• Molecules and Cells
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• 제42권11호
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• pp.804-809
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• 2019

Oncogenic gain-of-function mutations are clinical biomarkers for most targeted therapies, as well as represent direct targets for drug treatment. Although loss-of-function mutations involving the tumor suppressor gene, STK11 (LKB1) are important in lung cancer progression, STK11 is not the direct target for anticancer agents. We attempted to identify cancer transcriptome signatures associated with STK11 loss-of-function mutations. Several new sensitive and specific gene expression markers (ENO3, TTC39C, LGALS3, and MAML2) were identified using two orthogonal measures, i.e., fold change and odds ratio analyses of transcriptome data from cell lines and tissue samples. Among the markers identified, the ENO3 gene over-expression was found to be the direct consequence of STK11 loss-of-function. Furthermore, the knockdown of ENO3 expression exhibited selective anticancer effect in STK11 mutant cells compared with STK11 wild type (or recovered) cells. These findings suggest that ENO3-based targeted therapy might be promising for patients with lung cancer harboring STK11 mutations.

• International Journal of Oral Biology
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• 제44권2호
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• pp.31-36
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• 2019

Streptococcus mutans is one of the important bacteria that forms dental biofilm and cause dental caries. Virulence genes in S. mutans can be classified into the genes involved in bacterial adhesion, extracellular polysaccharide formation, biofilm formation, sugar uptake and metabolism, acid tolerance, and regulation. The genes involved in bacterial adhesion are gbps (gbpA, gbpB, and gbpC) and spaP. The gbp genes encode glucan-binding protein (GBP) A, GBP B, and GBP C. The spaP gene encodes cell surface antigen, SpaP. The genes involved in extracellular polysaccharide formation are gtfs (gtfB, gtfC, and gtfD) and ftf, which encode glycosyltransferase (GTF) B, GTF C, and GTF D and fructosyltransferase, respectively. The genes involved in biofilm formation are smu630, relA, and comDE. The smu630 gene is important for biofilm formation. The relA and comDE genes contribute to quorumsensing and biofilm formation. The genes involved in sugar uptake and metabolism are eno, ldh, and relA. The eno gene encodes bacterial enolase, which catalyzes the formation of phosphoenolpyruvate. The ldh gene encodes lactic acid dehydrogenase. The relA gene contributes to the regulation of the glucose phosphotransferase system. The genes related to acid tolerance are atpD, aguD, brpA, and relA. The atpD gene encodes $F_1F_0$-ATPase, a proton pump that discharges $H^+$ from within the bacterium to the outside. The aguD gene encodes agmatine deiminase system and produces alkali to overcome acid stress. The genes involved in regulation are vicR, brpA, and relA.

• 한국미생물·생명공학회지
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• 제46권4호
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• pp.334-345
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• 2018

Spore-forming Bacillus species are commercially available probiotic formulations for application in humans. They have health benefits and help prevent disease in hosts by combating entero-pathogens and ameliorating antibiotic-associated diarrhea. However, the molecular and cellular mechanisms of these benefits remain unclear. Here, we report the draft genome of a potential probiotic strain of Bacillus clausii B106. We mapped and compared the probiotic profile of B106 with other reference genomes. The draft genome analysis of B106 revealed the presence of ADI pathway genes, indicating its ability to tolerate acidic pH and bile salts. Genes encoding fibronectin binding proteins, enolase, as well as a gene cluster involved in the biosynthesis of exopolysaccharides underscored the potential of B106 to adhere to the intestinal epithelium and colonize the human gut. Genes encoding bacteriocins were also detected, indicating the antimicrobial ability of this isolate. The presence of genes encoding vitamins, including Riboflavin, Folate, and Biotin, also indicated the health-promoting ability of B106. Resistance of B106 to multiple antibiotics was evident from the presence of genes encoding resistance to chloramphenicol, ${\beta}$-lactams, Vancomycin, Tetracycline, fluoroquinolones, and aminoglycosides. The findings indicate the significance of B. clausii B106 administration during antibiotic treatment and its potential value as a probiotic strain to replenish the health-promoting and disease-preventing gut flora following antibiotic treatment.

