Tom Yoshizaki
Research interests
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InterestsLMP1-induced MMP-9 expression, Epstein Barr virus, NPC, head and neck surgery
Publications
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4.35Impact points
Epstein-Barr Virus latent membrane protein 1 induces Snail and epithelial-mesenchymal transition in metastatic nasopharyngeal carcinoma.
British journal of cancer. 03/2011; 104(7):1160-7.
Epstein-Barr Virus (EBV)-associated nasopharyngeal carcinoma (NPC) is distinctive among head-and-neck cancers in its undifferentiated histopathology and highly metastatic character. We have recently investigated the involvement of epithelial-mesenchymal transition (EMT) in NPC. In a previous study, ... [more] Epstein-Barr Virus (EBV)-associated nasopharyngeal carcinoma (NPC) is distinctive among head-and-neck cancers in its undifferentiated histopathology and highly metastatic character. We have recently investigated the involvement of epithelial-mesenchymal transition (EMT) in NPC. In a previous study, we found a close association of expression of LMP1, the principal EBV oncoprotein, with expression of Twist and induction of EMT. We analysed expression of Snail in 41 NPC tissues by immunohistochemistry. The role of Twist as well as Snail in EMT of NPC was investigated by using NP69SV40T human nasopharyngeal cells. In NPC tissues, overexpression of Snail is associated with expression of LMP1 in carcinomatous cells. In addition, expression of Snail positively correlated with metastasis and independently correlated inversely with expression of E-cadherin. Expression of Twist had no association with expression of E-cadherin. Further, in a human nasopharyngeal cell line, LMP1 induces EMT and its associated cellular motility and invasiveness. Expression of Snail is induced by LMP1 in these cells, and small hairpin RNA (shRNA) to Snail reversed the cellular changes. By contrast, Twist did not produce EMT in these nasopharyngeal cells. This study strengthens the association of EMT with the metastatic behaviour of NPC. These results suggest that induction of Snail by the EBV oncoprotein LMP1 has a pivotal role in EMT in NPC.
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4.34Impact points
Transcription factor AP-2beta inhibits expression and secretion of leptin, an insulin-sensitizing hormone, in 3T3-L1 adipocytes.
International journal of obesity (2005). 04/2010; 34(4):670-8.
We have previously reported an association between the activator protein-2beta (AP-2beta) transcription factor gene and type 2 diabetes. This gene is preferentially expressed in adipose tissue, and subjects with a disease-susceptible allele of AP-2beta showed stronger AP-2beta expression in adipose ... [more] We have previously reported an association between the activator protein-2beta (AP-2beta) transcription factor gene and type 2 diabetes. This gene is preferentially expressed in adipose tissue, and subjects with a disease-susceptible allele of AP-2beta showed stronger AP-2beta expression in adipose tissue than those without the susceptible allele. Furthermore, overexpression of AP-2beta led to lipid accumulation and induced insulin resistance in 3T3-L1 adipocytes. We found that overexpression of AP-2beta in 3T3-L1 adipocytes decreased the promoter activity of leptin, and subsequently decreased both messenger RNA (mRNA) and protein expression and secretion. Furthermore, knockdown of endogenous AP-2beta by RNA-interference increased mRNA and protein expression of leptin. Electrophoretic mobility shift and chromatin immunoprecipitation assays revealed specific binding of AP-2beta to leptin promoter regions in vitro and in vivo. In addition, site-directed mutagenesis of the AP-2-binding site located between position +34 and +42 relative to the transcription start site abolished the inhibitory effect of AP-2beta. Our results clearly showed that AP-2beta directly inhibited insulin-sensitizing hormone leptin expression by binding to its promoter. AP-2beta modulated the expression of leptin through direct interaction with its promoter region.
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2.11Impact points
Case report. Intra-arterial chemotherapy for laryngeal cancer via a non-bifurcating carotid artery.
The British journal of radiology. 10/2009; 82(982):e197-9.
The common carotid artery (CCA) usually divides into the internal carotid artery (ICA) and the external carotid artery (ECA). We present an extremely rare case of a non-bifurcating carotid artery through which intra-arterial chemotherapy for laryngeal cancer was administered. The CCA angiogram, as w... [more] The common carotid artery (CCA) usually divides into the internal carotid artery (ICA) and the external carotid artery (ECA). We present an extremely rare case of a non-bifurcating carotid artery through which intra-arterial chemotherapy for laryngeal cancer was administered. The CCA angiogram, as well as ultrasonographic evaluation of the carotid arteries, demonstrated a non-bifurcating CCA that subsequently constituted the ICA. Furthermore, several branches normally given off by the ECA arose directly from the single carotid artery. Superselective intra-arterial infusion of cis-diamminedichloroplatinum (II) (CDDP) was subsequently performed.
