Inflammation, Cell Cycle, and Neoplasia Review

Inflammation, Acute Phase Response, and Systemic Effects

• Inflammation can be monitored by checking blood proteins; during inflammatory processes, certain protein levels in the blood change.
• Anorexia nervosa (anorexia = lack of appetite) is described as a condition where patients are not hungry and do not want to eat.
• Other non-specific inflammatory presentations include:
  • Somnolence: extreme tiredness
  • Malaise: just not feeling right, no specific head or stomach pain, general unwellness
• These signs illustrate how the body can present in inflammation, ranging from mild symptoms to severe systemic involvement.
• Severe inflammation can progress to sepsis (blood poisoning):
  • Bacteria or systemic infection leading to widespread inflammation and organ dysfunction
  • May cause organ failure when multiple organs are affected
• Systemic vascular response: vasodilation can occur widely, causing a drop in blood pressure and systemic hypotension, contributing to organ dysfunction
• Acute phase response: a body-wide, rapid involvement of various tissues and proteins in response to inflammation
• White blood cell (WBC) response: WBC count may rise as part of cellular inflammatory response, but sometimes cells are not fully functional right away
• Lymphadenitis: inflamed lymph nodes, often checked in inflammatory conditions (e.g., swollen nodes in the neck)
• Inflammation can be linked to the cell cycle and tissue responses, including how cells may enter/exit the cycle to deal with injury or infection

The Cell Cycle, Cell States, and Basic Concepts

• Cell cycle overview (mitotic cycle): cells progress through distinct phases to divide and propagate
  • G0: a quiescent or resting state where cells are not actively preparing to divide; most cells reside in G0, performing their normal functions until a signal prompts division
  • G1: growth phase where cells prepare for DNA replication
  • S: DNA synthesis phase where the genome is replicated
  • G2: second growth phase preparing for mitosis
  • M: mitosis, followed by cytokinesis, producing two identical daughter cells
• Cells in G0 stay there until receiving signals to re-enter the cell cycle (G1, S, G2, M)
• Cell cycle progression involves extensive cellular preparation, including doubling organelles and proteins to ensure two viable daughter cells after division
• Concept of proliferation vs differentiation vs growth:
  • Proliferation: increase in cell number, usually by mitosis (one cell becomes two, then four, then eight, etc.)
  • Differentiation: educational/operational process by which cells acquire specialized characteristics and functions; a single stem cell can differentiate into multiple cell lineages
  • Growth: enlargement of a cell (less common than proliferation for most body cells); not typically how most tissues expand
• Balance in tissues:
  • Normal physiology involves a balance between proliferation and programmed cell death (apoptosis) to maintain tissue homeostasis
  • When proliferation outpaces controlled growth or differentiation, abnormal growth can occur
• Apoptosis: programmed cell death; a built-in self-destruct mechanism to remove aged or damaged cells
• Stem cells and differentiation pathways:
  • A stem cell can begin as an immature cell and differentiate along multiple pathways into specialized cell types
  • Differentiation can produce various cell types from a common progenitor, depending on cues and signals
• Cell turnover patterns by category of cells:
  • Labile cells: constantly divide (never leave mitosis); examples include cells in skin, GI tract, urinary tract, vagina, bone marrow
  • Stable (quiescent) cells: reside in G0 most of the time; can re-enter the cell cycle when needed to replace damaged cells
  • Permanent (amycratic) cells: do not divide; designed to remain in a non-dividing state for life
• Terminology to classify neoplastic processes by replication behavior:
  • Proliferation leads to increased cell numbers via mitosis
  • Differentiation is the process by which cells become specialized
  • Growth can be an increase in cell size, but most tissues primarily expand through proliferation

