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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. The results demonstrated that the metaverse enabled patients to connect with peers, share experiences, and receive emotional support. The anonymity provided by avatars helped reduce appearance-related anxiety and stigma associated with cancer treatment. A case study of a 19-year-old male with spinal Ewing's sarcoma highlighted the profound emotional relief fostered by metaverse interactions. The findings suggest that integrating virtual spaces into healthcare models can effectively address the unique needs of pediatric and AYA cancer patients, offering a transformative approach to delivering psychosocial support and fostering a global patient community. This innovative intervention has the potential to revolutionize patient care in the digital age.
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Insomnia can coexist with chronic pain and is a major cause of rapidly increasing medical expenses. However, insomnia has not been fully evaluated in patients with chronic pain. This retrospective study aimed to identify the risk factors for insomnia in patients with chronic non-cancer pain. A total of 301 patients with chronic non-cancer pain were enrolled. Patients with the Athens insomnia scale scoresâ ≥â 6 andâ <â 6 were classified into insomnia (+) and insomnia (-) groups, respectively. All patients completed self-report questionnaires as part of their chronic pain treatment approach. Univariate and multivariate analyses were performed to predict insomnia. We found that 219 of 301 (72.8%) patients met the AIS criteria for insomnia. Significant differences were depicted between patients with and without insomnia in terms of body mass index, numeric rating scale, pain catastrophizing scale, hospital anxiety, and depression scale (HADS), pain disability assessment scale, EuroQol 5 dimension (EQ5D), and pain self-efficacy questionnaire. Multiple regression analysis identified the numeric rating scale, HADS, and EQ5D scores as factors related to insomnia in patients with chronic non-cancer pain. Anxiety, depression, and disability were associated with a greater tendency toward insomnia. HADS and EQ5D scores are useful screening tools for preventing insomnia in patients with chronic non-cancer pain.
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Dolor Crónico , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Trastornos del Inicio y del Mantenimiento del Sueño/psicología , Masculino , Estudios Retrospectivos , Femenino , Dolor Crónico/psicología , Dolor Crónico/epidemiología , Persona de Mediana Edad , Factores de Riesgo , Adulto , Anciano , Dimensión del Dolor/métodos , Depresión/epidemiología , Encuestas y Cuestionarios , Ansiedad/epidemiología , Catastrofización/psicologíaRESUMEN
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. Here, we show the therapeutic potential of chemotherapeutic drugs (doxorubicin, cisplatin) and telomerase-specific oncolytic adenoviruses (OBP-301, p53-armed OBP-702) to induce ICD in human OS cells (U2OS, MNNG/HOS, SaOS-2) and murine OS cells (NHOS). OBP-702 induced more profound ICD via the secretion of adenosine triphosphate (ATP) and high-mobility group box protein B1 (HMGB1) compared with chemotherapy and OBP-301 in human OS cells. Murine NHOS cells were also more sensitive to OBP-702 than OBP-301. Subcutaneous NHOS tumor models demonstrated that intratumoral injection of OBP-702 significantly increased the tumor infiltration of cytotoxic CD8+ T cells and induced the abscopal effect against non-treated tumors compared with OBP-301. Our results suggest that OBP-702 is a promising antitumor reagent to induce ICD with secretion of ATP and HMGB1 and the abscopal effect against OS.
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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. The medical records of 9 patients with unresectable GCTB or resectable GCTB not eligible for resection, who received de-escalated denosumab treatment at Okayama University Hospital (Okayama, Japan) between April 2014 and December 2021, were retrospectively reviewed. The denosumab treatment interval was gradually extended to every 8, 12 and 24 weeks. The radiographic changes and clinical symptoms during standard and de-escalated denosumab therapy were assessed. The denosumab interval was de-escalated after a median of 12 months of a standard 4-weekly treatment. Imaging showed that the re-ossification of osteolytic lesions obtained with the 4-weekly treatment were sustained with 8- and 12-weekly treatments. The extraskeletal masses reduced significantly with standard treatment, while tumor reduction was sustained during de-escalated treatment. During the 24-weekly treatment, 2 patients remained stable, while 2 patients developed local recurrence. The clinical symptoms improved significantly with standard treatment and remained improved during de-escalated treatment. There were severe adverse events including osteonecrosis of the jaw (2 patients), atypical femoral fracture (1 patient) and malignant transformation of GCTB (1 patient). In conclusion, 12-weekly de-escalated denosumab treatment showed clinical benefits as a maintenance treatment in patients with unresectable GCTB, in addition to sustained stable tumor control and improved clinical symptoms with standard treatment. A 24-weekly treatment can also be administered, with careful attention paid to detecting local recurrence.