• 대한의생명과학회지
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• 제24권4호
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• pp.426-429
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• 2018

Chronic eosinophilic leukemia (CEL) is characterized by eosinophilia and organ damage. Imatinib is widely used for treating CEL, chronic myeloid leukemia (CML) and acute myeloid leukemia (AML). Unfortunately, the cancer cells gain resistance against the drug after prolonged molecular-targeted therapies. Imatinib-resistant EoL-1 (EoL-1-IR) cells were produced from chronic eosinophilic leukemia cells (EoL-1) after treatment with imatinib for a long duration. Two-dimensional electrophoresis (2-DE) analysis revealed numerous protein variations in the EoL-1 and EoL-1-IR sub-types. Compared to the EoL-1 cells, expression levels of TIP49, RBBP7, ${\alpha}$-enolase, adenosine deaminase, C protein, galactokinase, eukaryotic translation initiation factor, $IFN-{\gamma}$, and human protein homologous to DROER were increased, whereas core I protein, proteasome subunit p42, heterogeneous ribonuclear particle protein, chain B, and nucleoside diphosphate were decreased in the EoL-1-IR cells. Taken together, these results contribute to understanding the pathogenic mechanism of drug-resistant diseases.

• Radiation Oncology Journal
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• 제17권3호
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• pp.195-202
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• 1999

목적 : 국소 진행된 비소세포성 폐암의 치료에 있어서 예후 인자를 분석하고, 유도 화학요법이 생존율 및 치료 실패양상에 미치는 영향을 알아 보고자 본 연구를 시행하였다. 대상 및 방법 : 1986년 1월부터 1996년 10월까지 국소 진행된 비소세포성 폐암으로 진단받고 근치적 목적으로 방사선치료 혹은 병합요법(유도 화학요법 및 방사선치료)을 받은 130명의 환자를 대상으로 후향적 분석을 시행하였다. 방사선치료 단독군이 85명, 병합요법군이 45명이었다. 연령, 성별, 전신 수행능력, 병리조직학적 유형, 그리고 병기 등은 양군에서 고르게 분포하였다. 방사선치료는 6 MV 혹은 10 MV 선형가속기를 사용하였고, 일일 선량 $1.8\~2.0$ Gy를 주 5회 조사하였다. 총 방사선량은 129명에서 59.6 Gy 이상($56\~66$ Gy, 중앙값 60 Gy) 조사되었다. 유도 화학요법은 $2\~5$회(중앙값 2회) 시행하였다. 사용된 약제는 CAP (Cyclophosphamide, Adriamycin, Cisplatin)가 6명, MVP (Mitomycin, Vinblastine, Cisplatin)가 9명, MIC (Mitomycin, ifosfamide Cisplatin)이 13례, 그리고 EP (Etoposide, Cisplatin)가 17명에서 시행되었으며, 모든 요법이 Cis-platinum을 포함하였다. 결과 : 전체 환자의 생존율은 1, 2, 3 년 전체 생존율이 각각 41.5, 13.7, $7\%$였고, 중앙 생존기간은 11개월이었다. 치료 방법별 1, 2, 3 년 전체 생존율, 그리고 중앙 생존기간은, 방사선치료 단독군의 경우 각각 32.9, 10.5, $6\%$, 9개월이었으며, 병합요법군의 경우는 각각 57.8, 20, $7.6\%$, 14 개월이었다(p=0.0005). 최종 치료반응을 관찰할 수 있었던 126명 중 38명($30.2\%$)에서 완전관해를 보였고, 치료 방법별로 나누어 분석하였을 경우, 방사선치료 단독군에서 완전관해가 $25\%$ (21/84), 병합요법군의 경우는 $40.5\%$, (17/42)에서 완전관해를 보였다(p=0.09). 생존율에 영향을 미치는 예후인자는 혈색소치(p=0.04), NSE (neuron-specific enolase)치(p=0.004), 그리고 최종 치료반응(p=0.004)등이었다. 치료 방법별로 나누어서 분석한 결과, 방사선치료 단독군의 경우는 WSE치(p=0.006)와 최종 치료반응(p=0.003), 병합요법군의 경우는 최종 치료반응(p=0.007)이 예후인자였다. 치료 실패양상은 추적 관찰이 가능했고 치료에 대한 반응을 알 수 있었던 120명을 대상으로 분석한 결과, 양 군간에 특이한 차이를 보이지 않았다. 그러나, 치료에 완전관해를 보인 환자들을 대상으로 살펴보면 병합요법 군에서 원격전이가 감소하는 경향을 보였는데, 방사선치료 단독군은 19명중 11명에서, 병합요법군은 13명중 3명에서 원격전이가 발견되었다(p=0.07). 국소 실패는 완전관해를 보인 환자에서도 양 군에서 차이가 없었다(10/19 vs 6/13). 결론 : 국소 진행된 비소세포성 폐암의 경우 유도 화학요법을 시행함으로써, 방사선치료 단독보다 2년 생존율이 향상 되었고, 적어도 완전관해를 보인 경우는 원격전이가 감소하는 경향을 보였다. 그러나, 국소 실패양상 및 장기생존율에는 유도 화학요법이 도움이 되지 않았다. 따라서, 국소 제어율을 높이기 위한 다각적인 노력이 요구된다.

