Masanori Kawano

Pelvic sarcomas are rare malignant tumors arising from the bone or soft tissue and are associated with poor clinical outcomes. Their deep anatomical location and large tumor size often limit complete surgical resection, and optimal treatment strategies remain controversial. Carbon-ion radiotherapy (CIRT) has emerged as an advanced radiotherapeutic option; however, its clinical significance in pelvic sarcomas remains unclear. This study aimed to investigate clinical outcomes and prognostic factors in patients with pelvic sarcomas. We retrospectively reviewed 20 patients with pelvic sarcomas treated at a single institution between 2015 and 2025. Clinical characteristics, treatment modalities, and outcomes were analyzed. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method, and univariate analyses were performed to evaluate associations between clinical variables and survival outcomes. The median age at diagnosis was 70.5 years, and the median tumor size was 94.5 mm. Surgical resection was performed in two patients, while chemotherapy and radiotherapy were each administered in 60% of the patients. Among patients receiving radiotherapy, seven underwent CIRT. The median OS and PFS were 33 and 32 months, respectively. Larger tumor size (≥95 mm) was significantly associated with poorer overall survival [odds ratio (OR)=21.3, p=0.006], whereas treatment with CIRT was significantly associated with improved overall survival (OR=0.05, p=0.007). Two patients died from non-cancer-related causes following severe postoperative complications after surgery. In this retrospective exploratory analysis, tumor size and the use of carbon-ion radiotherapy were associated with survival in patients with pelvic sarcomas. Large tumor size was linked to unfavorable outcomes, whereas CIRT was associated with improved survival. Although limited by the small sample size and potential selection bias, these findings suggest that CIRT may represent a potential treatment option for selected patients with pelvic sarcomas and highlight the importance of individualized treatment strategies.

Glycogen synthase kinase-3β (GSK-3β) is a serine/threonine kinase known to function as a tumor suppressor by promoting ubiquitination and degradation of the Myc protein. In this study, we investigated the role of cyclin-dependent kinase 5 (CDK5) in regulating GSK-3β kinase activity, as well as Myc phosphorylation and ubiquitination. Four Ewing sarcoma cell lines were used in this study. Cells were transfected with a CDK5 expression vector, and cell proliferation, cell-cycle progression, and apoptosis were analyzed. We examined whether CDK5 alters the phosphorylation status of GSK-3β. In addition, siRNA-mediated knockdown and expression vectors were used to modulate CDK5 and GSK-3β expression, and the effects on Myc ubiquitination were evaluated. Compared with control cells, CDK5-overexpressing Ewing sarcoma cells showed increased proliferative capacity and enhanced cell-cycle progression. Under these conditions, dephosphorylation of GSK-3β at Tyr216 and phosphorylation at Ser9 as well as Ser389 - patterns consistent with the inactive form of GSK-3β - were observed. Concomitantly, ubiquitination of the Myc protein was reduced. In contrast, cells transfected with a GSK-3β expression vector exhibited increased Myc phosphorylation and ubiquitination. These findings suggest that functional impairment of GSK-3β and subsequent upregulation of Myc may promote the proliferation of Ewing sarcoma cells. Myc is normally phosphorylated by GSK-3β, which triggers its ubiquitination and proteasomal degradation. Although CDK5 is recognized as a cell-cycle-related kinase, our results demonstrate that CDK5 is associated with increased inhibitory phosphorylation of GSK-3β, resulting in functional suppression of its activity. As a result, GSK-3β-mediated phosphorylation of Myc is attenuated, leading to reduced ubiquitination and accumulation of Myc. Regulation of Myc expression through CDK5-mediated modulation of GSK-3β plays a critical role in controlling Ewing sarcoma cell proliferation and may represent a promising therapeutic target.

Japan is one of the most rapidly aging societies worldwide, and the incidence of rare malignancies such as sarcoma is expected to rise among the very elder

Liquid nitrogen-treated autografts are increasingly used in limb-salvage surgery because they preserve bone strength, maintain biological activity, and may enhance antitumor immunity. However, the true clinical performance of this technique remains controversial, particularly regarding graft survival and postoperative limb function. We retrospectively analyzed 10 patients (11 limbs) who underwent reconstruction with liquid nitrogen-treated autografts. Graft survival was assessed using Kaplan-Meier analysis, and postoperative function was evaluated using the International Society of Limb Salvage (ISOLS) score. Potential risk factors were analyzed using univariate statistics. At four years postoperatively, 72.7% of grafts remained available. Kaplan-Meier analysis demonstrated an impressively long mean graft survival of 156.5 months (95% confidence interval=96.1-217), underscoring the durability of this technique. No clinical variable - including age, diagnosis, fixation method, blood loss, or operative time - showed any significant association with graft failure. In contrast, graft length emerged as the sole parameter strongly linked to functional impairment, demonstrating a significant negative correlation with ISOLS scores. The primary weakness of this technique lies not in graft survival but in functional decline associated with longer graft segments. These results emphasize the need for careful patient selection and strategic planning yet firmly support liquid nitrogen-treated autografts as a promising reconstructive option - especially in anatomical regions unsuitable for endoprosthesis replacement and in younger patients requiring joint-preserving strategies.

