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Bayesian Survival Analysis of High-Dimensional Microarray Data for Mantle Cell Lymphoma Patients

  • Moslemi, Azam;Mahjub, Hossein;Saidijam, Massoud;Poorolajal, Jalal;Soltanian, Ali Reza
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.1
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    • pp.95-100
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    • 2016
  • Background: Survival time of lymphoma patients can be estimated with the help of microarray technology. In this study, with the use of iterative Bayesian Model Averaging (BMA) method, survival time of Mantle Cell Lymphoma patients (MCL) was estimated and in reference to the findings, patients were divided into two high-risk and low-risk groups. Materials and Methods: In this study, gene expression data of MCL patients were used in order to select a subset of genes for survival analysis with microarray data, using the iterative BMA method. To evaluate the performance of the method, patients were divided into high-risk and low-risk based on their scores. Performance prediction was investigated using the log-rank test. The bioconductor package "iterativeBMAsurv" was applied with R statistical software for classification and survival analysis. Results: In this study, 25 genes associated with survival for MCL patients were identified across 132 selected models. The maximum likelihood estimate coefficients of the selected genes and the posterior probabilities of the selected models were obtained from training data. Using this method, patients could be separated into high-risk and low-risk groups with high significance (p<0.001). Conclusions: The iterative BMA algorithm has high precision and ability for survival analysis. This method is capable of identifying a few predictive variables associated with survival, among many variables in a set of microarray data. Therefore, it can be used as a low-cost diagnostic tool in clinical research.

Aldose Reductase Inhibitor Fidarestat as a Promising Drug Targeting Autophagy in Colorectal Carcinoma: a Pilot Study

  • Pandey, Saumya
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.12
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    • pp.4981-4985
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    • 2015
  • Background: Colorectal cancer (CRC) is a leading cause of morbidity and mortality worldwide. Targeting autophagic cell death is emerging as a novel strategy in cancer chemotherapy. Aldose reductase (AR) catalyzes the rate limiting step of the polyol pathway of glucose metabolism; besides reducing glucose to sorbitol, AR reduces lipid peroxidation-derived aldehydes and their glutathione conjugates. A complex interplay between autophagic cell death and/or survival may in turn govern tumor metastasis. This exploratory study aimed to investigate the potential role of AR inhibition using a novel inhibitor Fidarestat in the regulation of autophagy in CRC cells. Materials and Methods: For glucose depletion (GD), HT-29 and SW480 CRC cells were rinsed with glucose-free RPMI-1640, followed by incubation in GD medium +/- Fidarestat ($10{\mu}M$). Proteins were extracted by a RIPA-method followed by Western blotting ($35-50{\mu}g$ of protein; n=3). Results: Autophagic regulatory markers, primarily, microtubule associated protein light chain (LC) 3, autophagy-related gene (ATG) 5, ATG 7 and Beclin-1 were expressed in CRC cells; glyceraldehyde-3 phosphate dehydrogenase (GAPDH) was used as an internal reference. LC3 II (14 kDa) expression was relatively high compared to LC3A/B I levels in both CRC cell lines, suggesting occurrence of autophagy. Expression of non-autophagic markers, high mobility group box (HMG)-1 and Bcl-2, was comparatively low. Conclusions: GD +/- ARI induced autophagy in HT-29 and SW-480 cells, thereby implicating Fidarestat as a promising therapeutic agent for colorectal cancer; future studies with more potent ARIs are warranted to fully dissect the molecular regulatory networks for autophagy in colorectal carcinoma.

