ABSTRACT
Recent interest in the neural bases of spatial navigation stems from the discovery of neuronal populations with strong, specific spatial signals. The regular firing field arrays of medial entorhinal grid cells suggest that they may provide place cells with distance information extracted from the animal's self-motion, a notion we critically review by citing new contrary evidence. Next, we question the idea that grid cells provide a rigid distance metric. We also discuss evidence that normal navigation is possible using only landmarks, without self-motion signals. We then propose a model that supposes that information flow in the navigational system changes between light and dark conditions. We assume that the true map-like representation is hippocampal and argue that grid cells have a crucial navigational role only in the dark. In this view, their activity in the light is predominantly shaped by landmarks rather than self-motion information, and so follows place cell activity; in the dark, their activity is determined by self-motion cues and controls place cell activity. A corollary is that place cell activity in the light depends on non-grid cells in ventral medial entorhinal cortex. We conclude that analysing navigational system changes between landmark and no-landmark conditions will reveal key functional properties.
Subject(s)
Entorhinal Cortex/physiology , Hippocampus/physiology , Models, Neurological , Pyramidal Cells/physiology , Spatial Behavior/physiology , Action Potentials/physiology , Animals , Entorhinal Cortex/cytology , Hippocampus/cytology , Neural Pathways/physiology , RatsABSTRACT
Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors in the world. The only serological marker widely used for the diagnosis of HCC is alpha-fetoprotein (AFP). Despite that AFP is widely used for the diagnosis of HCC, it has a limit as a serological marker due to its low sensitivity and specificity. The human cervical cancer proto-oncogene 1 (HCCR-1) was previously reported as a new biomarker for HCC. To further evaluate the HCCR-1 as a biomarker for HCC, we conducted the prospective cohort study. We evaluated the significance of simultaneous measurement of 2 tumor markers in the diagnosis of HCC in China, Japan and Korea. Two markers for HCC, AFP and HCCR-1, were measured in the sera obtained from 1,338 patients at the time of initial diagnosis of HCC. Of the 1338 HCC patients, 616 (46%) and 686 (51.3%) were sero-positive for AFP and HCCR-1, respectively. The positive rate for HCC was increased up to 74.1% in combined use of AFP and HCCR-1. Many cases (54%) for AFP-negative HCC were positive for HCCR-1 and vice versa. More importantly, the diagnostic rate for small HCC (< 2 cm) was significantly improved in the combined analysis of AFP and HCCR-1 to 56.9% although it was only 40.1% and 23.4% in the single analysis of HCCR-1 and AFP, respectively. Our result suggests that the HCCR-1 could be an useful biomarker for HCC while the diagnostic rate could be significantly improved in the combined use of HCCR-1 and AFP.
Subject(s)
Biomarkers, Tumor/blood , Carcinoma, Hepatocellular/blood , Liver Neoplasms/blood , Proto-Oncogene Proteins/blood , alpha-Fetoproteins/metabolism , Adult , Aged , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/pathology , Early Detection of Cancer/methods , Female , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/pathology , Male , Middle Aged , Prospective Studies , Proto-Oncogene Mas , ROC Curve , Tumor BurdenABSTRACT
NDRG (N-Myc downstream-regulated gene)-2 is a member of the NDRG family. Although it has been suggested that NDRG2 is involved in cellular differentiation and tumor suppression, its intracellular signal and regulatory mechanism are not well known. Here, we show the differential expression of NDRG2 in human colon carcinoma cell lines and tissues by reverse transcription-polymerase chain reaction and immunohistochemical analyses with monoclonal antibody against NDRG2. NDRG2 was strongly expressed in normal colonic mucosa and colonic adenomatous tissues (25 of 25) but not in all invasive cancer tissues [44 of 99 (44%)]. Most distinctive results indicated that the high expression level of NDRG2 has a positive correlation with tumor differentiation and inverse correlation with tumor invasion depth and Dukes' stage of colon adenocarcinoma. To investigate the roles of NDRG2 in tumorigenesis, we used in vitro cell culture system. SW620 colon cancer cell line with a low level of intrinsic NDRG2 protein was transfected with NDRG2-expressing plasmid. TOPflash luciferase reporter assay showed that the transcriptional activity of T-cell factor (TCF)/lymphoid enhancer factor (LEF) was reduced by NDRG2 introduction, but not by the introduction of mutant NDRG2 generated by deletion or site-directed mutagenesis. Intracellular beta-catenin levels were slightly reduced in the NDRG2-transfected SW620 cells and this regulation of beta-catenin stability and TCF/LEF activity were mediated through the modulation of glycogen synthase kinase-3beta activity by NDRG2 function. Our results suggest that NDRG2 might play a pivotal role as a potent tumor suppressor by the attenuation of TCF/beta-catenin signaling for the maintenance of healthy colon tissues.
Subject(s)
Adenocarcinoma/metabolism , Colorectal Neoplasms/metabolism , Gene Expression Regulation, Neoplastic , TCF Transcription Factors/genetics , Tumor Suppressor Proteins/metabolism , beta Catenin/genetics , Adenocarcinoma/genetics , Adenocarcinoma/secondary , Blotting, Western , Cell Membrane/metabolism , Colon/metabolism , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Cytosol/metabolism , Female , Humans , Immunoenzyme Techniques , Immunoprecipitation , Luciferases/metabolism , Male , Middle Aged , Neoplasm Staging , Phosphorylation , Promoter Regions, Genetic , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction , TCF Transcription Factors/metabolism , Transcription, Genetic , Transfection , Tumor Cells, Cultured , Tumor Suppressor Proteins/genetics , beta Catenin/metabolismABSTRACT
OBJECTIVE: The goal of this randomized, placebo controlled, double-blind study was to investigate the effects of transcutaneous irradiation with polychromatic visible polarized light (540-780 nm; 68% polarization; power density 3.0 E-10 W/cm(2)) on a subset population of human lymphocytes using flow cytometry. BACKGROUND DATA: The biomodulation and therapeutic effects of visible light of different wavelengths are well known, but the immunological effects of polychromatic visible polarized light have not been investigated sufficiently. METHODS: Before and after 28 consecutive days of irradiation, blood samples were collected from the subjects and the population count of the lymphocyte subset was measured. RESULTS: The absolute count of total lymphocytes, CD3(+) lymphocytes, and CD3(+)CD4(+) lymphocytes increased by 7% (p = 0.023), 9% (p = 0.058), and 13% (p = 0.021), respectively. Yet the absolute count of WBCs, CD3(+)CD8(+), CD19(+), and CD16(+)56(+) lymphocytes did not change significantly. CONCLUSION: The application of polychromatic visible polarized light with the aforementioned features increases the CD3(+)CD4(+) lymphocyte population. It is suggested that this regimen may be useful for the promotion of natural defenses in cell-mediated immunity.
