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| 1 | Mechanisms of resistance to EGFR tyrosine kinase inhibitors显示文摘Since the discovery that non-small cell lung cancer(NSCLC) is driven by epidermal growth factor receptor(EGFR) mutations, the EGFR tyrosine kinase inhibitors(EGFR-TKIs, e.g., ge fi tinib and elrotinib) have been effectively used for clinical treatment. However, patients eventually develop drug resistance. Resistance to EGFR-TKIs is inevitable due to various mechanisms, such as the secondary mutation(T790M), activation of alternative pathways(c-Met, HGF, AXL), aberrance of the downstream pathways(K-RAS mutations, loss of PTEN), impairment of the EGFR-TKIs-mediated apoptosis pathway(BCL2-like 11/BIM deletion polymorphism), histologic transformation, ATP binding cassette(ABC) transporter effusion, etc. Here we review and summarize the known resistant mechanisms to EGFR-TKIs and provide potential targets for development of new therapeutic strategies. | Lihua Huang Liwu Fu | 2015 | Acta Pharmaceutica Sinica B2015，5，5： | 42 |
| 2 | Targeting calcium signaling in cancer therapy显示文摘The intracellular calcium ions(Ca^(2+)) act as second messenger to regulate gene transcription,cell proliferation, migration and death. Accumulating evidences have demonstrated that intracellular Ca^(2+)homeostasis is altered in cancer cells and the alteration is involved in tumor initiation, angiogenesis,progression and metastasis. Targeting derailed Ca^(2+)signaling for cancer therapy has become an emerging research area. This review summarizes some important Ca^(2+)channels, transporters and Ca^(2+)-ATPases,which have been reported to be altered in human cancer patients. It discusses the current research effort toward evaluation of the blockers, inhibitors or regulators for Ca^(2+)channels/transporters or Ca^(2+)-ATPase pumps as anti-cancer drugs. This review is also aimed to stimulate interest in, and support for researchinto the understanding of cellular mechanisms underlying the regulation of Ca^(2+)signaling in different cancer cells, and to search for novel therapies to cure these malignancies by targeting Ca^(2+)channels or transporters. | Chaochu Cui Robert Merritt Liwu Fu Zui Pan | 2017 | Acta Pharmaceutica Sinica B2017，7，1： | 32 |
| 3 | Ore Genesis of the Kalatongke Cu-Ni Sulfide Deposits, Western China: Constraints from Volatile Chemical and Carbon Isotopic Compositions显示文摘The Kalatongke Cu-Ni sulfide deposits located in the East Junggar terrane, northern Xinjiang, western China are the largest magmatic sulfide deposits in the Central Asian Orogenic Belt (CAOB). The chemical and carbon isotopic compositions of the volatiles trapped in olivine, pyroxene and sulfide mineral separates were analyzed by vacuum stepwise-heating mass spectrometry. The results show that the released volatiles are concentrated at three temperature intervals of 200-400°C, 400-900°C and 900-1200°C. The released volatiles from silicate mineral separates at 400-900°C and 900-1200°C have similar chemical and carbon isotopic compositions, which are mainly composed of H2O (av. ~92 mol%) with minor H2, CO2, H2S and SO2, and they are likely associated with the ore-forming magmatic volatiles. Light δ13CCO2 values (from -20.86‰ to -12.85‰) of pyroxene indicate crustal contamination occurred prior to or synchronous with pyroxene crystallization of mantlederived ore-forming magma. The elevated contents of H2 and H2O in the olivine and pyroxene suggest a deep mantle-originated ore-forming volatile mixed with aqueous volatiles from recycled subducted slab. High contents of CO2 in the ore-forming magma volatiles led to an increase in oxygen fugacity, and thereby reduced the solubility of sulfur in the magma, then triggered sulfur saturation followed by sulfide melt segregation; CO2 contents correlated with Cu contents in the whole rocks suggest that a supercritical state of CO2 in the ore-forming magma system under high temperature and pressure conditions might play a key role in the assemblage