Takeshi Morii

Kyorin University, Edo, Tōkyō, Japan

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Publications (43)64.6 Total impact

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    ABSTRACT: We previously demonstrated that a family predisposed to lung cancer harbored a V843I substitution in the epidermal growth factor receptor (EGFR) protein. We report here the further characterization of this mutant EGFR protein in the context of tumorigenicity and resistance to tyrosine kinase inhibitors (TKIs) of EGFR activity.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 07/2014; · 4.55 Impact Factor
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    ABSTRACT: Zoledronate (Zol), an anti-osteoclastic and anticancer drug, is used to control bone metastasis in several cancer types, including non-small cell lung cancer (NSCLC). However, the mechanisms behind Zol resistance in NSCLC are unclear. Zol-resistant cell lines were developed by repeated treatment of A549 and H1650 NSCLC cell lines with Zol. We measured cell proliferation and apoptosis following Zol treatment and also examined the BCL2 superfamily expression. RNAi was used to confirm the role of key molecules in development of resistance. Repeated Zol treatment engendered resistance, in which apoptosis induction was attenuated. From the BCL2 superfamily, BAX was commonly down-regulated in resistant cells, and silencing of BAX in parental cell lines also induced drug resistance. Repeated treatment of NSCLC cell lines with Zol leads to drug resistance, which is in part due to BAX down-regulation.
    Anticancer research 12/2013; 33(12):5357-63. · 1.71 Impact Factor
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    ABSTRACT: The surgical management of soft tissue sarcoma (STS) in elderly patients has only been addressed in a few studies. The objective of the current study was to assess surgical outcomes in patients with STS aged 70 years and older and the association of older age with the survival after complete resection. A retrospective analysis was conducted in 158 elderly patients with localized STS who visited 11 institutions participating in Japanese Musculoskeletal Oncology Group between 1995 and 2006 and were treated by surgical resection. Univariate and multivariate analyses were performed to identify prognostic factors. Median follow-up period was 38 months. Histologically high-grade tumors were detected in 71% of the patients. Wide resection with adequate margins was performed in 66% of the cases. Systemic chemotherapy was performed in only 5 patients. Univariate analysis identified histological grade and gender as statistically significant prognostic factors for sarcoma-specific survival. Multivariate analysis did not identify significant prognostic factors for sarcoma-specific survival, although high grade sarcoma emerged as a potentially significant prognostic factor (P = 0.050). Local recurrence was detected in 19% of the patients. Multivariate analysis of local recurrence-free survival showed that tumor site and surgical margins were statistically significant prognostic factors. Older age was not identified as a prognostic factor for sarcoma-specific survival, which is not consistent with the findings of previous studies showing that older age was associated with decreased sarcoma-specific survival. Complete resection should be indicated and can lead to optimal treatment outcome for properly selected elderly patients.
    European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 09/2013; · 2.56 Impact Factor
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    ABSTRACT: BACKGROUND: Although intensive studies have been conducted to clarify the incidence, risks, and management methods of deep infection of tumor endoprostheses, limited data have been published in respect of the impact of such deep infection on the function of the corresponding limb. METHODS: Clinical data of 125 patients (infection group 57, control group 68) with malignant bone and soft tissue tumors around the knee enrolled with the Japanese Musculoskeletal Oncology Group were collected. We analyzed the impact of deep infection of tumor endoprostheses on the limb salvage status together with that on the function of the salvaged limb. The definition of deep infection was based on the recommendations of the Centers for Disease Control and Prevention. The functional evaluation was based on the functional classification system established by the International Society of Limb Salvage and the Musculoskeletal Tumor Society. RESULTS: Infection together with extracapsular resection was demonstrated to be a risk factor for late amputation. There were no significant differences in the functional scores for "pain," "support," "walking," or "gait" between the infection and control groups. The risk factors identified for a loss of score for "functional activities" were deep infection, age, duration of operation, and extracapsular resection. The infection group also showed a significant lower score loss in "emotion". As for the overall functional scores, the risk factors identified for lower scores were deep infection and age. The mean scores for the infection group and control group were 19.3 (64.3 %) and 21.6 (72 %), respectively. Although the difference was confirmed to be statistically significant, the actual difference was only 2.3 (10.6 % reduction). CONCLUSIONS: Infection was a major risk factor for late amputation. Limbs salvaged by management of deep infection may show loss of function; however, the impact may be limited.
