6,835 results match your criteria preclinical xenograft

Preclinical Models for Bladder Cancer Research.

Hematol Oncol Clin North Am 2021 Jun 16;35(3):613-632. Epub 2021 Apr 16.

Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA; VA Boston Healthcare System, West Roxbury, MA, USA. Electronic address:

At diagnosis, more than 70% of bladder cancers (BCs) are at the non-muscle-invasive bladder cancer (NMIBC) stages, which are usually treated with transurethral resection followed by intravesical instillation. For the remaining advanced cancers, systemic therapy is the standard of care, with addition of radical cystectomy in cases of locally advanced cancer. Because of the difference in treatment modalities, different models are needed to advance the care of NMIBC and advanced BC. Read More

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Comparative barrier membrane degradation over time: Pericardium versus dermal membranes.

Clin Exp Dent Res 2021 May 5. Epub 2021 May 5.

Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

Objective: The effectiveness of GBR procedures for the reconstruction of periodontal defects has been well documented. The objective of this investigation was to evaluate the degradation kinetics and biocompatibility of two resorbable collagen membranes in conjunction with a bovine xenograft material.

Materials And Methods: Lower premolars and first molars were extracted from 18 male Yucatan minipigs. Read More

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Preclinical evaluation for engraftment of CD34 cells gene-edited at the sickle cell disease locus in xenograft mouse and non-human primate models.

Cell Rep Med 2021 Apr 20;2(4):100247. Epub 2021 Apr 20.

Cellular and Molecular Therapeutics Branch, National Heart Lung and Blood Institutes (NHLBI)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, MD, USA.

Sickle cell disease (SCD) is caused by a 20A > T mutation in the β-globin gene. Genome-editing technologies have the potential to correct the SCD mutation in hematopoietic stem cells (HSCs), producing adult hemoglobin while simultaneously eliminating sickle hemoglobin. Here, we developed high-efficiency viral vector-free non-footprint gene correction in SCD CD34 cells with electroporation to deliver SCD mutation-targeting guide RNA, Cas9 endonuclease, and 100-mer single-strand donor DNA encoding intact β-globin sequence, achieving therapeutic-level gene correction at DNA (∼30%) and protein (∼80%) levels. Read More

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Interrogation of gender disparity uncovers androgen receptor as the transcriptional activator for oncogenic miR-125b in gastric cancer.

Cell Death Dis 2021 May 4;12(5):441. Epub 2021 May 4.

Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China.

There is a male preponderance in gastric cancer (GC), which suggests a role of androgen and androgen receptor (AR). However, the mechanism of AR signaling in GC especially in female patients remains obscure. We sought to identify the AR signaling pathway that might be related to prognosis and examine the potential clinical utility of the AR antagonist for treatment. Read More

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Mini-Patient-derived Xenograft Assay Based on Microfluidic Technology Promises to be an Effective Tool for Screening Individualized Chemotherapy Regimens for Advanced Non-Small Cell Lung Cancer.

Cell Biol Int 2021 May 4. Epub 2021 May 4.

Department of Shanghai Lung Cancer center, Shanghai Chest Hospital, Shanghai Jiao Tong University, 200030, Shanghai, China.

Background: Patient-derived xenograft (PDX) assay has been widely used in preclinical researches in patients with multidrug-resistant lung cancer.

Methods: 100 patients with non-small cell lung cancer (NSCLC) were divided into MiniPDX group and conventional group, with 50 cases in each group. The MiniPDX assay was established by enriching high-purity tumor cells using microfluidic technology to detect the drug sensitivity of NSCLC cells. Read More

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Targeting cancer homing into the lymph node with a novel anti-CCR7 therapeutic antibody: the paradigm of CLL.

MAbs 2021 Jan-Dec;13(1):1917484

Immunology Department, Hospital Universitario De La Princesa, IIS-IP, Madrid, Spain.

Lymph node (LN) is a key tissue in the pathophysiology of mature blood cancers, especially for chronic lymphocytic leukemia (CLL). Within the multiple de-regulated pathways affecting CLL homeostasis, the CC-chemokine receptor 7 (CCR7) grants homing of CLL cells into the LN where protective environments foster tumor progression. To cover the lack of specific therapies targeting the CCR7-dependence of CLL to enter into the LN, and aiming to displace the disease from LN, we generated CAP-100, an antibody that specifically binds to hCCR7 and neutralizes its ligand-binding site and signaling. Read More

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Detection of metabolic change in glioblastoma cells after radiotherapy using hyperpolarized C-MRI.

