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Grant Details

Grant Number: 5R01CA225002-03 Interpret this number
Primary Investigator: Backman, Vadim
Organization: Northwestern University
Project Title: Translating Buccal Nanocytology for Lung Cancer Screening Into Clinical Practice
Fiscal Year: 2020


Abstract

Project Summary The overarching goal of the Academic Industrial Partnership grant is to develop a population risk-stratification tool that will allow efficacious and cost-effective lung cancer screening. Lung cancer represents an ideal malignancy for screening because of its prevalence, identifiable risk groups (current/former smokers) and ability to surgically cure the disease if diagnosed early. However, there are no robust screening techniques with options such as low-dose CT (LDCT) scans fraught with cost and harm from large numbers of false positives. In order to make lung cancer screening viable, it is imperative to develop a test to pre-screen for LDCT by identifying the subset of patients who are likely to harbor lung cancers and would benefit from LDCT. The test must be sensitive to early disease (e.g. Stage I), low-cost, and able to be carried out in a primary care setting. The goal of this project is to develop such a test. One attractive approach is to exploit field carcinogenesis, the concept that the same genetic/environmental milieu that results in a lesion in one area of the lung will impact upon the entire aero digestive mucosa. The buccal (cheek) mucosa is a “molecular mirror” of lung carcinogenesis, although current techniques are inadequate to translate this phenomenon into a minimally intrusive screening test. The preliminary data show that the alteration of nanoscale architecture in buccal cells is exquisitely sensitive to field carcinogenesis and hence may serve as a robust biomarker for lung cancer. These nano-architectural changes can be detected in a practical and highly accurate fashion via a novel biophotonics technology, partial wave spectroscopic (PWS) microscopy (“nanocytology”). In this study, PWS technology will be refined and a prediction rule developed based on the PWS-detectable nanoscale alterations that is optimized for early stage, curable lung cancer. The goal of the proposed project is to finalize the remaining technology development aspects to translate nanocytology into a practical, accurate, and low- cost test, bring it to the point where it is viable for population screening, and conduct a pre-definitive clinical validation. The team envision that upon completion of this project, nanocytology will be ready for a definitive clinical trial leading to a launch in clinical practice. This novel paradigm could transform the clinical practice of lung cancer screening and thereby mitigate the large toll of this malignancy in Americans.



Publications

Early screening of colorectal cancer using feature engineering with artificial intelligence-enhanced analysis of nanoscale chromatin modifications.
Authors: Chang A. , Prabhala S. , Daneshkhah A. , Lin J. , Subramanian H. , Roy H.K. , Backman V. .
Source: Research square, 2023-10-31; , .
EPub date: 2023-10-31.
PMID: 37961494
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Early screening of colorectal cancer using feature engineering with artificial intelligence-enhanced analysis of nanoscale chromatin modifications.
Authors: Chang A. , Prabhala S. , Daneshkhah A. , Lin J. , Subramanian H. , Roy H.K. , Backman V. .
Source: medRxiv : the preprint server for health sciences, 2023-10-31; , .
EPub date: 2023-10-31.
PMID: 37961299
Related Citations

Local Volume Concentration, Packing Domains and Scaling Properties of Chromatin.
Authors: Carignano M. , Kröger M. , Almassalha L. , Agrawal V. , Li W.S. , Pujadas E.M. , Nap R.J. , Backman V. , Szleifer I. .
Source: Research square, 2023-10-17; , .
EPub date: 2023-10-17.
PMID: 37886531
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Early detection of lung cancer using artificial intelligence-enhanced optical nanosensing of chromatin alterations in field carcinogenesis.
Authors: Daneshkhah A. , Prabhala S. , Viswanathan P. , Subramanian H. , Lin J. , Chang A.S. , Bharat A. , Roy H.K. , Backman V. .
Source: Scientific reports, 2023-08-22; 13(1), p. 13702.
EPub date: 2023-08-22.
PMID: 37608214
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Denoising Autoencoder Trained on Simulation-Derived Structures for Noise Reduction in Chromatin Scanning Transmission Electron Microscopy.
Authors: Alvarado W. , Agrawal V. , Li W.S. , Dravid V.P. , Backman V. , de Pablo J.J. , Ferguson A.L. .
Source: ACS central science, 2023-06-28; 9(6), p. 1200-1212.
EPub date: 2023-06-05.
PMID: 37396862
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Differentiation-dependent chromosomal organization changes in normal myogenic cells are absent in rhabdomyosarcoma cells.
Authors: Ibarra J. , Hershenhouse T. , Almassalha L. , Walterhouse D. , Backman V. , MacQuarrie K.L. .
Source: Frontiers in cell and developmental biology, 2023; 11, p. 1293891.
EPub date: 2023-11-07.
PMID: 38020905
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Analysis of three-dimensional chromatin packing domains by chromatin scanning transmission electron microscopy (ChromSTEM).
Authors: Li Y. , Agrawal V. , Virk R.K.A. , Roth E. , Li W.S. , Eshein A. , Frederick J. , Huang K. , Almassalha L. , Bleher R. , et al. .
Source: Scientific reports, 2022-07-16; 12(1), p. 12198.
EPub date: 2022-07-16.
PMID: 35842472
Related Citations

