F. Lupidi

Significant prevalence of antibodies reacting with simian virus 40 mimotopes in sera from patients affected by glioblastoma multiforme

BACKGROUND Glioblastoma multiforme (GBM) is a rare tumor, which affects 1/100 000 individuals, but it represents 30% of central nervous system malignancies. GBM is a severe tumor responsible for 2% of all cancer-related deaths. Although characterized by genotypic and phenotypic heterogeneities, GBM invariably resists conventional chemo- and radiotherapies. Several chromosome alterations and gene mutations were detected in GBM. Simian virus 40 (SV40), a small DNA tumor virus, has been found in GBM specimens by some studies, while other investigations have not confirmed the association. METHODS An indirect enzyme-linked immunosorbent assay with 2 synthetic peptides mimicking SV40 antigens of viral capsid proteins 1-3 was employed to detect specific antibodies against SV40 in serum samples from GBM-affected patients, together with controls represented by patients affected by breast cancer and normal subjects of the same median age. RESULTS Our data indicate that in serum samples from GBM-affected patients (n = 44), the prevalence of antibodies against SV40 viral capsid protein antigens is statistically significantly higher (34%, P = .016 and P = .03) than in the control groups (15%), represented by healthy subjects (n = 101) and patients affected by breast cancer (n = 78), respectively. CONCLUSION Our data indicate that SV40, or a closely related yet undiscovered human polyomavirus, is associated with a subset of GBM and circulates in humans. Our study can be transferred to the clinical oncology application to discriminate different types of heterogeneous GBM, which in turn may address an innovative therapeutic approach to this fatal cancer.

Gamma knife radiosurgery in brain metastases from testicular tumors.

To our knowledge, there are no published reports on the effectiveness of radiosurgery in the management of brain metastases from testicular nonseminomatous germ cell tumor. The authors evaluate the results of gamma knife (GK) treatment in three patients with these unusual intracranial lesions. Between April 1995 and July 2001, three patients with brain metastasis from testicular nonseminomatous germ cell tumor underwent adjuvant radiosurgery at our department. The primary tumor had been surgically removed in all cases. At diagnosis, one patient was stage IB and two were stage III poor risk. Chemotherapy and whole brain radiotherapy were administered before radiosurgery in all cases. Pre-GK radiotherapy was administered with a daily fraction dosage of 1.8–2.0 Gy. The indications for radiosurgery were tumor volume <20 cm3, microsurgery too risky, refusal of surgery. All the lesions were located in eloquent brain areas. Post-GK high-dose chemotherapy with autologous peripheral-blood stem-cell rescue was administered in two cases due to systemic recurrence of the disease. All patients are still alive with a median and mean follow-up period after radiosurgery of 63 and 68.3 mo, respectively. They had no neurological deficits at the latest examination. Neuroradiological follow-up invariably showed tumor growth control (complete response in two cases and partial response in one) with typically delayed post-radiosurgical imaging changes (transient in two cases and long-lasting in one). In conclusion, GK seems to be highly effective and safe in brain metastases from testicular nonseminomatous germ cell tumor. In cases with diffuse metastatic brain involvement, the whole brain radiotherapy preceding radiosurgery should be delivered with ≤1.8 Gy daily fraction to prevent the risk of long-lasting post-radiosurgical imaging changes.

Diffusion-Tensor Imaging Tractography of the Corticospinal Tract for Evaluation of Motor Fiber Tract Radiation Exposure in Gamma Knife® Radiosurgery Treatment Planning

Aims: To assess the feasibility of diffusion-tensor imaging (DTI) fibertractography of the corticospinal tract (CST) performed with 3 T MRI as a tool for Gamma Knife®

Glioblastoma in a Patient with Professional Exposure to the Oncogenic Polyomavirus SV40

In previous investigations, the transforming sequences of simian virus 40 (SV40) had been found in human brain tumors, thereby suggesting a role for SV40 in human tumorigenesis. A recent study reported the case of a meningioma in a SV40-exposed scientist. The patients meningioma contained SV40 DNA sequences identical to those the patient had ever been exposed in the laboratory. The aim of this study was to investigate another case of SV40-exposed scientist with glioblastoma multiforme. After surgical resection of the larger neoplastic lesion, the patients tumor and blood samples were analyzed for SV40 sequences by PCR and filter hybridization. The differences among polymaviruses, such as SV40, BK and JC, and among SV40 strains were found in the T antigen (Tag) coding sequences and in the regulatory regions. Therefore, we analyzed the conserved SV40 regulatory region and Tag oncoprotein coding sequences in the patients specimen. The results did not reveal the SV40 DNA sequences detectable from this patient. Our data do not support in this clinical case the link between the SV40 exposure and the brain tumor.