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Mol Cancer Ther 9: 126\u2013133.", "score": 2.5, "uri_source": "plos_html", "id": "pone.0070194-Jeon1"}, {"bibliographic": {"DOI": "10.1002/jor.21056", "subtitle": [], "issued": {"date-parts": [[2009]]}, "prefix": "http://id.crossref.org/prefix/10.1002", "bib_source": "dx.doi.org", "subject": ["Medicine(all)"], "author": [{"given": "Takeshi", "family": "Hori"}, {"given": "Takashi", "family": "Kondo"}, {"given": "Masahiko", "family": "Kanamori"}, {"given": "Yoshiaki", "family": "Tabuchi"}, {"given": "Ryohei", "family": "Ogawa"}, {"given": "Qing-Li", "family": "Zhao"}, {"given": "Kanwal", "family": "Ahmed"}, {"given": "Taketoshi", "family": "Yasuda"}, {"given": "Shoji", "family": "Seki"}, {"given": "Kayo", "family": "Suzuki"}, {"given": "Tomoatsu", "family": "Kimura"}], "reference-count": 23, "ISSN": ["0736-0266", "1554-527X"], "member": "http://id.crossref.org/member/311", "source": "CrossRef", "score": 1.0, "deposited": {"timestamp": 1262044800000, "date-parts": [[2009, 12, 29]]}, "indexed": {"timestamp": 1409625119792, "date-parts": [[2014, 9, 2]]}, "type": "journal-article", "URL": "http://dx.doi.org/10.1002/jor.21056", "volume": "28", "publisher": "Wiley-Blackwell", "container-type": "journal", "title": "Ionizing radiation enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through up-regulations of death receptor 4 (DR4) and death receptor 5 (DR5) in human osteosarcoma cells", "container-title": "J. Orthop. Res.", "page": "n/a-n/a"}, "citation_groups": ["12"], "number": 16, "uri": "http://dx.doi.org/10.1002%2Fjor.21056", "original_citation": "HoriT, KondoT, KanamoriM, TabuchiY, OgawaR, et al. (2010) Ionizing radiation enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through up-regulations of death receptor 4 (DR4) and death receptor 5 (DR5) in human osteosarcoma cells. J Orthop Res 28: 739\u2013745.", "score": 2.5, "uri_source": "plos_html", "id": "pone.0070194-Hori1"}, {"bibliographic": {"DOI": "10.1111/j.1755-148x.2010.00729.x", "subtitle": ["A novel treatment for radioresistant uveal melanoma"], "issued": {"date-parts": [[2010, 6, 11]]}, "prefix": "http://id.crossref.org/prefix/10.1111", "bib_source": "dx.doi.org", "subject": ["Oncology", "Biochemistry, Genetics and Molecular Biology(all)", "Dermatology"], "author": [{"given": "Yixiong", "family": "Zhou"}, {"given": "Xin", "family": "Song"}, {"given": "Renbin", "family": "Jia"}, {"given": "Haibo", "family": "Wang"}, {"given": "Liyan", "family": "Dai"}, {"given": "Xiaofang", "family": "Xu"}, {"given": "Ping", "family": "Gu"}, {"given": "Shengfang", "family": "Ge"}, {"given": "Xianqun", "family": "Fan"}], "reference-count": 38, "ISSN": ["1755-1471"], "member": "http://id.crossref.org/member/311", "source": "CrossRef", "score": 1.0, "deposited": {"timestamp": 1291334400000, "date-parts": [[2010, 12, 3]]}, "indexed": {"timestamp": 1409653131198, "date-parts": [[2014, 9, 2]]}, "type": "journal-article", "URL": "http://dx.doi.org/10.1111/j.1755-148x.2010.00729.x", "volume": "23", "publisher": "Wiley-Blackwell", "container-type": "journal", "license": "failed-to-obtain-license", "issue": "5", "title": "Radiation-inducible human tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene therapy: a novel treatment for radioresistant uveal melanoma", "container-title": "Pigment Cell & Melanoma Research", "page": "661-674"}, "citation_groups": ["12", "30"], "number": 17, "uri": "http://dx.doi.org/10.1111%2Fj.1755-148x.2010.00729.x", "original_citation": "ZhouY, SongX, JiaR, WangH, DaiL, et al. (2010) Radiation-inducible human tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene therapy: a novel treatment for radioresistant uveal melanoma. Pigment Cell Melanoma Res 23: 661\u2013674.", "score": 2.5, "uri_source": "plos_html", "id": "pone.0070194-Zhou1"}, {"bibliographic": {"DOI": "10.1371/journal.pone.0054055", "subtitle": [], "issued": {"date-parts": [[2013, 