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Prognostic Factor Analysis of Overall Survival in Gastric Cancer from Two Phase III Studies of Second-line Ramucirumab (REGARD and RAINBOW) Using Pooled Patient Data

  • Fuchs, Charles S.;Muro, Kei;Tomasek, Jiri;Van Cutsem, Eric;Cho, Jae Yong;Oh, Sang-Cheul;Safran, Howard;Bodoky, Gyorgy;Chau, Ian;Shimada, Yasuhiro;Al-Batran, Salah-Eddin;Passalacqua, Rodolfo;Ohtsu, Atsushi;Emig, Michael;Ferry, David;Chandrawansa, Kumari;Hsu, Yanzhi;Sashegyi, Andreas;Liepa, Astra M.;Wilke, Hansjochen
    • Journal of Gastric Cancer
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    • v.17 no.2
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    • pp.132-144
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    • 2017
  • Purpose: To identify baseline prognostic factors for survival in patients with disease progression, during or after chemotherapy for the treatment of advanced gastric or gastroesophageal junction (GEJ) cancer. Materials and Methods: We pooled data from patients randomized between 2009 and 2012 in 2 phase III, global double-blind studies of ramucirumab for the treatment of advanced gastric or GEJ adenocarcinoma following disease progression on first-line platinum- and/or fluoropyrimidine-containing therapy (REGARD and RAINBOW). Forty-one key baseline clinical and laboratory factors common in both studies were examined. Model building started with covariate screening using univariate Cox models (significance level=0.05). A stepwise multivariable Cox model identified the final prognostic factors (entry+exit significance level=0.01). Cox models were stratified by treatment and geographic region. The process was repeated to identify baseline prognostic quality of life (QoL) parameters. Results: Of 1,020 randomized patients, 953 (93%) patients without any missing covariates were included in the analysis. We identified 12 independent prognostic factors of poor survival: 1) peritoneal metastases; 2) Eastern Cooperative Oncology Group (ECOG) performance score 1; 3) the presence of a primary tumor; 4) time to progression since prior therapy <6 months; 5) poor/unknown tumor differentiation; abnormally low blood levels of 6) albumin, 7) sodium, and/or 8) lymphocytes; and abnormally high blood levels of 9) neutrophils, 10) aspartate aminotransferase (AST), 11) alkaline phosphatase (ALP), and/or 12) lactate dehydrogenase (LDH). Factors were used to devise a 4-tier prognostic index (median overall survival [OS] by risk [months]: high=3.4, moderate=6.4, medium=9.9, and low=14.5; Harrell's C-index=0.66; 95% confidence interval [CI], 0.64-0.68). Addition of QoL to the model identified patient-reported appetite loss as an independent prognostic factor. Conclusions: The identified prognostic factors and the reported prognostic index may help clinical decision-making, patient stratification, and planning of future clinical studies.

Saprolegnia parasitica Isolated from Rainbow Trout in Korea: Characterization, Anti-Saprolegnia Activity and Host Pathogen Interaction in Zebrafish Disease Model

