論文 Does re-ossification after palliative radiotherapy for spinal bone metastases help maintain vertebral body height? The spine journal : official journal of the North American Spine Society,23(10):1540-1548 2023(Oct.) Author:Munehisa Kito; Yoshinori Tsukahara; Masanori Okamoto; Ayumu Fukazawa; Shota Ikegami; Atsushi Tanaka; Yukiko Komatsu; Hirokazu Ideta; Kaoru Aoki; Yasunari Fujinaga; Jun Takahashi Abstract:BACKGROUND CONTEXT: After palliative radiotherapy of spinal bone metastases, re-ossification is sometimes observed in bone with osteolytic changes. However, it remains unknown whether the re-ossification that is observed after radiotherapy is associated with preservation of vertebral body height. PURPOSE: To investigate whether re-ossification observed after palliative radiotherapy can contribute to the preservation of vertebral body height. STUDY DESIGN: This is a retrospective observational study. PATIENTS SAMPLE: We investigated 111 vertebral bodies in 54 patients that underwent palliative radiotherapy at a single center for painful osteolytic/mixed metastatic spinal tumors in solid tumors between 2016 and 2020. OUTCOME MEASURES: The outcome measures were the presence of re-ossification and vertebral body height reduction on the CT image. METHODS: Re-ossification was evaluated according to the MD Anderson response classification criteria, and sagittal CT images were used to evaluate vertebral body height. A vertebral body ID was assigned to the irradiated vertebral body, and continuous CT images obtained for each vertebral body ID were evaluated. The median number of evaluation periods for each vertebral body was 4, and the total number of periods was 463. Logistic regression analysis was performed to investigate factors related to the occurrence of vertebral body height reduction before the subsequent CT. As a subanalysis, factors related to re-ossification were investigated. RESULTS: The following primary cancer types were observed: lung cancer, 41 vertebral bodies; breast cancer, 19; renal cell cancer, 15; other, 36. A total of 62.2% showed re-ossification. The median time to confirmation of re-ossification by CT was 2 months. Factors significantly associated with vertebral body height reduction were presence of vertebral body height reduction before radiotherapy (odds ratio [OR] 6.8, 95% confidence interval [CI] 2.0-63, p=.01) and no re-ossification (OR 137, 95% CI 22-3469, p<.01). Factors associated with re-ossification were the type of cancer and total radiation dose. Those with lung cancer and those with a total radiation dose of 20 Gy or less were more prone to re-ossification. CONCLUSIONS: Re-ossification was observed in 62.2% of vertebral bodies after palliative radiotherapy for painful osteolytic/mixed metastatic spinal tumors. The re-ossification group demonstrated significantly less vertebral body height reduction when compared with the non-re-ossification group. The presence of re-ossification may potentially serve an important role in maintaining vertebral body height.
Muscle strength and functional recovery for soft-tissue sarcoma of the thigh: a prospective study. International journal of clinical oncology,28(7):922-927 2023(Jul.) Author:Atsushi Tanaka; Masanori Okamoto; Munehisa Kito; Yasuo Yoshimura; Kaoru Aoki; Shuichiro Suzuki; Akira Takazawa; Yukiko Komatsu; Hirokazu Ideta; Takaaki Ishida; Jun Takahashi Abstract:BACKGROUND: This study aimed to investigate changes in muscle strength and functional outcome before and after surgery for soft-tissue sarcoma of the thigh and to examine the timing of recovery. METHODS: From 2014 to 2019, 15 patients who underwent multiple resections of the thigh muscle for soft-tissue sarcoma of the thigh were included in this study. The muscle strength was measured with an isokinetic dynamometer for the knee joint and with a hand-held dynamometer for the hip joint. The functional outcome assessment was based on the Musculoskeletal Tumor Society (MSTS) score, Toronto Extremity Salvage Score (TESS), European Quality of Life-5 Dimensions (EQ-5D), and maximum walking speed (MWS). All measurements were conducted preoperatively and at 3, 6, 12, 18, and 24 months postoperatively, and the ratio of postoperative to preoperative value was used. A repeated-measures analysis of variance was performed to compare changes over time and to investigate the recovery plateau. Correlations between changes in muscle strength and functional outcomes were also examined. RESULTS: The muscle strength of the affected limb, MSTS score, TESS, EQ-5D, and MWS were significantly decreased at 3 months postoperatively. The recovery plateau was subsequently reached at 12 months postoperatively. The changes in muscle strength of the affected limb and functional outcome showed a significant correlation. CONCLUSIONS: The estimated postoperative recovery for soft-tissue sarcoma of the thigh is 12 months after surgery.
Clinical Outcome of Low-Grade Myofibroblastic Sarcoma in Japan: A Multicenter Study from the Japanese Musculoskeletal Oncology Group. Cancers,15(8) 2023(Apr. 15) Author:Munehisa Kito; Keisuke Ae; Masanori Okamoto; Makoto Endo; Kunihiro Ikuta; Akihiko Takeuchi; Naohiro Yasuda; Taketoshi Yasuda; Yoshinori Imura; Takeshi Morii; Kazutaka Kikuta; Teruya Kawamoto; Yutaka Nezu; Ichiro Baba; Shusa Ohshika; Takeshi Uehara; Takafumi Ueda; Jun Takahashi; Hirotaka Kawano Abstract:This retrospective multicenter study aimed to analyze the clinical features and prognosis of 24 patients diagnosed with LGMS between 2002 and 2019 in the Japanese sarcoma network. Twenty-two cases were surgically treated and two cases were treated with radical radiotherapy (RT). The pathological margin was R0 in 14 cases, R1 in 7 cases, and R2 in 1 case. The best overall response in the two patients who underwent radical RT was one complete response and one partial response. Local relapse occurred in 20.8% of patients. Local relapse-free survival (LRFS) was 91.3% at 2 years and 75.4% at 5 years. In univariate analysis, tumors of 5 cm or more were significantly more likely to cause local relapse (p < 0.01). In terms of the treatment of relapsed tumors, surgery was performed in two cases and radical RT was performed in three cases. None of the patients experienced a second local relapse. Disease-specific survival was 100% at 5 years. A wide excision aimed at the microscopically R0 margin is considered the standard treatment for LGMS. However, RT may be a viable option in unresectable cases or in cases where surgery is expected to cause significant functional impairment.
The usefulness of immunohistochemistry for phosphohistone H3 as a prognostic factor in myxoid liposarcoma. Scientific reports,13(1):4733-4733 2023(Mar. 23) Author:Akira Takazawa; Yasuo Yoshimura; Masanori Okamoto; Atsushi Tanaka; Munehisa Kito; Kaoru Aoki; Takeshi Uehara; Jun Takahashi; Hiroyuki Kato; Jun Nakayama Abstract:Myxoid liposarcoma (MLS) is a common subtype of liposarcoma. Although the prognosis is generally good, there are factors known to be associated with poor prognosis. Accurate indices are important to predict prognosis. We aimed to assess the usefulness of immunohistochemistry for phosphohistone H3 (PHH3) as a potential biomarker in comparison with Ki-67 antigen and other prognostic factors. Twenty-five patients with MLS were evaluated. Age, sex, depth of tumor, tumor size, surgical margin, oncological outcome, histological grade, presence of necrosis, proportion of round cell component (RC%), PHH3 index, and Ki-67 index were examined. Prognostic factors of the examination criteria were statistically analyzed, survival rate analyses were performed using the Kaplan-Meier method, and multivariate analysis was performed using Cox proportional-hazard regression analysis. The number of PHH3-positive tumor cells and the PHH3 and Ki-67 indices demonstrated a statistical correlation with the prognosis of MLS in univariate analysis (P < 0.001, P < 0.001, P = 0.01, respectively). PHH3 index and RC% were significant factors in multivariate analysis (P = 0.03, P = 0.02). The immunohistochemistry of PHH3 may be associated with prognosis and could serve as a valid criterion of histological grade in MLS.