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BACKGROUND: Clear cell sarcoma (CCS) and alveolar soft part sarcoma (ASPS) are rare, and standard systemic therapy is not established except for sunitinib in ASPS. It is known that CCS and ASPS have a common biological feature of melanoma and Xp11.2/TFE3 translocation renal cell carcinoma, and immune-checkpoint inhibitors (ICIs) are effective in these tumors. The authors conducted a phase 2 trial to evaluate the efficacy and safety of nivolumab for CCS and ASPS. METHODS: The number of patients expected to be enrolled was 15-25 and was determined based on the Bayesian design. The primary end point was the confirmed objective response rate (ORR) according to the central review and the secondary end points included ORR, progression-free survival (PFS), overall survival (OS), and safety. RESULTS: A total of 26 patients (CCS, 12; ASPS, 14) were enrolled. Efficacy and safety were analyzed on 25 and 26 patients, respectively. The minimum number of responses required for a positive conclusion regarding the efficacy was four. However, only one patient (4.0%) with ASPS had a partial response. Complete response, stable disease, progression disease, and not evaluable were 0%, 60%, 32%, and 4.0%, respectively. Adverse events of grade 3 or 4 occurred in 57.7% (15 of 26). The median PFS was 4.9 months (95% confidence interval [CI], 3.7-8.6 months) and the median OS was 15.8 months (95% CI, 8.2-not reached). CONCLUSIONS: The primary end point of the ORR was not met for CCS and ASPS on the central review. Further studies are needed to evaluate ICIs in patients with ASPS.
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Unidirectional porous hydroxyapatite (UDPHAp) was developed as a remarkable scaffold characterized by a distinct structure with unidirectional pores oriented in the horizontal direction and connected through interposes. We evaluated the radiographic changes, clinical outcomes, and complications following UDPHAp implantation for the treatment of bone tumors. Excellent bone formation within and around the implant was observed in all patients treated with intralesional resection and UDPHAp implantation for benign bone tumors. The absorption of UDPHAp and remodeling of the bone marrow space was observed in 45% of the patients at a mean of 17 months postoperatively and was significantly more common in younger patients. Preoperative cortical thinning was completely regenerated in 84% of patients at a mean of 10 months postoperatively. No complications related to the implanted UDPHAp were observed. In a pediatric patient with bone sarcoma, when the defect after fibular resection was filled with UDPHAp implants, radiography showed complete resorption of the implant and clear formation of cortex and marrow in the resected part of the fibula. The patient could walk well without crutches and participate in sports activities. UDPHAp is a useful bone graft substitute for the treatment of benign bone tumors, and the use of this material has a low complication rate. We also review and discuss the potential of UDPHAp as a bone graft substitute in the clinical setting of orthopedic surgery.