Association Between p53 Arg72Pro Polymorphism and the Risk of Human Papillomavirus-related Head and Neck Squamous Cell Carcinoma: A Meta-analysis

  • Xia, Ling-Yun;Zeng, Xian-Tao;Li, Cheng;Leng, Wei-Dong;Fan, Ming-Wen
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.6127-6130
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    • 2013
  • This study aimed to investigate the association between p53 Arg72Pro polymorphism and the risk of human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) by conducting meta-analysis. The PubMed database was searched for relevant studies until May 30, 2013. Relevant studies were selected and data were extracted by two independent authors. Overall, subgroup, and sensitivity analyses were then conducted using the Comprehensive Meta-Analysis v2.2 software. Wild-genotype ArgArg was considered as reference [odds ratio (OR) = 1.00]. Nine studies involving 1071 HNSCC cases were obtained. Meta-analysis results indicated no association between p53 Arg72Pro polymorphism and the risk of HPV-related HNSCC: for Pro/Pro vs. Arg/Arg, OR = 1.17, 95% confidence interval (CI) = 0.70-1.98; for Arg/Pro vs. Arg/Arg, OR = 1.25, 95% CI = 0.97-1.72; and for (Pro/Pro + Arg/Pro) vs. Arg/Arg, OR = 1.28, 95% CI = 0.95-1.70. These meta-analysis results were supported by subgroup and sensitivity analysis results. In conclusions, p53 Arg72Pro polymorphism is a potential marker of HP infection-related HNSCC rather than a susceptibility gene polymorphism.

Characterization of Campylobacters Newly Isolated from Swine Gastric Mucosa

  • Lee, Yeon-Hee;Lee, Jin-Hui;Cho, Hyun-Joo;Shin, En-Joo;Park, Jong-Hwan;Park, Jae-Hak
    • Journal of Microbiology and Biotechnology
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    • v.9 no.6
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    • pp.778-783
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    • 1999
  • Campylobacter is a pathogen for both humans and animals that can be transferred from animals to humans. Four isolates, which grew under 5-10% $CO_2$ and had small and translucent colonies, were obtained from swine gastric mucosa and characterized using various methods. These bacteria were gram negative, spirally shaped with round ends. One or two non-sheathed polar flagella were observed under electron microscopy. A PCR with species-specific protein (SSP) primers for 16S rRNA gene in Campylobacter produced a typical 462 bp fragment. The isolates had various biochemical and molecular characteristics which differentiated them from other Campylobacters. The isolates were catalase and oxidase positive, urease (rapid) negative, nitrate reduction positive, indoxyl acetate hydrolysis positive, y-glutamyl transpeptidase negative, and alkaline phosphatase negative. All four isolates showed growth at $37^{\circ}C{\;}and{\;}42^{\circ}C{\;}but{\;}not{\;}at{\;}25^{\circ}C$, were resistant to cephalotin and cefoperazone, and susceptible to carbenicillin. The isolates showed various results in the reduction of chloride to triphenyl tetrazolium (TTC) and a susceptibility to nalidixic acid. Western blot analysis of these isolates with antiserum raised against one isolate showed different patterns from those of reference strains. A dendrogram drawn with the RAPD results showed that these isolates belonged to a new Campylobacter spp. group different from those of C. jejuni, C. doylei, C. lari, and C. coli.

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Associations Between XRCC1 Arg399Gln, Arg194Trp, and Arg280His Polymorphisms and Risk of Differentiated Thyroid Carcinoma: A Meta-analysis

  • Du, Yang;Han, Li-Yuan;Li, Dan-Dan;Liu, Hui;Gao, Yan-Hui;Sun, Dian-Jun
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.9
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    • pp.5483-5487
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    • 2013
  • Background: Associations between Arg399Gln, Arg194Trp and Arg280His polymorphisms of the XRCC1 gene and risk of differentiated thyroid carcinoma (DTC) have been widely studied but the findings are contradictory. Methods: We performed a meta-analysis in the present study using STATA 11.0 software to clarify any associations. Electronic literature databases and reference lists of relevant articles revealed a total of 10, 6 and 6 published studies for the Arg399Gln, Arg194Trp and Arg280His polymorphisms, respectively. Results: No significant associations were observed between Arg399Gln and DTC risk in all genetic models within the overall and subgroup meta-analyses, while the Trp/Trp vs Arg/Arg and recessive model of the Arg194Trp polymorphism was associated with DTC susceptibility, and the dominant model of Arg280His polymorphism contributed to DTC susceptibility in Caucasians. Conclusions: Our meta-analysis suggests that XRCC1 Arg194Trp may be a risk factor for DTC development.

