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The Chinese-German Journal of Clinical Oncology 2005年第2期4卷 83-85页

作者：张振蔚张雪梅吴华赵明鲜于志群周健赖世英武汉华中科技大学同济医学院附属同济医院核医学科 430030

To establish a method to evaluate the effects of chemosensitizer onP-glycoprotein using ^(99m)Tc-MIBI, and observe the changes of ^(99m)Tc-MIBI uptake kinetics andP-glycoprotein levels after using verapamil in MDR human breast cells MCF-7/Adr. Methods: MDR breastcarcinoma cells, MCF-7/Adr, were incubated and different protocols were performed. Protocol Ⅰ: achemosensitizer, verapamil (10 μmol/L), was added into cell culture medium, while in control group,the same volume of DMEM was given. Cells were harvested after 2 h incubation with ^(99m)*** Ⅱ: Verapamil (10 μmol/L) was added into cell culture medium and incubated for 20 min, 40min, 60 min, 80 min, 8 h, 24 h, 48 h and 72 h respectively. Cells were harvested after 2 hincubation with ^(99m)Tc-MIBI. The radioactivity of the cells was measured and P-glycoproteinexpression levels were determined with immunohistochemical stain. Results: Protocol Ⅰ: After 2hincubation with verapamil the cellular uptake of ^(99m)Tc-MIBI was remarkably higher than controlgroup (t=2.33, P 0.05). Protocol Ⅱ: In verapamil group, ^(99m)Tc-MIBI uptake was increased withincubation time prolonging (F=58.2, P 0.05). Conclusion: ^(99m)Tc-MIBImay be used to evaluate the qualitative as well as quantitative change of P-glycoprotein expressionlevels induced by the chemosensitizer, verapamil.

关键词： multidrug resistance chemosensitizer breast tumor P-glycoprotein ^(99m)Tc-MIBI

γ-生育三烯酚可能用做新型胃癌化疗增敏剂(英文)

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中国药理学与毒理学杂志 2015年第S1期29卷 11-12页

作者： GautamSETHI Department of Pharmacology Yong Loo Lin School of Medicine Cancer Science Institute of Singapore National University of Singapore Singapore 117957

Gamma-tocotrienol,a member of vitamin E superfamily has attracted great attention of late for its anti-proliferative and anti-carcinogenic potential against different *** example,our group had previously reported that anti-proliferative and chemosensitizing effects ofγ-tocotrienol are associated with its ability to suppress activation of signal transducers and activator of transcription 3(STAT3),apro-inflammatory transcription factor that plays a pivotal role in the survival,proliferation,angiogenesis and chemoresistance of hepatocellular ***,the potential of gamma-tocotrienol to overcome chemoresistance in gastric cancer,which is one of the deadliest cancers in Asia-pacific region,has never been explored ***,we analyzed the efficacy of gamma-tocotrienol in combination with capecitabine to modulate tumor growth and survival in gastric cancer cell lines and xenograft mouse *** proliferation and apoptosis assays indicated that gamma-tocotrienol potentiated capecitabine induced programmed cell death in various gastric cancer cell ***-tocotrienol also inhibited expression of Bcl-2,Bcl-xL,cyclin-D1,COX-2,ICAM-1,VEGF,CXCR4,MMP-9 proteins,induced PARP cleavage and inhibited constitutive and capecitabine-induced NF-κB activation in gastric cancer *** vivo studies using xenograft model of human gastric cancer demonstrated that gamma-tocotrienol alone suppressed tumor growth and this effect was further potentiated in conjunction with *** the markers of proliferation index Ki-67 and the micro vessel density CD31 were significantly downregulated in tumor tissues by the combination of capecitabine and *** compared to the vehicle control,gamma-tocotrienol further suppressed the NF-κB activation and expression of cyclin D1,COX-2,ICAM-1,MMP-9 and survivin in tumor tissues obtained from treatment *** our results suggest for the first time that gamma-tocotrienol can potentiate the effects of

关键词： gastric cancer gamma-tocotrienol chemosensitizer

Targeting lncRNA16 by GalNAc-siRNA conjugates facilitates chemotherapeutic sensibilization via the HBB/NDUFAF5/ROS pathway