  • Shin, Sangyeop;Kulatunga, D.C.M.;Dananjaya, S.H.S.;Nikapitiya, Chamilani;Lee, Jehee;De Zoysa, Mahanama
    • Mycobiology
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    • v.45 no.4
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    • pp.297-311
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    • 2017
  • Saprolegniasis is one of the most devastating oomycete diseases in freshwater fish which is caused by species in the genus Saprolegnia including Saprolegnia parasitica. In this study, we isolated the strain of S. parasitica from diseased rainbow trout in Korea. Morphological and molecular based identification confirmed that isolated oomycete belongs to the member of S. parasitica, supported by its typical features including cotton-like mycelium, zoospores and phylogenetic analysis with internal transcribed spacer region. Pathogenicity of isolated S. parasitica was developed in embryo, juvenile, and adult zebrafish as a disease model. Host-pathogen interaction in adult zebrafish was investigated at transcriptional level. Upon infection with S. parasitica, pathogen/antigen recognition and signaling (TLR2, TLR4b, TLR5b, NOD1, and major histocompatibility complex class I), pro/anti-inflammatory cytokines (interleukin $[IL]-1{\beta}$, tumor necrosis factor ${\alpha}$, IL-6, IL-8, interferon ${\gamma}$, IL-12, and IL-10), matrix metalloproteinase (MMP9 and MMP13), cell surface molecules ($CD8^+$ and $CD4^+$) and antioxidant enzymes (superoxide dismutase, catalase) related genes were differentially modulated at 3- and 12-hr post infection. As an anti-Saprolegnia agent, plant based lawsone was applied to investigate on the susceptibility of S. parasitica showing the minimum inhibitory concentration and percentage inhibition of radial growth as $200{\mu}g/mL$ and 31.8%, respectively. Moreover, natural lawsone changed the membrane permeability of S. parasitica mycelium and caused irreversible damage and disintegration to the cellular membranes of S. parasitica. Transcriptional responses of the genes of S. parasitica mycelium exposed to lawsone were altered, indicating that lawsone could be a potential anti-S. parasitica agent for controlling S. parasitica infection.

Monitoring of the mortalities in the aquaculture farms of South Korea (한국 주요 양식종의 수산동물 폐사피해 모니터링)

  • Kim, Jin Woo;Lee, Han Na;Jee, Bo Young;Woo, Sung Ho;Kim, Young Jae;Lee, Mu Kun
    • Journal of fish pathology
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    • v.25 no.3
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    • pp.271-277
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    • 2012
  • The practical monitoring was performed to survey the mortalities in aquaculture farms of olive flounder, rockfish, rainbow trout, Japanese eel, white shrimp and abalone in South Korea from May to November, 2011. The aquatic organism disease inspectors, who have the national licenses for the diagnosis and prevention of aquatic disease and have close relationship with the farms, investigated the rates and causes of mortalities according to the standard manual. In 70 flounder farms, the cumulative mortalities rate was 27.9%, and the mortalities were caused by scuticociliatosis, streptococcosis, VHS, non-infectious loss, vibriosis and gliding bacterial disease. The moralities rate of 30 rockfish farms was 13.6%, and those were mainly contributed by gill flukes and streptococcosis. Most of mortalities of rainbow trout were caused by non-infectious loss and protozoan white spot disease. The mortalities rate of Japanese eel was 0.6% by edwardsiellosis, protozoan white spot disease and gill flukes. The loss rate of white shrimp was 71.2%, and most of them was related with non-infectious ones, such as carnivalization, transportation loss, and the rest was caused by viral white spot disease. The mortalities rate in the abalone farms was 10.7% and all of them were related with non-infectious loss.

Phylogenetic classification and pathogenicity analysis of IHNV isolated from salmonids in Gangwon-do (강원도의 연어과 어류에서 분리된 IHNV 분리주의 계통분류 및 병원성 분석)

  • Lim, Jongwon;Go, Eunho;Hong, Suhee
    • Journal of fish pathology
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    • v.34 no.2
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    • pp.123-131
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    • 2021
  • This study investigated the phylogenetic classification and pathogenicity of 6 infectious hematopoietic necrosis virus (IHNV) strains isolated from salmonid fish in Gangwon-do, Korea. Based on the nucleotide sequence of mid-G region, all six strains belong to J genotype, of which 5 are J-Nagano type and 1 J-Shizuoka type. In a challenge test, 5 isolates of J-Nagano type IHNV showed a various mortalities as 2 isolates induced a high mortality of 100% and the other 3 isolates induced mortalities of 50, 30, and 20% after intraperitoneal injection in rainbow trout (Oncorhynchus mykiss). Meanwhile no mortality was occurred by 1 isolate of J-Shizuoka type virus. Thus, it seems that there might be no relation between genotype and pathogenicity within IHNV J genotypes. This is contrary to previous studies where reported a higher pathogenicity of J-Shizuoka type virus than J-Nagano type virus in rainbow trout. Further examination will be required to clarify this since only one J-Shizuoka type virus was analyzed in this study.

