Published in: Cancer Research 63, 2733-2736, June 1, 2003
http://cancerres.aacrjournals.org/cgi/content/abstract/63/11/2733

"Mouse Embryos Cloned from Brain Tumors".

Leyi Li, Michele C. Connelly, Cynthia Wetmore 1, Tom Curran and James I. Morgan @

Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, Tennessee 38105

1 Present address: Division of Pediatric Hematology/Oncology, Mayo Clinic and Cancer Center, Rochester, MN 55905.

@ To whom requests for reprints should be addressed, at Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, 332 North Lauderdale, Memphis, Tennessee 38105.
E-mail:   jim.morgan@stjude.org

The abbreviations used are: GFAP, glial fibrillary acidic protein; ICM, inner cell mass.



Abstract:
Introduction:
Materials and Methods:
Results and Discussion:
   Fig. 1:  Expression of neuronal and glial markers in cells:
   Fig. 2:  Nuclear remodeling and preimplantation development:
   Table 1: Development of embryos from transplanted medulloblastoma nuclei:
   Fig. 3:  Day 7.5 embryo derived from a transplanted medulloblastoma nucleus:
   Fig. 4:  PCR confirmation of the presence of lacZ and neo genes in postimplantation embryos:
Acknowledgments:
Footnotes:
References:
Additional References for Chromatin Reprogramming:
Further Studies of Riboregulators:
PubMed Related References:
Other Links:
Further Information and Feedback:



Abstract:

Cancer cells escape from growth control by accumulating genetic and epigenetic alterations. In rare instances, epigenetic changes alone are oncogenic. Furthermore, agents that modify DNA methylation or chromatin structure can restore a normal phenotype to cells harboring oncogenic mutations. However, it is unclear to what extent epigenetic reprogramming can reverse oncogenesis. Using somatic nuclear transfer, we show that medulloblastomas arising in Ptc1+/- mice can direct preimplantation development. Additionally, blastocysts
derived from medulloblastoma nuclei form postimplantation embryos with typical cell layers. Thus, tumor cells can be epigenetically reprogrammed into normal cell types. This approach could lead to a general strategy for assessing genetic and epigenetic contributions to tumorigenesis.



Introduction:

Cancers arise through the accumulation of genetic mutations (1) and epigenetic modifications (2 , 3) . Although many proto-oncogenes and tumor suppressor genes are widely expressed, the mutation of these genes is associated with cancer of specific organs or cell types (4 , 5) . This suggests that, to some extent, malignant growth depends on epigenetic factors that are governed by the cellular context in which a tumor arises. Teratocarcinomas can arise through purely epigenetic changes and represent an extreme case in which the
transformed phenotype can be abrogated under appropriate conditions (6, 7, 8) . Indeed, in early chimera studies, it was demonstrated that teratocarcinoma cells are able to contribute to the germ line, ultimately giving rise to adult mice (6) . In a frog renal carcinoma model, the transfer of nuclei from tumor cells into oocytes was reported to reverse oncogenesis and to direct development to the tadpole stage (9) . Although this was suggested to occur through epigenetic reprogramming, subsequently it was found that the transforming gene, which was encoded by a Herpesvirus episome (10) , was lost during the nuclear transfer procedure (11) . Here, we investigate the possibility of whether a tumor cell nucleus, in which transformation is caused by somatic mutation, can be epigenetically reprogrammed into normal tissues.

Materials and Methods:

Tumor Cell Culture.
Medulloblastomas were collected from Ptc1 heterozygous mice and minced, and dissociated cells were cultured on poly-D-lysine in DMEM supplemented with 2 mM L-glutamine and 10% fetal bovine serum at 37°C in 10% CO2 in air. Subsequently, cells were passaged in the same medium after detachment with trypsin. For
immunohistochemistry, cells were fixed in 4% paraformaldehyde and were processed according to standard techniques with antibodies to medium and heavy chains of neurofilament (1:200; Zymed Laboratories, San Francisco, CA), synaptophysin (1:100; Zymed Laboratories), neuron-specific enolase (1:200; DAKO Corporation, Carpinteria, CA), or GFAP (1:200; DAKO Corporation). Bound antibodies were detected using appropriate secondary antibodies conjugated to Texas Red-X or Oregon Green 500 (each, 1:500; Molecular Probes, Eugene, OR).

Nuclear Transfer.
Female B6D2F1 mice were superovulated, and oocytes were harvested according to standard techniques (12) . An enucleation pipette attached to a PiezoDrill (Burleigh, NY) was used to cut through the zona pellucida, and the metaphase II spindle was aspirated (removal was confirmed by Hoechst 33258 staining). Subsequent transfer of medulloblastoma nuclei and embryo culture was as described by Wakayama et al. (13) .

Genotyping.
DNA was isolated from embryos, deciduas, and surrounding uterine tissue by standard techniques. Genotyping was performed using PCR for lacZ and neo genes contained within the Ptc1 targeting vector (14) . One set of primers (5'-GCTGGGATCCGCCATTGTCAGACATG-3' and 5'-GCTGGAATTCCGCCGATACTGAC-3') amplified a 295-bp fragment of the lacZ gene whereas the other set amplified a 520-bp fragment of the neo gene. PCR for lacZ was run for 30 cycles with denaturation at 94°C for 30 s, annealing at 55°C for 30 s, and extension at 72°C for 30 s. PCR products were analyzed on a 1.0% agarose gel.

Results and Discussion:

Medulloblastoma, the most common malignant pediatric brain tumor, originates from granule neuron precursors in the developing cerebellum (15) . Ptc1, a tumor suppressor gene, has been implicated in familial and sporadic medulloblastoma in humans (16) . Furthermore, ~14% of Ptc1 heterozygous mice develop medulloblastoma (14 , 17) , but the incidence increases to ~95% in the absence of p53 (18) , which suggests that additional mutations contribute to tumorigenesis. We cultured cells from tumors arising spontaneously in two female Ptc1+/- mice at 3 months (SJMM4) and 7 months (SJMM2) of age, respectively. These tumor cells were chosen for investigation, because their karyotypes were grossly normal during early passages, an important criterion for nuclear transfer. Transplantation of SJMM2 and SJMM4 directly into the flank of immunodeficient mice resulted in tumor formation; and SJMM2, at passage 10, formed colonies in soft agar. Although the levels of Ptc1 were low in the majority of cultures examined, SJMM2 expressed very high steady-state levels of protein.

