IP Library Granted Patent US 12,253,521
Granted Patent B2
US 12,253,521 · App. 18/344,286 · Granted Mar 18, 2025

Early detection of colorectal cancer

Inventors: Carole A. Oskeritzian (Columbia, SC); Franklin Berger (Columbia, SC); Alena P. Chumanevich (Lexington, SC); John W. Fuseler (Columbia, SC); Nabihah I. Kumte (Columbia, SC); Ahmed Aladhami (Columbia, SC)
Assignee: UNIVERSITY OF SOUTH CAROLINA
G01N33/57419A61B10/0096A61B10/02G01N1/30G01N33/5091G01N2001/302
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,253,521
App. No.
18/344,286
Granted
Mar 18, 2025
Kind
B2
Abstract

Methods and systems for detection of precancerous colorectal cancerous lesions and early stage colorectal cancer are described. The methods and systems include examination of a rectal cell sample for the presence of mast cells in a field effect detection regime. The methods can incorporate swab-based cell collection, optionally storage and transportation of a cell sample, and/or computer-aided diagnosis.

Claims (26)

1. A method for detection of colorectal cancer or precancerous colon polyps, the method comprising:

swabbing a rectal area of a subject and thereby collecting a cell sample on the swab;

sealing the cell sample in a container, the container carrying a buffer solution; and

detecting according to a computerized imaging approach the presence or quantity of sloughed colonic mast cells in the sample, wherein the computerized imaging approach comprises identifying areas of the stained cell sample that include slain-positive cells, and isolating individual regions of interest in the identified areas according to a Hue, Saturation, Intensity (HSI) color model;

wherein the presence of the sloughed colonic mast cells in the cell sample indicates the presence of colorectal cancer or precancerous polyps in the colon of the subject.

2. The method of claim 1 , wherein the swab is a flocked swab.

3. The method of claim 1 , wherein all or a portion of the swab is sealed in the container with the cell sample.

4. The method of claim 1 , wherein the step of detecting the presence or quantity of sloughed colonic mast cells in the sample comprises staining the cell sample.

5. The method of claim 4 , further comprising concentrating, fixing, or washing the cell sample prior to staining the cell sample.

6. The method of claim 4 , wherein the stain utilized in staining the cell sample comprises methylene blue or chloroacetate esterase.

7. The method of claim 6 , wherein the stain comprises chloroacetate esterase, the method further comprising counterstaining the cell sample with hematoxylin.

8. The method of claim 1 , wherein the computerized imaging approach further comprises the definition of boundary conditions for a morphometric descriptor.

9. The method of claim 8 , wherein the morphometric descriptor includes area or integrated optical density.

10. The method of claim 1 , wherein the isolated individual regions of interest comprise a Hue value between 214 and 255, a Saturation value between 15 and 208, and an Intensity value between 61 and 150.

11. The method of claim 1 , wherein the step of detecting the presence or quantity of sloughed colonic mast cells in the sample comprises contacting the cell sample with an antibody directed against mast cell restricted tryptase.

12. The method of claim 1 , further comprising storing or transporting the sealed container carrying the cell sample prior to detecting the presence or quantity of sloughed colonic mast cells in the sample.

13. A method for detection of colorectal cancer or precancerous colon polyps, the method comprising:

swabbing a rectal area of a subject and thereby collecting a cell sample on the swab;

sealing the cell sample in a container, the container carrying a buffer solution; and

detecting according to a computerized imaging approach the presence or quantity of sloughed colonic mast cells in the sample, wherein the computerized imaging approach comprises identifying areas of the stained cell sample that include stain-positive cells, and isolating individual regions of interest in the identified areas according to a Hue, Saturation, Intensity (HSI) color model, wherein the isolated individual regions of interest comprise a Hue value between 214 and 255, a Saturation value between 15 and 208, and an Intensity value between 61 and 150;

wherein the presence of the sloughed colonic mast cells in the cell sample indicates the presence of colorectal cancer or precancerous polyps in the colon of the subject.

