Publications by authors named "Hidetatsu Outani"
Effective therapeutic strategies for epithelioid sarcoma (EpS), a high-grade soft tissue sarcoma characterized by loss of integrase interactor 1 (INI1), have not yet been developed. The present study therefore investigated the association between INI1 loss and upregulation of the aurora kinase A (AURKA)/polo-like kinase 1 (PLK1)/cell division cycle 25C (CDC25C) axis, as well as the therapeutic relevance of this axis in EpS. Notably, our findings showed that the reintroduction of INI1 in VA-ES-BJ cells significantly reduced proliferation, mitigated tumorigenicity, and negatively regulated the expression of AURKA and its downstream effectors, as well as the activation of PLK1 and CDC25C.
View Article and Find Full Text PDFArticle Synopsis
- Osteosarcoma exhibits distinct genetic features between younger and elderly patients, influencing their treatment responses.
- Genetic analysis of 204 patients revealed specific mutations associated with age, indicating that younger patients tend to have alterations like CCNE1 and MYC, while older patients show changes like CDK4 and MDM2.
- The study concludes that understanding these genetic differences could enhance chemotherapy selection and treatment strategies for osteosarcoma, advocating for the early use of cancer genome profiling.
Background: Bone metastasis (BM) is a common and fatal condition in patients with castration-resistant prostate cancer (CRPC). However, there are no useful blood biomarkers for CRPC with BM, and the mechanism underlying BM is unclear. In this study, we investigated precise blood biomarkers for evaluating BM that can improve the prognosis of patients with CRPC.
View Article and Find Full Text PDFHDAC Inhibitors Induce HLA Class I Molecules through the SOX10-IRF1 Axis in Clear Cell Sarcoma Cells.
Biol Pharm Bull
November 2024
Although immune checkpoint inhibitors (ICIs) are an effective treatment for clear cell sarcoma (CCS), a rare melanocytic sarcoma with a poor prognosis, their efficacies are still limited. Therefore, a novel therapeutic strategy is required to improve the efficacy of ICIs. We previously reported that histone deacetylase (HDAC) inhibitors increased melanoma immunogenicity through the SOX10-IRF1 pathway and may improve the efficacy of ICIs for melanoma.
View Article and Find Full Text PDFArticle Synopsis
- * The patient group consisted of nearly equal numbers of men and women, with a mean age of 62 years, and the UE procedures were performed by various types of surgeons, including plastic, orthopedic, and general surgeons.
- * Results showed high rates of inappropriate surgical techniques, with many patients requiring re-excisions and subsequent soft-tissue reconstruction, highlighting the need for improved education on sarcoma management for all surgeons.
Article Synopsis
- Retroperitoneal dedifferentiated liposarcoma has a high recurrence rate, and this study seeks to identify effective surgical treatment strategies for recurrent cases.
- Analysis of 118 patients showed that the first and second surgeries significantly improved overall survival, while no major benefits were seen after a third surgery.
- Prognosis is influenced by tumor malignancy level, with low-grade tumors having better outcomes post-surgery compared to high-grade malignancies, suggesting careful consideration is needed before repeated surgeries.
Article Synopsis
- * A case study focusing on a 51-year-old man with advanced UPS showed significant positive response to the drug pazopanib, which targets multiple cancer-related proteins.
- * Genomic analysis identified coamplification of specific genes linked to patient response; after 3 years on pazopanib, the tumor shrank, indicating this genetic profile may predict better treatment outcomes.
Article Synopsis
- A multicenter study in Japan compared clinical outcomes for patients with pelvic bone sarcomas treated with surgery versus particle beam therapy (carbon-ion and proton).
- The study included 116 patients, with 57 receiving surgery and 59 undergoing particle beam therapy, revealing differences in median age at diagnosis and tumor size between the groups.
- Overall survival, local control, and metastasis-free survival rates were similar between the groups, but in chordoma patients, the particle beam therapy showed significantly better local control rates compared to surgery.
