Prostate cancer SD Flashcards

(42 cards)

1
Q

where is the location of the prostate gland?

A

The prostate gland surrounds the neck of the
bladder and urethra, weighs about 20g and is
enclosed in a fibrous capsule

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2
Q

what are the 3 zones of the prostate gland?

A

*The peripheral zone accounts for 70%
*The transition zone 5%
*The central zone 25%.

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3
Q

what zone in the prostate generally enlarges with age?

A

The transition zone gradually enlarges with
age

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4
Q

what zone of the prostate gland does cancer mostly arise from?

A

peripheral zone

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5
Q

what is the prostates function?

A

part of the male reproductive system
*Major role in seminal fluid production

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6
Q

what surrounds the prostate?

A

fibro-muscular stroma
–Muscular contraction during ejaculation
This contains a thick sheet of connective tissue and a layer of smooth muscle surrounding the entire prostate gland.

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7
Q

where does testosterone bind on the androgen receptor?

A

in the ligand binding domain

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8
Q

what does 5ar convert testosterone to?

A

diHydro testosterone

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9
Q

what does most prostatic diseases cause and result in?

A

cause enlargement of the prostate,
–Compression of the intraprostatic portion of the urethra
–Impaired urine flow
–Increased risk of urinary infections
–Acute retention of urine requiring urgent relief by catheterisation.

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10
Q

what are the 3 major prostate pathologies?

A

prostatitis, BPH, prostatic carcinoma

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11
Q

how does genetics increase your chances of developing prostate cancer?

A

A family history of the disease is relevant: 2-3 fold risk if a first-degree relative was diagnosed with PCa under 50 years of age.

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12
Q

what race are most at risk of prostate cancer?

A

3 fold risk for African or Caribbean men compared to caucasian; the risk in
China and Japan is lower.

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13
Q

how do you diagnoise prostate cancer?

A

digital rectal examination

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14
Q

what are advantages and disadvantages oof DRE?

A

Immediate, very quick, cheap test, once a mass is identified additional tests can occur
Downside - Mass has already reached certain size to be detected by touch

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15
Q

what is PSA?

A

Prostate Specific Antigen (PSA)
Blood Test
PSA is a 34 kDa serine protease (KLK3 gene) primarily produced by the prostatic ductal epithelium – AR REGULATED GENE

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16
Q

what would an abnormal PSA show?

A

Abnormal prostate - Increased AR = increased PSA

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17
Q

what can PSA levels be affected by?

A

Prostate Biopsy, DRE, Ejaculation, BPH, Prostatitis, intense exercise

18
Q

how is PSA measured? what are the limits?

A

Measured in serum which usually has an upper limit set at 3-4 ng/ml for
normal serum PSA.

19
Q

what is the main purpose of PSA?

A

We use PSA to monitor effectiveness of treatment – “is the drug working?”

20
Q

what are the limitations of PSA?

A

20% of patients missed
PSA levels could be raised by BPH or urinary tract infection

21
Q

what is TRUS?

A

Trans Rectal Ultra Sonography (TRUS) / Biopsy
Follow up from positive DRE and PSA test
*Ultrasound allows imaging of prostate

22
Q

what is the gleason grade?

A

For stratifying prostate cancer
the most common grade of the cells in a tissue sample may
be grade 3 cells, followed by grade 4 cells.

23
Q

what does prostatic bone metastases often present as?

A

as localised
bone pain, back pain from vertebral
metastases being a common initial
manifestation of the tumour.

24
Q

when may some patients decide to do waitful watching?

A

where some cancer do not progress/ spread- they have been growing very slowly
willl be monitored closely for changes
if the situation changes then treatment can begin

25
what are the ways of removing the prostate?
Keyhole surgery by hand – surgeon makes five or six small incisions and removes the prostate using a thin, lighted tube with a small camera on the tip and special surgical tools *Robot-assisted surgery – surgeon uses three robotic arms (one for the camera and two for the surgical tools) to do the operation. The ‘Da Vinci® Robot’.
26
how is prostate surgery done by the da vinci robot?
Complex blood vessels and nerves surround the prostate *Less infection, blood loss, faster healing, Less time in hospital *Freeman and Sunderland Royal both now have these systems
27
what is androgen deprivation therapy?
LHRH agonists (Chemical Castration) Luteinizing hormone-releasing hormone (LHRH) agonists are drugs that lower the amount of testosterone made by the testicles. *E.g. Zoladex
28
how does zoladex work?
Goserelin is a synthetic decapeptide hormone analogue of LHRH. –The continuous agonist presence leads to DECREASED levels of LHRH Receptor levels on pituitary gland
29
how does casodex work?
Potent AR inhibition *Leads to tumour shrinkage Binds AR directly –AR STILL ENTERS THE NUCLEUS –Casodex prevents gene transcription
30
what does casodex lower?
Does NOT lower testosterone levels – blocks AR
31
what are prostate cancer cells driven by?
androgens
32
what is a resistance mechanism or CRCP?
Ligand Binding Domain mutation – resistance mechanism
33
what does the ligand binding domain mutation allow?
Allows OTHER hormones to bind to AR: *allows multiple agonists to activate AR* –Oestrogens, Progesterone, Glucocorticoids –Antagonists can become AGONISTS.... E.g. 1st gen anti-androgen flutamide became a strong agonist with T877A mutation –T877A Allows conformational change of the receptor to activate genes
34
what is taxanes/ docetaxal used for?
commonly used for men with advanced prostate cancer.
35
after relapse what can cells becoeme resistant to?
bicalutamide
36
when is enzalutamide reserved for?
patients with metastasis, CRPC disease
37
how does enzalutamide work?
enzalutamide inhibits AR- testosterone binding with higher affinity than bicalutamide this inhibition blocks the change induced by AR-testosterone binding it inhibits AR-testosterone nuclear transloactionand DNA transcription it lacks partial AR agonist activity that occurs with bicalutamide resistance
38
what does Abiraterone do?
it prevents testosterone biosynthesis
39
what is the MOA of abiraterone?
inhibits CYP17 (effects 17- hydroxylase/lyase activity) which prevent conversion of progestens to androgens = No substrate for AR Decreases cortisol ACTH is activated Increased mineralocorticoids Treat with prednisone/dexamethasone to lower ACTH
40
what are AR variants resistant to?
Resistant to ADT, Enzalutamide & Abiraterone
41
what do AR variants lead to?
Lead to enhanced migratory capacity, invasiveness, elevated resistance to apoptosis
42
how do AR variants work?
Works Independent of testosterone (No LBD)