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PURPOSE: The second-look arthroscopic score of pullout repair for medial meniscus posterior root tears (MMPRTs) is associated with contemporaneous clinical scores and progression of cartilage damage. However, the relationship among these scores, midterm clinical scores and magnetic resonance imaging (MRI) evaluations is unknown. The relationship between the second-look arthroscopic score at 1 year and the clinical scores or MRI at 3 years was evaluated. METHODS: Sixty-three patients were included. Medial meniscus extrusion (MME) was evaluated preoperatively and at 3 years postoperatively. Clinical scores were evaluated preoperatively, and 1 and 3 years postoperatively. Meniscal healing status was assessed using the semiquantitative second-look arthroscopic score at 1 year postoperatively. Correlation coefficients between patient characteristics, postoperative clinical scores or second-look arthroscopic score and the change in MME (ΔMME) were evaluated. Multiple regression analysis was performed on the ΔMME to evaluate the effects of patient characteristics and second-look arthroscopic scores. RESULTS: No significant correlation was observed between patient characteristics and ΔMME. In contrast, a significant correlation was found between the second-look arthroscopic score and ΔMME (p < 0.001) and visual analogue scale pain score (p = 0.016) at 3 years postoperatively. In the subitems of the second-look arthroscopic score, width (p < 0.001) and stability (p = 0.009) scores also showed significant correlations with ΔMME. Multiple regression analysis showed a significant association between the second-look arthroscopic score and ΔMME (p = 0.001). CONCLUSIONS: The second-look arthroscopic score at 1 year postoperatively correlated with the ΔMME and clinical score at 3 years postoperatively. Second-look arthroscopic scores predict midterm meniscal function after pullout repair of MMPRTs. LEVEL OF EVIDENCE: Level IV.
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PURPOSE: This study aimed to evaluate the association between the progression of medial joint space (MJS) narrowing, medial meniscus extrusion (MME) and clinical scores and the tibial tunnel position in pullout repairs for medial meniscus posterior root tears (MMPRTs). METHODS: This retrospective study examined 54 patients. Changes in MJS (ΔMJS), MME (ΔMME) and clinical scores and their relationship with the tibial tunnel position were evaluated using correlation coefficients. The distance from the anatomical to technical attachment position in the tibial tunnel position was measured in the anterior and medial directions, and the direct distance was measured using the Pythagorean theorem. RESULTS: The mean ΔMJS and ΔMME were 0.6 ± 0.8 and 1.3 ± 1.3 mm, respectively, and the mean anterior, medial and direct distances were 1.4 ± 2.3, 2.2 ± 1.7 and 3.4 ± 1.7 mm, respectively. ΔMJS had a significant positive correlation with the medial (r = 0.580, p < 0.001) and direct (r = 0.559, p < 0.001) distances, while ΔMME had a significant positive correlation with direct distance (r = 0.295, p = 0.030). Several clinical scores were significantly negatively correlated with these distances. CONCLUSION: In transtibial pullout repair for MMPRTs, accurate tibial tunnel position delayed the progression of MJS narrowing and MME, leading to improved clinical outcomes. The progression of MJS narrowing was associated with the mediolateral direction of the tibial tunnel position, while the clinical scores were associated with the anteroposterior direction of the tibial tunnel position. These findings indicate the need to orient the tip of the guide in a more posterolateral direction when creating the tibial tunnel. LEVEL OF EVIDENCE: Level IV.
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Tibia , Lesiones de Menisco Tibial , Humanos , Estudios Retrospectivos , Lesiones de Menisco Tibial/cirugía , Masculino , Femenino , Persona de Mediana Edad , Tibia/cirugía , Adulto , Meniscos Tibiales/cirugía , Progresión de la Enfermedad , Articulación de la Rodilla/cirugía , Artroscopía/métodosRESUMEN
BACKGROUND: Very large chest wall resections can lead to acute thoracic insufficiency syndrome due to the interdependence of lung expansion and thoracic volume. Chest wall tumor surgeries often encounter complications, with the size of the chest wall defect being a significant predictor. Several methods for large chest wall reconstruction have been described, aiming to provide stability, prevent flail chest, and ensure airtight closure. However, no single method fulfills all requirements. Composite chest wall reconstruction using titanium plates and Gore-Tex patches has shown the potential to minimize physiologic abnormalities caused by extensive defects. CASE PRESENTATION: A 42-year-old man with myxofibrosarcoma underwent multiple surgeries, chemotherapies, and radiation therapies due to repeated local recurrences. After right arm amputation and resection of the right third to fifth ribs, a local recurrence was detected. A 30 × 40 cm chest wall defect was resected en bloc, and a titanium plate was used for three-dimensional formability, preventing flail chest and volume loss. The Gore-Tex patch was then reconstructed into an arch shape, allowing lateral thoracic mobility. The patient recovered well and did not experience respiratory dysfunction or local recurrence but later succumbed to distant metastasis. CONCLUSIONS: In this case, the combination of a titanium plate and a Gore-Tex patch proved effective for reconstructing massive lateral chest wall defects. The approach provided stability, preserved thoracic volume, and allowed for lateral mobility. While the patient achieved a successful outcome in terms of local recurrence and respiratory function, distant metastasis remained a challenge for myxofibrosarcoma patients, and its impact on long-term prognosis requires further investigation. Nevertheless, the described procedure offers promise for managing extensive chest wall defects.
