scholarly journals GSK3 Kinase Inhibitor, CHIR, Suppress Transcription of Tissue Specific POU2F1 Isoform in Burkitt Namalwa Lymphoma Cells

2021 ◽  
Vol 496 (1) ◽  
pp. 32-35
Author(s):  
E. V. Pankratova ◽  
T. N. Portseva ◽  
A. A. Makarova ◽  
Yu. V. Ilyin ◽  
A. G. Stepchenko ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Tumor Cells ◽  
Kinase Inhibitor ◽  
Malignant Tumors ◽  
B Cell Lymphoma ◽  
Selective Inhibition ◽  
Alternative Promoters ◽  
Tissue Specific ◽  
Human Malignant Tumors ◽  
In Cells

Abstract POU2F1 (Oct-1) is a transcription factor, the overexpression of which is found in many human malignant tumors; a significant increase in its level in cells determines the malignant potential of the tumor. POU2F1 is represented in cells by several isoforms that are transcribed from alternative promoters. In Burkitt’s B-cell lymphoma Namalwa, the concentration of tissue-specific isoform Oct-1L is several times higher than in normal B cells. We tested the potential to inhibit the transcription of individual Oct-1 isoforms using the GSK3 kinase inhibitor CHIR, an aminopyrimidine derivative. We have shown that CHIR specifically affects the expression of the tissue-specific isoform Oct-1L, significantly reducing the level of mRNA and Oct-1L protein. However, CHIR does not change the amount of mRNA and protein of the ubiquitous isoform Oct-1A in Namalwa tumor cells. The results obtained show that it is possible to develop a system for selective inhibition of Oct-1 transcription factor isoforms in human cells to suppress drug resistance of tumor cells with a high POU2F1 content.

scholarly journals Specific Visualization of Tumor Cells Using Upconversion Nanophosphors

Acta Naturae ◽  
2014 ◽  
Vol 6 (4) ◽  
pp. 48-53 ◽  
Author(s):  
E. A. Grebenik ◽  
A. N. Generalova ◽  
A. V. Nechaev ◽  
E. V. Khaydukov ◽  
K. E. Mironova ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Self Assembly ◽  
Malignant Tumors ◽  
Emission Spectra ◽  
Biological Tissues ◽  
Medical Diagnostics ◽  
Breast Adenocarcinoma ◽  
Wide Range ◽  
Two Component ◽  
Human Malignant Tumors

The development of targeted constructs on the basis of photoluminescent nanoparticles with a high photo- and chemical stability and absorption/emission spectra in the transparency window of biological tissues is an important focus area of present-day medical diagnostics. In this work, a targeted two-component construct on the basis of upconversion nanophosphors (UCNPs) and anti-tumor 4D5 scFv was developed for selective labeling of tumor cells overexpressing the HER2 tumor marker characteristic of a number of human malignant tumors. A high affinity barnase : barstar (Bn : Bs) protein pair, which exhibits high stability in a wide range of pH and temperatures, was exploited as a molecular adapter providing self-assembly of the two-component construct. High selectivity for the binding of the two-component 4D5 scFv-Bn : UCNP-Bs construct to human breast adenocarcinoma SK-BR-3 cells overexpressing HER2 was demonstrated. This approach provides an opportunity to produce similar constructs for the visualization of different specific markers in pathogenic tissues, including malignant tumors.

scholarly journals Krüppel-Like Factor 6 Splice Variant 1: An Oncogenic Transcription Factor Involved in the Progression of Multiple Malignant Tumors

2021 ◽  
Vol 9 ◽  
Author(s):  
Kang Hu ◽  
Qing-Kang Zheng ◽  
Rui-Jie Ma ◽  
Chao Ma ◽  
Zhi-Gang Sun ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Splice Variant ◽  
Malignant Tumors ◽  
Biological Processes ◽  
Action Mechanism ◽  
Splicing Isoforms ◽  
Specificity Protein ◽  
Human Malignant Tumors ◽  
Oncogenic Transcription Factor