of huge Cu and Ni elements. The volatiles released from constituent minerals of intrusion 1# have more CO2 and SO2 oxidized gases, higher CO2/CH4 and SO2/H2S ratios and lighter δ13CCO2 than those of intrusions 2# and 3#. This combination suggests that the higher oxidation state of the volatiles in intrusion 1# than intrusions 2# and 3#, which could be one of key ore-forming factors for large amounts of ores and high contents of Cu and Ni in intrusion 1#. The volatiles released at 200-400°C are dominated by H2O with minor CO2, N2+CO and SO2, with δ13CCO2 values (-25.66‰ to -22.98‰) within the crustal ranges, and are considered to be related to secondary tectonic-hydrothermal activities. | FU Piaoer TANG Qingyan ZHANG Mmgjie ZHANG Zhaowei LI Liwu LI Wenyuan | 2012 | Acta Geologica Sinica(English Edition)2012，86，3： | 11 |
| 4 | The role of ALDH2 in tumorigenesis and tumor progression:Targeting ALDH2 as a potential cancer treatment显示文摘A major mitochondrial enzyme for protecting cells from acetaldehyde toxicity is aldehyde dehydrogenase 2(ALDH2).The correlation between ALDH2 dysfunction and tumorigenesis/growth/metastasis has been widely reported.Either low or high ALDH2 expression contributes to tumor progression and varies among different tumor types.Furthermore,the ALDH2*2 polymorphism(rs671) is the most common single nucleotide polymorphism(SNP) in Asia.Epidemiological studies associate ALDH2*2 with tumorigenesis and progression.This study summarizes the essential functions and potential ALDH2 mechanisms in the occurrence,progression,and treatment of tumors in various types of cancer.Our study indicates that ALDH2 is a potential therapeutic target for cancer therapy. | Hong Zhang Liwu Fu | 2021 | Acta Pharmaceutica Sinica B2021，11，6： | 10 |
| 5 | Observations of atmospheric pollutants at Lhasa during 2014-2015:Pollution status and the influence of meteorological factors显示文摘Atmospheric pollutants including SO_2, NO_2, CO, O_3 and inhalable particulate matter(PM2.5 and PM10) were monitored continuously from March 2014 to February 2015 to investigate characteristics of air pollution at Lhasa, Tibetan Plateau. Species exhibited similar seasonal variations except O_3, with the peaks in winter but low valleys in summer. The maximum O_3 concentration was observed in spring, followed by summer, autumn, and winter. The positive correlation between O_3 and PM10 in spring indicated similar sources of them, and was assumed to be turbulent transport. Temperature was the dominant meteorological factor for most species in spring. High temperature accelerates O_3 photochemistry, and favors air disturbance which is conductive to dust resuspension in spring. Relative humidity(RH) and atmospheric pressure were the main meteorological factors in summer. RH showed negative correlations with species, while atmospheric pressure posed opposite situation. Wind speed(WS) was the dominant meteorological factor in autumn, the negative correlations between WS and species indicated diffusion by wind. Most species showed non-significant correlations with meteorological factors in winter, indicating the dependence of pollution on source emission rather than restriction by meteorology. Pollution weather character indicated that emissions were from biomass burning and dust suspension, and meteorological factors also played an important role. Air stream injection from the stratosphere was observed during O_3 pollution period. Air parcels from Southwest Asia were observed during air pollution period in winter. An enhancement in air pollutants such as O_3 would be expected in the future, more attention should be given to countermeasures for prevention of air pollution in the future. | Bu Duo Lulu Cui Zhenzhen Wang Rui Li Liwu Zhang Hongbo Fu Jianmin Chen Huifang Zhang A.Qiong | 2018 | Journal of Environmental Sciences2018，30，1： | 9 |
