• Title/Summary/Keyword: Gene survival

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Prediction of an Essential Gene with Potential Drug Target Property in Streptococcus suis Using Comparative Genomics

  • Zaman, Aubhishek
    • Interdisciplinary Bio Central
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    • v.4 no.4
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    • pp.11.1-11.8
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    • 2012
  • Genes that are indispensable for survival are referred to as essential gene. Due to the momentous significance of these genes for cellular activity they can be selected potentially as drug targets. Here in this study, an essential gene for Streptococcus suis was predicted using coherent statistical analysis and powerful genome comparison computational method. At first the whole genome protein scatter plot was generated and subsequently, on the basis of statistical significance, a reference genome was chosen. The parameters set forth for selecting the reference genome was that the genome of the query (Streptococcus suis) and subject must fall in the same genus and yet they must vary to a good degree. Streptococcus pneumoniae was found to be suitable as the reference genome. A whole genome comparison was performed for the reference (Streptococcus pneumoniae) and the query genome (Streptococcus suis) and 14 conserved proteins from them were subjected to a screen for potential essential gene property. Among those 14 only one essential gene was found to be with impressive similarity score between reference and query. The essential gene encodes for a type of 'Clp protease'. Clp proteases play major roles in degrading misfolded proteins. Results found here should help formulating a drug against Strptococcus suis which is responsible for mild to severe clinical conditions in human. However, like many other computational studies, the study has to be validated furthermore through in vitro assays for concrete proof.

Association between ABCB1 Immunohistochemical Expression and Overall Survival in Gastric Cancer Patients

  • de Oliveira, Juliana;Felipe, Aledson Vitor;Neto, Ricardo Artigiani;Oshima, Celina Tizuko;de Souza Silva, Marcelo;Forones, Nora Manoukian
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.16
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    • pp.6935-6938
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    • 2014
  • Gastric cancer (GC) is one of the most common malignancies worldwide. The ABCB1 protein, a member of the ATP-binding cassette (ABC) transporter family, encoded by the ABCB1 gene, considerably influences the distribution of drugs across cell membranes as well as multidrug resistance (MDR) of antineoplastic drugs. In contrast to the extensive knowledge on the pharmacological action of ABCB1 protein, the correlation between the clinical-pathological data and ABCB1 protein expression in patients with GC remains unclear. The aim was to investigate association between ABCB1 expression and overall survival in GC patients. Human tumor fragments from 57 GC patients were examined by immunohistochemistry assay. We observed lower survival rate of patients with GC who were positive for ABCB1 expression (p=0.030). Based on these observations, we conclude that GC patients with positive ABCB1 protein immunohistochemical expression in their tumors suffer shorter overall survival.

Survival Factor Gene FgSvf1 Is Required for Normal Growth and Stress Resistance in Fusarium graminearum

  • Li, Taiying;Jung, Boknam;Park, Sook-Young;Lee, Jungkwan
    • The Plant Pathology Journal
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    • v.35 no.5
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    • pp.393-405
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    • 2019
  • Survival factor 1 (Svf1) is a protein involved in cell survival pathways. In Saccharomyces cerevisiae, Svf1 is required for the diauxic growth shift and survival under stress conditions. In this study, we characterized the role of FgSvf1, the Svf1 homolog in the homothallic ascomycete fungus Fusarium graminearum. In the FgSvf1 deletion mutant, conidial germination was delayed, vegetative growth was reduced, and pathogenicity was completely abolished. Although the FgSvf1 deletion mutant produced perithecia, the normal maturation of ascospore was dismissed in deletion mutant. The FgSvf1 deletion mutant also showed reduced resistance to osmotic, fungicide, and cold stress and reduced sensitivity to oxidative stress when compared to the wild-type strain. In addition, we showed that FgSvf1 affects glycolysis, which results in the abnormal vegetative growth in the FgSvf1 deletion mutant. Further, intracellular reactive oxygen species (ROS) accumulated in the FgSvf1 deletion mutant, and this accumulated ROS might be related to the reduced sensitivity to oxidative stress and the reduced resistance to cold stress and fungicide stress. Overall, understanding the role of FgSvf1 in F. graminearum provides a new target to control F. graminearum infections in fields.