Krüppel-like factor 6 (KLF6) is one of the most studied members of the specificity protein/Krüppel-like factor (SP/KLF) transcription factor family. It has a typical zinc finger structure and plays a pivotal role in regulating the biological processes of cells. Recently, it has been considered to play a role in combatting cancer. Krüppel-like factor 6 splice variant 1 (KLF6-SV1), being one of the alternative KLF6 splicing isoforms, participates in tumor occurrence and development and has the potential to become a new target for molecular targeted therapy, although its action mechanism remains to be determined. The purpose of this article is to provide a comprehensive and systematic review of the important role of KLF6-SV1 in human malignant tumors to provide novel insights for oncotherapy.

scholarly journals Transcription factor activity rhythms and tissue-specific chromatin interactions explain circadian gene expression across organs

2017 ◽  
Author(s):  
Jake Yeung ◽  
Jérôme Mermet ◽  
Céline Jouffe ◽  
Julien Marquis ◽  
Aline Charpagne ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Gene Networks ◽  
Integrated Analysis ◽  
Alternative Promoters ◽  
Enhancer Activity ◽  
Chromosome Conformation ◽  
Tissue Specific ◽  
Mouse Tissues ◽  
Liver And Kidney ◽  
Specific Regulation

AbstractTemporal control of physiology requires the interplay between gene networks involved in daily timekeeping and tissue function across different organs. How the circadian clock interweaves with tissue-specific transcriptional programs is poorly understood. Here we dissected temporal and tissue-specific regulation at multiple gene regulatory layers by examining mouse tissues with an intact or disrupted clock over time. Integrated analysis uncovered two distinct regulatory modes underlying tissue-specific rhythms: tissue-specific oscillations in transcription factor (TF) activity, which were linked to feeding-fasting cycles in liver and sodium homeostasis in kidney; and co-localized binding of clock and tissue-specific transcription factors at distal enhancers. Chromosome conformation capture (4C-Seq) in liver and kidney identified liver-specific chromatin loops that recruited clock-bound enhancers to promoters to regulate liver-specific transcriptional rhythms. Furthermore, this looping was remarkably promoter-specific on the scale of less than ten kilobases. Enhancers can contact a rhythmic promoter while looping out nearby nonrhythmic alternative promoters, confining rhythmic enhancer activity to specific promoters. These findings suggest that chromatin folding enables the clock to regulate rhythmic transcription of specific promoters to output temporal transcriptional programs tailored to different tissues.

scholarly journals Patterns of tumor progression predict small and tissue-specific tumor-originating niches

2018 ◽  
Author(s):  
Thomas Buder ◽  
Andreas Deutsch ◽  
Barbara Klink ◽  
Anja Voss-Böhme
Keyword(s):  
Tumor Cells ◽  
Malignant Tumors ◽  
Tumor Development ◽  
Tumor Formation ◽  
Tissue Type ◽  
Human Tissues ◽  
Cell Type ◽  
Tissue Specific ◽  
Specific Tumor ◽  
A Cell

AbstractCancer development is a multistep process in which cells increase in malignancy through progressive alterations. The early phase of this process is hardly observable which aggravates an understanding of later tumor development. We shed light on this initial phase with a cell-based stochastic model calibrated with epidemiological data from the tissue scale. Our model allows to estimate the number of tumor cells needed for tumor formation in human tissues based on data on the diagnosed ratios of benign and malignant tumors. We find that the minimal number of cells needed for tumor formation is surprisingly small and largely depends on the tissue type. Our results point towards the existence of tumor-originating niches in which the fate of tumor development is early decided. Our estimate for the human colon agrees well with the size of the stem cell niche in colonic crypts. Our estimates might help to identify the tumor-originating cell type, e.g. our analysis suggests for glioblastoma that the tumors originate from a cell type competing in a range of 300 - 1900 cells.SummaryWe estimate the number of tumor cells needed for tumor formation in human tissues and propose the existence of small and tissue-specific tumor-originating niches which might help to find tumor-originating cell types, in particular in glioblastoma.