This study investigated the postoperative outcomes of patients with pathological fractures who had undergone tumor resection and reconstruction using tumor endoprostheses for femoral bone metastases over the past 10 years. We conducted a retrospective case series of patients who underwent tumor resection and endoprosthetic reconstruction for femoral metastases and pathological fractures between January 2016 and December 2024. The minimum follow-up period was 6 months or until death. Postoperative survival was the primary outcome. Statistical analyses were performed using the IBM SPSS Statistics version 25. Kaplan–Meier survival curves were generated, and the chi-square and Mann–Whitney U tests were used for comparisons. Eighteen patients were retrospectively analyzed. The cohort included 7 men and 11 women, with a median age of 68.5 years (range, 38–88 years). Primary malignancies included breast cancer (n = 8), renal cell carcinoma (n = 4), prostate cancer (n = 2), and one case each of non-small cell lung cancer, follicular thyroid carcinoma, gastric cancer, and hepatocellular carcinoma. At the final follow-up, 7 patients were alive and 11 had died. Fifteen patients (83.3%) survived for more than 6 months after surgery. The estimated median postoperative survival time was 18 months. Among the 16 patients who received postoperative chemotherapy, the estimated median survival was 41 months. Postoperative chemotherapy was significantly associated with survival of ≥ 6 months ( P < .05). Reconstruction using tumor endoprostheses appears to be a reliable and effective surgical option for patients with femoral bone metastases and pathological fractures, particularly when postoperative chemotherapy can be administered. However, these findings should be interpreted with caution given the retrospective design and limited sample size.

In recent years, pembrolizumab has demonstrated significant efficacy in treating tumors characterized by a high tumor mutational burden and high microsatellite instability. Tropomyosin receptor kinase (TRK) inhibitors have shown considerable efficacy against tumors harboring neurotrophic receptor tyrosine kinase (NTRK) fusion genes, highlighting the growing importance of personalized medicine in cancer treatment. Advanced sequencing technologies enable the rapid analysis of numerous genetic abnormalities in tumors, facilitating the identification of patients with positive biomarkers. These advances have increased the likelihood of providing effective, tailored treatments. NTRK fusion genes are present in various cancer types, including sarcomas, and the TRK inhibitors larotrectinib and entrectinib have been effectively used for these malignancies. Consequently, the treatment outcomes for NTRK fusion-positive tumors have improved significantly, reflecting a shift toward more personalized therapeutic approaches. This review focuses on NTRK fusion-positive sarcomas and comprehensively evaluates their epidemiology, clinical features, and radiological and histological characteristics. We also investigated the treatment landscape, including the latest methodologies involving TRK inhibitors, and discussed the long-term efficacy of these inhibitors, and their optimal order of use. Notably, larotrectinib has demonstrated a high response rate in infantile fibrosarcoma, and its efficacy has been confirmed even in advanced cases. However, further research is warranted to optimize treatment duration and subsequent management strategies. The accumulation of clinical cases worldwide will play a pivotal role in refining the treatment approaches for tumors associated with NTRK fusion genes.

[This corrects the article DOI: 10.32604/or.2023.044085.].

An important factor in the emergence and progression of osteosarcoma (OS) is the dysregulated expression of microRNAs (miRNAs). Transcription factor 7-like 1 (TCF7L1), a member of the T cell factor/lymphoid enhancer factor (TCF/LEF) transcription factor family, interacts with the Wnt signaling pathway regulator β-catenin and acts as a DNA-specific binding protein. This study sought to elucidate the impact of the interaction between miR-329-3p and TCF7L1 on the growth and apoptosis of OS and analyze the regulatory expression relationship between miRNA and mRNA in osteosarcoma cells using a variety of approaches. MiR329-3p was significantly downregulated, while TCF7L1 was considerably up-regulated in all examined OS cell lines. Additionally, a clinical comparison study was performed using the TCGA database. Subsequently, the regulatory relationship between miR-329-3p and TCF7L1 on the proliferation and apoptosis of OS cells was verified through in vitro and in vivo experiments. When miR-329-3p was transfected into the OS cell line, the expression of TCF7L1 decreased, the proliferation of OS cells was inhibited, the cytoskeleton disintegrated, and the nucleus condensed to form apoptotic bodies. The expression of proteins that indicate apoptosis increased simultaneously. The cell cycle was arrested in the G0/G1 phase, and the G1/S transition was blocked. The introduction of miR-329-3p also inhibited downstream Cyclin D1 of the Wnt pathway. Xenograft experiments indicated that the overexpression of miR-329-3p significantly inhibited the growth of OS xenografts in nude mice, and the expression of TCF7L1 and c-Myc in tumor tissues decreased. MiR-329-3p was significantly reduced in OS cells and played a suppressive role in tumorigenesis and proliferation by targeting TCF7L1 both in vitro and in vivo. Osteosarcoma cell cycle arrest and pathway inhibition were observed upon the regulation of TCF7L1 by miR-329-3p. Summarizing these results, it can be inferred that miR-329-3p exerts anticancer effects in osteosarcoma by inhibiting TCF7L1.

