scholarly journals Nrf2/Keap1-Pathway Activation and Reduced Susceptibility to Chemotherapy Treatment by Acidification in Esophageal Adenocarcinoma Cells

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2806
Author(s):  
Lucie Storz ◽  
Philipp Walther ◽  
Olga Chemnitzer ◽  
Orestis Lyros ◽  
Stefan Niebisch ◽  
...  
Keyword(s):  
Esophageal Adenocarcinoma ◽  
Squamous Epithelium ◽  
Acid Reflux ◽  
Cellular Damage ◽  
Pathway Activation ◽  
Cellular Context ◽  
Vitro Model ◽  
Nfκb Pathway ◽  
Eac Cells

Chronic acid reflux causes cellular damage and inflammation in the lower esophagus. Due to these irritating insults, the squamous epithelium is replaced by metaplastic epithelium, which is a risk factor for the development of esophageal adenocarcinoma (EAC). In this study, we investigated the acid susceptibility in a Barrett’s cell culture in vitro model, using six cell lines, derived from squamous epithelium (EPC1 and EPC2), metaplasia (CP-A), dysplasia (CP-B), and EAC (OE33 and OE19) cells. Cells exposed to acidic pH showed a decreased viability dependent on time, pH, and progression status in the Barrett’s sequence, with the highest acid susceptibility in the squamous epithelium (EPC1 and EPC2), and the lowest in EAC cells. Acid pulsing was accompanied with an activation of the Nrf2/Keap1- and the NFκB-pathway, resulting in an increased expression of HO1—independent of the cellular context. OE33 showed a decreased responsiveness towards 5-FU, when the cells were grown in acidic conditions (pH 6 and pH 5.5). Our findings suggest a strong damage of squamous epithelium by gastroesophageal reflux, while Barrett’s dysplasia and EAC cells apparently exert acid-protective features, which lead to a cellular resistance against acid reflux.

scholarly journals Helicobacter pylori-induced Sonic Hedgehog Expression is Regulated by NFκB Pathway Activation: The Use of a Novel In vitro Model to Study Epithelial Response to Infection

Helicobacter ◽  
2014 ◽  
Vol 20 (1) ◽  
pp. 19-28 ◽  
Author(s):  
Michael A. Schumacher ◽  
Rui Feng ◽  
Eitaro Aihara ◽  
Amy C. Engevik ◽  
Marshall H. Montrose ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Sonic Hedgehog ◽  
In Vitro Model ◽  
Pathway Activation ◽  
Vitro Model ◽  
Nfκb Pathway

scholarly journals Crocetin Mitigates Irradiation Injury in an In Vitro Model of the Pubertal Testis: Focus on Biological Effects and Molecular Mechanisms

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1676
Author(s):  
Giulia Rossi ◽  
Martina Placidi ◽  
Chiara Castellini ◽  
Francesco Rea ◽  
Settimio D'Andrea ◽  
...  
Keyword(s):  
In Vitro Model ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Cellular Damage ◽  
X Rays ◽  
Adolescent Cancer ◽  
Radiation Induced ◽  
Vitro Model ◽  
Underlying Mechanisms

Infertility is a potential side effect of radiotherapy and significantly affects the quality of life for adolescent cancer survivors. Very few studies have addressed in pubertal models the mechanistic events that could be targeted to provide protection from gonadotoxicity and data on potential radioprotective treatments in this peculiar period of life are elusive. In this study, we utilized an in vitro model of the mouse pubertal testis to investigate the efficacy of crocetin to counteract ionizing radiation (IR)-induced injury and potential underlying mechanisms. Present experiments provide evidence that exposure of testis fragments from pubertal mice to 2 Gy X-rays induced extensive structural and cellular damage associated with overexpression of PARP1, PCNA, SOD2 and HuR and decreased levels of SIRT1 and catalase. A twenty-four hr exposure to 50 μM crocetin pre- and post-IR significantly reduced testis injury and modulated the response to DNA damage and oxidative stress. Nevertheless, crocetin treatment did not counteract the radiation-induced changes in the expression of SIRT1, p62 and LC3II. These results increase the knowledge of mechanisms underlying radiation damage in pubertal testis and establish the use of crocetin as a fertoprotective agent against IR deleterious effects in pubertal period.

