neoplasia clinical features

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Questions and Answers

What role does Bcl2 play in relation to apoptosis?

Bcl2 is involved in DNA repair during genomic injury.

Bcl2 triggers apoptosis by releasing cytochrome c.

Bcl2 is a protein that initiates the immune response to infections.

Bcl2 stabilizes the mitochondrial membrane, preventing apoptosis. (correct)

Which of the following best describes the effect of genetic mutations on apoptosis?

They increase the levels of energy stores in apoptotic cells.

They enhance the apoptotic response in cancer cells.

They decrease the apoptotic barrier and contribute to cancer progression. (correct)

They have no effect on cellular metabolism and energy stores.

What is the significance of the t(14;18) translocation in follicular lymphoma?

It leads to increased activity of chaperone proteins.

It enhances the immune response against tumor cells.

It contributes to the production of cytotoxic T-lymphocytes.

It results in overexpression of Bcl2 and inhibition of apoptosis. (correct)

Which condition is primarily associated with the evasion of apoptosis in cancer cells?

Decreased energy stores from metabolic alterations. Signup and view all the answers

What happens to B-cells during somatic hypermutation if they evade apoptosis?

They accumulate and can lead to lymphoma. Signup and view all the answers

What is a characteristic of normal cells regarding telomere shortening?

They can divide indefinitely due to telomerase. Signup and view all the answers

How do cancer cells achieve limitless replicative potential?

By acquiring mutations in IDH. Signup and view all the answers

What main advantage do cancer cells gain from the Warburg effect?

Production of metabolic intermediates for cellular components. Signup and view all the answers

What does aerobic glycolysis produce per molecule of glucose in cancer cells?

2 molecules of ATP. Signup and view all the answers

What is a consequence of mutations in IDH (isocitrate dehydrogenase)?

Production of oncometabolites that enhance carcinogenesis. Signup and view all the answers

Which statement is true regarding telomerase in normal cells?

Normal cells do not generally have telomerase activity. Signup and view all the answers

What role do metabolic intermediates generated via the Warburg effect play in cancer cells?

They are essential for cellular component synthesis. Signup and view all the answers

What is a common misconception about cancer cells and energy production?

Cancer cells do not require ATP for survival. Signup and view all the answers

What characterizes the behavior of oncogenes in relation to growth signals?

Gain-of-function mutations that promote cell growth Signup and view all the answers

How do tumor suppressor genes contribute to cell cycle regulation?

They inhibit cell proliferation and maintain growth control Signup and view all the answers

What is the main impact of mutations in proto-oncogenes?

They lead to increased self-sufficiency in growth signaling Signup and view all the answers

Which mechanism describes cancer cells' ability to evade the immune system?

Modification of surface antigens to avoid detection Signup and view all the answers

What effect does the Warburg effect have on cancer cell metabolism?

Increases reliance on anaerobic glycolysis for energy production Signup and view all the answers

How do alterations in telomere biology contribute to cancer cell immortality?

They enable an indefinite number of cell divisions Signup and view all the answers

What is a potential consequence of cancer immunoediting?

Development of more aggressive tumor phenotypes Signup and view all the answers

Which option correctly describes a function of signal transduction pathways?

They can both induce cell division and influence gene expression Signup and view all the answers

Which characteristic is not associated with neoplasia?

Neoplasms arise from multiple independent cells Signup and view all the answers

What triggers the disorder of cell growth known as neoplasia?

A series of genomic alterations Signup and view all the answers

Which of the following is a hallmark of cancer related to cell survival?

Evasion of apoptosis Signup and view all the answers

In cancer formation, which process allows for tumor promotion and progression?

Genetic or epigenetic changes Signup and view all the answers

Which characteristic allows cancer cells to maintain uncontrolled proliferation?

Self-sufficiency in growth signals Signup and view all the answers

What is indicated by the term 'limitless replicative potential' in cancer cells?

Their unregulated cell division Signup and view all the answers

Which metabolic alteration is commonly associated with cancer cells?

Altered cellular metabolism favoring glycolysis Signup and view all the answers

What role do carcinogens play in the context of neoplasia?

