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Hypoxia-inducible Factor 1 Alpha (HIF-1α) as a Prognostic Indicator in Patients with Gastric Tumors: A Meta-analysis

  • Zhang, Zhi-Gang;Zhang, Qiu-Ning;Wang, Xiao-Hu;Tian, Jin-Hui
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.7
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    • pp.4195-4198
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    • 2013
  • Background and Objective: Though researched for years, the prognostic role of hypoxia-inducible factor 1 alpha (HIF-$1{\alpha}$) in gastric cancer is still controversial. We thus undertook a systematic review to assess the relationship. Method: A systematically literature search of Pubmed, Embase, Web of Science, China Biological Medicine Disc and Cochrane Library was undertaken in February 2013, and the reference lists of articles were retrieved. Results: 12 trials (1,555 participants) were included to assess the association between HIF-$1{\alpha}$ expression and survival. Summary hazard ratios (HRs) were calculated. HIF-$1{\alpha}$ expression was significantly correlated with poor overall survival of gastric cancer patients (HR=1.34, 95%CI: 1.13-1.58; P=0.0009), but not with poor disease free survival of gastric cancer patients (HR=1.67, 95%CI: 0.99-2.82; P=0.06). Conclusion: HIF-$1{\alpha}$ was associated with poor OS, but not DFS, especially for Asian patients. But studies evaluating relationships of HIF-$1{\alpha}$ with OS and DFS in non-Asian gastric cancer patients appear needed.

Inhibition of Inducible Nitric Oxide Synthase by Agaricus bisporus Extract in RAW 264.7 Macrophages

  • Ahn, Ji-Yun;Lee, Hyun-Jung;Moon, Mi-Kyung;Kim, Su-Na;Ha, Tae-Youl
    • Preventive Nutrition and Food Science
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    • v.13 no.4
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    • pp.362-365
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    • 2008
  • Agaricus bisporus, also known as white button mushroom, is one of the most popular mushrooms consumed in Korea. This mushroom contains high concentrations of flavanoids and exhibits antioxidant activity. In this study, we examined the effects of Agaricus bisporus ethanol extract (ABE) on lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 cells. Nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) protein levels were assessed in cells treated with $100\;{\mu}M$ LPS in the presence or absence of ABE. 0.5 mg/mL of ABE suppressed NO production significantly. Moreover, ABE inhibited levels of iNOS protein. Taken together, these results suggest that ABE exerts anti-inflammatory activity in LPS-induced inflammation in RAW 264.7 cells.

Effect of Heat Shock Protein 70 on Inducible Nitric Oxide Synthase during Sepsis in Rats (패혈증에서 Heat Shock Protein 70의 과도발현이 Inducible Nitric Oxide Synthase의 발현에 미치는 효과)

  • Lee, Yong Keun;Shin, Hyo-Keun;Kwon, Woon Yong;Suh, Gil Joon;Youn, Yeo Kyu
    • Journal of Trauma and Injury
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    • v.21 no.1
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    • pp.59-65
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    • 2008
  • Purpose: The aim of this study was to evaluate the effect of overexpression of heat shock protein 70 (HSP70) on the expression of inducible nitric oxide synthase and on the concentration of nitric oxide and to determine the mechanism for the relationship between HSP70 and inducible nitric oxide synthase (iNOS) in sepsis. Methods: Experiments were performed on male Sprague-Dawley rats, and sepsis was induced by using cecal ligation and puncture (CLP). Glutamine (GLN) or saline was administered 1 h after initiation of sepsis. We acquired serum and lung tissues from the rats 12 h or 24 h after initiation of sepsis. We analyzed the concentration of nitric oxide, the expression of HSP70 in the lung, and the gene expression of iNOS in the lung. Results: In CLP+GLN, glutamine given after initiation of sepsis enhanced the expression of HSP70 in the lung at 12 h (CLP+GLN vs. CLP:: $47.19{\pm}10.04$ vs. $33.22{\pm}8.28$, p = 0.025) and 24 h (CLP+GLN vs. CLP: $47.06{\pm}10.60$ vs. $31.90{\pm}4.83$, p = 0.004). In CLP+GLN, glutamine attenuated the expression of iNOS mRNA in the lung at 12 h (CLP+GLN vs. CLP: $4167.17{\pm}951.59$ vs. $5513.73{\pm}1051.60$, p = 0.025) and 24 h (CLP+GLN vs. CLP: $9,437.65{\pm}2,521.07$ vs. $18,740.27{\pm}8,241.20$, p = 0.016) and reduced the concentration of nitric oxide in serum at 12 h (CLP+GLN vs. CLP: $0.86{\pm}0.48$ vs. $3.82{\pm}2.53{\mu}mol/L$, p = 0.016) and 24 h (CLP+GLN vs. CLP: $0.39{\pm}0.25$ vs. $1.85{\pm}1.70{\mu}mol/L$, p = 0.025). Conclusion: The overexpression of HSP70 induced by the administration of glutamine in sepsis attenuated the gene expression of iNOS and reduced the concentration of nitric oxide.

