Publications by authors named "Toshiyuki Kunisada"

Background: Myxoid liposarcoma, a rare type of tumor, accounts for approximately 30% of all liposarcomas. Myxoid liposarcomas harboring the FUS/CHOP fusion gene have shown promising results with trabectedin in basic research and some clinical experiments. However, the efficacy and safety of trabectedin in chemotherapy-naive soft tissue sarcomas or FUS/CHOP fusion gene-positive myxoid liposarcomas have not yet been established.

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  • * It aims to determine if having surgery followed by three courses of adjuvant chemotherapy is as effective as the standard approach of chemotherapy followed by surgery and then more chemotherapy.
  • * The trial is a large, randomized phase III study that began in November 2022 and seeks to confirm that the new treatment method is not inferior regarding overall survival rates.
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The lack of circulating biomarkers for tumor monitoring is a major problem in Ewing sarcoma management. The development of methods for accurate tumor monitoring is required, considering the high recurrence rate of drug-resistant Ewing sarcoma. Here, we describe a sensitive analytical technique for tumor monitoring of Ewing sarcoma by detecting circulating extracellular vesicles secreted from Ewing sarcoma cells.

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  • This study focused on developing a high-performance AI model to detect osteosarcoma from X-ray images, aiming to enhance early diagnosis and treatment in pediatric and young adult populations.
  • Traditional models had lower sensitivity (60%-70%), while the new model achieved a sensitivity of 95.52% and specificity of 96.21% by using carefully annotated data from an experienced oncologist.
  • The study emphasizes the importance of high-quality training data and suggests that data-centric AI could revolutionize diagnostic processes in oncology, with potential applications for other rare cancers as well.
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This study investigated the potential of the metaverse in providing psychological support for pediatric and AYA cancer patients, with a focus on those with rare cancers. The research involved ten cancer patients and survivors from four distinct regions in Japan, who participated in metaverse sessions using customizable avatars, facilitating interactions across geographical and temporal barriers. Surveys and qualitative feedback were collected to assess the psychosocial impact of the intervention.

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Osteosarcoma (OS), the most frequent primary malignant tumor of bone in children and adolescents, is refractory to immune checkpoint inhibitors due to its poor antitumor immune response. Chemotherapy and virotherapy induce immunogenic cell death (ICD) and antitumor immune responses, leading to the abscopal effect in untreated tumors. We previously demonstrated the antitumor activity of the telomerase-specific replication-competent oncolytic adenoviruses OBP-301 and p53-armed OBP-702 in human OS cells.

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Giant cell tumor of bone (GCTB) is a locally aggressive intermediate bone tumor. Denosumab has shown effectiveness in GCTB treatment; however, the benefits of denosumab de-escalation for unresectable GCTB have not been well discussed. The present study investigated the efficacy and safety of denosumab de-escalation for GCTB.

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  • Unidirectional porous hydroxyapatite (UDPHAp) serves as an innovative scaffold with horizontally oriented and interconnected pores, aimed at treating bone tumors.* -
  • Clinical studies showed excellent bone regeneration around UDPHAp implants, with significant absorption and remodeling of the material occurring mostly in younger patients.* -
  • No complications were reported, and in one case of a pediatric patient, UDPHAp led to complete resorption and recovery, allowing the child to resume walking and sports activities.*
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Soft-tissue sarcoma (STS) is a heterogeneous group of rare tumors originating predominantly from the embryonic mesoderm. Despite the development of combined modalities including radiotherapy, STSs are often refractory to antitumor modalities, and novel strategies that improve the prognosis of STS patients are needed. We previously demonstrated the therapeutic potential of two telomerase-specific replication-competent oncolytic adenoviruses, OBP-301 and tumor suppressor p53-armed OBP-702, in human STS cells.

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  • PRRX1 is a transcription factor linked to developmental processes and is found to be highly expressed in some cancers, impacting patient survival prognosis.
  • Research involving MPNST samples revealed that high levels of PRRX1 correlate with poor outcomes, and manipulating PRRX1 levels affected tumor behavior.
  • It was discovered that PRRX1 interacts with TOP2A, promoting cancer-related pathways, suggesting that disrupting this interaction could lead to new treatments for cancers with elevated PRRX1.
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Bone and soft-tissue sarcomas are rare malignancies with histological diversity and tumor heterogeneity, leading to the lack of a common molecular target. Telomerase is a key enzyme for keeping the telomere length and human telomerase reverse transcriptase (hTERT) expression is often activated in most human cancers, including bone and soft-tissue sarcomas. For targeting of telomerase-positive tumor cells, we developed OBP-301, a telomerase-specific replication-competent oncolytic adenovirus, in which the hTERT promoter regulates adenoviral E1 gene for tumor-specific viral replication.

