INFOCOM Corporation

Tokyo, Japan

INFOCOM Corporation

Tokyo, Japan
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Nagamatsu G.,Keio University | Nagamatsu G.,Japan Science and Technology Agency | Saito S.,Japan National Institute of Advanced Industrial Science and Technology | Saito S.,INFOCOM Corporation | And 7 more authors.
Journal of Biological Chemistry | Year: 2012

Somatic cell reprogramming is achieved by four reprogramming transcription factors (RTFs), Oct3/4, Sox2, Klf4, and c-Myc. However, in addition to the induction of pluripotent cells, these RTFs also generate pseudo-pluripotent cells, which do not show Nanog promoter activity. Therefore, it should be possible to fine-tune the RTFs to produce only fully pluripotent cells. For this study, a tagging system was developed to sort induced pluripotent stem (iPS) cells according to the expression levels of each of the four RTFs. Using this system, the most effective ratio (Oct3/4-high, Sox2-low, Klf4-high, c-Myc-high) of the RTFs was 88 times more efficient at producing iPS cells than the worst effective ratio (Oct3/4-low, Sox2-high, Klf4-low, c-Myclow). Among the various RTF combinations, Oct3/4-high and Sox2-low produced the most efficient results. To investigate the molecular basis, microarray analysis was performed on iPS cells generated under high (Oct3/4-high and Sox2-low) and low (Oct3/4-low and Sox2-high) efficiency reprogramming conditions. Pathway analysis revealed that the G protein-coupled receptor (GPCR) pathway was up-regulated significantly under the high efficiency condition and treatment with the chemokine, C-C motif ligand 2, a member of the GPCR family, enhanced somatic cell reprogramming 12.3 times. Furthermore, data from the analysis of the signature gene expression profiles of mouse embryonic fibroblasts at 2 days after RTF infection revealed that the genetic modifier, Whsc1l1 (variant 1), also improved the efficiency of somatic cell reprogramming. Finally, comparison of the overall gene expression profiles between the high and low efficiency conditions will provide novel insights into mechanisms underlying somatic cell reprogramming. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.


Zhou H.,CAS Shanghai Institutes for Biological Sciences | Saito S.,Japan National Institute of Advanced Industrial Science and Technology | Saito S.,INFOCOM Corporation | Piao G.,CAS Shanghai Institutes for Biological Sciences | And 8 more authors.
BMC Systems Biology | Year: 2011

Background: Type 2 diabetes mellitus (T2DM) is a complex systemic disease, with significant disorders of metabolism. The liver, a central energy metabolic organ, plays a critical role in the development of diabetes. Although gene expression levels are able to be measured via microarray since 1996, it is difficult to evaluate the contributions of one altered gene expression to a specific disease. One of the reasons is that a whole network picture responsible for a specific phase of diabetes is missing, while a single gene has to be put into a network picture to evaluate its importance. In the aim of identifying significant transcriptional regulatory networks in the liver contributing to diabetes, we have performed comprehensive active regulatory network survey by network screening in 4 weeks (w), 8-12 w, and 18-20 w Goto-Kakizaki (GK) rat liver microarray data.Results: We identify active regulatory networks in GK rat by network screening in the following procedure. First, the regulatory networks are compiled by using the known binary relationships between the transcriptional factors and their regulated genes and the biological classification scheme, and second, the consistency of each regulatory network with the microarray data measured in GK rat is estimated to detect the active networks under the corresponding conditions. The comprehensive survey of the consistency between the networks and the measured data by the network screening approach in the case of non-insulin dependent diabetes in the GK rat reveals: 1. More pathways are active during inter-middle stage diabetes; 2. Inflammation, hypoxia, increased apoptosis, decreased proliferation, and altered metabolism are characteristics and display as early as 4weeks in GK strain; 3. Diabetes progression accompanies insults and compensations; 4. Nuclear receptors work in concert to maintain normal glycemic robustness system.Conclusion: Notably this is the first comprehensive network screening study of non-insulin dependent diabetes in the GK rat based on high throughput data of the liver. Several important pathways have been revealed playing critical roles in the diabetes progression. Our findings also implicate that network screening is able to help us understand complex disease such as diabetes, and demonstrate the power of network systems biology approach to elucidate the essential mechanisms which would escape conventional single gene-based analysis. © 2011 Zhou et al; licensee BioMed Central Ltd.


