Publications by authors named "Shinji Miwa"

Background/aim: Metastatic breast cancer is a recalcitrant disease with a poor prognosis. Novel targets and therapies are necessary to improve the survival rate of patients with metastatic breast cancer. Previous pre-clinical and clinical studies, have demonstrated the effectiveness of oral recombinant methioninase (o-rMETase) against breast cancer.

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The clinical utility of P-glycoprotein (P-gp) in osteosarcoma remains controversial. This retrospective cohort study aimed to investigate the association between P-gp expression and clinicopathological factors, chemotherapy (CTx) response, and prognosis in osteosarcoma. Twenty-three osteosarcoma patients treated at our institution between 2007 and 2013 were included.

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Background And Aim: Hutchinson-Gilford Progeria Syndrome (HGPS) and progeroid laminopathies (PL) are rare genetic disorders characterized by accelerated aging and early onset cardiovascular complications. Despite recent advances in the genetic diagnosis of HGPS and PL and the advent of lonafarnib treatment, the epidemiology and clinical characteristics of these disorders in Asia remain unclear. This study aimed to assess the prevalence, clinical features, and diagnostic trends of the HGPS and PL in Japan.

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The orbital Edelstein effect and orbital Hall effect, where a charge current induces a nonequilibrium orbital angular momentum, offer a promising method for efficiently manipulating nanomagnets using light elements. Despite extensive research, understanding the Onsager's reciprocity of orbital transport remains elusive. In this study, we experimentally demonstrate the Onsager's reciprocity of orbital transport in an orbital Edelstein system by utilizing nonlocal measurements.

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Introduction: Soft tissue metastasis of breast cancer is very rare. Specifically, metastasis to the upper arm has only been reported in 10 cases, including this one, to the best of our knowledge. Distant lymph node metastasis of breast cancer is also infrequent, with only one documented case of brachial lymph node metastasis.

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Primary leiomyosarcoma of the bone (LMSB) is an exceptionally rare malignant bone tumor. We report a case of a 60-year-old woman with LMSB of the talus initially misdiagnosed as idiopathic transient osteoporosis of the talus based on clinical and initial MRI findings, which showed extensive bone marrow edema without soft tissue invasion. Despite initial improvement with off-loading treatment, the patient's symptoms recurred, and subsequent imaging revealed progression and soft tissue involvement.

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Background: Although undifferentiated pleomorphic sarcoma (UPS), previously termed as malignant fibrous histiocytoma (MFH), is one of the most common soft tissue sarcomas, the number of studies focusing on UPS remains limited. This retrospective study aimed to identify prognostic factors and assess the clinical impact of chemotherapy on the development of metastasis in patients with UPS.

Methods: This study included 147 patients with UPS who underwent tumor resection.

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Sarcomas, including osteosarcoma and soft tissue sarcoma, are heterogeneous and rare diseases with limited treatment options and a high metastatic potential. Despite advancements in immunotherapy and targeted therapies, many sarcoma patients have limited durable responses to these treatments. Therefore, individualized precision medicine and novel drug discovery are greatly needed.

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Background/aim: Recent studies have shown that ivermectin, developed as an anti-parasitic drug, has efficacy against several cancer types. Methionine restriction, including the use of recombinant methioninase (rMETase), has been developed to target methionine addiction, a fundamental hallmark of cancer, termed the Hoffman effect. Metastatic colorectal cancer (CRC) is a recalcitrant disease that requires novel and disruptive treatment approaches.

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Undifferentiated pleomorphic sarcoma (UPS)/malignant fibrous histiocytoma (MFH) is the second most common soft-tissue sarcoma. The standard treatment options for UPS/MFH include tumor excision with appropriate surgical margins, radiation therapy, and chemotherapy. Preferable clinical outcomes can be expected in patients with resectable disease, whereas the clinical outcomes in patients with metastatic disease are unsatisfactory despite multidisciplinary treatment.

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Background/aim: Peritoneal carcinomatosis is the end stage for patients with gastrointestinal cancer, with survival ranging between 2 and 9 months. Pancreatic acinar cell carcinoma (PACC) is rare and can result in peritoneal metastases. The efficacy of chemotherapy for patients with PACC is unknown, and a systemic treatment strategy has not been established.

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Background/aim: Cisplatinum (CDDP) is used as first-line therapy in lung cancer. To further improve the therapeutic efficacy of CDDP, we focused on methionine addiction of cancer, known as the Hoffman effect. The present study aimed to determine the synergistic efficacy of the combination of CDDP and recombinant methioninase (rMETase) to target methionine addiction of lung cancer.

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Background/aim: Eribulin is a microtubule inhibitor used in the treatment of various malignancies, including soft-tissue sarcoma. However, the development of eribulin resistance is a recalcitrant clinical problem. The present study demonstrates that super eribulin-resistant HT1080 human fibrosarcoma cells become highly malignant but can be eradicated synergistically by the combination of eribulin and methionine restriction in nude mice.

