Search

The success of tumor oncolytic virotherapy is limited by the poor penetration of virus in tumors. Interstitial collagen fibers and the narrow spacing between cancer cells are major barriers hindering the movement of large viral particles. To bypass the cellular barrier, we tested the hypothesis that the void space produced by cancer cell apoptosis enhances the initial spread and efficacy of oncolytic herpes simplex virus (HSV). In mice with mammary tumors, apoptosis was induced by doxycycline-regulated expression/activation of CD8/caspase-8, paclitaxel, or paclitaxel plus tumor necrosis factor–related apoptosis-inducing ligand (TRAIL). In both collagen-poor and collagen-rich tumors, apoptosis or necrosis increased the initial intratumoral spread of HSV. Compared with the isolated pattern of HSV infection generally located in the center of control tumors, apoptosis induction and a single i.t. injection of virus produced an interconnected and diffuse pattern of infection, which extended from the tumor center to the periphery. This interconnected pattern of viral infection correlated with the formation of void spaces and channel-like structures in apoptosis-rich tumor areas. We also show that the i.t. injection of HSV after caspase-8 activation or paclitaxel-TRAIL pretreatment retards tumor growth, whereas HSV administration before tumor cell death induction did not improve therapeutic efficacy. Hence, our findings show that the induction of cancer cell death before the injection of oncolytic HSV enhances intratumoral virus delivery/penetration and antitumor efficacy. [Cancer Res 2008;68(10):3795–802]

Supplementary Figure 4 from Cancer Cell–Associated MT1-MMP Promotes Blood Vessel Invasion and Distant Metastasis in Triple-Negative Mammary Tumors

Supplementary Figure 1 from Cancer Cell–Associated MT1-MMP Promotes Blood Vessel Invasion and Distant Metastasis in Triple-Negative Mammary Tumors

Supplementary Table 1 from Cancer Cell–Associated MT1-MMP Promotes Blood Vessel Invasion and Distant Metastasis in Triple-Negative Mammary Tumors

Supplementary Figure 3 from Cancer Cell–Associated MT1-MMP Promotes Blood Vessel Invasion and Distant Metastasis in Triple-Negative Mammary Tumors

Supplementary Figure 6 from Cancer Cell Death Enhances the Penetration and Efficacy of Oncolytic Herpes Simplex Virus in Tumors

Supplementary Figure 5 from Cancer Cell Death Enhances the Penetration and Efficacy of Oncolytic Herpes Simplex Virus in Tumors

Supplementary Figure 3 from Cancer Cell Death Enhances the Penetration and Efficacy of Oncolytic Herpes Simplex Virus in Tumors

Supplementary Video from Cancer Cell–Associated MT1-MMP Promotes Blood Vessel Invasion and Distant Metastasis in Triple-Negative Mammary Tumors

Supplementary Figure 2 from Cancer Cell–Associated MT1-MMP Promotes Blood Vessel Invasion and Distant Metastasis in Triple-Negative Mammary Tumors

Supplementary Figure 2 from Cancer Cell Death Enhances the Penetration and Efficacy of Oncolytic Herpes Simplex Virus in Tumors

Supplementary Figure 1 from Cancer Cell Death Enhances the Penetration and Efficacy of Oncolytic Herpes Simplex Virus in Tumors

Supplementary Figure Legends 1-4, Table 1, Movie Legend from Cancer Cell–Associated MT1-MMP Promotes Blood Vessel Invasion and Distant Metastasis in Triple-Negative Mammary Tumors

Supplementary Figure Legends 1-6 from Cancer Cell Death Enhances the Penetration and Efficacy of Oncolytic Herpes Simplex Virus in Tumors

