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Statements

Subject Item: n2:33917452
rdf:type: n4:CitationPaper
rdfs:seeAlso: n7:10.3390%2Fijms22073782 n8:0 n10:33917452 n11:0
bibo:cites: n2:19915524 n2:33248456 n2:11586292 n2:19118207 n2:11160825 n2:19487817 n2:23624917 n2:19487818 n2:20690820 n2:24357458 n2:10933231 n2:2027027 n2:21637948 n2:19854168 n2:11882906 n2:2827051 n2:25542864 n2:21123617 n2:15837516 n2:7806579 n2:17645776 n2:15758009 n2:3021931 n2:16123809 n2:7979242 n2:28327179 n2:9989517 n2:27193555 n2:19514083 n2:26511214 n2:2841267 n2:25845427 n2:8389708 n2:8620517 n2:3052284 n2:32354122 n2:1512163 n2:12389885 n2:9526994 n2:18854838 n2:23937436 n2:10211986 n2:9004416 n2:25120667 n2:10218097 n2:8612967 n2:10574710 n2:23562674 n2:21512826 n2:8832660 n2:15961063 n2:29156679 n2:26427041 n2:10797573 n2:3005894 n2:22652173 n2:6188316 n2:2153310 n2:17022644 n2:10214487 n2:29069715 n2:22576165 n2:8625273
n4:pmcid: PMC0
bibo:doi: 10.3390%2Fijms22073782
n9:contains: _:vb139051089 _:vb139051045

Subject Item: _:vb139051045
rdf:type: n9:Section
dc:title: introduction
n9:contains: _:vb139051088 _:vb139051072 _:vb139051073 _:vb139051074 _:vb139051075 _:vb139051076 _:vb139051077 _:vb139051078 _:vb139051079 _:vb139051080 _:vb139051081 _:vb139051082 _:vb139051083 _:vb139051084 _:vb139051085 _:vb139051086 _:vb139051087 _:vb139051056 _:vb139051057 _:vb139051058 _:vb139051059 _:vb139051060 _:vb139051061 _:vb139051062 _:vb139051063 _:vb139051064 _:vb139051065 _:vb139051066 _:vb139051067 _:vb139051068 _:vb139051069 _:vb139051070 _:vb139051071 _:vb139051046 _:vb139051047 _:vb139051048 _:vb139051049 _:vb139051050 _:vb139051051 _:vb139051052 _:vb139051053 _:vb139051054 _:vb139051055

Subject Item: _:vb139051046
rdf:type: n4:Context
rdf:value: This cancer accounts for 12% to 15% of all intracranial tumors and about 50% of astrocytomas [>>1<<]. Patients with GBM have a poor prognosis of just 12–15 months following standard therapy, with only 3–5% of patients surviving up to five years after diagnosis [2,3]. The current GBM treatment includes maximal resection, followed by
n4:mentions: n2:26511214

Subject Item: _:vb139051047
rdf:type: n4:Context
rdf:value: Patients with GBM have a poor prognosis of just 12–15 months following standard therapy, with only 3–5% of patients surviving up to five years after diagnosis [>>2<<,3]. The current GBM treatment includes maximal resection, followed by radiotherapy with concomitant and adjuvant Temozolomide (TMZ) chemotherapy [4]. Despite these aggressive therapeutic regimens, GBM’s poor prognosis is mainly due to its
n4:mentions: n2:25542864

Subject Item: _:vb139051048
rdf:type: n4:Context
rdf:value: Patients with GBM have a poor prognosis of just 12–15 months following standard therapy, with only 3–5% of patients surviving up to five years after diagnosis [2,>>3<<]. The current GBM treatment includes maximal resection, followed by radiotherapy with concomitant and adjuvant Temozolomide (TMZ) chemotherapy [4]. Despite these aggressive therapeutic regimens, GBM’s poor prognosis is mainly due to its
n4:mentions: n2:19514083

Subject Item: _:vb139051049
rdf:type: n4:Context
rdf:value: The current GBM treatment includes maximal resection, followed by radiotherapy with concomitant and adjuvant Temozolomide (TMZ) chemotherapy [>>4<<]. Despite these aggressive therapeutic regimens, GBM’s poor prognosis is mainly due to its high propensity for tumor recurrence. Its recurrence is inevitable after a median survival time of 32 to 36 weeks [5,6]. The recurrence most often
n4:mentions: n2:15758009