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Background/aim: Drug-resistant osteosarcoma is a highly aggressive malignancy with limited therapeutic options. Recombinant methioninase (rMETase) targets the methionine addiction of cancer and acts synergistically with many cancer-chemotherapy agents. The present study investigated the synergistic efficacy of the combination of rMETase, chloroquine (CQ) which targets autophagy, and rapamycin (RAPA) which targets mTOR, on human 143B osteosarcoma cells .

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Background/aim: Trabectedin is a DNA-binding agent that has shown moderate efficacy for soft-tissue sarcomas. We have previously shown that methionine restriction enhances trabectedin efficacy on both parental and trabectedin-resistant HT1080 (TR-HT1080) cells The aim of the present study was to determine whether fibrosarcoma cells that acquire trabectedin resistance become more malignant but maintain sensitivity to methionine restriction Materials and Methods: TR-HT1080 was established by culturing HT1080 cells in stepwise increasing concentrations of trabectedin. An wound-healing invasion assay was used to compare malignancy of HT1080 and TR-HT1080.

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Background/aim: A1-R (A1-R) expresses green fluorescent protein (GFP) and has the ability to selectively target and inhibit all major cancer types in murine models without persistently infecting healthy tissue. A1-R is being developed for tumor targeting by oral administration. The aim of the present study was to demonstrate real-time imaging of orally-administered A1-R in a fibrosarcoma nude-mouse model and to visualize its trafficking through the gastrointestinal system to the tumor and normal organs.

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Background/aim: Ivermectin is a widely-used anti-parasitic agent and has shown early promise as an anticancer agent. Recombinant methioninase (rMETase) is a methionine-depleting enzyme targeting the methionine addiction of cancer and has broad efficacy against all tested cancer types. However, the combination efficacy of ivermectin and rMETase on breast cancer cells remains unexplored.

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Aims: The Birmingham Orthopaedic Oncology Meeting (BOOM), held in January 2024, convened 309 delegates from 53 countries to discuss and refine 21 consensus statements on the optimal management of chondrosarcoma.

Methods: With representation from Europe (43%; n = 133), North America (17%; n = 53), South America (16%; n = 49), Asia (13%; n = 40), Australasia (5%; n = 16), the Middle East (4%; n = 12), and Africa (2%; n = 6), the combined experience of treating bone sarcomas among attendees totalled approximately 30,000 cases annually, equivalent to 66 years of experience in the UK alone. The meeting's process began with the formation of a local organizing committee, regional leads, and a scientific committee comprising representatives from 150 specialist units across 47 countries.

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: Developing high-performance artificial intelligence (AI) models for rare diseases is challenging owing to limited data availability. This study aimed to evaluate whether a novel three-class annotation method for preparing training data could enhance AI model performance in detecting osteosarcoma on plain radiographs compared to conventional single-class annotation. : We developed two annotation methods for the same dataset of 468 osteosarcoma X-rays and 378 normal radiographs: a conventional single-class annotation (1C model) and a novel three-class annotation method (3C model) that separately labeled intramedullary, cortical, and extramedullary tumor components.

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Article Synopsis
  • A 66-year-old patient with metastatic prostate cancer was treated with a low-methionine diet and oral recombinant methioninase (o-rMETase) after previous therapies, aiming to assess long-term effects on cancer progression.
  • Since starting the methionine restriction in September 2022, the patient's prostate-specific antigen (PSA) levels remained stable under 2 ng/ml, with stable lymph node metastases observed in subsequent PET scans.
  • The study concludes that methionine restriction may effectively prevent cancer progression, suggesting the need for further clinical trials to explore its potential benefits.
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Article Synopsis
  • The study explored the effectiveness of rMETase in combination with gemcitabine for treating advanced soft-tissue sarcomas, particularly focusing on HT1080 fibrosarcoma cells and gemcitabine-resistant cells that showed elevated c-MYC levels.
  • Results indicated that rMETase enhanced the cytotoxic effects of gemcitabine on fibrosarcoma cells, but not on normal fibroblasts, suggesting a targeted approach could be beneficial for treating resistant sarcoma types.
  • Overall, rMETase shows potential as an effective therapy for overcoming gemcitabine resistance in sarcoma, indicating it could be a promising option in future clinical applications.
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Background/aim: Chronic lymphocytic leukemia (CLL) is currently incurable. CLL is characterized by disordered DNA methylation. The aim of the present study was to target methylation with methionine restriction in a patient with progressive CLL.

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Background/aim: Ifosfamide is used clinically with doxorubicin as first-line chemotherapy for soft-tissue sarcoma. However, ifosfamide efficacy for soft-tissue sarcoma is limited due to frequent occurence of ifosfamide resistance and thus more effective therapy is needed. The present study aimed to determine the synergy of recombinant methioninase (rMETase) plus ifosfamide against HT1080 human fibrosarcoma cells in vitro.

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Background/aim: Salmonella typhimurium A1-R (A1-R) targets and inhibits a wide range of cancer types without continuously infecting healthy tissue. Chloroquine, an antimalarial drug, induces apoptosis and inhibits autophagy in cancer cells. The aim of the present study was to determine the synergy of A1-R plus chloroquine on HT1080 human fibrosarcoma cells in vitro and in a nude-mouse model.

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