| 6 | Olmutinib(HM61713) reversed multidrug resistance by inhibiting the activity of ATPbinding cassette subfamily G member 2 in vitro and in vivo显示文摘Overexpressing of ATP-binding cassette(ABC) transporters is the essential cause of multidrug resistance(MDR), which is a significant hurdle to the success of chemotherapy in many cancers.Therefore, inhibiting the activity of ABC transporters may be a logical approach to circumvent MDR.Olmutinib is an epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor(TKI), which has been approved in South Korea for advanced EGFR T790 M-positive non-small cell lung cancer(NSCLC). Here,we found that olmutinib significantly increased the sensitivity of chemotherapy drug in ABCG2-overexpressing cells. Furthermore, olmutinib could also increase the retention of doxorubicin(DOX) and rhodamine 123(Rho 123) in ABC transporter subfamily G member 2(ABCG2)-overexpressing cells. In addition, olmutinib was found to stimulate ATPase activity and inhibit photolabeling of ABCG2 with [^(125) I]-iodoarylazidoprazosin(IAAP). However, olmutinib neither altered ABCG2 expression at protein and m RNA levels nor blocked EGFR, Her-2 downstream signaling of AKT and ERK. Importantly,olmutinib enhanced the efficacy of topotecan on the inhibition of S1-MI-80 cell xenograft growth. All the results suggest that olmutinib reverses ABCG2-mediated MDR by binding to ATP bind site of ABCG2 and increasing intracellular chemotherapeutic drug accumulation. Our findings encouraged to further clinical investigation on combination therapy of olmutinib with conventional chemotherapeutic drugs in ABCG2-overexpressing cancer patients. | Zhiqiang Zhang Xiaoran Guo Kenneth K.W.To Zhen Chen Xiaona Fang Min Luo Chunling Ma Jianhua Xu Shirong Yan Liwu Fu | 2018 | Acta Pharmaceutica Sinica B2018，8，4： | 9 |
| 7 | A comparative study of bismuth-based photocatalysts with titanium dioxide for perfluorooctanoic acid degradation显示文摘Bismuth-based material has been broadly studied due to their potential applications in various areas,especially used as promising photocatalysts for the removal of persistent organic pollutants(POPs) and several approaches have been adopted to tailor their features.Herein,the bismuth-based photocatalysts(BiOCl,BiPO4,BiOPO4/BiOCl) were synthesized by hydrothermal method and advanced characterization techniques(XRD,SEM,EDS elemental mapping,Raman and UV-vis DRS) were employed to analyze their morphology,crystal structure,and purity of the prepared photocatalysts.These synthesized photocatalysts offered a praiseworthy activity as compared to commercial TiO2(P25) for the degradation of model pollutant perfluorooctanoic acid(PFOA) under 254 nm UV light.It was interesting to observe that all synthesized photocatalysts show significant degradation of PFOA and their photocatalytic activity follows the order:bismuth-based catalysts> TiO2(P25)> without catalyst.Bismuth-based catalysts degraded the PFOA by almost 99.99% within 45 min while this degradation efficiency was 66.05% with TiO2 under the same reaction condition.Our work shows that the bismuth-based photocatalysts are promising in PFOA treatment. | Aziz-Ur-Rahim Bacha Iqra Nabi Zhaoyang Fu Kejian Li Hanyun Cheng Liwu Zhang | 2019 | Chinese Chemical Letters2019，30，12： | 5 |
| 8 | Secalonic acid D induces cell apoptosis in both sensitive and ABCG2-overexpressing multidrug resistant cancer cells through upregulating c-Jun expression显示文摘Secalonic acid D(SAD) could inhibit cell growth in not only sensitive cells but also multidrug resistant(MDR) cells. However, the molecular mechanisms need to be elucidated. Here, we identified that SAD possessed potent cytotoxicity in 3 pairs of MDR and their parental sensitive cells including S1-MI-80 and S1,H460/MX20 and H460, MCF-7/ADR and MCF-7 cells. Furthermore, SAD induced cell G2/M phase arrest via the downregulation of cyclin B1 and the increase of CDC2 phosphorylation. Importantly, JNK pathway upregulated the expression of c-Jun in protein level and increased c-Jun phosphorylation induced by SAD, which was linked to cell apoptosis via c-Jun/Src/STAT3 pathway. To investigate the mechanisms of upregulation of c-Jun