• Title/Summary/Keyword: risk expression

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Polarization of M2 Macrophages by Interaction between Prostate Cancer Cells Treated with Trichomonas vaginalis and Adipocytes

  • Chung, Hyo-Yeoung;Kim, Jung-Hyun;Han, Ik-Hwan;Ryu, Jae-Sook
    • Parasites, Hosts and Diseases
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    • v.58 no.3
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    • pp.217-227
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    • 2020
  • Trichomonas vaginalis causes inflammation of the prostate and has been detected in tissues of prostate cancers (PCa), prostatitis and benign prostatic hyperplasia. Obesity is a risk factor for PCa and causes a chronic subclinical inflammation. This chronic inflammation further exacerbates adipose tissue inflammation as results of migration and activation of macrophages. Macrophages are the most abundant immune cells in the PCa microenvironment. M2 macrophages, known as Tumor-Associated Macrophages, are involved in increasing cancer malignancy. In this study, conditioned medium (TCM) of PCa cells infected with live trichomonads contained chemokines that stimulated migration of the mouse preadipocytes (3T3-L1 cells). Conditioned medium of adipocytes incubated with TCM (ATCM) contained Th2 cytokines (IL-4, IL-13). Macrophage migration was stimulated by ATCM. In macrophages treated with ATCM, expression of M2 markers increased, while M1 markers decreased. Therefore, it is suggested that ATCM induces polarization of M0 to M2 macrophages. In addition, conditioned medium from the macrophages incubated with ATCM stimulates the proliferation and invasiveness of PCa. Our findings suggest that interaction between inflamed PCa treated with T. vaginalis and adipocytes causes M2 macrophage polarization, so contributing to the progression of PCa.

Polymorphic Lengths of Dinucleotide $(GT)^n$ Repeats in Upstream of Human nNOS Exon 1f Gene Play a Role in Modulating the nNOS Transcription: Clinical Implications

  • Shin, Mi-Kyung;Kim, Kyung-Nam;Kim, Chul-Eung;Lee, Sung-Keun;Kang, Ju-Hee;Park, Chang-Shin
    • Molecular & Cellular Toxicology
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    • v.4 no.1
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    • pp.11-15
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    • 2008
  • The expression of neuronal nitric oxide synthase (nNOS) is regulated by various spliced first exons (exon 1a-1i), sharing differentially common exon 2 in diverse human tissues. The highly complex structure and regulation of human nNOS gene gave limitations of information for the precise mechanism of nNOS regulation. In the present study, we report that the repeats of polymorphic dinucleotides $(GT)^nA(TG)^n$ repeats located in just upstream to the exon 1f in human nNOS gene play suppressive role in transcription, as shown in the characteristics of Z-DNA motif in other genes. In neuronal and trophoblast cells transfected transiently with luciferase construct without dinucleotide repeats at the 5'-flanking region of exon 1f in nNOS gene, the luciferase activity was increased markedly. However, the presence of the dinucleotide repeats dramatically suppressed the luciferase activity to the basal level, and which was dependent on the length of $(GT)^n$ and $(TG)^n$ repeats. More importantly, we found the polymorphisms in the length of dinucleotide repeats in human. Furthermore, we show for the first time here that there is a significant association of the lengths of polymorphic dinucleotide $(GT)^n$ and $(TG)^n$ repeats with the risk of schizophrenia.

Cluster Analysis of SNPs with Entropy Distance and Prediction of Asthma Type Using SVM (엔트로피 거리와 SVM를 이용한 SNP 군집분석과 천식 유형 예측)

