scholarly journals PHLPP1 Overexpression was Associated With a Good Prognosis With Decreased AKT Activity in Gastric Cancer

2022 ◽  
Vol 21 ◽  
pp. 153303382110670
Author(s):  
Sun Yi Park ◽  
Sang-Ho Jeong ◽  
Eun-Jung Jung ◽  
Young-Tae Ju ◽  
Chi-Young Jeong ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Line ◽  
In Vitro Study ◽  
Good Prognosis ◽  
Signet Ring Cell ◽  
Cancer Tissue ◽  
Cancer Subtypes ◽  
Chemotherapy Drugs ◽  
Study Results

Introduction: The aim of this study was to perform a clinicopathologic analysis of PHLPP1 expression in gastric cancer patients and analyze AKT activity with chemotherapy drug treatment in cancer subtypes. Materials and Methods: Surgically resected gastric cancer tissue specimens were obtained from 309 patients who underwent gastrectomy, and PHLPP1 expression was validated by tissue microarray analysis with immunohistochemistry. We assessed whether PHLPP1 selectively dephosphorylates Ser473 of AKT in an in-vitro study. Results: We found that the PHLPP1 overexpression (OE) group showed significantly greater proportions of differentiated subtype samples and early T stage samples, lower lymph node metastasis, and lower TNM stage than the PHLPP1 underexpression (UE) group. The overall survival of the PHLPP1-OE group was significantly higher (53.39 ± 0.96 months) than that of the PHLPP1-UE group (47.82 ± 2.57 months) ( P = .01). In vitro analysis, we found that the PHLPP1-OE group showed a significant decrease in relative AKT S-473 levels in both cell lines (MKN-74 and KATO-III). We found that treatment with chemotherapy drugs decreased the activity of Ser473 in the MKN-74 cell line with PHLPP1 OE, but it did not affect the activity of Ser473 in KATO-III cells. Conclusion: We found that patients who overexpressed PHLPP1 showed low recurrence and good prognosis. PHLPP1 was found to work by lowering the activity of AKT Ser473 in gastric cancer. Additionally, we found a clue regarding the mechanism of chemotherapeutic drug resistance in a cell line of signet ring cell origin and will uncover this mechanism in the future.

Assessment of mechanical and biocompatible performance of ultra-large nitinol endovascular devices fabricated via a low-energy laser joining process

2021 ◽  
pp. 088532822110195
Author(s):  
Moataz Elsisy ◽  
Mahdis Shayan ◽  
Yanfei Chen ◽  
Bryan W Tillman ◽  
Catherine Go ◽  
...  
Keyword(s):  
Laser Power ◽  
In Vitro Study ◽  
Spot Size ◽  
Laser Joining ◽  
Study Results ◽  
Energy Laser ◽  
Joining Process ◽  
Endovascular Devices ◽  
Low Energy Laser

Nitinol is an excellent candidate material for developing various self-expanding endovascular devices due to its unique properties such as superelasticity, biocompatibility and shape memory effect. A low-energy laser joining technique suggests a high potential to create various large diameter Nitinol endovascular devices that contain complex geometries. The primary purpose of the study is to investigate the effects of laser joining process parameters with regard to the mechanical and biocompatible performance of Nitinol stents. Both the chemical composition and the microstructure of the laser-welded joints were evaluated using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS). In vitro study results on cytotoxicity demonstrated that the joining condition of 8 Hz frequency and 1 kW laser power showed the highest degree of endothelial cell viability after thermal annealing in 500°C for 30 min. Also, in vitro study results showed the highest oxygen content at 0.9 kW laser power, 8 Hz frequency, and 0.3 mm spot size after the thermal annealing. Mechanical performance test results showed that the optimal condition for the highest disconnecting force was found at 1 Hz frequency and 1 kW power with 0.6 mm spot size. Two new endovascular devices have been fabricated using the optimized laser joining parameters, which have demonstrated successful device delivery and retrieval, as well as acute biocompatibility.

scholarly journals Formulation of Piperine–Chitosan-Coated Liposomes: Characterization and In Vitro Cytotoxic Evaluation

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3281
Author(s):  
Syed Sarim Imam ◽  
Sultan Alshehri ◽  
Mohammad A. Altamimi ◽  
Afzal Hussain ◽  
Wajhul Qamar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Line ◽  
Therapeutic Efficacy ◽  
Cancer Cell Line ◽  
Permeation Study ◽  
Study Results

