Lec 71/72: Neoplasia I/II Flashcards
Aflatoxins:
- Associated Cancer: hepatocellular carcinoma
- Comments: in some countries is the most common cancer (stored grains)
Alkylating agents:
- Associated Cancer: leukemia/lymphoma
- Comments: side effect of chemotherapy
Alcohol:
- Associated Cancer: squamous cell carcinoma of oropharynx and upper esophagus, pancreatic carcinoma and hepatocellular carcinoma
Arsenic
- Associated Cancer: squamous cell carcinoma of skin (back in the day women in England would apply arsenic to the skin to lighten it so people would’t know they worked in the field), lung cancer (present in cigarettes), and angiosarcoma of liver
- Comments: in cigarettes
Asbestos:
- Associated Cancer: lung carcinoma and mesothelioma (pleura)
- Comments: exposure to asbestos are more likely to develop lung cancer than mesothelium
Cigarette smoke:
- Associated Cancer: carcinoma of oropharynx, esophagus, lung, kidney and bladder (entire system is lined urothelium, carcinogens cleared in this system and hang out and bath the surfaces)
- Comments: most common world wide; most important is polycyclic hydrocarbons
Nitrosamines:
- Associated Cancer: stomach carcinoma
- Comments: responsible for high rate of stomach carcinoma in Japan
Napthylamine:
- Associated Cancer: urothelial carcinoma of bladder
- Comments: derived from cigarette smoke
Vinyl chloride:
- Associated Cancer: angiosarcoma of the liver
- Comments: occupational exposure, used to PVC pipes (well studied = high yield)
Nickel, chromium, beryllium or silica
- Associated Cancer: lung carcinoma
- Comments: occupational exposure
EBV
- Associated Cancer: nasopharyngeal carcinoma (Chinese male or African individual are more prone and presents as a neck mass), Burkitt lymphoma and CNS lymphoma in AIDS
HHV-8 (human herpes virus)
- Associated Cancer: Kaposi sarcoma (tumor of endothelial cells, raised purple lesions; older Eastern European males; tx excise tumor; AIDS patients = tx the virus; transplants = tx, slightly reduce immunosuppression)
HBV and HCV (hepatitis) B - DNA C -RNA
- Associated Cancer: hepatocellular carcinoma
HTLV-1
- Associated Cancer: adult T-cell leukemia/lymphoma
High risk HPV (subtypes 16, 18, 31, 33)
- Associated Cancer: squamous cell carcinoma of vulva, vagina, anus, and cervix (adenocarcinoma of cervix)
Ionizing radiation: nuclear reactor accidents
- associated cancer: papillary carcinoma of the thyroid (seen in chernoble), AML, CML
- comment: generates hydroxyl free radicals
Nonionizing radiation: UVB sunlight most common source
- basal cell carcinoma, squamous cell carcinoma and melanoma of skin
- Damages of DNA of pyrimidine dimers in DNA, normally excised, but over run ability
- xeroderma pignosa
What is the role of proto-oncogenes?
- essential for cell growth and differentiation
- mutation = oncogene, leads to unregulated cell growth
- growth factors, growth factor receptors, signal transducers, cell cycle regulators
PDGFB: platelet derived growth factor
- overexpression, autocrine loop
- Astrocytoma
ERBB2 (HER2/neu) epidermal growth factor receptor
- amplication
- subset of breast carcinoma
RET: neural growth factor receptor
- Medullary carcinoma of thyroid (MEN2A, MEN2B and sporadic medullary carcinoma of thyroid)
- point mutation (RET testing and proactively removal thyroid)
KIT (stem cell growth factor receptor)
- GI stromal tumor
RAS gene family: GTP-binding protein
- point mutation
- carcinomas, melanoms, and lymphoma
ABL: tyrosine kinase
- t (9:22) with BCR
- CML and some types of ALL (in adults) philadelphi ph+
c-MYC:
burkitt lymphoma
- translocation (8-14) involving IgH
over expression of myc will result in over transcription of growth factor
N-MYC:
neuroblastoma
over expression of myc will result in over transcription of growth factor
L-MYC:
lung carcinoma
over expression of myc will result in over transcription of growth factor
3 Things that make the growth a neoplasia
- Irreversible
- Not regulated
- Monoclonal
Neoplasm
Abnormal mass of tissue whose growth exceeds and is uncoordinated with normal tissue.
- No use to the host
- Persists beyond stimulus
Dysplasia
Change in size, shape or organization of a cell
Hamartoma
A benign, tumor-like, disorganized structure containing tissue that is normal for that organ
What do cancer cells excrete to keep them alive longer?
Anti-apoptotic BCL6
Pleomorphism
Change in size and shape
Progression tumor pathway
Primary neoplasm –> progressive growth –> invasion –> detachment –> embolization –> survival in circulation –> arrest –> extravasation –> evade host defense –> progressive growth –> metastasis
Why are cancer cells more motile?
Loss of E-cadherin = no intercellular adhesion = movement
Travel via lymphatic spread
Carcinomas
Travel via hematogenous (blood) spread
Mostly sarcomas with some carcinomas (most that enter blood do not end up metastasizing)
How does cancer inhibit the immune system?
- Activates PD-1 and CTLA4 in T cells to lower activity
- Increase in myeloid-derived suppressor cells
- Increase in T regulatory cells
- Decreased expression of HLA-DR in APCs
- Switch Macrophages from M1 to M2 = Increased IL-10
How do you inherit cancer
KO of both alleles involved
What viruses are connected with liver cancer?
Hepatitis B and C
p53
tumor suppressing gene
Protooncogenes
Caretaker pathway - Absolutely necessary for cell growth and differentiation
Mutations to proto-oncogenes
Oncogenes
CDK4
Important for cell cycle G1 phase progression (G1-S phase)
ABL
Protooncogene that is important for cell differentiation and division as well as adhesion. Deletion of its SH3 domain turns it into an oncogene
CCND1
Produces cyclin D-1. Regulate CDKs. Important for protein production during the cell cycle. Oncogene results typically in mantle cell lymphoma.
Cyclins and CDK complexes
Drive cell cycle by phosphorylating certain proteins.
Staging system for cancer
Tumor, Node, Metastasis (TNM)
Rb mutation
Results in constitutively free E2F allowing progression through the cell cycle and uncontrolled cell growth
Diagnosing a tumor
- Biopsy
- Immuno staining
- Serum tumor markers
