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Lecture 2

Lecture 2 -Cancer Screening and Monitoring.docx

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Biochemistry 3386B
L.Graham Smith

Lecture 2: Cancer Screening and Monitoring  Cancer (and its complications) are the second leading cause of death  20% of deaths in the US are attributed to cancer  Males: lung, colon/rectum, prostate  Females: lung, colon/rectum, breast (ovarian and uterine are also prevalent) What is Cancer?  a group of diseases characterized by uncontrolled growth and division of cells (proliferation) that may invade surrounding tissues  the abnormal mass of tissue is called a tumor  Benign Tumor: not considered to be a cancer because it remains localized in the same place that it originated (no spreadin) can often be removed by surgery (but may regrow back in the same place)  Malignant Tumor: considered cancerous because it invades and destroys other tissues, can become mestatic (spread through blood and invade different tissues) results in a poor prognosis  Cancer develops as a consequence of multiple genetic mutations (often not just one) which occur over a period of time  Mutations: o In genes that disrupt cell cycle, differentiation or apoptosis (pathways)  Pathways are normally under strict contro ensuring a balance is maintained and there is a stability of tissue structure  In Cancer the balance is lost and favors proliferation over apoptosis Two Types of Genes Involved 1. Oncogenes - normally involved with proliferative functions - in cancer they become more active  overexpress the protein 2. Tumor Suppressor Genes - metabolic ―breaks‖ of the proliferative phase – inhibit proliferation - out of control proliferative phase The Role of Laboratory Tests Detection (Screening)  the purpose of a screening test is to detect or exclude cancer in an otherwise healthy individual  want this test to have a very low False Negative rate (ie. The sensitivity should be close to 100%)  a negative screening test means that the patient is free of the disease (cancer)  Example:  PAP smear (cervical cancer)  Mammography (breast cancer) Note: False Negative: missed diagnosis False Positive: wrong diagnosis (more testing required – undue stress) Confirmation  used to confirm a diagnosis of cancer in an individual who are suspected of having cancer on the basis of clinical signs and symptoms (or a positive screening test)  In contrast to the screening tests, a confirmation test should have a low False Positive rate (ie. The specificity should be near 100%)  Example: elevated urinary catecholamines as a sign of pheochromocytoma; use a biopsy as the confirmation test Classification and Staging  Surgical pathologists have developed ways to classify and stage cancers based on: o Size o Extent of invasion of surrounding tissues by the cancer o Degree of involvement of the lymph nodes (if any) o Presence or absence of mestasis Monitoring  Patients require follow up monitoring to detect recurrence of cancer – so an early repeat treatment can be offered  Use tumor markers to monitor this  Treatments: o Chemotherapy o Surgical therapy o Radiotherapy o Hormone therapy  Example: CEA (carcinoembryonic antigen) in the follow up of colon cancer patients Tumor Marker A substance or process whose deviation from normal can be detected in an assay. Ideal: marker is positive in all cases of cancer and negative in the absence of cancer Also:  Easy and inexpensive to measure  Specific to the malignant tissue (and only be produced by that tissue)  Have plasma levels proportional to the tumor mass  Have an abnormal plasma level, urine level or both in the presence of micro metastases (at a stage at which no clinical or presently available diagnostic methods reveal their presence  Have high plasma levels, urine levels or both that are stable (not subject to wild fluctuations)  If present in normal plasma, occur at much lower levels than the ones associated with any stage of cancer Major Criteria 1. Predict a higher or lower risk for eventual recurrence 2. Should change as the current status of the tumor changes over time 3. They should precede and predict recurrences before they are clinically detectable Hormones (used as tumor markers)  High insulin = pancreatic insulinoma  High catecholamines = pheochromocytoma  High ACTH = ectopic production (small lung cancers) cause an increase in cortisol – stimulates adrenals Oncofetal Proteins  Hormones normally only produced during embryonic development in the fetus  Found in high concentrations in adults when the genes that control them are deactivated in cancers  Examples: o CEA (carcinoembryonic antigen) – colorectal cancer (best used to monitor treatment response o á-fetoprotein (AFP) – liver cell cancers o HCG—testicular cancers (non-seminiferous) Test for the return of these markers after surgery. Cell Surface Antigens  Antigenic markers on cell surface membranes  Most markers of this group are named with CA (carbohydrate antigen) prefix  Examples: o CA-125: advanced ovarian cancer – best used to monitor response to treatment (after chemotherapy) o CA-19-9: advanced pancreatic cancer – best used to monitor response to treatment, but has limited value because there is a lack of treatment options for this cancer (aggressive with a poor prognosis) o PSA: prostate specific antigen (the most studies) Tumor Markers Class of Biochemical Examples Use Increased production of Hormones, Enzyme Confirmation, diagnosis endogenous biochemical and monitoring Synthesis of biochemical of Oncofetal proteins, cell surface Monitoring and prognosis previously quiescent genes antigens, enzymes (silent genes amped up) Receptors Estrogen Receptor (Breast) Prognosis and treatment Androgen Receptor (Prostate) Modification of usual cell or Gamma-glutamyl transferase(GGT) Diagnosis organ function 5’-nucleosidase PSA and Prostate Cancer (PC)  The prostate gland is about the size of a walnut  At the base of the urinary bladder  Surrounds the proximal portion of the urethra  Epithelial cells of the prostate secrete prostate specific antigen (PSA) which is added to semen and helps with its liquefaction  When males age, their prostate gland gets bigger due to benign prostate hyperplasia (BPH)  Most males will develop a slow growing prostate cancer and eventually die WITH it but not OF it  Some males develop an aggressive form of prostate cancer  The increase in PSA is in both BPH and PC  these can also both result in urinary symptoms  Rapidly growing PCs invade the capsule of the gland and can spread to other organs metastasize (bone, rdver lungs) o This is the 3leading cause of deaths in terms of cancer for men (after lung and colo-rectal)  Risk Factors: o Age o Family history o Environmental or dietary factors (saturated fats?) o Hormones (androgens/testosterone)  Symptoms: o Urinary:  Narrowing of urinary stream
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