Unscheduled DNA Repair in Human Lens Epithelium following ‘in vivo’ and ‘in vitro’ Ultraviolet Irradiation

1982 ◽  
Vol 14 (3) ◽  
pp. 160-166 ◽  
Author(s):  
Günther Grabner ◽  
Wilhelm Brenner
Keyword(s):  
Dna Repair ◽  
Ultraviolet Irradiation ◽  
Lens Epithelium ◽  
Human Lens ◽  
Human Lens Epithelium

Transfection of CTGF siRNA inhibits transdifferentiation in human lens epithelium cell line B3 in vitro

2020 ◽  
Vol 1 (1) ◽  
pp. 17-23
Author(s):  
Hua Zhuang ◽  
◽  
Jing Wu ◽  
Wei Xu ◽  
Jian-Zhang Hu ◽  
...  
Keyword(s):  
Smooth Muscle Actin ◽  
Negative Control ◽  
Tissue Growth ◽  
Lens Epithelium ◽  
Cell Counting ◽  
Human Lens ◽  
Posterior Capsular Opacification ◽  
Epithelium Cell ◽  
Human Lens Epithelium

AIM: To investigate the expression of connective tissue growth factor (CTGF) and α-smooth muscle actin (α-SMA) in human lens epithelium cell (HLEC) line B3 after transfection by liposome-coated small interfering RNA (siRNA) targeting CTGF. METHODS: HLECs were transfected with siRNA targeting CTGF, labeled with 5’-fluorescein isothiocyanate (5’-FITC) and coated with lipofectamine. The transfection ratio was evaluated via fluorescence intensity. Cell counting kit-8 (CCK-8) assay was performed to assess cytoviability of both non-transfected and transfected HLECs. Quantitative reverse transcription-polymerase chain reaction (RT-PCR), cell immunochemistry and Western blot analysis were conducted to detect the expression changes of CTGF and α-SMA after transfection. RESULTS: A highly effective transfection ratio was observed in siRNA co-transfected with lipofectamine. The transfection ratio reached 95% at 24h. The proliferation of HLECs was inhibited by siRNA after 72h transfection. The expression of CTGF and α-SMA significantly decreased in HLECs after transfected by CTGF siRNA for 24h. This effect was not found in negative control siRNA. CONCLUSION: siRNA targeting CTGF decrease CTGF and α-SMA expression in HLECs, which is a potential therapeutic strategy for posterior capsular opacification.

Pharmacological targeting of differential DNA repair, radio-sensitizes WRN-deficient cancer cells in vitro and in vivo

2021 ◽  
Vol 186 ◽  
pp. 114450
Author(s):  
Pooja Gupta ◽  
Bhaskar Saha ◽  
Subrata Chattopadhyay ◽  
Birija Sankar Patro
Keyword(s):  
Dna Repair ◽  
Cancer Cells

scholarly journals Inactivating Mutations of the IK Gene Weaken Ku80/Ku70-Mediated DNA Repair and Sensitize Endometrial Cancer to Chemotherapy

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2487
Author(s):  
Chao Gao ◽  
Guangxu Jin ◽  
Elizabeth Forbes ◽  
Lingegowda S. Mangala ◽  
Yingmei Wang ◽  
...  
Keyword(s):  
Dna Repair ◽  
Endometrial Cancer ◽  
Protein Interactions ◽  
Somatic Mutations ◽  
The Cancer Genome Atlas ◽  
Response To Chemotherapy ◽  
Tcga Dataset ◽  
Inactivating Mutations

IK is a mitotic factor that promotes cell cycle progression. Our previous investigation of 271 endometrial cancer (EC) samples from the Cancer Genome Atlas (TCGA) dataset showed IK somatic mutations were enriched in a cluster of patients with high-grade and high-stage cancers, and this group had longer survival. This study provides insight into how IK somatic mutations contribute to EC pathophysiology. We analyzed the somatic mutational landscape of IK gene in 547 EC patients using expanded TCGA dataset. Co-immunoprecipitation and mass spectrometry were used to identify protein interactions. In vitro and in vivo experiments were used to evaluate IK’s role in EC. The patients with IK-inactivating mutations had longer survival during 10-year follow-up. Frameshift and stop-gain were common mutations and were associated with decreased IK expression. IK knockdown led to enrichment of G2/M phase cells, inactivation of DNA repair signaling mediated by heterodimerization of Ku80 and Ku70, and sensitization of EC cells to cisplatin treatment. IK/Ku80 mutations were accompanied by higher mutation rates and associated with significantly better overall survival. Inactivating mutations of IK gene and loss of IK protein expression were associated with weakened Ku80/Ku70-mediated DNA repair, increased mutation burden, and better response to chemotherapy in patients with EC.

scholarly journals MODL-16. ABEMACICLIB, A SELECTIVE CDK4/6 INHIBITOR, RESTRICTS GROWTH OF PEDIATRIC GLIAL-LINEAGE TUMORS IN VITRO AND IN VIVO