Chromatin as self-returning walks: From population to single cell and back.
Authors: Shim A.R. , Huang K. , Backman V. , Szleifer I. .
Source: Biophysical reports, 2022-03-09; 2(1), p. 100042.
EPub date: 2021-12-10.
PMID: 36425085
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Early Upper Aerodigestive Tract Cancer Detection Using Electron Microscopy to Reveal Chromatin Packing Alterations in Buccal Mucosa Cells.
Authors: Bugter O. , Li Y. , Wolters A.H.G. , Agrawal V. , Dravid A. , Chang A. , Hardillo J. , Giepmans B.N.G. , Baatenburg de Jong R.J. , Amelink A. , et al. .
Source: Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada, 2021 Aug; 27(4), p. 878-888.
PMID: 34108070
Related Citations

Origins of subdiffractional contrast in optical coherence tomography.
Authors: Eid A. , Winkelmann J.A. , Eshein A. , Taflove A. , Backman V. .
Source: Biomedical optics express, 2021-06-01; 12(6), p. 3630-3642.
EPub date: 2021-05-26.
PMID: 34221684
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Spike-in normalization for single-cell RNA-seq reveals dynamic global transcriptional activity mediating anticancer drug response.
Authors: Wang X. , Frederick J. , Wang H. , Hui S. , Backman V. , Ji Z. .
Source: NAR genomics and bioinformatics, 2021 Jun; 3(2), p. lqab054.
EPub date: 2021-06-17.
PMID: 34159316
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Nanoscale chromatin imaging and analysis platform bridges 4D chromatin organization with molecular function.
Authors: Li Y. , Eshein A. , Virk R.K.A. , Eid A. , Wu W. , Frederick J. , VanDerway D. , Gladstein S. , Huang K. , Shim A.R. , et al. .
Source: Science advances, 2021 Jan; 7(1), .
EPub date: 2021-01-01.
PMID: 33523864
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Evidence for possible association of vitamin D status with cytokine storm and unregulated inflammation in COVID-19 patients.
Authors: Daneshkhah A. , Agrawal V. , Eshein A. , Subramanian H. , Roy H.K. , Backman V. .
Source: Aging clinical and experimental research, 2020 Oct; 32(10), p. 2141-2158.
EPub date: 2020-09-02.
PMID: 32876941
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Characterizing chromatin packing scaling in whole nuclei using interferometric microscopy.
Authors: Eid A. , Eshein A. , Li Y. , Virk R. , Van Derway D. , Zhang D. , Taflove A. , Backman V. .
Source: Optics letters, 2020-09-01; 45(17), p. 4810-4813.
PMID: 32870863
Related Citations

Physical and data structure of 3D genome.
Authors: Huang K. , Li Y. , Shim A.R. , Virk R.K.A. , Agrawal V. , Eshein A. , Nap R.J. , Almassalha L.M. , Backman V. , Szleifer I. .
Source: Science advances, 2020 Jan; 6(2), p. eaay4055.
EPub date: 2020-01-10.
PMID: 31950084
Related Citations

Disordered chromatin packing regulates phenotypic plasticity.
Authors: Virk R.K.A. , Wu W. , Almassalha L.M. , Bauer G.M. , Li Y. , VanDerway D. , Frederick J. , Zhang D. , Eshein A. , Roy H.K. , et al. .
Source: Science advances, 2020 Jan; 6(2), p. eaax6232.
EPub date: 2020-01-08.
PMID: 31934628
Related Citations

Multimodal interference-based imaging of nanoscale structure and macromolecular motion uncovers UV induced cellular paroxysm.
Authors: Gladstein S. , Almassalha L.M. , Cherkezyan L. , Chandler J.E. , Eshein A. , Eid A. , Zhang D. , Wu W. , Bauer G.M. , Stephens A.D. , et al. .
Source: Nature communications, 2019-04-10; 10(1), p. 1652.
EPub date: 2019-04-10.
PMID: 30971691
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