Cd(2+) causes damages to several human tissues. Although the toxicological and carcinogenetic mechanisms of Cd(2+) have been previously established, some basic questions on this toxicant remain unclear. In this study, we constructed Met-cad 1.57, a new fluorescent resonance energy transfer (FRET)-based Cd(2+) indicator, which contains a portion of a Cd(2+)-binding protein (CadR) obtained from Pseudomonas putida as the Cd(2+) sensing key. We produced a human embryonic kidney cell line HEK-MCD157 which stably expresses the Met-cad 1.57 for further investigations. Both fluorescence spectroscopy and FRET microscopic ratio imaging were used to monitor the Cd(2+) concentration within the living HEK-MCD157 cells. The dissociation constant of Met-cad 1.57 was approximately 271 nM. The function of Ca(2+) channels as a potential Cd(2+) entry gateway was further confirmed in the HEK-MCD157 cells. The organelle-targeted property of the protein-based Cd(2+) indicator directly reveals the nucleus accumulation phenomena. In summary, a human kidney cell line that stably expresses the FRET-based Cd(2+) indicator Met-cad 1.57 was constructed for reliable and convenient investigations to determine the Cd(2+) concentration within living cells, including the identification of the entry pathway of Cd(2+) and sub-cellular sequestration.

G-Quadruplex DNA formed in the promoter regions of proto-oncogenes would block the transcription process and eventually suppress the development of tumors, so compounds that stabilize G-quadruplex DNA are potential antitumor drugs. This article describes the interactions of three phenanthroline compounds, a-c, with proto-oncogene c-kit2 and c-myc G-quadruplex DNAs by means of polymerase chain reaction (PCR) stop assay, fluorescence resonance energy transfer melting (FRET melting) assay, fluorescence indicator displacement (FID) assay, UV/VIS absorption, fluorescence, and circular dichroism (CD) spectroscopies. All three compounds displayed selectivity for the G-quadruplex over duplex, with binding constants (Ka ) for the both quadruplexes varying from 0.49×10(6) to 3.32×10(6)  M(-1) (4.1- to 33.2-fold specificity). Compounds a, b, and c were potential stabilizers for the c-kit2 G-quadruplex with the melting-temperature increase (ΔTm ) values of 12-15°. CD Spectra indicated that a-c disrupted the structure of c-kit2 G-quadruplex, whereas no significant change was observed for c-myc G-quadruplex.

BACKGROUND AND OBJECTIVES:

Pancreastatin is a derived peptide of chromogranin A (CgA). Pancreastatin has the potential to be a diagnostic and predictive tumor marker in detecting NETs.

METHODS:

Radioimmunoassay tests of pancreastatin and CgA were performed on 103 patient specimens collected at Mount Sinai Medical Center between 1/2010 and 7/2012. Patient demographics, diagnostic tests, surgical procedures, pathologic findings, adjuvant treatments, and survival were retrospectively reviewed. Statistical analysis utilized SPSS v20 software.

RESULTS:

Mean pancreastatin levels were significantly higher in the 92 NETs patients than in the 11 non-NETs patients (227.261 vs. 59.727, P < 0.05). Twenty-seven of the 92 patients with elevated pancreastatin levels (mean = 240.67), had normal CgA levels (mean = 4.65). Pancreastatin had sensitivity and specificity of 64% (59/92), and 100% (11/11). CgA had lower sensitivity and specificity of 43% (40/92), and 64% (7/11). In all 27 instances the pancreastatin concentration was found to be sole indicator of NET disease. When controlling for the level of CgA for the entire sample, a statistically significant difference was not found in the mean pancreastatin levels between both patient groups (P = 0.139, R = 0.484).

CONCLUSION:

Pancreastatin has greater sensitivity and specificity in diagnosing NETs than CgA. Further investigation of pancreastatin's diagnostic and predictive value is warranted. J. Surg. Oncol. © 2013 Wiley Periodicals, Inc.

PURPOSE:

To evaluate the linguistic and psychometric properties of the Functional Living Index-Cancer (FLIC) in assessing the quality of life of Chinese cancer patients.

