GST-Theta1 Enzyme Expression Levels in Brain Tumor and Their Relationship with the Clinical Data of the Patients

The BIRC (baculoviral IAP repeat-containing; BIRC) family genes encode for Inhibitor of Apoptosis (IAP) proteins. The dysregulation of the expression levels of the genes in question in cancer tissue as compared to normal tissue suggests that the apoptosis process in cancer cells was disturbed, which may be associated with the development and chemoresistance of triple negative breast cancer (TNBC). In our study, we determined the expression level of eight genes from the BIRC family using the Real-Time PCR method in patients with TNBC and compared the obtained results with clinical data. Additionally, using bioinformatics tools (Ualcan and The Breast Cancer Gene-Expression Miner v4.5 (bc-GenExMiner v4.5)), we compared our data with the data in the Cancer Genome Atlas (TCGA) database. We observed diverse expression pattern among the studied genes in breast cancer tissue. Comparing the expression level of the studied genes with the clinical data, we found that in patients diagnosed with breast cancer under the age of 50, the expression levels of all studied genes were higher compared to patients diagnosed after the age of 50. We observed that in patients with invasion of neoplastic cells into lymphatic vessels and fat tissue, the expression levels of BIRC family genes were lower compared to patients in whom these features were not noted. Statistically significant differences in gene expression were also noted in patients classified into three groups depending on the basis of the Scarff-Bloom and Richardson (SBR) Grading System.

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Emerging mosquito resistance to piperonyl butoxide-synergized pyrethroid insecticide and its mechanism

10.1101/2021.09.29.462303 ◽

2021 ◽

Author(s):

Guofa Zhou ◽

Yiji Li ◽

Brook Jeang ◽

Xiaoming Wang ◽

Daibin Zhong ◽

...

Keyword(s):

Culex Quinquefasciatus ◽

Resistance Mechanisms ◽

Piperonyl Butoxide ◽

World Health ◽

Metabolic Enzyme ◽

Enzyme Expression ◽

Glutathione S Transferase ◽

Expression Levels ◽

P450 Enzyme ◽

Health Organization

Piperonyl butoxide (PBO)-synergized pyrethroid products are widely available for the control of pyrethroid-resistant mosquitoes. To date, no study has formally examined mosquito resistance to PBO-synergized insecticides. We used Culex quinquefasciatus as a model mosquito examined the insecticide resistance mechanisms of mosquitoes to PBO-synergized pyrethroid using modified World Health Organization tube bioassays and biochemical analysis of metabolic enzyme expressions prior- and post-PBO exposure. We measured mosquito mortalities and metabolic enzyme expressions in mosquitoes with/without pre-exposure to different PBO concentrations and exposure durations. We found that field Culex quinquefasciatus mosquitoes were resistant to all insecticides tested, including PBO-synergized pyrethroids (mortality ranged from 3.7±4.7% to 66.7±7.7%), except malathion. Field mosquitoes had elevated levels of carboxylesterase (COE, 3.8-fold) and monooxygenase (P450, 2.1-fold) but not glutathione S-transferase (GST) compared to susceptible mosquitoes. When the field mosquitoes were pre-exposed to 4% PBO, the 50% lethal concentration of deltamethrin was reduced from 0.22% to 0.10%, compare to 0.02% for susceptible mosquitoes. Knockdown resistance gene mutation (L1014F) rate was 62% in field mosquitoes. PBO pre-exposure suppressed P450 enzyme expression levels by 25~34%, GST by 11%, and had no impact on COE enzyme expression. Even with the optimal PBO concentration and exposure duration, field mosquitoes had significantly higher P450 enzyme expression levels after PBO exposure compared to laboratory controls. These results demonstrate that PBO alone may not be enough to control highly pyrethroid resistant mosquitoes due to the multiple resistance mechanisms. Mosquito resistance to PBO-synergized insecticide should be closely monitored.

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Activin A Stimulates AKR1C3 Expression and Growth in Human Prostate Cancer

Endocrinology ◽

10.1210/en.2011-2065 ◽

2012 ◽

Vol 153 (12) ◽

pp. 5726-5734 ◽

Cited By ~ 25

Author(s):

Johannes Hofland ◽

Wytske M. van Weerden ◽

Jacobie Steenbergen ◽

Natasja F. J. Dits ◽

Guido Jenster ◽

...

Keyword(s):

