大剂量异环磷酰胺联合方案治疗青少年晚期软组织肉瘤

研究大剂量异环磷酰胺(IFO)治疗多柔比星(ADM)和常规剂量IFO失败的青少年晚期软组织肉瘤的疗效及不良反应。对27例青少年晚期软组织肉瘤(术后化疗10例,进展期患者17例)采用IFO总量12g/m2持续静脉滴注6d治疗,每3周为1个疗程。进展期17例患者CR5例,PR2例,总有效率41.18%,随访4~48个月,中位生存期(22±3.35)个月,中位缓解时间(7.00±1.75)个月。主要不良反应为骨髓抑制,Ⅲ、Ⅳ度中性粒细胞减少占48.57%。初步研究结果提示,大剂量IFO治疗青少年晚期软组织肉瘤有一定的疗效,对常规ADM及IFO治疗失败后可作为挽救治疗方法。     

凋亡抑制因子Livin在骨肉瘤的表达及意义

目的探讨凋亡抑制因子Livin在骨肉瘤中的表达及其与骨肉瘤生物学特性的关系。方法采用免疫组织化学SABC法检测45例骨肉瘤、30例骨软骨瘤凋亡抑制蛋白Livin表达,并分析其与临床病理因素的关系。结果凋亡抑制蛋白Livin在骨肉瘤中表达阳性率为62．2％,在骨软骨瘤中为3．3％,二者间有统计学差异（P〈0．01）。Livin的高表达与骨肉瘤WHO组织分型无关,但与Price病理分级、Enneking外科分期、肺转移有关。结论凋亡抑制因子Livin在侵袭转移的骨肉瘤中高表达,提示其在骨肉瘤的发生、发展中起重要作用。     

Does Systemic Chemotherapy Influence Skeletal Growth of Young Osteosarcoma Patients as a Treatment-Related Late Adverse Effect?

The aim of this study was to investigate the influence of systemic chemotherapy on the skeletal growth of young osteosarcoma patients as a treatment-related late adverse effect. We reviewed the height data of 20 osteosarcoma patients (13 males and 7 females) aged ≤18 years. The average (±SD) age at diagnosis was 14.5 (±3.3) years. The average follow-up interval was 89.6 months. After wide resection of the affected bones, reconstruction with tumor prostheses and auto-bone grafting was carried out in 11 and 9 cases, respectively. Pearson’s correlation coefficient was calculated to evaluate the association between actual and predicted (using Paley’s multiplier method) heights. Z-scores were used to compare the initial and final heights with the Japanese national growth curve. Actual and predicted heights were correlated according to Pearson’s correlation coefficient (R = 0.503). Z-analysis showed that statistical significance (p = 0.04) was noted for the height data Z-scores of patients between ≤10 years and >10 years at the final follow-up. Systemic chemotherapy did not reduce skeletal growth in young osteosarcoma patients as a late adverse effect based on two different evaluation methods. However, patients aged ≤10 years at diagnosis may develop a short stature after systemic chemotherapy.     

Predictors and Treatment Outcomes of Pediatric Osteosarcoma in Diverse Socioeconomic Backgrounds in Southeast Asia: A Retrospective Multicenter Study

Background: Pediatric osteosarcoma outcomes among developed and developing countries have not been previously compared. Countries in Southeast Asia (SEA) have a wide variety of socioeconomic statuses. A multi-institutional retrospective study was conducted to determine the prognostic factors and outcomes for pediatric osteosarcoma in SEA. Methods: Pediatric patients with osteosarcoma treated between 1998 and 2017 in 4 SEA pediatric oncology centers were studied. Countries were classified using the World Bank Atlas method. Kaplan–Meier method and Cox’s Proportion Hazard Model were applied to estimate survival outcomes and identify prognostic factors. Results: In all, 149 patients with osteosarcoma with a mean age of 12.48±3.66 years were enrolled. The localized to metastatic disease ratio was 1.5:1. The 5-year overall survival (OS) and event-free survival (EFS) were 53.8% and 42%, respectively. Prognostic factors associated with outcomes were country, stage of disease, MTX-containing regimens, and surgery type (p-value <0.05). In patients with localized disease, EFS was superior with limb-salvage surgery (62%) than amputation or rotationplasty (40%) (p-value 0.009). MTX-containing chemotherapies provided higher OS (45.3%) and EFS (37.9%) than non-MTX regimens (12.3% and 10.7%, respectively) among metastatic patients (p-value 0.004 and 0.005, respectively). Metastatic disease was an independent prognostic factor for death but not relapse outcome.  Conclusion: The disease outcomes in SEA were acceptable compared to developed countries. The stage of disease was the only independent prognostic factor. MTX-containing regimens and limb-salvage surgery should be considered where possible.     

Successful limb salvage in progressive proximal tibia osteosarcoma following denosumab chemotherapy: A case report

Rationale:Osteosarcoma (OS) is a primary malignant bone tumor that originates in the mesenchymal tissue. It is the most common type of pleomorphic tumor occurring in children and adolescents. Currently, there is no established systematic treatment for OS that progresses during standard preoperative chemotherapy.Patient concerns and diagnoses:We describe a 14-year-old male patient with a 4-month history of pain in the upper right leg. Based on the results of percutaneous biopsy, a diagnosis of OS was made. After admission, the patient was treated with first-line chemotherapy agents. After a single course of treatment, the tumor progressed locally and no limb salvage was feasible.Interventions and outcomes:Intervention with denosumab combined with chemotherapy led to a significant reduction in tumor volume and ossification of soft tissue, which successfully resulted in limb salvage rather than amputation. The patient showed no evidence of recurrent or distant metastasis at 6-month follow-up.Lessons:Treatment with receptor activator of nuclear factor-ĸB ligand inhibitor denosumab combined with standard chemotherapy is effective for advanced OS progressing after chemotherapy. We recommend denosumab therapy for successful limb salvage in patients with high-grade OS associated with osteolytic bone destruction and refractory to preoperative neoadjuvant chemotherapy.     

