Unit 1 Exam Ch 1 2 3 Flashcards
Cancer
Group of diseases, characterized by unregulated growth
Germ Layer
a group of cells in an embryo that interact with each
other as the embryo develops and contribute to the formation of all organs and tissues
Ten Hallmarks of most cancers
Sustained Proliferation Evading growth suppressors Avoiding immune destruction Activating invasion and metastasis Inducing angiogenesis Genome instability and mutation Resisting Cell death Deregulating cellular epigenetics
Evading Growth Suppressors
Cancer cells do not respond to growth inhibitory signals and acquire mutations that interfere with inhibition
Avoiding immune suppression
Successful cancer cells may be those that do not
stimulate an immune response or can interfere with the
immune response so as to avoid immune destruction
Unlimited replicative potential
Normal cells replicate for a certain number of generations and become senescent, after shortening of telomeres (Cancer cells’ telomeres aren’t shortening) and have unlimited replicative potential
Tumor-Promoting inflammation
• Inflammation is an immune response that can
facilitate the ability of acquiring the core
hallmarks of cancer.
• In addition, inflammatory cells can release
oxygen species that are mutagenic
Invasion and Metastasis
Cancer cells invade other tissues and migrate to other parts of the body, causing multi-system cancers
Invasion and Metastasis
Cancer cells invade other tissues and migrate to other parts of the body, causing multi-system cancers
Cancer cells induce angiogenesis, growth of new blood vessels, needed for tumor survival. Altering the balance between angiogenic
inducers and inhibitors can activate the
angiogenic switch
Sustained Angiogenesis
Evading Apoptosis
Normal cells are able to be destroyed via apoptosis
Cancer cells evade those mechanisms to continue unregulated growth.
Genome instability and mutation
Faulty DNA pathways contribute to genome instability
Reprogramming energy metabolism
Uncontrolled cell division demands increases in
fuel and biosynthetic precursors that is obtained
by adjusting energy metabolism
Grows in clusters of cells called foci Do not exhibit contact inhibition Can grow in low serum media Round morphology Exhibit "anchorange independence"
Morphology and characteristics of cancer cells
Anchorage independence
Cancer cells Lose contact with the media and won’t die
Benign Tumor
No evidence of cancer Does not metastasize Some can be life-threatening well-defined borders well differentiated Lost regulation of the cell cycle
Malignant
Not encapsulated Invades and metastasized Large, rapid growth Poorly differentiated increased nuclear to cytoplasm ratios Nuclear hyperchromasia and prominent nuclei (stains brightly)
Neoplasia
New growth, not reversible
Dysplasia
Disordered growth, often resulting in neoplasia
Tumor
Abnormal growth, benign or malignant
Cancer
Malignant neoplasm or tumor that invades nearby tissue
benign epithelial tissue
adenoma, papilloma
beningn mesenchyme tissue
Fibroma, Lipoma
Benign Melanocytes
Nevus (Mole)
Benign Lymphocytes
Benign lymphoid hyperplasia
Malignant epithelial tissue
Adenocarcinoma
Papillary carcinoma
Malignant mesenchyme tissue
Sarcoma
Malignant Melanocytes
Melanoma
Malignant Lymphocytes
Lymphoma
Breast Cancer Main site of metastasis
Lungs, liver, bones
Colon Cancer Main site of metastasis
Liver, peritoneum, lungs
Lung Cancer main site of metastasis
Adrenal gland, liver, lungs
Melanoma main site of metastasis
Lungs, Skin, muscle, liver
Why are the liver and lungs common sites for metastasis?
Blood flows through both organs frequently (Portal vein, lungs)
Why are malignant tumors so life-threatening?
