Anti-Lung carcinoma-associated antigen Hybridoma [5H23 Hybridoma]

Purpose To investigate predictors of cognitive decline after whole brain radiotherapy (WBRT) for brain metastases. Methods A secondary analysis of a phase 2 clinical trial was conducted in patients who received stereotactic radiosurgery for 1-10 brain metastases and WBRT (NCT01046123). The Montreal Cognitive Assessment (MoCA) was performed at baseline and every 3 months after WBRT. Baseline T2-weighted fluid attenuation inversion recovery magnetic resonance imaging was independently assessed by two neuroradiologists for the presence of white matter hyperintensities (WMH) using the Fazekas visual rating scale. WMH were also manually segmented for volumetric analysis. Univariable and multivariable logistic regression were used to test the association between baseline variables and MoCA score decline. Results Forty-six patients survived >= 3 months after treatment. Age (OR 1.12 (1.04-1.21), p < 0.01), baseline WMH volume (OR 1.20, 95% CI 1.06-1.52, p = 0.02) and baseline Fazekas score >= 3/6 (OR 6.4, 95% CI 1.7-24.7, p < 0.01) were predictive of MoCA score decline. In multivariable analysis, age was the only significant predictor of MoCA decline. However, all three patients with pre-treatment leukoencephalopathy (Fazekas score = 6/6) had notable adverse outcomes due to cognitive impairment: one required full-time home nursing support and two were institutionalized. Conclusion A greater decline in cognition after WBRT was observed in older patients and patients with a higher baseline WMH burden. Although this study is small and hypothesis-generating, we propose that radiation oncologists should exercise caution in prescribing WBRT if leukoencephalopathy is present on pre-treatment imaging. Trial Registration: clinicaltrials.gov identifier NCT01046123. First posted January 11, 2010.

Tumor-targeting chemotherapeutic drug delivery platforms based on pH stimulus and "smart" drug nanocarriers have received increasing interest in precise control of spatial and temporal drug release to target lung cancer cells and reduce serious side effects compared to conventional cancer chemotherapy. Incorporation of bioactive targeting agent into drug nanocarriers offers new opportunities to improve the targeting specificity and maximize the anti-cancer therapeutic effects. Up to date, there has been limited study on the construction of effective pH-responsive tumor-targeting drug delivery systems based on bioactive targeting agents. Herein, we report the preparation of highly porous sulfate doped HAp (S-HAp) nanospheres via a facile hydrothermal approach, and apply surface-modified S-HAp nanospheres with PEG and folic acid (FA) as novel drug nanocarriers for effective pH-responsive chemotherapeutic drug delivery towards lung cancer treatment. The drug release profile shows anti-cancer doxorubicin (DOX) loaded S-HAp/PEG/FA/DOX display effective pH-triggered drug release under small pH variations. The extremely high surface area and FA surface functionalization enable a high drug loading capacity and strong anti-cancer killing effects. This is the first demonstration of highly porous sulfate doped HAp nanospheres with FA modification as biodegradable carriers for drug delivery. We believe this work can be extended to other drug carrier designs as well as pH-responsive nanoplatform construction for effective tumor-targeting cancer therapy.