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Szewczyk K, Jiang L, Khawaja H, Miranti CK, Zohar Y. Microfluidic Applications in Prostate Cancer Research. MICROMACHINES 2024; 15:1195. [PMID: 39459070 PMCID: PMC11509716 DOI: 10.3390/mi15101195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 09/13/2024] [Accepted: 09/23/2024] [Indexed: 10/28/2024]
Abstract
Prostate cancer is a disease in which cells in the prostate, a gland in the male reproductive system below the bladder, grow out of control and, among men, it is the second-most frequently diagnosed cancer (other than skin cancer). In recent years, prostate cancer death rate has stabilized and, currently, it is the second-most frequent cause of cancer death in men (after lung cancer). Most deaths occur due to metastasis, as cancer cells from the original tumor establish secondary tumors in distant organs. For a long time, classical cell cultures and animal models have been utilized in basic and applied scientific research, including clinical applications for many diseases, such as prostate cancer, since no better alternatives were available. Although helpful in dissecting cellular mechanisms, these models are poor predictors of physiological behavior mainly because of the lack of appropriate microenvironments. Microfluidics has emerged in the last two decades as a technology that could lead to a paradigm shift in life sciences and, in particular, controlling cancer. Microfluidic systems, such as organ-on-chips, have been assembled to mimic the critical functions of human organs. These microphysiological systems enable the long-term maintenance of cellular co-cultures in vitro to reconstitute in vivo tissue-level microenvironments, bridging the gap between traditional cell cultures and animal models. Several reviews on microfluidics for prostate cancer studies have been published focusing on technology advancement and disease progression. As metastatic castration-resistant prostate cancer remains a clinically challenging late-stage cancer, with no curative treatments, we expanded this review to cover recent microfluidic applications related to prostate cancer research. The review includes discussions of the roles of microfluidics in modeling the human prostate, prostate cancer initiation and development, as well as prostate cancer detection and therapy, highlighting potentially major contributions of microfluidics in the continuous march toward eradicating prostate cancer.
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Affiliation(s)
- Kailie Szewczyk
- Department of Aerospace and Mechanical Engineering, University of Arizona, Tucson, AZ 85721, USA; (K.S.); (L.J.)
| | - Linan Jiang
- Department of Aerospace and Mechanical Engineering, University of Arizona, Tucson, AZ 85721, USA; (K.S.); (L.J.)
| | - Hunain Khawaja
- Cancer Biology Graduate Interdisciplinary Program, University of Arizona, Tucson, AZ 85724, USA;
| | - Cindy K. Miranti
- Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85721, USA;
- University of Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA
| | - Yitshak Zohar
- Department of Aerospace and Mechanical Engineering, University of Arizona, Tucson, AZ 85721, USA; (K.S.); (L.J.)
- University of Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA
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Gao S, Li X, Hu Z, Wang Z, Hao X. Dual targeting negative enrichment strategy for highly sensitive and purity detection of CTCs. Front Chem 2024; 12:1400988. [PMID: 38831912 PMCID: PMC11144890 DOI: 10.3389/fchem.2024.1400988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 04/15/2024] [Indexed: 06/05/2024] Open
Abstract
Circulating tumor cells (CTCs) have significant clinical value in early tumor detection, dynamic monitoring and immunotherapy. CTC detection stands out as a leading non-invasive approach for tumor diagnostics and therapeutics. However, the high heterogeneity of CTCs and the occurrence of epithelial-mesenchymal transition (EMT) during metastasis pose challenges to methods relying on EpCAM-positive enrichment. To address these limitations, a method based on negative enrichment of CTCs using specific leukocyte targets has been developed. In this study, aiming to overcome the low purity associated with immunomagnetic beads targeting solely the leukocyte common antigen CD45, we introduced CD66b-modified immunomagnetic beads. CD66b, a specific target for neutrophils with abundant residues, was chosen as a complementary approach. The process involved initial collection of nucleated cells from whole blood samples using density gradient centrifugation. Subsequently, magnetically labeled leukocytes were removed by magnetic field, enabling the capture of CTCs with higher sensitivity and purity while retaining their activity. Finally, we selected 20 clinical blood samples from patients with various cancers to validate the effectiveness of this strategy, providing a new generalized tool for the clinical detection of CTCs.
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Affiliation(s)
- Siying Gao
- School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan, China
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, China
| | - Xuejie Li
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, China
| | - Zhiyuan Hu
- School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan, China
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, China
- Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
- School of Nanoscience and Technology, SinoDanish College, University of Chinese Academy of Sciences, Beijing, China
| | - Zihua Wang
- Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
| | - Xiaopeng Hao
- Department of General Surgery, First Medical Center of Chinese PLA General Hospital, Beijing, China
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Dhaka S, Tripathi R, Doval DC, Mehta A, Maheshwari U, Koyyala VPB, Singh J. Role of Circulating Tumor Cells in Determining Prognosis in Metastatic Breast Cancer. South Asian J Cancer 2023; 12:62-67. [PMID: 36851934 PMCID: PMC9966169 DOI: 10.1055/s-0042-1753477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2022] Open
Abstract
Dinesh Chandra DovalBackground Circulating tumor cells (CTCs) in the peripheral blood may play a major role in the metastatic spread of breast cancer. This study was conducted to assess the role of CTCs to determine the prognosis in terms of survival in metastatic breast cancer patients. Methods This prospective study of 36 patients was conducted at the Hospital from April 2016 to May 2018. Details of each patient related to the demographic profile, tumor type, treatment, and follow-up information were recorded. The number of CTCs in the peripheral blood was measured by Celsee PREP 400 sample processing system and Celsee Analyzer imaging station. Results There was a positive correlation between the number of site of metastasis with number of CTCs ( p -value < 0.001). In the patients with clinical/partial response, a significant reduction in the number of CTCs after 1 month of therapy was observed ( p -value = 0.003). When the number of CTCs at baseline and 6 months were compared with the positron emission tomography response at 6 months, a statistically significant difference in CTCs in patients having partial response after 6 months was observed ( p -value = 0.001). On comparison with the responder groups, a statistically significant reduction in CTCs at baseline and 6 months was observed ( p -value = 0.001). Patients with CTCs less than 5 and more than or equal to 5 after 1 month of treatment had a mean progression-free survival of 11.1 months and 7.5 months ( p -value = 0.04) and a mean overall survival of 11.6 and 9.6 months ( p -value = 0.08), respectively. Conclusion Assessment of CTCs provides a more quantifiable response than radiographic evaluation and at a much earlier time point and is also a better predictor of survival.
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Affiliation(s)
- Sonia Dhaka
- Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India.,Equal Contribution
| | - Rupal Tripathi
- Department of Research, Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India.,Equal Contribution
| | - Dinesh Chandra Doval
- Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India
| | - Anurag Mehta
- Department of Laboratory Services, Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India
| | - Udip Maheshwari
- Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India
| | | | - Jatinderpal Singh
- Department of Gastroenterology, SGHS Super Speciality Hospital, Mohali, Punjab, India
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He S, Yu S, Wei J, Ding L, Yang X, Wu Y. New horizons in the identification of circulating tumor cells (CTCs): An emerging paradigm shift in cytosensors. Biosens Bioelectron 2022; 203:114043. [PMID: 35121449 DOI: 10.1016/j.bios.2022.114043] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 01/02/2022] [Accepted: 01/24/2022] [Indexed: 12/11/2022]
Abstract
Circulating tumor cells (CTCs) are cancer cells that are shed from a primary tumor into the bloodstream and function as seeds for cancer metastasis at distant locations. Enrichment and identification methods of CTCs in the blood of patients plays an important role in diagnostic assessments and personalized treatments of cancer. However, the current traditional identification methods not only impact the viability of cells, but also cannot determine the type of cancer cells when the disease is unknown. Hence, new methods to identify CTCs are urgently needed. In this context, many advanced and safe technologies have emerged to distinguish between cancer cells and blood cells, and to distinguish specific types of cancer cells. In this review, at first we have briefly discussed recent advances in technologies related to the enrichment of CTCs, which lay a good foundation for the identification of CTCs. Next, we have summarized state-of-the-art technologies to confirm whether a given cell is indeed a tumor cell and determine the type of tumor cell. Finally, the challenges for application and potential directions of the current identification methods in clinical analysis of CTCs have been discussed.
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Affiliation(s)
- Sitian He
- College of Public Health, Zhengzhou University, Zhengzhou, 450001, China
| | - Songcheng Yu
- College of Public Health, Zhengzhou University, Zhengzhou, 450001, China
| | - Jinlan Wei
- College of Public Health, Zhengzhou University, Zhengzhou, 450001, China
| | - Lihua Ding
- College of Public Health, Zhengzhou University, Zhengzhou, 450001, China
| | - Xiaonan Yang
- Institute of Intelligent Sensing, Zhengzhou University, Zhengzhou, 450001, China.
| | - Yongjun Wu
- College of Public Health, Zhengzhou University, Zhengzhou, 450001, China.
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Wen Y, Mensah NN, Song X, Zhu J, Tan WS, Chen X, Li J. A hydrogel with supramolecular surface functionalization for cancer cell capture and multicellular spheroid growth and release. Chem Commun (Camb) 2022; 58:681-684. [PMID: 34919108 DOI: 10.1039/d1cc05846k] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
A hydrogel scaffold with a non-fouling but specific cancer cell-adhesive surface was fabricated through surface modification using β-cyclodextrin-based host-guest chemistry. Interestingly, the hydrogel surface not only selectively captured specific cancer cells, but also grew the cells into multicellular spheroids. The spheroids could be released without damaging the cell viability through replacing the host moieties on the scaffold, and the released spheroids showed no changes in size or morphology.
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Affiliation(s)
- Yuting Wen
- Department of Biomedical Engineering, National University of Singapore, 15 Kent Ridge Crescent, 119276, Singapore.
| | - Nana Nyarko Mensah
- Department of Biomedical Engineering, National University of Singapore, 15 Kent Ridge Crescent, 119276, Singapore.
- Institute of Materials Research and Engineering, A*STAR (Agency for Science, Technology and Research), 2 Fusionopolis Way, 138634, Singapore
| | - Xia Song
- Department of Biomedical Engineering, National University of Singapore, 15 Kent Ridge Crescent, 119276, Singapore.
| | - Jingling Zhu
- Department of Biomedical Engineering, National University of Singapore, 15 Kent Ridge Crescent, 119276, Singapore.
| | - Wui Siew Tan
- Institute of Materials Research and Engineering, A*STAR (Agency for Science, Technology and Research), 2 Fusionopolis Way, 138634, Singapore
| | - Xinwei Chen
- Institute of Materials Research and Engineering, A*STAR (Agency for Science, Technology and Research), 2 Fusionopolis Way, 138634, Singapore
| | - Jun Li
- Department of Biomedical Engineering, National University of Singapore, 15 Kent Ridge Crescent, 119276, Singapore.