1, 14]]}, "abstract": "Background: Human sodium iodide symporter (hNIS) gene over-expression is under active consideration worldwide as an alternative target molecule for breast cancer (BC) diagnosis and targeted radio-iodine treatment. However, the field demands better stratified analysis of endogenous hNIS expression across major BC subtypes. Therefore, we have analyzed subtype-specific variation of hNIS overexpression in breast tumor tissue samples by immunohistochemistry (IHC) and also report the development of a homogeneous, quantitative analysis method of digital IHC images. Methods: hNIS expression was analyzed from 108 BC tissue samples by IHC. Sub-cellular localization of hNIS protein was analyzed by dual immunofluorescence (IF) staining method using hNIS and HER2 antibodies. An ImageJ based two-step digital analysis method was developed and applied for the bias-free analysis of the images. Results: Staining of the tumor samples show 70% cases are hNIS positive indicating high incidence of hNIS positive cases in BC. More importantly, a subtype specific analysis done for the first time shows that hNIS expression is overly dominated in estrogen receptor (ER) positive cases than the receptor negative cases. Further, 56% of the ER+ve, PgR+ve, HER2-ve and 36% of ER+ve, PgR+ve, HER2+ve cases show highest intensity staining equivalent to the thyroid tissue. A significant positive correlation is also observed between hNIS and estrogen receptor expression (p\u200a=\u200a0.0033, CI\u200a=\u200a95%) suggesting hNIS mediated targeted radio-iodine therapy procedures may benefit both ER+ve, PgR+ve, HER2\u2013ve as well as HER2+ve cases. Further, in a few cases, hNIS and HER2 protein localization is demonstrated by overlapping membrane co-expression. ImageJ based image analysis method shows over 70% match with manual pathological scoring method. Conclusion: The study indicates a positive link between hNIS and ER expression in BC. The quantitative IHC image analysis method reported here will further help in patient stratification and potentially benefit global clinical assessment where hNIS mediated targeted 131I radio-ablative therapy is aimed.", "prefix": "http://id.crossref.org/prefix/10.1371", "bib_source": "dx.doi.org", "subject": ["Agricultural and Biological Sciences(all)", "Medicine(all)", "Biochemistry, Genetics and Molecular Biology(all)"], "author": [{"affiliation": "Functional Molecular Imaging Lab, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai, India", "given": "Sushmita", "family": "Chatterjee"}, {"affiliation": "Functional Molecular Imaging Lab, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai, India", "given": "Renu", "family": "Malhotra"}, {"affiliation": "Functional Molecular Imaging Lab, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai, India", "given": "Frency", "family": "Varghese"}, {"affiliation": "Functional Molecular Imaging Lab, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai, India", "given": "Amirali B.", "family": "Bukhari"}, {"affiliation": "Molecular Pathology, Tata Memorial Hospital, Parel, Mumbai, India", "given": "Asawari", "family": "Patil"}, {"affiliation": "Department of Radiation Oncology, Tata Memorial Hospital, Parel, Mumbai, India", "given": "Ashwini", "family": "Budrukkar"}, {"affiliation": "Department of Surgery, Tata Memorial Hospital, Parel, Mumbai, India", "given": "Vani", "family": "Parmar"}, {"affiliation": "Department of Medical Oncology, Tata Memorial Hospital, Parel, Mumbai, India", "given": "Sudeep", "family": "Gupta"}, {"affiliation": "Functional Molecular Imaging Lab, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai, India", "given": "Abhijit", "email": "[email protected]", "family": "De"}], "reference-count": 0, "ISSN": ["1932-6203"], "member": "http://id.crossref.org/member/340", "source": "CrossRef", "score": 