373
13 Vibrational Spectroscopy: Disease Diagnostics and Beyond
still developing with new biomarkers [73] being identified that may be considered
as adjuncts to existing cervical cytology and pathology methods. Biomarkers such
as p16
INK4A
have been found to be useful for low-grade lesions [176, 177, 178,
179] making them particularly attractive. thus, a correlation and explanation of
the spectral information with these new biomarkers is a new challenge for biospectroscopists working on future cancer diagnostic systems. the study outlined
above demonstrates how multivariate regression techniques can help to associate
specific spectral signatures with specific biomarkers, potentially paving the way for
“spectro-markers” of disease.
13.4 Analysis of the Effects of Anticancer Agents [98, 99]
the previous sections demonstrate how vibrational spectroscopy, coupled with
multivariate statistical techniques can be utilized for high sensitivity and specificity
disease screening, but also to analyse the underlying biochemical changes at a cellular level. this analytical capability opens up the possibility of a range of in vitro
applications.
For the design of new anticancer drugs, an in-depth understanding of the mechanisms underlying their biological effects is required. the in vitro study of the interaction of anticancer drugs with mammalian cells is therefore important to elucidate
the mechanisms of action of the drug on its biological targets and thereby maximise
efficacy and guide development strategies. the prevalence of such studies is likely
to increase following the Eu directive (2010/63/Eu) on the replacement, reduction
and refinement (RRR) of animal experimentation in scientific studies. vibrational
spectroscopy has great potential to explore sub-cellular biochemical structure as
exemplified by its use in studies investigating the action of various agents on biological macromolecules as well as their interaction with cancer cells [100–106]. It
can provide high content information as it can examine spectral changes in the cell
membrane, cytoplasm and nucleus of the target cells simultaneously and highlight
the biochemical interaction of external agents with the cell or its physiological response [98, 99]. validation of the technique of Raman spectroscopy in the quantitative measurement of the biochemical and physiological effects of known chemotherapeutic agents is required, however, before it may be used for studies of novel
chemical treatments. the study of the spectroscopic signatures of the biochemical
effects of commercially available anticancer drugs may be helpful before application for the evaluation of the novel anticancer agents.
Cisplatin (cis-diamminedichloroplatinum (II)) is a well established chemotherapeutic agent with a known mode of action. In the nucleus, it binds with dNA
forming inter-strand and intra-strand crosslinks which lead to cell cycle arrest and
apoptosis [107]. the formation of inter-strand and intra-strand crosslinks between
cisplatin and dNA leads to conformational changes of the dNA. to understand the
changes caused in dNA conformation due to the adducts formed by cisplatin, the
formation of 1,2-gg or 1,3-gtg intra-strand cross-links and their characterization
13 Vibrational Spectroscopy: Disease Diagnostics and Beyond
still developing with new biomarkers [73] being identified that may be considered
as adjuncts to existing cervical cytology and pathology methods. Biomarkers such
as p16
INK4A
have been found to be useful for low-grade lesions [176, 177, 178,
179] making them particularly attractive. thus, a correlation and explanation of
the spectral information with these new biomarkers is a new challenge for biospectroscopists working on future cancer diagnostic systems. the study outlined
above demonstrates how multivariate regression techniques can help to associate
specific spectral signatures with specific biomarkers, potentially paving the way for
“spectro-markers” of disease.
13.4 Analysis of the Effects of Anticancer Agents [98, 99]
the previous sections demonstrate how vibrational spectroscopy, coupled with
multivariate statistical techniques can be utilized for high sensitivity and specificity
disease screening, but also to analyse the underlying biochemical changes at a cellular level. this analytical capability opens up the possibility of a range of in vitro
applications.
For the design of new anticancer drugs, an in-depth understanding of the mechanisms underlying their biological effects is required. the in vitro study of the interaction of anticancer drugs with mammalian cells is therefore important to elucidate
the mechanisms of action of the drug on its biological targets and thereby maximise
efficacy and guide development strategies. the prevalence of such studies is likely
to increase following the Eu directive (2010/63/Eu) on the replacement, reduction
and refinement (RRR) of animal experimentation in scientific studies. vibrational
spectroscopy has great potential to explore sub-cellular biochemical structure as
exemplified by its use in studies investigating the action of various agents on biological macromolecules as well as their interaction with cancer cells [100–106]. It
can provide high content information as it can examine spectral changes in the cell
membrane, cytoplasm and nucleus of the target cells simultaneously and highlight
the biochemical interaction of external agents with the cell or its physiological response [98, 99]. validation of the technique of Raman spectroscopy in the quantitative measurement of the biochemical and physiological effects of known chemotherapeutic agents is required, however, before it may be used for studies of novel
chemical treatments. the study of the spectroscopic signatures of the biochemical
effects of commercially available anticancer drugs may be helpful before application for the evaluation of the novel anticancer agents.
Cisplatin (cis-diamminedichloroplatinum (II)) is a well established chemotherapeutic agent with a known mode of action. In the nucleus, it binds with dNA
forming inter-strand and intra-strand crosslinks which lead to cell cycle arrest and
apoptosis [107]. the formation of inter-strand and intra-strand crosslinks between
cisplatin and dNA leads to conformational changes of the dNA. to understand the
changes caused in dNA conformation due to the adducts formed by cisplatin, the
formation of 1,2-gg or 1,3-gtg intra-strand cross-links and their characterization