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#33108147   2020/10/27 To Up

Resveratrol enhances apoptosis induced by the heterocyclic aromatic amines in p53-wt LoVo cells, but not in p53-deficient HaCaT cells.

In the present study, we investigated the influence of resveratrol on PhIP treated human colon cancer cells and compared the effect to HaCaT cells considered as normal, human keratinocytes. Our results show that resveratrol decreases DNA damage in both cell types, it increases the sensitivity of LoVo cells to apoptosis and has no effect on PhIP-treated HaCaT cells. We confirm that PhIP-induced apoptosis is p53 and caspase 3/7 dependent. Interestingly, normal cells such as HaCaT, which lack functional p53 are more resistant to PhIP treatment.
Katarzyna Kuryłowicz, Agnieszka Cierniak, Ewelina Madej, Łukasz Skalniak, Agnieszka Wolnicka-Głubisz

1284 related Products with: Resveratrol enhances apoptosis induced by the heterocyclic aromatic amines in p53-wt LoVo cells, but not in p53-deficient HaCaT cells.

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#33107799   2020/10/27 To Up

Detecting Immune Response to Therapies Targeting PDL1 and BRAF by Using Ferumoxytol MRI and Macrin in Anaplastic Thyroid Cancer.

Background Anaplastic thyroid cancer (ATC) is aggressive with a poor prognosis, partly because of the immunosuppressive microenvironment created by tumor-associated macrophages (TAMs). Purpose To understand the relationship between TAM infiltration, tumor vascularization, and corresponding drug delivery by using ferumoxytol-enhanced MRI and macrin in an ATC mouse model. Materials and Methods ATC tumors were generated in 6-8-week-old female B6129SF1/J mice through intrathyroid injection to model orthotopic tumors, or intravenously to model hematogenous metastasis, and prospectively enrolled randomly into treatment cohorts ( = 94 total; August 1, 2018, to January 15, 2020). Mice were treated with vehicle or combined serine/threonine-protein kinase B-Raf (BRAF) kinase inhibitor (BRAFi) and anti-PDL1 antibody (aPDL1). A subset was cotreated with therapies, including an approximately 70-nm model drug delivery nanoparticle (DDNP) to target TAM, and an antibody-neutralizing colony stimulating factor 1 receptor (CSF1R). Imaging was performed at the macroscopic level with ferumoxytol-MRI and microscopically with macrin. Genetically engineered -null allografts were used and complemented by a GFP-transgenic derivative and human xenografts. Tumor-bearing organs were processed by using tissue clearing and imaged with confocal microscopy and MRI. Two-tailed Wilcoxon tests were used for comparison (≥five per group). Results TAM levels were higher in orthotopic thyroid tumors compared with pulmonary metastatic lesions by 79% ± 23 (standard deviation; < .001). These findings were concordant with ferumoxytol MRI, which showed 136% ± 88 higher uptake in thyroid lesions ( = .02) compared with lung lesions. BRAFi and aPDL1 combination therapy resulted in higher tumor DDNP delivery by 39% ± 14 in pulmonary lesions ( = .004). Compared with the untreated group, tumors following BRAFi, aPDL1, and CSF1R-blocking antibody combination therapy did not show greater levels of TAM or DDNP ( = .82). Conclusion In a mouse model of anaplastic thyroid cancer, ferumoxytol MRI showed 136% ± 88 greater uptake in orthotopic thyroid tumors compared with pulmonary lesions, which reflected high vascularization and greater tumor-associated macrophage (TAM) levels. Serine/threonine-protein kinase B-Raf inhibitor and anti-programmed death ligand 1 antibody elicited higher local TAM levels and 43% ± 20 greater therapeutic nanoparticle delivery but not higher vascularization in pulmonary tumors. © RSNA, 2020 See also the editorial by Luker in this issue.
Thomas S C Ng, Viswanath Gunda, Ran Li, Mark Prytyskach, Yoshiko Iwamoto, Rainer H Kohler, Sareh Parangi, Ralph Weissleder, Miles A Miller

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#33106151   2020/10/26 To Up

The Evaluation of Effect of Aurora Kinase Inhibitor CCT137690 in Melanoma and Melanoma Cancer Stem Cell.

Dysregulation of the cell cycle is one of the main causes of melanomagenesis. Genome-wide studies showed that expression of Aurora -A and -B significantly has been upregulated in melanoma. However, there is no FDA approved drug targeting aurora kinases in the treatment of melanoma. In addition, the development of resistance to chemotherapeutic agents in the treatment of melanoma and, as a result, the relapse due to heterogeneous cell groups in patients is a second phenomenon that causes treatment failure. Therefore, there is an urgent need for therapeutic alternatives targeting both melanoma and melanoma cancer stem cells (MCSCs) in treatments. At this stage, cell cycle regulators become promising targets.
Fatma Sogutlu, Cagla Kayabasi, Besra Ozmen Yelken, Aycan Asik, Roya Gasimli, Sezgi Kipcak, Sunde Yılmaz Susluer, Cigir Biray Avci, Cumhur Gunduz

2428 related Products with: The Evaluation of Effect of Aurora Kinase Inhibitor CCT137690 in Melanoma and Melanoma Cancer Stem Cell.

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#33105843   2020/10/22 To Up

Gastrointestinal Nematode-Derived Antigens Alter Colorectal Cancer Cell Proliferation and Migration through Regulation of Cell Cycle and Epithelial-Mesenchymal Transition Proteins.