1.0, "deposited": {"timestamp": 1393977600000, "date-parts": [[2014, 3, 5]]}, "editor": [{"given": "Pranela", "family": "Rameshwar"}], "indexed": {"timestamp": 1410304702727, "date-parts": [[2014, 9, 9]]}, "type": "journal-article", "URL": "http://dx.doi.org/10.1371/journal.pone.0054055", "volume": "8", "update-policy": "http://dx.doi.org/10.1371/journal.pone.corrections_policy", "publisher": "Public Library of Science (PLoS)", "issue": "1", "title": "Quantitative Immunohistochemical Analysis Reveals Association between Sodium Iodide Symporter and Estrogen Receptor Expression in Breast Cancer", "container-title": "PLoS ONE", "page": "e54055"}, "citation_groups": ["12", "13"], "number": 18, "word_count": 4298, "uri": "http://dx.doi.org/10.1371%2Fjournal.pone.0054055", "original_citation": "ChatterjeeS, MalhotraR, VargheseF, BukhariAB, PatilA, et al. (2013) Quantitative immunohistochemical analysis reveals association between sodium iodide symporter and estrogen receptor expression in breast cancer. PLoS One 8: e54055.", "score": 2.5, "id": "pone.0070194-Chatterjee1"}, {"bibliographic": {"DOI": "10.1371/journal.pone.0016023", "subtitle": [], "issued": {"date-parts": [[2011, 1, 19]]}, "abstract": "Introduction: The presence, relevance and regulation of the Sodium Iodide Symporter (NIS) in human mammary tissue remains poorly understood. This study aimed to quantify relative expression of NIS and putative regulators in human breast tissue, with relationships observed further investigated in vitro. Methods: Human breast tissue specimens (malignant n\u200a=\u200a75, normal n\u200a=\u200a15, fibroadenoma n\u200a=\u200a10) were analysed by RQ-PCR targeting NIS, receptors for retinoic acid (RAR\u03b1, RAR\u03b2), oestrogen (ER\u03b1), thyroid hormones (THR\u03b1, THR\u03b2), and also phosphoinositide-3-kinase (PI3K). Breast cancer cells were treated with Retinoic acid (ATRA), Estradiol and Thyroxine individually and in combination followed by analysis of changes in NIS expression. Results: The lowest levels of NIS were detected in normal tissue (Mean(SEM) 0.70(0.12) Log10 Relative Quantity (RQ)) with significantly higher levels observed in fibroadenoma (1.69(0.21) Log10RQ, p", "prefix": "http://id.crossref.org/prefix/10.1371", "bib_source": "dx.doi.org", "subject": ["Agricultural and Biological Sciences(all)", "Medicine(all)", "Biochemistry, Genetics and Molecular Biology(all)"], "author": [{"given": "James", "family": "Ryan"}, {"given": "Catherine E.", "family": "Curran"}, {"given": "Emer", "family": "Hennessy"}, {"given": "John", "family": "Newell"}, {"given": "John C.", "family": "Morris"}, {"given": "Michael J.", "family": "Kerin"}, {"given": "Roisin M.", "family": "Dwyer"}], "reference-count": 0, "ISSN": ["1932-6203"], "member": "http://id.crossref.org/member/340", "source": "CrossRef", "score": 1.0, "deposited": {"timestamp": 1394064000000, "date-parts": [[2014, 3, 6]]}, "editor": [{"given": "Marian", "family": "Ludgate"}], "indexed": {"timestamp": 1410318992827, "date-parts": [[2014, 9, 10]]}, "type": "journal-article", "URL": "http://dx.doi.org/10.1371/journal.pone.0016023", "volume": "6", "update-policy": "http://dx.doi.org/10.1371/journal.pone.corrections_policy", "publisher": "Public Library of Science (PLoS)", "container-type": "journal", "issue": "1", "title": "The Sodium Iodide Symporter (NIS) and Potential Regulators in Normal, Benign and Malignant Human Breast Tissue", "container-title": "PLoS ONE", "page": "e16023"}, "citation_groups": ["13", "34"], "number": 19, "uri": "http://dx.doi.org/10.1371%2Fjournal.pone.0016023", "original_citation": "RyanJ, CurranCE, HennessyE, NewellJ, MorrisJC, et al. (2011) The sodium iodide symporter (NIS) and potential regulators in normal, benign and malignant human breast tissue. PLoS One 6: e16023.", "score": 