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Questions and Answers
What is the primary reason why tumors require angiogenesis?
What is the primary reason why tumors require angiogenesis?
What characterizes blood vessels in growing cancers?
What characterizes blood vessels in growing cancers?
What is the role of endothelial cells in tumor growth?
What is the role of endothelial cells in tumor growth?
What is the result of leaky blood vessels in tumors?
What is the result of leaky blood vessels in tumors?
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What controls angiogenesis in tumors?
What controls angiogenesis in tumors?
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Who are the producers of angiogenesis activators?
Who are the producers of angiogenesis activators?
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What can release proangiogenic basic fibroblast growth factors (bFGF) stored in the ECM?
What can release proangiogenic basic fibroblast growth factors (bFGF) stored in the ECM?
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How are angiogenesis inhibitors produced?
How are angiogenesis inhibitors produced?
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What is the zone that represents the maximal distance across which oxygen, nutrients, and waste can diffuse from blood vessels?
What is the zone that represents the maximal distance across which oxygen, nutrients, and waste can diffuse from blood vessels?
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What happens to tumors that do not induce angiogenesis early in their development?
What happens to tumors that do not induce angiogenesis early in their development?
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What is the result of a 'gain-of-function' mutation in a signaling pathway?
What is the result of a 'gain-of-function' mutation in a signaling pathway?
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Which of the following proteins is an example of an oncoprotein that promotes cell growth?
Which of the following proteins is an example of an oncoprotein that promotes cell growth?
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What is the normal function of CDKIs?
What is the normal function of CDKIs?
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What is the result of a loss-of-function mutation in a CDKI?
What is the result of a loss-of-function mutation in a CDKI?
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What is the name of the protein resulting from the translocation of the ABL gene in CML?
What is the name of the protein resulting from the translocation of the ABL gene in CML?
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What is the normal function of proto-oncogenes?
What is the normal function of proto-oncogenes?
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Which hallmark of cancer refers to cancer cells' ability to grow without external signals?
Which hallmark of cancer refers to cancer cells' ability to grow without external signals?
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What mechanism allows cancer cells to avoid programmed cell death?
What mechanism allows cancer cells to avoid programmed cell death?
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Which hallmark of cancer involves increased blood vessel formation to supply nutrients to tumors?
Which hallmark of cancer involves increased blood vessel formation to supply nutrients to tumors?
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How do cancer cells typically behave towards their surrounding cellular environment?
How do cancer cells typically behave towards their surrounding cellular environment?
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What characteristic of cancer cells allows them to persist and multiply despite systemic challenges?
What characteristic of cancer cells allows them to persist and multiply despite systemic challenges?
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What is a consequence of genomic instability in cancer cells?
What is a consequence of genomic instability in cancer cells?
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Which statement regarding tumor suppressor genes is true?
Which statement regarding tumor suppressor genes is true?
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What is the primary function of the retinoblastoma gene (RB)?
What is the primary function of the retinoblastoma gene (RB)?
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Which of the following cancers is NOT commonly associated with biallelic loss of the retinoblastoma gene (RB)?
Which of the following cancers is NOT commonly associated with biallelic loss of the retinoblastoma gene (RB)?
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Why is the TP53 gene often referred to as the 'guardian of the genome'?
Why is the TP53 gene often referred to as the 'guardian of the genome'?
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What percentage of human cancers feature defects in the TP53 gene?
What percentage of human cancers feature defects in the TP53 gene?
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In what way does a mutation in the retinoblastoma gene (RB) affect its function?
In what way does a mutation in the retinoblastoma gene (RB) affect its function?
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What comparison do cancer stem cells have to normal stem cells in terms of therapy resistance?
What comparison do cancer stem cells have to normal stem cells in terms of therapy resistance?
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Which factor contributes to genomic instability in cancer cells?
Which factor contributes to genomic instability in cancer cells?
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Which of the following conditions is associated with inherited mutations in DNA repair systems?
Which of the following conditions is associated with inherited mutations in DNA repair systems?
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What is a common characteristic of BRCA1 and BRCA2 mutations?
What is a common characteristic of BRCA1 and BRCA2 mutations?
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What aspect of genomic instability is commonly observed in certain carcinomas, such as colon cancer?
What aspect of genomic instability is commonly observed in certain carcinomas, such as colon cancer?
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What characterizes 'fragile sites' within the genome?
What characterizes 'fragile sites' within the genome?
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What is the primary function of p53 protein when DNA damage occurs?
What is the primary function of p53 protein when DNA damage occurs?
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Which of the following is a consequence of p53 mutation or inhibition?
Which of the following is a consequence of p53 mutation or inhibition?
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What is the role of E6 protein from high-risk human papillomaviruses in relation to p53?
What is the role of E6 protein from high-risk human papillomaviruses in relation to p53?
