Investigation of chemotherapy-induced brain structural alterations in breast cancer patients with generalized q-sampling MRI and graph theoretical analysis.

BACKGROUND: Breast neoplasms are the most common cancer among women in Taiwan. Cognitive deficits are common complications of breast cancer survivors treated with chemotherapy. The most frequently observed disorders involve executive function and memory impairment. With improvements in tumor intervention and the consequent increase in the number of cancer survivors, the quality of life of patients has become an important issue. We are interested in the early effects of chemotherapy on the brain structures of patients. In addition, generalized q-sampling imaging (GQI), a wide range of q-space datasets for a more accurate and sophisticated diffusion MR approach, was first used in this topic. METHODS: As diffusion tensor imaging (DTI) is associated with restrictions in the resolution of crossing fibers, we attempted to use GQI, which can overcome these difficulties and is advantageous over DTI for tractography of the crossing fibers. This cross-sectional study included two groups: breast cancer survivors who had completed their chemotherapy (n = 19) and healthy controls (n = 20). All participants underwent diffusion MRI exams and neuropsychological assessments. We included four parts in our image analysis, i.e., voxel-based statistical analysis, multiple regression analysis, graph theoretical analysis and network-based statistical analysis. RESULTS: The results from the voxel-based statistical analysis showed significantly lower GFA and NQA values in the breast cancer group than those in the control group. We found significant positive correlations between the FACT-Cog and GQI indices. In the graph theoretical analysis, the breast cancer group demonstrated significantly longer characteristic path length. Adjuvant chemotherapy affected the integrity of white matter and resulted in poor cognitive performance, as indicated by the correlations between the neuropsychological assessment scales and the GQI indices. In addition, it was found that the characteristic path lengths in the breast cancer group increased, indicating that the brain network integration became worse. CONCLUSIONS: Our study demonstrated alterations in structural brain networks and associated neuropsychological deficits among breast cancer survivors.

Chemical evaluation and cytotoxic mechanism investigation of Clinacanthus nutans extract in lymphoma SUP-T1 cells.

Clinacanthus nutans has been used as herbal medicine with antidiabetic, blood pressure lowering, and diuretic properties in Singapore, Thailand, and Malaysia. The in vitro cellular study showed the chloroform extract possessed significant cytotoxicity against leukemia K562 and lymphoma Raji cells. The clinical study reported that administration of plant could treat or prevent relapse in 12 cancer patients. However, detailed mechanism of the anticancer effects and chemical profiles are not thoroughly studied. The chemical study did show that the acetone extract (MHA) exerted the highest antiproliferative effect on human leukemia MOLT-4 cells and lymphoma SUP-T1 cells in dose-dependent cytotoxicity. We found that the use of MHA increased apoptosis by 4.28%-43.65% and caused disruption of mitochondrial membrane potential (MMP) by 11.79%-26.93%, increased reactive oxygen species (ROS) by 19.54% and increased calcium ion by 233.83%, as demonstrated by annexin-V/PI, JC-1, H2 DCFDA, and Flou-3 staining assays, respectively. MHA-induced ER stress was confirmed by increase expression of CHOP and IRE-1α with western blotting assay. In conclusion, we identified good bioactivity in Clinacanthus nutans and recognize its potential effect on cancer therapy, but further research is needed to determine the use of the plant.