Subject Item: _:vb139051050
rdf:type: n4:Context
rdf:value: Its recurrence is inevitable after a median survival time of 32 to 36 weeks [>>5<<,6]. The recurrence most often occurs in the form of a local continuous growth within 2 to 3 cm from the border of the original lesion [7,8,9]. Choucair et al. reported that more than 90% of patients with glioma show recurrence at the
n4:mentions: n2:2827051

Subject Item: _:vb139051051
rdf:type: n4:Context
rdf:value: Its recurrence is inevitable after a median survival time of 32 to 36 weeks [5,>>6<<]. The recurrence most often occurs in the form of a local continuous growth within 2 to 3 cm from the border of the original lesion [7,8,9]. Choucair et al. reported that more than 90% of patients with glioma show recurrence at the
n4:mentions: n2:3021931

Subject Item: _:vb139051052
rdf:type: n4:Context
rdf:value: The recurrence most often occurs in the form of a local continuous growth within 2 to 3 cm from the border of the original lesion [>>7<<,8,9]. Choucair et al. reported that more than 90% of patients with glioma show recurrence at the original tumor location and the multiple lesions develop in 5% after standard treatment [6]. In spite of this, the extracranial GBM
n4:mentions: n2:1512163

Subject Item: _:vb139051053
rdf:type: n4:Context
rdf:value: The recurrence most often occurs in the form of a local continuous growth within 2 to 3 cm from the border of the original lesion [7,>>8<<,9]. Choucair et al. reported that more than 90% of patients with glioma show recurrence at the original tumor location and the multiple lesions develop in 5% after standard treatment [6]. In spite of this, the extracranial GBM metastases
n4:mentions: n2:2841267

Subject Item: _:vb139051054
rdf:type: n4:Context
rdf:value: The recurrence most often occurs in the form of a local continuous growth within 2 to 3 cm from the border of the original lesion [7,8,>>9<<]. Choucair et al. reported that more than 90% of patients with glioma show recurrence at the original tumor location and the multiple lesions develop in 5% after standard treatment [6]. In spite of this, the extracranial GBM metastases
n4:mentions: n2:9989517

Subject Item: _:vb139051055
rdf:type: n4:Context
rdf:value: Choucair et al. reported that more than 90% of patients with glioma show recurrence at the original tumor location and the multiple lesions develop in 5% after standard treatment [>>6<<]. In spite of this, the extracranial GBM metastases are rare, only 0.4 to 0.5% [10]. Thus, the prognostic biomarkers about cancer outcomes (e.g., disease recurrence and progression, and overall survival) are important for the treatment
n4:mentions: n2:3021931

Subject Item: _:vb139051056
rdf:type: n4:Context
rdf:value: In spite of this, the extracranial GBM metastases are rare, only 0.4 to 0.5% [>>10<<]. Thus, the prognostic biomarkers about cancer outcomes (e.g., disease recurrence and progression, and overall survival) are important for the treatment and management of GBM patients.
n4:mentions: n2:21512826

Subject Item: _:vb139051057
rdf:type: n4:Context
rdf:value: The extracellular matrix (ECM) plays an important role in numerous cellular functions during normal and pathological processes, such as differentiation, apoptosis, neurite outgrowth, tumor invasion, and metastasis [>>11<<,12,13]. Glioma cells seem to create a permissive environment for invasion through attachment to the ECM via cell surface receptors and subsequent ECM degradation [14].
n4:mentions: n2:10214487

Subject Item: _:vb139051058
rdf:type: n4:Context
rdf:value: The extracellular matrix (ECM) plays an important role in numerous cellular functions during normal and pathological processes, such as differentiation, apoptosis, neurite outgrowth, tumor invasion, and metastasis [11,>>12<<,13]. Glioma cells seem to create a permissive environment for invasion through attachment to the ECM via cell surface receptors and subsequent ECM degradation [14].
n4:mentions: n2:9004416

