Cancer Biology Tumour Markers Widest Definition Imaging Techniques Cannon Ball Multiple Metastases

Cancer Biology Tumour Markers Widest Definition Imaging Techniques Cannon Ball Multiple Metastases www.phwiki.com

Cancer Biology Tumour Markers Widest Definition Imaging Techniques Cannon Ball Multiple Metastases

Pojmann, Karen, Contributing Editor has reference to this Academic Journal, PHwiki organized this Journal Cancer Biology Tumour Markers Prof. Kenneth Bagshawe FRS Tumour Markers Widest Definition The concept of tumour markers can mean anything that helps in the diagnosis of cancer In a more restricted sense it refers to the biochemical detection of cancer Imaging Techniques Detected by: x-ray +/- contrast media Ultra sound Computerised Tomography (CT) Magnetic resonance imaging (MRI) Gamma Camera in addition to radioisotopes (Nuclear Medicine)

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Cannon Ball Multiple Metastases Diffuse Metastases-Be as long as e in addition to After Chemotherapy

Detection of Tumour Markers Those detected on cancer tissue i) Biochemical methods Oestrogen receptors in breast cancer ii) Genetic methods Mutated genes BRCA1 in addition to BRCA2 in breast cancer iii) Antibody methods Carcinoembryonic antigen (CEA) Secreted by cancers into the blood Detection by: Biochemical techniques steroids in adrenocortical cancer Immunoassay proteins, glycoproteins Ancient History 1848 Bence Jones Multiple myeloma 1929 Ascheim-Zondek hCG-trophoblast 1932 Harvey Cushing Pituitary Basophils

The First Tumour Marker It is known as Bence –Jones proteinuria, a marker as long as multiple myeloma a malignancy of the plasma cell. Often referred to as a paraproteinuria It is a monoclonal gammopathy with any class of immunoglobulin Cancers of Endocrine Organs Adrenocortical Phaeochromocytoma Insulinoma Gastrinoma Carcinoid Medullary Ca Thyroid Cortisol adrenaline & nor adrenaline insulin, C peptide gastrin 5-HIAA Calcitonin Ectopic product syndromes Cancers sometimes produce substances inappropriate to the cell type of origin Bronchial carcinomas may produce ACTH, parathormone in addition to human Chorionic Gonadotrophin (hCG)

Protein markers of common cancers detected by immunossay in blood Human Chorionic gonadotrophin (hCG) Pregnancy Trophoblastic disease – Choriocarcinoma Germ cell cancers of testis in addition to ovary Alfa- feto protein (AFP) Germ cell cancers of testis in addition to ovary Hepatoma Protein markers continued Carcinoembryonic antigen (CEA) Colon, stomach etc Prostate Specific antigen (PSA) CA125- Ovary CA153- Breast Measurement of Tumour Markers 1930-1963 Bioassays on Urine 1958 Immunoassays- serum 1960 Radioimmunoassay- serum or urine 1968 Immunometric assay serum or urine- Commercial Kits 1975 Dip Stick Tests

What Is An Assay Unknown Antibody Production Immunogen (Antigen) Rabbit Sheep Antiserum Mouse Horse etc Antisera contain many different antibodies directed at one or more sites on immunogen (polyclonal) Burnett (1957)- Clonal selection Theory One Cell – identical antibodies Antibody Production Kohler & Milstein (1975) Immortalise an antibody producing cell by fusion with a malignant cell Hybridoma Hybridomas proliferate Identical (monoclonal) antibodies

RISING levels of these serum markers indicate disease progression FALLING levels in addition to slowing of rate of increase may indicate response to therapy BUT interpretation has to take account of the HALF -LIFE (t1/2) Half Life Of Common Tumour Markers Depends On Molecular Weight MW TM T1/2(D) ROUTE <70 hCG, PSA 2.3 renal 70 aFP 6 mixed > 70 all others 10 hepatic Median Doubling Times reflect different growth rates of cancers CANCER TM T2(D) Choriocarcinoma hCG 3 Germ cell aFP 6 Breast CA153, CEA 30 Ovary CA125 30 Pancreas CA199 30 Colon CEA, CA199 30 Prostate PSA 128

Cell Numbers Time Scale- Cell Numbers Human Chorionic Gonadotrophin-(HCG) C-Terminal Peptide

Pojmann, Karen CMYK Magazine Contributing Editor www.phwiki.com

Normal Placental Villi hCG V Cell Numbers Human Chorionic Gonadotrophin (hCG) Normal Pregnancy: Mostly Intact molecule ( in addition to subunits) Mole, Choriocarcinoma: Fragmented hCG molecules

Trophoblastic Tumour Choriocarcinoma Germ Cell Tumour

Problems Only a fraction of the i.v injected antibody gets into tumour: Most of the antibody stays in blood until excreted or metabolised Heterogeneity of cancer cell: not all cancer cells express the marker Potential Solutions Antibody directed enzyme prodrug therapy (ADEPT)

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