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Palladium nanoplates scotch breast cancer lung metastasis by constraining epithelial-mesenchymal transition

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National Science Review 2021年第7期8卷 124-136页

作者： Shunhao Wang Jingchao Li Mei Chen Liting Ren Wenya Feng Lining Xu Xiaolan Chen Tian Xia Nanfeng Zheng Sijin Liu State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental Sciences Chinese Academy of Sciences University of Chinese Academy of Sciences State Key Laboratory for Physical Chemistry of Solid Surfaces Collaborative Innovation Center of Chemistry for Energy Materials Department of Chemistry Xiamen University College of Materials Science and Engineering Hunan University Division of Nanomedicine Department of Medicine California Nano Systems Institute University of CaliforniaLos Angeles

metastasis accounts for the majority of cancer deaths in many tumor types including breast ***-mesenchymal transition(EMT) is the driving force for the occurrence and progression of metastasis, however, no targeted strategies to block the EMT program are currently available to combat metastasis. Diverse engineered nanomaterials(ENMs) have been reported to exert promising anti-cancer effects, however, no ENMs have been designed to target EMT. Palladium(Pd) nanomaterials, a type of ENM, have received substantial attention in nanomedicine due to their favorable photothermal performance for cancer therapeutics. Herein, Pd nanoplates(Pd PL) were found to be preferentially biodistributed to both primary tumors and metastatic tumors. Importantly, Pd PL showed a significant inhibition of lung metastasis with and without near-infrared(NIR) irradiation. Mechanistic investigations revealed that EMT was significantly compromised in breast cancer cells upon the Pd PL treatment, which was partially due to the inhibition of the transforming growth factor-beta(TGF-β) signaling. Strikingly, the Pd PL was found to directly interact with TGF-β proteins to diminish TGF-β functions in activating its downstream signaling, as evidenced by the reduced phosphorylation of Smad2. Notably,TGF-β-independent pathways were also involved in undermining EMT and other important biological processes that are necessary for metastasis. Additionally, NIR irradiation elicited synergistic effects on PdPL-induced inhibition of primary tumors and metastasis. In summary, these results revealed that the Pd PL remarkably curbed metastasis by inhibiting EMT signaling, thereby indicating the promising potential of Pd PL as a therapeutic agent for treating breast cancer metastasis.

关键词： palladium nanoplates tumor targeting lung metastasis epithelial-mesenchymal transition TGF-β

Synthesis of selective PAK4 inhibitors for lung metastasis of lung cancer and melanoma cells

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Acta Pharmaceutica Sinica B 2022年第6期12卷 2905-2922页

作者： Peilu Song Fan Zhao Dahong Li Jiqiang Qu Miao Yao Yuan Su Hanxun Wang Miaomiao Zhou Yujie Wang Yinli Gao Feng Li Dongmei Zhao Fengjiao Zhang Yu Rao Mingyu Xia Haitao Li Jian Wang Maosheng Cheng Key Laboratory of Structure-Based Drug Design&Discovery of Ministry of Education Shenyang Pharmaceutical UniversityShenyang 110016China MOE Key Laboratory of Protein Sciences School of Pharmaceutical SciencesMOE Key Laboratory of Bioorganic Phosphorus Chemistry Chemical BiologyTsinghua UniversityBeijing 100084China MOE Key Laboratory of Protein Sciences Beijing Advanced Innovation Center for Structural BiologyTsinghua-Peking Joint Center for Life SciencesSchool of Life Sciences and School of MedicineTsinghua UniversityBeijing 100084China School of Traditional Chinese Materia Medica Shenyang Pharmaceutical UniversityShenyang 110016China School of Life Science and Biopharmaceutics Shenyang Pharmaceutical UniversityShengyang 110016China Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China Department of Cell Biology Key Laboratory of Cell BiologyMinistry of Public Healthand Key Laboratory of Medical Cell BiologyMinistry of EducationChina Medical UniversityShenyang 110001China

The p21 activated kinase 4(PAK4) is serine/threonine protein kinase that is critical for cancer *** by X-ray crystallography and structure-based optimization,we report a novel subseries of C-3-substituted 6-ethynyl-1 H-indole derivatives that display high potential and specificity towards group Ⅱ *** these inhibitors,compound 55 exhibited excellent inhibitory activity and kinase selectivity,displayed superior anti-migratory and anti-invasive properties against the lung cancer cell line A549 and the melanoma cell line *** 55 exhibited potent in vivo antitumor metastatic efficacy,with over 80% and 90% inhibition of lung metastasis in A549 or B16-BL6 lung metastasis models,*** mechanistic studies demonstrated that compound 55 mitigated TGF-β1-induced epithelial-mesenchymal transition(EMT).

