scholarly journals Indoleamine 2,3-Dioxygenase 1: A Promising Therapeutic Target in Malignant Tumor

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaotian Song ◽  
Qianqian Si ◽  
Rui Qi ◽  
Weidan Liu ◽  
Miao Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Drug Targets ◽  
Biological Function ◽  
Malignant Tumors ◽  
Therapeutic Strategies ◽  
Comprehensive Analysis ◽  
The Other ◽  
Indoleamine 2,3 Dioxygenase ◽  
Promising Therapeutic Target ◽  
Multistep Process

Tumorigenesis is a complex multifactorial and multistep process in which tumors can utilize a diverse repertoire of immunosuppressive mechanisms to evade host immune attacks. The degradation of tryptophan into immunosuppressive kynurenine is considered an important immunosuppressive mechanism in the tumor microenvironment. There are three enzymes, namely, tryptophan 2,3-dioxygenase (TDO), indoleamine 2,3-dioxygenase 1 (IDO1), and indoleamine 2,3-dioxygenase 2 (IDO2), involved in the metabolism of tryptophan. IDO1 has a wider distribution and higher activity in catalyzing tryptophan than the other two; therefore, it has been studied most extensively. IDO1 is a cytosolic monomeric, heme-containing enzyme, which is now considered an authentic immune regulator and represents one of the promising drug targets for tumor immunotherapy. Collectively, this review highlights the regulation of IDO1 gene expression and the ambivalent mechanisms of IDO1 on the antitumoral immune response. Further, new therapeutic targets via the regulation of IDO1 are discussed. A comprehensive analysis of the expression and biological function of IDO1 can help us to understand the therapeutic strategies of the inhibitors targeting IDO1 in malignant tumors.

scholarly journals Analyzing the whole-transcriptome profiles of ncRNAs and predicting the competing endogenous RNA networks in cervical cancer cell lines with cisplatin resistance

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Huimin Lv ◽  
Shanshan Jin ◽  
Binbin Zou ◽  
Yuxiang Liang ◽  
Jun Xie ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cervical Cancer ◽  
Reporter Gene ◽  
Biological Function ◽  
Malignant Tumors ◽  
Luciferase Reporter ◽  
Sequencing Analysis ◽  
Luciferase Reporter Gene ◽  
Network Analyses ◽  
Whole Transcriptome

Abstract Background Cervical cancer (CC) is one of the most common malignant tumors in women. In order to identify the functional roles and the interaction between mRNA and non-coding RNA (ncRNA, including lncRNA, circRNA and miRNA) in CC cisplatin (DDP) resistance, the transcription profile analysis was performed and a RNA regulatory model of CC DDP resistance was proposed. Methods In this study, whole-transcriptome sequencing analysis was conducted to study the ncRNA and mRNA profiles of parental SiHa cells and DDP resistant SiHa/DDP cells. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed for pathway analysis based on the selected genes with significant differences in expression. Subsequently, ceRNA network analyses were conducted using the drug resistance-related genes and signal-transduction pathways by Cytoscape software. Furthermore, a ceRNA regulatory pathway, namely lncRNA-AC010198.2/hsa-miR-34b-3p/STC2, was selected by RT-qPCR validation and literature searching. Further validation was done by both dual-luciferase reporter gene assays and RNA pull-down assays. Besides that, the changes in gene expression and biological function were further studied by performing si-AC010198.2 transfection and DDP resistance analyses in the SiHa and SiHa/DDP cells, respectively. Results Using bioinformatics and dual-luciferase reporter gene analyses, we found that AC010198.2/miR-34b-3p/STC2 may be a key pathway for DDP resistance in CC cells. Significant differences in both downstream gene expression and the biological function assays including colony formation, migration efficiency and cell apoptosis were identified in AC010198.2 knockdown cells. Conclusions Our study will not only provide new markers and potential mechanism models for CC DDP resistance, but also discover novel targets for attenuating it.

scholarly journals MicroRNA as a Novel Modulator in Head and Neck Squamous Carcinoma

2010 ◽  
Vol 2010 ◽  
pp. 1-15 ◽  
Author(s):  
Li-Hsin Chen ◽  
Kun-Ling Tsai ◽  
Yi-Wei Chen ◽  
Cheng-Chia Yu ◽  
Kuo-Wei Chang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Head And Neck ◽  
Stress Responses ◽  
Squamous Carcinoma ◽  
Therapeutic Strategies ◽  
The Other ◽  
Physiological Conditions ◽  
The Past ◽  
Differential Ability

MicroRNAs have emerged as important regulators of cell proliferation, development, cancer formation, stress responses, cell death, and other physiological conditions in the past decade. On the other hand, head and neck cancer is one of the top ten most common cancers worldwide. Recent advances in microRNAs have revealed their prominent role in regulating gene expression and provided new aspects of applications in diagnosis, prognosis, and therapeutic strategies in head and neck squamous carcinoma. In the present paper, we focus on microRNAs showing significant differences between normal and tumor cells or between cells with differential ability of metastasis. We also emphasize specific microRNAs that could modulate tumor cell properties, such as apoptosis, metastasis, and proliferation. These microRNAs possess the potential to be applied on clinical therapy in the future.