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Science China(Life Sciences) 2024年第4期67卷 663-679页

作者： Yanfang Liu Yan Wang Bing Liu Wenzhong Liu Yuanyuan Ma Yiren Cao Shi Yan Panpan Zhang Lixin Zhou Qimin Zhan Nan Wu Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Thoracic Surgery IIPeking University Cancer Hospital and InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Laboratory of Molecular OncologyPeking University Cancer Hospital and InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Thoracic Oncology IIPeking University Cancer Hospital and InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Department of PathologyPeking University Cancer Hospital and InstituteBeijing 100142China Peking University International Cancer Institute Beijing 100191China Institute of Cancer Research Shenzhen Bay LaboratoryShenzhen 518132China

Chemoresistance is a significant barrier to effective cancer *** mechanisms for chemoresistance include reactive oxygen species(ROS)accumulation and expression of chemoresistance-promoting ***,we report a novel function of lncRNA16 in the inhibition of ROS generation and the progression of *** analyzing the serum levels of lncRNA16 in a cohort of 35 patients with non-small cell lung cancer(NSCLC)and paired serum samples pre-and post-treatment from 10 NSCLC patients receiving neoadjuvant platinum-based chemotherapy,performing immunohistochemistry(IHC)assays on 188 NSCLC tumor samples,using comprehensive identification of RNA-binding proteins by mass spectrometry(ChIRP-MS)assays,as well as RNA immunoprecipitation(RIP)and RNA pull-down analyses,we discovered that patients with increased serum levels of lncRNA16 exhibited a poor response to platinum-based *** expression of hemoglobin subunit beta(HBB)and NDUFAF5 significantly increases with the development of ***16 binds to HBB and promotes HBB accumulation by inhibiting ***16 can also inhibit ROS generation via the HBB/NDUFAF5 axis and function as a scaffold to facilitate the colocalization of HBB and NDUFAF5 in the ***,preclinical studies in mouse models of chemo-resistant NSCLC have suggested that lncRNA16 targeting by trivalent N-acetylgalactosamine(GalNAc)-conjugated siRNA restores chemosensitivity and results in tumor growth inhibition with no detectable toxicity in ***,lncRNA16 is a promising therapeutic target for overcoming chemoresistance,and the combination of first-line platinum-based chemotherapy with lncRNA16 intervention can substantially enhance anti-tumor efficacy.

关键词： chemoresistance lncRNARNA interference ROs chemosensitizer

VHH212 nanobody targeting the hypoxia-inducible factor 1α suppresses angiogenesis and potentiates gemcitabine therapy in pancreatic cancer in vivo

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Cancer Biology & Medicine 2021年第3期18卷 772-787页

作者： Guangbo Kang Min Hu He Ren Jiewen Wang Xin Cheng Ruowei Li Bo Yuan Yasmine Balan Zixuan Bai He Huang Department of Biochemical Engineering School of Chemical Engineering&TechnologyTianjin UniversityTianjin 300350China Key Laboratory of Systems Bioengineering(Ministry of Education) Tianjin UniversityTianjin 300072China Department of Gastroenterology Center of Tumor Immunology and CytotherapyMedical Research Center of The Affiliated Hospital of Qingdao UniversityQingdao 266003China Department of Chemical and Biological Engineering University of OttawaOttawa KIN 6N5Canada