They initiate and promote genetic damage Signup and view all the answers

What is the primary process that allows tumors to grow beyond a certain size (1-2 mm3)?

Angiogenesis induction Signup and view all the answers

Which cytokine is primarily involved in promoting neoangiogenesis in growing tumors?

Vascular endothelial growth factor Signup and view all the answers

What effect do newly formed blood vessels in tumors typically exhibit?

Leaky and dilated properties Signup and view all the answers

Why is the metastatic process considered inefficient in cancer?

Only a small percentage of circulating tumor cells develop into metastases Signup and view all the answers

What is a critical mechanism that influences tumor cell invasion and metastasis?

Epigenetic regulation of cell adhesion molecules Signup and view all the answers

What characterizes lymphovascular invasion in cancer metastasis?

It involves the invasion of lymphatic circulation. Signup and view all the answers

Which of the following types of cancer is characterized by perineural invasion?

Melanoma Signup and view all the answers

What is the primary mechanism through which circulating cancer cells are destroyed during bloodborne metastasis?

Mechanical forces Signup and view all the answers

What defines angiotropism in cancer behavior?

Traveling along the outside of blood vessels. Signup and view all the answers

Which statement about metastasis is incorrect?

Vascular invasion is only relevant for sarcomas. Signup and view all the answers

Which statement correctly explains the relationship between telomeres and cancer cell replication?

Most cancer cells manage telomere length to avoid cellular senescence. Signup and view all the answers

How does the Warburg effect aid in the metabolic adaptation of cancer cells?

It provides essential intermediates for nucleotide and lipid synthesis. Signup and view all the answers

What is a common characteristic of normal cells regarding their replicative potential?

They typically divide around 60-70 times before cell division ceases. Signup and view all the answers

What role do mutant IDH enzymes play in cancer metabolism?

They produce metabolites that may promote cancer gene expression. Signup and view all the answers

Which is NOT a consequence of the Warburg effect in tumors?

Dependence on efficient aerobic respiration to meet energy demands. Signup and view all the answers

Why do most normal cells lack telomerase activity?

They do not need to maintain unlimited replicative potential. Signup and view all the answers

What is a likely reason that cancer cells prefer aerobic glycolysis over oxidative phosphorylation?

It generates essential building blocks for rapid cell division. Signup and view all the answers

Which statement best describes the difference in energy production between normal cells and cancer cells?

Cancer cells exhibit a preference for glycolysis even in adequate oxygen conditions. Signup and view all the answers

Which tumor type is most likely to cause bronchial obstruction?

Mucoepidermoid carcinoma Signup and view all the answers

What is a primary factor contributing to cancer cachexia?

Systemic inflammation Signup and view all the answers

Which of the following best describes the role of IL-6 in cancer-related anemia?

Decreases iron absorption Signup and view all the answers

What is the most common cause of hypercalcemia in patients with cancer?

Osteolytic bone growth Signup and view all the answers

Which are typical presentations of functional pituitary adenomas?

Acromegaly and hypertension Signup and view all the answers

What term is used for diseases caused by the presence of a neoplasm but not by its physical presence in an organ?

Paraneoplastic syndromes Signup and view all the answers

Which mechanism enhances cancer-related hypercoagulability?

Increased extrinsic vascular compression Signup and view all the answers

What effect does cancer have on the renal response to anemia?

Diminished erythropoietin production Signup and view all the answers

In patients with pancreatic adenocarcinoma, what condition can be associated with the presence of nonbacterial thrombotic endocarditis?

Thrombosis Signup and view all the answers

What is a consequence of increased production of hepcidin in advanced cancer?

Decreased iron absorption from the gut Signup and view all the answers

In what way can an invading tumoral mass present clinically detailed effects distinct from the tumor itself?

Paraneoplastic symptoms and syndromes Signup and view all the answers

What type of cancer is often associated with hemorrhage into vessels leading to RBC loss?

Rectal adenocarcinoma Signup and view all the answers

Which abnormality is most frequently seen in patients with malignancy?