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3.01Impact points
Up-regulation of CC chemokine receptor 6 on tonsillar T cells and its induction by in vitro stimulation with alpha-streptococci in patients with pustulosis palmaris et plantaris.
Clinical and experimental immunology. 07/2009; 157(1):71-82.
Pustulosis palmaris et plantaris (PPP) is a tonsil-related disease; tonsillectomy is somewhat effective in treating the condition. However, the aetiological association between the tonsils and PPP has not yet been elucidated fully. Recently, some chemokines and chemokine receptors, including CC chem... [more] Pustulosis palmaris et plantaris (PPP) is a tonsil-related disease; tonsillectomy is somewhat effective in treating the condition. However, the aetiological association between the tonsils and PPP has not yet been elucidated fully. Recently, some chemokines and chemokine receptors, including CC chemokine receptor (CCR) 4, CCR6 and CX chemokine receptor (CXCR) 3, have been reported to play important roles in the development of psoriasis, a disease related closely to PPP. In this study, we found that CCR6 expression on both tonsillar and peripheral blood T cells was up-regulated more intensively in PPP patients than in non-PPP patients (P < 0.001 for both), but CCR4 and CXCR3 expressions were not. In vitro stimulation with alpha-streptococcal antigen enhanced CCR6 expression significantly on tonsillar T cells in PPP patients (P < 0.05), but this was not observed in non-PPP patients. The chemotactic response of tonsillar T cells to the CCR6 ligand CC chemokine ligand (CCL) 20 was significantly higher in PPP patients than in non-PPP patients (P < 0.05). The percentage of CCR6-positive peripheral blood T cells decreased after tonsillectomy in PPP patients (P < 0.01); this decrease correlated with an improvement of skin lesions (P < 0.05, r = -0.63). The numbers of CCR6-positive cells and the expression of CCL20 were increased significantly in pathological lesions compared with non-pathological lesions in PPP skin (P < 0.01, P < 0.05 respectively). These results suggest that a novel immune response to alpha-streptococci may enhance CCR6 expression on T cells in tonsils and that CCR6-positive T cells may move to peripheral blood circulation, resulting in recruitment to target skin lesions expressing CCL20 in PPP patients. This may be one of the key roles in pathogenesis of the tonsil-related disease PPP.
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7.14Impact points
Phosphorylated ezrin is associated with EBV latent membrane protein 1 in nasopharyngeal carcinoma and induces cell migration.
Oncogene. 03/2009;
Tumor metastasis is a complex phenomenon that is the culmination of effects of numerous cellular factors. We have shown that the Epstein-Barr virus (EBV) oncoprotein, latent membrane protein 1 (LMP1), is capable of inducing a wide range of such factors in cell culture, expression of which is also el... [more] Tumor metastasis is a complex phenomenon that is the culmination of effects of numerous cellular factors. We have shown that the Epstein-Barr virus (EBV) oncoprotein, latent membrane protein 1 (LMP1), is capable of inducing a wide range of such factors in cell culture, expression of which is also elevated in the LMP1-expressing tumor, nasopharyngeal carcinoma (NPC), a highly invasive neoplasm. Recently, the membrane crosslinker protein, ezrin, has been implicated in tumor cell metastasis and malignant progression. In this study, we evaluated the possible role of LMP1 and ezrin in the pathophysiology of NPC. We show that C-terminal phosphorylation of ezrin is increased by the expression of LMP1 in nasopharyngeal (NP) cells through a protein kinase C (PKC) pathway. LMP1 enhances the organization of a ternary complex of CD44, ezrin and F-actin, which is a prerequisite for ezrin phosphorylation. In NPC tissues, the expression of phosphoezrin and LMP1 is directly correlated. Silencing of endogenously expressed ezrin suppresses LMP1-induced cell motility and invasiveness. Moreover, the inhibition of ezrin phosphorylation by PKC inhibitor suppresses migration and invasion of NP cells. These data show that the phosphorylation of ezrin and its recruitment to the cell membrane linked to F-actin and CD44 is a process required for LMP1-stimulated cell motility and invasion of NP cells.Oncogene advance online publication, 23 February 2009; doi:10.1038/onc.2009.20.
