p53-Armed Oncolytic Virotherapy Improves Radiosensitivity in Soft-Tissue Sarcoma by Suppressing BCL-xL Expression.

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.

Light and heavy chain deposition disease with focal amyloid deposition diagnosed with mass spectrometry: a case report.

BACKGROUND: Light and heavy chain deposition disease (LHCDD) is a rare condition characterised by the deposition of immunoglobulin components in the kidneys. Similarly, Amyloidosis is also caused by the deposition of light chain and/or heavy chain components of immunoglobulins which are folded into amyloid fibrils characterised by Congophilic deposits that exhibit apple-green birefringence under polarised light. Only a handful of reports describing LHCDD with amyloid fibril deposition have been previously published, however, none have characterized the composition of the deposited immunoglobulin components via mass spectrometry. CASE PRESENTATION: We report a case of a 79-year-old Japanese woman with nephrotic syndrome. Bone marrow aspiration revealed a slight proliferation of plasma cells (under 10%). Immunofluorescence assessment of renal biopsy showed amyloid-like deposits in the glomerulus that were positive for IgA and kappa. Further, the Congo red staining of the deposits was faintly positive, and only a slight birefringence was detected. Electron microscopy confirmed fine fibrillar structures and non-amyloid deposits. Finally, mass spectrometry revealed that the deposits were composed of abundant amounts of light chain with small amounts of heavy chain. Therefore, the patient was diagnosed with LHCDD and focal amyloid deposition. Chemotherapy was subsequently initiated, which resulted in haematological and renal response. Under polarised light, faint birefringence with Congo red staining and periodic acid-methenamine silver positivity indicated that the deposits were mostly non-amyloid fibrils with a small component of amyloid fibrils. Generally, the diagnosis of heavy- and light-chain amyloidosis is defined by greater heavy chain deposition compared to the light chain. However, in our case, contrary to the definition, the light-chain deposition was far greater than that of the heavy-chain. CONCLUSIONS: This is the first case of LHCDD with focal amyloid deposition diagnosed by analysing the glomerular deposits by mass spectrometry.

Hip Fractures after Intramedullary Nailing Fixation for Atypical Femoral Fractures: Three Cases.

Secondary hip fractures (SHFs) rarely occur after intramedullary nailing (IMN) fixation without femoral neck fixation for atypical femoral fractures (AFFs). We report three cases of older Japanese women who sustained SHFs presumably caused by osteoporosis and peri-implant stress concentration around the femoral neck after undergoing IMN without femoral neck fixation for AFF. All cases were fixed with malalignment. In AFF patients, postoperative changes due to postoperative femoral bone malalignment may affect the peri-implant mechanical environment around the femoral neck, which can result in insufficiency fractures. At the first AFF surgery, we recommend femoral neck fixation after adequate reduction is achieved.

Telomerase-specific oncolytic immunotherapy for promoting efficacy of PD-1 blockade in osteosarcoma.

Immune checkpoint inhibitors including anti-programmed cell death 1 (PD-1) antibody have recently improved clinical outcome in certain cancer patients; however, osteosarcoma (OS) patients are refractory to PD-1 blockade. Oncolytic virotherapy has emerged as novel immunogenic therapy to augment antitumor immune response. We developed a telomerase-specific replication-competent oncolytic adenovirus OBP-502 that induces lytic cell death via binding to integrins. In this study, we assessed the combined effect of PD-1 blockade and OBP-502 in OS cells. The expression of coxsackie and adenovirus receptor (CAR), integrins αvß3 and αvß5, and programmed cell death ligand 1 (PD-L1) was analyzed in two murine OS cells (K7M2, NHOS). The cytopathic activity of OBP-502 in both cells was analyzed using the XTT assay. OBP-502-induced immunogenic cell death was assessed by analyzing the level of extracellular ATP and high-mobility group box protein B1 (HMGB1). Subcutaneous tumor models for K7M2 and NHOS cells were used to evaluate the antitumor effect and number of tumor-infiltrating CD8+ cells in combination therapy. K7M2 and NHOS cells showed high expression of integrins αvß3 and αvß5, but not CAR. OBP-502 significantly suppressed the viability of both cells, in which PD-L1 expression and the release of ATP and HMGB1 were significantly increased. Intratumoral injection of OBP-502 significantly augmented the efficacy of PD-1 blockade on subcutaneous K2M2 and NHOS tumor models via enhancement of tumor-infiltrating CD8+ T cells. Our results suggest that telomerase-specific oncolytic virotherapy is a promising antitumor strategy to promote the efficacy of PD-1 blockade in OS.

