Cancer Biology Overview
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Questions and Answers

Infectious agents are not implicated in carcinogenesis.

False (B)

Increased cellular proliferation due to chronic inflammation can lead to a decreased risk of cancer in certain tissues.

False (B)

Precursor lesions are changes of epithelial cells that suggest a lower risk of developing cancer.

False (B)

Proto-oncogenes are mutated or overexpressed forms of the oncogenes.

<p>False (B)</p> Signup and view all the answers

Oncogenes normally prevent uncontrolled growth.

<p>False (B)</p> Signup and view all the answers

Breast cancer is the most common type of cancer based on estimated new cases in 2018.

<p>True (A)</p> Signup and view all the answers

The cancer incidence rate is approximately 600 per 100,000 people per year.

<p>False (B)</p> Signup and view all the answers

Overproduction or unregulated activity of transcription factors can contribute to self-sufficiency in growth signals in cancer cells.

<p>True (A)</p> Signup and view all the answers

Translocation of the MYC gene in some leukemias leads to underexpression of target genes controlling cell cycling and survival.

<p>False (B)</p> Signup and view all the answers

Cancer mortality rates are lower for men when compared to women.

<p>False (B)</p> Signup and view all the answers

Asian/Pacific Islander women experience the highest cancer mortality rates when compared to other groups based on race/ethnicity and sex.

<p>False (B)</p> Signup and view all the answers

Mutations that activate cyclin genes or inactivate negative regulators are not involved in self-sufficiency of growth signals.

<p>False (B)</p> Signup and view all the answers

For tumor development to occur due to a dysfunctional RB gene, only one copy of the RB gene needs to be dysfunctional.

<p>False (B)</p> Signup and view all the answers

There were around 20.3 million estimated cancer survivors in the U.S. in 2016.

<p>False (B)</p> Signup and view all the answers

In familial retinoblastoma, an individual inherits two defective copies of the RB gene through the germline.

<p>False (B)</p> Signup and view all the answers

Approximately 38.4% of men and women will be diagnosed with cancer at some point during their lifetimes.

<p>True (A)</p> Signup and view all the answers

The protein encoded by the TP53 gene, p53, is activated only by DNA damage.

<p>False (B)</p> Signup and view all the answers

Worldwide estimates are that approximately 13 million new cancer cases were diagnosed in 2012.

<p>False (B)</p> Signup and view all the answers

It is estimated that by 2030, the number of new cancer cases per year will rise to approximately 23.6 million worldwide.

<p>True (A)</p> Signup and view all the answers

Activated p53 drives the transcription of CDKN1A (p21), which promotes RB phosphorylation and progression of the cell cycle.

<p>False (B)</p> Signup and view all the answers

The majority of human tumors demonstrate biallelic mutations in the TP53 gene.

<p>True (A)</p> Signup and view all the answers

Loss of p53 function in cancer cells can occur through mutations in the TP53 gene or by the overexpression of the p53 activator MDM2.

<p>False (B)</p> Signup and view all the answers

The BCL2 family of proteins, specifically BCL2, BCL-XL and MCL1, promote apoptosis.

<p>False (B)</p> Signup and view all the answers

Evasion of immune surveillance is a hallmark of cancer.

<p>True (A)</p> Signup and view all the answers

In follicular B-cell lymphomas, high levels of BCL2 result from a (14;18) translocation that fuses the BCL2 gene with regulatory elements of an immunoglobulin light chain gene.

<p>False (B)</p> Signup and view all the answers

Tumor-promoting inflammation is a process that inhibits malignancy.

<p>False (B)</p> Signup and view all the answers

Inhibitors of MDM2 and BCL2 family members are being explored as cancer therapies because they promote apoptosis through the intrinsic pathway.

<p>True (A)</p> Signup and view all the answers

Angiogenesis is a process that is essential for tumor growth beyond a diameter of 1 to 2 cm.