关键词： Anti-cancer PAK4 inhibitor Kinase selectivity Cocrystallization lung metastasis EMT

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Inhalable nanoparticles with enhanced cuproptosis and cGAS-STING activation for synergistic lung metastasis immunotherapy

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3697-3710页

作者： Chongzheng Yan Huaiyou Lv Yafei Feng Yuhan Li Zhongxi Zhao Department of Pharmaceutics Key Laboratory of Chemical Biology of Ministry of EducationSchool of Pharmaceutical SciencesCheelloo College of MedicineShandong UniversityJinan 250012China Key University Laboratory of Pharmaceutics&Drug Delivery Systems of Shandong Province School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China Department of Pharmacy Yantai Yuhuangding Hospital Affiliated to Qingdao UniversityYantai 264001China

Due to the insufficient Cu^(+)accumulation,Cu^(+)efflux mechanism,and highly immunosuppressive tumor microenvironment(TME)in lung metastasis,the cuproptosis efficacy is ***,an inhalable nanodevice(CLDCu)is constructed to successfully overcome the drawbacks of *** consists of a Cu^(2+)-chitosan shell and low molecular weight heparin-tocopherol succinate(LMWH-TOS,LT)core with disulfiram(DSF)*** prepared CLDCu can be inhaled and accumulate in large amounts in lung lesions(63.6%)with 56.5 times higher than intravenous *** tumor cells,the mild acidity triggers the co-release of DSF and Cu2+,thus generating bis(diethyldithiocarbamate)-copper(CuET)to block Cu^(+)efflux protein ATP7B and forming toxic Cu^(+),leading to enhanced ***,the released chitosan cooperates with CLDCu-induced cuproptosis to activate stimulator of interferon genes(STING)pathway,which significantly potentiates dendritic cells(DCs)maturation,as wells as evokes innate and adaptive *** lung metastatic mice model,CLDCu is found to induce cuproptosis and reverse the immunosuppressive TME by inhalation ***,CLDCu combined with anti-programmed cell death protein ligand-1 antibody(aPD-L1)provokes stronger antitumor ***,nanomedicine that combines cuproptosis with STING activation is a novel strategy for tumor immunotherapy.

关键词： Cuproptosis cGAS-STING activation Disulfiram Inhalation administration Tumor microenvironment PD-L1 checkpoint blockade lung metastasis Immunotherapy

Exosomes derived from pulmonary metastatic sites enhance osteosarcoma lung metastasis by transferring the miR-194/215 cluster targeting MARCKS

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2039-2056页

作者： Pei Yu Yubao Han Lulu Meng Yanyuan Tian Zhiwei Jin Jun Luo Chao Han Wenjun Xu Lingyi Kong Chao Zhang State Key Laboratory of Natural Medicines Jiangsu Key Laboratory of Bioactive Natural Product ResearchSchool of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing 211198China

