|
1
|
Kerdkumthong K, Roytrakul S, Songsurin K, Pratummanee K, Runsaeng P, Obchoei S. Proteomics and Bioinformatics Identify Drug-Resistant-Related Genes with Prognostic Potential in Cholangiocarcinoma. Biomolecules 2024; 14:969. [PMID: 39199357 PMCID: PMC11352417 DOI: 10.3390/biom14080969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Revised: 07/21/2024] [Accepted: 08/05/2024] [Indexed: 09/01/2024] Open
Abstract
Drug resistance is a major challenge in the treatment of advanced cholangiocarcinoma (CCA). Understanding the mechanisms of drug resistance can aid in identifying novel prognostic biomarkers and therapeutic targets to improve treatment efficacy. This study established 5-fluorouracil- (5-FU) and gemcitabine-resistant CCA cell lines, KKU-213FR and KKU-213GR, and utilized comparative proteomics to identify differentially expressed proteins in drug-resistant cells compared to parental cells. Additionally, bioinformatics analyses were conducted to explore the biological and clinical significance of key proteins. The drug-resistant phenotypes of KKU-213FR and KKU-213GR cell lines were confirmed. In addition, these cells demonstrated increased migration and invasion abilities. Proteomics analysis identified 81 differentially expressed proteins in drug-resistant cells, primarily related to binding functions, biological regulation, and metabolic processes. Protein-protein interaction analysis revealed a highly interconnected network involving MET, LAMB1, ITGA3, NOTCH2, CDH2, and NDRG1. siRNA-mediated knockdown of these genes in drug-resistant cell lines attenuated cell migration and cell invasion abilities and increased sensitivity to 5-FU and gemcitabine. The mRNA expression of these genes is upregulated in CCA patient samples and is associated with poor prognosis in gastrointestinal cancers. Furthermore, the functions of these proteins are closely related to the epithelial-mesenchymal transition (EMT) pathway. These findings elucidate the potential molecular mechanisms underlying drug resistance and tumor progression in CCA, providing insights into potential therapeutic targets.
Collapse
Affiliation(s)
- Kankamol Kerdkumthong
- Department of Biochemistry, Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University, Hat Yai District, Songkhla 90110, Thailand; (K.K.); (K.S.); (K.P.); (P.R.)
| | - Sittiruk Roytrakul
- Functional Proteomics Technology Laboratory, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Tani 12120, Thailand;
| | - Kawinnath Songsurin
- Department of Biochemistry, Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University, Hat Yai District, Songkhla 90110, Thailand; (K.K.); (K.S.); (K.P.); (P.R.)
| | - Kandawasri Pratummanee
- Department of Biochemistry, Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University, Hat Yai District, Songkhla 90110, Thailand; (K.K.); (K.S.); (K.P.); (P.R.)
| | - Phanthipha Runsaeng
- Department of Biochemistry, Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University, Hat Yai District, Songkhla 90110, Thailand; (K.K.); (K.S.); (K.P.); (P.R.)
- Center of Excellence for Biochemistry, Faculty of Science, Prince of Songkla University, Hat Yai District, Songkhla 90110, Thailand
| | - Sumalee Obchoei
- Department of Biochemistry, Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University, Hat Yai District, Songkhla 90110, Thailand; (K.K.); (K.S.); (K.P.); (P.R.)
- Center of Excellence for Biochemistry, Faculty of Science, Prince of Songkla University, Hat Yai District, Songkhla 90110, Thailand
| |
Collapse
|
|
2
|
Kong SH, Bae JM, Kim JH, Kim SW, Han D, Shin CS. Protein Signatures of Parathyroid Adenoma according to Tumor Volume and Functionality. Endocrinol Metab (Seoul) 2024; 39:375-386. [PMID: 38509667 PMCID: PMC11066450 DOI: 10.3803/enm.2023.1827] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 11/22/2023] [Accepted: 12/21/2023] [Indexed: 03/22/2024] Open
Abstract
BACKGRUOUND Parathyroid adenoma (PA) is a common endocrine disease linked to multiple complications, but the pathophysiology of the disease remains incompletely understood. The study aimed to identify the key regulator proteins and pathways of PA according to functionality and volume through quantitative proteomic analyses. METHODS We conducted a retrospective study of 15 formalin-fixed, paraffin-embedded PA samples from tertiary hospitals in South Korea. Proteins were extracted, digested, and the resulting peptides were analyzed using liquid chromatography-tandem mass spectrometry. Pearson correlation analysis was employed to identify proteins significantly correlated with clinical variables. Canonical pathways and transcription factors were analyzed using Ingenuity Pathway Analysis. RESULTS The median age of the participants was 52 years, and 60.0% were female. Among the 8,153 protein groups analyzed, 496 showed significant positive correlations with adenoma volume, while 431 proteins were significantly correlated with parathyroid hormone (PTH) levels. The proteins SLC12A9, LGALS3, and CARM1 were positively correlated with adenoma volume, while HSP90AB2P, HLA-DRA, and SCD5 showed negative correlations. DCPS, IRF2BPL, and FAM98A were the main proteins that exhibited positive correlations with PTH levels, and SLITRK4, LAP3, and AP4E1 had negative correlations. Canonical pathway analysis demonstrated that the RAN and sirtuin signaling pathways were positively correlated with both PTH levels and adenoma volume, while epithelial adherence junction pathways had negative correlations. CONCLUSION Our study identified pivotal proteins and pathways associated with PA, offering potential therapeutic targets. These findings accentuate the importance of proteomics in understanding disease pathophysiology and the need for further research.
Collapse
Affiliation(s)
- Sung Hye Kong
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Jeong Mo Bae
- Department of Pathology, Seoul National University Hospital, Seoul, Korea
| | - Jung Hee Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Sang Wan Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Dohyun Han
- Transdisciplinary Department of Medicine & Advanced Technology, Seoul National University Hospital, Seoul, Korea
| | - Chan Soo Shin
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| |
Collapse
|
|
3
|
Samartha MVS, Arora S, Palei S, Gupta V, Saxena S. Multiomics studies for neuro-oncology. RADIOMICS AND RADIOGENOMICS IN NEURO-ONCOLOGY 2024:133-160. [DOI: 10.1016/b978-0-443-18508-3.00003-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
4
|
Nisar N, Mir SA, Kareem O, Pottoo FH. Proteomics approaches in the identification of cancer biomarkers and drug discovery. Proteomics 2023. [DOI: 10.1016/b978-0-323-95072-5.00001-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2023]
|
|
5
|
Wani S, Humaira, Farooq I, Ali S, Rehman MU, Arafah A. Proteomic profiling and its applications in cancer research. Proteomics 2023. [DOI: 10.1016/b978-0-323-95072-5.00015-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2023]
|
|
6
|
Cancer proteomics: An overview. Proteomics 2023. [DOI: 10.1016/b978-0-323-95072-5.00009-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2023]
|
|
7
|
Hassan T, Firdous P, Nissar K, Ahmad MB, Imtiyaz Z. Role of proteomics in surgical oncology. Proteomics 2023. [DOI: 10.1016/b978-0-323-95072-5.00012-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2023]
|
|
8
|
Proteomics: Application of next-generation proteomics in cancer research. Proteomics 2023. [DOI: 10.1016/b978-0-323-95072-5.00016-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2023]
|
|
9
|
Cancer proteomics: Application of case studies in diverse cancers. Proteomics 2023. [DOI: 10.1016/b978-0-323-95072-5.00003-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2023]
|
|
10
|
Nisa MU, Farooq S, Ali S, Eachkoti R, Rehman MU, Hafiz S. Proteomics: A modern tool for identifying therapeutic targets in different types of carcinomas. Proteomics 2023. [DOI: 10.1016/b978-0-323-95072-5.00013-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2023]
|
|
11
|
Circulating and non-circulating proteins and nucleic acids as biomarkers and therapeutic molecules in ovarian cancer. Genes Dis 2022. [DOI: 10.1016/j.gendis.2022.07.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
|
|
12
|
Kwon YW, Jo HS, Bae S, Seo Y, Song P, Song M, Yoon JH. Application of Proteomics in Cancer: Recent Trends and Approaches for Biomarkers Discovery. Front Med (Lausanne) 2021; 8:747333. [PMID: 34631760 PMCID: PMC8492935 DOI: 10.3389/fmed.2021.747333] [Citation(s) in RCA: 107] [Impact Index Per Article: 26.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Accepted: 08/26/2021] [Indexed: 12/12/2022] Open
Abstract
Proteomics has become an important field in molecular sciences, as it provides valuable information on the identity, expression levels, and modification of proteins. For example, cancer proteomics unraveled key information in mechanistic studies on tumor growth and metastasis, which has contributed to the identification of clinically applicable biomarkers as well as therapeutic targets. Several cancer proteome databases have been established and are being shared worldwide. Importantly, the integration of proteomics studies with other omics is providing extensive data related to molecular mechanisms and target modulators. These data may be analyzed and processed through bioinformatic pipelines to obtain useful information. The purpose of this review is to provide an overview of cancer proteomics and recent advances in proteomic techniques. In particular, we aim to offer insights into current proteomics studies of brain cancer, in which proteomic applications are in a relatively early stage. This review covers applications of proteomics from the discovery of biomarkers to the characterization of molecular mechanisms through advances in technology. Moreover, it addresses global trends in proteomics approaches for translational research. As a core method in translational research, the continued development of this field is expected to provide valuable information at a scale beyond that previously seen.