<p>False (B)</p> Signup and view all the answers

Carcinogenic agents typically cause genetic damage.

<p>True (A)</p> Signup and view all the answers

Chemical carcinogens have highly reactive nucleophile groups that directly damage DNA.

<p>False (B)</p> Signup and view all the answers

Hypoxia inhibits angiogenesis through the action of HIF-1α on the transcription of the proangiogenic factor VEGF.

<p>False (B)</p> Signup and view all the answers

The protein p53 stimulates the synthesis of the angiogenesis inhibitor thrombospondin-1 and also represses expression of VEGF.

<p>True (A)</p> Signup and view all the answers

Only nuclear fission is an established carcinogen.

<p>False (B)</p> Signup and view all the answers

Ionizing radiation causes chromosome breakage, rearrangements, and more frequently point mutations.

<p>False (B)</p> Signup and view all the answers

VEGF inhibitors are a curative treatment for many advanced cancers.

<p>False (B)</p> Signup and view all the answers

The formation of pyrimidine dimers within DNA, caused by UV rays, can lead to squamous cell carcinomas and melanomas of the skin.

<p>True (A)</p> Signup and view all the answers

HTLV-1 is an oncogenic DNA virus causing T cell leukemia in Japan and the Caribbean.

<p>False (B)</p> Signup and view all the answers

The HTLV-1 viral protein, Tax, inhibits cellular growth and promotes apoptosis.

<p>False (B)</p> Signup and view all the answers

HPV is only associated with cervical cancer and not with benign warts.

<p>False (B)</p> Signup and view all the answers

The primary function of the E6 and E7 oncoproteins from HPV is to enhance the function of the p53 and RB tumor suppressors.

<p>False (B)</p> Signup and view all the answers

High-risk strains of HPV have a lesser affinity for p53 and RB than low-risk strains.

<p>False (B)</p> Signup and view all the answers

The Malaysian National HPV Vaccination Programme provides protection against all 40 oncogenic HPV types.

<p>False (B)</p> Signup and view all the answers

Gardasil vaccine protects against 2 HPV types and Cervarix protects against 4.

<p>False (B)</p> Signup and view all the answers

EBV is solely implicated in the pathogenesis of Burkitt lymphoma.

<p>False (B)</p> Signup and view all the answers

Epstein-Barr Virus (EBV) is associated with a reduced risk of developing lymphomas.

<p>False (B)</p> Signup and view all the answers

Flashcards

Cancer Genes

These are the basic physical units of inheritance that are altered in cancer.

Oncogenes

These genes, when mutated, activate uncontrolled cell growth, contributing to cancer.

Tumor Suppressor Genes

These genes normally restrain cell growth, but when mutated, they fail to control this growth, promoting cancer.

Environmental Factors in Carcinogenesis

Genetic changes that lead to cancer can be influenced by environmental factors like smoking, alcohol, diet, and infections.

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Chronic Inflammation and Cancer

Chronic inflammation can trigger excessive cell growth, increasing the risk of cancer development in certain tissues.

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Lifetime Cancer Risk

The likelihood of developing cancer during a person's lifetime. It is estimated that around 38.4% of men and women will be diagnosed with cancer in their lifetime. This statistic highlights the significant impact of cancer on populations.

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Cancer Incidence

The number of new cancer cases diagnosed in a specific period of time. It helps understand the scale of the disease and how it affects different populations.

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Cancer Survivors

The total number of people alive after a cancer diagnosis. This figure highlights the growing population of cancer survivors and the importance of post-treatment care and support.

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Cancer Mortality

The number of cancer deaths in a specific period of time. It helps understand the impact of cancer on mortality rates and the need for effective treatments and prevention strategies.

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Cancer Prevalence by Sex

Cancer affects both men and women, but some cancers are more common in one sex than the other. For instance, breast cancer is more common in women, while prostate cancer is more common in men.