Synovial sarcoma (SS), a rare subtype of soft-tissue sarcoma distinguished by expression of the fusion gene SS18-SSX, predominantly affects the extremities of young patients. Existing anticancer drugs have limited efficacy against this malignancy, necessitating the development of innovative therapeutic approaches. Given the established role of SS18-SSX in epigenetic regulation, we focused on bromodomain and extra-terminal domain protein (BET) inhibitors and epigenetic agents.
View Article and Find Full Text PDFBackground: Sarculator is a validated nomogram designed to predict overall survival (OS) in extremity soft tissue sarcoma (STS). Inflammation plays a critical role in cancer development and progression. There were no reports which investigated the relationship between Sarculator and inflammation.
View Article and Find Full Text PDFBackground: We investigated whether non-enhancement MRI features, including measurement of the heterogeneity of the tumor with MR T2 imaging by calculating coefficient of variation (CV) values, were associated with the prognosis of non-metastatic malignant peripheral nerve sheath tumors (MPNST).
Methods: This retrospective study included 42 patients with MPNST who had undergone surgical resection (mean age, 50 years ± 21; 20 male participants). Non-enhancement MR images were evaluated for signal intensity heterogeneity on T1- and T2-weighted imaging, tumor margin definition on T1- and T2-weighted imaging, peritumoral edema on T2-weight imaging, and CV.
Targeting the Clear Cell Sarcoma Oncogenic Driver Fusion Gene by HDAC Inhibition.
Cancer Res Commun
July 2023
Article Synopsis
- Clear cell sarcoma (CCS) is a rare and aggressive cancer with no effective treatment, driven by a fusion gene that researchers targeted in this study.
- High-throughput drug screening identified vorinostat, a histone deacetylase inhibitor, as effective in reducing the fusion gene’s expression, though it only slightly altered the chromatin structure around the gene.
- Combining vorinostat with the BRD4 inhibitor JQ1 showed a synergistic effect in suppressing CCS cell proliferation, highlighting a new therapeutic strategy for treating tumors linked to fusion genes.
What Are the Complications, Function, and Survival of Tumor-devitalized Autografts Used in Patients With Limb-sparing Surgery for Bone and Soft Tissue Tumors? A Japanese Musculoskeletal Oncology Group Multi-institutional Study.
Clin Orthop Relat Res
November 2023
Article Synopsis
- Tumor-devitalized autografts are biological reconstruction methods used after tumor excision in aggressive bone or soft tissue tumors, providing benefits like no disease transmission risk and better fit for the implant site, but they also have limitations including reduced healing potential and biomechanical strength.
- The study aimed to investigate rates of complications (like fracture and infection), 5-year and 10-year graft survival, union rates of the graft-host junction, and overall limb function related to these autografts.
- Conducted as a retrospective study across 26 sarcoma centers in Japan, the research analyzed data from 494 patients over a 25-year period, focusing on the outcomes and factors affecting the effectiveness of these treatments.
Article Synopsis
- * A review of medical records from 2004 to 2018 identified eight patients who underwent ten local surgeries at areas previously treated with CIRT, with reasons including skin toxicity, bone collapse, and tumor regrowth.
- * While local surgery is deemed feasible for select patients post-CIRT, particularly those with bone-related issues, careful monitoring of infection risks and the prescribed irradiation dose at surgical sites is crucial.
WT1 Trio Peptide-Based Cancer Vaccine for Rare Cancers Expressing Shared Target WT1.
Cancers (Basel)
January 2023
Article Synopsis
- There is currently no standard treatment for most rare cancers, leading to a clinical trial of a biweekly WT1 tri-peptide vaccine designed for patients with recurrent or advanced rare cancers.
- The trial focused on patients with WT1-expressing tumors and aimed to measure immune response through antibody production and skin reactions, while also assessing treatment safety and effectiveness.
- Results showed that the biweekly vaccine led to significantly higher antibody production and a comparable safety profile, suggesting WT1-targeted immunotherapy could be a promising option for treating rare cancers.
