Experimental and Therapeutic Medicine
·
2019
·Vol. 18
·期 4
·2924-2932
·
IF 1.448
Jingjing Wang,Yongzhong Ning,Shu Li,Yun Wang,Jinhua Liang,Chunming Jin,Hairun Yan,Yongcun Huang
Acinetobacter baumannii is an important cause of hospital‑acquired, multidrug‑resistant (MDR) infections occurring worldwide. Anti‑microbial combination regimens may be the only feasible treatment option for affected patients. In the present study, the efficacy of the combined therapy of meropenem with colistin, ampicillin‑sulbactam, tazobactam and vancomycin against clinical strains of MDR A. baumannii was determined. Anti‑microbial susceptibility testing was performed and resistance genes were characterized by a multiplex polymerase chain reaction (PCR)‑reverse line blot assay. The genetic background of New Delhi metallo‑β‑lactamase 1 (NDM‑1) was analysed by primer walking. The presence of NDM‑1 was detected using the modified Hodge test and the EDTA‑combined disk test. To screen for synergistic drug effects, the fractional inhibitory concentration index was calculated using a checkerboard assay. The results of the PCR as well as the sequence analyses suggested that NDM‑1 was located downstream of the ISAba125 element. In addition, a synergistic effect was determined for meropenem + vancomycin, meropenem + tazobactam and meropenem + ampicillin + sulbactam in two strains each, and in four strains for meropenem + colistin. A total of five A. baumannii strains with resistance to numerous antibiotics and carrying numerous resistance genes were identified. In the strains of A. baumannii, the NDM‑1 gene was integrated in a transposon structure with a copy of the ISAba125 insertion sequence. However, the genetic background was not identical among the different species and strains. The genetic variability of NDM‑1 may facilitate the rapid dissemination of this gene. In conclusion, meropenem may enhance the efficacy of antibiotics in A. baumannii strains with NDM‑1‑associated MDR.
研究领域:
微生物学
·
传染病学
·
临床医学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
·
2024
·Vol. 151
·期 1
·1-11
·
IF 2.7
Lin Ruohong,Cheng Jiaxing,Zhao Jinlong,Zhou Liang,Li Jian,Yang Xinchun
Background Colorectal cancer (CRC) is the third most common cancer globally, with advanced stages presenting significant treatment challenges. Recently years, drug combination therapy has become a promising strategy for cancer treatment. Objective To evaluate the therapeutic efficacy of the combination of the anti-angiogenic drug PEP06 ( TB01) and the cytotoxic drug Trifluridine/Tipiracil (TAS-102) in human CRC HCT-116 xenograft mouse model. And quantitative assessment of the interaction between TB01 and TAS-102 in the treatment based on pharmacological effects. Methods This study utilized the human CRC HCT-116 xenograft nude mouse model to evaluate the antitumor effects of TAS-102 and TB01, both as mono-therapies and in combination therapies. Results The combination therapy not only demonstrated significantly inhibited tumor growth in a dose-dependent manner, but also seems to reduce the common toxicity associated with such treatments, as shown by the maintenance of body weights in the treated mice. Conclusion The synergistic effect observed from the combined use of TAS-102 and TB01 suggests a promising new treatment avenue for refractory CRC patients, meriting further investigation and potential clinical application.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE
·
2022
·Vol. 57
·期 13
·7056-7067
·
IF 4.682
Guan Meng,Xuan Yang,Gao Yating,Liu Yining,Zhang Shubiao
Bacterial infections are closely associated with tumor growth and metastasis. Bacteriostasis can not only inhibit the growth and metastasis of tumors during their early diagnosis and treatment but also prevent bacterial infections after recovery. In this study, we synthesized Ag@GQD which consisted of nitrogen-doped graphene quantum dots (N-GQD) wrapped around Ag NPs through the photocatalytic reduction method. Multifunctional nanoprobes (Ag/DOX@GQD) were obtained by doxorubicin (DOX) loading. Ag@GQD exhibited high stability, low cytotoxicity, and good photoacoustic imaging performance. The effective photothermal performance of Ag@GQD enabled us to achieve the controlled release of DOX from probes using near-infrared light and pH response during the treatment of tumors using chemo-photothermal combination therapy. Results from cell-based experiments revealed that combination therapy was superior to single-drug therapy. Besides, Ag@GQD could effectively kill Staphylococcus aureus and Escherichia coli and can be expected to inhibit the growth and metastasis of tumors caused by bacteria and in reducing bacterial infections after recovery.