    Journal of Orthopaedic Science 04/2013; · 0.96 Impact Factor
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    ABSTRACT: BACKGROUND: The incidence of endoprosthesis failure has been well studied, but few studies have described the clinical characteristics of deep infection in tumor prostheses. This study aimed to analyze the characteristics of deep infection in tumor endoprostheses around the knee. METHODS: We analyzed clinical data of 57 patients with deep infections involving tumor endoprostheses around the knee enrolled from the Japanese Musculoskeletal Oncology Group. Profile of clinical presentation including time between surgery and infection, initial symptoms/blood tests and microbial cultures was evaluated. In addition pre-, intra-, and postoperative clinical factors influencing clinical presentation and treatment outcomes of infections were analyzed. RESULTS: Mean interval between the initial operation and diagnosis was 13 months, and mean time required for infection control was 12 months. The most common pathogen was Staphylococcus. Infection control rates were significantly higher when prostheses were removed rather than salvaged. Ten-year prosthesis survival and limb salvage rates were 41.6% and 75.6%, respectively. Analysis of underlying clinical factors suggested that soft-tissue condition significantly influenced the duration of the infection control period and likelihood of limb salvage. CONCLUSIONS: Infection control is a prolonged process. Deep infection frequently results in amputation or prosthesis loss. Intensive analysis of clinical characteristics may aid infection control.
    BMC Musculoskeletal Disorders 01/2013; 14(1):51. · 1.88 Impact Factor
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    ABSTRACT: In the present study, we evaluated the safety and effectiveness of SYT-SSX-derived peptide vaccines in patients with advanced synovial sarcoma. A 9-mer peptide spanning the SYT-SSX fusion region (B peptide) and its HLA-A*2402 anchor substitute (K9I) were synthesized. In Protocols A1 and A2, vaccines with peptide alone were administered subcutaneously six times at 14-day intervals. The B peptide was used in Protocol A1, whereas the K9I peptide was used in Protocol A2. In Protocols B1 and B2, the peptide was mixed with incomplete Freund's adjuvant and then administered subcutaneously six times at 14-day intervals. In addition, interferon-α was injected subcutaneously on the same day and again 3 days after the vaccination. The B peptide and K9I peptide were used in Protocols B1 and B2, respectively. In total, 21 patients (12 men, nine women; mean age 43.6 years) were enrolled in the present study. Each patient had multiple metastatic lesions of the lung. Thirteen patients completed the six-injection vaccination schedule. One patient developed intracerebral hemorrhage after the second vaccination. Delayed-type hypersensitivity skin tests were negative in all patients. Nine patients showed a greater than twofold increase in the frequency of CTLs in tetramer analysis. Recognized disease progression occurred in all but one of the nine patients in Protocols A1 and A2. In contrast, half the 12 patients had stable disease during the vaccination period in Protocols B1 and B2. Of note, one patient showed transient shrinkage of a metastatic lesion. The response of the patients to the B protocols is encouraging and warrants further investigation.
    Cancer Science 06/2012; 103(9):1625-30. · 3.48 Impact Factor
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    Journal of Orthopaedic Science 04/2012; · 0.96 Impact Factor
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    ABSTRACT: Postoperative wound complications, including surgical site infections, which frequently occur in the course of management of musculoskeletal sarcomas, sometimes necessitate repeat surgeries, including amputation, and may result in a prolonged healing time, prolonged hospital stay, or fatal outcome. A comprehensive understanding of surgical site infections associated with specific diseases is needed to reduce the risk. This series comprised 84 patients with malignant soft tissue tumors treated at our institute. The occurrence rate, management modality and clinical course of surgical site infections, impact of surgical site infections on the length of hospitalization, risk factors for the development of surgical site infections, and the impact of surgical site infections on the oncological outcomes were analyzed. Surgical site infection was defined according to Centers for Disease Control and Prevention guidelines. Surgical site infections occurred in 7 cases (8.3%). Although successful clinical cure was achieved in all cases, surgical site infection was identified as one of the independent risk factors for prolongation of hospitalization. Both univariate and multivariate analyses identified larger intraoperative blood loss and a trunk location as risk factors associated with deep infections. No association was detected between age, tumor grade, chemotherapy, tumor volume, or plastic surgery and the risk of surgical site infections. Although the differences were not statistically significant, patients with surgical site infections showed worse oncological outcomes in terms of local recurrence and total survival. The incidence rate of surgical site infection was larger than that associated with conventional orthopedic surgeries, such as osteosynthesis, spine surgery, or arthroplasty. Surgical site infections remain a critical and frequent complication of surgical treatment of soft-tissue malignancies and often result in prolongation of hospital stay. Although practical options to prevent surgical site infections seem quite limited, the present data provide a rationale for perioperative evaluation in patients at a high risk of surgical site infections.