Collapse
Affiliation(s)
- Yang Woo Kwon
- Neurodegenerative Diseases Research Group, Korea Brain Research Institute, Daegu, South Korea
| | - Han-Seul Jo
- Neurodegenerative Diseases Research Group, Korea Brain Research Institute, Daegu, South Korea
| | - Sungwon Bae
- Neurodegenerative Diseases Research Group, Korea Brain Research Institute, Daegu, South Korea
| | - Youngsuk Seo
- Neurodegenerative Diseases Research Group, Korea Brain Research Institute, Daegu, South Korea
| | - Parkyong Song
- Department of Convergence Medicine, Pusan National University School of Medicine, Yangsan, South Korea
| | - Minseok Song
- Department of Life Sciences, Yeungnam University, Gyeongsan, South Korea
| | - Jong Hyuk Yoon
- Neurodegenerative Diseases Research Group, Korea Brain Research Institute, Daegu, South Korea
| |
Collapse
|
|
13
|
Pediatric Tuberculosis: The Impact of "Omics" on Diagnostics Development. Int J Mol Sci 2020; 21:ijms21196979. [PMID: 32977381 PMCID: PMC7582311 DOI: 10.3390/ijms21196979] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 09/15/2020] [Accepted: 09/17/2020] [Indexed: 02/07/2023] Open
Abstract
Tuberculosis (TB) is a major public health concern for all ages. However, the disease presents a larger challenge in pediatric populations, partially owing to the lack of reliable diagnostic standards for the early identification of infection. Currently, there are no biomarkers that have been clinically validated for use in pediatric TB diagnosis. Identification and validation of biomarkers could provide critical information on prognosis of disease, and response to treatment. In this review, we discuss how the “omics” approach has influenced biomarker discovery and the advancement of a next generation rapid point-of-care diagnostic for TB, with special emphasis on pediatric disease. Limitations of current published studies and the barriers to their implementation into the field will be thoroughly reviewed within this article in hopes of highlighting future avenues and needs for combating the problem of pediatric tuberculosis.
Collapse
|
|
14
|
Jazayeri MH, Sadri M, Mostafaie A, Nedaeinia R. Identification of an Immunoglobulin M (IgM) Antibody Against Enolase 1 Protein (ENO1) Derived from HEK-293 Cells in Patients with Kidney Failure. Int J Pept Res Ther 2020. [DOI: 10.1007/s10989-019-09919-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
|
|
15
|
Petricoin E, Wulfkuhle J, Howard M, Pierobon M, Espina V, Luchini A, Liotta LA. RPPA: Origins, Transition to a Validated Clinical Research Tool, and Next Generations of the Technology. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1188:1-19. [PMID: 31820380 DOI: 10.1007/978-981-32-9755-5_1] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
RPPA technology has graduated from a research tool to an essential component of clinical drug discovery research and personalized medicine. Next generations of RPPA technology will be a single clinical instrument that integrates all the steps of the workflow.
Collapse
Affiliation(s)
- Emanuel Petricoin
- Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA
| | - Julie Wulfkuhle
- Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA
| | - Marissa Howard
- Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA
| | - Marielena Pierobon
- Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA
| | - Virginia Espina
- Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA
| | - Alessandra Luchini
- Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA
| | - Lance A Liotta
- Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA.
| |
Collapse
|
|
16
|
Proteomic Differences in Feline Fibrosarcomas Grown Using Doxorubicin-Sensitive and -Resistant Cell Lines in the Chick Embryo Model. Int J Mol Sci 2018; 19:ijms19020576. [PMID: 29443940 PMCID: PMC5855798 DOI: 10.3390/ijms19020576] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2018] [Revised: 02/09/2018] [Accepted: 02/12/2018] [Indexed: 12/19/2022] Open
Abstract
Proteomic analyses are rapid and powerful tools that are used to increase the understanding of cancer pathogenesis, discover cancer biomarkers and predictive markers, and select and monitor novel targets for cancer therapy. Feline injection-site sarcomas (FISS) are aggressive skin tumours with high recurrence rates, despite treatment with surgery, radiotherapy, and chemotherapy. Doxorubicin is a drug of choice for soft tissue sarcomas, including FISS. However, multidrug resistance is one of the major causes of chemotherapy failure. The main aim of the present study was to identify proteins that differentiate doxorubicin-resistant from doxorubicin-sensitive FISS using two-dimensional gel electrophoresis (2DE), followed by matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS) analysis. Using the three-dimensional (3D) preclinical in ovo model, which resembles features of spontaneous fibrosarcomas, three significantly (p ≤ 0.05) differentially expressed proteins were identified in tumours grown from doxorubicin-resistant fibrosarcoma cell lines (FFS1 and FFS3) in comparison to the doxorubicin-sensitive one (FFS5): Annexin A5 (ANXA5), Annexin A3 (ANXA3), and meiosis-specific nuclear structural protein 1 (MNS1). Moreover, nine other proteins were significantly differentially expressed in tumours grown from the high doxorubicin-resistant cell line (FFS1) in comparison to sensitive one (FFS5). This study may be the first proteomic fingerprinting of FISS reported, identifying potential candidates for specific predictive biomarkers and research targets for doxorubicin-resistant FISS.