研究领域:
生物医学工程
·
纳米医学
·
肿瘤学
·
微生物学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2014
·Vol. 2
·期 38
·6560-6570
·
IF 0
Haiqin Song,Haihua Xiao,Minhua Zheng,Ruogu Qi,Lesan Yan,Xiabin Jing
Anticancer drugs of gemcitabine and oxaliplatin combined in a clinic regimen (GEMOX regimen) were co-loaded to a biodegradable polymer platform for drug delivery.
研究领域:
药学
·
肿瘤学
✓ 已验证
DOI
PubMed
BIOMATERIALS
·
2015
·
IF 8.557
Tao Bao,Wenyan Yin,Xiaopeng Zheng,Xiao Zhang,Jie Yu,Xinghua Dong,Yuan Yong,Fuping Gao,Liang Yan,Zhanjun Gu,Yuliang Zhao
Engineering design of plasmonic nanomaterials as on-demand theranostic nanoagents with imaging, drug carrier, and photothermal therapy (PTT) functions have profound impact on treatment of cancer. Here, a facile ‘one-pot’ template-free hydrothermal route was firstly developed for synthesis of plasmonic oxygen deficiency molybdenum oxide hollow nanospheres functionalized by poly(ethylene glycol) (PEG-MoO 3–x HNSs). The as-prepared PEG-MoO 3–x HNSs not only have good biocompatibility but also exhibit obvious localized surface plasmon resonance (LSPR) absorption in the near-infrared (NIR) region. Especially, due to its intrinsic mesoporous properties and effective photothermal conversion efficiency upon 808-nm NIR laser irradiation, the PEG-MoO 3–x HNSs can be applied as a pH/NIR laser dual-responsive camptothecin (CPT) drug delivery nanoplatform for chemotherapy as well as PTT to cancer cells. A remarkably improved synergistic therapeutic effect to pancreatic (PANC-1) tumor-bearing mice was obtained compared to the result of chemotherapy or PTT alone. Apart from its application for drug delivery, the PEG-MoO 3–x HNSs can also be employed as an effective contrast nanoagent for photoacoustic (PAT) imaging because of its high NIR absorption , making it promising as a theranostic nanoagent for PAT imaging-guided chemo-photothermal combinational cancer therapy in the nanomedicine field.
研究领域:
生物医学工程
·
肿瘤治疗
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Death & Disease
·
2017
·Vol. 8
·期 10
·e3095
·
IF 5.965
Xu Junjie,Zheng Longbo,Chen Jiang,Sun Yin,Lin Hui,Jin Ren-an,Tang Minyue,Liang Xiao,Cai Xiujun
Although sorafenib is currently used as a standard treatment for advanced hepatocellular carcinoma, low response rate, transient and limited efficacy, primary and acquired resistance and negative side-effects gain increasing attentions, suggesting the need for better efficacious combination therapy. Here, we demonstrated that the sorafenib-induced or hypoxia-induced hypoxia inducible factor (HIF)-2 α could bind to an hypoxia responsive element within 500 bp region of androgen receptor (AR) promoter and thus transcriptionally suppress AR. Importantly, In vitro and In vivo studies suggested a specific and potent HIF-2 α inhibitor, PT-2385, could significantly enhance sorafenib efficacy by suppressing HIF-2 α , increasing AR and suppressing downstream pSTAT3/pAKT/pERK pathways. Clinical samples further confirmed the role of HIF-2 α and AR. It is promising that PT-2385 could alleviate the undesirable side-effects of sorafenib treatment by sorafenib-PT-2385 combination therapy, which may shed light for late-stage HCC patients.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2021
·Vol. 19
·期 1
·1-11
·
IF 10.435
Kong Hanjing,Fang Chao,Chu Qiang,Hu Zefeng,Fu Yike,Han Gaorong,Li Xiang,Zhou Yi
Nanoparticles, presenting catalytic activity to induce intracellular oxidative species, have been extensively explored for tumor treatment, but suffer daunting challenges in the limited intracellular H 2 O 2 and thus suppressed therapeutic efficacy. Here in this study, a type of composite nanoparticles, consisting CaO 2 core and Co-ferrocene shell, is designed and synthesized for combinational tumor treatment. The findings indicate that CaO 2 core can be hydrolyzed to produce large amounts of H 2 O 2 and calcium ions at the acidic tumor sites. Meanwhile, Co-ferrocene shell acts as an excellent Fenton catalyst, inducing considerable ROS generation following its reaction with H 2 O 2 . Excessive cellular oxidative stress triggers agitated calcium accumulation in addition to the calcium ions released from the particles. The combined effect of intracellular ROS and calcium overload causes significant tumor inhibition both in vitro and in vivo.
