Module 8: Cancer Flashcards
Define: Tumor
- abnormal growth, prolifeariton of cells (not just inflammatory swelling)
- caused by neoplasm or new growth
Define: neoplasm
new growth of cells/ tumor
Benign Tumor/Neoplasm Definition and Characteristics and how to name
- Definition:
- non-invasive, non-cancerous, but can be harmful
- Characteristics:
- encapsulated
- well-differentiated
- retain some normal tissue STRUCTURE
- non-invasive
- do not spread to lymph nodes or distant locations
- slow growing
- rarely mitotic
- can cause one instance of tissue breakdown:
- impinge upon blood supply due to growth
- Naming:
- “oma” names
Malignant Tumor/Neoplasm Definition, Characteristics, and Naming
- Definition: cancerous
- Characteristics
- rapid growth rate
- mitotis cells visible (can see cells in various stages of mitosis)
- loss of differenatiation (anaplasia)
- cells dont look like original cells
- irregular shape and size of nucleus
- loss of normal tissue structure
- capsule lost or compromised
- invasive
- spread to distant sites (metastasis)
- they lose cell-cell adhesion, will break off and spread
- Named:
- “carcinoma” or “oma”
Adenocarcinoma
- ductal or glandular derived tumor
- vs. adenoma benign
Sarcoma
- connective tissue derive tumor
- osteosarcoma vs osteoma
Lymphoma
lymphatic tissue derived
no benign versions
Leukemia
Blood cell derived
Leiomyosarcoma
smooth muscle cell derived
ex. uterine cancer
vs. Leiomyoma = uterine polyp
Define and Characterize: Transformation
- Definition: the process by which a cell becomes cancerous
- autonomy
- **loss of contact inhibition**
- anchorage independent
- immortal
- anaplastic
- pleomorphic
- undifferentiated
Transformation and Autonomy
loss of normal cell cycle control, decreased need for external growth factors.
Replicates out of control on its own
Transformation and Loss of Contact Inhibition
continued growth despite lack of space
margins are uneven
Transformation and Anchorage Independence
lack of need for attachment surface
i.e. normal epithelial cells will only grow when attached to basement membrane
Transformation and Immortality
cells will continue to divide despite number of cell cycles ( most cells die off at 10-50 cycles)
- ex. HeLa cells
- Henrietta Lacks, cervical cancer cells that kept replicating
Transformation and Anaplastic Cells
- cells become “without form”, appear abnormal
Transformation and Pleomorphism
- cells begin to have “many forms”, variable shape and size
Transformation and Undifferentiated Cells
- cells are not like mature, fully specialized as the cell type that they should be
Cancer Cell Metabolism
- prefer glycolysis even in the presence of oxygen
- called the “Warburg Effect”:
- only glycolosis occurring even in the presence of oxygen
- Results in: glucose to pyruvate to lactate
- lactic acid production
- anaerobic
- HIGH glucose use
- will often result in increased food intake with weightloss
Cancer Cell Blood Supply
- tumors >1mm require their own blood supply
- advanced cancer cells will secrete angiogenic factors to increase blood vessel growth
- normal angiogenesis in adults is very limited
- HOWEVER, these new blood vessels are formed poorly meaning that they will break more readily and cause hemorrhage.
Cancer Cell Telomeres
- Cancer cells have many more cycles of cell division than normal
- normal cells are limited by telomeres which shorten with each division
- telomeres = end of chromosomes
- normal cells are limited by telomeres which shorten with each division
- Germ cells, stem cells, and CANCER cells have telomerase– an enzyme that replaces telomeres and allows continuous cell division
Define and Characterize: Stem Cell
- undifferentiated cells which have the ability to give rise to other cells
- Characteristicis:
- differentiation
- asymmetric cell division
- embryonic stem cells are pluripotent
- adult stem cells are multipotent
Stem Cells and Asymmetric Cell Division
- mitosis creates on stem cell to self-renew, and one cell which will differentiate
Define and Characterize: Embryonic Stem Cells
undifferentiated cells in an embryo that renew and have the potential to become any cell type
- aka PLURIPOTENT
Define and Characterize: Adult Stem Cells
cells in an adult that renew and have the potential to develop into a few cell types
- MULTIPOTENT
Intestinal Stem Cells
cells lining the intestine have a short lifesspan (~1 week), and are replenished by intestinal stem cells
Hematopoeitic Stem Cells
cells in the bone marrow that form red blood cells, lymphocytes, and neutrophils
Mesenchymal Stem Cells
- cells in certain connective tissues (bone marrow, adipose, etc.) that can produce chondrocytes, osteocytes, adipocytes, but also a broad range of cells–blood vessels, neurons, muscle cells
- used to inject into horses for regeneration
- new therapy trials allow for injection into humans
Cancer Cell Clonal Selection
- As cells in the body transform from benign to malignant, they may outcompete neighboring cells
- faster
- uninhibited growth
- less dependence on adhesion and nearby signaling molecules
- use of glycolysis
- self-selection
- multiple progressive, stepwise accumulation of mutations pushes change in favor of malignancyu
Type of Tissue Biopsy
- Excisional Biopsy
- remove whole tumor
- Incisional Biopsy
- tissue from tumor, usually from the cortex, as the center is dead
- Core Needle Biopsy
- take an “earth core sample”
- Fine Needle Aspiration
- aspirate a needle in the tumor
- Exfoliative Cytology
- usually for skin; scraping
Methods of Cancer Diagnosis
- hereditary cancer syndromes
- Predictive Markers
- Circulating Tumor Fragments
- Carcinomas of Unknown Primary
- Microarray analysis
- see all of the RNA in a timor
Tumor Markers: General Types
- hormones
- enzymes
- genes
- antigens
- antibodies