Collapse
|
|
17
|
Capek I. Polymer decorated gold nanoparticles in nanomedicine conjugates. Adv Colloid Interface Sci 2017; 249:386-399. [PMID: 28259207 DOI: 10.1016/j.cis.2017.01.007] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2016] [Revised: 01/10/2017] [Accepted: 01/11/2017] [Indexed: 02/06/2023]
Abstract
Noble metal, especially gold nanoparticles and their conjugates with biopolymers have immense potential for disease diagnosis and therapy on account of their surface plasmon resonance (SPR) enhanced light scattering and absorption. Conjugation of noble metal nanoparticles to ligands specifically targeted to biomarkers on diseased cells allows molecular-specific imaging and detection of disease. The development of smart gold nanoparticles (AuNPs) that can deliver therapeutics at a sustained rate directly to cancer cells may provide better efficacy and lower toxicity for treating cancer tumors. We highlight some of the promising classes of targeting systems that are under development for the delivery of gold nanoparticles. Nanoparticles designed for biomedical applications are often coated with polymers containing reactive functional groups to conjugate targeting ligands, cell receptors or drugs. Using targeted nanoparticles to deliver chemotherapeutic agents in cancer therapy offers many advantages to improve drug/gene delivery and to overcome many problems associated with conventional radiotherapy and chemotherapy. The targeted nanoparticles were found to be effective in killing cancer cells which were studied using various anticancer assays. Cell morphological analysis shows the changes occurred in cancer cells during the treatment with AuNPs. The results determine the influence of particle size and concentration of AuNPs on their absorption, accumulation, and cytotoxicity in model normal and cancer cells. As the mean particle diameter of the AuNPs decreased, their rate of absorption by the intestinal epithelium cells increased. These results provide important insights into the relationship between the dimensions of AuNPs and their gastrointestinal uptake and potential cytotoxicity. Furthermore gold nanoparticles efficiently convert the absorbed light into localized heat, which can be exploited for the selective laser photothermal therapy of cancer. We also review the emerging technologies for the fabrication of targeted gold colloids as imagining agents.
Collapse
Affiliation(s)
- Ignác Capek
- Slovak Academy of Sciences, Polymer Institute, Institute of Measurement Sciences, Dúbravská cesta, Bratislava, Slovakia.
| |
Collapse
|
|
18
|
Gadducci A, Cosio S, Zanca G, Genazzani AR. Evolving Role of Serum Biomarkers in the Management of Ovarian Cancer. WOMENS HEALTH 2016; 2:141-58. [DOI: 10.2217/17455057.2.1.141] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
The availability of an ideal serum tumor marker would be of great clinical benefit for both the diagnosis and management of patients with epithelial ovarian cancer. Serum cancer antigen 125 assay significantly increases the diagnostic reliability of ultrasound in discriminating a malignant from a benign ovarian mass, especially in postmenopausal women, and it is the only well validated tumor marker for monitoring disease course. Several other tumor-associated antigens have been assessed, including glycoprotein antigens other than cancer antigen 125, soluble cytokeratin fragments, kallikreins, cytokines and cytokine receptors, vascular endothelial growth factor, D-dimer, and lisophosphatidic acid. This article assesses the potential diagnostic and prognostic role of these novel biomarkers, both alone and in combination with cancer antigen 125. The future for serum tumor marker research is represented by the emerging technology of proteomics, which may allow scientific advances comparable to those achieved with the introduction of monoclonal antibody technology.
Collapse
Affiliation(s)
- Angiolo Gadducci
- Department of Procreative Medicine, Division of Gynecology and Obstetrics, University of Pisa, Via Roma 56, Pisa, 56127, Italy, Tel.: +39 50 992 609; Fax: +39 50 553 410
| | - Stefania Cosio
- Department of Procreative Medicine, Division of Gynecology and Obstetrics, University of Pisa, Via Roma 56, Pisa, 56127, Italy, Tel.: +39 50 992 609; Fax: +39 50 553 410
| | - Giulia Zanca
- Department of Procreative Medicine, Division of Gynecology and Obstetrics, University of Pisa, Via Roma 56, Pisa, 56127, Italy, Tel.: +39 50 992 609; Fax: +39 50 553 410
| | - Andrea Riccardo Genazzani
- Department of Procreative Medicine, Division of Gynecology and Obstetrics, University of Pisa, Via Roma 56, Pisa, 56127, Italy, Tel.: +39 50 992 609; Fax: +39 50 553 410
| |
Collapse
|
|
19
|
Greening DW, Ji H, Chen M, Robinson BWS, Dick IM, Creaney J, Simpson RJ. Secreted primary human malignant mesothelioma exosome signature reflects oncogenic cargo. Sci Rep 2016; 6:32643. [PMID: 27605433 PMCID: PMC5015102 DOI: 10.1038/srep32643] [Citation(s) in RCA: 80] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2016] [Accepted: 08/11/2016] [Indexed: 02/07/2023] Open
Abstract
Malignant mesothelioma (MM) is a highly-aggressive heterogeneous malignancy, typically diagnosed at advanced stage. An important area of mesothelioma biology and progression is understanding intercellular communication and the contribution of the secretome. Exosomes are secreted extracellular vesicles shown to shuttle cellular cargo and direct intercellular communication in the tumour microenvironment, facilitate immunoregulation and metastasis. In this study, quantitative proteomics was used to investigate MM-derived exosomes from distinct human models and identify select cargo protein networks associated with angiogenesis, metastasis, and immunoregulation. Utilising bioinformatics pathway/network analyses, and correlation with previous studies on tumour exosomes, we defined a select mesothelioma exosomal signature (mEXOS, 570 proteins) enriched in tumour antigens and various cancer-specific signalling (HPGD/ENO1/OSMR) and secreted modulators (FN1/ITLN1/MAMDC2/PDGFD/GBP1). Notably, such circulating cargo offers unique insights into mesothelioma progression and tumour microenvironment reprogramming. Functionally, we demonstrate that oncogenic exosomes facilitate the migratory capacity of fibroblast/endothelial cells, supporting the systematic model of MM progression associated with vascular remodelling and angiogenesis. We provide biophysical and proteomic characterisation of exosomes, define a unique oncogenic signature (mEXOS), and demonstrate the regulatory capacity of exosomes in cell migration/tube formation assays. These findings contribute to understanding tumour-stromal crosstalk in the context of MM, and potential new diagnostic and therapeutic extracellular targets.
Collapse
Affiliation(s)
- David W. Greening
- Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia
| | - Hong Ji
- Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia
| | - Maoshan Chen
- Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia
| | - Bruce W. S. Robinson
- National Centre for Asbestos Related Diseases, School of Medicine and Pharmacology, University of Western Australia, 6009, Australia
- Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Perth, Western Australia, 6009, Australia
| | - Ian M. Dick
- National Centre for Asbestos Related Diseases, School of Medicine and Pharmacology, University of Western Australia, 6009, Australia
| | - Jenette Creaney
- National Centre for Asbestos Related Diseases, School of Medicine and Pharmacology, University of Western Australia, 6009, Australia
- Australian Mesothelioma Tissue Bank, Sir Charles Gairdner Hospital, Perth, Western Australia, 6009, Australia
| | - Richard J. Simpson
- Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia
| |
Collapse
|
|
20
|
Shruthi BS, Vinodhkumar P, Selvamani. Proteomics: A new perspective for cancer. Adv Biomed Res 2016; 5:67. [PMID: 27169098 PMCID: PMC4854039 DOI: 10.4103/2277-9175.180636] [Citation(s) in RCA: 58] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2013] [Accepted: 04/09/2013] [Indexed: 12/23/2022] Open
Abstract
In the past decades, several ground breaking discoveries in life science were made. The completion of sequencing the human genome certainly belongs to the key tasks successfully completed, representing a true milestone in the biomedicine. The accomplishment of the complete genome also brings along a new, even more challenging task for scientists: The characterization of the human proteome. Proteomics, the main tool for proteome research, is a relatively new and extremely dynamically evolving branch of science, focused on the evaluation of gene expression at proteome level. Due to the specific properties of proteins, current proteomics deals with different issues, such as protein identification, quantification, characterization of post-translational modification, structure and function elucidation, and description of possible interactions. This field incorporates technologies that can be applied to serum and tissue in order to extract important biological information in the form of biomarkers to aid clinicians and scientists in understanding the dynamic biology of their system of interest, such as a patient with cancer. The present review article provides a detail description of proteomics and its role in cancer research.