NMR Biomed 2021 May 3:e4514. Epub 2021 May 3.

Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA.

Dynamic nuclear polarization (DNP) of C-labeled substrates enables the use of magnetic resonance imaging (MRI) to monitor specific enzymatic reactions in tumors and offers an opportunity to investigate these differences. In this study, DNP-MRI chemical shift imaging with hyperpolarized [1- C] pyruvate was conducted to evaluate the metabolic change in glycolytic profiles after radiation of two glioma stem-like cell-derived gliomas (GBMJ1 and NSC11) and an adherent human glioblastoma cell line (U251) in an orthotopic xenograft mouse model. The DNP-MRI showed an increase in Lac/Pyr at 6 and 16 h after irradiation (18% ± 4% and 14% ± 3%, respectively; mean ± SEM) compared with unirradiated controls in GBMJ1 tumors, whereas no significant change was observed in U251 and NSC11 tumors. Read More

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Preclinical Evaluation of Carfilzomib for Infant -Rearranged Acute Lymphoblastic Leukemia.

Front Oncol 2021 15;11:631594. Epub 2021 Apr 15.

Division of Children's Leukaemia and Cancer Research, Telethon Kids Cancer Centre, Telethon Kids Institute, University of Western Australia, Perth, WA, Australia.

Background: Infants with -rearranged B-cell precursor acute lymphoblastic leukemia (ALL) have poor outcomes. There is an urgent need to identify novel agents to improve survival. Proteasome inhibition has emerged as a promising therapeutic strategy for several hematological malignancies. Read More

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PD-1 Inhibition Enhances Blinatumomab Response in a UCB/PDX Model of Relapsed Pediatric B-Cell Acute Lymphoblastic Leukemia.

Front Oncol 2021 13;11:642466. Epub 2021 Apr 13.

Oncology, Cancer and Blood Disease Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.

Immune therapies such as blinatumomab, CD19-directed bispecific CD3 T-cell Engager (BiTE), have resulted in significant improvements in outcomes for relapsed B-cell acute lymphoblastic leukemia (B-ALL). However, up to half of blinatumomab treated patients do not respond completely or relapse after therapy. As a result, there is a need to identify potential strategies to improve the efficacy of BiTE therapy. Read More

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A Novel Multidrug-Resistant Cell Line from an Italian Intrahepatic Cholangiocarcinoma Patient.

Cancers (Basel) 2021 Apr 23;13(9). Epub 2021 Apr 23.

Division of Medical Oncology, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo (Torino), Italy.

Chemotherapy resistance is a relevant clinical issue in tumor treatment, in particular in biliary tract carcinoma (BTC), for which there are no effective therapies, neither in the first nor in the second line. The development of chemoresistant cell lines as experimental models to investigate the mechanisms of resistance and identify alternative druggable pathways is mandatory. In BTC, in which genetics and biological behavior depend on the etiology, ethnicity, and anatomical site of origin, the creation of models that better recapitulate these characteristics is even more crucial. Read More

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Assessment of Tumorigenic Potential in Mesenchymal-Stem/Stromal-Cell-Derived Small Extracellular Vesicles (MSC-sEV).

Pharmaceuticals (Basel) 2021 Apr 9;14(4). Epub 2021 Apr 9.

Institute of Molecular and Cellular Biology, A*STAR, 8A Biomedical Grove, Singapore 138648, Singapore.

Mesenchymal-stem/stromal-cell-derived small extracellular vesicles (MSC-sEV) have been shown to ameliorate many diseases in preclinical studies. However, translating MSC-sEV into clinical use requires the development of scalable manufacturing processes for highly reproducible preparations of safe and potent MSC-sEVs. A major source of variability in MSC-sEV preparations is EV producer cells. Read More

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Preclinical activity of cobimetinib alone or in combination with chemotherapy and targeted therapies in renal cell carcinoma.

Future Oncol 2021 Apr 28. Epub 2021 Apr 28.

Department of Nephrology, The Second People's Hospital of Yibin, Yibin, Sichuan, 644000, PR China.