Objective:We aimed to develop a novel anti-HIF-1αintrabody to decrease gemcitabine resistance in pancreatic cancer ***:Surface plasmon resonance and glutathione S-transferase pull-down assays were conducted to identify the binding affinity and specificity of anti-HIF-1αVHH212[a single-domain antibody(nanobody)].Molecular dynamics simulation was used to determine the protein-protein interactions between hypoxia-inducible factor-1α(HIF-1α)and *** real-time polymerase chain reaction(PCR)and Western blot analyses were performed to identify the expressions of HIF-1αand VEGF-A in pancreatic ductal adenocarcinoma cell *** efficiency of the VHH212 nanobody in inhibiting the HIF-1 signaling pathway was measured using a dual-luciferase reporter ***,a PANC-1 xenograft model was developed to evaluate the anti-tumor efficiency of combined *** analysis was conducted to detect the expressions of HIF-1αand VEGF-A in tumor ***:VHH212 was stably expressed in tumor cells with low cytotoxicity,high affinity,specific subcellular localization,and neutralization of HIF-1αin the cytoplasm or *** binding affinity between VHH212 and the HIF-1αPAS-B domain was 42.7 n *** competitive inhibition of the HIF-1αheterodimer with an aryl hydrocarbon receptor nuclear translocator was used to inhibit the HIF-1/VEGF pathway in *** with single agent gemcitabine,co-treatment with gemcitabine and a VHH212-encoding adenovirus significantly suppressed tumor growth in the xenograft model with 80.44%tumor ***:We developed an anti-HIF-1αnanobody and showed the function of VHH212 in a preclinical murine model of PANC-1 pancreatic *** combination of VHH212 and gemcitabine significantly inhibited tumor *** results suggested that combined use of anti-HIF-1αnanobodies with first-line treatment may in the future be an effective treatment for pancreatic cancer.

关键词： Pancreatic cancer nanobody therapeutic intracellular antibody HIF-1αinhibitor gemcitabine chemosensitizer

Cancer immunity and therapy using hyperthermia with immunotherapy, radiotherapy, chemotherapy, and surgery

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Journal of Cancer Metastasis and Treatment 2017年第1期3卷 218-230页

作者： Yohsuke Yagawa Keishi Tanigawa Yasunobu Kobayashi Masakazu Yamamoto Bio-Thera Clinic Tokyo 1600022Japan Department of Surgery Institute of GastroenterologyTokyo Women’s Medical UniversityTokyo 1628666Japan.

Hyperthermia is a type of medical modality for cancer treatment using the biological effect of artificially induced *** though the intrinsic effects of elevated body temperature in cancer tissues are poorly understood,increasing the temperature of the body has been recognized as a popular therapeutic method for tumorous lesions as well as infectious diseases since ancient *** accumulated evidence has shown that hyperthermia amplifies immune responses in the body against cancer while decreasing the immune suppression and immune escape of *** also shows that hyperthermia inhibits the repair of damaged cancer cells after chemotherapy or *** perceptions indicate that hyperthermia has potential for cancer therapy in conjunction with immunotherapy,chemotherapy,radiotherapy,and ***,the anticancer effect of hyperthermia alone has not yet been adequately exploited because deep heating techniques and devices to aggregate heat effects only in cancer tissues are difficult in practical *** review article focuses on the current understanding concerning cancer immunity and involvement of hyperthermia and the innate and adoptive immune *** potential for combination therapy with hyperthermia and chemotherapy,radiotherapy,and surgery is also discussed.

关键词： Hyperthermia cancer immunity chemosensitizer radiosensitizer combination cancer therapy hyperthermic intraoperative peritoneal chemotherapy

Sensitizing　effects　of　aradio－　and　chemo－sensitizer，metronidazol　amino　acidum　natrium（CMNa）

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Journal of Medical Colleges of PLA(China) 1994年第2期9卷 93-97页

作者：孟祥顺赵芳高建国朱勤郑秀龙由慧萍马煌如

Radio-and chemo-sensitizing effects of a new sensitizer, metronidazol amino acidum natrium (CMNa), were studied by the methods of cell surviving fraction (in viiro), tumor growth delay (in vivo) and clinical observation. When the hypoxic V79 cells were exposed to γ-ray and CMNa, the cell surviving fraction decreased markedly as compared with radiation alone. The sensitizer enhancement ratio (SER) value was 1. 26-2. 32. When the mice bearing Lewis . B16 melanoma or EMT6 tumors were treated with single dose or fractionated radiation (with or without CMNa) or with antitumor agents (with or without CMNa) the tumor increasing velocity slowed down and the days of tumor growth delay increased significantly when CMNa was given *** 96 cases of lung cancer and 80 cases of esophageal cancer patients treated with routine chemotherapy or radiotherapy combined with CMNa, the percentage of CR+PR increased significantly. These results showed that CMNa may be an effective radio- and chemo-sensitizer.

关键词： radiosensitizer chemosensitizer metronidazol amino acidum natrium (CMNa) esophageal neoplasms lung neoplasms human

Low-levels of graphene inhibit cellular xenobiotic defense system mediated by efflux transporters Abstract

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Low-levels of graphene inhibit cellular xenobiotic defense s...