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How does loss of cell-cell contact contribute to cell proliferation?
How does loss of cell-cell contact contribute to cell proliferation?
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Which of the following is NOT a direct consequence of p53 activation?
Which of the following is NOT a direct consequence of p53 activation?
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Which of these is a mechanism by which p53 prevents tumor development?
Which of these is a mechanism by which p53 prevents tumor development?
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What is a common symptom of cancer that can be identified through history taking?
What is a common symptom of cancer that can be identified through history taking?
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What is a diagnostic technique used in the laboratory diagnosis of cancer?
What is a diagnostic technique used in the laboratory diagnosis of cancer?
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What is a type of antigen that can be used in the diagnosis of cancer? (MACA)
What is a type of antigen that can be used in the diagnosis of cancer? (MACA)
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What is an important aspect of treating malignancy?
What is an important aspect of treating malignancy?
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What can be observed during the examination of a patient with suspected cancer?
What can be observed during the examination of a patient with suspected cancer?
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What is a type of test used in the laboratory diagnosis of cancer? (MACA)
What is a type of test used in the laboratory diagnosis of cancer? (MACA)
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Why must a doctor understand carcinogens and factors causing malignancy?
Why must a doctor understand carcinogens and factors causing malignancy?
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What should a Doctor of Chiropractic recognize as potential indicators of neoplasia?
What should a Doctor of Chiropractic recognize as potential indicators of neoplasia?
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Which locations are identified as common sites of metastasis?
Which locations are identified as common sites of metastasis?
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What does an alteration in local tissue tone potentially indicate?
What does an alteration in local tissue tone potentially indicate?
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Why is it significant for a Doctor of Chiropractic to recognize lymphatic-rich areas?
Why is it significant for a Doctor of Chiropractic to recognize lymphatic-rich areas?
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What role does knowledge of malignancy-predisposing conditions play for a doctor?
What role does knowledge of malignancy-predisposing conditions play for a doctor?
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What might palpation of alterations in joint areas signify?
What might palpation of alterations in joint areas signify?
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How can local tissue tone alterations influence the likelihood of metastasis?
How can local tissue tone alterations influence the likelihood of metastasis?
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Which of the following is NOT a primary treatment modality for cancer?
Which of the following is NOT a primary treatment modality for cancer?
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Which of the following is an example of an alternative immune stimulation method used in cancer treatment?
Which of the following is an example of an alternative immune stimulation method used in cancer treatment?
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Which of the following is a type of molecule that can be used to stimulate the immune system in cancer treatment? (MACA)
Which of the following is a type of molecule that can be used to stimulate the immune system in cancer treatment? (MACA)
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Which of the following is NOT a factor that contributes to spontaneous remission of cancer?
Which of the following is NOT a factor that contributes to spontaneous remission of cancer?
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What is the primary reason why a doctor of chiropractic should be aware of the signs and symptoms of neoplasia?
What is the primary reason why a doctor of chiropractic should be aware of the signs and symptoms of neoplasia?
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Which of the following is NOT a potential benefit of knowing about neoplasia for a doctor of chiropractic?
Which of the following is NOT a potential benefit of knowing about neoplasia for a doctor of chiropractic?
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What is the primary cause of cancer-related morbidity and mortality?
What is the primary cause of cancer-related morbidity and mortality?
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What is the first step in the process of invasion?
What is the first step in the process of invasion?
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What is the name of the enzyme overexpressed in malignant tumors of the breast, colon, and stomach?
What is the name of the enzyme overexpressed in malignant tumors of the breast, colon, and stomach?
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What is the result of ECM degradation in invasion?
What is the result of ECM degradation in invasion?
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What is the consequence of ECM alterations in invasion?
What is the consequence of ECM alterations in invasion?
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Which of the following is NOT a characteristic of tumor cells recognized by the immune system as nonself?
Which of the following is NOT a characteristic of tumor cells recognized by the immune system as nonself?
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What is the primary mechanism of antitumor activity mediated by T cells?
What is the primary mechanism of antitumor activity mediated by T cells?
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Which of the following is TRUE regarding the role of natural killer (NK) cells in antitumor immunity?
Which of the following is TRUE regarding the role of natural killer (NK) cells in antitumor immunity?
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Which of the following is NOT a factor contributing to the evasion of the immune system by tumor cells?
Which of the following is NOT a factor contributing to the evasion of the immune system by tumor cells?
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What type of immune cells are primarily responsible for the osteolytic nature of bone metastases in breast cancer?
What type of immune cells are primarily responsible for the osteolytic nature of bone metastases in breast cancer?
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Which mechanism allows tumors to evade the immune system through the alteration of antigen expression?
Which mechanism allows tumors to evade the immune system through the alteration of antigen expression?
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What is a direct consequence of chronic inflammation induced by necrosis?
What is a direct consequence of chronic inflammation induced by necrosis?
