scholarly journals Advanced Xenograft Model with Cotransplantation of Patient-Derived Organoids and Endothelial Colony-Forming Cells for Precision Medicine

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Junhye Kwon ◽  
Sungryong Oh ◽  
Misun Park ◽  
Joon Seog Kong ◽  
Sunyi Lee ◽  
...  
Keyword(s):  
Precision Medicine ◽  
Clinical Data ◽  
Evaluation Model ◽  
Colorectal Cancer Patient ◽  
Xenograft Model ◽  
Sequencing Analysis ◽  
Endothelial Colony Forming Cells ◽  
Evaluation Models ◽  
Xenograft Models ◽  
Dna Sequencing Analysis

Preclinical evaluation models have been developed for precision medicine, with patient-derived xenograft models (PDXs) and patient-derived organoids (PDOs) attracting increasing attention. However, each of these models has application limitations. In this study, an advanced xenograft model was established and used for drug screening. PDO and endothelial colony-forming cells (ECFCs) were cotransplanted in NRGA mice (PDOXwE) to prepare the model, which could also be subcultured in Balb/c nude mice. Our DNA sequencing analysis and immunohistochemistry results indicated that PDOXwE maintained patient genetic information and tumor heterogeneity. Moreover, the model enhanced tumor growth more than the PDO-bearing xenograft model (PDOX). The PDO, PDOXwE, and clinical data were also compared in the liver metastasis of a colorectal cancer patient, demonstrating that the chemosensitivity of PDO and PDOXwE coincided with the clinical data. These results suggest that PDOXwE is an improvement of PDOX and is suitable as an evaluation model for precision medicine.

scholarly journals Sex-dependent liver cancer xenograft models for predicting clinical data in the evaluation of anticancer drugs

2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Sungryong Oh ◽  
Joohee Jung
Keyword(s):  
Liver Cancer ◽  
Adverse Effects ◽  
Anticancer Drugs ◽  
Clinical Data ◽  
Xenograft Model ◽  
In Vitro Test ◽  
Incidence And Mortality ◽  
Significant Difference ◽  
Xenograft Models

Abstract Background The incidence and mortality of liver cancer show a great difference between the sexes. We established sex-dependent liver cancer xenograft models and investigated whether such sex-dependent models could be used to simultaneously evaluate the therapeutic and adverse effects of anticancer drugs for drug screening. Results In the in-vitro test, the cytotoxicity of anticancer drugs (cisplatin, 5-fluorouracil, and doxorubicin) was compared between male- and female-derived liver cancer cell lines. Cisplatin and 5-fluorouracil exhibited cytotoxicity without sex-difference, but doxorubicin showed dose-dependently significant cytotoxicity only in male-derived cells. Our results showed a strong correlation between preclinical and clinical data with the use of sex-dependent liver cancer xenograft models. Moreover, the male-derived Hep3B-derived xenograft model was more sensitive than the female-derived SNU-387-derived xenograft model against doxorubicin treatment. Doxorubicin showed more severe cardiotoxicity in the male xenograft model than in the female model. We investigated the occurrence frequency of doxorubicin-related cardiotoxicity using data obtained from the Korea Institute of Drug Safety & Risk Management Database, but no significant difference was observed between the sexes. Conclusions Our results suggest that sex-dependent xenograft models are useful tools for evaluating the therapeutic and adverse effects of anticancer drugs, because sex is an important consideration in drug development.

scholarly journals Repurposing cabozantinib with therapeutic potential in KIT-driven t(8;21) acute myeloid leukaemias

2021 ◽  
Author(s):  
Kuan-Wei Su ◽  
Da-Liang Ou ◽  
Yu-Hsuan Fu ◽  
Hwei-Fang Tien ◽  
Hsin-An Hou ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Ribosome Biogenesis ◽  
Kinase Inhibitor ◽  
Therapeutic Potential ◽  
Xenograft Model ◽  
Sequencing Analysis ◽  
Dependent Manner ◽  
Leukocyte Activation ◽  
Mouse Xenograft Model ◽  
Acute Myeloid

