Four-dimensional elastic light-scattering fingerprints as preneoplastic markers in the rat model of colon carcinogenesis☆

Roy, Hemant K.; Liu, Yang; Wali, Ramesh K.; Kim, Young L.; Kromine, Alexei K.; Goldberg, Michael J.; Backman, Vadim

doi:10.1053/j.gastro.2004.01.009

Cited by 109 publications

(108 citation statements)

References 47 publications

(57 reference statements)

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“…Our group has recently reported that alterations in fractal dimension preceded development of ACF in the azoxymethane-treated rat and adenomas in the MIN mouse (30). Moreover, we have shown that fractal dimension is a sensitive early marker in cancer prevention (31). Thus, the demonstration of complete normalization of fractal dimension with short-term PEG treatment in this study supports the contention that PEG reverses the earliest changes of colon carcinogenesis.…”

Section: Discussionsupporting

confidence: 85%

“…The fractal dimension of fresh colonic tissue (within 1 hour of sacrifice) was determined using fourdimensional elastic light-scattering fingerprinting, as previously described (31). Briefly, these determinations are based on the fact that Fourier transformation of the angular distribution (at 550 nm wavelength) of the scattered light yield two-point mass density correlation function between local tissue regions separated by distance r (1 Am < r < 50…”

Section: Experimental Animal Protocolmentioning

confidence: 99%

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Chemoprevention of colon carcinogenesis by polyethylene glycol: suppression of epithelial proliferation via modulation of SNAIL/β-catenin signaling

Roy

Kunte

Koetsier

et al. 2006

Molecular Cancer Therapeutics

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Polyethylene glycol (PEG) is one of the most potent chemopreventive agents against colorectal cancer; however, the mechanisms remain largely unexplored. In this study, we assessed the ability of PEG to target cyclin D1 -B-catenin -mediated hyperproliferation in the azoxymethane-treated rat model and the human colorectal cancer cell line, HT-29. Azoxymethane-treated rats were randomized to AIN-76A diet alone or supplemented with 5% PEG-8000. After 30 weeks, animals were euthanized and biopsies of aberrant crypt foci and uninvolved crypts were subjected to immunohistochemical and immunoblot analyses. PEG markedly suppressed both early and late markers of azoxymethane-induced colon carcinogenesis (fractal dimension by 80%, aberrant crypt foci by 64%, and tumors by 74%). In both azoxymethane-treated rats and HT-29 cells treated with 5% PEG-3350 for 24 hours, PEG decreased proliferation (45% and 52%, respectively) and cyclin D1 (78% and 56%, respectively). Because B-catenin is the major regulator of cyclin D1 in colorectal cancer, we used the T-cell factor (Tcf) -TOPFLASH reporter assay to show that PEG markedly inhibited B-catenin transcriptional activity. PEG did not alter total B-catenin expression but rather its nuclear localization, leading us to assess E-cadherin expression (a major determinant of B-catenin subcellular localization), which was increased by 73% and 71% in the azoxymethane-rat and HT-29 cells, respectively. We therefore investigated the effect of PEG treatment on levels of the negative regulator of E-cadherin, SNAIL, and observed a 50% and 75% decrease, respectively. In conclusion, we show, for the first time, a molecular mechanism through which PEG imparts its antiproliferative and hence profound chemopreventive effect.

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Section: Discussionsupporting

confidence: 85%

Section: Experimental Animal Protocolmentioning

confidence: 99%

Chemoprevention of colon carcinogenesis by polyethylene glycol: suppression of epithelial proliferation via modulation of SNAIL/β-catenin signaling

Roy

Kunte

Koetsier

et al. 2006

Molecular Cancer Therapeutics

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“…Indeed, in experimental models, we have demonstrated that utilization of a panel of markers increased performance characteristics to > 95 percent. 10,12 Limitations of this study include the modest number of patients and the lack of CRCs. Additionally, in any colonoscopy-based study, the potential for missed adenomas must be considered (estimated to be 27 percent).…”

Section: Discussionmentioning

confidence: 99%

Spectral Slope from the Endoscopically-Normal Mucosa Predicts Concurrent Colonic Neoplasia: A Pilot Ex-Vivo Clinical Study

Roy¹,

Turzhitsky²,

Kim³

et al. 2008

Diseases of the Colon &Amp; Rectum

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Purpose-We previously reported that analysis of histologically normal intestinal epithelium for spectral slope, a marker for aberrations in nanoscale tissue architecture, had outstanding accuracy in identifying field carcinogenesis in preclinical colorectal cancer models. In this study, we assessed the translatability of spectral slope analysis to human colorectal cancer screening.Methods-Subjects (n=127) undergoing colonoscopy had spectral slope determined from two endoscopically normal midtransverse colonic biopsies using four dimensional elastic lightscattering fingerprinting and correlated with clinical findings.Results-Four dimensional elastic light-scattering fingerprinting analysis showed the submicron particles size progressively shifted towards larger sizes in subjects with harboring neoplasia. There was a corresponding decrease in spectral slope values from the endoscopically normal mucosa in subjects harboring adenomas (n=41) and advanced adenomas (n=10), compared to neoplasia-free subjects (p<0.00001). These factors did not appear to be confounded by either age or adenoma location. For detecting advanced adenomas, spectral slope had a negative and positive predictive value of 95 percent and 50 percent respectively.Conclusions-We demonstrate, for the first time, that spectral slope in "normal" mucosa accurately risk-stratify patients for colonic neoplasia. This proof of concept study serves to underscore the promise of four-dimensional elastic light-scattering fingerprinting analysis for colorectal cancer screening.

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“…We have recently developed four dimensional elastic light scattering fingerprinting (4D-ELF) 10 which allows heretofore unprecedented quantification of the colonic mucosal microvasculature. Using this approach, we observed that mucosal microvascular blood content was increased in the histologically normal mucosa of two experimental models of colonic neoplasia, the azoxymethane (AOM)-treated rat and the MIN mouse 11 .…”

Section: Introductionmentioning

confidence: 99%

Spectroscopic Microvascular Blood Detection From the Endoscopically Normal Colonic Mucosa: Biomarker for Neoplasia Risk

et al. 2008

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Background & Aims-We have previously utilized a novel biomedical optics technology, fourdimensional elastically-scattered light fingerprinting, to demonstrate that in experimental colon carcinogenesis, the predysplastic epithelial microvascular blood content is markedly elevated. In order to assess the potential clinical translatability of this putative field effect marker, we characterized the early increase in blood supply (EIBS) in humans in vivo.

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Four-dimensional elastic light-scattering fingerprints as preneoplastic markers in the rat model of colon carcinogenesis☆

Cited by 109 publications

References 47 publications

Chemoprevention of colon carcinogenesis by polyethylene glycol: suppression of epithelial proliferation via modulation of SNAIL/β-catenin signaling

Chemoprevention of colon carcinogenesis by polyethylene glycol: suppression of epithelial proliferation via modulation of SNAIL/β-catenin signaling

Spectral Slope from the Endoscopically-Normal Mucosa Predicts Concurrent Colonic Neoplasia: A Pilot Ex-Vivo Clinical Study

Spectroscopic Microvascular Blood Detection From the Endoscopically Normal Colonic Mucosa: Biomarker for Neoplasia Risk

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