毛细血管扩张型骨肉瘤影像与病理对照分析

目的　探讨毛细血管扩张型骨肉瘤影像与病理表现特征。方法　分析 12例毛细血管扩张型骨肉瘤临床、影像及病理资料。结果　临床特征为肿瘤好发于长骨干骺端 ,下肢多见 ,少有血清碱性磷酸酶增高。X线、CT特征为溶骨性与膨胀性骨破坏 ;肿瘤破坏区和软组织肿块内多发小囊变和液 -液平面 ;皮质变薄 ,多发筛孔样破坏 ;骨膜反应及放射状骨针较常见。病理组织学特征为典型骨肉瘤肿瘤细胞和多发血窦及“彩带样”结构。结论　毛细血管扩张型骨肉瘤具有一定的临床、影像及组织学特征     

Tenascin-C : 骨肉瘤预后标志物

背景：在过去的数十年间,转移性骨肉瘤的治疗一直是亟待解决的临床难题。细胞外基质蛋白作为肿瘤微环境关键组成成份,在骨肉瘤进展过程中发挥着重要作用。在此,我们通过基因芯片技术分析不同转移能力骨肉瘤细胞系基因表达,在编码细胞外基质蛋白基因中寻找与骨肉瘤进展相关的基因,并通过免疫组化技术检测这些基因在骨肉瘤标本中的表达,以评价其与临床预后的关系。 方法：通过基因芯片技术分析骨肉瘤细胞系MG63-wt及其高转移亚系MG63-A1的基因表达差异。对两个细胞系间表达差异达4倍以上的基因通过Gene Ontology方法筛选编码细胞外基质蛋白的基因。通过RT-PCR和western blot验证候选基因的表达水平,免疫组化检测候选基因在骨肉标本中的表达以分析其与临床预后的关系。 结果：基因芯片检测和Gene Ontology分析发现一个重要的细胞外基质蛋白――Tenascin-C的表达在高转移骨肉瘤细胞系MG63-A1中明显降低。RT-PCR和western blot分别在mRNA水平和蛋白质水平证实其表达水平。免疫组化检测发现Tenascin-C在骨肉瘤标本中的阳性表达见于细胞外间隙。Tenascin-C低表达组（＜20％）患者的预后较差,差异有统计学意义。 结论：Tenascin-C的表达水平与骨肉瘤患者预后呈正相关。Tenascin-C在骨肉瘤进展中的生物学作用有待进一步的体外细胞模型研究和更大样本临床研究。     

PTEN和Caspase-3在骨肉瘤中的表达

目的探讨抑癌基因PTEN蛋白和Caspase-3在骨肉瘤中的表达及在其发生发展中的可能作用。方法用免疫组织化学方法检测PTEN和Caspase-3在38例骨肉瘤及20例骨软骨瘤中的表达。结果PTEN蛋白在骨肉瘤中,表达阳性率为55.3%。在对照组骨软骨瘤中为90.0%,骨肉瘤与骨软骨瘤相比有显著差异(P<0.01)。Caspase-3在骨肉瘤中表达阳性率为52.6%,在对照组骨软骨瘤中为85.0%,骨肉瘤与骨软骨瘤相比有显著差异(P<0.05)。结论PTEN蛋白和Caspase-3与骨肉瘤的发生有关。     

蜂毒素诱导骨肉瘤细胞U2OS凋亡与坏死的实验研究

目的:研究蜂毒素是否能够诱导骨肉瘤细胞U2OS凋亡与坏死.方法:U2OS经不同浓度蜂毒素处理后,采用台盼蓝排染法测定细胞增殖抑制率,利用单克隆抗体,通过流式细胞仪检测AnnexinV、Apo2.7及Fas蛋白的表达.结果:64 mg/L蜂毒素作用U2OS 12 h、24 h,其坏死率在80%以上.16 mg/L、32 mg/L蜂毒素对细胞增殖有明显抑制作用,并且可诱导细胞凋亡和坏死的产生,增加细胞Aap2.7及 Fas 蛋白的表达.结论:蜂毒素高剂量有明显杀伤U2OS的作用,低剂量具有促细胞凋亡作用,并能上调Fas蛋白的表达.     

骨肉瘤与活化B淋巴细胞融合疫苗的抗肿瘤效应

目的　建立骨肉瘤与活化 B淋巴细胞融合的肿瘤疫苗 ,探讨其生物学与抗肿瘤特性 .方法　以 50 0 g· L-1 聚乙二醇为融合剂 ,将 C3 h小鼠来源的 HGRPT基因缺陷型 LM9骨肉瘤细胞与脂多糖活化的小鼠 B淋巴细胞进行融合 .经HAT选择性培养基筛选后 ,再观察该融合瘤株的体内外生长特性 ,对小鼠的致瘤性以及抗肿瘤活性 .结果　该融合瘤株体外生长缓慢 ,对 C3 h小鼠无致瘤性 ,杂交瘤细胞细胞表达B7(70 .6% ) H- 2 Kb (53.4% ) ,融合疫苗保护的小鼠可获 1 0 0 %无瘤生存 (8/ 8)而 LM9和射线照射后的 L M9对照组小鼠全部死亡 (0 / 8) ,皮下接种融合疫苗治疗的荷瘤小鼠可获得80 %无瘤生存 .结论　活化 B淋巴细胞融合骨肉瘤细胞可能改变其生物学特性 ,对小鼠有较好的预防和治疗作用 ,说明了细胞融合方法构建的肿瘤疫苗具有潜在的应用价值