• Title/Summary/Keyword: progression

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The Neutrophil to Lymphocyte Ratio is an Independent Prognostic Factor in Patients with Metastatic Gastric Cancer

  • Musri, Fatma Yalcin;Mutlu, Hasan;Eryilmaz, Melek Karakurt;Salim, Derya Kivrak;Gunduz, Seyda;Coskun, Hasan Senol
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.3
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    • pp.1309-1312
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    • 2016
  • Inflammation can play an important role in cancer progression and the prognostic importance of neutrophil to lymphocyte ratio (NLR), a marker of inflammation, in cancer is a current investigation topic. In the present study, we aimed to determine whether there is a prognostic link between NLR and metastatic gastric cancer (mGC). A total of 143 patients from the Akdeniz University and Antalya Training and Research Hospital database were retrospectively analyzed. The median NLR value was 3.34. The median overall survival (OS) and median progression-free survival (PFS) were 11.6 and 7.9 months, respectively, in patients with NLR<3.34 while these values were 8.3 and 6.2 months respectively in patients with NLR>3.34 (p<0.001 and p=0.011, respectively). Our study showed that increased NLR is an independent prognostic factor associated with short survival in patients with mGC.

Retrospective Study of Gemcitabine Based Chemotherapy for Unresectable or Recurrent Esophagus Squamous Cell Carcinoma Refractory to First Line Chemotherapy

  • Wang, Mei;Gu, Jun;Wang, Hai-Xing;Wu, Mei-Hong;Li, Yong-Mei;Wang, Ya-Jie
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.4153-4156
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    • 2012
  • Purpose: To investigate the efficacy and toxicity of a combination of gemcitabine with nedaplatin (GN) or cisplatin (GC) for patients with unresectable or recurrent esophagus squamous cell carcinoma. Methods: Gemcitabine was administered at 1 g/m2 intravenously on days 1 and 8; and nedaplatin or cisplatin were administered at 80 mg/m2 intravenously on day 1. We analyzed the response rate, overall survival time, progression-free survival time, and toxicity in 21 patients treated with GN and 27 patients treated with GC. Results: In patients treated with gemcitabine plus nedaplatin, the ORR was 47.6%, the median progression-free survival time was 4.1 months, and the median survival time was 9.3 months. In patients treated with gemcitabine plus cisplatin, the ORR was 48.2%, the median progression-free survival time was 3.9 months, and the median survival time was 9.1 months, respectively. There were no statistically significant differences in ORR, PFS and OS between the two groups. In both, the most commonly observed toxicities were thrombocytopenia and fatigue. Nausea and vomiting was more frequent in the GC group than in the GN group. Conclusion: Gemcitabine based chemotherapy was effective and tolerable for patients with unresectable or recurrent esophagus squamous cell carcinoma refractory to first line chemotherapy.

Inhibitory Effect of Nicotine on Apoptosis Induced by Endoplasmic Reticulum Stress

  • Lee, Dong-Hee
    • Biomolecules & Therapeutics
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    • v.15 no.4
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    • pp.240-244
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    • 2007
  • Cigarette smoking causes serious health problems in humans, especially if smoking habits are established during their adolescence. Nicotine is known to mutate DNA and interfere with apoptosis. Apoptosis is considered as a potent defense mechanism against cellular damaging agents. This study aims to investigate the effect of nicotine on the progression of apoptosis induced under ER stress conditions using four different established cell lines: HEK293, 3T3-L1, C2C12, and HepG2. When treated with nicotine, the progression of apoptosis was notably inhibited in the four cell lines according to the assays of caspase-3 activation and DNA fragmentation. In ER-stressed cells, nicotine appears to inhibit the progression of apoptosis in a concentration-dependent manner. When cells were treated with nicotine prior to ER stress, GRP94 level significantly increased compared to other ER stress markers of PDI and GRP78. This observation suggests that the inhibitory effect of nicotine may results from up-regulation of GRP94, an anti-apoptotic chaperone, under nicotine treatment. Taken together, the present study strongly implies that nicotine may inhibit apoptosis, caused by prolonged ER stress, based on promotion of GRP94 expression.