Collapse
Affiliation(s)
- Basavaradhya Sahukar Shruthi
- Department of Oral and Maxillofacial Pathology and Microbiology, Vishnu Dental College, Vishnupur, Bhimavarm, Andhra Pradesh, India
| | - Palani Vinodhkumar
- Department of Pedodontics, Sri Balaji Dental College and Hospital, Chennai, Tamil Nadu, India
| | - Selvamani
- Department of Oral and Maxillofacial Pathology and Microbiology, College of Dental Sciences, Davangere, Karnataka, India
| |
Collapse
|
|
21
|
Petrillo A, Fusco R, Catalano O. Imaging Modalities. Updates Surg 2016. [DOI: 10.1007/978-88-470-5767-8_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
|
|
22
|
Su MN, Ye J, Li QW, Li SH, Ge W, Chen X, Jiang H, Wang XM. Novel in situ biosynthesized fluorescent zinc nanoclusters for specific cellular bio-imaging. CHINESE CHEM LETT 2015. [DOI: 10.1016/j.cclet.2015.07.021] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
|
|
23
|
Prediction of individual response to anticancer therapy: historical and future perspectives. Cell Mol Life Sci 2014; 72:729-57. [PMID: 25387856 PMCID: PMC4309902 DOI: 10.1007/s00018-014-1772-3] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2012] [Revised: 10/23/2014] [Accepted: 10/27/2014] [Indexed: 02/06/2023]
Abstract
Since the introduction of chemotherapy for cancer treatment in the early 20th century considerable efforts have been made to maximize drug efficiency and at the same time minimize side effects. As there is a great interpatient variability in response to chemotherapy, the development of predictive biomarkers is an ambitious aim for the rapidly growing research area of personalized molecular medicine. The individual prediction of response will improve treatment and thus increase survival and life quality of patients. In the past, cell cultures were used as in vitro models to predict in vivo response to chemotherapy. Several in vitro chemosensitivity assays served as tools to measure miscellaneous endpoints such as DNA damage, apoptosis and cytotoxicity or growth inhibition. Twenty years ago, the development of high-throughput technologies, e.g. cDNA microarrays enabled a more detailed analysis of drug responses. Thousands of genes were screened and expression levels were correlated to drug responses. In addition, mutation analysis became more and more important for the prediction of therapeutic success. Today, as research enters the area of -omics technologies, identification of signaling pathways is a tool to understand molecular mechanism underlying drug resistance. Combining new tissue models, e.g. 3D organoid cultures with modern technologies for biomarker discovery will offer new opportunities to identify new drug targets and in parallel predict individual responses to anticancer therapy. In this review, we present different currently used chemosensitivity assays including 2D and 3D cell culture models and several -omics approaches for the discovery of predictive biomarkers. Furthermore, we discuss the potential of these assays and biomarkers to predict the clinical outcome of individual patients and future perspectives.
Collapse
|
|
24
|
Akbani R, Becker KF, Carragher N, Goldstein T, de Koning L, Korf U, Liotta L, Mills GB, Nishizuka SS, Pawlak M, Petricoin EF, Pollard HB, Serrels B, Zhu J. Realizing the promise of reverse phase protein arrays for clinical, translational, and basic research: a workshop report: the RPPA (Reverse Phase Protein Array) society. Mol Cell Proteomics 2014; 13:1625-43. [PMID: 24777629 DOI: 10.1074/mcp.o113.034918] [Citation(s) in RCA: 136] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Reverse phase protein array (RPPA) technology introduced a miniaturized "antigen-down" or "dot-blot" immunoassay suitable for quantifying the relative, semi-quantitative or quantitative (if a well-accepted reference standard exists) abundance of total protein levels and post-translational modifications across a variety of biological samples including cultured cells, tissues, and body fluids. The recent evolution of RPPA combined with more sophisticated sample handling, optical detection, quality control, and better quality affinity reagents provides exquisite sensitivity and high sample throughput at a reasonable cost per sample. This facilitates large-scale multiplex analysis of multiple post-translational markers across samples from in vitro, preclinical, or clinical samples. The technical power of RPPA is stimulating the application and widespread adoption of RPPA methods within academic, clinical, and industrial research laboratories. Advances in RPPA technology now offer scientists the opportunity to quantify protein analytes with high precision, sensitivity, throughput, and robustness. As a result, adopters of RPPA technology have recognized critical success factors for useful and maximum exploitation of RPPA technologies, including the following: preservation and optimization of pre-analytical sample quality, application of validated high-affinity and specific antibody (or other protein affinity) detection reagents, dedicated informatics solutions to ensure accurate and robust quantification of protein analytes, and quality-assured procedures and data analysis workflows compatible with application within regulated clinical environments. In 2011, 2012, and 2013, the first three Global RPPA workshops were held in the United States, Europe, and Japan, respectively. These workshops provided an opportunity for RPPA laboratories, vendors, and users to share and discuss results, the latest technology platforms, best practices, and future challenges and opportunities. The outcomes of the workshops included a number of key opportunities to advance the RPPA field and provide added benefit to existing and future participants in the RPPA research community. The purpose of this report is to share and disseminate, as a community, current knowledge and future directions of the RPPA technology.
Collapse
Affiliation(s)
- Rehan Akbani
- From the *University of Texas M.D. Anderson Cancer Center, Houston, Texas
| | | | - Neil Carragher
- §Edinburgh Cancer Research UK Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, Scotland, UK
| | - Ted Goldstein
- ¶Center for Biomolecular Science and Engineering, University of California, Santa Cruz, California
| | | | - Ulrike Korf
- **German Cancer Research Center (DKFZ), Heidelberg, Germany
| | | | - Gordon B Mills
- From the *University of Texas M.D. Anderson Cancer Center, Houston, Texas
| | | | - Michael Pawlak
- §§§The Natural and Medical Sciences Institute, Reutlingen, Germany
| | | | - Harvey B Pollard
- ¶¶Uniformed Services University of the Health Sciences, Bethesda, Maryland
| | - Bryan Serrels
- §Edinburgh Cancer Research UK Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, Scotland, UK
| | - Jingchun Zhu
- ¶Center for Biomolecular Science and Engineering, University of California, Santa Cruz, California
| |
Collapse
|
|
25
|
Microtexturing of the conductive PEDOT:PSS polymer for superhydrophobic organic electrochemical transistors. BIOMED RESEARCH INTERNATIONAL 2014; 2014:302694. [PMID: 24579079 PMCID: PMC3919119 DOI: 10.1155/2014/302694] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/30/2013] [Revised: 11/15/2013] [Accepted: 11/18/2013] [Indexed: 12/15/2022]
Abstract
Superhydrophobic surfaces are bioinspired, nanotechnology artifacts, which feature a reduced friction coefficient, whereby they can be used for a number of very practical applications including, on the medical side, the manipulation of biological solutions. In this work, we integrated superhydrophobic patterns with the conducting polymer PEDOT:PSS, one of the most used polymers in organic electronics because highly sensitive to ionized species in solution. In doing so, we combined geometry and materials science to obtain an advanced device where, on account of the superhydrophobicity of the system, the solutions of interest can be manipulated and, on account of the conductive PEDOT:PSS polymer, the charged molecules dispersed inside can be quantitatively measured. This original substrate preparation allowed to perform electrochemical measurements on ionized species in solution with decreasing concentration down to 10−7 molar. Moreover, it was demonstrated the ability of the device of realizing specific, combined time and space resolved analysis of the sample. Collectively, these results demonstrate how a tight, interweaving integration of different disciplines can provide realistic tools for the detection of pathologies. The scheme here introduced offers breakthrough capabilities that are expected to radically improve both the pace and the productivity of biomedical research, creating an access revolution.