Simultaneous expression of both neural and glial markers is a feature characteristic of medulloblastoma (15) . After passage three, the great majority of cultured cells coexpressed glial and neuronal markers, including GFAP, neurofilament (Fig. 1) , neuron-specific enolase, and synaptophysin. Although the tumors from which the cell cultures were derived could be grown in allografts and formed colonies in agar at passage 12 and 13 (SJMM2), it is formally possible that some of the cultured cells lost their tumorigenic capacity during monolayer culture. The cells were used for nuclear transfer between passage 5 and 12 to completely exclude contamination by non-tumor-derived neuronal cells, which do not survive passage in culture, and to minimize the accumulation of mutations arising in culture. To assess the reproducibility of phenotypes, multiple batches of cells from each passage were used. Normal mouse spleen cells (from B6D2F1 mice) were used as a source of control nuclei to compare the efficiency of developmental progression after nuclear transfer.

Fig. 1. Expression of neuronal and glial markers in cells cultured from the SJMM2 medulloblastoma. Confocal images of:
A, neurofilament medium and heavy chains;
B, GFAP;
C, merge, neurofilament and GFAP. Similar colocalization was observed in cells from the SJMM4 medulloblastoma and with antibodies to neuron-specific enolase and synaptophysin. Scale bar, 20 µm.


The initial stage of preimplantation development involves nuclear remodeling and the formation of pronuclei (12) . The order and timing of cell division and differentiation during preimplantation development is geared strictly to a zygotic clock (19) . Therefore, if the transferred medulloblastoma nuclei do not cease uncontrolled cell proliferation, they would not be able to direct preimplantation development. After transfer (n = 1669), ~75% of medulloblastoma nuclei increased dramatically in size (Fig. 2, A–C) and subsequently formed pronuclei with one or more pronucleolus within 24 h (Fig. 2C ; Table 1 ). For comparison, ~84% of spleen cell-derived nuclei (n = 212) progressed to the same stage (Table 1) . 72 h after activation, ~27% of the transferred oocytes had progressed to the 2-cell stage (Fig. 2D ; Table 1 ), 10% to the 4/8-cell stage (Fig. 2, E and F ; Table 1 ), and 10% had developed into morulae or blastocysts (Fig. 2, G and H ; Table 1 ). No substantial differences in cloning efficiency were observed between the two tumor cell cultures (Table 1) or among cells from different passage numbers. The equivalent results for spleen cell-derived nuclei were 35, 17, and 29%, respectively (Table 1) . This apparent enhanced efficiency seems to be related to the increased number of cloned embryos
that die soon after transfer (Table 1) , possibly as a result of the more stringent methods required to remove nuclei from tumor cells. Noticeably, although medulloblastoma-derived embryos died, none exhibited uncontrolled proliferation resembling tumorigenesis.

Fig. 2. Nuclear remodeling and preimplantation development of transplanted medulloblastoma nuclei.

A, SJMM2 medulloblastoma cells in culture.
B, enucleated oocytes immediately after the injection of medulloblastoma nuclei (arrowheads).
C, activated oocytes with pronuclei formed from medulloblastoma nuclei; arrows, pronuclei containing prominent pronucleoli.
D, 2-cell cloned embryos.
E, 4-cell cloned embryos.
F, 8-cell cloned embryos.
G, pre- and postcompaction cloned morulae.
H, cloned blastocyst.
I, hatching cloned blastocyst.
J, ICM explant derived from a cloned blastocyst. All of the panels are at same magnification. Scale bar, 20 µm.




                   Table 1. Development of embryos from transplanted medulloblastoma nuclei in vitro.

 
Donor nuclei Oocytes injected h postactivation

24 h 72 h

Pronucleus Dead cells 2-cell 4/8-cell Morula and blastocyst

Tumor SJMM2 1196 918 (76.8%) 670 (56.0%) 307 (25.7%) 115 (9.6%) 104 (8.7%)
Tumor SJMM4 473 336 (71.0%) 231 (48.8%) 137 (29.0%) 45 (9.5%) 60 (12.7%)
Spleen cell 212 178 (84.0%) 40 (18.9%) 75 (35.4%) 35 (16.5%) 62 (29.2%)

Blastocysts derived from medulloblastoma were morphologically indistinguishable from those derived from spleen cell nuclei: they formed blastocyst cavities surrounded by trophoblast cells, and ICMs could be identified (Fig. 2H) . Blastocyst cavities gradually accumulated fluid and expanded, and, when maintained for longer periods, blastocysts hatched from the zona pellucida (Fig. 2I) . Again, there was no evidence of the uncontrolled cell growth characteristic of cultured tumor cells.

We cultivated medulloblastoma-derived blastocysts for extended periods under the same conditions that were used to propagate the parental medulloblastoma cells. After 2 days in culture, blastocysts hatched from the zona pellucida, trophoblast cells spread onto the culture dishes, and an ICM formed in the center of the expanded trophoblast regions (Fig. 2J) . The ICM cells subsequently differentiated, and, in marked contrast to medulloblastoma cells, both trophoblasts and ICM cells ceased proliferation. Thus, reprogrammed medulloblastoma nuclei lost the capacity for extensive proliferation characteristic of tumor cells in vitro.

Postimplantation development occurs under conditions of even more rigid and complex control than preimplantation development (12) . To establish whether medulloblastoma-derived embryos could direct later stages of development, we transferred cloned blastocysts into pseudo-pregnant females. Recipients were sacrificed at various stages of pregnancy, and decidua were fixed and sectioned or were processed for DNA analysis. Although evidence of implantation was observed even at late stages of gestation, no viable embryos were recovered subsequent to E8.5. Even when maintained well past term, none of the recipients developed tumors (n = 29). However, we were able to identify viable embryos and embryos undergoing resorption at E7.5 and E8.5. At 7.5 days of development, the embryos appeared grossly normal, and they contained embryonic ectoderm, mesoderm, endoderm, ectoplacental cones, chorion, amnion, Reichert’s membrane, yolk sac cavity, and amniotic cavity (Fig. 3) . Later embryos (8.5 days of development) showed more extensive differentiation with cephalic vesicles and neural tube.

Fig. 3. A day 7.5 embryo derived from a transplanted SJMM4 medulloblastoma nucleus stained with H&E.
B, a higher magnification of the boxed area in A to show the three distinguishable germ layers. pla, ectoplacental cone; end, embryonic endoderm; mes, embryonic mesoderm; ect, embryonic ectoderm. Scale bar, 20 µm.


