目的 总结鼻窦镜辅助下经单鼻孔入路垂体瘤显微手术切除术的经验及初步体会。方法 鼻窦镜辅助下，经单侧鼻腔，严格中线入路打开蝶窦前壁，暴露鞍底然后在神经显微镜下行垂体瘤切除，最后鼻窦镜下鞍底重建。结果2l例患者中16例一次手术全切除，3例次全切除，l例巨大生长激素（growth homone，GH）腺瘤大部分切除，后经改良翼点入路二次手术切除，l例巨大催乳素（prolactin，PRL）腺瘤分2次经蝶肿瘤切除，术后患者症状均改善。尿崩2例，分别于术后7d、15d停止；脑脊液漏l例，保守治疗2周治愈结论耳鼻喉科医师解剖熟悉，鼻窦镜下显露鞍底准确充分，神经外科医师显微镜下可克服内镜单手操作的不便，二者结合有利于减少经单鼻孑L入路垂体瘤切除 的创伤，提高安全性，是一种有效的方法。

We previously found that 2-chloroethyl-3-sarcosinamide-1-nitrosourea (SarCNU), a new chloroethylnitrosoureaanalogue presently in phase I clinical trials, is aselective cytotoxin that enters cells via the extraneuronaltransporter for monoamine transmitters (EMT). In thisstudy, we assessed whether EMT expression correlates withSarCNU cytotoxicity by determining EMT expression in 23human tumor cell lines with reverse-transcription PCR.Western blot analysis was used to measure protein levels ofthe DNA repair genes, O6-methylguanine-DNA methyltransferase(MGMT), and excision repair cross-complementing rodentrepair deficiency gene 2 (ERCC2). SarCNU cytotoxicitywas determined by the sulforhodamine B colorimetric anticancer-drug screening assay and correlated with gene expression.Almost all of the cell lines screened were positivefor EMT expression. However, seven cell lines (MGR-1,MGR-2, T98-G, SKI-1, SKNSH, 297, and GBM) expressedlow levels of EMT. Although there was no linear correlationbetween SarCNU cytotoxicity and EMT expression,SarCNU cytotoxicity significantly correlated with ERCC2protein levels, and MGMT-rich (Mer1) cell lines (MGMTprotein level >0.1) were more resistant to SarCNU thanMGMT-poor (Mer2) cell lines (MGMT protein level <0.1). Moreover, multiple regression analysis indicated that thebest correlation with SarCNU cytotoxicity was attainablewith EMT plus MGMT and ERCC2 expression. This studysuggests that in human tumor cell lines both EMT and DNArepair factors, specifically, MGMT and ERCC2, are importantdeterminants of SarCNU activity. Because EMT is expressedin a wide variety of human tumors, SarCNU shouldbe a more widely effective alternative chemotherapeuticagent.

背景与目的：化疗是胶质瘤重要的辅助治疗方法，然而，疗效肯定的化疗方案不多。我们前期对恶性胶质瘤体外化疗药物敏感性试验研究表明，替尼泊甙（teniposide，vM-26）和顺铂（cisplatin，DDP）是对胶质瘤敏感性相对较高的药物。所以.我们采用VM-26+DDP联合化疗方案治疗恶性胶质瘤患者.探讨其疗效和不良反应。方法：总结分析中山大学肿瘤防治中心神经肿瘤科收治的经手术后病理确诊的恶性胶质瘤患者20例.所有病例均接受了手术后的辅助放射治疗。vM-26 300mg/m，分3～5天静滴；DDP80 mg/m2，分3～5天静滴；每周期3～4周.对接受大于或等于2周期化疗者按wHO疗效评价标准进行疗效评价。不良反应评价按美国国立癌症研究所（National Cancer Insitute，NCI）评价标准。结果：15例患者进入疗效评价和生存分析。l例（7%）完全缓解（complete response），2例（13%）部分缓解（parhal resp0㈧，PR），9例（60%）稳定（stabledlsease，SD），3例（20%）进展（progressIve dlsease，PD）。客观有效率（CR+PR）为20%，有效加稳定率（CR+PR+SDl为80%。全组1年生存率为58%。vM-26+DDP联合化疗的主要不良反应为骨髓抑制.Ⅲ、Ⅳ度粒细胞减少4例，占20%（4/20），但可在一周内自行恢复或经短期（3～5天）G CSF对症处理后恢复正常。无因粒细胞减少延迟治疗及减小剂量病例。结论：vM 26+DDP联合化疗治疗恶性胶质瘤.有与其它常用化疗方案相似的客观有效率，和更高的疾病稳定率，不良反应耐受性好，值得进一步扩大病例深入研究。