    Journal of Orthopaedic Science 11/2011; 17(1):51-7. · 0.96 Impact Factor
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    ABSTRACT: Plasma d-dimer levels have been associated with the status of tumor progression or oncological outcomes in cancer. Although there are many evidences suggesting the involvement of procoagulant trend in musculoskeletal sarcoma, no clinical data on d-dimer levels and oncological outcome of musculoskeletal sarcoma has been reported. In this study, we included a total of 85 patients who were diagnosed with musculoskeletal sarcoma and treated at our institute. Plasma d-dimer levels were determined before performing any clinical intervention, including open biopsy, chemotherapy, radiotherapy or tumor resection. We evaluated the effect of d-dimer levels and other clinicopathological factors on oncological outcomes of patients. Upregulation of plasma d-dimer levels proved to be an independent risk factor for metastasis and lethal outcome of patients with musculoskeletal sarcoma. Upregulation of plasma d-dimer levels were indicated poor oncological outcome in metastasis and total survival rate of musculoskeletal sarcoma patients. Hence d-dimer levels may be a helpful marker for evaluating the tumor progression status and prognosis of musculoskeletal sarcoma.
    BMC Musculoskeletal Disorders 11/2011; 12:250. · 1.88 Impact Factor
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    Journal of Orthopaedic Science 07/2011; 16(4):487. · 0.96 Impact Factor
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    ABSTRACT: We have previously reported that recombinant human plasminogen-related protein B (rPRP-B), a putative 9-kDa protein that closely resembles the activation peptide of plasminogen, has shown significant inhibition of tumor growth through inhibition of angiogenesis. Based on recent reports suggesting a close relationship between rheumatoid arthritis (RA) and angiogenesis, we hypothesized that this compound would regulate inflammatory conditions in RA. The present study therefore tested the effects of rPRP-B in the treatment of collagen-induced arthritis (CIA) to elucidate the mechanisms underlying these effects. DBA/1J mice immunized with type II collagen to induce CIA were monitored to assess the effects of rPRP-B on clinical severity of the disease. Pathological changes in joints, including vessel formation and vascular endothelial growth factor (VEGF) production, were examined histologically. Bone destruction was radiologically evaluated. In vitro studies on the effects of rPRP-B on cell proliferation and production of VEGF in interleukin (IL)-1β or basic fibroblast growth factor (bFGF)-stimulated human synoviocytes were also performed. Development of CIA was effectively inhibited by rPRP-B. Radiological examinations revealed that the protein reduced bone destruction in CIA. CIA-induced vessel formation and VEGF expression in vivo were also reduced. In vitro mechanistic studies demonstrated that rPRP-B affected human synoviocyte proliferation and VEGF production stimulated by IL-1β and bFGF. Given the ability to effectively promote multistep anti-angiogenic activities, including cell growth inhibition and cytokine regulation, rPRP-B represents a promising candidate for a novel therapeutic agent against RA.
    Journal of Orthopaedic Science 05/2011; 16(4):443-50. · 0.96 Impact Factor
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    ABSTRACT: Desmoplastic fibroblastoma (collagenous fibroma) is a recently described tumor thought to arise predominantly from subcutaneous tissue or skeletal muscle. The natural evolution of this tumor on magnetic resonance imaging has never been described, to the best of our knowledge. We herein report a case of desmoplastic fibroblastoma arising in the thigh and show the longitudinal magnetic resonance imaging findings. A 60-year-old Japanese man presented with swelling of the medial side of his right thigh, and he complained of nighttime pain and slight tenderness. Magnetic resonance imaging demonstrated a 4 × 4 cm mass in the right thigh. Open biopsy was performed. The mass was diagnosed histologically as a benign fibrous tumor, and we maintained follow-up without surgical therapy. After one year, magnetic resonance imaging showed an increase in tumor size to 4 × 5 cm, but the histologic findings were the same as those obtained one year earlier. Resection was performed with narrow surgical margins. Pathologic diagnosis was desmoplastic fibroblastoma. Two years after surgery, the patient is free from pain and shows no signs or symptoms of recurrence. The natural evolution of desmoplastic fibroblastoma is characterized by no changes in patterns on magnetic resonance imaging despite increasing size. This finding is clinically helpful for distinguishing desmoplastic fibroblastoma with increasing pain from the desmoid tumor.