To confirm that the postimplantation embryos originated from transplanted medulloblastoma nuclei, we performed PCR to identify the ß-galactosidase (lacZ) and neomycin resistance (neo) genes present in the targeting vector. A 295-bp amplicon from lacZ and a 520-bp amplicon from Ptc1-neo were detected in the decidua and embryos, although surrounding uterine tissues were negative for both genes (Fig. 4) .


Fig. 4. PCR confirmation of the presence of lacZ and neo genes in postimplantation embryos derived from transplanted medulloblastoma nuclei.
Lane 1, positive control; Lane 6, negative control.
Lanes 2 and 3 contain DNA extracted from implantations No. 1 (E8.5-day embryo derived from SJMM2) and No. 4 (E6.5-day embryo derived from SJMM4), respectively.
Lanes 4 and 5 contain DNA extracted from maternal uterine tissues from recipients for implantations No. 1 and No. 4, respectively.
Arrows, the positions of authentic lacZ, neo, and Ptc1 amplicons.
The endogenous Ptc1 allele serves as DNA loading control.



These results demonstrate that epigenetic reprogramming of medulloblastoma nuclei by somatic nuclear transfer abrogates the tumorigenic phenotype: uncontrolled proliferation is suppressed and normal patterns of differentiation are restored. Although transplanted medulloblastoma nuclei are less efficient than spleen cell-derived nuclei, they, nevertheless, directed all of preimplantation development. Moreover, they gave rise to postimplantation embryos that had undergone tissue differentiation and early stages of organogenesis. Remarkably, no malignancies were observed in any of the recipient mice, and normal proliferation control was observed in cultured blastocysts. Thus, the tumorigenic mutations that underlie medulloblastoma must act within the context of the cerebellar granule cell lineage, and those changes will not necessarily support malignant cell proliferation in the context of other cell lineages. It will now be important to establish whether the medulloblastoma nuclei preferentially produce tumors in the cerebellum using chimeric mouse approaches. This analysis may also reveal whether medulloblastoma-derived nuclei harbor mutations that preclude further embryonic development or the genesis of specific tissue types. The successful reprogramming of medulloblastoma nuclei by somatic nuclear transfer encourages exploration of the utility of anticancer agents that target chromatin and DNA methylation for the treatment of this devastating pediatric cancer.

ACKNOWLEDGMENTS

We thank Karen Forbes, Hiro Kimura, Jennifer Parris, and Nichola Wigle for technical expertise and Drs. Mary Dickinson, Ciaran Faherty, Brigid Hogan, Andy MacMahon, and Teruhiko Wakayama for advice and discussions.

FOOTNOTES

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Supported in part by NIH Cancer Center Support CORE Grant CA21765, the American Lebanese Syrian Associated Charities (ALSAC), and the Pediatric Brain Tumor Foundation of the United States (to C. W.); NIH Grants CA 84139, CA 96832 and NS 36558 (to T. C.); and NIH Grants NS 40361, NS 40749, and ES 10772 (to J. I. M.).

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Additional References for Chromatin Reprogramming:

1. Frenster JH, "Activator RNA Exchange during Interphase Chromatin Reprogramming".

2. Byrne JA, Simonsson S, Western PS, and Gurdon JB, "Nuclei of Adult Mammalian Somatic Cells are Directly Reprogrammed to oct-4 Stem Cell Gene Expression by Amphibian Oocytes", Current Biology, vol 13, no. 14, pp. 1206-1213 (July 15, 2003).

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4. Goldstein L, “Stable Nuclear RNA Returns to Post-Division Nuclei Following Release to Cytoplasm during Mitosis”, Exp. Cell Res. vol. 89,  no. 2, pp. 421-425 (December, 1974).

5. Geiss G, Jin G, Guo J, Bumgarner R, Katze MG, and Sen GC, "A Comprehensive View of Regulation of Gene Expression by Double-Stranded RNA-Mediated Cell Signaling", J. Biol. Chem. vol. 276, pp. 30178-30182 (2001).

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7. Gottesfeld JM,  and Barbas III CF, "RNA as a Transcriptional Activator", Chemistry and Biology, vol 10, no.7, pp. 584-585 (July, 2003).
 


Further Topics in:  Euchromatin,  active DNA, and  RNA  ribo-regulators:

Reviews and Research:

Links to Euchromatin Activator RNA Reviews:
Links to Euchromatin Activator RNA Research:
Links to Ultrastructural Probes of DNase I-Sensitive Sites:
Links to RNA as a Therapeutic Agent:
Links to Hodgkin Lymphoma Immuno-Pathology:
Links to Activated T-Lymphocyte Immunotherapy:
Links to Medical Systems Biology:

"Ultrastructural Probes of Active DNA Sites, and the RNA Activators of DNA".
 



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131:  Kazanov D, Shapira I, Pick M, Kolker O, Liberman E, Deutsch V, Strier L,
Dvory-Sobol H, Kunik T, Arber N.
 Oncogenic transformation of normal enterocytes by overexpression of cyclin D1.
Dig Dis Sci. 2003 Jul;48(7):1251-61.
PMID: 12870780 [PubMed - indexed for MEDLINE]

132:  Penn A.
 Molecular alterations critical to the development of arteriosclerotic plaques:
a role for environmental agents.
Environ Health Perspect. 1989 May;81:189-92. Review.
PMID: 2667979 [PubMed - indexed for MEDLINE]

133:  Torchia EC, Jaishankar S, Baker SJ.
 Ewing tumor fusion proteins block the differentiation of pluripotent marrow
stromal cells.
Cancer Res. 2003 Jul 1;63(13):3464-8.
PMID: 12839926 [PubMed - indexed for MEDLINE]

134:  Katz MG, Mansfield J, Gras L, Trounson AO, Cram DS.
 Diagnosis of trisomy 21 in preimplantation embryos by single-cell DNA
fingerprinting.
Reprod Biomed Online. 2002 Jan-Feb;4(1):43-50.
PMID: 12470352 [PubMed - indexed for MEDLINE]

135:  Kominami T, Takata H.
 Process of pigment cell specification in the sand dollar, Scaphechinus
mirabilis.
Dev Growth Differ. 2002 Apr;44(2):113-25.
PMID: 11940098 [PubMed - indexed for MEDLINE]

136:  Okazaki IM, Hiai H, Kakazu N, Yamada S, Muramatsu M, Kinoshita K, Honjo T.