Acoustic emission monitoring of damage progression in CFRP retrofitted RC beams

  • Nair, Archana;Cai, C.S.;Pan, Fang;Kong, Xuan
    • Structural Monitoring and Maintenance
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    • v.1 no.1
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    • pp.111-130
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    • 2014
  • The increased use of carbon fiber reinforced polymer (CFRP) in retrofitting reinforced concrete (RC) members has led to the need to develop non-destructive techniques that can monitor and characterize the unique damage mechanisms exhibited by such structural systems. This paper presented the damage characterization results of six CFRP retrofitted RC beam specimens tested in the laboratory and monitored using acoustic emission (AE). The focus of this study was to continuously monitor the change in AE parameters and analyze them both qualitatively and quantitatively, when brittle failure modes such as debonding occur in these beams. Although deterioration of structural integrity was traceable and can be quantified by monitoring the AE data, individual failure mode characteristics could not be identified due to the complexity of the system failure modes. In all, AE was an effective non-destructive monitoring tool that can trace the failure progression in RC beams retrofitted with CFRP. It would be advantageous to isolate signals originating from the CFRP and concrete, leading to a more clear understanding of the progression of the brittle damage mechanism involved in such a structural system. For practical applications, future studies should focus on spectral analysis of AE data from broadband sensors and automated pattern recognition tools to classify and better correlate AE parameters to failure modes observed.

Non-classical role of Galectin-3 in cancer progression: translocation to nucleus by carbohydrate-recognition independent manner

  • Kim, Seok-Jun;Chun, Kyung-Hee
    • BMB Reports
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    • v.53 no.4
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    • pp.173-180
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    • 2020
  • Galectin-3 is a carbohydrate-binding protein and regulates diverse functions, including cell proliferation and differentiation, mRNA splicing, apoptosis induction, immune surveillance and inflammation, cell adhesion, angiogenesis, and cancer-cell metastasis. Galectin-3 is also recommended as a diagnostic or prognostic biomarker of various diseases, including heart disease, kidney disease, and cancer. Galectin-3 exists as a cytosol, is secreted in extracellular spaces on cells, and is also detected in nuclei. It has been found that galectin-3 has different functions in cellular localization: (i) Extracellular galectin-3 mediates cell attachment and detachment. (ii) cytosolic galectin-3 regulates cell survival by blocking the intrinsic apoptotic pathway, and (iii) nuclear galectin-3 supports the ability of the transcriptional factor for target gene expression. In this review, we focused on the role of galectin-3 on translocation from cytosol to nucleus, because it happens in a way independent of carbohydrate recognition and accelerates cancer progression. We also suggested here that intracellular galecin-3 could be a potent therapeutic target in cancer therapy.

Role of Transforming Growth Factor-β in Tumor Invasion and Metastasis

  • Kim, Eun-Sook;Moon, Aree
    • Toxicological Research
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    • v.23 no.3
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    • pp.197-205
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    • 2007
  • Cancer metastasis is a major determinant of cancer patient mortality. Mounting evidence favors a strong positive role for $TGF-{\beta}$ in human cancer progression. The complex pattern on cross-talk of $TGF-{\beta}$ and the related other signaling pathways is an important area of investigation that will ultimately contribute to understanding of the bifunctional role of $TGF-{\beta}$ in cancer progression. This review summarizes some of the current understanding of $TGF-{\beta}$ signaling with a major focus in its contribution to the tumor cell invasion and metastasis. Five issues are addressed in this review: (1) $TGF-{\beta}$ signaling, (2) $TGF-{\beta}$ and EMT, (3) $TGF-{\beta}$ and MMP, (4) $TGF-{\beta}$ and Ras, and (5) Role of $TGF-{\beta}$ in invasion and metastasis. Due to the bifunctional cellular effects of $TGF-{\beta}$, as a tumor promoter and a tumor suppressor, more precisely defined $TGF-{\beta}$ signaling pathways need to be elucidated. According to the current literature, $TGF-{\beta}$ is clearly a major factor stimulating tumor progression through a complex spectrum of the interplay and cross-talk between various signaling molecules. Understanding the role of $TGF-{\beta}$ in invasion and metastasis will provide valuable information on establishing strategies to manipulate $TGF-{\beta}$ signaling which should be a high priority for the development of anti-metastatic therapeutics.

Effect of the Water Extract of Albizzia julibrissin on Cell Cycle Progression in the Human Leukemic Jurkat Cells (백혈병세포주 Jurkat의 세포주기 억제에 미치는 합환피(Albizzia julibrissin) 물 추출물의 효과)

  • Hwang, Sang-Gu;Lee, Hyung-Chul;Kim, Dae-Geun;An, Won-Gun;Jeon, Byung-Hun
    • Korean Journal of Pharmacognosy
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    • v.33 no.1 s.128
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    • pp.29-34
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    • 2002
  • Albizzia julibrissin belonging to the family Leguminosae has been used for the treatment of contusion, sore throat, amnesia, and insomnia in Oriental traditional medicine. The water extract of A. julibrissin induced apoptosis in Jurkat T-acute lymphoblastic leukemia (ALL) cells as measured by cell morphology. The capability of this herb medicine to induce apoptosis was associated with proteolytic cleavage of specific target protein such as beta-catenin protein suggesting the possible involvement of caspases. The purpose of the present study is also to investigate the effect of A. julibrissin on cell cycle progression. Our results showed that GI checkpoint related gene products (cyclin D1, cyclin dependent kinase 4, retinoblastoma, E2F1) were decreased in their protein levels in a dose-dependent manners after treatment of the extract. These results indicate that the increase of apoptotic cell death by A. julibrissin may be due to the inhibition of cell cycle progression in wild type p53-lacking Jurkat cells.

