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ABSTRACT: PURPOSE: We evaluated whether preoperative chemotherapy with S-1 and concurrent radiotherapy is feasible and efficacious in the treatment of advanced oral squamous cell carcinoma. METHODS: Participants comprised 39 patients with oral carcinoma (stage III, n = 15; stage IVA, n = 24). All patients received a total radiation dose of 40 Gy, in once-daily 2-Gy fractions, and received S-1 at 65 mg/m(2)/day for 5 consecutive days, over 4 consecutive weeks with concurrent radiotherapy. RESULTS: Hematological toxicity was mild and reversible. The most common non-hematological toxicity was grade 3 mucositis, but this was transient and tolerable. Radical surgery was performed for 37 patients, with the remaining 2 patients declining the surgery. Postoperatively, local failure developed in 1 patient, and neck failure in 2 patients. Distant metastases were identified in 4 patients. At a median follow-up of 38.0 months (range 23-88 months), locoregional control, disease-specific survival, and overall survival rates at 3 years were 91.5, 83.8, and 83.8 %, respectively. CONCLUSION: Concurrent administration of S-1 and radiotherapy combined with surgery offers a well-tolerated method of successfully treating advanced oral squamous cell carcinoma. The locoregional control rate remains high even at 3 years of follow-up, and no serious adverse effects have been encountered.
Cancer Chemotherapy and Pharmacology 02/2013; · 2.83 Impact Factor
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Tomoko Ota,
Hirofumi Jono,
Kazutoshi Ota,
Satoru Shinriki,
Mitsuharu Ueda,
Takanao Sueyoshi,
Ken Nakatani,
Yukihiro Hiraishi,
Takeshi Wada,
Shigeyuki Fujita,
Konen Obayashi, Masanori Shinohara,
Yukio Ando
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ABSTRACT: The presence of drug-resistant cancer cells has been associated with poor clinical outcomes. Cisplatin is one of the most effective chemotherapeutic agents commonly used for several malignancies including oral squamous cell carcinoma (OSCC). Although cisplatin resistance is a major obstacle in cancer treatment, mechanisms by which it develops are not well understood. Midkine (MK), a heparin-binding growth factor, has various cancer-related functions. In this study, we investigated whether MK is involved in cisplatin resistance in OSCC. We demonstrated that the Sa-3R cell line, which is OSCC cisplatin-resistant, exhibited lower MK expression with slow growth compared with its parent, Sa-3 cells. In Sa-3 cells, downregulation of MK expression significantly reduced cisplatin sensitivity, cell growth, and the expression of cyclin D1 and cyclin E1. MK knockdown suppressed cellular cisplatin accumulation via induction of ATP-binding cassette efflux transporters. These data suggest that MK may play important roles in cisplatin resistance in OSCC by modulating both cell growth and intracellular cisplatin accumulation.
Oncology Reports 05/2012; 27(5):1674-80. · 1.84 Impact Factor
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Keiko Teshima,
Ryuji Murakami,
Ryoji Yoshida,
Hideki Nakayama,
Akimitsu Hiraki,
Toshinori Hirai,
Yuji Nakaguchi,
Naoko Tsujita,
Etsushi Tomitaka,
Mitsuhiro Furusawa,
Yasuyuki Yamashita, Masanori Shinohara
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ABSTRACT: We retrospectively evaluated the relationship between computed tomography (CT)- and histopathological findings of parotid and submandibular glands in six patients treated for advanced oral cancer. Eligibility criteria were a pathologic diagnosis of oral squamous cell carcinoma, preoperative chemoradiation therapy (CRT) with a total dose of 30 Gy and oral S-1 (80 mg/m²/day), the availability of morphological assessments by CT and of functional assessments with the Saxon test before- and 2 weeks after CRT, and the availability of histopathological slides of irradiated parotid and submandibular glands. In the histopathological interpretation, gland structures were divided into acinar-, duct-, and adipose cells and other tissues. The Mann-Whitney test and the Spearman rank correlation test were used to determine histopathological changes. After 30-Gy irradiation, saliva production and parotid and submandibular volumes were significantly decreased (P < 0.05 each). Histopathological analysis demonstrated that 30-Gy irradiation resulted in a loss of acinar cells although acinar cells in the submandibular gland were relatively retained; the median acinar rate in the parotid and submandibular glands was 1.1% and 19.0%, respectively. The CT values after CRT were inversely correlated with adipose ratios (r = -0.98, P < 0.01) and there was a strong correlation between CT values before and after CRT (r = 0.97, P < 0.01). Our results suggested that acinar cell loss is a main contributor to changes in the volume and function of irradiated human parotid and submandibular glands. The CT value may reflect the adipose ratio rather than salivary function.