2.5, "uri_source": "plos_html", "id": "pone.0070194-Ryan1"}, {"bibliographic": {"DOI": "10.1023/a:1021321409159", "subtitle": [], "issued": {"date-parts": [[2003, 1]]}, "prefix": "http://id.crossref.org/prefix/10.1007", "bib_source": "dx.doi.org", "subject": ["Oncology", "Cancer Research"], "author": [{"given": "Geeta", "family": "Upadhyay"}, {"given": "Rajesh", "family": "Singh"}, {"given": "Gaurav", "family": "Agarwal"}, {"given": "Saroj K.", "family": "Mishra"}, {"given": "Lily", "family": "Pal"}, {"given": "Prasanta K.", "family": "Pradhan"}, {"given": "Birendra K.", "family": "Das"}, {"given": "Madan M.", "family": "Godbole"}], "reference-count": 22, "ISSN": ["0167-6806", "1573-7217"], "member": "http://id.crossref.org/member/297", "source": "CrossRef", "score": 1.0, "deposited": {"timestamp": 1356652800000, "date-parts": [[2012, 12, 28]]}, "indexed": {"timestamp": 1410053709597, "date-parts": [[2014, 9, 7]]}, "type": "journal-article", "URL": "http://dx.doi.org/10.1023/a:1021321409159", "volume": "77", "publisher": "Springer Science + Business Media", "container-type": "journal", "issue": "2", "title": "Functional Expression of Sodium Iodide Symporter (NIS) in Human Breast Cancer Tissue", "container-title": "Breast Cancer Res Treat", "page": "157-165"}, "citation_groups": ["14"], "number": 20, "uri": "http://dx.doi.org/10.1023%2Fa:1021321409159", "original_citation": "UpadhyayG, SinghR, AgarwalG, MishraSK, PalL, et al. (2003) Functional expression of sodium iodide symporter (NIS) in human breast cancer tissue. Breast Cancer Res Treat 77: 157\u2013165.", "score": 2.5, "uri_source": "plos_html", "id": "pone.0070194-Upadhyay1"}, {"bibliographic": {"DOI": "10.1016/s0140-6736(05)66544-0", "subtitle": [], "issued": {"date-parts": [[2005, 5]]}, "prefix": "http://id.crossref.org/prefix/10.1016", "bib_source": "dx.doi.org", "subject": ["Medicine(all)"], "title": "Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials", "reference-count": 20, "ISSN": ["0140-6736"], "member": "http://id.crossref.org/member/78", "source": "CrossRef", "score": 1.0, "deposited": {"timestamp": 1392940800000, "date-parts": [[2014, 2, 21]]}, "indexed": {"timestamp": 1410296840192, "date-parts": [[2014, 9, 9]]}, "type": "journal-article", "URL": "http://dx.doi.org/10.1016/s0140-6736(05)66544-0", "volume": "365", "publisher": "Elsevier BV", "container-type": "journal", "license": "failed-to-obtain-license", "issue": "9472", "author": [{"given": "O", "family": "Abe"}, {"given": "R", "family": "Abe"}, {"given": "K", "family": "Enomoto"}, {"given": "K", "family": "Kikuchi"}, {"given": "H", "family": "Koyama"}], "container-title": "The Lancet", "page": "1687-1717"}, "citation_groups": ["15"], "number": 21, "uri": "http://dx.doi.org/10.1016%2Fs0140-6736(05)66544-0", "original_citation": "GEBCTC (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365: 1687\u20131717.", "score": 2.5, "uri_source": "plos_html", "id": "pone.0070194-G1"}, {"bibliographic": {"DOI": "10.1038/86297", "subtitle": [], "issued": {"date-parts": [[2001, 4, 1]]}, "prefix": "http://id.crossref.org/prefix/10.1038", "bib_source": "dx.doi.org", "subject": ["Immunology"], "author": [{"given": "Mark J.", "family": "Smyth"}, {"given": "Dale I.", "family": "Godfrey"}, {"given": "Joseph A.", "family": "Trapani"}], "reference-count": 85, "ISSN": ["1529-2908"], "member": "http://id.crossref.org/member/339", "source": "CrossRef", "score": 1.0, "deposited": {"timestamp": 1313971200000, "date-parts": [[2011, 8, 22]]}, "indexed": {"timestamp": 1409804907779, "date-parts": [[2014, 9, 4]]}, "type": "journal-article", "URL": "http://dx.doi.org/10.1038/86297", "volume": "2", "publisher": "Nature Publishing Group", "container-type": "journal", "issue": "4", "title": "A fresh look at tumor immunosurveillance and immunotherapy", "container-title": "Nat. Immunol.", "page": "293-299"}, "citation_groups": ["17", "18"], "number": 