protein by SAD, the mR NA expression level and degradation of c-Jun were examined. We found that SAD did not alter the mR NA level of c-Jun but inhibited its proteasome-dependent degradation. Taken together, these results implicate that SAD induces cancer cell death through c-Jun/Src/STAT3 signaling axis by inhibiting the proteasome-dependent degradation of c-Jun in both sensitive cells and ATP-binding cassette transporter sub-family G member 2(ABCG2)-mediated MDR cells. | Hong Zhang Liyan Huang Liyang Tao Jianye Zhang Fang Wang Xu Zhang Liwu Fu | 2019 | Acta Pharmaceutica Sinica B2019，9，3： | 5 |
| 9 | KRAS mutation:from undruggable to druggable in cancer显示文摘Cancer is the leading cause of death worldwide,and its treatment and outcomes have been dramatically revolutionised by targeted therapies.As the most frequently mutated oncogene,Kirsten rat sarcoma viral oncogene homologue(KRAS)has attracted substantial attention.The understanding of KRAS is constantly being updated by numerous studies on KRAS in the initiation and progression of cancer diseases.However,KRAS has been deemed a challenging therapeutic target,even“undruggable”,after drugtargeting efforts over the past four decades.Recently,there have been surprising advances in directly targeted drugs for KRAS,especially in KRAS(G12C)inhibitors,such as AMG510(sotorasib)and MRTX849(adagrasib),which have obtained encouraging results in clinical trials.Excitingly,AMG510 was the first drug-targeting KRAS(G12C)to be approved for clinical use this year.This review summarises the most recent understanding of fundamental aspects of KRAS,the relationship between the KRAS mutations and tumour immune evasion,and new progress in targeting KRAS,particularly KRAS(G12C).Moreover,the possible mechanisms of resistance to KRAS(G12C)inhibitors and possible combination therapies are summarised,with a view to providing the best regimen for individualised treatment with KRAS(G12C)inhibitors and achieving truly precise treatment. | Lamei Huang Zhixing Guo Fang Wang Liwu Fu | 2021 | Signal Transduction and Targeted Therapy2021，6，12： | 5 |
| 10 | Characteristics of the pollutant emissions in a tunnel of Shanghai on a weekday显示文摘Tunnel displays a typical semi-closed environment, and multitudes of the pollutants tend to accumulate. The samples of gaseous pollutants and particulate matter(PM) were collected from the Xiangyin tunnel at Shanghai to investigate the characteristics of the pollutant emissions. The results indicated that both gaseous pollutants and PM exhibited much higher concentrations during the rush hours in the morning and at night due to vehicle emission. Two peaks of the PM concentration were observed in the scope of 0.7‐1.1 and 3.3–4.7 μm, accounting for 14.6% and 20.3% of the total concentrations, respectively.Organic matter(OM), EC, and many water-soluble ions were markedly higher at the rush hours in the morning than those at night, implicating comprehensive effects of vehicle types and traffic volume. The particle number concentrations exhibited two peaks at Aitken mode(25 nm and 100 nm) and accumulation mode(600 nm), while the particle volume concentration displayed high values at the accumulation mode(100–500 nm) and coarse mode(2.5–4.0 μm). The peak around 100 nm was detected in the morning rush hours, but it diminished with the decrease of the traffic volume. Individual-particle analysis revealed that main particles in the tunnel were Fe-rich particles, K-rich particles, mineral particles,Ca–S rich particles and Al–Si particles. The particles collected at the rush hours displayed marked different morphologies, element concentrations and particle sizes compared to the ones collected at the non-rush period. The data presented herein could shed a light on the feature of vehicle emissions. | Rui Li Ya Meng Hongbo Fu Liwu Zhang Xingnan Ye Jianmin Chen | 2018 | Journal of Environmental Sciences2018，30，9： | 4 |
