Under normal physiological conditions, IGF-1 (insulin-like growth factor-1) has important biological effects. However, many studies have found that IGF-1 is closely related to the occurrence and ...development of breast cancer. But up to now, the cellular properties of IGF-1 have not been systematically explored in breast cancer cell. It is well-known that the cellular properties and behaviors of IGF-1/IGF-1R are closely related to its biological functions. In the current study, we used the breast cancer cell line as a model to explore the biological characteristics of IGF-1/IGF-1R, and found that IGF-1/IGF-1R can be internalized into the cytoplasm. In addition, we also found that IGF-1R can also enter cell nuclei under the mediation of IGF-1. Further research found that the nuclear-localized IGF-1R has important potential biological effects, which is closely associated to the proliferation of breast cancer cell, this may be achieved by regulating IGF-1R-mediated intracellular signaling. The current research has laid the foundation for investigating the relationship between IGF-1/IGF-1R system and the occurrence and development of breast cancer.
We aimed to conduct a meta-analysis to accurately evaluate the potential association between ADIPOQ rs2241766 gene SNP and breast cancer risk. A systematic literature search on Cochrane Library, ...PubMed, Embase, Web of Science and China National Knowledge Infrastructure (CNKI) identified 8 articles with 1692 cases and 1890 controls. Strength of association was evaluated by pooled odds ratio (OR), 95 % confidence interval (CI) and p value. Funnel plots and Begger's regression test were applied for testing the publication bias. Statistical analysis of all data was performed by Stata 12.0. The meta-analysis results indicated that the ADIPOQ rs2241766 gene polymorphism did not significantly associated with the risk of breast cancer for these genetic models (TT vs. TG + GG: OR = 1.20, 95 % CI = 0.77-1.89, p=0.417; TT + TG vs. GG: OR = 1.05, 95 % CI = 0.71-1.56, p=0.805; T vs. G: OR =1.17, 95 % CI = 0.79-1.74, p=0.437). This study indicated that no significant relationship between the ADIPOQ rs2241766 SNP and breast cancer. Further large-scale and well-designed studies will be indispensable to confirm our result.
Hydroxycamptothecin (HCPT) has antitumor activity in various cancers, but its poor bioavailability and efflux limit its clinical application. Verapamil has been demonstrated to improve the ...bioavailability of many drugs. However, the effect of verapamil on the pharmacokinetics of HCPT was not clear.
The effect of verapamil on the pharmacokinetics of HCPT was investigated to clarify the drug-drug interaction between HCPT and verapamil.
The pharmacokinetic profiles of oral administration of HCPT (50 mg/kg) in two group of Sprague-Dawley rats (six rats each), with pre-treatment of verapamil (10 mg/kg/day) for 7 days were investigated, with the group without verapamil pre-treatment as control. Additionally, the metabolic stability and transport of HCPT in the presence or absence of verapamil were also investigated with the employment of the rat liver microsomes and Caco-2 cell transwell model.
Verapamil significantly increased the peak plasma concentration (from 91.97 ± 11.30 to 125.30 ± 13.50 ng/mL), and decrease the oral clearance (from 63.85 ± 10.79 to 32.95 ± 6.17 L/h/kg). The intrinsic clearance rate was also significantly decreased (from 39.49 ± 0.42 to 28.64 ± 0.30 μL/min/mg protein) by the preincubation of verapamil. The results of Caco-2 cell transwell experiments showed the efflux of HCPT was inhibited by verapamil, as the efflux ratio decreased from 1.82 to 1.21.
The system exposure of HCPT was increased by verapamil. Verapamil may exert this effect through inhibiting the activity of CYP3A4 or P-gp, which are related to the metabolism and transport of HCPT.
An as-synthesized Eu(III) complex, denoted as Eu(N-DPNQ)(TTD)
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, was prepared and characterized, and the antenna mechanism between these ligands and central metal emitter was studied. Here DPNQ ...means 10-ethyl-10H-indolo 2′,3':5,6pyrazino2,3-f1,10phenanthroline and TTD is 4,4,4-trifluoro-1-(thiophen-2-yl)butane-1,3-dione. We find that Eu(N-DPNQ)(TTD)
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emission intensity dependents on oxygen concentration, and O
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-sensing skill of Eu(N-DPNQ)(TTD)
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in polymer composite nanofibers of poly (vinylpyrrolidone) (PVP) prepared by electrospinning is investigated. Results reveal that the emission quenching of Eu(N-DPNQ)(TTD)
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is caused by the ground state (triplet) oxygen quenching on antenna ligands triplet state. The Eu(N-DPNQ)(TTD)
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doped composite nanofiber with a loading level of 6 wt% exhibits the best result with sensitivity of 2.43 and response time of 10 s, along with linear response.