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Tórax Paradójico , Sarcoma , Neoplasias Torácicas , Pared Torácica , Masculino , Humanos , Adulto , Pared Torácica/cirugía , Titanio , Mallas Quirúrgicas , Neoplasias Torácicas/cirugía , Sarcoma/patología , PolitetrafluoroetilenoRESUMEN
OBJECTIVE: Precise assessment of spinal instability is critical before and after radiotherapy (RT) for evaluating the effectiveness of RT. Therefore, we retrospectively evaluated the efficacy of RT in spinal instability over a period of 6 months after RT, utilizing the spinal instability neoplastic score (SINS) in patients with painful spinal metastasis. We retrospectively evaluated 108 patients who received RT for painful vertebral metastasis in our institution. Mechanical pain at metastatic vertebrae, radiological responses of irradiated vertebrae, and spinal instability were assessed. Follow-up assessments were done at the start of and at intervals of 1, 2, 3, 4, and 6 months after RT, with the pain disappearing in 67%, 85%, 93%, 97%, and 100% of the patients, respectively. The median SINS were 8, 6, 6, 5, 5, and 4 at the beginning and after 1, 2, 3, 4, and 6 months of RT, respectively. Multivariate analysis revealed that posterolateral involvement of spinal elements (PLISE) was the only risk factor for continuous potentially unstable/unstable spine at 1 month. In conclusion, there was improvement of pain, and recalcification results in regaining spinal stability over time after RT although vertebral body collapse and malalignment occur in some irradiated vertebrae. Clinicians should pay attention to PLISE in predicting continuous potentially unstable/unstable spine.
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Neoplasias de la Columna Vertebral , Humanos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias de la Columna Vertebral/radioterapia , Neoplasias de la Columna Vertebral/secundario , Estudios Retrospectivos , Anciano , Adulto , Inestabilidad de la Articulación/etiología , Dolor/etiología , Dolor/radioterapia , Anciano de 80 o más AñosRESUMEN
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. Here, we demonstrate in vitro and in vivo antitumor effects of OBP-702 in combination with ionizing radiation against human STS cells (HT1080, NMS-2, SYO-1). OBP-702 synergistically promoted the antitumor effect of ionizing radiation in the STS cells by suppressing the expression of B-cell lymphoma-X large (BCL-xL) and enhancing ionizing radiation-induced apoptosis. The in vivo experiments demonstrated that this combination therapy significantly suppressed STS tumors' growth. Our results suggest that OBP-702 is a promising antitumor reagent for promoting the radiosensitivity of STS tumors.