Inhibition of NGLY1 inactivates the transcription factor Nrf1 and potentiates proteasome inhibitor cytotoxicity

2017 ◽  
Author(s):  
Carolyn Bertozzi ◽  
Fred Tomlin ◽  
Ulla Gerling-Driessen ◽  
Yi-Chang Liu ◽  
Ryan Flynn ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Small Molecule ◽  
Proteasome Inhibitor ◽  
Activation Mechanism ◽  
Cancer Drugs ◽  
Small Molecule Library ◽  
Library Screen ◽  
In Cells

We discovered that the proteostasis modulating transcription factor Nrf1 requires cytosolic de-N-glycosylation by the N-glycanase NGly1 as part of its activation mechanism. Through a covalent small molecule library screen, we discovered an inhibitor of NGly1 that blocks Nrf1 activation in cells and potentiates the activity of proteasome inhibitor cancer drugs. The requirement of NGly1 for Nrf1 activity likely underlies several pathologies associated with a rare hereditary deficiency in NGly1.

Inhibition by dihydrorifampicin of RNA polymerases I and II isolated from nuclei of Rous sarcoma cells and human tumor cells HEp-2

1979 ◽  
Vol 44 (9) ◽  
pp. 2722-2736 ◽  
Author(s):  
Jindřich Kára ◽  
Zdeněk Hostomský
Keyword(s):  
Tumor Cells ◽  
Human Tumor ◽  
Tumor Cell Line ◽  
Selective Inhibition ◽  
Rna Polymerases ◽  
Embryonic Cells ◽  
Human Tumor Cells ◽  
Ribonucleic Acids ◽  
Rous Sarcoma ◽  
Sarcoma Cells

Dihydrorifampicin, a rifampicin derivative hydrogenated at the 18-19 carbon atoms of the aliphatic ansa chain of the rifampicin molecule, inhibits the enzymatic activity of RNA polymerases I and II, isolated from the nuclei of avian tumor cells (Rous sarcoma) and from the human tumor cell line HEp-2. The RNA polymerases from these tumors have been separated and partially purified by chromatography on DEAE Sephadex A-25 and characterized by the sensitivity to α-amanitin. The [3H]UMP-labeled ribonucleic acids synthesized in the isolated nuclei of Rous sarcoma cells in the presence and absence of DHR were analyzed by sedimentation analysis in sucrose density gradients. It was found that the synthesis of rRNAs and mRNAs is very significantly inhibited by dihydrorifampicin, whereas the synthesis of tRNAs is much less inhibited at the same DHR concentration (100μg/ml). The observed cytostatic effect of DHR on the growth of human tumor cells HEp-2 and embryonic cells in culture is apparently mediated by the selective inhibition of RNA polymerases I and II in human and avian cells. The relationship between the molecular structure of DHR and its affinity to RNA polymerases of eukaryotic cells is discussed.

Penile Lymphoepithelioma-Like Carcinoma: A Rare Case With PD-L1 Expression

2021 ◽  
pp. 106689692098834
Author(s):  
Raquel Machado-Neves ◽  
Bernardo Teixeira ◽  
Elsa Fonseca ◽  
Pedro Valente ◽  
Joaquim Lindoro ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Tumor Cells ◽  
Rare Case ◽  
Malignant Tumors ◽  
Squamous Cell Carcinomas ◽  
The Third ◽  
The Past ◽  
First Case ◽  
Lymphoplasmacytic Infiltrate

