JOURNAL OF SEPARATION SCIENCE
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2021
·Vol. 44
·期 21
·3914-3923
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IF 3.645
Zhao-Yang Wang,Hai-Long Wu,Yue-Yue Chang,Tong Wang,Wei Chen,Gao-Yan Tong,Ru-Qin Yu
An intelligent chemometric second-order calibration method called alternating trilinear decomposition- assisted multivariate curve resolution combined with high-performance liquid chromatography–diode array detection was used for the simultaneous quantification of nine tyrosine kinase inhibitors in three complex biological systems. The method allows simultaneous quantification of the components in different biological matrices without the need for cumbersome pre-treatment steps, complex elution conditions, and complete peak separation. Even with the varying time shift, severe peak overlap, and various unknown interferences, the proposed method can extract pure chromatographic and spectroscopic information for each analyte, while providing accurate qualitative and quantitative results of nine common tyrosine kinase inhibitors in three different biological matrices. All the drugs were eluted in 7 min. The results showed that the nine drugs in each matrix showed good linearity ( r > 0.984) in the calibration range with a root mean square error of calibration less than 0.9 μg/mL. The average spiked recoveries of the target analytes were all in the range of 83.4–110.0%, with standard deviations less than 9.0%. Finally, the classical method was used to validate the proposed method. In comparison to the traditional method, the proposed strategy is accuracy, simultaneous, and interference-free.
研究领域:
分析化学
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药物分析
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生物医学
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2022
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IF 5.999
Jianbo Lin,Rujie Zheng,Liping Huang,Yuanrong Tu,Xu Li,Jianfeng Chen
Molecularly targeted drugs are flourishing in the clinical treatment of non-small cell lung cancer (NSCLC). However, the treatment of a single drug (such as Gefitinib (Geb)) had defects such as poor pharmacokinetics , insufficient drug delivery, and considerable toxic side effects, which greatly affect its therapeutic efficacy against NSCLC. To solve these issues, this study developed a new nanocomposite heterogeneous platform (MSNs@Ag@Geb-FA) that combined photothermal therapy and molecular targeted therapy. The high specific surface area empowered mesoporous silicon dioxide (SiO 2 ) heterostructure the ability to efficiently load Ag photothermal agents and anti-tumor drug Geb. Meanwhile, a favorable pH response (degradation of residual MnO 2 ) achieved the controlled release of Ag and Geb. Besides, the targeting and endocytosis properties of nano drugs were greatly improved through the modification of folic acid (FA). Both in vivo and in vitro experiments authenticated that this nanocomposite heterogeneous platform could effectively integrate the multiple tumor suppressor properties of Ag nanoparticles and cooperate with Geb to hasten A549 cell apoptosis, thereby achieving a favorable anti-tumor effect. This heterogeneous structure of the nanocomposite heterogeneous platform could provide an effective strategy for the treatment of NSCLC.
研究领域:
纳米技术
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药学
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癌症研究
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生物医学工程
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DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
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2023
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IF 4.1
Hao Chi,Sheng Tian,Xiu Li,Yuchu Chen,Qiumin Xu,Qixiao Wang,Wenwan Shi,Michael Adu-Frimpong,Shanshan Tong
In order to improve the separation process of affinity chromatography that has silica as the main carrier material, we sought to construct Lipid [email protected] 4B affinity chromatography model. We extracted the lipid rafts from U251 cells with a descaler method and sucrose density gradient centrifugation. Afterwards, it was discovered via immunofluorescence that the lipid rafts contain a large amount of tropomyosin-related kinase A (TrkA) protein. Also, agarose powder in the lyophilised state was pretreated, before the lipid rafts were coupled to the agarose gel in a coupling buffer of alkaline pH. CNBr-Sepharose 4B affinity gel packing was characterised using UV spectrophotometric, immunofluorescence and scanning electron microscopic techniques, wherein and the results showed that the lipid rafts were successfully coupled to the agarose gels. Three compounds were used to verify the specific sorption of Sepharose 4B and CNBr-Sepharose 4B, which showed no specific sorption on the materials. Of note, the prepared Lipid [email protected] 4B agarose gels packed with TrkA-rich target proteins could be successfully validated for the active drug gefitinib with high affinity sorption efficiency and eluted with good recovery and reproducibility. This study broadens the range of affinity chromatography carrier materials and provides a reference for research in active drug screening.