研究领域:
纳米技术
·
癌症研究
·
化学疗法
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2022
·Vol. 20
·期 1
·1-15
·
IF 9.429
Chen Sheng,Song Yonghong,Yan Xu,Dong Liang,Xu Yunjun,Xuan Shouhu,Shu Quan,Cao Baoqiang,Hu Jinlong,Xing Hanye,Wu Wenshu,Zha Zhengbao,Lu Yang
Bioactive materials have been extensively developed for the adjuvant therapy of cancer. However, few materials can meet the requirements for the postoperative resection of hepatocellular carcinoma (HCC) due to massive bleeding and high recurrence. In particular, combination therapy for HCC has been highly recommended in clinical practice, including surgical resection, interventional therapy, ablation therapy and chemotherapy. Herein, an injectable magnetic colloidal gel (MCG) was developed by controllable electrostatic attraction between clinically available magnetic montmorillonites and amphoteric gelatin nanoparticles. The optimized MCG exhibited an effective magnetic heating effect, remarkable rheological properties, and high gel network stability, realizing the synergistic treatment of postoperative HCC by stimuli-responsive drug delivery, hemostasis and magnetic hyperthermia. Furthermore, a minimal invasive MCG-induced interventional magnetic hyperthermia therapy (MHT) under ultrasound guidance was realized on hepatic tumor rabbits, providing an alternative therapeutics to treat the postoperative recurrence. Overall, MCG is a clinically available injectable formulation for adjuvant therapy after HCC surgical resection.
研究领域:
生物材料
·
肿瘤学
·
外科手术
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2019
·
IF 6.361
Yujuan Chen,Abdur Rauf Khan,Dexin Yu,Yujia Zhai,Jianbo Ji,Yikang Shi,Guangxi Zhai
Traditional cancer therapies carry a risk of serious side effects and toxicity. Developing an alternative treatment modality that is highly effective, has low toxicity and is noninvasive is urgently required. Here, we exploited molybdenum oxide (MoOx) nanosheets as a drug carrier and degradable photothermal agent to provide a chemo-photothermal combination cancer therapy. The MoOx nanosheets were synthesized by a one-pot hydrothermal method and then modified with pluronic F127 to improve physiological stability and biocompatibility. The F127-modified nanosheets (MoOX@F127) showed ultrahigh drug loading efficiency (DLE) of doxorubicin (DOX) (DLE%; 65%, W (load DOX) /[W (load DOX) + W MoOx@F127 ]), strong near-infrared (NIR) absorption and desirable pH-dependent degradability. After intravenous injection, MoOx@F127 nanosheets were degraded at physiological pH and were rapidly excreted from normal organs, while they were effectively accumulated and retained long-term in the more acidic tumor tissue. This simultaneously ensured effective tumor ablation after NIR irradiation and avoided long-term retention and toxicity in vivo . Compared to chemotherapy or photothermal therapy alone, in vitro and in vivo tumor ablation studies have shown a notably improved synergistic effect of the combination therapy. Our study presents a multifunctional nanosystem with a desirable degradability for chemo-photothermal combination cancer therapy that has great potential in biomedical applications.