scholarly journals The metabolic milieu in melanoma: Role of immune suppression by CD73/adenosine

Tumor Biology ◽  
2019 ◽  
Vol 41 (4) ◽  
pp. 101042831983713 ◽  
Author(s):  
Anna Passarelli ◽  
Marco Tucci ◽  
Francesco Mannavola ◽  
Claudia Felici ◽  
Francesco Silvestris
Keyword(s):  
Immune Suppression ◽  
Immune Escape ◽  
Prognostic Biomarker ◽  
Therapeutic Strategies ◽  
The Other ◽  
Immune Checkpoints ◽  
Receptor Signalling ◽  
Promising Therapeutic Target ◽  
Translational Strategies

The mechanisms leading to immune escape of melanoma have been largely investigated in relation to its tumour immunogenicity and features of inflamed microenvironment that promote the immune suppression during the disease progression. These findings have recently led to advantages in terms of immunotherapy-based approaches as rationale for overcoming the immune escape. However, besides immune checkpoints, other mechanisms including the adenosine produced by ectonucleotidases CD39 and CD73 contribute to the melanoma progression due to the immunosuppression induced by the tumour milieu. On the other hand, CD73 has recently emerged as both promising therapeutic target and unfavourable prognostic biomarker. Here, we review the major mechanisms of immune escape activated by the CD39/CD73/adenosine pathway in melanoma and focus potential therapeutic strategies based on the control of CD39/CD73 downstream adenosine receptor signalling. These evidences provide the basis for translational strategies of immune combination, while CD73 would serve as potential prognostic biomarker in metastatic melanoma.

Die Anämie bei malignen Tumorerkrankungen

1989 ◽  
Vol 28 (05) ◽  
pp. 193-200 ◽  
Author(s):  
E. Aulbert
Keyword(s):  
Cellular Uptake ◽  
Tumor Tissue ◽  
Malignant Tumors ◽  
The Other ◽  
Novikoff Hepatoma ◽  
Cellular Accumulation ◽  
Tumor Mass ◽  
Proliferation Activity ◽  
Morris Hepatoma ◽  
Cellular Incorporation

Cellular uptake of 67Ga-labelled transferrin by the tumor tissue was studied in rats with tumors of different malignancy and different tumor mass using the slowly growing Morris hepatoma 5123C, the moderately growing Novikoff hepatoma and the very fast and aggressive Yoshida hepatoma AH130. The cellular accumulation of 67Ga-transferrin was found to correlate with the proliferation activity of the tumor. The 67Ga-transferrin concentration in the very fast growing Yoshida hepatoma was 4.8 times higher than the concentration in the slowly growing Morris hepatoma. The uptake of 67Ga-transferrin by the tumors resulted in a faster disappearance of circulating 67Ga-transferrin from the blood. The rate of disappearance correlated with the proliferation activity and the spread of the tumors. Using tumors of identical size the elimination of 67Ga-transferrin from the blood was much faster in the rats with Yoshida hepatoma than in those with the slowly growing Morris hepatoma. On the other hand, using tumors of different tumor size it could be demonstrated that the rate of disappearance of 67Ga-transferrin from the blood correlated directly with tumor mass. It is concluded that cellular incorporation of transferrin within the tumor cells results in a loss of circulating transferrin, which correlates with tumor mass and proliferation of tumor. This mechanism is supposed to be the cause for the hypotransferrinemia seen in patients with malignant tumors.

New cancer drug targets identified in adrenocortical carcinoma through gene expression profiling

2018 ◽  
Author(s):  
Raimunde Liang ◽  
Isabel Weigand ◽  
Barbara Altieri ◽  
Stefan Kircher ◽  
Sonja Steinhauer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Adrenocortical Carcinoma ◽  
Expression Profiling ◽  
Drug Targets ◽  
Cancer Drug

Reparação óssea no implante dental

2020 ◽  
Vol 12 (45) ◽  
pp. 63-66
Author(s):  
Halim Nagem Filho ◽  
Reinaldo Francisco Maia ◽  
Reinaldo Missaka ◽  
Nasser Hussein Fares
Keyword(s):  
Gene Expression ◽  
Titanium Surface ◽  
Close Contact ◽  
The Other ◽  
Main Function ◽  
Indirect Interaction ◽  
M2 Macrophages ◽  
Activated Macrophages ◽  
M1 Macrophages ◽  
High Production