Hypercalcemia Signup and view all the answers

Study Notes

Apoptosis and Bcl2

Bcl2 is an anti-apoptotic protein, meaning it inhibits the process of programmed cell death.
It acts by blocking the release of cytochrome c from mitochondria, a crucial step in the apoptotic cascade.

Genetic Mutations and Apoptosis

Genetic mutations can disrupt the balance between pro-apoptotic and anti-apoptotic signaling pathways.
In some cases, mutations can increase resistance to apoptosis, leading to the survival of cells that would normally undergo programmed death.

t(14;18) Translocation and Follicular Lymphoma

The t(14;18) translocation is a hallmark of follicular lymphoma.
It results in the overexpression of the Bcl2 gene, leading to the suppression of apoptosis in B-cells, driving the development of the lymphoma.

Apoptosis Evasion and Cancer

Evasion of apoptosis is a hallmark of cancer cells, contributing to their uncontrolled growth and survival.
Cancer cells often develop mechanisms that allow them to bypass normal apoptotic pathways, enabling their persistence.

B-cell Somatic Hypermutation

During somatic hypermutation, B-cells undergo DNA rearrangements and mutations to diversify their antibody repertoire.
If B-cells acquire mutations that lead to an increase in their anti-apoptotic signaling, they are more likely to survive and proliferate.

Telomere Shortening in Normal Cells

Telomeres, protective caps at the ends of chromosomes, shorten with each cell division in normal cells.
This shortening eventually triggers cellular senescence, limiting the number of times a cell can divide.

Limitless Replicative Potential in Cancer Cells

Cancer cells circumvent telomere shortening through the reactivation of telomerase, an enzyme that maintains telomere length.
As a result, cancer cells gain the ability to divide indefinitely, contributing to their immortality.

Warburg Effect and Cancer Cells

The Warburg effect, also known as aerobic glycolysis, is a metabolic shift observed in cancer cells.
It involves the production of ATP through glycolysis even in the presence of oxygen, providing cancer cells with a rapid source of energy for rapid growth.

Aerobic Glycolysis and Cancer Cell Energy Production

The Warburg effect produces two ATP molecules per molecule of glucose in cancer cells.
This is in contrast to the much higher ATP yield (38 ATP) obtained through complete oxidative phosphorylation in normal cells.

Mutations in IDH (Isocitrate Dehydrogenase)

Mutations in IDH enzymes, particularly IDH1 and IDH2, lead to the production of oncometabolites.
These oncometabolites can alter cellular signaling pathways, promoting cell proliferation and survival.

Telomerase in Normal Cells

Telomerase is typically inactive in normal, differentiated cells, contributing to the limited replicative potential of these cells.
Its reactivation is crucial for cancer cell immortality.

Metabolic Intermediates and Cancer Cells

Metabolic intermediates generated via the Warburg effect, such as lactate and pyruvate, are key signaling molecules in cancer cells.
They activate specific signaling pathways, promoting tumor growth and enhancing resistance to therapy.

Cancer Cells and Energy Production

Cancer cells do not necessarily produce more energy than normal cells.
The Warburg effect is not about increased energy production per se, but rather a shift in energy production mechanisms.

Oncogenes and Growth Signals

Oncogenes are mutated or dysregulated genes that promote uncontrolled cellular growth and division.
They often act as dominant gain-of-function mutations, enhancing the activity of signaling pathways that drive cell proliferation.

Tumor Suppressor Genes and Cell Cycle Regulation

Tumor suppressor genes act as brakes on the cell cycle, preventing uncontrolled growth.
Mutations in tumor suppressor genes can lead to a loss of cell cycle control, contributing to cancer development.

Mutations in Proto-oncogenes

Proto-oncogenes are normal genes involved in regulating cell growth.
Mutations in proto-oncogenes can lead to their conversion into oncogenes, promoting uncontrolled cell proliferation.

Cancer Cells and Immune Evasion

Cancer cells can evade the immune system by expressing proteins that inhibit immune cell function.
They can also suppress immune responses by altering their surface antigens, making them less recognizable to immune cells.

Warburg Effect and Cancer Cell Metabolism

The Warburg effect alters the metabolic landscape of cancer cells, shifting their energy production towards glycolysis.
This change provides rapid energy for growth, but it also creates metabolic vulnerabilities that can be targeted by therapeutic strategies.