Most malignant tumors of the penis are squamous cell carcinomas (SCC), being divided in 2 groups, one human papillomavirus (HPV)-related and another non-HPV-related, with lymphoepithelioma-like carcinoma (LELC) being one of the rarest HPV-related SCC. In this article, we report a case of a 50-year-old man who presented testicular swelling and pain for the past 3 months. A penile mass was identified, and the patient was submitted to a total penectomy. The penectomy specimen showed an ulcerated lesion at the glans reaching the cavernous bodies. Microscopic examination showed undifferentiated epithelial cells with syncytial growth pattern mix with a dense lymphoplasmacytic infiltrate, consistent with LELC. The tumor cells expressed p16 and all 3 different clones of PDL1 (22C3, SP263, and SP142). The patient is alive and well with a follow-up of 3 months. To our knowledge, this is the third LELC of the penis reported in literature and the first case reported with PDL1 expression.

scholarly journals Parallel G-quadruplexes recruit the HSV-1 transcription factor ICP4 to promote viral transcription in herpes virus-infected human cells

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Ilaria Frasson ◽  
Paola Soldà ◽  
Matteo Nadai ◽  
Sara Lago ◽  
Sara N. Richter
Keyword(s):  
Transcription Factor ◽  
Early Gene ◽  
Proximity Ligation Assay ◽  
Gene Promoters ◽  
Herpes Simplex Virus 1 ◽  
Direct Binding ◽  
Simplex Virus ◽  
In Cells ◽  
Hsv 1

AbstractG-quadruplexes (G4s) are four-stranded nucleic acid structures abundant at gene promoters. They can adopt several distinctive conformations. G4s have been shown to form in the herpes simplex virus-1 (HSV-1) genome during its viral cycle. Here by cross-linking/pull-down assay we identified ICP4, the major HSV-1 transcription factor, as the protein that most efficiently interacts with viral G4s during infection. ICP4 specific and direct binding and unfolding of parallel G4s, including those present in HSV-1 immediate early gene promoters, induced transcription in vitro and in infected cells. This mechanism was also exploited by ICP4 to promote its own transcription. Proximity ligation assay allowed visualization of G4-protein interaction at the single selected G4 in cells. G4 ligands inhibited ICP4 binding to G4s. Our results indicate the existence of a well-defined G4-viral protein network that regulates the productive HSV-1 cycle. They also point to G4s as elements that recruit transcription factors to activate transcription in cells.

scholarly journals Primary Cranial Vault Lymphoma Extending between Subcutaneous Tissue and Brain Parenchyma without Skull Destruction after Mild Head Trauma: A Case Report and Literature Review

2021 ◽  
pp. 1118-1123
Author(s):  
Kengo Setta ◽  
Takaaki Beppu ◽  
Yuichi Sato ◽  
Hiroaki Saura ◽  
Junichi Nomura ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Head Trauma ◽  
Dura Mater ◽  
Subcutaneous Tissue ◽  
Bone Destruction ◽  
B Cell Lymphoma ◽  
Brain Parenchyma ◽  
Skin Tumor ◽  
Cranial Vault ◽  
The Brain

Malignant lymphoma of the head rarely arises outside of the brain parenchyma as primary cranial vault lymphoma (PCVL). A case of PCVL that invaded from subcutaneous tissue into the brain, passing through the skull, and occurred after mild head trauma is reported along with a review of the literature. The patient was a 75-year-old man with decreased activity. One month before his visit to our hospital, he bruised the left frontal area of his head. Magnetic resonance imaging showed homogeneously enhanced tumors with contrast media in the subcutaneous tissue corresponding to the head impact area and the cerebral parenchyma, but no obvious abnormal findings in the skull. A biopsy with craniotomy was performed under general anesthesia. The pathological diagnosis was diffuse large B-cell lymphoma. On histological examination, tumor cells grew aggressively under the skin. Tumor cells invaded along the emissary vein into the external table without remarkable bone destruction and extended across the skull through the Haversian canals in the diploe. Tumor cells were found only at the perivascular areas in the dura mater and extended into the brain parenchyma. Considering the history of head trauma and the neuroimaging and histological findings, the PCVL in the present case arose primarily under the skin, passed though the skull and dura mater, and invaded along vessels and reached the brain.

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