scholarly journals TB-3 miR-33a depletion accelerate medulloblastoma generation and invasion

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi6-vi6
Author(s):  
Yohei Mineharu ◽  
Yasuzumi Matsui ◽  
Yuki Oichi ◽  
Takahiko Kamata ◽  
Takaaki Morimoto ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Nude Mice ◽  
Transgenic Mouse Model ◽  
Tumor Formation ◽  
Tumor Stem Cell ◽  
Histopathological Analysis ◽  
Spontaneous Generation ◽  
Potential Therapeutic Target ◽  
Stem Cell Maintenance ◽  
Infiltrative Tumor

Abstract Background and purposes: Lipid metabolism have been shown to be associated with tumorigenicity in various malignancies. The purpose of this study was to investigate the association of miR-33, a key regulator of lipid metabolism, in tumorigenicity and progression of medulloblastoma. Methods: Incidence of medulloblastoma and histopathological findings were compared between ptch1+/- mice and ptch1+/- miR-33a-/- mice. Tumors extracted from these mice were transplanted subcutaneously in nude mice (n=14 for ptch1+/-, n=19 for ptch1+/- miR-33a-/-) and in C57BL/6 mice (n=12 for each). Gene expression profile was compared between tumors from ptch1+/- mice and those from ptch1+/- miR-33a-/- mice. Results: Knockout of miR-33a in ptch1+/- transgenic mouse model increased the incidence of spontaneous generation of medulloblastoma from 34.5% to 84.0% (p< 0.001) at 12 months. Histopathological analysis showed infiltrative tumor borders in ptch1+/- miR-33a-/- tumors as compared with ptch1+/- ones. Tumor formation was observed in 21.4% for ptch1+/- tumors and 68.4% for ptch1+/- miR-33a-/- tumors in nude mice (p= 0.008). It was observed in 0% and 16.7% in immune competent mice. RNA sequencing detected that SCD1 and SREBF1 was upregulated in tumors from miR-33a knockout mice. Discussion: Our results demonstrated that depletion of miR-33a accelerated medulloblastoma generation and invasion. miR-33a may also be important for immune evasion. SCD1, which is reported to play a role in tumor stem cell maintenance and metastasis, can be a potential therapeutic target for medulloblastoma.

scholarly journals MBRS-22. SIGNIFICANCE OF RNF213 IN TUMORGENICITY OF MEDULLOBLASTOMA

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii402-iii402
Author(s):  
Yohei Mineharu ◽  
Yuki Oichi ◽  
Takahiko Kamata ◽  
Yasuzumi Matsui ◽  
Takaaki Morimoto ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Mouse Model ◽  
Cerebrovascular Disease ◽  
Wnt Signaling ◽  
Transgenic Mouse ◽  
Molecular Mechanism ◽  
Genomic Instability ◽  
Transgenic Mouse Model ◽  
Spontaneous Generation ◽  
Rnf213 Gene

Abstract RNF213 gene, initially identified as a disease-causing gene for moyamoya cerebrovascular disease, has recently been recognized as a tumor regulator. The gene is known to be associated with WNT signaling, lipid metabolism, angiogenesis and genomic instability. The purpose of this study was to investigate the association of RNF213 in tumorgenicity of medulloblastoma. Incidence of medulloblastoma and histopathological findings were compared among ptch1+/-, ptch1+/- rnf213+/-, and ptch1+/- rnf213-/- mice. Knockout of rnf213 in ptch1+/- transgenic mouse model increased the incidence of spontaneous generation of medulloblastoma from 19.8% (ptch1+/-) to 76.5% (rnf213+/- ptch1+/-) at 9 months (p < 0.001). Heterozygous knockout was equivalent to homozygous knockout. Haploinsufficiency of rnf213 seems to be associated with tumorgenicity in medulloblastoma. Molecular mechanism of medulloblastoma generation needs to be further investigated.

scholarly journals Efficient and Consistent Orthotopic Osteosarcoma Model by Cell Sheet Transplantation in the Nude Mice for Drug Testing

2021 ◽  
Vol 9 ◽  
Author(s):  
Hongwei Wu ◽  
Zhengxi He ◽  
Xianan Li ◽  
Xuezheng Xu ◽  
Wu Zhong ◽  
...  
Keyword(s):  
Cell Suspension ◽  
Nude Mice ◽  
Bone Growth ◽  
Cell Sheet ◽  
Bone Destruction ◽  
Tumor Formation ◽  
Histopathological Analysis ◽  
Similar Amount ◽  
Osteosarcoma Cell ◽  
Imaging Results