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii414-iii414
Author(s):  
Muh-Lii Liang ◽  
Tsung-Han Hsieh ◽  
Tai-Tong Wong
Keyword(s):  
Dna Repair ◽  
Therapeutic Strategy ◽  
Target Genes ◽  
Rna Seq ◽  
Downstream Target ◽  
Rb Phosphorylation ◽  
Glial Lineage

Abstract BACKGROUND Glial-lineage tumors constitute a heterogeneous group of neoplasms, comprising gliomas, oligodendrogliomas, and ependymomas, which account for 40%–50% of all pediatric central nervous system tumors. Advances in modern neuro-oncological therapeutics are aimed at improving neoadjuvant chemotherapy and deferring radiotherapy because radiation exposure may cause long-term side effects on the developing brain in young children. Despite aggressive treatment, more than half the high-grade gliomas (pHGGs) and one-third of ependymomas exhibit recurrence within 2 years of initial treatment. METHODS By using integrated bioinformatics and through experimental validation, we found that at least one gene among CCND1, CDK4, and CDK6 was overexpressed in pHGGs and ependymomas. RESULTS The use of abemaciclib, a highly selective CDK4/6 inhibitor, effectively inhibited cell proliferation and reduced the expression of cell cycle–related and DNA repair–related gene expression, which was determined through RNA-seq analysis. The efficiency of abemaciclib was validated in vitro in pHGGs and ependymoma cells and in vivo by using subcutaneously implanted ependymoma cells from patient-derived xenograft (PDX) in mouse models. Abemaciclib demonstrated the suppression of RB phosphorylation, downstream target genes of E2F, G2M checkpoint, and DNA repair, resulting in tumor suppression. CONCLUSION Abemaciclib showed encouraging results in preclinical pediatric glial-lineage tumors models and represented a potential therapeutic strategy for treating challenging tumors in children.

4-Acetylantrocamol LT3 Inhibits Glioblastoma Cell Growth and Downregulates DNA Repair Enzyme O6-Methylguanine-DNA Methyltransferase

2021 ◽  
pp. 1-17
Author(s):  
Shih-Yu Lee ◽  
I-Chuan Yen ◽  
Jang-Chun Lin ◽  
Min-Chieh Chung ◽  
Wei-Hsiu Liu
Keyword(s):  
Dna Repair ◽  
Cell Viability ◽  
Colony Formation ◽  
Dna Methyltransferase ◽  
Growth Factor Receptor ◽  
Repair Enzyme ◽  
U251 Cell ◽  
Methylguanine Dna Methyltransferase

Glioblastoma multiforme (GBM) is a deadly malignant brain tumor that is resistant to most clinical treatments. Novel therapeutic agents that are effective against GBM are required. Antrodia cinnamomea has shown antiproliferative effects in GBM cells. However, the exact mechanisms and bioactive components remain unclear. Thus, the present study aimed to investigate the effect and mechanism of 4-acetylantrocamol LT3 (4AALT3), a new ubiquinone from Antrodia cinnamomeamycelium, in vitro. U87 and U251 cell lines were treated with the indicated concentration of 4AALT3. Cell viability, cell colony-forming ability, migration, and the expression of proteins in well-known signaling pathways involved in the malignant properties of glioblastoma were then analyzed by CCK-8, colony formation, wound healing, and western blotting assays, respectively. We found that 4AALT3 significantly decreased cell viability, colony formation, and cell migration in both in vitro models. The epidermal growth factor receptor (EGFR), phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR), Hippo/yes-associated protein (YAP), and cAMP-response element binding protein (CREB) pathways were suppressed by 4AALT3. Moreover, 4AALT3 decreased the level of DNA repair enzyme O6-methylguanine-DNA methyltransferase and showed a synergistic effect with temozolomide. Our findings provide the basis for exploring the beneficial effect of 4AALT3 on GBM in vivo.

scholarly journals Somatic Variants in the Human Lens Epithelium: A Preliminary Assessment

2016 ◽  
Vol 57 (10) ◽  
pp. 4063 ◽  
Author(s):  
Rosana Mesa ◽  
Manoj Tyagi ◽  
George Harocopos ◽  
David Vollman ◽  
Steven Bassnett
Keyword(s):  
Lens Epithelium ◽  
Human Lens ◽  
Preliminary Assessment ◽  
Human Lens Epithelium

An Immunoperoxidase Study of Human Lens Epithelium

1990 ◽  
Vol 2 (1) ◽  
pp. 71-73 ◽  
Author(s):  
Margaret J. Jeffrey ◽  
W.T. Green ◽  
D.L. Boase ◽  
M.N. Jeffrey
Keyword(s):  
Lens Epithelium ◽  
Human Lens ◽  
Human Lens Epithelium
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