NMDA (n-methyl-d-aspartate) Change Expression Level of Transcription Factors (Egr-1, c-jun, Junb, Fosb) mRNA in the Cerebellum Tissue of Balb/c Mouse (NMDA투여에 의한 transcription factor (Egr-1, C-Jun, JunB, FosB)의 발현 변화 양상)

  • Ha, Jong-Su;Kim, Jae-Wha;Song, Jae-Chan
    • Journal of Life Science
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    • v.25 no.9
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    • pp.1043-1050
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    • 2015
  • Glutamate is one of the principle transmitters in the CNS. Ionotropic receptors of glutamate, selectively activated by N-methyl-D-aspartate (NMDA), play an important role in the processes of cell development, learning, memory, and etc. On the other hand, many studies discovered that over-activation of glutamate receptors leads to neurodegeneration and are known to be implicated in major areas of brain pathology. Any sustained effect of a transient NMDA receptor activation is likely to involve signaling to the nucleus and to trigger coordinated changes in gene expression. Classically, a set of immediate-early genes are induced first; some of genes are by themselves transcription factors that control expression of other target genes. This study provides understanding of changes of inducible transcription factors mRNA levels with RT-PCR by inducing over-activation of NMDA receptor with intraperitoneal NMDA injection. The experimental conditions were varied by 1, 5, 25, and 125 g/ of body weight NMDA and measured transcription factors mRNA levels are Egr-1, c-Jun, JunB, and FosB. Based on result obtained, inducible transcription factors mRNA in NMDA injection to mice with 5 g/body weight showed the greatest change. And ITF mRNA showed greatest change 24 hr after injection. The expression level of JunB mRNA was markedly changed. Up to the present days, no study clearly understood how ITF mRNA affected the apoptosis of purkinje cells in the cerebellum. The current study improves the understanding of the mechanism of apoptosis of purkinje cells in the cerebellum.

The Expression of Hypoxia Inducible Factor-1 $\alpha$ by Desferrioxamine Induces Radioresistance in Mouse Hepatoma Cell Line (쥐의 간암 세포에서 Desferrioxamine에 의해 유도된 Hypoxia Inducible Factor-1 $\alpha$가 방사선 저항성을 초래함)

  • Kwon, Byung-Hyun
    • Radiation Oncology Journal
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    • v.22 no.3
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    • pp.217-224
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    • 2004
  • Purpose: It is well known that the radiosensitivity of tumor cells can be significantly reduced under hypoxic conditions. Hypoxia-inducible factor-1 $\alpha$ (HIF-1 $\alpha$) plays a pivotal role in the essential adaptive responses to hypoxia. Therefore this study investigated the relationship between HIF-1 $\alpha$ expression and radiosensitivity. M Mouse hepatoma cell line hepafcic7 and HIF-1 $\beta$-deficient mutant cell line hepa1C4 were used to analyze the role of HIF-1 a. on radiosensitivity. These cells were exposed for 6 h to desferrioxamine (DFX) before radiation. HIF-1$\alpha$. expression was examined by Western blot. Apoptosis was assessed by DNA fragmentation, propidium iodide staining, and apoptotic cell death detection ELISA kit. Radiation sensitivity was determined using MTT assay. The radiobioiogical parameters, surviving fractions at 2 Gy and 8 Gy, and mean inactivation dose (MID) from the linear-quadratic model were used to assess radiation sensitivity in the statistical analyses. Results: The expression of HIF-1 $\alpha$. was Increased, whereas apoptosis was decreased, by radiation In the presence of DFX In hepal cl c7, but not In hepal C4. The radlosensitivity of hepal C4 cells was not significantly affected by DFX treatment. The radiosensitivlty of hepal cl c7 cells was significantly decreased in the presence of DFX Conclusion: The expression of HIF-1 w by hypoxia-mimic agent DFX reduced apoptosls and radiosensitlvity in mouse hepatoma cell line hepafclc7. These results suggested that HIF-1 u could be Induced by irradiation in hypoxic ceils of tumor masses, and that this mlght Increase radioresistance in hypoxic cells.