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Questions and Answers
What is the main route for nodal/regional metastases in carcinomas?
What is the main route for nodal/regional metastases in carcinomas?
Which mechanism is NOT involved in the destruction of circulating cancer cells during vascular dissemination?
Which mechanism is NOT involved in the destruction of circulating cancer cells during vascular dissemination?
What distinguishes sarcomas from carcinomas with regard to metastatic routes?
What distinguishes sarcomas from carcinomas with regard to metastatic routes?
Which of the following cancer behaviors involves traveling along the outside of blood vessels?
Which of the following cancer behaviors involves traveling along the outside of blood vessels?
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What characteristic is associated with some cancers that grow specifically along nerves?
What characteristic is associated with some cancers that grow specifically along nerves?
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What primary factors influence the site of distant metastasis for cancer cells?
What primary factors influence the site of distant metastasis for cancer cells?
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Which process describes the transition of epithelial cells to a mesenchymal phenotype, aiding in cancer metastasis?
Which process describes the transition of epithelial cells to a mesenchymal phenotype, aiding in cancer metastasis?
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What is the primary function of CD8 T lymphocytes in immune surveillance?
What is the primary function of CD8 T lymphocytes in immune surveillance?
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What generally characterizes malignant tumors as opposed to benign tumors?
What generally characterizes malignant tumors as opposed to benign tumors?
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Which molecular change allows tumors to make themselves 'invisible' to the immune system?
Which molecular change allows tumors to make themselves 'invisible' to the immune system?
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Which factor is most likely associated with prostate carcinoma metastasis?
Which factor is most likely associated with prostate carcinoma metastasis?
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How do local macrophages contribute to the activation of CD8+ T-cells in the immune response against tumors?
How do local macrophages contribute to the activation of CD8+ T-cells in the immune response against tumors?
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What is required before a tumor can definitively be classified as benign or malignant?
What is required before a tumor can definitively be classified as benign or malignant?
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Which mechanism do tumors use to suppress the immune system's response?
Which mechanism do tumors use to suppress the immune system's response?
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What is the role of cancer immunoediting in tumor development?
What is the role of cancer immunoediting in tumor development?
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In which state can immunodeficiency result in an increased risk for cancer?
In which state can immunodeficiency result in an increased risk for cancer?
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What effect does the expression of CTLA-4 by tumor cells have on activated T-cells?
What effect does the expression of CTLA-4 by tumor cells have on activated T-cells?
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What characterizes an immunosuppressed host's experience with cancer development?
What characterizes an immunosuppressed host's experience with cancer development?
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Which mechanism contributes to anemia in advanced cancer?
Which mechanism contributes to anemia in advanced cancer?
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What is a common paraneoplastic syndrome associated with gastric adenocarcinoma?
What is a common paraneoplastic syndrome associated with gastric adenocarcinoma?
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Which of the following is a potential effect of cancer-related hypercalcemia?
Which of the following is a potential effect of cancer-related hypercalcemia?
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How does cancer affect metabolic rate in cachexia?
How does cancer affect metabolic rate in cachexia?
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What is a common consequence of thrombosis in cancer patients?
What is a common consequence of thrombosis in cancer patients?
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What effect does a growth hormone-secreting adenoma have if it appears before epiphyseal closure?
What effect does a growth hormone-secreting adenoma have if it appears before epiphyseal closure?
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Which statement about benign tumors is NOT true?
Which statement about benign tumors is NOT true?
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Which inflammatory mediator is known to increase hepcidin production in cancer-related anemia?
Which inflammatory mediator is known to increase hepcidin production in cancer-related anemia?
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What is emphasized regarding cancer cachexia?
What is emphasized regarding cancer cachexia?
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What type of cancer is primarily associated with non-bacterial thrombotic endocarditis?
What type of cancer is primarily associated with non-bacterial thrombotic endocarditis?
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Which condition arises due to chronic inflammatory reactions caused by infiltrating cancers?
Which condition arises due to chronic inflammatory reactions caused by infiltrating cancers?
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Which effect does pancreatic cancer have when it invades the head of the pancreas?
Which effect does pancreatic cancer have when it invades the head of the pancreas?
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In which context might children experience gigantism due to functional pituitary adenomas?
In which context might children experience gigantism due to functional pituitary adenomas?
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Which cancer-related condition leads to increased production of calcemic humoral substances?
Which cancer-related condition leads to increased production of calcemic humoral substances?
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Which statement is true about the replicative potential of normal cells?
Which statement is true about the replicative potential of normal cells?
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What role does telomerase play in most human cancers?
What role does telomerase play in most human cancers?
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Why do cancer cells typically engage in aerobic glycolysis instead of oxidative phosphorylation?
Why do cancer cells typically engage in aerobic glycolysis instead of oxidative phosphorylation?
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What is a consequence of the Warburg effect in cancer cells?
What is a consequence of the Warburg effect in cancer cells?
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What does mutant IDH produce that enhances carcinogenesis?
What does mutant IDH produce that enhances carcinogenesis?