    Journal of Medical Case Reports 04/2011; 5:139.
  • Journal of Orthopaedic Science 03/2011; 16(3):321-5. · 0.96 Impact Factor
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    ABSTRACT: Malignant pigmented villonodular synovitis (PVNS) (or malignant giant cell tumor of tendon sheath (GCTTS) is an extremely rare condition defined as a malignant lesion occurring with concomitant or previously documented PVNS at the same site. To date, only less than 20 cases have been reported in English literatures. We report a case of malignant PVNS in the knee in a 56-year-old woman with unpredictable rapid progression. This case raised a caution that when atypical components in specimens of recurrent benign PVNS are detected, even if low-grade or tiny, both pathologists and surgeons should consider the risk of malignant PVNS, which could display aggressive clinical progression.
    The Open Orthopaedics Journal 01/2011; 5:13-6.
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    ABSTRACT: Although patients with musculoskeletal tumors are at risk of venous thromboembolism (VTE), few detailed studies on the incidence, clinical course, and risk factors of this condition have been reported. A total of 299 patients with musculoskeletal tumors during the preceding 3 years were enrolled. D-dimer (DD) levels on admission and on postoperative days 1, 7, and 14 were routinely assessed. For patients who were receiving chemotherapy, an examination was performed every 2-3 days for the survey. Multidetector-row computed tomography (MDCT) was used for the detection of VTE in patients with DD levels > 10 μg/ml. The incidence of clinically detected VTE and the clinical courses of the patients with VTE were reviewed. The risk factors for VTE were analyzed. For statistical analysis, Fisher's exact test, the Mann-Whitney U-test, and logistic regression were used. VTE was detected in eight cases (2.7%). Six cases were detected postoperatively, and the remaining two cases were detected during chemotherapy. Pulmonary embolism was evident in four cases. No VTE-related lethal events were detected during the study period. In the univariate analysis, malignancy (P = 0.003), chemotherapy (P = 0.004), plastic surgery (P = 0.006), tumor size (P = 0.008), and elevated DD levels at admission (P = 0.03) were found to be significant risk factors for VTE. Among these factors, the multivariate analysis indicated that tumor size (P = 0.00 006), plastic surgery (P 0. 01), and chemotherapy (P = 0.02) were independent risk factors. The incidence and risk factors for VTE in the management of musculoskeletal tumor patients by screening DD levels combined with MDCT were analyzed. For patients at risk, prospective surveys for VTE should be considered in the future.
    Journal of Orthopaedic Science 11/2010; 15(6):810-5. · 0.96 Impact Factor
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    ABSTRACT: Understanding the mechanisms of drug resistance to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) is essential to develop novel chemotherapies for non-small cell lung cancer (NSCLC). Therefore, we analyzed the expression and function of ATP-binding cassette (ABC) transporters in EGFR TKI-resistant NSCLC. In three newly established AG1478-resistant NSCLC cell lines, we evaluated the expression profile of ABC transporters and genotyping of ABCG2 by real-time polymerase chain reaction and elucidated their function by Hoechst dye efflux analyses. The growth-inhibitory effect of the topoisomerase I inhibitor Hoechst 33342, which is extruded by ABCG2, was also investigated in these cells using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. In AG1478-resistant cells, significantly less ABCG2 was expressed, and the ratios of the cells with a strong ability to extrude Hoechst dye were remarkably smaller than in the parent cells. Because of the ABCG2 downregulation and loss of function due to C421A/C421A homozygosity, PC-14AG50R was thus considered to be more sensitive to Hoechst 33342 than the parental cells. All AG1478-resistant cells were more sensitive to the combination of Hoechst 33342 and AG1478 than to single agent. Resistance to EGFR TKI in NSCLC is associated with the downregulation of ABCG2 expression. A topoisomerase I inhibitor alone or in combination with EGFR TKI might offer a promising strategy for treating NSCLC that is resistant to EGFR TKI.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 11/2010; 5(11):1726-33. · 4.55 Impact Factor
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    ABSTRACT: Although zoledronic acid (ZOL) has been reported to show anti-tumour effects on various malignant tumours, few studies have reported the molecular mechanisms of resistance to ZOL. A drug-resistant cell line was developed by repeatedly treating human osteosarcoma cell line HOS with ZOL. Expression status of drug resistance-related molecules including ATP-binding cassette (ABC) and heat-shock protein 27 (HSP27) was confirmed in order to analyse molecular mechanisms of the drug resistance. Repeated treatment with ZOL induced drug resistance with down-regulation of apoptosis in the resistant cell line. Although ABC expression was down-regulated, up-regulation of HSP27 in the resistant cell line was confirmed. The resistance was overcome by HSP27 silencing. Resistance to ZOL in osteosarcoma cells may be induced by a molecular mechanism different from conventional efflux pump-based resistance. Up-regulation of HSP27 expression may play a role in the development of ZOL resistance in HOS cells.
