Abstract 6588: Omics integration provides insight into esophageal cancer inhibitory mechanisms of a cranberry extract

2020 ◽  
Author(s):  
Katherine M. Weh ◽  
Connor L. Howard ◽  
Bridget A. Tripp ◽  
Jennifer L. Clarke ◽  
Amy B. Howell ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Omics Integration ◽  
Inhibitory Mechanisms ◽  
Insight Into

scholarly journals Downregulation of miR-135b-5p Suppresses Progression of Esophageal Cancer and Contributes to the Effect of Cisplatin

2021 ◽  
Vol 11 ◽  
Author(s):  
Yuzhu Di ◽  
Yanan Jiang ◽  
Xiuyun Shen ◽  
Jing Liu ◽  
Yang Gao ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Western Blot ◽  
Real Time ◽  
Real Time Pcr ◽  
High Morbidity ◽  
Complementary Gene ◽  
Enhanced Expression ◽  
Direct Binding ◽  
Esophageal Epithelial Cells ◽  
Insight Into

Esophageal cancer (EC) is one of the commonest human cancers, which accompany high morbidity. MicroRNAs (miRNAs) play a pivotal role in various cancers, including EC. Our research aimed to reveal the function and mechanism of miR-135b-5p. Our research identified that miR-135b-5p was elevated in EC samples from TCGA database. Correspondingly real-time PCR assay also showed the miR-135b-5p is also higher expressed in Eca109, EC9706, KYSE150 cells than normal esophageal epithelial cells (Het-1A). CCK8, Edu, wound healing, Transwell assay, and western blot demonstrated miR-135b-5p inhibition suppresses proliferation, invasion, migration and promoted the apoptosis in Eca109 and EC9706 cells. Moreover, the miR-135b-5p inhibition also inhibited xenograft lump growth. We then predicted the complementary gene of miR-135b-5p using miRTarBase, TargetScan, and DIANA-microT. TXNIP was estimated as a complementary gene for miR-135b-5p. Luciferase report assay verified the direct binding site for miR-135b-5p and TXNIP. Real-time PCR and western blot assays showed that the inhibition of miR-135b-5p remarkably enhanced the levels of TXNIP in Eca109 and EC9706 cells. Furthermore, cisplatin (cis-diamminedichloroplatinum II, DDP) decreased miR-135b-5p expression and increased TXNIP expression. Enhanced expression of miR-135b-5p attenuated the inhibitory ability of cisplatin (cis-diamminedichloroplatinum II, DDP) in Eca109 cells, accompanied by TXNIP downregulation. In conclusion, the downregulation of miR-135b-5p suppresses the progression of EC through targeting TXNIP. MiR-135b-5p/TXNIP pathway contributes to the anti-tumor effect of DDP. These findings may provide new insight into the treatment of EC.

scholarly journals Insight into Yeast–Mycotoxin Relations

Agriculture ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1291
Author(s):  
László Attila Papp ◽  
Enikő Horváth ◽  
Ferenc Peles ◽  
István Pócsi ◽  
Ida Miklós
Keyword(s):  
Secondary Metabolites ◽  
Yeast Species ◽  
Toxigenic Fungi ◽  
Toxin Binding ◽  
Inhibitory Mechanisms ◽  
Control Growth ◽  
Public Pressure ◽  
Food And Feed ◽  
Antagonistic Yeast ◽  
Insight Into

Fungal mycotoxins are secondary metabolites that can be present in green forage, hay, or silage. Consumption of contaminated plants or agricultural products can cause various animal and human diseases, which is why problems associated with mycotoxins have received particular attention. In addition, public pressure to produce healthy food and feed is also increasing. As the results of several surveys indicate that yeasts can decrease toxic effects by binding or converting secondary metabolites or control growth of harmful fungi, this article provides an overview of the yeast species that can have great potential in detoxification. The most important antagonistic yeast species against toxigenic fungi are described and the mode of their inhibitory mechanisms is also discussed. We provide an insight into toxin binding and biotransformation capacities of yeasts and examples of their use in silo. Issues requiring further study are also mentioned.

Incidence of therapy-related leukemia following chemoradiotherapy for esophageal cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15663-e15663
Author(s):  
H. Tsujimura ◽  
N. Mimura ◽  
M. Ise ◽  
C. Sakai ◽  
H. Shimada ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Late Onset ◽  
Myelogenous Leukemia ◽  
Concurrent Radiotherapy ◽  
Secondary Neoplasm ◽  
Localized Disease ◽  
Palliative Setting ◽  
Insight Into ◽  
Massive Bone