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Viroterapia Oncolítica , Tolerancia a Radiación , Sarcoma , Proteína p53 Supresora de Tumor , Proteína bcl-X , Sarcoma/terapia , Sarcoma/radioterapia , Humanos , Viroterapia Oncolítica/métodos , Proteína bcl-X/genética , Proteína bcl-X/metabolismo , Línea Celular Tumoral , Animales , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Ratones , Apoptosis , Adenoviridae/genéticaRESUMEN
BACKGROUND: The purpose of this study was to examine two techniques for Carpal Tunnel Syndrome, mini-Open Carpal Tunnel Release (mini-OCTR) and Endoscopic Carpal Tunnel Release (ECTR), to compare their therapeutic efficacy. METHODS: Sixteen patients who underwent mini-OCTR in palmar incision and 17 patients who underwent ECTR in the wrist crease incision were included in the study. All patients presented preoperatively and at 1, 3, and 6 months postoperatively and were assessed with the Visual Analogue Scale (VAS) and the Disabilities of Arm, Shoulder and Hand Score (DASH). We also assessed the pain and cosmetic VAS of the entire affected hand or surgical wound, and the patient's satisfaction with the surgery. RESULTS: In the objective evaluation, both surgical techniques showed improvement at 6 months postoperatively. The DASH score was significantly lower in the ECTR group (average = 3 months: 13.6, 6 months: 11.9) than in the mini-OCTR group (average = 3 months: 27.3, 6 months: 20.6) at 3 and 6 months postoperatively. Also, the pain VAS score was significantly lower in the ECTR group (average = 17.1) than in the mini-OCTR group (average = 36.6) at 3 months postoperatively. The cosmetic VAS was significantly lower in the ECTR group (average = 1 month: 15.3, 3 months: 12.2, 6 months: 5.41) than in the mini-OCTR group (average = 1 month: 33.3, 3 months: 31.2, 6 months: 24.8) at all time points postoperatively. Patient satisfaction scores tended to be higher in the ECTR group (average = 3.3) compared to the mini-OCTR group (average = 2.7). CONCLUSIONS: ECTR in wrist increase incision resulted in better pain and cosmetic recovery in an early postoperative phase compared with mini-OCTR in palmar incision. Our findings suggest that ECTR is an effective technique for patient satisfaction.
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Síndrome del Túnel Carpiano , Humanos , Síndrome del Túnel Carpiano/cirugía , Muñeca , Resultado del Tratamiento , Endoscopía/métodos , DolorRESUMEN
PURPOSE: We aimed to evaluate the longitudinal changes in medial meniscus extrusion (MME) and clinical scores at multiple time points up to 3 years after pullout repair for medial meniscus posterior root tears (MMPRTs). METHODS: This retrospective case series study included 64 patients who underwent pullout repair for MMPRTs and four MRI evaluations (preoperatively and at 3 months, 1 year, and 3 years postoperatively). MME was measured during the same time points. Clinical scores were assessed four times: preoperatively and at 1, 2, and 3 years postoperatively. Additionally, a multivariate analysis was performed on the change in MME (ΔMME) from the preoperative measurement point to 3 years postoperatively. RESULTS: The ΔMME per month from the preoperative measurement point to 3 months postoperatively, from 3 months to 1 year postoperatively, and from 1 to 3 years postoperatively were 0.30, 0.05, and 0.01 mm/month, respectively. All clinical scores significantly improved 3 years postoperatively (p < 0.001). In a multiple regression analysis for ΔMME from the preoperative measurement point to 3 years postoperatively, sex significantly affected the outcome (p = 0.039). CONCLUSION: Following pullout repair for MMPRTs with well-aligned lower extremities, although MME progression could not be entirely prevented, the rate of progression decreased over time, and clinical scores improved. In particular, MME progressed markedly during the first 3 months postoperatively. Additionally, sex had a significant influence on MME progression, suggesting that males may be able to expand the indications of pullout repair for MMPRTs.
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Imagen por Resonancia Magnética , Meniscos Tibiales , Lesiones de Menisco Tibial , Humanos , Lesiones de Menisco Tibial/cirugía , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Meniscos Tibiales/cirugía , Meniscos Tibiales/diagnóstico por imagen , Resultado del Tratamiento , Artroscopía/métodos , Factores SexualesRESUMEN
BACKGROUND: Only a few studies have assessed signal intensity after pullout repair for medial meniscus posterior root (MMPR) tears (MMPRTs) based on mid-term magnetic resonance imaging (MRI) evaluations. Therefore, this study aimed to assess the quantitative signal intensity of repaired posterior roots over time, up to 3 years postoperatively, and the related factors. METHODS: This study included 36 patients who underwent pullout repair for MMPRTs and MRI examinations using the same MRI system. The signal intensity of the repaired posterior roots was quantitatively evaluated using the signal-to-noise quotient (SNQ). Medial meniscus extrusion (MME), the SNQ for MMPR, and clinical scores were assessed over 3 years postoperatively. RESULTS: MME progressed over time until 3 years postoperatively, and its progression during this period was 1.61 ± 1.44 mm. The SNQ for MMPR decreased over time until 3 years postoperatively, and the change in the SNQ from 3 months to 3 years postoperatively (ΔSNQ) was 2.69 ± 1.69. All clinical scores significantly improved (p < 0.001). ΔSNQ was significantly correlated with body weight (correlation coefficient = -0.424, p = 0.010) and body mass index (correlation coefficient = -0.330, p = 0.050). However, ΔSNQ was not significantly correlated with preoperative or postoperative clinical scores. CONCLUSION: After pullout repair for MMPRTs, MME progressed to 3 years postoperatively. However, the signal intensity of the repaired posterior roots decreased, and clinical scores improved over time until 3 years postoperatively. Patient weight and body mass index were significantly correlated with the reduced signal intensity of the repaired posterior roots, suggesting that weight assessment in patients with MMPRTs is crucial. LEVEL OF EVIDENCE: IV.