Aims Breast cancer (BC) is the most frequently diagnosed cancer, ranking sixth as the cause of death among females in China. Zinc finger HIT-type containing 1 (Znhit1) is a pivotal factor for ...inhibition of gene mutation and cell proliferation. Due to the unknown function of Znhit1 in cancers, we aimed to explore the role of Znhit1 in BC as well as the underlying mechanisms. Main methods Znhit1 expression in clinical specimens and cell lines of BC was measured by quantitative reverse transcription PCR and Western blot analysis. Then, the effects of Znhit1 overexpression on cell proliferation, apoptosis and invasion of BC cells as well as in vivo tumor growth were assessed. The interactions among Znhit1, PTEN and the downstream PI3K/Akt/mTOR pathway were evaluated by Western blot analysis. Finally, the role of Znhit1 in prognosis was analyzed in clinical specimens. Key findings Znhit1 was down-regulated in BC cell lines and clinical specimens. Znhit1 overexpression induced apoptosis and repressed proliferation and invasion of BC cells. Moreover, Znhit1 overexpression induced cell cycle arrest at G0/G1 stage. In vivo data showed that Znhit1 overexpression inhibited BC tumor growth in mice. Further experiments showed Znhit1 affected BC through up-regulating PTEN, along with inactivation of the PI3K/Akt/mTOR pathway. We finally proved that high expression of Znhit1 indicated improved prognosis. Significance Znhit1 overexpression inhibited BC tumorigenesis possibly through PTEN-mediated inactivation of the PI3K/Akt/mTOR pathway. Additionally, high expression of Znhit1 indicated improved prognosis.
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•four anthracene-derived dyes were synthesized for Cu2+-assisted CO sensing.•The quenching mechanism was a static one by forming a non-fluorescent complex with Cu2+.•Such quenching ...effect could be reversed by CO, showing recovered fluorescence.•These dyes were explored for cellular endogenous CO imaging.
Endogenous CO acts as an important messenger for signal transduction and therapeutic effect in the human body. Fluorescent imaging appears to be a promising method for endogenous CO recognition, but traditional luminescent probes based on Pd-complexes suffered from defects of high cost. In this work, four anthracene-derived dyes having an = N—N = group were synthesized for Cu2+-assisted CO sensing. Their molecular structure, photophysical performance and spectral response to Cu2+ and CO were analyzed in detail. The optimal probe showed good selectivity and quenching effect to Cu2+, with PLQY (photoluminescence quantum yield) decreased from 0.33 to 0.04. The quenching mechanism was found as a static quenching mechanism by forming a non-fluorescent complex with Cu2+ (stoichiometric ratio = 1:1), as revealed by single crystal, EPR (electron paramagnetic resonance), and XPS (X-ray photoelectron spectroscopy) analysis. Such quenching effect could be reversed by CO, showing recovered fluorescence, with PLQY recovered to 0.32 within 328 s. Discussion on cellular endogenous CO imaging was included as well.
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal).
This article has been retracted at the ...request of the Editor-in-Chief.
Given the comments regarding this article “This paper belongs to a set of over 400 papers (as per February 2020) that share very similar Western blots with tadpole-like shaped bands, the same background pattern, and striking similarities in title structures, paper layout, bar graph design, and - in a subset - flow cytometry panels”, the journal requested the authors to provide the raw data. However, the authors were not able to fulfil this request and therefore the Editor-in-Chief decided to retract the article.
Summary
Cancer immunotherapy has been increasingly applied in the treatment of advanced malignancies. Consequently, immune checkpoints have become a major concern. As PD‐1 is an important ...immunomodulatory protein, the blockade of PD‐1 and its ligand PD‐L1 is a promising tumour immunotherapy for human carcinoma. In this review, we first discuss the role of the PD‐1/PD‐L1 interaction in gastrointestinal tract cancers. Targeting PD‐1 and PD‐L1 in immune cells and tumour cells may show remarkable efficiency in gastrointestinal tract cancers. Second, the PD‐1/PD‐L1‐associated signalling pathway involved in cancer immunotherapy in gastrointestinal tract cancers is discussed. Most importantly, this review summarizes the PD‐1/PD‐L1‐targeted immunotherapy combinations with relevant signalling pathways, which may result in a breakthrough for the treatment of gastrointestinal tract cancers, such as gastric cancer, colorectal cancer and liver cancer. Meanwhile, the review provides a deeper insight into the mechanism of checkpoint blockade immunotherapies.
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