Osteosarcoma is a big challenge on clinical treatment. The breakthrough associated with osteosarcoma in basic research and translational research depends on the reliable establishment of an animal model, whereby mice are frequently used. However, a traditional animal modeling technique like tumor cell suspension injection causes batch dynamics and large mice consumption. Here, we suggested a novel approach in establishing an orthotropic osteosarcoma model in nude mice rapidly by cell sheet culture and transplantation. Our findings demonstrated that the 143b osteosarcoma cell sheet orthotopically implanted into the nude mice could form a visible mass within 10 days, whereas it took over 15 days for a similar amount of cell suspension injection to form a visible tumor mass. Living animal imaging results showed that a tumor formation rate was 100% in the cell sheet implantation group, while it was 67% in the cell suspension injection group. The formed tumor masses were highly consistent in both growth rate and tumor size. Massive bone destruction and soft tissue mass formation were observed from the micro CT analysis, suggesting the presence of osteosarcoma. The histopathological analysis demonstrated that the orthotropic osteosarcoma model mimicked the tumor bone growth, bone destruction, and the lung metastasis. These findings imply that such a cell sheet technology could be an appropriate approach to rapidly establish a sustainable orthotropic osteosarcoma model for tumor research and reduce mice consumption.

scholarly journals MBRS-23. SIGNIFICANCE OF mi-R33 IN GENERATION AND PROGRESSION OF MEDULLOBLASTOMA

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii402-iii402
Author(s):  
Yasuzumi Matsui
Keyword(s):  
Lipid Metabolism ◽  
Transgenic Mouse Model ◽  
Spontaneous Generation ◽  
Preclinical Models ◽  
Treatment Needs ◽  
Medulloblastoma Cell Line ◽  
Cytotoxic Treatment ◽  
Important Regulator

Abstract Lipid metabolism has been shown to be associated with tumorigenicity in various malignancies. The purpose of this study was to investigate the association of miR-33, a key regulator of lipid metabolism, in tumorigenicity and progression of medulloblastoma. miR-33a is an only isotype of miR-33 in rodents although miR-33b is also detected in human. Incidence of medulloblastoma and histopathological findings were compared between ptch1+/- mice and ptch1+/- miR-33a-/- mice. Effect of miR-33b upregulation by cordycepin was tested in DAOY medulloblastoma cells both in vitro and in vivo. Knockout of miR-33a in ptch1+/- transgenic mouse model increased the incidence of spontaneous generation of medulloblastoma from 19.8% to 49.5% (p < 0.001) at 10 months. Cordycepin, which upregulates miR-33b, prevented tumor growth in DAOY human medulloblastoma cell line, but the effect was not evident in an orthotopic mouse medulloblastoma model. Although miR-33 seems to be an important regulator of medulloblastoma, treatment efficacy of cordycepin was not enough. Combination treatment with immunotherapy or cytotoxic treatment needs to be tested to show survival benefit in preclinical models.

Mechanism Research of Reversal of Multidrug Resistance by the Application of 5-Bromotetrandrine and Magnetic Nanoparticle of Fe3O4 Combined with Daunorubicin in a Human-Nude Mice Xenograft Model

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5058-5058
Author(s):  
Bao-An Chen ◽  
Ya-nan Wu ◽  
Jian Cheng ◽  
Feng Gao ◽  
Wen-lin Xu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Nude Mice ◽  
Magnetic Nanoparticle ◽  
Multiple Drug Resistance ◽  
Xenograft Model ◽  
Tumor Formation ◽  
Multiple Drug ◽  
Inhibition Rate ◽  
Group 5

Abstract Objective: To establish the xenograft leukemia model with stable multiple drug resistance in nude mice; to investigate the reversal effect of 5-Bromotetrandrine and Magnetic nanoparticle of Fe3O4 combined with DNR in vivo and to search for the possible reversal mechanisms. Methods: K562 and K562/A02 cells were respectively inoculated subcutaneously into back of athymic nude mice (1×107 cells/each) to establish the xenograft models. The tumor formation was evaluated by animal ultrasonic inspection. Tumors-bearing nude mice were assigned randomly to five groups which were treated with NS (A group); DNR 1mg/kg (B group); nanoparticle of Fe3O4 combined with DNR 0.63mg/kg(C group): 5-BrTet 2.5mg/kg combined with DNR(D group); 5-Bromotetrandrine 2.5mg/kg and Magnetic nanoparticle of Fe3O4 combined with DNR 0.63mg/kg(E group) respectively. The incidence of tumor formation, growth characteristics, weight and volume of tumor were observed. The histopathologic examination of tumors and organs were detected. For resistant tumors, the protein levels of P-glycoprotein (P-gp) were detected by Western blot. Results: The tumor incidence was 100% in the nude mice inoculated with either K562 or K562/A02 cells. In 6 to 9 days,the tumors reached a volume of more than 1 00 mm3. In vivo, MTT assay showed K562/A02 tumor maintained the drug resistance. For K562 cells xenograft tumors, there were no apparent differences in tumor suppression effect between the B AC AD AE group. For K562/A02 cells xenograft tumors, 5-BrTet and Magnetic nanoparticle of Fe3O4 combined with DNR significantly suppressed growth of tumor: the inhibition rate was 62.76% while DNR alone be used, the inhibition rate was 3.68%. Pathologic examination of resistant tumors showed the tumors necrosis obviously in E group. Application of 5-BrTet and Magnetic nanoparticle of Fe3O4 inhibited the overexpression of P-gp. Conclusion: The xenograft leukemia nude mice model was maintain the multiple drug resistance. 5-Bromotetrandrine and Magnetic nanoparticle of Fe3O4 combined with DNR had a significant tumor-suppressing effect on MDR leukemia cells xenograft model.

