A comparative study of eight cell lines derived from human testicular teratocarcinoma

Andrews, Peter W.; Bronson, David L.; Benham, Frances; Strickland, Sidney; Knowles, Barbara B.

doi:10.1002/ijc.2910260304

Cited by 198 publications

(98 citation statements)

References 51 publications

(54 reference statements)

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“…Shef5 was derived at the University of Sheffield and became adapted as described in [8]. NTERA2 cl.D1, 1777Nrpmet, 2102Ep, 1156QE, and TERA-1 were derived from testicular teratocarcinomas [18][19][20][21][22], while human embryonal carcinoma cell line (NCCIT) was derived from an extragonadal germ cell tumor [23]. HCT116 is from American Type Culture Collection (Manassas, VA, www.atcc.org).…”

Section: Cell Linesmentioning

confidence: 99%

Human Embryonic Stem Cells Fail to Activate CHK1 and Commit to Apoptosis in Response to DNA Replication Stress

et al. 2012

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Pluripotent cells of the early embryo, to which embryonic stem cells (ESCs) correspond, give rise to all the somatic cells of the developing fetus. Any defects that occur in their genome or epigenome would have devastating consequences. Genetic and epigenetic change in human ESCs appear to be an inevitable consequence of long-term culture, driven by selection of variant cells that have a higher propensity for self-renewal rather than either differentiation or death. Mechanisms underlying the potentially separate events of mutation and subsequent selection of variants are poorly understood. Here, we show that human ESCs and their malignant counterpart, embryonal carcinoma (EC) cells, both fail to activate critical S-phase checkpoints when exposed to DNA replication inhibitors and commit to apoptosis instead. Human ESCs and EC cells also fail to form replication protein A, cH2AX, or RAD51 foci or load topoisomerase (DNA) II binding protein 1 onto chromatin in response to replication inhibitors. Furthermore, direct measurements of single-stranded DNA (ssDNA) show that these cells fail to generate the ssDNA regions in response to replication stress that are necessary for the activation of checkpoints and the initiation of homologous recombination repair to protect replication fork integrity and restart DNA replication. Taken together, our data suggest that pluripotent cells control genome integrity by the elimination of damaged cells through apoptosis rather than DNA repair, and therefore, mutations or epigenetic modifications resulting in an imbalance in cell death control could lead to genetic instability.

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Section: Cell Linesmentioning

confidence: 99%

Human Embryonic Stem Cells Fail to Activate CHK1 and Commit to Apoptosis in Response to DNA Replication Stress

et al. 2012

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“…The study of human NSs is facilitated by the existence of cell lines representing most non-seminomatous cell types (Pattillo et al, 1971;Fogh and Trempe, 1975;Andrews et al, 1980;Oosterhuis et al, 1985;Casper et al, 1987;Pera et al, 1987;Damjanov et al, 1993; Keitz et al, 1995). Experiments can be performed using cell lines of pluripotent EC cells, which can be induced to differentiate by exposure to certain agents (e.g.…”

mentioning

confidence: 99%

Glycolipids of human primary testicular germ cell tumours

Olie

Fenderson²,

Daley³

et al. 1996

Br J Cancer

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Summary The glycolipid content of human non-seminomatous germ cell tumour cell lines correlates with their differentiation lineage. To analyse whether this reflects the situation in primary tumours, we studied five embryonal carcinomas, five yolk sac tumours and nine (mixed) non-seminomas, using thin-layer chromatography and carbohydrate immunostaining. We also analysed the glycolipid content of 19 seminomas to reveal their relationship with non-seminomas. Lactosylceramide (CDH) was detected in all embryonal carcinomas, but in fewer than half of the seminomas. Seminomas and embryonal carcinomas contained globoseries glycolipids, including globotriosylceramide (Gb3), globoside (Gb4), galactosyl globoside (Gb5) and sialyl galactosyl globoside (GL7). The lacto-series glycolipid Lex was found in all embryonal carcinomas, but only in one seminoma. Gangliosides GD3 and GT3 were detected in many seminomas, but rarely in embryonal carcinomas. Yolk sac tumours displayed a heterogeneous glycolipid profile. Compared with seminomas and pure embryonal carcinomas, differentiated non-seminomas had reduced levels of globo-series glycolipids, especially Gb3 and Gb5, whereas CDH, Lex, GD3 and GT3 were found in the majority of cases. Thus, the glycolipid content of non-seminoma cell lines reflects the situation in primary tumours. Globo-series glycolipids are similarly expressed in seminomas and embryonal carcinomas. The expression of Gb3 and Gb5 is reduced in non-seminomas upon differentiation. Lex expression in non-seminomas, including embryonal carcinomas, allows discrimination from seminomas. Expression of gangliosides in seminomas might indicate their maturation from ganglioside-negative precursor cells. Reprogramming of these precursors would result in the formation of Lex-expressing embryonal carcinomas.

