Background
Patients with advanced oral or oropharyngeal cancer sometimes require surgery and adjuvant postoperative radiotherapy (PORT), which may cause dysphagia. However, the efficacy of ...rehabilitation treatment for PORT-induced dysphagia remains unclear. This study aimed to determine whether rehabilitation treatment during PORT after surgery is effective for dysphagia.
Methods
We retrospectively studied 55 patients with oral or oropharyngeal cancer who received PORT. Of these, 25 received rehabilitation treatment for swallowing during PORT. The Functional Oral Intake Scale (FOIS) score at 6 months after treatment was used as the swallowing outcome. We performed multivariate linear regression and stratified analyses using the FOIS score (poor oral intake group: FOIS score <5, good oral intake group: FOIS score ≧5) before PORT.
Results
The median (interquartile range) FOIS scores at 6 months post-PORT were 6 (5–6) and 6 (4–7) in the non-rehabilitation and rehabilitation groups, respectively. Multivariate linear regression revealed that rehabilitation treatment was a significant independent factor for a better FOIS score. Stratified analysis of the changes in the FOIS score from pre-PORT values to those obtained 6 months after treatment showed a significant difference in the good oral intake group between the rehabilitation and non-rehabilitation groups. There was no significant difference in the FOIS score from pre-PORT values to those obtained 6 months after treatment between the rehabilitation and non-rehabilitation groups in the poor oral intake group.
Conclusion
Rehabilitation treatment during PORT may achieve better swallowing outcomes in patients with advanced oral or oropharyngeal cancer.
PURPOSEThe aim of this study is to establish a standardized measurement method and to examine the intra- and inter-reliabilities and absolute reliability of measuring skin mechanical properties using ...a skin elasticity meter (Cutometer®).METHODSTen healthy participated in the study. Skin mechanical properties were measured at four sites: upper arm, lower arm, upper leg and lower leg on both sides in supine position using a non-invasive skin elasticity meter by two trained different raters. The measurements include quantitative indices of the maximal distensibility (R0), elasticity (R2, R5, R7), and viscoelasticity (R6). Intra- and inter- relative reliabilities were determined using the intraclass correlation coefficient (ICC) (1,1) and ICC (2,1) methods, respectively. The absolute reliability was assessed via the Bland-Altman analysis. Moreover, we evaluated the minimal detectable change at a 95% confidence level (MDC95).RESULTSAt each site, the ICC (1,1) values were >0.90, and the ICC (2,1) values were >0.50. The Bland-Altman analysis did not reveal any fixed errors, and several sites and parameters have proportional errors.CONCLUSIONSIn this study, intra- and inter-reliabilities were measured at "excellent" and more than "moderate" levels, respectively. However, because some proportional errors were observed, the limits of reliability agreement should be considered when using the proposed methods. We believe that the results of this study can be applied to clinical research in field of rehabilitation treatment.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients frequently show physical dysfunction due to loss of muscle mass. This study aimed to clarify the reliability and validity of ...ultrasound in evaluating muscle mass and to analyze the patterns of change in muscle mass before and after allo-HSCT. We conducted a prospective observational study using data from 68 patients who had undergone their first allo-HSCT. We evaluated the thickness of the quadriceps, biceps, and suprahyoid muscle. Three individual evaluators underwent this examination for each muscle before transplantation and on days 30, 90, and 180 after allo-HSCT. Inter-rater reliability was calculated using the interclass correlation (ICC), and the level of correlation between muscle mass measured by ultrasound and psoas muscle mass assessed using computed tomography (CT) was assessed using Pearson correlation. ICC values ranged from 0.897 to 0.977 in the measurement. The correlation scores were 0.730, 0.546 and 0.579 between psoas muscle and the biceps, quadriceps, and suprahyoid muscle. The thickness of the biceps and quadriceps muscle were both significantly decreased after allo-HSCT from baseline. These results showed that the ultrasound technique was a reliable tool for evaluating muscle mass and detecting changes in muscle mass following allo-HSCT.
Summary
Background
osteosarcoma is a rare, primary malignant bone tumour with limited available treatments for advanced or recurrent disease, resulting in a poor prognosis for patients. TAS-115 is a ...novel tyrosine kinase inhibitor under investigation in a phase I study in patients with solid tumours. We report data of osteosarcoma patients in the expansion cohort of this ongoing study.
Patients and methods
an analysis of this multicentre, open-label study was performed 6 months after the final patient was enrolled, and included patients aged ≥15 years, with unresectable or recurrent osteosarcoma, and who had refractory to standard therapy or for whom no standard therapy was available. TAS-115 650 mg/day was orally administered in a 5 days on/2 days off schedule.
Results
a total of 20 patients with osteosarcoma were enrolled. The most common adverse drug reactions (ADRs) were neutrophil count decreased (75%), aspartate aminotransferase increased (50%), and platelet count decreased (50%); 85% of patients had grade ≥ 3 ADRs. Long-term disease control (>1 year) with TAS-115 was achieved in three patients. The best overall response was stable disease (50%); no patient achieved a complete or partial response. Median progression-free survival was 3 months; 4-month and 12-month progression-free rates were 42% and 31%, respectively.
Conclusion
the safety and tolerability of TAS-115 and long-term disease stability for patients with unresectable or recurrent osteosarcoma were confirmed in this study, suggesting that TAS-115 is a promising novel therapy for advanced osteosarcoma patients. Trial registration number: JapicCTI-132333 (registered on November 8, 2013).
Background and Objectives
The aim of this study is to assess the survival, function, radiographic appearance, and modes of failure of extracorporeal irradiated (ECI) autografts in a long‐term ...setting.
Methods
We retrospectively reviewed 87 patients who were treated for bone and soft tissue tumors using ECI autografts between 1988 and 2009.