Subject Item: _:vb139051059
rdf:type: n4:Context
rdf:value: Glioma cells seem to create a permissive environment for invasion through attachment to the ECM via cell surface receptors and subsequent ECM degradation [>>14<<]. In addition, glioma cells synthesize and deposit ECM proteins, such as tenascin-C (TN-C), laminin (LM), fibronectin (FN), and type IV collagen (C-IV), which facilitate the tumor cell motility [14]. FN is a glycoprotein found in ECM as
n4:mentions: n2:8832660

Subject Item: _:vb139051060
rdf:type: n4:Context
rdf:value: In addition, glioma cells synthesize and deposit ECM proteins, such as tenascin-C (TN-C), laminin (LM), fibronectin (FN), and type IV collagen (C-IV), which facilitate the tumor cell motility [>>14<<]. FN is a glycoprotein found in ECM as aggregates or fibrils [13,15,16]. It has many biological functions including cell adhesion, migration, and invasion, and mediates a variety of adhesive events by binding to fibrinogen/fibrin,
n4:mentions: n2:8832660

Subject Item: _:vb139051061
rdf:type: n4:Context
rdf:value: FN is a glycoprotein found in ECM as aggregates or fibrils [13,15,>>16<<]. It has many biological functions including cell adhesion, migration, and invasion, and mediates a variety of adhesive events by binding to fibrinogen/fibrin, collagen, heparin sulfate, and hyaluronic acid.
n4:mentions: n2:8612967

Subject Item: _:vb139051062
rdf:type: n4:Context
rdf:value: FN is found at the gliomesenchymal junction of tumors, in tumor-associated blood vessels [>>17<<], and focally within and around glioma cells in situ [18], and is expressed by GBM cell lines in vitro [19].
n4:mentions: n2:6188316

Subject Item: _:vb139051063
rdf:type: n4:Context
rdf:value: FN is found at the gliomesenchymal junction of tumors, in tumor-associated blood vessels [17], and focally within and around glioma cells in situ [>>18<<], and is expressed by GBM cell lines in vitro [19].
n4:mentions: n2:2027027

Subject Item: _:vb139051064
rdf:type: n4:Context
rdf:value: FN is found at the gliomesenchymal junction of tumors, in tumor-associated blood vessels [17], and focally within and around glioma cells in situ [18], and is expressed by GBM cell lines in vitro [>>19<<]. The glioma cells express FN receptors, cluster around FN in vivo, and migrate in response to FN in vitro [20]. In addition, of several ECMs tested, GBM cells migrate most efficiently on FN [21]. Migration along FN positive mesenchymal
n4:mentions: n2:8625273

Subject Item: _:vb139051065
rdf:type: n4:Context
rdf:value: In addition, of several ECMs tested, GBM cells migrate most efficiently on FN [>>21<<]. Migration along FN positive mesenchymal cells may lead to the gathering of glioma cells in the perivascular regions and along the meninges [22].
n4:mentions: n2:8620517

Subject Item: _:vb139051066
rdf:type: n4:Context
rdf:value: Migration along FN positive mesenchymal cells may lead to the gathering of glioma cells in the perivascular regions and along the meninges [>>22<<].
n4:mentions: n2:9526994

Subject Item: _:vb139051067
rdf:type: n4:Context
rdf:value: Vimentin (VIM), a 57-kDa protein, is belonged to type III of six different intermediate filament families [>>23<<]. It is normally present in cells of mesenchymal origin from the nucleus to the plasma membrane [24], and it provides cell structural support and maintains tissue integrity [25]. Moreover, it is also expressed in epithelial cells and is
n4:mentions: n2:7979242

Subject Item: _:vb139051068
rdf:type: n4:Context
rdf:value: It is normally present in cells of mesenchymal origin from the nucleus to the plasma membrane [>>24<<], and it provides cell structural support and maintains tissue integrity [25].
n4:mentions: n2:3052284

Subject Item: _:vb139051069
rdf:type: n4:Context
rdf:value: It is normally present in cells of mesenchymal origin from the nucleus to the plasma membrane [24], and it provides cell structural support and maintains tissue integrity [>>25<<]. Moreover, it is also expressed in epithelial cells and is associated with metastatic disease [26,27], endothelial cell adhesion [28], migration, and/or invasive properties [27,29]. The VIM expression is detected in cancer cell lines and
n4:mentions: n2:15837516