  • Lee, Jung-Seob;Shin, Ki-Seob;Wee, Kyu-Bum
    • The KIPS Transactions:PartB
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    • v.18B no.2
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    • pp.67-72
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    • 2011
  • Single nucleotide polymorphisms (SNPs) are a very important tool for the study of human genome structure. Cluster analysis of the large amount of gene expression data is useful for identifying biologically relevant groups of genes and for generating networks of gene-gene interactions. In this paper we compared the clusters of SNPs within asthma group and normal control group obtained by using hierarchical cluster analysis method with entropy distance. It appears that the 5-cluster collections of the two groups are significantly different. We searched the best set of SNPs that are useful for diagnosing the two types of asthma using representative SNPs of the clusters of the asthma group. Here support vector machines are used to evaluate the prediction accuracy of the selected combinations. The best combination model turns out to be the five-locus SNPs including one on the gene ALOX12 and their accuracy in predicting aspirin tolerant asthma disease risk among asthmatic patients is 66.41%.

An alternative method to reduce anaphylaxis by moxibustion

  • Jeong, Hyun-Ja;Nam, Sun-Young;Lee, Byong-Joo;Kim, Min-Gi;Kim, Jeong-Hwa;Kim, Hyung-Min
    • CELLMED
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    • v.4 no.2
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    • pp.12.1-12.12
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    • 2014
  • Epinephrine is a critical drug for patients at risk for anaphylaxis. Here, we suggest moxibustion as an alternative method to reduce anaphylaxis. Moxibustion was applied to the Shimen (CV5) acupoint and found to attenuate compound 48/80-induced mortality. Capsazepine, a transient receptor potential vanilloid (TRPV) 1 antagonist, significantly improved overall survival rates compared to groups treated with moxibustion or 2-aminoethoxydiphenyl borate (an activator of TRPV1, 2, and 3). Probenecid (a TRPV2 agonist) also increased survival rate and reduced histamine levels. Survival rates increased by moxibustion and probenecid were completely inhibited by ruthenium red (a TRPV2 and 3 antagonist) and gadolinium chloride (general TRPV antagonist), respectively. Passive cutaneous anaphylaxis and ear swelling were significantly reduced by moxibustion and probenecid (p < 0.05). In cardiomyocytes, TRPV2 was over-expressed by compound 48/80 and histamine but this increased TRPV2 expression decreased to baseline with moxibustion and probenecid treatment. In addition, intracellular calcium levels increased by compound 48/80 were reduced by probenecid. Overall, these findings suggest that the reduction of anaphylaxis caused by moxibustion could represent a new mechanism of moxibustion related to the regulation of TRPV2 activation and promotion of epinephrine secretion.

Serum Periplakin as a Potential Biomarker for Urothelial Carcinoma of the Urinary Bladder

  • Matsumoto, Kazumasa;Ikeda, Masaomi;Matsumoto, Toshihide;Nagashio, Ryo;Nishimori, Takanori;Tomonaga, Takeshi;Nomura, Fumio;Sato, Yuichi;Kitasato, Hidero;Iwamura, Masatsugu
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9927-9931
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    • 2014
  • The objectives of this study were to examine serum periplakin expression in patients with urothelial carcinoma of the urinary bladder and in normal controls, and to examine relationships with clinicopathological findings. Detection of serum periplakin was performed in 50 patients and 30 normal controls with anti-periplakin antibodies using the automatic dot blot system, and a micro-dot blot array with a 256 solid-pin system. Levels in patients with urothelial carcinoma of the urinary bladder were significantly lower than those in normal controls (0.31 and 5.68, respectively; p<0.0001). The area under the receiver-operator curve level for urothelial carcinoma of the urinary bladder was 0.845. The sensitivity and specificity, using a cut-off point of 4.045, were 83.7% and 73.3%, respectively. In addition, serum periplakin levels were significantly higher in patients with muscle-invasive cancer than in those with nonmuscle-invasive cancer (P = 0.03). In multivariate Cox proportional hazards regression analysis, none of the clinicopathological factors was associated with an increased risk for progression and cancer-specific survival. Examination of the serum periplakin level may play a role as a non-invasive diagnostic modality to aid urine cytology and cystoscopy.

