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A biomimetic nanoplatform for customized photothermal therapy of HNSCC evaluated on patient-derived xenograft models

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International Journal of Oral Science 2023年第1期15卷 87-98页

作者： Qi Wu Lan Chen Xiaojuan Huang Jiayi Lin Jiamin Gao Guizhu Yang Yaping Wu Chong Wang Xindan Kang Yanli Yao Yujue Wang Mengzhu Xue Xin Luan Xin Chen Zhiyuan Zhang Shuyang Sun Department of Oral and Maxillofacial-Head&Neck Oncology Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of Medicine/College of StomatologyShanghai Jiao Tong University/National Center for Stomatology/National Clinical Research Center for Oral Diseases/Shanghai Key Laboratory of Stomatology/Shanghai Research Institute of StomatologyShanghaiChina Shanghai Frontiers Science Center for Chinese Medicine Chemical Biology Institute of Interdisciplinary Integrative Medicine ResearchShanghai University of Traditional Chinese MedicineShanghaiChina School of Chemical Engineering and Technology Shaanxi Key Laboratory of Energy Chemical Process IntensificationInstitute of Polymer Science in Chemical EngineeringXi’an Jiao Tong UniversityXi’anChina

Cancer cell membrane(CCM)derived nanotechnology functionalizes nanoparticles(NPs)to recognize homologous cells,exhibiting translational potential in accurate tumor therapy.However,these nanoplatforms are majorly generated from fixed cell lines and are typically evaluated in cell line-derived subcutaneous-xenografts(CDX),ignoring the tumor heterogeneity and differentiation from inter-and intra-individuals and microenvironments between heterotopic-and orthotopic-tumors,limiting the therapeutic efficiency of such nanoplatforms.Herein,various biomimetic nanoplatforms(CCM-modified gold@Carbon,i.e.,Au@C-CCM)were fabricated by coating CCMs of head and neck squamous cell carcinoma(HNSCC)cell lines and patient-derived cells on the surface of Au@C NP.The generated Au@C-CCMs were evaluated on corresponding CDX,tongue orthotopic xenograft(TOX),immunecompetent primary and distant tumor models,and patient-derived xenograft(PDX)models.The Au@C-CCM generates a photothermal conversion efficiency up to 44.2% for primary HNSCC therapy and induced immunotherapy to inhibit metastasis via photothermal therapy-induced immunogenic cell death.The homologous CCM endowed the nanoplatforms with optimal targeting properties for the highest therapeutic efficiency,far above those with mismatched CCMs,resulting in distinct tumor ablation and tumor growth inhibition in all four models.This work reinforces the feasibility of biomimetic NPs combining modular designed CMs and functional cores for customized treatment of HNSCC,can be further extended to other malignant tumors therapy.

关键词： xenograft patient custom

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Transitioning of renal transplant pathology from allograft to xenograft and tissue engineering pathology:Are we prepared?

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World Journal of Transplantation 2023年第3期13卷 86-95页

作者： Muhammed Mubarak Department of Histopathology Sindh Institute of Urology and TransplantationKarachi 74200SindhPakistan

Currently,the most feasible and widely practiced option for patients with endstage organ failure is the transplantation of part of or whole organs,either from deceased or living donors.However,organ shortage has posed and is still posing a big challenge in this field.Newer options being explored are xenografts and engineered/bioengineered tissues/organs.Already small steps have been taken in this direction and sooner or later,these will become a norm in this field.However,these developments will pose different challenges for the diagnosis and management of problems as compared with traditional allografts.The approach to pathologic diagnosis of dysfunction in these settings will likely be significantly different.Thus,there is a need to increase awareness and prepare transplant diagnosticians to meet this future challenge in the field of xenotransplantation/regenerative medicine.This review will focus on the current status of transplant pathology and how it will be changed in the future with the emerging scenario of routine xenotransplantation.

关键词： Xenotransplantation Bioengineered tissues Pathology Allograft xenograft

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Next generation patient-derived prostate cancer xenograft models

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Asian Journal of Andrology 2014年第3期16卷 407-412页

作者： Dong Lin Hui Xue Yuwei Wang Rebecca Wu Akira Watahiki Xin Dong Hongwei Cheng Alexander W Wyatt Colin C Collins Peter W Gout Yuzhuo Wang The Vancouver Prostate Centre Vancouver Genera Hospital Vancouver Department of Experimental Therapeutics British Columbia Cancer Agency Vancouver Department of Urologic Sciences Faculty of Medicine University of British Columbia Vancouver. British Columbia. Canada.

