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Advantages and limitations in the establishment and utilization of patient-derived xenografts in gastric cancer
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作者 Zuhua Chen Lin Shen 《Oncology and Translational Medicine》 2017年第1期3-9,共7页
Owing to the high genetic heterogeneity of tumors, small number of therapeutic strategies available, and frequent presentation of drug resistance, the prognosis for patients with advanced gastric cancer(AGC) are unsat... Owing to the high genetic heterogeneity of tumors, small number of therapeutic strategies available, and frequent presentation of drug resistance, the prognosis for patients with advanced gastric cancer(AGC) are unsatisfactory. The utility of traditional cancer cell lines in translational research is limited by their poor correspondence to the genomic alterations and expression profiles that occur in actual patient tumors. In the last decade, increasing attention has been given to patient-derived tumor xenografts(PDTXs), which can faithfully recapitulate the histopathology, molecular characteristics, and therapeutic responses of the patient's tumor. However, the widespread development and utilization of PDTXs is restricted by factors such as the timeframe of establishment, lymphoma transformation during passaging, the immunodeficient microenvironment, and pharmacokinetic differences between mice and humans. In this review, we summarize the establishment and characterization of PDTX models for gastric cancer(GC). We then weigh the advantages and limitations of PDTXs when used to evaluate novel compounds, identify effective biomarkers, demonstrate resistance mechanisms, and predict clinical outcomes. 展开更多
关键词 patient-derived tumor xenograft (PDTX) GASTRIC cancer (GC) PRECLINICAL research
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Delivery of triptolide with reduction-sensitive polymer nanoparticles for liver cancer therapy on patient-derived xenografts models 被引量:7
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作者 Mengxue He Ling Yu +7 位作者 Yuanyuan Yang Binhua Zou Wen Ma Meng Yu Jiandong Lu Guoliang Xiong Zhiqiang Yu Aimin Li 《Chinese Chemical Letters》 SCIE CAS CSCD 2020年第12期3178-3182,共5页
Hepatocellular carcinoma(HCC)has become the fourth predominant cause of cancer-related deaths worldwide,and HCC is still one of the worst prognoses for survival as it is poorly responsive to both chemotherapy and surg... Hepatocellular carcinoma(HCC)has become the fourth predominant cause of cancer-related deaths worldwide,and HCC is still one of the worst prognoses for survival as it is poorly responsive to both chemotherapy and surgical treatment due to drug resista nce and great toxic effects.Triptolide(TP),a key ingredient from the traditional Chinese medical herb,has been utilized to treat inflammation and antitumor for centuries.However,investigations of this potent agent have been met with only limited success due to the severe systemic toxicities in patients and low water solubility as well as its high toxicity over the past two decades.Herein,we reported the development of a reduction-responsive drug delive ry system loaded with TP fo r glutathione(GSH)-trigge red drug release for cancer therapy.With the GSH-sensitive TP loaded nanoparticles,the remarkable increases in tumor accumulation and amelioration of drug toxicity in animals are demonstrated,which is likely due to sustained stepwise release of active TP within cancer cells.Moreover,in a patient-derived tumor xenograft model of liver cancer,administration of tritolide nanoparticles enhances the antitumor efficacy relative to administration of free TP.These findings indicate that GSH-sensitive release of TP may be a promising strategy for cancer treatment. 展开更多
关键词 TRIPTOLIDE Hepatocellular carcinoma Reduction-sensitive polymer patient-derived xenografts Drug therapy
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Molecular phenotypes reveal heterogeneous engraftments of patient-derived hepatocellular carcinoma xenografts
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作者 Jianyong Zhuo Di Lu +8 位作者 Jianguo Wang Zhengxing Lian Jiali Zhang Huihui Li Beini Cen Xuyong Wei Qiang Wei Haiyang Xie Xiao Xu 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2021年第4期470-479,共10页
Objective:Patient-derived xenograft(PDX)models provide a promising preclinical platform for hepatocellular carcinoma(HCC).However,the molecular features associated with successful engraftment of PDX models have not be... Objective:Patient-derived xenograft(PDX)models provide a promising preclinical platform for hepatocellular carcinoma(HCC).However,the molecular features associated with successful engraftment of PDX models have not been revealed.Methods:HCC tumor samples from 76 patients were implanted in immunodeficient mice.The molecular expression was evaluated by immunohistochemistry.Patient and tumor characteristics as well as tumor molecular expressions were compared for PDX engraftment using the Chi-square test.The independent prediction parameters were identified by logistic regression analyses.Results:The engraftment rate for PDX models from patients with HCC was 39.47%(30/76).Tumors from younger patients and patients with elevated preoperative alpha-fetoprotein level had higher engraftment rates.Tumors with poor differentiation and vascular invasion were related to engraftment success.The positive expression of CK19,CD133,glypican-3(GPC3),and Ki67 in tumor samples was associated with engraftment success.Logistic regression analyses indicated that GPC3 and Ki67 were two of the strongest predictors of PDX engraftment.Tumors with GPC3/Ki67 phenotypes showed heterogeneous engraftment rates,with 71.9%in GPC3^(+)/Ki67^(+)tumors,30.8%in GPC3^(-)/Ki67^(+)tumors,15.0%in GPC3^(+)/Ki67^(-)tumors,and 0 in GPC3^(-)/Ki67^(-)tumors.Conclusions:Successful engraftment of HCC PDXs was significantly related to molecular features.Tumors with the GPC3+/Ki67+phenotype were the most likely to successfully establish HCC PDXs. 展开更多