Physical obstruction
Invading other organs and compromising their functions
Competing for nutrients, oxygen, and produce waste product
Mutation
Alteration of DNA sequence
Carcinogen
Agent that causes cancer
Mutagen
Agent that causes mutation
*Not all mutations cause cancer
Translolcation
DNA mutations whereby a part of one chromosome is transferred to or exahnged for anohter part of a different chromosome
Proliferation
Cell division, cell growth
Apoptosis
Programmed cell death
Differentiation
cells enter an inactive phase of cell growth and can lead to unregulated cell growth
Leukemia
Overproduction of white blood cells or their precursors in the blood or bone marrow
Proto-Oncogenes
NOrmal genes that can be activated by mutation to be oncogenic
All normall cells have proto-oncogenes
Oncogenes
Mutated genes that produce an increased amount of protein products
Characteristics of Oncogenes
Cause increased activity and uncontrolled cell division
Always in “on” state
Platelet dereived growth factor (PDGFR)
Glioblastoma, myeloid leukemia
Acts in a dominant manner to initiate tumor formation (one allele is sufficient for the effect)
Tumor Suppressor Genes
Code for proteins that have a role in inhibiting borth growth and tumor formation
Tumor Suppressor Genes mode of function
Mutation results in a loss of function of genes that control growth
Tumor suppressor genes mode of inheritance (Dominance vs Recessive)
Recessive in nature (both must mutate to lose function)
Knudson’s Two-Hit Hypothesis
Explains the methods of tumor suppressor genes
States that both alleles must be mutated to trugger carcinogenesis.
Explains certain individuals have an increased risk for cancer
The have inherited a mutated tumor suppressor allele
Haploinsufficiency
only one mutated allele can lead to the cancerous phenotype. One allele (normal) produces half the quantity of protein product produced by normal cells, and this is not enough to suppress tumor formation in these cases
Stem Cells
Undifferentiated cells that still have the ability to self-renew and produce differentiated progeny
Self-Renewal
A stem celll or other progenitor cell gives rise to a new daughter cell with equivalent developmental potential.
Environmental factors contributing to human carcinogenesis
UV radiation, toxins, form pyrimidine dimers and cause mutations
Reproductive life influential factors contributing to human carcinogenesis
Age of menstruation, and age of reproduction in women, contraception and fertility treatments alter ovulation, HPV, HIV, Kaposi’s Sarcoma, HSV 8
Diet and Exercise influential factors contirbuting to human carcinogenesis
Breast cancer can be reduced by 25%, certain diets from certain regions increase certain cancers
Alcohol influential factors contributing to human carcinogenesis
Max intake 28g, accounts for 389,000 cases in the U.S per year (Mouth, Esophageal, breast, and Liver cancer)
Smoking influential factors contributing to human carcinogenesis
Causes lung, pancreatic, bladder, kindey, mouth, stomach, and liver cancer. Accounts for 40% of all cancer deaths
Lung cancer is the main cancer worldwide
Number of carcinogens found in cigarette smoke
81
Additional Influences contributing to human carcinogenesis
LIfespan o the cell, free radicals, disorders related to metabolism
Red meat contributes to cancer development
Increases lumenal carcinogens through home, micronbial metabolism of protein rescues and barbequeing heterocyclic amines
How does fat contribute to cancer development?
Induces hepatic synthesis of bile acids; clonoc microbes covert Ba to 2YBA= Carcinogenic
Fruit and Vegetables’ affect on cancer development
Suppresses colon cancer due to antioxidant and antineoplastic properties (Vitamin C, folate), selenium, calcium, and bioactive phytochemical compounds
Rate of Colon cancer for African People
Less than 5 per 100,000
Marijuana’s affects on cancer cells
THC and other cannabinoids slow grouth and reduce spread of some forms of cancer
Types of Cancer Therapies
Cytostatic and cytotoxic
Cytostatic Cancer therapy
Halts proliferation
Cytotoxic Cancer Therapy
Kills the cancer cells
How to determine what the best drug or treatment is for cancer
THe best drug is the one that can be used in the lowert dose with minimal side effects
Therapeutic index
Value between the minimum effective dose and maximum tolerated dose
The larger the value, the better the drug
Many Drugs are given at the MTD (Maximum tolerated dose)
easiest method of cancer treatment
Surgery
Works for some cancers, not others
Does not address metastasis
Chemotherapy Methods of treatment
Target DNA, RNA, and Protein to disrupt the cell cycle
Main aim of chemotherapy treatments
Cause DNA Damage and trigger apoptosis
Side effects of Chemotherapy
Alopecia, ulcers, anemia
Interventional Studies (Clinical Trial)
Research subjects are assigned to a treatment or intervention and their outcomes are measured (Phase 1-4)
Phase I clinical trial
Researchers test an experimental drug or treatment in a small group of people (20-80) for the first time. Evaluates safety, dosage, and range. Identifies side effects
Phase II Clinical trial
Larger group (100-300), determines if it’s effective and further evaluates safety
Phase III Clinical Trial
1,000 to 3,000 participants to confirm effectivness, monitor side effects, compare to commonly used treatments, and collect information for safety
Phase IV clinical Trial
Post-marketing studies delineate additional ifo including drug’s risk, benefits, and optimal use
Gene
a specific stretch of DNA that programs the amino acid sequence of a polypeptide
4 parts of a gene
Promoter
Terminator
Start codon
Stop Codon
Operon
Cluster of genes under the control of the same promoter
True or false: Operons only occur in Eukaryotic organisms
FALSE:
Operons only occur in prokaryotes
3 Parts of a nucleotide
5-Carbon Sugar
Phosphate group
NItrogenous Base
Purines
Adenine
Guanine
Pyrimidines
Cytosine
Thymine
Uracil
Which is more stable: DNA or RNA?