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3.01Impact points
Selective expansion of T cell receptor (TCR) V beta 6 in tonsillar and peripheral blood T cells and its induction by in vitro stimulation with Haemophilus parainfluenzae in patients with IgA nephropathy.
Clinical and experimental immunology. 01/2008; 151(1):25-33.
IgA nephropathy (IgAN), the most common form of primary glomerulonephritis, is recognized as a disease that often becomes worse during acute tonsillitis. Although many reports have shown that tonsillectomy is an effective treatment for IgAN patients, the immunological evidence has not yet been inves... [more] IgA nephropathy (IgAN), the most common form of primary glomerulonephritis, is recognized as a disease that often becomes worse during acute tonsillitis. Although many reports have shown that tonsillectomy is an effective treatment for IgAN patients, the immunological evidence has not yet been investigated fully. In this study, we compared the expression of T cell receptor (TCR) V beta families in tonsillar T cells of IgAN patients to those of non-IgAN patients. The reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometric analyses showed that the TCR V beta 6 was used more frequently in tonsillar T cells of IgAN patients than in those of non-IgAN patients (P < 0.01 each). Similarly, the proportions of TCR V beta 6-positive cells in peripheral blood T cells were significantly higher in IgAN patients than in non-IgAN patients (P < 0.05). After tonsillectomy, the proportions decreased in IgAN patients (P < 0.05), but did not in non-IgAN patients. Furthermore, in vitro stimulation with Haemophilus parainfluenzae antigen, which is reported to deposit in the glomerular mesangium of IgAN, enhanced expression of TCR V beta 6 in tonsillar T cells from both IgAN and non-IgAN patients. These results suggest that TCR V beta 6-positive tonsillar T cells might be activated by H. parainfluenzae, move into the kidney through blood circulation and induce glomerulonephritis.
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2.55Impact points
Membrane localization of protein-tyrosine phosphatase 1B is essential for its activation of sterol regulatory element-binding protein-1 gene expression.
Biochemical and biophysical research communications. 12/2007; 363(3):626-32.
Sterol regulatory element-binding protein-1 (SREBP-1) is a key transcription factor in stimulating lipogenesis in the liver. Protein-tyrosine phosphatase 1B (PTP1B) induces SREBP-1 gene expression via protein phosphatase 2A (PP2A) activation. PTP1B is reported to be anchored on the endoplasmic retic... [more] Sterol regulatory element-binding protein-1 (SREBP-1) is a key transcription factor in stimulating lipogenesis in the liver. Protein-tyrosine phosphatase 1B (PTP1B) induces SREBP-1 gene expression via protein phosphatase 2A (PP2A) activation. PTP1B is reported to be anchored on the endoplasmic reticulum (ER) via its C-terminal tail, and change in intracellular localization of PTP1B by C-terminal-truncation did not alter its inhibitory effects on insulin signaling. In this study, we investigated whether the change in intracellular localization of PTP1B could influence SREBP-1 gene expression. Overexpression of C-terminal truncated PTP1B (PTP1BdeltaCT) in rat Fao cells did not induce SREBP-1 gene expression. Furthermore, PTP1BdeltaCT failed to bind PP2A, resulting in impaired PP2A activation, whereas overexpression of wild-type PTP1B (PTP1BWT) associated with PP2A. Moreover, a membrane-targeted PTP1BDeltaCT activated PP2A with restored PP2A binding, despite the absence of its C-terminal region. Finally, overexpression of PTP1BdeltaCT into mouse primary cultured hepatocytes failed to enhance SREBP-1c mRNA, whereas membrane-targeted PTP1BdeltaCT led to enhanced SREBP-1c mRNA in hepatocytes as well as PTP1BWT. In conclusion, membrane localization of PTP1B is essential for PP2A activation, which is crucial for its enhancement of SREBP-1 gene expression.
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0.50Impact points
Cricoid ossification mimicking an impacted foreign body.
The Journal of laryngology and otology. 08/2006; 120(7):E24.