Hypothalamic aging is considered to be critical for systemic aging, and the accumulation of "exhausted glial cells" in the hypothalamus may contribute to brain dysfunction. In this study, we used normal aging mice and investigated aging-specific transcriptional identities of microglia and astrocytes in the hypothalamus. We confirmed that normal aging promoted anxiety, induced impairment of motor coordination and reduced physical strength of muscle in mice. To investigate the senescence of hypothalamic glial cells, we isolated CD11b-positive microglia and ACSA-2-positive astrocytes from the hypothalamus of aged mice using magnetic-activated cell sorting (MACS). The mRNA level of p16INK4A was dramatically increased in the hypothalamic microglia of aged mice compared to young mice. Furthermore, the expression of programmed cell death 1 (PD-1) as well as A1-like astrocyte mediators in the hypothalamic microglia was dramatically induced by aging, indicating that normal aging may produce PD-1-enriched "exhausted microglia" in the hypothalamus. Furthermore, neuroinflammatory A1-like reactive astrocytes with a p16INK4A-positive senescent state were predominantly detected in the hypothalamus of aged mice. Exhausted microglia were also detected in the prefrontal cortex of aged mice, whereas astrocytic neuroinflammation was milder than that observed in the hypothalamus, even with p16INK4A-positive senescence. These results suggest that the production of PD-1-enriched exhausted and senescent microglia and neuroinflammatory A1-like reactive astrocytes in the hypothalamus may partly contribute to aging-related emotional and physical dyscoordination.

Regular exercise may be associated with better self-rated health and sleep status. However, this correlation among various age groups, such as young, middle-aged, and older people, as well as during the COVID-19 pandemic, has not been examined. This study examined the correlation between regular exercise and self-rated health and sleep quality among adults in Japan during the COVID-19 pandemic. Data were collected using an online survey conducted between February 26 and 27, 2021. A total of 1410 adults in Japan (age range, 20–86 years) completed the online survey. Regular exercise was divided into: (1) more than 30 min of moderate exercise a day, (2) more than 2 days per week, and (3) continuous for 1 year or longer. Self-rated health and sleep quality were assessed using the Likert scale. After adjusting for multiple confounders, regular exercise was correlated with decreased poor self-rated health and poor sleep quality in middle-aged adults, however, no significant correlation was observed among young and older adults. The promotion of regular exercise among middle-aged people during the COVID-19 pandemic may contribute to better self-rated health and sleep quality status.

Undifferentiated pleomorphic sarcoma (UPS) is the second most common soft tissue sarcoma. For patients with unresectable or metastatic disease, chemotherapies are considered, but in many cases they are not curative. There is a need to identify specific molecular dysregulations that can be therapeutic targets. We focused on neurotensin receptor 1 (NTSR1), which belongs to the G-protein-coupled receptor. NTSR1 expression was upregulated in specimens from patients with UPS. Real-time polymerase chain reaction showed that expression of NTSR1 messenger RNA was 5- to 7-fold increased in UPS cells compared with myoblasts. Western blot showed a high expression of NTSR1 protein in UPS cell lines. Knockdown of NTSR1 prevented UPS cell proliferation and invasion. We confirmed that SR48692, an inhibitor of NTSR1, exhibited antitumor activities in UPS cells. The combination index showed that SR48692 and standard chemotherapeutic drugs prevented UPS cell proliferation synergistically. Mouse xenograft models showed that SR48692 inhibited extracellular signal-regulated kinase phosphorylation and enhanced the response to standard chemotherapeutic drugs. Inhibition of NTSR1 improved the effect of standard chemotherapeutic drugs for UPS. SR48692 may be a new drug for targeted UPS therapy.