Analysis of Color Characteristics of Marine Oil Spills Using PlanetScope Images (PlanetScope 영상을 이용한 해양 유출유의 색상 특성 분석)

  • Jonggu Kang;Youjeong Youn;Seoyeon Kim;Yemin Jeong;Soyeon Choi;Yungyo Im;Youngmin Seo;Yangwon Lee
    • Korean Journal of Remote Sensing
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    • v.39 no.5_2
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    • pp.875-883
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    • 2023
  • In this letter, we used PlanetScope imagery to conduct experiments on the color characteristics for oil type classification of marine oil spills through Red-Green-Blue (RGB) histogram analysis. The histograms of marine oil spills can be divided into three categories (dark black tones, light silver tones, and light rainbow tones) according to the distribution of pixel values in each band. Thick oil layers with dark black tones can be classified as heavy oil, while thin oil layers with light silver and rainbow tones can be classified as light oil. As more images are analyzed in the future, these oil spill detection and classification methods will become more generalized and reliable.

Backbone 1H, 15N, and 13C Resonance Assignments and Secondary Structure of a Novel Protein OGL-20PT-358 from Hyperthermophile Thermococcus thioreducens sp. nov.

  • Wilson, Randall C.;Hughes, Ronny C.;Curto, Ernest V.;Ng, Joseph D.;Twigg, Pamela D.
    • Molecules and Cells
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    • v.24 no.3
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    • pp.437-440
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    • 2007
  • $OGL-20P^T$-358 is a novel 66 amino acid residue protein from the hyperthermophile Thermococcus thioreducens sp. nov., strain $OGL-20P^T$, which was collected from the wall of the hydrothermal black smoker in the Rainbow Vent along the mid-Atlantic ridge. This protein, which has no detectable sequence homology with proteins or domains of known function, has a calculated pI of 4.76 and a molecular mass of 8.2 kDa. We report here the backbone $^1H$, $^{15}N$, and $^{13}C$ resonance assignments of $OGL-20P^T$-358. Assignments are 97.5% (316/324) complete. Chemical shift index was used to determine the secondary structure of the protein, which appears to consist of primarily ${\alpha}$-helical regions. This work is the foundation for future studies to determine the three-dimensional solution structure of the protein.

A New Analytical Method for Erythromycin in Fish by Liquid Chromatography/Tandem Mass Spectrometry

  • Park, Mi-Jung;Park, Mi-Seon;Lee, Tae-Seek;Shin, Il-Shik
    • Food Science and Biotechnology
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    • v.17 no.3
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    • pp.508-513
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    • 2008
  • Erythromycin has been used to treat Streptococosis, Edwardsiel1osis, Vibriosis, Bacterial enteritis in the cultured fish. In this study, a rapid and effective erythromycin analysis method with new sample treatment protocol and liquid chromatography/tandem mass spectrometry (LC/MS/MS) system for fish products was developed. For the erythromycin extraction from fish muscle, the solvent mixture composed of 0.2% meta-phosphoric acid and methanol (6:4) showed good recovery rate, and the optimum extraction solvent volume was 20 mL. Erythromycin detection using LC/MS/MS were carried out under electro spray ionization (ESI) positive condition and erythromycin mass value 576.2 and 157.9. And the detection limit of the established method was 0.005 mg/kg in fish products. The recovery rate of the developed method applied to the fish species were as following, olive flounder, $87.6{\pm}5.0%$; black rockfish, $87.2{\pm}6.4%$; eel, $85.2{\pm}4.8%$; and rainbow trout, $86.0{\pm}6.2%$. In the established method in this study, the correlation of coefficient values ($R^2$) of erythromycin calibration curve (n=11) was 0.9998.