AbstractCabozantinib is an orally available, multi-target tyrosine kinase inhibitor approved for the treatment of several solid tumours and known to inhibit KIT tyrosine kinase. In acute myeloid leukaemia (AML), aberrant KIT tyrosine kinase often coexists with t(8;21) to drive leukaemogenesis. Here we evaluated the potential therapeutic effect of cabozantinib on a selected AML subtype characterised by t(8;21) coupled with KIT mutation. Cabozantinib exerted substantial cytotoxicity in Kasumi-1 cells with an IC50 of 88.06 ± 4.32 nM, which was well within clinically achievable plasma levels. The suppression of KIT phosphorylation and its downstream signals, including AKT/mTOR, STAT3, and ERK1/2, was elicited by cabozantinib treatment and associated with subsequent alterations of cell cycle- and apoptosis-related molecules. Cabozantinib also disrupted the synthesis of an AML1-ETO fusion protein in a dose- and time-dependent manner. In a mouse xenograft model, cabozantinib suppressed tumourigenesis at 10 mg/kg and significantly prolonged survival of the mice. Further RNA-sequencing analysis revealed that mTOR-mediated signalling pathways were substantially inactivated by cabozantinib treatment, causing the downregulation of ribosome biogenesis and glycolysis, along with myeloid leukocyte activation. We suggest that cabozantinib may be effective in the treatment of AML with t(8;21) and KIT mutation. Relevant clinical trials are warranted.

scholarly journals Gamma-radiated immunosuppressed tumor xenograft mice can be a new ideal model in cancer research

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hamid Khodayari ◽  
Saeed Khodayari ◽  
Solmaz Khalighfard ◽  
Arash Tahmasebifar ◽  
Mahboubeh Tajaldini ◽  
...  
Keyword(s):  
Gamma Radiation ◽  
High Capacity ◽  
Xenograft Model ◽  
Tumor Xenograft ◽  
Whole Body ◽  
Cell Injection ◽  
Tumor Tissues ◽  
Post Radiation ◽  
Xenograft Models ◽  
Xenograft Mice

AbstractTumor xenograft models can create a high capacity to study human tumors and discover efficient therapeutic approaches. Here, we aimed to develop the gamma-radiated immunosuppressed (GIS) mice as a new kind of tumor xenograft model for biomedical studies. First, 144 mice were divided into the control and treated groups exposed by a medical Cobalt-60 apparatus in 3, 4, and 5 Gy based on the system outputs. Then, 144 BALB/c mice were divided into four groups; healthy, xenograft, radiation, and radiation + xenograft groups. The animals in the xenograft and radiation + xenograft groups have subcutaneously received 3 × 106 MCF-7 cells 24 h post-radiation. On 3, 7, 14, and 21 days after cell injection, the animals were sacrificed. Then, the blood samples and the spleen and tumor tissues were removed for the cellular and molecular analyses. The whole-body gamma radiation had a high immunosuppressive effect on the BALB/c mice from 1 to 21 days post-radiation. The macroscopic and histopathological observations have proved that the created clusters' tumor structure resulted in the xenograft breast tumor. There was a significant increase in tumor size after cell injection until the end of the study. Except for Treg, the spleen level of CD4, CD8, CD19, and Ly6G was significantly decreased in Xen + Rad compared to the Xen alone group on 3 and 7 days. Unlike IL-4 and IL-10, the spleen level of TGF-β, INF-γ, IL-12, and IL-17 was considerably decreased in the Xen + Rad than the Xen alone group on 3 and 7 days. The spleen expressions of the VEGF, Ki67, and Bax/Bcl-2 ratio were dramatically increased in the Xen + Rad group compared to the Xen alone on 3, 7, 14, and 21 days. Our results could confirm a new tumor xenograft model via an efficient immune-suppressive potential of the whole-body gamma radiation in mice.

scholarly journals Comparison of the Accuracy of Two Conventional Phenotypic Methods and Two MALDI-TOF MS Systems with That of DNA Sequencing Analysis for Correctly Identifying Clinically Encountered Yeasts