A 54-year-old man complained of severe throat pain and showed subglottic oedema on fibre-optic endoscopy with a distinctly narrowed subglottic space on anteroposterior radiography of the neck and dense linear opacity at the level of the cricoid cartilage on lateral plain radiography. These findings ... [more] A 54-year-old man complained of severe throat pain and showed subglottic oedema on fibre-optic endoscopy with a distinctly narrowed subglottic space on anteroposterior radiography of the neck and dense linear opacity at the level of the cricoid cartilage on lateral plain radiography. These findings suggested a foreign body just posterior to the cricopharyngeus, but a computed tomography (CT) scan demonstrated a dense calcified ridge on the posterior lamina of the cricoid cartilage but no foreign body.The patient improved symptomatically with systemic antibiotics and topical steroids, and gastrointestinal endoscopy did not detect any foreign body. This is a rare case of vertical ossification of the cricoid lamina masquerading as a foreign body.
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2.40Impact points
Promotion of metastasis in nasopharyngeal carcinoma by Epstein-Barr virus latent membrane protein-1.
Histology and histopathology. 02/2002; 17(3):845-50.
Nasopharyngeal carcinoma (NPC) is a malignant tumor associated with Epstein-Barr virus (EBV). Latent membrane protein-1 (LMP-1) is an EBV-encoded oncoprotein and is detected in approximately 50-70% of patients with NPC. LMP-1 is thought to play an essential role in tumorigenesis of NPC. In addition ... [more] Nasopharyngeal carcinoma (NPC) is a malignant tumor associated with Epstein-Barr virus (EBV). Latent membrane protein-1 (LMP-1) is an EBV-encoded oncoprotein and is detected in approximately 50-70% of patients with NPC. LMP-1 is thought to play an essential role in tumorigenesis of NPC. In addition to its transforming properties, LMP-1 has been suggested to be associated with promotion of metastasis. Metastasis is a phenomenon composed of multiple sequential cascades. Reduction of tumor cell adhesion, degradation of extracellular matrix, basement membrane, enhancement of cell motility, and promotion of neovascularization are thought to be essential steps. LMP-1 down-regulates expression of E-cadherin, induces matrix metalloproteinase-9 and urokinase type-plasminogen activator through activation of NF-kappaB and AP-1, and enhances cell motility via ets-1 activation. LMP-1 also induces vascular endothelial growth factor through cyclooxygenase-2 activation and interleukin-8 through NF-kappaB activation. Clinical studies suggested the association of these factors with metastatic status of patients with NPC. In this review, the role of LMP-1 in the metastasis of NPC is discussed.
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[Expression of pharyngeal- tumor- metastasis related genes and possibility of the gene therapy--Suppressive effects of aspirin on the tumor metastasis]
Nippon Jibiinkoka Gakkai kaiho. 09/2001; 104(8):791-5.
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3.86Impact points
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6.75Impact points
Induction of interleukin-8 by Epstein-Barr virus latent membrane protein-1 and its correlation to angiogenesis in nasopharyngeal carcinoma.
Clinical cancer research : an official journal of the American Association for Cancer Research. 08/2001; 7(7):1946-51.
PURPOSE: The EBV latent membrane protein-1 (LMP-1) is a multifunctional protein. Recently, the contribution of LMP-1 to the metastasis of nasopharyngeal carcinoma (NPC) has been suggested. Angiogenesis is a key step for metastasis. Thus, the association of LMP-1 to neovascularization of NPC was exam... [more] PURPOSE: The EBV latent membrane protein-1 (LMP-1) is a multifunctional protein. Recently, the contribution of LMP-1 to the metastasis of nasopharyngeal carcinoma (NPC) has been suggested. Angiogenesis is a key step for metastasis. Thus, the association of LMP-1 to neovascularization of NPC was examined in this study. EXPERIMENTAL DESIGN: The association of LMP-1 to angiogenesis in 39 patients with NPC was evaluated by immunohistochemical study, and then induction of angiogenic factors by LMP-1 was examined by ELISA and luciferase reporter assay. RESULTS: In an immunohistochemical study, the expression of LMP-1 was significantly correlated to microvessel counts (P = 0.0003), suggesting that LMP-1 may induce some angiogenic factors. Therefore, we studied the relationship between LMP-1 expression and interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) expression by immunohistochemical analysis. IL-8, VEGF, and bFGF expression were correlated to microvessel counts, but only IL-8 expression was significantly correlated to LMP-1 expression (P < 0.0001). Transfection with LMP-1 expression plasmid induced IL-8 protein expression in C33A cells. The expression of LMP-1 transactivated IL-8 promoter, as demonstrated by IL-8 promoter luciferase reporter assay. Mutation of the nuclear factor kappaB responsive element in the IL-8 promoter region completely abolished transactivation by LMP-1, whereas mutation of the activator protein responsive element did not affect promoter activity. CONCLUSION: These results suggested that LMP-1 induces expression of IL-8 through the nuclear factor kappaB binding site, which may contribute in part to angiogenesis in NPC.