Subject Item: _:vb139051070
rdf:type: n4:Context
rdf:value: Moreover, it is also expressed in epithelial cells and is associated with metastatic disease [>>26<<,27], endothelial cell adhesion [28], migration, and/or invasive properties [27,29].
n4:mentions: n2:17022644

Subject Item: _:vb139051071
rdf:type: n4:Context
rdf:value: Moreover, it is also expressed in epithelial cells and is associated with metastatic disease [26,>>27<<], endothelial cell adhesion [28], migration, and/or invasive properties [27,29].
n4:mentions: n2:33248456

Subject Item: _:vb139051072
rdf:type: n4:Context
rdf:value: Moreover, it is also expressed in epithelial cells and is associated with metastatic disease [26,27], endothelial cell adhesion [>>28<<], migration, and/or invasive properties [27,29].
n4:mentions: n2:11160825

Subject Item: _:vb139051073
rdf:type: n4:Context
rdf:value: Moreover, it is also expressed in epithelial cells and is associated with metastatic disease [26,27], endothelial cell adhesion [28], migration, and/or invasive properties [>>27<<,29]. The VIM expression is detected in cancer cell lines and in most tumor types and is significantly associated with a poorer differentiation grade in lung cancers [30,31,32]. In addition, it has been reported the close relationship
n4:mentions: n2:33248456

Subject Item: _:vb139051074
rdf:type: n4:Context
rdf:value: Moreover, it is also expressed in epithelial cells and is associated with metastatic disease [26,27], endothelial cell adhesion [28], migration, and/or invasive properties [27,>>29<<]. The VIM expression is detected in cancer cell lines and in most tumor types and is significantly associated with a poorer differentiation grade in lung cancers [30,31,32]. In addition, it has been reported the close relationship between
n4:mentions: n2:10574710

Subject Item: _:vb139051075
rdf:type: n4:Context
rdf:value: The VIM expression is detected in cancer cell lines and in most tumor types and is significantly associated with a poorer differentiation grade in lung cancers [>>30<<,31,32]. In addition, it has been reported the close relationship between the VIM expression level and local recurrence in oral squamous cell carcinomas [33,34]. In particular, VIM is also regarded as a marker of epithelial–mesenchymal
n4:mentions: n2:25120667

Subject Item: _:vb139051076
rdf:type: n4:Context
rdf:value: The VIM expression is detected in cancer cell lines and in most tumor types and is significantly associated with a poorer differentiation grade in lung cancers [30,>>31<<,32]. In addition, it has been reported the close relationship between the VIM expression level and local recurrence in oral squamous cell carcinomas [33,34]. In particular, VIM is also regarded as a marker of epithelial–mesenchymal
n4:mentions: n2:23562674

Subject Item: _:vb139051077
rdf:type: n4:Context
rdf:value: The VIM expression is detected in cancer cell lines and in most tumor types and is significantly associated with a poorer differentiation grade in lung cancers [30,31,>>32<<]. In addition, it has been reported the close relationship between the VIM expression level and local recurrence in oral squamous cell carcinomas [33,34]. In particular, VIM is also regarded as a marker of epithelial–mesenchymal
n4:mentions: n2:18854838

Subject Item: _:vb139051078
rdf:type: n4:Context
rdf:value: In addition, it has been reported the close relationship between the VIM expression level and local recurrence in oral squamous cell carcinomas [>>33<<,34]. In particular, VIM is also regarded as a marker of epithelial–mesenchymal transition (EMT), and the upregulation of VIM expression is observed in tumor types, such as prostate and breast cancers, malignant melanoma, and CNS tumors
n4:mentions: n2:10797573

Subject Item: _:vb139051079
rdf:type: n4:Context
rdf:value: In addition, it has been reported the close relationship between the VIM expression level and local recurrence in oral squamous cell carcinomas [33,>>34<<]. In particular, VIM is also regarded as a marker of epithelial–mesenchymal transition (EMT), and the upregulation of VIM expression is observed in tumor types, such as prostate and breast cancers, malignant melanoma, and CNS tumors [35].
n4:mentions: n2:19915524