Recently, we reported highly active transforming growth factor (TGF)-β and bone morphogenetic protein (BMP) signaling in human chondrosarcoma samples and concurrent downregulation of paternally expressed gene 10 (PEG10). PEG10 expression was suppressed by TGF-β signaling, and PEG10 interfered with the TGF-β and BMP-SMAD pathways in chondrosarcoma cells. However, the roles of PEG10 in bone tumors, including chondrosarcoma, remain unknown. Here, we report that PEG10 promotes SW1353 chondrosarcoma cell growth by preventing TGF-β1-mediated suppression. In contrast, PEG10 knockdown augments the TGF-β1-induced motility of SW1353 cells. Individually, TGF-β1 and PEG10 siRNA increase AKT phosphorylation, whereas an AKT inhibitor, MK2206, mitigates the effect of PEG10 silencing on cell migration. SW1353 cell invasion was enhanced by BMP-6, which was further increased by PEG10 silencing. The effect of siPEG10 was suppressed by inhibitors of matrix metalloproteinase (MMP). BMP-6 induced expression of MMP-1, -3, and -13, and PEG10 lentivirus or PEG10 siRNA downregulated or further upregulated these MMPs, respectively. PEG10 siRNA increased BMP-6-induced phosphorylation of p38 MAPK and AKT, whereas the p38 inhibitor SB203580 and MK2206 diminished SW1353 cell invasion by PEG10 siRNA. SB203580 and MK2206 impeded the enhancing effect of PEG10 siRNA on the BMP-6-induced expression of MMP-1, -3, and -13. Our findings suggest dual functions for PEG10: accelerating cell growth by suppressing TGF-β signaling and inhibiting cell motility and invasion by interfering with TGF-β and BMP signaling via the AKT and p38 pathways, respectively. Thus, PEG10 might be a molecular target for suppressing the aggressive phenotypes of chondrosarcoma cells.

BACKGROUND Apparent diffusion coefficient (ADC) histogram analyses have been used to differentiate tumor grades and predict therapeutic responses in various anatomic sites with moderate success. PURPOSE To determine the ability of diffusion-weighted imaging (DWI) with a whole-tumor ADC histogram analysis to differentiate benign peripheral neurogenic tumors (BPNTs) from soft tissue sarcomas (STSs). STUDY TYPE Retrospective study, single institution. SUBJECTS In all, 25 BPNTs and 31 STSs. FIELD STRENGTH/SEQUENCE Two-b value DWI (b-values = 0, 1000s/mm2 ) was at 3.0T. ASSESSMENT The histogram parameters of whole-tumor for ADC were calculated by two radiologists and compared between BPNTs and STSs. STATISTICAL TESTS Nonparametric tests were performed for comparisons between BPNTs and STSs. P < 0.05 was considered statistically significant. The ability of each parameter to differentiate STSs from BPNTs was evaluated using area under the curve (AUC) values derived from a receiver operating characteristic curve analysis. RESULTS The mean ADC and all percentile parameters were significantly lower in STSs than in BPNTs (P < 0.001-0.009), with AUCs of 0.703-0.773. However, the coefficient of variation (P = 0.020 and AUC = 0.682) and skewness (P = 0.012 and AUC = 0.697) were significantly higher in STSs than in BPNTs. Kurtosis (P = 0.295) and entropy (P = 0.604) did not differ significantly between BPNTs and STSs. DATA CONCLUSION Whole-tumor ADC histogram parameters except kurtosis and entropy differed significantly between BPNTs and STSs. LEVEL OF EVIDENCE 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

Highlights • Hypertrophic pachymeningitis is a rare disease characterized by inflammatory fibrosis and thickening of the dura mater. • There is an established relationship between HTLV-1 infection and primary SS. • MRI is considered to be the best radiological diagnostic tool. • Laminectomy and excision of the thickened dura has shown to be the best mode of treatment. • Due to the risk of recurrence, long-term follow-up is very important for correct evaluation of surgical treatment of HSP., Introduction Reports of hypertrophic spinal pachymeningitis associated with human T-cell lymphotrophic virus-1 (HTLV-1) infection and Sjogren’s syndrome in the English literature are still very rare. Presentation of case We hereby present a case of a 78-year-old female with a history of lower extremity weakness after a fall, which fully resolved after conservative treatment. However, the symptoms recurred 4 years later, and the patient became unable to walk. The patient had no superficial or deep sensation below the level of T9, and she also had urinary retention. Magnetic resonance imaging showed that hypertrophic dura mater was compressing the spinal cord from T2 to T10. Blood testing revealed increased anti-HTLV-1 antibody, rheumatoid factor, elevation of anti-SS-A antibody and antinuclear antibody. The cerebrospinal fluid contained markedly elevated levels of total protein and cell numbers. Biopsy of the labial gland of the lip revealed chronic sialadenitis. Discussion In collaboration with a neurologist, we diagnosed this patient with hypertrophic spinal pachymeningitis associated with HTLV-1 infection and Sjogren’s syndrome. We performed laminectomy at the affected spinal levels, resected the thickened dura, and maintained the patient on steroid therapy. The patient attained a marked recovery; she could walk with a cane and her urinary retention was improved. Conclusion For the management of HSP associated with HTLV-1 and SS, we recommend surgical decompression with subsequent prolonged steroid therapy and prolonged close monitoring to achieve a good long-term outcome.

