Highly-enhanced active beam-wander-correction for free-space quantum communications.

In practical applications to free-space quantum communications, the utilization of active beam coupling and stabilization techniques offers notable advantages, particularly when dealing with limited detecting areas or coupling into single-mode fibers(SMFs) to mitigate background noise. In this work, we introduce highly-enhanced active beam-wander-correction technique, specifically tailored to efficiently couple and stabilize beams into SMFs, particularly in scenarios where initial optical alignment with the SMF is misaligned. To achieve this objective, we implement a SMF auto-coupling algorithm and a decoupled stabilization method, effectively and reliably correcting beam wander caused by atmospheric turbulence effects. The performance of the proposed technique is thoroughly validated through quantitative measurements of the temporal variation in coupling efficiency(coincidence counts) of a laser beam(entangled photons). The results show significant improvements in both mean values and standard deviations of the coupling efficiency, even in the presence of 2.6 km atmospheric turbulence effects. When utilizing a laser source, the coupling efficiency demonstrates a remarkable mean value increase of over 50 %, accompanied by a substantial 4.4-fold improvement in the standard deviation. For the entangled photon source, a fine mean value increase of 14 % and an approximate 2-fold improvement in the standard deviation are observed. Furthermore,the proposed technique successfully restores the fidelity of the polarization-entangled state, which has been compromised by atmospheric effects in the free-space channel, to a level close to the fidelity measured directly from the source. Our work will be helpful in designing spatial light-fiber coupling system not only for free-space quantum communications but also for high-speed laser communications.

Leptomeningeal seeding in patients with brain metastases treated by gamma knife radiosurgery.

To characterize the development of leptomeningeal seeding (LMS) in patients with brain metastases after gamma knife radiosurgery (GKRS). Eight hundred and twenty-seven patients that underwent GKRS as a part of an initial treatment plan for brain metastases between January 2002 and December 2010 were included in the study. Six hundred and fifty patients were treated with GKRS alone and 177 patients received GKRS combined with upfront whole brain radiation therapy (WBRT). Actuarial curves for overall survival (OS) and the development of LMS were plotted using the Kaplan-Meier method. Median overall survival for all patients was 55 weeks (95 % CI, 47.8-62.2), and the overall incidence of LMS was 5.3 %. The actuarial rates for LMS at 6 and 12 months were 3.1 and 5.8, respectively. Uni- and multivariate analysis suggested that breast cancer and a large number of metastases (n ≥ 4) are significant risk factors of LMS (P < 0.05). Regarding treatment modalities, the addition of WBRT was found to have a significant impact on lowering the risk of LMS by multivariate analysis (P = 0.045). LMS is an important pattern of CNS failure. The risk of LMS following GKRS may be associated with multiple lesions, breast cancer, and the omission of WBRT. Additional data from large-scale, randomized controlled trials are required to identify risk factors associated with the LMS more accurately.

Trans-differentiation of neural stem cells: a therapeutic mechanism against the radiation induced brain damage.

Radiation therapy is an indispensable therapeutic modality for various brain diseases. Though endogenous neural stem cells (NSCs) would provide regenerative potential, many patients nevertheless suffer from radiation-induced brain damage. Accordingly, we tested beneficial effects of exogenous NSC supplementation using in vivo mouse models that received whole brain irradiation. Systemic supplementation of primarily cultured mouse fetal NSCs inhibited radiation-induced brain atrophy and thereby preserved brain functions such as short-term memory. Transplanted NSCs migrated to the irradiated brain and differentiated into neurons, astrocytes, or oligodendrocytes. In addition, neurotrophic factors such as NGF were significantly increased in the brain by NSCs, indicating that both paracrine and replacement effects could be the therapeutic mechanisms of NSCs. Interestingly, NSCs also differentiated into brain endothelial cells, which was accompanied by the restoration the cerebral blood flow that was reduced from the irradiation. Inhibition of the VEGF signaling reduced the migration and trans-differentiation of NSCs. Therefore, trans-differentiation of NSCs into brain endothelial cells by the VEGF signaling and the consequential restoration of the cerebral blood flow would also be one of the therapeutic mechanisms of NSCs. In summary, our data demonstrate that exogenous NSC supplementation could prevent radiation-induced functional loss of the brain. Therefore, successful combination of brain radiation therapy and NSC supplementation would provide a highly promising therapeutic option for patients with various brain diseases.

Prognostic implications of the DNA damage response pathway in glioblastoma.

Genomic instability and resistance to genotoxic therapies for glioblastoma (GBM) suggest aberrant DNA damage response (DDR), since DDR maintains the genomic integrity against genotoxic insults including anti-tumor therapies. To elucidate the biological and clinical meaning of DDR in GBM, we retrospectively investigated the immunohistochemical expression of DDR proteins (ATM, Chk1, Chk2, TopBP1, Rad17, p53, Nbs1, MDC1, γH2AX and RPA1) in 69 GBM surgical samples and their relation with GBM patient survival. Remarkably, higher expression of ATM revealed significantly longer overall survival (OS) and progression-free survival (PFS) (p<0.05). Upon multivariate analysis, expression level of ATM was an independent factor for longer OS (p=0.020) and longer PFS (p=0.019). Since ATM induces cell cycle arrest or apoptosis through cell cycle regulators in response to genotoxic insults, these results indicate that aberrant DDR signaling through ATM in GBM may be associated with resistance to genotoxic anti-tumor therapeutics. Conclusively, we emphasize that the identification of DDR machinery, which can be involved in unstable genomic status or genotoxic therapies in GBM, is very important to predict patient outcome.

The expression of DNA damage checkpoint proteins and prognostic implication in metastatic brain tumors.