Results
The 56 patients had a minimum follow‐up of 10 years, and the median follow‐up period was 16.5 years. The reimplantation procedures included 24 osteoarticular grafts, 16 intercalary grafts, 10 autograft‐prosthetic composite grafts, and 6 hemicortical grafts. The 15‐year graft and event‐free survival rates were 76.8% and 47.9%, respectively. Infection and structural failure were the most common reasons for additional surgery. The time for additional surgery was significantly longer in patients with composite grafts (P < .01). The median Musculoskeletal Tumor Society score and the International Society of Limb Salvage score were 80% and 84%, respectively.
Conclusions
ECI autografts are a durable option for reconstruction after resection of musculoskeletal tumors and provide good function over more than 15 years. Most graft failures occurred within 5 years of the index surgery. However, composite grafts showed a tendency to fail more than 10 years after the surgery.
Linear ubiquitin chains generated by the linear ubiquitin chain assembly complex (LUBAC) play an important role in NF‐κB activation. However, the regulation of linear ubiquitin chain generation by ...LUBAC is not well characterized. Here, we identified two deubiquitinating enzymes (DUBs), ovarian tumor DUB with linear linkage specificity (OTULIN/Gumby/FAM105B) and cylindromatosis (CYLD) that can cleave linear polyubiquitin chains and interact with LUBAC via the N‐terminal PNGase/UBA or UBX (PUB) domain of HOIP, a catalytic subunit of LUBAC. HOIP interacts with both CYLD and OTULIN even in unstimulated cells. The interaction of CYLD and OTULIN with HOIP synergistically suppresses LUBAC‐mediated linear polyubiquitination and NF‐κB activation. Moreover, introduction of a HOIP mutant unable to bind either deubiquitinase into HOIP‐null cells augments the activation of NF‐κB by TNF‐α stimulation. Thus, the interactions between these two deubiquitinases and the LUBAC ubiquitin ligase are involved in controlling the extent of TNF‐α‐induced NF‐κB activation in cells by fine‐tuning the generation of linear ubiquitin chains by LUBAC. The interaction of HOIP with OTULIN is also involved in OTULIN suppressing the canonical Wnt signaling pathway activation by LUBAC. Our observations provide molecular insights into the roles of ligase–deubiquitinase interactions in regulating molecular events resulting from linear ubiquitin conjugation.
Clear cell sarcoma (CCS) is a rare but chemotherapy-resistant and often fatal high-grade soft-tissue sarcoma (STS) characterized by melanocytic differentiation under control of ...microphthalmia-associated transcription factor (MITF). Eribulin mesilate (eribulin) is a mechanistically unique microtubule inhibitor commonly used for STS treatment, particularly liposarcoma and leiomyosarcoma. In this study, we examined the antitumor efficacy of eribulin on four human CCS cell lines and two mouse xenograft models. Eribulin inhibited CCS cell proliferation by inducing cell-cycle arrest and apoptosis, shrunk CCS xenograft tumors, and increased tumor vessel density. Eribulin induced MITF protein upregulation and stimulated tumor cell melanocytic differentiation through ERK1/2 inactivation (a MITF negative regulator)
and
Moreover, tumor reoxygenation, probably caused by eribulin-induced vascular remodeling, attenuated cell growth and inhibited ERK1/2 activity, thereby upregulating MITF expression and promoting melanocytic differentiation. Finally, downregulation of MITF protein levels modestly debilitated the antiproliferative effect of eribulin on CCS cells. Taken together, eribulin suppresses CCS through inhibition of cell proliferation and promotion of tumor differentiation by acting both directly on tumor cells and indirectly through tumor reoxygenation.
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.
A total of 217 patients with extremity STS were included. The Sarculator-predicted 10-year probability of OS (pr-OS) was stratified into two subgroups: lower risk (10-year pr-OS ≥ 60%) and higher risk (10-year pr-OS < 60%). The modified Glasgow prognostic score (mGPS) varied from 0 to 2.
Out of the 217 patients, 67 were classified as higher risk, while 150 were lower risk. A total of 181 patients had an mGPS of 0, and 36 had a score of 1 or 2. The 5-year OS was 83.3%. When patients were divided into two groups according to the 10-year pr-OS, those with a higher risk had poorer OS than those with a lower risk. Among the patients with a higher risk, those with an mGPS of 1 or 2 had poorer OS compared to those with a score of 0.
The mGPS could potentially play an important role in identifying patients who are at high risk of death and metastasis in the higher-risk group on the Sarculator.
Sarcoma is a rare type of cancer for which new therapeutic agents are required. Ferroptosis is a nonapoptotic cell death triggered by iron-mediated lipid peroxidation. We found that TFRC, an iron ...uptake protein, was expressed at higher levels in sarcoma cell lines than in noncancer and carcinoma cell lines. Glutathione peroxidase 4 (GPX4) protects cells against ferroptosis, and its inhibition using RAS-selective lethal 3 (RSL3) had an antitumor effect that was more pronounced in sarcoma cell lines, particularly synovial sarcoma cells, compared to non-sarcoma cells. Because NF-κB can provoke ferroptosis, we examined the role of SHARPIN, an activator of NF-κB, in sarcoma. We found that SHARPIN expression was significantly associated with reduced survival in cohorts of patients with cancer, including sarcoma. In addition, SHARPIN promoted the sensitivity of sarcoma cells to ferroptosis. Further analyses revealed that the PGC1α/NRF2/SLC7A11 axis and BNIP3L/NIX-mediated mitophagy are regulated through NF-κB and PRMT5 downstream of SHARPIN. Our findings suggest that ferroptosis could have a therapeutic effect in sarcoma, particularly in subpopulations with high TFRC and SHARPIN expression.
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