METHODS:

The English FLIC was translated into Traditional Chinese by the standard forward-backward procedure. After cognitive debriefing, a Traditional Chinese FLIC was administered to 500 cancer patients in a major public hospital in Hong Kong. Of which, 200 were invited to complete the questionnaire in 2 weeks. To identify a scale structure appropriate to Chinese, exploratory and confirmatory factor analyses were performed on two randomly split halves of the sample.

RESULTS:

We identified five scales of the Traditional Chinese FLIC which assess the physical, psychological, hardship, nausea and social aspects. These five scales and the overall scale demonstrated satisfactory fit and had the alpha coefficient ranged from 0.68 to 0.92. The intra-class correlation coefficient ranged from 0.67 to 0.88. In addition, all FLIC scales were negatively associated with the Eastern Cooperative Oncology Group performance status and, also except for the psychological scale, had lower scores in patients who were treated by chemotherapy.

CONCLUSIONS:

The Traditional Chinese FLIC is an appropriate health indicator for Chinese cancer patients.

Based on regional heterogeneity of environmental characteristics and factors influencing those characteristics, environmental units may be classified into homogeneous zones. Then, essential strategies and mitigation measures in each zone may be developed and environmental quality may be holistically improved using a system of environmental management regionalization (EMRZ). Here, an EMRZ scheme for China was devised by outlining regional management using integrated qualitative and quantitative methods. First, the land was subdivided into four environmental management domains using China's three physical geographic domains. Second, using a regionalization indicator system, the environmental characteristics of neighboring provinces in four domains was quantified using the one-dimensional Euclidean distance method; regions with high similarity were merged into one environmental management region (EMR) and the preliminary draft of EMRs was obtained. Based on the preliminary scheme, eight EMRs using prefecture-level administrative regions were obtained through boundary adjustment based on important natural geographical boundaries and existing regional plans. These include the Northeastern China Region, the North China Plain Region, the Loess Plateau Region, Southeast Coast Region, the Middle Reaches of the Yangtze River, the Southwestern China Region, the Northwestern China Region, and the Tibetan Plateau Region. Priority environmental problems of each EMR were discussed. The main contribution of this study is that it develops a novel methodological framework for EMRZ integrating qualitative and quantitative methodologies, and considers the spatial contiguity of each EMR and the spatial integrity of each administrative unit. Future research will focus on priority goals and establishment of suitable environmental management policies for each EMR based on known local environmental problems.

BACKGROUND:

AAA+ nuclear coregulator cancer associated (ANCCA) is found to be overexpressed in various cancer types and could play a role in common and fundamental cellular processes. A recent study suggested that ANCCA was a likely driver whose expression explained the behavior of differentially expressed proliferation-related genes in lung adenocarcinoma. However, protein expression of ANCCA in lung adenocarcinoma and its association with clinicopathologic parameters and commonly reported driver mutations remains unexplored.

METHODS:

ANCCA expression was evaluated by immunohistochemistry in 143 surgically resected lung adenocarcinomas and was correlated with clinicopathologic and molecular variables including adenocarcinoma histologic subtypes, tumor, node, metastasis status, relapse-free survival, overall survival, EGFR mutations, KRAS mutations, HER2 mutations and ALK fusions.

RESULTS:

Positive ANCCA expression was significantly associated with male sex, smokers, poorly differentiated tumors, nonlepidic predominant subtype, more advanced T stage, lymph nodal metastasis and late disease stage. Cox multivariate analysis revealed that ANCCA-positive expression was an independent predictor of worse relapse-free survival [hazard ratio (HR) 1.736, 95 % confidence interval (CI) 1.075-2.804; P = .024) and overall survival (HR 7.758, 95 % CI 2.955-20.370; P < .001). The addition of ANCCA protein expression to the prognostic model using pathologic stage markedly improved the prognostic accuracy; the concordance index increased from .692 to .788, and the Akaike information criterion decreased from 354.20 to 336.11.

CONCLUSIONS:

We have identified ANCCA protein expression as a novel independent poor prognostic indicator in lung adenocarcinoma. Prospective studies are warranted to validate its potential prognostic value in combination with the current staging system.

