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1.  Inhibition of Indoleamine-2,3-dioxygenase (IDO) in Glioblastoma Cells by Oncolytic Herpes Simplex Virus 
Advances in Virology  2012;2012:815465.
Successful oncolytic virus treatment of malignant glioblastoma multiforme depends on widespread tumor-specific lytic virus replication and escape from mitigating innate immune responses to infection. Here we characterize a new HSV vector, JD0G, that is deleted for ICP0 and the joint sequences separating the unique long and short elements of the viral genome. We observed that JD0G replication was enhanced in certain glioblastoma cell lines compared to HEL cells, suggesting that a vector backbone deleted for ICP0 may be useful for treatment of glioblastoma. The innate immune response to virus infection can potentially impede oncolytic vector replication in human tumors. Indoleamine-2,3-dioxygenase (IDO) is expressed in response to interferon γ (IFNγ) and has been linked to both antiviral functions and to the immune escape of tumor cells. We observed that IFNγ treatment of human glioblastoma cells induced the expression of IDO and that this expression was quelled by infection with both wild-type and JD0G viruses. The role of IDO in inhibiting virus replication and the connection of this protein to the escape of tumor cells from immune surveillance suggest that IDO downregulation by HSV infection may enhance the oncolytic activity of vectors such as JD0G.
doi:10.1155/2012/815465
PMCID: PMC3424635  PMID: 22924042
2.  Trends and importance of radiosurgery for the development of functional neurosurgery 
Surgical Neurology International  2012;3(Suppl 1):S3-S9.
Functional neurosurgery includes surgery conducted to ablate, augment, or modulate targets that lead to improvement in neurological function or behavior. Surgical approaches for this purpose include destructive lesioning with different mechanical or biologic agents or energy sources, non-destructive electrical modulation, and cellular or chemical augmentation. Our purpose was to review the role of stereotactic radiosurgery used for functional indications and to discuss future applications and potential techniques. Imaging and neurophysiological research will enable surgeons to consider new targets and circuits that may be clinically important. Radiosurgery is one minimal access approach to those targets.
doi:10.4103/2152-7806.91604
PMCID: PMC3400481  PMID: 22826808
Radiosurgery; functional neurosurgery; stereotactic
3.  Ectopic Matrix Metalloproteinase 9 Expression in Human Brain Tumor Cells Enhances Oncolytic HSV Vector Infection 
Gene therapy  2010;17(10):1200-1205.
Oncolytic HSV (oHSV) vectors have shown promise in the treatment of patients with recurrent brain tumors although few complete responses have accrued. Impediments to effective therapy include limited vector distribution on delivery, a consequence of injected virion particle trapping in the tumor extracellular matrix (ECM). To enhance virus delivery and spread, we investigated the use of the matrix metalloproteinase 9 (MMP9) as a means to degrade collagen type IV, a major component of the ECM and basement membranes of gliomas that is absent in normal brain tissue. SK-N-AS neuroblastoma cells were transduced for constitutive, elevated expression of MMP9, which did not enhance tumor cell migration in vitro or tumor progression in a murine xenograft brain tumor model. MMP9 expression afforded increased distribution of oHSV vector-infected tumor cell spheroids and afforded vector infection over larger areas of brain tumors in vivo. These results suggest that vector delivery and distribution in vivo can be improved by compromising the ECM, potentially enhancing oncolytic efficacy.
doi:10.1038/gt.2010.66
PMCID: PMC3228315  PMID: 20463757
4.  First year experience with newly developed Leksell Gamma Knife® Perfexion™ 
A new model of Leksell Gamma Knife® (LGK), known as Perfexion™ (LGK PFX), was introduced by Elekta Instrument, AB, Sweden, in 2006. This model has a radically different design from the earlier models U, B, C and 4C. Dosimetric characteristics of LGK PFX, technical differences between LGK PFX and LGK 4C, experience gained with acceptance testing and commissioning of the LGK PFX, and comparison between LGK PFX and LGK 4C are presented in this study. Excellent agreement is found between the manufacturers recommended values of absorbed dose rate, relative output factors for 4 and 8 mm collimators, coincidence of mechanical and dosimetric isocenter, FWHM for beam profiles for various collimators and those reported in the present study. Excellent agreement is also found between the dosimetric characteristics of LGK PFX and LGK 4C for the 4 and 8 mm collimators. Examples of clinical cases treated with LGK PFX and impact of LGK PFX on workflow and dosimetric conformity of treatment planning is also given. The set up and treatment of patients on the LGK PFX is much more efficient since it is a fully automated system. The system also provides more options to generate plan with high dosimetric conformity.
doi:10.4103/0971-6203.54848
PMCID: PMC2807679  PMID: 20098561
Leksell Gamma Knife PERFEXION; Leksell Gamma Knife dosimetry; Leksell Gamma Knife treatment planning

Results 1-4 (4)