Cancer Detection and Diagnosis
Early Cancer May Not Have Any symptoms
Pap Test
Mammograms
Mammograms
Mammograms Mammograms Mammograms Blood tests
Prostate-specific antigen (PSA)Carcinoembryonic antigen (CEA)Fecal Occult Blood Test (FOBT)
TISSUEBIOPSY
Tumour grading
Microscopic examination - - likely behavior- responsiveness to treatment.
"grade"
a low number grade (grade I or II) refers to cancers with fewer cell abnormalities than those with higher numbers (grade III, IV).
Tumour Staging
1. How large is the tumour, and how far has it invaded into surrounding tissues?
2. Have cancer cells spread to regional lymph nodes?
3. Has the cancer spread (metastasized) to other regions of the body?
Surgery
Advantages:
quick & effective;
largest no of cures;
confirmation of excision
Disadvantages:
no guarantee of complete removal;
critical normal tissues invasion
ineffective for metastasis.
Biological effects
Rad is the unit of absorbed dose1 rad =100erg/g
Gy (Gray) 1 Gy = 100rads = joule/kg
Adjuvant radiotherapyBioreductive drug adjuvant therapy
Harmless prodrugUnder certain conditions is converted to a cytotoxic metabolite
E.g. AQ4N (alkylaminoanthraquinone N-oxide)
Harmless in oxic cellsConverted into cytotoxic AQ4 in hypoxic cells
combined with radiotherapy or chemotherapy
Classes of chemo agents
Methotrexate, 5-fluorouracil, cytosine arabinoside, 6-mercaptopurine
Analogues of normal metabolites
Function in 3 ways Substitution Competition for catalytic site Competition for regulatory site
1) Antimetabolites:
antimetabolites serine hydroxymethyltransferase (SHMT)
thymidylate synthase (TS) dihydrofolate reductase (DHFR)
methotrexate
choriocarcinoma
Folic acid antagonist
Dihydrofolate reductase
Reduced synthesis of A & G
Cytotoxicity reversed by leucovorin
Classes of chemo agents
Bacterial or fungal derivatives that affect cellular processes like DNA or protein synthesis
2) Antibiotics
Topoisomerase inhibitors
Doxorubicin (Adriamycin) Fungal anthracycline that has multiple effects 1) it intercalates within the DNA 2) causes single and double strand breaks and 3) inhibits topoisomerase II. Used against
leukaemias, breast, lung and ovarian cancer
Classes of chemo agents
substitute alkyl groups for H atoms forming DNA adducts
2 functional groups which can form inter / intra strand crosslinks in DNA
3) Alkylating agents
Nitrogen mustard derivativescyclophosphamide, chlorambucil, melphalan ethyleneimine derivatives thiotepanitrosoureas BCNU, CCNU alkyl sulphonates busulphan
3) Alkylating agents - examples
Cyclophosphamidetrade name: Cytoxan®
Metabolic activation of cyclophosphamide creates guanine adducts that block cell proliferationUsed in combination with methotrexate and 5-FU against several cancers including breast, colon, ovarian and lung cancers.
3) Alkylating agents - examples
Cisplatin
forms adducts at N-7 position of purines creating inter or intrastrand crosslinks that disrupt DNA synthesis.
Effective against ovarian and testicular cancers and has minimal effects on the bone marrow
Classes of chemo agents
Vinca alkaloids like vincristine, vinblastine & paclitaxel, prevent tubulin polymerisation resulting in mitotic arrest
4) Plant alkaloids
Taxol (a terpene from yew trees) causes a similar effect by preventing tubulin depolymerisation. Used against testicular and ovarian cancers and leukaemias
Drug resistance
individual differences in chemosensitivity in cancer patients
leads to accruing resistance during treatment.
Several genetic factors influence the chemosensitivity of cancer cells, including genes involved in drug uptake and secretion, drug metabolism, DNA repair and apoptosis
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