The poor outcome of advanced renal cell carcinoma (RCC) necessitates new treatments. Cobimetinib is a MEK inhibitor and approved for the treatment of melanoma. This work investigated the efficacy of cobimetinib alone and in combination with anti-RCC drugs. Read More

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Targeting the metabolic vulnerability of acute myeloid leukemia blasts with a combination of venetoclax and 8-chloro-adenosine.

J Hematol Oncol 2021 Apr 26;14(1):70. Epub 2021 Apr 26.

Hematology Malignancies Research Institute, Gehr Family Center for Leukemia Research, City of Hope Medical Center, Kaplan CRB, 1026, 1500 East Duarte Road, Duarte, CA, 91010, USA.

Background: BCL-2 inhibition through venetoclax (VEN) targets acute myeloid leukemia (AML) blast cells and leukemic stem cells (LSCs). Although VEN-containing regimens yield 60-70% clinical response rates, the vast majority of patients inevitably suffer disease relapse, likely because of the persistence of drug-resistant LSCs. We previously reported preclinical activity of the ribonucleoside analog 8-chloro-adenosine (8-Cl-Ado) against AML blast cells and LSCs. Read More

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Repurposing F-FMISO as a PET tracer for translational imaging of nitroreductase-based gene directed enzyme prodrug therapy.

Theranostics 2021 7;11(12):6044-6057. Epub 2021 Apr 7.

Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Jonas Lies vei 65, N-5021, Bergen, Norway.

Nitroreductases (NTR) are a family of bacterial enzymes used in gene directed enzyme prodrug therapy (GDEPT) that selectively activate prodrugs containing aromatic nitro groups to exert cytotoxic effects following gene transduction in tumours. The clinical development of NTR-based GDEPT has, in part, been hampered by the lack of translational imaging modalities to assess gene transduction and drug cytotoxicity, non-invasively. This study presents translational preclinical PET imaging to validate and report NTR activity using the clinically approved radiotracer, F-FMISO, as substrate for the NTR enzyme. Read More

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Quantitative self-assembly of pure drug cocktails as injectable nanomedicines for synergistic drug delivery and cancer therapy.

Theranostics 2021 31;11(12):5713-5727. Epub 2021 Mar 31.

The First Affiliated Hospital, Zhejiang University School of Medicine; NHC Key Laboratory of Combined Multi-Organ Transplantation; Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Zhejiang Province, Hangzhou, PR China.

New strategies to fabricate nanomedicines with high translational capacity are urgently desired. Herein, a new class of self-assembled drug cocktails that addresses the multiple challenges of manufacturing clinically useful cancer nanomedicines was reported. With the aid of a molecular targeted agent, dasatinib (DAS), cytotoxic cabazitaxel (CTX) forms nanoassemblies () through one-pot process, with nearly quantitative entrapment efficiency and ultrahigh drug loading of up to 100%. Read More

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Modeling human pancreatic ductal adenocarcinoma for translational research: current options, challenges, and prospective directions.

Ann Pancreat Cancer 2020 Dec 29;3. Epub 2020 Dec 29.

Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy with one of the lowest survival rates. Early detection, an improved understanding of tumor biology, and novel therapeutic discoveries are needed in order to improve overall patient survival. Scientific progress towards meeting these goals relies upon accurate modeling of the human disease. Read More

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December 2020

PBRM1 Deficiency Confers Synthetic Lethality to DNA Repair Inhibitors in Cancer.

Cancer Res 2021 Apr 22. Epub 2021 Apr 22.

ATIP-Avenir group, Inserm Unit U981, Gustave Roussy, Villejuif, France.

Inactivation of (), a specific subunit of the PBAF chromatin remodeling complex, occurs frequently in cancer, including 40% of clear cell renal cell carcinomas (ccRCC). To identify novel therapeutic approaches to targeting PBRM1-defective cancers, we used a series of orthogonal functional genomic screens that identified PARP and ATR inhibitors as being synthetic lethal with deficiency. The PBRM1/PARP inhibitor synthetic lethality was recapitulated using several clinical PARP inhibitors in a series of model systems and in a xenograft model of ccRCC. Read More

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Chimeric CTLA4-CD28-CD3z T Cells Potentiate Antitumor Activity Against CD80/CD86-Positive B Cell Malignancies.

Front Immunol 2021 2;12:642528. Epub 2021 Apr 2.