Prostate Cancer ◽

Activin A ◽

High Ratio ◽

Enzyme Expression ◽

Steroidogenic Enzyme ◽

Expression Levels ◽

Androgen Synthesis ◽

Castration Resistant ◽

Dehydrogenase Enzyme ◽

Xenograft Models

Abstract Local androgen synthesis in prostate cancer (PC) may contribute to the development of castration-resistant PC (CRPC), but pathways controlling intratumoral steroidogenic enzyme expression in PC are unknown. We investigated the effects of activin, a factor involved in the regulation of PC growth and steroidogenic enzyme expression in other steroidogenic tissues, on intratumoral steroidogenesis in PC. Activin A effects and regulation of the activin-signaling pathway molecules were studied in the PC cell lines LNCaP, VCaP, and PC-3 and in 13 individual PC xenograft models. Also, expression levels of inhibin βA- and βB-subunits (INHBA and INHBB) and of the activin antagonist follistatin were quantitated in patient PC tissues. Activin A induced the expression and enzyme activity of 17β-hydroxysteroid dehydrogenase enzyme AKR1C3 in LNCaP and VCaP cells. Inhibition of endogenous activin A action in the PC-3 cell line decreased AKR1C3 levels and consequently testosterone synthesis. In return, androgens suppressed INHBA expression in both VCaP cells and the PC xenograft models. The antiproliferative effects of activin A were opposed by physiological concentrations of androstenedione in LNCaP cells. In patient PC tissues, expression levels of INHBA were increased in CRPC samples and correlated with AKR1C3 levels. Moreover, a high ratio of activin subunits to follistatin was associated with a worse metastasis-free survival in patients. In conclusion, activin A is controlled by androgens in PC models and regulates local androgen production. Activin A thus seems to mediate (residual) intratumoral androgen levels and could form a novel therapeutic target in CRPC.

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Genetic characterization of a mouse line with primary aldosteronism

Journal of Molecular Endocrinology ◽

10.1530/jme-16-0200 ◽

2017 ◽

Vol 58 (2) ◽

pp. 67-78 ◽

Cited By ~ 3

Author(s):

L G Perez-Rivas ◽

Y Rhayem ◽

S Sabrautzki ◽

C Hantel ◽

B Rathkolb ◽

...

Keyword(s):

Candidate Genes ◽

Primary Aldosteronism ◽

Point Mutations ◽

Mouse Line ◽

Enzyme Expression ◽

Steroidogenic Enzyme ◽

Knock Out ◽

Expression Levels ◽

To Come ◽

Aldosterone To Renin Ratio

In an attempt to define novel genetic loci involved in the pathophysiology of primary aldosteronism, a mutagenesis screen after treatment with the alkylating agent N-ethyl-N-nitrosourea was established for the parameter aldosterone. One of the generated mouse lines with hyperaldosteronism was phenotypically and genetically characterized. This mouse line had high aldosterone levels but normal creatinine and urea values. The steroidogenic enzyme expression levels in the adrenal gland did not differ significantly among phenotypically affected and unaffected mice. Upon exome sequencing, point mutations were identified in seven candidate genes (Sspo, Dguok, Hoxaas2, Clstn3, Atm, Tipin and Mapk6). Subsequently, animals were stratified into wild-type and mutated groups according to their genotype for each of these candidate genes. A correlation of their genotypes with the respective aldosterone, aldosterone-to-renin ratio (ARR), urea and creatinine values as well as steroidogenic enzyme expression levels was performed. Aldosterone values were significantly higher in animals carrying mutations in four different genes (Sspo, Dguok, Hoxaas2 and Clstn3) and associated statistically significant adrenal Cyp11b2 overexpression as well as increased ARR was present only in mice with Sspo mutation. In contrast, mutations of the remaining candidate genes (Atm, Tipin and Mapk6) were associated with lower aldosterone values and lower Hsd3b6 expression levels. In summary, these data demonstrate association between the genes Sspo, Dguok, Hoxaas2 and Clstn3 and hyperaldosteronism. Final proofs for the causative nature of the mutations have to come from knock-out and knock-in experiments.

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miR-TV: an interactive microRNA Target Viewer for microRNA and target gene expression interrogation for human cancer studies

Database ◽

10.1093/database/baz148 ◽

2020 ◽

Vol 2020 ◽

Cited By ~ 5

Author(s):

Chao-Yu Pan ◽

Wen-Chang Lin

Keyword(s):

Gene Expression ◽

Clinical Data ◽

Mirna Expression ◽

Mirna Target ◽

Target Gene ◽

Biological Data ◽

Expression Levels ◽

Target Gene Expression ◽

Cellular Processes ◽

Interactive Interface

Abstract MicroRNAs (miRNAs) have been identified in many organisms, and they are essential for gene expression regulation in many critical cellular processes. The expression levels of these genes and miRNAs are closely associated with the progression of diseases such as cancers. Furthermore, survival analysis is a significant indicator for evaluating the criticality of these cellular processes in cancer progression. We established a web tool, miRNA Target Viewer (miR-TV), which integrates 5p-arm and 3p-arm miRNA expression profiles, mRNA target gene expression levels in healthy and cancer populations, and clinical data of cancer patients and their survival information. The developed miR-TV obtained miRNA-seq, mRNA-seq and clinical data from the Cancer Genome Atlas and potential miRNA target gene predictions from miRDB, targetScan and miRanda. The data presentation was implemented using the D3 javascript toolkit. The D3 toolkit is frequently used to provide an easy-to-use interactive interface. Our miR-TV provides a user-friendly and interactive interface, which can be beneficial for biomedical researchers to freely interrogate miRNA expression information and their potential target genes. We believe that such a data visualization bioinformatics tool is excellent for obtaining information from massive biological data. Database URL: http://mirtv.ibms.sinica.edu.tw

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