Effect of physical therapy on early knee osteoarthritis with medial meniscal posterior tear assessed by MRI T2 mapping and 3D-to-2D registration technique: A prospective intervention study.

Objectives: The purpose of this study was to verify that exercise aimed at improving knee kinematics in early-stage knee osteoarthritis (OA) patients with medial meniscus posterior root tears (MMPRTs) reduces knee adduction angle during gait and prevents rapid cartilage degeneration in the medial compartment of the knee.Methods: Subjects were randomly assigned to an adapting alignment exercise (AAE) group, with the goal of improving knee kinematics, and a muscle training and exercise (MTE) group. Before the start of the six-month intervention and following its completion, we performed an analysis of knee kinematics during gait using a 3D-to-2D registration technique and identified the area of cartilage degeneration using MRI T2 mapping.Results: The amount of change between pre- and post-intervention measurements of the maximum angle of adduction was 0.48° (95% CI: -0.14, 1.09) in the MTE group and -0.40° (-0.84, 0.04) in the AAE group (p = .039). The amount of change in the area of cartilage degeneration according to MRI T2 mapping expressed as MTE/AAE group was 7.7 mm2 (-0.4, 15.8)/-2.7 mm2 (-10.8, 5.3) at the posterior knee (p = .043).Conclusion: AAE could be a potential treatment method that improves the natural course of knee OA with MMRPTs.

Mini-open excision of osteoid osteoma using intraoperative O-arm/Stealth navigation.

BACKGROUND: Although osteoid osteomas have traditionally been treated by surgical excision, radiofrequency ablation (RFA) has gained favor as a less invasive procedure. However, RFA is contraindicated for osteoid osteomas close to the skin or crucial neurovascular structures, and is not covered by national health insurance in Japan. The aim of the present study was to evaluate the efficacy of surgical excision of osteoid osteomas using intraoperative navigation. METHODS: We performed a retrospective review of five patients with osteoid osteoma who underwent a mini-open excision using O-arm/Stealth navigation at our institution. The osteoid osteomas were excised using a cannulated cutter or curetted out with the assistance of navigation. RESULTS: Complete excision was achieved in all patients, which was confirmed by pathological examination. The mean skin incision was 2.1 cm (range, 1.5 to 3.0 cm) and the mean duration required for setup three-dimensional image was 15 min (range, 12 to 20 min). Although the mean visual analog scale score was 7 (range, 4 to 8) before surgery, all patients experienced relief from their characteristic pain immediately after surgery, with the mean scores of 2.2 (range, 1 to 3) and 0 at 2 days and 4 weeks after surgery, respectively. There was no intra-operative complication related to the navigation and no recurrence was observed during the mean follow-up period of 25 months (range, 13 to 33 months). CONCLUSIONS: Mini-open excision using intraoperative O-arm/Stealth navigation is a safe and accurate procedure for patients with osteoid osteoma, which could cover the limitation of RFA.

Synthesis and evaluation of novel opioid ligands with a C-homomorphinan skeleton.

As the reports about C-homomorphinans with the seven-membered C-ring are much fewer than those of morphinan derivatives with a six-membered C-ring, we attempted to synthesize C-homomorphinan derivatives and to evaluate their opioid activities. C-Homomorphinan 5 showed sufficient binding affinities to the opioid receptors. C-Homomorphinan derivatives possessing the δ address moiety such as indole (NTI-type), quinoline, or benzylidene (BNTX-type) functionalities showed the strongest binding affinities for the δ receptor among the three types of opioid receptors, which indicated that the C-homomorphinan skeleton sufficiently functions as a message-part in the ligand. Although NTI-type compound 8 and quinoline compound 9 with C-homomorphinan scaffold exhibited lower affinities and selectivities for the δ receptor than the corresponding morphinan derivatives did, both the binding affinity and selectivity for the δ receptor of BNTX-type compound 12 with a seven-membered C-ring were improved compared with the corresponding compounds with a six-membered C-ring including BNTX itself. BNTX-Type compound 12 was the most selective δ receptor antagonist among the tested compounds.

