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Promising xenograft animal model recapitulating the features of human pancreatic cancer

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World Journal of Gastroenterology 2020年第32期26卷 4802-4816页

作者： Jin-Xin Miao Jian-Yao Wang Hao-Ze Li Hao-Ran Guo Louisa S Chard Dunmall Zhong-Xian Zhang Zhen-Guo Cheng Dong-Ling Gao Jian-Zeng Dong Zhong-De Wang Yao-He Wang Sino-British Research Centre for Molecular Oncology National Centre for International Research in Cell and Gene TherapyAcademy of Medical SciencesZhengzhou UniversityZhengzhou 450000Henan ProvinceChina Academy of Chinese Medical Sciences Henan University of Chinese MedicineZhengzhou 450000Henan ProvinceChina Centre for Biomarkers and Biotherapeutics Barts Cancer InstituteQueen Mary University of LondonLondon EC1M6BQUnited Kingdom Department of Cardiology Beijing Anzhen HospitalCapital Medical UniversityBeijing 100029China Department of animal Dairy and Veterinary SciencesUtah State UniversityLogan UT 84341United States

BACKGROUND Multiple sites of metastasis and desmoplastic reactions in the stroma are key features of human pancreatic cancer(PC).There are currently no simple and reliable animal models that can mimic these features for accurate disease modeling.AIM To create a new xenograft animal model that can faithfully recapitulate the features of human PC.METHODS Interleukin 2 receptor subunit gamma(IL2RG)gene knockout Syrian hamster was created and characterized.A panel of human PC cell lines were transplanted into IL2RG knockout Syrian hamsters and severe immune-deficient mice subcutaneously or orthotopically.Tumor growth,local invasion,remote organ metastasis,histopathology,and molecular alterations of tumor cells and stroma were compared over time.RESULTS The Syrian hamster with IL2RG gene knockout(named ZZU001)demonstrated an immune-deficient phenotype and function.ZZU001 hamsters faithfully recapitulated most features of human PC,in particular,they developed metastasis at multiple sites.PC tissues derived from ZZU001 hamsters displayed desmoplastic reactions in the stroma and epithelial to mesenchymal transition phenotypes,whereas PC tissues derived from immune-deficient mice did not present such features.CONCLUSION ZZU001 hamsters engrafted with human PC cells are a superior animal model compared to immune-deficient mice.ZZU001 hamsters can be a valuable animal model for better understanding the molecular mechanism of tumorigenesis and metastasis and the evaluation of new drugs targeting human PC.

关键词： Pancreatic cancer Xenotrans plantation Syrian hamster IL-2 receptor gamma chain gene Metastasis animal model

Preclinical in vivo research of magnesium-based implants for fracture treatment: A systematic review of animal model selection and study design

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Journal of Magnesium and Alloys 2021年第2期9卷 351-361页

作者： Yu Sun Heike Helmholz Regine Willumeit-Römera Division of Metallic Biomaterials Institute of Materials ResearchHelmholtz-Zentrum Geesthacht21502 GeesthachtGermany Department of Orthopedics First Hospital of China Medical UniversityShenyang 110001China

Background:Degradable magnesium implants are promising for clinical fracture treatment,providing less stress-shielding mechanical support and superior bone-strengthening benefits to traditional materials.The quality of preclinical research is essential for developing Mg implants;however,there are considerable variations in the model selection and study design in published studies,posing challenges for safe and effective clinical translation of lab discoveries.Objective:The purpose of this systematic review is to investigate the current progress on in vivo research of Mg implants for fracture treatment,focusing on model selection,Mg materials,implant design,methodological and analyzing techniques,aiming to provide comprehensive guidance for future preclinical research.Materials and methods:Pub Med and Embase online databases were searched to identify researches investigating Mg implants in animal models of fracture from 1960 to December 2019,using a combination of keywords:magnesium and fracture.Eligible studies were included without language restriction.Data extraction was conducted for qualitative analysis.Meta-analysis was not performed due to extensive heterogeneities among studies.Results:Twenty studies published from 2014 to 2019 were included.Publication information,animal model,methodological quality,implants preparation,and evaluation techniques were extracted.The methodological assessment revealed low to high risk of bias among studies.Both rodent and non-rodent species were selected,and the anatomical sites for inducing fractures included both cranial-facial and limb bones.Pure Mg and alloys with or without surface modification were evaluated,covering implant designs of both intra-medullary and extra-medullary fixation.Radiological and histological evaluations were commonly conducted.Conclusions:Published in vivo evidence confirmed the role of Mg-based implants in promoting fracture healing.However,considering heterogeneity in animal selection,implant preparation,and evaluation methods,there still lacks