关键词 Hepatocellular carcinoma patient-derived xenografts heterogeneous establishment molecular phenotype
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Characterization of drug responses of mini patient-derived xenografts in mice for predicting cancer patient clinical therapeutic response 被引量:24
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作者 Feifei Zhang Wenjie Wang +11 位作者 Yuan Long Hui Liu Jijun Cheng Lin Guo Rongyu Li Chao Meng Shan Yu Qingchuan Zhao Shun Lu Lili Wang Haitao Wang Danyi Wen 《Cancer Communications》 SCIE 2018年第1期643-654,共12页
Background:Patient-derived organoids and xenografts(PDXs)have emerged as powerful models in functional diag-nostics with high predictive power for anticancer drug response.However,limitations such as engraftment failu... Background:Patient-derived organoids and xenografts(PDXs)have emerged as powerful models in functional diag-nostics with high predictive power for anticancer drug response.However,limitations such as engraftment failure and time-consuming for establishing and expanding PDX models followed by testing drug efficacy,and inability to subject to systemic drug administration for ex vivo organoid culture hinder realistic and fast decision-making in selecting the right therapeutics in the clinic.The present study aimed to develop an advanced PDX model,namely MiniPDX,for rapidly testing drug efficacy to strengthen its value in personalized cancer treatment.Methods:We developed a rapid in vivo drug sensitivity assay,OncoVee®MiniPDX,for screening clinically relevant regimens for cancer.In this model,patient-derived tumor cells were arrayed within hollow fiber capsules,implanted subcutaneously into mice and cultured for 7 days.The cellular activity morphology and pharmacokinetics were systematically evaluated.MiniPDX performance(sensitivity,specificity,positive and negative predictive values)was examined using PDX as the reference.Drug responses were examined by tumor cell growth inhibition rate and tumor growth inhibition rate in PDX models and MiniPDX assays respectively.The results from MiniPDX were also used to evaluate its predictive power for clinical outcomes.Results:Morphological and histopathological features of tumor cells within the MiniPDX capsules matched those both in PDX models and in original tumors.Drug responses in the PDX tumor graft assays correlated well with those in the corresponding MiniPDX assays using 26 PDX models generated from patients,including 14 gastric cancer,10 lung cancer and 2 pancreatic cancer.The positive predictive value of MiniPDX was 92%,and the negative predictive value was 81%with a sensitivity of 80%and a specificity of 93%.Through expanding to clinical tumor samples,Min-iPDX assay showed potential of wide clinical application.Conclusions:Fast in vivo MiniPDX assay based on capsule implantation was developed-to assess drug responses of both PDX tumor grafts and clinical cancer specimens.The high correlation between drug responses of paired MiniPDX and PDX tumor graft assay,as well as translational data suggest that MiniPDX assay is an advanced tool for personalized cancer treatment. 展开更多
关键词 Personalized cancer therapy Cancer precision medicine patient-derived xenograft(PDX) MiniPDX Drug response In vivo
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Personalized treatment based on mini patient-derived xenografts and WES/RNA sequencing in a patient with metastatic duodenal adenocarcinoma 被引量:14
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作者 Peng Zhao Hui Chen +3 位作者 Danyi Wen Shuo Mou Feifei Zhang Shusen Zheng 《Cancer Communications》 SCIE 2018年第1期586-592,共7页
Background:Treatment guidelines for a variety of cancers have been increasingly used in clinical practice,and have resulted in major improvement in patient outcomes.However,recommended regimens(even first-line treat-m... Background:Treatment guidelines for a variety of cancers have been increasingly used in clinical practice,and have resulted in major improvement in patient outcomes.However,recommended regimens(even first-line treat-ments)are clearly not ideal for every patients.In the present study,we used mini patient-derived xenograft(mini-PDX)and next-generation sequencing to develop personalized treatment in a patient with metastatic duodenal adenocarcinoma.Methods:Resected metachronous metastatic tumor tissues were implanted into SCID mice to determine the sensitivity to a variety of drug regimens.Mutation profiles were assessed using both DNA whole-exome sequencing(DNA-WES)and RNA sequencing.The results of the analyses were used to select optimal treatment for the patient with metastatic duodenal adenocarcinoma.Results:Assessment with mini-PDX models took only 7 days.The results showed high sensitivity to S-1 plus cis-platin,gemcitabine plus cisplatin and everolimus alone.The patient received gemcitabine plus cisplatin initially,but the treatment was terminated due to toxicity.The patient was then switched to treatment with S-1 alone.The overall disease-free survival was 34 months.DNA-WES and RNA sequencing identified KRAS mutation(A146T),TP53(C229Yfs*10)and RICTOR amplification in the metastatic duodenal adenocarcinoma.These findings provided further support to the results of the mini-PDX,and suggest mTOR inhibitors should be used if and when relapse eventually occurs in this patient.Conclusions:Mini-PDX model combined with WES/RNA sequencing can rapidly assess drug sensitivity in cancer patients and reveal key genetic alterations.Further research on this technology for personalized therapy in patients with refractory malignant tumors is warranted. 展开更多