 Constitutive expression of AID leads to tumorigenesis.
J Exp Med. 2003 May 5;197(9):1173-81.
PMID: 12732658 [PubMed - indexed for MEDLINE]

137:  Vincent S, Mirshari M, Nicolas C, Adenis C, Dhellemmes P, Soto Ares G,
Maurage CA, Baranzelli MC, Giangaspero F, Ruchoux MM.
 Large-cell medulloblastoma with arrestin-like protein expression.
Clin Neuropathol. 2003 Jan-Feb;22(1):1-9.
PMID: 12617187 [PubMed - indexed for MEDLINE]

138:  Chott A, Guenther P, Huebner A, Selzer E, Parwaresch RM, Horny HP, Valent
P.
 Morphologic and immunophenotypic properties of neoplastic cells in a case of
mast cell sarcoma.
Am J Surg Pathol. 2003 Jul;27(7):1013-9.
PMID: 12826896 [PubMed - indexed for MEDLINE]

139:  Perry A.
 Medulloblastomas with favorable versus unfavorable histology: how many small
blue cell tumor types are there in the brain?
Adv Anat Pathol. 2002 Nov;9(6):345-50. Review.
PMID: 12409643 [PubMed - indexed for MEDLINE]

140:  Reik W, Santos F, Dean W.
 Mammalian epigenomics: reprogramming the genome for development and therapy.
Theriogenology. 2003 Jan 1;59(1):21-32. Review.
PMID: 12499015 [PubMed - indexed for MEDLINE]

141:  Kurosaka S, Imai H.
 [Cell-cycle coordination and nuclear reprogramming in nuclear transfer embryos]
Tanpakushitsu Kakusan Koso. 2002 Oct;47(13):1804-9. Review. Japanese. No
abstract available.
PMID: 12385101 [PubMed - indexed for MEDLINE]

142:  DiBerardino MA, Mizell M, Hoffner NJ, Friesendorf DG.
 Frog larvae cloned from nuclei of pronephric adenocarcinoma.
Differentiation. 1983;23(3):213-7. No abstract available.
PMID: 6602076 [PubMed - indexed for MEDLINE]

143:  Osada T, Kusakabe H, Akutsu H, Yagi T, Yanagimachi R.
 Adult murine neurons: their chromatin and chromosome changes and failure to
support embryonic development as revealed by nuclear transfer.
Cytogenet Genome Res. 2002;97(1-2):7-12.
PMID: 12438731 [PubMed - indexed for MEDLINE]

144:  Mann MR, Bartolomei MS.
 Epigenetic reprogramming in the mammalian embryo: struggle of the clones.
Genome Biol. 2002;3(2):REVIEWS1003. Epub 2002 Jan 29. Review.
PMID: 11864375 [PubMed - indexed for MEDLINE]

145:  Grippo PJ, Nowlin PS, Demeure MJ, Longnecker DS, Sandgren EP.
 Preinvasive pancreatic neoplasia of ductal phenotype induced by acinar cell
targeting of mutant Kras in transgenic mice.
Cancer Res. 2003 May 1;63(9):2016-9.
PMID: 12727811 [PubMed - indexed for MEDLINE]

146:  Waterland RA, Jirtle RL.
 Transposable elements: targets for early nutritional effects on epigenetic gene
regulation.
Mol Cell Biol. 2003 Aug;23(15):5293-300.
PMID: 12861015 [PubMed - indexed for MEDLINE]

147:  Wechsler-Reya RJ.
 Analysis of gene expression in the normal and malignant cerebellum.
Recent Prog Horm Res. 2003;58:227-48. Review.
PMID: 12795421 [PubMed - indexed for MEDLINE]

148:  Rakyan VK, Chong S, Champ ME, Cuthbert PC, Morgan HD, Luu KV, Whitelaw E.
 Transgenerational inheritance of epigenetic states at the murine Axin(Fu)
allele occurs after maternal and paternal transmission.
Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2538-43. Epub 2003 Feb 24.
PMID: 12601169 [PubMed - indexed for MEDLINE]

149:  Simons JW.
 Genetic, epigenetic, dysgenetic, and non-genetic mechanisms in tumorigenesis.
Crit Rev Oncog. 1995;6(3-6):261-73. Review.
PMID: 9012586 [PubMed - indexed for MEDLINE]

150:  Baron V, De Gregorio G, Krones-Herzig A, Virolle T, Calogero A, Urcis R,
Mercola D.
 Inhibition of Egr-1 expression reverses transformation of prostate cancer cells
in vitro and in vivo.
Oncogene. 2003 Jul 3;22(27):4194-204.
PMID: 12833142 [PubMed - indexed for MEDLINE]

151:  Kansal AR, Torquato S, Chiocca EA, Deisboeck TS.
 Emergence of a subpopulation in a computational model of tumor growth.
J Theor Biol. 2000 Dec 7;207(3):431-41.
PMID: 11082311 [PubMed - indexed for MEDLINE]

152:  Kuhholzer-Cabot B, Brem G.
 Aging of animals produced by somatic cell nuclear transfer.
Exp Gerontol. 2002 Dec;37(12):1317-23. Review.
PMID: 12559401 [PubMed - indexed for MEDLINE]

153:  Siu IM, Lal A, Blankenship JR, Aldosari N, Riggins GJ.
 c-Myc promoter activation in medulloblastoma.
Cancer Res. 2003 Aug 15;63(16):4773-6.
PMID: 12941792 [PubMed - indexed for MEDLINE]

154:  Hansis C, Edwards RG.
 Cell differentiation in the preimplantation human embryo.
Reprod Biomed Online. 2003 Mar;6(2):215-20. Review.
PMID: 12676002 [PubMed - indexed for MEDLINE]

155:  Rubin H.
 The sources of heritable variation in cellular growth capacities.
Cancer Metastasis Rev. 1987;6(1):85-9. Review.
PMID: 3297372 [PubMed - indexed for MEDLINE]

156:  Fung KM, Rorke LB, Giasson B, Lee VM, Trojanowski JQ.
 Expression of alpha-, beta-, and gamma-synuclein in glial tumors and
medulloblastomas.
Acta Neuropathol (Berl). 2003 Aug;106(2):167-75. Epub 2003 May 28.
PMID: 12783249 [PubMed - indexed for MEDLINE]

157:  Fan Y, Nikitina T, Morin-Kensicki EM, Zhao J, Magnuson TR, Woodcock CL,
Skoultchi AI.
 H1 linker histones are essential for mouse development and affect nucleosome
spacing in vivo.
Mol Cell Biol. 2003 Jul;23(13):4559-72.
PMID: 12808097 [PubMed - indexed for MEDLINE]

158:  Paul S, Regulier E.
 [Molecular basis of oncogenesis]
Ann Biol Clin (Paris). 2001 Jul-Aug;59(4):393-402. Review. French.
PMID: 11470634 [PubMed - indexed for MEDLINE]

