Module 2: Neoplasia

During cell culture: ________ (cancer cells/normal cells) have less nutritional requirements and have the possibility of becoming "immortal" & _________ (cancer cells/normal cells) have a finite (limited) life span.

(Cancer cells) have less nutritional requirements and have the possibility of becoming "immortal" & (normal cells) have a finite life span.

Why are the liver and lungs the most frequently involved secondary sites for sarcomas to spread?

(slide 49 in Neoplasia) Long story short, the lungs and liver have very small veins and capillaries in the lungs, where it is much easier for a clump of cancer, (sarcoma to be specific, to get stuck.

How can the pain of cancer effect the patient?

-Pressure -obstruction -invasion of sensitive structures (places with >nerve endings -tissue damage -inflammation

Damage to regulatory genes can lead to damage of other genes that:

-encode growth factors/receptors -regulate apoptosis -regulate the repair of damaged DNA

What are the risk factors for cancer? hint: there's a shit ton

-genetics -virus causes. example: HPV -tobacco and alcohol use -sexual/reproductive behavior -sex hormones -air pollution -work hazards -UV radiation -ionizing radiation -diet. more detail on another card

What parts of a persons diet can be a risk factor for cancer?

-low fiber -nitrates. think lunch meat - omega 6 fatty acids. but omega 3 fatty acids can decrease risk -obesity -xenobiotics which are foreign substance: acts like a drug, hormone, or toxin

The suffix for benign tumors is:

-oma example: fibroma, adenoma, cystadenoma

What are the 3 ways that malignant neoplasms disseminate/spread?

1. "seeding" 2. Lymphatic spread 3. Hematogenous spread

What are the 3 categories of nomenclature of malignant tumors?

1. -sarcoma: sarc means flesh, so its origin is *connective* tissue 2. -carcinoma: epithelial origin 3. lymphomas & leukemias: lymphoma is solid mass of tissue and leukemia circulates bloodstream)

metastasis requires what 3 steps?

1. Invasion/penetration into blood vessels, lymphatic vessels, or body cavities and then break off from the original mass which is called shedding) 2. Transport to a second site, clumps are the most effective 3. Arrest, adherence, and proliferation at secondary site. remember: "the 3 S's = Stop, Stick, and Start growing)

What 3 factors of tumors can effect the host?

1. Location/size. Example: 1cm pituitary adenoma or 5mm leiomyoma in the wall of a renal artery 2. Hormone production. Example: a pancreatic islet cell producing excessive insulin 3. Ulceration: breaking through a surface causing bleeding and infection

What are the two exceptions to the "-oma" rule when it comes to the nomenclature of benign tumors? Why are they exceptions?

1. Lymphoma 2. melanoma Both of these are actually malignant, not benign

What are the 3 types of oncogenes?

1. Proto-oncogenes: "turn on" gene, gene that, in their normal state, lead to proliferation 2. tumor suppressor genes: genes that, when in normal state, "turn off" cell proliferation 3. "proof-reading" genes: genes that look for DNA error and repair enzymes

What 6 components does cancer transformation require?

1. Self sufficiency in growth signals: proto-genesis "turned on" 2. Insensitivity to antigrowth signals: tumor suppressive cells "turned off" 3. Evading apoptosis: Have telomerase active so it continues to build up telomeres. which leads to number 4. 4. Limitless replicative potential 5. Sustained angiogenesis: Needs its own blood supply 6. Tissue invasion and metastasis: becomes Hitler and takes over

What are the 2 main reasons why tumor cells are able to survive under less-favorable conditions?

1. Tumor cells require much less oxygen. That means that they also have less mitochondria, produce less ATP, and use glycolysis instead of oxidative phosphorylation. 2. Since glycolysis produces lactic acid as a biproduct, tumor cells are able to better tolerate it than a normal cell would.

2 examples of carcinoma in situ are:

1. cervical cancer 2. breast cancer. Example: DCIS, ductal carcinoma in situ)

Look at the differentiation chart on slide 13 in lecture "neoplasia". Why is this chart significant?