关键词 Duodenal adenocarcinoma Mini patient-derived xenograft Whole-exome sequencing RNA sequencing Somatic mutation Personalized therapy
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Novel dual inhibitor for targeting PIM1 and FGFR1 kinases inhibits colorectal cancer growth in vitro and patient-derived xenografts in vivo 被引量:3
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作者 Fanxiang Yin Ran Zhao +11 位作者 Dhilli Rao Gorja Xiaorong Fu Ning Lu Hai Huang Beibei Xu Hanyong Chen Jung-Hyun Shim Kangdong Liu Zhi Li Kyle Vaughn Laster Zigang Dong Mee-Hyun Lee 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2022年第11期4122-4137,共16页
Colorectal cancer(CRC) is the second most common cause of cancer-related death in the world. The pro-viral integration site for Moloney murine leukemia virus 1(PIM1) is a proto-oncogene and belongs to the serine/threo... Colorectal cancer(CRC) is the second most common cause of cancer-related death in the world. The pro-viral integration site for Moloney murine leukemia virus 1(PIM1) is a proto-oncogene and belongs to the serine/threonine kinase family, which are involved in cell proliferation, migration,and apoptosis. Fibroblast growth factor receptor 1(FGFR1) is a tyrosine kinase that has been implicated in cell proliferation, differentiation and migration. Small molecule HCI-48 is a derivative of chalcone, a class of compounds known to possess anti-tumor, anti-inflammatory and antibacterial effects. However,the underlying mechanism of chalcones against colorectal cancer remains unclear. This study reports that HCI-48 mainly targets PIM1 and FGFR1 kinases, thereby eliciting antitumor effects on colorectal cancer growth in vitro and in vivo. HCI-48 inhibited the activity of both PIM1 and FGFR1 kinases in an ATPdependent manner, as revealed by computational docking models. Cell-based assays showed that HCI-48inhibited cell proliferation in CRC cells(HCT-15, DLD1, HCT-116 and SW620), and induced cell cycle arrest in the G2/M phase through modulation of cyclin A2. HCI-48 also induced cellular apoptosis, as evidenced by an increase in the expression of apoptosis biomarkers such as cleaved PARP, cleaved caspase 3 and cleaved caspase 7. Moreover, HCI-48 attenuated the activation of downstream components of the PIM1 and FGFR1 signaling pathways. Using patient-derived xenograft(PDX) murine tumor models,we found that treatment with HCI-48 diminished the PDX tumor growth of implanted CRC tissue expressing high protein levels of PIM1 and FGFR1. This study suggests that the inhibitory effect of HCI-48 on colorectal tumor growth is mainly mediated through the dual-targeting of PIM1 and FGFR1kinases. This work provides a theoretical basis for the future application of HCI-48 in the treatment of clinical CRC. 展开更多
关键词 PIM1 FGFR1 Colorectal cancer HCI-48 Targeted therapy Small moleculecompound ofchalcone patient-derived xenograft model ATPKinase activity
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Patient-derived organoids (PDOs) and PDO-derived xenografts (PDOXs): New opportunities in establishing faithful pre-clinical cancer models
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作者 Ergang Wang Kun Xiang +1 位作者 Yun Zhang Xiao-Fan Wang 《Journal of the National Cancer Center》 2022年第4期263-276,共14页
One of the major bottlenecks in advancing basic cancer research and developing novel cancer therapies is the lack of in vitro pre-clinical models that faithfully recapitulate tumor properties in the patients.Monolayer... One of the major bottlenecks in advancing basic cancer research and developing novel cancer therapies is the lack of in vitro pre-clinical models that faithfully recapitulate tumor properties in the patients.Monolayer cultures of cancer cell lines usually lose the heterogeneity of the parental tumors,while patient-derived xenograft(PDX)suffers from its time-and resource-intensive nature.The emergence of organoid culture system and its application in cancer research provides a unique opportunity to develop novel in vitro cancer pre-clinical models.Here we review the recent advances in utilizing organoids culture system and other related three-dimensional culture systems in studying cancer biology,performing drug screening,and developing cancer therapies.In particular,we discuss the advantages of applying xenograft initiated from patient-derived organoids(PDOs)as a faithful cancer pre-clinical model in basic cancer research and precision medicine. 展开更多
关键词 patient-derived organoid patient-derived xenograft PDO-derived xenograft
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Patient-derived non-small cell lung cancer xenograft mirrors complex tumor heterogeneity 被引量:9
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作者 Xuanming Chen Cheng Shen +15 位作者 Zhe Wei Rui Zhang Yongsheng Wang Lili Jiang Ke Chen Shuang Qiu Yuanli Zhang Ting Zhang Bin Chen Yanjun Xu Qiyi Feng Jinxing Huang Zhihui Zhong Hongxia Li Guowei Che Kai Xiao 《Cancer Biology & Medicine》 SCIE CAS CSCD 2021年第1期184-198,共15页
