体外药敏试验ATP-TCA与流式细胞仪在肝癌化疗中的应用

目的 探讨体外化疗药敏试验系统（ATP-TCA系统）联合流式细胞仪（FCM）在肝癌化疗中的应用及其结果之间的关系。方法 取24例肝癌切除，活检或穿刺组织行体外药敏试验和流式细胞仪P170检测，并分析二者间的关系。结果 ATP-TCA的可评估率为91.67%;10种化疗药物的敏感率分别为：氟尿嘧啶5.00%，诺消灵5.00%，顺铂14.26%，足叶乙甙19.05%，草酸铂19.05%,丝裂霉素23.81%，表阿霉素28.57%，开普拓45.46%，健择47.62%，泰素63.64%；P170检测阳性率为57.14%；丝裂霉素，表阿霉素的敏感率在P170阴性表达时高，开普拓健择，泰素的敏感率高且在P170阳性表达和阴性表达时无显著差异。结论 ATP-TCA法联合FCM可较好用于肝癌化疗药物的筛选；丝裂霉素，表阿霉素可用于P170阴性表达的病人，开普拓，健择，泰素可用于P170阳性表达的病人。     

ATP生物荧光肿瘤体外药敏检测技术在治疗非小细胞肺癌胸水中的临床应用

目的：研究三磷酸腺苷-生物荧光肿瘤体外药敏检测技术(ATP-TCA)在非小细胞肺癌(NSCLC)化疗中的应用,为临床治疗方案的选择提供依据。方法：选择52例伴有胸水的NSCLC患者,根据患者及家属治疗意愿分为经验治疗组和药敏治疗组。经验治疗组20例患者根据经验给予(紫杉醇联合卡铂,PTX+CBP)标准方案全身化疗;药敏治疗组32例患者对胸水标本分别进行顺铂(DDP) 、诺维本(NVB) 、紫杉醇(PTX) 、卡铂(CBP) 、健择(GEM)、PTX+CBP、NVB+CBP、GEM + DDP体外药敏检测,根据体外药敏检测结果选用化疗方案,比较2组患者治疗有效率。结果:体外药敏试验,单一用药中NVB和PTX对 NSCLC的体外敏感率最高,均为28.1 % ;GEM的体外敏感率次之,为25%;CBP的体外敏感率为21.9%;DDP的体外敏感率最低,为17.6%。联合用药方案显示较好的治疗效果,其中GEM + DDP 的体外敏感率最高,达55.9%;PTX+CBP的体外敏感率次之,达50%; NVB+CBP的体外敏感率最低,为40.6%。药敏治疗组患者有效率为65.6%,经验治疗组有效率为40.0%,两组有效率比较差异有统计学意义（P＜0.05）。结论：不同化疗药物对NSCLC的体外敏感率不同;根据药敏试验结果选择化疗方案可取得更
好的临床治疗效果。     

Effect of two durations of short-term intermittent hypoxia on ventilatory chemosensitivity in humans

The purpose of this study was to clarify the influence of duration of intermittent hypoxia per day on ventilatory chemosensitivity. Subjects were assigned to three different groups according to the duration of exposure to intermittent hypoxia (12.3 ± 0.2% O₂): a first group (H-1, n = 6) was exposed to hypoxia for 1 h per day, the second group (H-2, n = 6) was exposed for 3 h per day, and the third (C, n = 7) was used as control. Hypoxic and hypercapnic ventilatory responses (HVR and HCVR) were determined before and after 1 week of intermittent hypoxia. HVR was increased significantly (P < 0.05) after intermittent hypoxia in both the H-1 and H-2 groups. However, there was no significant difference in magnitude of increased HVR between H-1 and H-2 groups. HCVR did not show any changes in all groups after intermittent hypoxia. These results suggest that 1 h of daily exposure is as equally effective as 3 h of daily exposure to severe hypoxia for a short period for enhancing ventilatory chemosensitivity to hypoxia.     