Journal of Radiation Research 04/2012; 53(3):492-6. · 1.68 Impact Factor
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ABSTRACT: Branching morphogenesis (BrM), an essential step for salivary gland development, requires epithelial-mesenchymal interactions. BrM is impaired when the surrounding mesenchyme is detached from the salivary epithelium during the pseudoglandular stage. It is believed that the salivary mesenchyme is indispensable for BrM, however, an extracellular matrix gel with exogenous EGF can be used as a substitute for the mesenchyme during BrM in the developing salivary epithelium. Stem/progenitor cells isolated from salivary glands in humans and rodents can be classified as mesenchymal stem cell-like, bone-marrow-derived, duct cell-like, and embryonic epithelium-like cells. Salivary-gland-derived progenitor (SGP) cells isolated from duct-ligated rats, mice, and swine submandibular glands share similar characteristics, including intracellular laminin and α6β1-integrin expression, similar to the embryonic salivary epithelia during the pseudoglandular stage. Progenitor cells also isolated from human salivary glands (human SGP cells) having the same characteristics differentiate into hepatocyte-like cells when transplanted into the liver. Similar to the dissociated embryonic salivary epithelium, human SGP cells aggregate to self-organize into branching organ-like structures on Matrigel plus exogenous EGF. These results suggest the possibility that tissue stem cells organize rudiment-like structures, and the embryonic cells that organize into whole tissues during development are preserved even in adult tissues.
Stem cells international. 01/2012; 2012:502136.
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Takuya Tanaka,
Hideki Nakayama,
Yoshihiro Yoshitake,
Atsushi Irie,
Masashi Nagata,
Kenta Kawahara,
Yasuo Takamune,
Ryoji Yoshida,
Yoshihiro Nakagawa,
Hidenao Ogi,
Satoru Shinriki,
Kazutoshi Ota,
Akimitsu Hiraki,
Tetsuro Ikebe,
Yasuharu Nishimura, Masanori Shinohara
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ABSTRACT: Nuclear factor-κB (NF-κB) activation contributes to the development of metastasis, thus leading to a poor prognosis in many cancers, including OSCC. However, little in vivo experimental data are available about the effects of NF-κB inhibition on OSCC metastasis. OSCC sublines were established from a GFP-expressing parental cell line, GSAS, and designated GSAS/N3 and N5 according to the in vivo passage number after cervical lymph node metastasis by a serial orthotopic transplantation model. In vitro migration and invasion were assessed in these cells, and the NF-κB activities and expression of NF-κB-regulated metastasis-related molecules were also examined. In in vivo experiments, the metastasis and survival of tumor-engrafted mice were monitored. Furthermore, the effects of a selective NF-κB inhibitor, NEMO-binding domain (NBD) peptide, on metastasis in GSAS/N5-engrafted mice were assessed, and engrafted tongue tumors were immunohistochemically examined. Highly metastatic GSAS/N3 and N5 cells showed an enhanced NF-κB activity, thus contributing to increased migration, invasion, and a poor prognosis compared with the parent cells. Furthermore, the expression levels of NF-κB-regulated metastasis-related molecules, such as fibronectin, β1 integrin, MMP-1, -2, -9, and -14, and VEGF-C, were upregulated in the highly metastatic cells. The NBD peptide suppressed metastasis and tongue tumor growth in GSAS/N5-inoculated mice, and was accompanied by the downregulation of the NF-κB-regulated metastasis-related molecules in engrafted tongue tumors. Our results suggest that the selective inhibition of NF-κB activation by NBD peptide may provide an effective approach for the treatment of highly metastatic OSCC.