Leiomyosarcoma of the femur arising from an aneurysmal bone cyst treated seven years before: A case report and literature review. Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association,27(6):1359-1362 2022(Nov.) Author:Tetsuhiko Mimura; Yasuo Yoshimura; Kenji Sano; Nobuhito Araki; Masanori Okamoto; Munehisa Kito; Atsushi Tanaka; Shuichiro Suzuki; Akira Takazawa; Kaoru Aoki
Influence of the adductor compartment resection on muscle strength and postoperative function in soft-tissue sarcoma of the thigh. Japanese journal of clinical oncology,52(4):370-374 2022(Apr. 06) Author:Atsushi Tanaka; Masanori Okamoto; Munehisa Kito; Yasuo Yoshimura; Kaoru Aoki; Shuichiro Suzuki; Akira Takazawa; Yukiko Komatsu; Takaaki Ishida; Jun Takahashi Abstract:OBJECTIVE: To predict the muscle strength and postoperative function for soft-tissue sarcoma arising from the adductor compartment of the thigh. METHODS: Between 2003 and 2019, 17 cases that underwent resection of the adductor muscle group (adductor longus, adductor magnus, adductor brevis, gracilis and pectineus) for soft-tissue sarcoma in the adductor compartment of the thigh were included. The muscle strength was measured with an isokinetic dynamometer for the knee joint and with a hand-held dynamometer for the hip joint (ratio of affected to unaffected side). The Musculoskeletal Tumor Society score, Toronto Extremity Salvage Score, European Quality of Life-5 Dimensions and maximum walking speed were used to assess postoperative function and examine correlations with muscle strength. RESULTS: In 13 cases that underwent an isolated resection of the adductor compartment, reduced adduction strength correlated with increased number of resected muscles in the adductor muscle group (P < 0.001). Postoperative function was maintained, showing no correlations with adduction strength. In four cases that underwent combined resections of other compartments, a decrease was observed in adduction strength as well as the muscle strength of other resected muscles, in addition to a decline in postoperative function. In the 4 or 5 adductor muscle resection group, the comparison between isolated and combined resection revealed comparable results for adduction strength but a significant decrease in postoperative function for the combined resection group. CONCLUSIONS: Postoperative function can be preserved for isolated adductor compartment resection. Combined resections of multiple muscles in other compartments and most adductor muscles may result in decreased postoperative function.
Points of consideration when performing surgical procedures for proximal femoral bone metastasis. Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association,27(1):229-234 2022(Jan.) Author:Atsushi Tanaka; Masanori Okamoto; Munehisa Kito; Yasuo Yoshimura; Kaoru Aoki; Shuichiro Suzuki; Akira Takazawa; Jun Takahashi Abstract:BACKGROUND: To assess the points of consideration when performing surgical procedures for proximal femoral bone metastasis. METHODS: Fourty patients who underwent surgery for proximal femoral bone metastasis from 2009 to 2019 were included. Prognostic assessments were performed based on the Katagiri scoring system. The low-risk group underwent endoprosthetic replacement (EPR) following resection, while the high-risk group underwent internal fixation (IF). For the intermediate-risk group, one of the surgical procedures was chosen depending on general and local condition. Survival period, walking ability, and treatment failure were evaluated. RESULTS: Sixteen and 24 patients underwent EPR and IF, respectively. Although walking reacquisition rate was 94% (15 of 16 patients) for EPR and 75% (18 of 24 patients) for IF (p = 0.210), the median time to walking was shorter in IF compared to EPR (EPR, 29 days, interquartile range [IQR] 23-40; IF, 14 days, IQR 9-24; p = 0.014). Neither EPR nor IF resulted in treatment failure for those with survival periods of <1 year. The treatment failure rate for those with survival periods of ≥1 year was significantly different between EPR (9%, 1 of 11 patients) and IF (50%, 5 of 10 patients) (p = 0.038). All five patients of treatment failure for IF were renal cancer with no bone formation in the intermediate-risk group. Of the 13 patients who underwent IF for the intermediate-risk group, treatment failure did not occur in 5 patients with bone formation. CONCLUSIONS: Although EPR is a more reliable treatment than IF, patients with life expectancy of <1 year are sufficiently manageable with IF. For the intermediate-risk group, EPR should be selected for cases without expected bone formation, and IF can be considered for cases with expected bone formation due to the risk of treatment failure for IF at ≥ 1 year after surgery.
Antitumor Effect of Sclerostin against Osteosarcoma Cancers,13(23):6015-6015 2021(Nov. 29) Author:Hirokazu Ideta; Kazushige Yoshida; Masanori Okamoto; Jun Sasaki; Munehisa Kito; Kaoru Aoki; Yasuo Yoshimura; Shuichiro Suzuki; Atsushi Tanaka; Akira Takazawa; Hisao Haniu; Takeshi Uemura; Takashi Takizawa; Atsushi Sobajima; Takayuki Kamanaka; Jun Takahashi; Hiroyuki Kato; Naoto Saito Abstract:Various risk factors and causative genes of osteosarcoma have been reported in the literature; however, its etiology remains largely unknown. Bone formation is a shared phenomenon in all types of osteosarcomas, and sclerostin is an extracellular soluble factor secreted by osteocytes that prevents bone formation by inhibiting the Wnt signaling pathway. We aimed to investigate the antitumor effect of sclerostin against osteosarcoma. Osteosarcoma model mice were prepared by transplantation into the dorsal region of C3H/He and BALB/c-nu/nu mice using osteosarcoma cell lines LM8 (murine) and 143B (human), respectively. Cell proliferations were evaluated by using alamarBlue and scratch assays. The migratory ability of the cells was evaluated using a migration assay. Sclerostin was injected intraperitoneally for 7 days to examine the suppression of tumor size and extension of survival. The administration of sclerostin to osteosarcoma cells significantly inhibited the growth and migratory ability of osteosarcoma cells. Kaplan–Meier curves and survival data demonstrated that sclerostin significantly inhibited tumor growth and improved survival. Sclerostin suppressed the proliferative capacity and migratory ability of osteosarcoma cells. Osteosarcoma model mice inhibited tumor growth and prolonged survival periods by the administration of sclerostin. The effect of existing anticancer drugs such as doxorubicin should be investigated for future clinical applications.
Impact of Smoking History on Pulmonary Metastasis-free Survival in Patients With Soft-tissue Sarcoma Cancer Diagnosis & Prognosis,1(2):89-94 2021(May 03) Author:MASATAKE MATSUOKA; MASANORI OKAMOTO; TAMOTSU SOMA; ISAO YOKOTA; RYUTA ARAI; TOMOHIRO ONODERA; EIJI KONDO; NORIMASA IWASAKI; HIROAKI HIRAGA Abstract:Background/Aim: Although smoking history is predictive of poor pulmonary metastasis-free survival (PMFS) in patients with epithelial tumors, the impact of smoking history on PMFS in those with soft-tissue sarcoma (STS) is not known. Patients and Methods: Patients undergoing treatment for STS at our institutes between 2008 and 2017 were enrolled. Patients were excluded if they had metastatic lesion, or had a histopathological classification demonstrating small round-cell sarcoma. The impact of smoking history on PMFS and overall survival was examined with multivariate analysis using a Cox proportional hazards model. Results: A total of 250 patients were retrospectively reviewed. Patients with smoking history had worse PMFS on multivariate analysis (hazard ratio=2.00, 95% confidence interval=1.12-3.60). On the other hand, smoking history did not significantly affect overall survival (hazard ratio=1.26, 95% confidence interval=0.61-2.58). Conclusion: Patients with STS need to be followed-up by frequent clinical assessments if they have a smoking history.
Distal femoral impaction bone grafting in revision for tumor endoprosthesis. The Knee,29:42-48 2021(Mar.) Author:Munehisa Kito; Masanori Okamoto; Kaoru Aoki; Atsushi Tanaka; Yukiko Komatsu; Shuichiro Suzuki; Akira Takazawa; Yasuo Yoshimura; Jun Takahashi Abstract:BACKGROUND: Reconstruction using tumor endoprosthesis has been widely used in cases with large bone defects caused by bone and soft tissue tumor resection of the distal femur which extend into the knee joint. However, reconstruction failure can lead to major problems in the long term. We have been performing impaction bone grafting with allogeneic cancellous bone during revision surgery for tumor endoprosthesis of the distal femur to compensate for the thinness and fragility of the remaining femur. The aim of this study is to examine the surgical method, problems, and clinical outcomes of revision surgery with impaction bone grafting. METHODS: Three patients who underwent revision surgery for tumor endoprosthesis using impaction bone grafting at our institution with more than 2 years of follow-up were included. RESULTS: Union between the graft and host bone were achieved in all cases. The mean time to radiographic union was 1.0 year (0.6-1.5 years). Although intraoperative penetration to the anterior cortex of the distal femur occurred in 2 cases, there were no postoperative fractures. There were no failures of tumor endoprosthesis at final observation. CONCLUSION: Good short-term results were observed in 3 patients who underwent revision tumor endoprosthesis with impaction bone grafting following a bone and soft tissue tumor resection of the distal femur. The method was considered to be a useful treatment option. Impaction bone grafting is an established surgical option that can be applied to revision surgery for tumor endoprosthesis.