159:  Khalili K, Del Valle L, Otte J, Weaver M, Gordon J.
 Human neurotropic polyomavirus, JCV, and its role in carcinogenesis.
Oncogene. 2003 Aug 11;22(33):5181-91. Review.
PMID: 12910255 [PubMed - indexed for MEDLINE]

160:  Krtolica A, Campisi J.
 Integrating epithelial cancer, aging stroma and cellular senescence.
Adv Gerontol. 2003;11:109-16. Review.
PMID: 12820530 [PubMed - indexed for MEDLINE]

161:  Grummt I, Pikaard CS.
 Epigenetic silencing of RNA polymerase I transcription.
Nat Rev Mol Cell Biol. 2003 Aug;4(8):641-9. Review.
PMID: 12923526 [PubMed - indexed for MEDLINE]

162:  Jeanisch R, Eggan K, Humpherys D, Rideout W, Hochedlinger K.
 Nuclear cloning, stem cells, and genomic reprogramming.
Cloning Stem Cells. 2002;4(4):389-96. Review.
PMID: 12630413 [PubMed - indexed for MEDLINE]

163:  Khalili K, Del Valle L, Wang JY, Darbinian N, Lassak A, Safak M, Reiss K.
 T-antigen of human polyomavirus JC cooperates withIGF-IR signaling system in
cerebellar tumors of the childhood-medulloblastomas.
Anticancer Res. 2003 May-Jun;23(3A):2035-41. Review.
PMID: 12894576 [PubMed - indexed for MEDLINE]

164:  D'Amico M, Wu K, Di Vizio D, Reutens AT, Stahl M, Fu M, Albanese C,
Russell RG, Muller WJ, White M, Negassa A, Lee HW, DePinho RA, Pestell RG.
 The role of Ink4a/Arf in ErbB2 mammary gland tumorigenesis.
Cancer Res. 2003 Jun 15;63(12):3395-402.
PMID: 12810676 [PubMed - indexed for MEDLINE]

165:  Wilhelmsson U, Eliasson C, Bjerkvig R, Pekny M.
 Loss of GFAP expression in high-grade astrocytomas does not contribute to tumor
development or progression.
Oncogene. 2003 May 29;22(22):3407-11.
PMID: 12776191 [PubMed - indexed for MEDLINE]

166:  Dragani TA.
 10 years of mouse cancer modifier loci: human relevance.
Cancer Res. 2003 Jun 15;63(12):3011-8. Review.
PMID: 12810618 [PubMed - indexed for MEDLINE]

167:  Tognon M, Corallini A, Martini F, Negrini M, Barbanti-Brodano G.
 Oncogenic transformation by BK virus and association with human tumors.
Oncogene. 2003 Aug 11;22(33):5192-200. Review.
PMID: 12910256 [PubMed - indexed for MEDLINE]

168:  Chopra A, Brown KM, Rood BR, Packer RJ, MacDonald TJ.
 The use of gene expression analysis to gain insights into signaling mechanisms
of metastatic medulloblastoma.
Pediatr Neurosurg. 2003 Jul;39(2):68-74.
PMID: 12845196 [PubMed - indexed for MEDLINE]

169:  Bignold LP.
 Pathogenetic mechanisms of nuclear pleomorphism of tumour cells based on the
mutator phenotype theory of carcinogenesis.
Histol Histopathol. 2003 Apr;18(2):657-64. Review.
PMID: 12647815 [PubMed - indexed for MEDLINE]

170:  Hair A, Razin SV, Vasetskii ES.
 [Changes in chromatin organization during early development and carcinogenesis]
Ontogenez. 2002 Mar-Apr;33(2):85-9. Review. Russian.
PMID: 11969077 [PubMed - indexed for MEDLINE]

171:  Bielanska M, Tan SL, Ao A.
 Chromosomal information derived from single blastomeres isolated from
cleavage-stage embryos and cultured in vitro.
Fertil Steril. 2003 Jun;79(6):1304-11.
PMID: 12798875 [PubMed - indexed for MEDLINE]

172:  Eberhart CG, Burger PC.
 Anaplasia and grading in medulloblastomas.
Brain Pathol. 2003 Jul;13(3):376-85. Review.
PMID: 12946027 [PubMed - indexed for MEDLINE]

173:  Lin SY, Elledge SJ.
 Multiple tumor suppressor pathways negatively regulate telomerase.
Cell. 2003 Jun 27;113(7):881-9.
PMID: 12837246 [PubMed - indexed for MEDLINE]

174:  Wilmut I, Paterson L.
 Somatic cell nuclear transfer.
Oncol Res. 2003;13(6-10):303-7. Review.
PMID: 12725518 [PubMed - indexed for MEDLINE]

175:  Matzke MA, Mette MF, Kanno T, Matzke AJ.
 Does the intrinsic instability of aneuploid genomes have a causal role in
cancer?
Trends Genet. 2003 May;19(5):253-6. Review.
PMID: 12711216 [PubMed - indexed for MEDLINE]

176:  Lanzi C, Cassinelli G, Cuccuru G, Zaffaroni N, Supino R, Vignati S, Zanchi
C, Yamamoto M, Zunino F.
 Inactivation of Ret/Ptc1 oncoprotein and inhibition of papillary thyroid
carcinoma cell proliferation by indolinone RPI-1.
Cell Mol Life Sci. 2003 Jul;60(7):1449-59.
PMID: 12943231 [PubMed - indexed for MEDLINE]

177:  Tanaka C, Uzawa K, Shibahara T, Yokoe H, Noma H, Tanzawa H.
 Expression of an inhibitor of apoptosis, survivin, in oral carcinogenesis.
J Dent Res. 2003 Aug;82(8):607-11.
PMID: 12885844 [PubMed - indexed for MEDLINE]

178:  Chen CC, Tseng TH, Hsu JD, Wang CJ.
 Tumor-promoting effect of GGN-MRP extract from the Maillard reaction products
of glucose and glycine in the presence of sodium nitrite in C3H10T1/2 cells.
J Agric Food Chem. 2001 Dec;49(12):6063-7.
PMID: 11743809 [PubMed - indexed for MEDLINE]

179:  Khoo SK, Kahnoski K, Sugimura J, Petillo D, Chen J, Shockley K, Ludlow J,
Knapp R, Giraud S, Richard S, Nordenskjold M, Teh BT.
 Inactivation of BHD in sporadic renal tumors.
Cancer Res. 2003 Aug 1;63(15):4583-7.
PMID: 12907635 [PubMed - indexed for MEDLINE]