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Which factor contributes to the immunosuppressive environment in tumors?
Which factor contributes to the immunosuppressive environment in tumors?
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How do infiltrating leukocytes and stromal cells contribute to tumor growth?
How do infiltrating leukocytes and stromal cells contribute to tumor growth?
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What mechanism is associated with the switch of macrophages to M2 phenotype in tumor environments?
What mechanism is associated with the switch of macrophages to M2 phenotype in tumor environments?
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What is the role of integrins in tumor cells regarding apoptosis and oncogene stimulation?
What is the role of integrins in tumor cells regarding apoptosis and oncogene stimulation?
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What is necessary for the movement and migration of cancer cells?
What is necessary for the movement and migration of cancer cells?
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What happens to tumor cells once they are in circulation?
What happens to tumor cells once they are in circulation?
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What is organ tropism in the context of tumor cells?
What is organ tropism in the context of tumor cells?
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What factor may contribute to the dormancy of established metastases?
What factor may contribute to the dormancy of established metastases?
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Study Notes
Induction and Activation of Nuclear Regulatory Factors
- Initiate and regulate DNA transcription and biosynthesis of cellular components for cell division
- Include synthesis of ribosomes, organelles, membrane components, and cell cycle regulatory proteins
Autocrine Stimulation and Cell Cycle Progression
- Cells produce their own growth factors, such as platelet-derived growth factor (PDGF) and transforming growth factor α (TGF-α)
- Stimulate stroma to increase production of growth factors, mostly through PAMP and DAMP signals
- Cells can also have receptor "gain-of-function" mutations, leading to over-expression or altered functioning of growth factor receptors
Insensitivity to Growth-Inhibitory Signals
- Tumor suppressor genes, such as retinoblastoma gene (RB) and TP53, regulate cell cycle progression and arrest
- Loss of function or mutation in these genes can lead to uncontrolled cell growth and division
- TP53 is often referred to as the "guardian of the genome"
Evasion of Apoptosis
- Apoptosis, or programmed cell death, occurs through extrinsic and intrinsic pathways
- Overexpression of anti-apoptotic proteins, such as BCL2, can inhibit apoptosis and promote cancer cell survival
- Chemotherapy and radiation therapy kill cancer cells by inducing apoptosis through the intrinsic pathway
Limitless Replicative Potential (Immortality)
- Normal cells have a limited replicative potential due to telomere shortening, leading to mitotic crisis and death
- Cancer cells often maintain telomere length through telomerase upregulation or alternative mechanisms, allowing for infinite replication
- Cancer stem cells, which have self-renewal capabilities, are thought to be present in all types of cancers
Sustained Angiogenesis
- Tumors require a blood supply for oxygen and nutrient delivery, as well as waste removal
- Tumors stimulate angiogenesis, leading to the formation of new, abnormal blood vessels
- Angiogenesis is regulated by a balance of promoters and inhibitors, including factors produced by tumor cells, inflammatory cells, and stromal cells
Hallmarks of Cancer
- Self-sufficiency in growth signals
- Growth factor binds to specific membrane receptor
- Activated receptor triggers signal proteins, leading to transmission of signal across cytosol and into the nucleus
- Parallel metabolic changes and correlation with other signals, including mechanical tension, PAMP, and DAMP
- Signaling path "gain-of-function" can convert proto-oncogenes to oncogenes
- Insensitivity to growth-inhibitory signals
- Retinoblastoma gene (RB) regulates cell cycle progression and is often lost in various tumors
- TP53 gene regulates cell cycle arrest, DNA repair, and apoptosis in response to DNA damage, hypoxia, and telomere shortening
- Loss of contact inhibition leads to uncontrolled proliferation
- Altered cellular metabolism
- Evasion of apoptosis
- Limitless replicative potential (immortality)
- Sustained angiogenesis
- Invasion and metastasis
- Evasion of immune surveillance
- Genomic instability
- Tumor-promoting inflammation
Self-Sufficiency in Growth Signals
- Growth signals are normally temporary and limited
- Activated growth factor receptors lead to gain-of-function mutations, promoting cell growth and proliferation
- Examples of oncogenes: RAS (30% of all studied cancers), RAF, PI3K, AKT
- BCR-ABL protein in CML responds well to BCR-ABL kinase inhibitors like imatinib
Insensitivity to Growth-Inhibitory Signals
- Retinoblastoma gene (RB) is a tumor suppressor gene that regulates cell cycle progression
- TP53 gene is a tumor suppressor gene that triggers cell cycle arrest, DNA repair, and apoptosis in response to DNA damage
- Loss of contact inhibition leads to uncontrolled proliferation
