Design, synthesis and biological evaluation of 4-aniline-thieno2,3-dpyrimidine derivatives as MNK1 inhibitors against renal cell carcinoma and nasopharyngeal carcinoma.

Design, synthesis and biological evaluation of 4-aniline-thieno[2,3-d]pyrimidine derivatives as MNK1 inhibitors against renal cell carcinoma and nasopharyngeal carcinoma. Bioorg Med Chem. 2019 Apr 17;: Authors: Zhang M, Jiang L, Tao J, Pan Z, He M, Su D, He G, Jiang Q Abstract MAP Kinase Interacting Serine/Threonine Kinase 1 (MNK1) play important roles in the signaling transduction of MAPK pathways. It is significantly overexpressed in renal clear cell carcinoma and head-neck squamous cell carcinoma tissues in both mRNA and protein levels. Based on the crystallographic structure of MNK1 protein and binding modes analysis of known MNK inhibitors, we have designed and synthesized a series of 4-aniline-thieno[2,3-d]pyrimidine derivatives as potential MNK1 inhibitors. These synthetic compounds are tested in biochemical and cell proliferation assays, and six of them display potent inhibitory capacity against MNK1 kinase and cancer cell lines. Compound 12dj with strongest inhibitory capacity is transferred to molecular mechanism studies, and the results indicated that 12dj remarkably suppresses the phosphorylation of EIF4E, a substrate of MNK1. And the expression levels of MNK1, ERK1/2 and pERK1/2 are not affected by compound 12dj incubation in SUNE-1 and 786-O cells. In summary, our works suggested that these novel 4-aniline-thieno[2,3-d]pyrimidine based MNK1 inhibitors might be attractive lead compounds for targeted therapy of renal cell carcinoma and nasoph...
Source: Bioorganic and Medicinal Chemistry - Category: Chemistry Authors: Tags: Bioorg Med Chem Source Type: research

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Conclusions: Recurrent CA-CDI in children in our population is less common than previously reported. This study supports first-line treatment with the standard, short course metronidazole in most cases of primary CA-CDI.
Source: The Pediatric Infectious Disease Journal - Category: Infectious Diseases Tags: Original Studies Source Type: research
In the print version of the article “Covered and uncovered biliary metal stents provide similar relief of biliary obstruction during neoadjuvant therapy in pancreatic cancer: a randomized trial” by Seo et al (Gastrointest Endosc 2019;90:602-12.e4), there was a typographical error in Figure 1. The complete corrected figure appea rs below.
Source: Gastrointestinal Endoscopy - Category: Gastroenterology Tags: Erratum Source Type: research
The sequence of events leading to the development of colorectal cancer, currently the third most common malignancy in Western countries, is effectively disrupted by the resection of its precursor lesions. Colonoscopy is the mainstay in lesion detection, and endoscopic polypectomy is the conventional therapeutic response for the overwhelming majority of identified polyps. Approximately 2% of lesions are larger (>20  mm) and are laterally spreading lesions (LSLs). EMR is considered the standard of care for the majority of these because it has been proved to be safer, less resource-intensive, and less expensive than surgery.
Source: Gastrointestinal Endoscopy - Category: Gastroenterology Authors: Tags: Original article Source Type: research
Endoscopic surveillance is currently recommended in patients with Barrett's esophagus (BE) to detect prevalent and incident dysplasia/esophageal adenocarcinoma. This strategy is underpinned by the concepts that (1) dysplasia can be treated endoscopically to prevent early gastric cancer (EAC),1 and (2) early-stage EAC (without symptomatic dysphagia and muscularis propria invasion) can be successfully treated (endoscopically) with excellent long-term survival.2
Source: Gastrointestinal Endoscopy - Category: Gastroenterology Authors: Tags: Original article Source Type: research
Authors: Zeng X, Liu Q, Yang Y, Jia W, Li S, He D, Ma R Abstract Placenta-specific protein 8 (PLAC8) is a conserved protein with a molecular weight of 12.5 kDa. The specific function of this protein has not been fully elucidated, however, PLAC8 has been found to play an important tumor regulatory role in certain types of cancer, including colon, pancreatic and liver cancer. PLAC8 also participates in the regulation of the cell cycle, autophagy, epithelial-mesenchymal transition and other cellular functions, indicating its potential as a molecular target worth further investigation. The present study investigated th...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Authors: Nomura M, Takahashi H, Fujii M, Miyoshi N, Haraguchi N, Hata T, Matsuda C, Yamamoto H, Mizushima T, Mori M, Doki Y Abstract The T3 subdivision has been reported to predict prognosis in rectal cancer. However, few studies describe a correlation between T3 subdivision and prognosis in colon cancer. The current study aimed validate the correlation between the invasion distance (ID) beyond the muscularis propria and prognosis in colorectal cancer. The present retrospective study included 148 consecutive patients with pathologically confirmed T3 colorectal cancer, who underwent resection between January 2008 an...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Authors: Wang Y, Zhang B, Gao G, Zhang Y, Xia Q Abstract Guanine nucleotide exchange factor T (GEFT), a member of the Rho guanine nucleotide exchange factor family, is expressed in a variety of tumors. In the present study, the expression and clinical significance of GEFT in malignant digestive tract tumors was assessed. Tumor and adjacent control samples from 180 patients were tested. Positive GEFT expression rates were 80, 83.33 and 86.67% in esophageal squamous carcinoma (ESCC), gastric carcinoma (GC) and colorectal cancer (CRC), respectively. GEFT expression was associated with diffuse type carcinoma according ...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Authors: Yuan S, Luan X, Han G, Guo K, Wang S, Zhang X Abstract It is well established that long intergenic non-protein coding RNA 1638 (LINC01638) promotes the development and progression of breast cancer, whereas its roles in other human diseases are currently unknown. In the present study, expression of LINC01638 and ROCK2 was analyzed using quantitative PCR, ELISA and western blot. Receiver operating characteristic curve was used for diagnostic analysis. Cell transfections were performed to analyze interactions between LINC01638 and ROCK2, while Transwell assays were performed to analyze invasion and migration ...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Authors: Li J, Zhang B, Bai Y, Liu Y, Zhang B, Jin J Abstract Sphingosine kinase 1 (SPHK1), an ATP-dependent protein, has previously been demonstrated to be upregulated in several types of human cancer and to play an important role in tumor development and progression. However, the role of SPHK1 in predicting long-term prognosis in patients with papillary thyroid carcinoma (PTC) remains unclear. The purpose of the present study was to assess the significance of SPHK1 expression and its associations with clinicopathological characteristics and prognostic outcome in patients with PTC. Immunohistochemistry staining wa...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
In conclusion, the DEGs and hub genes identified in the present study may be used to understand the molecular pathways involved in the initiation and progression of malignant melanoma. Furthermore, the present study may aid in the identification of possible targets for the diagnosis and treatment of melanoma. PMID: 31620197 [PubMed]
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
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