Osteosarcoma growth suppression by riluzole delivery via iron oxide nanocage in nude mice.
- 作者列表："Raghubir M","Rahman CN","Fang J","Matsui H","Mahajan SS
:Osteosarcomas are the most commonly occurring malignant bone cancer in young individuals. The survival rate of patients with metastatic osteosarcoma is low and has been stagnant for over two decades. We previously demonstrated that the glutamate release inhibitor, riluzole inhibits osteosarcoma cell growth. Towards the development of more effective therapy, we investigated the delivery of riluzole in human metastatic osteosarcoma xenografts in mice. We compared the efficacy of riluzole delivery by intraperitoneally injecting either free riluzole or riluzole released via two different shapes of iron oxide nanoparticles (nanocage or nanosphere) of size 15±2.5 nm. We monitored tumor size using Vernier calipers and bioluminescence assay and found a significant reduction in tumor size in the riluzole‑treated groups when injected, either in free form or via nanoparticles, compared to the control groups (PBS, nanosphere or nanocage). Importantly, nanocage‑delivered riluzole was most effective in reducing tumor size in the xenograft nude mice. While riluzole delivery induced apoptosis in tumor tissues in all three groups of riluzole‑treated animals, it was highest in tumors from the nanocage‑delivered riluzole group. Therefore, we conclude that riluzole is an effective drug to reduce tumor size in osteosarcoma and the efficacy of riluzole as a apoptotic and tumor‑reducing drug is enhanced when delivered via nanocage.
: 骨肉瘤是年轻人中最常见的恶性骨癌。转移性骨肉瘤患者的生存率很低，并且已经停滞了二十多年。我们以前证明了谷氨酸释放抑制剂利鲁唑抑制骨肉瘤细胞生长。为了开发更有效的疗法，我们研究了利鲁唑在小鼠人转移性骨肉瘤移植瘤中的递送。我们通过腹腔注射游离的利鲁唑或通过两种不同形状的大小为 15 ± 2.5 nm的氧化铁纳米颗粒 (纳米球或纳米球) 释放的利鲁唑，比较了利鲁唑给药的疗效。我们使用游标卡尺和生物发光试验监测肿瘤大小，发现注射时利鲁唑组肿瘤大小显著减少，无论是游离形式还是通过纳米颗粒，与对照组 (PBS、纳米球或纳米球) 相比。重要的是，nanocage ‑ 递送的利鲁唑在减少异种移植裸鼠的肿瘤大小方面最有效。虽然利鲁唑给药诱导了所有三组利鲁唑治疗组动物肿瘤组织的凋亡，但在纳米给药利鲁唑组的肿瘤中凋亡最高。因此，我们得出结论，利鲁唑是一种有效的减少骨肉瘤肿瘤大小的药物，当通过纳米给药时，利鲁唑作为凋亡和肿瘤减少药物的疗效增强。
METHODS:OBJECTIVE:Large inoperable sacral chordomas show unsatisfactory local control rates even when treated with high dose proton therapy (PT). The aim of this study is assessing feasibility and reporting early results of patients treated with PT and concomitant hyperthermia (HT). METHODS: :Patients had histologically proven unresectable sacral chordomas and received 70 Gy (relative biological effectiveness) in 2.5 Gy fractions with concomitant weekly HT. Toxicity was assessed according to CTCAE_v4. A volumetric tumor response analysis was performed. RESULTS: :Five patients were treated with the combined approach. Median baseline tumor volume was 735 cc (range, 369-1142). All patients completed PT and received a median of 5 HT sessions (range, 2-6). Median follow-up was 18 months (range, 9-26). The volumetric analysis showed an objective response of all tumors (median shrinkage 46%; range, 9-72). All patients experienced acute Grade 2-3 local pain. One patient presented with a late Grade 3 iliac fracture. CONCLUSION:Combining PT and HT in large inoperable sacral chordomas is feasible and causes acceptable toxicity. Volumetric analysis shows promising early results, warranting confirmation in the framework of a prospective trial. ADVANCES IN KNOWLEDGE: :This is an encouraging first report of the feasibility and early results of concomitant HT and PT in treating inoperable sacral chordoma.
METHODS:BACKGROUND:National guidelines recommend screening and treatment for cancer-related bone disease and continued monitoring of bone-modifying agents. It is unclear whether a standardized screening tool is utilized to identify eligible patients and ensure appropriate supportive care is implemented. The purpose of this study was to evaluate current prescribing practices and optimize management of bone-modifying agents. METHODS:A retrospective chart review was performed to identify patients who received hormone deprivation therapy or had bone metastases through Hematology/Oncology or Urology clinics from 1 November 2016 to 31 October 2017. The primary endpoints of this study were the incidence of completed baseline dual-energy X-ray absorptiometry (DEXA) scan for patients on hormone deprivation therapy and percent of patients started on a bone-modifying agent for the prevention of skeletal-related events secondary to bone metastasis. Secondary endpoints included percent of patients with dental examinations prior to initiation, adequate calcium and vitamin D supplementation, incidence of osteonecrosis of the jaw or flu-like symptoms and education, and percent of bisphosphonate doses appropriately adjusted based on renal function. RESULTS:A total of 375 patients were assessed for baseline DEXA scans and bone-modifying therapy. Of the 226 patients on hormone deprivation therapy, 111 (49%) patients were appropriately screened with a DEXA scan prior to initiation of hormone deprivation therapy. Among the 149 patients with bone metastases, only 94 (63.1%) patients were started on a bone-modifying agent. CONCLUSIONS:Opportunities have been identified to optimize management of patients with cancer-related bone disease. Implementation of standardized tools may increase the rate of appropriate screening and initiation of bone-modifying therapy when warranted.
METHODS:PURPOSE:Low skeletal muscle mass has been associated with poor prognosis in patients with advanced lung cancer. However, little is known about the relationship between skeletal muscle mass and overall survival in patients with bone metastases from lung cancer. The objective of the present study was to evaluate the prognostic value of low trunk muscle mass in predicting overall survival in these patients. METHODS:The data from 198 patients who were diagnosed with bone metastases from lung cancer from April 2009 to May 2017 were retrospectively reviewed. The areas of the psoas and paravertebral muscles were measured at the level of the third lumbar vertebra on computed tomography scans taken at the time nearest to the diagnosis of bone metastasis. Muscle area was evaluated for male and female cohorts separately using different cutoff points. Cox proportional hazards analysis was performed to evaluate the factors independently associated with overall survival. RESULTS:The overall survival of patients in the lowest quartile for psoas muscle area or paravertebral muscle area was significantly shorter than that of patients above the 25th percentile for muscle area (p < 0.001). Multivariate analyses showed that paravertebral muscle mass (hazard ratio, 1.73; 95% confidence interval, 1.17-2.56; p = 0.006), epidermal growth factor receptor-targeted therapy, and performance status were independent prognostic factors. CONCLUSIONS:Low paravertebral muscle mass was associated with shorter survival, independently of known prognostic factors.