Nagamatsu G.,Keio University | Kosaka T.,Japan Science and Technology Agency | Saito S.,Japan National Institute of Advanced Industrial Science and Technology | Saito S.,INFOCOM Corporation | And 9 more authors.
Stem Cells | Year: 2013

Germ cells are similar to pluripotent stem cells in terms of gene expression patterns and the capacity to convert to pluripotent stem cells in culture. The factors involved in germ cell development are also able to reprogram somatic cells. This suggests that germ cells are useful tools for investigating the mechanisms responsible for somatic cell reprograming. In this study, the expression of reprograming factors in primordial germ cells (PGCs) was analyzed. PGCs expressed Oct3/4, Sox2, and c-Myc but not Klf4. However, Klf2, Klf5, Essrb, or Essrg, which were expressed in PGCs, could compensate for Klf4 during somatic cell reprograming. Furthermore, PGCs could be converted to a pluripotent state by infection with any of the known reprogramming factors (Oct3/4, Sox2, Klf4, and c-Myc). These cells were designated as multipotent PGCs (mPGCs). Contrary to differences in the origins of somatic cells in somatic cell reprogramming, we hypothesized that the gene expression levels of the reprogramming factors would vary in mPGCs. Candidate genes involved in the regulation of tumorigenicity and/or reprogramming efficiency were identified by comparing the gene expression profiles of mPGCs generated by the exogenous expression of c-Myc or L-Myc. © AlphaMed Press.


Duren Z.,CAS Academy of Mathematics and Systems Science | Duren Z.,Beihang University | Wang Y.,CAS Academy of Mathematics and Systems Science | Saito S.,Japan National Institute of Advanced Industrial Science and Technology | And 2 more authors.
Chinese Control Conference, CCC | Year: 2012

The remarkable discovery of induced pluripotent stem cells (iPSCs) demonstrates that cell can be reprogrammed from somatic cell to a pluripotent state by the enforced expression of defined transcriptional factors. However, the underlying mechanism for cell reprogramming remains unknown and the regulatory interactions within this biological process have not been worked out. In particular from the gene regulatory network perspective, it is not clear how the four factors initialize the reprogramming process, propagate the information in a fine tuned way, and finally lead to the dramatic phenotype changes. In this paper, we analyze the time course gene expression data during cell reprogramming in mouse. We propose a three-stage procedure to infer gene regulatory networks. Specifically, we identify the major players during cell reprogramming by selecting differentially expressed genes in the first stage. Then in the second stage we utilize a new method to reveal strong correlations among those selected genes from short time series data. Finally the gene regulatory relationships are modeled by ordinary differential equations (ODE), the correlations are filtered by applying strong regularization, and directed and signed gene regulatory network for cell reprogramming is reconstructed. Preliminary analysis of the inferred network shows that short time series data provide biological insights for the dynamical process during reprogramming. © 2012 Chinese Assoc of Automati.


Shibata T.,National Cancer Center Research Institute | Saito S.,National Cancer Center Research Institute | Saito S.,Infocom Corporation | Kokubu A.,National Cancer Center Research Institute | And 3 more authors.
Cancer Research | Year: 2010

In multicellular organisms, adaptive responses to oxidative stress are regulated by NF-E2 - related factor 2 (NRF2), a master transcription factor of antioxidant genes and phase II detoxifying enzymes. Aberrant activation of NRF2 by either loss-of-function mutations in the Keap1 gene or gain-of-function mutations in the Nrf2 gene occurs in a wide range of human cancers, but details of the biological consequences of NRF2 activation in the cancer cells remain unclear. Here, we report that mutant NRF2 induces epithelial cell proliferation, anchorage-independent growth, and tumorigenicity and metastasis in vivo. Genome-wide gene expression profiling revealed that mutant NRF2 affects diverse molecular pathways including the mammalian target of rapamycin (mTOR) pathway. Mutant NRF2 upregulates RagD, a small G-protein activator of the mTOR pathway, which was also overexpressed in primary lung cancer. Consistently, Nrf2-mutated lung cancer cells were sensitive to mTOR pathway inhibitors (rapamycin and NVP-BEZ235) in both in vitro and an in vivo xenograft model. The gene expression signature associated with mutant NRF2 was a marker of poor prognosis in patients with carcinoma of the head and neck region and lung. These results show that oncogenic Nrf2 mutation induces dependence on the mTOR pathway during carcinogenesis. Our findings offer a rationale to target NRF2 as an anticancer strategy, and they suggest NRF2 activation as a novel biomarker for personalized molecular therapies or prognostic assessment. ©2010 AACR.