180:  von Beroldingen CH.
 The developmental potential of synchronized amphibian cell nuclei.
Dev Biol. 1981 Jan 15;81(1):115-26. No abstract available.
PMID: 6970148 [PubMed - indexed for MEDLINE]

181:  Gilbertson R.
 Paediatric embryonic brain tumours. biological and clinical relevance of
molecular genetic abnormalities.
Eur J Cancer. 2002 Mar;38(5):675-85. Review.
PMID: 11916550 [PubMed - indexed for MEDLINE]

182:  Jones PA.
 Epigenetics in carcinogenesis and cancer prevention.
Ann N Y Acad Sci. 2003 Mar;983:213-9. Review.
PMID: 12724226 [PubMed - indexed for MEDLINE]

183:  Kim NK, Ahn JY, Song J, Kim JK, Han JH, An HJ, Chung HM, Joo JY, Choi JU,
Lee KS, Roy R, Oh D.
 Expression of the DNA repair enzyme, N-methylpurine-DNA glycosylase (MPG) in
astrocytic tumors.
Anticancer Res. 2003 Mar-Apr;23(2B):1417-23.
PMID: 12820404 [PubMed - indexed for MEDLINE]

184:  Tycko B.
 Genetic and epigenetic mosaicism in cancer precursor tissues.
Ann N Y Acad Sci. 2003 Mar;983:43-54. Review.
PMID: 12724211 [PubMed - indexed for MEDLINE]

185:  Oshiro MM, Watts GS, Wozniak RJ, Junk DJ, Munoz-Rodriguez JL, Domann FE,
Futscher BW.
 Mutant p53 and aberrant cytosine methylation cooperate to silence gene
expression.
Oncogene. 2003 Jun 5;22(23):3624-34.
PMID: 12789271 [PubMed - indexed for MEDLINE]

186:  Benjamin R, Capparella J, Brown A.
 Classification of glioblastoma multiforme in adults by molecular genetics.
Cancer J. 2003 Mar-Apr;9(2):82-90. Review.
PMID: 12784873 [PubMed - indexed for MEDLINE]

187:  Tateno H, Akutsu H, Kamiguchi Y, Latham KE, Yanagimachi R.
 Inability of mature oocytes to create functional haploid genomes from somatic
cell nuclei.
Fertil Steril. 2003 Jan;79(1):216-8. No abstract available.
PMID: 12524093 [PubMed - indexed for MEDLINE]

188:  Hung KL.
 Familial medulloblastoma in non-twin siblings.
Surg Neurol. 1991 Jun;35(6):483-4. No abstract available.
PMID: 2053066 [PubMed - indexed for MEDLINE]

189:  Chen T, Ueda Y, Dodge JE, Wang Z, Li E.
 Establishment and maintenance of genomic methylation patterns in mouse
embryonic stem cells by Dnmt3a and Dnmt3b.
Mol Cell Biol. 2003 Aug;23(16):5594-605.
PMID: 12897133 [PubMed - indexed for MEDLINE]

190:  Flesken-Nikitin A, Choi KC, Eng JP, Shmidt EN, Nikitin AY.
 Induction of carcinogenesis by concurrent inactivation of p53 and Rb1 in the
mouse ovarian surface epithelium.
Cancer Res. 2003 Jul 1;63(13):3459-63.
PMID: 12839925 [PubMed - indexed for MEDLINE]

191:  Isachenko V, Folch J, Isachenko E, Nawroth F, Krivokharchenko A, Vajta G,
Dattena M, Alabart JL.
 Double vitrification of rat embryos at different developmental stages using an
identical protocol.
Theriogenology. 2003 Aug;60(3):445-52.
PMID: 12763158 [PubMed - indexed for MEDLINE]

192:  Vagner-Capodano AM, Zattara-Cannoni H, Quilichini B, Giocanti G; Groupe
Francais de Cytogenetique Oncologique.
 [From cytogenetics to cytogenomics of brain tumors: 1. Medulloblastoma]
Bull Cancer. 2003 Apr;90(4):315-8. Review. French.
PMID: 12801814 [PubMed - indexed for MEDLINE]

193:  Klein G.
 Introduction: genetic and epigenetic contributions to tumor evolution.
Semin Cancer Biol. 2002 Oct;12(5):327-30. No abstract available.
PMID: 12191631 [PubMed - indexed for MEDLINE]

194:  Jouneau A, Renard JP.
 Reprogramming in nuclear transfer.
Curr Opin Genet Dev. 2003 Oct;13(5):486-91.
PMID: 14550413 [PubMed - in process]

195:  Debinski W, Gibo D, Mintz A.
 Epigenetics in high-grade astrocytomas: opportunities for prevention and
detection of brain tumors.
Ann N Y Acad Sci. 2003 Mar;983:232-42. Review.
PMID: 12724228 [PubMed - indexed for MEDLINE]

196:  Fujiwara H, Tatsumi K, Kosaka K, Sato Y, Higuchi T, Yoshioka S, Maeda M,
Ueda M, Fujii S.
 Human blastocysts and endometrial epithelial cells express activated leukocyte
cell adhesion molecule (ALCAM/CD166).
J Clin Endocrinol Metab. 2003 Jul;88(7):3437-43.
PMID: 12843199 [PubMed - indexed for MEDLINE]

197:  Prather RS.
 Progress in cloning embryos from domesticated livestock.
Proc Soc Exp Biol Med. 1996 May;212(1):38-43. Review. No abstract available.
PMID: 8618949 [PubMed - indexed for MEDLINE]

198:  Liu XQ, Chen HK, Zhang XS, Pan ZG, Li A, Feng QS, Long QX, Wang XZ, Zeng
YX.
 Alterations of BLU, a candidate tumor suppressor gene on chromosome 3p21.3, in
human nasopharyngeal carcinoma.
Int J Cancer. 2003 Aug 10;106(1):60-5.
PMID: 12794757 [PubMed - indexed for MEDLINE]

199:  Alaoui-Jamali MA, Song DJ, Benlimame N, Yen L, Deng X, Hernandez-Perez M,
Wang T.
 Regulation of multiple tumor microenvironment markers by overexpression of
single or paired combinations of ErbB receptors.
Cancer Res. 2003 Jul 1;63(13):3764-74.
PMID: 12839972 [PubMed - indexed for MEDLINE]