Inactivation of SMAD$_4$ Tumor Suppressor gene during Gastric Cancer Progression

  • Shin, Young-Kee
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2006.11a
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    • pp.19-24
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    • 2006
  • Mothers against decapentaplegic homolog 4 (SMAD4) is a tumor suppressor gene associated with gastrointestinal carcinogenesis. The aim of the present study was to characterize more precisely its role in the development and progression of human gastric carcinoma. In this study, using tissue microarray analysis of 283 gastric cancers and related lesions, we found loss of SMAD4 protein expression in the cytoplasm (36/114, 32%) and in the nucleus (46/114, 40%) of gastric cancer cells. The loss of nuclear SMAD4 expression in primary tumors correlated significantly with poor survival, and was an independent prognostic marker in multivariate analysis. We also found a substantial decrease in SMAD4 expression at both the RNA and protein level in several human gastric carcinoma cell lines. To identify the genetic and/or epigenetic mechanisms of altered SMAD4 expression in gastric carcinoma, loss of heterozygosity (LOH), promoter hypermethylation, and exon mutations were examined. We found that LOH (20/70, 29%) and promoter hypermethylation (4/73, 5%) were associated with the loss of SMAD4 expression. SMAD4 protein levels wore also affected in certain gastric carcinoma cell lines following incubation with Mc132, a proteasome inhibitor. Taken together, our results indicate that the loss of SMAD4, especially loss of nuclear SMAD4 expression, is involved in gastric cancer progression. The loss of SMAD4 in gastric carcinomas is due to several mechanisms, including LOH, hypermethylation, and proteasome degradation.

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DRG2 Regulates G2/M Progression via the Cyclin B1-Cdk1 Complex

  • Jang, Soo Hwa;Kim, Ah-Ram;Park, Neung-Hwa;Park, Jeong Woo;Han, In-Seob
    • Molecules and Cells
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    • v.39 no.9
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    • pp.699-704
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    • 2016
  • Developmentally regulated GTP-binding protein 2 (DRG2) plays an important role in cell growth. Here we explored the linkage between DRG2 and G2/M phase checkpoint function in cell cycle progression. We observed that knockdown of DRG2 in HeLa cells affected growth in a wound-healing assay, and tumorigenicity in nude mice xenografts. Flow cytometry assays and [$^3H$] incorporation assays indicated that G2/M phase arrest was responsible for the decreased proliferation of these cells. Knockdown of DRG2 elicited down-regulation of the major mitotic promoting factor, the cyclin B1/Cdk1 complex, but upregulation of the cell cycle arresting proteins, Wee1, Myt1, and p21. These findings identify a novel role of DRG2 in G2/M progression.

SEVERE ACCIDENT ISSUES RAISED BY THE FUKUSHIMA ACCIDENT AND IMPROVEMENTS SUGGESTED

  • Song, Jin Ho;Kim, Tae Woon
    • Nuclear Engineering and Technology
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    • v.46 no.2
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    • pp.207-216
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    • 2014
  • This paper revisits the Fukushima accident to draw lessons in the aspect of nuclear safety considering the fact that the Fukushima accident resulted in core damage for three nuclear power plants simultaneously and that there is a high possibility of a failure of the integrity of reactor vessel and primary containment vessel. A brief review on the accident progression at Fukushima nuclear power plants is discussed to highlight the nature and characteristic of the event. As the severe accident management measures at the Fukushima Daiich nuclear power plants seem to be not fully effective, limitations of current severe accident management strategy are discussed to identify the areas for the potential improvements including core cooling strategy, containment venting, hydrogen control, depressurization of primary system, and proper indication of event progression. The gap between the Fukushima accident event progression and current understanding of severe accident phenomenology including the core damage, reactor vessel failure, containment failure, and hydrogen explosion are discussed. Adequacy of current safety goals are also discussed in view of the socio-economic impact of the Fukushima accident. As a conclusion, it is suggested that an investigation on a coherent integrated safety principle for the severe accident and development of innovative mitigation features is necessary for robust and resilient nuclear power system.