The osseointegration is the stable and functional union between the bone and a titanium surface. A new bone can be found on the surface of the implant about 1 week after its installation; the bone remodeling begins between 6 and 12 weeks and continues throughout life. After the implant insertion, depending on the energy of the surface, the plasma fluid immediately adheres, in close contact with the surface, promoting the adsorption of proteins and inducing the indirect interaction of the cells with the material. Macrophages are cells found in the tissues and originated from bone marrow monocytes. The M1 macrophages orchestrate the phagocytic phase in the inflammatory region and also produce inflammatory cytokines involved with the chronic inflammation and the cleaning of the wound and damaged tissues from bacteria. On the other hand, alternative-activated macrophages (M2) are activated by IL-10, the immune complex. Its main function consists on regulating negatively the inflammation through the secretion of the immunosuppressant IL-10. The M2 macrophages present involvement with the immunosuppression, besides having a low capacity for presenting antigens and high production of cytokines; these can be further divided into M2a, M2b, and M2c, based on the gene expression profile.

scholarly journals Analysis of the Mechanism by Which Glucose Inhibits Maltose Induction of MAL Gene Expression in Saccharomyces

Genetics ◽  
2000 ◽  
Vol 154 (1) ◽  
pp. 121-132
Author(s):  
Zhen Hu ◽  
Yingzi Yue ◽  
Hua Jiang ◽  
Bin Zhang ◽  
Peter W Sherwood ◽  
...  
Keyword(s):  
Gene Expression ◽  
Glucose Repression ◽  
Protein A ◽  
The Other ◽  
Maltose Permease ◽  
Inducer Exclusion ◽  
Glucose Inhibition ◽  
Independent Mechanism ◽  
Mal Genes

Abstract Expression of the MAL genes required for maltose fermentation in Saccharomyces cerevisiae is induced by maltose and repressed by glucose. Maltose-inducible regulation requires maltose permease and the MAL-activator protein, a DNA-binding transcription factor encoded by MAL63 and its homologues at the other MAL loci. Previously, we showed that the Mig1 repressor mediates glucose repression of MAL gene expression. Glucose also blocks MAL-activator-mediated maltose induction through a Mig1p-independent mechanism that we refer to as glucose inhibition. Here we report the characterization of this process. Our results indicate that glucose inhibition is also Mig2p independent. Moreover, we show that neither overexpression of the MAL-activator nor elimination of inducer exclusion is sufficient to relieve glucose inhibition, suggesting that glucose acts to inhibit induction by affecting maltose sensing and/or signaling. The glucose inhibition pathway requires HXK2, REG1, and GSF1 and appears to overlap upstream with the glucose repression pathway. The likely target of glucose inhibition is Snf1 protein kinase. Evidence is presented indicating that, in addition to its role in the inactivation of Mig1p, Snf1p is required post-transcriptionally for the synthesis of maltose permease whose function is essential for maltose induction.

scholarly journals Comprehensive analysis of coding sequence architecture features and gene expression in Arachis duranensis

2021 ◽  
Vol 27 (2) ◽  
pp. 213-222
Author(s):  
Shuwei Dong ◽  
Long Zhang ◽  
Wenhui Pang ◽  
Yongli Zhang ◽  
Chang Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Comprehensive Analysis ◽  
Coding Sequence ◽  
Sequence Architecture ◽  
Arachis Duranensis

scholarly journals A comprehensive analysis of novel disulfide bond introduction site into the constant domain of human Fab

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hitomi Nakamura ◽  
Moeka Yoshikawa ◽  
Naoko Oda-Ueda ◽  
Tadashi Ueda ◽  
Takatoshi Ohkuri
Keyword(s):  
Thermal Stability ◽  
Pichia Pastoris ◽  
Protein Stability ◽  
Disulfide Bond ◽  
Binding Activity ◽  
Comprehensive Analysis ◽  
The Other ◽  
Constant Domain ◽  
Intermolecular Disulfide Bond ◽  
Sds Page

AbstractGenerally, intermolecular disulfide bond contribute to the conformational protein stability. To identify sites where intermolecular disulfide bond can be introduced into the Fab’s constant domain of the therapeutic IgG, Fab mutants were predicted using the MOE software, a molecular simulator, and expressed in Pichia pastoris. SDS-PAGE analysis of the prepared Fab mutants from P. pastoris indicated that among the nine analyzed Fab mutants, the F130C(H):Q124C(L), F174C(H):S176C(L), V177C(H):Q160C(L), F174C(H):S162C(L), F130C(H):S121C(L), and A145C(H):F116C(L) mutants mostly formed intermolecular disulfide bond. All these mutants showed increased thermal stability compared to that of Fab without intermolecular disulfide bond. In the other mutants, the intermolecular disulfide bond could not be completely formed, and the L132C(H):F118C(L) mutant showed only a slight decrease in binding activity and β-helix content, owing to the exertion of adverse intermolecular disulfide bond effects. Thus, our comprehensive analysis reveals that the introduction of intermolecular disulfide bond in the Fab’s constant domain is possible at various locations. These findings provide important insights for accomplishing human Fab stabilization.

Sign in / Sign up

Export Citation Format

Share Document