Odorant Stimulation Promotes Survival of Rodent Olfactory Receptor Neurons via PI3K/Akt Activation and Bcl-2 Expression

  • Kim, So Yeun;Yoo, Seung-Jun;Ronnett, Gabriele V;Kim, Eun-Kyoung;Moon, Cheil
    • Molecules and Cells
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    • v.38 no.6
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    • pp.535-539
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    • 2015
  • Olfactory stimulation activates multiple signaling cascades in order to mediate activity-driven changes in gene expression that promote neuronal survival. To date, the mechanisms involved in activity-dependent olfactory neuronal survival have yet to be fully elucidated. In the current study, we observed that olfactory sensory stimulation, which caused neuronal activation, promoted activation of the phosphatidylinositol 3'-kinase (PI3K)/Akt pathway and the expression of Bcl-2, which were responsible for olfactory receptor neuron (ORN) survival. We demonstrated that Bcl-2 expression increased after odorant stimulation both in vivo and in vitro. We also showed that odorant stimulation activated Akt, and that Akt activation was completely blocked by incubation with both a PI3K inhibitor (LY294002) and Akt1 small interfering RNA. Moreover, blocking the PI3K/Akt pathway diminished the odorantinduced Bcl-2 expression, as well as the effects on odorant-induced ORN survival. A temporal difference was noted between the activation of Akt1 and the expression of Bcl-2 following odorant stimulation. Blocking the PI3K/Akt pathway did not affect ORN survival in the time range prior to the increase in Bcl-2 expression, implying that these two events, activation of the PI3K pathway and Bcl-2 induction, were tightly connected to promote post-translational ORN survival. Collectively, our results indicated that olfactory activity activated PI3K/Akt, induced Bcl-2, and promoted long term ORN survival as a result.

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.

In vitro Arsanilic Acid Induction of Apoptosis in Rat Hepatocytes

  • Yuan, Hui;Gong, Zhi;Yuan, li-Yun;Han, Bo;Han, Hong-Ryul
    • Asian-Australasian Journal of Animal Sciences
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    • v.19 no.9
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    • pp.1328-1334
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    • 2006
  • This paper aimed to study the toxicity of arsanilic acid on rat primary hepatocytes in vitro by a modification of the perfusion method. The conditions included concentrations of 0, 1.085, 10.85, 108.5, 1,085 and 10,850 mg/kg arsanilic acid in RPMI 1,640 medium at rat hepatocytes plates respectively, each group had five repeats at $37^{\circ}C$ for 48 h. The rat primary hepatocytes survival ratio, DNA Ladder, activities of glutathione peroxidase (GSH-px), superoxide dismutase (SOD) and catalase (CAT) in hepatocytes, activity of SOD in the medium and the expression of gene bax in hepatocytes were measured at 12 h, 24 h and 48 h respectively. The results showed that arsanilic acid decreased the activities of GSH-px and SOD, and increased the activity of CAT in all dosages, and affected as positive DNA ladder. Although the SOD activities of both hepatocytes and medium in 1.085 mg/L arsanilic acid were significantly lower than the base line at 12 h, CAT activity in 10.85 mg/L arsanilic acid was significantly higher than the base line at 48 h, and all of the DNA ladders were positive, which means 1.085 mg/L arsanilic acid induced apoptosis at 24 h. The gene expression of bax was significantly upregulated in 1.085 mg/L arsanilic acid or higher for 24 h.The parameters in 1,085 mg/L and 10,850 mg/L arsanilic acid had more severe changes than the others at any time indicating that these levels of arsanilic acid were toxic hazards for hepatocyte survival. It was concluded that arsanilic acid induced a dosage- and time-dependent gene expression of bax, 1.085 mg/L arsanilic acid could be involved in rat liver cell apoptosis at 24 h. Arsanilic acid as additives in livestock feed could present potential toxic implications for farm animals.

The Relationship DNA Methylation of $p16^{INK4a}$ and Colorectal Cancer

  • Hong, Young-Seoub;You, Chang-Hun;Roh, Mee-Sook;Kim, Na-Young;Lee, Kyung-Eun;Kim, Hyo-Jun;Lee, Hyun-Jae;Kwak, Jong-Young;Kim, Joon-Youn
    • Molecular & Cellular Toxicology
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    • v.3 no.4
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    • pp.320-325
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    • 2007
  • Promoter hypermethylation of the $p16^{INK4a}$ gene was investigated in 52 sets of samples of tumor tissue and adjacent normal tissue from Korean patients with colorectal cancer, using the proposed modified the Real-time PCR/SYBR Green detection method presented in this study. In normal tissue, 29 of 52 patients (56%) were methylated and in tumor tissue, 23 of 52 patients (44%) were methylated. The 34 cases (65.4%) showed a concordant DNA methylation pattern in both normal tissue and tumor tissue. Analyzing the association between the clinicopathologic features and DNA methylation status of the $p16^{INK4a}$ gene, the DNA methylation status according to by Duke's stage was different while other clinicopathological characteristics, including the age, sex, tumor stage, and histologic type of the patient were not found to be correlated with $p16^{INK4a}$ methylation. With multivariate logistic regression, it was observed that the DNA methylation status of $p16^{INK4a}$ gene in normal tissue was correlated with the DNA methylation status of the $p16^{INK4a}$ gene in tumor tissue (P=0.026). According to a Kaplan-Meier survival analysis, a difference in the survival rate by DNA methylation status was found, but it was not significant.