Neoplasia: From Normal Growth to Tumors

• Neoplasia: abnormal growth characterized by new, uncontrolled proliferation; the root terms:
  • Prefix neo- means "new"
  • Plasia means growth; hence neoplasia = new growth, i.e., abnormal growth that deviates from normal cell cycling
• Tumor vs cancer: all cancers are tumors, but not all tumors are cancerous
  • Tumor: abnormal growth; can be benign or malignant
  • Cancer: malignant neoplasm; typically refers to a cancer that can invade and metastasize
• Benign vs malignant distinctions:
  • Benign tumors: well differentiated (cells resemble normal tissue); usually grow slowly and remain localized; may compress surrounding tissue but do not invade or metastasize
  • Malignant tumors: anaplastic (poorly differentiated); faster growth with loss of normal tissue architecture; invade surrounding tissues and can metastasize; more likely to be life-threatening
• Tumor margins and encapsulation:
  • Benign tumors often develop a capsule (a surrounding connective tissue layer) that helps delineate the tumor and makes surgical removal easier
  • Malignant tumors typically lack a clear capsule; edges are infiltrative and edges are difficult to define
• Growth behavior and tissue invasion:
  • Benign tumors generally do not invade surrounding tissue and rarely metastasize
  • Malignant tumors invade, destroy surrounding tissue, and can enter blood or lymphatic systems to spread
• Tumor spread (metastasis) mechanisms:
  • Direct invasion/extension: cancer cells infiltrate adjacent tissues via creeping growth and penetration
  • Seeding (intra-organ spread): cancer cells disseminate within body cavities or fluids, forming multiple nodules or implants on surfaces or organs
  • Metastasis: cancer cells detach, intravasate into blood or lymphatics, survive circulation, extravasate at distant sites, and establish new tumors
• Carcinogenesis: development of cancer via a multi-stage process
  • Three phases: initiation, promotion, progression
  • Initiation: damage to a cell causing a mutation that may predispose to cancer
  • Can be caused by one large exposure or multiple smaller exposures (e.g., UV exposure for skin cancer)
  • Promotion: mutated cells are stimulated to divide; growth factors or hormones can act as promoters; removal of promoters can halt progression
  • Progression: continued mutations and clonal evolution leading to increasingly abnormal and malignant cells
• Complete carcinogens: substances that both mutate DNA (initiation) and promote tumor growth in one exposure; often associated with a worse prognosis due to rapid progression or high mutational burden
• Tumor naming conventions (educational focus):
  • Add -oma to tissue name for benign tumors (e.g., lipoma from adipose tissue)
  • Carcinoma: malignant tumor arising from epithelial tissue
  • Sarcoma: malignant tumor arising from connective tissue (soft tissue or bone)
  • Osteoma: benign bone tumor
  • Osteosarcoma: malignant bone tumor (bone sarcoma)
  • Papilloma: benign epithelial tumor with a papillary or finger-like appearance
• How to interpret tumor names in practice:
  • If you see a tumor name ending in -oma, expect a typically benign tumor unless context indicates otherwise
  • If the name includes carcinoma, expect a malignant epithelial-derived tumor; sarcoma indicates a malignant mesenchymal (connective tissue) tumor
• Key table-based comparisons (as referenced in course materials):
  • Benign vs malignant across characteristics such as differentiation, growth rate, invasion, metastasis, and mortality
  • A specific table (e.g., Table 6.2) provides a side-by-side comparison of nine malignant tumor categories; use these classifications to guide analysis and exam questions
• Representative benign examples:
  • Lipoma: benign adipose tissue tumor; common in older animals; slow-growing; typically not dangerous
• Representative malignant examples:
  • Squamous cell carcinoma: malignant epithelial tumor; can spread via lymphatics or blood; invasive and destructive
  • Other carcinomas and sarcomas depend on tissue of origin; malignant tumors are not well-differentiated and often show rapid, disorganized growth
• Clinical features and prognosis considerations:
  • Benign tumors have lower mortality risk when localized, but can cause issues by compressing nearby structures (e.g., compressing a blood vessel or brain tissue)
  • Malignant tumors have higher mortality risk due to invasion and metastasis; prognosis depends on differentiation, rate of growth, invasion, and metastatic potential
• Terminology recap: important rules of thumb for exams
  • Carcinoma = malignant epithelial tumor
  • Sarcoma = malignant connective tissue tumor
  • - oma = benign tumor name ending; not a universal rule, but a common convention in many organ systems
  • Benign tumors are well differentiated and encapsulated; malignant tumors are poorly differentiated, invasive, and may metastasize

Clinical and Real-World Relevance, Implications, and Wrap-Up

• Sentinel and diagnostic considerations:
  • Lymph node assessment (e.g., checking for metastasis) is common in cancer workups; nodes may be referred to as “sentinel nodes” in clinical practice
  • Tumors lacking clear margins or showing invasion require careful surgical planning and may necessitate adjunctive therapies
• Patient prognosis and treatment considerations:
  • Benign tumors generally have favorable outcomes if completely resected; malignant tumors require comprehensive management due to invasion and metastasis
  • Prognosis is influenced by tumor differentiation, growth rate, invasion, metastasis, and overall patient health
• Ethical and practical implications:
  • Early detection and accurate classification of tumors are critical to prevent unnecessary aggressive treatments or under-treatment
  • Balancing risks and benefits of surgery, radiation, chemotherapy, and targeted therapies requires patient-centered decision making
  • Overdiagnosis and overtreatment considerations can arise when tumors are detected incidentally; clinicians must weigh quality of life against potential benefits
• Connections to foundational principles:
  • Inflammation and immune response intersect with cancer biology (e.g., chronic inflammation as a cancer risk factor, immune surveillance against tumors)
  • The concept of cell cycle control, differentiation, and apoptosis underpins normal tissue homeostasis and disruption in neoplasia
  • The multi-step model of carcinogenesis (initiation, promotion, progression) aligns with accumulation of mutations and clonal evolution observed in many cancers
• Quick recap of essential terms to memorize:
  • Inflammation signs: anorexia, somnolence, malaise, sepsis, vasodilation, organ failure
  • Acute phase response; WBC response; lymphadenitis
  • Cell cycle: G0, G1, S, G_2, M
  • Proliferation, differentiation, growth, apoptosis
  • Labile, stable, permanent (amycrytic) cells
  • Neoplasia; neo- + plasia; benign vs malignant
  • Tumor naming: -oma (benign), carcinoma (malignant epithelial), sarcoma (malignant connective tissue), osteoma, osteosarcoma, lipoma, papilloma
  • Metastasis: direct invasion, seeding, and metastatic spread via blood/lymph
  • Carcinogenesis: initiation, promotion, progression; complete carcinogens

Key Equations and Notational References

• Cell proliferation progression (doubling):
  • One cell becomes two, then four, then eight:
  • N = 2^n where $n$ is the number of completed cell divisions
• Cell cycle states (conceptual):
  • G0 ightarrow G1
    ightarrow S
    ightarrow G_2
    ightarrow M
    ightarrow ext{cytokinesis}
    ightarrow ext{new daughter cells}
• Other core terms (LaTeX-ready):
  • ext{apoptosis} for programmed cell death
  • ext{neoplasia} = ext{new growth (abnormal)}
  • ext{carcinogenesis} = ext{initiation}
    ightarrow ext{promotion}
    ightarrow ext{progression}

End of notes.