Abstract B10: Vorinostat exposure results in decreased lamin B1 expression and nuclear structure normalization in an in vitro model of esophageal adenocarcinoma progression

2013 ◽  
Author(s):  
Vivek Nandakumar ◽  
Nanna Hansen ◽  
Kathryn Hernandez ◽  
Patti Senechal ◽  
Miranda Slaydon ◽  
...  
Keyword(s):  
Nuclear Structure ◽  
Esophageal Adenocarcinoma ◽  
In Vitro Model ◽  
Lamin B1 ◽  
Vitro Model

scholarly journals No Cytotoxic and Inflammatory Effects of Empagliflozin and Dapagliflozin on Primary Renal Proximal Tubular Epithelial Cells under Diabetic Conditions In Vitro

2020 ◽  
Vol 21 (2) ◽  
pp. 391 ◽  
Author(s):  
Patrick C. Baer ◽  
Benjamin Koch ◽  
Janina Freitag ◽  
Ralf Schubert ◽  
Helmut Geiger
Keyword(s):  
Epithelial Cells ◽  
Cell Injury ◽  
Cellular Damage ◽  
Tubular Epithelial Cells ◽  
Urinary Glucose ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular ◽  
Vitro Model ◽  
Renal Proximal Tubular

Gliflozins are inhibitors of the renal proximal tubular sodium-glucose co-transporter-2 (SGLT-2), that inhibit reabsorption of urinary glucose and they are able to reduce hyperglycemia in patients with type 2 diabetes. A renoprotective function of gliflozins has been proven in diabetic nephropathy, but harmful side effects on the kidney have also been described. In the current project, primary highly purified human renal proximal tubular epithelial cells (PTCs) have been shown to express functional SGLT-2, and were used as an in vitro model to study possible cellular damage induced by two therapeutically used gliflozins: empagliflozin and dapagliflozin. Cell viability, proliferation, and cytotoxicity assays revealed that neither empagliflozin nor dapagliflozin induce effects in PTCs cultured in a hyperglycemic environment, or in co-medication with ramipril or hydro-chloro-thiazide. Oxidative stress was significantly lowered by dapagliflozin but not by empagliflozin. No effect of either inhibitor could be detected on mRNA and protein expression of the pro-inflammatory cytokine interleukin-6 and the renal injury markers KIM-1 and NGAL. In conclusion, empa- and dapagliflozin in therapeutic concentrations were shown to induce no direct cell injury in cultured primary renal PTCs in hyperglycemic conditions.

P130 HISTONE DEACETYLASES EXPRESSION AND ACTIVITY IN ESOPHAGEAL ADENOCARCINOMA CELLS IN VITRO

2019 ◽  
Vol 32 (Supplement_2) ◽  
Author(s):  
Thieme René ◽  
Nowotny Robert ◽  
Maly Ronja ◽  
Lyros Orestis ◽  
K Hansen Finn ◽  
...  
Keyword(s):  
Histone Deacetylases ◽  
In Vitro Model ◽  
Treatment Options ◽  
Regulation Of Gene Expression ◽  
Inhibition Of Proliferation ◽  
Hdac Activity ◽  
Vitro Model ◽  
H3 Acetylation ◽  
Eac Cells