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9.43Impact points
Induction of cyclooxygenase-2 by Epstein-Barr virus latent membrane protein 1 is involved in vascular endothelial growth factor production in nasopharyngeal carcinoma cells.
Proceedings of the National Academy of Sciences of the United States of America. 07/2001; 98(12):6905-10.
Cyclooxygenase-2 (COX-2) is an inducible form of COX and is overexpressed in diverse tumors, raising the possibility of a role for COX-2 in carcinogenesis. In addition, COX-2 contributes to angiogenesis. The Epstein-Barr virus (EBV) oncoprotein, latent membrane protein 1 (LMP1), is detected in at le... [more] Cyclooxygenase-2 (COX-2) is an inducible form of COX and is overexpressed in diverse tumors, raising the possibility of a role for COX-2 in carcinogenesis. In addition, COX-2 contributes to angiogenesis. The Epstein-Barr virus (EBV) oncoprotein, latent membrane protein 1 (LMP1), is detected in at least 70% of nasopharyngeal carcinoma (NPC) and all EBV-infected preinvasive nasopharyngeal lesions. We found that in specimens of LMP1-positive NPC, COX-2 is frequently expressed, whereas LMP1-negative NPC rarely express the enzyme. We next found that expression of LMP1 in EBV-negative nasopharyngeal epithelial cells induced COX-2 expression. Coexpression of IkappaBalpha(S32A/S36A), which is not phosphorylated and prevents NF-kappaB activation, with LMP1 showed that NF-kappaB is essential for induction of COX-2 by LMP1. We also demonstrate that NF-kappaB is involved in LMP1-induced cox-2 promoter activity with the use of reporter assays. Two major regions of LMP1, designated CTAR1 and CTAR2, are signal-transducing domains of LMP1. Constructs expressing either CTAR1 or CTAR2 induce COX-2 but to a lesser extent than wild-type LMP1, consistent with the ability of both regions to activate NF-kappaB. Furthermore, we demonstrate that LMP1-induced COX-2 is functional because LMP1 increased production of prostaglandin E(2) in a COX-2-dependent manner. Finally, we demonstrate that LMP1 increased production of vascular endothelial growth factor (VEGF). Treatment of LMP1-expressing cells with the COX-2-specific inhibitor (NS-398) dramatically decreased production of VEGF, suggesting that LMP1-induced VEGF production is mediated, at least in part, by COX-2. These results suggest that COX-2 induction by LMP1 may play a role in angiogenesis in NPC.
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5.49Impact points
Induction of c-Met proto-oncogene by Epstein-Barr virus latent membrane protein-1 and the correlation with cervical lymph node metastasis of nasopharyngeal carcinoma.
The American journal of pathology. 07/2001; 159(1):27-33.
Nasopharyngeal carcinoma (NPC) is distinctive in head and neck carcinomas for its close association with Epstein-Barr virus and its highly metastatic nature. Up-regulation of cell motility is essential for enhancement of metastatic potential. The expression of c-Met proto-oncogene, a high-affinity r... [more] Nasopharyngeal carcinoma (NPC) is distinctive in head and neck carcinomas for its close association with Epstein-Barr virus and its highly metastatic nature. Up-regulation of cell motility is essential for enhancement of metastatic potential. The expression of c-Met proto-oncogene, a high-affinity receptor for hepatocyte growth factor/scatter factor, has been reported to correlate with metastatic ability of the tumor cell. We observed close association of c-Met expression with cervical lymph node metastasis (P = 0.0272) in 39 NPC specimens studied immunohistochemically. Epstein-Barr virus-encoding latent membrane protein-1 (LMP-1) is a primary oncogene and is suggested to enhance the metastatic property of NPC. Previously, we reported that LMP-1 enhanced the motility of Madin-Darby canine kidney (MDCK) epithelial cells that was mediated by activation of Ets-1 transcription factor. Therefore, we examined the interrelationships of LMP-1, Ets-1, and c-Met. In immunohistochemical studies, the expression of LMP-1, Ets-1, and c-Met correlated significantly with each other in NPC (LMP-1 versus Ets-1, P < 0.0001; Ets-1 versus c-Met, P = 0.0012; LMP-1 versus Met, P = 0.0005). Transfection of LMP-1-expressing plasmid in MDCK cells induced c-Met protein expression. The c-Met protein was also induced by Ets-1 expression, and induction of c-Met by LMP-1 was suppressed by introducing a dominant-negative form of Ets-1 in LMP-1-expressing MDCK cells. These results suggest that LMP-1 induces c-Met through the activation of Ets-1, which may contribute in part to the highly metastatic potential of NPC.