Objective:Patient-derived xenograft(PDX)models have shown great promise in preclinical and translational applications,but their consistency with primary tumors in phenotypic,genetic,and pharmacodynamic heterogeneity h... Objective:Patient-derived xenograft(PDX)models have shown great promise in preclinical and translational applications,but their consistency with primary tumors in phenotypic,genetic,and pharmacodynamic heterogeneity has not been well-studied.This study aimed to establish a PDX repository for non-small cell lung cancer(NSCLC)and to further elucidate whether it could preserve the heterogeneity within and between tumors in patients.Methods:A total of 75 surgically resected NSCLC specimens were implanted into immunodeficient NOD/SCID mice.Based on the successful establishment of the NSCLC PDX model,we compared the expressions of vimentin,Ki67,EGFR,and PD-L1 proteins between cancer tissues and PDX models using hematoxylin and eosin staining and immunohistochemical staining.In addition,we detected whole gene expression profiling between primary tumors and PDX generations.We also performed whole exome sequencing(WES)analysis in 17 first generation xenografts to further assess whether PDXs retained the patient heterogeneities.Finally,paclitaxel,cisplatin,doxorubicin,atezolizumab,afatininb,and AZD4547 were used to evaluate the responses of PDX models to the standard-of-care agents.Results:A large collection of serially transplantable PDX models for NSCLC were successfully developed.The histology and pathological immunohistochemistry of PDX xenografts were consistent with the patients’tumor samples.WES and RNA-seq further confirmed that PDX accurately replicated the molecular heterogeneities of primary tumors.Similar to clinical patients,PDX models responded differentially to the standard-of-care treatment,including chemo-,targeted-and immuno-therapeutics.Conclusions:Our established PDX models of NSCLC faithfully reproduced the molecular,histopathological,and therapeutic characteristics,as well as the corresponding tumor heterogeneities,which provides a clinically relevant platform for drug screening,biomarker discovery,and translational research. 展开更多
关键词 patient-derived xenograft(PDX) non-small cell lung cancer(NSCLC) tumor heterogeneity
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Translational pancreatic cancer research:a comparative study on patient-derived xenograft models 被引量:2
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作者 Mercedes Rubio-Manzanares Dorado Luis Miguel Marín Gómez +7 位作者 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 《World Journal of Gastroenterology》 SCIE CAS 2018年第7期794-809,共16页
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 develo... 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 < 0.001). There were no significant differences in tumour 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 of viable xenografts could make the subcutaneous model the best option for experimentation in pancreatic cancer. 展开更多
关键词 Immunohistological analysis PANCREATIC cancer patient-derived xenograft Animal model NUDE mice
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Spontaneous xenogeneic GvHD in Wilms'tumor Patient-Derived xenograft models and potential solutions 被引量:1
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作者 Seyed Mostafa Monzavi Ahad Muhammadnejad +3 位作者 Maryam Behfar Amir Arsalan Khorsand Samad Muhammadnejad Abdol-Mohammad Kajbafzadeh 《Animal Models and Experimental Medicine》 CAS CSCD 2022年第4期389-396,共8页
Severely immunocompromised NOD.Cg-PrkdcIl2rg(NOG)mice are among the ideal animal recipients for generation of human cancer models.Transplantation of human solid tumors having abundant tumor-i nfiltrating lymphocytes(T... Severely immunocompromised NOD.Cg-PrkdcIl2rg(NOG)mice are among the ideal animal recipients for generation of human cancer models.Transplantation of human solid tumors having abundant tumor-i nfiltrating lymphocytes(TILs)can induce xenogeneic graft-versus-host disease(xGvHD)following engraftment and expansion of the TILs inside the animal body.Wilms’tumor(WT)has not been recognized as a lymphocyte-predominant tumor.However,3 consecutive generations of NOG mice bearing WT patient-derived xenografts(PDX)xenotransplanted from a single donor showed different degrees of inflammatory symptoms after transplantation before any therapeutic intervention.In the initial generation,dermatitis,auto-amputation of digits,weight loss,lymphadenopathy,hepatitis,and interstitial pneumonitis were observed.Despite antibiotic treatment,no response was noticed,and thus the animals were prematurely euthanized(day 47 posttransplantation).Laboratory and histopathologic evaluations revealed lymphoid infiltrates positively immunostained with anti-human CD3 and CD8 antibodies in the xenografts and primary tumor,whereas no microbial infection or lymphoproliferative disorder was found.Mice of the next generation that lived longer(91 days)developed sclerotic skin changes and more severe pneumonitis.Cutaneous symptoms were milder in the last generation.The xenografts of the last 2 generations also contained TILs,and lacked lymphoproliferative transformation.The systemic immunoinflammatory syndrome in the absence of microbial infection and posttransplant lymphoproliferative disorder was suggestive of xGvHD.While there are few reports of xGvHD in severely immunodeficient mice xenotransplanted from lymphodominant tumor xenografts,this report for the first time documented serial xGvHD in consecutive passages of WT PDX-bearing models and discussed potential solutions to prevent such an undesired complication. 展开更多