Rationale: Precision medicine and tumor-agnostic treatment strategies have recently been promoted for clinical use. One of the most successful treatments in patients with neurotrophic tyrosine receptor kinase (NTRK) fusion-positive tumors is targeting the tropomyosin receptor kinase (TRK) with an inhibitor. The TRK inhibitors, larotrectinib, and entrectinib, have been approved in many countries. Nevertheless, the most effective administration regimen for these TRK inhibitors is uncertain. To date, no reports have shown the efficacy of sequential treatment with larotrectinib and entrectinib in patients with NTRK fusion-positive tumors. In this report, we present a patient with NTRK fusion-positive sarcoma arising from the anterior mediastinum, with tumor progression after 4 months of entrectinib use. The patient took larotrectinib subsequently and maintained disease control for more than 21 months. Patient concerns: A 48-year-old female visited a physician because she experienced difficulty in breathing and chest and back pain with no obvious cause 2 months ago. Computed tomography (CT)-guided biopsy was performed at a district general hospital, and histopathological examination revealed a small round cell tumor. She was referred to our hospital, and a second CT-guided biopsy was performed to confirm the pathological diagnosis. Considering the results of the histopathological examination, Ewing sarcoma was suspected, but a specific fusion gene was not detected due to poor quality specimens. Diagnoses: After 3 regimens of cytotoxic chemotherapy, biopsy was repeated, and specimens were analyzed using next-generation sequencing. The PHF20-NTRK1 fusion gene was detected, and the tumor was finally diagnosed as an NTRK fusion-positive sarcoma. Interventions: She was administered the TRK inhibitor entrectinib, but the tumor started to grow after 4 months of medication, and she stopped taking entrectinib. After 1 cycle of cytotoxic chemotherapy, another TRK inhibitor, larotrectinib, was administered. Outcomes: Her stable disease was maintained for more than 21 months. Here, we have shown that sequential administration of both drugs can be effective. Lessons: In the treatment of NTRK fusion-positive tumors, there are cases in which 2 approved first-generation TRK inhibitors can be used sequentially.

Although gelatin–thrombin matrix sealants have been used successfully in other surgery types, their effect on reducing blood loss during single-level transforaminal lumbar interbody fusion is unclear. We thus examined the efficacy of gelatin–thrombin matrix sealants for reducing blood loss during such surgery. We analyzed 102 patients who underwent single-level transforaminal lumbar interbody fusion for lumbar degenerative disease. We compared body mass index, surgical time, intraoperative blood loss, postoperative blood loss, true total blood loss, hidden blood loss, the proportion of blood transfusion, blood pressure pre- and post-surgery (systolic and diastolic), and pre-and post-surgery laboratory data (hemoglobin, hematocrit, platelets, prothrombin time, activated partial thromboplastin time, and D-dimer) between patients in whom gelatin–thrombin matrix sealants were (GTMS group) or were not (control group) used during surgery. One-week postoperative epidural hematoma size was measured using magnetic resonance imaging. The GTMS and control groups included 54 (24 males and 30 females) and 48 patients (19 males and 29 females). Intraoperative, true total, and hidden blood loss; epidural hematoma size; and hospitalization duration were significantly lower in the GTMS than in the control group. Intraoperative blood loss correlated with surgical time (R = 0.523, P = .001), body mass index (R = 0.221, P = .036), and the amount of gelatin–thrombin matrix sealant used (r = −0.313, P = .002). In multivariate linear regression analysis using intraoperative blood loss as the dependent variable, surgical time (standardization coefficient 0.516, P = .001) and amount of gelatin–thrombin matrix sealant used (standardization coefficient −0.220, P = .032) were independently related factors. In our study, the GTMS group had significantly less intraoperative true total and hidden blood loss than did the control group. Thus, use of gelatin–thrombin matrix sealants reduce perioperative blood loss in transforaminal lumbar interbody fusion.