Shibata T.,National Cancer Center Research Institute | Shibata T.,National Cancer Center Hospital | Kokubu A.,National Cancer Center Research Institute | Saito S.,Infocom Corporation | And 8 more authors.
Neoplasia | Year: 2011

Esophageal squamous cancer (ESC) is one of the most aggressive tumors of the gastrointestinal tract. A combination of chemotherapy and radiation therapy (CRT) has improved the clinical outcome, but the molecular background determining the effectiveness of therapy remains unknown. NRF2 is a master transcriptional regulator of stress adaptation, and gainof- function mutation of NRF2 in cancer confers resistance to stressors including anticancer therapy. Direct resequencing analysis revealed that Nrf2 gain-of-function mutation occurred recurrently (18/82, 22%) in advanced ESC tumors and ESC cell lines (3/10). The presence of Nrf2 mutation was associated with tumor recurrence and poor prognosis. Short hairpin RNA-mediated down-regulation of NRF2 in ESC cells that harbor only mutated Nrf2 allele revealed that themutant NRF2 conferred increased cell proliferation, attachment-independent survival, and resistance to 5-fluorouracil and γ-irradiation. Based on the Nrf2 mutation status, gene expression signatures associated with NRF2 mutation were extracted from ESC cell lines, and their potential utility for monitoring and prognosis was examined in a cohort of 33 pre-CRT cases of ESC. Themolecular signatures of NRF2 mutation were significantly predictive and prognostic for CRT response. In conclusion, recurrent NRF2 mutation confers malignant potential and resistance to therapy in advanced ESC, resulting in a poorer outcome. Molecular signatures of NRF2 mutation can be applied as predictive markers of response to CRT, and efficient inhibition of aberrant NRF2 activation could be a promising approach in combination with CRT. © 2011 Neoplasia Press, Inc. All rights reserved.


Kosaka T.,Keio University | Nagamatsu G.,Keio University | Nagamatsu G.,Japan Science and Technology Agency | Saito S.,Japan National Institute of Advanced Industrial Science and Technology | And 4 more authors.
Cancer Science | Year: 2013

Considering the similarities between the transcriptional programming involved in cancer progression and somatic cell reprogramming, we tried to identify drugs that would be effective against malignant cancers. We used the early transposon Oct4 and Sox2 enhancer (EOS) system to select human prostate cancer (PCA) cells expressing high levels of OCT4. Patients with metastatic castration-resistant PCA that does not respond to treatment with docetaxel have few therapeutic options. The OCT4-expressing PCA cells selected using the EOS system showed increased tumorigenicity and high resistance to docetaxel, both in vitro and in vivo. By using their gene expression data, expression signature-based prediction for compound candidates identified an antiviral drug, ribavirin, as a conversion modulator from drug resistance to sensitivity. Treatment of PCA cells with ribavirin decreased their resistance against treatment with docetaxel. This indicated that ribavirin reversed the gene expression, including that of humoral factors, in the OCT4-expressing PCA cells selected using the EOS system. Thereby, ribavirin increased the efficacy of docetaxel for cancer cells. We propose a novel cell reprogramming approach, named drug efficacy reprogramming, as a new model for identifying candidate antitumor drugs. © 2013 Japanese Cancer Association.


Trademark
Infocom LLC | Date: 2011-03-31

Business management software for small or medium businesses; Computer software for use in general purpose database management; Computer and electronic devices software in the fields of business and private networks, and establishing and arranging of doing business and private contacts; Computer and electronic devices software for the distribution of information and interactive documents and multimedia content containing text, images, video and sound to users in the field communications; Program-related instructions, hardware and documentation in electronic format for business and private network purposes; Software for computers and electronic devices; and internet services.


Patent
Asahikawa University and Infocom Corporation | Date: 2016-07-27

[Problem] The present invention provides analysis technology relating to video data of a fluorescent contrast agent shot by a microscope during an operation, and addresses the problem of providing a method and system allowing information such as BV, BF and MTT, and vascular wall thickness, to be estimated by fluorescent contrast agent analysis, by applying perfusion analysis methods, which allow estimation of information such as BV, BF and MTT, to fluorescent contrast agent analysis. [Solution] The method for image processing of intravascular hemodynamics according to the present invention is characterized by shooting video using infrared light, wherein the object of shooting is a portion of a blood vessel injected with a standard amount of a fluorescent contrast agent; performing image analysis of a shape of a chronological change curve of intensity values which are image outputs from the video shooting; and calculating relative data for blood volume and blood flow based on results of the image analysis.


Patent
National University Corporation Asakikawa Medical University and Infocom Corporation | Date: 2014-09-19

[Problem] The present invention provides analysis technology relating to video data of a fluorescent contrast agent shot by a microscope during an operation, and addresses the problem of providing a method and system allowing information such as BV, BF and MTT, and vascular wall thickness, to be estimated by fluorescent contrast agent analysis, by applying perfusion analysis methods, which allow estimation of information such as BV, BF and MTT, to fluorescent contrast agent analysis. [Solution] The method for image processing of intravascular hemodynamics according to the present invention is characterized by shooting video using infrared light, wherein the object of shooting is a portion of a blood vessel injected with a standard amount of a fluorescent contrast agent; performing image analysis of a shape of a chronological change curve of intensity values which are image outputs from the video shooting; and calculating relative data for blood volume and blood flow based on results of the image analysis.

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