Suppression of tumorigenicity in Wilms tumor by the p15.5-p14 region of chromosome 11

Science ◽  
1991 ◽  
Vol 254 (5029) ◽  
pp. 293-295
Author(s):  
SF Dowdy ◽  
CL Fasching ◽  
D Araujo ◽  
KM Lai ◽  
E Livanos ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Line ◽  
Nude Mice ◽  
Wilms Tumor ◽  
Genetic Locus ◽  
Tumor Cell Line ◽  
Tumor Formation ◽  
The Other ◽  
Chromosome 11

Wilms tumor has been associated with genomic alterations at both the 11p13 and 11p15 regions. To differentiate between the involvement of these two loci, a chromosome 11 was constructed that had one or the other region deleted, and this chromosome was introduced into the tumorigenic Wilms tumor cell line G401. When assayed for tumor-forming activity in nude mice, the 11p13-deleted, but not the 11p15.5-p14.1-deleted chromosome, retained its ability to suppress tumor formation. These results provide in vivo functional evidence for the existence of a second genetic locus (WT2) involved in suppressing the tumorigenic phenotype of Wilms tumor.

Introduction of a normal human chromosome 11 into a Wilms' tumor cell line controls its tumorigenic expression

Science ◽  
1987 ◽  
Vol 236 (4798) ◽  
pp. 175-180 ◽  
Author(s):  
B. Weissman ◽  
P. Saxon ◽  
Pasquale ◽  
G. Jones ◽  
A. Geiser ◽  
...  
Keyword(s):  
Human Chromosome ◽  
Tumor Cell ◽  
Cell Line ◽  
Wilms Tumor ◽  
Tumor Cell Line ◽  
Chromosome 11 ◽  
Normal Human

Induction of mouse tenascin expression by a human sarcomatoid wilms' tumor cell line growing in nude mice

1993 ◽  
Vol 54 (5) ◽  
pp. 868-874 ◽  
Author(s):  
Jan Fredrik Talts ◽  
Enno Aufderheide ◽  
Lydia Sorokin ◽  
Göran Ocklind ◽  
Ragnar Mattsson ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Line ◽  
Nude Mice ◽  
Wilms Tumor ◽  
Tumor Cell Line

Preclinical evaluation of XPO1 inhibition in Wilms tumors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3580-3580
Author(s):  
Michael Vincent Ortiz ◽  
Armaan Siddiquee ◽  
Daoqi You ◽  
Prabhjot Singh Mundi ◽  
Lianna Marks ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Line ◽  
Nuclear Export ◽  
Wilms Tumor ◽  
Therapeutic Option ◽  
Tumor Cell Line ◽  
In Vivo Models ◽  
Favorable Histology ◽  
Rhabdoid Tumors ◽  
1Q Gain

3580 Background: XPO1 is a nuclear export protein that selectively transports tumor and growth regulatory proteins out of the nucleus, thereby effectively inhibiting their function. We previously utilized the Virtual Inference of Protein-activity by Enriched Regulon analysis (VIPER) algorithm to discover that malignant rhabdoid tumors were dependent upon XPO1 inhibition and then evaluated a preclinical cohort using selinexor (KPT-330), the first-in-class selective inhibitor of nuclear export, to demonstrate that XPO1 inhibition was sufficient to cause cell cycle arrest, apoptosis, and disease control in multiple cell line and patient derived xenograft (PDXs) models. Our subsequent analysis revealed that the most common childhood kidney tumor, Wilms tumor, has even high higher inferred activity of XPO1 than rhabdoid tumors leading to our hypothesis that XPO1 inhibition is an effective therapeutic strategy to treat Wilms tumors. Methods: A panel of 9 Wilms tumor cell lines and 3 Wilms tumor PDXs were genomically characterized and tested to evaluate the pre-clinical efficacy of XPO1 inhibition in Wilms tumors. Results: Proliferation rate, increased XPO1 protein expression, and loss of function mutations in TP53 correlated with in vitro Wilms tumor cell line sensitivity to selinexor. Evaluation of co-segregation of all single nucleotide variant changes using with inferred activity of XPO1 on VIPER in all TGCA tumors demonstrates a strong association with TP53 alterations. XPO1 inhibition was effective in all Wilms tumor models tested, most significantly in MSKREN-57196, a favorable histology Wilms tumor PDX with somatic 1q gain as well as WTX and MYCN mutations, as well as in MSKREN-31827, a diffusely anaplastic TP53 mutant Wilms tumor PDX. Eltanexor (KPT-8602) is an XPO1 inhibitor with decreased CNS penetration and an improved toxicity profile; this drug was tested in these in vivo models and found to be at least as effective as selinexor. Conclusions: Somatic 1q gain in favorable histology Wilms tumors and TP53 mutations in diffusely anaplastic Wilms tumors have a particularly poor prognosis in the relapsed setting. Our study demonstrates that XPO1 inhibition may provide a rational therapeutic option to treat such high-risk Wilms tumors. Future clinical trials evaluating XPO1 inhibitors should evaluate its efficacy in children with relapsed Wilms tumors.