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Kalinkova L, Nikolaieva N, Smolkova B, Ciernikova S, Kajo K, Bella V, Kajabova VH, Kosnacova H, Minarik G, Fridrichova I. miR-205-5p Downregulation and ZEB1 Upregulation Characterize the Disseminated Tumor Cells in Patients with Invasive Ductal Breast Cancer. Int J Mol Sci 2021; 23:ijms23010103. [PMID: 35008529 PMCID: PMC8744876 DOI: 10.3390/ijms23010103] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 12/20/2021] [Accepted: 12/21/2021] [Indexed: 12/31/2022] Open
Abstract
Background: Dissemination of breast cancer (BC) cells through the hematogenous or lymphogenous vessels leads to metastatic disease in one-third of BC patients. Therefore, we investigated the new prognostic features for invasion and metastasis. Methods: We evaluated the expression of miRNAs and epithelial-to-mesenchymal transition (EMT) genes in relation to CDH1/E-cadherin changes in samples from 31 patients with invasive ductal BC including tumor centrum (TU-C), tumor invasive front (TU-IF), lymph node metastasis (LNM), and CD45-depleted blood (CD45-DB). Expression of miRNA and mRNA was quantified by RT-PCR arrays and associations with clinico-pathological characteristics were statistically evaluated by univariate and multivariate analysis. Results: We did not verify CDH1 regulating associations previously described in cell lines. However, we did detect extremely high ZEB1 expression in LNMs from patients with distant metastasis, but without regulation by miR-205-5p. Considering the ZEB1 functions, this overexpression indicates enhancement of metastatic potential of lymphogenously disseminated BC cells. In CD45-DB samples, downregulated miR-205-5p was found in those expressing epithelial and/or mesenchymal markers (CTC+) that could contribute to insusceptibility and survival of hematogenously disseminated BC cells mediated by increased expression of several targets including ZEB1. Conclusions: miR-205-5p and potentially ZEB1 gene are promising candidates for markers of metastatic potential in ductal BC.
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Affiliation(s)
- Lenka Kalinkova
- Department of Genetics, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, 84505 Bratislava, Slovakia; (L.K.); (N.N.); (S.C.); (K.K.); (H.K.)
| | - Nataliia Nikolaieva
- Department of Genetics, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, 84505 Bratislava, Slovakia; (L.K.); (N.N.); (S.C.); (K.K.); (H.K.)
| | - Bozena Smolkova
- Department of Molecular Oncology, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, 84505 Bratislava, Slovakia; (B.S.); (V.H.K.)
| | - Sona Ciernikova
- Department of Genetics, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, 84505 Bratislava, Slovakia; (L.K.); (N.N.); (S.C.); (K.K.); (H.K.)
| | - Karol Kajo
- Department of Genetics, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, 84505 Bratislava, Slovakia; (L.K.); (N.N.); (S.C.); (K.K.); (H.K.)
- Department of Pathology, St. Elisabeth Cancer Institute, 81250 Bratislava, Slovakia
| | - Vladimir Bella
- Department of Senology, St. Elisabeth Cancer Institute, 81250 Bratislava, Slovakia;
| | - Viera Horvathova Kajabova
- Department of Molecular Oncology, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, 84505 Bratislava, Slovakia; (B.S.); (V.H.K.)
| | - Helena Kosnacova
- Department of Genetics, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, 84505 Bratislava, Slovakia; (L.K.); (N.N.); (S.C.); (K.K.); (H.K.)
| | - Gabriel Minarik
- Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, 81108 Bratislava, Slovakia;
| | - Ivana Fridrichova
- Department of Genetics, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, 84505 Bratislava, Slovakia; (L.K.); (N.N.); (S.C.); (K.K.); (H.K.)
- Correspondence: ; Tel.: +421-02-32295188
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7
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Yonet-Tanyeri N, Ahlmark BZ, Little SR. Advances in Multiplexed Paper-Based Analytical Devices for Cancer Diagnosis: A Review of Technological Developments. ADVANCED MATERIALS TECHNOLOGIES 2021; 6:2001138. [PMID: 34447879 PMCID: PMC8384263 DOI: 10.1002/admt.202001138] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Indexed: 05/14/2023]
Abstract
Cancer is one of the leading causes of death worldwide producing estimated cost of $161.2 billion in the US in 2017 only. Early detection of cancer would not only reduce cancer mortality rates but also dramatically reduce healthcare costs given that the 17 million new cancer cases in 2018 are estimated to grow 27.5 million new cases by 2040. Analytical devices based upon paper substrates could provide effective, rapid, and extremely low cost alternatives for early cancer detection compared to existing testing methods. However, low concentrations of biomarkers in body fluids as well as the possible association of any given biomarker with multiple diseases remain as one of the greatest challenges to widespread adoption of these paper-based devices. However, recent advances have opened the possibility of detecting multiple biomarkers within the same device, which could be predictive of a patient's condition with unprecedented cost-effectiveness. Accordingly, this review highlights the recent advancements in paper-based analytical devices with a multiplexing focus. The primary areas of interest include lateral flow assay and microfluidic paper-based assay formats, signal amplification approaches to enhance the sensitivity for a specific cancer type, along with current challenges and future outlook for the detection of multiple cancer biomarkers.
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Affiliation(s)
- Nihan Yonet-Tanyeri
- Department of Chemical Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States
| | - Benjamin Z Ahlmark
- Department of Chemical Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States
| | - Steven R Little
- Department of Chemical Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States
- The McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15219, United States
- Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States
- Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States
- Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States
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8
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Local Anesthetics and Recurrence after Cancer Surgery-What's New? A Narrative Review. J Clin Med 2021; 10:jcm10040719. [PMID: 33670434 PMCID: PMC7918400 DOI: 10.3390/jcm10040719] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 01/27/2021] [Accepted: 02/08/2021] [Indexed: 12/16/2022] Open
Abstract
The perioperative use of regional anesthesia and local anesthetics is part of almost every anesthesiologist’s daily clinical practice. Retrospective analyses and results from experimental studies pointed towards a potential beneficial effect of the local anesthetics regarding outcome—i.e., overall and/or recurrence-free survival—in patients undergoing cancer surgery. The perioperative period, where the anesthesiologist is responsible for the patients, might be crucial for the further course of the disease, as circulating tumor cells (shed from the primary tumor into the patient’s bloodstream) might form new micro-metastases independent of complete tumor removal. Due to their strong anti-inflammatory properties, local anesthetics might have a certain impact on these circulating tumor cells, either via direct or indirect measures, for example via blunting the inflammatory stress response as induced by the surgical stimulus. This narrative review highlights the foundation of these principles, features recent experimental and clinical data and provides an outlook regarding current and potential future research activities.
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Viator JA, Hazur M, Sajewski A, Tarhini A, Sanders ME, Edgar RH. Photoacoustic detection of circulating melanoma cells in late stage patients. JOURNAL OF INNOVATIVE OPTICAL HEALTH SCIENCES 2020; 13:2050023. [PMID: 34163541 PMCID: PMC8218985 DOI: 10.1142/s1793545820500236] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Melanoma is the deadliest skin cancer and is responsible for over 7000 deaths in the US annually. The spread of cancer, or metastasis, is responsible for these deaths, as secondary tumors interrupt normal organ function. Circulating tumor cells, or those cells that spread throughout the body from the primary tumor, are thought to be responsible for metastasis. We developed an optical method, photoacoustic flow cytometry, in order to detect and enumerate circulating melanoma cells (CMCs) from blood samples of patients. We tested the blood of Stage IV melanoma patients to show the ability of the photoacoustic flow cytometer to detect these rare cells in blood. We then tested the system on archived blood samples from Stage III melanoma patients with known outcomes to determine if detection of CMCs can predict future metastasis. We detected between 0 and 66 CMCs in Stage IV patients. For the Stage III study, we found that of those samples with CMCs, 2 remained disease free and 5 developed metastasis. Of those without CMCs, 6 remained disease free and 1 developed metastasis. We believe that photoacoustic detection of CMCs provides valuable information for the prediction of metastasis and we postulate a system for more accurate prognosis.
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Affiliation(s)
- John A Viator
- Department of Engineering, Duquesne University, 600 Forbes Avenue Pittsburgh, Pennsylvania 15282, USA
| | - Marc Hazur
- Department of Engineering, Duquesne University, 600 Forbes Avenue Pittsburgh, Pennsylvania 15282, USA
| | - Andrea Sajewski
- Department of Bioengineering, University of Pittsburgh, 3700 O'Hara Street Pittsburgh, PA 15260, USA
| | - Ahmad Tarhini
- Moffitt Comprehensive Cancer Center and Research Institute, 10920 McKinley Drive Tampa, Florida 33612, USA
| | - Martin E Sanders
- Acousys Biodevices Inc, 1777 Highland Drive Ann Arbor, Michigan 48108, USA
| | - Robert H Edgar
- Department of Bioengineering, University of Pittsburgh, 3700 O'Hara Street Pittsburgh, PA 15260, USA
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10
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Liu S, Zhao Y, Xu Y, Sang M, Zhao R, Gu L, Shan B. MAGE-A genes as predictors of the outcome of laryngeal squamous cell carcinoma. Oncol Lett 2020; 20:59. [PMID: 32793312 DOI: 10.3892/ol.2020.11920] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Accepted: 06/29/2020] [Indexed: 01/02/2023] Open
Abstract
Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors in the head and neck area. Melanoma-associated antigens A (MAGE-A) are strictly tumor-specific and are expressed in several types of tumors. To date, no studies have reported the potential of MAGE-A genes as markers for circulating tumor cells (CTCs) in patients with LSCC. The present study aimed to evaluate the expression and the possible prognostic significance of MAGE-A in the peripheral blood of patients with LSCC. In the present study, the expression of MAGE-A genes was determined by multiplex semi-nested PCR and restriction endonuclease treatment of the peripheral blood of patients with LSCC. The association between MAGE-A gene expression and clinicopathological parameters and prognosis was evaluated. The results demonstrated that the expression of MAGE-A was associated with the predictors that indicate poor prognosis. The expression levels of MAGE-A and each individual MAGE-A gene were also associated with a shorter overall survival time of patients with LSCC. In conclusion, the results of the present study suggested that the expression of MAGE-A genes may be a potential prognostic marker for patients with LSCC.
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Affiliation(s)
- Shenghui Liu
- Department of Otolaryngology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China.,Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China
| | - Yan Zhao
- Department of Otolaryngology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China
| | - Yuru Xu
- Department of Otolaryngology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China
| | - Meixiang Sang
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China.,Tumor Research Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China
| | - Ruili Zhao
- Department of Otolaryngology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China
| | - Lina Gu
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China
| | - Baoen Shan
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China.,Tumor Research Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China
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11
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Abstract
With active screening for early detection and advancements in treatment, there has been a significant decrease in mortality from breast cancer. However, a significant proportion of patients with non-metastatic breast cancer at time of diagnosis will relapse. Therefore, it is suggested that the dissemination of bloodstream tumor cells (circulating tumor cells, CTCs) undetectable by currently available diagnostic tools occurs during the early stages of breast cancer progression, and may be the potential source of micrometastases responsible for treatment failures. Here, we review the clinical significance of CTCs, as detected by the FDA-approved CellSearch® System, in both metastatic and non-metastatic breast cancer patients. Studies so far suggest that CTCs are prognostic of poorer outcomes in breast cancer patients; however, there is currently insufficient data to support use of CTC data to guide treatment. Therefore, there are ongoing studies to evaluate the utility of assessing CTC phenotypes to develop personalized breast cancer treatment, which will be reviewed in this chapter.
