Neoplasia: General

Question 1

Malignant tumor cells characteristic:

Answer 1

• Undifferentiated cell
• Do not look like their tissue of origin
• Heterogeneous (change, diverse–> difficult to tx)
• Loss of normal feature
• Pleomorphic (multiple shapes and sizes)
• Little evidence of normal function
• Can spread (metastasis) and produce new blood vessels into the tumor (angiogenesis)

Question 2

Malignant cells undergo frequent mitosis, have an abnormal looking nucleus, abnormal heterogeneous cells and more blood vessels. These changes are due to:

Answer 2

• Loss of contact inhibition (will continue to grow and spread despite touching each other. and surrounding tissues, growth in clumps and will alter surrounding cells)
• Increase in growth factor secretion
• Increase in oncogene expression
• Loss of tumor suppressor genes

Question 3

Systemic effects of malignant tumors:

Answer 3

• Cachexia (total body wasting)
• Paraneoplastic syndromes (biochemical, neurological, hematoligical derangements caused by abnormal compounds that tumors can release)
• Immunosuppression (more susceptible to infections)

Question 4

The main site of metastasis: Common sites:

Answer 4

Liver **

Brain, lung, bone, abdomen and lymph nodes.

Question 5

Why is the immune systems is not able to elimined the cancer cells?

Answer 5

-When cancer cells enter the circulation, immune cells may be able to recognize the abnormal cancer cells but however, they are coated with platelets, this provides them with protection as they move throughout the circulation until they find another place to attach, and move into a tissue to cause metastasis.

Question 6

Properties of Tumor Cells to be able to metastasize:

Answer 6

• Produce laminin and laminin receptors
• Attach to neighboring cells (laminin bind to the laminin receptor on collagen in the extracellular matrix)
• It gain access to blood vessels primarily through smaller veins (much thinner than arteries wall)
• Once in the intracellular matrix, release collagenase to break trhough the collagen and the basement membrane
• Go through the connective tissue stroma, recognize fibronectin and able to release other enzymes that can dissolve components on the interstitial matrix.
• Capable to release autocrine motility factors that assist the cell in moving
• As the tumor growth, in the center, there is development of necrotic regions due to his requirement in nutrient and oxygen. It will release more factors (Tumor angiogenesis factor - TAF and Vascular endothelial growth factor - VEGF) to stimulate further angiogenesis (for blood and lymphatics)

Question 7

Lyme nodes are particularly monitored closely because:

Answer 7

There is progressive encroachment of tumor cells into lymph nodes near the site of origin. The cancer cells will spread in the lymphatic vessels and invade local lymph nodes. It can diverted to neirghboring nodes and new metastatic growths. Lymph flow can be reversed due to tumor cells.

Question 8

Histological grading of tumors with the:

Answer 8

Gleason Scale:
Grade I (well differentiated)
Grade II (moderately differentiated): increase mitoses and variation in size and shape.
Grade III and IV (poorly differentiated)

Question 9

Tumor release cytokines, hormones, etc. which cause paraneoplastic syndromes:

Answer 9

• Tumor production of enzymes or fetal proteins
• Tumor stimulation of antibody production
• Metabolism of steroids by the tumor
• Tumor production of protein hormones

Question 10

The Immunological Syndrome is

Answer 10

When Antibody or T-cells stimulating the cross-reaction with other normal tissue (abnormal antibodies eg. will alter ion channels in the brain)

Question 11

Cachexia is when the person does not want to eat anymore. It is caused by: (physiopathology)

Answer 11

Paraneoplastic syndromes, where the tumor release cytokine (TNFa, IL6, IFNy) –> act on hypothalamus –> anorexia –> metabolize adipose tissue and skeletal muscle –> catabolism/liver –> inflammatory proteins.

Question 12

Cancer cell at the beginning:

Answer 12

• Initial cancer cell has to multiply about 30 doublings before you have the smallest detectable tumour mass.
• Because of the exponential phenomenon, it only take 10 more doublings before you are dead.

Question 13

What is the problem with tumors in the cell cycle?

Answer 13

• The tumor cell will rapidly dividing (not usually faster than normal cell)
• Usually, some cells in the tumor will differentiate and die. The problem is when some of them continually proliferating. (subclone who stay in live and accumulate)
• Problem: Imbalance between production and elimination

Question 14

Immune surveillance of the tumor:

Answer 14

• Antigen presenting cells will ingest the tumor antigens and present to the cytotoxic T cell so that it will be induced to kill the tumor cell. (usually just slow down the tumor growth bc it can mutates and resist the the immune system)
• CD8 and NK cells will recognize the tumor cells are abnormal and wiil get rid of it with various methods. (ideally kill enough of the tumor to creat an equilibrium so the tumor cannot grow more, but can be heterogenous and still escape)

Question 15

Mechanisms of tumor escape the immune systems:

Answer 15

• Tumor can block antibodies that are produced
• Tumor can attack your cytotoxic T cells or even release toxic compounds.
• Can alter the surface antigens so they are no longer recognized and can escape the immune systems.
• Tumor have many ways to keep accumulating mutations to becoming resistant to immune attack

Question 16

Cellular carcinogenesis: 3 steps:

Answer 16

• Initiation (first accumulation of problems in the cancer cell)
• Promotion (involve changes that allow the cell to modify and multiply)
• Progression (development of subclones and metastasize)