LRIG1 Enhances Chemosensitivity by Modulating BCL-2 Expression and Receptor Tyrosine Kinase Signaling in Glioma Cells

Purpose

Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) are an inhibitor of receptor tyrosine kinases (RTKs) that was discovered in recent years, and many studies showed that LRIG1 is a tumor suppressor gene and may be related to tumor drug resistance. In this study, we explored whether LRIG1 protein expression can improve the chemosensitivity of glioma cells and what was its mechanism.

Materials and Methods

We collected 93 cases of glioma tissues and detected the expression of LRIG1 and BCL-2. We constructed a multidrug resistance cell line U251/multidrug resistance (MDR) and examined the change of LRIG1 and BCL-2 at mRNA and protein expression levels. LRIG1 expression was upregulated in U251/MDR cells and we detected the change of multidrug resistance. Meanwhile, we changed the expression of LRIG1 and BCL-2 and explored the relationship between LRIG1 and BCL-2. Finally, we also explored the relationship between LRIG1 and RTKs.

Results

LRIG1 was negatively correlated with BCL-2 expression in glioma tissue and U251/MDR cells, and upregulation of LRIG1 can enhance chemosensitivity and inhibit BCL-2 expression. Furthermore, LRIG1 was negatively correlated with RTKs in U251/MDR cells.

Conclusion

These results demonstrated that LRIG1 can improve chemosensitivity by modulating BCL-2 expression and RTK signaling in glioma cells.     

恶性实体瘤化疗患儿ATP生物荧光肿瘤体外药敏检测研究

目的 探讨ATP生物荧光肿瘤体外药敏检测技术(ATP-TCA)指导恶性实体瘤患儿临床化疗的意义,为恶性肿瘤患儿的个性化治疗提供参考.方法 应用ATP-TCA检测50例恶性实体瘤患儿(15例恶性神经源性肿瘤、8例恶性生殖细胞肿瘤、10例肾母细胞瘤、10例肝母细胞瘤、6例横纹肌肉瘤、1例肾上腺皮质癌)标本的8种单独用药和8种联合用药方案的敏感性.结果 (1)50例儿童恶性实体瘤标本中,46例结果具有可评价性,ATP-TCA总可评价率为92%(46/50).(2)不同个体的肿瘤在药物敏感方面具有明显的异质性.(3)各种恶性实体瘤患儿体外敏感率较高的药物组合如下:恶性神经源性肿瘤:卡铂+表阿霉素+异环磷酰胺(12/15、80.0%)、长春新碱+环磷酰胺+顺铂+氮烯脒胺(11/15、73.3%);恶性生殖细胞肿瘤:顺铂+长春新碱+博来霉素(8/8、100%)、金喜素+更生霉素+异环磷酰胺(8/8、100%)、三氧化二砷(As2O3)(7/8、87.5%);肾母细胞瘤:长春新碱+更生霉素(6/7、85.7%)、卡铂+依托泊苷(6/8、75.0%);肝母细胞瘤:长春新碱+环磷酰胺+顺铂+依托泊苷(8/9、88.9%)、卡铂+异环磷酰胺+替尼泊甙(7/9、77.8%)、顺铂+依托泊苷+金喜素(7/9、77.8%);横纹肌肉瘤:长春新碱+环磷酰胺+顺铂+依托泊苷(5/5、100%);肾上腺皮质癌:药物体外抑制率最高者为长春新碱+环磷酰胺+阿霉素.(4)As2O3对儿童恶性生殖细胞肿瘤、恶性神经源性肿瘤单药敏感率较高,分别是87.5%(7/8)、46.7%(7/15).紫杉醇对恶性神经源性肿瘤和横纹肌肉瘤化疗敏感性较高,分别为40.0%(6/15)、60.0%(3/5),吉西他滨对儿童生殖细胞肿瘤和横纹肌肉瘤敏感性较高,分别为50.0%(4/8)、60.0%(3/5).结论 ATP-TCA是一种适用于儿童实体瘤药敏检测并与临床相关性较好的实验技术,对抗儿童恶性肿瘤药物筛选、已有药物新适应证研究、联合化疗方案筛选和评估具有实际应用价值.     