22, "uri": "http://dx.doi.org/10.1038%2F86297", "original_citation": "SmythMJ, GodfreyDI, TrapaniJA (2001) A fresh look at tumor immunosurveillance and immunotherapy. Nat Immunol 2: 293\u2013299.", "score": 2.5, "uri_source": "plos_html", "id": "pone.0070194-Smyth1"}, {"bibliographic": {"DOI": "10.1089/104303403765255110", "subtitle": [], "issued": {"date-parts": [[2003, 5, 20]]}, "prefix": "http://id.crossref.org/prefix/10.1089", "bib_source": "dx.doi.org", "subject": ["Molecular Biology", "Molecular Medicine", "Genetics"], "author": [{"given": "Steven A.", "family": "Rosenberg"}, {"given": "James C.", "family": "Yang"}, {"given": "Richard M.", "family": "Sherry"}, {"given": "Patrick", "family": "Hwu"}, {"given": "Suzanne L.", "family": "Topalian"}, {"given": "Douglas J.", "family": "Schwartzentruber"}, {"given": "Nicholas P.", "family": "Restifo"}, {"given": "Leah R.", "family": "Haworth"}, {"given": "Claudia A.", "family": "Seipp"}, {"given": "Linda J.", "family": "Freezer"}, {"given": "Kathleen E.", "family": "Morton"}, {"given": "Sharon A.", "family": "Mavroukakis"}, {"given": "Donald E.", "family": "White"}], "reference-count": 36, "ISSN": ["1043-0342", "1557-7422"], "member": "http://id.crossref.org/member/278", "source": "CrossRef", "score": 1.0, "deposited": {"timestamp": 1313107200000, "date-parts": [[2011, 8, 12]]}, "indexed": {"timestamp": 1409856181184, "date-parts": [[2014, 9, 4]]}, "type": "journal-article", "URL": "http://dx.doi.org/10.1089/104303403765255110", "volume": "14", "publisher": "Mary Ann Liebert Inc", "container-type": "journal", "issue": "8", "title": "Inability to Immunize Patients with Metastatic Melanoma Using Plasmid DNA Encoding the gp100 Melanoma-Melanocyte Antigen", "container-title": "Human Gene Therapy", "page": "709-714"}, "citation_groups": ["18"], "number": 23, "uri": "http://dx.doi.org/10.1089%2F104303403765255110", "original_citation": "RosenbergSA, YangJC, SherryRM, HwuP, TopalianSL, et al. 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The present study showed that I-131 therapy can modulate microenvironment of breast cancer and improve the therapeutic effect by enhancing NK cell cytotoxicity to the tumor cells. The susceptibility of breast cancer cells to NK cell was increased by precedent I-131 treatment in vitro. Tumor burden in mice treated with I-131 plus NK cell was significantly lower than that in mice treated with NK cell or I-131 alone. The up-regulation of Fas, DR5 and MIC A/B on irradiated tumor cells could be the explanation for the enhancement of NK cell cytotoxicity to tumor cells. 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Therefore, it is expected that pretreatment with I-131 will", "truncated_after": true}, "references": ["pone.0070194-Upadhyay1"], "word_position": 361, "id": "14"}, {"section": "Discussion", "flags": "pos", "context": {"truncated_before": true, "text_before": "control techniques, improved chemotherapy regimens, and targeted treatments has resulted in immense gains in survival in individuals with breast cancer ", "citation": "[21]", "text_after": ". Unfortunately, the triple negative breast cancers, a subset of", "truncated_after": true}, "references": ["pone.0070194-G1"], "word_position": 3024, "id": "15"}, {"section": "Discussion", "word_position": 3075, "references": ["pone.0070194-Dent1"], "id": "16", "context": {"truncated_before": true, "text_before": "to metastasize to distant visceral organs, and have a worse outcome with a high rate of recurrence after adjuvant treatment ", "citation": "[4]", "text_after": ". Thus, the need for development of successful therapeutic options", "truncated_after": true}}, {"section": "Discussion", "word_position": 3111, "references": ["pone.0070194-Sutlu1", "pone.0070194-Smyth1"], "id": "17", "context": {"truncated_before": true, "text_before": "outcome is urgent. An attractive