Department of Obstetrics and Gynecology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

The adoptive transfer of chimeric antigen receptor T (CAR T) cells have been recognized as a promising therapeutic strategy for the treatment of hematological malignancies; however, clinical success using CAR T cells for the treatment of solid tumors are still limited since the T-cell function is inhibited by negative signals in the microenvironment of solid tumors. CTLA4 is a well-known immune checkpoint molecule, thus we developed a novel CAR by converting this negative signal to positive signal. The CAR developed consists of the extracellular and transmembrane domains of CTLA4 and the cytoplasmic domains of CD28 and CD3z (CTLA4-CAR T). Read More

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Entinostat, a selective HDAC1/2 inhibitor, potentiates the effects of olaparib in homologous recombination proficient ovarian cancer.

Gynecol Oncol 2021 Apr 15. Epub 2021 Apr 15.

Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address:

Objective: Poly ADP ribose polymerase inhibitors (PARPi) are most effective in BRCA1/2 mutated ovarian tumors. Better treatments are needed for homologous recombination HR-proficient cancer, including CCNE1 amplified subtypes. We have showndhown that histone deacetylase inhibitors (HDACi) sensitize HR-proficient ovarian cancer to PARPi. Read More

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Anticancer effects of radiation therapy combined with Polo-Like Kinase 4 (PLK4) inhibitor CFI-400945 in triple negative breast cancer.

Breast 2021 Apr 1;58:6-9. Epub 2021 Apr 1.

Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, M5G 2C1, Canada; Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, M5G 2C1, Canada.

Development of novel multimodality radiotherapy treatments in metastatic breast cancer, especially in the most aggressive triple negative (TNBC) subtype, is of significant clinical interest. Here we show that a novel inhibitor of Polo-Like Kinase 4 (PLK4), CFI-400945, in combination with radiation, exhibits a synergistic anti-cancer effect in TNBC cell lines and patient-derived organoids in vitro and leads to a significant increase in survival to tumor endpoint in xenograft models in vivo, compared to control or single-agent treatment. Further preclinical and proof-of-concept clinical studies are warranted to characterize molecular mechanisms of action of this combination and its potential applications in clinical practice. Read More

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Deep-learning and MR images to target hypoxic habitats with evofosfamide in preclinical models of sarcoma.

Theranostics 2021 11;11(11):5313-5329. Epub 2021 Mar 11.

Department of Cancer Physiology, Moffitt Cancer Center, Tampa, US.

Hypoxic regions (habitats) within tumors are heterogeneously distributed and can be widely variant. Hypoxic habitats are generally pan-therapy resistant. For this reason, hypoxia-activated prodrugs (HAPs) have been developed to target these resistant volumes. Read More

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Histotripsy for the Treatment of Cholangiocarcinoma Liver Tumors: In Vivo Feasibility and Ex Vivo Dosimetry Study.

IEEE Trans Ultrason Ferroelectr Freq Control 2021 Apr 15;PP. Epub 2021 Apr 15.

Histotripsy is a non-invasive, non-ionizing, and non-thermal focused ultrasound ablation method that is currently being developed for the treatment of liver cancer. Promisingly, histotripsy has been shown for ablating primary (hepatocellular carcinoma, HCC) and metastatic (colorectal liver metastasis, CLM) liver tumors in preclinical and early clinical studies. The feasibility of treating cholangiocarcinoma (CC), a less common primary liver tumor that arises from the bile ducts, has not been explored previously. Read More

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Testing Cancer Immunotherapy in a Human Immune System Mouse Model: Correlating Treatment Responses to Human Chimerism, Therapeutic Variables and Immune Cell Phenotypes.

Front Immunol 2021 29;12:607282. Epub 2021 Mar 29.

Division of Medical Oncology, School of Medicine, University of Colorado, Aurora, CO, United States.

Over the past decade, immunotherapies have revolutionized the treatment of cancer. Although the success of immunotherapy is remarkable, it is still limited to a subset of patients. More than 1500 clinical trials are currently ongoing with a goal of improving the efficacy of immunotherapy through co-administration of other agents. Read More

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Directly targeting c-Myc contributes to the anti-multiple myeloma effect of anlotinib.

Cell Death Dis 2021 Apr 14;12(4):396. Epub 2021 Apr 14.

Hongqiao International Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Chemical Biology Division of Shanghai Universities E-Institutes, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China.