Facile Nanolization Strategy for natural borneol to Achieve increased toxicity and chemosensitization to lung cancer

全国环境纳米技术及生物效应学术研讨会

作者： Su Liu Wei Jiang Bing Wu Jing Yu Haiyan Yu Xu-Xiang Zhang Cristina Torres-Duarte Gary N.Cherr State Key Laboratory of Pollution Control and Resource Reuse School of the Environment Nanjing University Bodega Marine Laboratory University of CaliforniaDavis California USA Departments of Environmental Toxicology and Nutrition University of CaliforniaDavis California USA

Dose is one of the most important factors of nanomaterial（NM） toxicity. Low levels of NMs are considered to be safe[1]. In this study, we analyzed the potential toxicity of Graphene at relatively low concentration on plasma membrane ABC transporter activity of Human cell line HepG2. In the cell membrane, ABC transporters are common and are known to play a crucial role in multidrug resistance（MDR） [2, 3], where they function as efflux pumps and are responsible for chemotherapeutic drug resistance in cancer cells. ABC transporters can also pump xenobiotics out of the cell using an ATPdependent mechanism, thus reducing potential toxic effects. The results showed that Graphene（＜0.5 μg/mL） did not decrease cell viability, generate reactive oxygen species（ROS） and cause cell apoptosis. However, Graphene at non-toxic concentration could increase Calcein-AM（CAM, an indicator of membrane ABC transporter activities） accumulation, indicating inhibition of ABC transporters’ activities. This inhibition could be observed even at 0.005μg/mL, which is 100-times and lower than its lowest toxic concentration from cytotoxicity experiments. The inhibition of ABC transporters significantly sensitized the toxicity of paraquat, a toxic and widely used herbicide and a known substrate of ABC transporters. The potential mechanism of inhibition of membrane transporter activities caused by Graphene was further analyzed by gene expression, protein expression and membrane integrity and function. Based on above results, we assume that Graphene can damage cell membrane functions, and thus causing an inhibition of potentially all plasma membrane transporter（P-gp/MRP/BCRP） activity. This study shows the amplification of environmental effects of Graphene at non-toxic concentrations, which could significantly cause the inhibition of ABC transporters’ activities.

关键词： Graphene ABC transporter Cytotoxicity chemosensitizer

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Facile Nanolization Strategy for natural borneol to Achieve ...

Amphiphilic Copolymeric Micelles for Doxorubicin and Curcumin Co-delivery to Reverse Multidrug Resistance in Breast Cancer

第十一届全国化学生物学学术会议

作者： Riming Yuan Yanyu Huang Jianfei Cao Tianfeng Chen Department of Chemistry Jinan University

Combination chemotherapy is widely used as an enhanced therapeutic regimen in the ***（NB）,a natural Chinese medicine,displays great potential as a chemosensitzer due to its excellent cell permeability,favorable body tolerance and low physical ***,the poor water solubility and unstable distribution of NB limit its therapeutic outcomes in ***,an oil-in-water Nano emulsion of Borneol（NBNPs） is developed as a new class of chemosensitizer to improve the therapeutic index of gefitinib（GFT）,an epidermal growth factor receptor（EGFR） inhibitor for non-small cell lung cancer（NSCLC） *** nanolization of NBNPs displays excellent cancer-targeted ability between NSCLC and normal lung fibroblast cells,and outperforms NB by drastically enhancing the uptake efficiency and cytotoxicity of GFT against NSCLC growth in both cell and tumor xenograft *** studies reveal that the NBNPs realize strong chemosensitzation with GFT by regulating 12 specific protein targets in A549 NSCLC cells,including the cancer cell surface target FADD and EGFR-regulatory protein *** to the strong synergistic effect between NBNPs and GFT,the combined therapy not only enhances the anticancer ability of GFT against NSCLC proliferation,but also avoids a heavy double toxicity in vivo by reducing the dosage of NBNPs and GFT required for a single treatment.

关键词： Borneol Nano emulsion chemosensitizer combined therapy

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Amphiphilic Copolymeric Micelles for Doxorubicin and Curcumi...