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Questions and Answers
What characterizes the majority of p53 mutations?
What characterizes the majority of p53 mutations?
Which of the following differentiates apoptosis from necrosis?
Which of the following differentiates apoptosis from necrosis?
How does phosphorylation influence p53 and Mdm2 during cellular stress?
How does phosphorylation influence p53 and Mdm2 during cellular stress?
What is the significance of p53's short half-life in normal cells?
What is the significance of p53's short half-life in normal cells?
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What is a primary feature of first-generation CAR T-cell therapy?
What is a primary feature of first-generation CAR T-cell therapy?
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Which side effect is most commonly associated with CAR T-cell therapy?
Which side effect is most commonly associated with CAR T-cell therapy?
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What mutation in the Ras protein is commonly associated with cancers?
What mutation in the Ras protein is commonly associated with cancers?
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Which pathway does Ras primarily activate to promote cell cycle progression?
Which pathway does Ras primarily activate to promote cell cycle progression?
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What is the primary function of Immediate Early Genes (IEGs)?
What is the primary function of Immediate Early Genes (IEGs)?
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Which of the following accurately describes the mechanism of action of Gamma Knife radiotherapy?
Which of the following accurately describes the mechanism of action of Gamma Knife radiotherapy?
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What inspired Dr. William Coley to explore cancer treatments?
What inspired Dr. William Coley to explore cancer treatments?
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What key process does angiogenesis facilitate in cancer development?
What key process does angiogenesis facilitate in cancer development?
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Which statement about Bcl-2 is true?
Which statement about Bcl-2 is true?
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What is the primary mechanism of action of Keytruda?
What is the primary mechanism of action of Keytruda?
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What is a significant effect of Ras mutations in oncogenesis?
What is a significant effect of Ras mutations in oncogenesis?
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Which of the following is a potential side effect of anti-PD-1 therapy such as Keytruda?
Which of the following is a potential side effect of anti-PD-1 therapy such as Keytruda?
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What average survival extension does Provenge therapy provide for prostate cancer?
What average survival extension does Provenge therapy provide for prostate cancer?
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What role do SH2 domains play in signal transduction?
What role do SH2 domains play in signal transduction?
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What is a common outcome of immune evasion in cancerous cells?
What is a common outcome of immune evasion in cancerous cells?
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What triggers apoptosis in cells?
What triggers apoptosis in cells?
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Which step is NOT part of the multi-step tumor progression process?
Which step is NOT part of the multi-step tumor progression process?
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How does necrosis differ from apoptosis?
How does necrosis differ from apoptosis?
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What is the role of the protein p53 in cells?
What is the role of the protein p53 in cells?
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What characteristic mutation of p53 often affects its function in cancers?
What characteristic mutation of p53 often affects its function in cancers?
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What is the primary function of anti-apoptotic proteins like Bcl-2?
What is the primary function of anti-apoptotic proteins like Bcl-2?
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How many mutations are typically required for epithelial cancers to develop?
How many mutations are typically required for epithelial cancers to develop?
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What is the purpose of the apoptosome formed by Cytochrome C and Apaf-1?
What is the purpose of the apoptosome formed by Cytochrome C and Apaf-1?
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What is a key characteristic of genomic instability in cancers?
What is a key characteristic of genomic instability in cancers?
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In familial polyposis caused by APC mutations, what is the expected condition by age 20?
In familial polyposis caused by APC mutations, what is the expected condition by age 20?
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Which cancer risk factor is contributed to by chronic inflammation as seen in Kostmann Syndrome?
Which cancer risk factor is contributed to by chronic inflammation as seen in Kostmann Syndrome?
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What does the term 'Darwinian evolution of cancer' refer to?
What does the term 'Darwinian evolution of cancer' refer to?
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How does long-term aspirin use benefit cancer prevention?
How does long-term aspirin use benefit cancer prevention?
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What is the primary cause of cachexia in cancer patients?
What is the primary cause of cachexia in cancer patients?
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What is one of the benefits of NSAID use in cancer prevention?
What is one of the benefits of NSAID use in cancer prevention?
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Genomic instability in tumors primarily contributes to which aspect of cancer progression?
Genomic instability in tumors primarily contributes to which aspect of cancer progression?
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How does chronic inflammation affect tumor growth?
How does chronic inflammation affect tumor growth?
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Which type of agents are characterized by different thresholds for mutagenic and mitogenic effects?
Which type of agents are characterized by different thresholds for mutagenic and mitogenic effects?
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What factor primarily drives the risk associated with birth control pills in cancer?
What factor primarily drives the risk associated with birth control pills in cancer?
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What is a primary characteristic of rational cancer treatment compared to traditional approaches?
What is a primary characteristic of rational cancer treatment compared to traditional approaches?
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Which statement correctly describes Darwinian selection in tumor development?
Which statement correctly describes Darwinian selection in tumor development?
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What role do microarrays play in cancer treatment?
What role do microarrays play in cancer treatment?
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What distinguishes RNA sequencing (RNA-seq) from traditional microarrays?