Subject Item: _:vb139051080
rdf:type: n4:Context
rdf:value: In particular, VIM is also regarded as a marker of epithelial–mesenchymal transition (EMT), and the upregulation of VIM expression is observed in tumor types, such as prostate and breast cancers, malignant melanoma, and CNS tumors [>>35<<].
n4:mentions: n2:21637948

Subject Item: _:vb139051081
rdf:type: n4:Context
rdf:value: EMT is a process in which epithelial cells lose apical–basal polarity and cell-to-cell contacts but gain a mesenchymal phenotype, including increased cell-to-ECM contacts and cell migration [13,>>36<<,37]. This process decreases the expression of epithelial markers such as E-cadherin and increases the expression of mesenchymal proteins such as FN, N-cadherin, VIM, and the matrix metalloprotease (MMP)-2.
n4:mentions: n2:19487817

Subject Item: _:vb139051082
rdf:type: n4:Context
rdf:value: EMT is a process in which epithelial cells lose apical–basal polarity and cell-to-cell contacts but gain a mesenchymal phenotype, including increased cell-to-ECM contacts and cell migration [13,36,>>37<<]. This process decreases the expression of epithelial markers such as E-cadherin and increases the expression of mesenchymal proteins such as FN, N-cadherin, VIM, and the matrix metalloprotease (MMP)-2.
n4:mentions: n2:19487818

Subject Item: _:vb139051083
rdf:type: n4:Context
rdf:value: factors such as transforming growth factor-beta (TGF-β), growth factors that act via receptor tyrosine kinases, including fibroblast growth factor, hepatic growth factor, and platelet-derived growth factor, and Wnt and Notch proteins [>>38<<]. Among these, TGF-β has received more attention as a key inducer of EMT during embryogenesis, tissue fibrosis, and cancer progression.
n4:mentions: n2:17645776

Subject Item: _:vb139051084
rdf:type: n4:Context
rdf:value: Upon TGF-β treatment, epithelial cells changed from cuboidal to an elongated spindle shape and showed decreased expression of epithelial markers and enhanced expression of mesenchymal proteins such as FN and VIM [>>39<<]. This evidence implicates increased TGF-β signaling as a major effector of EMT in tumor progression and metastasis [40]. Cancer cells often increase their production of active TGF-β, which triggers EMT, allows the cells to become motile
n4:mentions: n2:7806579

Subject Item: _:vb139051085
rdf:type: n4:Context
rdf:value: This evidence implicates increased TGF-β signaling as a major effector of EMT in tumor progression and metastasis [>>40<<]. Cancer cells often increase their production of active TGF-β, which triggers EMT, allows the cells to become motile and invasive, and enhances angiogenesis in close proximity to the tumor microenvironment, providing an invasive route
n4:mentions: n2:16123809

Subject Item: _:vb139051086
rdf:type: n4:Context
rdf:value: their production of active TGF-β, which triggers EMT, allows the cells to become motile and invasive, and enhances angiogenesis in close proximity to the tumor microenvironment, providing an invasive route for cancer cell metastasis [13,>>41<<].
n4:mentions: n2:11586292

Subject Item: _:vb139051087
rdf:type: n4:Context
rdf:value: Iwadate et al. reported that high expression of TGF-β around necrotic regions is significantly correlated with shorter progression-free survival and overall survival in patients with GBM [>>42<<]. In addition, Park and Schwarzbauer concluded that exogenous administration of FN induces an EMT response including upregulation of the EMT markers FN, Snail, N-cadherin, VIM, and MMP2, in addition to the acquisition of cell migratory
n4:mentions: n2:27193555

Subject Item: _:vb139051088
rdf:type: n4:Context
rdf:value: Park and Schwarzbauer concluded that exogenous administration of FN induces an EMT response including upregulation of the EMT markers FN, Snail, N-cadherin, VIM, and MMP2, in addition to the acquisition of cell migratory behavior [>>43<<]. Moreover, they also suggested that FN enhances the effect of endogenous TGF-β to induce EMT and then increased levels of FN to facilitate tumorigenesis.
n4:mentions: n2:23624917