Cancer Science 12/2011; 103(3):455-63. · 3.33 Impact Factor
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Satoru Shinriki,
Hirofumi Jono,
Mitsuharu Ueda,
Kazutoshi Ota,
Tomoko Ota,
Takanao Sueyoshi,
Yuichi Oike,
Mutsuko Ibusuki,
Akimitsu Hiraki,
Hideki Nakayama, Masanori Shinohara,
Yukio Ando
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ABSTRACT: Lymph node metastasis is associated with resistance to conventional therapy and poor survival of patients with oral squamous cell carcinoma (OSCC). Although lymphangiogenesis is well known to be associated with the occurrence of lymph node metastasis in various cancers, the precise mechanisms of lymphangiogenesis in OSCC are largely unknown. IL-6, a potent pro-inflammatory cytokine, has been shown to play active roles in various cancers, including OSCC. This study aimed to investigate the involvement of IL-6 signalling in lymphatic metastasis and to evaluate the efficacy of tocilizumab, a humanized anti-human IL-6 receptor antibody, as an anti-lymphangiogenic agent for OSCC. This investigation confirmed that levels of expression of IL-6 protein and VEGF-C mRNA in OSCC tissues were significantly correlated with lymph node metastasis in patients with OSCC, as assessed by immunohistochemical analysis and real-time quantitative RT–PCR. In vitro studies showed that IL-6 regulated VEGF-C mRNA expression in a human OSCC cell line, SAS cells, through the phosphoinositide 3-kinase-Akt pathway. In addition, treatment with tocilizumab led to markedly reduced VEGF-C mRNA expression and OSCC-related lymphangiogenesis in SAS xenografts. Together, these data suggest that tocilizumab acted as expected: it inhibited lymph node metastasis in OSCC by reducing tumour lymphangiogenesis. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology 06/2011; 225(1):142 - 150. · 6.32 Impact Factor
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Satoru Shinriki,
Hirofumi Jono,
Mitsuharu Ueda,
Kazutoshi Ota,
Tomoko Ota,
Takanao Sueyoshi,
Yuichi Oike,
Mutsuko Ibusuki,
Akimitsu Hiraki,
Hideki Nakayama, Masanori Shinohara,
Yukio Ando
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ABSTRACT: Lymph node metastasis is associated with resistance to conventional therapy and poor survival of patients with oral squamous cell carcinoma (OSCC). Although lymphangiogenesis is well known to be associated with the occurrence of lymph node metastasis in various cancers, the precise mechanisms of lymphangiogenesis in OSCC are largely unknown. IL-6, a potent pro-inflammatory cytokine, has been shown to play active roles in various cancers, including OSCC. This study aimed to investigate the involvement of IL-6 signalling in lymphatic metastasis and to evaluate the efficacy of tocilizumab, a humanized anti-human IL-6 receptor antibody, as an anti-lymphangiogenic agent for OSCC. This investigation confirmed that levels of expression of IL-6 protein and VEGF-C mRNA in OSCC tissues were significantly correlated with lymph node metastasis in patients with OSCC, as assessed by immunohistochemical analysis and real-time quantitative RT-PCR. In vitro studies showed that IL-6 regulated VEGF-C mRNA expression in a human OSCC cell line, SAS cells, through the phosphoinositide 3-kinase-Akt pathway. In addition, treatment with tocilizumab led to markedly reduced VEGF-C mRNA expression and OSCC-related lymphangiogenesis in SAS xenografts. Together, these data suggest that tocilizumab acted as expected: it inhibited lymph node metastasis in OSCC by reducing tumour lymphangiogenesis.