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Which of the following statements about telomere function is NOT accurate?
Which of the following statements about telomere function is NOT accurate?
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What is a correct statement regarding metabolic pathways in cancer cells?
What is a correct statement regarding metabolic pathways in cancer cells?
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What is a primary reason cancer cells rely on the Warburg effect despite its inefficiency?
What is a primary reason cancer cells rely on the Warburg effect despite its inefficiency?
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Study Notes
Immune Response Abilities
- Immune surveillance is a normal process that involves the constant scanning of the body by the immune system, destroying abnormal cells.
- Cells harboring infectious agents or malignant cells are targets of immune surveillance.
- Immune surveillance is performed by several cells, specifically CD8 T lymphocytes, Natural Killer cells, and Macrophages.
- Many cancers express abnormal antigens due to mutations.
- These mutations produce abnormal proteins expressed on MHC I, or a high number of cells undergoing cell death.
- Tumor antigens are ingested by local macrophages or dendritic cells, which migrate to local lymph nodes and present these antigens to naïve CD8+ T-cells.
- Activated, antigen-specific CD8+ T-cells then migrate to the tumor to kill tumor cells.
Cancer Immunodeficiency
- Immunodeficiency increases the risk of cancer.
- Cancers arising in immunocompetent hosts may be invisible to the immune system.
- Cancers may suppress host immunity.
Cancer Immunoediting
- Cancer immunoediting describes the process of "natural selection" for cancer cells that evade immune elimination.
- Antigen-negative variations of cancer cells are selected for growth.
- MHC molecules may be reduced or completely lost in expression.
Immune System Suppression
- The immune system has "checkpoint" pathways to prevent overstimulation.
- Cancer cells can downregulate the activity of the immune system by activating these checkpoints.
- Cancer cells may express PD-L1, PD-L2 which activate PD-1 on T cells.
- Cancer cells may also activate CTLA-4 on T cells, sending an inhibitory stimulus to activated T cells.
Replication Potential
- Normal cells have a limited capacity to divide 60-70 times.
- Progressive telomere shortening limits the capacity to divide.
- Telomeres shorten with each division.
- Most human cancers maintain appropriate telomere length via upregulation of telomerase.
Cancer Metabolism
- Cells normally generate energy via aerobic respiration.
- Cancer cells generate energy via aerobic glycolysis.
- This is known as the Warburg effect.
Warburg Effect Explained
- The Warburg effect produces 2 molecules of ATP per glucose.
- This is an inefficient process, even in the presence of ample oxygen.
- This pathway is similar to anaerobic glycolysis.
- It occurs in cells with limited oxygen supply.
Warburg Effect and Metabolic Intermediates
- Aerobic glycolysis generates metabolic intermediates crucial for cancer cells to synthesize cellular components.
- This is important in cancer cells because they require duplication of cellular components for rapid division.
- DNA, RNA, proteins, lipids, and organelles are all cellular components produced via aerobic glycolysis.
Oxidative Phosphorylation
- Oxidative phosphorylation does not generate the metabolic intermediates necessary for rapid cell division.
Oncometabolism
- Genetic mutations can affect enzymes involved in the Krebs cycle.
- Mutations in IDH, for example, produce an oncometabolite.
- This metabolite enhances carcinogenesis by influencing the expression of cancer genes.
Metastasis
- Distant spread of cancer cells, known as metastasis, is initiated by the invasion of circulating cells into vascular or lymphatic spaces.
- Before metastasis, tumor cells invade a blood vessel or a lymphatic channel, known as lymphovascular invasion.
Avenues of Metastatic Growth
- Metastasis is preceded by the invasion of the vascular system or peripheral nervous system.
- Lymphovascular invasion can occur through lymphatic circulation, the main route for nodal/regional metastases.
- This is characteristic of carcinomas.
- Lymphovascular invasion can occur through vascular circulation, the main route for distant metastases.
- This is characteristic of sarcomas and some carcinomas.
- Perineural invasion occurs when some neurotropic cancers grow along nerves.
- Angiotropism is the ability of cancer cells to travel along blood vessels without entering the bloodstream.
- Some cancers seed body cavities, such as ovarian carcinoma in the peritoneum.
Lung Metastasis
- Lung metastasis is identified in 30-55% of all cancer patients.
Lymphatic Circulation
- 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, including mechanical stress, apoptosis, and immune mechanisms.
- Cancer cells protect themselves by aggregating in clumps and shielding themselves with platelets.
Homing of Tumor Cells to Secondary Deposits
- During bloodborne metastasis, tumor cells must adhere to the endothelium and egress through the basement membrane.
- The site of distant metastasis depends on the anatomic location of the primary tumor, and the venous drainage of the primary tumor.
- Most metastases occur in the first location available.
Metastasis Tropism
- The site of distant metastasis is also influenced by the tropism of particular tumors for specific tissues.
- For example, prostate carcinoma metastasis has a predilection for bone.
Epithelial to Mesenchymal Transition
- EMT is the process of epithelial cells acquiring mesenchymal phenotype.
