复发性骨肉瘤细胞系的建立和表征: OSA 1777。
- 作者列表："Thanindratarn P","Li X","Dean DC","Nelson SD","Hornicek FJ","Duan Z
:Osteosarcoma (OSA) is the most common primary bone malignancy overall and is responsible for considerable adolescent mortality. Approximately 850 patients are newly diagnosed with OSA in the United States each year. While the 5-year survival rate for localized OSA has improved from <20% over 40 years ago to over 65% today, progress has dwindled over the past three decades. Therapeutic stagnation has occurred, in part, as a result of limited preclinical models and the overall heterogeneity of OSA among patients. In this study, we report the establishment and characterization of a novel OSA cell line: OSA 1777. This cell line was isolated from the recurrent tumor specimen of a 19-year-old female who initially experienced 99% tumor necrosis after neoadjuvant chemotherapy and eventually had local recurrence and metastases. We present OSA 1777 growth characteristics, tumor markers, chemotherapeutic sensitivities, and oncogenic spheroid formation. In a two-dimensional (2D) monolayer culture, OSA 1777 exhibited a spindle shape and 60 h doubling time. STR DNA profiling revealed a unique genomic identity not matching any existing human cancer cell lines from the ATCC or DSMZ databases. Consistent with the mesenchymal origin, western blot was positive for vimentin and negative for the carcinoma marker cytokeratin. Within three-dimensional (3D) culture, the cells formed spheroids of similar patterning and smaller size compared with MNNG-HOS and U2OS cell lines. The chemotherapeutic drug sensitivity of OSA 1777 was evaluated in both 2D and 3D culture systems. In summary, we report OSA 1777 as a novel biological model of OSA amenable to future studies focused on OSA that recurs despite an initially strong chemotherapeutic response. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:902-910, 2020.
: 骨肉瘤 (OSA) 是最常见的原发性骨恶性肿瘤，是相当大的青少年死亡率的原因。在美国，每年大约有 850 例新诊断为OSA的患者。虽然局部OSA的 5 年生存率从 40 年前的 <20% 提高到今天的 65% 以上，但在过去的 30 年里，进展已经减少。治疗停滞的发生部分是由于有限的临床前模型和患者OSA的总体异质性。在这项研究中，我们报道了一个新的OSA细胞系的建立和表征: OSA 1777。该细胞系是从一名 19 岁女性的复发肿瘤标本中分离出的，该女性在新辅助化疗后最初经历了 99% 的肿瘤坏死，最终出现局部复发和转移。我们介绍了OSA 1777 生长特征、肿瘤标志物、化疗敏感性和致癌球体形成。在二维 (2D) 单层培养中，OSA 1777 呈纺锤形，倍增时间为 60 h。STR DNA分析发现一个独特的基因组身份与ATCC或DSMZ数据库中任何现有的人类癌症细胞系不匹配。与间充质来源一致，western blot对波形蛋白阳性，对癌标志物细胞角蛋白阴性。在三维 (3D) 培养中，与MNNG-HOS和U2OS细胞系相比，细胞形成了类似图案和较小尺寸的球体。在 2D和 3D培养系统中评价OSA 1777 的化疗药物敏感性。总之，我们报道OSA 1777 是一种新的OSA生物学模型，适合未来的研究，重点是OSA尽管最初有强烈的化疗反应但仍复发。©2019 骨科研究学会。由Wiley journals，Inc.发表J Orthop Res 38:902-910，2020。
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.