Telomere Biology and Cancer Cell Immortality

Telomere shortening is a natural barrier to limitless cell division.
Cancer cells overcome this barrier by reactivating telomerase, an enzyme that prevents telomere shortening, leading to their immortality.

Cancer Immunoediting

Cancer immunoediting describes the process of immune system interaction with tumor cells.
It can lead to tumor cell elimination, but it can also promote the evolution of more aggressive and immune-resistant cancer cells.

Signal Transduction Pathways

Signal transduction pathways are complex networks that relay messages from outside a cell to its interior.
They regulate various cellular processes, including growth, proliferation, and apoptosis.

Hallmarks of Cancer

Eight fundamental changes in the physiology of cancer cells
Self-sufficiency in growth signals
Insensitivity to growth inhibition
Evasion of apoptosis
Ability to evade host immune response
Limitless replicative potential (immortality)
Altered cellular metabolism
Sustained angiogenesis
Ability to invade and metastasize

Neoplasia

Disorder of cell growth triggered by series of genomic alterations
Excessive proliferation is independent of and uncontrolled by physiologic growth signals
Alterations give neoplastic cells survival and growth advantage
Alterations affect a single cell and its clonal progeny
Neoplasms are clonal: neoplastic cells derive from a single mother cell

Carcinogenesis

Cancer formation is initiated by genetic or epigenetic changes
Carcinogens are agents that cause this damage, thus increasing the risk for cancer
Damage overcomes repair mechanisms, but is not lethal
Disruption of key regulatory systems allows for tumor promotion (growth) and progression (spread)
Disrupted systems include proto-oncogenes, tumor suppressor genes, regulators of apoptosis, and repair mechanisms

Limitless Replicative Potential (Immortality)

Most normal cells have capacity to divide 60-70 times
Limited by progressive telomere shortening
Telomeres shorten with each division → eventually divisions stop
Maintained telomere length seen in virtually all types of cancer
Usually (85-95%) from up-regulation of telomerase
Normal cells do not have telomerase

Altered Cellular Metabolism

Cells normally generate energy via aerobic respiration (oxidative phosphorylation)
Generates 36 molecules of ATP per molecule of glucose
Cancer cells generate energy via aerobic glycolysis: Warburg effect
Generation of 2 molecules of ATP per molecule of glucose
Even in the presence of ample oxygen
Metabolic pathway similar to anaerobic glycolysis
Occurs in cells with limited oxygen supply
Why cancer cells use such an inefficient process: Aerobic glycolysis generates numerous metabolic intermediates

Warburg Effect

Necessary for synthesis of cellular components
Important in frequently dividing cancer cells, which require duplication/synthesis of all cellular components
Also important in frequently dividing normal cells, e.g. in embryonic tissues
Oxidative phosphorylation does not generate these necessary metabolic intermediates

Oncometabolism

Many genetic mutations affect enzymes that participate in Krebs cycle
e.g. mutations in IDH (isocitrate dehydrogenase)
Mutant IDH catalyzes reaction that produces oncometabolite
Metabolite that enhances carcinogenesis by influencing expression of cancer genes

Sustained Angiogenesis

Like normal tissues, tumors require: Delivery of oxygen and other nutrients, removal of waste products
Tumors smaller than 1mm3 can receive oxygen and nutrients by diffusion from host vasculature
Need to be able to induce angiogenesis to enlarge beyond 1-2 mm3
Growing cancers stimulate neoangiogenesis
Process by which new vessels sprout from previously existing capillaries
Accomplished by secreting pro-angiogenic cytokines such as VEGF (vascular endothelial growth factor) or FGF (fibroblast growth factor)

Effects of Neoangiogenesis on Cancer Growth

Supply of oxygen, needed nutrients
Secretion of growth factors by endothelial cells
Stimulates growth of tumor cells
New vessels are leaky and dilated
Simplified access to vascular system for metastasis by tumor cells

