Methylmercury-l-Cysteine targeting L-type amino acid transporter conjugate cytotoxicity on C6 glioma cells.

Glioma is the most common primary tumor in the brain, accounting for about 40~50% of intracranial primary tumors. Most chemotherapeutic drugs have difficulty in penetrating the blood-brain barrier, and their clinical applications are greatly limited. We evaluated the effects of methylmercury-L-cysteine (MeHg-L-cys) and methylmercury chloride (MMC) on apoptosis of C6 glioma cells. L-type amino acid transporter (LAT1) was used to investigate the targeted transport function and cytotoxicity of MeHg- L-cys in glioma. MeHg-L-cys enhanced the ability of targeting glioma cells and reduced the adverse reactions to normal brain tissues. Therefore, it is significantly important to develop new anti-glioma drugs targeting the blood-brain barrier.

Expression and localisation of urokinase-type plasminogen activator gene in gliomas.

Urokinase-type plasminogen activator (uPA) activity is related to the malignant biological behaviour of tumours. In the present study, we examined the presence and distribution of uPA in human gliomas. The amounts of uPA were measured by Northern blotting hybridisation and immunohistochemistry in 43 gliomas and five normal brain specimens. Their relation to the clinical history was comprehensively analysed. All tissues expressed 2.5 kb transcripts of uPA mRNA. The uPA mRNA levels were significantly higher in high grade gliomas than they were in low grade gliomas and normal brain tissue (P < 0.01). Levels of uPA mRNA expression in tumour tissues with recurrence within 18 months postoperatively and survival less than 3 years were significantly higher than counterparts (P < 0.01). The uPA mRNA was also expressed in tumour cells near necrotic areas. The uPA protein expression was consistent with the uPA mRNA expression. The distribution of uPA protein immunoreactivity was mainly in tumour cells and microvascular endothelial cells of glioblastomas and anaplastic astrocytomas, localising in the cytoplasm, especially at sites of vascular proliferation and at the leading edges of tumours. These results suggest that expression of the uPA gene is associated with the malignant progression of gliomas and may play an important role in the recurrence and invasive behaviors of higher grade gliomas.

Expression of the simian virus 40 large tumor antigen (Tag) and formation of Tag-p53 and Tag-pRb complexes in human brain tumors.

BACKGROUND: The presence of simian virus 40 (SV40) in human brain tumors remains a controversial issue. Even if SV40 does exist in brain tumors, the questions of whether it is associated with brain tumorigenesis and by what mechanisms are unknown. METHODS: SV40 large tumor antigen (Tag) was investigated by immunoprecipitation, silver staining, and Western blot analysis in 65 brain tumor cases and 8 cases of normal brain tissue. Tag-p53 and Tag-pRb complexes were screened by immunoprecipitation and Western blot analysis in 18 and 15 Tag positive tumor tissues, respectively. RESULTS: Tag was found in all 8 cases of ependymoma and 2 cases of choroid plexus papilloma, 90% of pituitary adenoma cases (9 of 10), 73% of astrocytoma cases (11 of 15), 70% of meningioma cases (7 of 10), 50% of glioblastoma multiforme cases (4 of 8), and 33% of medulloblastoma cases (2 of 6). Five oligodendroglioma cases, 1 pineocytoma case, and 8 cases of normal brain tissue were negative for Tag. The Tag-p53 complex was detected in all 18 Tag positive tumors tested and the Tag-pRb complex was detected in all 15 Tag positive tumors tested. CONCLUSIONS: SV40 Tag not only is expressed in brain tumors; it also can form specific complexes with tumor suppressors p53 and pRb. SV40 is correlated with brain tumorigenesis. The inactivation of p53 and pRb due to the formation of Tag-p53 and Tag-pRb complexes possibly is a significant mechanism in the etiopathogenesis of brain tumors.