Question 17

Tumor had characteristic deatures that cancer cells will display to avoid immune destruction which are:

Answer 17

• Sustain proliferative growth
• Resisting cell death
• induce angiogenesis
• Gene instability
• Enhance regional inflammation
• invade surrounding tissue

Question 18

Proto-oncogenes are:

Answer 18

Genes that are involved in normal cell growth

Question 19

3 differents ways Proto-oncogenes can be altered:

Answer 19

1. Gene amplifications: more receptors –> more growth
2. Translocation/transposition: relocation of a gene that is now next to a new promoter which increase production of a protein –> stimulate growth
3. Point mutation: too much of a normal growth-stimulating protein or an abnormal hyperactive or degradation resistant protein –> hyperactive growth and act for a long period

Question 20

Gene amplification:

Answer 20

Production of extra copies of a gene that will be located all in one section of a chromosome, or released into the nucleus as double minutes (little collections of the amplified gene)

Question 21

Burkitt lymphoma gene altered:

Answer 21

• Translocation between the chromosomes 8 and 14 –> Increased transcription of C-myc. –> increase cell growth of the affected cell
• Burkitt lymphoma is caused by Epstein Bass Virus (EBV/HHV4) (B lymphocytes) combined with malaria

Question 22

Translocations that is more common in lymphomas and leukemias:

Answer 22

The translocation will create an abnormal tyrosine kinase, which is part of the intracellular signaling process for cell growth so that you activate these growth factor signaling pathways with the continually turned on tyrosine kinase.

Question 23

The chronic myelogenous leukemia is characterized by:

Answer 23

the Philadelphia chromosome where there is a fused gene on chromosome 22 that codes for an abnormal protein called the BCR-ABL fusion protein (translocations proto-oncogenes)

Question 24

Chromosomes painting is:

Answer 24

a sophisticated technique to visualize translocations in chromosomes.

Question 25

RAS proto-oncogene is:

Answer 25

• The mutation interfering with RAS inactivation.
• It will lead to the non-activation of GTP resulting in activation of transcription of the MYC protein, block hydrolysis of GTP to GDP, resulting in constant cell cycle progression. (acquire autonomy growth)

Question 26

When the growth factors bind to the growth factors receptor what normally occurs?

Answer 26

• The growth factors receptor bind to the dimerized receptor –>cell signaling system activation
• The activation of RAS will involve the GTP and GDP to going back and forth.

Question 27

Difference between Benign and Malignant Tumors:

Answer 27

• Benign tumors resemble the tissue of origin and are well
differentiated; malignant tumors are poorly or completely
undifferentiated (anaplastic).
• Benign tumors are slow-growing, whereas malignant
tumors generally grow faster.
• Benign tumors are well circumscribed and have a capsule; malignant tumors are poorly circumscribed and invade the surrounding normal tissues.
• Benign tumors remain localized to the site of origin,
whereas malignant tumors are locally invasive and metastasize to distant sites.

Question 28

Oncoproteins promote uncontrolled cell proliferation by several mechanisms:

Answer 28

• Stimulus-independent expression of growth factor and
  its receptor, setting up an autocrine loop of cell proliferation
  -Mutations in genes encoding growth factor receptors or
  tyrosine kinases leading to constitutive signaling (eg. fusion of ABL tyrosine kinase with BCR)
• Mutations in genes encoding signaling molecules (eg. RAS mutation affecting GDP-GTP)
• Overproduction or unregulated activity of transcription
  factors (eg. MYC translocation)
• Mutations that activate cyclin genes or inactivate negative regulators of cyclins and cyclin-dependent kinases

Question 29

Cancer cells are able to resist cell death because of

Answer 29

The BCL-2 is overexpress–>block apoptosis by blocking the normal signaling mechanisms

Question 30

Tumor supressor genes and what happen if its mutated?

Answer 30

• Are normal genes that prevent the growth of cancer cells.

- If mutated of one of the paired gene for an oncogene, progression of tumor growth will start.

Question 31

RB Gene (Governor of the Cell Cycle) is:

Answer 31

• The RB genes codes for a protein that suppresses cell growth.
• It attaches to the transcription factor that binds DNA to block transcription.

Question 32

Retinoblastoma is an example of:

Answer 32

RB Gene mutation (Tumor suppresor genes mutation)

Question 33

Retinoblastoma pathology:

Answer 33

• Abnormality occurs in the stem cells from retina
• If one of the arms of chromosome 13 is destroyed, you will still have the normal protein.
• If you lose the second locus, then you don’t make any more of the protein.
• Hereditary retinoblastoma: will start off with one mutated gene.

Question 34

P-53 Gene (Guardian of the Genome) is:

Answer 34

• A sensor of multiple forms of stress (DNA damage, activated oncogenes, hypoxia, RNA depletion, telomere erosion) –> Major defenses against cancer
• P53 will either cause the cell to die by triggering apoptosis or it will stop cell division to try to allow the cell to fix itself.

Question 35

The neoplastic epigenome: 2 categories:

Answer 35

1. Hypomethylation: overexpression of growth factors or oncogenes, alterations in DNA repair.
2. Hypermethylation: Causes transcriptional silencing of the tumor suppressor genes, end up with oncogenes.

Question 36

Cryosurgery is:

Answer 36

freeze just one area and avoid a major surgery.