Factors Affecting the Efficiency of Introducing Growth Hormone Gene into Mud Loach : Gene Transfer via Electroporation (미꾸라지에 성장호르몬 유전자 이식을 위한 최적 조건 개발)

  • Kim Dong Soo;Nam Yoon Kwon
    • Journal of Aquaculture
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    • v.8 no.3
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    • pp.241-249
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    • 1995
  • Sperm from mud loach (Misgurnus mizolepis) were electroporated in the presence of plasmid DNA, pRSV/luc or pMT/hGH over a range of field strength of 0-1,625 V/cm with capacitance from 0 to 1,000 ${\mu}F$, and the effects of electroporation on fertilization, hatching, early survival, and efficiency of gene transfer were investigated. Average fertilization rate, hatching rate and early survival rate up to yolk sac absorption of all experimental groups were not significuntly different (P>0.05). The proportion of fish carrying pRSV/luc based on the polymerase chain reaction (PCR) analysis was ranged from 0 to $20\%$, however, the values of gene transfer efficiency from the different eledctroporation conditions were not significantly different. PCR analysis of pMT/hGH transferred groups revealed that screening of pMT/hGH transferred fish by PCR was difficult because of significant nonspecific amplifications resulted from the homologous sequences in the genome of mud loach.

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BRCA1 Gene Mutations and Influence of Chemotherapy on Autophagy and Apoptotic Mechanisms in Egyptian Breast Cancer Patients

  • Abdel-Mohsen, Mohamed Ahmed;Ahmed, Omiama Ali;El-Kerm, Yasser Mostafa
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.3
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    • pp.1285-1292
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    • 2016
  • Background: It is well established that mutations in the BRCA1 gene are a major risk factor for breast cancer. Induction of cancer cell death and inhibition of survival are the main principles of cancer therapy. In this context, autophagy may have dual roles in cancer, acting on the one hand as a tumor suppressor and on the other as a mechanism of cell survival that can promote the growth of established tumors. Therefore, understanding the role of autophagy in cancer treatment is critical. Moreover, defects in apoptosis, programmed cell death, may lead to increased resistance to chemotherapy. Purpose: The aim of the present study was to detect BRCA1 gene mutations in order to throw more light on their roles as risk factors for breast cancer in Egypt. Secondly the role of autophagy and apoptosis in determining response to a fluorouracil, doxorubicin, cyclophosphamide (FAC) regimen was investigated. Materials and Methods: Forty-five female breast cancer cases and thirty apparently healthy females were enrolled in the present study. Serum levels of autophagic biomarkers, Beclin 1 and LC3 as well as the serum levels of apoptosis biomarkers Bcl-2 and Caspase-3 were measured before and after chemotherapy. Results: BRCA1 mutations were found in 5 (16.7%) and 44 (99.8%) of the controls and cancer patients, the most frequent being 5382insC followed by C61G and 185 delAG. The results revealed that chemotherapy caused elevation in serum concentration levels of the autophagic biomarkers (Beclin 1 and LC3). This elevation was associated with a significant decrease in serum concentration levels of Bcl-2 and significant increase in caspase-3 concentration levels (apoptotic markers). Conclusions: The results of the present study indicate a very high level of BRCA mutations in breast cancer cases in Egypt and point to involvement of autophagic and apoptotic machinery activation in response to FAC chemotherapy.

Clinical Features of Lung Cancer in Japanese Patients Aged Under 50

  • Igata, Fumiyasu;Uchino, Junji;Fujita, Masaki;Iwasaki, Akinori;Watanabe, Kentaro
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.7
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    • pp.3377-3380
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    • 2016
  • The proportion of lung cancer patients under 50 years old is small at approximately 5-10%, but as with patients older than 50, the number is on the rise. Although lung cancer treatment strategies have undergone extensive transformation in recent years based on the presence or absence of oncogenic driver mutations, there are few reports regarding these mutations in the young or the relationship between clinical setting and prognosis. Therefore, we conducted a study of clinical features in 36 patients under the age of 50 who were diagnosed with primary lung cancer from October 2008 to November 2015. The 22 patients in stages I through III A underwent operations, and all 17 whose lung cancer were detected through screening were candidates for surgery. Gene analysis was conducted for 26 (72.2%); 10 (38.5%) were positive for EGFR gene mutations, and ALK gene translocation was present in 4 (15.4%). In stage IV patients, the median progression free survival (PFS) in the ALK translocation positive and negative patients was 518 days and 130 days, respectively, and the median overall survival (OS) was not reached and 280 days, respectively. A trend toward extended PFS (p=0.203) and OS (p=0.056) was observed in patients positive for ALK translocation. We must strive for early detection by increasing screening rates and evaluate oncogenic driver mutations important for prognosis of lung cancer in the young.