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Cancer Prevalence by Race/Ethnicity

Cancer affects populations differently based on race/ethnicity. Certain groups may experience higher cancer mortality rates due to factors like socioeconomic disparities, access to healthcare, and genetic predispositions. Understanding these disparities is crucial for addressing health equity.

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Global Cancer Burden

The global burden of cancer is significant, with millions of new cases and deaths annually. It highlights the need for international collaboration to address cancer prevention, diagnosis, and treatment.

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Future Prognosis of Cancer

The number of cancer cases is projected to increase significantly in the coming years, mainly driven by factors like population growth and aging. This underscores the need for continued research and resources to combat the growing cancer burden.

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MYC's Role in Cancer

MYC is a transcription factor that regulates cell cycling and survival. Translocation of MYC can lead to overexpression and unregulated activity, contributing to cancer development.

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Cyclins & CDKs in Cancer

Cyclins and cyclin-dependent kinases (CDKs) are key regulators of the cell cycle. Mutations activating cyclin genes or inactivating CDK regulators can drive uncontrolled cell growth.

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RB: The Cell Cycle Brake

RB is a tumor suppressor gene that acts as a 'brake' on the cell cycle. Both copies of RB must be dysfunctional for uncontrolled cell growth to occur. Familial retinoblastoma is caused by inheriting one copy of the defective RB gene.

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TP53: The Guardian of the Genome

TP53 is a tumor suppressor gene known as the 'guardian of the genome' because it monitors cellular stress. TP53 can be activated by DNA damage, hypoxia, or inappropriate growth signals. It then triggers cell cycle arrest, DNA repair, senescence, or apoptosis.

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p53's DNA Damage Response

p53, the protein encoded by TP53, can be activated by phosphorylation in response to DNA damage. Activated p53 triggers the production of p21 (encoded by CDKN1A), which blocks the phosphorylation of RB, arresting the cell cycle in G1 phase.

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p53's Final Decision

If DNA damage is beyond repair, p53 can induce cellular senescence or apoptosis, preventing damaged cells from replicating.

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TP53 Mutations & Cancer

Mutations in both copies of TP53 are found in about 70% of human tumors, demonstrating the importance of this gene in cancer suppression.

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Evasion of Immune Surveillance

Cancer cells evade the immune system, allowing them to grow and spread unchecked.

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Tumor-Promoting Inflammation

Inflammation can actually promote tumor growth and spread, making it a key factor in cancer development.

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Carcinogenic Agents

Substances that can cause cancer by altering the genetic makeup of cells, leading to uncontrolled growth.

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Chemical Carcinogens

Highly reactive chemicals that directly damage DNA, potentially triggering cancer.

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Radiation Carcinogenesis

Any type of radiation, including sunlight, X-rays, and nuclear sources, that damages DNA and can lead to cancer development.

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UV Rays and Skin Cancer

UV rays can cause pyrimidine dimers in DNA, leading to mutations that can contribute to skin cancers.

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Viral and Microbial Oncogenesis

Viruses and bacteria that can directly contribute to cancer development.

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HTLV-1 Leukemia

HTLV-1, a viral agent, is known to cause a specific type of leukemia, highlighting the link between viruses and cancer.

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How do cancer cells evade apoptosis?

Cancer cells often evade death by overexpressing anti-apoptotic proteins like BCL2, BCL-XL, and MCL1. These proteins block the action of pro-apoptotic proteins like BAX and BAK, preventing programmed cell death.

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What is the genetic abnormality in B-cell lymphoma?

In many follicular B-cell lymphomas, BCL2 levels are abnormally high due to a translocation that fuses the BCL2 gene with regulatory elements of the immunoglobulin heavy chain gene. This results in increased BCL2 expression.

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How do MDM2 inhibitors work against cancer?

MDM2 is a p53 inhibitor that can promote cancer cell survival by blocking the tumor suppressor activity of p53. Inhibitors of MDM2 can effectively target cancer cells by reactivating the p53 pathway leading to apoptosis.

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What is the significance of limitless replicative potential in cancer?

