Elevated levels of plasma lactate dehydrogenase is an unfavorable prognostic factor in patients with epidermal growth factor receptor mutation-positive non-small cell lung cancer, receiving treatment with gefitinib or erlotinib.

Treatment with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has been shown to prolong survival in patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). The present study performed a retrospective analysis to investigate the association between the plasma lactate dehydrogenase (LDH) levels and survival in patients with EGFR mutation-positive NSCLC receiving treatment with EGFR-TKIs. The medical charts of patients with EGFR mutation-positive NSCLC who were receiving treatment with EGFR-TKIs at Toyama University Hospital between 2007 and 2014 were assessed. The data from 65 patients were included in the analysis. Patients with higher plasma LDH levels exhibited shorter progression-free survival (6.2 vs. 13.2 months; P<0.01) and overall survival (10.5 vs. 36.1 months; P<0.01) periods compared with patients with lower plasma LDH levels. A Cox proportional hazards model identified that the plasma LDH level was associated with the progression-free survival (P=0.05) and overall survival (P<0.01). An association was demonstrated between the pretreatment plasma LDH level and the survival in patients with EGFR mutation-positive NSCLC receiving treatment with EGFR-TKIs. Close observation is required in EGFR mutation-positive NSCLC patients exhibiting high plasma LDH levels following the initiation of treatment with EGFR-TKIs.出版社サイトへのリンク：https://doi.org/10.3892/mco.2016.77

Plasma neuron-specific enolase level as a prognostic marker in patients with non-small cell lung cancer receiving gefitinib.

Determination of the presence of epidermal growth factor receptor (EGFR) gene mutation is useful for predicting the efficacy of gefitinib. However, the survival rate following the initiation of treatment with gefitinib varies among individuals. A retrospective study was conducted to investigate the associations of the pretreatment serum pro-gastrin-releasing peptide (pro-GRP) and plasma neuron-specific enolase (NSE) levels to the patient survival rate following initiation of treatment with gefitinib in non-small cell lung cancer (NSCLC) patients receiving gefitinib treatment. Patients with NSCLC harboring EGFR gene mutations who received gefitinib therapy between 2004 and 2012 were included in the study. Data from a total of 41 patients were analyzed. The serum pro-GRP level was measured in 31 patients and the plasma NSE in 22 patients. The progression-free survival (PFS) (P=0.013) and overall survival (OS) (P=0.014, log-rank test) rates decreased as the plasma NSE level increased. Statistical analysis using a Cox proportional hazards regression model adjusted for age, gender, performance status (PS) and disease stage showed that higher NSE levels were associated with shorter PFS (P=0.021) and OS (P=0.0024). By contrast, no association was detected between the serum level of pro-GRP and survival rate. The results suggest that pretreatment NSE measurement could be clinically useful in patients with NSCLC scheduled to receive gefitinib treatment.出版社サイトへのリンク: https://doi.org/10.3892/mco.2015.56

Correlation functions of the integrable higher-spin XXX and XXZ spin chains through the fusion method

For the integrable higher-spin XXX and XXZ spin chains we present multiple-integral representations for the correlation function of an arbitrary product of Hermitian elementary matrices in the massless ground state. We give a formula expressing it by a single term of multiple integrals. In particular, we explicitly derive the emptiness formation probability (EFP). We assume $2s$-strings for the ground-state solution of the Bethe ansatz equations for the spin-$s$ XXZ chain, and solve the integral equations for the spin-$s$ Gaudin matrix. In terms of the XXZ coupling $\Delta$ we define $\zeta$ by $\Delta=\cos \zeta$, and put it in a region $0 \le \zeta < \pi/2s$ of the gapless regime: $-1 < \Delta \le 1$ ($0 \le \zeta < \pi$), where $\Delta=1$ ($\zeta=0$) corresponds to the antiferromagnetic point. We calculate the zero-temperature correlation functions by the algebraic Bethe ansatz, introducing the Hermitian elementary matrices in the massless regime, and taking advantage of the fusion construction of the $R$-matrix of the higher-spin representations of the affine quantum group.Comment: 50 pages, no figur

Usefulness of the Palliative Prognostic Index in patients with lung cancer.

The usefulness of the Palliative Prognostic Index (PPI) has been successfully validated in a variety of clinical settings. However, while lung cancer is the leading cause of death worldwide, patients with lung cancer accounted for only 6.9-25.8 % of the study populations in these previous studies. We conducted a retrospective study to evaluate the usefulness of the PPI for survival prediction in patients with lung cancer. Patients with lung cancer who were admitted to our hospital between 2009 and 2013 to receive palliative care were enrolled. The association between the Palliative Prognostic Index, determined based on the data recorded in the clinical charts at the last admission to our hospital, and survival was evaluated. The patient group with a PPI of >6 showed a significantly shorter survival time than the patient group with a PPI of ≤ 6 (P < 0.0001, log-rank test). The sensitivity and specificity of the PPI determined using the cutoff value of 6 for predicting less than 3 weeks of survival were 61.3 and 86.8 %, respectively. However, the sensitivity decreased to 50.0 % when the assessment was carried out in only patients with small cell lung carcinoma. Our findings suggest the existence of a close association between the PPI and survival in patients with lung cancer receiving palliative care. However, the sensitivity of the index for predicting less than 3 weeks of survival was relatively low in patients with small cell lung carcinoma

