Predictive value of tumor-infiltrating lymphocytes for pathological response to neoadjuvant chemotherapy in breast cancer patients with axillary lymph node metastasis.

PURPOSE: We investigated the role of tumor-infiltrating lymphocytes (TILs) in pretreatment primary breast cancer to predict pathological response to neoadjuvant chemotherapy (NAC) in patients with clinical node-positive disease (cN +). METHODS: The subjects of this study were 60 patients with cN + , who received NAC followed by breast surgery with axillary lymph node dissection (ALND). We conducted a semi-quantitative assessment of TILs in pretreatment primary tumors and their association with clinicopathological factors and axillary lymph node metastasis. RESULTS: We observed a higher number of TILs in tumors with negative hormone receptors, positive human epidermal growth factor receptor 2, or high Ki67. TILs were associated with a favorable response to NAC in primary tumors. The rate of axillary pathologic complete response (Ax-pCR) was significantly higher in patients with a high number of TILs than in patients with a low number of TILs (72.0% versus 17.1%, p < 0.001). In multivariable analysis, a high number of TILs was a significant predictor of Ax-pCR as well as of pCR of the primary tumor after NAC. Importantly, all patients with HER2-positive tumors in the high TILs group showed Ax-pCR on ALND. CONCLUSION: TILs in pretreatment primary breast cancer had the potential to predict therapeutic efficacy of NAC in patients with clinical node-positive disease.

Neurogenesis enhances response specificity to spatial pattern stimulation in hippocampal cultures.

OBJECTIVE: Adult neurogenesis in the hippocampus facilitates cognitive functions such as pattern separation in mammals. However, it remains unclear how newborn neurons mediate changes in neural networks to enhance pattern separation ability. Here, we developed an in vitro model of adult neurogenesis using rat hippocampal cultures in order to investigate whether newborn neurons can be directly incorporated into neural networks related to pattern separation to produce functional improvements. METHOD: We optimized at schedule of basic fibroblast growth factor (bFGF) administration to enhance neurogenesis, and then used a microelectrode array system to evaluate the responses of neural cultures to two different spatial pattern stimuli (L and inverted L shapes) before and after training. RESULTS: We found that early synaptic response times to a given pattern were shortened after training, and that this effect was more pronounced in cultures treated with bFGF. Furthermore, bFGF-treated cultures showed improved response specificity after training as indicated by calculated Kullback-Leibler divergence values, suggesting that pattern separation was better achieved in cultures with enhanced neurogenesis. CONCLUSION: Neural networks containing greater numbers of immature neurons exhibited higher response specificity to spatial pattern stimulation, suggesting the improvement of the pattern separation by neurogenesis enhancement. SIGNIFICANCE: These results are the first in vitro demonstration that neurogenesis improves pattern separation. Our novel in vitro system will be a useful tool for investigating the contribution of adult neurogenesis to cognitive functions.

Photoinduced cytotoxicity of a photochromic diarylethene via caspase cascade activation.

The photo-generated closed-ring isomer of bis(5-methyl-2-phenylthiazoyl)perfluorocyclopentene shows cytotoxicity to Madin-Darby canine kidney (MDCK) cells through a caspase cascade and induces apoptosis of cells.