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9.43Impact points
Visualization, direct isolation, and transplantation of midbrain dopaminergic neurons.
Proceedings of the National Academy of Sciences of the United States of America. 06/2001; 98(11):6423-8.
To visualize and isolate live dopamine (DA)-producing neurons in the embryonic ventral mesencephalon, we generated transgenic mice expressing green fluorescent protein (GFP) under the control of the rat tyrosine hydroxylase gene promoter. In the transgenic mice, GFP expression was observed in the de... [more] To visualize and isolate live dopamine (DA)-producing neurons in the embryonic ventral mesencephalon, we generated transgenic mice expressing green fluorescent protein (GFP) under the control of the rat tyrosine hydroxylase gene promoter. In the transgenic mice, GFP expression was observed in the developing DA neurons containing tyrosine hydroxylase. The outgrowth and cue-dependent guidance of GFP-labeled axons was monitored in vitro with brain culture systems. To isolate DA neurons expressing GFP from brain tissue, cells with GFP fluorescence were sorted by fluorescence-activated cell sorting. More than 60% of the sorted GFP(+) cells were positive for tyrosine hydroxylase, confirming that the population had been successfully enriched with DA neurons. The sorted GFP(+) cells were transplanted into a rat model of Parkinson's disease. Some of these cells survived and innervated the host striatum, resulting in a recovery from Parkinsonian behavioral defects. This strategy for isolating an enriched population of DA neurons should be useful for cellular and molecular studies of these neurons and for clinical applications in the treatment of Parkinson's disease.
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4.72Impact points
Expression of tissue inhibitor of matrix metalloproteinase-2 correlates with activation of matrix metalloproteinase-2 and predicts poor prognosis in tongue squamous cell carcinoma.
International journal of cancer. Journal international du cancer. 02/2001; 95(1):44-50.
Matrix metalloproteinase 2 (MMP-2) plays a crucial role in invasion and metastasis of malignant tumors. Membrane type 1-MMP (MT1-MMP) was originally identified as an activator of MMP-2. Tissue inhibitor of MMP-2 (TIMP-2) was identified as an inhibitor of MMP-2 and MT1-MMP. However, TIMP-2 was report... [more] Matrix metalloproteinase 2 (MMP-2) plays a crucial role in invasion and metastasis of malignant tumors. Membrane type 1-MMP (MT1-MMP) was originally identified as an activator of MMP-2. Tissue inhibitor of MMP-2 (TIMP-2) was identified as an inhibitor of MMP-2 and MT1-MMP. However, TIMP-2 was reported to be essential for cell-mediated activation of MMP-2 and thus, the contribution of TIMP-2 to tumor invasion has remained controversial. This study was designed to analyze the role of TIMP-2 for activation of MMP-2 and its prognostic value in tongue squamous cell carcinoma (SCC). Expression of MMP-2, MT1-MMP and TIMP-2 protein was analyzed by immunohistochemistry, and their association with clinical factors was evaluated in 51 patients treated surgically for tongue SCC. Expression of MMP-2, MT1-MMP and TIMP-2 was significantly correlated with local and distant metastatic tumor recurrence and poor prognosis (MMP-2 and MT1-MMP, p < 0.0001; TIMP-2, p = 0.0002). Activation of MMP-2, analyzed by gelatin zymography in 17 fresh specimens, was remarkably associated with expression of MMP-2 (r = 0.779, p < 0.0001), MT1-MMP (r = 0.674, p < 0.0022) and TIMP-2 (r = 0.858, p < 0.0001). Increased expression of TIMP-2, as well as MMP-2 and MT1-MMP, was an important prognostic factor in patients with tongue SCC.
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1.24Impact points
Clinical evaluation of staging system for nasopharyngeal carcinoma: comparison of fourth and fifth editions of UICC TNM classification.
The Annals of otology, rhinology, and laryngology. 01/2001; 109(12 Pt 1):1125-9.