1. moving from top to bottom, it shows that normal cells go from totally undifferentiated, like they are just blue prints, to highly differentiated and specialized. 2. Moving from bottom to top, it explains that a cancer cell would start out at super differentiated, specialized, and it even take "acts" and preform like a normal call would.. But the further that you move up the chart, the cancer cell becomes less and less differentiated, to the point that when it gets to the top, if you were to look at it through a microscope, you wouldn't have a clue what it was. anaplasia: complete lack of differentiation.

What are the 4 ways that cancers grow?

1. progressive infiltration 2. invasion 3. destruction 4. penetrating the surrounding tissue

What is a biochemical difference between normal cells and tumor cells?

A tumor cell can actually produce fetal enzymes. Example: the metabolism of liver tumor cells are much simpler than that of adult liver cells.

What is the difference between anaplasia and pleomorphism?

Anaplasia is "what they're called" and pleomorphism is "what they look like". remember: pleo=multi, morph=shape/size

Tell the story of telomerase and how it can lead to immortality:

At the end of a DNA strand/chromosome, there is a telomere on each end. These telomeres are cells that are unable to replicate and eventually brake off the end of the strand. Telomerase is an enzyme that comes along and can re-attach the telomeres. Cancer cells have telomerase and can cause them to live much longer than the average.

What is skip metastasis?

Basically when a cancer is in the lymphatic system, it doesn't necessarily affect all lymph noes and can skip some of them. Which is why a lot of the times, surgeon have to remove more nodes than you would think (picture on slide 48 of Neoplasia)

What is a huge contributing factor why cancer patients lose lots of weight? Think about cancer biologically

Because tumor cells need less oxygen = they have less mitochondria= produce less ATP through glycolosis. So the patient quickly burns through what little energy they do have.

Why is understanding tumor angiogenesis important clinically?

Because we use the density of intratumor micro-vascularity to help diagnose breast cancer. Also, angiogenesis inhibitors have the potential for use in treatment in the future. example: cartilage has no blood vessels because it has "anti-angiogenesis factors" which prevents forming blood vessels. If we could harness this, we could cure cancer

Benign tumors are normally ___________ (well-differentiated/poorly differentiated) and _______________ (do/do not) resemble there counterparts.

Benign tumors are normally well-differentiated and do resemble there counterparts. they may even produce hormones!

Benign tumors ___________ (do/do not) have the ability to infiltrate, invade, and metastasis?

Benign tumors do not have the ability to infiltrate, invade, and metastasis

Carcinoma in situ have not yet broken through the ______________.

Carcinoma in situ have not yet broken through the basement membrane

Carcinoma in situ is pre-_____________ NOT pre- ___________.

Carcinoma in situ is pre-invasive NOT pre-cancerous. Its already cancerous, is just chillin waiting to make a move

Carcinoma in situ may be erroneously, which means wrongly, confused with ______________.

Carcinoma in situ may be erroneously confused with benign tumors.

Carcinomas (cancerous) are made up of ____________ tissue which is why when the metastasize, they typically do it by ______________spread.

Carcinomas (cancerous) are made up of epithelial tissue which is why when the metastasize, they typically do it by lymphatic spread.

Define anaplastic cells:

Complete lack of differentiation

Debulking a tumor with surgery/radiation can cause the surviving cells to:

Debulking a tumor with surgery/radiation can cause the surviving cells to go into active growth which makes them able to be killed by chemotherapy. This could also be considered a bad thing because that means that the cancer is growing quickly

Define Differentiation

Differentiation is the process of cells differentiating from one another. this process for the most part is irreversible) This is important because the more different the cells are, the more specialized they become. When a cell is not differentiated at all, this is an example of cancer.

What is "doubling time" in relation to the cell growth cycle?

Doubling time means that the tumor cell cannot complete the cell growth cycle more RAPIDLY, but they can be triggered to cycle cell growth more OFTEN

TRUE OR FALSE -BENIGN TUMORS: Are poorly to well-differentiated, have a varying rate of growth, partake in local invasion, and sometimes metastasis. -MALIGNANT TUMORS: Are well differentiated, have a slow growth rate, have local growth but NOT local invasion, and NEVER metastasis.

