Multicentre, Randomized, Parallel, Double-Blind, Vehicle Controlled Study To Evaluate The Efficacy And Safety Of Actikerall® Solution In The Field-Directed Treatment Of Actinic Keratoses Grade I To II (Field Cancerization)

The main purpose of this vehicle-controlled study is to determine the efficacy and safety of a solution of Actikerall® (containing 5-fluorouracil 0.5% and salicylic acid 10.0%) in the field-directed treatment of grade I-II actinic keratosis, when it is applied to the affected area once daily for 12 weeks.
A secondary objective of this study is to evaluate the efficacy of Actikerall® solution on subclinical actinic keratosis lesions in a subset of patients.

开始日期2014-10-01

申办/合作机构

Almirall SA

[+1]

NCT01358851 / Completed临床2期

A Prospective Comparator Controlled Randomized Exploratory Study on the Efficacy of LAS 41005 Compared to Cryotherapy in Subjects With Hyperkeratotic Actinic Keratosis

The aim of this study is to evaluate the efficacy and safety of LAS 41005 compared to cryotherapy in subjects with moderate to severe hyperkeratotic actinic keratosis (punch biopsies).

开始日期2011-04-01

申办/合作机构

Almirall SA

EUCTR2010-022980-37-DE / Not yet recruitingN/A

A prospective comparator controlled randomized exploratory study on the efficacy of LAS 41005 compared to cryotherapy in subjects with hyperkeratotic actinic keratosis

开始日期2010-12-09

申办/合作机构

Almirall Hermal GmbH

100 项与 TYMS x COX 相关的临床结果

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100 项与 TYMS x COX 相关的转化医学

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0 项与 TYMS x COX 相关的专利（医药）

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项与 TYMS x COX 相关的文献（医药）

2022-11-01·Journal of Integrative Medicine

Analysis of mechanisms of Shenhuang Granule in treating severe COVID-19 based on network pharmacology and molecular docking

Article

作者: Yang, Hong-Qiang ; Xu, Xiang-Ru ; Wu, Xin-Xin ; Guo, Quan ; Pu, Yu-Ting ; Sun, Yu-Ting ; Zhang, Wen ; Sun, Li-Hua ; Wang, Bei ; Peng, Wei ; Fang, Bang-Jiang ; Zhou, Shuang

OBJECTIVESevere cases of coronavirus disease 2019 (COVID-19) are expected to have a worse prognosis than mild cases. Shenhuang Granule (SHG) has been shown to be a safe and effective treatment for severe COVID-19 in a previous randomized clinical trial, but the active chemical constituents and underlying mechanisms of action remain unknown. The goal of this study is to explore the chemical basis and mechanisms of SHG in the treatment of severe COVID-19, using network pharmacology.METHODSUltra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was employed to screen chemical constituents of SHG. Putative therapeutic targets were predicted by searching traditional Chinese medicine system pharmacology database and analysis platform, SwissTargetPrediction, and Gene Expression Omnibus (GEO) databases. The target protein-protein interaction network and enrichment analysis were performed to investigate the hub genes and presumptive mechanisms. Molecular docking and molecular dynamics simulations were used to verify the stability and interaction between the key chemical constituents of SHG and COVID-19 protein targets.RESULTSForty-five chemical constituents of SHG were identified along with 131 corresponding therapeutic targets, including hub genes such as HSP90AA1, MMP9, CXCL8, PTGS2, IFNG, DNMT1, TYMS, MDM2, HDAC3 and ABCB1. Functional enrichment analysis indicated that SHG mainly acted on the neuroactive ligand-receptor interaction, calcium signaling pathway and cAMP signaling pathway. Molecular docking showed that the key constituents had a good affinity with the severe acute respiratory syndrome coronavirus 2 protein targets. Molecular dynamics simulations indicated that ginsenoside Rg4 formed a stable protein-ligand complex with helicase.CONCLUSIONMultiple components of SHG regulated multiple targets to inhibit virus invasion and cytokine storm through several signaling pathways; this provides a scientific basis for clinical applications and further experiments.