PIK3CA and AKT Gene Polymorphisms in Susceptibility to Osteosarcoma in a Chinese Population

  • He, Mao-Lin;Wu, Yang;Zhao, Jin-Min;Wang, Zhe;Chen, Ying-Bin
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.9
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    • pp.5117-5122
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    • 2013
  • Purpose: To explore the association between PIK3CA and AKT single nucleotide polymorphisms(SNP) and osteosarcoma susceptibility. Methods: TaqMan polymerase chain reaction(PCR) was used to detect the genotypes of SNPs (rs7646409, rs6973569 and rs9866361) in peripheral blood samples from 59 patients with osteosarcoma and from 63 healthy controls. Unconditional logistic regression was used to analyze the correlation between SNPs and osteosarcoma risk. Results: No statistically significant difference was found between osteosarcoma patients and healthy controls in the genotype of AKT rs6973569 (P=0.7). However, after stratified analysis, the genotype AA of AKT rs6973569 carried a higher risk of osteosarcoma metastasis (OR:2.94, 95%CL:1.00-8.59); the difference of rs7646409 genotype distributions between the case and control groups was statistically significant (P=0.032). Taking genotype TT as a reference, the risk of osteosarcoma increased three fold in patients with genotype CC (OR:3.47, 95%CL:1.26-9.56). A statistically significant difference was found between the alleles C and T (P=0.005). Further analysis showed that the risk factor was more pronounced in male patients with Enneking's stage IIB and osteoblastic osteosarcoma. PIK3CA rs9866361 did not fit Hardy-Weinberg equilibrium (P<0.05). Conclusions: Genotype CC in locus PIK3CA rs7646409 may increase the risk of osteosarcoma in the Chinese population.

Sequence Analysis of E2 Glycoprotein from Indian Isolate of Classical Swine Fever Virus (CSFV)

  • Bajwa, Mehak;Verma, Ramneek;Deka, Dipak;Dhol, Gagandeep Singh;Barman, Nagendra Nath
    • Microbiology and Biotechnology Letters
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    • v.43 no.1
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    • pp.22-30
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    • 2015
  • CSF is a major concern for the swine industry, representing currently the most epizootically dangerous disease to the species. Numerous CSFV isolates with various degrees of virulence have already been isolated worldwide, ranging from low virulent strains that do not result in any apparent clinical signs to highly virulent strains that cause a severe per acute hemorrhagic fever with very high mortality. The molecular epidemiology of CSFVs has proven to be an essential tool for effective disease control and the development of safe and effective vaccines. Therefore, this study cloned and sequenced local CSFV isolates, and conducted a phylogenetic analysis based on the E2 glycoprotein encoding sequences.The RNA was extracted from PK15 cell culture passaged CSFV isolates, the cDNA prepared, and the complete E2 gene amplified with a product size of 1186 bp. The gelpurified PCR product was cloned into a pGEMT easy vector and the positive clone commercially sequenced. Aligning the nucleotide (1119 bp) and amino acid (373) sequences with 29 reference strains revealed nucleotide and amino acid sequence identities of 82.60-97.80% and 88.70-98.70%, respectively, indicating a higher mutation rate of the field CSFV strains. The phylogenetic analysis based on the complete E2 amino acid sequences also revealed a reliable differentiation of all the analyzed strains into specific genetic groups and subgroups, plus the local isolate (CSFV-E2) was found to cluster with the CSFV subgroup 2.2. Thus, the full-length E2 cds proved to be most suitable for a reliable and statistically significant phylogenetic analysis of CSFV isolates.