The Journal of Pathology 05/2011; 225(1):142-50. · 6.32 Impact Factor
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ABSTRACT: Nucleostemin (NS) has been reported as essential for stem and cancer cell proliferation. To investigate the significance of NS in oral squamous cell carcinomas (OSCCs), we examined NS expression in neoplastic tissue of the tongue and in OSCC cell lines. Nucleostemin expression in the histological samples showed positive correlation with Ki-67 expression. Furthermore, NS expression was associated with cellular proliferation in OSCC cell lines using siRNA, which upregulated p27, a cyclin-dependent kinase inhibitor. Regarding OSCC differentiation, NS expression did not influence cornification or oral epithelial differentiation markers such as involucrin and cytokeratin19. Thus, NS is widely expressed in normal and neoplastic oral epithelial tissues, and is likely a marker of proliferation.
Cancer Science 03/2011; 102(7):1418-23. · 3.33 Impact Factor
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Etsushi Tomitaka,
Ryuji Murakami,
Keiko Teshima,
Tomoko Nomura,
Yuji Nakaguchi,
Hideki Nakayama,
Mika Kitajima,
Toshinori Hirai,
Yushi Araki, Masanori Shinohara,
Yasuyuki Yamashita
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ABSTRACT: To evaluate longitudinal changes in parotid volumes and saliva production over 2 years after 30 Gy irradiation.
We retrospectively evaluated 15 assessable patients treated for advanced oral cancer. Eligibility criteria were a pathologic diagnosis of squamous cell carcinoma, preoperative radiation therapy with a total dose of 30 Gy delivered in 15 fractions, and the availability of longitudinal data of morphological assessments by computed tomography and functional assessments with the Saxon test spanning 2 years after radiation therapy. In the Saxon test, saliva production was measured by weighing a folded sterile gauze pad before and after chewing; the low-normal value is 2 g/2 min. Repeated-measures analysis of variance with Bonferroni adjustment for multiple comparisons was used to determine the longitudinal changes.
The normalized ipsilateral parotid volumes 2 weeks and 6-, 12- and 24 months after radiation therapy were found to be 72.5, 63.7, 66.9 and 78.1%, respectively; the normalized contralateral volumes were 69.8, 64.6, 72.2 and 82.0%, respectively. The bilateral parotid volumes were significantly decreased after radiation therapy (P < 0.01). The nadir appeared at 6 months post-radiation therapy and the volumes substantially recuperated 24 months after radiation therapy (P < 0.01). Mean saliva production before radiation therapy was 3.7 g; the longitudinal changes after radiation therapy were 31.3, 38.0, 43.3 and 69.6%, respectively. Substantial recuperation of saliva production was observed 24 months after radiation therapy (P = 0.01).
Although parotid volumes and saliva production were decreased after 30 Gy irradiation, we observed the recuperation of morphological and functional changes in the parotid glands 2 years after radiation therapy.
Japanese Journal of Clinical Oncology 01/2011; 41(4):503-7. · 1.78 Impact Factor
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ABSTRACT: Staphylococcus aureus is the most frequently isolated pathogen in gram-positive sepsis often complicated by a blood clotting disorder, and is the leading cause of infective endocarditis induced by bacterial destruction of endocardial tissues. The bacterium secretes cysteine proteases referred to as staphopain A (ScpA) and staphopain B (SspB). To investigate virulence activities of staphopains pertinent to clotting disorders and tissue destruction, we examined their effects on collagen, one of the major tissue components, and on plasma clotting. Both staphopains prolonged the partial thromboplastin time of plasma in a dose- and activity-dependent manner, with SspB being threefold more potent than ScpA. Staphopains also prolonged the thrombin time of both plasma and fibrinogen, indicating that these enzymes can cause impaired plasma clotting through fibrinogen degradation. Whereas SspB cleaved the fibrinogen Aα-chain at the C-terminal region very efficiently, ScpA degraded it rather slowly. This explains the superior ability of the former enzyme to impair fibrinogen clottability. Enzymically active staphopains, at concentrations as low as 10 nM, degraded collagen with comparable efficiency. These results show novel virulence activities of staphopains in degrading fibrinogen and collagen, and suggest an involvement of staphopains in the clotting impairment and tissue destruction caused by staphylococcal infection.
