Week 9 - Neoplasia Flashcards

Question

malignant tumours

Answer 1

``` endophytic less differentiated no capsule invade and metastasise necrosis and irregular heterogenous grow quickly ```

Answer 2

translocation between 8 and 14 gene for c-myc next to gene which codes for and promotes immunoglobulin G action. The c-myc is left under the control of the IgG enhancers, becoming constitutively active and leading to a cancer of B lymphocytes

Answer 3

Competence factors are those that trigger the cell to enter the cycle i.e. to go from g0 to g1 extrinsic cell cycle factor

Answer 4

Commitment factors tend to push the cell through G1 and round the cell cycle. There’s a checkpoint at the end of g1 and the commitment factors are pushing the cell through this checkpoint so that it can complete the cycle once it’s entered the cycle. extrinsic cell cycle factor

Answer 5

Surface squamous epithelia eg skin, cervix, oesophagus | benign

Answer 6

glandular epithelia eg colon, breast, ovary | benign

Answer 7

Adipocytes (fat cell) | benign

Answer 8

Fibrocytes (fibroblast) | benign

Answer 9

Chondrocytes (cell of cartilage | benign

Answer 10

smooth muscle | benign

Answer 11

``` striated muscle (skeletal muscle cell) benign ```

Answer 12

bone | benign

Answer 13

germ cells | benign

Answer 14

sarcoma instead of oma apart from: squamous cell carcinoma Teratocarcinoma melanoma - skin (melanocytes) - no benign melanomas seminoma - semen lymphoma - lymph nodes - no benign lymphomas leukaemia - blood

Answer 15

in squamous cell carcinomas

Answer 16

response to neoplasia - abnormally dense connective tissue (stroma)

Answer 17

lymphatic vessels haematogenous (bloodstream) (often venous as the walls are thinner and easier to penetrate) transcoelomic (spread across a body cavity) changes in cell-cell or cell-matrix adhesion is necessary for invasion cadherins for cell-cell and adherins for cell-matrix cancer cells signal stromal fibroblasts to secrete matrix metallo proteases to break down cell matrix

Answer 18

T - tumour size (1-4) N - lymph node involvement (0 - none, 1- few nearby, 2-many nearby M - extent of metastasis (o - none, 1 - one, 2 - many

Answer 19

Pre-invasive stages are called intra-epithelial neoplasms – benign CIN – cervical intra-epithelial neoplasm * abnormal nuclei (pleomorphism & hyperchromasia) * abnormal mitoses * loss of nuclear polarity * loss of differentiation * These abnormal cells HAVE NOT INVADED They stay on the epithelial side of the basement membrane – intra-epithelial (benign)

Answer 20

a linear relationship between the amount of carcinogen delivered in a single dose and the number of tumours which develop.

Answer 21

time lag between the administration of a carcinogen and appearance of macroscopic tumours. The length of this time lag is dose dependent, as high doses reduce it, low doses extend it.

Answer 22

There is a threshold dose of carcinogen, below which no tumours form.

Answer 23

the alteration of a normal cell to a potentially cancerous cell

Answer 24

a process which permits the clonal amplification of the initiated cell. Promoters are not mutagens, they induce proliferation (“fix* the mutation”=make permanent )

Answer 25

Sometimes a third stage is added: acquisition of further mutations within the neoplastic clone drive progression to a malignant neoplasm.

Answer 26

Primary diploid cells in tissue culture only undergo a defined number of cell divisions before senescence

Answer 27

immortalise human cells | Some retroviruses are oncogenic but do not carry oncogenes

Answer 28

repairs DNA in telomeres lost during cell division. In stem cells and 90% of cancers express it

Answer 29

• Cell proliferation • Cell death • Signalling to/from cells & matrix • Monitor & maintain genetic stability/genomic integrity • Regulate and maintain tissue architecture o Movement o Adhesion In cancer

Answer 30

p53 is in very low concentrations in normal situations. When DNA is damaged, p53 is stabilized and its concentration increases. Acts as a transcription factor inducing the expression of protein p21, a cdk inhibitor, binding to it so that it can’t phosphorylate Rb which inhibits almost all cdk/cyclin complexes, leading to cell cycle arrest in G1 and G2. If repair is impossible, apoptosis occurs. p53 is mutated in ~50% of cancers. If p53 is mutated at one allele, then the probability of generating functional p53 tetramers is significantly reduced. Mutated p53 permits the survival and replication of cells with damaged DNA. Mutating p53 makes the cell genetically unstable Deregulation of both Rb and p53 is essential if replicative senescence is to be overcome p53 is an exception in that only one damaged allele can cause cancer – a cell with damaged DNA is free to proliferate dangerously.