Validation and Application of a Real-time PCR Protocol for the Specific Detection and Quantification of Clavibacter michiganensis subsp. sepedonicus in Potato

  • Cho, Min Seok;Park, Duck Hwan;Namgung, Min;Ahn, Tae-Young;Park, Dong Suk
    • The Plant Pathology Journal
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    • v.31 no.2
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    • pp.123-131
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    • 2015
  • Clavibacter michiganensis subsp. sepedonicus (Cms) multiplies very rapidly, passing through the vascular strands and into the stems and petioles of a diseased potato. Therefore, the rapid and specific detection of this pathogen is highly important for the effective control of the pathogen. Although several PCR assays have been developed for detection, they cannot afford specific detection of Cms. Therefore, in this study, a computational genome analysis was performed to compare the sequenced genomes of the C. michiganensis subspecies and to identify an appropriate gene for the development of a subspecies-specific PCR primer set (Cms89F/R). The specificity of the primer set based on the putative phage-related protein was evaluated using genomic DNA from seven isolates of Cms and 27 other reference strains. The Cms89F/R primer set was more specific and sensitive than the existing assays in detecting Cms in in vitro using Cms cells and its genomic DNA. This assay was also able to detect at least $1.47{\times}10^2copies/{\mu}l$ of cloned-amplified target DNA, 5 fg of DNA using genomic DNA or $10^{-6}$ dilution point of 0.12 at $OD_{600}$ units of cells per reaction using a calibrated cell suspension.

Identification of Fusarium fujikuroi Isolated from Barnyard Grass and Possibility of Inoculum Source of Bakanae Disease on Rice (피에서 분리한 Fusarium fujikuroi의 동정 및 벼 키다리병의 전염원 가능성)

  • Choi, Hyo-Won;Lee, Yong-Hwan;Hong, Sung-Kee;Kim, Wan-Gyu;Lee, Young-Kee;Chun, Se-Chul
    • Research in Plant Disease
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    • v.17 no.1
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    • pp.82-85
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    • 2011
  • Bakanae disease symptom were observed in barnyard grass in paddy field in Heanam, Jeonnam. The infected plants were blighted and white mass of spore were formed on the stem. Fusarium species were isolated from infected stem and the isolates were identified as Fusarium fujikuroi based on their morphological and molecular characteristics. The isolates of F. fujikuroi were assigned to reference of F. fujikuroi among related Fusarium species based on the translation elongation factor 1-alpha gene sequence. Pathogenicity of the fungal isolates was confirmed on seedlings of rice and barnyard grass by artificial inoculation. The results indicated that barnyard grass can be inoculum source of Bakanae disease on rice. Thus, effective weed management is necessary to Bakanae disease control and healthy seed production.

A morphological study of vomeronasal organ of Korean black goat (Capra aegagrus hircus) (한국흑염소 보습코기관의 형태학적 관찰)

  • Park, Changnam;Yang, Wonjun;Bae, Yeonji;Lee, Yongduk;Kang, Wanchoul;Ahn, Meejung;Shin, Taekyun
    • Korean Journal of Veterinary Research
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    • v.53 no.1
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    • pp.55-60
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    • 2013
  • The vomeronasal organ (VNO) plays an important role in reproduction and social activities in ruminants including goats. A morphological study on the structure of VNO and its epithelial cells was carried out in Korean black goats. Grossly, the VNO of Korean goats opens into mouth through incisive ducts. Microscopically, the epithelium of VNO consisted of medial sensory epithelium and lateral non-sensory epithelium. Several blood vessels and nerve bundles were observed in the lamina propria encased by vomeronasal cartilage. Immunohistochemical staining showed that protein gene product (PGP) 9.5 was immunostained in the receptor cells of the sensory epithelium and in some cells of the non-sensory epithelium. Galectin-3 was mainly observed in the supporting cells of sensory and non-sensory epithelium. Lectins including wheat germ agglutinin, Ulex europaeus agglutinin, Bandeiraea simplicifolia lectin Isolectin B4, Dolichos biflorus agglutinin and soybean agglutinin used in this study were bound in VNO sensory, non-sensory epithelia as well as in the lamina propria with varying intensity. Collectively, this is a first descriptive morphological study of VNO of Korean black goat with special reference to lectin histochemistry.