The present research work is designed to prepare and evaluate piperine liposomes and piperine–chitosan-coated liposomes for oral delivery. Piperine (PPN) is a water-insoluble bioactive compound used for different diseases. The prepared formulations were evaluated for physicochemical study, mucoadhesive study, permeation study and in vitro cytotoxic study using the MCF7 breast cancer cell line. Piperine-loaded liposomes (PLF) were prepared by the thin-film evaporation method. The selected liposomes were coated with chitosan (PLFC) by electrostatic deposition to enhance the mucoadhesive property and in vitro therapeutic efficacy. Based on the findings of the study, the prepared PPN liposomes (PLF3) and chitosan coated PPN liposomes (PLF3C1) showed a nanometric size range of 165.7 ± 7.4 to 243.4 ± 7.5, a narrow polydispersity index (>0.3) and zeta potential (−7.1 to 29.8 mV). The average encapsulation efficiency was found to be between 60 and 80% for all prepared formulations. The drug release and permeation study profile showed biphasic release behavior and enhanced PPN permeation. The in vitro antioxidant study results showed a comparable antioxidant activity with pure PPN. The anticancer study depicted that the cell viability assay of tested PLF3C2 has significantly (p < 0.001)) reduced the IC50 when compared with pure PPN. The study revealed that oral chitosan-coated liposomes are a promising delivery system for the PPN and can increase the therapeutic efficacy against the breast cancer cell line.

scholarly journals Enhancing Anti-Tumoral Potential of CD-NHF by Modulating PI3K/Akt Axis in U87 Ex Vivo Glioma Model

2021 ◽  
Vol 22 (8) ◽  
pp. 3873
Author(s):  
Gabriel Luta ◽  
Mihail Butura ◽  
Adrian Tiron ◽  
Crina E. Tiron
Keyword(s):  
Cell Line ◽  
Ex Vivo ◽  
Glioma Cells ◽  
In Vitro Study ◽  
Immunofluorescent Staining ◽  
Expression Levels ◽  
Disease Diagnostics ◽  
Phosphorylated Akt ◽  
Significant Impairment

Background: In the latest years, there has been an increased interest in nanomaterials that may provide promising novel approaches to disease diagnostics and therapeutics. Our previous results demonstrated that Carbon-dots prepared from N-hydroxyphthalimide (CD-NHF) exhibited anti-tumoral activity on several cancer cell lines such as MDA-MB-231, A375, A549, and RPMI8226, while U87 glioma tumor cells were unaffected. Gliomas represent one of the most common types of human primary brain tumors and are responsible for the majority of deaths. In the present in vitro study, we expand our previous investigation on CD-NHF in the U87 cell line by adding different drug combinations. Methods: Cell viability, migration, invasion, and immunofluorescent staining of key molecular pathways have been assessed after various treatments with CD-NHF and/or K252A and AKTVIII inhibitors in the U87 cell line. Results: Association of an inhibitor strongly potentiates the anti-tumoral properties of CD-NHF identified by significant impairment of migration, invasion, and expression levels of phosphorylated Akt, p70S6Kinase, or by decreasing expression levels of Bcl-2, IL-6, STAT3, and Slug. Conclusions: Using simultaneously reduced doses of both CD-NHF and an inhibitor in order to reduce side effects, the viability and invasiveness of U87 glioma cells were significantly impaired.

In vitro study of the cytotoxic effects of microcystin-LR, cylindrospermopsin and their mixture in the neuronal SH-SY5Y cell line

2018 ◽  
Vol 295 ◽  
pp. S141
Author(s):  
M.G. Hinojosa ◽  
D. Gutierrez-Praena ◽  
A.I. Prieto ◽  
L. Espinar-López ◽  
A.M. Cameán ◽  
...  
Keyword(s):  
Cell Line ◽  
In Vitro Study ◽  
Vitro Study ◽  
Cytotoxic Effects

scholarly journals CDK10 Regulates Gastric Cancer Metastasis By Inhibiting lncRNA-C5ORF42-5 Via Phosphorylation Level of AKT/ERK

2021 ◽  
Author(s):  
Zi-Jian Deng ◽  
Dong-Wen Chen ◽  
Xi-Jie Chen ◽  
Jia-Ming Fang ◽  
Liang Xv ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
High Throughput ◽  
Cancer Metastasis ◽  
High Throughput Sequencing ◽  
Gastric Cancer Cells ◽  
Related Proteins