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Malignant peripheral nerve sheath tumors (MPNSTs) are malignant tumors that are derived from Schwann cell lineage around peripheral nerves. As in many other cancer types, cancer stem cells (CSCs) have been identified in MPNSTs, and they are considered the cause of treatment resistance, recurrence, and metastasis. As an element defining the cancer stemness of MPNSTs, we previously reported a molecular mechanism by which exogenous adrenaline activates a core cancer stemness factor, YAP/TAZ, through β2 adrenoceptor (ADRB2).

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  • Alveolar soft part sarcoma (ASPS) is an ultra-rare cancer linked to a specific gene fusion caused by a chromosomal translocation, which typically occurs in adolescents and young adults.
  • This cancer grows slowly, often metastasizing to the lungs, bones, and brain, and complete surgical removal is the primary treatment approach, with radiotherapy used when surgery isn't adequate.
  • New treatment options like tyrosine kinase inhibitors and immune checkpoint inhibitors have shown promise, especially since traditional chemotherapy is often ineffective against ASPS.*
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Purpose: Soft tissue sarcomas (STS) of the forearm are rare. We aim to assess their oncological and functional outcomes.

Methods: We retrospectively evaluated 34 patients who underwent surgical excision for forearm STS at our institution between 1993 and 2020.

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Malignant wounds (MWs) are rare skin lesions, which accompany ulceration, necrosis and infection caused by infiltration or damage by malignant tumor. The present study aimed to investigate the bacterial etiology implicated in MW in soft tissue sarcoma (STS), and the effectiveness of culture-guided perioperative antibacterial administration. A retrospective evaluation was conducted on medical records of patients who presented with MW between 2006 and 2020.

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Background: Alveolar soft part sarcoma (ASPS) is a rare histological subtype of soft-tissue sarcoma, which remains refractory to conventional cytotoxic chemotherapy. We aimed to characterize ASPS and investigate whether the oncological outcome has improved over the past decade.

Methods: One hundred and twenty patients with newly diagnosed ASPS from 2006 to 2017, identified from the Bone and Soft-Tissue Tumor Registry in Japan, were analyzed retrospectively.

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  • Giant cell tumor of bone (GCTB) is generally a benign tumor but can rarely transform into a higher-grade malignant form known as secondary malignant GCTB (SMGCTB), often after prior treatment.
  • A study at Okayama University Hospital found that 4% of GCTB patients developed SMGCTB, with tumors located in the distal ulna, distal femur, and sacrum, and characterized by both GCTB and malignant components.
  • The findings suggest higher Ki67 and p53 expression in the malignant parts of SMGCTB, indicating a potential association with malignant transformation, highlighting the need for further research on treatment methods and molecular therapies.
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  • The JCOG1610 trial aimed to compare preoperative denosumab treatment to curettage with local therapy for patients with giant cell tumor of bone, focusing on relapse-free survival as the main outcome.
  • Patient enrollment started in October 2017 but was halted in December 2020 due to low participant numbers, with only 18 patients registered across 13 institutions at that time.
  • Results indicated that preoperative denosumab did not show superiority over the traditional method in preventing tumor relapse, with similar relapse-free survival rates observed in both treatment groups after one and two years.
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  • - The guidelines aim to provide evidence-based recommendations for improving the diagnosis, treatment, and prognosis of patients with soft tissue tumors.
  • - A multidisciplinary team created 22 clinical questions (CQs) and developed guidelines based on systematic reviews of evidence and expert input, following specific development methods.
  • - The recommendations are designed to help healthcare professionals make better decisions in treating soft tissue tumors, ultimately enhancing patient care in this area.
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Soft-tissue sarcoma is a rare cancer that accounts for approximately 1% of all malignant tumors. Although they occur in various age groups, soft-tissue sarcomas account for 8% of all malignant tumors developing in adolescents and young adults, suggesting that they are not rare in this age group. This study aimed to evaluate the clinical and pathological characteristics of soft-tissue sarcoma in adolescents and young adults.

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Background: Preoperative chemotherapy is widely applied to high-grade localized soft tissue sarcomas (STSs); however, the prognostic significance of histological response to chemotherapy remains controversial. This study aimed to standardize evaluation method of histological response to chemotherapy with high agreement score among pathologists, and to establish a cut-off value closely related to prognosis.

Methods: Using data and specimens from the patients who had registered in the Japan Clinical Oncology Group study, JCOG0304, a phase II trial evaluating the efficacy of perioperative chemotherapy with doxorubicin (DOX) and ifosfamide (IFO), we evaluated histological response to preoperative chemotherapy at the central review board.

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Background: Osteosarcoma (OS) is a malignant bone tumor primarily affecting children and adolescents. The prognosis of chemotherapy-refractory OS patients is poor. We developed a tumor suppressor p53-expressing oncolytic adenovirus (OBP-702) that exhibits antitumor effects against human OS cells.

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