Clinical Chem Proteins & Tumour Markers

BRCA1

________ tumours show more aggressive clinicopathological features than BRCA2.

liver

Most plasma proteins are synthesized in the _____, except immunoglobulins & protein hormones

Prealbumin, albumin, α2-Macroglobulin, Immunoglobulins

Different types of plasma protein

thyroid hormones

Prealbumin are small transporter proteins, what do they transport?

A

Prealbumin also binds to retinol-binding protein for the transportation of vitamin __

liver, central nervous

prealbumin is synthesised in the l____ & choroid plexus of the _________ system

glucocorticoid, NSAIDs

the production of prealbumin is stimulated by g______ hormones, androgens & N_____

amniotic

Albumin is a small protein found in blood, CSF, interstitial fluid, urine & a____ fluid

liver, insulin, cortisol

Albumin is synthesised in _____
Albumin is stimulated by hormones, e.g. i_____, c______ & growth hormone

proinflammatory

Albumin production is inhibited by p_______ substances

protein

Albumin production is regulated by colloidal osmotic pressure and p______ intake

albumin

These are the two primary function of which plasma protein?
maintain the colloidal osmotic pressure in the intravascular & extravascular compartments

serves as a transport protein for fatty acids, phospholipids, cholesterol, amino acids, hormones, bilirubin, drugs, toxins, metallic ions & gas

protease

α2-Macroglobulin is a serine ______ inhibitor

enzymes

α2-Macroglobulin inhibits _____ in the kinin, complement, coagulation & fibrinolytic pathways

cytokines, growth factors

α2-Macroglobulin is also a carrier protein for c_____, g_____ f_____ & cations

liver, immunologic, inflammatory

α2-Macroglobulin is a very large glycoprotein synthesised mainly in the _____, which modulates i_____ & i_____ reactions

antibodies

Immunoglobulins functions as a____

directly by the tumours
as an effect of the tumours on healthy tissue
other cells of the body in response to cancer

How are tumour markers produced?

Carcinoembryonic Antigen (CEA)
α1-fetoprotein (AFP)

Name two examples of tumour markers

in embryonic tissue of gut, pancreas & liver

Where is Carcinoembryonic Antigen (CEA) expressed?

embryonic, liver

α1-fetoprotein (AFP) is a major glycoprotein in fetal plasma
α1-fetoprotein (AFP) is usually synthesised by e______ yolk sac and fetal l_____

malignant

α1-fetoprotein (AFP) can be produced and secreted by certain _____ tumours

screening
diagnosis
prognosis
treatment outcome prediction/monitoring treatment
relapse

What are tumour markers used for?

Because they aren't sensitive enough. For screening, tumour markers usually elevated when the cancer is already well-establish

Why aren't tumour markers not usually used for screening and diagnosis?

increases, aggressiveness, size

Prognosis - Concentration level of tumour markers i______ with tumour progression
May reflect the a_______ and s_____ of tumour and predict outcome

efficacy

Tumour markers determine the most suitable treatment approach and monitor the e_____ of therapy

Immunoassays, High-performance liquid chromatography, Immunohistochemistry & immunofluorescence

Three different laboratory measurement

Immunoassays

most commonly used
automated testing & relative ease of use

High-performance liquid chromatography

used to detect small molecules, e.g., catecholamine metabolites
more labour intensive & requires more experience and skill

Immunohistochemistry & immunofluorescence

solid tumour tissue markers from fine-needle aspirate or biopsy samples
determine particular cell type & subcellular location

lack of standardisation between different assays, vary in concentration by orders of magnitude

Two main considerations when using laboratory measurement

use of same methodology or same kit for monitoring

How to correct the lack of standardisation between different assays?

take note of dilution protocols and risk of antigen excess

How to correct the vary in concentration by orders of magnitude?

encode for proteins function in cell growth and division

What do oncogenes usually do?

inhibit cell proliferation, limit the growth and development of tumours
repair DNA damage and initiate apoptosis of abnormal cells

what do tumour suppressor genes usually do?

Serum-based tumour marker: cancer antigen 15-3 (CA15-3), Tissue-based tumour markers, DNA markers

Different markers used in breast cancer

MUC1, prognostic, treatment, metastatic

CA15-3 is the product of ____ gene
This tumour marker is used as p_____ indicator, in determining the suitable therapy and t_____ monitoring in m_____ breast cancer

biopsy

Tissue-based tumour markers is a _____

estrogen receptor
progesterone receptor
HER2 protein receptor

three different types of receptors that may be found with tissue based tumour marker

hormone

ER/PR-positive patients have a better prognosis with ______ therapy

HER2-amplified

_______ tumours is likely to be successfully treatmed with trastuzumab

BRCA1
BRCA2

Two different mutated genes that could be found with DNA markers (breast cancer)

aggressive

BRCA1 tumours show more ______ clinicopathological features than BRCA2

Serum-based tumour marker: CEA, DNA markers

Two different markers used to detect Colorectal Cancer

it isnt sensitive enough, so it is only used for prognosis and to monitor patient's response to treatment and recurrence

Why arent CEA commonly used to screen for colorectal cancer?

pancreatitis

CEA may also be elevated in inflammatory bowel diseases, p_____, alcoholic cirrhosis, during pregnancy and in smokers

KRAS, BRAF, NRAS

DNA markers look for mutations in ____, ____ and _____ genes via real-time PCR (colorectal cancer)

MLH1

microsatellite instability status (MSI) is caused by protein expression of DNA mismatch repair genes, i.e., ____, MSH2, MSH6, PMS2, via immunohistochemistry