FAAAAAALSE

True or false Malignant tumors sometimes for a fibrous capsule.

False, definitely false. Malignant tumors NEVER form a capsule.

True or False: The cell growth cycle can be sped up

False. The process of the cell growth cycle happens in a set amount of time. kind of like human pregnancies are 9 months. BUT, the cell can undergo the cell growth cycle more frequently. this is called "doubling time"

_______________ is the most frequently reported symptom of cancer

Fatigue. This is because of the decrease in supply of ATP and also the increase in need of ATP caused by nutritional status, decreased muscle contractility, and secondary biochemical changes

Not all, but most, benign tumors develop _____________ that separates them from the normal surrounding tissue

Fibrous capsule

The location of a cancer metastasizing sometimes has patterns but not always. For example, breast cancer likes to metastasize to the __________ and prostate cancer likes to metastasize to __________.

For example, breast cancer likes to metastasize to the axillary lymph nodes and prostate cancer likes to metastasize to bone.

Why is the growth fraction important when it comes to treating cancer?

Growth fraction is important because of the way that chemotherapy works. Chemotherapy works by killing ANY cell in the cell growth cycle. any "pregnant" cell, cancerous or not.

What is "growth fraction" in relation to the cell growth cycle?

Growth fraction is the portion of cells within a tumor that are actively replicating

Cancer Grading and Staging: T/N/M M= Metastasis What are the levels?

M0= No metastasis M1= There is metastasis M2= No longer used (suspected metastasis)

Malignant tumors have __________ (increased/decreased) cell-to-cell adhesion, so they ________ (lose/gain) CAMs. They also have _________(increased/decreased) cell motility, which is also called Pseudopodia

Malignant tumors have DECREASED)cell-to-cell adhesion so the LOSE CAMs. They also have INCREASED cell motility (also called Pseudopodia)

A 3 part question: 1. What type of enzymes to malignant tumors have high levels of? 2. What do the enzymes do? 3. What are some examples of these enzymes?

Malignant tumors have high levels of Lytic enzymes. The enzymes cause damage to the normal extracellular matrix. Some examples: Protease, lysosomes and collagenases

______________ (benign/malignant) tumors show a wide variation in their rate of growth. Many can grow slowly for years and then suddenly triple in size.

Malignant tumors show a wide variation in their rate of growth. Many can grow slowly for years and then suddenly triple in size.

Define pleomorphic

Many shapes and sizes

Wat is the difference between morbidity and mortality?

Morbidity = the # of CASES Mortality= the # of DEATHS Ex: lots of people get the flue (high morbidity) but not many people die from it (low mortality)

Cancer Grading and Staging: T/N/M N= Lymph Node involvement What are the levels?

N0= Lymph nodes not involved N1= Adjacent lymph nodes involved N2= Distant lymph nodes involved

Dysplastic cells are often found:

Near other "cancerous foci". So dysplastic cells kind of surround cancer because they're "pre-cancerous"

Neoplasia compete with ___________ cells for their metabolic needs. They also increase in size regardless of their ____________ and the ______________ of their host.

Neoplasia compete with normal cells for their metabolic needs. They also increase in size regardless of their local environment and the health status of their host.

Normal cell division, proliferation, and differentiation is strictly regulated by ______________.

Normal cell division, proliferation, and differentiation is strictly regulated by genetic control

What is the name of the type of genes that "turn on" resting cells so that they can divide, and "turn off" proliferating cells so they don't over multiply?

Regulatory genes

Sarcomas (cancerous) are made up of ____________ tissue which is why when the metastasize, they typically do it by ______________spread.

Sarcomas (cancerous) are made up of connective tissue which is why when the metastasize, they typically do it by hematogenous spread.

What is the process of "seeding" and what enhances it?

Seeding is the process of a malignant neoplasm "spreading like flowers". Seeding is enhanced by the LACK of intracellular adhesion, because it makes them break apart and spread easier. remember the story of the surgeon and the dog with breast cancer, and how it spread to his stomach -Seeding occurs in body cavities. -ovarian cancers tend to seed often.