Tranilast [N-(3′,4′-dimethoxycinnamoyl)-anthranilic acid], initially developed as an antiallergic drug, also exhibits a growth inhibitory effect on various types of cancer. Osteosarcoma is treated mainly with high-dose methotrexate, doxorubicin, cisplatin and ifosfamide; however, 20–30 % of patients cannot be cured of metastatic disease. We investigated whether tranilast enhances the anticancer effects of chemotherapeutic drugs and analyzed its mechanism of action in osteosarcomas. Tranilast inhibited proliferation of HOS, 143B, U2OS and MG-63 osteosarcoma cells in a dose-dependent manner, as well as enhancing the effects of cisplatin and doxorubicin. The average combination index at effect levels for tranilast in combination with cisplatin was 0.57 in HOS, 0.4 in 143B, 0.39 in U2OS and 0.51 in MG-63 cells. Tranilast and cisplatin synergistically inhibited the viability of osteosarcoma cells. In flow cytometric analysis, although tranilast alone did not induce significant apoptosis, the combination of tranilast and cisplatin induced early and late apoptotic cell death. Expression of cleaved caspase-3, cleaved poly(ADP-ribose) polymerase and p-H2AX was enhanced by tranilast in combination with cisplatin. Tranilast alone increased expression of p21 and Bim protein in a dose-dependent manner. Cell cycle analysis using flow cytometry demonstrated that the combination of tranilast and cisplatin increased the number of cells in the G2/M phase. Compared with cisplatin alone, the combination increased levels of phospho-cyclin-dependent kinase 1 (Y15). In the 143B xenograft model, tumor growth was significantly inhibited by combined tranilast and cisplatin compared with the controls, whereas cisplatin alone did not significantly inhibit tumor growth. In conclusion, tranilast has a cytostatic effect on osteosarcoma cells and enhances the effect of anticancer drugs, especially cisplatin. Enhanced sensitivity to cisplatin was mediated by increased apoptosis through G2/M arrest. Since tranilast has been clinically approved and has few adverse effects, clinical trials of osteosarcoma chemotherapy in combination with tranilast are expected.

Aneurysmal bone cysts (ABCs) are benign bony lesions frequently accompanied by multiple cystic lesions and aggressive bone destruction. They are relatively rare lesions, representing only 1% of bone tumors. The pathogenesis of ABCs has yet to be elucidated. In the present study, a series of 22 cases of primary and secondary ABC from patients treated in Department of Orthopedic Surgery, Kagoshima University Hospital (Kagoshima, Japan) from 2001–2015 were retrospectively analyzed. The average age at the time of diagnosis of primary ABC was 17.9 years. Intralesional curettage and artificial bone grafting were performed in the majority of the patients with primary ABC. The local recurrence rate following curettage for primary ABC was 18%, and the cause of local recurrence was considered to be insufficient curettage. Although no adjuvant therapy was administered during the surgeries, it may assist the prevention of local recurrence in certain cases. The cases of secondary ABC were preceded by benign bone tumors, including fibrous dysplasia, giant cell tumors, chondroblastoma and non-ossifying fibroma. The features of the secondary ABC typically reflected those of the preceding bone tumor. In the majority of cases, distinguishing the primary ABC from the secondary ABC was possible based on characteristic features, including age of the patient at diagnosis and the tumor location. In cases that exhibit ambiguous features, including a soft tissue mass or a thick septal enhancement on the preoperative magnetic resonance images, a biopsy must be obtained in order to exclude other types of aggressive bone tumors, including giant cell tumor, osteosarcoma and telangiectatic osteosarcoma.