Despite the significant advances in the treatment of multiple myeloma (MM), this disease is still considered incurable because of relapse and chemotherapy resistance, underscoring the need to seek novel therapies with different mechanisms. Anlotinib, a novel multi-targeted tyrosine kinase inhibitor (TKI), has exhibited encouraging antitumor activity in several preclinical and clinical trials, but its effect on MM has not been studied yet. In this study, we found that anlotinib exhibits encouraging cytotoxicity in MM cells, overcomes the protective effect of the bone marrow microenvironment and suppresses tumor growth in the MM mouse xenograft model. Read More

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Humanized anti-DEspR IgG4 antibody increases overall survival in a pancreatic cancer stem cell-xenograft peritoneal carcinomatosis rat model.

BMC Cancer 2021 Apr 14;21(1):407. Epub 2021 Apr 14.

Whitaker Cardiovascular Institute and Department of Medicine, Boston University School of Medicine, Boston, MA, USA.

Background: Pancreatic peritoneal carcinomatosis (PPC), with the worst median overall-survival (mOS), epitomizes the incurability of metastatic cancer. Cancer stem cells (CSCs) underpin this incurability. However, inhibitors of CSC-stemness fail to increase mOS in cancer patients despite preclinical tumor-reduction. Read More

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High-throughput screening identifies idasanutlin as a resensitizing drug for venetoclax-resistant neuroblastoma cells.

Mol Cancer Ther 2021 Apr 13. Epub 2021 Apr 13.

Molenaar group, Princess Máxima Center for pediatric oncology

Neuroblastoma tumors frequently overexpress the anti-apoptotic protein B cell lymphoma/leukemia 2 (BCL-2). We previously showed that treating BCL-2-dependent neuroblastoma cells with the BCL-2 inhibitor venetoclax results in apoptosis, but unfortunately partial therapy resistance is observed. The current study describes the identification of drugs capable of resensitizing venetoclax-resistant neuroblastoma cells to venetoclax. Read More

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Construction of patient-derived tumor models to evaluate anticancer agents and cancer immunotherapy.

Oncol Lett 2021 May 22;21(5):406. Epub 2021 Mar 22.

Medical-Industrial Translational Research Center, Fukushima Medical University, Fukushima, Fukushima 960-1295, Japan.

An assay system using patient-derived tumor models represents a promising preclinical cancer model that replicates the disease better than traditional cell culture models. Patient-derived tumor organoid (PDO) and patient-derived tumor xenograft (PDX) models have been previously established from different types of human tumors to recapitulate accurately and efficiently their tissue architecture and function. However, these models have low throughput and are challenging to construct. Read More

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Novel Preclinical Patient-Derived Lung Cancer Models Reveal Inhibition of HER3 and MTOR Signaling as Therapeutic Strategies for NRG1 Fusion-Positive Cancers.

J Thorac Oncol 2021 Apr 8. Epub 2021 Apr 8.

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.

Introduction: NRG1 rearrangements produce chimeric ligands that subvert the ERBB pathway to drive tumorigenesis. A better understanding of the signaling networks that mediate transformation by NRG1 fusions is needed to inform effective therapeutic strategies. Unfortunately, this has been hampered by a paucity of patient-derived disease models that faithfully recapitulate this molecularly defined cancer subset. Read More

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Exploiting the reactive oxygen species imbalance in high-risk paediatric acute lymphoblastic leukaemia through auranofin.

Br J Cancer 2021 Apr 9. Epub 2021 Apr 9.

Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.

Background: The prognosis for high-risk childhood acute leukaemias remains dismal and established treatment protocols often cause long-term side effects in survivors. This study aims to identify more effective and safer therapeutics for these patients.

Methods: A high-throughput phenotypic screen of a library of 3707 approved drugs and pharmacologically active compounds was performed to identify compounds with selective cytotoxicity against leukaemia cells followed by further preclinical evaluation in patient-derived xenograft models. Read More

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Antimicrobial Susceptibility of Corynebacterium bovis Isolates from Immunodeficient Rodents.

Comp Med 2021 Apr 8. Epub 2021 Apr 8.

Corynebacterium bovis, the causative agent of hyperkeratotic dermatitis in immunodeficient mice, is a significant problemin preclinical oncology research. Infection results in lifelong skin colonization and a decrease in successful engraftment ofpatient-derived xenograft tumor models. The use of antimicrobial agents for C. Read More

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