Characterization of 17.94, a novel anaplastic Wilms' tumor cell line

2012 ◽  
Vol 205 (6) ◽  
pp. 319-326 ◽  
Author(s):  
Keith W. Brown ◽  
Adrian Charles ◽  
Anthony Dallosso ◽  
Gillian White ◽  
Jessica Charlet ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Line ◽  
Wilms Tumor ◽  
Tumor Cell Line

scholarly journals Establishment of a Conditionally Immortalized Wilms Tumor Cell Line with a Homozygous WT1 Deletion within a Heterozygous 11p13 Deletion and UPD Limited to 11p15

PLoS ONE ◽  
2016 ◽  
Vol 11 (5) ◽  
pp. e0155561 ◽  
Author(s):  
Artur Brandt ◽  
Katharina Löhers ◽  
Manfred Beier ◽  
Barbara Leube ◽  
Carmen de Torres ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Line ◽  
Wilms Tumor ◽  
Tumor Cell Line

Lateral Gene Transfer Contributing to Leukemogenesis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1235-1235
Author(s):  
Joo Hyun Lee ◽  
Cynthia R. Giver ◽  
Sravanti Rangaraju ◽  
Edmund K Waller
Keyword(s):  
Bone Marrow ◽  
Gene Transfer ◽  
Tumor Cell ◽  
Cell Line ◽  
Tumor Cell Line ◽  
Hematopoietic Stem ◽  
Precursor Frequency ◽  
Marrow Cells

Abstract The uncontrolled proliferation of genetically mutated cells is the commonly understood mechanism for cancer growth and invasion, with accumulation of new mutations in daughter cells leading to clonal diversity of cancer derived from a single founding event. The genetic alterations are passed to new generations by cell division and vertical gene transfer. Viral transmission of oncogenes represents a known mechanism of lateral gene transfer in cancer initiation. Some experimental systems have also suggested that circulating DNA or micro-vesicles may contribute to lateral oncogene transfer in tumorigenesis. We hypothesized that interactions between leukemic cells and adjacent normal hematopoietic stem or progenitor cells may provide an alternative mechanism for the accumulation of mutated genes and the multiplicity of distinct clones in leukemia. To test this hypothesis, we performed experiments to determine whether tumorigenic properties could be transferred from a tumor cell line to normal mouse bone marrow cells using both in vivo and in vitro and systems. B6-GFP+ mice were injected i.v. with 200,000 C1498-Luc cells (a B6-derived NKT-cell-like mouse tumor cell line expressing luciferase and DSRed). Bioluminescent imaging was used to monitor the progression of tumor cell growth in recipients. At 1 month after tumor-cell inoculation, marrow from these mice was harvested and FACS-sorted for GFP+ cells (to eliminate C1498 cells), and then cultured on irradiated stromal cell layers in 96-well plates in a limiting dilution analysis for Poisson analysis of GFP+ clonogenic precursor frequency on day 9. On day 10, cells were harvested from culture and GFP+ cells resorted onto fresh stromal layers for second and third determinations of GFP+ clonogenic precursor frequency on days 15 and 18. As shown in Figure 1, the frequency of clonogenic precursors increased with each successive determination for marrow from C1498-injected mice, while control cultures from non-injected mice showed no increase in precursor frequency, suggesting that exposure to C1498 cells conferred a growth advantage to the marrow cells in the tumor-cell injected mice. Similar results were obtained using an in vitro system of co-culture using C1498 cells and GFP+ bone marrow cells, followed by serial rounds of GFP+ sorting and Poisson analysis, showing increases in clonogenic frequency over 5 successive sorts and re-cultures over a 2-month period, while control cultures showed decreased clonogenic frequencies over the course of the experiment. To confirm these observations in vivo, B6-GFP mice were injected with C1498-Luc and marrow was harvested after a month and sorted for GFP+ cells. The sorted marrow was transplanted into 11Gy-irradiated (FVB x B6albino)F1 recipients (5 x 106 cells per recipient, n=5). Control recipients were irradiated and transplanted with GFP+ marrow from non-injected donors. All recipients developed full hematopoietic engraftment with GFP+ cells. At 6 months post-transplant, a tumor was observed near the left shoulder of one of the recipients of C1498-exposed GFP+ marrow. Figure 2 shows IVIS GFP imaging of this mouse with the GFP+ tumor along with control animals. The tumor was not positive for luciferase expression. The mouse was sacrificed and the tumor excised and a portion was dissociated for flow cytometric analysis and culturing (with other segments reserved for subsequent histological and genetic analysis). Both GFP+ and non-GFP cells were found in the dissociated tumor cell suspension. The GFP+ cells were hematopoietic in origin (CD45+) and exhibited a mixed phenotype containing markers expressed on C1498 (DX5+) and myeloid lineage cells (CD11b+) as well as Sca-1, a stem cell marker. Cultures of the GFP+ tumor yielded a population of GFP+ mononuclear cells. These data are consistent with a model in which growth-promoting or transforming genes from cancer cells become incorporated within a healthy hematopoietic stem or progenitor cell, which contributes to the genetic diversity of the cancer through the initiation a new transformed clone. Genetic analysis with deep sequencing will compare the DNA sequences between the parental C1498 cell line, sorted populations of clonogenic GFP+ cells obtained from the in vitro and in vivo experiments, and the GFP+ tumor cells to confirm the transformation of healthy bone marrow hematopoietic stem cells with genetic sequences derived from the C1498 cells. Disclosures No relevant conflicts of interest to declare.