Background: Dedifferentiated liposarcoma occurs predominantly in the retroperitoneum. Given the paucity of cases, information on the clinical characteristics of this entity in the extremities and trunk wall is quite limited. In particular, the significance of preoperative evaluation and principles of intraoperative management of the different components, i.
View Article and Find Full Text PDFArticle Synopsis
- This study analyzed the effectiveness of two chemotherapy regimens in high-risk soft tissue sarcoma patients: gemcitabine plus docetaxel (GD) versus the standard Adriamycin plus ifosfamide (AI).
- Results showed that after treatment, the estimated 3-year overall survival was 91.4% for AI compared to 79.2% for GD, indicating that GD was not as effective as AI.
- Despite GD having milder side effects, it should not be adopted as a standard treatment for this type of cancer, as per the findings from the trial.
Article Synopsis
- This study analyzed the clinical outcomes of 187 patients with pelvic and retroperitoneal bone and soft tissue sarcoma (BSTS) treated at specialized centers in Japan.
- The 3-year overall survival (OS) rate was 71.7%, while local control (LC) and progression-free survival (PFS) rates were 79.1% and 48.6%, respectively, with osteosarcoma showing significantly worse outcomes.
- Key poor prognostic factors identified included larger tumor size, soft tissue tumors, presence of distant metastasis, and age, impacting overall survival, local control, and progression-free survival.
Background: Few studies have described the characteristics and prognostic factors of patients with metastatic extrauterine leiomyosarcoma (euLMS). Therefore, we retrospectively investigated the clinicopathological features, clinical outcomes, and prognostic factors of patients with euLMS. Methods: We recruited 61 patients with metastatic euLMS treated from 2006 to 2020 and collected and statistically analyzed information on patient-, tumor-, and treatment-related factors.
View Article and Find Full Text PDFArticle Synopsis
- The distal femur is a frequent location for bone tumors, and surgical resection followed by prosthetic replacement is a common treatment method.
- A study involving 125 patients treated between 1998 and 2014 found that the Kyocera Modular Limb Salvage (KMLS) systems showed long-term effectiveness, with a mean follow-up of over 11 years.
- However, results indicated significant issues, including high rates of additional surgeries and implant failure, particularly related to stem breakage and aseptic loosening, highlighting the need for careful monitoring and consideration of implant type.
The Wilms' tumor gene WT1 is highly expressed in various malignancies and may be a common target antigen for cancer immunotherapy. In our group, peptide-based cancer vaccines targeting WT1 CTL epitopes were developed as an immunotherapy for these malignancies. In the present study, WT1 epitope-specific immune responses were analyzed in 31 patients with advanced sarcoma with human leukocyte antigen-A*24:02- and WT1-expressing tumors who received the WT1-235 peptide vaccine as monotherapy.
View Article and Find Full Text PDFIntroduction: Few studies have described the characteristics and prognostic factors of patients with malignant peripheral nerve sheath tumour (MPNST). In this study, we retrospectively investigated the clinicopathological features, clinical outcomes, and prognostic factors of these patients. .
View Article and Find Full Text PDFArticle Synopsis
- * A review of 97 patient medical records revealed a median OS of 7 months, with 1- and 2-year OS rates of 35.4% and 19.2%, respectively.
- * Key independent predictors for longer OS were found to be single bone metastasis, good performance status, and administration of systemic chemotherapy, with the best-case scenario extending OS to 14.5 months.
Retroperitoneal sarcomas are rare neoplasms that occur in the retroperitoneum. Complete surgical resection is the only effective treatment option. The prediction of prognosis by histological diagnosis has not yet been established.
View Article and Find Full Text PDFArticle Synopsis
- Pelvic osteosarcoma has a worse prognosis than other types, and its poor outcomes are linked to factors like older age, larger tumor size, and higher rates of metastasis at diagnosis.
- The study compared pelvic osteosarcoma to femoral osteosarcoma using data from the Bone Tumor Registry in Japan and used statistical analysis to assess the impact of surgical treatment.
- Results suggest that surgical resection can improve survival rates for pelvic osteosarcoma, and decisions about surgery should consider the tumor stage and the patient's age.