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12
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An intravenous wire captures rare tumour cells. Nat Biomed Eng 2019; 2:635-636. [PMID: 31015682 DOI: 10.1038/s41551-018-0294-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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13
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Yadav DK, Bai X, Yadav RK, Singh A, Li G, Ma T, Chen W, Liang T. Liquid biopsy in pancreatic cancer: the beginning of a new era. Oncotarget 2018; 9:26900-26933. [PMID: 29928492 PMCID: PMC6003564 DOI: 10.18632/oncotarget.24809] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2017] [Accepted: 02/25/2018] [Indexed: 12/21/2022] Open
Abstract
With dismal survival rate pancreatic cancer remains one of the most aggressive and devastating malignancy. Predominantly, due to the absence of a dependable methodology for early identification and limited therapeutic options for advanced disease. However, it takes over 17 years to develop pancreatic cancer from initiation of mutation to metastatic cancer; therefore, if diagnosed early; it may increase overall survival dramatically, thus, providing a window of opportunity for early detection. Recently, genomic expression analysis defined 4 subtypes of pancreatic cancer based on mutated genes. Hence, we need simple and standard, minimally invasive test that can monitor those altered genes or their associated pathways in time for the success of precision medicine, and liquid biopsy seems to be one answer to all these questions. Again, liquid biopsy has an ability to pair with genomic tests. Additionally, liquid biopsy based development of circulating tumor cells derived xenografts, 3D organoids system, real-time monitoring of genetic mutations by circulating tumor DNA and exosome as the targeted drug delivery vehicle holds lots of potential for the treatment and cure of pancreatic cancer. At present, diagnosis of pancreatic cancer is frantically done on the premise of CA19-9 and radiological features only, which doesn't give a picture of genetic mutations and epigenetic alteration involved. In this manner, the current diagnostic paradigm for pancreatic cancer diagnosis experiences low diagnostic accuracy. This review article discusses the current state of liquid biopsy in pancreatic cancer as diagnostic and therapeutic tools and future perspectives of research in the light of circulating tumor cells, circulating tumor DNA and exosomes.
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Affiliation(s)
- Dipesh Kumar Yadav
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
| | - Xueli Bai
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
| | - Rajesh Kumar Yadav
- Department of Pharmacology, Gandaki Medical College, Tribhuwan University, Institute of Medicine, Pokhara 33700, Nepal
| | - Alina Singh
- Department of Surgery, Bir Hospital, National Academy of Medical Science, Kanti Path, Kathmandu 44600, Nepal
| | - Guogang Li
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
| | - Tao Ma
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
| | - Wei Chen
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
| | - Tingbo Liang
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
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14
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Cui H, Qin Y, Liu GL, Padua GW. MDA-MB-231 and HeLa cells attachment to nanostructured zein surfaces. J BIOACT COMPAT POL 2018. [DOI: 10.1177/0883911518769681] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Detection and characterization of tumor cells are important for cancer diagnosis and therapy. Various surface attachment methods have been proposed for the capture and enumeration of cancer cells, including immunoaffinity and nanostructured surfaces. Zein, a corn protein, has shown good biocompatibility with human liver cells (HL-7702) and mice fibroblasts (NIH3T3). In previous work, it was found that tissue transglutaminase coated on zein substrates enhanced adhesion and spreading of NIH3T3 fibroblast cells. In the present study, cancer cell adhesion to nanostructured zein substrates was investigated. MDA-MB-231 and HeLa cells were used as cancer cell surrogates. MDA-MB-231 cell immobilization was enhanced on zein films, prepared with 80% ethanol, over glass surfaces. The application of tissue transglutaminase onto nanostructured zein substrates further increased cell spreading and adhesion. Cell immobilization increased linearly with the tissue transglutaminase content of the substrate. The effect of substrate morphology was also investigated by seeding cells on electrospun zein fibers. HeLa cell adhesion was also enhanced by zein substrates. This study provided preliminary supporting evidence for developing a zein platform for circulating tumor cells’ immobilization.
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Affiliation(s)
- Hemiao Cui
- Department of Food Science and Human Nutrition, University of Illinois at Urbana–Champaign, Urbana, IL, USA
| | - Ying Qin
- Department of Food Science and Human Nutrition, University of Illinois at Urbana–Champaign, Urbana, IL, USA
| | - Gang L Liu
- Department of Electrical and Computer Engineering, University of Illinois at Urbana–Champaign, Urbana, IL, USA
| | - Graciela W Padua
- Department of Food Science and Human Nutrition, University of Illinois at Urbana–Champaign, Urbana, IL, USA
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15
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Gu L, Sang M, Yin D, Liu F, Wu Y, Liu S, Huang W, Shan B. MAGE-A gene expression in peripheral blood serves as a poor prognostic marker for patients with lung cancer. Thorac Cancer 2018; 9:431-438. [PMID: 29430849 PMCID: PMC5879056 DOI: 10.1111/1759-7714.12571] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Revised: 11/06/2017] [Accepted: 11/06/2017] [Indexed: 12/19/2022] Open
Abstract
Background MAGE‐A genes belong to the cancer/testis antigens family. The prognostic significance of MAGE‐A expression in the peripheral blood of patients with lung cancer is unknown. Therefore, this study evaluated the expression and possible prognostic significance of MAGE‐A in the peripheral blood of patients with lung cancer. Methods In this study, we detected MAGE‐A gene expression in the peripheral blood of 150 patients with lung cancer and 30 healthy donors using multiplex semi‐nested PCR and analyzed their correlation with clinicopathological risk factors. Results MAGE‐A expression was associated with factors indicating poor prognosis. The expression of MAGE‐A and each individual MAGE‐A gene were also associated with low overall survival in patients with lung cancer. Conclusion The expression of MAGE‐A genes in peripheral blood may act as a poor prognostic marker in patients with lung cancer.
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Affiliation(s)
- Lina Gu
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Meixiang Sang
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.,Tumor Research Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Danjing Yin
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Fei Liu
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yunyan Wu
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Shina Liu
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Weina Huang
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Baoen Shan
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.,Tumor Research Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
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16
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A portable optical reader and wall projector towards enumeration of bio-conjugated beads or cells. PLoS One 2017; 12:e0189923. [PMID: 29267367 PMCID: PMC5739450 DOI: 10.1371/journal.pone.0189923] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2017] [Accepted: 12/05/2017] [Indexed: 01/03/2023] Open
Abstract
Measurement of the height of a packed column of cells or beads, which can be direclty related to the number of cells or beads present in a chamber, is an important step in a number of diagnostic assays. For example, haematocrit measurements may rapidly identify anemia or polycthemia. Recently, user-friendly and cost-efficient Lab-on-a-Chip devices have been developed towards isolating and counting cell sub-populations for diagnostic purposes. In this work, we present a low-cost optical module for estimating the filling level of packed magnetic beads within a Lab-on-a-Chip device. The module is compatible with a previously introduced, disposable microfluidic chip for rapid determination of CD4+ cell counts. The device is a simple optical microscope module is manufactured by 3D printing. An objective lens directly interrogates the height of packed beads which are efficiently isolated on the finger-actuated chip. Optionally, an inexpensive, battery-powered Light Emitting Diode may project a shadow of the microfluidic chip at approximately 50-fold magnification onto a nearby surface. The reader is calibrated with the filling levels of known concentrations of paramagnetic beads within the finger actuated chip. Results in direct and projector mode are compared to measurements from a conventional, inverted white-light microscope. All three read-out methods indicate a maximum variation of 6.5% between methods.
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17
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Kim DD, Yang CS, Chae HD, Kwak SG, Jeon CH. Melanoma antigen-encoding gene family member A1-6 and hTERT in the detection of circulating tumor cells following CD45 - depletion and RNA extraction. Oncol Lett 2017; 14:837-843. [PMID: 28693240 PMCID: PMC5494678 DOI: 10.3892/ol.2017.6226] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2016] [Accepted: 03/23/2017] [Indexed: 12/31/2022] Open
Abstract
A total of 76 blood samples from patients without malignant disease and 107 blood samples from patients with malignant disease were investigated for the presence of circulating tumor cells (CTCs). To detect CTCs, hematopoietic cells were removed from the blood samples and different RNA extraction methods were used to amplify the melanoma antigen-encoding gene family member A1-family member A6 (MAGE A1-6) and the human telomerase reverse transcriptase (hTERT) gene as potential CTC markers. Comparison between four methods for extracting RNA from the blood was performed. The samples were enriched by cluster of differentiation 45 (CD45) antibody capturing, and the reverse transcription-quantitative polymerase chain reaction was used to amplify the MAGE A1-6 and hTERT genes. MAGE A1-6 and hTERT gene expression levels were also evaluated in 14 cancer cell lines, and the MAGE A1-6 and hTERT expression levels were 85.7 and 100%, respectively. The RNeasy method demonstrated the most sensitivity in the SNU1 cells mixed with blood, although the differences between methods was non-significant. The positive expression levels of MAGE A1-6 and hTERT was 11.8% in the control group and 58.9% in those with malignant disease. In the 70 patients with colorectal cancer, positive expression levels of MAGE A1-6 or hTERT were significantly higher in stages T3 and T4 compared with in stages T1 and T2. The CTC detection method involving CD45 antibody capture, RNA extraction and MAGE A1-6 and hTERT reverse transcription resulted in good rates of sensitivity and specificity. Thus, the present study concluded that MAGE A1-6 and hTERT genes may be potential and practical markers for CTCs in a clinical setting.
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Affiliation(s)
- Dae-Dong Kim
- Department of Surgery, School of Medicine, Catholic University of Daegu, Daegu 42472, Republic of Korea
| | - Chun-Seok Yang
- Department of Surgery, School of Medicine, Catholic University of Daegu, Daegu 42472, Republic of Korea
| | - Hyun-Dong Chae
- Department of Surgery, School of Medicine, Catholic University of Daegu, Daegu 42472, Republic of Korea
| | - Sang-Gyu Kwak
- Department of Medical Statistics, School of Medicine, Catholic University of Daegu, Daegu 42472, Republic of Korea
| | - Chang-Ho Jeon
- Department of Laboratory Medicine, School of Medicine, Catholic University of Daegu, Daegu 42472, Republic of Korea
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18
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Chakravarthi BVSK, Nepal S, Varambally S. Genomic and Epigenomic Alterations in Cancer. THE AMERICAN JOURNAL OF PATHOLOGY 2017; 186:1724-35. [PMID: 27338107 DOI: 10.1016/j.ajpath.2016.02.023] [Citation(s) in RCA: 138] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/17/2015] [Revised: 01/27/2016] [Accepted: 02/23/2016] [Indexed: 12/20/2022]
Abstract
Multiple genetic and epigenetic events characterize tumor progression and define the identity of the tumors. Advances in high-throughput technologies, like gene expression profiling, next-generation sequencing, proteomics, and metabolomics, have enabled detailed molecular characterization of various tumors. The integration and analyses of these high-throughput data have unraveled many novel molecular aberrations and network alterations in tumors. These molecular alterations include multiple cancer-driving mutations, gene fusions, amplification, deletion, and post-translational modifications, among others. Many of these genomic events are being used in cancer diagnosis, whereas others are therapeutically targeted with small-molecule inhibitors. Multiple genes/enzymes that play a role in DNA and histone modifications are also altered in various cancers, changing the epigenomic landscape during cancer initiation and progression. Apart from protein-coding genes, studies are uncovering the critical regulatory roles played by noncoding RNAs and noncoding regions of the genome during cancer progression. Many of these genomic and epigenetic events function in tandem to drive tumor development and metastasis. Concurrent advances in genome-modulating technologies, like gene silencing and genome editing, are providing ability to understand in detail the process of cancer initiation, progression, and signaling as well as opening up avenues for therapeutic targeting. In this review, we discuss some of the recent advances in cancer genomic and epigenomic research.