• Molecules and Cells
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• 제28권3호
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• pp.175-181
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• 2009

In hypertriglyceridaemic individuals, atherosclerogenesis is associated with the increased concentrations of very low density lipoprotein (VLDL) and VLDL-associated remnant particles. In vitro studies have suggested that VLDL induces foam cells formation. To reveal the changes of the proteins expression in the process of foam cells formation induced by VLDL, we performed a proteomic analysis of the foam cells based on the stimulation of differentiated THP-1 cells with VLDL. Using two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser-desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis, 14 differentially expressed proteins, containing 8 up-regulated proteins and 6 down-regulated proteins were identified. The proteins are involved in energy metabolism, oxidative stress, cell growth, differentiation and apoptosis, such as adipose differentiation-related protein (ADRP), enolase, S100A11, heat shock protein 27 and so on. In addition, the expression of some selected proteins was confirmed by Western blot and RT-PCR analysis. The results suggest that VLDL not only induces lipid accumulation, but also brings about foam cells diverse characteristics by altering the expression of various proteins.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3851-3854
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• 2013

Objective: To explore changes in the serum tumor makers, hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) and vascular endothelial growth factor (VEGF) level and their relations in patients with non-small cell lung cancer (NSCLC) before and after intervention. Materials and Methods: Forty patients with NSCLC and 40 healthy individuals undergoing physical examination in our hospital provided the observation and control groups. HIF-$1{\alpha}$ and VEGF levels in serum were detected by enzyme-linked immuno-sorbent assay (ELISA) in the observation group before and after intervention and in control group on the day of physical examination, along with serum carcino-embryonic antigen (CEA), neuron-speci ic enolase (NSE) and squamous cell carcinoma antigen (SCC) levels in the observation group with a fully automatic biochemical analyzer. Clinical effects and improvement of life quality in the observation group were also evaluated. Results: The total effective rate and improvement of life quality after treatment in observation group were 30.0% and 32.5%, respectively. Serum HIF-$1{\alpha}$ and VEGF levels in the control group were lower than that in observation group (p<0.01), but remarkably elevatedafter intervention (p<0.01). In addition, serum CEA, NSE and SCC levels were apparently lowered by treatment (p<0.01). Serum HIF-$1{\alpha}$ demonstrated a positive relation with VEGF level (p<0.01) and was inversely related with CEA, NSE and SCC levels (p<0.01). Conclusions: Significant correlations exist between marked increase of serum HIF-$1{\alpha}$ and VEGF levels and decrease of indexes related to hematological tumor markers in NSCLC patients after intervention.

