放射损伤对鼻咽癌外周血CD4+CD25high调节性T细胞的影响

目的通过分析放疗前后鼻咽癌(NPC)患者外周血CD4+CD25high调节T(Tr)细胞比例及其变化规律.初步探讨NPC患者免疫抑制机制和放疗对免疫抑制的影响,为有效提高NPC的治疗疗效提供参考.方法采用流式细胞术检测36例初治的鼻咽癌患者放疗前、放疗后和30例正常健康者(对照组)外周血中T细胞亚群及CD4+CD25high T细胞比例.结果放疗前鼻咽癌患者CD3+、CD4+、CD8+T细胞比例及CD4/CD8比值接近正常对照组(P＞0.05);而CD4+CD25high Tr细胞比例明显高于正常对照组[分别为(2.76±1.06)%,(2.06±0.98)%,P＜0.05];放疗结束时,与放疗前比较,外周血CD4+T细胞比例减低、但差异无统计学意义(P＞0.05);CD4+/CD8+比值减低(P＜0.05),而CD4+CD25high Tr细胞比例明显升高,差异有统计学意义[(4.88±1.02)%,P＜0.05].结论CD4+CD25high Tr细胞可能是鼻咽癌患者免疫抑制的重要原因之一,与鼻咽癌免疫逃逸有关.放疗后外周血CD4+CD25high Tr细胞比例比CD4+/CD8+比值更能敏感反映免疫功能状态,有可能成为鼻咽癌的更有效的免疫监测指标.     

Effects of NMDA receptor antagonists in squirrel monkeys trained to discriminate the competitive NMDA receptor antagonist NPC 12626 from saline

Because excitatory amino acids have been implicated in several physiological phenomena, antagonists of excitatory amino acid function may have significant therapeutic potential as anticonvulsant, neuroprotectants and anxiolytics. Drug discrimination procedures in animals have proven useful to compare and contrast the behavioral effects of site-selective NMDA antagonists. In the only previous study using a competitive NMDA antagonist as a training drug, rat wwere trained to discriminate NPC 12626 (2-amino-4,5(1,2-cyclohexyl)-7-phosphonoheptanoic acid) from nondrug. The major goal of the present study was to establish and characterize a nonhuman primate model of NPC 12626 discrimination. Adult male squirrel monkeys were trained to discriminate NPC 12626 from saline under a two-lever fixed ratio-30 schedule of food reinforcement. The monkeys required between 80 and 120 training sessions to acquire this discrimination after the training dose had been raised from 3 to 20 mg/kg i.m. The competitive NMDA antagonists CGP 37849 (D,L-(E)-2-amino-4-methyl-5-phosphono-3-pentanoic acid) and CPPene (D-3-(2-carboxypiperazin-4-yl)-1-propenyl-1-phosphonic acid) substituted completely for NPC 12626, while the potent noncompetitive NMDA antagonist, dizocilpine (MK-801), did not. These results reflect a profile of discriminative stimulus effects which support that observed in rats and establish a primate model for use in further study of the behavioral effects of the competitive NMDA antagonists.     

鼻咽癌放射治疗后眼部损伤

本文报道了近10年鼻咽癌放射治疗后出现眼部损伤13例（14只眼），其中鼻咽癌Ⅱ期7例，Ⅲ期6例．放射性白内障3例（4只眼），视网膜病变5例．视神经病变4例，合并白内障1例．发病时间为单程放疗后3年-6年，再程放疗后2年4个月-3年9个月．经临床及CT检查均排除鼻咽癌的复发和转移．发病原因均系由射线直接引起晶状体囊下上皮细胞损伤和放射性血管损伤所致，与放射野的设置、总放射量、分割剂量、存活时间、肿瘤的复发、个人身体状况等多种因素有关．我们认为预防和减少本病的发生，根据临床具体情况，周密制定放疗方案，对随访复查病人眼部检查应列为常规项目．同时对发病机理，眼部表现，治疗方法等进行了简单的讨论．     