Isolated lymphatic vessel lumen perfusion system for assessing nanomaterial movements and nanomaterial-induced responses in lymphatic vessels NANO TODAY,36 2021(Feb.) Author:Chika Kuroda; Kumiko Ajima; Katsuya Ueda; Atsushi Sobajima; Kazushige Yoshida; Takayuki Kamanaka; Jun Sasaki; Haruka Ishida; Hisao Haniu; Masanori Okamoto; Kaoru Aoki; Hiroyuki Kato; Naoto Saito Abstract:Nanomaterials have recently been investigated extensively for a wide variety of biological applications, including drug delivery, bioimaging, and regenerative medicine. However, they have found little clinical use because of the lack of an established method for assessing their safety in living organisms. In particular, much remains unknown about the biokinetics of nanomaterials. Nanomaterials may be administered intravenously and reach various tissues via the bloodstream or injected directly into subcutaneous tissue or lesions such as tumors. These nanomaterials are known to enter lymphatic vessels, migrate to the lymph system, and accumulate in lymph nodes. To clarify their biokinetics, therefore, importance should be placed on elucidating their interactions with lymphatic vessels. However, little is known about their movements in, and influence on, the lymphatic vessels. In this study, we developed and assessed the isolated lymphatic vessel lumen perfusion system to allow us to visually and quantitatively elucidate the interactions between nanomaterials and lymphatic vessels, and thereby the biosafety of nanomaterials. The vessel is removed from a living rat and studied in vitro. This perfusion system, compared to in vivo examinations, allows higher-resolution, more detailed examination of the movement of nanomaterials and the lymphatic vessel's reaction to this movement. In addition, the new system also enables both quantitative and histological assessment of a single lymphatic vessel's physiological reaction to nanomaterials. Use of this system to provide essential information about nanomaterial biokinetics is expected to contribute significantly to the development of a wide variety of biological applications of nanomaterials. (C) 2020 Elsevier Ltd. All rights reserved.
Carbon fibers for treatment of cancer metastasis in bone. RSC advances,10(55):33071-33079 2020(Sep. 07) Author:Takayuki Kamanaka; Hisao Haniu; Manabu Tanaka; Takashi Takizawa; Kaoru Aoki; Masanori Okamoto; Atsushi Sobajima; Kazushige Yoshida; Hirokazu Ideta; Tetsuhiko Mimura; Haruka Ishida; Katsuya Ueda; Takeshi Uemura; Jin Hee Kim; Yoong Ahm Kim; Hiroyuki Kato; Naoto Saito Abstract:When cancer metastasizes to bone, the resulting pain and functional disorders due to bone destruction adversely affect the patient's quality of life. We have developed a new cancer metastasis control system consisting of anticancer agents conjugated to carbon fibers (CFs), which are nonbiodegradable, carriers of a wide variety of molecules with extremely high affinity for bone. In the evaluation of cancer suppression effects on Walker 256 cancer cells, cisplatin (CDDP)-conjugated CFs (CF-CDDP) were found to be as effective in cancer suppression as CDDP. In the evaluation of the cancer suppression effects of local injection in the rat model of tibial cancer bone metastasis, similar cancer suppression was noted in the CF-CDDP group and CDDP group; however, blood Pt concentrations were significantly lower in the CF-CDDP group. Experiments with CDDP and CF-CDDP injected into bone actually destroyed by cancer metastases revealed the presence of significantly more newly formed bone tissue with the administration of CF-CDDP. Local administration of CF-CDDP is expected to become the first therapy to suppress cancer growth with low prevalence of adverse reactions, and to repair bone damaged by metastasis.
Metastases of soft tissue sarcoma to the liver: A Historical Cohort Study from a Hospital-based Cancer Registry. Cancer medicine,9(17):6159-6165 2020(Sep.) Author:Masanori Okamoto; Masatake Matsuoka; Tamotsu Soma; Ryuta Arai; Hidenori Kato; Toru Harabayashi; Hirohumi Adachi; Toshiki Shinohara; Tamotsu Sagawa; Noriaki Nishiyama; Toshikazu Nambu; Wataru Sakai; Hiroaki Suzuki; Hiroyuki Kato; Hiroaki Hiraga Abstract:BACKGROUND: Hepatic metastasis of soft tissue sarcoma is rare compared to lung metastasis, and the literature is scarce. We examined the risk of hepatic metastasis according to the site of occurrence and histological type. METHODS: From a Hospital-based Cancer Registry, 658 patients registered between 2007 and 2017 with soft tissue sarcomas were evaluated. The exclusion criteria were gastrointestinal stromal tumors, tumors of unknown origin, and follow-up periods of less than 1 month. SPSS 25 was used for statistical analysis. RESULTS: The risk of hepatic metastasis was significantly higher in the retroperitoneum (HR, 5.981; 95% CI, 2.793-12.808) and leiomyosarcoma (HR, 4.303; 95% CI, 1.782-10.390). Multivariate analysis showed that the risk of hepatic metastasis as first distant metastasis was high in leiomyosarcoma (HR, 4.546; 95% CI, 2.275-9.086) and retroperitoneal onset (HR, 4.588; 95% CI, 2.280-9.231). The 2-year survival rate after hepatic metastasis was 21.7%. CONCLUSIONS: The onset of hepatic metastasis indicates a poor prognosis. However, hepatic metastasis from retroperitoneal sarcoma and leiomyosarcoma may be the first distant metastasis in some cases. For retroperitoneal sarcoma and leiomyosarcoma, additional screening for hepatic metastasis such as contrast CT should be considered during staging and follow-up after treatment.
A Review of T-Cell Related Therapy for Osteosarcoma INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,21(14):4877-4877 2020(Jul.) Author:Yoshida, Kazushige; Okamoto, Masanori; Aoki, Kaoru; Takahashi, Jun; Saito, Naoto Abstract:Osteosarcoma is one of the most common primary malignant tumors of bone. The combination of chemotherapy and surgery makes the prognosis better than before, but therapy has not dramatically improved over the last three decades. This is partially because of the lack of a novel specialized drug for osteosarcoma, which is known as a tumor with heterogeneity. On the other hand, immunotherapy has been one of the most widely used strategies for many cancers over the last ten years. The therapies related to T-cell response, such as immune checkpoint inhibitor and chimeric antigen receptor T-cell therapy, are well-known options for some cancers. In this review, we offer the accumulated knowledge of T-cell-related immunotherapy for osteosarcoma, and discuss the future of the therapy.
Applications of Carbon Nanotubes in Bone Regenerative Medicine NANOMATERIALS,10(4):- 2020(Apr.) Author:Tanaka, Manabu; Aoki, Kaoru; Haniu, Hisao; Kamanaka, Takayuki; Takizawa, Takashi; Sobajima, Atsushi; Yoshida, Kazushige; Okamoto, Masanori; Kato, Hiroyuki; Saito, Naoto Abstract:NANOMATERIALS
Continued growth of locally aggressive fibrous dysplasia of 22 years duration after reaching adulthood: a case report J Surg Case Rep. 2020 Feb 11;2020(2):rjz406.,2020(2) 2020(Feb. 11) Author:Yamagishi Y, Okamoto M, Yoshimura Y, Kito M, Aoki K, Takahashi J Abstract:J Surg Case Rep. 2020 Feb 11;2020(2):rjz406.