A pilot study comparing the efficacy of radiofrequency and microwave diathermy in combination with intra-articular injection of hyaluronic acid in knee osteoarthritis.

[Purpose] This study aimed to compare the efficacy of radiofrequency diathermy with that of microwave diathermy in combination with intra-articular injection of hyaluronic acid into the knee of patients with osteoarthritis (OA). [Subjects] A total of 17 patients with knee OA were enrolled. The participants were randomly divided into two groups: a radiofrequency diathermy group (RF group, 9 subjects), and a microwave diathermy group (MW group, 8 subjects). [Methods] Subjects received radiofrequency or microwave thermal therapy 3 times at 1-week intervals. Intra-articular injection of hyaluronic acid was administered 10 min before every thermal therapy session. The outcome was evaluated using the Japan Orthopaedic Association (JOA) and the Lequesne Index (LI) at baseline, at weeks 1 (1 week after the first thermal therapy) and 3 (1 week after the last thermal therapy). [Results] The JOA scale increased significantly after three sessions of thermal therapy in the RF group, while no significant increase was observed in the MW group. LI decreased significantly after 3 weeks in the RF group. In the MW group, there was no significant difference in LI between the two time points. [Conclusion] This study revealed that symptom relief in patients with knee OA was greater with radiofrequency diathermy than with microwave diathermy with concurrent use of hyaluronic acid injection, presumably due to the different heating characteristics of the two methods.

Magnetically promoted rapid immunoreactions using functionalized fluorescent magnetic beads: a proof of principle.

BACKGROUND: Accurate detection and monitoring of disease-related biomarkers is important in understanding pathophysiology. We devised a rapid immunoreaction system that uses submicrometer polymer-coated fluorescent ferrite (FF) beads containing both ferrites (magnetic iron oxide) and fluorescent europium complexes. METHODS: FF beads were prepared by encapsulation of hydrophobic europium complexes into the polymer layers of affinity magnetic beads using organic solvent. A sandwich immunoassay using magnetic collection of antibody-coated FF beads to a specific place was performed. Brain natriuretic peptide and prostate-specific antigen were selected as target detection antigens to demonstrate the feasibility of this approach. An immunohistochemical staining using magnetic collection of antibody-coated FF beads onto carcinoma cell samples was also performed. RESULTS: The sandwich immunoassays, taking advantage of the magnetic collection of antibody-coated FF beads, detected target antigens within 5 min of sample addition. Without magnetic collection, the sandwich immunoassay using antibody-coated FF beads required long times, similar to conventional immunoassays. Using the magnetic collection of antibody-coated FF beads, immunohistochemical staining enabled discrimination of carcinoma cells within 20 min. CONCLUSIONS: This proof of principle system demonstrates that immunoreactions involving the magnetic collection of antibody-coated FF beads allow acceleration of the antigen-antibody reaction. The simple magnetic collection of antibody-coated FF beads to a specific space enables rapid detection of disease-related biomarkers and identification of carcinoma cells.

Posterior buttress plate with locking compression plate for Hoffa fracture.