组织基质金属蛋白酶抑制剂-1、2在鼻咽癌浸润与转移中的机制初探

[目的 ]探讨组织基质金属蛋白酶抑制剂 - 1、2 (Tissue lnhibitors of the MMP- 1、2 ,TIMP- 1、2 )与鼻咽癌浸润与转移的关系。 [方法 ]应用免疫组化 S- P法 ,检测 4 8例鼻咽癌组织 ,16例鼻咽粘膜炎组织中 TIMP- 1,TIMP- 2的表达。 [结果 ]鼻咽癌与鼻咽粘膜炎两组患者 ,TIMP- 1,TIMP- 2比较有统计学意义 (P<0 .0 1) ;随着鼻咽癌原发灶从 T1 期到 T3期以及鼻咽癌临床分期从 期到 期 ,TIMP- 1都有增加的趋势。 [结论 ]TIMP- 1可能作为鼻咽癌局部浸润的信号。     

Projections of the zona incerta in the cat, with stimulation controls.

In eight cats single electrolytic lesions were placed in the zona incerta, and resultant fiber degeneration studies were made. In seven additional cats, stimulating electrodes were chronically implanted bilaterally into the zona incerta, H₂ (lenticular fasciculus), or H (prerubral) fields of Forel. The animals were placed in a two-compartment shuttle box, and a routinely established procedure of subthalamic stimulation was instituted. When the sensory (nociceptive) or motor manifestations and reactions were established, small lesions were made through both poles of the electrodes. The brains were studied by silver techniques for degenerating axons and terminals. Findings in the latter group of animals with physiologic substrates, compared to those in the first group, indicated that the zona incerta contains at least two major physiologic-anatomic components with differential fiber projections. The first component is a medial zona incerta proper or caudalis, paleospinothalamic, nociceptive-conducting system which causes typical escape responses. Its unequivocal projections are to the nucleus of the H₁ field, posterior and dorsal hypothalamus, part of the intralaminar system, ventromedial and ventralis anterior nuclei, nucleus reuniens, reticular nucleus, pulvinar, posterior nucleus, central gray, red nucleus, and the central tegmental tract. The second constitutent concerns pyramidal-extrapyramidal motor type responses that arise with avoidance reactions from other portions of the zona incerta. In these cases there is heavy projection to the caudate, entopenduncular, globus pallidus, and putamen nuclei. In contrast, degeneration from the nociceptive part of the zona incerta or H₂ and H fields to these nuclei is minimal.     

Noninvasive diagnosis of nasopharyngeal carcinoma: nasopharyngeal brushings reveal high Epstein-Barr virus DNA load and carcinoma-specific viral BARF1 mRNA

Nasopharyngeal carcinoma (NPC) is the most prevalent ENT-tumour in Indonesia. We investigated the primary diagnostic value of Epstein-Barr virus (EBV) DNA load and mRNA detection in noninvasive nasopharyngeal (NP) brushings, obtained prospectively from consecutive Indonesian ENT-patients with suspected NPC (N=106) and controls. A subsequent routine NP biopsy was taken for pathological examination and EBER-RISH, yielding 85 confirmed NPC and 21 non-NPC tumour patients. EBV DNA and human DNA load were quantified by real-time PCR. NP brushings from NPC patients contained extremely high EBV DNA loads compared to the 88 non-NPC controls (p<0.0001). Using mean EBV DNA load in controls plus 3 SD as cut-off value, specificity, sensitivity, positive and negative predictive values were 98, 90, 97 and 91%, respectively. Epstein-Barr nuclear antigen 1 (EBNA1) and the carcinoma-specific BARF1 mRNA were detected by nucleic acid sequence based amplification and found in 86 and 74% of NP brushings, confirming NPC tumour cell presence. EBV RNA positivity was even higher in fresh samples stored at -80 degrees C until RNA expression analyses (88% for both EBNA1 and BARF1). EBV RNA-negative NP brushings from proven NPC cases had the lowest EBV DNA loads, indicating erroneous sampling. No EBV mRNA was detected in NP brushings from healthy donors and non-NPC patients. In conclusion, EBV DNA load measurement combined with detection of BARF1 mRNA in simple NP brushings allows noninvasive NPC diagnosis. It reflects carcinoma-specific EBV involvement at the anatomical site of tumour development and reduces the need for invasive biopsies. This procedure may be useful for confirmatory diagnosis in large serological NPC screening programs and has potential as prognostic tool.     