关键词： Magnesium Implant Fracture animal model Study design Biomaterial

Thinking Path and Method for Establishing the Disease/ Chinese Medicine Syndrome Conjugated Pattern of a Mammary Hyperplasia animal model

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Chinese Journal of Integrative Medicine 2010年第5期16卷 457-463页

作者：马民翟贺宁 Medical College of Jinan University

Mammary hyperplasia （MHP） is the most commonly encountered mammary disease in women at the child-bearing stage. Especially, atypical hyperplasia which belongs to the precancerous category, is the disease for class Ⅰ prevention of breast cancer. Therefore, advancing the clinical efficacy of MHP treatment is of critical importance. Chinese medicine （CM） and drugs show a peculiar effect in this field; the clinical or experimental researches concerning MHP treatment by CM compounds or patent drugs have been increasing gradually in recent years, but the thinking paths and methods for establishing the MHP animal model are divergent. Particularly, the disease/CM syndrome conjugated model （D/S model） has rarely been studied. For this reason, the pathogenetic mechanism, the establishment of an animal disease model, as well as the thinking paths and methods for establishing the D/S model of MHP are discussed and summarized preliminarily in this paper by the authors. This could provide a new way of thinking and method for creating the MHP model in modern medicine.

关键词： mammary hyperplasia animal model thinking path

Establishment of an animal model of extra-vertebral foramen cervical nerve entrapment by local electrical stimulation and selection of suitable stimulation parameters

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Neural Regeneration Research 2011年第29期6卷 2284-2289页

作者： Jinwu Wang Juliet Hou Qi Li Jian Tang Biyu Rui Shangchun Guo Haitao Jiang Cunyi Fan You Wang Zhenan Zhu Kerong Dai Guang H Yue Department of Orthopedic Surgery the Ninth People＇s Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200011 China Department of Physical Medicine ＆ Rehabilitation the Cleveland Clinic Cleveland Ohio 44195 USA Department of Orthopaedic Surgery the Sixth Municipal People＇s Hospital Shanghai Jiao Tong University Shanghai 200233 China Biomedical Engineering the Cleveland Clinic Cleveland Ohio 44195 USA

A rat model of extra-vertebral foramen cervical nerve entrapment was established according to the following parameters： stimulation intensity 20 V; frequency 50 Hz; pulse width 200 μs; duration 333 ms/s for a total of 8 hours. After the electrical stimulation, rats exhibited mild muscle fiber atrophy, mild inflammatory exudates, connective tissue local fibrosis and chondrocyte metaplasia. Mean muscle fiber cross-sectional area was reduced. The nerve myelin sheath continuity was partially demyelinated. The microstructure of nerve cells was disrupted and these symptoms worsened with prolongation of the stimulation. The shoulder, neck and upper extremity muscles on the tested side demonstrated positive sharp waves and fibrillations. The severity increased with continuation of the stimulation. High amplitude and polyphasic motor unit potentials gradually appeared. Similar findings were seen in the contralateral side, but at a less severe level.

关键词： chronic neck-shoulder pain electrical stimulation extra-vertebral foramen cervical nerve entrapment syndrome animal model

Recent advances of optical imaging in animal stroke model

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Frontiers of Optoelectronics 2013年第2期6卷 134-145页

作者： Zhen WANG Britton Chance Center for Biomedical Photonics Wuhan National Laboratory for Optoelectronics Huazhong University of Science and Technology Wuhan 430074 China MoE Key Laboratory for Biomedical Photonics Department of Biomedical Engineering Huazhong University of Science and Technology Wuhan 430074 China

Stroke is a major health concern and an intensive research subject due that it is the major cause of death and the leading cause of disability worldwide. The past three decades of clinical disappointments in treating stroke must compel us to rethink our strategy. New effective protocol for stroke could greatly benefit from the advances in optical imaging technologies. This review focuses on the latest advance of applications of three optical imaging techniques in animal model of stroke, such as photoacoustic （PA） imaging, laser speckle contrast imaging （LSCI） and two-photon microscopy （TPM）. The potential roles of those techniques in the future of stroke management are also discussed.