The Regulation of Bone Metabolism and Disorders by Wnt Signaling INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,20(22):- 2019(Nov.) Author:Maeda, Kazuhiro; Kobayashi, Yasuhiro; Koide, Masanori; Uehara, Shunsuke; Okamoto, Masanori; Ishihara, Akihiro; Kayama, Tomohiro; Saito, Mitsuru; Marumo, Keishi Abstract:INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Risk factor for wound complications following wide resection of soft tissue sarcoma in the adductor compartment of the thigh. Japanese journal of clinical oncology,49(10):932-937 2019(Oct. 01) Author:Munehisa Kito; Keisuke Ae; Hirotaka Koyanagi; Tabu Gokita; Hideto Furuoka; Masanori Okamoto; Atsushi Tanaka; Shuichiro Suzuki; Akira Takazawa; Kaoru Aoki; Yasuo Yoshimura Abstract:BACKGROUND: The purpose of this study was to investigate deep-seated soft tissue sarcoma (STS) occurring in the adductor compartment of the thigh that underwent wide resection and to clarify the high-risk group for wound complications. PATIENTS AND METHODS: From 2000 to 2017, we reviewed 104 cases of deep-seated STS occurring in the adductor compartment of the thigh that were treated at four specialized facilities with expertise in sarcoma treatment. RESULTS: Wound complications occurred in 40 cases (38.5%), of which 23 cases (22.1%) were cases with major wound complications (MWC). In univariate analysis, BMI (P < 0.01), maximum tumor diameter (P < 0.01), operation time (P < 0.01), amount of intraoperative bleeding (P < 0.01), and intraoperative intervention to the femoral artery and vein (P < 0.01) were significantly associated with wound complications. In multivariate analysis, the associated parameters were BMI (P < 0.01), maximum tumor diameter (P = 0.02), and intraoperative intervention to the femoral artery and vein (P = 0.01). When limited to cases with MWC, univariate analysis showed that maximum tumor diameter (P < 0.01), diabetes mellitus (P = 0.03), operation time (P < 0.01), amount of intraoperative bleeding (P < 0.01), and intraoperative intervention to the femoral artery and vein (P = 0.02) were significantly associated parameters. In multivariate analysis, maximum tumor diameter (P = 0.02) and amount of intraoperative bleeding (P = 0.04) were associated parameters. CONCLUSIONS: For patients with risk factors for wound complications, control of bleeding are crucial when resecting deep-seated STS in the adductor compartment of the thigh. In cases with large tumors, surgeons should be especially cautious of cases requiring interventions that surround the femoral artery and vein in order to attain an appropriate surgical margin.
Organ accumulation and carcinogenicity of highly dispersed multi-walled carbon nanotubes administered intravenously in transgenic rasH2 mice International Journal of Nanomedicine,14:6465-6480 2019(Aug.) Author:Sobajima A, Haniu H, Nomura H, Tanaka M, Takizawa T, Kamanaka T, Aoki K, Okamoto M, Yoshida K, Sasaki J, Ajima K, Kuroda C, Ishida H, Okano S, Ueda K, Kato H, Saito N Abstract:International Journal of Nanomedicine
Combined treatment using Mohs' paste and neoadjuvant chemotherapy for giant gluteal soft tissue sarcoma with malignant fungating wound: a case report. Journal of Surgical Case Reports,2019(5):rjz137 2019(May 09) Author:Nemoto K, Okamoto M, Kito M, Aoki K, Suzuki S, Takazawa A, Yoshimura Y, Kato H. Abstract:Journal of Surgical Case Reports
Clinical outcome of osteosarcoma and its correlation with programmed death-ligand 1 and T cell activation markers ONCOTARGETS AND THERAPY,12:2513-2518 2019(Apr.) Author:Yoshida, Kazushige; Okamoto, Masanori; Sasaki, Jun; Kuroda, Chika; Ishida, Haruka; Ueda, Katsuya; Okano, Satomi; Ideta, Hirokazu; Kamanaka, Takayuki; Sobajima, Atsushi; Takizawa, Takashi; Kito, Munehisa; Aoki, Kaoru; Uemura, Takeshi; Haniu, Hisao; Kato, Hiroyuki; Saito, Naoto Abstract:ONCOTARGETS AND THERAPY
Using the Barthel Index to Assess Activities of Daily Living after Musculoskeletal Tumour Surgery: A Single-centre Observational Study. Progress in rehabilitation medicine,4:20190010-20190010 2019(Mar. 26) Author:Masanori Okamoto; Munehisa Kito; Yasuo Yoshimura; Kaoru Aoki; Shuichiro Suzuki; Atsushi Tanaka; Akira Takazawa; Kazushige Yoshida; Yoshikazu Ido; Takaaki Ishida; Keiko Kawasaki; Hiroyuki Kato Abstract:OBJECTIVE: The objective of the current study was to find the factors affecting the activities of daily living, as evaluated by the Barthel Index, at the end of rehabilitation after musculoskeletal tumour surgery. Further, we evaluated whether the Barthel Index correlates with functional scores that are specific to musculoskeletal tumours at final follow-up. METHODS: The activities of daily living of 190 patients who underwent postoperative rehabilitation after surgery to treat musculoskeletal tumours were evaluated at the end of the program using the Barthel Index. Functional evaluation at the time of final follow-up observation was evaluated using the Musculoskeletal Tumour Society Score and the Toronto Extremity Salvage Score. RESULTS: The post-rehabilitation Barthel Index was significantly lower in elderly patients aged more than 60 years and in those with malignant tumours and tumours larger than 10 cm. Malignancy and large tumour size were risk factors for a low Barthel Index. There was significant correlation between the Musculoskeletal Tumour Society Score/Toronto Extremity Salvage Score at final functional evaluation and the Barthel Index at the end of rehabilitation. CONCLUSION: The Barthel Index is a simple method to assess the activities of daily living and can potentially predict disease-specific health-related quality of life at final functional evaluation after musculoskeletal tumour surgery.
The status quo of treatment and clinical outcomes for patients over 80 years of age with high-grade soft tissue sarcoma: report from the soft tissue tumor registry in Japan Japanese Journal of Clinical Oncology,48(10):900-905 2018(Oct. 01) Author:Masanori Okamoto Abstract:Japanese Journal of Clinical Oncology
Different aggregation and shape characteristics of carbon materials affect biological responses in RAW264 cells International Journal of Nanomedicine,13:6079-6088 2018(Oct.) Author:Chika Kuroda, Katsuya Ueda, Hisao Haniu, Haruka Ishida, Satomi Okano, Takashi Takizawa, Atsushi Sobajima, Takayuki Kamanaka, Kazushige Yoshida, Masanori Okamoto, Tamotsu Tsukahara, Yoshikazu Matsuda, Kaoru Aoki, Hiroyuki Kato, Naoto Saito Abstract:International Journal of Nanomedicine
Titanium Fiber Plates for Bone Tissue Repair Advanced Materials,30(4):- 2018(Jan. 25) Author:Takashi Takizawa; Noboru Nakayama; Hisao Haniu; Kaoru Aoki; Masanori Okamoto; Hiroki Nomura; Manabu Tanaka; Atsushi Sobajima; Kazushige Yoshida; Takayuki Kamanaka; Kumiko Ajima; Ayumu Oishi; Chika Kuroda; Haruka Ishida; Satomi Okano; Shinsuke Kobayashi; Hiroyuki Kato; Naoto Saito Abstract:Titanium plates are widely used in clinical settings because of their high bone affinity. However, owing to their high elastic modulus, these plates are not suitable for bone repair since their proximity to the bone surface for prolonged periods can cause stress shielding, leading to bone embrittlement. In contrast, titanium fiber plates prepared by molding titanium fibers into plates by simultaneously applying compression and shear stress at normal room temperature can have an elastic modulus similar to that of bone cortex, and stress shielding will not occur even when the plate lies flush against the bone's surface. Titanium fibers can form a porous structure suitable for cell adhesion and as a bone repair scaffold. A titanium fiber plate is combined with osteoblasts and shown that the titanium fiber plate is better able to facilitate bone tissue repair than the conventional titanium plate when implanted in rat bone defects. Capable of being used in close contact with bone for a long time, and even capable of promoting bone repair, titanium fiber plates have a wide range of applications, and are expected to make great contributions to clinical management of increasing bone diseases, including bone fracture repair and bone regenerative medicine.
Successful treatment of adult pleomorphic rhabdomyosarcoma with bone invasion in the lower leg by chemotherapy and biological reconstruction: A case report Journal of Orthopaedic Science,24(5):930-935 2018 Author:Atsushi Tanaka; Yasuo Yoshimura; Takashige Momose; Ken'ichi Isobe; Kaoru Aoki; Munehisa Kito; Masanori Okamoto; Shuichiro Suzuki; Kenji Sano; Hiroyuki Kato Abstract:JOURNAL OF ORTHOPAEDIC SCIENCE
Massive trapezial metastasis from gastric adenocarcinoma resected and reconstructed with a vascularized scapular bone graft: A case report Medicine (United States),96(50):- 2017(Dec. 01) Author:Masanori Okamoto; Hiroshi Yamazaki; Yasuo Yoshimura; Kaoru Aoki; Atsushi Tanaka; Hiroyuki Kato Abstract:Rationale:Isolated metastasis to the hand bones is very rare. Only seven cases of metastasis to the trapezium have been reported. To the best of our knowledge, this is the first report of a single metastasis to the trapezium from a gastric adenocarcinoma.Patient concerns:A 62-year-old man presented with pain and massive swelling in the right carpometacarpal joint of the thumb.Diagnoses:The patient was diagnosed with trapezial metastasis of advanced gastric adenocarcinoma.Interventions:The patient underwent systemic chemotherapy with cisplatin and S-1, radiotherapy to the metastatic bone, and treatment with denosumab. One year later, the huge metastatic tumor was resected, and the hand was reconstructed using vascularized scapular bone.Outcomes:Eighteen months postoperatively, the patient was satisfied with the appearance of the reconstructed hand and was able to use his right thumb in activities of daily living.Lessons:Although rare, metastasis to the trapezium should be considered in patients with persistent and progressive thumb CMC joint pain.