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Imagen por Resonancia Magnética , Lesiones de Menisco Tibial , Humanos , Imagen por Resonancia Magnética/métodos , Lesiones de Menisco Tibial/cirugía , Lesiones de Menisco Tibial/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Adulto , Meniscos Tibiales/cirugía , Meniscos Tibiales/diagnóstico por imagen , Artroscopía/métodos , Estudios Retrospectivos , Estudios de SeguimientoRESUMEN
BACKGROUND: Paired related-homeobox 1 (PRRX1) is a transcription factor in the regulation of developmental morphogenetic processes. There is growing evidence that PRRX1 is highly expressed in certain cancers and is critically involved in human survival prognosis. However, the molecular mechanism of PRRX1 in cancer malignancy remains to be elucidated. METHODS: PRRX1 expression in human Malignant peripheral nerve sheath tumours (MPNSTs) samples was detected immunohistochemically to evaluate survival prognosis. MPNST models with PRRX1 gene knockdown or overexpression were constructed in vitro and the phenotype of MPNST cells was evaluated. Bioinformatics analysis combined with co-immunoprecipitation, mass spectrometry, RNA-seq and structural prediction were used to identify proteins interacting with PRRX1. RESULTS: High expression of PRRX1 was associated with a poor prognosis for MPNST. PRRX1 knockdown suppressed the tumorigenic potential. PRRX1 overexpressed in MPNSTs directly interacts with topoisomerase 2 A (TOP2A) to cooperatively promote epithelial-mesenchymal transition and increase expression of tumour malignancy-related gene sets including mTORC1, KRAS and SRC signalling pathways. Etoposide, a TOP2A inhibitor used in the treatment of MPNST, may exhibit one of its anticancer effects by inhibiting the PRRX1-TOP2A interaction. CONCLUSION: Targeting the PRRX1-TOP2A interaction in malignant tumours with high PRRX1 expression might provide a novel tumour-selective therapeutic strategy.
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ADN-Topoisomerasas de Tipo II , Transición Epitelial-Mesenquimal , Proteínas de Homeodominio , Proteínas de Unión a Poli-ADP-Ribosa , Humanos , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , ADN-Topoisomerasas de Tipo II/genética , ADN-Topoisomerasas de Tipo II/metabolismo , Pronóstico , Proteínas de Unión a Poli-ADP-Ribosa/genética , Proteínas de Unión a Poli-ADP-Ribosa/metabolismo , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Ratones , Animales , Neoplasias de la Vaina del Nervio/genética , Neoplasias de la Vaina del Nervio/patología , Neoplasias de la Vaina del Nervio/metabolismo , Transducción de SeñalRESUMEN
Inorganic biomaterials are used in various orthopedic and dental implants. Nevertheless, they cause clinical issues such as loosening of implants and patient morbidity. Therefore, inspired by mussel adhesive proteins, we aimed to design an adhesive and dimer-forming highly active bone morphogenetic protein-2 (BMP-2) using bioorthogonal chemistry, in which recombinant DNA technology was combined with enzymatic modifications, to achieve long-term osseointegration with titanium. The prepared BMP-2 exhibited substantially higher binding activity than wild-type BMP-2, while the adhered BMP-2 was more active than soluble BMP-2. Therefore, the adhesive BMP-2 was immobilized onto titanium wires and screws and implanted into rat bones, and long-term osteogenesis was evaluated. Adhesive BMP-2 promoted the mechanical binding of titanium to bones, enabling efficient bone regeneration and effective stabilization of implants. Thus, such adhesive biosignaling proteins can be used in regenerative medicine.
