Advances and challenges in label-free nonlinear optical imaging using two-photon excitation fluorescence and second harmonic generation for cancer research

Nonlinear optical imaging (NLOI) has emerged to be a promising tool for bio-medical imaging in recent times. Among the various applications of NLOI, its utility is the most significant in the field of pre-clinical and clinical cancer research. This review begins by briefly covering the core principles involved in NLOI, such as two-photon excitation fluorescence (TPEF) and second harmonic generation (SHG). Subsequently, there is a short description on the various cellular components that contribute to endogenous optical fluorescence. Later on the review deals with its main theme--the challenges faced during label-free NLO imaging in translational cancer research. While this review addresses the accomplishment of various label-free NLOI based studies in cancer diagnostics, it also touches upon the limitations of the mentioned studies. In addition, areas in cancer research that need to be further investigated by label-free NLOI are discussed in a latter segment. The review eventually concludes on the note that label-free NLOI has and will continue to contribute richly in translational cancer research, to eventually provide a very reliable, yet minimally invasive cancer diagnostic tool for the patien

Estimating the risk of squamous cell cancer induction in skin following nonlinear optical imaging

High power femto-second (fs) laser pulses used for in-vivo nonlinear optical (NLO) imaging can form cyclobutane pyrimidine dimers (CPD) in DNA, which may lead to carcinogenesis via subsequent mutations. Since UV radiation from routine sun exposure is the primary source of CPD lesions, we evaluated the risk of CPD-related squamous cell carcinoma (SCC) in human skin due to NLO imaging relative to that from sun exposure. We developed a unique cancer risk model expanding previously published estimation of risk from exposure to continuous wave (CW) laser. This new model showed that the increase in CPD-related SCC in skin from NLO imaging is negligible above that due to regular sun exposur

In vivo nonlinear spectral imaging as a tool to monitor early spectroscopic and metabolic changes in a murine cutaneous squamous cell carcinoma model

Timely detection of cutaneous squamous cell carcinoma with non-invasive modalities like nonlinear spectral imaging (NLSI) can ensure efficient preventive or therapeutic measures for patients. In this study, in vivo NLSI was used to study spectral characteristics in murine skin treated with 7, 12-dimethylbenz(a) anthracene. The results show that NLSI could detect emission spectral changes during the early preclinical stages of skin carcinogenesis. Analyzing these emission spectra using simulated bandpass filters at 450-460 nm and 525-535 nm, gave parameters that were expressed as a ratio. This ratio was increased and thus suggestive of elevated metabolic activity in early stages of skin carcinogenesis. (C) 2014 Optical Society of Americ

The landscape of cancer genes and mutational processes in breast cancer

All cancers carry somatic mutations in their genomes. A subset, known as driver mutations, confer clonal selective advantage on cancer cells and are causally implicated in oncogenesis(1), and the remainder are passenger mutations. The driver mutations and mutational processes operative in breast cancer have not yet been comprehensively explored. Here we examine the genomes of 100 tumours for somatic copy number changes and mutations in the coding exons of protein-coding genes. The number of somatic mutations varied markedly between individual tumours. We found strong correlations between mutation number, age at which cancer was diagnosed and cancer histological grade, and observed multiple mutational signatures, including one present in about ten per cent of tumours characterized by numerous mutations of cytosine at TpC dinucleotides. Driver mutations were identified in several new cancer genes including AKT2, ARID1B, CASP8, CDKN1B, MAP3K1, MAP3K13, NCOR1, SMARCD1 and TBX3. Among the 100 tumours, we found driver mutations in at least 40 cancer genes and 73 different combinations of mutated cancer genes. The results highlight the substantial genetic diversity underlying this common disease

Mutational Processes Molding the Genomes of 21 Breast Cancers

All cancers carry somatic mutations. The patterns of mutation in cancer genomes reflect the DNA damage and repair processes to which cancer cells and their precursors have been exposed. To explore these mechanisms further, we generated catalogs of somatic mutation from 21 breast cancers and applied mathematical methods to extract mutational signatures of the underlying processes. Multiple distinct single- and double-nucleotide substitution signatures were discernible. Cancers with BRCA1 or BRCA2 mutations exhibited a characteristic combination of substitution mutation signatures and a distinctive profile of deletions. Complex relationships between somatic mutation prevalence and transcription were detected. A remarkable phenomenon of localized hypermutation, termed "kataegis,'' was observed. Regions of kataegis differed between cancers but usually colocalized with somatic rearrangements. Base substitutions in these regions were almost exclusively of cytosine at TpC dinucleotides. The mechanisms underlying most of these mutational signatures are unknown. However, a role for the APOBEC family of cytidine deaminases is proposed