Variation in the timing of plant phenology caused by phenotypic plasticity is a sensitive measure of how organisms respond to weather and climate variability. Although continental-scale gradients in climate and consequential patterns in plant phenology are well recognized, the contribution of underlying genotypic difference to the geography of phenology is less well understood. We hypothesize that different temperate plant genotypes require varying amount of heat energy for resuming annual growth and reproduction as a result of adaptation and other ecological and evolutionary processes along climatic gradients. In particular, at least for some species, the growing degree days (GDD) needed to trigger the same spring phenology events (e.g., budburst and flower bloom) may be less for individuals originated from colder climates than those from warmer climates. This variable intrinsic heat energy requirement in plants can be characterized by the term growth efficiency and is quantitatively reflected in the timing of phenophases-earlier timing indicates higher efficiency (i.e., less heat energy needed to trigger phenophase transitions) and vice versa compared to a standard reference (i.e., either a uniform climate or a uniform genotype). In this study, we tested our hypothesis by comparing variations of budburst and bloom timing of two widely documented plants from the USA National Phenology Network (i.e., red maple-Acer rubrum and forsythia-Forsythia spp.) with cloned indicator plants (lilac-Syringa x chinensis 'Red Rothomagensis') at multiple eastern US sites. Our results indicate that across the accumulated temperature gradient, the two non-clonal plants showed significantly more gradual changes than the cloned plants, manifested by earlier phenology in colder climates and later phenology in warmer climates relative to the baseline clone phenological response. This finding provides initial evidence supporting the growth efficiency hypothesis, and suggests more work is warranted. More studies investigating genotype-determined phenological variations will be useful for better understanding and prediction of the continental-scale patterns of biospheric responses to climate change.

There is considerable evidence to suggest that drug actions at the kappa opioid receptor (KOR) may represent a means to control pain perception and modulate reward thresholds. As a G protein-coupled receptor (GPCR), the activation of KOR promotes Gαi/o protein coupling and the recruitment of βarrestins. It has become increasingly evident that GPCRs can transduce signals that originate independently via G protein pathways and βarrestin pathways; the ligand-dependent bifurcation of such signaling is referred to as ″functional selectivity″ or ″signaling bias.″ Recently, a KOR agonist, 6'-guanidinonaltrindole (6'-GNTI), was shown to display bias towards the activation of G protein-mediated signaling over βarrestin2 recruitment. Therefore, we investigated whether such ligand bias was preserved in striatal neurons. While the reference KOR agonist, U69,593 induces the phosphorylation of ERK1/2 and Akt, 6'-GNTI only activates the Akt pathway in striatal neurons. Using pharmacological tools and βarrestin2 knockout mice, we show that KOR-mediated ERK1/2 phosphorylation in striatal neurons requires βarrestin2, while Akt activation depends upon G protein signaling. These findings reveal a point of KOR signal bifurcation that can be observed in an endogenous neuronal setting and may prove to be an important indicator when developing biased agonists at the KOR.

Background/Aims:

Mindfulness-based stress reduction (MBSR) has enhanced cognition, positive emotion, and immunity in younger and middle-aged samples; its benefits are less well known for older persons. Here we report on a randomized controlled trial of MBSR for older adults and its effects on executive function, left frontal asymmetry of the EEG alpha band, and antibody response.

Methods:

Older adults (n = 201) were randomized to MBSR or waiting list control. The outcome measures were: the Trail Making Test part B/A (Trails B/A) ratio, a measure of executive function; changes in left frontal alpha asymmetry, an indicator of positive emotions or approach motivation; depression, mindfulness, and perceived stress scores, and the immunoglobulin G response to a protein antigen, a measure of adaptive immunity.

Results:

MBSR participants had a lower Trails B/A ratio immediately after intervention (p < 0.05); reduced shift to rightward frontal alpha activation after intervention (p = 0.03); higher baseline antibody levels after intervention (p < 0.01), but lower antibody responses 24 weeks after antigen challenge (p < 0.04), and improved mindfulness after intervention (p = 0.023) and at 21 weeks of follow-up (p = 0.006).

Conclusions:

MBSR produced small but significant changes in executive function, mindfulness, and sustained left frontal alpha asymmetry. The antibody findings at follow-up were unexpected. Further study of the effects of MBSR on immune function should assess changes in antibody responses in comparison to T-cell-mediated effector functions, which decline as a function of age.