背景与目的：脑胶质瘤手术切除程度与病人预后直接相关，但在某些部位，不易做到彻底切除，且易导致神经功能损害。本研究探讨侧裂区胶质瘤手术彻底切除的可能性以及肿瘤切除程度对术后神经功能的影响。方法：对22例侧裂区胶质瘤在显微镜下切除，大脑中动脉主要的分支血管予以保留，术后若出现神经功能障碍，根据可能的原因进行治疗。结果：全部病例均在显微镜下行肿瘤全切除或次全切除，7例病人肿瘤切除后“桥状”保留通过瘤中心的功能血管。6例病人肿瘤切除术后出现肌力下降，其中5例半年后恢复，复查KPs 70分以上。结论：侧裂区胶质瘤在显微镜下可以积极切除，术后多数病人不发生神经功能障碍，即使发生，其功能障碍大都能恢复。

We examined the O6-methylguanine-DNA methyltransferase(MGMT) protein as well as MGMT activity levels and the excisionrepair cross-complementing rodent repair deficiency gene,ERCC2 (XPD), protein levels in 14 human tumor cell lines notselected for chloroethylnitrosourea (CENU) resistance. Theseresults were compared with 1,3-bis-(2-chloroethyl)-1-nitrosourea(BCNU) cytotoxicity and UV light sensitivity. MGMTprotein correlated significantly with MGMT activity (r=0.9497,p=0.0001). There was no significant linear correlation betweenBCNU cytotoxicity and MGMT content as determined by bothWestern analysis (r=0.139, p=0.6348) and activity assay (r=0.131, p=0.6515). However, MGMT-rich cell lines were foundto be more resistant than MGMT-poor cell lines to BCNU (t=2.2375, p=0.0225) but not to UV (t=1.1734, p=0.1317).Furthermore, the most BCNU-sensitive cell lines were allMGMT-poor. UV sensitivity was significantly correlated toBCNU cytotoxicity (r=0.858, p=0.0001). Significant correlationswere found between ERCC2 protein levels and BCNUcytotoxicity (r=0.786, p=0.0009) or UV sensitivity (r=5 0.874, p=5 0.0001). Our results confirm that MGMT plays an importantrole in CENU resistance, but not in UV resistance. The correlationof UV sensitivity with BCNU cytotoxicity suggests thatnucleotide excision repair is an important modifying factor ofMGMT-mediated innate CENU resistance in human tumor celllines, especially in highly resistant cell lines. ERCC2 may beimplicated in this process.

The preoperative diagnosis of cavernous sinus invasion remains difficult and controversial, and there are currentlyno reliable histological or molecular markers that predict pituitary tumour behaviour and response to treatment.We evaluated 45 patients with pituitary adenoma. The results have shown that the sensitivity of MRI for indicatingcavernous sinus invasion in this prospective study was 60%, specificity 85%, positive predictive value 83.33%,negative predictive value 62.96%. Forty-five specimens of pituitary adenomas were analyzed for expression of F8,VEGF, Ki-67, c-myc, bcl-2, nm23 and MMP-9 immunoreactivity using immunoperoxidase staining. MVD wasassessed using F8-related antigen. The results have shown that MVD of invasive pituitary adenomas was significantlyhigher than that of noninvasive (P<0.001). There was an association between the invasion of pituitaryadenomas and Ki-67 LI (P=0.039) or the expression of VEGF (P<0.001) and MMP-9 (P<0.001). But c-mycLI and bcl-2 expression have no association with invasiveness of pituitary adenomas (P=0.061 vs. P=0.201). Onthe other hand, there is an inverse relationship between nm23 expression and tumor invasion (P<0.001). Inconclusion, parasellar extension of pituitary adenomas through the medial wall of the cavernous sinus diagnosed atsurgery, can be determined by radiology with sensitive gadolinium-enhanced MRI. Although our study has shownthat MVD and the expression of VEGF, Ki-67, nm23 and MMP-9 have associations with invasiveness of pituitaryadenomas, they are lack of specificity. These markers can only provide some useful informations on the therapeuticstrategy of pituitary adenomas.