Psychological stress in aged female mice causes acute hypophagia independent of central serotonin 2C receptor activation

Sex differences exist in the activation of the hypothalamic-pituitary-adrenal axis following exposure to stress, and the stress response is further affected by aging. This study was conducted to elucidate the mechanism of hypophagia in aged female mice exposed to stress. Immediately after a stress load, aged female mice exhibited acute hypophagia and a rise in plasma corticosterone levels. The administration of a serotonin 2C receptor (5-T2CR) antagonist suppressed plasma corticosterone but did not affect the reduction in food intake. In contrast, an endogenous ghrelin enhancer, rikkunshito (RKT), significantly inhibited the reduction in food intake. An increase in peripheral acylated ghrelin levels during fasting, which occurs in young mice, was not observed in aged female mice. Moreover, in these mice, significantly increased levels of ghrelin and gastric preproghrelin mRNA expression were observed in the fed status. Moreover, plasma ghrelin levels were elevated by RKT and not by the 5-HT2CR antagonist. In female mice, the hypothalamic non-edited (INI) and partially edited mRNA 5-HT2CR isoforms (VNV, VNI, VSV or VSI) decreased with age, while in male mice, the editing isoform was unchanged by aging or stress. Estrogen receptor alpha (ER alpha)-positive cell counts in the arcuate nucleus of young male mice exposed to stress and control aged male mice were increased compared with those in young control mice. In aged male mice exposed to stress, the number of ER alpha-expressing cells in the paraventricular nucleus were significantly increased compared with those in aged control mice; in female mice, there was no increase in the number of ER alpha-positive cells. Hypophagia in aged female mice exposed to stress may be independent of 5-HT2CR activation. It seems likely that the mechanisms may be caused by sex dependent, differential regulation in 5-HT2CR mRNA expression, peripheral acylated ghrelin secretion and/or hypothalamic ER alpha expression

CRF receptor 1 antagonism and brain distribution of active components contribute to the ameliorative effect of rikkunshito on stress-induced anorexia

Rikkunshito (RKT), a Kampo medicine, has been reported to show an ameliorative effect on sustained hypophagia after novelty stress exposure in aged mice through serotonin 2C receptor (5-HT2CR) antagonism. We aimed to determine (1) whether the activation of anorexigenic neurons, corticotropin-releasing factor (CRF), and pro-opiomelanocortin (POMC) neurons, is involved in the initiation of hypophagia induced by novelty stress in aged mice; (2) whether the ameliorative effect of RKT is associated with CRF and POMC neurons and downstream signal transduction; and (3) the plasma and brain distribution of the active components of RKT. The administration of RKT or 5-HT2CR, CRF receptor 1 (CRFR1), and melanocortin-4 receptor antagonists significantly restored the decreased food intake observed in aged male C57BL/6 mice in the early stage after novelty stress exposure. Seven components of RKT exhibited antagonistic activity against CRFR1. Hesperetin and isoliquiritigenin, which showed antagonistic effects against both CRFR1 and 5-HT2CR, were distributed in the plasma and brain of male Sprague-Dawley rats after a single oral administration of RKT. In conclusion, the ameliorative effect of RKT in this model is assumed to be at least partly due to brain-distributed active components possessing 5-HT2CR and CRFR1 antagonistic activities

Vulnerability to psychological stress-induced anorexia in female mice depends on blockade of ghrelin signal in nucleus tractus solitarius

Background and Purpose Women have a higher incidence of eating disorders than men. We investigated whether the effects of ghrelin on feeding are affected by sex and stress, and to elucidate the mechanisms that may cause sex differences in stress-mediated anorexia, focusing on ghrelin. Experimental Approach Acylated ghrelin was administered to naive and psychologically stressed male and female C57BL/6J mice, followed by measurements of food intake and plasma hormone levels. Ovariectomy was performed to determine the effects of ovary-derived oestrogen on stress-induced eating disorders in female mice. The numbers ofAgrporc-FosmRNA-positive cells and estrogen receptor alpha/c-Fos protein-double-positive cells were assessed. Key Results Ghrelin administration to naive female mice caused a higher increase in food intake, growth hormone secretion,AgrpmRNA expression in the arcuate nucleus andc-Fosexpression in the nucleus tractus solitarius (NTS) than in male mice. In contrast, psychological stress caused a more sustained reduction in food intake in females than males. The high sensitivity of naive females to exogenous ghrelin was attenuated by stress exposure. The stress-induced decline in food intake was not abolished by ovariectomy. Estrogen receptor-alpha but not -beta antagonism prevented the decrease in food intake under stress. Estrogen receptor-alpha/c-Fos-double-positive cells in the NTS were significantly increased by stress only in females. Conclusion and Implications Stress-mediated eating disorders in females may be due to blockade of ghrelin signalling via estrogen receptor-alpha activation in the NTS. Targeting the ghrelin signal in the brain could be a new treatment strategy to prevent these disorders