Comparative Efficacy of Antifungal Agents for Aquaculture Fish and their Eggs (양식 어류와 이들 난에 대한 항곰팡이성 약물들의 효과 비교)

  • Lee, Bo-Young;Lee, Deok-Chan
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.42 no.1
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    • pp.34-40
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    • 2009
  • In fresh water fish hatcheries and farms, Saprolegniales often cause serious mortality to the fish and their eggs. Malachite green is an effective antifungal agent, but is carcinogenic to fish and humans. Alternative antifungal agents are needed. Presently, we tested various concentrations of MBT-01108 (Opuntia ficus-indica extracts) alone and in combination with bronopol, formalin and sodium chloride (MBT-01108 mixture) on in vitro mycelial growth and in vivo remediation of adult eel, Anguilla japonica, infected with Saprolegnia sp. and fertilized eggs of chum salmon, Oncorhynchus keta, to evaluate the compounds' antifungal efficacy on eyed-egg and hatching rates. MBT-Oll08 mixtures incorporating bronopol and formalin at respective concentrations of 50 and 30 parts per million (ppm), and 100 and 20 ppm were most effective in controlling Saprolegnia in vitro and in vivo (P<0.05). Repeated daily exposures to 50 ppm and 100 ppm MBT-01108 were more effective than exposure every 2-3 days post-fertilization for the inhibition of Saprolegnia infection of rainbow trout, Oncorhynchus mykiss eggs as compared with control (0 ppm).

Studies on Effects of Ea4-Peptide of Rainbow Trout Pro-IGF-I on Heart Development, Vasculogenesis and Hematopoiesis in Fish Embryos by Transgenesis

  • Chun, Chang-Zoon;Maria J. Chen;Thomas T. Chen
    • Proceedings of the Korean Society of Developmental Biology Conference
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    • 2003.10a
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    • pp.20-21
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    • 2003
  • Insulin-like growth factors (IGFs) are mitogenic peptide hormones that regulate embryonic development, postnatal growth and cellular differentiation in vertebrates IGFs are initially translated as pre-pro-peptides and then proteolytically processed to yield the mature IGFs and E-peptides. Like the C-peptide of pro-insulin, the E-peptides of pro-IGFs are generally believed to possess little or no biological activity other than their potential roles in the biosynthesis of the mature IGFs. Like human IGF-1, previous studies in our laboratory showed that the recombinant trout Ea4-peptide of pro-IGF-1 exhibited a dose-dependent mitegenic activity in cultured BALB/3T3 fibroblasts and other non-oncogenic transformed cells (Tian et al., 1999) We have also shown by in vitro and in vivo studies that Ea4-peptide possessed novel anti-tumor activities (Chen et al., 2002, Kuo and Chen, 2002; Kuo and Chen 2003). Recent results of studies conducted in chorionicallantoic membrane of developing chicken embryos revealed that Ea4-peptide of trout pro-IGF-1 also possesses a dose-dependent antiangiogenic activity. Together these results raised the question whether Ea4-peptide of trout pro-IGF-1 may affect heart and blood vessel development and hematopoiesis in fish embryos. (중략)

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A study on efficacy and safety of Bio-Gammamix by oral administratiion to cultured fish (양식어류에 있어서 생약제제(바이오감마믹스)의 경구투여에 의한 효능 및 안전성에 관한 연구)

  • Heo, Gang-joon;Kim, Byeung-gie;Yeh, Jae-gill;kim, Jeong-ho
    • Korean Journal of Veterinary Research
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    • v.34 no.3
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    • pp.627-633
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    • 1994
  • A study on efficacy and safety of Bio-Gammamix was performed to use for the preventive drug against bacterial diseases to mirror carp(Cyprinus carpio), rainbow trout(Salmo gairdneri), eel(Anguilla japonica) and flounder(Paralichthys olivaceus). The main ingredients of Bio-Gammamix were ferrous fumarate and mixed extrated powders of licorice root, ox bile and garlic. The test drug was proved to improve feeding habit and feed efficiency and decrease cumulative mortality remarkably. After administration, no side effects and histopathological changes were observed. We can prevent outbreaks of bacterial diseases of fish by the dosage of 1kg/ton of fish body weight perorally once or two times in a day for 7 days and Bio-Gammamix is thought to be used effectively an widely against most bacterial fish pathogens.

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