关键词： optical imaging photoacoustic （PA） imaging laser speckle contrast imaging （LSCI） two-photon micro- scopy （TPM） animal model stroke

An animal model of cerebral palsy induced by prenatal exposure to lipopolysaccharide and hypoxia

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Neural Regeneration Research 2010年第14期5卷 1100-1103页

作者： Gang Chen Yanrong HU Wei Liu Jiang Li Linbao Wen Jianxin Li Lihui Zhao Xiaopeng Yang Yi Zhu Zhenzhu Sun Guangming Chi Department of Neurosurgery People's Hospital of Xinjiang Uygur Autonomous Region Urumqi 830001 Xinjiang Uygur Autonomous Region China Department of Neurology People's Hospital of Xinjiang Uygur Autonomous Region Urumqi 830001 Xinjiang Uygur Autonomous Region China Department of Pathology People's Hospital of Xinjiang Uygur Autonomous Region Urumqi 830001 Xinjiang Uygur Autonomous Region China Medical Research Center People's Hospital of Xinjiang Uygur Autonomous Region Urumqi 830001 Xinjiang Uygur Autonomous Region China

BACKGROUND： Neonatal cerebral palsy is mainly caused by prenatal factors. At present, an animal model of prenatal infection and early postnatal hypoxia does not exist. OBJECTIVE： To observe morphology and motor performance following prenatal infection and hypoxic insult-induced brain damage of neonatal rats to verify the feasibility to establish a model of cerebral palsy. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Laboratories of Xinjiang Center for Disease Control and Prevention from September 2007 to June 2008. MATERIALS： The hypoxic incubator was purchased from Shanghai Pediatric Medical Institute, China. Lipopolysaccharide （LPS, Escherichia coil, 055： B5） was purchased from Sigma-Aldrich （St. Louis, MO, USA）. METHODS： A total of 27 Wistar rats, aged 7 days, were randomly assigned to sham-surgery group （n = 15） with no carotid artery incision or hypoxia treatment, hypoxia/ischemia （H/I） group （n = 12） undergoing ligature of the right common carotid artery followed by exposure to hypoxia at postnatal day 7 （P7）, and LPS/H group （n = 19）, in which pregnant rats were exposed in utero to LPS followed by prenatal hypoxia at embryonic day 16. MAIN OUTCOME MEASURES： Behavior, compound muscle action potential, and pathological changes were observed in 28-day-old rats. RESULTS： The footprint repeat space showed that left limb footprint repeatability in the H/I and LPS/H groups was lower than in the sham-surgery group （P 〈 0.05）. The space between the footprints was larger and unstable. Hind limb quadricep compound muscle action potential in the H/I and LPS/H groups showed lower wave amplitude compared with the sham-surgery group （P〈 0.05） Hematoxylin and eosin staining showed irregular cells around the ventricle, as well as periventricular leukomalacia. CONCLUSION： An animal model of cerebral palsy was established, which simulated the human condition most likely associated with occurrence of this disease. This model could be used for experimental studies related to

关键词： inflammation hypoxia animal model cerebral palsy periventricular leukomalacia brain injury neural regeneration

Large animal models of human cauda equina injury and repair: evaluation of a novel goat model

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Neural Regeneration Research 2015年第1期10卷 60-64页

作者： Wen-tao Chen Pei-xun Zhang Feng Xue Xiao-feng Yin Cao-yuan Qi Jun Ma Bo Chen You-lai Yu Jiu-xu Deng Bao-guo Jiang Department of Trauma and Orthopedics Peking University People’s Hospital Department of Radiology Beijing Tian Tan HospitalCapital Medical University

Previous animal studies of cauda equina injury have primarily used rat models, which display significant differences from humans. Furthermore, most studies have focused on electrophysio- logical examination. To better mimic the outcome after surgical repair of cauda equina injury, a novel animal model was established in the goat. Electrophysiological, histological and magnetic resonance imaging methods were used to evaluate the morphological and functional outcome after cauda equina injury and end-to-end suture. Our results demonstrate successful establish- ment of the goat experimental model of cauda equina injury. This novel model can provide detailed information on the nerve regenerative process following surgical repair of cauda equina injury.