e15663 Background: The combination of chemotherapy and concurrent radiotherapy (CRT) has recognized as a curative alternative for several stage of esophageal cancer. On the other hands, a sufficiently long survival time has increased treatment-related late toxicities. However, the frequency and the pathogenesis of secondary malignancies that is the most serious late-onset complication are still unclear. Methods: From July 2000 to March 2008, 348 patients with esophageal squamous cell carcinoma underwent CRT. All patients received chemotherapy consisting with nedaplatin (80 mg/m2, div day1) and fluorouracil (700 mg/m2, ci day 1–5) and concurrent long T field irradiation (2 Gy daily, up to 30 Gy). A hundred patients received a single course as the neoadjuvant setting. Two cycles of CRT as the definitive or palliative setting were administered in 248 patients. Median and average follow-up durations are 8 and 21 months (1 to 92), respectively. Results: Four patients, who achieved CR after CRT, developed leukemia. Case1, 60-yo-male, developed overt acute myeloid leukemia (AML) from myelodysplastic syndrome 48 months after CRT. Cytogenetic analysis showed complicated abnormalities including deletion 5q. Case2, 64-yo-male, developed AML M0 with t(9;22)(q34;q11) 44 months after CRT. Case3, 72-yo-male, developed Burkitt leukemia with t(8;14)(q24;q32) 19 months after CRT. Case4, 65-yo-male, developed myeloid crisis of chronic myelogenous leukemia with complicated abnormalities including t(9;22)(q34;q11) 48 months after CRT. Case 1 and 3 had localized disease and received single course of neoadjuvant CRT. Case 2 and 4 had advance disease and received 2 courses of CRT. All patients eventually died of leukemia. Conclusions: Since platinum and fluorouracil have shown relatively low chance of secondary neoplasm, our data demonstrates that the concurrent radiotherapy which involves massive bone marrow tissue may increase the risk of leukomogenesis. To this end, atypical cytogenetic abnormalities seen in the present cases give a new insight into the biology of therapy-related leukemia. Notably, this is the first report presenting the incidence of secondary leukemia by nedaplatin. No significant financial relationships to disclose.

A Standardized Clinical Pathway Approach to Esophageal Cancer

2019 ◽  
Author(s):  
Andrea Wirsching ◽  
Donald E Low
Keyword(s):  
Esophageal Cancer ◽  
Clinical Pathway ◽  
Postoperative Morbidity ◽  
Enhanced Recovery ◽  
Clinical Pathways ◽  
Early Mobilization ◽  
Postoperative Recovery ◽  
Tumor Board ◽  
Enteral Feedings ◽  
Insight Into

Clinical pathways associated with the surgical treatment of esophageal cancer patients represent an important development to maximize the opportunity for clinical and cost efficiency in patient care. The main goals implemented in standardized clinical pathways are a comprehensive preoperative workup and tumor board presentation; anesthesia management dedicated to enable enhanced recovery and standardized steps of postoperative recovery, including early mobilization; efficient removal of tubes, catheters, and lines; and early enteral feedings. Recent studies report a decreased length of hospital and intensive care unit stay and decreased costs associated with the routine application of these pathways. Some reports have also shown a decrease in postoperative morbidity and mortality related to the implementation and refinement of standardized clinical pathways. The present review is dedicated to all aspects of standardized clinical pathways for esophagectomy and aims to give an insight into key components of the clinical pathway, which have evolved over the last 20 years at our institution.   This review contains 3 figures, 8 tables, and 33 tables. Key words: clinical pathway, costs, enhanced recovery, esophageal cancer, esophagectomy, hospital stay, implementation, length of stay, outcome, standardized pathway

Computational insight into the mechanisms of action and selectivity of Afraxis PAK inhibitors

2020 ◽  
Vol 12 (5) ◽  
pp. 367-385
Author(s):  
Di Han ◽  
Huiqun Wang ◽  
Wei Cui ◽  
Beibei Zhang ◽  
Bo-Zhen Chen
Keyword(s):  
Molecular Dynamics ◽  
Mechanisms Of Action ◽  
Structural Basis ◽  
Free Energies ◽  
Activity Data ◽  
Experimental Activity ◽  
Inhibitory Mechanisms ◽  
Dynamics Simulations ◽  
Insight Into ◽  
Binding Free Energies

Aim: The p21-activated kinases (PAKs) are involved in many important biological activity regulations. FRAX019, FRAX414, FRAX597, FRAX1036 and G-5555 were identified as PAKs inhibitors. Their detailed inhibitory mechanisms deserve further investigation. Results: Molecular dynamics simulations and further calculations for the PAK1/inhibitor and PAK4/inhibitor complexes indicate that their binding free energies are basically consistent with the trend of experimental activity data. Conclusion: The anchoring of residues Leu347PAK1 and Leu398PAK4 is the structural basis for designing Afraxis PAK inhibitors. This study discloses the inhibitory mechanisms of FRAX019, FRAX414, FRAX597, FRAX1036 and G-5555 toward PAK1 and PAK4 and some clues to enhance kinase activities and selectivities, which will provide valuable information to the development of more potent and selective PAK inhibitors.

scholarly journals Anticancer Compound Plumbagin and Its Molecular Targets: A Structural Insight into the Inhibitory Mechanisms Using Computational Approaches

PLoS ONE ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. e87309 ◽  
Author(s):  
Mohammad S. Jamal ◽  
Shadma Parveen ◽  
Mohd A. Beg ◽  
Mohd Suhail ◽  
Adeel G. A. Chaudhary ◽  
...  
Keyword(s):  
Molecular Targets ◽  
Computational Approaches ◽  
Inhibitory Mechanisms ◽  
Structural Insight ◽  
Insight Into ◽  
Anticancer Compound

scholarly journals MicroRNA provides insight into understanding esophageal cancer

