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.