Microbiology 11/2010; 157(Pt 3):786-92. · 3.06 Impact Factor
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Kazutoshi Ota,
Hiromi Fujimori,
Mitsuharu Ueda,
Hirofumi Jono,
Satoru Shinriki,
Tomoko Ota,
Takanao Sueyoshi,
Manabu Taura,
Ayaka Taguma,
Hirofumi Kai, Masanori Shinohara,
Yukio Ando
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ABSTRACT: Midkine (MK) expression has been documented to be inversely correlated with the prognosis of patients with various tumors, but the mechanism of this relationship has not been well characterized. Recent studies have also correlated p53 expression with prognosis of patients with oral squamous cell carcinoma (OSCC). We evaluated the relationship between MK expression and clinicopathological features of patients with OSCC to clarify the influence of p53 status on MK expression in OSCC cells. Our results showed that patients with MK over-expression in OSCC cells had a significantly lower 5-year survival rate compared with patients with low MK expression. Immunohistochemical analyses demonstrated overexpression of MK protein in OSCC samples with mutant p53. Cell culture experiments with human lingual squamous cell carcinoma revealed that the MK gene was regulated by the wild-type p53 gene. Thus, MK expression may affect prognosis via the p53 status and mutation of the p53 gene, and MK may be an attractive target for therapeutic intervention in patients with cancer cells with mutant p53.
International Journal of Oncology 10/2010; 37(4):797-804. · 2.40 Impact Factor
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ABSTRACT: The aims of this study were to investigate midkine (MK) expression patterns in salivary gland tumors (SGTs) and to evaluate the correlation between MK expression and the degree of malignancy. We performed immunohistochemistry to examine MK expression in specimens of adenoid cystic carcinoma (ACC), mucoepidermoid carcinoma (MEC), and pleomorphic adenoma (PA). In addition, we performed immunohistochemistry for CD31 and measured microvessel density (MVD), which is an indicator of angiogenesis. Immunohistochemistry showed that MK protein expression was significantly higher in specimens of malignant SGTs (ACC [P<0.01] and MEC [P<0.001]) than in benign SGT (PA) samples. Furthermore, MVD values tended to be higher in cases that exhibited high expression of MK, which indicated a significant correlation between the degree of MK expression and MVD (P<0.001). These results suggest that MK may play important roles in malignant transformation and tumor angiogenesis in SGTs.
Oral Oncology 09/2010; 46(9):657-61. · 2.86 Impact Factor
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Keiko Teshima,
Ryuji Murakami,
Etsuji Tomitaka,
Tomoko Nomura,
Ryo Toya,
Akimitsu Hiraki,
Hideki Nakayama,
Toshinori Hirai, Masanori Shinohara,
Natsuo Oya,
Yasuyuki Yamashita
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ABSTRACT: To evaluate whether saliva production reflects the parotid volume during the course of radiation therapy (RT) in patients with head-and-neck cancer.
Twenty patients with advanced oral squamous cell carcinomas, who were treated with preoperative chemo-RT, underwent morphological assessment with CT or MRI and functional assessment with the Saxon test. For the Saxon test, saliva production was measured by weighing a gauze pad before and 2 min after chewing without swallowing; the low-normal value is 2 g. Saliva production and parotid volumes before and 2 weeks after RT were compared with the paired t-test, the Spearman rank correlation test and the Fisher exact test.
After 30 Gy irradiation, mean saliva production was decreased from 4.2 to 1.0 g (P < 0.01); the reduction in saliva production ranged from 1.7 to 5.4 g (mean 3.2 g). The mean parotid volume was decreased from 68.2 to 47.9 cm(3) (P < 0.01); the post-RT:pre-RT parotid volume ratio ranged from 54% to 85% (mean 71%). Although the initial parotid ;volume was correlated with initial saliva production (r = 0.47, P = 0.04), no significant correlation was noted after RT (r = 0.08, P = 0.71), and there were considerable individual variations. The parotid volume ratio was inversely correlated with the saliva-reduction amount (r = - 0.79, P < 0.01).