Osteosarcoma,a prevalent primary malignant bone tumor,often presents with lung metastases,severely impacting patient survival *** vesicles,particularly exosomes,play a pivotal role in the formation and progression of osteosarcoma-related pulmonary ***,the communication between primary osteosarcoma and exosome-mediated pulmonary lesions remains obscure,with the potential impact of pulmonary metastatic foci on osteosarcoma progression largely *** study unveils an innovative mechanism by which exosomes originating from osteosarcoma pulmonary metastatic sites transport the miR-194/215 cluster to the primary tumor *** transportation enhances lung metastatic capability by downregulating myristoylated alanine-rich C-kinase substrate(MARCKS)*** this phenomenon,in this study we employ cationic bovine serum albumin(CBSA)to form nanoparticles(CBSA-anta-194/215)via electrostatic interaction with antagomir-miR-194/*** nanoparticles are loaded into nucleic acid-depleted exosomal membrane vesicles(anta-194/215@Exo)targeting osteosarcoma lung metastatic *** with bioengineered exosome mimetics(anta-194/215@Exo)not only impedes osteosarcoma progression but also significantly prolongs the lifespan of tumor-bearing *** findings suggest that pulmonary metastatic foci-derived exosomes initiate primary osteosarcoma lung metastasis by transferring the miR-194/215 cluster targeting MARCKS,making the miR-194/215 cluster a promising therapeutic target for inhibiting the progression of patients with osteosarcoma lung metastases.

关键词： lung–bone transmission miR-194/215 cluster Exosome lung metastasis Epithelial–mesenchymal transition Vasculogenic mimicry Bioengineered exosome mimetics Osteosarcoma

Successful treatment for esophageal carcinoma with lung metastasis by induction chemotherapy followed by salvage esophagectomy: Report of a case

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World Journal of Gastroenterology 2006年第25期12卷 4101-4103页

作者： Shin Ichi Kosugi Tatsuo Kanda Tadashi Nishimaki Satoru Nakagawa Kazuhito Yajima Manabu Ohashi Katsuyoshi Hatakeyama Division of Digestive and General Surgery Niigata University Graduate School of Medical and Dental Sciences Niigata CityJapan First department of Surgery Faculty of Medicine University of the RyukyusOkinawaJapan

We here report a case of a 51-year-old man with lung metastasis from esophageal carcinoma that was initially treated by combination chemotherapy consisting of fluorouracil and nedaplatin. Because metastatic disease disappeared, salvage esophagectomy was performed. Although chest wall recurrence developed at the thoracotomy wound, prolonged survival of 48 months was achieved by local tumor resection and additional chemotherapy. This combination chemotherapy is regarded as a promising and considerable treatment for metastatic esophageal carcinoma.

关键词： Esophageal carcinoma lung metastasis Induction chemotherapy Fluorouracil Nedaplatin Salvage esophagectomy

Tryptophan 2,3-dioxygenase-positive matrix fibroblasts fuel breast cancer lung metastasis via kynurenine-mediated ferroptosis resistance of metastatic cells and T cell dysfunction

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Cancer Communications 2024年第11期44卷 1261-1286页

作者： Yongcan Liu Shanchun Chen Xueying Wan Rui Wang Haojun Luo Chao Chang Peijin Dai Yubi Gan Yuetong Guo Yixuan Hou Yan Sun Yong Teng Xiaojiang Cui Manran Liu Key Laboratory of Laboratory Medical Diagnostics Chinese Ministry of EducationChongqing Medical UniversityChongqingP.R.China Department of Thyroid and Breast Surgery The Second Affiliated Hospital of Chongqing Medical UniversityChongqingP.R.China Experimental Teaching Center of Basic Medicine Science Chongqing Medical UniversityChongqingP.R.China Department of Cell Biology and Medical Genetics Basic Medical SchoolChongqing Medical UniversityChongqingP.R.China Department of Hematology and Medical Oncology Winship Cancer InstituteEmory University School of MedicineAtlantaGeorgiaUSA Wallace H.Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory UniversityAtlantaGeorgiaUSA Department of Surgery Department of Obstetrics and GynecologySamuel Oschin Comprehensive Cancer InstituteCedars-Sinai Medical CenterLos AngelesCaliforniaUSA

