CELL CYCLE AND CANCER CHEMOTHERAPY Flashcards
Cancers occur through the following 6 mechanisms
- Epigenetic alteration
- Alterations in genes that stimulate cellular growth
- Mutation of G-protein coupled receptors (GPCRs).
- Loss of tumor suppressor gene function
- Loss of cell death
- Stimulation of apoptosis in immune cells
% of HPV infections that transform to cervical cancer
1%
Addition of chromosomes — and —- and the loss of chromosomes 2q, 3p and 11q have been detected in patients with cervical cancer
1q
3q
Addition of chromosomes 1q and 3q and the loss of chromosomes —, — and —- have been detected in patients with cervical cancer
2q, 3p and 11q
The gene located in chromosome 3q whose expression is frequently in cervical cancer
Fragile histidine triad gene (FHIT)
The fragile histidine triad gene (FHIT) is located on which chromosome
3q
T/F: FHIT (fragile histidine triad gene) expression is frequently increased in cervical cancer
F.
Reduced
T/F: Over expression of p16 and c-myc are detected in early events in cervical cancer
T
Over expression of — and — are detected in early events in cervical cancer
p16 and c-myc
Mutations in the —or — genes are suggested to be a late event for cervical carcinogenesis
K-RAS or H-RAS
T/F: Mutations in the K-RAS or H-RAS genes are suggested to be an early event for cervical carcinogenesis
F
Late event
T/F: The receptor-binding cancer antigen (RCAS1) is also expressed among cervical cancer patients.
T
T/F: Cellular transformation could also be associated with the integration of HPV DNA into the host genome
T
— and — bind to and inactivate p53 and Rb, respectively, resulting in transformation of cervical epithelial cells
E6 and E7
p53 is bound and inactivated by —
E6
Rb is bound and inactivated by —
E7
Types of endometrial cancer according to clinicopathological variables
Type l and Type ll
T/F: Type I endometrial cancer arises from preneoplastic lesion hyperplasia that has undergone unchecked estrogenic stimulation
T
—, — and — are suggested to be early events in endometrial carcinogenesis
- Loss of PTEN (phosphatase and tensin homologue) expression
- K-RAS mutation
- MSI (microsatellite instability)
Type II carcinomas develop from –
Atrophic endometrium
T/F: Type ll endometrial carcinomas are frequently serous or clear cell adenocarcinomas
T
— mutations occur in ~90% of serous adenocarcinomas
TP53 mutations
P16 inactivation, HER2 overexpression and reduced E-cadherin expression are observed in ~—, — and —% of cases, respectively
P16 inactivation = 45%
HER2 overexpression = 70%
Reduced E-cadherin expression in 80%
T/F: RCAS1 expression is increased in endometrial adenocarcinoma
T
Serous borderline tumor and low-grade serous adenocarcinoma of the ovaries are due to mutations in — and —
K-RAS and BRAF
T/F: Ovarian cancer has frequent mutations in TP53 and occasional over expression of HER-2/neu, AKT2 and MYC
T
Endometrioid and clear cell adenocarcinomas of the ovary are associaed with mutations of — and —
PTEN and PIK3CA
Mucinous adenocarcinoma of the ovary is associated with mutations in —
K-RAS
% of ovarian cancers attributable to inherited mutations of cancer susceptibility genes, including BRCA1 and BRCA2
10%
—, — and —have been reported to play pivotal roles in proliferation and dissemination of ovarian cancer.
- Lysophosphatidic acid
- Heparin-binding EGF (HB-EGF)
- Amphiregulin
The most commonly mutated gene HPV negative vulva cancer
TP53
In HPV negative vulva cancer there is addition of — and — chromosomes
7p and 8q
In HPV negative vulva cancer there is loss of — chromosomes
2q
T/F: HPV-negative ( − ) vulvar cancer contained one or more somatic mutations in TP53, CDKN2A, HRAS, KRAS, PIK3CA, PPP2R1A and PTEN
T
HPV-positive (+) vulvar cancer has a TP53 mutation in —% of cases
17%
In HPV positive vulva cancer there is addition of the — chromosome
3q
In HPV positive vulva cancer there is loss of the — chromosome
11q
For vaginal cancer HPV secretes — and — proteins
E6 and E7 proteins
In vaginal cancer E6 proteins cause — mutation
TP53
In vaginal cancer E7 proteins cause mutation
Rb
4 clinical applications of molecular basis of gynaecologic cancers
- Prevention of gynaecologic cancers
- Early detection and prompt treatment
- Determination of appropriate treatment options
- Monitoring
The 5 phases of the cell cycle
G0, G1, S, G2 and M
Define cell cycle
This is a series of steps that both normal cells and cancer cells go through in order to form new cells
G0 phase (resting stage):
The cell has not yet started dividing. Depending on the type of cell, G0 can last from a few hours to a few years
G1 phase:
The cell starts making more proteins and growing larger. This phase lasts about 18 to 30 hours.
Duration of G0
A few hours to a few years depending on cell type
