Pharmacological properties and therapeutic potential of saffron (Crocus sativus L.) in osteosarcoma.
藏红花 (番红花) 在骨肉瘤中的药理特性和治疗潜力。
- 作者列表："Ege B","Yumrutas O","Ege M","Pehlivan M","Bozgeyik I
OBJECTIVES:In this comprehensive study, we aimed to investigate pharmacological properties and therapeutic significance of saffron in osteosarcoma cancer cells. METHODS:Plant materials were obtained from Safranbolu district of Karabuk, Turkey. For the determination of anticancer properties, thiazolyl blue tetrazolium bromide (MTT) cell viability, colony formation, wound closure, DNA ladder assays and gene expression analysis by real-time PCR were performed. Also, cellular inflammation, total antioxidant and oxidants status were determined. KEY FINDINGS:Dichloromethane and hexane extracts of saffron were significantly inhibited cell proliferation and interfered with colony forming and migration capabilities of U2-OS osteosarcoma cancer cells. Also, both extracts induced the activation of tumour suppressor CDKN2B gene and altered cellular morphology resembling the induction of apoptosis. However, DNA fragmentation was not observed after extract treatments. Saffron was also found to have no significant effect on cellular inflammation. Unexpectedly, both dichloromethane and hexane extracts of saffron had no marked effect on cellular total antioxidant and oxidant status. Lastly, vanillic acid, resveratrol, caffeic acid and 4-hydroxybenzoic acid were found to be highly rich in our extracts. CONCLUSIONS:Findings of this study demonstrated significant antiproliferative and antitumorigenic properties of saffron in osteosarcoma.
目的: 在这项综合研究中，我们旨在探讨藏红花在骨肉瘤癌细胞中的药理学特性和治疗意义。 方法: 植物材料从土耳其卡拉布克的萨夫兰博卢区获得。为了确定抗癌特性，进行了噻唑蓝四唑溴铵 (MTT) 细胞活力、集落形成、伤口闭合、DNA梯状试验和实时PCR的基因表达分析。此外，测定细胞炎症、总抗氧化剂和氧化剂状态。 关键发现: 藏红花的二氯甲烷和己烷提取物显著抑制细胞增殖，并干扰U2-OS骨肉瘤癌细胞的集落形成和迁移能力。同样，两种提取物都诱导了肿瘤抑制因子CDKN2B基因的激活，并改变了类似于诱导凋亡的细胞形态。然而，提取处理后未观察到DNA片段化。还发现藏红花对细胞炎症无显著影响。出乎意料的是，藏红花的二氯甲烷和己烷提取物对细胞总抗氧化和氧化状态没有明显影响。最后，我们发现香草酸、白藜芦醇、咖啡酸和 4-羟基苯甲酸在我们的提取物中含量很高。 结论: 本研究结果证明了saffron在骨肉瘤中的显著抗增殖和抗肿瘤特性。
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.