A Case of Vaginal Varices that Caused Massive Bleeding after Vaginal Delivery

Article信州医学雑誌 64(1):35-39 (2016)journal articl

Dual role of N-acetyl-aspartyl-glutamate metabolism in cancer monitor and therapy

We uncovered the neurotransmitter N-acetyl-aspartyl-glutamate (NAAG) as a reservoir providing glutamate to promote cancer growth, and demonstrated that inhibition of NAAG hydrolysis by targeting glutamate carboxypeptidase II is a viable strategy for cancer therapy. Our study also suggests that NAAG concentration in plasma could be a non-invasive measurement to monitor cancer progression

Metabolic Recycling Enhances Proliferation in MYC-Transformed Lymphoma B Cells

Relapses negatively impact cancer patient survival due to the tumorigenesis ability of surviving cancer cells post-therapy. Efforts are needed to better understand and combat this problem. This study hypothesized that dead cell debris post-radiation therapy creates an advantageous microenvironment rich in metabolic materials promoting the growth of remaining live cancer cells. In this study, live cancer cells are co-cultured with dead cancer cells eradicated by UV radiation to mimic a post-therapy environment. Isotopic labeling metabolomics is used to investigate the metabolic behavior of cancer cells grown in a post-radiation-therapy environment. It is found that post-UV-eradicated dead cancer cells serve as nutritional sources of off-the-shelf and precursor metabolites for surviving cancer cells. The surviving cancer cells then take up these metabolites, integrate and upregulate multiple vital metabolic processes, thereby significantly increasing growth in vitro and probably in vivo beyond their intrinsic fast-growing characteristics. Importantly, this active metabolite uptake behavior is only observed in oncogenic but not in non-oncogenic cells, presenting opportunities for therapeutic approaches to interrupt the active uptake process of oncogenic cells without affecting normal cells. The process by which living cancer cells re-use vital metabolites released by dead cancer cells post-therapy is coined in this study as metabolic recycling of oncogenic cells

PAPER Detection of TCP Performance Degradation Using Link Utilization Statistics ∗

SUMMARY In this paper, we propose a method of detecting TCP performance degradation using only bottleneck-link utilization statistics: mean and variance. The variance of link utilization normally increases as the mean link-utilization increases. However, because link-utilization has a maximum of 100%, as the mean approaches 100%, the possible range of fluctuation becomes narrow and the variance decreases to zero. In this paper, using the M/G/R processor sharing model, we relate this phenomenon to the behavior of flows. We also show that by using this relationship, we can detect TCP performance degradation using the mean and variance of link utilization. In particular, this method enables a network operator to determine whether or not the degradation originates from the congestion of his/her own network. Because our method requires us to measure only link utilization, the cost of performance management can be greatly decreased compared with the conventional method, which requires dedicated functions for directly measuring the TCP performance. key words: TCP, performance, link utilization, measurement 1

Establishment of a novel model of endometriosis-associated ovarian cancer by transplanting uterine tissue from Arid1a/Pten knockout mice

Abstract Although endometriosis is primarily benign, it has been identified as a risk factor for endometriosis-associated ovarian cancer (EAOC). Genetic alterations in ARID1A, PTEN, and PIK3CA have been reported in EAOC; however, an appropriate EAOC animal model has yet to be established. Therefore, the present study aimed to create an EAOC mouse model by transplanting uterine pieces from donor mice, in which Arid1a and/or Pten was conditionally knocked out (KO) in Pax8-expressing endometrial cells by the administration of doxycycline (DOX), onto the ovarian surface or peritoneum of recipient mice. Two weeks after transplantation, gene KO was induced by DOX and endometriotic lesions were thereafter removed. The induction of only Arid1a KO did not cause any histological changes in the endometriotic cysts of recipients. In contrast, the induction of only Pten KO evoked a stratified architecture and nuclear atypia in the epithelial lining of all endometriotic cysts, histologically corresponding to atypical endometriosis. The induction of Arid1a; Pten double-KO evoked papillary and cribriform structures with nuclear atypia in the lining of 42 and 50% of peritoneal and ovarian endometriotic cysts, respectively, which were histologically similar to EAOC. These results indicate that this mouse model is useful for investigating the mechanisms underlying the development of EAOC and the related microenvironment

cDNA expression library screening revealed novel functional genes involved in clear cell carcinogenesis of the ovary in vitro

