ________ _____ ______ ______ with _____ _____
pseudostratified ciliated columnar epithelium with goblet cells
what is the difference between carcinoma in situ and benign tumor?
carcinoma has not invaded the underlying basement membrane, but it has a high chance of doing so and become malignant . And because of this high potential, if left untreated will likely lead to malignancy, so surgical removal is often recommended.
benign tumors most likely will not lead t malignancy. eg . freckles.
(whether it is carcinoma in situ or benign, you can tell by histology)
CANCER PATHOLOGY: DR. DAVID SCHAEFFER. A hypertrophy is an increase in the ___ of cells within an organ, while an atrophy is a reduction in the ____ or ___ of cells within an organ.
A hypertrophy is an increase in the size of cells within an organ, while an atrophy is a reduction in the size or number of cells within an organ.
what is the spectrum of cancer?
mild dysplasia < moderate < severe dysplasia < carcinoma in situ (know for sure very likely to develop into malignancy) < invasive cancer
Explain penetrance and expressivity(in the context of genetics)
In medical genetics, the penetrance of a disease-causing mutation is the proportion of individuals with the mutation who exhibit clinical symptoms. For example, if a mutation in the gene responsible for a particular autosomal dominant disorder has 95% penetrance, then 95% of those with the mutation will develop the disease, while 5% will not, even if they have the mutation.
Different degrees of expressivity in different individuals may be due to variation in the allelic constitution of the rest of the genome or to environmental factors
describe the inheritance mode of FAP. Mutations in which gene causes FAP?
Familal Adenomatous Polyposis . Inheritance pattern is autosomal dominant. Mutations in the APC gene causes FAP. Those affected have 100% chance of developing colon cancer in their 40s, unless surgical removal of polyps is performed.
composition of neoplasm: Supportive stroma made up of __________ tissue and blood vessels. The stroma is ___ neoplastic. When large quantities of fibrous tissue are present in the supporting stroma the tumor is said to be _______ and ______.
connective;
NOT;
scirrhous and desmoplastic (desm- means knot, literally knot formation)
Give 7 examples of tissues that are mesenchymal in origin.
Bone
Cartilage
Fat
smooth muscle
striated muscle
vessels
fibrous tissue
how do you call a neoplasm of plasma cells?
multiple myeloma
how do you call a neoplasm of marrow lymphotcyte?
lymphocytic lymphoma
how do you call a neoplasm of granulocytes?
myeloid leukemia
What are the apoptosis regulators (one positve and one negative regulator)?
in some cancers, upregulation of bcl2 means reduction of apoptosis, while upregulation of bax means increased apoptosis.
what are the 3 types of colon adenoma , and which type predisposes the person to have a higher risk of developing adenocarcinoma?
- tubular adenoma
- villous adenoma
- tubulovillous adenoma
villous adenoma has a higher risk of developing into an adenocarcinoma
size of adenoma and risk of cancer: 1-2 cm , > 2CM
1-2cm : 10%
> 2cm : 46%
PRINCIPLES OF CANCER THERAPY. CHRISTINE SIMMONS. List the components of the diagnosis of cancer.
1. All cancers should be confirmed by tissue diagnosis
- cancer type (histology eg. carcinoma or lymphoma)
- benign or malignant
- site of origin (ie. primary or secondary)
- staging
AJCC system of cancer staging, what is the hallmark of stages I,II,III,IV?
I: tumor invasion to submucosa
II: tumor invasion to muscularis propria
III: invasion to regional lymph nodes (or invasion to serosa)
IV: metastasis
What are the implications of lymph node metastases in cancer patients ? (3)
1. only epithelial cancers can spread to the regional lymph nodes
2. indicates probable widespread disease
3. lymph node metastasis indicates the need for more treatment to eradicate microscopic cancer
define curative, adjuvant, neo-adjuvant, maintenacne , and palliative treaments
Curative: complete ablation of all maligant tissues (surgery, radiation, systemic therapy)
Adjuvant, neo-adjuvant: increase probability of cure (by eradicating microscoptic cancer)
Maintenance: Prevent relapse (low dose chemotherapy, and molecularly targeted therapy)
Palliative: Relief of symptoms
describe systemic approaches of cancer treatments. (4)
1. chemotherapy
2. hormone therapy (only works in certain types of cancers like breast or testicular cancer)
3. biological therapy (molecularly targeted, often targets growth factor receptors, these drugs are often tyrosine kinase receptors. A good example would be cetuximab that competitively bind and inactivate EGF receptors )
4. Monoclonal antibodies.
ANTICANCER THERAPY 1. JENNIFER SHABBITS. compare and contrast apoptosis and necrosis
1. apoptosis is highly organized, necrosis is not
2. apoptosis is controlled fragmentation, necrosis is uncontrolled cell lysis
3. apoptosis does not result in inflammatory response, necrosis does
4. apoptosis is triggered by cytotoxic drugs, necrosis is triggered by cellular injury