Initial clinical presentation of single soft tissue metastasis of medullary thyroid carcinoma without primary tumor in the thyroid gland WORLD JOURNAL OF SURGICAL ONCOLOGY,15:- 2017(Dec.) Author:Masanori Okamoto; Akira Takazawa; Kaoru Aoki; Yasuo Yoshimura; Hiroyuki Kato; Toshiaki Otsuki; Kazuma Maeno; Tomonobu Koizumi Abstract:Background: Single soft tissue metastasis of medullary thyroid carcinoma is extremely rare. In addition, several occult medullary thyroid carcinomas with distant metastasis were reported, but undetectable primary lesion at diagnosis was also extremely rare.
Case presentation: A 74-year-old man was admitted to our hospital because of a painful nodule in his left buttock for over 1 year. Needle biopsy was performed, and the histological findings revealed adenocarcinoma positive for thyroid transcription factor-1. No evidence of a primary tumor, including the lung and thyroid gland, could be found elsewhere despite detailed examinations, including thyroid echography, chest computed tomography, and fluorodeoxyglucose-positron emission tomography. The soft tissue tumor was resected with a wide margin. Immunohistochemical analysis showed the tumor cells to be positive for cytokeratin-AE1/3, cytokeratin 7, synaptophysin, chromogranin A, calcitonin, and carcinoembryonic antigen, but negative for cytokeratin 20, Napsin A, Pax8, and p40, resulting in a diagnosis of metastasis of medullary thyroid carcinoma.
Conclusion: Initial presentation with a single metastasis to soft tissue and undetectable primary tumor in the thyroid gland is an extremely rare clinical manifestation in patients with medullary thyroid carcinoma.
Prediction of muscle strength and postoperative function after knee flexor muscle resection for soft tissue sarcoma of the lower limbs Orthopaedics & Traumatology: Surgery & Research,103(7) 2017(Nov.) Author:Masanori Okamoto
Clinical outcomes of patients 80 years of age and older with soft tissue sarcoma JOURNAL OF ORTHOPAEDIC SCIENCE,22(5):951-957 2017(Sep.) Author:Masanori Okamoto; Yasuo Yoshimura; Kaoru Aoki; Munehisa Kito; Atsushi Tanaka; Shuichiro Suzuki; Akira Takazawa; Ken'ichi Isobe; Hiroyuki Kato Abstract:Objectives: Although soft tissue sarcoma (STS) is rare, its incidence is increasing among older patients. Few studies have compared the outcomes between conservative and surgical treatments for STS patients aged >= 80 years. We assessed the outcomes of both treatments in this population and the association between older age and surgical outcome.
Methods: We recruited consecutive patients with STS aged >= 80 years treated at our institution between January 2006 and May 2014. We recommended surgical resection for all patients without multiple distant metastases. Overall survival and sarcoma-specific survival were assessed using the Kaplan-Meier method.
Results: Of the 39 patients with STS who presented at our institution, 37 were included in this analysis (19 men and 18 women with a median age of 85 [range 80-94] years). Tumors were classified as Stage IB (n = 3), IIA (n = 6), IIB (n = 3) or III (n = 24). Four patients underwent conservative therapy and 33 underwent surgical resection. The most common tumor site was the lower extremity, and the majority of tumors were classified as undifferentiated pleomorphic sarcoma. The follow-up rate was 100%. One-year sarcoma-specific survival rates were 25.0% in the conservative therapy group and 90.9% in the surgical resection group. No associations were found between age >= 85 years and perioperative complications or clinical outcome.
Conclusions: Surgical resection had relatively few complications, given the age group, and improved the prognosis of older patients with STS. Surgical resection of STS with curative intent should be considered in older patients. (C) 2017 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.
In Vitro and In Vivo Evaluation of a Three-Dimensional Porous Multi-Walled Carbon Nanotube Scaffold for Bone Regeneration NANOMATERIALS,7(2):- 2017(Feb.) Author:Manabu Tanaka; Yoshinori Sato; Mei Zhang; Hisao Haniu; Masanori Okamoto; Kaoru Aoki; Takashi Takizawa; Kazushige Yoshida; Atsushi Sobajima; Takayuki Kamanaka; Hiroyuki Kato; Naoto Saito Abstract:Carbon nanotubes (CNTs) have attracted a great deal of attention for the biological and medical science fields because of their characteristic physical and biological properties. In this study, we investigated the capacity of the 3D porous CNT scaffold (CNT porous block; CNTp) for bone regenerative medicine. Surface observations using a scanning electron microscope (SEM), crystal depositions on the surface of CNTps immersed in simulated body fluid (SBF), and evaluations of protein adsorption and controlled releasing were conducted to assess physical properties. The cell proliferation and cell morphology were observed using SEM and fluorescent microscopy. CNTps were implanted into critical-size mouse calvarial defects and evaluated for their osteoconductive ability and in vivo controlled release of recombinant human BMP-2 (rhBMP-2). Interconnected porous HA ceramics (IP-CHAs) were used for comparison. CNTps have multiporous structures with interporous connections with networks of multiwalled CNTs. Crystals containing calcium and phosphate were deposited in CNTps and on the surface of the CNT networks by immersing CNTps in SBF. CNTps adsorbed more significantly and released protein more gradually than IP-CHAs. Preosteoblasts seeded onto CNTps filled pores with stretched actin filaments and filopodia. Compared with IP-CHAs, CNTps showed significantly higher cell proliferation, better osteoconduction, and more bone generation with rhBMP-2. In this study, CNTps demonstrated good osteoconductive ability, cell attachment and proliferation capacity, and growth factor retaining ability. CNTps have the potential not only as artificial bones for the treatment of bone defects, but also as scaffolds for regenerative medicine using tissue engineering approaches.
A three-dimensional block structure consisting exclusively of carbon nanotubes serving as bone regeneration scaffold and as bone defect filler PLOS ONE,12(2):- 2017(Feb.) Author:Manabu Tanaka; Yoshinori Sato; Hisao Haniu; Hiroki Nomura; Shinsuke Kobayashi; Seiji Takanashi; Masanori Okamoto; Takashi Takizawa; Kaoru Aoki; Yuki Usui; Ayumu Oishi; Hiroyuki Kato; Naoto Saito Abstract:Many recent studies have been conducted to assess the ability of composite materials containing carbon nanotubes (CNTs) with high bone affinity to serve as scaffolds in bone regenerative medicine. These studies have demonstrated that CNTs can effectively induce bone formation. However, no studies have investigated the usefulness of scaffolds consisting exclusively of CNTs in bone regenerative medicine. We built a three-dimensional block entity with maximized mechanical strength from multi-walled CNTs (MWCNT blocks) and evaluated their efficacy as scaffold material for bone repair. When MWCNT blocks containing recombinant human bone morphogenetic protein-2 (rhBMP-2) were implanted in mouse muscle, ectopic bone was formed in direct contact with the blocks. Their bone marrow densities were comparable to those of PET-reinforced collagen sheets with rhBMP-2. On day 1 and day 3, MC3T3-E1 preosteoblasts were attached to the scaffold surface of MWCNT blocks than that of PET-reinforced collagen sheets. They also showed a maximum compression strength comparable to that of cortical bone. Our MWCNT blocks are expected to serve as bone defect filler and scaffold material for bone regeneration.