scholarly journals Concurrent overexpression of RET/PTC1 and TTF1 confers tumorigenicity to thyrocytes

2013 ◽  
Vol 20 (6) ◽  
pp. 767-776 ◽  
Author(s):  
Toyoshi Endo ◽  
Tetsuro Kobayashi
Keyword(s):  
Nude Mice ◽  
Cell Types ◽  
Tumor Formation ◽  
Mrna Levels ◽  
Thyroid Transcription Factor 1 ◽  
Thyroid Transcription Factor ◽  
Extracellular Signal ◽  
Tumorigenic Potential ◽  
Uptake Activity ◽  
Transcription Factor 1

A variant located on 14q13.3 nearest to thyroid transcription factor-1 (TTF1) predisposes individuals to thyroid cancer, but whether this variant is related to the RET/PTC rearrangement associated with human papillary thyroid carcinomas (PTCs) is unknown. The aims of this study were to investigate the effects of RET/PTC1 on the expression of thyroid-specific genes in thyrocytes and their relationship with malignant transformation of the thyrocytes. In the absence or presence of TSH, an extracellular signal-regulated kinase was phosphorylated in FRTL5 cells that stably expressed RET/PTC1, and these cells grew independently of TSH. FRTL (RET/PTC1) cells produced 566% more thyroglobulin mRNA and 474% more Na+/I− symporter mRNA than did the control FRTL (pcDNA) cells. FRTL (RET/PTC1) cells expressed 468% more Ttf1 mRNA than did FRTL (pcDNA) cells, but these two cell types did not differ significantly with respect to Pax8 or Ttf2 mRNA levels. When FRTL (RET/PTC1) cells and FRTL (pcDNA), cells were injected into each of nine nude mice, each mouse developed a single tumor at the site of FRTL (RET/PTC1) cell injection; in contrast, tumor formation never occurred at sites of FRTL (cDNA) cells injection. Tumors resulting from FRTL (RET/PTC1) cells retained 125I-uptake activity; moreover, the cells invaded into surrounding skeletal muscle. When overexpression of Ttf1 in FRTL (RET/PTC1) cells was silenced, the cells completely lost their tumorigenic potential. Exogenous TTF1 cDNA enhanced the tumorigenicity of BHP18-21v cells, human PTC cells that express RET/PTC1, in nude mice. These results indicated that concurrent overexpression of RET/PTC1 and TTF1 confers tumorigenicity to FRTL5 and BHP18-21v cells in nude mice.

scholarly journals Growth-inhibitory Activity and Downregulation of the Class II Tumor-suppressor Gene H-rev107 in Tumor Cell Lines and Experimental Tumors

1997 ◽  
Vol 136 (4) ◽  
pp. 935-944 ◽  
Author(s):  
Christine Sers ◽  
Urban Emmenegger ◽  
Knut Husmann ◽  
Katharina Bucher ◽  
Ann-Catherine Andres ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Cell Lines ◽  
Nude Mice ◽  
Class Ii ◽  
Tumor Formation ◽  
Pancreatic Tumors ◽  
Rat Tissues ◽  
Transformed Cell Lines

The H-rev107 gene is a new class II tumor suppressor, as defined by its reversible downregulation and growth-inhibiting capacity in HRAS transformed cell lines. Overexpression of the H-rev107 cDNA in HRAS-transformed ANR4 hepatoma cells or in FE-8 fibroblasts resulted in 75% reduction of colony formation. Cell populations of H-rev107 transfectants showed an attenuated tumor formation in nude mice. Cells explanted from tumors or maintained in cell culture for an extended period of time no longer exhibited detectable levels of the H-rev107 protein, suggesting strong selection against H-rev107 expression in vitro and in vivo. Expression of the truncated form of H-rev107 lacking the COOH-terminal membrane associated domain of 25 amino acids, had a weaker inhibitory effect on proliferation in vitro and was unable to attenuate tumor growth in nude mice. The H-rev107 mRNA is expressed in most adult rat tissues, and immunohistochemical analysis showed expression of the protein in differentiated epithelial cells of stomach, of colon and small intestine, in kidney, bladder, esophagus, and in tracheal and bronchial epithelium. H-rev107 gene transcription is downregulated in rat cell lines derived from liver, kidney, and pancreatic tumors and also in experimental mammary tumors expressing a RAS transgene. In colon carcinoma cell lines only minute amounts of protein were detectable. Thus, downregulation of H-rev107 expression may occur at the level of mRNA or protein.

Sign in / Sign up

Export Citation Format

Share Document