- Cancer stem cells are hard to identify and may arise from normal stem cells or acquired genetic lesions
Genomic Instability
- High frequency of mutations within the genome of a cell line
- DNA is most vulnerable during replication, and "fragile sites" may exist along exposed chromatin
- Inherited mutations of genes involved in DNA repair systems increase the risk of cancer and neurodegenerative diseases
- Examples of genes involved in DNA repair: BRCA1, BRCA2, and xeroderma pigmentosum
Diagnosis of Cancer
- Exposure to carcinogens such as asbestos, pesticides, and other substances at work, home, or during travel can be a risk factor
- Symptoms include unexplained growths, lumps, bleeding, or blood in sputum, stool, or urine
- Changes in bowel or bladder habits, visible moles, discharge, hoarseness, indigestion, and difficulty swallowing can also be indicative of cancer
- Unusual coughing or other persisting symptoms should be investigated
Examination
- Inspection: obvious changes in warts or moles, sores that don't heal, anemia, hypoxia, clubbing nails, and thromboflebitis
- Auscultation: listening to lung and abdominal sounds for signs of obstruction
- Palpation: feeling for growths, lumps, or changes in tissue firmness, including palpating lymph nodes at joints
Laboratory Diagnosis of Cancer
- Histological diagnosis: examination of cytological samples, fine needle aspiration, and biopsy
- Biochemical assays: measuring levels of substances like prostate-specific antigen, human chorionic gonadotropin, and catecholamine metabolites
- Receptor analysis and tumor antigen tests, including tests for MAGE-1 and other tumor-associated antigens
Treatment of Malignancy
- Treatment is not usually an emergency, and patients should be well-informed and keep a journal
- Surgery, radiation, chemotherapy, molecular therapies, and alternative immune stimulation may be used
- Immune stimulation approaches include PAMP/TLR, hyperthermia, miRNA, and spontaneous remission
Importance for the Doctor of Chiropractic
- Recognizing symptoms and signs of neoplasia is essential for early diagnosis and referral
- Knowing about carcinogens and factors causing malignancy can help with patient counseling
- Understanding conditions that predispose to malignancy can inform patient care
- Palpating soft tissue tone alteration, stiffness, and/or adhesions can be a sign of possible neoplasia
- Joint areas are lymphatic-rich and may be associated with neoplasia
- Liver, lung, and brain are common sites of metastasis, and alterations in local tissue tone may indicate their presence
Invasion and Metastasis
- Complex interactions between cancer cells and normal stroma lead to invasion and metastasis, the major causes of cancer-related morbidity and mortality.
- Only a few metastases are produced despite millions of cells being released into the circulation each day from a primary tumor.
- Invasion occurs in four steps:
- Loosening of cell-cell contacts: inactivation, alterations, or downregulation of epithelial surface proteins and intercellular adhesion molecules (e.g., cadherins).
- Basement membranes and ECM degradation: mediated by proteolytic enzymes (matrix metalloproteases and cathepsins), release of stored growth factors, and reduced concentrations of metalloproteinase inhibitors.
- ECM alterations: fragmented ECM fibers expose different adhesion sites, increased stiffness, and altered integrin response.
- Locomotion/migration: tumor cells attach to the matrix at the leading edge, detach at the trailing edge, and contract the actin cytoskeleton to ratchet forward.
Vascular Dissemination and Homing of Tumor Cells
- Many tumors arrest in the first capillary bed they encounter (e.g., lung and liver).
- Tumor cells in circulation are vulnerable to destruction (mechanical shear stress, apoptosis, and immune defenses).
- Tumor cells tend to aggregate in clumps due to adhesions among tumor cells and between tumor cells and blood cells (particularly platelets).
- Some tumors show organ tropism due to expression of adhesion or chemokine receptors whose ligands are expressed by endothelial cells at the metastatic site.
Evading Immunity
- Tumor cells can be recognized by the immune system as nonself and destroyed.
- Immunosuppressed patients have an increased risk of developing cancer.
- Cell proteins presented on the cell surface by MHC class I molecules are recognized by CD8+ CTLs as tumor antigens.
- Antitumor activity is mediated by cell-mediated mechanisms, including:
- T-cell mediated cytotoxicity: clear protective role against virus-associated neoplasms.
- Natural killer cell cytotoxicity: capable of destroying tumor cells without prior sensitization.
- Macrophage-mediated cytotoxicity: activated macrophages exhibit cytotoxicity against tumor cells.
Chronic Inflammation
- Necrosis induces chronic and extensive inflammation, leading to systemic signs and symptoms (e.g., anemia, fatigue, and cachexia).
- Infiltrating leukocytes and activated stromal cells secrete growth factors, cytokines, and proteases that promote angiogenesis, fibroblast proliferation, and collagen deposition.
- Stromal cell-cancer cell interactions increase the resistance of cancer cells to chemotherapy.
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Description
This quiz covers the initiation and regulation of DNA transcription, biosynthesis of cellular components, and autocrine stimulation in cell cycle progression.