研究领域:
生物化学
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药学
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生物技术
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分析化学
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产品关联
DOI
PubMed
高影响因子
OncoTargets and Therapy
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2023
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IF 4
Zhenzhen Pan,Qiufang Chen,Xiulan Zheng,Kai Wang,Yalei Duan,Kang Xiao,Zhirong Jia,Xuansheng Ding
Background Although gefitinib brings about tremendous advances in the treatment of non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations, most of patients become incurable due to drug resistance. JuBei oral liquid (JB) has been widely used to treat pneumonia in clinic. Components of JB were reported to induce apoptosis in NSCLC, which indicated that JB could be a potential antitumor agent for NSCLC patients. In this study, we investigated the effect of JB on gefitinib-sensitive PC-9 and gefitinib-resistant PC-9/GR, H1975 cells as well as its underlying molecular mechanisms.Methods PC-9, PC-9/GR and H1975 cells were treated with JB, LY294002, SCH772984, gefitinib alone or in combination. Then, cell viability, colony formation, cell death, expression of mitochondria-dependent pathway proteins, expression of EGFR, PI3K/AKT, MAPK signal pathway proteins, Bcl-2 mitochondrial translocation, ROS generation and cell apoptosis were examined by MTT, colony forming, live/dead cell staining, Western blot, immunofluorescence and flow cytometry assay.Results Our results showed that JB significantly induced cell growth inhibition and apoptotic cell death in PC-9, PC-9/GR and H1975 cells. JB activated mitochondria-mediated apoptotic pathway through inhibiting Bcl-2 mitochondrial translocation while inducing Bax translocated into mitochondria along with accumulated ROS production, thereby increasing the release of cytochrome c, subsequently cleaving procaspase9 into cleaved-caspase9 and then cleaving procaspase3 into cleaved-caspase3. Furthermore, the employment of protein kinase inhibitors LY294002 and SCH772984 revealed that the induction of mitochondria-mediated apoptosis by JB was reliant on inactivation of PI3K/AKT and MAPK signal pathways. Moreover, JB could synergize with gefitinib to induce apoptosis in PC-9, PC-9/GR and H1975 cells.Conclusion These data indicated that JB could be a potential therapeutic agent for NSCLC patients harboring EGFR mutations as well as those under gefitinib resistance.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
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2023
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IF 10.2
Yong Huang,Yi Lin,Bowen Li,Fu Zhang,Chenyue Zhan,Xin Xie,Zhuo Yao,Chongzhi Wu,Yuan Ping,Jianliang Shen
Ferroptosis has emerged as a potent form of no-apoptotic cell death that offers a promising alternative to avoid the chemoresistance of apoptotic pathways and serves as a vulnerability of cancer. Herein, we have constructed a biomimetic self-assembly nano-prodrug system that enables the co-delivery of gefitinib (Gefi), ferrocene (Fc) and dihydroartemisinin (DHA) for the combined therapy of both ferroptosis and apoptosis. In the tumor microenvironment, this nano-prodrug is able to disassemble and trigger drug release under high levels of GSH. Interestingly, the released DHA can downregulate GPX4 level for the enhancement of intracellular ferroptosis from Fc, further executing tumor cell death with concomitant chemotherapy by Gefi. More importantly, this nano-prodrug provides highly homologous targeting ability by coating related cell membranes and exhibits outstanding inhibition of tumor growth and metastasis, as well as no noticeable side-effects during treatments. This simple small molecular self-assembled nano-prodrug provides a new reasonably designed modality for ferroptosis-combined chemotherapy.