Cancer cells, unlike normal cells, can replicate indefinitely. This limitless replication potential allows tumors to grow uncontrollably and evade the normal cellular aging process.

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Why is angiogenesis essential for tumor growth?

Solid tumors require their own blood supply to grow beyond a certain size. The process of forming new blood vessels to supply the tumor is called angiogenesis.

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What factors influence angiogenesis?

The balance between angiogenic (promoting blood vessel formation) and anti-angiogenic (inhibiting blood vessel formation) factors produced by tumor and stromal cells regulates the process of angiogenesis.

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How does hypoxia induce angiogenesis?

Hypoxia, a condition of low oxygen, triggers angiogenesis by activating HIF-1α, a transcription factor that stimulates the expression of VEGF (vascular endothelial growth factor), a potent angiogenic factor.

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How do VEGF inhibitors work?

VEGF inhibitors target the process of angiogenesis by blocking the growth of new blood vessels that supply tumors. While these drugs can prolong survival, they are not curative.

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What is Tax?

A viral protein encoded by the HTL-1 genome that promotes cell proliferation, enhances cell survival, and disrupts cell cycle control.

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What is HPV?

A family of viruses that can cause benign warts as well as cervical cancer.

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What are the oncoproteins produced by HPV?

Two viral proteins, E6 and E7, produced by HPV, that inhibit the function of tumor suppressor genes p53 and RB, respectively.

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How do high-risk HPV strains differ from low-risk strains in terms of their oncoproteins?

High-risk HPV strains have E6 and E7 proteins that bind more effectively to their targets (p53 and RB) compared to low-risk strains, contributing to a higher risk of cancer development.

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What is EBV and what types of cancers is it linked to?

A virus implicated in the development of various cancers, including Burkitt lymphomas, lymphomas in immunocompromised individuals, Hodgkin lymphoma, certain T-cell and NK-cell tumors, nasopharyngeal carcinoma, a subset of gastric carcinoma, and rarely sarcomas.

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What is nasopharyngeal carcinoma?

A type of cancer associated with the Epstein-Barr Virus (EBV), primarily affecting the nasopharynx (upper part of the throat).

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Study Notes

Basic Pathology (AHBS 2319) - Week 8

  • Neoplasia: Defined as "new growth"
  • Neoplasm: Often referred to as a tumor
  • Oncology: The study of tumors (oncos = tumor, logos = study of)
  • Cancer: The common term for all malignant tumors
  • Benign tumor: Mesenchymal tissues: The suffix "-oma" indicates cell of origin
    • Fibroblastic cell = fibroma
    • Lipid cell = lipoma
    • Smooth muscle = leiomyoma
  • Benign tumor: Epithelial tissue
    • Based on cells of origin and microscopic architecture
    • Adenoma (based on origin of cell)
      • Benign epithelial neoplasm that forms glandular patterns
      • Tumors derived from glands
    • Papilloma (based on microscopic architecture)
      • Benign neoplasm
      • Microscopically visible finger-like projections
    • Polyp
      • Neoplasm produces a macroscopically visible projections above a mucosal surface
      • Commonly restricted to benign tumors in the G1 tract, respiratory tract, and genitourinary tract
  • Malignant tumor: Mesenchymal tissues
    • Usually called sarcoma
    • Sarcoma = "fleshy tumor" -Fibroblastic cell = fibrosarcoma -Lipid cell = liposarcoma -Smooth muscle = leiomyosarcoma
  • Malignant tumor: Epithelial tissue
    • Called carcinoma
    • Squamous cell carcinoma (Squamous cell type)
    • Adenocarcinoma (glandular growth pattern)
  • Teratoma (Dermoid cyst): Made up of variety of parenchymal cell types
    • Arises from totipotential cells
    • A benign type
  • Inappropriate nomenclature: e.g., melanoma = CA of melanocyte, seminoma = CA of testicular origin, hepatoma = CA of hepatocyte, lymphoma = CA of lymphoid tissue, leukemia = CA of hematopoietic cells
    • "oma" used for benign tumors, not malignant tumors