Abstract Aim The response of EAC patients to common chemotherapeutic regimens is relatively low (approx. 50%). Improving the response rate in cancer patients is challenging and novel therapeutic treatment options are needed. Histone deacetylases (HDAC), an enzyme class with promising novel features, are involved the regulation of gene expression affecting the epigenom. Methods The expression of Zn2+-dependent HDACs and the endogenous HDAC activity were characterized in a Berrett’s esophagus in vitro model, containing cells from squamous epithelium, Barrett’s metaplasia, dysplasia and EAC. Proliferation assays were carried out in EAC cells to determine cell response to an experimental, HDAC1-3 specific, HDAC inhibitor (HDACi) in comparison to vorinostat (pan HDACi). The HDAC activity, the p21 expression, and the histone H3 acetylation were investigated under HDACi treatment. Results All Zn2+-dependent HDACs were expressed by each stage of the Berrett’s esophagus in vitro model. However, the expression intensity was variable. Vorinostat showed an inhibition of proliferation in the EAC cells OE33 and OE19 (IC50 of 1.1μM and 1.8μM), while the experimental HDACi DDK137 revealed an increased anti proliferative effect (IC50 of 0.4μM and 0.6μM), a higher HDAC activity reduction, and higher increase in H3 acetylation. The p21 mRNA-expression showed a cell line, time and inhibitor specific increase. The highest increase was determined in OE33 cells (2.5fold) by DDK137 after 48h, while no increase in p21 was measured under vorinostat treatment. Conclusion We could show a pharmacological more potent HDACi than vorinostat in EAC cells in vitro. However, further studies are necessary to evaluate the significance of HDACi and whether HDACi are able to increase chemosensitivity in EAC patients.

scholarly journals Chondroprotective Effects of Genistein against Osteoarthritis Induced Joint Inflammation

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1180 ◽  
Author(s):  
Feng-Cheng Liu ◽  
Chih-Chien Wang ◽  
Jeng-Wei Lu ◽  
Chian-Her Lee ◽  
Shao-Chi Chen ◽  
...  
Keyword(s):  
In Vitro Model ◽  
Joint Inflammation ◽  
Pathway Activation ◽  
Anti Cancer ◽  
Oa Chondrocytes ◽  
Anti Inflammatory ◽  
Vitro Model ◽  
Nitric Oxide Synthase 2 ◽  
Oxide Synthase

Genistein is an isoflavone extracted from soybean (Glycine max). This compound has anti-inflammatory, anti-oxidative, and anti-cancer effects; however, the mechanism underlying the effects of genistein on IL-1β-stimulated human osteoarthritis (OA) chondrocytes remains unknown. Our objectives in this study were to explore the anti-inflammatory effects of genistein on IL-1β-stimulated human OA chondrocytes and to investigate the potential mechanisms which underlie them. Our results from an in-vitro model of osteoarthritis indicate that genistein inhibits the IL-1β-induced expression of the catabolic factors nitric oxide synthase 2 (NOS2), cyclooxygenase 2 (COX-2), and matrix metalloproteinases (MMPs). Genistein was shown to stimulate Ho-1 expression, which has been associated with Nrf-2 pathway activation in human chondrocytes. In a rat model, genistein was also shown to attenuate the progression of traumatic osteoarthritis. Taken together, these results demonstrate the effectiveness of genistein in mediating the inflammation associated with joint disorders. Our results also indicate that genistein could potentially serve as an alternative therapeutic treatment for OA.

scholarly journals Exposure of mammary cells to lipid activates gene expression changes associated with ER-negative breast cancer via chromatin remodeling.

2020 ◽  
Author(s):  
Shivangi Yadav ◽  
Ranya Virk ◽  
Carolina Chung ◽  
David Van Derway ◽  
Duojian Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Posttranslational Modifications ◽  
Chromatin Accessibility ◽  
Pathway Activation ◽  
Chromatin Packing ◽  
One Carbon Metabolism ◽  
Vitro Model ◽  
Lipid Metabolism Genes

Improved understanding of local breast biology that favors the development of estrogen receptor-negative (ER-) breast cancer (BC) would foster better prevention strategies. We have previously shown that overexpression of specific lipid metabolism genes is associated with the development of ER- BC. We now report results of exposure of MCF-10A cells and mammary organoids to representative medium- and long-chain polyunsaturated fatty acids. This exposure caused a dynamic and profound change in gene expression, accompanied by changes in chromatin packing density, chromatin accessibility and histone posttranslational modifications (PTMs). We identified 38 metabolic reactions that showed significantly increased activity, including reactions related to one-carbon metabolism. Among these reactions are those that produce S-adenosyl-L-methionine for histone PTMs. Utilizing both an in-vitro model and samples from women at high risk for ER- BC, we show that lipid exposure engenders gene expression, signaling pathway activation, and histone marks associated with the development of ER- BC.

