Purpose Cidofovir (CDV) is a FDA approved nucleoside antiviral agent used to treat severe human cytomegalovirus (HCMV) infection. Until now, no clear therapeutic effects of CDV have been reported outside of the setting of viral infection, including a potential role for CDV as an antineoplastic agent for the treatment of brain tumors. Experimental Design We investigated CDV cytotoxicity against glioblastoma (GBM) cells, U87MG and primary SF7796, in vitro and in vivo, using an intracranial xenograft model. Standard techniques for cell culturing, immunohistochemistry, Western blotting, and real-time PCR were employed. The survival of athymic mice (n= 8–10 per group) bearing GBM tumors, treated with CDV alone or in combination with radiation, was analyzed by the Kaplan-Meier method and evaluated with a two-sided log-rank test. Results CDV possesses potent antineoplastic activity against HCMV infected GBM cells. This activity is associated with inhibition of HCMV gene expression and with activation of cellular apoptosis. Surprisingly, we also determined that CDV induces GBM cell death in the absence of HCMV infection. CDV is incorporated into tumor cell DNA, which promotes double-stranded DNA breaks and induces apoptosis. In the setting of ionizing radiation treatment (RT), the standard of care for GBM in humans, CDV augments radiation-induced DNA damage and further promotes tumor cell death. Combined CDV and RT treatment significantly extended the survival of mice bearing intracranial GBM tumors. Conclusion We have identified a novel anti-glioma property of the FDA approved drug CDV, which heightens RT cytotoxic effect, the standard of care therapy for GBM.
Objective: To assess the safety and efficacy of hyperbaric oxygen (HBO) for treating radiation cystitis a long-term follow-up study was done in patients with prostate cancer, the second most common malignancy in Japan. Patients and Methods: A total of 38 patients at an age of 68 ± 8 years with radiation cystitis following irradiation of prostate cancer were treated with HBO at 2 absolute atmospheric pressures for 90 min daily. The average number of HBO treatment sessions in each patient was 62 ± 12. The follow-up period was 11.6 ± 3.7 years. We evaluated objective and subjective symptoms periodically with special reference to the initiation timing of HBO therapy. Results: High efficacy ratios of objective and subjective findings were obtained at 2 and 4 (79–95%) years, respectively. After 7 years’ follow-up, these ratios decreased slightly (72–83%) but still remained stable thereafter (75–88%) without any serious accident. Comparison of late morbidity scores before and 11.6 years after HBO therapy showed significant improvement (p < 0.0005). Twenty-eight patients (74%) obtained nonrecurrent outcome. They had received 18% lower (p < 0.001) radiation dosage than recurrent patients. The interval between the onset of hematuria and start of HBO treatment in nonrecurrent patients was 30% shorter (p < 0.001) than that of recurrent patients. Conclusions: We elucidated the long-term safety and beneficial effect of HBO therapy of radiation cystitis in patients with prostate cancer. Early application of HBO treatment after the onset of hematuria appears to produce favorable outcome.
Here, we report biodegradable temperature-triggered covalent gelation systems exhibiting a longer and controllable duration time of the gel state by a "mixing strategy" utilizing a thiol-ene reaction. We synthesized a tri-block copolymer of poly(caprolactone-co-glycolic acid) and PEG (tri-PCG) as a temperature-responsive injectable polymer (IP) and attached acryloyl groups on both termini (tri-PCG-Acryl). A tri-PCG micelle solution containing hydrophobic hexa-functional polythiol (Solution-A) and a tri-PCG-Acryl micelle solution (Solution-B) were mixed together. After mixing, the solution was still in the sol state at r.t., but exhibited an irreversible sol-to-gel transition in response to temperature. The duration time of the gel state while soaking in PBS could be altered from 1 day to 93 days by changing the mixing ratio of Solution-A/B. The physical strengths of the hydrogels were also controllable by changing the mixing ratio. The IP system showed good biocompatibility and a long duration time of the gel state after subcutaneous implantation.
Neurovascular interventional radiology (neuro-IR) procedures tend to require an extended fluoroscopic exposure time and repeated digital subtraction angiography. To evaluate the actual measurement of eye lens dose using a direct eye dosemeter in neuro-IR physicians is important. Direct dosimetry using the DOSIRIS™ (IRSN, France) [3 mm dose equivalent, Hp(3)] was performed on 86 cases. Additionally, a neck personal dosemeter (glass badge) [0.07 mm dose equivalent, Hp(0.07)] was worn outside the protective apron to the left of the neck. The average doses per case of neuro-IR physicians were 0.04 mSv/case and 0.02 mSv/case, outside and inside the radiation protection glasses, respectively. The protective effect of radiation protection glasses was approximately 60%. The physician eye lens dose tended to be overestimated by the neck glass badge measurements. A correct evaluation of the lens dose [Hp(3)] using an eye dosemeter such as DOSIRIS™ is needed for neuro-IR physicians.
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