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ABSTRACT: This study seeks to discuss the efficiency of minimally invasive surgery of posterior long segmental fixation plus direct decompression in patients with spinal metastatic tumors. Twenty-five patients received minimally invasive surgery of long segmental fixation combined with direct decompression from posterior approach. Pain and neurologic improvement in these patients pre- and post operation were evaluated by Denis' Pain Scale and Frankel Score, respectively. Seventeen patients (68.0%) showed significant decreases in Denis' Pain score after surgery (p < 0.0001). Paralysis symptoms were improved in nineteen patients (76.0%). The Frankel Score exhibited significant difference between pre-operation and post-operation (p < 0.0001). Operation time and blood loss in this cohort were 324 ± 90 minutes and 1047 ± 730 ml, respectively. No fatal complications were observed as a result of surgery. In conclusion, minimally invasive surgery of posterior long segmental fixation combined with direct decompression is a safe and efficient strategy to release pain and improve neurological function in patients with spinal metastatic tumors.
International journal of surgery (London, England) 12/2012;
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Naofumi Asano,
Michiro Susa,
Seiichi Hosaka,
Robert Nakayama, Eisuke Kobayashi,
Katsuhito Takeuchi,
Keisuke Horiuchi,
Yoshihisa Suzuki,
Ukei Anazawa,
Makio Mukai,
Yoshiaki Toyama,
Hiroo Yabe,
Hideo Morioka
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ABSTRACT: Myxoid/round cell liposarcoma (MRCL), unlike other soft tissue sarcomas, has been associated with unusual pattern of metastasis to extrapulmonary sites. In an attempt to elucidate the clinical features of MRCL with metastatic lesions, 58 cases, from the medical database of Keio University Hospital were used for the evaluation. 47 patients (81%) had no metastases, whereas 11 patients (11%) had metastases during their clinical course. Among the 11 patients with metastatic lesions, 8 patients (73%) had extrapulmonary metastases and 3 patients (27%) had pulmonary metastases. Patients were further divided into three groups; without metastasis, with extrapulmonary metastasis, and with pulmonary metastasis. When the metastatic patterns were stratified according to tumor size, there was statistical significance between the three groups (P = 0.028). The 8 cases with extrapulmonary metastases were all larger than 10 cm. Similarly, histological grading had a significant impact on metastatic patterns (P = 0.027). 3 cases with pulmonary metastatic lesions were all diagnosed as high grade. In conclusion, large size and low histological grade were significantly associated with extrapulmonary metastasis.
Sarcoma 01/2012; 2012:345161.
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Mitsuhiko Osaki,
Fumitaka Takeshita,
Yui Sugimoto,
Nobuyoshi Kosaka,
Yusuke Yamamoto,
Yusuke Yoshioka, Eisuke Kobayashi,
Tesshi Yamada,
Akira Kawai,
Toshiaki Inoue,
Hisao Ito,
Mitsuo Oshimura,
Takahiro Ochiya
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ABSTRACT: Pulmonary metastases are the main cause of death in patients with osteosarcoma, however, the molecular mechanisms of metastasis are not well understood. To detect lung metastasis-related microRNA (miRNA) in human osteosarcoma, we compared parental (HOS) and its subclone (143B) human osteosarcoma cell lines showing lung metastasis in a mouse model. miR-143 was the most downregulated miRNA (P < 0.01), and transfection of miR-143 into 143B significantly decreased its invasiveness, but not cell proliferation. Noninvasive optical imaging technologies revealed that intravenous injection of miR-143, but not negative control miRNA, significantly suppressed lung metastasis of 143B (P < 0.01). To search for miR-143 target mRNA in 143B, microarray analyses were performed using an independent RNA pool extracted by two different comprehensive miR-143-target mRNA collecting systems. Western blot analyses revealed that MMP-13 was mostly protein downregulated by miR-143. Immunohistochemistry using clinical samples clearly revealed MMP-13-positive cells in lung metastasis-positive cases, but not in at least three cases showing higher miR-143 expression in the no metastasis group. Taken together, these data indicated that the downregulation of miR-143 correlates with the lung metastasis of human osteosarcoma cells by promoting cellular invasion, probably via MMP-13 upregulation, suggesting that miRNA could be used to develop new molecular targets for osteosarcoma metastasis.
Molecular Therapy 03/2011; 19(6):1123-30. · 6.87 Impact Factor
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Eisuke Kobayashi,
Mari Masuda,
Robert Nakayama,
Hitoshi Ichikawa,
Reiko Satow,
Miki Shitashige,
Kazufumi Honda,
Umio Yamaguchi,
Ayako Shoji,
Naobumi Tochigi,
Hideo Morioka,
Yoshiaki Toyama,
Setsuo Hirohashi,
Akira Kawai,
Tesshi Yamada
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ABSTRACT: Pulmonary metastasis is the most significant prognostic determinant for osteosarcoma, but methods for its prediction and treatment have not been established. Using oligonucleotide microarrays, we compared the global gene expression of biopsy samples between seven osteosarcoma patients who developed pulmonary metastasis within 4 years after neoadjuvant chemotherapy and curative resection, and 12 patients who did not relapse. We identified argininosuccinate synthetase (ASS) as a gene differentially expressed with the highest statistical significance (Welch's t test, P = 2.2 x 10(-5)). Immunohistochemical analysis of an independent cohort of 62 osteosarcoma cases confirmed that reduced expression of ASS protein was significantly correlated with the development of pulmonary metastasis after surgery (log-rank test, P < 0.05). Cox regression analysis revealed that ASS was the sole significant predictive factor (P = 0.039; hazard ratio, 0.319; 95% confidence interval, 0.108-0.945). ASS is one of the enzymes required for the production of a nonessential amino acid, arginine. We showed that osteosarcoma cells lacking ASS expression were auxotrophic for arginine and underwent G(0)-G(1) arrest in arginine-free medium, suggesting that an arginine deprivation therapy could be effective in patients with osteosarcoma. Recently, phase I and II clinical trials in patients with melanoma and hepatocellular carcinoma have shown the safety and efficacy of plasma arginine depletion by stabilized arginine deiminase. Our data indicate that in patients with osteosarcoma, reduced expression of ASS is not only a novel predictive biomarker for the development of metastasis, but also a potential target for pharmacologic intervention.