High-dose chemotherapy and surgical treatment have improved the prognosis of osteosarcoma. However, more than 20% of patients with osteosarcoma still have a poor prognosis. We investigated the expression and function of casein kinase 2 (CK2) in osteosarcoma growth. We then examined the effects of CX-4945, a CK2 inhibitor, on osteosarcoma growth in vitro and in vivo to apply our findings to the clinical setting. We examined the expression of CK2α and CK2β by western blot analysis, and performed WST-1 assays using CK2α and CK2β siRNA or CX-4945. Flow cytometry and western blot analyses were performed to evaluate apoptotic cell death. Xenograft models were used to examine the effect of CX-4945 in vivo. Western blot analysis revealed upregulation of CK2α and CK2β in human osteosarcoma cell lines compared with human osteoblast cells or mesenchymal stem cells. WST assay showed that knockdown of CK2α or CK2β by siRNA inhibited the proliferation of human osteosarcoma cells. Treatment with 3 µM of CX-4945 inhibited osteosarcoma cell proliferation; however, the same concentration of CX-4945 did not affect the proliferation of human mesenchymal stem cells. Additionally, treatment with CX-4945 inhibited the proliferation of human osteosarcoma cells in a dose-dependent manner. Western blot and flow cytometry analyses showed that treatment with CX-4945 promoted apoptotic death of osteosarcoma cells. The xenograft model showed that treatment with CX-4945 significantly prevented osteosarcoma growth in vivo compared with control vehicle treatment. Our findings indicate that CK2 may be an attractive therapeutic target for treating osteosarcoma.

The purpose of the present study was to analyze the effect of treatment of Paget's disease of bone (PDB) with bone scintigraphy using a computer-assisted diagnosis system (BONENAVI) that quantitatively evaluates bone metabolism. Seven patients with PDB (three male, four female; average age, 60 years; age range, 33–80 years) underwent bone scintigraphy and measurement of serum alkaline phosphatase (ALP), bone-specific ALP (BAP), serum cross-linked N-telopeptide (NTx) of type I collagen, urinary NTx, and deoxypyridinoline (DPD) before and after bisphosphonate treatment. Bone scan index (BSI), artificial neural network (ANN) value, and hotspot number (HSn) were calculated using BONENAVI software. Mean follow-up period was 22 months (range, 11–35 months). Among three BONENAVI parameters (ANN, BSI, and HSn), only BSI was significantly lower after bisphosphonate treatment as compared with before. All bone metabolic markers excluding DPD were significantly lower following bisphosphonate treatment than before. Bone formation markers (ALP and BAP) were significantly lower than bone resorption markers (U-NTx and S-NTx). The correlation of BONENAVI parameters with four bone metabolic markers was analyzed before and after bisphosphonate treatment. Before treatment, the majority of the four markers did not correlate with the BONENAVI parameters. In contrast, post-treatment ALP, BAP, and U-NTx were significantly correlated with BSI and HSn. To the best of our knowledge, this is the first study to evaluate the treatment of PDB by bone scintigraphy using a computer-assisted diagnosis system that quantitatively evaluates bone metabolism. The findings demonstrated that, using BONENAVI software, bone scintigraphy is able to quantitatively and spatially evaluate the bisphosphonate treatment effect, particularly in patients with polyostotic PDB.

Allograft bone is a widely used as a convenient tool for reconstructing massive bone defects in orthopedic surgery. However, allografts are associated with the risk of viral disease transmission. One of the viruses transmitted in this manner is human T-lymphotropic virus type 1 (HTLV-1), which is found worldwide but is unevenly distributed. The southwestern parts of Japan are a highly endemic for HTLV-1. We investigated the HTLV-1 seroprevalence in candidate allograft donors at the regional bone bank in Kagoshima, Japan during its first 5 years of service. Between 2008 and 2012, we collected 282 femoral heads at the Kagoshima regional bone bank from living donors with osteoarthritis of the hip joint. Among the 282 candidate donors, 32 donors (11.3 %) were seropositive for anti-HTLV-1 antibody; notably, this prevalence is higher than that reported for blood donors in this area. Additionally, to determine if HTLV-1 genes are detectable after processing, we examined the bone marrow of the femoral heads from seropositive donors by conducting PCR assays. Our results confirm the existence of viral genes following the heat treatment processing of the femoral heads. Therefore, it is important to inactivate a virus completely by heat-treatment. Together, our findings highlight the importance of HTLV-1 screening at bone banks, particularly in HTLV-1-endemic areas such as southwest Japan.