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“…The synthetic details of compounds 5 to 8 will appear elsewhere. 3 Radiolabeled ( 125 I) Ammonium 2-(2 ¶-Phosphoryloxyphenyl)-6-Iodo-4-(3H)-Quinazolinone ( 125 IQ 2-P ) (8). Phosphate buffer (10 AL, 0.01 mol/L, pH 7.4) and ammonium 2-(2 ¶-phosphoryloxyphenyl)-6-tributylstannyl-4-(3H)-quinazolinone (6; 1 AL of 5 Ag/AL DMSO solution) were placed in a reaction vial coated with 1,3,4,6-tetrachloro-3a,6a-diphenylglycouril (Iodogen, 10 Ag).…”

Section: Methodsmentioning

confidence: 99%

“…After an overnight incubation at 37jC, the medium was removed and the cells were reincubated for up to 24 h with 4 (fluorescence microscope studies, 0.2 -20 Ag/200 AL) or 8 (autoradiography, 100 ACi/200 AL) in medium (pH 7.4). To ascertain the cell-mediated alkaline phosphatase specificity of 127 IQ 2-P (4) hydrolysis, the same medium was added to chambers containing no cells as well as to chambers containing NE cells, known to express alkaline phosphatase on the exterior surface of their plasma membrane (8), and 10 mmol/L levamisole, a specific inhibitor of alkaline phosphatase (15,16). After incubation, the cells were repeatedly washed in PBS and then fixed in ice-cold ethanol.…”

Section: Chemical Studiesmentioning

confidence: 99%

“…Further studies have shown that IQ 2-P(I) (10) is not hydrolyzed by alkaline phosphatase and the injection of 125 IQ 2-P(I) (7) into normal mice leads to the localization of approximately 10% to 15% ID/g in liver and kidneys. 3 On the other hand, IQ 2-P (4) and 125 IQ 2-P (8) are readily hydrolyzed by alkaline phosphatase and their pharmacokinetics in normal mice following i.v. injection show minimal retention in all normal tissues (0.01 -0.4% ID/g at 24 h after injection).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

In silico design, synthesis, and biological evaluation of radioiodinated quinazolinone derivatives for alkaline phosphatase–mediated cancer diagnosis and therapy

Chen

Wang

Kirichian

et al. 2006

Molecular Cancer Therapeutics

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As part of the development of enzyme-mediated cancer imaging and therapy, a novel technology to entrap waterinsoluble radioactive molecules within solid tumors, we show that a water-soluble, radioactive quinazolinone prodrug, ammonium 2-(2 ¶-phosphoryloxyphenyl)-6-[ 125 I]iodo-4-(3H)-quinazolinone ( 125 IQ 2-P ), is hydrolyzed by alkaline phosphatase to a water-insoluble, radiolabeled drug, 2-(2 ¶-hydroxyphenyl)-6-[ 125 I]iodo-4-(3H)-quinazolinone ( 125 IQ 2-OH ). Biodistribution data suggest the existence of two isoforms of the prodrug (IQ 2-P(I) and IQ 2-P ), and this has been confirmed by their synthesis and characterization. Structural differences of the two isoforms have been examined using in silico molecular modeling techniques and docking methods to describe the interaction/binding between the isoforms and human placental alkaline phosphatase (PLAP), a tumor cell, membrane-associated, hydrolytic enzyme whose structure is known by X-ray crystallographic determination. Docking data show that IQ 2-P , but not IQ 2-P(I) , fits the active binding site of PLAP favorably and interacts with the catalytic amino acid Ser 92 , which plays an important role in the hydrolytic process. The binding free energies (#G binding ) of the isoforms to PLAP predict that IQ 2-P will be the better substrate for PLAP. The in vitro incubation of the isoforms with PLAP leads to the rapid hydrolysis of IQ 2-P only and confirms the in silico expectations. Fluorescence microscopy shows that in vitro incubation of IQ 2-P with mouse and human tumor cells causes the extracellular, alkaline phosphatasemediated hydrolysis of the molecule and precipitation of fluorescent crystals of IQ 2-OH . No hydrolysis is seen in the presence of normal mouse and human cells. Furthermore, the intratumoral injection of 125 IQ 2-P into alkaline phosphatase -expressing solid human tumors grown s.c. in nude rats results in efficient hydrolysis of the compound and retention of f70% of the injected radioactivity, whereas similar injection into normal tissues (e.g., muscle) does not produce any measurable hydrolysis (f1%) or retention of radioactivity at the injected site. These studies support the enzyme-mediated cancer imaging and therapy technology and show the potential of such quinazolinone derivatives in the in vivo radiodetection ( 123 I/ 124 I) and therapy ( 131 I) of solid tumors.

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A comparative study of eight cell lines derived from human testicular teratocarcinoma

Cited by 198 publications

References 51 publications

Human Embryonic Stem Cells Fail to Activate CHK1 and Commit to Apoptosis in Response to DNA Replication Stress

Human Embryonic Stem Cells Fail to Activate CHK1 and Commit to Apoptosis in Response to DNA Replication Stress

Glycolipids of human primary testicular germ cell tumours

In silico design, synthesis, and biological evaluation of radioiodinated quinazolinone derivatives for alkaline phosphatase–mediated cancer diagnosis and therapy

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