Physico-Chemical, In Vitro, and In Vivo Evaluation of a 3D Unidirectional Porous Hydroxyapatite Scaffold for Bone Regeneration MATERIALS,10(1):- 2017(Jan.) Author:Manabu Tanaka; Hisao Haniu; Takayuki Kamanaka; Takashi Takizawa; Atsushi Sobajima; Kazushige Yoshida; Kaoru Aoki; Masanori Okamoto; Hiroyuki Kato; Naoto Saito Abstract:The unidirectional porous hydroxyapatite HAp (UDPHAp) is a scaffold with continuous communicated pore structure in the axial direction. We evaluated and compared the ability of the UDPHAp as a three-dimensional (3D) bone tissue engineering scaffold to the interconnected calcium porous HAp ceramic (IP-CHA). To achieve this, we evaluated in vitro the compressive strength, controlled rhBMP-2 release behavior, adherent cell morphology, cell adhesion manner, and cell attachment of UDPHAp. As a further in vivo experiment, UDPHAp and IP-CHA with rhBMP-2 were transplanted into mouse calvarial defects to evaluate their bone-forming ability. The Results demonstrated that the maximum compressive strengths of the UDPHAp was 7.89 +/- 1.23 MPa and higher than that of IP-CHA (1.92 +/- 0.53 MPa) (p = 0.0039). However, the breaking energies were similar (8.99 +/- 2.72 vs. 13.95 +/- 5.69 mJ, p = 0.055). The UDPHAp released rhBMP-2 more gradually in vivo. Cells on the UDPHAp adhered tightly to the surface, which had grown deeply into the scaffolds. A significant increase in cell number on the UDPHAp was observed compared to the IP-CHA on day 8 (102,479 +/- 34,391 vs. 32,372 +/- 29,061 estimated cells per scaffold, p = 0.0495). In a mouse calvarial defect model, the percentages of new bone area (mature bone + trabecular bone) in the 2x field were 2.514% +/- 1.224% for the IP-CHA group and 7.045% +/- 2.055% for the UDPHAp group, and the percentage was significantly higher in the UDPHAp group (p = 0.0209). While maintaining the same strength as the IP-CHA, the UDPHAp with 84% porosity showed a high cell number, high cell invasiveness, and excellent bone formation. We believe the UDPHAp is an excellent material that can be applied to bone regenerative medicine.
Clinical outcome of dedifferentiated liposarcoma in the extremities: A retrospective case series of 7 patients JOURNAL OF ORTHOPAEDIC SCIENCE,21(5):673-677 2016(Sep.) Author:Munehisa Kito; Yasuo Yoshimura; Ken'ichi Isobe; Kaoru Aoki; Shuichiro Suzuki; Atsushi Tanaka; Masanori Okamoto; Kenji Sano; Hiroyuki Kato Abstract:Background: Wide resection is the generally recommended surgical treatment for dedifferentiated liposarcoma (DDLPS) in the extremities. However, it may be appropriate to distinguish the surgical margin of low-grade atypical lipomatous tumor (ALT)/well-differentiated liposarcoma (WDLPS) area from the high-grade dedifferentiated area, because the low-and high-grade areas can be clearly separated, both radiologically and histologically. This study re-evaluated the details of surgical margin of DDLPS in the extremities, and aimed to investigate the optimal surgical margin and the usefulness of adjuvant therapy for DDLPS in the extremities.
Methods: Seven patients diagnosed with DDLPS in the extremities and treated between 1995 and 2013 were analyzed. The use of adjuvant therapy before and after surgery was assessed, and the surgical margins for the ALT/WDLPS and dedifferentiated areas were re-evaluated by using the specimens resected at surgery. Subsequently, the recurrence rates, metastatic rates, and oncological outcomes were examined.
Results: Four and three patients had wide (adequate wide margin, n = 3; inadequate wide margin, n = 1) and marginal margins for the dedifferentiated area, respectively, while three and four patients had wide (adequate wide margin, n = 2; inadequate wide margin, n = 1) and marginal margins for the ALT/WDLPS area, respectively. Postoperative radiotherapy was performed in three patients with an inadequate wide margin or a marginal margin for the dedifferentiated area. No patient had local recurrence. Distant metastases occurred in two patients. These patients died of their disease. The other five patients were disease-free.
Conclusion: The ALT/WDLPS and dedifferentiated areas in the tumor margin may be better to be considered separately in determining the appropriate resection extent for DDLPS in the extremities. Postoperative radiotherapy may provide good local control for cases with a narrow surgical margin. (C) 2016 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.
Knee extension strength and post-operative functional prediction in quadriceps resection for soft-tissue sarcoma of the thigh Bone and Joint Research,5(6) 2016 Author:Tanaka, A.; Yoshimura, Y.; Aoki, K.; Kito, M.; Okamoto, M.; Suzuki, S.; Momose, T.; Kato, H.
Specific biological responses of the synovial membrane to carbon nanotubes SCIENTIFIC REPORTS,5:- 2015(Sep.) Author:Hiroki Nomura; Seiji Takanashi; Manabu Tanaka; Hisao Haniu; Kaoru Aoki; Masanori Okamoto; Shinsuke Kobayashi; Takashi Takizawa; Yuki Usui; Ayumu Oishi; Hiroyuki Kato; Naoto Saito Abstract:Biological evaluation of carbon nanotubes (CNTs) is typically performed in the lung or abdominal cavity; however, biological reactions to CNTs are predicted to be markedly different in other tissues. In applications of CNTs as reinforcement for artificial joints and drug delivery systems, including their use in bone regeneration, the intra-articular synovial membrane makes contact with the CNTs. Herein, we analyzed the reaction of the synovial membrane with multiwalled CNTs (MWCNTs). Injection of MWCNTs into rat knee joints revealed their dose-dependent incorporation into deep synovial membranes and the formation of granulation tissue, without long-term inflammation. MWCNTs were incorporated into human fibroblast-like synoviocytes (HFLSs), with less cytotoxicity than that observed in macrophages (RAW264 cells). Moreover, MWCNTs inhibited the release of cytokines and chemokines from HFLSs. The reaction of the synovial membrane with MWCNTs differed from that observed in other tissues; thus, detailed biological evaluation at each target site is necessary for clinical applications.
An advanced in situ imaging method using heavy metal-doped hollow tubes to evaluate the biokinetics of carbon nanotubes in vivo NPG ASIA MATERIALS,7(7):- 2015(Jul.) Author:Shinsuke Kobayashi; Shuji Tsuruoka; Yuki Usui; Hisao Haniu; Kaoru Aoki; Seiji Takanashi; Masanori Okamoto; Hiroki Nomura; Manabu Tanaka; Shigetoshi Aiso; Misae Saito; Hiroyuki Kato; Naoto Saito Abstract:The biosafety of carbon nanotubes (CNTs) is a concern, and CNT biokinetics is a key biosafety issue. CNTs labeled with carbon isotopes, functionalized with moieties, or coated with colloidal metal particles have been used to monitor CNT biokinetics, though major technical issues (such as isotope preparation and handling or change in CNT surface properties) remain. The present report aims at establishing an advanced and simple in situ imaging method of CNTs monitoring in vivo involving the use of CNTs filled with heavy metal particles (peapods). Gadolinium (Gd)-peapods containing GdCl3 were synthesized using double-walled CNTs. The limits of Gd-peapods detection on magnetic resonance imaging (MRI) in solutions and agarose gel cubes were 1.3 mu g ml(-1) and 4 mu g ml(-1), respectively. The peapods in rats was easily visualized by MRI and the change in signal intensity was dose dependent. This newly developed method can be used to monitor CNT biokinetics in vivo without tedious tissue preparation.
Endocytosis of Multiwalled Carbon Nanotubes in Bronchial Epithelial and Mesothelial Cells BIOMED RESEARCH INTERNATIONAL,2015:- 2015 Author:Kayo Maruyama; Hisao Haniu; Naoto Saito; Yoshikazu Matsuda; Tamotsu Tsukahara; Shinsuke Kobayashi; Manabu Tanaka; Kaoru Aoki; Seiji Takanashi; Masanori Okamoto; Hiroyuki Kato Abstract:Bronchial epithelial cells and mesothelial cells are crucial targets for the safety assessment of inhalation of carbon nanotubes (CNTs), which resemble asbestos particles in shape. Intrinsic properties of multiwalled CNTs (MWCNTs) are known to cause potentially hazardous effects on intracellular and extracellular pathways. These interactions alter cellular signaling and affect major cell functions, resulting in cell death, lysosome injury, reactive oxygen species production, apoptosis, and cytokine release. Furthermore, CNTs are emerging as a novel class of autophagy inducers. Thus, in this study, we focused on the mechanisms of MWCNT uptake into the human bronchial epithelial cells (HBECs) and human mesothelial cells (HMCs). We verified that MWCNTs are actively internalized into HBECs and HMCs and were accumulated in the lysosomes of the cells after 24-hour treatment. Next, we determined which endocytosis pathways (clathrin-mediated, caveolae-mediated, and macropinocytosis) were associated with MWCNT internalization by using corresponding endocytosis inhibitors, in two nonphagocytic cell lines derived from bronchial epithelial cells and mesothelioma cells. Clathrin-mediated endocytosis inhibitors significantly suppressed MWCNT uptake, whereas caveolae-mediated endocytosis and macropinocytosis were also found to be involved in MWCNT uptake. Thus, MWCNTs were positively taken up by nonphagocytic cells, and their cytotoxicity was closely related to these three endocytosis pathways.