• 대한약침학회지
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• 제8권2호
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• pp.23-28
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• 2005

Objective : It has long been known about the osteogenic effect of CTF-HAS on bone tissues. However, it has not been determined the effect of CTF-HAS on cancer cells. The purpose of this study is to screen the CTF-HAS mediated differentially expressed genes in cancer cells such as HepG2 hepatoma cells lines. Methods : CTF-HAS was prepared by boiling and stored at $-70^{\circ}C$ until use. For proteomic analysis, total protein was analyzed by 2D gel electrophoresis and Q-TOF mass spectrometer. Results : In proteomic analysis, three spots were identified by 2D-gel electrophoresis and Q-TOF analysis. One down-regulated protein was heat shock 70kDa protein 5 and up-regulated proteins were chaperonin and 2-phospho -pyruvate-hydratase ${\alpha}-enolase$ by 1.5mg/ml of CTF-HAS. Discussion : Proteomic analysis approach were performed to screen the differential expression genes. The screened genes will be used for the better understanding in therapeutic effect of CTF-HAS on cancer field.

• Asian-Australasian Journal of Animal Sciences
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• 제24권9호
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• pp.1288-1302
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• 2011

The aim of this study was to analyze the proteome expression of bovine satellite cells from longissimus dorsi (LD), deep pectoral (DP) and semitendinosus (ST) muscle depots during in vitro myogenic differentiation. Proteomic profiling by twodimensional gel electrophoresis and mass spectrometry of differentiating satellite cells revealed a total of 38 proteins that were differentially regulated among the three depots. Among differentially regulated proteins, metabolic proteins like lactate dehydrogenase (LDH), malate dehydrogenase (MDH) were found to be up regulated in ST, while alpha-enolase (NNE) in LD and DP depot satellite cells were down regulated. Also, our analysis found that there was a prominent up regulation of cytoskeletal proteins like actin, actincapping protein and transgelin along with chaperone proteins like heat shock protein beta 1 (HSPB 1) and T-complex protein 1 (TCP-1). Among other up regulated proteins, LIM domain containing protein, annexin 2 and Rho GDP-dissociation inhibitor 1 (Rho GDI) are observed, which were already proven to be involved in the myogeneis. More interestingly, satellite cells from ST depot were found to have a higher myotube formation rate than the cells from the other two depots. Taken together, our results demonstrated that, proteins involved in glucose metabolism, cytoskeletal modeling and protein folding plays a key role in the myogenic differentiation of bovine satellite cells.

• Biomolecules & Therapeutics
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• 제18권4호
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• pp.386-395
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• 2010

Bone marrow-derived mesenchymal stem cells (BM-MSC) are a multipotent cell population that can differentiate into neuron-like cells. Previously it has been reported that murine BM-MSC can differentiate into neuron-like cells by co-treatment with a Rho-associated kinase (ROCK) inhibitor -Y27632 and $CoCl_2$. In this study, we compared several ROCK inhibitors for the ability to induce human BM-MSCs to differentiate into neuron-like cells in the presence of $CoCl_2$. Y27632 with high specificity for ROCK at 1-30 ${\mu}M$ was best at inducing neuronal differentiation of MSCs. Compared to HA1077 and H1152, which also effectively induced morphological change into neuron-like cells, Y27632 showed less toxicity even at 100 ${\mu}M$, and resulted in longer multiple branching processes at a wide range of concentrations at 6 h and 72 h post-induction. H89, however, which has less specificity by inhibition of protein kinase A, S6 kinase 1 and MSK1 with similar or greater potency, was less effective at inducing neuronal differentiation of MSCs. Simvastatin, which can inhibit Rho, Ras, and Rac by blocking the synthesis of isoprenoid intermediates, showed little activity for inducing morphological changes of MSCs into neuron-like cells. Accordingly, the expression patterns for neuronal cell markers,including ${\beta}$-tubulin III, neuron-specific enolase, neurofilament, and microtubule-associated protein, were consistent with the pattern of the morphological changes. The data suggest that the ROCK inhibitors with higher specificity are more effective at inducing neuronal differentiation of MSCs.