Subject Item: _:vb139051089
rdf:type: n9:Section
dc:title: discussion
n9:contains: _:vb139051104 _:vb139051105 _:vb139051106 _:vb139051107 _:vb139051108 _:vb139051109 _:vb139051110 _:vb139051111 _:vb139051112 _:vb139051113 _:vb139051114 _:vb139051115 _:vb139051116 _:vb139051117 _:vb139051090 _:vb139051091 _:vb139051092 _:vb139051093 _:vb139051094 _:vb139051095 _:vb139051096 _:vb139051097 _:vb139051098 _:vb139051099 _:vb139051100 _:vb139051101 _:vb139051102 _:vb139051103

Subject Item: _:vb139051090
rdf:type: n4:Context
rdf:value: The recurrent brain tumors are classified into three subtypes—local recurrence, remote brain metastasis, and spinal metastasis [>>44<<]. More than 90% of patients with malignant glioma showed local recurrence, the remote brain metastasis developed in 5% of patients, and the spinal metastasis was less than 1% (10). In this study, among the 151 malignant glioma cases,
n4:mentions: n2:29156679

Subject Item: _:vb139051091
rdf:type: n4:Context
rdf:value: Possible dissemination routes for remote brain metastasis of GBM are the following: meningeal–subarachnoid space, subependymal route, intraventricular route, and direct brain penetration [>>45<<]. The underlying pathophysiologic mechanism may be simultaneously neoplastic transformation [46,47].
n4:mentions: n2:8389708

Subject Item: _:vb139051092
rdf:type: n4:Context
rdf:value: The underlying pathophysiologic mechanism may be simultaneously neoplastic transformation [>>46<<,47].
n4:mentions: n2:2153310

Subject Item: _:vb139051093
rdf:type: n4:Context
rdf:value: The underlying pathophysiologic mechanism may be simultaneously neoplastic transformation [46,>>47<<].
n4:mentions: n2:3005894

Subject Item: _:vb139051094
rdf:type: n4:Context
rdf:value: Different molecular factors such as p53 mutation, Ki-67/MIB-1 labeling index, and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation have been correlated with GBM recurrences [>>48<<,49]. Li et al. highlighted the differences in clinical features, molecular subtypes, and gene alterations between primary and recurrent GBMs [50].
n4:mentions: n2:11882906

Subject Item: _:vb139051095
rdf:type: n4:Context
rdf:value: Different molecular factors such as p53 mutation, Ki-67/MIB-1 labeling index, and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation have been correlated with GBM recurrences [48,>>49<<]. Li et al. highlighted the differences in clinical features, molecular subtypes, and gene alterations between primary and recurrent GBMs [50].
n4:mentions: n2:12389885

Subject Item: _:vb139051096
rdf:type: n4:Context
rdf:value: Li et al. highlighted the differences in clinical features, molecular subtypes, and gene alterations between primary and recurrent GBMs [>>50<<]. The appearance of new genetic mutations or epigenetic aspects and malignant phenotypes in the process of recurrence increases the difficulty of treatment for recurrent GBM [51,52,53]. A glycoprotein FN is expressed by GBM cell lines in
n4:mentions: n2:26427041

Subject Item: _:vb139051097
rdf:type: n4:Context
rdf:value: The appearance of new genetic mutations or epigenetic aspects and malignant phenotypes in the process of recurrence increases the difficulty of treatment for recurrent GBM [>>51<<,52,53]. A glycoprotein FN is expressed by GBM cell lines in vitro and is also regarded as a marker of TGF-β-induced EMT [19,40]. Therefore, we hypothesized that the expression of FN is activated during GBM progression via the
n4:mentions: n2:23937436

Subject Item: _:vb139051098
rdf:type: n4:Context
rdf:value: The appearance of new genetic mutations or epigenetic aspects and malignant phenotypes in the process of recurrence increases the difficulty of treatment for recurrent GBM [51,>>52<<,53]. A glycoprotein FN is expressed by GBM cell lines in vitro and is also regarded as a marker of TGF-β-induced EMT [19,40]. Therefore, we hypothesized that the expression of FN is activated during GBM progression via the TGF-β-induced
n4:mentions: n2:15961063