As the global incidences of colorectal cancer rises, there is a growing importance in understanding the interaction between external factors, such as common infections, on the initiation and progression of this disease. While certain helminth infections have been shown to alter the severity and risk of developing colitis-associated colorectal cancer, whether these parasites can directly affect colorectal cancer progression is unknown. Here, we made use of murine and human colorectal cancer cell lines to demonstrate that exposure to antigens derived from the gastrointestinal nematode significantly reduced colorectal cancer cell proliferation in vitro. Using a range of approaches, we demonstrate that antigen-dependent reductions in cancer cell proliferation and viability are associated with increased expression of the critical cell cycle regulators p53 and p21. Interestingly, -derived antigens significantly increased murine colorectal cancer cell migration, which was associated with an increased expression of the adherens junction protein β-catenin, whereas the opposite was true for human colorectal cancer cells. Together, these findings demonstrate that antigens derived from a gastrointestinal nematode can significantly alter colorectal cancer cell behavior. Further in-depth analysis may reveal novel candidates for targeting and treating late-stage cancer.
Brittany-Amber Jacobs, Sharon Prince, Katherine Ann Smith

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#33105719   2020/10/22 To Up

Curcumin's Beneficial Effects on Neuroblastoma: Mechanisms, Challenges, and Potential Solutions.

Curcumin, a natural polyphenolic compound derived from the South Asian turmeric plant (), has well-characterized antioxidant, anti-inflammatory, anti-protein-aggregate, and anticancer properties. Neuroblastoma (NB) is a cancer of the nervous system that arises primarily in pediatric patients. In order to reduce the multiple disadvantages and side effects of conventional oncologic modalities and to potentially overcome cancer drug resistance, natural substances such as curcumin are examined as complementary and supportive therapies against NB. In NB cell lines, curcumin by itself promotes apoptosis and cell cycle arrest through the suppression of serine-threonine kinase Akt and nuclear factor kappa of activated B-cells (NF-κB) signaling, induction of mitochondrial dysfunction, and upregulation of p53 and caspase signaling. While curcumin demonstrates anti-NB efficacy in vitro, cross-validation between NB cell types is currently lacking for many of its specific mechanistic activities. Furthermore, curcumin's low bioavailability by oral administration, poor absorption, and relative insolubility in water pose challenges to its clinical introduction. Numerous curcumin formulations, including nanoparticles, nanocarriers, and microemulsions, have been developed, with these having some success in the treatment of NB. In the future, standardization and further basic and preclinical trials will be required to ensure the safety of curcumin formulations. While the administration of curcumin is clinically safe even at high doses, clinical trials are necessary to substantiate the practical efficacy of curcumin in the prevention and treatment of NB.
Kevin Zhai, Aranka Brockmüller, Peter Kubatka, Mehdi Shakibaei, Dietrich Büsselberg

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#33105449   2020/10/23 To Up

Diagnostic Criteria for Differentiated Vulvar Intraepithelial Neoplasia and Vulvar Aberrant Maturation.

The aim of the study was to describe the features required for diagnosis of differentiated vulvar intraepithelial neoplasia (dVIN) and vulvar aberrant maturation (VAM).
Debra S Heller, Tania Day, Jill I Allbritton, James Scurry, Gianluigi Radici, Kathryn Welch, Mario Preti,

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#33104965   2020/10/26 To Up

Integrated Microarray to Identify the Hub miRNAs and Constructed miRNA-mRNA Network in Neuroblastoma Via Bioinformatics Analysis.

Neuroblastomas (NB) are childhood malignant tumors originating in the sympathetic nervous system. MicroRNAs (miRNAs) play an essential regulatory role in tumorigenesis and development. In this study, NB miRNA and mRNA expression profile data in the Gene Expression Omnibus database were used to screen for differentially expressed miRNAs (DEMs) and genes (DEGs). We used the miRTarBase and miRSystem databases to predict the target genes of the DEMs, and we selected target genes that overlapped with the DEGs as candidate genes for further study. Annotations, visualization, and the DAVID database were used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis on the candidate genes. Additionally, the protein-protein interaction (PPI) network and miRNA-mRNA regulatory network were constructed and visualized using the STRING database and Cytoscape, and the hub modules were analyzed for function and pathway enrichment using the DAVID database and BiNGO plug-in. 107 DEMs and 1139 DEGs were identified from the miRNA and mRNA chips, respectively. 4390 overlapping target genes were identified using the two databases, and 405 candidate genes which intersected with the DEGs were selected. These candidate genes were enriched in 363 GO terms and 24 KEGG pathways. By constructing a PPI network and a miRNA-mRNA regulatory network, three hub miRNAs (hsa-miR-30e-5p, hsa-miR-15a, and hsa-miR-16) were identified. The target genes of the hub miRNAs were significantly enriched in the following pathways: microRNAs in cancer, the PI3K-Akt signaling pathway, pathways in cancer, the p53 signaling pathway, and the cell cycle. In summary, our results have identified candidate genes and pathways related to the underlying molecular mechanism of NB. These findings provide a new perspective for NB research and treatment.
Bo Chen, Zhongyan Hua, Xiuni Qin, Zhijie Li

1280 related Products with: Integrated Microarray to Identify the Hub miRNAs and Constructed miRNA-mRNA Network in Neuroblastoma Via Bioinformatics Analysis.

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