关键词 graft-versus-host disease patient-derived xenograft models tumor-infiltrating lymphocytes Wilms’tumor
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Specific bone region localization of osteolytic versus osteoblastic lesions in a patient-derived xenograft model of bone metastatic prostate cancer 被引量:1
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作者 Takeshi Hirata Seung Chol Park +12 位作者 Michelle T.Muldong Christina N.Wu Tomonori Yamaguchi Amy Strasner Omer Raheem Hiromi Kumon Robert L.Sah Nicholas A.Cacalano Catriona H.M.Jamieson Christopher J.Kane Koichi Masuda Anna A.Kulidjian Christina A.M.Jamieson 《Asian Journal of Urology》 2016年第4期229-239,共11页
Objective:Bone metastasis occurs in up to 90%of men with advanced prostate cancer and leads to fractures,severe pain and therapy-resistance.Bone metastases induce a spectrum of types of bone lesions which can respond ... Objective:Bone metastasis occurs in up to 90%of men with advanced prostate cancer and leads to fractures,severe pain and therapy-resistance.Bone metastases induce a spectrum of types of bone lesions which can respond differently to therapy even within individual prostate cancer patients.Thus,the special environment of the bone makes the disease more complicated and incurable.A model in which bone lesions are reproducibly induced that mirrors the complexity seen in patients would be invaluable for pre-clinical testing of novel treatments.The microstructural changes in the femurs of mice implanted with PCSD1,a new patient-derived xenograft from a surgical prostate cancer bone metastasis specimen,were determined.Methods:Quantitative micro-computed tomography(micro-CT)and histological analyses were performed to evaluate the effects of direct injection of PCSD1 cells or media alone(Control)into the right femurs of Rag2/gc/male mice.Results:Bone lesions formed only in femurs of mice injected with PCSD1 cells.Bone volume(BV)was significantly decreased at the proximal and distal ends of the femurs(p<0.01)whereas BV(p<0.05)and bone shaft diameter(p<0.01)were significantly increased along the femur shaft.Conclusion:PCSD1 cells reproducibly induced bone loss leading to osteolytic lesions at the ends of the femur,and,in contrast,induced aberrant bone formation leading to osteoblastic lesions along the femur shaft.Therefore,the interaction of PCSD1 cells with different bone region-specific microenvironments specified the type of bone lesion.Our approach can be used to determine if different bone regions support more therapy resistant tumor growth,thus,requiring novel treatments. 展开更多
关键词 Bone metastatic prostate cancer patient-derived xenograft microenvironment Microstructural CT Osteolytic lesions Osteoblastic lesions
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Application of patient-derived tumor models in anticancer drug development and individualized medicine
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作者 Kai-Ling Chen Yu-Fei Deng +1 位作者 Xiao-Ying Hou Yu-Chen Liu 《Life Research》 2024年第1期3-9,共7页
Malignant tumor is the second leading cause of death due to its high incidence, lack of effective treatment and poor prognosis. The evaluation of anticancer drugs used to based on NCI-60 cell line models, but the limi... Malignant tumor is the second leading cause of death due to its high incidence, lack of effective treatment and poor prognosis. The evaluation of anticancer drugs used to based on NCI-60 cell line models, but the limited heterogeneity and the divorce from clinical practice of models lead to extremely low success rate of novel anticancer drugs during clinical trials (less than 10%). In recent years, because of the high heterogeneity and human derived tumor matrix, patient-derived tumor models have been gradually applied to the preclinical evaluation of various antitumor drugs, which shows certain advantages in predicting the clinical efficacy of antitumor drugs. Optimize the drug combination through patient-derived tumor models to achieve individualized medicine has gradually become an indispensable strategy in clinical cancer therapy. The current review summarized the development of patient-derived tumor models, characterized the application, advantages and challenges of them in preclinical antitumor drug evaluation and clinical precise medicine, which will provide a scientific basis and novel insights for further basic research, drug development and clinical application. 展开更多
关键词 patient-derived xenograft(PDX) patient-derived organoid(PDO) patient-derived cell(PDC) individualized medicine
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Conversion therapy in advanced perihilar cholangiocarcinoma based on patient-derived organoids:A case report
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作者 Yong-Gang He Ling-Yu Zhang +4 位作者 Jing Li Zheng Wang Chong-Yu Zhao Lu Zheng Xiao-Bing Huang 《World Journal of Gastrointestinal Oncology》 SCIE 2024年第10期4274-4280,共7页