approach to reducing the rate of recurrences in these individuals is use of immunotherapeutic strategies ", "citation": "[6], [22]", "text_after": ". However, because of the complexities of tumor microenvironments, effective", "truncated_after": true}}, {"section": "Discussion", "word_position": 3158, "references": ["pone.0070194-Smyth1", "pone.0070194-Rosenberg1"], "id": "18", "context": {"truncated_before": true, "text_before": "immunotherapy, such as tumor-derived suppression cytokines, the absence of danger signals, loss of MHC class molecules, and low antigen levels ", "citation": "[22], [23]", "text_after": ". To overcome these impediments, modulation of the tumor microenvironment", "truncated_after": true}}, {"section": "Discussion", "word_position": 3249, "references": ["pone.0070194-Fogler1"], "id": "19", "context": {"truncated_before": true, "text_before": "activation by cytokines, they are capable of extravasation and infiltration into most tissues that contain pathogen infected or malignant cells ", "citation": "[24]", "text_after": ". NK92 is a human NK cell line first established", "truncated_after": true}}, {"section": "Discussion", "word_position": 3272, "references": ["pone.0070194-Gong1"], "id": "20", "context": {"truncated_before": true, "text_before": "a human NK cell line first established in 1994 from a 50-year-old male patient with an aggressive NK cell lymphoma ", "citation": "[25]", "text_after": ". The NK92 cell line has been examined clinically as", "truncated_after": true}}, {"section": "Discussion", "word_position": 3289, "references": ["pone.0070194-Gong1", "pone.0070194-Tonn1"], "id": "21", "context": {"truncated_before": true, "text_before": "NK cell lymphoma [25]. The NK92 cell line has been examined clinically as a treatment for advanced sarcoma and leukemia ", "citation": "[25], [26]", "text_after": ". The parental NK92 cell line is highly dependent on", "truncated_after": true}}, {"section": "Discussion", "word_position": 3344, "references": ["pone.0070194-Tonn1", "pone.0070194-Tam1"], "id": "22", "context": {"truncated_before": true, "text_before": "been shown to be virtually identical to the parental cell line, may be a more appropriate choice for clinical therapies ", "citation": "[26], [27]", "text_after": ". Nagashima et al. [28] reported that NK92-MI sustained proliferation", "truncated_after": true}}, {"section": "Discussion", "word_position": 3349, "references": ["pone.0070194-Nagashima1"], "id": "23", "context": {"truncated_before": true, "text_before": "identical to the parental cell line, may be a more appropriate choice for clinical therapies [26], [27]. Nagashima et al. ", "citation": "[28]", "text_after": " reported that NK92-MI sustained proliferation in the absence of exogenously", "truncated_after": true}}, {"section": "Discussion", "word_position": 3419, "references": ["pone.0070194-Sutlu1"], "id": "24", "context": {"truncated_before": true, "text_before": "cells are carried out by two main mechanisms. The first mechanism is granule-dependent cytotoxicity, where upon triggering by activating receptors ", "citation": "[6]", "text_after": ". Upon recognition of the ligands on the surface of", "truncated_after": true}}, {"section": "Discussion", "word_position": 3455, "references": ["pone.0070194-Moretta1"], "id": "25", "context": {"truncated_before": true, "text_before": "NK cell receptors, various intracellular signaling pathways drive NK cells toward cytotoxic action, which results in cytolysis of target cells ", "citation": "[29]", "text_after": ". When NK cells are activated by MIC A/B, which", "truncated_after": true}}, {"section": "Discussion", "word_position": 3491, "references": ["pone.0070194-Lanier1"], "id": "26", "context": {"truncated_before": true, "text_before": "NKG2D on the tumor surface, perforin and granzyme B are released to the tumor cell, resulting