Background:Tumor metastasis is a major threat to cancer patient *** organ-specific niche plays a pivotal role in tumor organotropic *** serve as a vital component of the metastatic microenviron-ment,but how heterogeneous metastasis-associated fibroblasts(MAFs)promote organotropic metastasis is poorly ***,we aimed to decipher the heterogeneity of MAFs and elucidate the distinct roles of these fibroblasts in pulmonary metastasis formation in breast ***:Mouse models of breast cancer pulmonary metastasis were estab-lished using an in vivo selection method of repeated injections of metastatic cells purified from the mouse ***-cell RNA-sequencing(scRNA-seq)was employed to investigate the heterogeneity of *** mice were used to examine the contribution of tryptophan 2,3-dioxygenase-positive matrix fibroblasts(TDO2^(+)MFs)in lung ***:We uncovered 3 subtypes of MAFs in the lung metastatic microenviron-ment,and their transcriptome profiles changed dynamically as lung metastasis *** the predominant subtype,MFs were exclusively marked by platelet-derived growth factor receptor alpha(PDGFRA)and mainly located on the edge of the metastasis,and T cells were enriched around ***,high MF sig-natures were significantly associated with poor survival in breast cancer *** metastases were markedly diminished,and the suppression of T cells was dramatically attenuated in MF-depleted experimental metastatic mouse *** found that TDO2^(+)MFs controlled pulmonary metastasis by producing kynurenine(KYN),which upregulated ferritin heavy chain 1(FTH1)level in dis-seminated tumor cells(DTCs),enabling DTCs to resist ***,TDO2^(+)MF-secreted chemokines C-C motif chemokine ligand 8(CCL8)and C-C motif chemokine ligand 11(CCL11)recruited T ***2^(+)MF-derived KYN induced T cell *** knockout of Tdo2 in MFs diminished lung metastasis and enhanced

关键词： Matrix fibroblasts lung metastasis Tryptophan 2 3-dioxygenase T cell dysfunction Ferropto-sis

TNFR2 is a potent prognostic biomarker for post-transplant lung metastasis in patients with hepatocellular carcinoma

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Chinese Journal of Cancer Research 2023年第1期35卷 66-80页

作者： Huigang Li Zuyuan Lin Jianyong Zhuo Modan Yang Wei Shen Zhihang Hu Yichen Ding Hao Chen Chiyu He Xinyu Yang Siyi Dong Xuyong Wei Beicheng Sun Shusen Zheng Ren Lang Di Lu Xiao Xu Zhejiang University School of Medicine Hangzhou 310058China Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Department of Hepatobiliary and Pancreatic SurgeryAffiliated Hangzhou First People's HospitalZhejiang University School of MedicineHangzhou 310006China The Institute for Organ Repair and Regenerative Medicine of Hangzhou Hangzhou 310006China Institute of Organ Transplantation Zhejiang UniversityHangzhou 310003China National Center for Healthcare Quality Management in Liver Transplant Hangzhou 310003China Department of Hepatobiliary Surgery the Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China Department of Hepatobiliary and Pancreatic Surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Hepatobiliary and Pancreatic Surgery Shulan(Hangzhou)HospitalHangzhou 311112China NHC Key Laboratory of Combined Multi-organ Transplantation Hangzhou 31003China Department of Hepatobiliary Surgery Beijing Chaoyang Hospital Affiliated to Capital Medical UniversityBeijing 100020China

Objective:lung metastasis is a common and fatal complication of liver transplantation for hepatocellular carcinoma(HCC).The precise prediction of post-transplant lung metastasis in the early phase is of great ***:The mRNA profiles of primary and paired lung metastatic lesions were analyzed to determine key signaling *** enrolled 241 HCC patients who underwent liver transplantation from three *** microarrays were used to evaluate the prognostic capacity of tumor necrosis factor(TNF),tumor necrosis factor receptor 1(TNFR1),and TNFR2,particularly for post-transplant lung ***:Comparison of primary and lung metastatic lesions revealed that the TNF-dependent signaling pathway was related to lung metastasis of *** expression of TNF was degraded in comparison to that in para-tumor tissues(Plung metastasis(hazard ratio:1.146;Plung metastasis,and a novel nomogram was established *** nomogram achieved excellent prognostic efficiency(area under time-dependent receiver operating characteristic=0.755,concordance-index=0.779)and was superior to conventional models,such as the Milan ***:TNFR2 is a potent prognostic biomarker for predicting post-transplant lung metastasis in patients with HCC.A nomogram incorporating TNFR2 deserves to be a helpful prognostic tool in liver transplantatio

