Cancer Flashcards
(43 cards)
Properties of Cancer
- uncontrolled growth
- invasion and metastasis
- clonal dominance
- loss of differentiation
Mutant subclones are heterogeneous with respect to…
- invasiveness
- metastatic ability
- antigenicity
- responsiveness to chemotherapy
Types of cancer therapy
- surgery
- radiotherapy
- chemotherapy
- immunotherapy
limitations in treating cancer
- lack of tumor specific antigen
- tumor cell heterogeneity
micrometastasis
What are the causes of human cancer
- environmental carcinogens
- UV radiation
- other ionizing radiation
- virus
- lifestyle, diet, immune status
- hereditary factors or genes
- unknown
ionizing and uv radiation can cause…
chromosome breakage, translocations and point mutations
Radiation differs from chemical carcinogens in that…
chemical carcinogens cause single stranded DNA adducts, radiation can cause both single and double stranded DNA breaks
DNA oncogenic viruses
- HPV
- Epstein- Barr virus
- Hep B Virus
malignant types of HPV
16 and 18 are found in almost 100% of invasive squamous cell carcinoma and carcinoma in situ of cervix
which early gene products in HPV cause tumors
E6- inactivates tumor suppressor TP53
E7- inactivates tumor suppressor RB
Tumors associated with EBV
- Burkitt’s Lymphoma (all associated with t(8:14)-MYC gene
- B cell lymphoma in immune compromised (AIDS)
- Hodgkin’s Disease
- Nasopharyngeal Cancer
Hepatitis B virus is associated with…
Hepatocellular cancer. injury and regeneration predispose to mutations with environmental genes
Role of HBx-protein in hepatocellular cancer
disrupts growth control by activating protooncogenes, may inactivate TP53
lifestyle mechanisms of cancer (4)
- sun bathers have increased risk skin cancer
- promiscuous women have increased risk of cervical cancer
- nulliparous women have increased risk of breast cancer
- obese men have increased risk of esophageal cancer
diet mechanisms of cancer (3)
- women who eat fatty food have increased risk of breast cancer
- men who smoke and drink have increased risk of head and neck cancer
- people who eat red meat have increased risk of colon cancer
Hereditary factors or genes
- P53 - Li-Fraumani syndrome
- BRCA1 and BRCA2 - breast cancer
- Lynch Syndrome and microsatelite instability genes
- inherited RB
two key properties of cancer
- property of uncontrolled growth
2. property of invasion and metastasis
what are Oncogenes
genes that code for products (oncoproteins) associated with neoplastic formation. these are not regulated by normal growth factors or signals.
what are Protooncogenes
normal genes that affect growth and differentiation. retroviral transduction (v-onc), where changes in situ convert to c-onc
Activation of oncogenes (protooncogenes to oncogenes) (3)
- point mutations- RAS most common
- chromosomal translocation- moved near promoter or chimeric gene product
- gene amplification- N-MYC in neuroblastoma, HER-2 in breast cancer
5 basic categories of oncogenes
- growth factors
- growth factor receptors
- signal transducing proteins
- nuclear transcription factors
- cyclins and cyclin dependent kinases
cancer suppressor genes (antioncogenes)
cancer can be promoted due to inactivation of genes who’s products suppress cell proliferation.
- growth inhibatory factors
- molecules that regulate cell adhesion
- molecules that regulate signal tranduction
- molecules that regulate nuclear transcription and cell cycle
role of TP53
senses DNA damage, arresting cell in G1 of cell cycle and inducing DNA repair.
it increases CDK1 p21 (CDKN1A), preventing phosphorylation of RB.
It induces GADD45, which aids in DNA repair
Li-Fraumani Syndrome
inherit one mutant TP53 or RB, leading to market increased risk in multiple types of malignancies. still requires mutation of the second normal allele.
can be inactivated by certain DNA viruses like oncogenic HPV, HBV, and possibly EBV