BACKGROUND Patient-derived organoids(PDOs)have been demonstrated to predict the response to drugs in multiple cancer types.However,it remains unclear about its application in cholangiocarcinoma.CASE SUMMARY A 59-year-... BACKGROUND Patient-derived organoids(PDOs)have been demonstrated to predict the response to drugs in multiple cancer types.However,it remains unclear about its application in cholangiocarcinoma.CASE SUMMARY A 59-year-old woman was admitted to the hospital due to upper abdominal pain for over 8 months.According to relevant examinations,she was diagnosed as perihilar cholangiocarcinoma(pCCA)with intrahepatic metastasis and perihilar lymphatic metastasis.After multidisciplinary team discussion,percutaneous transhepatic cholangiodrainage was performed to relieve biliary obstruction,and puncture biopsy was conducted to confirm the pathological diagnosis.Transarterial chemoembolization with nab-paclitaxel was used in combination with toripalimab and lenvatinib,but the levels of tumor markers including alpha fetal protein,carcinoembryonic antigen,carbohydrate antigen 15-3 and cancer antigen 125 were still raised.The PDO for drug screening showed sensitive to gemcitabine and cisplatin.Accordingly,the chemotherapy regimen was adjusted to gemcitabine and cisplatin in combination with toripalimab and lenvatinib.After 4 cycles of treatment,the tumor was assessed resectable,and radical surgical resection was performed successfully.One year after surgery,the patient was still alive,and no recurrence or occurred.CONCLUSION PDOs for drug sensitivity contribute to screening effective chemotherapy drugs for advanced pCCA,promoting conversion therapy and improving the prognosis. 展开更多
关键词 patient-derived organoids Perihilar cholangiocarcinoma Conversion therapy Drug screening Intrahepatic metastasis Case report
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Patient-derived xenograft model in colorectal cancer basic and translational research
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作者 Xiaofeng Liu Zechang Xin Kun Wang 《Animal Models and Experimental Medicine》 CAS CSCD 2023年第1期26-40,共15页
Colorectal cancer(CRC)is one of the most popular malignancies globally,with 930000 deaths in 2020.The evaluation of CRC-related pathogenesis and the discovery of po-tential therapeutic targets will be meaningful and h... Colorectal cancer(CRC)is one of the most popular malignancies globally,with 930000 deaths in 2020.The evaluation of CRC-related pathogenesis and the discovery of po-tential therapeutic targets will be meaningful and helpful for improving CRC treat-ment.With huge efforts made in past decades,the systematic treatment regimens have been applied to improve the prognosis of CRC patients.However,the sensitivity of CRC to chemotherapy and targeted therapy is different from person to person,which is an important cause of treatment failure.The emergence of patient-derived xenograft(PDX)models shows great potential to alleviate the straits.PDX models possess similar genetic and pathological characteristics as the features of primary tu-mors.Moreover,PDX has the ability to mimic the tumor microenvironment of the original tumor.Thus,the PDX model is an important tool to screen precise drugs for individualized treatment,seek predictive biomarkers for prognosis supervision,and evaluate the unknown mechanism in basic research.This paper reviews the recent advances in constructed methods and applications of the CRC PDX model,aiming to provide new knowledge for CRC basic research and therapeutics. 展开更多
关键词 colorectal cancer drug discovery patient-derived xenograft model precision medicine tumor microenvironment
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A biomimetic nanoplatform for customized photothermal therapy of HNSCC evaluated on patient-derived xenograft models
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作者 Qi Wu Lan Chen +13 位作者 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 《International Journal of Oral Science》 SCIE CAS CSCD 2023年第1期87-98,共12页
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 gener... 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. 展开更多
关键词 xenograft PATIENT CUSTOM
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Antiangiogenic therapy for human pancreatic carcinoma xenografts in nude mice 被引量:15
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作者 LinJia Mei-HuaZhang +1 位作者 Shi-ZhenYuan Wen-GeHuang 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第3期447-450,共4页
AIM: To investigate the anti-tumor effects of antiangiogenic therapy (a combination of TNP-470, an antiangiogenic compound, with gemcitabine, an antimetabolite) on human pancreatic carcinoma xenografts and its mechani... AIM: To investigate the anti-tumor effects of antiangiogenic therapy (a combination of TNP-470, an antiangiogenic compound, with gemcitabine, an antimetabolite) on human pancreatic carcinoma xenografts and its mechanism. METHODS: A surgical orthotopic implantation (SOI) model was established by suturing small pieces of SW1990 pancreatic carcinoma into the tail of pancreas in nude male mice. Mice then received either single therapy (n = 24) or combined therapy (n = 32). Mice receiving single therapy were randomly divided into control group, G100 group receiving 100 mg/kg gemcitabine IP on d O, 3, 6 and 9 after transplantation, and T30 group receiving 30 mg/kg TNP-470 s.c on alternate days for 8 wk. Mice receiving combined therapy were randomly divided into control group, T15 group, G50 group and combination group (TNP-470 30 mg/kg and gemcitabine 50 mg/kg). Animals were killed 8 wk after transplantation. Transplanted tumors, liver, lymph node and peritoneum were removed. Weight of transplanted tumors, the T/C rate (the rate of mean treated tumor weight to mean control tumor