Neoplasia: Cancer & Tumor Growth – Flashcards

highly regulated Cell growth regulated by cytokines (growth factors) Suppressor genes stop cell division and may promote apoptosis of damaged cells Number of cell divisions limited by the length of telomeres (the ends of an arm of a chromosome)

Neoplastic or tumor growth loses some or all of these regulations by genetic mutation Theory: six or more mutations must occur to achieve malignancy

Neoplasia = "New Growth" Each neoplastic growth begins as a genetically altered stem cell. The gene alterations (mutations) are responsible for the disordered, proliferative activity that produces too many cells. Abnormal population of mutated cells often have some similarities to original cell line, but can become unrecognizable.

In response to irritation/inflammation cells regenerate and form "hyperplastic" growths process is regulated Neoplastic cells also divide actively. cells are enlarged mutational changes lead to unregulated process Can be clinically and histologically difficult to differentiate between the two.

: gene products that promote normal growth Have the potential to become an oncogene either via mutation or increased expression

mutated form of a proto-oncogene, usually resulting in an accelerated activity of the affected proto-oncogene Mutations can occur in: Amount of growth factor Binding of factor to receptor Receptor signaling Growth response to transcription signal

genes that inhibit cell growth Slow the cell cycle Inhibit proliferation from growth signals Stop cell division when cells are damaged (to allow time for DNA repair or for apoptosis signaling) Inheriting one defective suppressor gene greatly increases the chance of cancer

Loss of growth inhibition is a positive feedback cycle: Mutations occur during cell division The more a cell divides, the more likely mutations and chromosomal instabilities occur The more mutations occur, the more likely cells will be able to overcome obstacles to growth (tumor suppressor genes) Multiple mutations are necessary to cause a malignant neoplasm

Most genetic alterations occur within an individual's lifetime (i.e., occur in somatic cells and are not passed on) Inherited gene mutations NOT common but possible Cancer-predisposing mutations can occur in germline cells

Physical, chemical and microbiological agents Some are considered mutagens (agents that can cause mutations)

Telomeres shorten with each cell division (eventually signal cell death when short enough) Some tumor cells are able to maintain their telomeres via reactivation of telomerase, allowing them to replicate over and over again May occur in only a few percent of tumor cells (i.e., not all tumor cells are immortal)

Growths that do not invade adjacent tissues nor spread (metastasize) to distant sites Considered benign unless they are growing in a restricted space or secrete hormones that interfere with regulation Cells are differentiated, slow growing, often encapsulated

Metastasize (spread) to distant sites and invade adjacent tissue Tend to be less differentiated, faster growing, have necrotic centers Frequently recur after treatment

Tumor cell division takes the same time as a normal cell to divide Percentage of cells engaged in cell division Most chemo therapy attacks only one particular phase of cell division

Tumor size results from a balance between cell growth and cell death A 'typical' tumor could double in 6 days but actual doubling takes about 80 days. Difference represents cell loss. Most of the tumor's existence is spent in an undetectable state Tumors of 1 cm size (detectable) have undergone 30 doublings (~6.5 years) Much of prognosis depends on early detection

Initiation Promotion Progression

the occurrence of a mutation or DNA damage to permit growth

growth in response to a stimulus another mutation, nutritional factors, hormones, infections, ???

entry of the cell into the positive feedback cycle As neoplastic progression accelerates, cells develop an ability for angiogenesis (new blood vessel growth), invasion, and metastasis Permanent or irreversible

Metastasis: spread of cancer cells from site of origin to distant tissues and organs Defining characteristic of cancer Major cause of death from cancer Contributes to pain and suffering from cancer Local spread is the first step in metastatic process Generally spread by blood or lymph (specific cancers seem to preferentially spread by one or the other) Attacked by immune system - less than 1/10,000 cells survive to metastasize Cancers have characteristic metastatic sites (e.g., breast to bone, colon to liver)

Biologic markers produced by cancer cells Found in blood, spinal fluid, urine, or tumor plasma membranes Hormones, enzymes, genes, antigens, antibodies Allows to screen individuals at high risk for cancer Can reflect the overall tumor cell mass Enables cancer therapy assessment If a person has a tumor removed, tumor markers can be followed to detect a recurrence. NOT foolproof: some non-malignant diseases also produce tumor markers.

Suffix "-oma" means swelling or tumor Prefix is the cell of origin Benign: "-oma" suffix Adenoma (gland or duct epithelium), lipoma (fat), neuroma (nerve), myoma (muscle) Malignant: "carcinoma" or "sarcoma" suffix Carcinoma = from epithelial tissues Sarcoma = from connective tissues Adenocarcinoma, liposarcoma, neuroblastoma, myosarcoma Some exceptions: lymphoma, melanoma, hepatoma, leukemia

histologic characterization by cell differentiation, uniformity, etc.

a numerical estimate of prognosis usually I - IV with higher numbers worse prognosis Most common method of staging TNM (Tumor size, lymph Node involvement and Metastasis) Reveals whether benign or malignant If malignant it reveals differentiation and whether it has spread beyond the site of origin Cancer confined to organ of origin Cancer that is locally invasive Cancer spread to regional structures Cancer spread to distant sites