There is a critical need for more effective therapeutic approaches for prostate cancer. Research in this area, however, has been seriously hampered by a lack of clinically relevant, experimental in vivo models of the disease. This review particularly focuses on the development of prostate cancer xenograft models based on subrenal capsule grafting of patients＇ tumor tissue into nonobese diabetic/ severe combined immunodeficient （NOD/ SCID） mice. This technique allows successful development of transplantable, patient-derived cancer tissue xenograft lines not only from aggressive metastatic, but also from localized prostate cancer tissues. The xenografts have been found to retain key biological properties of the original malignancies, including histopathological and molecular characteristics, tumor heterogeneity, response to androgen ablation and metastatic ability. As such, they are highly clinically relevant and provide valuable tools for studies of prostate cancer progression at cellular and molecular levels, drug screening for personalized cancer therapy and preclinical drug efficacy testing; especially when a panel of models is used to cover a broader spectrum of the disease. These xenograft models could therefore be viewed as next-generation models of prostate cancer.

关键词： effective therapeutic patient-derived xenograft

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Translational pancreatic cancer research:a comparative study on patient-derived xenograft models

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World Journal of Gastroenterology 2018年第7期24卷 794-809页

作者： Mercedes Rubio-Manzanares Dorado Luis Miguel Marín Gómez Daniel Aparicio Sánchez Sheila Pereira Arenas Juan Manuel Praena-Fernández Juan Jose Borrero Martín Francisco Farfán López Miguel ángel Gómez Bravo Jordi Muntané Relat Javier Padillo Ruiz Department of Hepatobiliary and Pancreatic Surgery Virgen del Rocio University Hospital Oncology Surgery Cell Therapy and Organ Transplantation Group Institute of Biomedicine of Seville (IBiS) Virgen del Rocio University Hospital University of Seville Statistics Methodology and Evaluation of Research Unit Virgen del Rocio University Hospital Pathology Department Virgen del Rocio University Hospital

AIM To assess the viability of orthotopic and heterotopic patient-derived pancreatic cancer xenografts implanted into nude mice.METHODS This study presents a prospective experimental analytical follow-up of the development of tumours in mice upon implantation of human pancreatic adenocarcinoma samples. Specimens were obtained surgically from patients with a pathological diagnosis of pancreatic adenocarcinoma. Tumour samples from pancreatic cancer patients were transplanted into nude mice in three different locations(intraperitoneal, subcutaneous and pancreatic). Histological analysis(haematoxylin-eosin and Masson's trichrome staining) and immunohistochemical assessment of apoptosis(TUNEL), proliferation(Ki-67), angiogenesis(CD31) and fibrogenesis(α-SMA) were performed. When a tumour xenograft reached the target size, it was reimplanted in a new nude mouse. Three sequential tumour xenograft generations were generated(F1, F2 and F3).RESULTS The overall tumour engraftment rate was 61.1%. The subcutaneous model was most effective in terms of tissue growth(69.9%), followed by intraperitoneal(57.6%) and pancreatic(55%) models. Tumour development was faster in the subcutaneous model(17.7 ± 2.6 wk) compared with the pancreatic(23.1 ± 2.3 wk) and intraperitoneal(25.0 ± 2.7 wk) models(P = 0.064). There was a progressive increase in the tumour engraftment rate over successive generations for all three models(F1 28.1% vs F2 71.4% vs F3 80.9%, P xenograft differentiation and cell proliferation between human samples and the three experimental models among the sequential generations of tumour xenografts. However, a progressive decrease in fibrosis, fibrogenesis, tumour vascularisation and apoptosis was observed in the three experimental models compared with the human samples. All three pancreatic patient-derived xenograft models presented similar histological and immunohistochemical characteristics.CONCLUSION In our experience, the faster development andgreatest number o

关键词： Immunohistological analysis Pancreatic cancer Patient-derived xenograft Animal model Nude mice

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Hemo oxygenase-1 induction in vitro and in vivo can yield pancreas islet xenograft survival and improve islet function

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Chinese Medical Journal 2011年第20期124卷 3378-3385页

作者： CHEN Xi SU Chang ZHANG Zheng-yun ZHANG Ming-jun GU Wei-qiong LI Xiao-ying LI Hong-wei ZHOU Guang-wen Department of Surgery Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 China Department of Endocrine and Metabolism Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 China Department of Surgery Shanghai First Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200080 China