This study aimed to identify and compare risk factors for surgical site infection (SSI) and non-surgical site infections (non-SSIs), particularly urinary tract infection (UTI), after spine surgery. We retrospectively reviewed 825 patients (median age 59.0 years (range 33–70 years); 442 males) who underwent spine surgery at Kagoshima University Hospital from January 2009 to December 2014. Patient parameters were compared using the Mann–Whitney U and Fisher’s exact tests. Risk factors associated with SSI and UTI were analyzed via the multiple logistic regression analysis. P

11512 Background: Whereas one of oncolytic viruses (OVs), inducing selective tumor killing and systemic anti-tumor immunity, was approved by FDA in 2015, the best OV that more safely and efficiently treats intractable cancers has not been successfully developed. By our platform technology to efficiently construct next-generation OVs, i.e., “conditionally replicating adenoviruses (CRAs) that target and/or treat tumor cells with multiple factors” (m-CRAs), we identified that among candidates, survivin-responsive m-CRAs (Surv.m-CRAs) exhibited the most potent antitumor efficacy and cancer selectivity ( i.e., safety) in preclinical studies ( Cancer Res, 2005 et al.). Here we present the data of First-In-Human phase I clinical trial of Surv.m-CRA-1 for musculoskeletal tumors (MST). Methods: This single-arm, open label study included 9 patients with unresectable and advanced MST. Patients underwent a single intratumoral injection of either 1×10^10 viral particle (vp) (low), 1×10^11 vp (mid) or 1×10^12 vp (high). The primary endpoints were safety and tolerability. The secondary endpoints included the local control of treated tumor at one month, defined by RECIST and Choi criteria, analysis of dissemination of Surv.m-CRA-1, serum cytokine and adenoviral antibody. Long-term follow-up was done in some patients. Results: Four patients (44.4%) had grade 3 or higher adverse events, including lymphopenia, leukocytopenia and mildly elevated liver transaminase in 2, 1 and 1 patient, respectively. Virus excretions, including second peak of viremia from viral replication in tumor, were observed in 1, 2 and 3 patients of low, mid and high dose, respectively. Out of 9 patients, 5 PR, 3 SD and 1 PD by Choi, and 8 SD and 1 PD by RECIST were observed. During follow-up, another 1 and 2 patients became PR by Choi and RECIST, respectively. Of note, long-term PR (over 2 years) after a single injection of Surv.m-CRA-1 was achieved in two chordoma cases in low dose. Conclusions: Surv.m-CRA-1 was well tolerated and showed antitumor activity for prolonged periods against advanced MST. We about to start Phase I/II study of multiple injections of Surv.m-CRA-1 for advanced solid tumors in two-arms for musculoskeletal tumors and pancreatic cancer. Clinical trial information: R000026464 .

Malignant soft-tissue sarcoma resection is associated with a relatively high incidence of surgical site infection (SSI). The known risk factors for SSI following soft-tissue sarcoma resection include tumor size and location, prolonged surgery, and massive blood loss. The geriatric nutritional risk index (GNRI) was used as a tool to help predict the occurrence of SSI after major surgery. We investigated the utility of the GNRI as a predictor of SSI following soft-tissue sarcoma resection. We retrospectively reviewed 152 patients who underwent surgical resection of soft-tissue sarcoma in our institute, and found that the incidence of SSI was 18.4% (28/152). The SSI and non-SSI groups significantly differed regarding surgical time, diameter of the skin incision, maximum tumor diameter, instrumentation, presence of an open wound, preoperative chemotherapy, preoperative C-reactive protein concentration, and GNRI. Binomial logistic regression analysis showed that the risk factors for SSI following soft-tissue sarcoma surgery were male sex, larger skin incision diameter, larger maximum tumor diameter, presence of an open wound, and lower GNRI. Our findings indicate that malnutrition is a risk factor for SSI after soft-tissue sarcoma resection, and suggest that appropriate assessment and intervention for malnutrition may reduce the incidence of SSI.