Collapse
|
|
26
|
MALDI-MS-Based Profiling of Serum Proteome: Detection of Changes Related to Progression of Cancer and Response to Anticancer Treatment. INTERNATIONAL JOURNAL OF PROTEOMICS 2012; 2012:926427. [PMID: 22900176 PMCID: PMC3413974 DOI: 10.1155/2012/926427] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/23/2012] [Revised: 06/12/2012] [Accepted: 06/12/2012] [Indexed: 01/25/2023]
Abstract
Mass spectrometry-based analyses of the low-molecular-weight fraction of serum proteome allow identifying proteome profiles (signatures) that are potentially useful in detection and classification of cancer. Several published studies have shown that multipeptide signatures selected in numerical tests have potential values for diagnostics of different types of cancer. However due to apparent problems with standardization of methodological details, both experimental and computational, none of the proposed peptide signatures analyzed directly by MALDI/SELDI-ToF spectrometry has been approved for routine diagnostics. Noteworthy, several components of proposed cancer signatures, especially those characteristic for advanced cancer, were identified as fragments of blood proteins involved in the acute phase and inflammatory response. This indicated that among cancer biomarker candidates to be possibly identified by serum proteome profiling were rather those reflecting overall influence of a disease (and the therapy) upon the human organism, than products of cancer-specific genes. Current paper focuses on changes in serum proteome that are related to response of patient's organism to progressing malignancy and toxicity of anticancer treatment. In addition, several methodological issues that affect robustness and interlaboratory reproducibility of MS-based serum proteome profiling are discussed.
Collapse
|
|
27
|
Gentile F, Coluccio ML, Coppedè N, Mecarini F, Das G, Liberale C, Tirinato L, Leoncini M, Perozziello G, Candeloro P, De Angelis F, Di Fabrizio E. Superhydrophobic surfaces as smart platforms for the analysis of diluted biological solutions. ACS APPLIED MATERIALS & INTERFACES 2012; 4:3213-3224. [PMID: 22620470 DOI: 10.1021/am300556w] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/27/2023]
Abstract
The aim of this paper is to expound on the rational design, fabrication and development of superhydrophobic surfaces (SHSs) for the manipulation and analysis of diluted biological solutions. SHSs typically feature a periodic array or pattern of micropillars; here, those pillars were modified to incorporate on the head, at the smallest scales, silver nanoparticles aggregates. These metal nanoclusters guarantee superior optical properties and especially SERS (surface enhanced Raman scattering) effects, whereby a molecule, adsorbed on the surface, would reveal an increased spectroscopy signal. On account of their two scale-hybrid nature, these systems are capable of multiple functions which are (i) to concentrate a solution, (ii) to vehicle the analytes of interest to the active areas of the substrate and, therefore, (iii) to measure the analytes with exceptional sensitivity and very low detection limits. Forasmuch, combining different technologies, these devices would augment the performance of conventional SERS substrates and would offer the possibility of revealing a single molecule. In this work, similar SHSs were used to detect Rhodamine molecules in the fairly low atto molar range. The major application of this novel family of devices would be the early detection of tumors or other important pathologies, with incredible advances in medicine.
Collapse
Affiliation(s)
- Francesco Gentile
- BioNEM Laboratory, Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro , Catanzaro, 88100 Italy
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
28
|
Zhao YB, Wang YH, Abuduwaili•Wushour. Application of SELDI-TOF-MS and LCM to screen protein markers for early diagnosis of liver metastasis of colorectal carcinoma. Shijie Huaren Xiaohua Zazhi 2012; 20:296-303. [DOI: 10.11569/wcjd.v20.i4.296] [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] [Indexed: 02/07/2023] Open
Abstract
AIM: To screen protein markers for liver metastases of colorectal cancer using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry protein chip (SELDI-TOF-MS) in combination with laser capture microdissection (LCM) technology.
METHODS: Normal colorectal cells, primary tumor cells and liver metastatic cells were obtained from 24 colorectal cancer patients with liver metastases using the LCM technology. Protein profiling was performed using SELDI-TOF-MS technology. Differentially expressed proteins were analyzed using Biomarker Wizard software and identified by querying the database.
RESULTS: Fifteen differentially expressed proteins were found between primary tumor cells and normal colorectal cells, of which 12 were up-regulated and 3 down-regulated. Nine differentially expressed proteins were found between liver metastatic cells and primary tumor cells, of which 5 were up-regulated and 4 down-regulated. Twenty differentially expressed proteins were identified by querying ExPasy protein database, including integral membrane protein 2C, DNA repair protein RAD51 homolog 4, cell cycle checkpoint protein RAD1, human epididymis protein 4, centromere protein R, and pleckstrin homology domain family member 3. Apoptosis regulator Bax-γ, S100A11, Raf kinase inhibitor protein (RKIP) and heat shock protein 27 (HSP-27) displayed most obvious differential expression among normal colorectal cells, primary tumor cells and liver metastatic cells (all P < 0. 01).
CONCLUSION: SELDI-TOF-MS technology combined with LCM may allow to screen highly sensitive and specific protein markers for colorectal cancer and liver metastases of colorectal cancer.
Collapse
|
|
29
|
Widłak P, Pietrowska M, Wojtkiewicz K, Rutkowski T, Wygoda A, Marczak L, Marczyk M, Polańska J, Walaszczyk A, Domińczyk I, Składowski K, Stobiecki M, Polański A. Radiation-related changes in serum proteome profiles detected by mass spectrometry in blood of patients treated with radiotherapy due to larynx cancer. JOURNAL OF RADIATION RESEARCH 2011; 52:575-581. [PMID: 21768750 DOI: 10.1269/jrr.11019] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/31/2023]
Abstract
The study aimed to detect features of human serum proteome that were associated with exposure to ionizing radiation. The analyzed group consisted of 46 patients treated with radical radiotherapy for larynx cancer; patients were irradiated with total doses in a range from 51 to 72 Gy. Three consecutive blood samples were collected from each patient: before the start, 2 weeks after the start, and 4-6 weeks after the end of radiotherapy. The low-molecular-weight fraction of the serum proteome (2,000-13,000 Da) was analyzed by the MALDI-ToF mass spectrometry. Proteome profiles of serum samples collected before the start of radiotherapy and during the early stage of the treatment were similar. In marked contrast, mass profiles of serum samples collected several weeks after the end of the treatment revealed clear changes. We found that 41 out of 312 registered peptide ions changed their abundance significantly when serum samples collected after the final irradiation were compared with samples collected at the two earlier time points. We also found that abundances of certain serum peptides were associated with total doses of radiation received by patients. The results of this pilot study indicate that features of serum proteome analyzed by mass spectrometry have potential applicability as a retrospective marker of exposure to ionizing radiation.
Collapse
Affiliation(s)
- Piotr Widłak
- Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland.
| | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
30
|
Pietrowska M, Polańska J, Walaszczyk A, Wygoda A, Rutkowski T, Składowski K, Marczak Ł, Stobiecki M, Marczyk M, Polański A, Widłak P. Association between plasma proteome profiles analysed by mass spectrometry, a lymphocyte-based DNA-break repair assay and radiotherapy-induced acute mucosal reaction in head and neck cancer patients. Int J Radiat Biol 2011; 87:711-9. [DOI: 10.3109/09553002.2011.556174] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
|
|
31
|
Puig-Costa M, Oliveras-Ferraros C, Flaquer S, Llopis-Puigmarti F, Pujol-Amado E, Martin-Castillo B, Vazquez-Martin A, Cufí S, Ortiz R, Roig J, Codina-Cazador A, Menendez JA. Antibody microarray-based technology to rapidly define matrix metalloproteinase (MMP) signatures in patients undergoing resection for primary gastric carcinoma. J Surg Oncol 2011; 104:106-9. [PMID: 21308687 DOI: 10.1002/jso.21887] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2010] [Accepted: 01/11/2011] [Indexed: 01/01/2023]
|
|
32
|
Joshi S, Tiwari A, Mondal B, Sharma A. Oncoproteomics. Clin Chim Acta 2011; 412:217-26. [DOI: 10.1016/j.cca.2010.10.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2010] [Revised: 10/03/2010] [Accepted: 10/03/2010] [Indexed: 11/29/2022]
|
|
33
|
Mueller C, Liotta LA, Espina V. Reverse phase protein microarrays advance to use in clinical trials. Mol Oncol 2010; 4:461-81. [PMID: 20974554 PMCID: PMC2981612 DOI: 10.1016/j.molonc.2010.09.003] [Citation(s) in RCA: 102] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2010] [Revised: 09/15/2010] [Accepted: 09/16/2010] [Indexed: 12/18/2022] Open
Abstract
Individualizing cancer therapy for molecular targeted inhibitors requires a new class of molecular profiling technology that can map the functional state of the cancer cell signal pathways containing the drug targets. Reverse phase protein microarrays (RPMA) are a technology platform designed for quantitative, multiplexed analysis of specific phosphorylated, cleaved, or total (phosphorylated and non-phosphorylated) forms of cellular proteins from a limited amount of sample. This class of microarray can be used to interrogate tissue samples, cells, serum, or body fluids. RPMA were previously a research tool; now this technology has graduated to use in research clinical trials with clinical grade sensitivity and precision. In this review we describe the application of RPMA for multiplexed signal pathway analysis in therapeutic monitoring, biomarker discovery, and evaluation of pharmaceutical targets, and conclude with a summary of the technical aspects of RPMA construction and analysis.