Background The induced expression of heme oxygenase-1 （HO-1） in donor islets improves allograft survival. Cobalt protoporphyrin （CoPP） could significantly enhance the expression of HO-1 mRNA and protein in rat islet safely. Our work was to study how to protect pancreatic islet xenograft by CoPP-induction. Methods Islet xenografts treated with CoPP-induction and CoPP＋ Zinc protoporphyrin （ZnPP） in vitro and in vivo were randomly transplanted into murine subrenal capsule; then the graft survival time was compared by blood glucose level and pathological examination and meanwhile the interferon ~ （IFN-y）, tumor necrosis factor a （TNF-a）, interleukin 10 （IL-10） and IL-113 level in serum and their mRNA and HO-1 mRNA and protein expression were examined. Results Islets with CoPP-induction under low- and high-glucose stimulation exhibited much higher insulin secretion compared with other three groups. CoPP-induction could increase higher expression of HO-1 （mRNA： 3.33- and 76.09- fold in vitro and in vivo; protein： 2.85- and 58.72-fold）. The normoglycemia time in induction groups （（14.63±1.19） and （16.88±1.64） days） was significantly longer. The pathological examination showed less lymphocyte infiltration in induction groups. The IL-10 level and its mRNA in induction groups were significantly higher. Conclusions The HO-1 induced by CoPP would significantly improve function, prolong normoglycemia time and reduce lymphocyte infiltration. Meanwhile CoPP-induction in vivo had more beneficial effects than in vitro. Its mechanism could be related to immune-modulation of IL-10.

关键词： pancreatic islet transplantation cobalt protoporphyrin xenograft heme oxygenase interleukin 10

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Circulating tumor DNA dynamics analysis in a xenograft mouse model with esophageal squamous cell carcinoma

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World Journal of Gastroenterology 2021年第41期27卷 7134-7143页

作者： Hiroyuki Terasawa Hideaki Kinugasa Kazuhiro Nouso Shumpei Yamamoto Mami Hirai Takehiro Tanaka Akinobu Takaki Hiroyuki Okada Department of Gastroenterology and Hepatology Okayama University Graduate School of MedicineDentistry and Pharmaceutical SciencesOkayama 7008558Japan Department of Pathology Okayama University Graduate School of MedicineDentistry and Pharmaceutical SciencesOkayama 7008558Japan

BACKGROUND It remains unclear which factors,such as tumor volume and tumor invasion,influence circulating tumor DNA(ctDNA),and the origin of ctDNA in liquid biopsy is always problematic.To use liquid biopsies clinically,it will be very important to address these questions.AIM To assess the origin of ctDNA,clarify the dynamics of ctDNA levels,assess ctDNA levels by using a xenograft mouse after treatment,and to determine whether tumor volume and invasion are related to ctDNA levels.METHODS Tumor xenotransplants were established by inoculating BALB/c-nu/nu mice with the TE11 cell line.Groups of mice were injected with xenografts at two or four sites and sacrificed at the appropriate time point after xenotransplantation for ctDNA analysis.Analysis of ctDNA was performed by droplet digital PCR,using the human telomerase reverse transcriptase(hTERT)gene.RESULTS Mice given two-site xenografts were sacrificed for ctDNA at week 4 and week 8.No hTERT was detected at week 4,but it was detected at week 8.However,in four-site xenograft mice,hTERT was detected both at week 4 and week 6.These experiments revealed that both tumor invasion and tumor volume were asso ciated with the detection of ctDNA.In resection experiments,hTERT was detected at resection,but had decreased by 6 h,and was no longer detected 1 and 3 d after resection.CONCLUSION We clarified the origin and dynamics of ctDNA,showing that tumor volume is an important factor.We also found that when the tumor was completely resected,ctDNA was absent after one or more days.