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Affiliation(s)
| | - Saroj Nepal
- Department of Pathology and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama
| | - Sooryanarayana Varambally
- Department of Pathology and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama.
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19
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Cordone I, Masi S, Summa V, Carosi M, Vidiri A, Fabi A, Pasquale A, Conti L, Rosito I, Carapella CM, Villani V, Pace A. Overexpression of syndecan-1, MUC-1, and putative stem cell markers in breast cancer leptomeningeal metastasis: a cerebrospinal fluid flow cytometry study. Breast Cancer Res 2017; 19:46. [PMID: 28399903 PMCID: PMC5387324 DOI: 10.1186/s13058-017-0827-4] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2016] [Accepted: 03/03/2017] [Indexed: 01/09/2023] Open
Abstract
Background Cancer is a mosaic of tumor cell subpopulations, where only a minority is responsible for disease recurrence and cancer invasiveness. We focused on one of the most aggressive circulating tumor cells (CTCs) which, from the primitive tumor, spreads to the central nervous system (CNS), evaluating the expression of prognostic and putative cancer stem cell markers in breast cancer (BC) leptomeningeal metastasis (LM). Methods Flow cytometry immunophenotypic analysis of cerebrospinal fluid (CSF) samples (4.5 ml) was performed in 13 consecutive cases of BCLM. Syndecan-1 (CD138), MUC-1 (CD227) CD45, CD34, and the putative cancer stem cell markers CD15, CD24, CD44, and CD133 surface expression were evaluated on CSF floating tumor cells. The tumor-associated leukocyte population was also characterized. Results Despite a low absolute cell number (8 cell/μl, range 1–86), the flow cytometry characterization was successfully conducted in all the samples. Syndecan-1 and MUC-1 overexpression was documented on BC cells in all the samples analyzed; CD44, CD24, CD15, and CD133 in 77%, 75%, 70%, and 45% of cases, respectively. A strong syndecan-1 and MUC-1 expression was also documented by immunohistochemistry on primary breast cancer tissues, performed in four patients. The CSF tumor population was flanked by T lymphocytes, with a different immunophenotype between the CSF and peripheral blood samples (P ≤ 0.02). Conclusions Flow cytometry can be successfully employed for solid tumor LM characterization even in CSF samples with low cell count. This in vivo study documents that CSF floating BC cells overexpress prognostic and putative cancer stem cell biomarkers related to tumor invasiveness, potentially representing a molecular target for circulating tumor cell detection and LM treatment monitoring, as well as a primary target for innovative treatment strategies. The T lymphocyte infiltration, documented in all CSF samples, suggests a possible involvement of the CNS lymphatic system in both lymphoid and cancer cell migration into and out of the meninges, supporting the extension of a new form of cellular immunotherapy to LM. Due to the small number of cases, validation on large cohorts of patients are warranted to confirm these findings and to evaluate the impact and value of these results for diagnosis and management of LM. Electronic supplementary material The online version of this article (doi:10.1186/s13058-017-0827-4) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Iole Cordone
- Regina Elena National Cancer Institute, Clinical Pathology Division, Via Elio Chianesi 53, 00144, Rome, Italy.
| | - Serena Masi
- Regina Elena National Cancer Institute, Clinical Pathology Division, Via Elio Chianesi 53, 00144, Rome, Italy
| | - Valentina Summa
- Regina Elena National Cancer Institute, Clinical Pathology Division, Via Elio Chianesi 53, 00144, Rome, Italy
| | - Mariantonia Carosi
- Regina Elena National Cancer Institute, Histopathology Department, Via Elio Chianesi 53, 00144, Rome, Italy
| | - Antonello Vidiri
- Regina Elena National Cancer Institute, Radiology Department, Via Elio Chianesi 53, 00144, Rome, Italy
| | - Alessandra Fabi
- Regina Elena National Cancer Institute, Medical Oncology Department, Via Elio Chianesi 53, 00144, Rome, Italy
| | - Alessia Pasquale
- Regina Elena National Cancer Institute, Clinical Pathology Division, Via Elio Chianesi 53, 00144, Rome, Italy
| | - Laura Conti
- Regina Elena National Cancer Institute, Clinical Pathology Division, Via Elio Chianesi 53, 00144, Rome, Italy
| | - Immacolata Rosito
- Regina Elena National Cancer Institute, Clinical Pathology Division, Via Elio Chianesi 53, 00144, Rome, Italy
| | - Carmine Maria Carapella
- Regina Elena National Cancer Institute, Neuro-Surgery Department, Via Elio Chianesi 53, 00144, Rome, Italy
| | - Veronica Villani
- Regina Elena National Cancer Institute, Neuro-Oncology Division, Via Elio Chianesi 53, 00144, Rome, Italy
| | - Andrea Pace
- Regina Elena National Cancer Institute, Neuro-Oncology Division, Via Elio Chianesi 53, 00144, Rome, Italy
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20
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Lou HY, Zhao W, Hanson L, Zeng C, Cui Y, Cui B. Dual-Functional Lipid Coating for the Nanopillar-Based Capture of Circulating Tumor Cells with High Purity and Efficiency. LANGMUIR : THE ACS JOURNAL OF SURFACES AND COLLOIDS 2017; 33:1097-1104. [PMID: 28059522 PMCID: PMC8491572 DOI: 10.1021/acs.langmuir.6b03903] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/20/2023]
Abstract
Clinical studies of circulating tumor cells (CTC) have stringent demands for high capture purity and high capture efficiency. Nanostructured surfaces have been shown to significantly increase the capture efficiency yet suffer from low capture purity. Here we introduce a dual-functional lipid coating on nanostructured surfaces. The lipid coating serves both as an effective passivation layer that helps prevent nonspecific cell adhesion and as a functionalized layer for antibody-based specific cell capture. In addition, the fluidity of lipid bilayers enables antibody clustering that enhances the cell-surface interaction for efficient cell capture. As a result, the lipid-coating method helps promote both the capture efficiency and capture purity of nanostructure-based CTC capture.
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Affiliation(s)
- Hsin-Ya Lou
- Department of Chemistry, Stanford University, Stanford, California 94305, United States
| | - Wenting Zhao
- Department of Materials Science and Engineering, Stanford University, Stanford, California 94305, United States
| | - Lindsey Hanson
- Department of Chemistry, Stanford University, Stanford, California 94305, United States
| | - Connie Zeng
- Department of Chemistry, Stanford University, Stanford, California 94305, United States
| | - Yi Cui
- Department of Materials Science and Engineering, Stanford University, Stanford, California 94305, United States
- Stanford Institute for Materials and Energy Sciences, SLAC National Accelerator Laboratory, Menlo Park, California 94025, United States
| | - Bianxiao Cui
- Department of Chemistry, Stanford University, Stanford, California 94305, United States
- Corresponding Author:
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21
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Mendoza A, Torrisi DM, Sell S, Cady NC, Lawrence DA. Grating coupled SPR microarray analysis of proteins and cells in blood from mice with breast cancer. Analyst 2017; 141:704-12. [PMID: 26539568 DOI: 10.1039/c5an01749a] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Biomarker discovery for early disease diagnosis is highly important. Of late, much effort has been made to analyze complex biological fluids in an effort to develop new markers specific for different cancer types. Recent advancements in label-free technologies such as surface plasmon resonance (SPR)-based biosensors have shown promise as a diagnostic tool since there is no need for labeling or separation of cells. Furthermore, SPR can provide rapid, real-time detection of antigens from biological samples since SPR is highly sensitive to changes in surface-associated molecular and cellular interactions. Herein, we report a lab-on-a-chip microarray biosensor that utilizes grating-coupled surface plasmon resonance (GCSPR) and grating-coupled surface plasmon coupled fluorescence (GCSPCF) imaging to detect circulating tumor cells (CTCs) from a mouse model (FVB-MMTV-PyVT). GCSPR and GCSPCF analysis was accomplished by spotting antibodies to surface cell markers, cytokines and stress proteins on a nanofabricated GCSPR microchip and screening blood samples from FVB control mice or FVB-MMTV-PyVT mice with developing mammary carcinomas. A transgenic MMTV-PyVT mouse derived cancer cell line was also analyzed. The analyses indicated that CD24, CD44, CD326, CD133 and CD49b were expressed in both cell lines and in blood from MMTV-PyVT mice. Furthermore, cytokines such as IL-6, IL-10 and TNF-α, along with heat shock proteins HSP60, HSP27, HSc70(HSP73), HSP90 total, HSP70/HSc70, HSP90, HSP70, HSP90 alpha, phosphotyrosine and HSF-1 were overexpressed in MMTV-PyVT mice.
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Affiliation(s)
- A Mendoza
- Wadsworth Center, New York State Department of Health, 150 New Scotland Avenue, Albany, NY 12208, USA
| | - D M Torrisi
- Wadsworth Center, New York State Department of Health, 150 New Scotland Avenue, Albany, NY 12208, USA
| | - S Sell
- Wadsworth Center, New York State Department of Health, 150 New Scotland Avenue, Albany, NY 12208, USA
| | - N C Cady
- SUNY Polytechnic Institute, 257 Fuller Road, Albany, NY 12203, USA.
| | - D A Lawrence
- Wadsworth Center, New York State Department of Health, 150 New Scotland Avenue, Albany, NY 12208, USA
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22
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Alvarez Cubero MJ, Lorente JA, Robles-Fernandez I, Rodriguez-Martinez A, Puche JL, Serrano MJ. Circulating Tumor Cells: Markers and Methodologies for Enrichment and Detection. Methods Mol Biol 2017; 1634:283-303. [PMID: 28819860 DOI: 10.1007/978-1-4939-7144-2_24] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
Cancer is a leading cause of disease worldwide; however, nowadays many points of its initiation processes are unknown. In this chapter, we are focusing on the role of liquid biopsies in cancer detection and progression. CTCs are one of the main components of liquid biopsies, they represent a subset of tumor cells that have acquired the ability to disseminate from the primary tumor and intravasate to the circulatory system. The greatest challenge in the detection of CTCs is their rarity in the blood. Human blood consists of white blood cells (5-10 × 106/mL), red blood cells (5-9 × 109/mL), and platelets (2.5-4 × 108/mL); very few CTCs will be present even in patients with known metastatic disease, with often less than one CTC per mL of blood. CTCs are found in frequencies on the order of 1-10 CTCs per mL of whole blood in patients with metastatic disease, and it is reduced in half for non-metastatic stages. Therefore, accurate methodologies for their capture and analysis are really important. The main aim of the present chapter is to describe different methodologies for CTCs capturing and analysis.
