ISSN:0148-396X    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0148-396X    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

OBJECTIVES:Shunts frequently require surgical replacement because occlusions block the ventricular tubing. We have examined the hypothesis that a surgical laser coupled to an optical fiber can deliver sufficient energy to disrupt the occlusion in situ and thus afford a less invasive method of repair.METHODS:Choroid plexus tissue found in shunts explanted from patients, model tissues such as polyacrylamide gel, and animal tissues inserted into shunts were examined. Occlusions were fragmented by pulsed laser energy of 2.09-µm wavelength and 300-microsecond duration delivered via a flexible optical fiber several meters in length. The methods and conditions were similar to those likely to be used for preclinical in vivo studies.RESULTS:Short-lived vapor bubbles generated at the fiber tip disrupted occlusions within the shunt and expelled tissue blocking the inflow holes. Energy requirements to disrupt and remove occlusions in vitro were determined. Laser pulse energies and exposure thresholds that cause intentional damage to shunts also were determined.CONCLUSION:Laser energies needed to disrupt occlusions were below the energy needed to damage the shunt components. Our results show that a strategy using surgical lasers and optical fibers is feasible and suggest that the procedure could be used to repair blocked shunts without requiring surgical replacement.

ISSN:0148-396X    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0148-396X    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0148-396X    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

OBJECTIVE:Using the well-characterized F98 rat glioma model, the purpose of the present study was to determine whether the delivery of boronophenylalanine (BPA) could be enhanced by prior administration of the bradykinin analog Cereport (Alkermes, Inc., Cambridge, MA) (previously known as Receptor-Mediated Permeabilizer-7), which produces a transient, pharmacologically mediated opening of the blood-brain barrier.METHODS:Two series of experiments were performed in F98 glioma-bearing rats that had received either intracarotid (i.c.) or intravenous infusions of Cereport (at doses ranging from 1.5 to 7.5 µg/kg of body weight), followed by i.c. (or intravenous) injection of BPA (300 mg/kg of body weight). Animals were killed 0.5, 2.5, or 4 hours later, samples of blood, skin, muscle, and eye were obtained, brains were removed, and tumors were excised for boron determination by direct current plasma-atomic emission spectroscopy.RESULTS:Averaged over all time points, i.c. infusion of Cereport significantly enhanced tumor boron uptake (P= 0.0001), compared with the excipient (saline) control values. Tumor boron values were equivalent at 0.5 (36.0 µg/g) and 2.5 hours (38.5 µg/g) after i.c. administration of Cereport and BPA and then decreased by 33% (to 25.7 µg/g) at 4 hours. These tumor boron uptake values were significantly different (α = 0.05), compared with values measured at the corresponding times after i.c. administration of BPA without Cereport (22.6, 21.8, and 15.3 µg/g, respectively). Although no time-related effects were observed, i.c. administration of Cereport followed by intravenous administration of BPA also significantly enhanced (α = 0.05) tumor boron uptake at 0.5, 2.5, and 4 hours (27.4, 30.3, and 28.0 µg/g, respectively), compared with values obtained without Cereport (11.3, 13.4, and 15.2 µg/g, respectively). Boron levels in normal brain tissue from tumor-bearing and non-tumor-bearing cerebral hemispheres and in blood were not significantly different from those measured in saline-treated control animals.CONCLUSION:This study established that i.c. infusion of Cereport significantly increased delivery of BPA to F98 rat gliomas, and this could enhance the efficacy of boron neutron capture therapy of this tumor.

ISSN:0148-396X    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0148-396X    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0148-396X    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

OBJECTIVE:Experimental brain tumor gene therapy with the herpes simplex virus thymidine kinase (HSV-tk) gene has demonstrated that not only HSV-tk transduced but surrounding non-HSV-tk transduced cells are killed when given ganciclovir. This so-called bystander effect has recently been shown to be dependent on connexin-mediated intercellular communication. To assess potential susceptibility to the bystander effect, we examined levels of connexin-26 and connexin-43 expression in a series of primary brain tumors. Connexin-26 expression has not previously been studied in primary brain tumors and connexin-43 expression has not been studied in nonastrocytic primary brain tumors. We also attempted to enhance the bystander effect in vitro by overexpressing connexin in tumor cells with high basal levels of connexin expression.METHODS:Western blot analysis and immunohistochemistry were used to determine levels of connexin-26 and connexin-43 expression in a series of primary brain tumors. Wild-type 9L gliosarcoma cells were transfected in vitro with the connexin-43 gene and the HSV-tk gene or the HSV-tk gene alone. The bystander effect of each transfectant was then assessed and compared.RESULTS:Most of the primary brain tumors tested, including low-grade astrocytomas, anaplastic astrocytomas, glioblastomas, oligodendrogliomas, gangliogliomas, meningiomas, and medulloblastomas, showed connexin-26 and connexin-43 expression. Bystander experiments revealed a significant enhancement of the bystander effect in the gliosarcoma cells transfected with connexin-43 and HSV-tk, as compared with gliosarcoma cells transfected with HSV-tk alone.CONCLUSION:Most primary brain tumors express connexin-26 and connexin-43. This suggests that most primary brain tumors may be susceptible to the bystander effect of HSV-tk gene therapy. The bystander effect can be enhanced in vitro by overexpression of connexin-43 in a cell line with a high basal level of connexin-43 expression.

ISSN:0148-396X    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0148-396X    

出版商:OVID    

年代:1999

数据来源: OVID