Subject Item: _:vb139051099
rdf:type: n4:Context
rdf:value: The appearance of new genetic mutations or epigenetic aspects and malignant phenotypes in the process of recurrence increases the difficulty of treatment for recurrent GBM [51,52,>>53<<]. A glycoprotein FN is expressed by GBM cell lines in vitro and is also regarded as a marker of TGF-β-induced EMT [19,40]. Therefore, we hypothesized that the expression of FN is activated during GBM progression via the TGF-β-induced EMT
n4:mentions: n2:32354122

Subject Item: _:vb139051100
rdf:type: n4:Context
rdf:value: A glycoprotein FN is expressed by GBM cell lines in vitro and is also regarded as a marker of TGF-β-induced EMT [>>19<<,40]. Therefore, we hypothesized that the expression of FN is activated during GBM progression via the TGF-β-induced EMT pathway. Thus, IHC staining of FN, VIM, and TGF-β in paired human primary and recurrent malignant glioma specimens was
n4:mentions: n2:8625273

Subject Item: _:vb139051101
rdf:type: n4:Context
rdf:value: A glycoprotein FN is expressed by GBM cell lines in vitro and is also regarded as a marker of TGF-β-induced EMT [19,>>40<<]. Therefore, we hypothesized that the expression of FN is activated during GBM progression via the TGF-β-induced EMT pathway. Thus, IHC staining of FN, VIM, and TGF-β in paired human primary and recurrent malignant glioma specimens was
n4:mentions: n2:16123809

Subject Item: _:vb139051102
rdf:type: n4:Context
rdf:value: for each IHC staining was assessed by using a semiquantitative four-grade system: Grade 0, no expression; Grade 1, minimal expression; Grade 2, moderate expression; Grade 3, marked expression with generalized or focal distribution [>>54<<]. The clinical information and the results of IHC staining were summarized in Table 2.
n4:mentions: n2:10933231

Subject Item: _:vb139051103
rdf:type: n4:Context
rdf:value: However, FN is a high-molecular-weight extracellular matrix glycoprotein that binds to membrane-spanning receptor proteins and therefore plays a major role in cell adhesion, growth, migration, and differentiation [55,>>56<<]. It elicits intracellular signaling by inducing integrin clustering that results in the recruitment and activation of tyrosine kinases including focal adhesion kinase (FAK), Src family kinases (SFK), and their substrates [57]. Therefore,
n4:mentions: n2:20690820

Subject Item: _:vb139051104
rdf:type: n4:Context
rdf:value: It elicits intracellular signaling by inducing integrin clustering that results in the recruitment and activation of tyrosine kinases including focal adhesion kinase (FAK), Src family kinases (SFK), and their substrates [>>57<<]. Therefore, FN plays an important role in the pathogenesis of cancer [13,58,59,60,61,62]. Ohnishi et al. demonstrated that FN is deposited in the extracellular matrix of tumors and plays a critical role in the biological behaviors of the
n4:mentions: n2:19118207

Subject Item: _:vb139051105
rdf:type: n4:Context
rdf:value: Therefore, FN plays an important role in the pathogenesis of cancer [13,>>58<<,59,60,61,62].
n4:mentions: n2:28327179

Subject Item: _:vb139051106
rdf:type: n4:Context
rdf:value: Therefore, FN plays an important role in the pathogenesis of cancer [13,58,59,>>60<<,61,62]. Ohnishi et al. demonstrated that FN is deposited in the extracellular matrix of tumors and plays a critical role in the biological behaviors of the cancer cells, particularly in FN-stimulated cell migration in vivo [63]. In recent
n4:mentions: n2:10218097

Subject Item: _:vb139051107
rdf:type: n4:Context
rdf:value: Therefore, FN plays an important role in the pathogenesis of cancer [13,58,59,60,>>61<<,62]. Ohnishi et al. demonstrated that FN is deposited in the extracellular matrix of tumors and plays a critical role in the biological behaviors of the cancer cells, particularly in FN-stimulated cell migration in vivo [63]. In recent
n4:mentions: n2:21123617

Subject Item: _:vb139051108
rdf:type: n4:Context
rdf:value: Therefore, FN plays an important role in the pathogenesis of cancer [13,58,59,60,61,>>62<<]. Ohnishi et al. demonstrated that FN is deposited in the extracellular matrix of tumors and plays a critical role in the biological behaviors of the cancer cells, particularly in FN-stimulated cell migration in vivo [63]. In recent
n4:mentions: n2:19854168