PLoS ONE ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. e109376 ◽  
Author(s):  
Qiao-Ting Chao ◽  
Tai-Fen Lee ◽  
Shih-Hua Teng ◽  
Li-Yun Peng ◽  
Ping-Hung Chen ◽  
...  
Keyword(s):  
Dna Sequencing ◽  
Sequencing Analysis ◽  
Maldi Tof Ms ◽  
Maldi Tof ◽  
Dna Sequencing Analysis ◽  
Phenotypic Methods ◽  
Tof Ms

scholarly journals Biotinylation of Deoxyguanosine at the Abasic Site in Double-Stranded Oligodeoxynucleotides

2016 ◽  
Vol 2016 ◽  
pp. 1-4
Author(s):  
Chun Wu
Keyword(s):  
Dna Polymerase ◽  
Click Reaction ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Sequencing Analysis ◽  
Abasic Site ◽  
Nylon Membrane ◽  
Abasic Sites ◽  
Polymerase Chain ◽  
Dna Sequencing Analysis ◽  
Endonuclease Digestion

Biotinylation of deoxyguanosine at an abasic site in double-stranded oligodeoxynucleotides was studied. The biotinylation of deoxyguanosine is achieved by copper-catalyzed click reaction after the conjugation of the oligodeoxynucleotide with 2-oxohex-5-ynal. The biotinylation enables visualization of the biotinylated oligodeoxynucleotides by chemiluminescence on a nylon membrane. In order to investigate the biotinylated site, the biotinylated oligodeoxynucleotides were amplified by the DNA polymerase chain reaction. Replacement of guanine opposing the abasic site with adenine generated by the activity of the terminal deoxynucleotidyl transferase of DNA polymerase was detected by DNA sequencing analysis and restriction endonuclease digestion. This study suggests that 2-oxohex-5-ynal may be useful for the detection of the unpaired deoxyguanosine endogenously generated at abasic sites in genomic DNA.

Enabling Precision Medicine in Cancer Care Through a Molecular Data Warehouse: The Moffitt Experience

2021 ◽  
pp. 561-569
Author(s):  
Steven A. Eschrich ◽  
Jamie K. Teer ◽  
Phillip Reisman ◽  
Erin Siegel ◽  
Chandan Challa ◽  
...  
Keyword(s):  
Cancer Research ◽  
Precision Medicine ◽  
Data Warehouse ◽  
Clinical Data ◽  
Molecular Data ◽  
Project Planning ◽  
Cancer Genome ◽  
Open Communication ◽  
Clinical Data Warehouse ◽  
Research Studies

PURPOSE The use of genomics within cancer research and clinical oncology practice has become commonplace. Efforts such as The Cancer Genome Atlas have characterized the cancer genome and suggested a wealth of targets for implementing precision medicine strategies for patients with cancer. The data produced from research studies and clinical care have many potential secondary uses beyond their originally intended purpose. Effective storage, query, retrieval, and visualization of these data are essential to create an infrastructure to enable new discoveries in cancer research. METHODS Moffitt Cancer Center implemented a molecular data warehouse to complement the extensive enterprise clinical data warehouse (Health and Research Informatics). Seven different sequencing experiment types were included in the warehouse, with data from institutional research studies and clinical sequencing. RESULTS The implementation of the molecular warehouse involved the close collaboration of many teams with different expertise and a use case–focused approach. Cornerstones of project success included project planning, open communication, institutional buy-in, piloting the implementation, implementing custom solutions to address specific problems, data quality improvement, and data governance, unique aspects of which are featured here. We describe our experience in selecting, configuring, and loading molecular data into the molecular data warehouse. Specifically, we developed solutions for heterogeneous genomic sequencing cohorts (many different platforms) and integration with our existing clinical data warehouse. CONCLUSION The implementation was ultimately successful despite challenges encountered, many of which can be generalized to other research cancer centers.

