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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 ***,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 ***,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 *** generated Au@C-CCMs were evaluated on corresponding CDX,tongue orthotopic xenograft(TOX),immunecompetent primary and distant tumor models,and patient-derived xenograft(PDX)*** 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 *** 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 *** 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 ***,organ shortage has posed and is still posing a big challenge in this *** options being explored are xenografts and engineered/bioengineered tissues/*** small steps have been taken in this direction and sooner or later,these will become a norm in this ***,these developments will pose different challenges for the diagnosis and management of problems as compared with traditional *** approach to pathologic diagnosis of dysfunction in these settings will likely be significantly ***,there is a need to increase awareness and prepare transplant diagnosticians to meet this future challenge in the field of xenotransplantation/regenerative *** 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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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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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 *** 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 *** In our experie

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

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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 *** use liquid biopsies clinically,it will be very important to address these *** 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 *** Tumor xenotransplants were established by inoculating BALB/c-nu/nu mice with the TE11 cell *** of mice were injected with xenografts at two or four sites and sacrificed at the appropriate time point after xenotransplantation for ctDNA *** of ctDNA was performed by droplet digital PCR,using the human telomerase reverse transcriptase(hTERT)*** Mice given two-site xenografts were sacrificed for ctDNA at week 4 and week *** hTERT was detected at week 4,but it was detected at week ***,in four-site xenograft mice,hTERT was detected both at week 4 and week *** experiments revealed that both tumor invasion and tumor volume were asso ciated with the detection of *** resection experiments,hTERT was detected at resection,but had decreased by 6 h,and was no longer detected 1 and 3 d after *** We clarified the origin and dynamics of ctDNA,showing that tumor volume is an important *** 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 *** biopsy is considered one of the most advanced non-invasive diagnostic systems useful,in the next future,for enabling personalized treatments in precision *** actions include,but are not limited to,early diagnosis,staging,prognosis,anticipation(lead time)and prediction of therapy responses,as well as follow *** system for validation of the proposed liquid biopsy approaches is highly *** 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 *** 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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Inhibitory effect of a new gossypol derivative apogossypolone (ApoG2) on xenograft of human prostate cancer cell line PC-3

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Journal of Medical Colleges of PLA(China) 2009年第5期24卷 274-282页

作者： Zhang Xianqing Huang Xiaofeng Mu Shijie Chen Rui An Qunxing Xia Aijun Wu Daocheng Department of Blood Transfusion Xijing Hospital Fourth Military Medical University Xi 'an 710032 China Central Laboratory Fourth Military Medical University Xi 'an 710032 China Key Laboratory of Biomedical Information Engineering of Ministry of Education Xi'an Jiaotong University Xi 'an 710038 China

Objective: To investigate the inhibitory effect of apogossypolone (ApoG2) on prostate cancer cell line PC-3 in vivo, and explore its mechanism. Methods: The models of transplantation tumors in Balb/c nu/nu mice were established via subcutaneous injection of PC-3 cells and the tumor-transplanted mice were divided into 4 groups: control group and three ApoG2 treatment groups, with 10 mice in each group. Volumes of the tumor were estimated every 2 d and the morphology of tumor tissues was observed. Immunohistochemistry was employed to observe the expression of Bcl-2, PCNA, CD31, caspase-3 and caspase-8 in tumor tissues. Results: ApoG2 (2.5 mg/kg-10 mg/kg) given intraperitoneally once a day can obviously inhibit the growth of subcutaneous prostatic carcinoma implant. The tumor volume decreased obviously when the treatment dosage was bigger than 5.0 mg/kg (P<0.01). Meanwhile, ApoG2 decreased the expression of PCNA and CD31, and enhanced the expression of caspases-3, caspase-8 in tumor tissues. Conclusion: ApoG2 exert an inhibitory effect on prostatic carcinoma possibly by inducing apoptosis and inhibiting tumor angiogenesis.

