Neoplasia Flashcards
What are the different techniques to diagnose cancer in the Lab?
1) Fine needle aspiration (inserts a very thin, hollow needle through the skin and into the suspicious area. The syringe attached to the needle suctions out a small sample of cells and sometimes fluid)
2) Exfoliative cytology (swabbing cell, Helpful in endometrial carcinoma, bronchogenic carcinoma, gastric carcinoma, bladder & prostate tumor)
3) Excisional biopsy (you remove the whole mass, therapy + diagnosis)
4) Incisional biopsy (small part)
5) Tumor markers (PSA, prostatic specific antigen, when elevated it either indicates inflammation or cancer, AFP for liver, etc)
6) Immunohistochemistry (We can provide patients with a specific treatment, like Mononucleoantibodies for patients with HER)
7) Molecular & cytogenic diagnosis
What are the types of carcinogenic agents?
1) Chemical carcinogenesis
2) Radiation carcinogenesis
3) Biological carcinogenesis
What are the mechanisms of carcinogens?
1) direct-acting compounds (Carcinogenetic compounds that do not require transformation for their carcinogenicity)
2) Indirect-acting compounds (require metabolic conversion in vivo to produce ultimate carcinogens capable of transforming cells, metabolized mainly by cytochrome P-450-dependent mono-oxygenases)
What is the mechanism of action of chemical carcinogenic products?
1) Initiation
- Sufficient dose of carcinogenic material
- “Permanent DNA damage/mutation”
- Rapid, irreversible & has memory
- They are not proliferation (just initiated)
2) Promotion
- Application of a “promoter” causing proliferation and clonal expansion of initiated “mutated” cells
- Promoters induces tumor in initiated cells but they are not tumorigenic
When will a chemical form a tumor?
When chemical carcinogens initiate a DNA mutation followed by repeated promotion, even if the promotion happened after a long period as initiation is a permanent damage
What are the types of carcinogenic chemicals?
1) Direct-acting alkylation agents:
- Activation independent
- Weak carcinogen
- Many therapeutic agents “interacting and damaging DNA “can also be carcinogenic for the same reason”, (cyclophosphamide, chlorambucil, busulfan, and melphalan)
2) Polycyclic aromatic hydrocarbon (aromatic amines) & azo dyes
- One of the most potent carcinogen
- Indirect-acting
- Found in factories, old types of gasoline, cigarette smoke, smoked meat
- ON skin = skin cancer, ON subcutaneous = sarcoma
- Mainly excreted by the liver (except for B-naphthalylamine)
3) Nitrosamines & Amides
- They are derived in the stomach from the reaction of nitrostable amines and nitrate (food preservative), which is converted to nitrites by bacteria, which can lead to gastric carcinoma
4) Naturally accruing carcinogens:
- Aflatoxin B1 (Africa & China), Hepatic carcinogen (produced by aspergillus flavus (in improperly stored corn, rice & peanuts)
5) Miscellaneous Agents:
1) Asbestos (bronchogenic cancer, Mesotheliomas, and GIT cancer)
2) Vinyl chloride (Hemangiosarcoma of the liver)
3) Insecticides (carcinogenic in animals)
What type of cancer can be caused by B-naphthylamine?
responsible for the 50-fold increase incidence of bladder cancer in heavily exposed workers in aniline dye and rubber industries
What are the types of radiation that cause carcinogenesis?
1) UV (ultra-violet radiation)
- Inhibits cell division
- Inactivation of enzymes
- Induction of mutation
- Death of cells
2) X-Ray
- Breaks the DNA strand
3) Radioisotopes
What is the risk order of organs that might develop cancer from radiation?
1) Hematological & thyroid
2) Grest, Lungs, & salivary glands
3) GIT, Skin & Bone
What are the types of cancer caused by UVB?
Squamous cell carcinoma, basal cell carcinoma, and possibly melanoma by the creation of pyrimidine dimers
What are the different types of microbial carcinogenesis?
1) Viral oncogenesis:
1a) Oncogenic RNA viruses
2a) Oncogenic DNA viruses
What are the types of oncogenic viral DNA?
1) Papillomaviruses (HPV)
2) Epstein-Barr virus (EBV)
3) Hepatitis B virus (HBV)
4) Kaposi sarcoma herpes virus (KSHV)
What is the mechanism by which the Oncogenic DNA virus causes cancer?
By injecting their genome into the host forming a stable association with the host cell genome
What are the types of cancers caused by HPV?
- Type 1,2,4 & 7 causes benign squamous papillomas (warts)
- 6 & 11 associated with low-grade dysplasia of the uterine cervix and genital warts
- High risk and most important are types 16 & 18 which are associated with high-grade dysplasia and cervical cancer
How does HPV cause cancer?
Their effective proteins are E6 & E7 in the cell cycle
1) Blocks and enhances p53 degradation (responsible for apoptosis) tumor suppressor genes
2) Blocks RB-E2F “tumor suppressor gene” (responsible for the growth arrest) promoting the proliferation of the cell
3) Associates with p21 (cell cycle inhibitor) presenting its inhibition by the formation of a complex with the Cyclin/CDK4 complex
What are the cancers caused by the oncogenic viral DNA Epstein-Barr virus?
- Herpes family member
- Increases the risk of infectious mononucleosis (B-lymphocyte infection
- Can lead to the development of:
1) Nasopharyngeal carcinoma
2) Lymphomas (B-cell lymphoma, Hodgkin’s lymphoma & African of Burkitt lymphoma)
Explain Kaposi sarcoma
- Causes a vascular tumor
- Caused by a herpes virus (Kaposi sarcoma herpesvirus “KSHV”)
- Unknown mechanism that causes vascular proliferation, but its genome contains homologous human oncogenes & cytokines that can contribute to the growth, survival, and proliferation of vessels
-Infects immunocompromised patients only most common neoplasm in AIDS patients, producing one or more reddish purple nodules on the skin - Nodules are due to the slit-like vascular spaces in the dermis
