Understanding Cancer and Its Development

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Questions and Answers

What is solitary cell dormancy in the context of tumor dormancy?

A phase of active proliferation of micrometastatic lesions.

A condition where a tumor mass continues to grow slowly.

A state where a disseminated tumor cell undergoes growth arrest. (correct)

A situation where tumors spread aggressively to other organs.

Which niche is specifically involved in enhancing micrometastatic outgrowth through neovascularization?

HSC niche, through secretion of CXCL12.

Osteogenic niche, via heterophilic cadherin interaction.

Stromal niche, by providing structural support.

Perivascular niche, through TGF-β stimulation. (correct)

What is a key limitation of studying tumor dormancy in vivo?

Complex interactions between immune cells and tumor cells.

Challenges in tracking asynchronous disseminated metastatic cells. (correct)

The inability to keep tumor cells dormant for extended periods.

Inability to observe the microenvironment of the tumor cells.

Which factor does NOT contribute to tumor dormancy mechanisms?

Removal of stroma that promotes cancer cell survival. Signup and view all the answers

What can result from hostile conditions for tumor cells?

Increased dormancy of tumor cells. Signup and view all the answers

What characterizes anaplastic tumors?

They lose differentiated traits and have obscure origins. Signup and view all the answers

Which of the following best describes the TNM classification system?

It includes T for primary tumor size, N for lymph node involvement, and M for metastasis. Signup and view all the answers

Melanoma derives from which type of cells?

Melanocytes Signup and view all the answers

What is a distinguishing feature of grading cancer?

It reflects the aggressive potential of the tumor. Signup and view all the answers

In the TNM classification, what does 'M0' signify?

Cancer has not spread to other parts of the body. Signup and view all the answers

Which is true about melanoma occurrences?

It accounts for roughly 1.5% of all cancer cases. Signup and view all the answers

What does the 'N' in TNM classification refer to?

Cancer cell infiltration into nearby lymph nodes. Signup and view all the answers

Which of the following statements about teratomas is true?

They can progress to become highly malignant. Signup and view all the answers

What is the primary difference between low grade (G1) and high grade (G3) cancers?

Low grade cancers tend to be less aggressive than high grade cancers. Signup and view all the answers

Which of the following is NOT one of the three factors considered in scoring cancers?

Tumor oxygenation levels Signup and view all the answers

What occurs during the initiation stage of tumorigenesis?

Uncontrolled cell proliferation occurs from DNA damage. Signup and view all the answers

Which stage of tumorigenesis is associated with irreversible change?

Tumor progression Signup and view all the answers

What is a common result of the promotion stage in cancer development?

Accumulation of additional mutations in initiated cells. Signup and view all the answers

Which term is synonymous with the development of malignant tumors?

Tumorigenesis Signup and view all the answers

Which statement about tumor stages is accurate?

Initiation can lead to benign cell states. Signup and view all the answers

What factor describes how 'ugly' the tumor cells look in cancer grading?

Nuclear pleomorphism Signup and view all the answers

Which enzyme is primarily responsible for the metabolism of ethanol and drugs in the liver?

CYP2E1 Signup and view all the answers

What is the primary result of DNA adduct formation caused by ultimate carcinogens?

Activation of DNA repair mechanisms Signup and view all the answers

Which cofactor is used during glucuronidation in Phase II metabolic reactions?

Uridindiphosphoglucuronic acid Signup and view all the answers

Which type of mutation is predominantly caused by Aflatoxin B1 affecting the p53 gene?

GC to TA transversion Signup and view all the answers

What is the role of glutathione-S-transferases in Phase II metabolic reactions?

Conjugation of glutathione Signup and view all the answers

Which enzyme class is directly involved in the detoxification of polyaromatic hydrocarbons?

CYP1A1 Signup and view all the answers

What is formed when Aflatoxin 8,9-epoxide reacts with guanine bases in DNA?

DNA adduct Signup and view all the answers

What is the ultimate consequence of the Ser249 mutation in the p53 gene?

Inactivation of p53 Signup and view all the answers

What is the consequence of lacking BRCA1 and BRCA2 in cells during DNA repair?

NHEJ is employed instead of HR Signup and view all the answers

Why are PARP inhibitors specifically effective in treating BRCA1/BRCA2 mutant cancer cells?