Ability to Invade and Metastasize

Major cause of cancer-related morbidity and mortality
Metastatic process is highly inefficient
< 0.01% of tumor cells entering into circulation develop into metastasis
Result of complex interplay between: Cancer cells, normal stroma
Likely highly controlled by epigenetic mechanisms
Epithelial tumor cells are normally attached to one another by cellular adhesion molecules (e.g., E-cadherin)
Downregulation of E-cadherin → dissociation of attached cells
Cells attach to laminin and destroy basement membrane (collagen type IV) via collagenase/matrix protease
Cells attach to fibronectin in the extracellular matrix and spread locally
Entrance into vascular or lymphatic spaces allows for metastasis (distant spread)

Lymphovascular Invasion

Before metastasis, tumor cells invade a blood vessel or a lymphatic channel = ‘lymphovascular invasion’
Invasion of lymphatic circulation → main route of nodal/regional metastases
Characteristic of carcinomas
Invasion of vascular circulation → main route of distant metastases
Characteristic of sarcomas and some carcinomas
Perineural invasion: Some cancers grow along nerves
Angiotropism: traveling along the outside of blood vessels without entering the bloodstream
Some cancers “seed” body cavities: e.g. ovarian carcinoma in peritoneum

Lung Metastases

Identified in 30-55% of all cancer patients

Lymphatic Circulation Metastases

Many cancers first metastasize via lymphatic circulation
Cancer cells deposit and grow within regional lymph nodes

Bloodborne Metastasis

Circulating cancer cells are vulnerable to destruction by several mechanisms
Sheer mechanical stress
Apoptosis (triggered by loss of cell-cell adhesion)
Immune mechanisms

Location of a Tumor

Critical determinant of clinical effects (morbidity, mortality) of a tumor

Metabolic Effects

Cancer Cachexia: Progressive loss of body fat and lean body mass
Equal loss of lean muscle and fat
Elevated basal metabolic rate
Evidence of systemic inflammation
Accompanied by: Weakness, anorexia, anemia
Weakness and reduced respiratory function → shortened survival

Anemia

Infiltrating cancers may provoke a chronic inflammatory reaction
Advanced cancer can present with signs and symptoms of extensive inflammation
Hepcidin production increased by IL-6 (and other inflammatory mediators)
Decreases iron absorption and transfer to developing erythroid precursors in bone marrow
Predisposes to iron-deficiency anemia

Hypercoagulability

Increased risk of: Thrombosis, Embolism, Non-bacterial thrombotic endocarditis
Mechanisms include: Tissue factor production by tumor, Accentuated platelet activation/accumulation, Extrinsic vascular compression and invasion

Hypercalcemia of Malignancy

Most common metabolic abnormality in the neoplastic setting
Most common cause of hypercalcemia
Primary hyperparathyroidism close second
Two general mechanisms
Osteolysis caused by cancer growing in bone
Production of calcemic humoral substances by soft tissue neoplasm
PTHRP (parathyroid hormone-related protein): related to but distinct from PTH

Hormonal Effects

Endocrine tumors, benign or malignant, may be functional
Able to synthesize and produce hormones
More typical of benign tumors

Somatotroph Adenoma

Second most frequent type of functional pituitary adenoma
Growth hormone-secreting adenoma
Gigantism if appearing in children prior to epiphyseal closure
Generalized increase in body size
Disproportionately long arms and legs
Acromegaly if appearing after epiphyseal closure
Enlargement of bones of face, hands, feet
Mandibular enlargement: prognathism
Continued growth of skin: coarse skin
Enlarged visceral organs
Variety of other disturbances: Diabetes mellitus, hypertension, heart failure

Paraneoplastic Syndromes

Disease ‘next to’ neoplasm
Caused by or resulting from presence of neoplasm in body
Not due to physical presence of tumor in organ affected
Occur in approximately 10 % of cancer patients
May be earliest manifestation of occult (hidden) neoplasm
May mimic metastatic disease and confound treatment
May cause significant clinical problems and even fatality

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Explore the fascinating topics of telomeres and cellular metabolism in cancer biology. This quiz delves into the mechanisms of replicative potential and the Warburg effect, crucial for understanding cancer cell behavior and energy production. Test your knowledge on how these factors contribute to cancer development.