关键词： Liquid biopsy Circulating tumor DNA xenograft Esophageal squamous cell carcinoma Dynamics of circulating tumor DNA

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Circulating microRNAs and liquid biopsy:murine xenograft models for technical validation of clinical protocols

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Journal of Cancer Metastasis and Treatment 2019年第6期4卷 87-97页

作者： Jessica Gasparello Matteo Allegretti Chiara Papi Elena Giordani Patrizio Giacomini Roberto Gambari Alessia Finotti Department of Life Sciences and Biotechnology Ferrara UniversityFerrara 44121Italy Oncogenomics and Epigenetics IRCCS Regina Elena National Cancer InstituteRome 00144Italy Interuniversity Consortium for Biotechnology(CIB) Trieste 34149Italy

In oncology,liquid biopsy is applied to detect with high efficiency clinically relevant analytes,such as tumor cells,cell-free nucleic acids,and exosomes in peripheral blood and other body fluids of cancer patients.Liquid biopsy is considered one of the most advanced non-invasive diagnostic systems useful,in the next future,for enabling personalized treatments in precision medicine.Medical actions include,but are not limited to,early diagnosis,staging,prognosis,anticipation(lead time)and prediction of therapy responses,as well as follow up.Experimental system for validation of the proposed liquid biopsy approaches is highly needed.In this review article we will discuss the establishment of xenotransplanted mouse model systems for the validation of liquid biopsy protocols aimed to identify changes in the miRNA plasma content.Human colon cancer HT-29 and LoVo cells have been xenotransplanted and miR-221-3p and miR-222-3p have been comparatively analyzed in cultured HT-29 and LoVo cells,xenotransplants and plasma samples.

关键词： Liquid biopsy circulating tumor RNA microRNA xenograft

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First report on establishment and characterization of the extrahepatic cholangiocarcinoma sarcoma cell line CBC2T-2

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World Journal of Gastroenterology 2023年第41期29卷 5683-5698页

作者： Ning-Zu Jiang Ming-Zhen Bai Chong-Fei Huang Ze-Long Ma Ru-Yang Zhong Wen-Kang Fu Long Gao Liang Tian Ning-Ning Mi Hai-Dong Ma Ya-Wen Lu Zi-Ang Zhang Jin-Yu Zhao Hai-Ying Yu Bao-Ping Zhang Xian-Zhuo Zhang Yan-Xian Ren Chao Zhang Yong Zhang Ping Yue Yan-Yan Lin Wen-Bo Meng The First Clinical Medical College Lanzhou UniversityLanzhou 730000Gansu ProvinceChina Department of General Surgery The First Hospital of Lanzhou UniversityLanzhou 730000Gansu ProvinceChina Laboratory of Biological Therapy and Regenerative Medicine Transformation Gansu Province The First Hospital of Lanzhou UniversityLanzhou 730000Gansu ProvinceChina Department of General Surgery The First Hospital of Lanzhou University and Laboratory of Biological Therapy and Regenerative Medicine Transformation Gansu ProvinceLanzhou 730000Gansu ProvinceChina

BACKGROUND Extrahepatic cholangiocarcinoma sarcoma is extremely rare in clinical practice.These cells consist of both epithelial and mesenchymal cells.Patient-derived cell lines that maintain tumor characteristics are valuable tools for studying the molecular mechanisms associated with carcinosarcoma.However,cholangiocarcinoma sarcoma cell lines are not available in cell banks.AIM To establish and characterize a new extrahepatic cholangiocarcinoma sarcoma cell line,namely CBC2T-2.METHODS We conducted a short tandem repeat(STR)test to confirm the identity of the CBC2T-2 cell line.Furthermore,we assessed the migratory and invasive properties of the cells and performed clonogenicity assay to evaluate the ability of individual cells to form colonies.The tumorigenic potential of CBC2T-2 cells was tested in vivo using nonobese diabetic/severe combined immunodeficient(NOD/SCID)mice.The cells were injected subcutaneously and tumor formation was observed.In addition,immunohistochemical analysis was carried out to examine the expression of epithelial marker CK19 and mesenchymal marker vimentin in both CBC2T-2 cells and xenografts.The CBC2T-2 cell line was used to screen the potential therapeutic effects of various clinical agents in patients with cholangiocarcinoma sarcoma.Lastly,whole-exome sequencing was performed to identify genetic alterations and screen for somatic mutations in the CBC2T-2 cell line.RESULTS The STR test showed that there was no cross-contamination and the results were identical to those of the original tissue.The cells showed round or oval-shaped epithelioid cells and mesenchymal cells with spindle-shaped or elongated morphology.The cells exhibited a high proliferation ratio with a doubling time of 47.11 h.This cell line has migratory,invasive,and clonogenic abilities.The chromosomes in the CBC2T-2 cells were polyploidy,with numbers ranging from 69 to 79.The subcutaneous tumorigenic assay confirmed the in vivo tumorigenic ability of CBC2T-2 cells in NOD/SCID mice.CBC2T-2 cells and xenografts were posi

