Background:Radiofrequency ablation (RFA) is an effective therapy for hepatocellular carcinoma (HCC). However, incomplete radiofrequency ablation (IRFA) can promote the progression of residual cancer cells, which is a serious problem in the clinical application of RFA. Therefore, it is of great significance to explore the mechanism and countermeasures of the progression of residual tumors after IRFA. Our previous study confirmed that IRFA can activate the hypoxia/ autophagy pathway of residual tumors in mice and then induce the proliferation of residual tumor cells. Additionally, we found a metal ruthenium complex [Ru(bpy)2(ipad)](ClO4)2 (Ru, where bpy = 2,2’-bipyridine and ipad = 2-(anthracene-9,10-dione-2-yl)imidazo[4,5-f][1,10]phenanthroline) can effectively inhibit hypoxia-inducible factor (HIF-1α) and has good anti-tumor effect in a hypoxic environment; however, whether Ru could suppress the proliferation of residual tumor cells after IRFA is unknown.Objective:This study intends to evaluate the effect of Ru in suppressing the proliferation of residual hepatocellular carcinoma after IRFA in a mice model.Methods:The Hepa1-6 xenograft mouse model was established in C57BL/6 mice to simulate clinical IRFA. H&E staining was used to evaluate the biosafety of major organs in the treated mice. TUNEL assay was employed to assess the antitumor effect. Immunohistochemically and immunofluorescence staining was performed to detect the expression of HIF-1α and autophagy-related proteins. The ELISA assay was used to examine the cytokines of interferon-gamma (IFN-γ) and interleukin 10 (IL-10).Results:Our findings revealed that the residual tumor relapsed via the HIF-1α/LC3B/P62 autophagy- related pathway after IRFA, while Ru could suppress this process. In addition, it was demonstrated that Ru could effectively activate the immune system of the mice and reverse the tumor immune suppression microenvironment after IRFA.Conclusion:The ruthenium complex Ru could suppress the proliferation of residual hepatocellular carcinoma cells after IRFA in the mice model. This study introduces a novel approach that combines the use of ruthenium complexes with IRFA, offering a potential solution to address the reoccurrence of residual liver cancer following IRFA in clinical settings.

06 Jan 2020·Molecular PharmaceuticsQ2 · MEDICINE

Targeted Theranostic of Cryptococcal Encephalitis by a Novel Polypyridyl Ruthenium Complex

Q2 · MEDICINE

Article

Author: Fu, Chen ; Wang, Qinghua ; Zhao, Zizhen ; Fu, Ailing

Cryptococcus neoformans (C. neoformans) is one of the most well-known zoonotic fungal pathogens. Cryptococcal encephalitis remains a major cause of morbidity and mortality in immunocompromised hosts. Effective and targeting killing of C. neoformans in the brain is an essential approach to prevent and treat cryptococcal encephalitis. In this study, a fluorescent polypyridyl ruthenium complex RC-7, {[phen₂Ru(bpy-dinonyl)](PF₆)₂ (phen = 1,10-phenanthroline, bpy-dinonyl = 4,4'-dinonyl-2,2'-bipyridine)}, was screened out, which showed a highly fungicidal effect on C. neoformans. The values of minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) in antifungal activities were significantly lower than fluconazole as the control. Moreover, RC-7 was prepared as a brain-targeting nanoliposome (RDP-liposome; RDP is a peptide derived from rabies virus glycoprotein) for in vivo application. The results revealed that the liposomes could accumulate in the encephalitis brain and play an antifungal role. Compared with the cryptococcal encephalitis model mice, the RDP-liposomes remarkably prolonged the survival days of the encephalitis-bearing mice from 10 days to 24 days. Here, we introduce a polypyridyl ruthenium complex that could be used as a novel antifungal agent, and this study may have a broad impact on the development of targeted delivery based on ruthenium complex-loaded liposomes for theranostics of cryptococcal encephalitis.

01 Jan 2019·Bratislava Medical JournalQ4 · MEDICINE

Dinuclear ruthenium(II) Schiff base complex: a first in vivo study in Swiss albino mice

Q4 · MEDICINE

Article

Author: Kahrovic, E. ; Muzika, V. ; Custovic, S. ; Cosovic, E. ; Zahirovic, A. ; Alicelebic, S.

OBJECTIVESDinuclear ruthenium(II) Schiff base complex was selected for in vivo study among many other novel metal-based compounds, because of its previously proved in vitro anticancer and antibacterial properties. The aim was to investigate the potential toxicity of this compound in animal model through biochemical and histopathological assessment.METHODSAdult Swiss albino mice of both sexes were divided into high-dose and low-dose group that received a single intraperitoneal dose of ruthenium complex (175 mg/kg and 25 mg/kg, respectively) and one control group (vehicle only). After a follow-up period of 14 days, animals were sacrificed to obtain blood samples and organs.RESULTSThe test compound was well tolerated in a low-dose group and did not cause any mortality. The histological findings and serum biochemistry suggested a reversible character of alterations found in vital organs of this group. However, in the high-dose group, adverse effects were more severe and indicated dose and gender-related toxicity.CONCLUSIONMild side effects found in a low-dose group together with excellent in vitro properties, made dinuclear ruthenium(II) Schiff base complex a promising candidate for further investigation and development as anticancer and antimicrobial agent (Tab. 4, Fig. 6, Ref. 32).

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Triple Negative Breast Cancer	Discovery	United States	Brooklyn College	15 Jun 2022

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