研究领域:
肿瘤学
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药学
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纳米技术
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Mass Spectrometry and Advances in the Clinical Lab
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2023
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IF 2.2
Fangjun Chen,Wenda Chen,Zhenxin Wang,Yingfei Peng,Beili Wang,Baishen Pan,Wei Guo
Introduction Tyrosine kinase inhibitors (TKIs) are widely used in tumor treatment. The detection of these medicines by liquid chromatography-tandem mass spectrometry (LC-MS/MS) can avoid the interference of structurally similar compounds. Objectives This study aimed to develop and validate a new LC-MS/MS assay for the quantification of eight tyrosine kinase inhibitors in human plasma and to preliminarily evaluate the clinical utility of the therapeutic drug monitoring method. Methods Plasma samples were prepared by simple protein precipitation and separated using an ultra-high-performance reversed phase column. Detection was achieved using a triple quadrupole mass spectrometer in the positive ionization mode. The assay was validated against standard guidelines. We reviewed and analyzed the results of 268 plasma samples obtained from patients administered imatinib and other TKIs collected from January 2020 to November 2021 at Zhongshan Hospital. The analytes were separated and quantified within 3.5 min. Results The newly developed method demonstrated linearity for the detected drug concentration in the range of 20 to 2000 ng/ml for gefitinib (r 2 = 0.991) and crizotinib (r 2 = 0.992), 50 to 5000 ng/ml for nilotinib (r 2 = 0.991) and imatinib (r 2 = 0.995), 1500–150,000 ng/ml for vemurafenib (r 2 = 0.998), 1000–100,000 ng/ml for pazopanib (r 2 = 0.993), 0.5–100 ng/ml for axitinib (r 2 = 0.992) and 5–500 ng/ml for sunitinib (r 2 = 0.991) and N-desethyl sunitinib (r 2 = 0.998). The lower limit of quantification (LLOQ) was 20 ng/ml for gefitinib and crizotinib, 50 ng/ml for nilotinib and imatinib, 1500 ng/ml for vemurafenib, 1000 ng/ml for pazopanib, 0.5, and 5 ng/ml for sunitinib and N-desethyl sunitinib, respectively. Specificity, precision, accuracy, and stability were tested, and met the requirements of the guidelines. At the same dose, there was no significant difference in plasma drug concentration between the original imatinib medicine and the generic medicine after patent expiration. Conclusion We developed a sensitive and reliable method for the quantification of eight TKIs.
研究领域:
医学检验
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肿瘤学
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药理学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL BIOCHEMISTRY
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2023
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IF 2.9
Yao Liu,Zhichao He,Heng Liang,Minzhen Han,Jinxingyi Wang,Qian Liu,Yanping Guan
Rapidly developing UHPLC-MS/MS bioassays with high throughput and quality are challenging yet desired in routine clinics. Methods & results A high-throughput UHPLC-MS/MS bioassay has been built for simultaneously quantifying gefitinib , ruxolitinib , dasatinib , imatinib , ibrutinib , methotrexate , cyclophosphamide and paclitaxel . After the protein precipitation with methanol, samples were separated on an Acquity BEH C 18 column following a gradient elution system with methanol and 2 mM ammonium acetate in water at 40 °C with a run time of 3 min (flow rate 0.4 mL/min). Mass quantification in the positive ion SRM mode was then performed with electrospray ionization . The method of specificity, linearity, accuracy, precision, matrix effects, recovery, stability, dilution integrity and carryover were all validated as per the guideline of the China Food and Drug Administration whose values met the admissible limits. Application of the bioassay to therapeutic drug monitoring revealed important variability in the studied anti-tumour drugs. Conclusion This validated approach was shown to be reliable and effective in clinical management, being a valuable support in therapeutic drug monitoring and subsequent individualized dosing optimization.
研究领域:
药理学
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临床医学
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分析化学
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产品关联
DOI
PubMed
高影响因子
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