In order to identify genes involved in the pathogenesis of clear cell carcinoma of the ovary (CCC), functional screening using a cDNA expression library was performed. We extracted mRNA from a CCC cell line (RMG-1), established a cDNA library using a retroviral vector, transfected that library into mouse NIH3T3 cells and sequenced the resultant foci. The tissue-type specific expression of isolated genes and their transforming activities were evaluated. Seven genes were isolated. Of these genes, the mRNA expression of SEC61B and DVL1 is significantly stronger in CCC than in other histological types (p < .05). Immunohistochemical staining reveals the stronger expression of SEC61B and C1ORF38 than normal ovarian tissues (p < .05). Focus formation is confirmed by the transfection of SEC61B, C1ORF38, and DVL1 into NIH3T3 cells. The present study identified novel genes including SEC61B, C1ORF38, and DVL1, involved in the pathogenesis of CCC. These genes may be additional therapeutic targets for CCC.Impact statement What is already known on this subject? Several important genetic abnormalities, including ARID1A and PIK3CA mutations, have been reported in ovarian clear cell carcinoma (CCC). What the results of this study add? SEC61B, C1ORF38, and DVL1 were newly detected as candidate genes involved in ovarian clear cell carcinogenesis. What the implications are of these findings for clinical practice and/or further research? Functional screening using a cDNA expression library may be a useful technique to identify functional genes for pathogenesis. The information obtained using this technique may provide new therapeutic targets of CCC

Uncovering the Role of N-Acetyl-Aspartyl-Glutamate as a Glutamate Reservoir in Cancer

N-acetyl-aspartyl-glutamate (NAAG) is a peptide-based neurotransmitter that has been extensively studied in many neurological diseases. In this study, we show a specific role of NAAG in cancer. We found that NAAG is more abundant in higher grade cancers and is a source of glutamate in cancers expressing glutamate carboxypeptidase II (GCPII), the enzyme that hydrolyzes NAAG to glutamate and N-acetyl-aspartate (NAA). Knocking down GCPII expression through genetic alteration or pharmacological inhibition of GCPII results in a reduction of both glutamate concentrations and cancer growth. Moreover, targeting GCPII in combination with glutaminase inhibition accentuates these effects. These findings suggest that NAAG serves as an important reservoir to provide glutamate to cancer cells through GCPII when glutamate production from other sources is limited. Thus, GCPII is a viable target for cancer therapy, either alone or in combination with glutaminase inhibition.publishe

A comparison of the life histories of two spider species Tricca lutetiana and Arctosa lamperti (Araneae: Lycosidae)

<p><b>a; Expressions of LCN2 and ACTB (internal control) in endometrial carcinoma cell lines by Semi-quantitative RT-PCR.</b> HHUA and RL95-2 strongly expressed LCN2, whereas Ishikawa and HEC1A moderately expressed it. <b>b; Expressions of LCN2 mRNA of endometrial carcinoma cell lines by RT-PCR, and the secreted LCN2 protein in the culture supernatant (SN) by Western blotting.</b> The expression of LCN2 in LCN2-silenced HHUA and RL95-2 (LCN2 shRNA-1) was markedly weaker than that in control cells (Control). The expression of LCN2 in LCN2-overexpressing HEC1B cells (LCN2 cDNA) was markedly stronger than that in control cells (Control). <b>c; Proliferation activity by WST-1 assay of HHUA, RL95-2 and HEC1B cells under normal culture conditions until 72 hours.</b> The results obtained indicated no significant difference in proliferation between LCN2-silenced cells (LCN2 shRNA-1 and 2) and control cells (Control) of HHUA and RL95-2, or between LCN2 overexpressing cells (LCN2 cDNA) and control cells (Control) of HEC1B.</p