关键词： lung metastasis hepatocellular carcinoma liver transplantation nomogram

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Risk stratification in gastric cancer lung metastasis: Utilizing an overall survival nomogram and comparing it with previous staging

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 357-381页

作者： Zhi-Ren Chen Mei-Fang Yang Zhi-Yuan Xie Pei-An Wang Liang Zhang Ze-Hua Huang Yao Luo Department of Science and Education Xuzhou Medical UniversityXuzhou Clinical CollegeXuzhou 221000Jiangsu ProvinceChina Department of Neurology Xuzhou Medical UniversityXuzhou 221000Jiangsu ProvinceChina Department of Neurology Clinical LaboratoryGastrointestinal SurgeryCentral Hospital of XuzhouCentral Hospital of XuzhouXuzhou 221000Jiangsu ProvinceChina Department of Public Health Xuzhou Central HospitalXuzhou 221000Jiangsu ProvinceChina Department of Gastroenterology Xuzhou Centre HospitalXuzhou 221000Jiangsu ProvinceChina Department of Public Health Xuzhou Medical UniversityXuzhou 221000Jiangsu ProvinceChina

BACKGROUND Gastric cancer(GC)is prevalent and aggressive,especially when patients have distant lung metastases,which often places patients into advanced *** identifying prognostic variables for lung metastasis in GC patients,it may be po-ssible to construct a good prediction model for both overall survival(OS)and the cumulative incidence prediction(CIP)plot of the *** To investigate the predictors of GC with lung metastasis(GCLM)to produce nomograms for OS and generate CIP by using cancer-specific survival(CSS)*** Data from January 2000 to December 2020 involving 1652 patients with GCLM were obtained from the Surveillance,epidemiology,and end results program *** major observational endpoint was OS;hence,patients were se-parated into training and validation *** analysis determined va-rious *** and multivariate Cox analyses validated the independent predictive *** distinction and calibration were performed with the time-dependent area under the curve(AUC)and calibration *** evaluate the accuracy and clinical usefulness of the nomograms,decision curve analysis(DCA)was *** clinical utility of the novel prognostic model was compared to that of the 7th edition of the American Joint Committee on Cancer(AJCC)staging system by utilizing Net Reclassification Improvement(NRI)and Integrated Discrimination Improvement(IDI).Finally,the OS prognostic model and Cox-AJCC risk stratification model modified for the AJCC system were *** For the purpose of creating the OS nomogram,a CIP plot based on CSS was *** multivariate regression analysis identified eleven significant prognostic factors(Pmetastasis,bone metastasis,primary site,surgery,regional surgery,treatment sequence,chemotherapy,radiotherapy,positive lymph node count,N staging,and time from diagnosis to *** was clear from the DCA(net benefit>0),time-de-pendent ROC curve(training/v

关键词： Gastric cancer lung metastasis Nomograms Surveillance Epidemiology Surveillance epidemiology and end results program database Overall survival Prognosis

Downregulation of HNRNPK in human cancer cells inhibits lung metastasis

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Animal Models and Experimental Medicine 2019年第4期2卷 291-296页

作者： Mengyuan Li Wenlong Zhang Xingjiu Yang Hongfei Liu Lin Cao Weisha Li Le Wang Guoxin Zhang Ran Gao Key Laboratory of Human Disease Comparative Medicine(National Health and Family Planning Commission) The Institute of Laboratory Animal ScienceChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingP.R.China Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases BeijingP.R.China

Background: lung cancer frequently occurs in the clinic, leading to poor prognosis and high mortality. Markers for early diagnosis of lung cancer are scarce, and further potential therapeutic targets are also urgently ***: We established a new mouse model in which the specific gene HNRNPK(heterogeneous nuclear ribonucleoprotein K) was downregulated after administration of doxycycline. The lung metastatic nodules were investigated using bioluminescence imaging, micro-CT, and autopsy ***: Compared with the short hairpin negative control group, less lung metastatic nodules were formed in the short hairpin RNA ***: Downregulation of HNRNPK in cancer cells can inhibit lung metastasis.

关键词： HNRNPK lung metastasis mouse model

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