Pathologic stage I non–small cell lung cancer with high levels of preoperative serum carcinoembryonic antigen: Clinicopathologic characteristics and prognosis

ObjectiveSurgery alone remains the standard therapy for patients with stage I non–small cell lung cancer. Although the preoperative serum level of carcinoembryonic antigen has been shown to be an independent prognostic factor, it has not yet been included in the staging system and does not alter the treatment strategy, especially in the selection of patients for adjuvant chemotherapy.MethodsFrom 1986 to 2003, preoperative and postoperative serum carcinoembryonic antigen levels were measured in 455 patients with completely resected pathologic stage I non–small cell lung cancer. We compared the clinicopathologic characteristics and outcomes among patients who had preoperative serum carcinoembryonic antigen levels within the normal range (N group, n = 323), patients who had high carcinoembryonic antigen levels before surgery but normal levels after surgery (HN group, n = 112), and patients who had high carcinoembryonic antigen levels before and after surgery (HH group, n = 20).ResultsThe significant characteristics of the HN group included the male sex, greater age, smoking, squamous cell histology, T2 status, lymphatic invasion, vascular invasion, and pleural invasion. Adenocarcinomas in patients of the HN group were more likely to be moderately to poorly differentiated. The 5-year survivals in the HN and HH groups were significantly lower (56.2% and 43.1%, respectively) than those in the N group (85.9%). Multivariate analysis revealed that greater age, non-adenocarcinoma histology, pleural invasion, and the carcinoembryonic antigen in the HN and HH groups were independent prognostic factors.ConclusionPatients with resected pathologic stage I non–small cell lung cancer and high preoperative serum carcinoembryonic antigen levels are a subgroup with a distinctly poor prognosis who display smoking-related clinicopathologic characteristics

Pilot Study on Clinical Effectiveness of Autofluorescence Imaging for Early Gastric Cancer Diagnosis by Less Experienced Endoscopists

This study aimed to assess and compare effectiveness of Autofluorescence imaging (AFI) in diagnosis of early gastric cancer (EGC) between experienced and less experienced endoscopists. Fifty selected images (20 neoplastic lesions and 30 benign lesions/areas) of both white light endoscopy (WLE) and AFI were blindly reviewed by two groups; first consisted of five experienced endoscopists and second included five less experienced endoscopists. Sensitivity, specificity, and accuracy were 70%, 78%, and 75%, respectively, for AFI and 81%, 76%, and 78%, respectively, for WLE in the experienced group. In the less experienced group, sensitivity, specificity and accuracy were 80%, 81% and 80%, respectively, for AFI and 65%, 77%, and 72%, respectively, for WLE. Interobserver variability for the less experienced group was better with AFI than WLE. AFI improved sensitivity of endoscopic diagnosis of neoplastic lesions by less experienced endoscopists, and its use could beneficially enhance the clinical effectiveness of EGC screening

TDP-43 regulates cholesterol biosynthesis by inhibiting sterol regulatory element-binding protein 2

Dyslipidemia is considered an essential component of the pathological process of amyotrophic lateral sclerosis (ALS), a fatal motor neuron disease. Although TAR DNA Binding Protein 43 kDa (TDP-43) links both familial and sporadic forms of ALS and cytoplasmic aggregates are a hallmark of most cases of ALS, the molecular mechanism and the in vivo relation of ALS dyslipidemia with TDP-43 have been unclear. To analyze the dyslipidemia-related gene expression by TDP-43, we performed expression microarray and RNA deep sequencing (RNA-Seq) using cell lines expressing high levels of TDP-43 and identified 434 significantly altered genes including sterol regulatory element-binding protein 2 (SREBP2), a master regulator of cholesterol homeostasis and its downstream genes. Elevated TDP-43 impaired SREBP2 transcriptional activity, leading to inhibition of cholesterol biosynthesis. The amount of cholesterol was significantly decreased in the spinal cords of TDP-43-overexpressed ALS model mice and in the cerebrospinal fluids of ALS patients. These results suggested that TDP-43 could play an essential role in cholesterol biosynthesis in relation to ALS dyslipidemia

Radial Transport Characteristics of Fast Ions Due to Energetic-Particle Modes inside the Last Closed-Flux Surface in the Compact Helical System