    Anticancer research 09/2010; 30(9):3565-71. · 1.71 Impact Factor
  • Journal of Orthopaedic Science 07/2010; 15(4):589-93. · 0.96 Impact Factor
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    ABSTRACT: Lethal events represent the most important complication in the treatment of hip fracture in elderly patients. Despite the increasing chance for treatment of such conditions, few data regarding risk factors associated with lethal events have been determined for ordinary hospitals with limited medical and human resources, particularly in Japan. The incidence of postoperative lethal events and related preoperative risk factors in extremely elderly patients (>80 years) with hip fracture were retrospectively analyzed in our hospital for the past 2 years. Lethal events occurred in 11 (10.7%) of 103 patients within 3 months postoperatively. In both univariate and multivariate analyses, an elevated number of co-morbidities and preoperative respiratory dysfunction were identified as significant risk factors. Delay in surgery was not a risk factor for lethal events. A valid reason for delay is the need to stabilize concurrent medical conditions due to multiple co-morbidities in extremely elderly patients with hip fracture. Considering the limited resources and extreme age of the subjects, the mortality rate in the present study was quite acceptable. Patients, families of patients, and physicians should recognize the increased risk of mortality for patients with significant risk factors in the surgical treatment of hip fracture.
    Journal of Orthopaedic Science 07/2010; 15(4):437-42. · 0.96 Impact Factor
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    ABSTRACT: Although deep infection remains one of the most difficult complications to manage in the treatment of musculoskeletal tumor reconstructed with an endoprosthesis, limited information with respect to its incidence and risk factors has been reported. This multicenter, retrospective, uncontrolled study reviewed the medical records of 82 patients who underwent reconstruction with an endoprosthesis or temporary spacer for bone-immature patients after resection of malignant bone tumor around the knee. Risk factors for deep infection and the impact of deep infection on prosthesis survival and oncological outcomes were analyzed. Deep infection was defined according to the Centers for Disease Control and Prevention (CDC) guidelines with minor modification. Deep infection occurred in 14 cases (17%), identified at a mean of 10.9 months (range <1 to 48 months) after initial surgery. Univariate analysis identified surface infection (P < 0.001) and skin necrosis (P < 0.001) as risk factors associated with deep infection. Conversely, tumor origin, chemotherapy, number of postoperative antibiotics, and length of bone resection were not associated with infection. Subclass analysis in femur cases identified a correlation between infection and the extent of partial resection of the quadriceps muscle (P = 0.04). In the multivariate analysis, surface infection represented an independent risk factor for deep infection (P = 0.03). Deep infection was a risk for endoprosthesis survival (P = 0.003) but did not affect the oncological outcome. A strong correlation between the condition of soft tissue and establishment of deep infection is suggested in this study. Although practical options for preventing deep infection seem limited, the present data allow a form of perioperative evaluation for patients with a higher risk of deep infection.
    Journal of Orthopaedic Science 05/2010; 15(3):331-9. · 0.96 Impact Factor

Publication Stats

126 Citations
64.60 Total Impact Points

Institutions

  • 2008–2013
    • Kyorin University
      • • Department of Orthopaedic Surgery
      • • School of Medicine
      Edo, Tōkyō, Japan
  • 2000–2011
    • Keio University
      • School of Medicine
      Tokyo, Tokyo-to, Japan
  • 2003
    • Massachusetts General Hospital
      Boston, Massachusetts, United States