BACKGROUND: Many difficulties are associated with treating fractures of the posterior condyle of the femur (Hoffa fractures). Anatomical reduction and internal fixation are optimum for such intra-articular fractures. Some surgeons use anteroposterior screws to achieve direct stability. However, screw fixation is not adequate in some cases. To increase stability, we treat Hoffa fractures with a posterior buttress plate; we use a twisted, 1/3 tubular plate at the posterior surface and a supplementary, locking compression plate (LCP) for additional stability. METHODS: Patients who had sustained Hoffa fractures between January 2006 and March 2009 were included in this study. Patients comprised three males and two females with a mean age of 73.6 years at the time of surgery. A 3.5-mm 1/3 tubular plate was twisted and applied to the posterolateral aspect of the distal femur. This was combined with an LCP on the distal femur to achieve a rafting effect. RESULTS: All fractures were healed within 15 weeks. There were no instances of nonunion, infection, or implant removal. The mean range of motion was -3° to 121°. Four patients had no pain in the treated limb and one had mild pain on weight bearing. The average Oxford Knee Score was 44.6 points. All patients achieved satisfactory joint function and regained their walking ability with good clinical results. CONCLUSIONS: Improved stability associated with this technique enables patients to begin range-of-motion training and return to their normal activities sooner; this resulted in good outcome.

Two Cases of Alice in Wonderland Syndrome with a Right Occipital Lobe Lesion Caused by Isolated Cortical Venous Thrombosis.

Alice in Wonderland syndrome (AIWS) is extremely rare, occurring more often in young individuals than in older adults. Symptoms of this syndrome typically include an altered body image, size perception, and time perception. However, the pathophysiology and lesions responsible for this syndrome remain unclear. In most cases, specific lesions cannot be identified using computed tomography or magnetic resonance imaging. Two patients with isolated cortical venous thrombosis in the right occipital area experienced transient visual symptoms of AIWS. Furthermore, a literature search indicated that AIWS with visual distortions is associated with right occipital lobe lesions, supporting the findings of our study.

Distribution and progression of cerebral amyloid angiopathy in early-onset V30M (p.V50M) hereditary ATTR amyloidosis.

BACKGROUND: Cerebral amyloid angiopathy (CAA) is becoming the most common and serious complications in long-lived hereditary ATTR amyloidosis patients. It is therefore imperative to elucidate the characteristics of ATTR-type CAA and develop useful biomarkers. METHODS: We enrolled 34 ATTRv amyloidosis patients with the V30M (p.V50M) variant for analysis with three-dimensional stereotactic surface projection z score imaging of Pittsburgh compound B (PiB)-PET. RESULTS: Eight patients exhibited central nervous system (CNS) symptoms. Seven patients suffered transient focal neurologic episodes, and 2 patients each experienced cerebellar haemorrhages or cognitive decline. The amount of 11C-PiB accumulation increased as a function of disease duration. 11C-PiB-PET abnormalities were seen at 8 years from onset and were associated with CNS manifestations from 12 years. The annual increase rate of the standardised uptake value ratio (SUVR) in female patients was significantly higher than in male patients. CNS amyloid deposition started in the upper middle surface of the cerebellar cortex, and then spread out over the entire surface of the cerebellum, Sylvian fissure, and anterior part of the longitudinal fissure of the cerebrum. CONCLUSIONS: PiB-PET is a useful biomarker for the early detection and treatment evaluation of ATTR-type CAA. Female gender is associated with more rapid progression of ATTR-type CAA.

Application of mesh plate for the treatment of an osteochondral fracture of the medial femoral condyle with medial wall fracture: A case report.

Osteochondral fractures of the medial femoral condyle accompanied by medial wall fracture are rare. Surgeons often have difficulty in selecting the most appropriate treatment, especially the plating technique for internal fixation since the available femoral locking plates are made to fit the femoral lateral condyle and there is no anatomical plate for the medial condyle. We, herein, report a case of a 44-year- old female patient who suffered from an osteochondral fracture of the medial femoral condyle accompanied by medial wall fracture treated by a low-profile mesh plate contoured to fit around the fracture site. Bone union was achieved at postoperative week 12 and the patient was able to return to her normal activities. At the 16-month follow-up exam, the patient's functional and clinical outcomes were satisfactory. Her Oxford knee score was 47 points, and the Western Ontario and McMaster Universities Arthritis Index scores were 2 points for pain and 5 points for physical function. We believe that the mesh plate has several advantages. This is the first report of using a mesh plate for the femur, and we were able to achieve good results. We conclude that treatment with a mesh plate can be applied in well- selected patients with medial femoral condyle osteochondral fracture and has the potential to be applied to the treatment of fractures in various regions in the future.