Human c-fms proto-oncogene: comparative analysis with an abnormal allele

1985 ◽  
Vol 5 (2) ◽  
pp. 422-426
Author(s):  
J S Verbeek ◽  
A J Roebroek ◽  
A M van den Ouweland ◽  
H P Bloemers ◽  
W J Van de Ven
Keyword(s):  
Comparative Analysis ◽  
Dna Sequencing ◽  
Sequencing Analysis ◽  
Base Pairs ◽  
Small Deletion ◽  
Viral Oncogene ◽  
Close Proximity ◽  
Genetic Sequences ◽  
Dna Sequencing Analysis

The organization of the human c-fms proto-oncogene has been determined and compared with an abnormal allele. The human v-fms homologous genetic sequences are dispersed discontinuously and colinearly with the viral oncogene over a DNA region of ca. 32 kilobase pairs. The abnormal c-fms locus contains a small deletion in its 3' portion. DNA sequencing analysis indicated that it was 426 base pairs in size and located in close proximity to a putative c-fms exon.

scholarly journals A COMPARATIVE ANALYSIS OF THE EFFICACY OF THREE PROGRAM-EVALUATION MODELS –A REVIEW ON THEIR IMPLICATION IN EDUCATIONAL PROGRAMS

2021 ◽  
Vol 9 (3) ◽  
pp. 326-336
Author(s):  
Zafar Iqbal ◽  
Muhammad Anees ◽  
Rahim Khan ◽  
Abdul Wadood ◽  
Shakila Malik
Keyword(s):  
Program Evaluation ◽  
Evaluation Model ◽  
Cost Effective ◽  
Educational Programs ◽  
Comparative Efficacy ◽  
Scholarly Journals ◽  
Cipp Model ◽  
Evaluation Models ◽  
High Standards ◽  
Kirkpatrick’S Model

Purpose of the study: This article reviews the comparative efficacy, theoretical and practical background of three program evaluation models (Stufflebeam’s CIPP model, Kirkpatrick’s model, and outcome-based evaluation models) and their implications in educational programs. The article discusses the strengths and limitations of the three evaluation models. Methodology: Peer-reviewed and scholarly journals were searched for articles related to program evaluation models and their importance. Keywords included program evaluation’, ‘assessment’, ‘CIPP model’, ‘evaluation of educational programs, ‘outcome-based model, and ‘planning’. Articles on Stufflebeam’s CIPP model, Kirkpatrick’s model, and outcome-based evaluation models were particularlyfocused because the review aimed at analysing these three models. The strengths and inadequacies of the three models were weighed and presented. Main Findings: The three models –outcome-based evaluation model, the Kirkpatric model, and the CIPP evaluation model –discussed in this review, have some strengths and weaknesses. Among the compared models, the CIPP model seems more appropriate for its implantation in evaluating educational programs because it is broader, comprehensive, flexible, cost-effective, and feasible. Applications of this study: Like other programs and projects, evaluation of educational programs is necessary to achieve high standards, better outcomes, and meet the objectives. Evaluation is employed before designing a particular educational program or during the already designed program. This review concludes that among different evaluation models, the CIPP evaluation model is more appropriate in evaluating educational programs because it is more comprehensive, efficient, and feasible.Employment of the CIPP model for evaluating educational programs can achieve plausible results about the overall progress of the educational programs. Novelty/Originality of this study: This review highlights the importance of different program evaluation models. It concludes that the CIPP evaluation model offers an excellent mechanism to evaluate educational programs at different stages.

scholarly journals Comparison of Angelica Species Roots Using Taste Sensor and DNA Sequencing Analysis

2012 ◽  
Vol 27 (6) ◽  
pp. 37-42 ◽  
Author(s):  
Young Hwa Kim ◽  
Goya Choi ◽  
Hye Won Lee ◽  
Gwan Ho Lee ◽  
Seong Wook Chae ◽  
...  
Keyword(s):  
Dna Sequencing ◽  
Sequencing Analysis ◽  
Dna Sequencing Analysis ◽  
Taste Sensor
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