| 11 | Establishment and characterization of arsenic trioxide resistant KB/ATO cells显示文摘Arsenic trioxide(ATO) is used as a chemotherapeutic agent for the treatment of acute promyelocytic leukemia. However, increasing drug resistance is reducing its efficacy. Therefore, a better understanding of ATO resistance mechanism is required. In this study, we established an ATO-resistant human epidermoid carcinoma cell line, KB/ATO, from its parental KB-3-1 cells. In addition to ATO, KB/ATO cells also exhibited cross-resistance to other anticancer drugs such as cisplatin, antimony potassium tartrate, and 6-mercaptopurine. The arsenic accumulation in KB/ATO cells was significantly lower than that in KB-3-1 cells. Further analysis indicated that neither application of P-glycoprotein inhibitor, breast cancer resistant protein(BCRP) inhibitor, or multidrug resistance protein 1(MRP1) inhibitor could eliminate ATO resistance. We found that the expression level of ABCB6 was increased in KB/ATO cells.In conclusion, ABCB6 could be an important factor for ATO resistance in KB/ATO cells. The ABCB6 level may serve as a predictive biomarker for the effectiveness of ATO therapy. | Yun-Kai Zhang Chunling Dai Chun-gang Yuan Hsiang-Chun Wu Zhijie Xiao Zi-Ning Lei Dong-Hua Yang X. Chris Le Liwu Fu Zhe-Sheng Chen | 2017 | Acta Pharmaceutica Sinica B2017，7，5： | 3 |
| 12 | Efficient TiO_2 photocatalysts froth surface hybridization of TiO_2 particles with graphite-like carbon显示文摘 | ZHANG Liwu FU Hongbo ZHU Yongfa | 2008 | Advanced Functional Materials2008，18，15： | 1 |
| 13 | 条件重编程原代肿瘤细胞的培养与应用显示文摘癌症仍然是威胁全球人类生命的重大公共卫生问题,需要在基础研究和临床前研究方面开展进一步的研究。尽管近年来高通量测序技术和个体化精准治疗取得了突破性进展,临床转化研究的高失败率却限制了抗肿瘤药物的创新,因此亟需对肿瘤研究模型进行优化。肿瘤细胞系、患者来源异种移植模型(PDX)及类器官的发展有力地推动了肿瘤生物学研究的发展,但价值有限。条件重编程(CR)是一种用于癌症研究的新型细胞培养方法,其将滋养层细胞和Rho相关的卷曲螺旋激酶(ROCK)抑制剂相结合,使原代上皮细胞能够快速、持续地增殖。本文中,我们介绍了CR模型的建立方法;并对CR细胞培养模型在癌症研究中的最新功能和应用进行了综述,包括肿瘤生物学特征的研究、治疗靶标的探索、个体化药物的筛选、抗肿瘤药物治疗反应机制的阐明及患者来源动物模型的完善;最后还详细讨论了CR细胞培养系统的一些主要缺陷。 | Mengjun Zhong Liwu Fu | 2020 | Gastroenterology Report2020，8，3： | 1 |
| 14 | A20 promotes colorectal cancer immune evasion by upregulating STC1 expression to block “eat-me” signal显示文摘Immune checkpoint inhibitors(ICIs)have induced durable clinical responses in a subset of patients with colorectal cancer(CRC).However,the dis-satisfactory response rate and the lack of appropriate biomarkers for selecting suitable patients to be treated with ICIs pose a major challenge to current immunotherapies.Inflammation-related molecule A20 is closely related to cancer immune response,but the effect of A20 on“eat-me”signal and immunotherapy efficacy remains elusive.We found that A20 downregulation prominently improved the antitumor immune response and the efficacy of PD-1 inhibitor in CRC in vitro and in vivo.Higher A20 expression was associated with less infiltration of immune cells including CD3(+),CD8(+)T cells and macrophages in CRC tissues and also poorer prognosis.Gain-and loss-A20 functional studies proved that A20 could decrease the“eat-me”signal calreticulin(CRT)protein on cell membrane translocation via upregulating stanniocalcin 1(STC1),binding to CRT and detaining in mitochondria.Mechanistically,A20 inhibited GSK3βphosphorylating STC1 at Thr86 to slow down the degradation of STC1 protein.Our findings reveal a new crosstalk between inflammatory molecule A20 and“eat-me”signal in CRC,which may represent a novel predictive biomarker for selecting CRC patients most likely to benefit from ICI therapy. | Min Luo Xueping Wang Shaocong Wu Chuan Yang Qiao Su Lamei Huang Kai Fu Sainan An Fachao Xie Kenneth Kin Wah To Fang Wang Liwu Fu | 2023 | Signal Transduction and Targeted Therapy2023，8，9： | 1 |