Molecular Cancer Therapeutics 02/2010; 9(3):535-44. · 5.23 Impact Factor
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Umio Yamaguchi,
Kazufumi Honda,
Reiko Satow, Eisuke Kobayashi,
Robert Nakayama,
Hitoshi Ichikawa,
Ayako Shoji,
Miki Shitashige,
Mari Masuda,
Akira Kawai,
Hirokazu Chuman,
Yukihide Iwamoto,
Setsuo Hirohashi,
Tesshi Yamada
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ABSTRACT: Osteosarcoma (OS) is the most frequent primary malignant bone tumor of children and young adults. Although the introduction of combined neoadjuvant chemotherapy has markedly improved survival, the outcome of OS patients with distant metastasis and/or poor response to chemotherapy is still unsatisfactory. Therefore there is a need to develop new therapeutic agents that suppress OS cell proliferation with higher efficacy. The protein kinases are a family of genes that play critical roles in various signaling pathways. Some cancer cells show addiction to constitutive activation of certain signaling pathways for proliferation and survival. To identify new drug targets for OS, we screened a panel of small interfering RNAs (siRNAs) that target 691 genes encoding human protein kinases and related proteins. We found that different constructs of siRNA specifically targeting polo-like 1 kinase (PLK1) significantly caused mitotic cell cycle arrest and subsequent apoptotic cell death in a variety of OS cell lines. siRNA targeting PLK1 also suppressed the growth of OS xenografts established in immunodeficient mice. Recently, phase I clinical trials of PLK1 chemical inhibitors have been reported. Our results indicate that PLK1 is a promising molecular target for pharmacologic intervention in OS.
Cancer Science 09/2009; 100(12):2268-74. · 3.33 Impact Factor
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ABSTRACT: Drug-induced liver injury is a major problem in drug development and clinical drug therapy. In most cases the mechanisms are still unknown, thus, it is difficult to predict or prevent these reactions. It has been known that halothane, an inhaled anesthetic, induces liver injury. To investigate the mechanisms of halothane-induced liver injury, we used a recently established mouse model of liver injury. The expression of transcription factors and cytokines specific for Th1 and Th2 (helper T cells), respectively, were compared between BALB/c and C57BL/6 mice. The mRNA expression ratios of mouse T-bet(a Th1-specific transcription factor)/GATA-binding protein (GATA-3, a Th2-specific transcription factor) and interferon gamma/interleukin (IL)-10 were lower in BALB/c mice compared with C57BL/6 mice, suggesting that a typical Th1 or Th2-dominant response could not be distinguished in halothane-induced liver injury. We observed increases of the plasma IL-17 level and hepatic macrophage inflammatory protein 2 expression in halothane-administrated BALB/c mice, as well as neutrophil infiltration. Neutralization of IL-17 suppressed the hepatotoxic effect of halothane. Administration of recombinant IL-17 (1 microg per mouse, single ip) to the halothane-treated mice resulted in a remarkable increase of alanine and aspartate aminotransferases. In conclusion, we demonstrated that IL-17 is involved in the halothane-induced liver injury.
Toxicological Sciences 08/2009; 111(2):302-10. · 4.65 Impact Factor
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Eisuke Kobayashi,
Akira Kawai,
Makoto Endo,
Yoshiyuki Suehara,
Ken Takeda,
Fumihiko Nakatani,
Takayuki Asano,
Minoru Sakuraba,
Hirokazu Chuman,
Kunihiko Seki,
Yasuo Beppu
Journal of Orthopaedic Science 12/2008; 13(6):566-71. · 0.84 Impact Factor
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ABSTRACT: The rare coexistence of intramuscular myxoma (IM) and fibrous dysplasia (FD) is known as Mazabraud's syndrome. IM tends to occur multifocally and is associated most frequently with polyostotic FD in Mazabraud's syndrome. We present an extremely rare combination of a solitary IM and monostotic FD as a variant of Mazabraud's syndrome, and discuss the importance of recognizing this rare coexistence for appropriate management of the patient.
Skeletal Radiology 07/2007; 36(6):523-9. · 1.54 Impact Factor
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ABSTRACT: The vast majority of soft tissue sarcomas metastasize initially to the lungs. We report a 71-year-old woman with malignant fibrous histiocytoma of the right buttock and thigh that metastasized to the bilateral adrenal glands without development of pulmonary metastasis. Whole-body [F-18]FDG PET-CT showed abnormal tracer uptakes in the bilateral adrenal glands in addition to high accumulation in the primary soft tissue tumors. CT-guided needle biopsy revealed that both of the adrenal lesions were metastatic malignant fibrous histiocytoma. There was no pulmonary or other visceral metastasis. To the authors' knowledge, this is the first report of malignant fibrous histiocytoma metastatic to the bilateral adrenal glands without development of pulmonary metastases. This case illustrates the excellence of [F-18]FDG PET-CT scan for diagnosis of occult metastases from soft tissue sarcomas.
Annals of Nuclear Medicine 01/2007; 20(10):695-8. · 1.50 Impact Factor