The most important therapeutic tool in brain metastasis is radiation therapy. However, resistance to radiation is a possible cause of recurrence or treatment failure. Recently, DNA damage checkpoint signaling pathway activation after irradiation has received increasing attention. The association between the expression levels and survival outcome was evaluated to find possible therapeutic targets in brain metastasis. Radiosensitivity of human non-small cell lung cancer cell lines was determined by checking their viability after treatment with varying doses of ionizing radiation (IR). The expression of DNA checkpoint proteins was analyzed by Western blots and immunohistochemistry. On the basis of the clinical data for the patients, the association between the expression of the components and patients' survival was investigated. The expression levels of TopBP1 and phosphorylated Chk1 (P-Chk1) protein were higher in radioresistant lung cancer cell lines compared to radiosensitive cell lines. We previously assessed radiation survival of lung cancer cell lines after treating them with Chk1 inhibitor, AZD7762. AZD7762 significantly sensitized both radioresistant and radiosensitive cells to IR. We also observed a strong inverse relationship between progression-free survival (PFS) and expression level of P-Chk1 and TopBP1. This study, which is the first clinical report that connects DNA damage checkpoints and prognosis of brain metastasis, supports these two proteins to be promising targets for overcoming the radioresistance in brain metastasis.

Efficacy of temozolomide as adjuvant chemotherapy after postsurgical radiotherapy alone for glioblastomas.

OBJECTIVES: The aim of this study was to assess the efficacy of adjuvant TMZ chemotherapy for newly diagnosed GBM patients who were treated with surgery followed by radiotherapy alone. MATERIAL AND METHODS: Between January 2003 and April 2005, 59 consecutive GBM patients underwent radiation therapy after surgical resection and subsequently received TMZ chemotherapy. For the comparative analysis, we selected 60 clinically matched GBM patients who underwent radiotherapy followed by nitrosourea-based chemotherapy (NUBC), at the same institution between June 1995 and April 2005. The study cohort was divided into two groups, those with adjuvant TMZ treatment and with NUBC. RESULTS: 59 patients with adjuvant TMZ treatment were assigned to the treatment group and 60 patients with NUBC to the control group. The median overall survival for the treatment group was 18.2 months (95% CI, 11.7-24.7 months), compared with the survival of 14.5 months (95% CI, 11.2-17.7 months) for the control group (p=0.019). The progression-free survival for the treatment group was 5.6 months (95% CI, 4.4-6.7 months), while the control group showed progression-free survival of 3.3 months (95% CT, 3.2-6.0 months) (p=0.030). Uni- and multivariate analysis revealed that extent of surgical resection, age > or =55 years and postoperative KPS were significantly associated with survival. CONCLUSION: Adjuvant TMZ chemotherapy provided a clinically relevant benefit of survival, as compared with NUBC. Thus, we suggest that adjuvant TMZ chemotherapy may be effective even for patients who did not receive concomitant chemoradiotherapy for GBM.

Efficacy of stereotactic radiosurgery as a salvage treatment for recurrent malignant gliomas.

BACKGROUND: The objective of this prospective cohort study was to determine the efficacy of stereotactic radiosurgery (SRS) as a salvage treatment in patients with recurrent malignant gliomas. METHODS: Between January 2000 and December 2006, 114 consecutive patients were treated with SRS as a salvage treatment for recurrent malignant gliomas at a single institution. Clinical outcome and its prognostic factors were analyzed and compared with the historical control group who were treated at the same institution between 1995 and 1999. RESULTS: The median overall survival from the time of diagnosis was 37.5 months (95% confidence interval [95% CI], 11.7-63.2 months) for patients with grade 3 gliomas (according to World Health Organization criteria) and was 23 months (95% CI, 16.2-29.3 months) for patients with glioblastomas. The median progression-free survival after SRS was 8.6 months (95% CI, 1.1-16.2 months) for patients with grade 3 gliomas and 4.6 months for patients with glioblastomas (95% CI, 4.0-5.2 months). With regard to treatment-related complications, radiation-induced necrosis was observed in 22 of 114 patients (24.4%). Compared with this historic control group, SRS significantly prolonged survival as a salvage treatment in patients with recurrent glioblastomas (23 months vs 12 months; P < .0001), but it was not found to provide a significant surgical benefit in patients with recurrent grade 3 gliomas (37.5 months vs 26 months; P = .789). On univariate analysis of prognostic factors, tumor volume (<10 mL) and low histologic grade were found to significantly influence better survival (P = .009 and P = .041, respectively). CONCLUSIONS: SRS is a safe and effective modality in selected patients with recurrent small-sized glioblastomas. However, the efficacy of SRS for recurrent grade 3 gliomas needs to be further evaluated in well-designed clinical studies.

Stereotactic device for Gamma Knife radiosurgery in experimental animals: technical note.

OBJECTIVE: Radiosurgery has become a well-established treatment modality for many intracranial lesions and the information obtained from animal experiments is crucial in devising new strategies with improved efficacy and less risk. We constructed a stereotactic device for rats which can be used for both usual laboratory work and radiosurgery using a Gamma Knife. MATERIALS AND METHODS: The stereotactic device was made by modifying the basic design of the ordinary stereotactic frames used for usual laboratory work. It was developed for both Gamma Knife model B and C. An auxiliary tool was also devised which facilitates the placement of the target point at the radiation isocenter. RESULTS: The reliability of the device was verified by checking the radiation profile and absorbed dose. The results of the experimental irradiation in normal and tumor-cell-inoculated rats demonstrated the usefulness of the device. CONCLUSIONS: The modified animal stereotactic frame described herein can be used for both the production of experimental animal models and for performing radiosurgery with a common apparatus.