scholarly journals 3114 Investigating the therapeutic potential of parthenolide in the treatment of hematopoietic neoplasms in dogs

2019 ◽  
Vol 3 (s1) ◽  
pp. 14-15
Author(s):  
Lisa J Schlein ◽  
Aubree Peterson ◽  
Barbara Rose ◽  
Douglas Thamm
Keyword(s):  
Mast Cell ◽  
Cell Lines ◽  
Standard Of Care ◽  
Chemotherapeutic Agents ◽  
Hematopoietic Cell ◽  
Pathway Activation ◽  
Nfκb Pathway ◽  
Hematopoietic Cell Lines

OBJECTIVES/SPECIFIC AIMS: Determine PTL’s mechanism(s) of action in a panel of canine hematopoietic cell lines; this will enable us to 1) verify that PTL is working as expected and 2) rationally select combination therapeutics. Characterize the in vitro sensitivity of canine hematopoietic cell lines to PTL in combination with other chemotherapeutic agents. Determine immunohistochemical NFκB expression in tissue microarrays of spontaneous canine neoplasms and correlate with outcome-linked data. Characterize the in vivo sensitivity of canine hematopoietic cell lines to PTL using a murine xenograft model. METHODS/STUDY POPULATION: Growth inhibition assays were performed using a panel of canine mast cell, histiocytic sarcoma, lymphoma, and leukemia cell lines, with PTL alone or in combination with redox-perturbing standard-of-care therapeutics. Cell death was assessed using flow cytometry. Immunofluorescence and immunoblotting were used to assess NFκB localization and phosphorylation of NFκB p65 (transcriptional activation), respectively. Intracellular glutathione with and without PTL and combination chemotherapeutics will be assessed spectrophotometrically. Archived spontaneous canine tumors will be evaluated immunohistochemically (IHC) for increased NFκB pathway activation relative to normal control tissues. Nude mice will receive intravenous, intraperitoneal, or subcutaneous injections of canine HS cells and will be treated with PTL or with PTL in combination with standard-of-care chemotherapeutics. RESULTS/ANTICIPATED RESULTS: Results: All immortalized canine cell lines evaluated are sensitive to PTL therapy and undergo dose-dependent apoptosis following exposure to drug. PTL exposure leads to inhibition of NFκB, as evidenced by immunofluorescent nuclear exclusion and decreased p65 phosphorylation. Some chemotherapeutics appear to synergize with PTL in vitro. Anticipated results: We expect to find increased IHC NFκB pathway activation in malignantly transformed tissues relative to controls. We expect standard-of-care therapeutics to synergize with PTL in vivo based on preliminary in vitro data. DISCUSSION/SIGNIFICANCE OF IMPACT: These studies will determine whether PTL therapy may be beneficial in dogs with a variety of hematopoietic neoplasms, either alone or in combination with other therapeutics that are currently in clinical use. Dogs with mast cell or histiocytic neoplasia are an excellent model for rare and deadly human diseases, which may also benefit from PTL therapy.

An in vitro model of an oral keratinizing squamous epithelium

1974 ◽  
Vol 82 (2) ◽  
pp. 144-146
Author(s):  
ARNE JEPSEN
Keyword(s):  
In Vitro Model ◽  
Squamous Epithelium ◽  
Vitro Model

scholarly journals Astrocytic gap junctional networks suppress cellular damage in an in vitro model of ischemia

2014 ◽  
Vol 444 (2) ◽  
pp. 171-176 ◽  
Author(s):  
Takanori Shinotsuka ◽  
Masato Yasui ◽  
Mutsuo Nuriya
Keyword(s):  
In Vitro Model ◽  
Cellular Damage ◽  
Vitro Model ◽  
Gap Junctional
Sign in / Sign up

Export Citation Format

Share Document