Subject Item: _:vb139051109
rdf:type: n4:Context
rdf:value: Ohnishi et al. demonstrated that FN is deposited in the extracellular matrix of tumors and plays a critical role in the biological behaviors of the cancer cells, particularly in FN-stimulated cell migration in vivo [>>63<<]. In recent studies, Park and Schwarzbauer explored that exogenous administration of FN induces an EMT response including upregulation of the EMT markers FN, Snail, N-cadherin, VIM, and MMP2, in addition to the acquisition of cell
n4:mentions: n2:10211986

Subject Item: _:vb139051110
rdf:type: n4:Context
rdf:value: Park and Schwarzbauer explored that exogenous administration of FN induces an EMT response including upregulation of the EMT markers FN, Snail, N-cadherin, VIM, and MMP2, in addition to the acquisition of cell migratory behavior [>>43<<]. Sahoo et al. provided key insights into the role of ECM-derived TGF-β signaling to promote tumor metastasis [64].
n4:mentions: n2:23624917

Subject Item: _:vb139051111
rdf:type: n4:Context
rdf:value: Sahoo et al. provided key insights into the role of ECM-derived TGF-β signaling to promote tumor metastasis [>>64<<]. Griggs et al. proposed a novel role for FN in EMT in which the assembly of FN serves to localize TGF-β1 signaling to drive EMT progression [65]. Although this study cannot reveal the causal relationships between FN and TGF-β, it does
n4:mentions: n2:29069715

Subject Item: _:vb139051112
rdf:type: n4:Context
rdf:value: in 17 matched probes of solid primary and recurrent human GBMs by real-time reverse transcription–polymerase chain reaction (RT-PCR) and by double-immunofluorescence staining to precisely identify EMT molecule-expressing cell types [>>66<<]. However, the expression of desmoplakin, VIM, FN, and TGF-β1 with its receptors TGF-βR1 and TGF-βR2 was almost unchanged.
n4:mentions: n2:25845427

Subject Item: _:vb139051113
rdf:type: n4:Context
rdf:value: However, the majority of GBMs do not show intrinsic E-cadherin expression [>>67<<], the classical “E-cadherin to N-cadherin switch” is unlikely to correlate with EMT in GBMs [68], and therefore, the term glial-to-mesenchymal transition (GMT) is coined [69].
n4:mentions: n2:22652173

Subject Item: _:vb139051114
rdf:type: n4:Context
rdf:value: However, the majority of GBMs do not show intrinsic E-cadherin expression [67], the classical “E-cadherin to N-cadherin switch” is unlikely to correlate with EMT in GBMs [>>68<<], and therefore, the term glial-to-mesenchymal transition (GMT) is coined [69]. Mahabir et al. investigated the EMT process in pairs of primary and recurrent GBMs [69].
n4:mentions: n2:22576165

Subject Item: _:vb139051115
rdf:type: n4:Context
rdf:value: majority of GBMs do not show intrinsic E-cadherin expression [67], the classical “E-cadherin to N-cadherin switch” is unlikely to correlate with EMT in GBMs [68], and therefore, the term glial-to-mesenchymal transition (GMT) is coined [>>69<<]. Mahabir et al. investigated the EMT process in pairs of primary and recurrent GBMs [69].
n4:mentions: n2:24357458

Subject Item: _:vb139051116
rdf:type: n4:Context
rdf:value: Mahabir et al. investigated the EMT process in pairs of primary and recurrent GBMs [>>69<<]. They found, by PCR analysis, that the expression of collagen, MMP-9, smooth muscle α-actin (α-SMA), CD44, FN, and YKL-40 are elevated in the recurrent glioma samples, and using IHC staining, they demonstrated that the expression level
n4:mentions: n2:24357458

Subject Item: _:vb139051117
rdf:type: n4:Context
rdf:value: α-actin (α-SMA), CD44, FN, and YKL-40 are elevated in the recurrent glioma samples, and using IHC staining, they demonstrated that the expression level of VIM, α-SMA, and CD44 is increased in 22 cases of clinically recurrent gliomas [>>69<<]. However, they did not address the relevance of other processes involved in mesenchymal–epithelial transition (MET) or GMT.
n4:mentions: n2:24357458