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New Haven, CT, United States

Dolled-Filhart M.,Historx Inc.
Methods in molecular biology (Clifton, N.J.) | Year: 2010

The analysis of protein expression in tissue by immunohistochemistry (IHC) presents three significant challenges. They are (1) the time-consuming nature of pathologist-based scoring of slides; (2) the need for objective quantification and localization of protein expression; and (3) the need for a highly reproducible measurement to limit intra- and inter-observer variability. While there are a variety of commercially available platforms for automated chromagen-based and fluorescence-based image acquisition of tissue microarrays, this chapter is focused on the analysis of fluorescent images by AQUA(R) analysis (Automated QUantitative Analysis) and the solutions offered by such a method for research and diagnostics. AQUA analysis is a method for molecularly defining regions of interest or "compartments" within a tissue section. The methodology can be utilized with tissue microarrays to provide rapid, quantitative, localized, and reproducible protein expression data that can then be used to identify statistically relevant correlations in populations. Ultimately this allows for a multiplexed, objective and standardized quantitative approach for biomarker research and diagnostic assay development for protein expression in tissue. Source

Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 200.00K | Year: 2008

DESCRIPTION (provided by applicant): Patient-specific therapies targeted to the phenotype of individual tumors represent the future of cancer treatment. The prototypes for this type of therapy are Herceptin and Tamoxifen, which are only given to patients e xpressing a particular level of HER2 and estrogen receptor (ER), respectively. It is likely that dozens of such therapies will be developed for a variety of tumors in the next decade. As with Herceptin and Tamoxifen, the diagnostic test for determining whi ch patients will be given what therapies will most likely involve immunohistochemical (IHC) staining of fixed tumor samples, since the routine HandE slide remains the standard for the anatomic diagnosis. Yet today's immunohistology labs have only the crude st of standards-usually a highly positive and a completely negative cell line or tissue control. The results from such stains are likely only accurate to at best one order of magnitude, even when newer automated quantitative stain readers are used. Further more, no attempt is made to assess the antigenic viability of patient samples. We believe that the future success of targeted therapy will be largely dependent upon the development of robust method of standardization for IHC that can be used to normalize r esults both across laboratories and across analysis platforms. Our goal is to develop a robust, adaptable immunohistochemical standard that can be processed alongside every patient tissue sample. This standard can then be used both to assess tissue antigen ic viability and to permit the quantification of biomarkers at the molecules-per-cell level. Public Health Relevance Statement: Patient-specific therapies represent the future of cancer treatment. Development of such therapies will require consiste nt and quantitative measures of patient tumors. Our goal is to develop robust, adaptable, and quantitative standards that can dramatically improve the analysis of patient tumors. These standards will help determine the most appropriate therapy for a patien t's tumor.

Interestingly, for prognosis, the significant biomarkers for Gefitinib-treated GBM patients (RTOG 0211) appeared to differ compared to historical, RT and non-Gefitinib-treated GBM patients. In Gefitinib-treated patients, those with higher levels of nuclear pAKT driven by PTEN loss, higher levels of nuclear pMAPK, and lower levels of nuclear pmTOR had significantly worse clinical outcomes. In contrast, in non-Gefitinib-treated patients, patients with PTEN-deficiency, and higher levels of EGFRvIII, total EGFR, IGFR1, NFkB and lower levels of nuclear Survivin appeared to have adverse clinical outcomes, highlighting the treatment-dependency of these biomarkers.

Historx Inc. | Date: 2013-07-09

Glioblastoma multiforme (GBM) is an aggressive form of brain cancer. Biomarkers for GBM that provide prognostic and predictive information are useful because they provide the physician valuable information regarding treatment options for GBM. The present invention provides a method to quantify such biomarkers. Thus, the method relates to the quantification of GSK3, S6, CREB, PTEN, AKT and mTOR biomarkers and the use of AQUA analysis to estimate a patients risk and benefit to treatment using an inhibitor of the AGC-family kinase. Unlike traditional IHC, the AQUA system is objective and produces quantitative in situ protein expression data on a continuous scale. The present invention uses the AQUA system to provide a robust and standardized diagnostic assay that can be used in a clinical setting to provide prognostic and predictive information.

UTI Ltd Partnership and Historx Inc. | Date: 2011-12-02

Disclosed herein are methods of identifying suitable patients for postoperative radiotherapy based on the discovery that the quantification of ER, beyond simple positive/negative characterization, can provide valuable predictive information for the treatment of cancer, specifically breast cancer, and more particularly may predict a group more likely to respond to RT and spare patients from a potentially harmful treatment. Furthermore, the true quantification of ER expression provides a continuous recurrence risk assessment for patients being treated with tamoxifen, and therefore the standardization of the data across sites and imaging platforms significantly reduces the misclassification of patients when compared to the current standard by which ER expression is determined.

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