Ch.26 bio235

What is a Lymphoma?

Cancer of lymphatic tissue that forms solid tumors.

Which specific lymphoma is caused by EBV in Africa?

Burkitt's lymphoma.

Which virus is an example of an agent causing sarcoma in chickens?

Rous Sarcoma Virus.

ALL: speed and lineage.

fast moving, lymphoid lineage.

AML: speed and lineage.

 fast moving, myeloid lineage.

CML: speed and lineage.

slow moving, myeloid lineage.

CLL: speed and lineage.

slow moving, lymphoid lineage.

About what percentage of cancer deaths are due to metastasis rather than the primary tumor?

~90%.

Gatekeepers 

Restrain cell proliferation

Examples of gatekeepers

P53, RB

Caretakers

Involved in DNA repair and chromosome sorting

Examples of caretakers

BRCA1, BRCA2

Taxol

Prevents microtubules from depolymerizing, meaning cells cannot complete division.

Define Epigenetics in the context of cancer.

Changes NOT in the DNA sequence itself but affecting gene expression.

Proto-oncogene

Normal gene involved in signal transduction (the "gas pedal").

Oncogene

Mutated, dysregulated version that drives uncontrolled cell division.

Hayflick limit

Normal somatic cells can only divide 50-60 times before telomeres become too short, leading to senescence.

Does cancer inheritance cause cancer directly?

No, but it increases susceptibility by passing on vulnerabilities in TSPs or proto-oncogenes.

Explain the mechanism of the Ames Test.

It uses histidine auxotroph bacteria; a chemical is a mutagen if it causes the bacteria to mutate back to a state where they can grow on histidine-deficient medium.

Explain the Two-hit hypothesis.

Since we have two copies of each gene, it may require two mutations (one in each copy) before cancer results.

Give an example of a precarcinogen that causes bladder cancer only after liver activation.

2-naphthylamine.

Give an example of a tumor marker detected via blood test.

PSA (Prostate Specific Antigen).

How are Phorbol esters (croton oil) used in the development of cancer?

They are used in the promotion step to artificially activate PKC.

How can thyroid cancer from radioactive iodine be prevented?

By taking potassium iodide pills or using iodized salt.

How do Alkylating Agents work?

They inhibit DNA function by crosslinking the double helix.

How do Antimetabolites work in chemotherapy?

They interfere with nucleotide synthesis or DNA building blocks, targeting rapidly dividing cells.

How do cancer cells overcome the Hayflick limit?

How do cancer cells overcome the Hayflick limit?

By upregulating telomerase to rebuild telomeres.

How do Metastatic cells travel through the body?

They downregulate E-cadherin (stop sticking), upregulate chemoattractant receptors, and produce proteases (like plasmin) to dissolve barriers.

How do X-rays cause DNA damage?

They are ionizing radiation that breaks bonds in DNA.

How does DNA Methylation silence genes?

It is a chemical modification of DNA that shuts off gene expression without changing the nucleotide sequence.

How does Histone Modification affect cancer risk?

DNA is attracted to positively charged histones (PO³-  ); if histones are modified such that DNA cannot unwrap, expression of TSPs may decrease, increasing cancer risk.

In a PET Scan, why do cancer cells appear as bright spots?

They metabolize faster than normal cells, taking up more of the radioactive label.

E6 in HPV infection

destroys P53

E7 in HPV infection

destroys RB

In the Wnt pathway logic, which protein is the TSP (brake) and which is the proto-oncogene (accelerator)?

APC is the TSP; Beta-catenin is the proto-oncogene.

In the Wnt Pathway, what happens when the Wnt ligand is ABSENT?

APC, axin, and GSK3 form a destruction complex that degrades beta-catenin.

In the Wnt Pathway, what happens when the Wnt ligand is PRESENT?

The destruction complex is inhibited, beta-catenin accumulates, enters the nucleus, and acts as a transcription factor for cell division.

List the five ways oncogenes can become activated.

1. Point mutation
2. Gene amplification
3. Chromosome translocation
4. Local DNA rearrangement
5. Insertional mutagenesis

List the Six Hallmarks of Cancer found in all tumors.

1. Self-sufficiency in growth signals
2. Insensitivity to anti-growth signals
3. Evasion of apoptosis
4. Limitless replication
5. Angiogenesis
6. Invasion and metastasis

Match the radioactive source to its historical/environmental context:
1. Radioactive Cesium
2. Radium
3. Radon

1. Chernobyl
2. Radium Girls
3. Homes

The normal mutation rate is 1 in 1 million per gene. How much higher is it in cancer cells?

Up to 1,000x higher.

The Philadelphia chromosome is an example of which type of oncogene activation?

Chromosome translocation (fusing two genes) seen in CML.

What are CAR-T Cells?

Patient T cells engineered to express a chimeric antigen receptor that specifically targets cancer cell surface antigens.

What are microRNAs (miRNAs) and how can they be carcinogenic?

Small RNA molecules (  ~12-15 bp) that silence mRNA. Underproduction of a TSP or overproduction of a proto-oncogene via miRNA can cause cancer.

What are pathologists looking for in a biopsy to identify cancer?

Elevated mitotic index ( >1% ), large irregular nuclei, high nuclear/cytoplasmic ratio, and loss of tissue organization.

What are Precarcinogens?

Chemicals that are not carcinogenic themselves but become so after being metabolized by the liver.