DNA is more stable, which is why RNA organisms are typically viruses and require a host
Mutations can be
Environmental or Endogenous processes during metabolism
Causes of mutation
Toxins (Asbestos)
Smoking
UV Light
Radiation
Central Dogma
DNA to RNA to Protein
Intron
Non-COding DNA Sequence, splicing removes them
Exon
Coding region of DNA
Spliceosome
a large RNA-protein complex that catalyses the removal of introns from nuclear pre-mRNA.
Translation
Synthesis of a protein from an MRNA template
Steps of Translation
Initiation (3’ Poly A tail added)
Elongation ( add 1 amino acid down the mrna to grow the polypeptide chain
Termination( Add 5’ Methylated cap)
TRNA
Anticodon complimentary to the MRNA
AUG
Methionine (Universal Start codon)
What makes the MRNA release from the ribosome TRNA complex
STOP CODON
polycistronic
two (bicistronic/dicistronic), three (tricistronic), or more separate proteins are encoded on a single molecule of messenger RNA (mRNA). In prokaryotes, polycistronic expression is commo
Which region of DNA is involved in regulating the expression of genes?
Promotor Region
The promotor region controls
When and where a gene is expressed and interacts with proteins that affect the activity of RNA polymerase
TATA Box CODing Sequence
TATAAA
TATA BOX (Definition)
An important rgulatory element for most genes
Located neae the start site of transcription
Binding of TATA Box Binding Protein (TBP) is important for initiation of transcription
Response element (RE)
Short sequence of DNA within the promoter that is recognized by a specific protein and contributes to the regulation of the gene
Response element can either be
Enhancer Element (EE) or Inhibitor Element (IE)
Mutations
Alterations in DNA Sequence
Base subsititutions can lead to Amino acid change or may be silent
Silent mutation
Does not affect Amino Acid Sequence
Missense Mutation
Amino Acid changes, polypeptide changes, structure and function of the protein is affected
Nonsense Mutation
Inadvertently causing a stop codon to be produced, stops translation early, and the polypeptide is incomplete
STOP CODONS
UAA
UAG
UGA
(DO not code for an Amino Acid)
Start codon
Methionine
Frameshift mutation
Addition or deletion
changes the reading frame and loss in gene functions
Diseases which cause Frameshift mutations
HIV
HTLV
They integrate into the genome and shut down functionality
Transitions
Substitution of one purine for another purine or
substitution of one pyrimidine for another pyrimidine
Transversions
T to A or G (Pyrimidine to Purine)
C to G or A (Pyrimidine to Purine)
A to T or C (Purine to Pyrimidine)
G to C or T (Purine to Pyrimidine)
Translocation
Exchange of part of one chromosome with a part of another chromosome
Burkitt’s Lymphoma Translocation
8: 14
Acute Myeloblastic Leukemia Translocation
8:21
Gene Amplification
Similar to translocation, but only at one gene in the same location
Example of gene amplification
Elephants have 20 copies of p53 gene, and have only a 5% cancer rate because the cells kill the cancer quickly
Chromothripsis
When fragments of single shattered chromosomes are peiced together
Chromothripsis is common in
Bone Cnacers
3 Possible reasons for chromothripsis
Ionizing radiation that leads to chromosome breaks
Telomere Defunction which may lead to end-end chromosome fusions
Aborted apoptosis such that cells which have initiated DNA Fragmentation push through and survive
DNAse
Enzyme that chops up DNA and those pieces could get picked up and annealed together