Effectiveness of Cement Augmentation on Early Postoperative Mobility in Patients Treated for Trochanteric Fractures with Cephalomedullary Nailing: A Prospective Cohort Study.

Fixation using cephalomedullary nails (CMNs) with additional cement augmentation (CA) was developed as a novel treatment option for the osteosynthesis of osteoporotic trochanteric fractures, though the effectiveness of CA on early postoperative mobility remains uncertain. This multicenter prospective cohort study aimed to estimate the effectiveness of CA on early postoperative mobility in patients with trochanteric fractures. We enrolled patients with femoral trochanteric fractures aged >60 years who were able to walk independently before the injury. The primary outcome was the postoperative 3-day cumulated ambulation score (CAS); the secondary outcome was the visual analog scale (VAS) pain score at rest and during movement on postoperative days 1−3. The outcomes of the patients treated using CMNs with or without CA were compared. Sixty-three eligible patients were categorized into CA (n = 32) and control (n = 31) groups. In univariate analysis, the CA group had significantly higher CAS values, lower VAS scores at rest on day 1 postoperatively, and lower VAS scores during movement on day 3. In multivariable linear regression analyses, the CA group had significantly higher CAS values (beta, 2.1; 95% confidence interval, 0.5 to 3.6; p = 0.01). The CA group had a negative adjusted beta value in their VAS scores during movement. This study indicated that CA was associated with a high CAS value in patients with geriatric trochanteric fractures. However, CA was not associated with pain reduction at rest and during movement during the initial postoperative days.

Moyamoya Disease-like Cerebrovascular Stenotic Lesions Are an Important Phenotype of POEMS Syndrome-associated Vasculopathy.

A 41-year-old woman was diagnosed with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome based on polyneuropathy, hepatosplenomegaly, sclerotic bone lesions, IgA-λ M-protein, and an elevated level of serum vascular endothelial growth factor. One month after the initiation of lenalidomide-dexamethasone with prophylactic aspirin, she developed facial paralysis, dysarthria, and left hemiplegia. Multiple cerebral infarctions and internal carotid artery stenosis were detected. Five months after switching to pomalidomide-dexamethasone, she again developed cerebral infarction. Progressed stenotic lesions in the bilateral internal carotid artery terminal portions were detected, showing a moyamoya disease-like appearance. Quasi-moyamoya disease can be an important phenotype of systemic vasculopathies of POEMS syndrome.

Delayed Detection of Hydrocephalus following Mildly Traumatic Subarachnoid Hemorrhage in Corticobasal Degeneration: A Case Report.

A 65-year-old woman presented with slowly progressive aphasia with gait disturbance associated with parkinsonism. She experienced a fall that resulted in a brain trauma. Brain imaging revealed a small amount of subarachnoid hemorrhage (SAH) with intraventricular bleeding. Despite conservative therapy, gait disturbance and hyporesponsiveness gradually deteriorated following that brain trauma. One month later, she was transferred to our hospital, and magnetic resonance imaging revealed prominent communicating hydrocephalus. A ventriculoperitoneal shunt and brain biopsy were performed. Neurosurgical intervention did not improve the patient's neurological condition. Clinical-pathological analysis confirmed the diagnosis of corticobasal degeneration (CBD) as an underlying disease relating to parkinsonism and aphasia. In patients with parkinsonism with high risks of falling, attention should be paid to neurological deterioration due to traumatic SAH-related hydrocephalus. Particularly, in patients with aphasia such as in those with CBD, delayed detection of posttraumatic complications might cause poor responsiveness to surgical intervention.

Citrus hassaku Extract Powder Increases Mitochondrial Content and Oxidative Muscle Fibers by Upregulation of PGC-1α in Skeletal Muscle.

Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is expressed in skeletal muscles and regulates systemic metabolism. Thus, nutraceuticals targeting skeletal muscle PGC-1α have attracted attention to modulate systemic metabolism. As auraptene contained in citrus fruits promotes lipid metabolism and improves mitochondrial respiration, it could increase mitochondrial function through PGC-1α. Therefore, we hypothesized that PGC-1α is activated by auraptene and investigated its effect using Citrus hassaku extract powder (CHEP) containing >80% of auraptene. C2C12 myotubes were incubated with vehicle or CHEP for 24 h; C57BL/6J mice were fed a control diet or a 0.25% (w/w) CHEP-containing diet for 5 weeks. PGC-1α protein level and mitochondrial content increased following CHEP treatment in cultured myotubes and skeletal muscles. In addition, the number of oxidative fibers increased in CHEP-fed mice. These findings suggest that CHEP-mediated PGC-1α upregulation induced mitochondrial biogenesis and fiber transformation to oxidative fibers. Furthermore, as CHEP increased the expression of the protein sirtuin 3 and of phosphorylated AMP-activated protein kinase (AMPK) and the transcriptional activity of PGC-1α, these molecules might be involved in CHEP-induced effects in skeletal muscles. Collectively, our findings indicate that CHEP mediates PGC-1α expression in skeletal muscles and may serve as a dietary supplement to prevent metabolic disorders.

Reduction quality and nail fixation ratio as bone-implant stability factors associated with reoperation for trochanteric fractures.

INTRODUCTION: Geriatric trochanteric fractures are a major global issue, and their incidence is steadily rising. Bone quality, fracture type, fracture reduction quality, implant selection, and implant placement affect bone-implant stability in osteoporotic fractures. Our aim in this study was to evaluate the association between bone-implant stability factors, including nail construct, and the rate of reoperation in a more extensive case series with comprehensive variables. METHODS: This was a retrospective cohort study of 390 patients with trochanteric fractures aged ≥60 years and treated with intramedullary nailing. The primary outcome was the rate of reoperation due to any cause. Univariate and multivariable logistic regression analyses were used to identify factors associated with reoperation. RESULTS: In this study, 15 patients (3.8%) required reoperation. Univariate analysis showed that the following variables were significantly different between patients who required reoperation and those who did not: T-score at the total hip and lumbar spine, cortical thickness index, fracture type, and reduction quality. Multivariable logistic regression analysis showed that the odds ratio (OR) for A3 fracture type was 2.76 (95% confidence interval [CI], 0.77-9.76; p=0.116) and that for inadequate reduction, assessed by computed tomography, was 2.94 (95% CI, 0.89-9.69; p=0.076). These were independent predictors of reoperation. There was only one case (6.7%) of reoperation among patients with a distal femoral fragment fixation ratio (FR) >0.8. Considering the intraoperative decision-making process, the combination of inadequate reduction and an FR ≤0.8 were associated with the highest reoperation at a rate of 9.3% (OR, 3.327; 95% CI, 1.091-10.142; p=0.043). CONCLUSIONS: Risk factors on bone-implant stability for reoperation were the reduction quality and fracture type. Regarding the intraoperative decision-making process, the selection of a nail length with an FR >0.8 is a better option when the intramedullary reduction has been maintained intraoperatively.

Oncolytic virotherapy reverses chemoresistance in osteosarcoma by suppressing MDR1 expression.

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. Here, we demonstrate the chemosensitizing effect of OBP-702 in human OS cells. MATERIALS AND METHODS: The in vitro and in vivo antitumor activities of doxorubicin (DOX) and OBP-702 were assessed using parental and DOX-resistant OS cells (U2OS, MNNG/HOS) and a DOX-resistant MNNG/HOS xenograft tumor model. RESULTS: DOX-resistant OS cells exhibited high multidrug resistant 1 (MDR1) expression, which was suppressed by OBP-702 or MDR1 siRNA, resulting in enhanced DOX-induced apoptosis. Compared to monotherapy, OBP-702 and DOX combination therapy significantly suppressed tumor growth in the DOX-resistant MNNG/HOS xenograft tumor model. CONCLUSION: Our results suggest that MDR1 is an attractive therapeutic target for chemoresistant OS. Tumor-specific virotherapy is thus a promising strategy for reversing chemoresistance in OS patients via suppression of MDR1 expression.