2011 ◽  
Vol 2 (4) ◽  
pp. 134-142 ◽  
Author(s):  
Xiaobo Li ◽  
Caitlin Wainscott ◽  
Yaguang Xi
Keyword(s):  
Esophageal Cancer ◽  
Insight Into

scholarly journals Integrative proteogenomic characterization of early esophageal cancer

2021 ◽  
Author(s):  
Lingling Li ◽  
Dongxian Jiang ◽  
Qiao Zhang ◽  
Hui Liu ◽  
Zhaoyu Qin ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Drug Target ◽  
Poor Prognosis ◽  
Trajectory Analysis ◽  
Phosphoglycerate Kinase ◽  
Omics Data ◽  
Early Esophageal Cancer ◽  
Esophageal Carcinogenesis ◽  
Insight Into

Abstract We performed a comprehensive genomic, proteomic, and phosphoproteomic analysis of 756 trace-tumor-samples from 124 esophageal cancer (EC) patients, covering 9 major histopathological stages and 22 substages. The results revealed a significant diversity of proteome patterns in the 22 substages. The integrated multi-omics data identified genomic-proteomic aberrations revealing the association of TP53, ATM, and EP400 mutations that affected cell cycle, DNA repair, and glycolysis, with poor prognosis. Proteome-based analysis elucidated the stage-specific molecular characterization and defined the cancer-driving waves along with the mutation accumulation in esophageal carcinogenesis and progression. Furthermore, the trajectory analysis identified 6 major tracks related to different clinical features during early EC progression. Growingly enhanced and hyperphosphorylated phosphoglycerate kinase 1 (PGK1, S203) was detected and considered as a drug target in EC progression. Collectively, this study provides insight into the understanding of the molecular mechanism of EC progression and a valuable resource for the development of therapeutic targets.

scholarly journals Overexpression of FOXO3, MYD88, and GAPDH Identified by Suppression Subtractive Hybridization in Esophageal Cancer Is Associated with Autophagy

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Mohammad Soltany-Rezaee-Rad ◽  
Negar Mottaghi-Dastjerdi ◽  
Neda Setayesh ◽  
Gholamreza Roshandel ◽  
Farzaneh Ebrahimifard ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Suppression Subtractive Hybridization ◽  
Potential Role ◽  
Subtractive Hybridization ◽  
Primary Response ◽  
Clinical Samples ◽  
Forkhead Box ◽  
Cancer Tissues ◽  
Upregulated Genes ◽  
Insight Into

To find genes involved in tumorigenesis and the development of esophageal cancer, the suppression subtractive hybridization (SSH) method was used to identify genes that are overexpressed in esophageal cancer tissues compared to normal esophageal tissues. In our SSH library, the forkhead box O3 (FOXO3), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and myeloid differentiation primary response 88 (MYD88) genes were the most highly upregulated genes, and they were selected for further studies because of their potential role in the induction of autophagy. Upregulation of these genes was also observed in clinical samples using qRT-PCR. In addition, coexpression analysis of the autophagy-related genes Beclin1, ATG12, Gabarapl, PIK3C3, and LC3 demonstrated a significant correlation between the differentially overexpressed genes and autophagy. Autophagy is an important mechanism in tumorigenesis and the development of chemoresistance in cancer cells. The upregulation of FOXO3, GAPDH, and MYD88 variants in esophageal cancer suggests a role for autophagy and provides new insight into the biology of esophageal cancer. We propose that FOXO3, GAPDH, and MYD88 are novel targets for combating autophagy in esophageal cancer.

scholarly journals Conformational states dynamically populated by a kinase determine its function

Science ◽  
2020 ◽  
Vol 370 (6513) ◽  
pp. eabc2754 ◽  
Author(s):  
Tao Xie ◽  
Tamjeed Saleh ◽  
Paolo Rossi ◽  
Charalampos G. Kalodimos
Keyword(s):  
Resistance Mechanisms ◽  
Regulatory Mechanisms ◽  
Resonance Spectroscopy ◽  
Activation Loop ◽  
Structural Elements ◽  
Conformational States ◽  
Abl Kinase ◽  
Inhibitory Mechanisms ◽  
Insight Into

Protein kinases intrinsically sample a number of conformational states with distinct catalytic and binding activities. We used nuclear magnetic resonance spectroscopy to describe in atomic-level detail how Abl kinase interconverts between an active and two discrete inactive structures. Extensive differences in key structural elements between the conformational states give rise to multiple intrinsic regulatory mechanisms. The findings explain how oncogenic mutants can counteract inhibitory mechanisms to constitutively activate the kinase. Energetic dissection revealed the contributions of the activation loop, the Asp-Phe-Gly (DFG) motif, the regulatory spine, and the gatekeeper residue to kinase regulation. Characterization of the transient conformation to which the drug imatinib binds enabled the elucidation of drug-resistance mechanisms. Structural insight into inactive states highlights how they can be leveraged for the design of selective inhibitors.

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