2021-01-01·Epigenetics Insights

The Clinical Significance of Promoter Methylation of Fluoropyrimidine Metabolizing and Cyclooxygenase Genes in Colorectal Cancer

Article

作者: Salem, Salem Eid ; Zekri, Abdelrahman N. ; Shouman, Samia A. ; Hussien, Marwa M. ; Fouad, Mariam Ahmed ; Badr, Doaa Mohamed ; Hafez, Hafez Farouk

Aims: This study investigated the impact of promoter methylation of flouropyrimidine (FP) metabolizing and cyclooxygenase 2 (COX2) genes on their mRNA expression and on the clinical outcome of colorectal cancer (CRC) patients. Methods: Methylation specific-PCR and real time-PCR of thymidylate synthase (TS), thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD) and COX2 were performed at baseline and after 3 and 6 months of FP therapy. Pairwise comparisons were conducted between the subgroups of CRC patients. The event free survival (EFS) and the hazard of progression were estimated by univariate and multivariate analyses. Results: At baseline CRC patients, both TS and TP were overexpressed, in spite of the unmethylation of TS and the full methylation of TP genes. Significant downexpression of DPD and COX2 were associated their promoter’s methylation. At the end of FP therapy, TS, DPD and COX2 were overexpressed by 7.52, 2.88 and 3.45 folds, respectively, while TP was downexpressed by 0.54 fold. However, no change was observed in the methylation status of genes with FP therapy. Pairwise comparisons revealed significant difference in the expression and the methylation status of genes according to the clinicopathological characters of CRC patients either at baseline or after FP therapy. The overexpression of DPD and COX2 genes were indicators for a poor EFS of CRC patients. Also, the high level of COX2 expression was found to be significantly correlated with the hazard of progression (HR = 1.73, 95% CI = 1.02-3.03). Conclusion: The promoter methylation of FP metabolizing and COX2 genes has significant impact on the expression and the treatment outcome of CRC patients.

2017-08-01·EBioMedicine1区 · 医学

Prognostic and Predictive Value of p21-activated Kinase 6 Associated Support Vector Machine Classifier in Gastric Cancer Treated by 5-fluorouracil/Oxaliplatin Chemotherapy

1区 · 医学

ArticleOA

作者: Zhen Han ; Xiaolong Qi ; Wei Liu ; Liying Zhao ; Yuming Jiang ; Yanfeng Hu ; Hao Liu ; Lei Huang ; Yajia Wen ; Sile Chen ; Shirong Cai ; Tuanjie Li ; Yang Yang ; Jiang Yu ; Sujuan Xi ; Guoxin Li ; Xiaohui Huang ; Cuicui Xiao

To determine whether p21-activated Kinase (PAK) 6 is a prognostic and predictive marker in gastric cancer (GC) and to construct a classifier that can identify a subset of patients who are highly sensitive to 5-fluorouracil/oxaliplatin chemotherapy. We retrospectively analyzed the expression levels of PAK6, cyclooxygenase 2, p21^WAF1, Ki-67, excision repair cross-complementing gene 1, and thymidylate synthase in 242 paraffin-embedded GC specimens of the training cohort by immunohistochemistry. Then, we used support vector machine (SVM)-based methods to develop a predictive classifier for chemotherapy (chemotherapy score - CS-SVM classifier). Further validation was performed in an independent cohort of 279 patients. High PAK6 expression was associated with poor prognosis and increased chemoresistance to 5-FU/oxaliplatin chemotherapy. The CS-SVM classifier distinguished patients with stage II and III GC into low- and high-CS-SVM groups, with significant differences in the 5-year disease-free survival (DFS) and overall survival (OS) in chemotherapy patients. Moreover, chemotherapy significantly prolonged the DFS and OS of the high CS-SVM patients in the training and validation cohorts. In conclusion, PAK6 was an independent prognostic factor and increased chemoresistance. The CS-SVM classifier distinguished a subgroup of stage II and III patients who would highly benefit from chemotherapy, thus facilitating patient counseling and individualizing the management.