eIF3S10在肺癌组织中的表达及与化疗反应的关系

目的:研究eIF3S10在肺癌中的表达及其与化疗反应的关系,探讨其在肺癌预后中的作用。方法:收集在湖南省肿瘤医院治疗的31例支气管纤维镜检肺癌组织和20例肺良性病变组织及10例肺癌边缘正常组织的石蜡组织切片。采用免疫组织化学技术检测eIF3S10蛋白在肺癌组织、肺良性病变组织和正常肺组织中的表达,并分析eIF3S10表达水平与患者化疗敏感性的关系。结果:肺正常组织和肺良性病变组织中eIF3S10阳性率分别为30%和15%,而肺癌组织中eIF3S10的阳性率达61%。eIF3S10表达水平与化疗敏感性存在一定相关性。结论:肺癌组织中有eIF3S10过表达,而肿瘤组织eIF3S10表达过高可能提示患者对化疗反应敏感。     

Phenotyping interindividual variability in obstructive sleep apnoea response to temazepam using ventilatory chemoreflexes during wakefulness

Centrally active agents have a variable impact in patients with obstructive sleep apnoea (OSA) that is unexplained. How to phenotype the individual OSA response is clinically important, as it may help to identify who will be at risk of respiratory depression and who will benefit from a centrally active agent. Based on loop gain theory, we hypothesized that OSA patients with higher central chemosensitivity have higher breathing instability following the use of a hypnosedative, temazepam. In 20 men with OSA in a double‐blind, placebo‐controlled cross‐over trial we tested the polysomnographically (PSG) measured effects of temazepam 10 mg versus placebo on sleep apnoea. Treatment nights were at least 1 week apart. Ventilatory chemoreflexes were also measured during wakefulness in each subject. The patients (mean ± standard deviation; 44 ± 12 years) had predominantly mild‐to‐moderate OSA [baseline apnoea–hypopnoea index (AHI) = 16.8 ± 14.1]. Patients’ baseline awake central chemosensitivity correlated significantly with both the change of SpO₂ nadir between temazepam and placebo (r = ?0.468, P = 0.038) and oxygen desaturation index (ODI; r = 0.485, P = 0.03), but not with the change of AHI (r = 0.18, P = 0.44). Peripheral chemosensitivity and ventilatory recruitment threshold were not correlated with the change of SpO₂ nadir, ODI or AHI (all P > 0.05). Mild–moderate OSA patients with higher awake central chemosensitivity had greater respiratory impairment during sleep with temazepam. Relatively simple daytime tests of respiratory control may provide a method of determining the effect of sedative–hypnotic medication on breathing during sleep in OSA patients.     

MTT法在检测细胞因子与细胞毒效应中的应用

抗癌效应细胞(NK、LAK、CTL、Mφ)细胞毒效应、细胞因子和肿瘤化疗药敏检测目前多采用同位素法,但存在着使用同位素而引起的弊端。寻找一种简便,敏感及安全的检测手段已成为当务之急。我们将MTT比色法用于抗癌效应细胞功能、细胞因子及化疗药敏测定,并与同位素方法进行了对比,结果表明两种方法具有良好的相关性,MTT法与后者相比更为简便、经济、安全和实用。     

Short-term intrahepatic FUdR infusion combined with bolus mitomycin C: Reduced risk for developing drug resistance

This study evaluates tumor response, survival, and development of resistance to HAI chemotherapy, comparing a combination of bolus MMC and short duration FUdR to short duration FUdR alone or to long duration FUdR alone, using a rat hepatic metastases model. After intrasplenic injection of 10⁷ K12/TRb colon cancer cells in BD-IX rats on day 0, hepatic metastases were evaluated and HA catheters were placed on day 14. The response was determined on day 28. Chemosensitivity of the hepatic metastases after HAI treatments was determined using the MTT assay. Bolus MMC with short duration FUdR as well as long-term FUdR alone provided better hepatic tumor response and survival than short-term FUdR alone. However, bolus MMC with short duration FUdR decreased the acquired resistance to FUdR, compared to long-term FUdR, without causing resistance to MMC. These results provide a rationale for using short duration of FUdR in combination with other drugs. © 1994 Wiley-Liss, Inc.