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MESH Headings
- Antibodies, Monoclonal/chemistry
- Antibodies, Monoclonal/metabolism
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/immunology
- Biomarkers, Tumor/metabolism
- Cell Count
- Cell Line, Tumor
- Cell Separation/instrumentation
- Cell Separation/methods
- Cell Survival
- Centrifugation, Density Gradient/methods
- Epithelial Cell Adhesion Molecule/genetics
- Epithelial Cell Adhesion Molecule/immunology
- Epithelial Cell Adhesion Molecule/metabolism
- Epithelial-Mesenchymal Transition/genetics
- Equipment Design
- ErbB Receptors/genetics
- ErbB Receptors/immunology
- ErbB Receptors/metabolism
- Ficoll/chemistry
- Fluorescent Dyes/chemistry
- Humans
- Immunoassay
- Keratins/genetics
- Keratins/immunology
- Keratins/metabolism
- Microfluidic Analytical Techniques/instrumentation
- Neoplasms/blood
- Neoplasms/diagnosis
- Neoplasms/immunology
- Neoplasms/pathology
- Neoplastic Cells, Circulating/immunology
- Neoplastic Cells, Circulating/metabolism
- Neoplastic Cells, Circulating/pathology
- Protein Binding
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Affiliation(s)
- M J Alvarez Cubero
- GENYO. Centre for Genomics and Oncological Research, Pfizer, University of Granada, Andalusian Regional Government, Av. de la Ilustración 114, 18016, Granada, Spain.
| | - J A Lorente
- GENYO. Centre for Genomics and Oncological Research, Pfizer, University of Granada, Andalusian Regional Government, Av. de la Ilustración 114, 18016, Granada, Spain
- Laboratory of Genetic Identification, University of Granada-Dept. of Legal Medicine - Faculty of Medicine, Granada, 18016, Spain
| | - I Robles-Fernandez
- GENYO. Centre for Genomics and Oncological Research, Pfizer, University of Granada, Andalusian Regional Government, Av. de la Ilustración 114, 18016, Granada, Spain
| | - A Rodriguez-Martinez
- GENYO. Centre for Genomics and Oncological Research, Pfizer, University of Granada, Andalusian Regional Government, Av. de la Ilustración 114, 18016, Granada, Spain
- Laboratory of Genetic Identification, University of Granada-Dept. of Legal Medicine - Faculty of Medicine, Granada, 18016, Spain
| | - J L Puche
- Integral Oncology Division, Clinical University Hospitals of Granada, Av. de las Fuerzas Armadas, 2, 18014, Granada, Spain
| | - M J Serrano
- GENYO. Centre for Genomics and Oncological Research, Pfizer, University of Granada, Andalusian Regional Government, Av. de la Ilustración 114, 18016, Granada, Spain
- Integral Oncology Division, Clinical University Hospitals of Granada, Av. de las Fuerzas Armadas, 2, 18014, Granada, Spain
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23
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Enrichment and Detection of Circulating Tumor Cells and Other Rare Cell Populations by Microfluidic Filtration. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 994:119-131. [PMID: 28560671 DOI: 10.1007/978-3-319-55947-6_6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
The current standard methods for isolating circulating tumor cells (CTCs) from blood involve EPCAM-based immunomagnetic approaches. A major disadvantage of these strategies is that CTCs with low EPCAM expression will be missed. Isolation by size using filter membranes circumvents the reliance on this cell surface marker, and can facilitate the capture not only of EPCAM-negative CTCs but other rare cells as well. These cells that are trapped on the filter membrane can be characterized by immunocytochemistry (ICC) , enumerated and profiled to elucidate their clinical significance. In this chapter, we discuss advances in filtration systems to capture rare cells as well as downstream ICC methods to detect and identify these cells. We highlight our recent clinical study demonstrating the feasibility of using a novel method consisting of automated microfluidic filtration and sequential ICC for detection and enumeration of CTCs, as well as circulating mesenchymal cells (CMCs), circulating endothelial cells (CECs), and putative circulating stem cells (CSCs). We hypothesize that simultaneous analysis of circulating rare cells in blood of cancer patients may lead to a better understanding of disease progression and development of resistance to therapy.
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24
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Shields Iv CW, Wang JL, Ohiri KA, Essoyan ED, Yellen BB, Armstrong AJ, López GP. Magnetic separation of acoustically focused cancer cells from blood for magnetographic templating and analysis. LAB ON A CHIP 2016; 16:3833-3844. [PMID: 27713979 DOI: 10.1039/c6lc00719h] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/20/2023]
Abstract
Liquid biopsies hold enormous promise for the next generation of medical diagnoses. At the forefront of this effort, many are seeking to capture, enumerate and analyze circulating tumor cells (CTCs) as a means to prognosticate and develop individualized treatments for cancer. Capturing these rare cells, however, represents a major engineering challenge due to their low abundance, morphology and heterogeneity. A variety of microfluidic tools have been developed to isolate CTCs from drawn blood samples; however, few of these approaches offer a means to separate and analyze cells in an integrated system. We have developed a microfluidic platform comprised of three modules that offers high throughput separation of cancer cells from blood and on-chip organization of those cells for streamlined analyses. The first module uses an acoustic standing wave to rapidly align cells in a contact-free manner. The second module then separates magnetically labeled cells from unlabeled cells, offering purities exceeding 85% for cells and 90% for binary mixtures of synthetic particles. Finally, the third module contains a spatially periodic array of microwells with underlying micromagnets to capture individual cells for on-chip analyses (e.g., staining, imaging and quantification). This array is capable of capturing with accuracies exceeding 80% for magnetically labeled cells and 95% for magnetic particles. Overall, by virtue of its holistic processing of complex biological samples, this system has promise for the isolation and evaluation of rare cancer cells and can be readily extended to address a variety of applications across single cell biology and immunology.
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Affiliation(s)
- C Wyatt Shields Iv
- NSF Research Triangle Materials Research Science and Engineering Center, Duke University, Durham, NC 27708, USA and Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA
| | - Jeffrey L Wang
- Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA
| | - Korine A Ohiri
- NSF Research Triangle Materials Research Science and Engineering Center, Duke University, Durham, NC 27708, USA and Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC 27708, USA
| | - Eric D Essoyan
- Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC 27708, USA
| | - Benjamin B Yellen
- NSF Research Triangle Materials Research Science and Engineering Center, Duke University, Durham, NC 27708, USA and Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA and Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC 27708, USA
| | | | - Gabriel P López
- NSF Research Triangle Materials Research Science and Engineering Center, Duke University, Durham, NC 27708, USA and Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA and Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC 27708, USA and Department of Chemical and Biological Engineering, University of New Mexico, Albuquerque, NM 87131, USA.
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Piegeler T, Beck-Schimmer B. Anesthesia and colorectal cancer – The perioperative period as a window of opportunity? Eur J Surg Oncol 2016; 42:1286-95. [DOI: 10.1016/j.ejso.2016.05.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2016] [Revised: 04/24/2016] [Accepted: 05/05/2016] [Indexed: 12/13/2022] Open
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Imamura T, Komatsu S, Ichikawa D, Kawaguchi T, Miyamae M, Okajima W, Ohashi T, Arita T, Konishi H, Shiozaki A, Morimura R, Ikoma H, Okamoto K, Otsuji E. Liquid biopsy in patients with pancreatic cancer: Circulating tumor cells and cell-free nucleic acids. World J Gastroenterol 2016; 22:5627-5641. [PMID: 27433079 PMCID: PMC4932201 DOI: 10.3748/wjg.v22.i25.5627] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2016] [Revised: 05/25/2016] [Accepted: 06/15/2016] [Indexed: 02/06/2023] Open
Abstract
Despite recent advances in surgical techniques and perioperative management, the prognosis of pancreatic cancer (PCa) remains extremely poor. To provide optimal treatment for each patient with Pca, superior biomarkers are urgently needed in all phases of management from early detection to staging, treatment monitoring, and prognosis. In the blood of patients with cancer, circulating tumor cells (CTCs) and cell-free nucleic acids (cfNAs), such as DNA, mRNA, and noncoding RNA have been recognized. In the recent years, their presence in the blood has encouraged researchers to investigate their potential use as novel blood biomarkers, and numerous studies have demonstrated their potential clinical utility as a biomarker for certain types of cancer. This concept, called “liquid biopsy” has been focused on as a less invasive, alternative approach to cancer tissue biopsy for obtaining genetic and epigenetic aberrations that contribute to oncogenesis and cancer progression. In this article, we review the available literature on CTCs and cfNAs in patients with cancer, particularly focusing on PCa, and discuss future perspectives in this field.
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Bhana S, Wang Y, Huang X. Nanotechnology for enrichment and detection of circulating tumor cells. Nanomedicine (Lond) 2016; 10:1973-90. [PMID: 26139129 DOI: 10.2217/nnm.15.32] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Circulating tumor cells (CTCs) are a hallmark of invasive behavior of cancer, responsible for the development of metastasis. Their detection and analysis have significant impacts in cancer biology and clinical practice. However, CTCs are rare events and contain heterogeneous subpopulations, requiring highly sensitive and specific techniques to identify and capture CTCs with high efficiency. Nanotechnology shows strong promises for CTC enrichment and detection owning to the unique structural and functional properties of nanoscale materials. In this review, we discuss the CTC enrichment and detection technologies based on a variety of functional nanosystems and nanostructured substrates, with the goal to highlight the role of nanotechnology in the advancement of basic and clinical CTC research.
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Affiliation(s)
- Saheel Bhana
- Department of Chemistry, The University of Memphis, Memphis, TN 38152, USA
| | - Yongmei Wang
- Department of Chemistry, The University of Memphis, Memphis, TN 38152, USA
| | - Xiaohua Huang
- Department of Chemistry, The University of Memphis, Memphis, TN 38152, USA
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ANDERGASSEN ULRICH, KÖLBL ALEXANDRAC, MAHNER SVEN, JESCHKE UDO. Real-time RT-PCR systems for CTC detection from blood samples of breast cancer and gynaecological tumour patients (Review). Oncol Rep 2016; 35:1905-15. [DOI: 10.3892/or.2016.4608] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2015] [Accepted: 11/15/2015] [Indexed: 11/06/2022] Open
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Lou XL, Sun J, Gong SQ, Yu XF, Gong R, Deng H. Interaction between circulating cancer cells and platelets: clinical implication. Chin J Cancer Res 2015; 27:450-60. [PMID: 26543331 DOI: 10.3978/j.issn.1000-9604.2015.04.10] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Metastasis is the main cause of cancer-associated mortality. During this complicated process, some cancer cells, also called circulating tumor cells (CTCs), detach from primary sites, enter bloodstream and extravasate at metastatic site. Thrombocytosis is frequently observed in patients with metastatic cancers suggesting the important role of platelets in metastasis. Therefore this review focuses on how platelets facilitate the generation of CTCs, protect them from various host attacks, such as immune assaults, apoptosis and shear stress, and regulate CTCs intravasation/extravasation. Platelet-derived cytokines and receptors are involved in this cascade. Identification the mechanisms underlie platelet-CTCs interactions could lead to the development of new platelet-targeted therapeutic strategy to reduce metastasis.
