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      Early breast cancer screening using iron/iron oxide-based nanoplatforms with sub-femtomolar limits of detection

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          Summary

          Proteases, including matrix metalloproteinases (MMPs), tissue serine proteases, and cathepsins (CTS) exhibit numerous functions in tumor biology. Solid tumors are characterized by changes in protease expression levels by tumor and surrounding tissue. Therefore, monitoring protease levels in tissue samples and liquid biopsies is a vital strategy for early cancer detection. Water-dispersable Fe/Fe 3O 4-core/shell based nanoplatforms for protease detection are capable of detecting protease activity down to sub-femtomolar limits of detection. They feature one dye (tetrakis(carboxyphenyl)porphyrin (TCPP)) that is tethered to the central nanoparticle by means of a protease-cleavable consensus sequence and a second dye (Cy 5.5) that is directly linked. Based on the protease activities of urokinase plasminogen activator (uPA), MMPs 1, 2, 3, 7, 9, and 13, as well as CTS B and L, human breast cancer can be detected at stage I by means of a simple serum test. By monitoring CTS B and L stage 0 detection may be achieved. This initial study, comprised of 46 breast cancer patients and 20 apparently healthy human subjects, demonstrates the feasibility of protease-activity-based liquid biopsies for early cancer diagnosis.

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          Ki67 Index, HER2 Status, and Prognosis of Patients With Luminal B Breast Cancer

          Maggie C. U. Cheang, Stephen Chia, David Voduc … (2009)
          Background Gene expression profiling of breast cancer has identified two biologically distinct estrogen receptor (ER)-positive subtypes of breast cancer: luminal A and luminal B. Luminal B tumors have higher proliferation and poorer prognosis than luminal A tumors. In this study, we developed a clinically practical immunohistochemistry assay to distinguish luminal B from luminal A tumors and investigated its ability to separate tumors according to breast cancer recurrence-free and disease-specific survival. Methods Tumors from a cohort of 357 patients with invasive breast carcinomas were subtyped by gene expression profile. Hormone receptor status, HER2 status, and the Ki67 index (percentage of Ki67-positive cancer nuclei) were determined immunohistochemically. Receiver operating characteristic curves were used to determine the Ki67 cut point to distinguish luminal B from luminal A tumors. The prognostic value of the immunohistochemical assignment for breast cancer recurrence-free and disease-specific survival was investigated with an independent tissue microarray series of 4046 breast cancers by use of Kaplan–Meier curves and multivariable Cox regression. Results Gene expression profiling classified 101 (28%) of the 357 tumors as luminal A and 69 (19%) as luminal B. The best Ki67 index cut point to distinguish luminal B from luminal A tumors was 13.25%. In an independent cohort of 4046 patients with breast cancer, 2847 had hormone receptor–positive tumors. When HER2 immunohistochemistry and the Ki67 index were used to subtype these 2847 tumors, we classified 1530 (59%, 95% confidence interval [CI] = 57% to 61%) as luminal A, 846 (33%, 95% CI = 31% to 34%) as luminal B, and 222 (9%, 95% CI = 7% to 10%) as luminal–HER2 positive. Luminal B and luminal–HER2-positive breast cancers were statistically significantly associated with poor breast cancer recurrence-free and disease-specific survival in all adjuvant systemic treatment categories. Of particular relevance are women who received tamoxifen as their sole adjuvant systemic therapy, among whom the 10-year breast cancer–specific survival was 79% (95% CI = 76% to 83%) for luminal A, 64% (95% CI = 59% to 70%) for luminal B, and 57% (95% CI = 47% to 69%) for luminal–HER2 subtypes. Conclusion Expression of ER, progesterone receptor, and HER2 proteins and the Ki67 index appear to distinguish luminal A from luminal B breast cancer subtypes.
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            The generalisation of student's problems when several different population variances are involved.

            B L WELCH (1947)
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              Real-time liquid biopsy in cancer patients: fact or fiction?

              Catherine Alix-Panabières, Klaus Pantel (2013)
              Distant metastases harbor unique genomic characteristics not detectable in the corresponding primary tumor of the same patient and metastases located at different sites show a considerable intrapatient heterogeneity. Thus, the mere analysis of the resected primary tumor alone (current standard practice in oncology) or, if possible, even reevaluation of tumor characteristics based on the biopsy of the most accessible metastasis may not reveal sufficient information for treatment decisions. Here, we propose that this dilemma can be solved by a new diagnostic concept: liquid biopsy, that is, analysis of therapeutic targets and drug resistance-conferring gene mutations on circulating tumor cells (CTC) and cell-free circulating tumor DNA (ctDNA) released into the peripheral blood from metastatic deposits. We discuss the current challenges and future perspectives of CTCs and ctDNA as biomarkers in clinical oncology. Both CTCs and ctDNA are interesting complementary technologies that can be used in parallel in future trials assessing new drugs or drug combinations. We postulate that the liquid biopsy concept will contribute to a better understanding and clinical management of drug resistance in patients with cancer.
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                Author and article information

                Contributors
                Gaohong Zhu
                Deryl L Troyer
                Stefan H Bossmann
                Martina Stenzel: Role: Associate Editor
                Journal
                Journal ID (nlm-ta): Beilstein J Nanotechnol
                Journal ID (iso-abbrev): Beilstein J Nanotechnol
                Title: Beilstein Journal of Nanotechnology
                Publisher: Beilstein-Institut (Trakehner Str. 7-9, 60487 Frankfurt am Main, Germany )
                ISSN (Electronic): 2190-4286
                Publication date Collection: 2016
                Publication date (Electronic): 7 March 2016
                Volume: 7
                Pages: 364-373
                Affiliations
                [1 ]Kansas State University, Department of Chemistry, 213 CBC Building, Manhattan, KS, USA
                [2 ]Kansas State University, Department of Anatomy & Physiology, 228 Coles Hall, Manhattan, KS, USA
                [3 ]The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, USA
                [4 ]Kansas State University, Department of Statistics, 101 Dickens Hall, Manhattan, KS, USA
                [5 ]The First Affiliated Hospital of Kunming Medical University, Department of Nuclear Medicine, 295 Xichang Road, Kunming, Yunnan, PR China
                Article
                DOI: 10.3762/bjnano.7.33
                PMC ID: 4901534
                PubMed ID: 27335730
                SO-VID: 38787211-3f54-4553-a549-efc2aabe0994
                Copyright © Copyright © 2016, Udukala et al; licensee Beilstein-Institut.
                License:

                This is an Open Access article under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                The license is subject to the Beilstein Journal of Nanotechnology terms and conditions: ( http://www.beilstein-journals.org/bjnano)

                History
                Date received : 22 December 2015
                Date accepted : 17 February 2016
                Categories
                Subject: Full Research Paper
                Subject: Nanoscience
                Subject: Nanotechnology

                Keywords: biophotonics,breast cancer,iron/iron oxide nanoparticle,liquid biopsy,nanodiagnostics detection,nanomedicine,sub-femtomolar limit of detection
                Data availability:
                Keywords: biophotonics, breast cancer, iron/iron oxide nanoparticle, liquid biopsy, nanodiagnostics detection, nanomedicine, sub-femtomolar limit of detection

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