HER2-enriched Tumors Have the Highest Risk of Local Recurrence in Chinese Patients Treated with Breast Conservation Therapy

  • Jia, Wei-Juan;Jia, Hai-Xia;Feng, Hui-Yi;Yang, Ya-Ping;Chen, Kai;Su, Feng-Xi
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.1
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    • pp.315-320
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    • 2014
  • Purpose: The purpose of this study was to investigate the recurrence pattern and characteristics of patients based on the 2013 St. Gallen surrogate molecular subtypes after breast-conserving surgery (BCS) in Chinese women. Methods: This retrospective analysis included 709 consecutive breast cancer patients undergoing BCS from 1999-2010 at our institution. Five different surrogate subtypes were created using combined expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2. Locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS) rates were calculated. Results: The 5-year LRRFS, DMFS, and DFS rates were 90.5%, 88.2%, and 81.5%, respectively. Multivariate analysis revealed that young age, node-positive disease, and HER2 enrichment were independent prognostic factors in LRRFS patients. There was also an independent prognostic role of lymph node-positive disease in DMFS and DFS patients. Patients with luminal A tumors had the most favorable prognosis, with LRRFS, DMFS, and DFS rates of 93.2%, 91.5%, and 87.4% at 5 years, respectively. Conversely, HER-2-enriched tumors exhibited the highest rate of locoregional recurrence (20.6%). Conclusion: Surrogate subtypes present with significant differences in RFS, DMFS, and LRRFS. Luminal A tumors have the best prognosis, whereas HER2-enriched tumors have the poorest.

Production of Recombinant Human Papillomavirus Type 52 L1 Protein in Hansenula polymorpha Formed Virus-Like Particles

  • Liu, Cunbao;Yao, Yufeng;Yang, Xu;Bai, Hongmei;Huang, Weiwei;Xia, Ye;Ma, Yanbing
    • Journal of Microbiology and Biotechnology
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    • v.25 no.6
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    • pp.936-940
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    • 2015
  • Human papillomavirus (HPV) type 52 is a high-risk HPV responsible for cervical cancer. HPV type 52 is common around the world and is the most common in some Asian regions. The available prophylactic HPV vaccines protect only from HPV types 16 and 18. Supplementing economical vaccines that target HPV type 52 may satisfactorily complement available prophylactic vaccines. A codon-adapted HPV 52 L1 gene was expressed in the methylotrophic yeast Hansenula polymorpha, which is used as an industrial platform for economical hepatitis B surface antigen particle production in China. We found that the recombinant proteins produced in this expression system could form virus-like particles (VLPs) with diameters of approximately 50 nm. This study suggests that the HPV 52 VLPs produced in this platform may satisfactorily complement available prophylactic vaccines in fighting against HPVs prevalent in Asia.

Correlation Analysis of KCNQ1 S140G Mutation Expression and Ventricular Fibrillation: Computer Simulation Study (KCNQ1 S140G 돌연변이 발현과 심실세동과의 상관관계 분석을 위한 컴퓨터 시뮬레이션 연구)

  • Jeong, Daun;Lim, Ki Moo
    • Journal of Biomedical Engineering Research
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    • v.38 no.3
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    • pp.123-128
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    • 2017
  • Background and aims: The KCNQ1 S140G mutation involved in $I_{ks}$ channel is a typical gene mutation affecting atrial fibrillation. However, despite the possibility that the S140G gene mutation may affect not only atrial but also ventricular action potential shape and ventricular responses, there is a lack of research on the relationship between this mutation and ventricular fibrillation. Therefore, in this study, we analyzed the correlation and the influence of the KCNQ1 S140G mutant gene on ventricular fibrillation through computer simulation studies. Method: This study simulated a 3-dimensional ventricular model of the wild type(WT) and the S140G mutant conditions. It was performed by dividing into normal sinus rhythm simulation and reentrant wave propagation simulation. For the sinus rhythm, a ventricular model with Purkinje fiber was used. For the reentrant propagation simulation, a ventricular model was used to confirm the occurrence of spiral wave using S1-S2 protocol. Results: The result showed that 41% shortening of action potential duration(APD) was observed due to augmented $I_{ks}$ current in S140G mutation group. The shortened APD contributed to reduce wavelength 39% in sinus rhythm simulation. The shortened wavelength in cardiac tissue allowed re-entrant circuits to form and increased the probability of sustaining ventricular fibrillation, while ventricular electrical propagation with normal wavelength(20.8 cm in wild type) are unlikely to initiate re-entry. Conclusion: In conclusion, KCNQ1 S140G mutation can reduce the threshold of the re-entrant wave substrate in ventricular cells, increasing the spatial vulnerability of tissue and the sensitivity of the fibrillation. That is, S140G mutation can induce ventricular fibrillation easily. It means that S140G mutant can increase the risk of arrhythmias such as cardiac arrest due to heart failure.