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Affiliation(s)
- Xiao-Liang Lou
- 1 Molecular Medicine and Genetics Center, 2 Department of Pathology, The Fourth Affiliated Hospital of Nanchang University, Nanchang 330000, China ; 3 Renmin Institute of Forensic Medicine, Nanchang 330000, China
| | - Jian Sun
- 1 Molecular Medicine and Genetics Center, 2 Department of Pathology, The Fourth Affiliated Hospital of Nanchang University, Nanchang 330000, China ; 3 Renmin Institute of Forensic Medicine, Nanchang 330000, China
| | - Shu-Qi Gong
- 1 Molecular Medicine and Genetics Center, 2 Department of Pathology, The Fourth Affiliated Hospital of Nanchang University, Nanchang 330000, China ; 3 Renmin Institute of Forensic Medicine, Nanchang 330000, China
| | - Xue-Feng Yu
- 1 Molecular Medicine and Genetics Center, 2 Department of Pathology, The Fourth Affiliated Hospital of Nanchang University, Nanchang 330000, China ; 3 Renmin Institute of Forensic Medicine, Nanchang 330000, China
| | - Rui Gong
- 1 Molecular Medicine and Genetics Center, 2 Department of Pathology, The Fourth Affiliated Hospital of Nanchang University, Nanchang 330000, China ; 3 Renmin Institute of Forensic Medicine, Nanchang 330000, China
| | - Huan Deng
- 1 Molecular Medicine and Genetics Center, 2 Department of Pathology, The Fourth Affiliated Hospital of Nanchang University, Nanchang 330000, China ; 3 Renmin Institute of Forensic Medicine, Nanchang 330000, China
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Court CM, Ankeny JS, Hou S, Tseng HR, Tomlinson JS. Improving pancreatic cancer diagnosis using circulating tumor cells: prospects for staging and single-cell analysis. Expert Rev Mol Diagn 2015; 15:1491-504. [PMID: 26390158 DOI: 10.1586/14737159.2015.1091311] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Pancreatic cancer (PC) is the fourth most common cause of cancer-related death in the USA, primarily due to late presentation coupled with an aggressive biology. The lack of adequate biomarkers for diagnosis and staging confound clinical decision-making and delay potentially effective therapies. Circulating tumor cells (CTCs) are a promising new biomarker in PC. Preliminary studies have demonstrated their potential clinical utility, and newer CTC isolation platforms have the potential to provide clinicians access to tumor tissue in a reliable, real-time manner. Such a 'liquid biopsy' has been demonstrated in several cancers, and small studies have demonstrated its potential applications in PC. This article reviews the available literature on CTCs as a biomarker in PC and presents the latest innovations in CTC research as well as their potential applications in PC.
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Affiliation(s)
- Colin M Court
- a 1 Department of Surgery, University of California , Los Angeles, USA.,b 2 VA Greater, Healthcare System , Los Angeles, USA
| | - Jacob S Ankeny
- a 1 Department of Surgery, University of California , Los Angeles, USA.,b 2 VA Greater, Healthcare System , Los Angeles, USA
| | - Shuang Hou
- a 1 Department of Surgery, University of California , Los Angeles, USA
| | - Hsian-Rong Tseng
- c 3 Department of Molecular and Medical Pharmacology, University of California , Los Angeles, USA
| | - James S Tomlinson
- a 1 Department of Surgery, University of California , Los Angeles, USA.,b 2 VA Greater, Healthcare System , Los Angeles, USA.,d 4 Center for Pancreatic Diseases, University of California , Los Angeles, USA
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31
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Hung JJ, Lin CC, Yang SH, Chen WS. Impact of circulating tumor cells in colorectal cancer patients undergoing laparoscopic surgery. World J Surg Proced 2015; 5:75-81. [DOI: 10.5412/wjsp.v5.i1.75] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2014] [Revised: 12/15/2014] [Accepted: 01/12/2015] [Indexed: 02/06/2023] Open
Abstract
Laparoscopic surgery has recently been widely used for various benign colorectal diseases as well as colorectal cancer. Although laparoscopic surgery has been shown to be with similar prognostic results for certain groups of colorectal cancer patients. The influence of laparoscopic procedures on the oncologist results, especially free tumor cell spreading is still a concern for some surgeons. Tumor cells found in the peripheral blood of patients with cancer are termed circulating tumor cells (CTCs). Presence of CTCs in the peripheral blood of patients with colorectal cancer has been reported to be associated with disease stage, poor prognosis, tumor progression, response to therapy, and drug resistance. Whether laparoscopic procedure enhances tumor spreading during operation remains unknown. Significantly less CTC detected during laparoscopic surgery than open surgery for colorectal cancer has been reported. In our previous experience, no significant elevation in CTC level was found in most patients during laparoscopic resection of colorectal cancer. We have shown that laparoscopic surgery had no significantly deleterious effect on CTCs in colorectal cancer patients. In this review, we aim at the impact of CTCs in patients with colorectal cancer undergoing laparoscopic surgery. The prognostic significance of CTCs in patients with colorectal cancer will also be addressed.
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Zhang J, Li S, Liu F, Zhou L, Shao N, Zhao X. SELEX aptamer used as a probe to detect circulating tumor cells in peripheral blood of pancreatic cancer patients. PLoS One 2015; 10:e0121920. [PMID: 25799539 PMCID: PMC4370620 DOI: 10.1371/journal.pone.0121920] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2014] [Accepted: 02/05/2015] [Indexed: 12/27/2022] Open
Abstract
Many studies have shown that the quantity and dynamics of circulating tumor cells (CTCs) in peripheral blood of patients afflicted with solid tumours have great relevance in therapeutic efficacy and prognosis. Different methods based on various strategies have been developed to isolate and identify CTCs, but their efficacy needs to be improved because of the rarity and complexity of CTCs. This study was designed to examine the possibility of using a SELEX aptamer (BC-15) as a probe to identify rare CTCs out of background nucleated cells. Aptamer BC-15 was selected from a random oligonucleotide library screened against human breast cancer tissue. Fluorescence staining showed that BC-15 had a high affinity for nuclei of human cancer cell lines of various origins as well as CTCs isolated from pancreatic cancer patients, whereas its binding capacity for non-tumor breast epithelial cells and leukocytes was almost undetectable. BC-15+/CD45- cells in cancer patient blood were also found to be cytokeratins 18-positive and aneuploid by immunofluorescence staining and fluorescent in situ hybridization, respectively. Finally, the aptamer method was compared with the well-established anti-cytokeratin method using 15 pancreatic cancer patient blood samples, and enumeration indicated no difference between these two methods. Our study establishes a novel way to identify CTCs by using a synthetic aptamer probe. This new approach is comparable with the anti-cytokeratin-based CTC identification method.
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Affiliation(s)
- Jinqiang Zhang
- State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shaohua Li
- Department of Biochemistry and Molecular Biology, Beijing Institute of Basic Medical Sciences, Beijing, China
| | - Fang Liu
- State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lanping Zhou
- State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ningsheng Shao
- Department of Biochemistry and Molecular Biology, Beijing Institute of Basic Medical Sciences, Beijing, China
| | - Xiaohang Zhao
- State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- * E-mail:
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Toss A, Mu Z, Fernandez S, Cristofanilli M. CTC enumeration and characterization: moving toward personalized medicine. ANNALS OF TRANSLATIONAL MEDICINE 2014; 2:108. [PMID: 25489582 DOI: 10.3978/j.issn.2305-5839.2014.09.06] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 06/20/2014] [Accepted: 08/28/2014] [Indexed: 12/27/2022]
Abstract
The primary cause of tumor-related death in breast cancer (BC) is still represented by distant metastasization. The dissemination of tumor cells from the primary tumor to distant sites through bloodstream cannot be early detected by standard imaging methods. The enumeration of circulating tumor cells (CTCs) represents an effective prognostic and predictive biomarker, which is able to monitor efficacy of adjuvant therapies, detect early development of (micro)metastases and at last, assess therapeutic responses of advanced disease earlier than traditional imaging methods. Moreover, since repeated tissue biopsies are invasive, costly and not always feasible, the assessment of tumor characteristics on CTCs, by a peripheral blood sample as a 'liquid biopsy', represents an attractive opportunity. The implementation of molecular and genomic characterization of CTCs could contribute to improve the treatment selection and thus, to move toward more personalized treatments. This review describes the current state of the art on CTC detection strategies, the evidence to demonstrate their clinical validity, and their potential impact for both future clinical trial design and, decision-making process in our daily practice.
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Affiliation(s)
- Angela Toss
- 1 Department of Oncology, Haematology and Respiratory Diseases, University of Modena and Reggio Emilia, Modena, Italy ; 2 Department of Medical Oncology, Thomas Jefferson University & Kimmel Cancer Center, Philadelphia, PA, USA
| | - Zhaomei Mu
- 1 Department of Oncology, Haematology and Respiratory Diseases, University of Modena and Reggio Emilia, Modena, Italy ; 2 Department of Medical Oncology, Thomas Jefferson University & Kimmel Cancer Center, Philadelphia, PA, USA
| | - Sandra Fernandez
- 1 Department of Oncology, Haematology and Respiratory Diseases, University of Modena and Reggio Emilia, Modena, Italy ; 2 Department of Medical Oncology, Thomas Jefferson University & Kimmel Cancer Center, Philadelphia, PA, USA
| | - Massimo Cristofanilli
- 1 Department of Oncology, Haematology and Respiratory Diseases, University of Modena and Reggio Emilia, Modena, Italy ; 2 Department of Medical Oncology, Thomas Jefferson University & Kimmel Cancer Center, Philadelphia, PA, USA
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Pukazhendhi G, Glück S. Circulating tumor cells in breast cancer. J Carcinog 2014; 13:8. [PMID: 25191136 PMCID: PMC4141360 DOI: 10.4103/1477-3163.135578] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2014] [Accepted: 06/05/2014] [Indexed: 11/08/2022] Open
Abstract
Circulating tumor cell (CTC) measurement in peripheral blood of patients with breast cancer offers prognostic information. In this review, we will try to identify evidence that could be used for prognosis, predictive power to draw this tool to clinical utility. We reviewed 81 manuscripts, and categorized those in discovery datasets, prognostic factors in metastatic breast cancer, identification of clinical utility in early breast cancer and in novel approaches. With each patient responding differently to chemotherapy, more efficient markers would improve clinical outcome. Current CTC diagnostic techniques use epithelial markers predominantly; however, the most appropriate method is the measurement of circulating DNA. It has been hypothesized that micrometastasis occurs early in the development of tumors. That implies the presence of CTCs in nonmetastatic setting. The origin of stimulus for malignant transformation is yet unknown. The role of microenvironment as a stimulus is also being investigated. It has been shown that CTCs vary in numbers with chemotherapy. The markers, which are followed-up in the primary tumors, are also being studied on the CTCs. There is discordance of the human epidermal growth factor receptor-2 status between the primary tumor and CTCs. This review summarizes our current knowledge about the CTCs. With genetic profiling and molecular characterization of CTCs, it is possible to overcome the diagnostic difficulties. Evidence for clinical utility of CTC as prognostic and predictive marker is increasing. Appropriate patient stratification according to CTC determination among other tests, would make personalized cancer therapy more feasible.