There was a correlation between decreased parotid gland volume and decreased saliva production in patients with head-and-neck cancer undergoing RT. Parotid volume reduction may predict parotid gland function.
Japanese Journal of Clinical Oncology 10/2009; 40(1):42-6. · 1.78 Impact Factor
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Satoru Shinriki,
Hirofumi Jono,
Kazutoshi Ota,
Mitsuharu Ueda,
Mareina Kudo,
Tomoko Ota,
Yuichi Oike,
Motoyoshi Endo,
Mutsuko Ibusuki,
Akimitsu Hiraki,
Hideki Nakayama,
Yoshihiro Yoshitake, Masanori Shinohara,
Yukio Ando
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ABSTRACT: The biological effect of interleukin-6 (IL-6) signaling in oral squamous cell carcinoma (OSCC) and whether IL-6 receptor (IL-6R)-mediated signaling can be a therapeutic target for OSCC are unclear. The aim of this study was to investigate the effects of inhibition of IL-6R-mediated signaling on OSCC progression and to evaluate the availability of tocilizumab, a humanized antihuman IL-6R antibody, as a therapeutic agent for OSCC.
We evaluated expression levels of IL-6 and IL-6R in 58 OSCC tissues and 4 OSCC cell lines by real-time quantitative reverse transcription-PCR and/or immunohistochemstry. We investigated the effects of tocilizumab on OSCC growth in vitro and in xenografts. Xenografts were analyzed by immunohistochemistry for phosphorylated signal transducer and activator of transcription 3 (pSTAT3), Ki-67, and CD31, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay was done.
Expression levels of IL-6 at both mRNA and protein levels in OSCC tissues were significantly higher than those in normal mucosal tissues. In addition, OSCC cell lines expressed higher levels of both IL-6 and IL-6R mRNA than did HaCaT keratinocytes. Tocilizumab significantly reduced in vivo growth of SAS cells with a drastic reduction of STAT3 phosphorylation in tumor cells in mice. Inhibition of IL-6 signaling significantly decreased vascular endothelial growth factor mRNA expression in SAS, and microvessel density and vessel diameter in SAS tumors in tocilizumab-treated mice.
Therapeutic approaches targeting IL-6R by tocilizumab may be effective for OSCC treatment by at least inhibiting angiogenesis.
Clinical Cancer Research 09/2009; 15(17):5426-34. · 7.74 Impact Factor
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Tomoko Nomura,
Ryuji Murakami,
Ryo Toya,
Keiko Teshima,
Aya Nakahara,
Toshinori Hirai,
Akimitsu Hiraki,
Hideki Nakayama,
Yoshihiro Yoshitake,
Kazutoshi Ota,
Takehisa Obayashi,
Yasuyuki Yamashita,
Natsuo Oya, Masanori Shinohara
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ABSTRACT: To determine the feasibility and efficacy of preoperative concurrent chemoradiation therapy (CCRT) with S-1, an oral fluoropyrimidine derivative, in patients with T4 oral squamous cell carcinoma (SCC).
Only patients with histologically proven T4 oral SCC were included. Radiotherapy (total dose, 30 Gy) was delivered in 2-Gy daily fractions over a period of 3 weeks. Concurrently, S-1 (80 mg/m(2)/day) was administered orally twice daily for 14 consecutive days.