weight), change of body weight, metastasis rate, and 9-wk survival rate were investigated. Tumor samples were taken from the control group, T30 group, G100 group and combination group. PCNA index (PI) and microvessel density (MVD) were investigated by immunohistochemical staining for PCNA and factor VIII, respectively. RESULTS: There was a significant inhibitory effect on primary tumor growth of pancreatic carcinoma in G100 group, compared to T30 group, whereas tumor metastasis was significantly inhibited in T30 group compared to G100 group. There was no significant improvement in survival rate in these two groups. No significant inhibitory effect on tumor growth and metastasis in T15 group and G50 group. However, significant anti-tumor and anti-metastatic effects were observed in the combination group with a significant improvement in survival rate. The inhibitory effect on tumor growth in combination group enhanced 2 times in comparison with G50 group and 5 times in comparison with T15 group. Moreover, 25% of the animals hearing tumors were cured by the combination therapy. The levels of MVD and PI were 14.50±5.93 and 0.41±0.02,12.38±1.60 and 0.30±0.07, 7.13±2.99 and 0.37±0.03, and 5.21±1.23 and 0.23±0.02 respectively in the control group, G100 group, T30 group and combination group. A significant inhibitory effect on PI level and MVD level was observed in G100 group and T30 group respectively whereas both MVD and PI levels were significantly inhibited in the combination group (P<0.05). CONCLUSION: Antiangiogenic therapy shows significant anti-tumor and anti-metastatic effects, and is helpful to reduce the dosage of cytotoxic drugs and the side effects. These effects are related to the antiangiogenic effect of TNP-470 and cytotoxic effect of gemcitabine. 展开更多
关键词 Pancreatic carcinoma TNP-470 Angiogenesis Inhibitors xenografts
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Experimental study on the inhibition effect of miR-106a inhibitor on tumor growth of ovarian cancer xenografts mice 被引量:2
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作者 Zhi-Hui Cai Li-Min Chen +4 位作者 Yi-Juan Liang Jun-Rong Shi You-Ju Ma Wei-Ming Wang Huan Yang 《Asian Pacific Journal of Tropical Medicine》 SCIE CAS 2016年第7期663-666,共4页
Objective:To study the inhibition effect of miR-106 a inhibitor on tumor growth of ovarian cancer xenografts mice.Methods:BALB/c mice were selected as experimental animals,ovarian cancer SKOV-3 cells transfected with ... Objective:To study the inhibition effect of miR-106 a inhibitor on tumor growth of ovarian cancer xenografts mice.Methods:BALB/c mice were selected as experimental animals,ovarian cancer SKOV-3 cells transfected with miR-106 a inhibitor and its negative control were inoculated subcutaneously,intratumoral injection of miR-106 a inhibitor and its negative control were continued after tumor formation,and they were enrolled as treatment group and model group,respectively.Tumor volume and weight as well as Ki-67 and programmed cell death 4(PDCD4) expression were determined;miR-106 a inhibitor and its negative control as well as miR-106 a mimic and its negative control were transfected into SKOV-3 cells,and expression of PDCD4 in cells was determined.Results:Tumor tissue volume and weight as well as mR NA expression and protein expression of Ki-67 in treatment group were significantly lower than those in the model group while m RNA expression and protein expression of PDCD4 were significantly higher than those in the model group;transfection of mi R-106 a mimic could decrease m RNA expression and protein expression of PDCD4 in SKOV-3 cells,and transfection of miR-106 a inhibitor could increase mR NA expression and protein expression of PDCD4 in SKOV-3 cells.Conclusions:Transfection of mi R-106 a inhibitor can inhibit the growth of tumor in ovarian cancer xenografts mice through increasing the expression of PDCD4. 展开更多
关键词 OVARIAN cancer xenografts miR-106a Programmed cell DEATH 4
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Gene transfer of somatostatin receptor type 2 by intratumoral injection inhibits established pancreatic carcinoma xenografts 被引量:9
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作者 Manoj Kumar 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第4期516-520,共5页
AIM: To investigate the therapeutic effect of somatostatin receptor type 2 (SSTR2) gene transfection on pancreatic carcinoma xenografts in vivo in experimental cancers. METHODS: Human pancreatic cancer cell line Panc-... AIM: To investigate the therapeutic effect of somatostatin receptor type 2 (SSTR2) gene transfection on pancreatic carcinoma xenografts in vivo in experimental cancers. METHODS: Human pancreatic cancer cell line Panc-1 was inoculated subcutaneously into the back of nude mice. When tumor nodules were grown as large as about 5 mmx5 mm days after inoculation, the mice were randomly divided into 3 groups (6 mice in each group). Group Ⅰ served as untreated control group. Group Ⅱ received an intratumoral injection of a combination of human cytomegalovirus promoter-6C (pCMV-6C) and lipofectamine 2000. Group Ⅲ received an intratumoral injection of a combination of pCMV-6C-SSTR2 and lipofectamine 2000. The rate of tumor growth was compared among these three groups. The expression of SSTR2 in these tumors was detected by immunohistochemistry and Western-blot. Apoptosis index (AI) in these tumors was examined by using TUNEL in situ. RESULTS: Intratumoral injection of a combination of pCMV-6C-SSTR2 and lipofectamine 2000 resulted in the expression of SSTR2 protein. The tumor size and weight in group Ⅲ (0.318±0.098 cm3, and 0.523±0.090 g, respectively) were significantly lower than those in group I (2.058±0.176 cms, and 1.412±0.146 g, respectively) and group Ⅱ (2.025±0.163 cm3, and 1.365±0.116 g, respectively) (P<0.05) The AI in group Ⅲ (1.47±0.13%) was significantly higher than that in groupⅠ(0.56±0.09%) and group Ⅱ (0.57±0.11%) (P<0.05). But there were no significant differences between groups Ⅰ and Ⅱ. CONCLUSION: Our data demonstrate that re-expression of SSTR2 gene has antitumor effects on experimental pancreatic cancer. Restoration of SSTR2 gene expression through gene transfer in vivo might be a potential gene therapy strategy for human pancreatic cancer. 展开更多
