Analysis of multiple growth regulatory proteins using dissociable staining antibody arrays on solid tumor biopsy specimens.

Growth of tumor cells is often a function of deregulated growth factor receptors and their corresponding intracellular signalling molecules. The dissociable antibody staining arrays have the versatility to rapidly identify the expression, activation, and localization of such molecules and pathways in biopsy specimens. This report describes a protocol to quantify the activity of a panel of signalling molecules in Wilms tumor biopsy specimens and surrounding nonmalignant renal cells. We propose that this technique can be used to rapidly identify multiple markers and may aid in the study of aberrant growth regulatory mechanisms and potential targets for therapeutics from pathologic specimens.

Susceptibility of mantle cell lymphomas to reovirus oncolysis.

Mantle cell lymphoma (MCL) an incurable B-cell, non-Hodgkin lymphoma (NHL) urgently requires new treatments. We assessed reovirus mediated oncolysis in a panel of human MCL cell lines. In vitro, we found the cytopathic effect of reovirus infection ranged from high to very limited and correlated with levels of Ras activation. In vivo, a single reovirus injection intra-tumorally resulted in complete regression of both the injected and the contra-lateral tumor in a subcutaneous bi-tumor model, in one out of three cell lines tested. Reovirus treatment of MCL seems feasible but will need to be guided by the presence of molecular determinants of reovirus susceptibility.

Methylation status of MGMT gene promoter in meningiomas.

Meningiomas are usually cured by surgical resection. However, approximately 10% are characterized by more aggressive clinical behavior and higher risk of recurrence. Typically, recurrent meningiomas require further surgical resection followed, in some cases, by radiotherapy. To date, no chemotherapeutic agent has proven to be effective in either preventing or treating recurrence. The alkylating chemotherapeutic agent, Temozolomide (TMZ) has shown to increase overall survival in patients with glioblastoma (GBM) but its effectiveness for other types of brain tumor is less known. The clinical benefit of TMZ seems to be limited to those GBM tumors with promoter methylation of the MGMT gene. In this study, we assessed if a biologic rationale exists to support the use of TMZ as a treatment for meningiomas by assessing the MGMT promoter methylation status in these tumors using methylation specific PCR. We investigated the MGMT promoter methylation status in 36 tumors (32 newly diagnosed; 4 recurrent). Histologically, the majority were grade I. Patients were primarily female (64%) with a mean age of 52. None of the meningiomas in our series showed MGMT gene promoter methylation. Based on these data, we conclude that there is no biological rational to suggest that TMZ might have significant anti-meningioma activity.