Vasculogenic mimicry (VM) has been observed in melanoma and in some nonmelanomatumor types. It is unknown whether a similar VM phenomenon exists in astrocytoma.The present study was to examine 45 astrocytomas (including World Health Organizationgrade II 15 cases, grade III 15 cases, and grade IV 15 cases) by CD34 endothelialmarker periodic acid–Schiff (PAS) dual staining to see if VM existing in these tumors. Theresults demonstrated that endothelium-lined vessels dominated the tumor microvasculatureand stained positively for PAS, laminin, and endothelial marker. PAS-positive patternof VM was found in two grade IV astrocytomas. Channels stained positively for PAS, laminin,and negatively for CD34 of the VM entrapped in the tumor tissue. Erythrocytes couldbe observed in some of these channels. In these networks of PAS-positive pattern, spots ofweak reaction for CD34 were observed, suggesting the incorporation of VM channel andnormal vessel. Furthermore, in astrocytoma, especially glioblastoma, focus of anaplastic tumorcells appeared with CD34 expression, whereas some tumor cells lost glial fibrillary acidprotein expression. It is assumed that genetically deregulated tumor cells in astrocytomacould lose the astrocyte-specific protein and express inappropriate markers not expected incells of astrocyte lineage. The present results suggest that VM phenomenon exists in somemalignant astrocytoma.

We previously have found that 2-chloroethyl-3-sarcosinamide-1-nitrosourea (SarCNU) is a selective cytotoxin that enters cellsvia the extraneuronal transporter for monoamine transmitters(EMT). Both in vitro and in vivo studies demonstrated thatSarCNU was more effective than BCNU against human gliomas.To clarify whether EMT expression correlates with antitumorefficacy of SarCNU, we determined human EMT (EMTh)and O6-methylguanine-DNA methyltransferase (MGMT) expressionin nine human xenograft models using semiquantitativereverse-transcription polymerase chain reaction. These resultswere compared with the antitumor effects of SarCNU andthe standard chloroethylnitrosourea antitumor agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). There was no significantcorrelation between EMTh expression and antitumor efficacy ofSarCNU or BCNU. Also, there was no significant correlationbetween MGMT expression and SarCNU efficacy. However, asignificant correlation was found between MGMT expressionand BCNU antitumor efficacy. Interestingly, multiple regressionanalysis demonstrated a significant correlation betweenSarCNU efficacy and EMTh plus MGMT expression, whereasthere was no correlation between BCNU efficacy and MGMTplus EMTh expression. Thus, the absence of a linear correlationbetween SarCNU efficacy and EMTh expression appears to bedue, at least in part, to the presence of DNA repair, specifically, MGMT, in these xenograft models. These studies suggest thatMGMT expression alone correlates with BCNU activity, whereas both EMTh and MGMT expression are important determinantsof SarCNU activity against human tumor xenograftmodels. SarCNU is in clinical trials and these results may haveimportant clinical implications.

Treatment of malignant brain tumors with chloroethylnitrosoureas (CENUs) in addition to surgical resection andradiotherapy remains the foundation of glioma therapy. However, the clinical response to CENUs is at best modest.A novel analogue of nitrosoureas, 2-chloroethyl-3-sarcosinamide-1-nitrosourea (SarCNU), as compared tothe standard CENU, 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU), has been demonstrated to have increased anticancereffects both in vitro and in vivo. Unfortunately, many human tumors have been known to be resistant toCENUs since they express DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). In order toassess whether SarCNU has an effect on MGMT positive tumors, we evaluated its antitumor efficacy using anMGMT positive human glioma (SF-767) nude mouse xenograft model. Since SF-767 has high MGMT levels,BCNU treatment (20mg/kg, Q4D 3 i.p.) alone did not result in a satisfactory anticancer effect (p>0:05). Asexpected, O6-benzylguanine (O6-BG) (100mg/kg), which was given prior to BCNU treatment, by depletingMGMTactivity, significantly enhanced BCNU antitumor efficacy (p<0:001). Moreover, SarCNU treatment (167mg/kg,Q4D 3 i.p.) alone had a better antitumor effect than O6-BG plus BCNU treatment (FD 51:7, pD 0:0004). However,in this xenograft model, O6-BG did not significantly enhance the anticancer efficacy of SarCNU (FD 0:8, pD 0:411). The SF-767 human glioma xenograft is positive for extraneuronal monoamine transporter EMT (EMT)as determined by reverse-transcription polymerase chain reaction (RT-PCR). Our present results suggest that Sar-CNU is also effective for MGMT positive tumor if they exhibit EMT.