关键词： Apogossypolone Prostate cancer PC-3 human prostatic carcinoma cell line xenograft

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Persimmon Leaf Flavonols Enhance the Anti-Cancer Effect of Heavy Ion Radiotherapy on Murine xenograft Tumors

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Journal of Cancer Therapy 2013年第7期4卷 1150-1157页

作者： Kayoko Kawakami Hiroshi Nishida Naoto Tatewaki Kiyomi Eguchi-Kasai Kazunori Anzai Takahiro Eitsuka Tetsuya Konishi Masao Hirayama Laboratory of Nutritional Biochemistry Niigata University of Pharmacy & Applied Life Sciences Niigata Japan National Institute of Radiological Sciences Chiba Japan

The cell cycle checkpoint system play a pivotal role in the cellular DNA damage response, and the discovery of checkpoint inhibitors is expected to sensitize current cancer therapies. Checkpoint signaling cascades are critically modulated by ATM (ataxia telangiectasia-mutated) and its related molecules. Generally, ATM primarily responds to ionizing irradiation-induced DNA double-strand breaks. Heavy ions from an accelerated carbon ion beam have been used to cure cancer because they are more effective than ionizing irradiation such as X-ray and γ-radiation in terms of biological damage. In a previous study, we demonstrated that a persimmon leaf flavonol (PLF) promoted the cytotoxic effect of chemotherapeutic agents on cancer cells through inhibition of checkpoint activities, especially in the ATM dependent pathway. The present study investigated whether PLF inhibits checkpoint activity during the DNA damage response induced by heavy ion irradiation. Treatment with PLF significantly increased the cytotoxicity of heavy ion irradiation in A549 adenocarcinoma cells. The phosphorylation of checkpoint proteins such as p53, SMC1, and Chk1 was increased by heavy ions. PLF reduced the phosphorylation of checkpoint proteins. Pre-treatment with PLF significantly prevented the decrease of mitotic cells in heavy ion-exposed cells. We further evaluated tumor volume in SCID mice inoculated with human lung adenocarcinoma A549 cells. The combination treatment of PLF and heavy ion resulted in a decrease of tumor volume compared with controls, although PLF itself did not exhibit any effect. These results indicate that PLF inhibits tumor growth through modulation of the DNA damage response. PLF may be useful for clinical application in combination with heavy ion radiotherapy.

关键词： DNA Damage Checkpoint Persimmon Leaf Flavonols Heavy Ion Irradiation xenograft

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Combination Therapy of Capecitabine with Cyclophosphamide as a Second-Line Treatment after Failure of Paclitaxel plus Bevacizumab Treatment in a Human Triple Negative Breast Cancer xenograft Model

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Journal of Cancer Therapy 2013年第7期4卷 1236-1241页

作者： Mieko Yanagisawa Keigo Yorozu Mitsue Kurasawa Yoichiro Moriya Naoki Harada Product Research Department Chugai Pharmaceutical Co. Ltd. Kamakura Japan

We examined the antitumor efficacy of the capecitabine (CAPE) plus cyclophosphamide (CPA) combination as a 2nd-line therapy after paclitaxel (PTX) plus bevacizumab (BEV) treatment in a xenograft model of human triple negative breast cancer (TNBC) cell line, MX-1. After tumor growth was confirmed, PTX (20 mg/kg;i.v.) + BEV (5 mg/kg;i.p.) treatment was started (Day 1). Each agent was administered once a week for 5 weeks and tumor regression was observed for at least the first 3 weeks. For 2nd-line treatment, we selected mice in which the tumor volume had increased from day 29 to day 36 and was within 130 - 250 mm3 on day 36. After randomization of mice selected on day 36, CPA (10 mg/kg;p.o.) and CAPE (539 mg/kg;p.o.) were administered daily for 14 days (days 36 - 49), followed by cessation of the drugs for 1 week. The tumor growth on day 57 was significantly suppressed in the CPA, CAPE and CAPE + CPA groups as compared with the control group (p < 0.05). Furthermore, the antitumor activity on day 57 of CAPE + CPA was significantly stronger than that of CPA or CAPE alone (p < 0.05). The thymidine phosphorylase (TP) level in tumor tissue was evaluated by immunohistochemistry on day 50, and was significantly higher in the CPA group than those in the control group (p < 0.05). Upregulation of TP in tumor tissues by CPA treatment would increase the 5-FU level in tumor tissues treated with CAPE. This would explain the possible mechanism that made CAPE + CPA superior to CAPE alone in the 2nd-line treatment. Our preclinical results suggest that the CAPE + CPA combination therapy may be effective as 2nd-line therapy after disease progression in PTX + BEV 1st-line treatment for TNBC patients.

关键词： Triple Negative Breast Cancer Capecitabine Cyclophosphamide Bevacizumab Paclitaxel xenograft Model

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