Abstract Background: Gastric cancer is the fourth most common malignant disease. Both CDK10 and long noncoding RNAs (lncRNAs) have been found to exert biological functions in multiple cancers. However, it is still unclear whether CDK10 represses tumor progression in gastric cancer by reducing potential targeting lncRNAs.Methods: The functions of CDK10 and lncRNA-C5ORF42-5 in proliferation, invasion and migration were assessed by MTS assays, colony formation assays, cell cycle and apoptosis assays, Transwell assays, wound healing assays and animal experiments. We used high-throughput sequencing to confirm the existence of lncRNA-C5ORF42-5 and quantitative real-time PCR was used to evaluate lncRNA expression. Then, with RNA-seq sequencing as well as GO function and KEGG enrichment analysis, we identified the signaling pathways in which lncRNA-C5ORF42-5 was involved in gastric cancer. Finally, western blotting was used to identify the genes regulated by lncRNA-C5ORF42-5.Results: Our results showed that CDK10 is expressed at relatively low levels in gastric cancer cell lines and inhibits the progression of gastric cancer cells both in vitro and in vivo. Next, based on high-throughput sequencing, we identified a novel lncRNA, lncRNA-C5ORF42-5, in the stable CDK10-overexpressing cell line compared with the CDK-knockdown cell line and their controls. Additionally, we confirmed that lncRNA-C5ORF42-5 acts as an oncogene to promote metastasis in gastric cancer in vitro and in vivo. We then ascertained that lncRNA-C5ORF42-5 is a major contributor to the function of CDK10 in gastric cancer metastasis by upregulating lncRNA-C5ORF42-5 to reverse the effects of CDK10 overexpression. Finally, we explored the mechanism by which lncRNA-C5ORF42-5 overexpression affects gastric cancer cells to elucidate whether lncRNA-C5ORF42-5 may increase the activity of the SMAD pathway of BMP signaling and promote the expression of EMT-related proteins, such as E-cadherin. Additionally, overexpression of lncRNA-C5ORF42-5 affected the phosphorylation levels of AKT and ERK.Conclusion: Our findings suggest that CDK10 overexpression represses gastric cancer tumor progression by reducing lncRNA-C5ORF42-5 and hindering activation of the related proteins in metastatic signaling pathways, which provides new insight into developing effective therapeutic strategies in the treatment of metastatic gastric cancer.

scholarly journals Patient-derived tumor spheroid cultures as a promising tool to assist personalized therapeutic decisions in breast cancer

2021 ◽  
Author(s):  
Sarah U Hofmann ◽  
Raichel Cohen-Harazi ◽  
Yael Maizels ◽  
Igor Koman
Keyword(s):  
Breast Cancer ◽  
Treatment Plan ◽  
Statistical Significance ◽  
Breast Cancer Tissue ◽  
Cancer Tissue ◽  
Intrinsic Resistance ◽  
Significant Group ◽  
Chemotherapy Drugs ◽  
Therapeutic Decisions

Breast cancer is the most common cause of cancer related death in women. Treatment of breast cancer has many limitations including a lack of accurate biomarkers to predict success of chemotherapy and intrinsic resistance of a significant group of patients to the gold standard of therapy. Therefore, new tools are needed to provide doctors with guidance in choosing the most effective treatment plan for a particular patient and thus to increase the survival rate for breast cancer patients. Here, we present a successful method to grow in vitro spheroids from primary breast cancer tissue. Samples were received in accordance with relevant ethical guidelines and regulations. After tissue dissociation, in vitro spheroids were generated in a scaffold-free 96-well plate format. Spheroid composition was investigated by immunohistochemistry (IHC) of epithelial (Pan Cytokeratin (panCK)), stromal (Vimentin) and breast cancer-specific markers (ER, PR, HER2, GATA-3). Growth and cell viability of the spheroids were assessed upon treatment with multiple anti-cancer compounds. Students t-test and two-way ANOVA test were used to determine statistical significance. We were able to successfully grow spheroids from 27 out of 31 samples from surgical resections of breast cancer tissue from previously untreated patients. Recapitulation of the histopathology of the tissue of origin was confirmed. Furthermore, a drug panel of standard first- and second-line chemotherapy drugs used to treat breast cancer was applied to assess the viability of the patient-derived spheroids and revealed variation between samples in the response of the spheroids to different drug treatments. We investigated the feasibility and the utility of an in vitro patient-derived spheroid model for breast cancer therapy, and we conclude that spheroids serve as a highly effective platform to explore cancer therapeutics and personalized treatment efficacy. These results have significant implications for the application of this model in clinical personalized medicine.

BIOAVAILABILITY OF BERYLLIUM OXIDE PARTICLES: AN IN VITRO STUDY IN THE MURINE J774A.1 MACROPHAGE CELL LINE MODEL

2005 ◽  
Vol 31 (3) ◽  
pp. 341-360 ◽  
Author(s):  
Gregory A. Day ◽  
Mark D. Hoover ◽  
Aleksandr B. Stefaniak ◽  
Robert M. Dickerson ◽  
Eric J. Peterson ◽  
...  
Keyword(s):  
Cell Line ◽  
In Vitro Study ◽  
Beryllium Oxide ◽  
Vitro Study ◽  
Macrophage Cell Line ◽  
Macrophage Cell ◽  
Line Model ◽  
Cell Line Model ◽  
Oxide Particles
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