Staging nasopharyngeal carcinoma (NPC) by the UICC 4th-edition TNM classification system (the old system) did not give an accurate prognosis because of the uneven distribution of patients in each stage. This system was revised in 1997 (the new system). To evaluate the performance of the new system, ... [more] Staging nasopharyngeal carcinoma (NPC) by the UICC 4th-edition TNM classification system (the old system) did not give an accurate prognosis because of the uneven distribution of patients in each stage. This system was revised in 1997 (the new system). To evaluate the performance of the new system, 35 patients with NPC who had been staged by the old system were restaged according to the new system. Restaging of the patients resulted in an overall "downstaging." Differences in the overall survival rates of the early group (stages I, II, III), stage IVA, stage IVB, and stage IVC patients were statistically significant (75%, 48%, 74%, and 0%. respectively; p = .01). T4 was a significant factor of poor outcome (hazard rate, 2.932; 95% CI, 1.667 to 8.545), whereas N3 was not (hazard rate, 0.858; 95% CI, 0.281 to 2.618). The new staging system is more useful than the old system.
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1.24Impact points
Internal carotid artery aneurysm presenting as a large pharyngeal mass.
The Annals of otology, rhinology, and laryngology. 08/2000; 109(7):690-2.
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5.42Impact points
Association of latent membrane protein 1 and matrix metalloproteinase 9 with metastasis in nasopharyngeal carcinoma.
Cancer. 08/2000; 89(4):715-23.
BACKGROUND: Nasopharyngeal carcinoma (NPC) is a highly metastatic carcinoma whose consistent association with Epstein-Barr virus (EBV) has been established. Latent membrane protein 1 (LMP1), an EBV membrane protein expressed in latent infection, is considered to be the EBV oncoprotein. Matrix metall... [more] BACKGROUND: Nasopharyngeal carcinoma (NPC) is a highly metastatic carcinoma whose consistent association with Epstein-Barr virus (EBV) has been established. Latent membrane protein 1 (LMP1), an EBV membrane protein expressed in latent infection, is considered to be the EBV oncoprotein. Matrix metalloproteinase 9 (MMP9), one of the MMP families, degrades Type IV collagen, a major component of extracellular matrix and is believed to be crucial for cancer invasion and metastasis. Although MMP9 is reported to be expressed in a variety of cancers, no reports concerning NPC have been published to date to the authors' knowledge. Recently, the authors have shown that LMP1 induces MMP9 in vitro cell line, which suggests the possibility of a mechanism in which LMP1 of EBV contributes to the metastasis and tumorigenesis of NPC by the induction of MMP9. METHODS: The expressions of LMP1 and MMP9 were immunohistochemically examined in 38 NPC sections, and the relation of these proteins were statistically analyzed. The authors also analyzed the associations of these proteins with clinical features. RESULTS: Both LMP1 and MMP9 proteins were predominantly immunolocalized in cancer nests. The expression of MMP9 showed a significant positive correlation with the expression of LMP1 (r = 0.75; P < 0.0001). Also, the expression of MMP9 correlated with lymph node metastasis (P = 0. 0004). CONCLUSIONS: The results suggest that the induction of MMP9 by LMP1 contributes to the metastatic potential of NPC.
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2.36Impact points
Bilateral Jejuno-mesenteric flap for reconstruction of complicated pharyngoesophageal defect.
American journal of surgery. 07/2000; 179(6):497-9.
The surgical management of an infectious and fistulous wound with a pharyngoesophageal tumor is one of the greatest challenges for head and neck and plastic surgeons. The free jejunal transfer has been the standard technique for pharyngoesophageal reconstruction, and the free omental flap has been o... [more] The surgical management of an infectious and fistulous wound with a pharyngoesophageal tumor is one of the greatest challenges for head and neck and plastic surgeons. The free jejunal transfer has been the standard technique for pharyngoesophageal reconstruction, and the free omental flap has been one of the most reliable methods for reconstructing contaminated wounds. A jejuno-mesenteric flap is suitable for such complicated wounds. Pharyngoesophageal defects are reconstructed by the jejunum, and contaminated and heavily irradiated neck wounds are covered with the mesenteric flaps connected with a revascularized jejunum. The technique described here possesses the advantages of both a free jejunal flap and an omentum flap. Therefore, it is a reliable method for reconstructing the pharyngoesophageal defects of complicated wounds.