关键词 Pancreatic Cancer xenografts Somatostatin receptor type 2 TRANSFECTION
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Effect of lentivirus-mediated integrin αVβ3-sh RNA on tumor growth of mice with lung cancer xenografts 被引量:1
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作者 Tao Liang Yong-Fu Ma +2 位作者 Jian Chu Dao-Xi Wang Yang Liu 《Asian Pacific Journal of Tropical Medicine》 SCIE CAS 2016年第2期160-163,共4页
Objective: To study the effect of lentivirus-mediated integrin αVβ3-sh RNA on tumor growth of mice with lung cancer xenograft. Methods: Lung cancer tissue, paracancer tissue and normal tissue were collected and inte... Objective: To study the effect of lentivirus-mediated integrin αVβ3-sh RNA on tumor growth of mice with lung cancer xenograft. Methods: Lung cancer tissue, paracancer tissue and normal tissue were collected and integrin αVβ3 expression was detected; BALB/c nude mice were selected, divided into integrin αVβ3 knockdown group(KD group) and negative control group(NC group), and inoculated with cells stably infected by integrin αVβ3-sh RNA lentivirus and cells stably infected by negative control-sh RNA lentivirus respectively, the growth of tumor tissue was continuously observed, and the number of apoptosis cells as well as the expression of angiogenesis, apoptosis and invasion genes in tumor tissue were detected. Results: m RNA content and protein content of integrin αVβ3 in lung cancer tissue were significantly higher than those in paracancer tissue and normal tissue; increasing trend of tumor tissue volume of KD group was weaker than that of NC group, and tumor volume at various points in time of KD group was lower than that of NC group; m RNA contents and protein contents of VEGF, FGF, EGF, Bcl-2, MMP-9, MMP-12 and MMP-13 in tumor tissue of KD group were lower than those of NC group, and apoptosis index as well as m RNA content and protein content of Bax were higher than those of NC group. Conclusions: The expression of integrin αVβ3 increases in lung cancer tissue, and lentivirus-mediated integrin αVβ3-sh RNA can inhibit tumor growth of mice with lung cancer xenografts. 展开更多
关键词 Lung cancer INTEGRIN α V β 3 xenografts ANGIOGENESIS Apoptosis INVASION
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Effects of the anti-tumor composition ofthe acetoacetate extract of vitex negundoseed on the growth of human cervical carcinomaxenografts in nude mice 被引量:2
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作者 Yanlin Cai Zhongdong Chen +3 位作者 Aiqiong Tang Bin Jiang Zhaohua Fan Jun Bai 《The Chinese-German Journal of Clinical Oncology》 CAS 2014年第3期105-109,共5页
Objective: The aim of our study was to investigate the effects of the anti-tumor composition of the acetoacetate extract of Vitex Negundo Seed (EVn-50) on the growth of human cervical carcinoma HeLa cells xenograft... Objective: The aim of our study was to investigate the effects of the anti-tumor composition of the acetoacetate extract of Vitex Negundo Seed (EVn-50) on the growth of human cervical carcinoma HeLa cells xenografts in nude mica and its possible molecular mechanism. Methods: Models of human cervical cancer HeLa cells xenografts transplanted subcuta- neously in nude mice were established and randomly divided into 7 groups (each group including 5 nude mice): saline group, Taxol group, EVn-50 group, comp-6 group, comp-7 group, comp-8 group and comp-10 group. The volume and weight of Xe- nograts were observed and compared. The alteration of the weight of nude mice, and the change of serum levels ofLDH, ALT, Cr and WBC counts were examined and compared. The apoptotic rate of human cervical carcinoma HeLa cells xenografts was analyzed by FCM. The expressions of P53 and Bcl-2 proteins of HeLa cells xenografts were determined by Western blot- ting. Results: EVn-50 and its fractionated extracts could significantly suppress the increasing volume and weight of human cervical carcinoma HeLa cells xenografts in nude mice models in time-dependent manner, yet had no significant effect on the weight of nude mice, the serum levels of LDH, ALT, Cr and WBC were counted. When the xenografts were treated with EVn-50 and its fractionated extracts for 16 days, the apoptotic rate of xenografts cells were significantly increased, and the expression of P53 protein was up-regulated and protein level of Bcl-2 was decreased. Conclusion: EVn-50 and its fractionated extracts could suppress the growth of human cervical carcinoma HeLa cells xenografts in nude mice, which may be related to its pro- motion on xenografts cells apoptosis through down-regulation of Bcl-2 expressionPand activation of P53 expression. 展开更多
关键词 cervical cancer EVn-50 xenografts apoptosis
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