We enrolled 46 patients. All underwent radiotherapy as planned; however, oral S-1 was discontinued in 3 patients who manifested acute toxicity. Grade 3 toxicities were mucositis (20%), anorexia (9%), and neutropenia (4%). We encountered no Grade 4 adverse events or serious postoperative morbidity requiring surgical intervention. After CCRT, 32 of the 46 patients underwent radical resection; in 17 (53%) of the operated patients, the pathologic response was complete. During follow-up ranging from 7 to 58 months (median, 22 months), tumor control failed in 5 (16%) of the 32 operated patients; there were 3 local and 2 regional failures. Of the 14 non-operated patients, 8 (57%) manifested local (n = 7) or regional failure (n = 1). The 3-year overall survival rate for all 46 patients was 69%; it was significantly higher for operated than for non-operated patients (82% vs. 48%; p = 0.0288).
Preoperative CCRT with S-1 is feasible and effective in patients with T4 oral SCC. Even in inoperable cases, CCRT with S-1 provides adequate tumor control.
International journal of radiation oncology, biology, physics 08/2009; 76(5):1347-52. · 4.59 Impact Factor
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Mutsuko Ibusuki,
Hiromi Fujimori,
Yutaka Yamamoto,
Kazutoshi Ota,
Mitsuharu Ueda,
Satoru Shinriki,
Masahiro Taketomi,
Sadatoshi Sakuma, Masanori Shinohara,
Hirotaka Iwase,
Yukio Ando
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ABSTRACT: Midkine, a heparin-binding growth factor, is up-regulated in many types of cancer. The aim of this study was to measure plasma midkine levels in patients with breast cancer and to assess its clinical significance. We examined plasma midkine levels in 95 healthy volunteers, 11 patients with ductal carcinoma in situ (DCIS), 111 patients with primary invasive breast cancer without distant metastasis (PIBC), and 25 patients with distant metastatic breast cancer (MBC), using an automatic immunoasssay analyzer (TOSOH AIA system). In PIBC, we studied the correlation between plasma midkine levels and clinicopathological factors. Immunoreactive midkine was detectable in the plasma of healthy volunteers, and a cut-off level of 750 pg/mL was established. In breast cancer patients, plasma midkine levels were increased above normal values. These elevated levels of midkine were seen in one (9.1%) of 11 patients with DCIS, 36 (32.4%) of 111 patients with PIBC, and 16 (64.0%) of 25 patients with MBC. Increased levels of midkine were correlated with menopausal status (P = 0.0497) and nuclear grade (P = 0.0343) in PIBC. Cancer detection rates based on midkine levels were higher than those based on three conventional markers including CA15-3 (P < 0.0001), CEA (P = 0.0077), and NCCST-439 (P < 0.0001). Detection rates of breast cancer using a combination of two conventional tumor markers (CA15-3/CEA, CA15-3/NCCST-439, or CEA/NCCST-439) with midkine is significantly higher than those using combination of three conventional tumor markers. Midkine may be a useful novel tumor marker for detection of breast cancer, superior to conventional tumor markers.
Cancer Science 06/2009; 100(9):1735-9. · 3.33 Impact Factor
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Satoru Shinriki,
Mitsuharu Ueda,
Kazutoshi Ota,
Masaaki Nakamura,
Mareina Kudo,
Mutsuko Ibusuki,
Jaemi Kim,
Yoshihiro Yoshitake,
Daiki Fukuma,
Hirofumi Jono,
Jun-Ichi Kuratsu, Masanori Shinohara,
Yukio Ando
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ABSTRACT: Serum amyloid A (SAA) is an acute-phase reactant, the blood level of which is often elevated in response to some types of neoplasia. Here, we investigated expression of the gene SAA1 and the protein SAA in head and neck squamous cell carcinoma (HNSCC) and normal oral mucosal tissues as well as blood SAA levels in HNSCC patients. Also, we investigated the effects of inhibiting signal transducer and activator of transcription 3 (STAT3) signaling on SAA1 expression in the HNSCC cell line SAS. Serum SAA levels in HNSCC patients were significantly higher than those in healthy volunteers. In addition, real-time quantitative reverse transcription-polymerase chain reaction analysis revealed a significantly higher SAA1 expression level in HNSCC than in normal mucosa (P < 0.0001). Furthermore, Western blot and immunohistochemical analyzes revealed that high expression of SAA in carcinomas was detected predominantly in tumor cells, but not in normal mucosal tissues. An inhibitor of STAT3 activation, AG490, significantly reduced SAA1 expression in SAS cells. These data demonstrated that SAA was up-regulated in HNSCC through the Janus kinase-STAT3 pathway.
