FINAL - CH 11 Flashcards
Origin of Cancer
Begins from the growth of a single abnormal cell
A mutation occurs, allowing a cell to undergo inappropriate cell division
Division produces more abnormal cells, resulting in a tumor formation
Certain cell(s) in the tumor can undergo further mutation to produce metastatic cells that are able to dissociate from the original tumor and colonize at new organ sites (metastasis)
Theories for metastasis
“Seed and soil”
Routes of blood supply theory
Steps to metastases
Tumor grows to infiltrate surrounding tissues
Breaks through basement membrane
Breaks down the connective tissue proteins
Attach to the endothelium and enter lymph/blood
Evade immune cells in lymph/blood
Lodge in capillaries
Attach and travel through endothelium
Proliferate and produce tumor
angiogenesis
local blood vessel formation
Characteristics of Cancer Cells
Divide continually May contain heritable mutations if germline lose their specialized identity Lack contact inhibition Induce angiogenesis Increased mutation rate Invasive Metastasize
Carcinogens
are substances that cause cancer by mutating DNA (mutagens)
Genes that control growth of cancer
Proto-oncogenes (accelerators) Tumor supressor (brakes)
Oncogenes
Mutated proto-oncogene
Different proto-oncogenes
HIST
HRAS
CDK4
HIST
Fibroblast growth factor
stomach cancer
HRAS
GTPase
Colon, lung, pancreatic cancer
CDK4
Cyclin dependent kinase
Malignant melanoma
Her-2/neu
Product of an oncogene
Excessive levels in approximately 25% of breast cancer patients
Too many receptors for epidermal growth factor - tyrosine kinase receptors
Result: Too many signals to divide
How are monoclonal antibodies made?
Inject animal with antigen
Get the B cells out
Fuse with myeloma from host
Make monoclonal antibody
How are oncogenes created?
Viruses integrated next to a proto-oncogene can cause transcription when the virus is transcribed - whoch activates a proto-oncogene to be active when it shouldn’t
A proto-oncogene in a new location may cause cancer (translocation in burkitt lymphoma, cytogenic rearrangement in leukemias)
Examples of tumor suppressor genes invloved in cancer
BRCA1
XPA
NF1
BRCA1
DNA repair protein complex
Familial breast/ovarian cancer
XPA
Nucleotide excision repair
Xeroderma pigmentosum
NF1
Down regulates ras protein
Neurofibromatosis 1
Two Hit Hypothesis
Two mutations are required
For somatic: 2 mutations needed in somatic cell
For germline: One mutation is already present, second mutation required for cancer, which is high in AD cases, creates a dominant “susceptibility”
If cell cycle does not allow time for ________, damaged DNA remains in __________ cells
DNA repair
all future daughter
Loss of control of _______ may contribute to loss of control of ______
telomere length
Cell cycle
In colon cancer: Loss of the ______ and other alterations are involved in the progression to malignant carcinoma and metastasis
TP53 gene
Function of TP53
Determines if a cell has repaired DNA damage
If can’t repair damage, p53 induces apoptosis
_____ human cancers involve abnormal p53
> 50%
Environmental factors contributing to cancer
Organic chemicals radon gas in homes foods UV exposure from the sun Cosmic radiation exposure in airplanes X-rays, CAT scans, chemotherapy, drugs
Retinoblastoma
Phenotype: Cancer of the retina
Etiology: Autosomal dominant mutation in Rb 1 gene, which is a tumor suppressor gene
Chronic myelogenous leukemia
Phenotype: Cancer in bone marrow
Etiology: Mutation in ABL gene, protein kinase oncogene
Li-fraumeni
Phenotype: causes many different types of cancer in family members at early age
Etiology: Mutation in p53 tumor supressor, transcription factor
Breast cancer
Phenotype: Breast/ovarian cancer
Etiology: Mutation in BRCA1 tumor suppressor gene, DNA repair protein complex
Colon cancer
Phenotype: Colon cancer
Etiology: Loss of APC gene, activation of the KRAS proto-oncogene, loss of the SMAD4 gene, Loss of the TP53 gene
Effect of translocations on cancer development
Displace genes so that they are under NEW regulatory control, so they can be improperly up or down regulated
Immunotherapy treatments for Cancer
Uses natural power of your immune system to fight cancer
Different Immunotherapy treatments
General Immunotherapy (Non-specific)
T-Cell Transfer Therapy
Immune Checkpoints
Monoclonal Antibodies (e.g. Herceptin)
Environment Impacts on Cancer: Diet
Fatty diets are correlated with increased estrogen and increased breast cancer
Red meat and processed meat increases colon cancer risk
Grilled red meat releases carcinogen called heterocyclic aromatic amines
Chemoprevention Foods
Lycopene (Tomatoes)
cruciferous vegetables (e.g broccoli, brussell sprouts, cauliflower) decrease risk of colon cancer)
Vitamin C (antioxidant that deactivate DNA damaging free radicals)
anti-inflammatory foods, e.g. flaxseed
Nutrigenomics
Branch of nutritional genomics
Studies the effects of foods and food constituents on gene expression
Other Cancer Treatment
Targeted therapies – e.g. Gleevac for CML
Angiogenesis inhibitors – inhibits blood vessel formation
e.g. Avastin helps treat colon cancer
Drugs that stimulate cells to regain specialized cell fxn
e.g. retinoic acid
Induce apoptosis of cancer cells
