Cancer Flashcards
Neoplasia
New growth - may be benign or malignant
Regulated growth & cellular differention
What distinguishes benign from malignant
Benign Tumor
Well differentiated, localized, and demarcated
Malignant Tumor
Less well differentiated, grow rapidly, invade neighboring tissues, spread to other body sites
Proliferation
the ability of a cell to divide and requires growth signal (eg growth factors)
Immortalized
Cancer cells ignore normal growth restraints and have a high proliferative capacity
Differentiation
The degree of specialization of a given cell. Become more specialized as they mature.
Terminally differentiated
Cells that no longer divide
Cancer cells
Less well differentiated or less mature than normal cells
Carcinoembryonic Antigen (CEA)
molecules normally only expressed in immature or less differentiated cells - normally produced before birth only
Inverse relationship
Between differentiation and the ability of a cell to proliferate
Cell Cycle
cell growth and division; many cancer cells show changes in the cell cycle and are autonomous (independent of normal growth controls)
3 causes of growth & maturity abnormalities
1) the ability to produce telomerase
2) Changes in pRB that governs the cell cycle rate
3) Changes in p53 that slows the cell cycle to allow for repair of DNA mutations before cell division
Events of the cell cycle
Mitosis, followed by cytokinesis, and interphase
Telomeres
Repeated sequences not used to make cell proteins
Immortalized
Cancer cells can replace telomeres by activating telomerase, thus can divide indefinitely
pRB
- Acts as a break to the cell as this protein governs cell cycle commitment
- Activity is governed by phosphorylation and disruption leads to increased cell proliferation, seen in cancer
p53
A cell protein that has a number of anti-cancer functions centered around DNA repair including:
- activation of DNA repair proteins
- Arrest of the cell cycle to allow DNA repair proteins to fix mutations
- Initiation of apoptosis if DNA damage cannot be reversed
Most cancers
Acquired, not inherited
Conversion of a normal cell into a cancer cell
Requires multiple mutations. Mutations may be point mutations or chromosomal rearrangements
Conversion of a normal cell into a cancer cell
Requires multiple mutations. Mutations may be point mutations or chromosomal rearrangements
Tumor Suppression genes
Normally restrain cell growth = “loss of function” eg, pRB, p53, APC, DCC
Mutate BOTH copies
Oncogenes
Normally promote growth as protooncogenes within cells. eg growth factors, receptors
Mutate ONE copy
Virus
DNA repair genes
Normally correct damage or mutations in the cellular DNA. Failure to fix these mutations increases the likelihood that cancer will arise
Carcinogenesis
The process of tumor formation and a series of mutations is required for cancer
Clonal Tumor Cells
Derived from a single progenitor cell and tumor cell markers identify cancer and reflect this clonality
Retionoblastoma
A rare childhood cancer of the eye that involves mutation in both alleles of the tumor suppressor gene (pRB)
Loss of pRB function
Unregulated growth or cancer
Hereditary Nonpolyposis Colon Cancer (HNPCC)
Colon cancer due to mutations in DNA repair genes
-The decrease in DNA repair leads to an increase in genome instability called mutator phenotype - increases the likelihood that an individual will develop cancer
Familial Adenomatous Polyposis (FAP)
Type of colon cancer
-Changes in both oncogenes and tumor suppressor genes are typically required to develop
Transformation
Multiple mutations are required for cancer to occur and often result in changes to growth and adherence that contribute to invasion, angiogenesis, and metastasis
Altered biochemical properties
Promote growth - secretes growth factors/hormones and promote spread
-Secretes protease
Chromosomal Changes
- Aneuploid - loss of diploid state
- Translocations and other rearrangements
- Metastasis
Aberrant Adherence Properties
-Loss of contact inhibition
-Anchorage independence
Cancer cells invade and spread
Initiation-Promotion theory
- Initiation (DNA mutation, irreversible) must occur first
- Promotion (stimulate cell proliferation, reversible in early stages) must follow initiation for tumors to form
- Progression obtains malignant phenotype including invasiveness, metastasis, autonomous growth and genomic instability
To be Malignant
- Invasion of neighboring tissues
- Angiogenesis - formation of new blood vessels
- Metastasis - spread to new sites
Clinical Manifestations of cancer
Distinct diseases with similar underlying cellular changes and common manifestations:
- Pain
- Cachexia - severe form of malnutrition, associated with anorexia, tumor necrosis factor (TNF)
- Declining hematopoiesis - Anemia often observed, tumors in bone or bone marrow suppression can contribute
Cancer screening & diagnosis
Cancer cells express TUMOR MARKERS and include:
-Prostate-specific antigen (PSA)
-CA-125
-Carcinoembroyonic antigen (CEA)
Markers are not diagnostic but changes in levels are often consistent with changes in tumor growth or responsiveness to treatment
Approaches to cancer treatment
- Surgery
- Chemo
- Radiation
TNM
Staging
Tumor - how many
Nodes - nodes involved
Metastasis - has it spread
Papanicolaou Test (PAP)
A cytologic method used to detect cancer cells
Cell differentiation
Process whereby proliferating cells are transformed into different and more specialized cell types
DNA synthesis
Takes place in the S phase of the cell cycle
Invasion
The direct extension and penetration by cancer cells to neighboring tissues
Hematogenic spread
Metastasis that occurs by way of the blood vessels