What distinguishes RNA sequencing (RNA-seq) from traditional microarrays?
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What is the primary goal of differentiation therapy in cancer treatment?
What is the primary goal of differentiation therapy in cancer treatment?
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How is liver cancer affected by the absence of the G2/M checkpoint?
How is liver cancer affected by the absence of the G2/M checkpoint?
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What is a unique benefit of small molecule drugs in cancer therapy?
What is a unique benefit of small molecule drugs in cancer therapy?
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What is the primary focus of Phase I clinical trials in cancer treatment development?
What is the primary focus of Phase I clinical trials in cancer treatment development?
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Which mechanism allows cancer cells to resist drug efficacy?
Which mechanism allows cancer cells to resist drug efficacy?
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What is a critical component of targeted therapies like those used for Bcr-Abl fusion in leukemia?
What is a critical component of targeted therapies like those used for Bcr-Abl fusion in leukemia?
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Study Notes
Immune-Based Therapy and Keytruda
- Bessie Dashiell's case inspired Dr. William Coley to explore cancer treatments.
- Observation: Post-infection immune responses could regress tumors.
- Modern extension: Keytruda (anti-PD-1 antibody) enhances immune response to target tumors.
- PD-1: Regulates immune self-tolerance; tumors exploit it to avoid immune attack.
- Anti-PD-1: Restores immune function, making tumors more susceptible to immune clearance.
- Overactive immune responses can result in autoimmunity (e.g., lupus).
Provenge Therapy
- Dendritic cell-based immunotherapy for prostate cancer.
- Extends survival by an average of 4.1 months.
- Procedure involves antigen loading and reinfusion of dendritic cells.
Apoptosis Basics
- Definition: Programmed cell death, a vital mechanism for eliminating damaged cells.
- Trigger events include DNA damage, loss of cell adhesion in cancer, and aberrant cell states (e.g., hypoxia, oncogene signaling).
- Key features include cell shrinkage, chromatin condensation, membrane blebbing, and formation of apoptotic bodies.
- Role of p53: Found through co-immunoprecipitation with viral proteins; frequently mutated in cancers (~50% of cases).
Other topics
- Stabilized under cellular stress (e.g., DNA damage).
- Activates cyclin inhibitor p21 for cell cycle arrest or apoptosis.
- Short-lived protein in healthy cells (degraded within 20 minutes).
- Missense mutations often disrupt DNA-binding domain.
- Elephants have 40 copies of the p53 gene, enhancing their anti-cancer mechanisms.
- Apoptosis is executed by caspases (proteolytic enzymes).
- Caspase Cascade: Pathway is tightly regulated to prevent unintended cell death.
- Apoptosis vs. Necrosis: Apoptosis is controlled, avoids inflammation; Necrosis is uncontrolled, causes inflammation and damage to surrounding tissue.
- Amplification of Mdm2, a p53 regulator, leads to its degradation in some cancers.
- Mutations enable cells to evade apoptosis, promoting cancer progression.
- Drugs targeting apoptotic resistance show promise in cancer therapy.
- Gene therapy conducted ex vivo on patient's T cells.
- Cells engineered to target CD19 antigen on B cells, both normal and cancerous.
- High remission rates observed (e.g., 27/30 patients achieved cancer disappearance).
- Ras protein: involved in signal transduction pathways regulating cell growth and survival.
- Ras protein: can become constitutively active, leading to uncontrolled cell growth in cancers.
- 1st Gen CAR T-Cells use CD3 signaling domain to activate TCR.
- 2nd Gen CAR T-Cells include a costimulatory domain for more robust proliferation.
- 3rd Gen CAR T-Cells use extra domain for improved persistence.
- Cytokine release syndrome (due to rapid T-cell activation) is a possible side effect.
Additional Topics
- Gamma Knife Radiotherapy uses cobalt-60 gamma radiation to precisely target tumors, minimizing damage to surrounding tissues.
- Ideal for treating inoperable brain cancers.
- Multi-step tumor progression pathways include activation of the cell cycle, escape from senescence, resistance to apoptosis, loss of cell adhesion, acquisition of migration, immune evasion, and angiogenesis.
- Some cancers have mutations that provide advantages in clonal populations, leading to evolutionary selection among cancer cells.
- Cancer progression involves genomic instability and a multi-step process with various steps.
- Chronic inflammation can promote interactions between stromal and pre-cancerous cells fostering cell division and increasing mutation rates
- Cancer cells evolve and compete for resources.
- Features include consistent mutation rate and similar mutational estimations.
- Markers like APC mutations are present in cancer development.
- Mechanisms to combat cancer include targeting apoptosis resistance and differentiation- based immune strategies.
- Small molecule drugs inhibit intracellular oncogenes or target internal processes.
- Monoclonal antibodies target extracellular proteins or surface markers.
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Description
Explore the advancements in cancer immunotherapy, including Keytruda and Provenge. Understand how immune responses are harnessed to fight tumors and the role of apoptosis in maintaining cellular health. This quiz dives into the mechanisms and implications of these treatments.