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Affiliation(s)
- Geetha Pukazhendhi
- Department of Medicine, Hematology Oncology Division, Miller School of Medicine, Miami, FL, USA
| | - Stefan Glück
- Department of Medicine, Hematology Oncology Division, Miller School of Medicine, Miami, FL, USA ; Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA
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King JD, Casavant BP, Lang JM. Rapid translation of circulating tumor cell biomarkers into clinical practice: technology development, clinical needs and regulatory requirements. LAB ON A CHIP 2014; 14:24-31. [PMID: 24190548 DOI: 10.1039/c3lc50741f] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/11/2023]
Abstract
The great hope in circulating tumor cell (CTC) research lies in the use of these rare cells as an accessible "fluid biopsy" that would permit frequent, minimally invasive sampling of tumor cells for similar molecular assays that are performed on traditional biopsies. Given the rarity of CTCs in peripheral circulation, microscale methods show great promise and superiority to capture and analyze these cells from patients with solid tumors. Novel technologies that produce validated CTC biomarkers may finally provide medical oncologists the tools needed to provide precise, personalized medical care for patients with advanced cancer. However, few CTC technologies demonstrate both experimental and clinical evidence of an accurate, reliable and reproducible assay that also meets the regulatory requirements to enter routine clinical practice. Many opportunities exist to incorporate clinical needs and regulatory benchmarks into technology development to more quickly garner FDA approval to direct decisions on patient care. This review will address: 1) device development tailored to address predictive, prognostic and/or therapeutic needs across the multitude of malignancies and disease stages; 2) validation benchmarks for clinical assay development; 3) early establishment of standard operating procedures for sample acquisition and analysis; 4) demonstration of clinical utility; 5) clinical qualification of a novel biomarker; and 6) integration of a newly validated and qualified technology into routine clinical practice. Early understanding and incorporation of these regulatory requirements into assay development can simplify and speed the integration of these novel technologies into patient care. Meeting these benchmarks will lead to the true personalization of cancer therapies, directing initial and subsequent treatments for each individual based on initial tumor characteristics while monitoring for emerging mechanisms of resistance in these continually evolving tumors.
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Affiliation(s)
- Jonathan D King
- Department of Medicine, Wisconsin Institutes for Medical Research, University of Wisconsin, 1111 Highland Ave., Madison, WI 53705, USA.
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36
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de Wit S, van Dalum G, Terstappen LWMM. Detection of circulating tumor cells. SCIENTIFICA 2014; 2014:819362. [PMID: 25133014 PMCID: PMC4124199 DOI: 10.1155/2014/819362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/02/2014] [Accepted: 05/17/2014] [Indexed: 05/11/2023]
Abstract
The increasing number of treatment options for patients with metastatic carcinomas has created an accompanying need for methods to determine if the tumor will be responsive to the intended therapy and to monitor its effectiveness. Ideally, these methods would be noninvasive and provide quantitative real-time analysis of tumor activity in a variety of carcinomas. Assessment of circulating tumor cells shed into the blood during metastasis may satisfy this need. Here we review the CellSearch technology used for the detection of circulating tumor cells and discuss potential future directions for improvements.
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Affiliation(s)
- Sanne de Wit
- Department of Medical Cell BioPhysics, Faculty of Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Carre, Room C4437, Hallenweg 23, 7522 NH Enschede, The Netherlands
| | - Guus van Dalum
- Department of Medical Cell BioPhysics, Faculty of Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Carre, Room C4437, Hallenweg 23, 7522 NH Enschede, The Netherlands
| | - Leon W. M. M. Terstappen
- Department of Medical Cell BioPhysics, Faculty of Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Carre, Room C4437, Hallenweg 23, 7522 NH Enschede, The Netherlands
- *Leon W. M. M. Terstappen:
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38
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Sang M, Wu X, Fan X, Sang M, Zhou X, Zhou N. Multiple MAGE-A genes as surveillance marker for the detection of circulating tumor cells in patients with ovarian cancer. Biomarkers 2013; 19:34-42. [PMID: 24320162 DOI: 10.3109/1354750x.2013.865275] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Ovarian cancer is a leading cause of death among gynecologic malignancies. In this study, we reported the expression of melanoma-associated antigens A (MAGE-A) genes in peripheral blood from 80 patients with ovarian cancer and 30 healthy donors. MAGE-As expression was associated with the factors indicating poor prognosis. The expressions of MAGE-As and each individual MAGE-A genes were also associated with low overall survival of patients with ovarian cancer. Our results suggested MAGE-A genes may have the potential to be surveillance markers for the detection of circulating tumor cells and represent a poor prognosis for patients with ovarian cancer.
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Affiliation(s)
- Meixiang Sang
- Department of Obstetrics and Gynecology, Bethune International Peace Hospital , Shijiazhuang, Hebei , People's Republic of China
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Barradas AMC, Terstappen LWMM. Towards the Biological Understanding of CTC: Capture Technologies, Definitions and Potential to Create Metastasis. Cancers (Basel) 2013; 5:1619-42. [PMID: 24305653 PMCID: PMC3875957 DOI: 10.3390/cancers5041619] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2013] [Revised: 10/03/2013] [Accepted: 10/22/2013] [Indexed: 12/14/2022] Open
Abstract
Circulating Tumor Cells (CTC) are rare cells originated from tumors that travel into the blood stream, extravasate to different organs of which only a small fraction will develop into metastasis. The presence of CTC enumerated with the CellSearch system is associated with a relative short survival and their continued presence after the first cycles of therapy indicates a futile therapy in patients with metastatic carcinomas. Detailed characterization of CTC holds the promise to enable the choice of the optimal therapy for the individual patients during the course of the disease. The phenotype, physical and biological properties are however not well understood making it difficult to assess the merit of recent technological advancements to improve upon the capture of CTC or to evaluate their metastatic potential. Here we will discuss the recent advances in the classification of CTC captured by the CellSearch system, the implications of their features and numbers. Latest capture platforms are reviewed and placed in the light of technology improvements needed to detect CTC. Physical properties, phenotype, viability and proliferative potential and means to assess their proliferation and metastatic capacity will be summarized and placed in the context of the latest CTC capture platforms.
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Affiliation(s)
- Ana M C Barradas
- Department of Medical Cell Biophysics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, PO Box 217, Enschede 7500AE, The Netherlands.
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Abstract
During metastasis, cancer cells disseminate to other parts of the body by entering the bloodstream in a process that is called intravasation. They then extravasate at metastatic sites by attaching to endothelial cells that line blood vessels and crossing the vessel walls of tissues or organs. This Review describes how cancer cells cross the endothelial barrier during extravasation and how different receptors, signalling pathways and circulating cells such as leukocytes and platelets contribute to this process. Identification of the mechanisms that underlie cancer cell extravasation could lead to the development of new therapies to reduce metastasis.
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Affiliation(s)
- Nicolas Reymond
- 1] Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, UK. [2] Centre de Recherche de Biochimie Macromoléculaire, Centre National de la Recherche Scientifique (CNRS) - UMR5237, 1919 Route de Mende, 34293 Montpellier, Cedex 5, France. [3]
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Broersen LHA, van Pelt GW, Tollenaar RAEM, Mesker WE. Clinical application of circulating tumor cells in breast cancer. Cell Oncol (Dordr) 2013; 37:9-15. [PMID: 24249155 DOI: 10.1007/s13402-013-0160-6] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/01/2013] [Indexed: 01/05/2023] Open
Abstract
Circulating tumor cells (CTCs) play a major role in the metastatic spread of breast cancer. CTC detection has proven to be an important parameter for predicting progression free and overall survival. Collection of CTCs is minimally invasive and can be performed more often than disseminated tumor cell (DTC) collection from bone marrow, thus providing a real-time "liquid biopsy". In this review, the most important techniques for enrichment and detection of CTCs are discussed for clinical application in low and higher staged breast cancer, as well as the genetic and molecular characterization of CTCs. For CTCs, the use of immunology-based enrichment techniques with multiple antibodies is recommended in a clinical setting, as well as the use of cytometric detection techniques, combined with RT-PCR for confirmation. Special attention is given to the value of cancer stem cell (CSC) activity, which may be the main cause of ineffectiveness of the control over metastatic lesions due to intratumor heterogeneity. Accumulating information on CSCs offers new paradigms to generate effective targets for the treatment of metastatic disease. Genetic and molecular characterization of CTCs has potential to stratify patients for optimal personalized treatment regimens. CTCs can be used for monitoring patients during treatment schedules.
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Affiliation(s)
- Leonie H A Broersen
- Department of Surgery, Leiden University Medical Center, Albinusdreef 2, P.O. Box 9600, 2300 RC, Leiden, The Netherlands
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Torino F, Bonmassar E, Bonmassar L, De Vecchis L, Barnabei A, Zuppi C, Capoluongo E, Aquino A. Circulating tumor cells in colorectal cancer patients. Cancer Treat Rev 2013; 39:759-72. [PMID: 23375250 DOI: 10.1016/j.ctrv.2012.12.007] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2012] [Revised: 12/10/2012] [Accepted: 12/12/2012] [Indexed: 12/11/2022]
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Eccles SA, Aboagye EO, Ali S, Anderson AS, Armes J, Berditchevski F, Blaydes JP, Brennan K, Brown NJ, Bryant HE, Bundred NJ, Burchell JM, Campbell AM, Carroll JS, Clarke RB, Coles CE, Cook GJR, Cox A, Curtin NJ, Dekker LV, dos Santos Silva I, Duffy SW, Easton DF, Eccles DM, Edwards DR, Edwards J, Evans DG, Fenlon DF, Flanagan JM, Foster C, Gallagher WM, Garcia-Closas M, Gee JMW, Gescher AJ, Goh V, Groves AM, Harvey AJ, Harvie M, Hennessy BT, Hiscox S, Holen I, Howell SJ, Howell A, Hubbard G, Hulbert-Williams N, Hunter MS, Jasani B, Jones LJ, Key TJ, Kirwan CC, Kong A, Kunkler IH, Langdon SP, Leach MO, Mann DJ, Marshall JF, Martin LA, Martin SG, Macdougall JE, Miles DW, Miller WR, Morris JR, Moss SM, Mullan P, Natrajan R, O’Connor JPB, O’Connor R, Palmieri C, Pharoah PDP, Rakha EA, Reed E, Robinson SP, Sahai E, Saxton JM, Schmid P, Smalley MJ, Speirs V, Stein R, Stingl J, Streuli CH, Tutt ANJ, Velikova G, Walker RA, Watson CJ, Williams KJ, Young LS, Thompson AM. Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer. Breast Cancer Res 2013; 15:R92. [PMID: 24286369 PMCID: PMC3907091 DOI: 10.1186/bcr3493] [Citation(s) in RCA: 287] [Impact Index Per Article: 23.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2013] [Accepted: 09/12/2013] [Indexed: 02/08/2023] Open
Abstract
INTRODUCTION Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years.