Estrogen deprivation and excess energy supply accelerate 7,12-dimethylbenz(a)anthracene-induced mammary tumor growth in C3H/HeN mice

  • Kim, Jin;Lee, Yoon Hee;Yoon Park, Jung Han;Sung, Mi-Kyung
    • Nutrition Research and Practice
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    • v.9 no.6
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    • pp.628-636
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    • 2015
  • BACKGROUND/OBJECTIVES: Obesity is a risk factor of breast cancer in postmenopausal women. Estrogen deprivation has been suggested to cause alteration of lipid metabolism thereby creating a cellular microenvironment favoring tumor growth. The aim of this study is to investigate the effects of estrogen depletion in combination with excess energy supply on breast tumor development. MATERIALS/METHODS: Ovariectomized (OVX) or sham-operated C3H/HeN mice at 4 wks were provided with either a normal diet or a high-fat diet (HD) for 16 weeks. Breast tumors were induced by administration of 7,12-dimethylbenz(a)anthracene once a week for six consecutive weeks. RESULTS: Study results showed higher serum concentrations of free fatty acids and insulin in the OVX+HD group compared to other groups. The average tumor volume was significantly larger in OVX+HD animals than in other groups. Expressions of mammary tumor insulin receptor and mammalian target of rapamycin proteins as well as the ratio of pAKT/AKT were significantly increased, while pAMPK/AMPK was decreased in OVX+HD animals compared to the sham-operated groups. Higher relative expression of liver fatty acid synthase mRNA was observed in OVX+HD mice compared with other groups. CONCLUSIONS: These results suggest that excess energy supply affects the accelerated mammary tumor growth in estrogen deprived mice.

Effect of Sulfur Enriched Young Radish Kimchi on the Induction of Apoptosis in AGS Human Gastric Adenocarcinoma Cells

  • Bak, Soon-Sun;Kong, Chang-Suk;Rhee, Sook-Hee;Rho, Chi-Woong;Kim, Nak-Ku;Choi, Keyng-Lag;Park, Kun-Young
    • Preventive Nutrition and Food Science
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    • v.12 no.2
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    • pp.79-83
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    • 2007
  • The effects of young radish (YR, yeolmu in Korean) on the induction of apoptosis were examined in AGS human gastric adenocarcinoma cells. The young radish kimchi (YRK) were made of YR cultivated in the soil without (Control YR kimchi: C-YRK) and with 1,818 g/m$^{3}$ sulfur (Sulfur YR kimchi: S-YRK), respectively. Methanol extracts from S-YRK exhibited higher inhibitory effect on the growth of AGS human gastric adenocarcinoma cells in a time dependent-manner compared to C-YRK at the same concentration. 4,6-diamidino-2-phenylindole (DAPI) staining showed that S-YRK induced apoptosis accompanied by the increased Bax but decreased Bcl-2 in mRNA expression. Moreover, S-YRK decreased the levels of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) mRNA expressions. The results suggested that S-YRK cultivated in the presence of sulfur elicited stronger anticancer activity than C-YRK in vitro. Dietary intakes of S-YRK may be beneficial to decrease the risk of cancer.