Classification, Nomenclature, Epidemiology - Characteristics of Benign and Malignant Neoplasms

  • Features: Differentiation and anaplasia, local invasion, metastasis

Differentiation and Anaplasia

  • Well-differentiated tumors: Cells resemble original tissue morphology; benign tumors generally well-differentiated
  • Poorly differentiated/undifferentiated tumors: Marked by morphologic and functional changes; hallmark of malignant transformation; lack of differentiation; loss of features/ functions that characterize benign tumors
  • Anaplasia: A condition of cells in which cells have poor cellular differentiation; losing morphological characteristics of mature cells

Local Invasion

  • A benign neoplasm remains localized at its site of origin, does not invade or metastasize to distant sites.
  • Most benign neoplasms are encapsulated; separated from host tissue by a fibrous capsule
  • Some benign neoplasms are not encapsulated, (e.g., leiomyoma of the uterus)
  • Cancers grow by progressive infiltration, invasion, destruction, penetration of surrounding tissue
  • Do not have well-defined capsules

Metastasis

  • Metastasis are secondary implants of a tumor; located in remote tissues; discontinuous from primary tumor
  • More than any other attribute, the property of metastasis identifies a neoplasm as malignant
  • Not all cancers have equal ability to metastasize (e.g., basal cell carcinomas of skin & most tumors of the CNS are highly invasive, but rarely metastasize)

Characteristics of Cancer

  • Benign tumors: Well-differentiated, slow-growing, well-circumscribed, remain localized
  • Malignant tumors: Poorly differentiated, fast-growing, poorly circumscribed, locally invasive, metastasize

Epidemiology of Cancer

  • Incidence of cancer varies with age, geographic factors, and genetic background
  • Geographic variation mostly due to different environmental exposures
  • Cancers can occur at any age but most common in older adults
  • Cancer mortality higher in men than women
  • Cancer incidence and mortality high in African American men
  • 2016 estimated 15.5 million survivors (expected to increase to 20.3 million by 2026)
  • ~38.4% of men and women diagnosed with cancer during lifetime
  • 2017, ~15,270 children and adolescents diagnosed with cancer, ~1,790 died

Cancer Genes

  • Oncogenes: Mutated/overexpressed proto-oncogenes that induce transformed phenotypes; promote increased cell growth
  • Tumor suppressor genes: Normally prevent uncontrolled growth; when mutated, allow transformed cell phenotype to develop

Carcinogenesis

  • Process by which normal cells are transformed into cancer cells
  • Initiation, Promotion, Progression (inherited/ acquired mutations)

Hallmarks of Cancer

  • Self-sufficiency in growth signals
  • Insensitivity to growth-inhibitory signals
  • Altered cellular metabolism
  • Evasion of apoptosis
  • Limitless replicative potential (immortality)
  • Sustained angiogenesis
  • Invasion and metastasis
  • Evasion of immune surveillance

Grading and Staging of Cancer

  • Grading (Differentiation): Done by a pathologist; evaluates microscopic appearance, mitotic activity, nuclear size/pleomorphism
  • Staging (Spreading): Done by a surgeon; gross anatomical appearance

Laboratory Diagnosis of Cancer

  • Morphologic methods
  • Tumor markers
  • Molecular diagnosis
  • Molecular profiling of tumors
  • Fine needle aspirates (FNAC)
  • Immunohistochemistry & flow cytometry
  • Assay of circulating tumor cells
  • DNA shed into blood, stool, sputum, & urine
  • Specific tests for cancer screening and monitoring

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Description

This quiz explores key concepts in cancer biology, including the role of infectious agents, cellular proliferation, and oncogenes. It highlights statistics and factors influencing cancer incidence and mortality rates across different demographics. Test your knowledge on these important topics in understanding cancer.

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