关键词： nerve regeneration spinal cord injury goat animal model radiography magneticresonance imaging diffusion tensor imaging fiber bundle diagnosis injury physiology neuroimaging NSFC grants neural regeneration

An animal model of Sudden Onset Sensorineural Hearing Loss with Vestibular Function Disturbances Induced By Mitochondrial Toxin

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Journal of Otology 2006年第2期1卷 86-93页

作者： PYYKK Ilmari Department of Otolaryngology Tampere University HospitalTeiskontie 3533520 TampereFinland (J.Z.I.P.)

Objective To establish an animal model of sudden onset sensorineural hearing loss (SSNHL) to study its mechanisms. Materials and methods The inner ear was exposed to 3-nitropropionic acid at 0.5 mol/L (3-NP (H)) and 0.3 mol/L (3-NP (L)) through the round window membrane for 30 minutes in 50 male guinea pigs. Thresholds of auditory brainstem responses(ABR) were established before the treatment and retested at 4 hours, 1 day, 3 days and 6 days following 3-NP exposure. Control animals were treated with phosphate buffered saline (PBS) and their ABRs were retested at 4 hours and 1 day after the treatment. animals were monitored for nystagmus and postural signs of vestibular dysfunction, using a digital video camera, following the treatment procedure. Specimens were taken at 12 hours, 1 day, 3 days and 7 days following 3-NP(H) exposure and embedded in JB4 for light microscopy observation. Results ABRs were lost in all animals tested at 4 hours following 3-NP (H) exposure. The rate of complete ABR loss decreased as post-treatment test time increased. ABRs were lost in 80% (4/5) of the animals at 1 day after exposure to 3-NP (L). Spontaneous horizontal nystagmus with a fast phase away from the treated ear developed in all 3-NP (H)-treated animals and in 20 % ( 1/5) of the animals exposed to 3-NP (L), except for the one treated bilaterally. Various degree of postural disturbances consistent with unilateral vestibular dysfunction, such as spontaneous barrel rolling towards the exposure side while walking, were seen in all animals exposed to 3-NP(H) and 40% (2/5) of animals exposed to 3-NP(L), except for the one animal treated bilaterally, which showed no signs of imbalance. Both nystagmus and postural disturbances resolved in 2 days following 3-NP exposure. Histological study showed temporary edema tin the organ or Corti, Claudius cells and the inner sulcus cells 3 days after 3-NP (H) treatment. Enlargement of intercellular space in the spiral prominence was first noticed at 12 hours post-3-NP (H) exposure, progressed at d

关键词： Hearing loss vertigo mitochondrial dysfunction animal model histology

A METHOD FOR ESTABLISHING AN animal model OF LIKE-AUDITARY NEUROPATHY

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Journal of Otology 2014年第1期9卷 48-51页

作者： GUO Weiwei CHEN Peipei WEI Xiaoquan YANG Shiming Department of Otolaryngology-Head and Neck Surgery Institute of Oto-Neurobiology Centre Otolaryngology Chinese PLA General Hospital Department of Otolaryngology-Head and Neck Surgery Nanjing Children's Hospital Nanjing Medical University

Objective: To establish an animal model of like-auditory neuropathy in neonatal rat. Methods The ani-mals were injected with phenylhydrazine hydrochloride or saline at 7-day of age. ABR and DPOAE were performed to assess the auditory function. The cochlea basilar membrane stretched preparation and cochlear frozen sections were prepared for immunohistochemical staining to examine the morphological change of hair cells and spiral ganglion cells (SGNs). Results At 7-day age the ABR waveI, III, V, latencies andI-III,I-V IWIs in the experimental group were significantly prolonged compared with those in the control group. The ABR thresholds were also elevated in the experimental group. We found there is no significant differ-ence in DPOAE in phenylhydrazine hydrochloride exposure group compare to control group. The cochlear hair cells showed no signs of loss in both group, but the total number of neurofilaments positive cells in SGNs were significantly reduced in the phenylhydrazine treated animals. Conclusion Our study suggests that phenylhydrazine hydrochloride can change the auditory function and induce peripheral nerve pathology by targeted mainly the SGNs in neonatal rat.

关键词： animal model Auditory brainstem response Distortion-product otoacoustic emission auditory neuropathy