研究领域:
肿瘤学
·
纳米医学
·
生物材料学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF HYPERTHERMIA
·
2024
·
IF 3
Guanghui Zi,Jin Chen,Yatu Peng,Yue Wang,Baowei Peng
Background Hyperthermia can play a synergistic role with chemotherapy in combination therapy. Although the association between caspase activation, apoptosis, and pyroptosis have been published for both cisplatin (CDDP) and hyperthermia therapies independently, the interactions between these molecular pathways in combination therapy are unknown. The present study aimed to investigate the possible interactions between caspase 8 activation, apoptosis, and pyroptosis in combination therapy.Methods Cells were treated with CDDP (15 µg/ml), followed by hyperthermia at optimized temperature (42.5 °C) in water-bath. After combination therapy, cell viability was analyzed by CCK-8, and cell death was analyzed by Annexin-V-FITC/PI and caspases activation. Immuno-staining and co-immuno-precipitation were used to examine the interaction between p62 and caspase-8. Pyroptosis was investigated by western blotting and transmission electron microscopy. E3 ligase Cullin 3 was knockdown by siRNA. In addition, caspase-8 activation was modulated by CRISPR-Cas9 gene-editing or pharmacological inhibition.Results Combination therapy promoted K63-linked polyubiquitination of caspase-8 and cellular accumulation of caspase-8. In turn, polyubiquitinated caspase-8 interacted with p62 and led to the activation of caspase-3. Knockdown of the E3 ligase Cullin 3 by siRNA reduced caspase-8 polyubiquitination and activation. In addition, combination therapy induced release of the pore-forming N-terminus from gasdermins and promoted pyroptosis along with caspase-8 accumulation and activation. Knockdown of caspase-8 by CRISPR/Cas9 based gene editing reduced the sensitivity of tumor cells to apoptosis and pyroptosis.Conclusions Our study presented a novel mechanism in which hyperthermia synergized with chemotherapy in promoting apoptosis and pyroptosis in a caspase-8 dependent manner.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2019
·
IF 4.396
Yilin Chen,Qing Chen,Qixin Zhu,Jinxue Liu,Yang Li,Xuemin Gao,Dengyue Chen,Xuan Zhu
Because of high drug payload and minimized burden of foreign materials in the course of metabolism and excretion, carrier-free nanomedicine based on self-assembly of small-molecule therapeutic agents has attracted considerable attention in cancer therapy. However, obstacles still remained, such as lack of targeting efficiency, poor physiological stability, and serious drug burst release. Herein, we developed a self-dual-targeting prodrug conjugate by coupling methotrexate (MTX) and doxorubicin (DOX) to a hyaluronic acid (HA) backbone which enveloped the small molecular drug coassemblies of DOX and indocyanine green for specific targeting and imaging-guided chemo-photothermal therapy (PTT). The constructed nanosystems exhibited a diameter of ∼200 nm, superior physiological stability, and improved photothermal effect. Taking advantage of functionality of MTX–HA–DOX conjugate, the nanosystems remarkably enhanced the accumulation in the tumor regions by enhanced penetration and retention effect and CD44/folate receptor-mediated endocytosis. Upon the stimuli of acid, the nanosystems showed the rapid disassembly followed by the accelerated drug release. Consequently, the nanosystems demonstrated highly efficient apoptosis in cancer cells and remarkable tumor ablation by synergy between chemotherapy and PTT upon the irradiation of near-infrared laser. The multifunctional nanosystems based on small molecular theranostic assemblies could provide a promising potential in developing dual-targeting drug delivery and imaging-guided combinational therapy.
研究领域:
纳米医学
·
癌症治疗
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2025
·Vol. 26
·期 5
·2193
·
IF 4.9
Yangyang Cheng,Haoyang Yu,Sitong Yang,Xiaolian Tian,Mengyu Zhao,Ling Ren,Xiuping Guo,Chujuan Hu,Jiandong Jiang,Lulu Wang
Liver fibrosis, caused by chronic hepatic injury, is a major threat to human health worldwide, as there are no specific drugs available for its treatment. Natural compounds, such as berberine (BBR) and quercetin (QR), have shown the ability to regulate energy metabolism and protect the liver without significant adverse effects. Additionally, combination therapy (the cocktail therapy approach), using multiple drugs, has shown promise in treating complicated conditions, including liver injury. In this study, we prepared a salt formulation of BBR and QR (BQS) to enhance their combined effect on liver fibrosis. The formation of BQS was confirmed using various analytical techniques, including nuclear magnetic resonance spectroscopy (NMR), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), powder X-ray diffractometry (PXRD), and scanning electron microscopy (SEM). The results demonstrated that the dissolution efficiency and bioavailability of QR significantly increased in the BQS form, aligning with that of BBR, compared to the physically mixed (BQP) form. Moreover, BQS exhibited a superior inhibitory effect on fibrosis compared to BQP in the human hepatic stellate cell line LX-2 by modulating lipid accumulation, inflammation, apoptosis, and the cell cycle. Furthermore, in a mouse model of hepatic fibrosis induced by methionine and choline-deficient (MCD) diets, BQS demonstrated enhanced anti-fibrotic activities compared to BQP. These findings suggest that BQS holds promise as a potential alternative treatment for liver fibrosis. Importantly, this study provides novel insights into achieving a cocktail effect through the salt formation of two or more drugs. The results highlight the potential of salt formulations in enhancing the therapeutic efficacy and consistent biological processes of drug combinations.
研究领域:
药理学
·
肝病学
·
药物开发
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）