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Regeneración Ósea , Titanio , Ratas , Animales , Humanos , Titanio/farmacología , Prótesis e Implantes , Osteogénesis , OseointegraciónRESUMEN
BACKGROUND: Despite good clinical results, repair of medial meniscus (MM) posterior root tears (MMPRTs) may not completely prevent knee osteoarthritis progression. This study evaluated changes in the medial joint space (MJS) during the first and second years after repair, compared to narrowing in the contralateral knee, using fixed-flexion view (FFV) radiographs. METHODS: Fifty-four patients who underwent pull-out repair for a unilateral MMPRT were included. FFV radiographs were obtained pre-operatively and at the 1- and 2-year post-repair timepoints to evaluate changes in the MJS and Kellgren-Lawrence grade bilaterally. Clinical outcomes were also evaluated. RESULTS: The change in the MJS was greater in MMPRT knees than in contralateral knees during the first year (0.48 ± 0.80 mm vs. 0.09 ± 0.49 mm, p < 0.001), but this difference lessened in the second year (0.09 ± 0.36 mm vs. 0.07 ± 0.38 mm, p = 0.285). Kellgren-Lawrence grade progression in MMPRT knees was less in the second year. Clinical outcomes significantly improved at both 1 and 2 years post-repair than the pre-operative values (p < 0.001), with continued improvement in clinical outcomes in the second year. There was no significant correlation between patient characteristics and the change in the MJS from preoperatively to 2 years postoperatively. CONCLUSION: Pull-out repair for MMPRTs did not completely prevent MJS narrowing, but the rate of narrowing decreased in the second year (mean, 0.09 mm) compared to that in the first year (mean, 0.48 mm). MJS narrowing in the second year after MM posterior root repair was comparable to that of the contralateral knee. Clinical outcomes further improved over the second year after repair. LEVEL OF EVIDENCE: IV.
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Articulación de la Rodilla , Meniscos Tibiales , Osteoartritis de la Rodilla , Lesiones de Menisco Tibial , Humanos , Femenino , Masculino , Lesiones de Menisco Tibial/cirugía , Lesiones de Menisco Tibial/diagnóstico por imagen , Estudios de Seguimiento , Persona de Mediana Edad , Meniscos Tibiales/cirugía , Meniscos Tibiales/diagnóstico por imagen , Osteoartritis de la Rodilla/cirugía , Osteoartritis de la Rodilla/diagnóstico por imagen , Adulto , Articulación de la Rodilla/cirugía , Articulación de la Rodilla/diagnóstico por imagen , Progresión de la Enfermedad , Radiografía , Estudios RetrospectivosRESUMEN
BACKGROUND: Soft tissue sarcoma (STS) has various histological types and is rare, making it difficult to evaluate the malignancy of each histological type. Thus, comprehensive histological grading is most important in the pathological examination of STS. The Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grading system is most commonly used in daily pathological analysis of STS. Among the FNCLCC grading system parameters, mitotic count is a key morphological parameter reflecting the proliferative activity of tumor cells, although its reproducibility may be lacking. Here, we compared the prognostic utility of the conventional and modified FNCLCC grading systems in JCOG1306. METHODS: We analyzed 140 patients with non-small round cell sarcoma. We performed Ki-67 immunostaining using open biopsy specimens before preoperative chemotherapy in all patients. We assessed histological grade in individual cases by conventional FNCLCC grading (tumor differentiation, mitotic count, and necrosis) and modified FNCLCC grading using the Ki-67 labeling index instead of mitotic count. We conducted univariable and multivariable Cox regression analyses to investigate the influence of grade on overall survival. RESULTS: In univariable analysis, prognosis was worse for patients with conventional FNCLCC Grade 3 tumors compared with Grade 1 or 2 tumors (hazard ratio [HR] 4.21, 95% confidence interval [CI] 1.47-12.05, P = 0.008). Moreover, prognosis was worse in patients with modified FNCLCC Grade 3 tumors compared with Grade 1 or 2 tumors (HR 4.90, 95% CI 1.64-14.65, P = 0.004). In multivariable analysis including both conventional and modified FNCLCC grading, the modified grading more strongly affected overall survival (HR 6.70, 95% CI 1.58-28.40, P = 0.010). CONCLUSIONS: The modified FNCLCC grading system was superior to the conventional system in predicting the prognosis of patients with non-small round cell sarcoma according to this supplementary analysis of data from the randomized controlled trial JCOG1306.