Collapse
Affiliation(s)
- Claudius Mueller
- George Mason University, Center for Applied Proteomics and Molecular Medicine, Manassas, VA 20110, USA
| | | | | |
Collapse
|
|
34
|
Zurrida S, Nolè F, Bonanni B, Mastropasqua MG, Arnone P, Gentilini O, Latronico A. Male breast cancer. Future Oncol 2010; 6:985-91. [PMID: 20528235 DOI: 10.2217/fon.10.55] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
Diagnosis and treatment modalities for female breast cancer have developed spectacularly in recent years. Unfortunately, this is not the case for male breast cancer. Because the disease is so rare, controlled clinical trials have almost never been performed and treatment is based on findings in women or small series of men. Similarly, while breast cancer in women is diagnosed at an increasingly early stage, male breast cancer is usually diagnosed late, when the chances of cure are diminished. This article reviews what is currently known about male breast cancer, with an emphasis on areas where evidence-based data are scarce. While it is possible that some recent developments in female breast cancer treatment could be applicable to men, but the way forward is to increase awareness of the disease, and for treatment centers to pool patients for inclusion in randomized clinical trials.
Collapse
Affiliation(s)
- Stefano Zurrida
- Division of Senology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
| | | | | | | | | | | | | |
Collapse
|
|
35
|
Pietrowska M, Polanska J, Marczak L, Behrendt K, Nowicka E, Stobiecki M, Polanski A, Tarnawski R, Widlak P. Mass spectrometry-based analysis of therapy-related changes in serum proteome patterns of patients with early-stage breast cancer. J Transl Med 2010; 8:66. [PMID: 20618994 PMCID: PMC2908576 DOI: 10.1186/1479-5876-8-66] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2010] [Accepted: 07/11/2010] [Indexed: 12/04/2022] Open
Abstract
Background The proteomics approach termed proteome pattern analysis has been shown previously to have potential in the detection and classification of breast cancer. Here we aimed to identify changes in serum proteome patterns related to therapy of breast cancer patients. Methods Blood samples were collected before the start of therapy, after the surgical resection of tumors and one year after the end of therapy in a group of 70 patients diagnosed at early stages of the disease. Patients were treated with surgery either independently (26) or in combination with neoadjuvant chemotherapy (5) or adjuvant radio/chemotherapy (39). The low-molecular-weight fraction of serum proteome was examined using MALDI-ToF mass spectrometry, and then changes in intensities of peptide ions registered in a mass range between 2,000 and 14,000 Da were identified and correlated with clinical data. Results We found that surgical resection of tumors did not have an immediate effect on the mass profiles of the serum proteome. On the other hand, significant long-term effects were observed in serum proteome patterns one year after the end of basic treatment (we found that about 20 peptides exhibited significant changes in their abundances). Moreover, the significant differences were found primarily in the subgroup of patients treated with adjuvant therapy, but not in the subgroup subjected only to surgery. This suggests that the observed changes reflect overall responses of the patients to the toxic effects of adjuvant radio/chemotherapy. In line with this hypothesis we detected two serum peptides (registered m/z values 2,184 and 5,403 Da) whose changes correlated significantly with the type of treatment employed (their abundances decreased after adjuvant therapy, but increased in patients treated only with surgery). On the other hand, no significant correlation was found between changes in the abundance of any spectral component or clinical features of patients, including staging and grading of tumors. Conclusions The study establishes a high potential of MALDI-ToF-based analyses for the detection of dynamic changes in the serum proteome related to therapy of breast cancer patients, which revealed the potential applicability of serum proteome patterns analyses in monitoring the toxicity of therapy.
Collapse
Affiliation(s)
- Monika Pietrowska
- Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland
| | | | | | | | | | | | | | | | | |
Collapse
|
|
36
|
Luo YX, Cui J, Wang L, Chen DK, Peng JS, Lan P, Huang MJ, Huang YH, Cai SR, Hu KH, Li MT, Wang JP. Identification of cancer-associated proteins by proteomics and downregulation of β-tropomyosin expression in colorectal adenoma and cancer. Proteomics Clin Appl 2009; 3:1397-406. [PMID: 21136959 DOI: 10.1002/prca.200900070] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2009] [Revised: 08/09/2009] [Accepted: 08/24/2009] [Indexed: 12/12/2022]
Abstract
Elucidating the molecular mechanism underlying the development of adenoma, the major precursor lesion of colorectal cancer (CRC), would provide a basis for early detection, prevention as well as treatment of CRC. Using the highly sensitive 2-D DIGE method coupled with MS, we identified 24 differentially expressed proteins in adenoma tissues compared with matched normal colonic mucosa and CRC tissues. Fifteen proteins were downregulated and three proteins were upregulated in adenoma tissues when compared with individual-matched normal colonic mucosa. Five proteins were downregulated, while one protein was upregulated in adenoma tissues when compared with matched CRC tissues. A protein, β-tropomyosin (TM-β), recently suggested to be a biomarker of esophageal squamous carcinoma, was downregulated in both adenoma and CRC tissues. Additionally, the reduction in the level of TM-β in adenoma and CRC tissues was further validated by Western blotting (p<0.05) and RT-PCR (p<0.001). Our findings suggest that downregulation of TM-β is involved in the early development of CRC and that differentially expressed proteins might serve as potential biomarkers for detection of CRC.