- **a lot of tumors put out the same markers so do not be tricked**
Cancer Staging: TMN
- T: Tumor in local tissuse
- T0 = breast free of lesion
- T1 = lesion <2cm in size
- T2 = lesion 2-5cm
- T3 = skin and/or chest wall involved by invasion
- N: Nodes
- N0 = no axillary lymph node involvement
- N1= mobile nodes involved
- N2 = fixed nodes involved
- M: Metastases
- M0 = no metastases
- M1 = demonstrable metastases
- M2 = suspected metastases
Define: proto-oncogene
genes that normally help cells grow
Define: Oncogene
when a proto-oncogene mutates or there are too many copies of it, it becomes a “bad” gene that can become permanently turned on or activated when it is not supposed ot be
Oncogene Acquisition vs. Inheritance
- Most cancer-causing mutations involving oncogenes are acquired, not inherited:
- chromosome rearrangements:
- changes in chromosome that put on gene next to another and allows one to activate the other
- Gene Duplication
- having extra copies of a gene which can lead to it making too much of a certain protein
- chromosome rearrangements:
Oncogenes and Viruses
- Retroviruses are RNA viruses and will transform itself into a DNA that will get stitched into the DNA of the cell that it is invading
- If placed in the correct spot can tranform a proto-oncogene into an oncogene and the cell with experience neoplastic transformation
- cell becomes cancerous
Tumor Suppressor Genes Normal Function and Abnormal Function
- normal genes that slow down cell divison, repaire DNA mistakes, and tells the cell when to die (apoptosis)
- When they malfunction cells can grow out of control which can lead to cancer
- inheritied abnormalities of tumor suppressor genes have been found in some family cancer syndroms
- abnormalities of the TP53 gene which codes for the p53 protein has been found in more than half of human cancers
Overactivity Mutation and Regulating Cell Cycle Checkpoints
- affects oncogenes
- overactivity mutation = gain of function
- only need one single mutation even to create an oncogene that will override the cell cycle checkpoints
- leads to cells that proliferate abnormally
Underactivity Mutation and Regulating the Cell Cycle Checkpoints
- Affects Tumor Supressor Genes
- underactivity mutation = loss of function
- have one mutation even that inactivates one copy of the tumor suppressor gene
- but has no effect because there is still one more copy
- second mutation event inactivates the second gene copy
- functionally eliminates the tumor suppressor gene
- cells begin to proliferate abnormally because the cell cycle checkpoints have been inactivated
- functionally eliminates the tumor suppressor gene
Epigenetic Changes and Cancer
- Epigenetic Changes: chemical modification of DNA that can silence or alter the expression of genes
- methylation, acetylation of histones, chromatin, or DNA
- ex. methylation of the promotor region of tumor suppressor gene leads to silenced tumor suppressor
- enzyme can no longer access DNA because it is blocked by the methyl group
- ex. histones helps fold the DNA tighter = enzymes can’t enter and replicate the DNA
- once it is acetylated, the DNA is not folded as tightly and replication of certain genes will occur more readily
- ex. methylation of the promotor region of tumor suppressor gene leads to silenced tumor suppressor
- methylation, acetylation of histones, chromatin, or DNA
- FASTER than full mutation of DNA
- DNA mutation has to escape proofreading
- CAN be inherited if occur in testes or ovum
Cancer and Inflammation
- Inflammation is linked to cancer in many ways
-
Chronic Inflammation predisposes certain organs and cell types to cancer
- recruit similar inflammatory cell types
- promotes continued proliferation
- Tumor signaling mimics and enhances inflammatory pathways
- **mostly caused by chronic inflammation**
Define: Etiology
the cause of a disease (not always known)
Define: Epidemiology
- study of incidence, prevalence and control of disease
Define: Incidence
Number of new cases of a disease in a given period divided by the total population
Define: Prevalence
proportion of individuals affected by or living with a disease at a point of time
- does not include people who have fully recovered/cleared the disease or died from the disease
Twins vs. Adopted Siblings and Genetic vs. Non-Genetic Factors
- twins: will have a similar risk if it is purely genetic
- adopted siblings, unrelated: will have similar risk if its purely environmental
Genetic and Non-Genetic Factors Contribute to Disease
- polygenic: many genes cause a specific trait
-
multifactorial: multiple environmental factors influence a trait
- in this case, recurrence risk calculations are more complex or unknown
-
empirical risk: observe and record disease rates in families to determine risk
- twins will have similar risk if it is purely genetic
- adopted siblings (unrelated) will have similar risk if it is purely environmental
Lifestyle-Associated Factors Affecting Health and Cancer
- tobacco
- alcohol
- lack of fruit and veg
- meat consumption
- lack of fiber
- overweight, obesity BMI>30.0
- lack of physical exercise
- infection
- occupation hazard
- sun exposure
- ionizing radiation
- post-menopause
Define: Genogram
a graphic representation of a family tree that displays detailed data on relationships among family members
Genogram Symbol for Male
Square
Genogram Symbol for Female
Circle
Genogram Symbol for Unknown Gender
?
Genogram Symbol for Pet
diamond with red dotted line attachment
Genogram Symbol for Adopted Child
Red dotted line attaching the gender of the child
Genogram Symbol for Foster Child
Green dotted line attaching a child
Genogram Symbol for Pregnancy, Miscarriage, and Abortion
Triangle
Genogram Symbol for Death
X
Genogram Symbol for Twins and Identical Twins
see pic