in mediation of apoptosis ", "citation": "[30]", "text_after": ". However, these processes are tightly controlled by a group", "truncated_after": true}}, {"section": "Discussion", "word_position": 3557, "references": ["pone.0070194-Moretta2"], "id": "27", "context": {"truncated_before": true, "text_before": "which are mainly specific for self MHC Class-I molecules. Members of the KIR family recognize HLA-A, B and C alleles ", "citation": "[31]", "text_after": ". The second mechanism is the triggering of apoptosis pathways", "truncated_after": true}}, {"section": "Discussion", "word_position": 3626, "references": ["pone.0070194-Zamai1"], "id": "28", "context": {"truncated_before": true, "text_before": "the TNF family and have been shown to induce target cell apoptosis when they bind their receptors on target cells ", "citation": "[32]", "text_after": ". In the current study, the levels of surface expression", "truncated_after": true}}, {"section": "Discussion", "word_position": 3727, "references": ["pone.0070194-Ishikawa1"], "id": "29", "context": {"truncated_before": true, "text_before": "that radiation therapy concomitantly up-regulates the levels of Fas, DR5, and MIC A/B in several tumor cells. Ishikawa et al. ", "citation": "[13]", "text_after": " reported that external radiation therapy enhanced Fas and DR5 expression", "truncated_after": true}}, {"section": "Discussion", "word_position": 3755, "references": ["pone.0070194-Zhou1"], "id": "30", "context": {"truncated_before": true, "text_before": "and DR5 expression in glioma cell lines and cytotoxicity of NK cells was enhanced after radiation therapy. Zhou et al. ", "citation": "[17]", "text_after": " reported that DR5 expression was enhanced in melanoma cell lines", "truncated_after": true}}, {"section": "Discussion", "word_position": 3788, "references": ["pone.0070194-Xu1"], "id": "31", "context": {"truncated_before": true, "text_before": "radiation therapy and treatment with TRAIL resulted in significantly increased tumor cell apoptosis caused by radiation therapy. Xu et al. ", "citation": "[33]", "text_after": " also reported that radiation therapy up-regulated the level of MIC", "truncated_after": true}}, {"section": "Discussion", "flags": "pos", "context": {"truncated_before": true, "text_before": "addition, I-131 therapy is applicable to treatment of multiple metastatic breast cancer, which can take up I-131 by hNIS expression ", "citation": "[34]", "text_after": ". Jeon et al. [15] reported that I-131 therapy can", "truncated_after": true}, "references": ["pone.0070194-Boelaert1"], "word_position": 3866, "id": "32"}, {"section": "Discussion", "flags": "pos", "context": {"truncated_before": true, "text_before": "applicable to treatment of multiple metastatic breast cancer, which can take up I-131 by hNIS expression [34]. Jeon et al. ", "citation": "[15]", "text_after": " reported that I-131 therapy can lead to up-regulated expression of", "truncated_after": true}, "references": ["pone.0070194-Jeon1"], "word_position": 3870, "id": "33"}, {"section": "Discussion", "flags": "pos", "context": {"truncated_before": true, "text_before": "of breast cancers are known to express hNIS and take up iodide, it would be applicable in the clinical setting ", "citation": "[19]", "text_after": ".", "truncated_after": false}, "references": ["pone.0070194-Ryan1"], "word_position": 3947, "id": "34"}, {"section": "Discussion", "flags": "pos", "context": {"truncated_before": true, "text_before": "agents such as a retinoic acid, and enhancement by hNIS inducible agents has been well investigated in breast cancer cells ", "citation": "[35]\u2013[37]", "text_after": ". hNIS expression in breast cancer cells by the inducible", "truncated_after": true}, "references": ["pone.0070194-Kogai1", "pone.0070194-Dohan1", "pone.0070194-Fortunati1"], "word_position": 4008, "id": "35"}]}]