Noncanonical Wnt5a enhances Wnt/beta-catenin signaling during osteoblastogenesis SCIENTIFIC REPORTS,4:- 2014(Mar.) Author:Masanori Okamoto; Nobuyuki Udagawa; Shunsuke Uehara; Kazuhiro Maeda; Teruhito Yamashita; Yuko Nakamichi; Hiroyuki Kato; Naoto Saito; Yasuhiro Minami; Naoyuki Takahashi; Yasuhiro Kobayashi Abstract:Wnt regulates bone formation through beta-catenin-dependent canonical and -independent noncanonical signaling pathways. However, the cooperation that exists between the two signaling pathways during osteoblastogenesis remains to be elucidated. Here, we showed that the lack of Wnt5a in osteoblast-lineage cells impaired Wnt/beta-catenin signaling due to the reduced expression of Lrp5 and Lrp6. Pretreatment of ST2 cells, a stromal cell line, with Wnt5a enhanced canonical Wnt ligand-induced Tcf/Lef transcription activity. Short hairpin RNA-mediated knockdown of Wnt5a, but not treatment with Dkk1, an antagonist of Wnt/beta-catenin signaling, reduced the expression of Lrp5 and Lrp6 in osteoblast-lineage cells under osteogenic culture conditions. Osteoblast-lineage cells from Wnt5a-deficient mice exhibited reduced Wnt/beta-catenin signaling, which impaired osteoblast differentiation and enhanced adipocyte differentiation. Adenovirus-mediated gene transfer of Lrp5 into Wnt5a-deficient osteoblast-lineage cells rescued their phenotypic features. Therefore, Wnt5a-induced noncanonical signaling cooperates with Wnt/beta-catenin signaling to achieve proper bone formation.
Biological responses according to the shape and size of carbon nanotubes in BEAS-2B and MESO-1 cells INTERNATIONAL JOURNAL OF NANOMEDICINE,9(1):1979-1990 2014 Author:Hisao Haniu; Naoto Saito; Yoshikazu Matsuda; Tamotsu Tsukahara; Yuki Usui; Kayo Maruyama; Seiji Takanashi; Kaoru Aoki; Shinsuke Kobayashi; Hiroki Nomura; Manabu Tanaka; Masanori Okamoto; Hiroyuki Kato Abstract:This study aimed to investigate the influence of the shape and size of multi-walled carbon nanotubes (MWCNTs) and cup-stacked carbon nanotubes (CSCNTs) on biological responses in vitro. Three types of MWCNTs - VGCF (R)-X, VGCF (R)-S, and VGCF (R) (vapor grown carbon fibers; with diameters of 15, 80, and 150 nm, respectively) - and three CSCNTs of different lengths (CS-L, 20-80 mu m; CS-S, 0.5-20 mu m; and CS-M, of intermediate length) were tested. Human bronchial epithelial (BEAS-2B) and malignant pleural mesothelioma cells were exposed to the CNTs (1-50 mu g/mL), and cell viability, permeability, uptake, total reactive oxygen species/superoxide production, and intracellular acidity were measured. CSCNTs were less toxic than MWCNTs in both cell types over a 24-hour exposure period. The cytotoxicity of endocytosed MWCNTs varied according to cell type/size, while that of CSCNTs depended on tube length irrespective of cell type. CNT diameter and length influenced cell aggregation and injury extent. Intracellular acidity increased independently of lysosomal activity along with the number of vacuoles in BEAS-2B cells exposed for 24 hours to either CNT (concentration, 10 mu g/mL). However, total reactive oxygen species/superoxide generation did not contribute to cytotoxicity. The results demonstrate that CSCNTs could be suitable for biological applications and that CNT shape and size can have differential effects depending on cell type, which can be exploited in the development of highly specialized, biocompatible CNTs.
Carcinogenicity evaluation for the application of carbon nanotubes as biomaterials in rasH2 mice SCIENTIFIC REPORTS,2:- 2012(Jul.) Author:Seiji Takanashi; Kazuo Hara; Kaoru Aoki; Yuki Usui; Masayuki Shimizu; Hisao Haniu; Nobuhide Ogihara; Norio Ishigaki; Koichi Nakamura; Masanori Okamoto; Shinsuke Kobayashi; Hiroyuki Kato; Kenji Sano; Naoyuki Nishimura; Hideki Tsutsumi; Kazuhiko Machida; Naoto Saito Abstract:The application of carbon nanotubes (CNTs) as biomaterials is of wide interest, and studies examining their application in medicine have had considerable significance. Biological safety is the most important factor when considering the clinical application of CNTs as biomaterials, and various toxicity evaluations are required. Among these evaluations, carcinogenicity should be examined with the highest priority; however, no report using transgenic mice to evaluate the carcinogenicity of CNTs has been published to date. Here, we performed a carcinogenicity test by implanting multi-walled CNTs (MWCNTs) into the subcutaneous tissue of rasH2 mice, using the carbon black present in black tattoo ink as a reference material for safety. The rasH2 mice did not develop neoplasms after being injected with MWCNTs; instead, MWCNTs showed lower carcinogenicity than carbon black. Such evaluations should facilitate the clinical application and development of CNTs for use in important medical fields.
Biocompatibility and bone tissue compatibility of alumina ceramics reinforced with carbon nanotubes NANOMEDICINE,7(7):981-993 2012(Jul.) Author:Nobuhide Ogihara; Yuki Usui; Kaoru Aoki; Masayuki Shimizu; Nobuyo Narita; Kazuo Hara; Koichi Nakamura; Norio Ishigaki; Seiji Takanashi; Masanori Okamoto; Hiroyuki Kato; Hisao Haniu; Naoko Ogiwara; Noboru Nakayama; Seiichi Taruta; Naoto Saito Abstract:The addition of carbon nanotubes (CNTs) remarkably improves the mechanical characteristics of base materials. CNT/alumina ceramic composites are expected to be highly functional biomaterials useful in a variety of medical fields. Biocompatibility and bone tissue compatibility were studied for the application of CNT/alumina composites as biomaterials. Methods & results: Inflammation reactions in response to the composite were as mild as those of alumina ceramic alone in a subcutaneous implantation study. In bone implantation testing, the composite showed good bone tissue compatibility and connected directly to new bone. An in vitro cell attachment test was performed for osteoblasts, chondrocytes, fibroblasts and smooth muscle cells, and CNT/alumina composite showed cell attachment similar to that of alumina ceramic. Discussion & conclusion: Owing to proven good biocompatibility and bone tissue compatibility, the application of CNT/alumina composites as biomaterials that contact bone, such as prostheses in arthroplasty and devices for bone repair, are expected.
Basic Potential of Carbon Nanotubes in Tissue Engineering Applications JOURNAL OF NANOMATERIALS,2012:--10 2012 Author:Hisao Haniu; Naoto Saito; Yoshikazu Matsuda; Tamotsu Tsukahara; Yuki Usui; Nobuyo Narita; Kazuo Hara; Kaoru Aoki; Masayuki Shimizu; Nobuhide Ogihara; Seiji Takanashi; Masanori Okamoto; Shinsuke Kobayashi; Norio Ishigaki; Koichi Nakamura; Hiroyuki Kato Abstract:Carbon nanotubes (CNTs) are attracting interest in various fields of science because they possess a high surface area-to-volume ratio and excellent electronic, mechanical, and thermal properties. Various medical applications of CNTs are expected, and the properties of CNTs have been greatly improved for use in biomaterials. However, the safety of CNTs remains unclear, which impedes their medical application. Our group is evaluating the biological responses of multiwall CNTs (MWCNTs) in vivo and in vitro for the promotion of tissue regeneration as safe scaffold materials. We recently showed that intracellular accumulation is important for the cytotoxicity of CNTs, and we reported the active physiological functions CNTs in cells. In this review, we describe the effects of CNTs in vivo and in vitro observed by our group from the standpoint of tissue engineering, and we introduce the findings of other research groups.