Humans dont create the enzyme telomerase anywhere except in:

Sperm cells

Define disseminate:

Spread

Cancer Grading and Staging: T/N/M T=tumor what are the levels?

T0= Tumor free T1= Tumor is <2cm T2= Tumor is 2-5cm T3= Tumor is >5cm

Describe the nuclei of an anaplastic cell:

The nuclei of anaplastic cells tend to be larger, very hyperchromic, which means dark, and varied in bizarre shapes and sizes, they have no orientation to each other, they're all special cancer snowflakes. Sidenote: Anaplastic cells also go through mitosis more often and are abnormal.

The cell -growth- cycle is basically what?

The pregnancy of a cell.

What is the process of "cell culture"?

The process of growing cells in a lab

Define metastasis:

The spread of cancer cells from their original site to distant site

When a normal cell turns into a tumor, benign or malignant, this process is called _____________.

Transformation

True or false Larger neoplasms and anaplastic neoplasms are more likely to metastasize

True

Ture or false Benign tumors remain localized at the site of origin and slowly expand

True

TRUE OR FALSE -BENIGN TUMORS: Are well differentiated, have a slow growth rate, have local growth but NOT local invasion, and NEVER metastasis. -MALIGNANT TUMORS: Are poorly to well-differentiated, have a varying rate of growth, partake in local invasion, and sometimes metastasis.

True (:

The process in which a tumor grows its own vascular blood supply is called:

Tumor Angiogenesis Remember, Angio = blood vessel, Genesis = formation of

Sarcomas more more likely to penetrate _________ (veins/arteries). Why?

Veins. This is because there is less pressure in veins and also because the walls of veins are thinner.

Define differentiation of a tumor cell:

When a tumor cell is differentiated, it acts and functions just like normal cells would.

When a cancer cell grows to rapidly, what can happen to it?

When cancer cells grow too rapidly, the can often contain central areas of ischemic necrosis because the tumor's blood supply isn't able to grow as fast and keep up. Remember: Oxygen can only diffuse about 1-2mm, otherwise it will need new blood supply

Define contact inhibition:

When cells dont want to be too close to other cells.

According to the nomenclature, what is a cystadenoma?

a mass or cyst on a hollow organ

Define carcinoma in situ

cancerous "in situation", so not on the move.

Define carcinogenesis

development, production or origin of cancer

Pain of cancer is influenced by:

fear anxiety sleep loss fatigue physical deterioration

According to the nomenclature, where would an adenoma take place?

glandular

Define autonomy

loss of responsiveness to normal growth controls, kind of has a mind of it's own. example: neoplasia

________ (benign/malignant) tumors range from well differentiated to totally undifferentiated. its a spectrum

malignant tumors range from well differentiated to totally undifferentiated

Dysplasia is disorderly but still ____________.

non-neoplastic, and cases that aren't severe may be reversible

During cell culture: __________ (cancer cells/normal cells) exhibit contact inhibition and __________ (cancer cells/normal cells) tend to pile up (puppy pile!) and form nodules.

normal cells exhibit contact inhibition & cancer cells tend to pile up (puppy pile!) and form nodules.

During cell culture: __________ (cancer cells/normal cells) require firm support for growth, which is called ______________ & ___________ (cancer cells/normal cells) do not require support for growth and can float suspended in clumps which is called ___________________

normal cells require firm support for growth called anchor-dependent & cancer cells do not require support for growth and can float suspended in clumps called anchor-independent

Local Invasion by Cancer: __________ from the growing mass leads to _____________ which further aids in the spread of cancer.

pressure from the growing mass leads to local tissue death which further aids in the spread of cancer.

What is "cancer cachexia"?

progressive loss of body fat and lean body mass, accompanied by profound weakness, anorexia and anemia. The size of the cancer can effect cancer cachexia.

Define oncogenes

regulatory genes, that if damaged, may lead to cancer

Benign tumors grow ___________ (slower/faster) than malignant tumors.

slower, but this can very! Exceptions: -benign tumors are influenced by hormone levels. example: pregnancy hormones -pressure constraints can also effect their rate of growth> Example: benign brain tumor could be slowed by hitting the skull