The internal behavior of fast ions interacting with magnetohydrodynamic bursts excited by energetic ions has been experimentally investigated in the compact helical system. The resonant convective oscillation of fast ions was identified inside the last closed-flux surface during an energetic-particle mode (EPM) burst. The phase difference between the fast-ion oscillation and the EPM, indicating the coupling strength between them, remains a certain value during the EPM burst and drives an anomalous transport of fast ions

Prenylated Quinolinecarboxylic Acid Derivative Prevents Neuronal Cell Death Through Inhibition of MKK4

The development of neuroprotective agents is necessary for the treatment of neurodegenerative diseases. Here, we report PQA-11, a prenylated quinolinecarboxylic acid (PQA) derivative, as a potent neuroprotectant. PQA-11 inhibits glutamate-induced cell death and caspase-3 activation in hippocampal cultures, as well as inhibits N-Methyl-4-phenylpyridinium iodide- and amyloid β1-42-induced cell death in SH-SY5Y cells. PQA-11 also suppresses mitogen-activated protein kinase kinase 4 (MKK4) and c-jun N-terminal kinase (JNK) signaling activated by these neurotoxins. Quartz crystal microbalance analysis and in vitro kinase assay reveal that PQA-11 interacts with MKK4, and inhibits its sphingosine-induced activation. The administration of PQA-11 by intraperitoneal injection alleviates 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced degeneration of nigrostriatal dopaminergic neurons in mice. These results suggest that PQA-11 is a unique MKK4 inhibitor with potent neuroprotective effects in vitro and in vivo. PQA-11 may be a valuable lead for the development of novel neuroprotectants

Inositols affect the mating circadian rhythm of Drosophila melanogaster

Accumulating evidence indicates that the molecular circadian clock underlies the mating behavior of Drosophila melanogaster. However, information about which food components affect circadian mating behavior is scant. The ice plant, Mesembryanthemum crystallinum has recently become a popular functional food. Here, we showed that the close-proximity (CP) rhythm of D. melanogaster courtship behavior was damped under low-nutrient conditions, but significantly enhanced by feeding the flies with powdered ice plant. Among various components of ice plants, we found that myo-inositol increased the amplitude and slightly shortened the period of the CP rhythm. Real-time reporter assays showed that myo-inositol and D-pinitol shortened the period of the circadian reporter gene Per2-luc in NIH 3T3 cells. These data suggest that the ice plant is a useful functional food and that the ability of inositols to shorten rhythms is a general phenomenon in insects as well as mammals

MiR-33a is a therapeutic target in SPG4-related hereditary spastic paraplegia human neurons

Recent reports, including ours, have indicated that microRNA (miR)-33 located within the intron of sterol regulatory element binding protein (SREBP) 2 controls cholesterol homeostasis and can be a potential therapeutic target for the treatment of atherosclerosis. Here, we show that SPAST, which encodes a microtubule-severing protein called SPASTIN, was a novel target gene of miR-33 in human. Actually, the miR-33 binding site in the SPAST 3′-UTR is conserved not in mice but in mid to large mammals, and it is impossible to clarify the role of miR-33 on SPAST in mice. We demonstrated that inhibition of miR-33a, a major form of miR-33 in human neurons, via locked nucleic acid (LNA)-anti-miR ameliorated the pathological phenotype in hereditary spastic paraplegia (HSP)-SPG4 patient induced pluripotent stem cell (iPSC)-derived cortical neurons. Thus, miR-33a can be a potential therapeutic target for the treatment of HSP-SPG4

Status Report of Neutral Kaon photo-production study using Neutral Kaon Spectrometer 2 (NKS2) at LNS-Tohoku(I. Nuclear Physics)

The approach described in this paper uses an array of Field Programmable Gate Array (FPGA) devices to implement a fault tolerant hardware system that can be compared to the running of fault tolerant software on a traditional processor. Fault tolerance is achieved is achieved by using FPGA with on the fly partial programmability feature. Major considerations while mapping to the FPGA includes the size of the area to be mapped and communication issues related to their communication. Area size selection is compared to the page size selection in Operating System Design. Communication issues between modules are compared to the software engineering paradigms dealing with module coupling, fan-in, fan-out and cohesiveness. Finally, the overhead associated with the downloading of the reconfiguration files is discussed