Apoptosis and Necrosis (LEC)

Neoplasm

New growth, abnormal mass of cells.

Benign

Grow slowly and remain localized to site of origin.

Malignant

Grow rapidly and may spread (metastasis); abnormal growth of tissue with unregulated growth.

Metastasis

Locally invasive; tumor invades surrounding tissues by sending out 'fingers' of cancerous cells, leading to distant spread via vasculature, lymphatic system, and trans-coelomic spaces.

Carcinoma

Malignant tumor growing from epithelial tissue. Many carcinomas affect glands that are involved with secretion.

Sarcoma

Malignant tumor growing from connective tissues – cartilage, fat, muscle, tendons, and bones.

Leukemia

Cancer of the blood or bone marrow.

Melanoma

Malignant tumor of melanocytes.

Hallmarks of Cancer

Characteristics that distinguish cancer cells and enable them to grow uncontrollably.

Ignores Anti-Growth Signals

Cancer cells can bypass normal signaling mechanisms that inhibit cell division.

Self-Sufficient Growth Signals

Cancer cells can produce their own growth signals to promote proliferation.

Avoids Apoptosis

Cancer cells evade programmed cell death, allowing them to survive longer than normal cells.

Sustained Angiogenesis

Cancer cells can stimulate the formation of new blood vessels to supply oxygen and nutrients.

Tissue Invasion and Metastasis

Cancer cells can invade surrounding tissues and spread to distant sites in the body.

Genomic Instability and Mutations

Cancer cells often exhibit high levels of genetic changes, leading to increased mutation rates.

Avoiding Immune Destruction

Cancer cells can evade detection and destruction by the immune system.

Deregulating Energy Metabolism

Cancer cells often alter their metabolism to support rapid growth and proliferation.

Tumor Promoting Inflammation

Chronic inflammation can enhance tumor growth and progression.

Limitless Ability to Reproduce

Cancer cells can replicate indefinitely, unlike normal somatic cells.

Clonal Evolution

Tumor growth develops through repeated rounds of mutation and proliferation, where cells acquire a selective growth advantage over neighboring cells.

Stem Cells

Tumors can contain cancer stem cells that possess indefinite proliferative potential, initially linked to leukemias.

Tumor Progression

Most human cancer cells are genetically unstable, characterized by defective repair of DNA damage or replication errors and loss of chromosome integrity (abnormal karyotype).

Primary Tumor

Location in which the cancer first arose.

Secondary Tumor (Metastases)

Location to which the cancer metastasized.

Modes of Spread of Malignant Neoplasms

The primary methods through which malignant tumors spread to other parts of the body.

Vascular Spread

Spread of malignant neoplasms through the bloodstream, primarily via veins.

Lymphatic Spread

Spread of malignant neoplasms through lymphatic vessels.

Trans-Coelomic Spread

Spread of malignant neoplasms across coelomic spaces, such as the peritoneal and pleural cavities.

Karyotyping

A laboratory technique used to visualize the entire genome by arranging chromosomes in a standard format, allowing the identification of chromosomal abnormalities such as extra chromosomes and structural changes.

Cytogenetic Studies

Analyses that include karyotyping to study the structure and number of chromosomes in cells, significant for diagnosing genetic disorders, prenatal screening, and cancer diagnostics.

Fluorescent In Situ Hybridization (FISH)

A technique where chromosomes are stained with fluorescent dyes to visualize specific DNA sequences and identify chromosomal abnormalities, such as translocation events.

Necrosis

A form of pathological cell death resulting from acute injury where the cell is unable to maintain homeostasis. Characterized by cellular swelling, loss of plasma membrane integrity, release of cell contents, surrounding tissue damage, and associated inflammation.

Apoptosis

A physiological process of programmed cell death that is genetically controlled. Features include cell shrinking, DNA aggregation, preservation of plasma membrane integrity, absence of damage to surrounding tissues, and no inflammatory response.

Intrinsic Apoptosis Pathway

The intrinsic apoptosis pathway is triggered by DNA damage, which brings a death signal leading to the upregulation of pro-apoptotic proteins. This results in the release of cytochrome c from the mitochondria, forming an apoptosome comprised of Apaf-1, cytochrome c, and procaspase 9. The formation of the apoptosome activates the caspase cascade, initiating caspase 9, which subsequently activates effector caspases such as caspase 3.

Extrinsic Apoptosis Pathway

The extrinsic apoptosis pathway is initiated by the binding of Fas ligand to its death receptor, leading to the recruitment of death domain adaptor proteins such as FADD and TRADD. This interaction promotes the formation of the death-inducing signaling complex (DISC), which activates the caspase cascade involving initiator caspases like caspase 8, eventually activating effector/executioner caspases such as caspase 3.

Caspases

Caspases are a family of protease enzymes, specifically cysteine-dependent aspartate-directed proteases. They are produced as inactive precursors known as procaspases and are activated through proteolytic cleavage. Once activated, they target various cytoplasmic and nuclear proteins as well as active DNAse within the cell.

Physiological Processes Involving Apoptosis

Examples include de-webbing of fingers and toes during fetal development, where excess tissue is removed through programmed cell death.

Methods to Assess Apoptosis

Caspase activity can be measured to assess apoptosis as it involves the cleavage of specific substrates by caspases. Additionally, annexin V can be utilized as it binds to phosphatidylserine when it is exposed on the outer leaflet of the plasma membrane, indicating a hallmark of early apoptosis. DNA laddering is another method, where DNAse causes cleavage of internucleosomal DNA into fragments of approximately 180-200 base pairs. Finally, the TUNEL assay (terminal uridine deoxynucleotidyl transferase nick end labeling) is a technique that detects DNA fragmentation, a characteristic feature of apoptosis.