Sinonasal neuro endocrine carcinoma extending into orbit — a case report

Small Cell Neuroendocrine Carcinomas of the Sinonasal tract are extremely uncommon and distinct neoplasms with aggressive clinical behavior. They have similar morphological and immunohistochemical features to those of small cell carcinomas of the lung. They should be distinguished from Olfactory Neuroblastomas. We report a case of this rare entity. A 46-year-old woman presented with a history of injury to the right eye with facial pain and proptosis as the primary symptoms. Later she developed nasal stuffiness. C.T. Scan revealed a space occupying lesion in the right nostril extending into ethmoid sinus and orbit. Functional endoscopic sinus surgery was done with decompression of the orbit. The biopsy material was obtained from ethmoid sinus and orbit. Histopathological examination of the biopsy specimen along with Immunohistochemical stains confirmed a Small Cell Neuroendocrine Carcinoma. Patient was treated with Radiotherapy and chemotherapy and responded well.     

9-顺式维甲酸协同γ-干扰素诱导神经母细胞瘤分化、凋亡及生长抑制的实验研究

目的 观察9-顺式维甲酸（9-cis retinoic acid，9-cis RA）联合γ干扰素（gammm interferon，γ-IFN）在体外诱导神经母细胞瘤（neuroblastoma，NB）SK-N-SH细胞分化、凋亡过程中细胞形态、周期的变化，探讨其协同作用的效果及其机制。方法 将细胞分为A（对照组）、B（9-cisRA用药组）、C（γ-IFN用药组）和D（9-cisRA和γ-IFN联合用药组）4组，在处理后适当的时间分别观察细胞形态学变化，进行分化神经节细胞计数，用Hoechst-PI荧光染色法观察细胞的凋亡和死亡，四甲基偶氮唑盐（MTT）法测定NB细胞抑制率，流式细胞仪（flow cytometry，FCM）检测细胞周期分布及其凋亡和死亡。结果 联合用药组细胞形态学分化明显，神经节细胞分化率显著高于其他各组（P〈0．01）；MTT法测定显示联合用药能显著提高NB细胞抑制率并明显优于单独用药；Hoechst-PI荧光染色及FCM钙依赖性磷脂结合蛋白V和碘化丙啶（annexin V／PI）染色法检测一致显示联合用药对于诱导NB细胞早期凋亡和坏死具有显著的协同作用；FCM细胞周期动力学分析发现联合用药组C0-G1期细胞比率增加，S期细胞比率减少。结论 9-cisRA联合γ-IFN在体外对NB细胞的分化、凋亡和生长抑制能产生明显的协同作用，为其联合应用于临床提供理论依据和指导。     

Plasma vasoactive intestinal polypeptide and other regulatory peptides in children with neurogenic tumours

Plasma regulatory peptide levels were studied in a group of 21 children with neurogenic tumours and in 22 control children. Plasma vasoactive intestinal polypeptide (VIP) levels were significantly higher in children with neurogenic tumours than in normal children or those with other tumours (P<0.05). There was no significant difference between the groups in plasma levels of gastrin, pancreatic glucagon or pancreatic polypeptide. The plasma VIP level may thus be a helpful diagnostic marker for neurogenic tumours in children.     

外源性Bax基因过表达对神经母细胞瘤SH-SY5Y细胞株Smac蛋白表达的影响

目的观察Bcl-2相关X蛋白（Bax）基因过表达对人神经母细胞瘤SH-SY5Y细胞第二个线粒体来源的半胱氨酸酶的激活剂（Smac）蛋白表达的影响。方法采用脂质体Lipofectamine 2000将携带人Bax基因的过表达质粒转入SH-SY5Y细胞（转染组）,同时设空载体组和未转染组。通过G-418筛选后获得转入目的基因的细胞克隆。Hoechst33258染色观察凋亡细胞,免疫印迹法法检测细胞中Bax、Smac蛋白表达,免疫荧光染色检测Bax、Smac蛋白在细胞中的分布。结果转染后用G-418持续筛选2周可获得G418抗性的细胞克隆。Smac主要分布于胞质,Bax主要位于细胞核。转染组SH-SY5Y细胞Bax蛋白表达水平（1.067±0.036）较空载体组（0.436±0.035）和未转染组（0.444±0.046）显著增高（P〈0.05）;转染组Smac蛋白表达水平（1.408±0.044）相比空载体组（0.708±0.021）和未转染组（0.748±0.041）显著增高（P〈0.05）;空载体和未转染组细胞Bax和Snac蛋白表达均无显著差异（P〉0.05）。转染组较未转染组细胞凋亡率显著增加（P〈0.05）。结论外源性Bax基因转入人神经母细胞瘤细胞中并稳定过表达,能够上调Smac蛋白表达,促进细胞凋亡。     

神经母细胞瘤复发的相关分子机制研究现状

神经母细胞瘤(NB)是儿童期最常见的颅外实体瘤,大部分患者在诊断时已出现远处转移,因此临床常见高危NB病例.高危NB病例容易复发和耐药,治疗反应差,5年总体生存率非常低.NB的复发机制迄今尚未完全清楚,可能与MYCN基因、肿瘤干细胞(CSC)、间变性淋巴瘤激酶(ALK)基因、DNA甲基化、微小RNA(miRNA)、细胞衰老、白细胞介素(IL)-6/信号传导及转录激活因子(STAT)3信号通路有关.笔者就NB复发的可能相关分子机制进行阐述.     