Melatonin inhibits telomerase activity in the MCF-7 tumor cell line both in vivo and in vitro

2003 ◽  
Vol 35 (3) ◽  
pp. 204-211 ◽  
Author(s):  
Mercedes M. Leon-Blanco ◽  
Juan M. Guerrero ◽  
Russel J. Reiter ◽  
Juan R. Calvo ◽  
David Pozo
Keyword(s):  
Tumor Cell ◽  
Cell Line ◽  
Tumor Cell Line ◽  
Telomerase Activity ◽  
Mcf 7

Suppression of the tumorigenic phenotype of a rat liver epithelial tumor cell line by the p11.2–p12 region of human chromosome 11

1995 ◽  
Vol 13 (4) ◽  
pp. 220-232 ◽  
Author(s):  
William B. Coleman ◽  
Karen D. McCullough ◽  
Gwyn L. Esch ◽  
Chris J. Civalier ◽  
Elizabeth Livanos ◽  
...  
Keyword(s):  
Human Chromosome ◽  
Tumor Cell ◽  
Cell Line ◽  
Rat Liver ◽  
Tumor Cell Line ◽  
Chromosome 11 ◽  
Epithelial Tumor ◽  
Epithelial Tumor Cell

Sensitive Tumor Cell Line for Annonaceous Acetogenins and High Therapeutic Efficacy at a Low Dose for Choriocarcinoma Therapy

2021 ◽  
Vol 17 (10) ◽  
pp. 2062-2070
Author(s):  
Hui Ao ◽  
Hao-Wen Li ◽  
Li-Kang Lu ◽  
Jing-Xin Fu ◽  
Mei-Hua Han ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Line ◽  
Low Dose ◽  
Drug Loading ◽  
Lethal Dose ◽  
Tumor Cell Line ◽  
A431 Cells ◽  
Annonaceous Acetogenins ◽  
New Type

Annonaceous acetogenins (ACGs) have attracted much attention because of excellent antitumor activity. However, the lack of selectivity and the accompanying serious toxicity have eventually prevented ACGs from entering clinical application. To decrease the side effects of ACGs, the cytotoxicity of ACGs on 10 types of tumor cell lines was investigated by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) test to identify one that was very sensitive to ACGs. Meanwhile, ACGs nanoparticles (ACGs-NPs) were prepared using poloxamer 188 (P188) as an excipient so as to solve the problem of poor solubility and the in vivo delivery of ACGs. ACG-NPs were 163.9±2.5 nm in diameter, negatively charged, and spherical with a high drug loading content (DLC) of 44.9±1.2%. MTS assays demonstrated that ACGs had strong cytotoxicity against JEG-3, HeLa, SiHa, MCF-7, A375, A2058, A875, U-118MG, LN- 229, and A431 cells, among which JEG-3 cell line was extremely sensitive to ACGs with a 50% inhibitory concentration (IC50) value of 0.26 ng/mL, a very encouraging discovery. ACGs-NPs demonstrated very good dose-dependent antitumor efficacy in a broad range of 45?1200 μg/kg on JEG-3 tumor-bearing mice. At a very low dose (1200 μg/kg), ACGs-NPs achieved a high tumor inhibition rate (TIR) of 77.6% through oral administration, displaying a significant advantage over paclitaxel (PTX) injections that are currently used as first-line anti-choriocarcinoma drugs. In the acute toxicity study, the half lethal dose (LD50) of ACGs-NPs was 135.5 mg/kg, which was over 100 times as of the effective antitumor dose, indicating good safety of ACGs-NPs. ACGs-NPs show promise as a new type of and potent anti-choriocarcinoma drug in the future.

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