200:  Prather RS, Hawley RJ, Carter DB, Lai L, Greenstein JL.
 Transgenic swine for biomedicine and agriculture.
Theriogenology. 2003 Jan 1;59(1):115-23. Review.
PMID: 12499023 [PubMed - indexed for MEDLINE]

201:  Larsen E, Gran C, Saether BE, Seeberg E, Klungland A.
 Proliferation failure and gamma radiation sensitivity of Fen1 null mutant mice
at the blastocyst stage.
Mol Cell Biol. 2003 Aug;23(15):5346-53.
PMID: 12861020 [PubMed - indexed for MEDLINE]

202:  Kim JM, Liu H, Tazaki M, Nagata M, Aoki F.
 Changes in histone acetylation during mouse oocyte meiosis.
J Cell Biol. 2003 Jul 7;162(1):37-46. Epub 2003 Jun 30.
PMID: 12835313 [PubMed - indexed for MEDLINE]

203:  Kuroki T, Trapasso F, Yendamuri S, Matsuyama A, Alder H, Williams NN,
Kaiser LR, Croce CM.
 Allelic loss on chromosome 3p21.3 and promoter hypermethylation of semaphorin
3B in non-small cell lung cancer.
Cancer Res. 2003 Jun 15;63(12):3352-5.
PMID: 12810670 [PubMed - indexed for MEDLINE]

204:  Elsheikh AS, Takahashi Y, Nagano M, Kanagawa H.
 Manipulated mouse embryos as bioassay system for water quality control.
Reprod Domest Anim. 2003 Jun;38(3):204-8.
PMID: 12753554 [PubMed - indexed for MEDLINE]

205:  Onishi A.
 Cloning of pigs from somatic cells and its prospects.
Cloning Stem Cells. 2002;4(3):253-9.
PMID: 12398806 [PubMed - indexed for MEDLINE]

206:  Sieber OM, Heinimann K, Tomlinson IP.
 Genomic instability--the engine of tumorigenesis?
Nat Rev Cancer. 2003 Sep;3(9):701-8. Review.
PMID: 12951589 [PubMed - indexed for MEDLINE]

207:  Pompetti F, Pilla D, Giancola R.
 Cancer therapy: switching off oncogenes.
Bioessays. 2003 Feb;25(2):104-7. Review.
PMID: 12539235 [PubMed - indexed for MEDLINE]

208:  Woods GL, White KL, Vanderwall DK, Li GP, Aston KI, Bunch TD, Meerdo LN,
Pate BJ.
 A mule cloned from fetal cells by nuclear transfer.
Science. 2003 Aug 22;301(5636):1063. Epub 2003 May 29. No abstract available.
PMID: 12775846 [PubMed - indexed for MEDLINE]

209:  Sato N, Maitra A, Fukushima N, van Heek NT, Matsubayashi H,
Iacobuzio-Donahue CA, Rosty C, Goggins M.
 Frequent hypomethylation of multiple genes overexpressed in pancreatic ductal
adenocarcinoma.
Cancer Res. 2003 Jul 15;63(14):4158-66.
PMID: 12874021 [PubMed - indexed for MEDLINE]

210:  Kalebic T.
 Epigenetic changes: potential therapeutic targets.
Ann N Y Acad Sci. 2003 Mar;983:278-85. Review.
PMID: 12724232 [PubMed - indexed for MEDLINE]

211:  Augustin R, Pocar P, Wrenzycki C, Niemann H, Fischer B.
 Mitogenic and anti-apoptotic activity of insulin on bovine embryos produced in
vitro.
Reproduction. 2003 Jul;126(1):91-9.
PMID: 12814351 [PubMed - indexed for MEDLINE]

212:  Fuks F.
 [DNA methyltransferases: from chromatin remodeling to cancer]
Med Sci (Paris). 2003 Apr;19(4):477-80. French.
PMID: 12836222 [PubMed - indexed for MEDLINE]

213:  Masui M, Takata H, Kominami T.
 Cell adhesion and the negative cell surface charges in embryonic cells of the
starfish Asterina pectinifera.
Electrophoresis. 2002 Jul;23(13):2087-95.
PMID: 12210263 [PubMed - indexed for MEDLINE]

214:  Falchetti ML, Pierconti F, Casalbore P, Maggiano N, Levi A, Larocca LM,
Pallini R.
 Glioblastoma induces vascular endothelial cells to express telomerase in vitro.
Cancer Res. 2003 Jul 1;63(13):3750-4.
PMID: 12839970 [PubMed - indexed for MEDLINE]

215:  Weiss B, Shannon K.
 Mouse cancer models as a platform for performing preclinical therapeutic
trials.
Curr Opin Genet Dev. 2003 Feb;13(1):84-9. Review.
PMID: 12573440 [PubMed - indexed for MEDLINE]

216:  Raetz EA, Kim MK, Moos P, Carlson M, Bruggers C, Hooper DK, Foot L, Liu T,
Seeger R, Carroll WL.
 Identification of genes that are regulated transcriptionally by Myc in
childhood tumors.
Cancer. 2003 Aug 15;98(4):841-53.
PMID: 12910530 [PubMed - indexed for MEDLINE]

217:  Weber A, Wittekind C, Tannapfel A.
 Genetic and epigenetic alterations of 9p21 gene products in benign and
malignant tumors of the head and neck.
Pathol Res Pract. 2003;199(6):391-7.
PMID: 12924439 [PubMed - indexed for MEDLINE]

218:  Petrenko O, Zaika A, Moll UM.
 deltaNp73 facilitates cell immortalization and cooperates with oncogenic Ras in
cellular transformation in vivo.
Mol Cell Biol. 2003 Aug;23(16):5540-55.
PMID: 12897129 [PubMed - indexed for MEDLINE]

219:  Sukoian MA, Beliaev ND, Budker VG, Gradov AA, Pak SD.
 [Genetic transformation of mouse cells by interphase nuclei enclosed in a lipid
membrane]
Dokl Akad Nauk SSSR. 1985;280(6):1445-8. Russian. No abstract available.
PMID: 3886337 [PubMed - indexed for MEDLINE]

220:  Going JJ.
 Epithelial carcinogenesis: challenging monoclonality.
J Pathol. 2003 May;200(1):1-3.
PMID: 12692834 [PubMed - indexed for MEDLINE]

221:  Jackson RJ, Engelman RW, Coppola D, Cantor AB, Wharton W, Pledger WJ.
 p21Cip1 nullizygosity increases tumor metastasis in irradiated mice.
Cancer Res. 2003 Jun 15;63(12):3021-5.
PMID: 12810620 [PubMed - indexed for MEDLINE]