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Antígeno Ki-67 , Clasificación del Tumor , Humanos , Antígeno Ki-67/análisis , Antígeno Ki-67/metabolismo , Femenino , Masculino , Pronóstico , Persona de Mediana Edad , Anciano , Adulto , Sarcoma/patología , Sarcoma/mortalidad , Sarcoma/metabolismoRESUMEN
We investigated the effects of a Tankyrase (TNKS-1/2) inhibitor on mechanical stress-induced gene expression in human chondrocytes and examined TNKS-1/2 expression in human osteoarthritis (OA) cartilage. Cells were seeded onto stretch chambers and incubated with or without a TNKS-1/2 inhibitor (XAV939) for 12 h. Uni-axial cyclic tensile strain (CTS) (0.5 Hz, 8% elongation, 30 min) was applied and the gene expression of type II collagen a1 chain (COL2A1), aggrecan (ACAN), SRY-box9 (SOX9), TNKS-1/2, a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), and matrix metalloproteinase-13 (MMP-13) were examined by real-time PCR. The expression of ADAMTS-5, MMP-13, nuclear translocation of nuclear factor-κB (NF-κB), and ß-catenin were examined by immunocytochemistry and Western blotting. The concentration of IL-1ß in the supernatant was examined by enzyme-linked immunosorbent assay (ELISA). TNKS-1/2 expression was assessed by immunohistochemistry in human OA cartilage obtained at the total knee arthroplasty. TNKS-1/2 expression was increased after CTS. The expression of anabolic factors were decreased by CTS, however, these declines were abrogated by XAV939. XAV939 suppressed the CTS-induced expression of catabolic factors, the release of IL-1ß, as well as the nuclear translocation of NF-κB and ß-catenin. TNKS-1/2 expression increased in mild and moderate OA cartilage. Our results demonstrated that XAV939 suppressed mechanical stress-induced expression of catabolic proteases by the inhibition of NF-κB and activation of ß-catenin, indicating that TNKS-1/2 expression might be associated with OA pathogenesis.
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Cartílago Articular , Osteoartritis , Tanquirasas , Humanos , beta Catenina/metabolismo , Cartílago Articular/metabolismo , Células Cultivadas , Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Interleucina-1beta/metabolismo , Metaloproteinasa 13 de la Matriz/genética , Metaloproteinasa 13 de la Matriz/metabolismo , FN-kappa B/metabolismo , Osteoartritis/metabolismo , Péptido Hidrolasas/efectos de los fármacos , Péptido Hidrolasas/metabolismo , Estrés Mecánico , Tanquirasas/antagonistas & inhibidoresRESUMEN
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. In this study, we present the diagnostic potential of green fluorescent protein (GFP)-expressing oncolytic adenovirus OBP-401 for assessing virotherapy sensitivity using bone and soft-tissue sarcomas. OBP-401-mediated GFP expression was significantly associated with the therapeutic efficacy of OBP-401 in human bone and soft-tissue sarcomas. In the tumor specimens from 68 patients, malignant and intermediate tumors demonstrated significantly higher expression levels of coxsackie and adenovirus receptor (CAR) and hTERT than benign tumors. OBP-401-mediated GFP expression was significantly increased in malignant and intermediate tumors with high expression levels of CAR and hTERT between 24 and 48 h after infection. Our results suggest that the OBP-401-based GFP expression system is a useful tool for predicting the therapeutic efficacy of oncolytic virotherapy on bone and soft-tissue sarcomas.