14. A method for detection of colorectal cancer or precancerous colon polyps, the method comprising:

swabbing a rectal area of a subject and thereby collecting a cell sample on the swab;

sealing the cell sample in a container, the container carrying a buffer solution; and

detecting according to a computerized imaging approach the presence or quantity of sloughed colonic mast cells in the sample, wherein the computerized imaging approach comprises identifying areas of the stained cell sample that include stain-positive cells, and isolating individual regions of interest in the identified areas according to a Hue, Saturation, Intensity (HSI) color model, and the computerized imaging approach comprises a definition of boundary conditions for a morphometric descriptor, wherein the isolated individual regions of interest comprise a Hue value between 214 and 255, a Saturation value between 15 and 208, and an Intensity value between 61 and 150;

wherein the presence of the sloughed colonic mast cells in the cell sample indicates the presence of colorectal cancer or precancerous polyps in the colon of the subject.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 10, 2023
From: OSKERITZIAN, CAROLE; FUSELER, JOHN W.; CHUMANEVICH, ALENA P.; BERGER, FRANKLIN G.; KUMTE, NABIHAH I.; ALADHAMI, AHMED
To: UNIVERSITY OF SOUTH CAROLINA
Reel/Frame 064196/0030 →
Continuity (3)
Continuation 16720309 · Dec 19, 2019
Provisional Application 62807403 · Feb 19, 2019
Related Publication 20230341402A1 · Oct 26, 2023
References Cited (108)
US 20140154690A1 · Loktionov · 2014 [cited by applicant]
US 20170166955A1 · Birnboim · 2017 [cited by examiner]
US 20180168490A1 · Jones · 2018 [cited by examiner]
US 20200049599A1 · Alexander · 2020 [cited by examiner]
JP 2018161469A · 2018 [cited by examiner]
Rajpoot et al., “SVM Optimization for Hyperspectral Colon Tissue Cell Classification,” International Conference on Medical Image Computing and Computer-Assisted Intervention, Springer, Berlin, Heidelberg, 2004, pp. 829-… [cited by examiner]
ACS, “Colorectal Cancer Facts & Figures 2017-2019” [cited by applicant]
Akin, et al. “Mast cell activation syndrome: Proposed diagnostic criteria” [cited by applicant]
Anderson, et al. “A fractal analysis of the radial distribution of bronchial capillaries around large airways” [cited by applicant]
Aon, et al. “The scale-free dynamics of eukaryotic cells” [cited by applicant]
Arock, et al. “Differentiation of human basophils: An overview of recent advances and pending questions” [cited by applicant]
Backman, et al. “Light-scattering technologies for field carcinogenesis detection: a modality for endoscopic prescreening” [cited by applicant]
Bartnikas, et al. “Epicutancous sensitization results in IgE-dependent intestinal mast cell expansion and food-induced anaphylaxis” [cited by applicant]
Bossuyt, et al. “The STARD Initiative” [cited by applicant]
Brown, et al “The fractal nature of nature: Power laws, ecological complexity and biodiversity” [cited by applicant]
Chumanevich, et al. “Sphingosine-1-Phosphate/Sphingosine-1-Phosphate Receptor 2 Axis Can Promote Mouse and Human Primary Mast Cell Angiogenic Potential through Upregulation of Vascular Endothelial Growth Factor-A and Ma… [cited by applicant]
Cinelli, et al. “Comparative analysis and physiological impact of different tissue biopsy methodologies used for the genotyping of laboratory mice” [cited by applicant]
Corpet, et al. “Point: From animal models to prevention of colon cancer. Systematic review of chemoprevention in min mice and choice of the model system” [cited by applicant]
Cui, et al. “Resveratrol suppresses colitis and colon cancer associated with colitis” [cited by applicant]
Da Silva, et al. “Mast cell function: A new vision of an old cell” [cited by applicant]
Damania, et al. “Nanocytology of rectal colonocytes to assess risk of colon cancer based on field cancerization” [cited by applicant]
De Robertis, et al. “The AOM/DSS murine model for the study of colon carcinogenesis: From pathways to diagnosis and therapy studies” [cited by applicant]
Di Ieva, A. “Fractal analysis of microvascular networks I malignant brain tumors” [cited by applicant]
Di Ieva, et al. “Fractal dimension as a quantitator of the microvasculature of normal and adenomatous pituitary tissue” [cited by applicant]
Dioguardi, et al. “Metrically measuring liver biopsy: a chronic hepatitis B and C computer-aided morphologic description” [cited by applicant]
Dioguardi, et al. “Liver fibrosis and tissue architectural change measurement using fractal-rectified metrics and Hurst's exponent” [cited by applicant]
Doubal, et al. “Fractal analysis of retinal vessels suggests that a distinct vasculopathy causes lacunar stroke” [cited by applicant]
Ferro, et al. “Fractal characteristics of May-Grünwald-Giemsa stained chromatin are independent prognostic factors for survival in multiple myeloma” [cited by applicant]