- This plays a role in wound healing and tissue development.
- EMT may facilitate acquisition of invasive/metastatic capabilities by cancerous cells.
Clinical Features of Neoplasia
- Benign tumors are slow-growing, well-circumscribed, distinct, and mobile.
- Malignant tumors are usually rapid-growing, poorly circumscribed, infiltrative, and fixed to surrounding tissues.
- A biopsy or excision is generally required to classify a tumor as benign or malignant.
Location of Neoplasia
- Neoplasia location is a critical determinant of clinical effects, specifically morbidity and mortality.
Clinical Features of Neoplasia
- Lung compression and respiratory failure can occur due to mesothelioma.
- Pathological fracture of the humerus can occur due to chondrosarcoma.
- Esophageal rupture can occur due to esophageal SCC.
- Brain herniation can occur due to glioblastoma multiforme.
- Hemorrhage can occur after invasion into vessel walls from rectal adenocarcinoma.
- Jaundice can occur from pancreatic carcinoma involving the head of the pancreas.
- Ventricular compression can occur due to cardiac fibromatosis.
Cancer Cachexia
- Cancer Cachexia is a progressive loss of body fat and lean body mass.
- It occurs when there is an equal loss of lean muscle and fat.
- There is an elevated basal metabolic rate, and evidence of systemic inflammation.
- Individuals with cancer cachexia may experience weakness, anorexia, and anemia.
- Weakness and reduced respiratory function shorten survival time.
Cancer and Anemia
- Infiltrating cancers may provoke a chronic inflammatory reaction.
- Advanced cancer can present with signs and symptoms of extensive inflammation.
- Hepcidin production is increased by IL-6, which decreases iron absorption and transfer to developing erythroid precursors in bone marrow.
- This increases the risk of iron-deficiency anemia.
Cancer and Anemia Explained
- TNFα, IL-1, IFN-γ, and other inflammatory mediators can also reduce renal response to anemia.
- This leads to less erythropoietin produced for any given level of anemia.
- These same cytokine mediators can also reduce marrow response to erythropoietin.
- This further limits erythropoiesis for any given level of erythropoietin.
- Hemorrhage, hemolysis, and blood loss can also contribute to reduced red blood cell levels.
Cancer and Hypercoagulability
- There is an increased risk of thrombosis, embolism, and non-bacterial thrombotic endocarditis in individuals with cancer.
- This is due to tissue factor production by the tumor, accentuated platelet activation/accumulation, and extrinsic vascular compression and invasion.
Hypercalcemia of Malignancy
- Hypercalcemia is the most common metabolic abnormality in the neoplastic setting.
- Primary hyperparathyroidism is the second most common cause of hypercalcemia.
- There are two major mechanisms underlying hypercalcemia:
- Osteolysis caused by cancer growing in bone
- Production of calcemic humoral substances by soft tissue neoplasm
- PTHRP (parathyroid hormone-related protein) is related to but distinct from PTH.
Hormonal Effects of Neoplasms
- Endocrine tumors, benign or malignant, may be functional.
- These tumors can synthesize and produce hormones.
- This is more typical of benign tumors.
Functional Pituitary Adenomas
- The second most frequent type of functional pituitary adenoma is a somatotroph adenoma, a growth hormone-secreting adenoma.
- In children, these adenomas can cause gigantism, which leads to an increase in body size with disproportionately long arms and legs.
- Other disturbances include diabetes mellitus, hypertension, and heart failure.
Functional Pituitary Adenomas Explained
- Acromegaly, the result of these adenomas in adults after epiphyseal closure, results in the enlargement of bones in the face, hands, and feet.
- Enlarged visceral organs, such as the thyroid, heart, liver, and adrenals are common.
- Diabetes mellitus, hypertension, and heart failure are also common.
Paraneoplastic Syndromes
- Paraneoplastic syndrome describes a disease "next to" a neoplasm.
- These syndromes are caused by the presence of cancer cells in the body, but not due to the physical presence of a tumor in the affected region.
- Paraneoplastic syndromes occur in about 10% of cancer patients.
- They can be the first sign of occult (hidden) neoplasm.
- Paraneoplastic syndromes can mimic metastatic disease, and confound treatment.
- These syndromes can cause significant clinical problems and even fatality.
Paraneoplastic Syndrome Explained
- Macroglossia, or an enlarged tongue, can occur with multiple myeloma.
- Hemorrhagic stroke can occur due to pheochromocytoma-induced hypertension.
- Paraneoplastic autoimmune multiorgan syndrome can occur due to lymphoma or leukemia.
- Leser-Trelat sign, the rapid appearance of multiple seborrheic keratoses, is typically associated with gastric adenocarcinoma.
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Description
This quiz explores the immune system's role in cancer surveillance and the impact of immunodeficiency on cancer risk. It covers key immune cells involved in recognizing and destroying abnormal cells and the challenges faced in immunocompromised individuals. Test your understanding of how the body's defenses interact with cancer development.