| 15 | PD0325901, an ERK inhibitor, enhances the efficacy of PD-1 inhibitor in non-small cell lung carcinoma显示文摘ERK pathway regulated the programmed death ligand-1(PD-L1)expression which was linked to the response of programmed death-1(PD-1)/PD-L1 blockade therapy.So it is deducible that ERK inhibitor could enhance the efficacy of PD-1 inhibitor in cancer immunotherapy.In this study,PD0325901,an oral potent ERK inhibitor,strongly enhanced the efficacy of PD-1 antibody in vitro and in vivo models in non-small cell lung carcinoma(NSCLC)cells.Mechanistically,PD0325901 or shRNA-ERK1/2 significantly downregulated the PD-L1 expression in NSCLC cells and increased the CD3+T cells infiltration and functions in tumor tissue.There was a positive correlation between the p-ERK1/2 expression and PD-L1 expression in patients with NSCLC.And the patients with low p-ERK1/2 expression were observed a high response rate of PD-1/PD-L1 blockage therapy.Our results demonstrate that PD0325901,an ERK inhibitor,can enhance the efficacy of PD-1 blockage against NSCLC in vitro and in vivo models.And the combination of ERK inhibitor such as PD0325901 and PD-1/PD-L1 blockage is a promising regimen and encouraged to be further confirmed in the treatment of patients with NSCLC. | Min Luo Yuhui Xia Fang Wang Hong Zhang Danting Su Chaoyue Su Chuan Yang Shaocong Wu Sainan An Suxia Lin Liwu Fu | 2021 | Acta Pharmaceutica Sinica B2021，11，10： | 1 |
| 16 | Au nanoring arrays as surface enhanced Raman spectroscopy substrate for chemical component study of individual atmospheric aerosol particle显示文摘Monolayer-ordered gold nanoring arrays were prepared by ion-sputtering method and used as surface enhanced Raman spectroscopy(SERS)substrates to test the individual atmospheric aerosols particle.Compared to other methods used for testing atmospheric aerosols particles,the collection and subsequent detection in our work is performed directly on the gold nanoring SERS substrate without any treatment of the analyte.The SERS performance can be tuned by changing the depth of the gold nanoring cavity as originating from coupling of dipolar modes at the inner and outer surfaces of the nanorings.The electric field exhibits uniform enhancement and polarization in the ordered Au nanoring substrate,which can improve the accuracy for detecting atmospheric aerosol particles.Combined with Raman mapping,the information about chemical composition of individual atmospheric aerosols particle and distribution of specific components can be presented visually.The results show the potential of SERS in enabling improved analysis of aerosol particle chemical composition,mixing state,and other related physicochemical properties. | Hanyun Cheng Xu Dong Yang Yang Yiqing Feng Tao Wang Muhammad Ali Tahir Liwu Zhang Hongbo Fu | 2021 | Journal of Environmental Sciences2021，33，2： | 1 |
| 17 | The enhancedphotoactivity of nanosized Bi2WO6catalyst for the degradationof 4-chlorophenol显示文摘 | Hongbo Fu Wenqing Yao Liwu Zhang etal | 2008 | Materials Research Bulletin2008，43，： | 1 |
| 18 | Fusobacterium nucleatum:a new player in regulation of cancer development and therapeutic response显示文摘A dysbiosis in microbial diversity or functionality can promote disease development.Emerging preclinical and clinical evidence emphasizes the interplay between microbiota and both disease evolution and the treatment response of different cancers.One bacterium that has garnered much attention in a few cancer microbiota studies is Fusobacterium nucleaum(Fn).To provide updated knowledge of the functional role of Fn in cancer prevention and management,this review summarizes the relationship among Fn,cancer,and chemoimmunotherapy response,with the potential mechanisms of action also intensively discussed,which will benefit the development of strategies to prevent or treat cancer via Fn-based therapeutic interventions. | Tengda Zhao Xueping Wang Liwu Fu Ke Yang | 2022 | Cancer Drug Resistance2022，5，2： | 1 |
| 19 | Characterization of tetrandrine, a potent inhibitor of P-glycoprotein-mediated multidrug resistance显示文摘 | Liwu Fu Yongju Liang Liwen Deng Yan Ding Liming Chen Yanli Ye Xiaoping Yang Qichao Pan | 2004 | Cancer Chemotherapy and Pharmacology2004，，4： | 1 |
| 20 | The enhancedphotoactivity of nanosized Bi2 W()6 catalyst for the degrada-tion of 4-chlorophenol 显示文摘 | Fu Hongbo Yao Wenqing Zhang Liwu | 2008 | Mater Res Bull2008，43，10： | 1 |
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