They inhibit DNA repair in cells that cannot use HR Signup and view all the answers

What role does PARP1 play in the cellular response to ssDNA breaks?

It binds to ssDNA breaks and activates self-ribosylation Signup and view all the answers

What occurs after PARP1 is inhibited in cells with ssDNA breaks?

ssDNA breaks accumulate leading to replication fork collapse Signup and view all the answers

What happens to dsDNA breaks in normal cells compared to BRCA1/BRCA2 mutant cells?

They are repaired using homologous recombination Signup and view all the answers

Which phase of the cell cycle primarily facilitates NHEJ repair?

G1 phase Signup and view all the answers

What is an outcome of the inhibition of PARP in cancer cells?

Induction of synthetic lethality in HR-deficient cells Signup and view all the answers

Which repair process is primarily error-prone and occurs when BRCA1 and BRCA2 are missing?

Non-homologous end joining Signup and view all the answers

Study Notes

Understanding of Cancer

Teratomas are tumors derived from germ cells that can progress to become highly malignant.
Melanoma, a type of skin cancer, arises from melanocytes, which are pigmented cells and originate from neural crest.
Anaplastic cancers, characterized by dedifferentiation and lost tissue-specific features, account for a small percentage of cancer cases
TNM classification system, used for cancer staging, categorizes tumors based on size (T), lymph node involvement (N), and metastasis (M)

DNA Damage and Genomic Instability in Cancer Development

Cancer development involves three stages: initiation, promotion, and progression.
Initiation involves DNA damage leading to persistent mutations due to inadequate repair or apoptosis.
Promotion involves initiated cells that accumulate more mutations and epigenetic changes, triggering uncontrolled cell proliferation.
Progression involves further genetic and epigenetic alterations leading to metastasis.

Metabolic Pathways and Carcinogenesis

Cytochrome P450 (CYP450) enzyme system is crucial for metabolizing xenobiotics (foreign compounds) and playing vital roles in activating and deactivating carcinogens.
Phase I enzymes like CYP450s, are important for modifying carcinogens to reactive metabolites. This includes the enzymes CYP1A1, CYP1A2, CYP2E1, and CYP3A4, which are involved in the metabolism of various compounds like polyaromatic hydrocarbons, aromatic amines, ethanol, AFB1, and drugs.
Phase II enzymes like glucuronidation, sulfatation, methylation, acetylation, and conjugation with glutathione are crucial in detoxifying cancer-causing substances by attaching larger molecules.

DNA Damage and Repair

Ultimate carcinogens can attack the DNA and form covalent bonds with DNA bases creating DNA adducts, which activate DNA repair mechanisms.
Aflatoxin B1 metabolized by Cyp3A4 creates a DNA adduct by reacting with the guanine base pair.
Aflatoxin B1-induced DNA adducts can cause mutations, promoting cancer development.

BRCA1/2 and DNA Repair

BRCA1 and BRCA2 are crucial in DNA repair, specifically in homologous recombination (HR), which is a high-fidelity mechanism.
Defective BRCA1/2 genes impair HR, leading cells to rely on error-prone non-homologous end joining (NHEJ) for DNA repair. This can lead to mutations and cancer development.

PARP Inhibitors in Cancer Therapy

PARP inhibitors, specifically targeting PARP1, can be used to exploit the synthetic lethality concept, effectively killing cancer cells with BRCA1/2 mutations.
PARP1 inhibitors work by disrupting the base excision repair (BER) pathway in the absence of functional BRCA1/2, leading to the accumulation of DNA damage and cell death.

Tumor Dormancy and Metastasis

Tumor dormancy, the state of a tumor remaining inactive, can involve cellular dormancy or tumor mass dormancy.
Metastasis is the spread of cancer cells to distant sites.
Metastatic niches, including perivascular, HSC, and osteogenic niches, can promote cell survival and facilitate exit from dormancy.

Key Questions about Metastasis

Hostile conditions, lack of oxygen/nutrients, can contribute to dormancy or influence metastasis.
Activation of developmental mechanisms in the wrong place at the wrong time can drive metastasis.
Immune cell attacks can also play a role in the dormancy and reactivation of metastatic cells.

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Description

This quiz explores key concepts related to cancer, including types of tumors such as teratomas and melanomas, as well as the stages of cancer development. It also covers the TNM classification system for cancer staging. Test your knowledge on the complexities of cancer and genomic instability.