Journal of Oral Pathology and Medicine 05/2009; 39(1):41-7. · 1.63 Impact Factor
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Yoko Oe,
Hirofumi Soejima,
Hideki Nakayama,
Takashi Fukunaga,
Koichi Sugamura,
Hiroaki Kawano,
Seigo Sugiyama,
Katsuhiko Matsuo, Masanori Shinohara,
Yuichi Izumi,
Hisao Ogawa
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ABSTRACT: Recently, several researchers have demonstrated the association between periodontal disease and coronary artery disease (CAD). Therefore, we herein investigate the association between periodontal diseases and the existence of CAD among the study population who received both coronary angiography and dental examination. A total of 174 consecutive patients with dental examination including radiography and coronary angiography in the same hospitalization were recruited (64.5 +/- 10.3 years, M/F: 94/80). A dentist assessed severity of periodontal status markers (bleeding on probing, probing depth >or=6 mm, teeth lost, alveolar bone resorption >half of root length by radiography and smoking status). We divided these patients into two groups according to whether they had CAD (CAD group, n = 99) or not (non-CAD group, n = 75) according to the results of coronary angiography. The composite periodontal risk scores calculated from periodontal status markers were higher in the CAD group than in the non-CAD group (P = 0.02). The composite periodontal scores were higher in the CAD group of age <60 years old population (P = 0.03) and in the CAD group of patients with normal glucose tolerance (P = 0.04). However, the difference was not significant in the age >or=60 years old population or those with diabetes mellitus or impaired glucose tolerance. In all populations, hypertension, glucose tolerance, statin therapy, and composite of periodontal risk scores were associated with CAD. Multivariate analyses revealed statin therapy, glucose tolerance, and periodontal risk scores were independent and significant risk factors for CAD. Composite periodontal risk scores were independent and significant predictive factors for CAD.
Heart and Vessels 03/2009; 24(2):103-7. · 2.05 Impact Factor
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ABSTRACT: Intravascular papillary endothelial hyperplasia is a benign nonneoplastic vascular lesion that consists of endothelial cells with abundant vascular tissue with papillary proliferation. An adult female had a painless growing dark red nodule on the left side of the lower lip and often touched and gnawed at it for more than 4 years. The lesion was a tender, smooth mass approximately 1 cm in diameter without discoloration reaction. Magnetic resonance imaging of the lesion showed specific findings. She was diagnosed clinically as having mimicked hemangioma, and the lesion was totally excised under local anesthesia. Histopathological examination revealed that papillary proliferated endothelial cells with venous pool, and the lesion was diagnosed as intravascular papillary endothelial hyperplasia associated with venous pool. There has been no recurrence for more than 1 year. Despite the benign nature of this lesion, it could have been mistaken for a malignant tumor because of its clinical course and radiologic findings.
International Journal of Dentistry 01/2009; 2009:940686.
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Hirofumi Soejima,
Yoko Oe,
Hideki Nakayama,
Katsuhiko Matsuo,
Takashi Fukunaga,
Koichi Sugamura,
Hiroaki Kawano,
Seigo Sugiyama, Masanori Shinohara,
Yuichi Izumi,
Hisao Ogawa
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ABSTRACT: We performed periodontal examination and measured serum antibody levels against Prevotella intermedia in patients with acute coronary syndrome (ACS). Composite periodontal risk scores were significantly higher in the ACS group than in the coronary artery disease (CAD) group. Serum antibody levels were higher in the ACS group than in the CAD group and those were significantly correlated with the composite periodontal risk scores. These results provided important information about the status of P. intermedia infection in patients with ACS.
International journal of cardiology 09/2008; 137(3):304-6. · 7.08 Impact Factor
