BIOMARKERS

1. A biologic feature that can be used to measure the
presence or progress of disease or the effects of
treatment.
For example, prostate specific antig (PSA) is a
biomarker for Cancer of the prostate

2.  Lipids
 Carbohydrates
 Small molecules
 Nucleic acids
 Proteins

3.  Biomarkers validated by genetic and molecular biology
methods can be classified into three types.
 Type 0 - Natural history markers
- Intracellular co enzymes
Type 1 - Drug activity markers
rubidium chloride is used as a radioactive
isotope to evaluate perfusion of heart muscle.
 Type 2 - Surrogate markers
"Death from heart disease" is the endpoint of
interest, but "cholesterol" is the surrogate marker.

4.  Diagnosis
 Treatment
-response therapy
- Efficacy
 Toxicity
 Safety
 Progression of disease
 Surrogate
 Prognosis

6.  Example 1:Biomarkers are urgently needed for the diagnosis
and monitoring of disease progression in Parkinson's disease.
Both DJ-1 and alpha-synuclein, two proteins critically
involved in Parkinson's disease pathogenesis.
 Example 2:Pathological cascades and potential biomarkers of
AD. Proteolytic cleavage of APP first by -secretase
followed by -secretase can produce A 42 and other shorter
A fragments. The subsequent aggregation of A 42 results
in oligomers and amyloid fibrils. Amyloid fibrils are
eventually deposited as senile plaques as shown. The toxicity
of oligomers and amyloid fibrils could lead to the cascade of
tau-hyperphosphorylation, which is otherwise bound to
microtubules, providing microtubule stability. Upon
hyperphosphorylation, tau dissociates from microtubules and
aggregates into NFT, which could eventually cause increased
cytoskeleton flexibility and neuronal death.

7.  Example 1:Trastuzumab and lapatinib. They target
the HER2 biomarker in women who have HER2-positive
breast cancer. These targeted therapies will not work in
women who do not have the biomarker, even if they
have breast cancer.

8.  Example 1:Toxicity tests are designed to
identify the hazardous properties of a chemical
substance, tested in an isolated form in
laboratory animals.Ex 1 s liver glutathione
content asan indicator of paracetamol
hepatotoxicity(19), but these cannot be used in
a general sense.

9.  Objective: To evaluate the utility of safety
biomarkers for monitoring organ safety in
humans.
 The isoenzymes of lactacte dehydrogenase and
creatinine kinase in combination with more
specific markers of cardiac injury, such as the
cardiac troponins, can provide information on
the relative severity, extent or duration of
myocardial injury.

10.  blood tests (i.e. blood urea nitrogen [BUN] and
serum creatinine) are the two factors used for the
monitoring kidney toxicity and functional
performance of the kidney . Significant changes in
BUN and/or serum creatinine can only be detected
after major injuries to the kidney have occurred, at
stage where the kidney has lost a substantial part
of its fie sensitive to injuries to specific segment of
the nephron (the basic kidney filtering
unit), would reflect the degree of toxicity to the
nephron. Histopathology was used to determine
the magnitude and extent of the kidney
injuries, factor-specific histological assays were
used to identify the origin of selected factors
detected in the urine (fig. 1).

11.  1.HIV infection is associated with increased risk of
cardiovascular complications. Plasma levels of the
coagulation biomarker D-dimer (DD) have been
correlated with increased mortality and
cardiovascular events in HIV-infected patients. In
SIVagm-infected PTMs(pig tailed macaques), DD
levels were highly indicative of AIDS progression
and increased mortality and were associated with
cardiovascular lesions, pointing to SIVagm-
infected PTMs as an ideal animal model for the
study of the mechanisms of HIV-associated
cardiovascular disease.

12.  2. plasma cytokine levels and RT-MLPA
analysis of whole blood-derived RNA was
performed to capture key immune system
parameters. Analysis of the plasma showed
higher levels of IL-18 in progressors compared
to non-progressors and analysis of the RNA
showed significantly lower gene expression of
Bcl2 but higher CCR7 in progressors compared
to non-progressors. This study shows several
markers that may predict the onset of active TB
at a very early stage after infection

13.  1.Human papilloma viruses (HPV) are causative
agents and alter the cell cycle in cervical
neoplasms, host genes interacting directly or
indirectly with HPV oncoproteins have been
identified in vitro.
 Recent research has centered on identifying the
host genes upregulated in association with HPV
infection, determining their suitability as
“surrogate markers” for HPV infection, and using
these markers to identify HPV-associated
epithelial lesions in tissue or cytologic specimens.

14.  2. Angiogenesis, a process well known to be
involved in tumour growth and metastasis, is the
target of several agents available today in the
treatment of cancer. Laboratory assays used to
detect proteins involved in angiogenesis.
 Surrogate biomarkers discussed include soluble
proteins found in the blood or urine, circulating
endothelial cells and their progenitors, and non-
invasive imaging techniques.

15.  In vitro tumor assay systems or serum biomarkers
that may be reliably used to (a) provide an
accurate early indication of prognosis (prognostic
test) or (b) to predict the effectiveness of an
alternative management strategy in a patient
whose disease has been documented to have
progressed or where the test suggests an
unfavorable outcome with the current strategy
(predictive test).
 estrogen receptor in breast cancer) currently exist
in the oncology arena, and it would be most
appropriate to firmly state that, to date, no such
test satisfies this criterion in the area of epithelial
ovarian cancer.

16. Screen for
disease Distinguish
Assess risk of
between benign
developing
versus malignant
disease
processes
Biomarker
includin
g staging
Monitor disease
status before
and after Predict
therapy response to
Determine therapy
prognosis
independent of
therapy