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1.  Axillary lymph node status, adjusted for pathologic complete response in breast and axilla after neoadjuvant chemotherapy, predicts differential disease-free survival in breast cancer 
Current Oncology  2013;20(3):e180-e192.
Our retrospective study in breast cancer patients evaluated whether integrating subtype and pathologic complete response (pcr) information into axillary lymph node restaging after neoadjuvant chemotherapy (nac) adds significance to its prognostic values.
Patients included in the analysis had stage ii or iii disease, with post-nac axillary lymph node dissection (alnd), without sentinel lymph node biopsy before completion of nac, with definitive subtyping data and subtype-oriented adjuvant treatments. The ypN grading system was used to restage axillary lymph node status, and ypN0 was adjusted by pcr in both breast and axilla into ypN0(pcr) and ypN0(non-pcr). Univariate and multivariate survival analyses were performed.
Among the 301 patients analyzed, 145 had tumours that were hormone receptor–positive (hr+) and negative for the human epidermal growth factor receptor (her2–), 101 had tumours that were positive for her2 (her2+), and 55 had tumours that were triple-negative. The rate of pcr in both breast and axilla was 11.7%, 43.6%, and 25.5% respectively for the 3 subtypes. Compared with the non-pcr patients, the pcr patients had better disease-free survival (dfs) and overall survival (os): p = 0.002 for dfs and p = 0.011 for os. In non-pcr patients, dfs and os were similar in the ypN0(non-pcr) and ypN1 subgroups, and in the ypN2 and ypN3 subgroups. We therefore grouped the ypN grading results into ypN0(pcr) (n = 75), ypN0– 1(non-pcr) (n = 175), and ypN2–3 (n = 51). In those groups, the 3-year dfs was 98%, 91%, and 56%, and the 3-year os was 100%, 91%, and 82% respectively. The differences in dfs and os between those three subgroups were significant (all p < 0.05 in paired comparisons). Multivariate Cox regression showed that subtype and ypN staging adjusted by pcr were the only two independent factors predicting dfs.
Axillary lymph node status after nac, adjusted for pcr in breast and axilla, predicts differential dfs in patients without prior sentinel lymph node biopsy.
PMCID: PMC3671025  PMID: 23737688
Breast cancer; neoadjuvant chemotherapy; axillary restaging; pathologic complete response; prognosis
2.  Loss of surface N-methyl-d-aspartate receptor proteins in mouse cortical neurones during anaesthesia induced by chloral hydrate in vivo 
BJA: British Journal of Anaesthesia  2009;102(4):515-522.
Anaesthetics may target ionotropic glutamate receptors in brain cells to produce their biological actions. Membrane-bound ionotropic glutamate receptors undergo dynamic trafficking between the surface membrane and intracellular organelles. Their subcellular distribution is subject to modulation by changing synaptic inputs and determines the efficacy and strength of excitatory synapses. It has not been explored whether anaesthesia has any impact on surface glutamate receptor expression. In this study, the effect of general anaesthesia on expression of N-methyl-d-aspartate (NMDA) receptors in the surface and intracellular pools of cortical neurones was investigated in vivo.
General anaesthesia was induced by intraperitoneal injection of chloral hydrate in adult male mice. Surface protein cross-linking assays were performed to detect changes in distribution of NMDA receptor subunits (NR1, NR2A, and NR2B) in the surface and intracellular compartments of cerebral cortical neurones.
Chloral hydrate did not alter the total amounts of NR1, NR2A, and NR2B proteins in cortical neurones. However, the drug reduced NR1 proteins in the surface pool of these neurones, and induced a proportional increase in NR1 in the intracellular pool. Similar redistribution of NR2B subunits was observed between the two distinct pools. The changes in NR1 and NR2B were rapid and remained throughout the duration of anaesthesia. NR2A proteins were not altered in the surface or intracellular pool in response to chloral hydrate.
These data demonstrate that subcellular expression of NR1 and NR2B in cortical neurones is sensitive to anaesthesia. Chloral hydrate reduces surface-expressed NMDA receptors (specifically NR2B-containing NMDA receptors) in these neurones in vivo.
PMCID: PMC2724878  PMID: 19224925
anaesthetics; cerebral cortex; glutamate receptor; NR1; NR2A; NR2B

Results 1-2 (2)