Collapse
Affiliation(s)
- Yan-Xin Luo
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, P. R. China; Gastrointestinal Institute, Sun Yat-Sen University, Guangzhou, P. R. China
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
37
|
A proteomic study on a human osteosarcoma cell line Saos-2 treated with diallyl trisulfide. Anticancer Drugs 2009; 20:702-12. [DOI: 10.1097/cad.0b013e32832e89c7] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
|
|
38
|
Mass spectrometry-based serum proteome pattern analysis in molecular diagnostics of early stage breast cancer. J Transl Med 2009; 7:60. [PMID: 19594898 PMCID: PMC2725033 DOI: 10.1186/1479-5876-7-60] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2009] [Accepted: 07/13/2009] [Indexed: 01/20/2023] Open
Abstract
Background Mass spectrometric analysis of the blood proteome is an emerging method of clinical proteomics. The approach exploiting multi-protein/peptide sets (fingerprints) detected by mass spectrometry that reflect overall features of a specimen's proteome, termed proteome pattern analysis, have been already shown in several studies to have applicability in cancer diagnostics. We aimed to identify serum proteome patterns specific for early stage breast cancer patients using MALDI-ToF mass spectrometry. Methods Blood samples were collected before the start of therapy in a group of 92 patients diagnosed at stages I and II of the disease, and in a group of age-matched healthy controls (104 women). Serum specimens were purified and the low-molecular-weight proteome fraction was examined using MALDI-ToF mass spectrometry after removal of albumin and other high-molecular-weight serum proteins. Protein ions registered in a mass range between 2,000 and 10,000 Da were analyzed using a new bioinformatic tool created in our group, which included modeling spectra as a sum of Gaussian bell-shaped curves. Results We have identified features of serum proteome patterns that were significantly different between blood samples of healthy individuals and early stage breast cancer patients. The classifier built of three spectral components that differentiated controls and cancer patients had 83% sensitivity and 85% specificity. Spectral components (i.e., protein ions) that were the most frequent in such classifiers had approximate m/z values of 2303, 2866 and 3579 Da (a biomarker built from these three components showed 88% sensitivity and 78% specificity). Of note, we did not find a significant correlation between features of serum proteome patterns and established prognostic or predictive factors like tumor size, nodal involvement, histopathological grade, estrogen and progesterone receptor expression. In addition, we observed a significantly (p = 0.0003) increased level of osteopontin in blood of the group of cancer patients studied (however, the plasma level of osteopontin classified cancer samples with 88% sensitivity but only 28% specificity). Conclusion MALDI-ToF spectrometry of serum has an obvious potential to differentiate samples between early breast cancer patients and healthy controls. Importantly, a classifier built on MS-based serum proteome patterns outperforms available protein biomarkers analyzed in blood by immunoassays.
Collapse
|
|
39
|
|
|
40
|
Andres AC. New perspectives for therapy choice. Cancer Treat Res 2009; 151:31-40. [PMID: 19593504 DOI: 10.1007/978-0-387-75115-3_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/28/2023]
Affiliation(s)
- Anne- Catherine Andres
- Department of Clinical Research, University of Bern, Tiefenaustrasse, Bern, Switzerland.
| |
Collapse
|
|
41
|
Proteomics: New technologies and clinical applications. Eur J Cancer 2008; 44:2737-41. [DOI: 10.1016/j.ejca.2008.09.007] [Citation(s) in RCA: 85] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2008] [Accepted: 09/23/2008] [Indexed: 12/26/2022]
|
|
42
|
Lee CJ, Ariztia EV, Fishman DA. Conventional and Proteomic Technologies for the Detection of Early Stage Malignancies: Markers for Ovarian Cancer. Crit Rev Clin Lab Sci 2008; 44:87-114. [PMID: 17175521 DOI: 10.1080/10408360600778885] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Our understanding of the tumor microenvironment continues to evolve and allows for the identification of biomarkers that should detect the presence of early stage malignancies. Recent advances in computational analysis and biomedical technologies have come together to elucidate signatures associated with cancer and that are capable of identifying unique tumor-specific proteins. Within the tumor microenvironment, we continue to characterize the proteophysiology of the different steps associated with tumor progression. The urgent need for biomarkers accurately detecting early-stage epithelial ovarian cancer has prompted us, and others, to engage in a search for specific peptide signatures that may discriminate transformed cells from those of the normal ovarian microenvironment. This endeavor also provides new insights into the biology of the disease, which may not only be applicable to detection but may also help to initiate new therapies and optimize patient care.
Collapse
Affiliation(s)
- Catherine J Lee
- Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York 10016, USA
| | | | | |
Collapse
|
|
43
|
Abstract
Cancer is a disease of "outlaw" cells that become mutated in regulatory mechanisms. They have lost normal self controls and relationships to the whole organism. Cancers can progress by several pathways from a normal cell to malignant cancer, from bad to worse. Questions about advisability of treatment for some cancers arise from the possibility that they are arrested during progression and so never become lethal. Techniques could be developed to determine the degree of progression and possibility for successful treatment. This article is intended to suggest a way of looking at cancer. It is not a review so references to research articles are infrequent.
Collapse
Affiliation(s)
- Meng Qiao
- Dana-Farber Cancer Institute, 44 Binney St., Boston, Massachusetts 02115, USA
| | | |
Collapse
|
|
44
|
Annunziata CM, Azad N, Dhamoon AS, Whiteley G, Kohn EC. Ovarian cancer in the proteomics era. Int J Gynecol Cancer 2008; 18 Suppl 1:1-6. [PMID: 18336391 DOI: 10.1111/j.1525-1438.2007.01096.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Ovarian cancer presents a diagnostic challenge because of its subtle clinical presentation and elusive cell of origin. Two new technologies of proteomics have advanced the dissection of the underlying molecular signaling events and the proteomic characterization of ovarian cancer: mass spectrometry and protein array analysis. Mass spectrometry can provide a snapshot of a proteome in time and space, with sensitivity and resolution that may allow identification of the elusive "needle in the haystack" heralding ovarian cancer. Proteomic profiling of tumor tissue samples can survey molecular targets during treatment and quantify changes using reverse phase protein arrays generated from tumor samples captured by microdissection, lysed and spotted in serial dilutions for high-throughput analysis. This approach can be applied to identify the optimal biological dose of a targeted agent and to validate target to outcome link. The evolution of proteomic technologies has the capacity to advance rapidly our understanding of ovarian cancer at a molecular level and thus elucidate new directions for the treatment of this disease.
Collapse
Affiliation(s)
- C M Annunziata
- Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1906, USA.
| | | | | | | | | |
Collapse
|
|
45
|
Callesen AK, Vach W, Jørgensen PE, Cold S, Tan Q, dePont Christensen R, Mogensen O, Kruse TA, Jensen ON, Madsen JS. Combined Experimental and Statistical Strategy for Mass Spectrometry Based Serum Protein Profiling for Diagnosis of Breast Cancer: A Case-Control Study. J Proteome Res 2008; 7:1419-26. [DOI: 10.1021/pr7007576] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- Anne K. Callesen
- Protein Research Group, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark, Department of Biochemistry, Pharmacology and Genetics, Odense University Hospital, Odense, Denmark, Department of Statistics, University of Southern Denmark, Odense, Denmark, Department of Oncology, Odense University Hospital, Odense, Denmark, and Department of Gynecology and Obstetrics, Odense University Hospital, Odense, Denmark
| | - Werner Vach
- Protein Research Group, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark, Department of Biochemistry, Pharmacology and Genetics, Odense University Hospital, Odense, Denmark, Department of Statistics, University of Southern Denmark, Odense, Denmark, Department of Oncology, Odense University Hospital, Odense, Denmark, and Department of Gynecology and Obstetrics, Odense University Hospital, Odense, Denmark
| | - Per E. Jørgensen
- Protein Research Group, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark, Department of Biochemistry, Pharmacology and Genetics, Odense University Hospital, Odense, Denmark, Department of Statistics, University of Southern Denmark, Odense, Denmark, Department of Oncology, Odense University Hospital, Odense, Denmark, and Department of Gynecology and Obstetrics, Odense University Hospital, Odense, Denmark
| | - Søren Cold
- Protein Research Group, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark, Department of Biochemistry, Pharmacology and Genetics, Odense University Hospital, Odense, Denmark, Department of Statistics, University of Southern Denmark, Odense, Denmark, Department of Oncology, Odense University Hospital, Odense, Denmark, and Department of Gynecology and Obstetrics, Odense University Hospital, Odense, Denmark
| | - Qihua Tan
