scholarly journals Gestagens in the treatment of endometriosis

2018 ◽  
Vol 64 (1) ◽  
pp. 54-61 ◽  
Author(s):  
Tatiana A. Fedotcheva ◽  
Nikolai L. Shimanovskiy
Keyword(s):  
Cancer Cells ◽  
Molecular Genetic ◽  
Reproductive Age ◽  
Antiproliferative Effect ◽  
Target Cells ◽  
Gynecological Diseases ◽  
Cervical Cancer Cells ◽  
Molecular Genetic Characterization

Endometriosis occurs in 10% of females of reproductive age and ranks third among gynecological diseases, being one of the causes of infertility. The success of endometriosis treatment depends on individually selected therapy based on molecular-genetic characterization of the patient endometrial tissue. The review addresses the mechanisms of endometriosis development and the role of gestagens in the pathogenesis of this disease. We describe the genetic and epigenetic mechanisms of endometriosis development, which lead to resistance to endogenous progesterone, a key link in the pathogenesis of endometriosis. Because gestagen monotherapy is considered as first-line treatment, we analyze the gestagen properties that underlie the indications for their use in endometriosis. In particular, gestagen should have high gestagenic activity and an antiproliferative effect on target cells. An original domestic drug, an oral gestagen Gestobutanoil based on 17a-acetoxy-3b-butanoyloxy-6-methyl-pregna-4,6-dien-20-one (AMP-17), is promising for clinical use. The gestagenic activity of AMP-17 in the Clauberg-McPhail test is 102-fold higher than that of progesterone. AMP-17 has a pronounced antiproliferative effect on estrogen-dependent targets, such as breast cancer cells, cervical cancer cells, etc.

scholarly journals Gestagens in the treatment of endometriosis

2018 ◽  
Vol 64 (1) ◽  
pp. 54-61
Author(s):  
Tatiana A. Fedotcheva ◽  
Nikolai L. Shimanovskiy
Keyword(s):  
Cancer Cells ◽  
Molecular Genetic ◽  
Reproductive Age ◽  
Antiproliferative Effect ◽  
Target Cells ◽  
Gynecological Diseases ◽  
Cervical Cancer Cells ◽  
Molecular Genetic Characterization

Endometriosis occurs in 10% of females of reproductive age and ranks third among gynecological diseases, being one of the causes of infertility. The success of endometriosis treatment depends on individually selected therapy based on molecular-genetic characterization of the patient endometrial tissue. The review addresses the mechanisms of endometriosis development and the role of gestagens in the pathogenesis of this disease. We describe the genetic and epigenetic mechanisms of endometriosis development, which lead to resistance to endogenous progesterone, a key link in the pathogenesis of endometriosis. Because gestagen monotherapy is considered as first-line treatment, we analyze the gestagen properties that underlie the indications for their use in endometriosis. In particular, gestagen should have high gestagenic activity and an antiproliferative effect on target cells. An original domestic drug, an oral gestagen Gestobutanoil based on 17a-acetoxy-3b-butanoyloxy-6-methyl-pregna-4,6-dien-20-one (AMP-17), is promising for clinical use. The gestagenic activity of AMP-17 in the Clauberg-McPhail test is 102-fold higher than that of progesterone. AMP-17 has a pronounced antiproliferative effect on estrogen-dependent targets, such as breast cancer cells, cervical cancer cells, etc.

scholarly journals Molecular Genetic Characterization of Individual Cancer Cells Isolated via Single-Cell Printing

PLoS ONE ◽  
2016 ◽  
Vol 11 (9) ◽  
pp. e0163455 ◽  
Author(s):  
Julian Riba ◽  
Nathalie Renz ◽  
Christoph Niemöller ◽  
Sabine Bleul ◽  
Dietmar Pfeifer ◽  
...  
Keyword(s):  
Single Cell ◽  
Cancer Cells ◽  
Genetic Characterization ◽  
Molecular Genetic ◽  
Cell Printing ◽  
Molecular Genetic Characterization

scholarly journals The potential oncogenic and MLN4924-resistant effects of CSN5 on cervical cancer cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Huilin Zhang ◽  
Ping He ◽  
Qing Zhou ◽  
Yan Lu ◽  
Bingjian Lu
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cervical Cancer Cell ◽  
Cervical Cancers ◽  
Cervical Cancer Cells