Fuseler, et al. “Modulation of the migration and differentiation potential of adult bone marrow stromal stem cells by nitric oxide” [cited by applicant]
Fuseler, et al. “Fractal and image analysis of the microvasculature in normal intestinal submucosa and intestinal polyps in Apc [cited by applicant]
Fuseler, et al. “Fractal and image analysis of morphological changes in the actin cytoskeleton of neonatal cardiac fibroblasts in response to mechanical stretch” [cited by applicant]
Fuseler, et al. “Analysis and quantitation of NF-κB nuclear translocation in tumor necrosis factor alpha (TNF-α) activated vascular endothelial cells” [cited by applicant]
Galli, et al. “IgE and mast cells in allergic disease” [cited by applicant]
Galli, et al. “Phenotypic and functional plasticity of cells of innate immunity: Macrophages, mast cells and neutrophils” [cited by applicant]
Galli, et al. “Immunomodulatory mast cells: Negative, as well as positive, regulators of immunity” [cited by applicant]
Gerber, et al. “The top skin-associated genes: A comparative analysis of human and mouse skin transcriptomes” [cited by applicant]
Giannou, et al. “Mast cells mediate malignant pleural effusion formation” [cited by applicant]
Gladstein, et al. “Correlating colorectal cancer risk with field carcinogenesis progression using partial wave spectroscopic microscopy” [cited by applicant]
Grizzi, et al. “Quantitative evaluation and modelling of two-dimensional neovascular network complexity: The surface fractal dimension” [cited by applicant]
Grizzi, et al. “A fractal scoring system for quantifying active collagen synthesis during chronic liver disease” Int'l. [cited by applicant]
Hamilton, et al. “Mast cell activation syndrome: A newly recognized disorder with systemic clinical manifestations” [cited by applicant]
Hart, et al. “Age-related changes in dermal mast cell prevalence in BALB/c mice: Functional importance and correlation with dermal mast cell expression of Kit” [cited by applicant]
Hart, et al. “Dermal mast cells determine susceptibility to ultraviolet B-induced systemic suppression of contact hypersensitivity responses in mice” [cited by applicant]
Hochberg, et al. “More powerful procedures for multiple significance testing” [cited by applicant]
Holm, S. “A simple sequentially rejective multiple test procedure” [cited by applicant]
Imperiale, et al. “Multitarget stool DNA testing for colorectal-cancer screening” [cited by applicant]
Irani, et al. “Two types of human mast cells that have distinct neutral protease compositions” [cited by applicant]
Jelinek, et al. “The morphology and classification of a ganglion cells in the rat retinae: A fractal analysis study” [cited by applicant]
Johnson-Henry, et al. “Probiotics reduce bacterial colonization and gastric inflammation in [cited by applicant]
Kalesnikoff, et al. “New developments in mast cell biology” [cited by applicant]
Kekelidze, et al. “Colorectal cancer: current imaging methods and future perspectives for the diagnosis, staging and therapeutic response evaluation” [cited by applicant]
Kucherlapati, et al. “An Msh2 conditional knockout mouse for studying intestinal cancer and testing anticancer agents” [cited by applicant]
Lagunoff, D. “Analysis of dye binding sites in mast cell granules” [cited by applicant]
Lahm, et al. “Identification of transgenic mice by direct PCR analysis of lysates of epithelial cells obtained from the inner surface of the rectum” [cited by applicant]
Mandelbrot, B.B. “The Fractal Geometry of Nature” [cited by applicant]
Manera, et al. “The use of fractal dimension and lacunarity in the characterization of mast cell degranulation in rainbow trout (Onchorhynchus mykiss)” [cited by applicant]
Marichal, et al. “Mast cells: potential positive and negative roles in tumor biology” [cited by applicant]
Marshall, J.S. “Mast-cell responses to pathogens” [cited by applicant]
McAlearney, et al. “Racial differences in colorectal cancer screening practices and knowledge within a low-income population” [cited by applicant]
McIntyre, et al. “Mouse models of colorectal cancer as preclinical models” [cited by applicant]
McNally, et al. “Fractal geometry in the nucleus” [cited by applicant]
Metz, C.E. “Basic principles of ROC analysis” [cited by applicant]
Moledina, et al. “Fractal branching quantifies vascular changes and predicts survival in pulmonary hypertension: a proof of principle study” [cited by applicant]
Moon, et al. “Mast cell mediators: Their differential release and the secretory pathways involved” [cited by applicant]
Moser, et al. “A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse” [cited by applicant]
Nezadal, et al. “The boxcounting: Critical study” [cited by applicant]
Oldford, et al. “Mast cells as targets for immunotherapy of solid tumors” [cited by applicant]
Oskeritzian, et al. “The sphingosine-1-phosphate/sphingosine-1-phosphate receptor 2 axis regulates early airway T-cell infiltration in murine mast cell-dependent acute allergic responses” [cited by applicant]