- Protein Research Group, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark, Department of Biochemistry, Pharmacology and Genetics, Odense University Hospital, Odense, Denmark, Department of Statistics, University of Southern Denmark, Odense, Denmark, Department of Oncology, Odense University Hospital, Odense, Denmark, and Department of Gynecology and Obstetrics, Odense University Hospital, Odense, Denmark
| | - René dePont Christensen
- Protein Research Group, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark, Department of Biochemistry, Pharmacology and Genetics, Odense University Hospital, Odense, Denmark, Department of Statistics, University of Southern Denmark, Odense, Denmark, Department of Oncology, Odense University Hospital, Odense, Denmark, and Department of Gynecology and Obstetrics, Odense University Hospital, Odense, Denmark
| | - Ole Mogensen
- Protein Research Group, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark, Department of Biochemistry, Pharmacology and Genetics, Odense University Hospital, Odense, Denmark, Department of Statistics, University of Southern Denmark, Odense, Denmark, Department of Oncology, Odense University Hospital, Odense, Denmark, and Department of Gynecology and Obstetrics, Odense University Hospital, Odense, Denmark
| | - Torben A. Kruse
- Protein Research Group, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark, Department of Biochemistry, Pharmacology and Genetics, Odense University Hospital, Odense, Denmark, Department of Statistics, University of Southern Denmark, Odense, Denmark, Department of Oncology, Odense University Hospital, Odense, Denmark, and Department of Gynecology and Obstetrics, Odense University Hospital, Odense, Denmark
| | - Ole N. Jensen
- Protein Research Group, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark, Department of Biochemistry, Pharmacology and Genetics, Odense University Hospital, Odense, Denmark, Department of Statistics, University of Southern Denmark, Odense, Denmark, Department of Oncology, Odense University Hospital, Odense, Denmark, and Department of Gynecology and Obstetrics, Odense University Hospital, Odense, Denmark
| | - Jonna S. Madsen
- Protein Research Group, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark, Department of Biochemistry, Pharmacology and Genetics, Odense University Hospital, Odense, Denmark, Department of Statistics, University of Southern Denmark, Odense, Denmark, Department of Oncology, Odense University Hospital, Odense, Denmark, and Department of Gynecology and Obstetrics, Odense University Hospital, Odense, Denmark
| |
Collapse
|
|
46
|
Abstract
Malignant pleural effusions (MPEs) are an important complication for patients with intrathoracic and extrathoracic malignancies. Median survival after diagnosis of an MPE is 4 months. Patients can present with an MPE as a complication of far-advanced cancer or as the initial manifestation of an underlying malignancy. Common cancer types causing MPEs include lymphomas, mesotheliomas, and carcinomas of the breast, lung, gastrointestinal tract, and ovaries. However, almost all tumor types have been reported to cause MPEs. New imaging modalities assist the evaluation of patients with a suspected MPE; however, positive cytologic or tissue confirmation of malignant cells is necessary to establish a diagnosis. Even in the presence of known malignancy, up to 50% of pleural effusions are benign, underscoring the importance of a firm diagnosis to guide therapy. Rapidly evolving interventional and histopathologic techniques have improved the diagnostic yield of standard cytology and biopsy. Management of an MPE remains palliative; it is critical that the appropriate management approach is chosen on the basis of available expertise and the patient's clinical status. This review summarizes the pathogenesis, diagnosis, and management of MPE. Studies in the English language were identified by searching the MEDLINE database (1980-2007) using the search terms pleura, pleural, malignant, pleurodesis, and thoracoscopy.
Collapse
Affiliation(s)
- John E Heffner
- Department of Medicine, Providence Portland Medical Center, Oregon Health and Science University, 5040 NE Hoyt St, Ste 540, Portland, OR 97213, USA.
| | | |
Collapse
|
|
47
|
Abstract
Procurement of pure populations of cells from heterogeneous histological sections can be accomplished utilizing tissue microdissection. At present, a variety of different manual and laser-based dissection tools are available and each method has particular strengths and weaknesses. The types of biomolecular analyses that can be performed on microdissected cells depend not only on the method of cell procurement, but also on the effects of upstream tissue handling and processing. Tissue preparation protocols include two major approaches; snap-freezing, or, fixation and embedding. Snap-freezing generally provides the best quality tissue for subsequent study, including proteomic analyses such as two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Tissue fixatives include either precipitating reagents or biomolecular cross-linkers. The fixed samples are then further processed and embedded in a wax medium. In general, the biomolecules recovered from fixed and embedded tissue specimens are lower in both quantity and quality than those from snap-frozen specimens, although they are useful for certain types of analyses. The protocols provided here for tissue handling and processing, preparation of tissue sections, and microdissection are derived from our experience at the Pathogenetics Unit of the National Cancer Institute.
Collapse
|
|
48
|
Abstract
Proteomic studies have generated numerous datasets of potential diagnostic, prognostic, and therapeutic significance in human cancer. Two key technologies underpinning these studies in cancer tissue are two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and mass spectrometry (MS). Although surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF)-MS is the mainstay for serum or plasma analysis, other methods including isotope-coded affinity tag technology, reverse-phase protein arrays, and antibody microarrays are emerging as alternative proteomic technologies. Because there is little overlap between studies conducted with these approaches, confirmation of these advanced technologies remains an elusive goal. This problem is further exacerbated by lack of uniform patient inclusion and exclusion criteria, low patient numbers, poor supporting clinical data, absence of standardized sample preparation, and limited analytical reproducibility (in particular of 2D-PAGE). Despite these problems, there is little doubt that the proteomic approach has the potential to identify novel diagnostic biomarkers in cancer. In therapeutic proteomics, the challenge is significant due to the complexity systems under investigation (i.e., cells generate over 10(5) different polypeptides). However, the most significant contribution of therapeutic proteomics research is expected to derive not from single experiments, but from the synthesis and comparison of large datasets obtained under different conditions (e.g., normal, inflammation, cancer) and in different tissues and organs. Thus, standardized processes for storing and retrieving data obtained with different technologies by different research groups will have to be developed. Shifting the emphasis of cancer proteomics from technology development and data generation to careful study design, data organization, formatting, and mining is crucial to answer clinical questions in cancer research.
Collapse
Affiliation(s)
- M A Reymond
- Department of Surgery, University of Magdeburg, Germany
| | | |
Collapse
|
|
49
|
|
|
50
|
Weng YQ, Qiu SJ, Liu YK, Fan J, Gao Q, Tang ZY. Down-regulation of beta-centractin might be involved in dendritic cells dysfunction and subsequent hepatocellular carcinoma immune escape: a proteomic study. J Cancer Res Clin Oncol 2007; 134:179-86. [PMID: 17619203 DOI: 10.1007/s00432-007-0267-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2006] [Accepted: 04/26/2007] [Indexed: 12/16/2022]
Abstract
AIMS Proteomic study was used to clarify the mechanism of hepatocellular carcinoma (HCC) immune escape concerning Dendritic cells (DCs') dysfunction and their association with HCC invasion. METHODS Human peripheral blood mononuclear cells (PBMCs) derived DCs from healthy donors were pulsed with soluble cell lysates prepared from different metastatic potential human HCC cell lines. The total protein of these DCs was analyzed by two-dimensional electrophoresis and Electro-Spray Mass Spectrometry. The allostimulatoy capacity and phenotype of these DCs were also evaluated. The clinical significance of beta-centractin, one of the largest quantitative changed spot, down-regulation in DCs was further evaluated in autologous PBMCs derived DCs pulsed with auto-tumor lysates in 26 HCC patients. RESULTS The expression of beta-centractin was found to be considerably lower either in DCs pulsed with HCCLM6 (high metastatic potential HCC cell line) lysates, accompanied by down-regulation of CD86 molecule and impaired allostimulatory capacity, than those of DCs pulsed with lysates from HCC cell lines with low or without metastatic potential or in DCs pulsed with lysates from HCC with invasiveness than those without invasiveness. CONCLUSIONS The down-regulation of beta-centractin in DCs pulsed with high metastatic potential HCC lysates might associate with DCs dysfunction and HCC invasiveness.
Collapse
Affiliation(s)
- Yong-Qiang Weng
- Liver Cancer Institute and Zhong Shan Hospital, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, Ministry of Education, 136 Yi Xue Yuan Road, Shanghai 200032, People's Republic of China.
| | | | | | | | | | | |
Collapse
|