Hemodialysis patients are at risk for bone loss and sarcopenia, characterized by reduced muscle mass and limited mobility/function. Osteoporosis and sarcopenia both increase the risk of hospitalization and death in affected individuals. Malnutrition also occurs as a complication of hemodialysis and has been identified as a risk factor for osteoporosis and sarcopenia. In this study, we examined the relationship between osteoporosis, muscle volume, walking ability, and malnutrition in hemodialysis patients.Forty-five hemodialysis patients were evaluated. Bone mineral density (BMD) and muscle volume were measured by dual-energy X-ray absorptiometry. Muscle volume and strength were evaluated using lean mass index (LMI), handgrip strength, and walking ability. The time required for a patient to walk 10 meters was measured to evaluate walking ability. The geriatric nutritional risk index (GNRI) was used to assess malnutrition.Multiple linear regression analysis showed that older age, female sex, lower LMI, and higher total type I procollagen N-terminal propeptide were correlated with lower BMD of lumbar spine. Higher age and lower LMI were correlated with lower BMD of the femoral neck. Female sex and lower GNRI were correlated with lower LMI. Longer duration of hemodialysis was correlated with lower walking ability.Our findings suggest that muscle preservation is required to maintain both lumbar spine and femoral neck BMD. Similarly, nutritional management is necessary to maintain BMD via preservation of muscle volume. Complementary nutritional therapies are needed to improve osteoporosis and sarcopenia in high-risk hemodialysis patients.

The treatment of glioblastoma is a critical health issue, owing to its resistance to chemotherapy. The current standard of treatment is surgical resection, followed by adjuvant radiotherapy and temozolomide treatment. Long‑term local treatment of glioblastoma is rarely achieved and the majority of the patients undergo relapse. Resistance to temozolomide emerges from numerous signalling pathways that are altered in glioblastoma, including the Hedgehog signalling pathway. Hence, further research is required to identify effective treatment modalities. We investigated the effect of vismodegib, arsenic trioxide and temozolomide on glioblastoma in vitro and in vivo to apply our findings to the clinical setting. WST‑1 assay revealed that glioblastoma proliferation was inhibited following treatment with these drugs either in single or in combination; this synergistic effect was confirmed by CalcuSyn software. Western blot analysis revealed an increase in the expression of cleaved caspase‑3 and γH2AX. Furthermore, there was marked inhibition and decreased tumour growth in mice that received combination therapy, unlike those that received single agent or vehicle treatment. Our results revealed that the combination of arsenic trioxide/vismodegib and temozolomide may be an attractive therapeutic method for the treatment of glioblastoma.

Predicting outcomes in patients with soft tissue sarcoma (STS) is challenging. To improve these predictions, we retrospectively analyzed common nutritional assessment systems, including Glasgow prognostic score (GPS), Geriatric Nutritional Risk Index (GNRI), neutrophil&ndash, lymphocyte ratio (NLR), platelet&ndash, lymphocyte ratio (PLR), and controlling nutritional (CONUT) score against outcomes in 103 patients with STS, of whom 15 (14.6%) died within 1 year of diagnosis. GPS, GNRI, NLR, PLR, and CONUT scores significantly differed between patients who died within one year and patients who lived longer. Binomial logistic regression analysis showed that male sex, older age at diagnosis, higher GPS, higher stage, and unresectable STS were risk factors for death within a year of diagnosis. Overall survival was evaluated by Cox proportional hazards models, which correlated higher NLR, higher PLR, larger maximum diameter of tumor, higher stage, and unresectable STS with poor prognosis. We next examined prognostic factors in the 93 patients with resectable STS, and found male sex, higher GPS, and higher stage were correlated with poor prognosis in these patients. Our findings suggest that GPS, NLR, and PLR are simple predictors of outcome in patients with STS. Nutritional therapies might improve their GPS and prognosis.