What does Flow Cytometry measure to detect cancer?

DNA content of cells; abnormal amounts indicate aneuploidy.

What happens during the Initiation step of cancer?

A permanent mutation occurs in DNA (likely a TSP or proto-oncogene) that is not repaired.

What happens when you fuse a normal cell with a cancer cell?

The resulting hybrid usually does NOT show cancer because the TSPs from the normal cell restrain the cancer.

What instrument is used to cut flash-frozen tissue sections during a biopsy?

A cryostat.

What is "The Snowflake Moment" in Sid Mukherjee's The Emperor of All Maladies?

The realization that while cancers seem as diverse as snowflakes, they can be sorted into categories (TSPs and oncogenes) affecting ~12 common pathways.

What is a Carcinoma?

Cancer of epithelial cells (skin, dry or mucous membrane).

What is a common example of Carcinoma mentioned in the text?

Cervical carcinoma, often caused by HPV.

What is a Lymphoma?

Cancer of lymphatic tissue that forms solid tumors.

What is a Sarcoma?

Cancer of supporting tissue, including cartilage, fat, bone, and muscle.

What is a Tumor Antigen?

A molecule normally made by certain cells but found at elevated concentrations in cancer; used as a blood indicator.

What is Aflatoxin and where is it found?

A potent mutagen/carcinogen produced by mold on peanuts or grain.

What is Avastin (bevacizumab)?

A monoclonal antibody that blocks angiogenesis by targeting VEGF signaling.

What is Herceptin (trastuzumab) used for?

It targets HER2 receptors overexpressed in some breast cancers to block growth signaling.

What is Immune Surveillance?

The immune system (especially CD8 CTLs and NK cells) detects and kills cancer cells displaying abnormal peptides on MHC I.

What is Leukemia?

Cancer of white blood cells, characterized as fluid tumors.

What is Li-Fraumeni syndrome?

A condition where an individual inherits one defective copy of P53.

What is Loss of Heterozygosity (LOH)?

When the second copy of a tumor suppressor gene is lost or mutated.

What is RAS?

The most commonly mutated oncogene in human cancer (found in   ~30% of cases).

What is the "one-word mechanism" for how radiation like X-rays and cosmic rays causes cancer?

Ionization.

What is the "snowball effect" in Tumor Progression?

As cells break more rules, genetic instability leads to faster accumulation of mutations and the evolution of harder-to-treat traits.

What is the function of APC (Adenomatous Polyposis Coli)?

It inhibits the Wnt pathway and is mutated in 2/3 of colon cancers.

What is the function of the E2 protein in the HPV genome?

It suppresses E6 and E7; its absence or disruption helps explain why some strains cause cancer.

What is the hallmark DNA mutation caused by UV light?

Thymidine dimers, specifically a CC → TT    mutation.

What is the significance of the HBV vaccine in the context of oncology?

It is 1 of 3 human infections that can be prevented by a vaccine which also prevents cancer.

What is Xeroderma Pigmentosum (XP)?

A genetic condition with defective nucleotide excision repair enzymes, leading to extreme UV sensitivity and high skin cancer rates.

What occurs during the Promotion step of cancer?

A mutated cell is pushed toward cell division by a factor like phorbol esters.

What pathological term describes HPV-infected cells visible on a Pap smear?

Koilocytosis (characterized by a perinuclear halo).

What percentage of breast cancers are linked to BRCA1/BRCA2 mutations and what is the underlying defect?

~10% of breast cancers; the defect is in DNA repair.

What role do integrins play in cancer prevention?

They detect anchorage dependence (attachment); if attachment is lost, apoptosis is triggered.

What triggers Angiogenesis in tumors?

Secretion of VEGF (Vascular Endothelial Growth Factor) and FGF (Fibroblast Growth Factor).

What vital tumor suppressor protein is frequently damaged by UV light?

P53.

What was the first rationally designed targeted cancer drug?

Gleevec (for CML).

Where was the HPV 18 genome famously found inserted?

In the HeLa cell genome.

Which bacteria causes stomach ulcers and can lead to stomach cancer?

Helicobacter pylori.

Which drug is specifically mentioned for the treatment of Chronic Myeloid Leukemia (CML)?

Gleevec.

Which liver enzyme is responsible for activating precarcinogens?

Cytochrome P450.

Which non-receptor tyrosine kinase is heavily implicated in cancer signal transduction?

Src kinase.

Which specific lymphoma is caused by EBV in Africa?

Burkitt's lymphoma.

Which strains of HPV are primarily associated with cervical cancer?

HPV 16 and 18.

Which three diseases are associated with Epstein-Barr Virus (EBV) in different regions?

1. Burkitt's lymphoma (Africa)
2. Nasopharyngeal carcinoma (Asia)
3. Mononucleosis (USA)

Which TSP controls the  G1 → S transition at the restriction point?

RB (Retinoblastoma).

Which virus is an example of an agent causing sarcoma in chickens?

Rous Sarcoma Virus.

Who pioneered the use of antifolates (antimetabolites) in childhood leukemia?

Sidney Farber.

Why is P53 called the "Guardian of the Genome"?

It triggers cell cycle arrest, apoptosis, and DNA repair; it is the most frequently mutated protein in human cancer.

Why is radioactive iodine particularly dangerous to the thyroid?

The thyroid scavenges iodine; if radioactive iodine is absorbed (e.g., after a nuclear accident), it leads to thyroid cancer.