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Affiliation(s)
- Suzanne A Eccles
- The Institute of Cancer Research, 15 Cotswold Road, London SM2 5MG, UK
| | - Eric O Aboagye
- Imperial College London, Exhibition Rd, London SW7 2AZ, UK
| | - Simak Ali
- Imperial College London, Exhibition Rd, London SW7 2AZ, UK
| | | | - Jo Armes
- Kings College London, Strand, London WC2R 2LS, UK
| | | | - Jeremy P Blaydes
- University of Southampton, University Road, Southampton SO17 1BJ, UK
| | - Keith Brennan
- University of Manchester, Oxford Road, Manchester M13 9PL, UK
| | - Nicola J Brown
- University of Sheffield, Western Bank, Sheffield S10 2TN, UK
| | - Helen E Bryant
- University of Sheffield, Western Bank, Sheffield S10 2TN, UK
| | - Nigel J Bundred
- University of Manchester, Oxford Road, Manchester M13 9PL, UK
| | | | | | - Jason S Carroll
- Cancer Research UK, Cambridge Research Institute/University of Cambridge, Trinity Lane, Cambridge CB2 1TN, UK
| | - Robert B Clarke
- University of Manchester, Oxford Road, Manchester M13 9PL, UK
| | - Charlotte E Coles
- Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge CB2 0QQ, UK
| | - Gary JR Cook
- Kings College London, Strand, London WC2R 2LS, UK
| | - Angela Cox
- University of Sheffield, Western Bank, Sheffield S10 2TN, UK
| | - Nicola J Curtin
- Newcastle University, Claremont Road, Newcastle upon Tyne NE1 7RU, UK
| | | | | | - Stephen W Duffy
- Queen Mary University of London, Mile End Road, London E1 4NS, UK
| | - Douglas F Easton
- Cancer Research UK, Cambridge Research Institute/University of Cambridge, Trinity Lane, Cambridge CB2 1TN, UK
| | - Diana M Eccles
- University of Southampton, University Road, Southampton SO17 1BJ, UK
| | - Dylan R Edwards
- University of East Anglia, Earlham Road, Norwich NR4 7TJ, UK
| | - Joanne Edwards
- University of Glasgow, University Avenue, Glasgow G12 8QQ, UK
| | - D Gareth Evans
- University of Manchester, Oxford Road, Manchester M13 9PL, UK
| | - Deborah F Fenlon
- University of Southampton, University Road, Southampton SO17 1BJ, UK
| | | | - Claire Foster
- University of Southampton, University Road, Southampton SO17 1BJ, UK
| | | | | | - Julia M W Gee
- University of Cardiff, Park Place, Cardiff CF10 3AT, UK
| | - Andy J Gescher
- University of Leicester, University Road, Leicester LE1 4RH, UK
| | - Vicky Goh
- Kings College London, Strand, London WC2R 2LS, UK
| | - Ashley M Groves
- University College London, Gower Street, London WC1E 6BT, UK
| | | | - Michelle Harvie
- University of Manchester, Oxford Road, Manchester M13 9PL, UK
| | - Bryan T Hennessy
- Royal College of Surgeons Ireland, 123, St Stephen’s Green, Dublin 2, Ireland
| | | | - Ingunn Holen
- University of Sheffield, Western Bank, Sheffield S10 2TN, UK
| | - Sacha J Howell
- University of Manchester, Oxford Road, Manchester M13 9PL, UK
| | - Anthony Howell
- University of Manchester, Oxford Road, Manchester M13 9PL, UK
| | | | | | | | - Bharat Jasani
- University of Cardiff, Park Place, Cardiff CF10 3AT, UK
| | - Louise J Jones
- Queen Mary University of London, Mile End Road, London E1 4NS, UK
| | - Timothy J Key
- University of Oxford, Wellington Square, Oxford OX1 2JD, UK
| | - Cliona C Kirwan
- University of Manchester, Oxford Road, Manchester M13 9PL, UK
| | - Anthony Kong
- University of Oxford, Wellington Square, Oxford OX1 2JD, UK
| | - Ian H Kunkler
- University of Edinburgh, South Bridge, Edinburgh EH8 9YL, UK
| | - Simon P Langdon
- University of Edinburgh, South Bridge, Edinburgh EH8 9YL, UK
| | - Martin O Leach
- The Institute of Cancer Research, 15 Cotswold Road, London SM2 5MG, UK
| | - David J Mann
- Imperial College London, Exhibition Rd, London SW7 2AZ, UK
| | - John F Marshall
- Queen Mary University of London, Mile End Road, London E1 4NS, UK
| | - Lesley Ann Martin
- The Institute of Cancer Research, 15 Cotswold Road, London SM2 5MG, UK
| | - Stewart G Martin
- University of Nottingham, University Park, Nottingham NG7 2RD, UK
| | | | | | | | | | - Sue M Moss
- Queen Mary University of London, Mile End Road, London E1 4NS, UK
| | - Paul Mullan
- Queen’s University Belfast, University Road, Belfast BT7 1NN, UK
| | - Rachel Natrajan
- The Institute of Cancer Research, 15 Cotswold Road, London SM2 5MG, UK
| | | | | | - Carlo Palmieri
- The University of Liverpool, Brownlow Hill, Liverpool L69 7ZX, UK
| | - Paul D P Pharoah
- Cancer Research UK, Cambridge Research Institute/University of Cambridge, Trinity Lane, Cambridge CB2 1TN, UK
| | - Emad A Rakha
- University of Nottingham, University Park, Nottingham NG7 2RD, UK
| | - Elizabeth Reed
- Princess Alice Hospice, West End Lane, Esher KT10 8NA, UK
| | - Simon P Robinson
- The Institute of Cancer Research, 15 Cotswold Road, London SM2 5MG, UK
| | - Erik Sahai
- London Research Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK
| | - John M Saxton
- University of East Anglia, Earlham Road, Norwich NR4 7TJ, UK
| | - Peter Schmid
- Brighton and Sussex Medical School, University of Sussex, Brighton, East Sussex BN1 9PX, UK
| | | | | | - Robert Stein
- University College London, Gower Street, London WC1E 6BT, UK
| | - John Stingl
- Cancer Research UK, Cambridge Research Institute/University of Cambridge, Trinity Lane, Cambridge CB2 1TN, UK
| | | | | | | | | | - Christine J Watson
- Cancer Research UK, Cambridge Research Institute/University of Cambridge, Trinity Lane, Cambridge CB2 1TN, UK
| | - Kaye J Williams
- University of Manchester, Oxford Road, Manchester M13 9PL, UK
| | - Leonie S Young
- Royal College of Surgeons Ireland, 123, St Stephen’s Green, Dublin 2, Ireland
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Wang H, Chen NG, Minev BR, Zimmermann M, Aguilar RJ, Zhang Q, Sturm JB, Fend F, Yu YA, Cappello J, Lauer UM, Szalay AA. Optical detection and virotherapy of live metastatic tumor cells in body fluids with vaccinia strains. PLoS One 2013; 8:e71105. [PMID: 24019862 PMCID: PMC3760980 DOI: 10.1371/journal.pone.0071105] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2013] [Accepted: 06/25/2013] [Indexed: 02/06/2023] Open
Abstract
Metastatic tumor cells in body fluids are important targets for treatment, and critical surrogate markers for evaluating cancer prognosis and therapeutic response. Here we report, for the first time, that live metastatic tumor cells in blood samples from mice bearing human tumor xenografts and in blood and cerebrospinal fluid samples from patients with cancer were successfully detected using a tumor cell-specific recombinant vaccinia virus (VACV). In contrast to the FDA-approved CellSearch system, VACV detects circulating tumor cells (CTCs) in a cancer biomarker-independent manner, thus, free of any bias related to the use of antibodies, and can be potentially a universal system for detection of live CTCs of any tumor type, not limited to CTCs of epithelial origin. Furthermore, we demonstrate for the first time that VACV was effective in preventing and reducing circulating tumor cells in mice bearing human tumor xenografts. Importantly, a single intra-peritoneal delivery of VACV resulted in a dramatic decline in the number of tumor cells in the ascitic fluid from a patient with gastric cancer. Taken together, these results suggest VACV to be a useful tool for quantitative detection of live tumor cells in liquid biopsies as well as a potentially effective treatment for reducing or eliminating live tumor cells in body fluids of patients with metastatic disease.
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Affiliation(s)
- Huiqiang Wang
- Genelux Corporation, San Diego Science Center, San Diego, California, United States of America
| | - Nanhai G. Chen
- Genelux Corporation, San Diego Science Center, San Diego, California, United States of America
- Department of Radiation Medicine and Applied Sciences, Rebecca & John Moores Comprehensive Cancer Center, University of California, San Diego, California, United States of America
| | - Boris R. Minev
- Genelux Corporation, San Diego Science Center, San Diego, California, United States of America
- Department of Radiation Medicine and Applied Sciences, Rebecca & John Moores Comprehensive Cancer Center, University of California, San Diego, California, United States of America
- UCSD Division of Neurosurgery, University of California, San Diego, California, United States of America
| | - Martina Zimmermann
- Department of Gastroenterology and Hepatology, University Hospital, Tuebingen, Germany
| | - Richard J. Aguilar
- Genelux Corporation, San Diego Science Center, San Diego, California, United States of America
| | - Qian Zhang
- Genelux Corporation, San Diego Science Center, San Diego, California, United States of America
- Department of Radiation Medicine and Applied Sciences, Rebecca & John Moores Comprehensive Cancer Center, University of California, San Diego, California, United States of America
| | - Julia B. Sturm
- Department of Gastroenterology and Hepatology, University Hospital, Tuebingen, Germany
| | - Falko Fend
- Institute of Pathology, University Hospital, Tuebingen, Germany
| | - Yong A. Yu
- Genelux Corporation, San Diego Science Center, San Diego, California, United States of America
- Department of Radiation Medicine and Applied Sciences, Rebecca & John Moores Comprehensive Cancer Center, University of California, San Diego, California, United States of America
| | - Joseph Cappello
- Genelux Corporation, San Diego Science Center, San Diego, California, United States of America
| | - Ulrich M. Lauer
- Department of Gastroenterology and Hepatology, University Hospital, Tuebingen, Germany
| | - Aladar A. Szalay
- Genelux Corporation, San Diego Science Center, San Diego, California, United States of America
- Department of Radiation Medicine and Applied Sciences, Rebecca & John Moores Comprehensive Cancer Center, University of California, San Diego, California, United States of America
- Department of Biochemistry, Rudolf Virchow Center for Experimental Biomedicine, and Institute for Molecular Infection Biology, University of Wuerzburg, Wuerzburg, Germany
- * E-mail:
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Balic M, Williams A, Lin H, Datar R, Cote RJ. Circulating tumor cells: from bench to bedside. Annu Rev Med 2012; 64:31-44. [PMID: 23092385 DOI: 10.1146/annurev-med-050311-163404] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Circulating tumor cells (CTCs) represent a surrogate biomarker of hematogenous metastases. In recent years, their detection has gained increasing interest. There is ample evidence regarding the ability to detect CTCs and their prognostic relevance, but their demonstrated predictive value in therapeutic response monitoring is clinically even more meaningful. Many clinical trials in the early and metastatic cancer setting now include CTCs as a monitoring parameter, and numerous translational studies attempting their molecular characterization are under way. There has been great progress in defining the clinical importance of CTCs, and it now seems likely that we may expect wider implementation of CTCs as a diagnostic oncology tool to monitor therapeutic response in real time. Novel technologies may further facilitate molecular characterization of CTCs and development of novel therapeutic targets, possibly leading to more powerful treatment strategies for cancer patients. As the detection and evaluation of CTCs are becoming an increasingly important diagnostic and prognostic tool, the goal of this review is to communicate the knowledge obtained through analysis of primary tumors and CTCs to oncologists and medical specialists in managing patients with cancer.
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Affiliation(s)
- Marija Balic
- Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, 8036, Austria.
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