Answer 31

>6 for solid cancers | less for leukaemia

Answer 32

MMR corrects mismatched bases (eg C-T instead of C-G) Corrects insertion/deletion loops by cutting a few bases either side of mistake. new DNA sealed by ligase. In absence of mismatch repair, mutation rate increases 100-1000x

Answer 33

Recognizes adjacent thymines crosslinked by UV and carcinogens attached to bases Defects in excision repair occurs in Xeroderma Pigmentosum

Answer 34

Repairs single strand and double strand breaks

Answer 35

block transcription and translation

Answer 36

A pattern of localized hypermutation in some cancer genomes – almost exclusively C>T

Answer 37

up to thousands of clustered chromosomal rearrangements occur in a single event in localised and confined genomic regions in one (or a few) chromosomes

Answer 38

translocation of 9 and 22 – leads to chronic myeloid leukemia

Answer 39

cancer cells release angiogenic factors - vessels are leaky at first Poor gas exchange in tumours – necrosis – reduced effect of cytotoxic drugs

Answer 40

Anatomy plays a part – colorectal cancer spreads to the liver due to its venous drainage to the hepatic portal vein Organ specificity – due to adhesion molecules that the cancer cells express – preferential attachment to different capillary beds some cancer cells cannot grow in certain environments (soil and seed hypothesis)

Answer 41

Evidence that both leukemias and solid tumours contain a small sub-population that • Self renew • Proliferate indefinitely • Can reproduce the cancer through serial transplantation

Answer 42

``` • Surgery o Remove or de-bulk local tumour • Radiotherapy o Local and regional disease • Chemotherapy o Systemic treatment for metastatic disease combination of drugs each with a different site of action needed for effective treatment ``` Immunotherapies – stimulate patients immune system to recognize and destroy cancer cells Synthetic lethality – in cancers which have defective DNA double strand repair, drugs which inhibit other major DNA repair pathways can lead to cell death in the cancer cell.

Answer 43

The epidermal growth factor receptor (EGFR) can become overactive by either amplification producing multiple copies of the gene or truncation of the gene causing the receptor produced to become constitutively active. The cell will act like it is constantly receiving growth factor signals and so proliferate excessively.

Answer 44

Smoking chemicals - 30% of cancer in UK Radiation - hiroshima has much higher rates of cancer, especially leukaemia Environmental factors - higher levels of stomach cancer and lower levels of breast cancer in japan compared to USA Occupational risk - chimney sweeps had higher rates of scrotal cancer, bladder cancer in dye industry, Sex workers show higher incidence for cervical and anal cancer – HPV Mesothelioma after asbestos exposure Chemical carcinogen - Synthetic o Polycyclic hydrocarbons – benzpyrene, benzanthracene, methyl choranthrene o Aromatic amines and Azo dyes – beta-napthylamine (activated in liver by addition of -OH then solubilized by addition glucuronyl but glucuronyl removed in bladder → activated → bladder cancer Naturally occurring o Nitrosamines o Aflatoxin Infectious agents - Parasites o Chronic irritation from schistosoma haematobium Bacteria o Infection with helicobacter pylori – major risk factor for the development of gastric carcinoma and gastric lymphoma Viruses o Both DNA and RNA viruses are known to cause cancer in animals o In humans  HPV – carcinoma cervix – present in 99.7% invasive cervical carcinoma  HBV, HCV – hepatocellular carcinoma  Epstein Barr virus – Burkitt’s lymphoma, ?Hodgkins lymphoma?  HTLV 1 - Adults T cell leukemia  HHV 8 – Kaposi’s sarcoma o Cancer is chronic, multi-stage disease over a long time, viral infection initiates. Difficult to show that the virus causes the cancer

Answer 45

Mutagens – most are metabolically inactive pro-carcinogens – need to be activated to an active form – ultimate carcinogen Ultimate carcinogen – highly reactive electrophilic molecule directly damages DNA

Answer 46

o Case/control studies – comparing infection with the virus in patients with/without cancer o Prospective cohort studies – follow a population infected with the virus to see if they develop cancer

Answer 47

Hep B vaccination available since 1980s – liver cancer decreasing in vaccinated population HPV vaccine – >98% efficacy

Answer 48

a recurrence

Answer 49

in children, where the cells have not fully differentiated