Abstract Background CSN5, a member of Cop9 signalosome, is essential for protein neddylation. It has been supposed to serve as an oncogene in some cancers. However, the role of CSN5 has not been investigated in cervical cancer yet. Methods Data from TCGA cohorts and GEO dataset was analyzed to examine the expression profile of CSN5 and clinical relevance in cervical cancers. The role of CSN5 on cervical cancer cell proliferation was investigated in cervical cancer cell lines, Siha and Hela, through CSN5 knockdown via CRISPR–CAS9. Western blot was used to detect the effect of CSN5 knockdown and overexpression. The biological behaviors were analyzed by CCK8, clone formation assay, 3-D spheroid generation assay and cell cycle assay. Besides, the role CSN5 knockdown in vivo was evaluated by xenograft tumor model. MLN4924 was given in Siha and Hela with CSN5 overexpression. Results We found that downregulation of CSN5 in Siha and Hela cells inhibited cell proliferation in vitro and in vivo, and the inhibitory effects were largely rescued by CSN5 overexpression. Moreover, deletion of CSN5 caused cell cycle arrest rather than inducing apoptosis. Importantly, CSN5 overexpression confers resistance to the anti-cancer effects of MLN4924 (pevonedistat) in cervical cancer cells. Conclusions Our findings demonstrated that CSN5 functions as an oncogene in cervical cancers and may serve as a potential indicator for predicting the effects of MLN4924 treatment in the future.

Paeonol triggers apoptosis in HeLa cervical cancer cells: the role of mitochondria-related caspase pathway

2021 ◽  
Author(s):  
Jikun Du ◽  
Daibo Song ◽  
Jinwen Li ◽  
Yuanhua Li ◽  
Baohong Li ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Caspase Pathway ◽  
Cervical Cancer Cells

scholarly journals Metabolic Flux in Both the Purine Mononucleotide and Histidine Biosynthetic Pathways Can Influence Synthesis of the Hydroxymethyl Pyrimidine Moiety of Thiamine in Salmonella enterica

2002 ◽  
Vol 184 (22) ◽  
pp. 6130-6137 ◽  
Author(s):  
Shara Allen ◽  
Julie L. Zilles ◽  
Diana M. Downs
Keyword(s):  
Metabolic Flux ◽  
Genetic Characterization ◽  
Molecular Genetic ◽  
Thiamine Pyrophosphate ◽  
Wild Type ◽  
Regulatory Pathway ◽  
Informational Suppressors ◽  
Pyrimidine Moiety ◽  
Molecular Genetic Characterization

ABSTRACT Together, the biosyntheses of histidine, purines, and thiamine pyrophosphate (TPP) contain examples of convergent, divergent, and regulatory pathway integration. Mutations in two purine biosynthetic genes (purI and purH) affect TPP biosynthesis due to flux through the purine and histidine pathways. The molecular genetic characterization of purI mutants and their respective pseudorevertants resulted in the conclusion that <1% of the wild-type activity of the PurI enzyme was sufficient for thiamine but not for purine synthesis. The respective pseudorevertants were found to be informational suppressors. In addition, it was shown that accumulation of the purine intermediate aminoimidazole carboxamide ribotide inhibits thiamine synthesis, specifically affecting the conversion of aminoimidazole ribotide to hydroxymethyl pyrimidine.

The Potential Oncogenic and MLN4924-Resistant Effects of CSN5 on Cervical Cancer Cells

2021 ◽  
Author(s):  
Huilin Zhang ◽  
Ping He ◽  
Qing Zhou ◽  
Yan Lu ◽  
Bingjian Lu
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cervical Cancer Cell ◽  
Cervical Cancers ◽  
Cervical Cancer Cells

Abstract BackgroundsCSN5, a member of Cop9 signalosome, is essential for protein neddylation. It has been supposed to serve as an oncogene in some cancers. However, the role of CSN5 has not been investigated in cervical cancer yet.MethodsData from TCGA cohorts and GEO dataset was analyzed to examine the expression profile of CSN5 in cervical cancers. The role of CSN5 on cervical cancer cell proliferation was investigated in cervical cancer cell lines, Siha and Hela, through CSN5 knockdown via CRISPR-CAS9. Western blot was used to detect the effect of CSN5 knockdown and overexpression. CCK8, clone formation assay and cell cycle assay were also employed. Besides, the role CSN5 knockdown in vivo was evaluated by xenograft tumor model. Moreover, MLN4924 was applied in Siha and Hela with CSN5 overexpression.ResultsWe found that downregulation of CSN5 in Siha and Hela cells inhibited cell proliferation in vitro and in vivo, and the inhibitory effects were largely rescued by CSN5 overexpression. Moreover, deletion of CSN5 caused cell cycle arrest rather than inducing apoptosis. Importantly, CSN5 overexpression confers resistance to the anti-cancer effects of MLN4924 (pevonedistat) in cervical cancer cells.ConclusionsOur findings demonstrated that CSN5 functions as an oncogene in cervical cancers and may serve as a potential indicator for predicting the effects of MLN4924 treatment in the future.

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