Carcinogenicity evaluation for the application of carbon nanotubes as biomaterials in rasH2 mice Scientific Reports,2:498 2012 Author:Seiji Takanashi; Kazuo Hara; Kaoru Aoki; Yuki Usui; Masayuki Shimizu; Hisao Haniu; Nobuhide Ogihara; Norio Ishigaki; Koichi Nakamura; Masanori Okamoto; Shinsuke Kobayashi; Hiroyuki Kato; Kenji Sano; Naoyuki Nishimura; Hideki Tsutsumi; Kazuhiko MacHida; Naoto Saito Abstract:The application of carbon nanotubes (CNTs) as biomaterials is of wide interest, and studies examining their application in medicine have had considerable significance. Biological safety is the most important factor when considering the clinical application of CNTs as biomaterials, and various toxicity evaluations are required. Among these evaluations, carcinogenicity should be examined with the highest priority
however, no report using transgenic mice to evaluate the carcinogenicity of CNTs has been published to date. Here, we performed a carcinogenicity test by implanting multi-walled CNTs (MWCNTs) into the subcutaneous tissue of rasH2 mice, using the carbon black present in black tattoo ink as a reference material for safety. The rasH2 mice did not develop neoplasms after being injected with MWCNTs
instead, MWCNTs showed lower carcinogenicity than carbon black. Such evaluations should facilitate the clinical application and development of CNTs for use in important medical fields.
Toxicoproteomic evaluation of carbon nanomaterials in vitro JOURNAL OF PROTEOMICS,74(12):2703-2712 2011(Nov.) Author:Hisao Haniu; Yoshikazu Matsuda; Yuki Usui; Kaoru Aoki; Masayuki Shimizu; Nobuhide Ogihara; Kazuo Hara; Masanori Okamoto; Seiji Takanashi; Norio Ishigaki; Koichi Nakamura; Hiroyuki Kato; Naoto Saito Abstract:Carbon nanotubes (CNTs) have already been successfully implemented in various fields, and they are anticipated to have innovative applications in medical science. However, CNTs have asbestos-like properties, such as their nanoscale size and high aspect ratio (>100). Moreover, CNTs may persist in the body for a long time. These properties are thought to cause malignant mesothelioma and lung cancer. However, based on conventional toxicity assessment systems, the carcinogenicity of asbestos and CNTs is unclear. The reason for late countermeasures against asbestos is that reliable, long-term safety assessments have not yet been developed by toxicologists. Therefore, a new type of long-term safety assessment, different from the existing methods, is needed for carbon nanomaterials. Recently, we applied a proteomic approach to the safety assessment of carbon nanomaterials. In this review, we discuss the basic concept of our approach, the results, the problems, and the possibility of a long-term safety assessment for carbon nanomaterials using the tmdcoproteomic approach. (C) 2011 Elsevier B.V. All rights reserved.
DJ-1 as a potential biomarker for the development of biocompatible multiwalled carbon nanotubes INTERNATIONAL JOURNAL OF NANOMEDICINE,6:2689-2695 2011 Author:Hisao Haniu; Tamotsu Tsukahara; Yoshikazu Matsuda; Yuki Usui; Kaoru Aoki; Masayuki Shimizu; Nobuhide Ogihara; Kazuo Hara; Seiji Takanashi; Masanori Okamoto; Norio Ishigaki; Koichi Nakamura; Hiroyuki Kato; Naoto Saito Abstract:Background: In the present study, we investigated whether DJ-1 could serve as a biomarker for assessing the biocompatibility of multiwalled carbon nanotubes (MWCNTs), using the highly purified carbon nanotube, HTT2800.
Methods: Using Western blot analysis, we determined DJ-1 protein levels in two different types of cells (one capable and the other incapable of HTT2800 endocytosis). Using quantitative real-time polymerase chain reaction, we also investigated the ability of purified nanotubes to alter DJ-1 mRNA levels.
Results: We demonstrated that the DJ-1 protein concentration was reduced, regardless of the cytotoxic activity of intracellular HTT2800. Furthermore, HTT2800 decreased the DJ-1 mRNA levels in a dose-dependent manner. This decrease in DJ-1 mRNA levels was not observed in the case of Sumi black or cup-stacked carbon nanotubes.
Conclusion: These data indicate that modification of DJ-1 expression is caused by the cell response to MWCNTs. We conclude that DJ-1 is a promising candidate biomarker for the development of biocompatible MWCNTs.
Effect of dispersants of multi-walled carbon nanotubes on cellular uptake and biological responses INTERNATIONAL JOURNAL OF NANOMEDICINE,6:3295-3307 2011 Author:Hisao Haniu; Naoto Saito; Yoshikazu Matsuda; Yoong-Ahm Kim; Ki Chul Park; Tamotsu Tsukahara; Yuki Usui; Kaoru Aoki; Masayuki Shimizu; Nobuhide Ogihara; Kazuo Hara; Seiji Takanashi; Masanori Okamoto; Norio Ishigaki; Koichi Nakamura; Hiroyuki Kato Abstract:Although there have been many reports about the cytotoxicity of multi-walled carbon nanotubes (MWCNTs), the results are still controversial. To investigate one possible reason, the authors investigated the influence of MWCNT dispersants on cellular uptake and cytotoxicity. Cytotoxicity was examined (measured by alamarBlue (R) assay), as well as intracellular MWCNT concentration and cytokine secretion (measured by flow cytometry) in human bronchial epithelial cells (BEAS-2B) exposed to a type of highly purified MWCNT vapor grown carbon fiber (VGCF (R), Showa Denko Kabushiki-gaisha, Tokyo, Japan) in three different dispersants (gelatin, carboxylmethyl cellulose, and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine). The authors also researched the relationship between the intracellular concentration of MWCNTs and cytotoxicity by using two cell lines, BEAS-2B and MESO-1 human malignant pleural mesothelioma cells. The intracellular concentration of VGCF was different for each of the three dispersants, and the levels of cytotoxicity and inflammatory response were correlated with the intracellular concentration of VGCF. A relationship between the intracellular concentration of VGCF and cytotoxic effects was observed in both cell lines. The results indicate that dispersants affect VGCF uptake into cells and that cytotoxicity depends on the intracellular concentration of VGCF, not on the exposed dosage. Thus, toxicity appears to depend on exposure time, even at low VGCF concentrations, because VGCF is biopersistent.
Elucidation mechanism of different biological responses to multi-walled carbon nanotubes using four cell lines INTERNATIONAL JOURNAL OF NANOMEDICINE,6:3487-3497 2011 Author:Hisao Haniu; Naoto Saito; Yoshikazu Matsuda; Yoong-Ahm Kim; Ki Chul Park; Tamotsu Tsukahara; Yuki Usui; Kaoru Aoki; Masayuki Shimizu; Nobuhide Ogihara; Kazuo Hara; Seiji Takanashi; Masanori Okamoto; Norio Ishigaki; Koichi Nakamura; Hiroyuki Kato Abstract:We examined differences in cellular responses to multi-walled carbon nanotubes (MWCNTs) using malignant pleural mesothelioma cells (MESO-1), bronchial epithelial cells (BEAS-2B), neuroblastoma cells (IMR-32), and monoblastic cells (THP-1), before and after differentiation. MESO-1, BEAS-2B and differentiated THP-1 cells actively endocytosed MWCNTs, resulting in cytotoxicity with lysosomal injury. However, cytotoxicity did not occur in IMR-32 or undifferentiated THP-1 cells. Both differentiated and undifferentiated THP-1 cells exhibited an inflammatory response. Carbon blacks were endocytosed by the same cell types without lysosomal damage and caused cytokine secretion, but they did not cause cytotoxicity. These results indicate that the cytotoxicity of MWCNTs requires not only cellular uptake but also lysosomal injury. Furthermore, it seems that membrane permeability or cytokine secretion without cytotoxicity results from several active mechanisms. Clarification of the cellular recognition mechanism for MWCNTs is important for developing safer MWCNTs.
Double triangular dorsal sliding flap を用いた中手骨型母指多指症の治療 日本手外科学会雑誌 = The journal of Japanese Society for Surgery of the Hand,26(5):438-440 2010(Sep. 13) Author:岡本 正則; 松田 智; 加藤 博之
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Wnt5a up-regulates the expression of Lrp5/6 during osteoblastogenesis 5th International Conference on Osteoimmunology 2014(Jun. 15) Presenter:Masanori Okamoto, Nobuyuki Udagawa, Teruhito Yamashita, Shunsuke Uehara, Hiroyuki Kato, Naoto Saito, Naoyuki Takahashi, Yasuhiro Kobayashi
Double triangular dorsal sliding flap を用いた中手骨型母指多指症の治療 日本手外科学会雑誌 = The journal of Japanese Society for Surgery of the Hand 26 5 438-440 2010(Sep. 13) Presenter:岡本 正則; 松田 智; 加藤 博之
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