Oskeritzian, C.A. “Mast cell plasticity and sphingosine-1-phosphate in immunity, inflammation and cancer” [cited by applicant]
Oskeritzian, et al. “Essential roles of sphingosine-1-phosphate receptor 2 in human mast cell activation, anaphylaxis, and pulmonary edema” [cited by applicant]
Oskeritzian, et al. “Distinct roles of sphingosine kinases 1 and 2 in human mast cell functions” [cited by applicant]
Parang, et al. “AOM/DSS model of colitis-associated cancer” [cited by applicant]
Patel, et al. “Colorectal cancer in the young” [cited by applicant]
Poutahidis, et al. “CD4 [cited by applicant]
Qian, et al. “Fractal dimension as a measure of altered actin cytoskeleton in MC3T3-E1 cells under simulated microgravity using 3-D/2-D clinostats” [cited by applicant]
Rafail, et al. “Complement deficiency promotes cutaneous wound healing in mice” [cited by applicant]
Reber, et al. “New models for analyzing mast cell functions in vivo” [cited by applicant]
Rho, et al. “Protein and glycomic plasma markers for early detection of adenoma and colon cancer” [cited by applicant]
Ribatti, D. “Mast cells and macrophages exert beneficial and detrimental effects on tumor progression and angiogenesis” [cited by applicant]
Rogers, et al. “Regulation of NF-κB activation and nuclear translocation by exogenous nitric oxide (NO) donors in TNF-α activated vascular endothelial cells” [cited by applicant]
Schneikert, et al. “The canonical Wnt signaling pathway and its APC partner in colon cancer development” [cited by applicant]
Schwartz, et al. “Tryptase levels as an indicator of mast-cell activation in systemic anaphylaxis and mastocytosis” [cited by applicant]
Sedivy, et al. “Short-term rhythmic proliferation of human breast cancer cell lines: Surface effects and fractal growth patterns” [cited by applicant]
Slaughter, et al. “Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin” [cited by applicant]
Smith, et al. “Fractal methods and results in cellular morphology-dimensions, lacunarity and multifractals” [cited by applicant]
Streba, et al. “A pilot study on the role of fractal analysis in the microscopic evaluation of colorectal cancers” [cited by applicant]
Subramanian, et al. “Nanoscale cellular changes in field carcinogenesis detected by partial wave spectroscopy” [cited by applicant]
Subramanian, et al. “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells” [cited by applicant]
Suzuki, et al. “Strain differences in the susceptibility to azoxymethane and dextran sodium sulfate-induced colon carcinogenesis in mice” [cited by applicant]
Taketo, M.M. “Wnt signaling and gastrointestinal tumorigenesis in mouse models” [cited by applicant]
Thamrin, et al. “Fractals for physicians” [cited by applicant]
Theoharides, et al. “Mast cells and inflammation” [cited by applicant]
Valent, et al. “Clinical and laboratory parameters of mast cell activation as basis for the formulation of diagnostic criteria” Int'l. [cited by applicant]
Varricchi, et al. “Are mast cells MASTers in cancer?” [cited by applicant]
Voehringer, D. (2013). Protective and pathological roles of mast cells and basophils. [cited by applicant]
Wallace, et al. “Race and prevalence of large bowel polyps among the low-income and uninsured in South Carolina” [cited by applicant]
Walter, et al. “Digital image processing and analysis” [cited by applicant]
Wedman, et al. “Mast cells and sphingosine-1-phosphate underlie prelesional remodeling in a mouse model of eczema” [cited by applicant]
Wedman, et al. “A New Image Analysis Method Based on Morphometric and Fractal Parameters for Rapid Evaluation of In Situ Mammalian Mast Cell Status” [cited by applicant]
Welch, et al. “Colorectal cancer on the decline-Why screening can't explain it all” [cited by applicant]
Wernersson, et al. “Mast cell secretory granules: Armed for battle” [cited by applicant]
Wick, et al. “Quantitative measurement of cell migration using time lapse video microscopy and non-linear system analysis” [cited by applicant]
Widman et al., “A new Image Analysis Method on Morphometric and Fractal Parameters for Rapid Evaluation of In Situ Mammalian Mast Cell Status,” [cited by applicant]
Wolf, et al. “Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society” [cited by applicant]
Wolters, et al. “Tissue-selective mast cell reconstitution and differential lung gene expression in mast cell-deficient KitW-sh/KitWash sash mice” [cited by applicant]
Zhang, et al. “A three-dimensional fractal analysis method for quantifying white matter structure in human brain” [cited by applicant]
Zouien, et al. “Applying fractal dimension and image analysis to quantify fibrotic collagen deposition and organization in the normal and hypertensive heart” [cited by applicant]
Zweig, et al. “Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine” [cited by applicant]