Involvement of K+ channels in the quercetin-induced inhibition of neuroblastoma cell growth

The effects of the flavonoid quercetin on cell proliferation and voltage-dependent K⁺ current were studied on mouse neuroblastoma×glioma hybrid cells. In the presence of 1 % fetal calf serum, quercetin inhibited both cell proliferation and K⁺ current with effective doses inducing half-maximum effects of 10 M and 70 M respectively. Valinomycin (1 nM) antagonized 80 % of the growth-inhibitory effects of 10 M quercetin. The results suggest that at least a part of the antiproliferative effect of quercetin is mediated by a K⁺ channel blockade. They further confirm a role for K⁺ channels in mitogenesis and cell proliferation.     

Short topotecan-based induction regimen in newly diagnosed high-risk neuroblastoma

Purpose

Topotecan is an active drug in relapsed neuroblastoma. We investigated the efficacy and toxicity of a topotecan-based induction regimen in newly diagnosed neuroblastoma.

Methods

Patients older than 1 year with either metastatic or localised stage 2-3 MYCN-amplified neuroblastoma received 2 courses of high-dose topotecan (HD-TPT) 6 mg/m² and high-dose cyclophosphamide (HD-CPM) 140 mg/kg, followed by 2 courses of ifosfamide, carboplatin and etoposide (ICE) every 28 days. After surgery on primary tumour, a fifth course with vincristine, doxorubicin and CPM was given, followed by high-dose chemotherapy with stem cell support. Response was assessed in accordance with the International Neuroblastoma Response Criteria.

Results

Of 35 consecutive patients, 33 had metastatic disease. The median length of induction phase was 133 days (range 91-207) and time to high-dose chemotherapy was 208 days (range 156-285). The median tumour volume reduction was 55% after two HD-TPT/HD-CPM courses and 80% after four courses. Radical surgery was performed in 16/27 patients after chemotherapy. After the fifth course, 29/34 patients (85%) had achieved a partial remission (12) or a CR/very good partial remission (17). CR of metastases was achieved in 13/32 (41%) and bone marrow was in complete remission in 16/24 patients (67%). Grade 4 neutropenia and/or thrombocytopenia occurred in 100% of HD-TPT/HD-CPM and in 95% of ICE courses, while non-haematological toxicities were manageable.

Conclusions

These data indicate that our induction regimen is feasible and well tolerated. A major response rate of 85% with 41% complete metastatic response confirms this regimen as effective induction in high-risk neuroblastoma.     

Challenges of laparoscopic resection of abdominal neuroblastoma with lymphadenectomy

BACKGROUND: The laparoscopic procedure involving total resection of abdominal neuroblastoma combined with lymphadenectomy has not been reviewed in English literature. The aim of this study was to evaluate the significance and accuracy of laparoscopic resection of abdominal neuroblastoma. METHODS: Since July 1997, five patients with abdominal neuroblastoma underwent laparoscopic resection combined with lymphadenectomy or sampling of the lymph nodes. The length of operation, intraoperative blood loss, resectability, and complications were retrospectively reviewed and evaluated. RESULTS: Four cases were managed laparoscopically, but one case was converted to open procedure because of poor visualization around large vessels. The mean operation time was 135 min and the intraoperative blood loss 52 ml. CONCLUSIONS: Good visualization of the primary tumor and large vessels is, arguably, the most important factor for successful completion of this procedure laparoscopically. Precise indicators for laparoscopic resection of abdominal neuroblastoma provide a better prognosis and a good quality of life for children with neuroblastoma.     

神经生长因子受体对神经母细胞瘤血管生成作用的研究(英文)

目的　神经生长因子受体 (TrkA)基因是神经母细胞瘤 (NB)良好预后的标识之一 ,其高表达不仅可以抑制NB增殖和诱导良性分化 ,对NB的血管生长可能有一定的影响。该实验探讨TrkA基因对NB血管生成的作用。方法　 1 5只裸鼠随机分为对照组、空载体组和实验组 (每组 5只 )。利用脂质体转染法将TrkA基因和pBPSTR1空载体转入NBSY5Y细胞 ,分别命名为SY5Y TrkA及SY5Y Vec细胞 ,未转染细胞为SY5Y细胞。将SY5Y ,SY5Y Vec ,SY5Y TrkA细胞分别接种在对照组、空载体组和实验组裸鼠皮下 ,接种 5 0d后处死动物 ,切除肿瘤 ,测量肿瘤体积 ;用RT PCR及免疫组织化学技术检测肿瘤内血管内皮生长因子 (VEGF)的表达 ;计算微血管密度 (MVD)。结果　SY5Y TrkA细胞TrkA表达明显高于SY5Y Vec及SY5Y细胞组 (P <0 .0 1 ) ;实验组肿瘤终体积小于对照组及空载体组 (0 .39± 0 .0 2cm3 vs 1 .74± 0 .4 9cm3 ) ;(0 .39± 0 .0 2cm3 vs 1 .80± 0 .75cm3 ) ,差异有显著性 (均P <0 .0 1 ) ;实验组VEGFmRNA表达低于对照组及空载体组 (0 .1 6± 0 .0 9vs 1 .4 5± 0 .77) ;(0 .1 6± 0 .0 9vs 1 .35± 0 .71 ) ,差异有显著性 (均P <0 .0 1 ) ;实验组VEGF蛋白表达低于对照组及空载体组 (2 .0 0± 0 .6 0vs 5 .6 7± 0 .4 9) ;(2 .0 0± 0 .6 0v