Epstein-Barr virus (EBV) serology for predicting distant metastases in a white juvenile patient with nasopharyngeal carcinoma and no clinical response to EBV lytic induction therapy

BACKGROUND: We describe a case of a 16-year-old white girl with Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC). METHODS.: At diagnosis, the patient had characteristic immunoglobulin (Ig)A and IgG responses to EBNA1, viral capsid antigen (VCA)-p18, and early antigens (EAs), with no detectable EBV DNA in her blood. Combined chemotherapy and radiotherapy resulted in complete remission. Eighteen months later, the patient's IgA responses to EBNA1 and p18 and both IgA and IgG anti-EA increased, without apparent recurrence. Five months later, lung metastases were found. She underwent surgical removal of the lung metastases and conventional chemotherapy, but had intraabdominal lymph node metastasis and mediastinal lesions develop. The patient was then treated with a novel treatment consisting of 5-fluorouracil plus valproic acid and subsequent valganciclovir to induce lytic EBV replication. This resulted in the first detectable EBV DNA levels in the blood but did not result in clinical response. RESULTS: The patient's disease progressed, and the patient declined further cancer treatment and died. CONCLUSION: In contrast to EBV DNA load, EBV serology was useful in predicting distant NPC metastasis after initial complete remission in this patient.     

Prognosis and histology in Stage I nasopharyngeal carcinoma (NPC)

During 1969-1975, 212 new patients with Stage I nasopharyngeal carcinoma (NPC) with a tumor apparently confined to the nasopharynx were treated at Queen Elizabeth Hospital, Kowloon, Hong Kong. The initial histologies of 137 patients were available for review and further studies. The primary tumors were histologically classified into two major types--squamous cell carcinoma (35 patients) and undifferentiated carcinoma (102 patients). The latter was further divided into 4 sub-types: lymphoepithelioma of the Schmincke type, lymphoepithelioma of the Regaud type, spindle cell carcinoma, and undifferentiated carcinoma of the nasopharyngeal type. Such histological typing of the initial tumor was not of value in predicting the clinical outcome, whether in terms of 5-year crude or disease-free survival rate, or the tendency of the tumor to develop recurrence at the primary site, or distant metastases after a standardized course of radiation therapy. There is no significant correlation between the extent of mononuclear infiltration nor fibrosis in the tumor stroma and the survival or tumor control rates.     

VEGF及其受体FIK-1在鼻咽癌中的表达及意义

目的研究VEGF及其受体FLK-1在鼻咽癌中的表达,探讨VEGF与鼻咽癌生长的关系,为临床治疗鼻咽癌提供理论依据。方法采用免疫组化sP法检测30例鼻咽黏膜慢性炎和40例鼻咽癌组织中VEGF、FLK-1的表达。结果VEGF和FLK-1在鼻咽黏膜慢性炎中的阳性率分别为20．00％（6／30）和13．33％（4／30）;在鼻咽癌中的阳性率分别为82．50％（33／40）和75．00％（30／40）,与鼻咽黏膜慢性炎组比较差异均有显著性（P〈0．001）。在鼻咽癌中VEGF和FLK-1的表达有显著相关性（r=0．582,P〈0．001）。结论在鼻咽癌中,VEGF及其受体FLK-1均呈高表达,VEGF可能通过旁分泌和自分泌方式对鼻咽癌的生长、增殖起着重要的调控作用,抑制VEGF的表达可以是治疗鼻咽癌的一个靶点。