关键词： Carcinosarcoma Drug resistance xenograft Cell line Establishment

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Establishment and characterization of a new human ampullary carcinoma cell line,DPC-X1

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World Journal of Gastroenterology 2023年第17期29卷 2642-2656页

作者： Hao Xu Chang-Peng Chai Xin Miao Huan Tang Jin-Jing Hu Hui Zhang Wen-Ce Zhou The Forth Department of General Surgery The First Hospital of Lanzhou UniversityLanzhou 730000Gansu ProvinceChina State Key Laboratory of Veterinary Etiological Biology Key Laboratory of Animal Virology of the Ministry of AgricultureLanzhou Veterinary Research InstituteChinese Academy of Agricultural SciencesLanzhou 730000Gansu ProvinceChina The Second Clinical Medical College Lanzhou UniversityLanzhou 730000Gansu ProvinceChina Department of General Surgery The Second Hospital of Lanzhou UniversityLanzhou 730000Gansu ProvinceChina

BACKGROUND An in-depth study of the pathogenesis and biological characteristics of ampullary carcinoma is necessary to identify appropriate treatment strategies. To date, only eight ampullary cancer cell lines have been reported, and a mixed-type ampullary carcinoma cell line has not yet been reported.AIM To establish a stable mixed-type ampullary carcinoma cell line originating from Chinese.METHODS Fresh ampullary cancer tissue samples were used for primary culture and subculture. The cell line was evaluated by cell proliferation assays, clonal formation assays, karyotype analysis, short tandem repeat(STR) analysis and transmission electron microscopy. Drug resistances against oxaliplatin, paclitaxel, gemcitabine and 5-FU were evaluated by cell counting kit-8 assay. Subcutaneous injection 1 × 106 cells to three BALB/c nude mice for xenograft studies. The hematoxylin-eosin staining was used to detect the pathological status of the cell line. The expression of biomarkers cytokeratin 7(CK7), cytokeratin 20(CK20), cytokeratin low molecular weight(CKL), Ki67 and carcinoembryonic antigen(CEA) were determined by immunocytochemistry assay.RESULTS DPC-X1 was continuously cultivated for over a year and stably passaged for more than 80 generations;its population doubling time was 48 h. STR analysis demonstrated that the characteristics of DPC-X1 were highly consistent with those of the patient’s primary tumor. Furthermore, karyotype analysis revealed its abnormal sub-tetraploid karyotype. DPC-X1 could efficiently form organoids in suspension culture. Under the transmission electron microscope, microvilli and pseudopods were observed on the cell surface, and desmosomes were visible between the cells. DPC-X1 cells inoculated into BALB/C nude mice quickly formed transplanted tumors, with a tumor formation rate of 100%. Their pathological characteristics were similar to those of the primary tumor. Moreover, DPC-X1 was sensitive to oxaliplatin and paclitaxel and resistant to gemcitabine and 5-FU. Immunohistochemistry showed tha

关键词： Ampullary carcinoma Cell line xenograft Drug resistance

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Xiaoyan decoction inhibits tumor growth and improves the immunity of mouse with A549 lung carcinoma xenograft

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TMR Cancer 2019年第4期2卷 227-232页

作者： Fan-Ming Kong Yang Yao Ren-Fen Deng Tian-Qi Chen Dong-Ying Liao Xiao-Jiang Li Ying-Jie Jia Department of Oncology First Teaching Hospital of Tianjin University of Traditional Chinese MedicineTianjin 300193China

Background:Previously,Xiaoyan decoction(XYD)has been found to have a potential anti-tumor effect in vitro.The aim of this study was to explore the effect of XYD in A549 lung carcinoma xenograft mouse model.Method:The A549 lung carcinoma xenograft mouse model were established and divided into control and experiment group.The dynamic growth of the xenograft tumors was observed and the immune cells such as T cell,regulatory T cell(Treg)were explored by Fluorescence-activated cell sorter(FACS)analysis.In this study,network pharmacology was used to screen the anti-cancer monomers in XYD,and their effect targets were also predicted.Result:The result showed that the tumor growth was inhibited and the percent of Treg was down-regulated(Pxenograft mouse model.

关键词： Non-small cell lung cancer XYD antitumor activity xenograft

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