222:  Fulka J Jr, Loi P, Fulka H, Kren R, Dean W, Mrazek M, Reik W.
 Nucleus replacement in Mammalian oocytes.
Cloning Stem Cells. 2002;4(3):181-7. Review.
PMID: 12398799 [PubMed - indexed for MEDLINE]

223:  Biernat W, Liberski PP, Kordek R, Zakrzewski K, Polis L, Budka H.
 Dysembryoplastic neuroectodermal tumor: an ultrastructural study of six cases.
Ultrastruct Pathol. 2001 Nov-Dec;25(6):455-67.
PMID: 11783910 [PubMed - indexed for MEDLINE]

224:  Kim HJ, Kim JE, Ha M, Kang SS, Kim JT, Park IS, Paek SH, Jung HW, Kim DG,
Cho GJ, Choi WS.
 Steroidogenic acute regulatory protein expression in the normal human brain and
intracranial tumors.
Brain Res. 2003 Jul 18;978(1-2):245-9.
PMID: 12834921 [PubMed - indexed for MEDLINE]

225:  Puck TT, Webb P, Johnson R.
 Cyclic AMP and the reverse transformation reaction.
Ann N Y Acad Sci. 2002 Jun;968:122-38. Review.
PMID: 12119272 [PubMed - indexed for MEDLINE]

226:  Ren ZG, Porzgen PP, Youn YH, Sieber-Blum M.
 Ubiquitous embryonic expression of the norepinephrine transporter.
Dev Neurosci. 2003 Jan-Feb;25(1):1-13.
PMID: 12876425 [PubMed - indexed for MEDLINE]

227:  Behrends U, Schneider I, Rossler S, Frauenknecht H, Golbeck A, Lechner B,
Eigenstetter G, Zobywalski C, Muller-Weihrich S, Graubner U, Schmid I, Sackerer
D, Spath M, Goetz C, Prantl F, Asmuss HP, Bise K, Mautner J.
 Novel tumor antigens identified by autologous antibody screening of childhood
medulloblastoma cDNA libraries.
Int J Cancer. 2003 Aug 20;106(2):244-51.
PMID: 12800201 [PubMed - indexed for MEDLINE]

228:  Liu ZJ, Maekawa M, Horii T, Morita M.
 The multiple promoter methylation profile of PR gene and ERalpha gene in tumor
cell lines.
Life Sci. 2003 Aug 29;73(15):1963-72.
PMID: 12899921 [PubMed - indexed for MEDLINE]

229:  Okamoto Y, Ozaki T, Miyazaki K, Aoyama M, Miyazaki M, Nakagawara A.
 UbcH10 is the cancer-related E2 ubiquitin-conjugating enzyme.
Cancer Res. 2003 Jul 15;63(14):4167-73.
PMID: 12874022 [PubMed - indexed for MEDLINE]

230:  Chen CM, Chen HL, Hsiau TH, Hsiau AH, Shi H, Brock GJ, Wei SH, Caldwell
CW, Yan PS, Huang TH.
 Methylation target array for rapid analysis of CpG island hypermethylation in
multiple tissue genomes.
Am J Pathol. 2003 Jul;163(1):37-45.
PMID: 12819009 [PubMed - indexed for MEDLINE]

231:  Sakharova NY, Lepikhova TN, Lepikhov KA, Malkova NV, Navolotskaya EV,
Chailakhyan LM.
 The effects of immunomodulating peptides on the preimplantation development of
mouse embryos.
Dokl Biol Sci. 2002 Jul-Aug;385:295-8. No abstract available.
PMID: 12474801 [PubMed - indexed for MEDLINE]

232:  Fu SW, Schwartz A, Stevenson H, Pinzone JJ, Davenport GJ, Orenstein JM,
Gutierrez P, Simmens SJ, Abraham J, Poola I, Stephan DA, Berg PE.
 Correlation of expression of BP1, a homeobox gene, with estrogen receptor
status in breast cancer.
Breast Cancer Res. 2003;5(4):R82-7. Epub 2003 Apr 22.
PMID: 12817998 [PubMed - indexed for MEDLINE]

233:  Shimozawa N, Ono Y, Kimoto S, Hioki K, Araki Y, Shinkai Y, Kono T, Ito M.
 Abnormalities in cloned mice are not transmitted to the progeny.
Genesis. 2002 Nov;34(3):203-7.
PMID: 12395385 [PubMed - indexed for MEDLINE]

234:  Gianaroli L, Magli MC, Ferraretti AP, Fortini D, Grieco N.
 Pronuclear morphology and chromosomal abnormalities as scoring criteria for
embryo selection.
Fertil Steril. 2003 Aug;80(2):341-9.
PMID: 12909497 [PubMed - indexed for MEDLINE]

235:  Schreiner CA.
 Genetic toxicity of naphthalene: a review.
J Toxicol Environ Health B Crit Rev. 2003 Mar-Apr;6(2):161-83. Review.
PMID: 12554433 [PubMed - indexed for MEDLINE]

236:  Chailakhyan TA, Vikhlyantseva EF, Chebotareva TN, Chailakhyan LM.
 The medium for microsurgical transfer of nuclei in mice: the osmolarity
phenomenon.
Dokl Biol Sci. 2003 Jan-Feb;388:86-8. No abstract available.
PMID: 12705140 [PubMed - indexed for MEDLINE]

237:  Louis DN, Pomeroy SL, Cairncross JG.
 Focus on central nervous system neoplasia.
Cancer Cell. 2002 Mar;1(2):125-8. Review. No abstract available.
PMID: 12086870 [PubMed - indexed for MEDLINE]

238:  Ellison DW, Clifford SC, Gajjar A, Gilbertson RJ.
 What's new in neuro-oncology? Recent advances in medulloblastoma.
Eur J Paediatr Neurol. 2003;7(2):53-66. Review. No abstract available.
PMID: 12697428 [PubMed - indexed for MEDLINE]

239:  Gullotta F.
 [The so-called medulloblastoma. Results of a comparative pathomorphological
study]
Monogr Gesamtgeb Neurol Psychiatr. 1967;118:1-60. German. No abstract available.

PMID: 6044572 [PubMed - indexed for MEDLINE]

240:  McCann J.
 Animal models offer insights into human brain tumors.
J Natl Cancer Inst. 2003 Feb 5;95(3):188. No abstract available.
PMID: 12569138 [PubMed - indexed for MEDLINE]

241:  Croul S, Otte J, Khalili K.
 Brain tumors and polyomaviruses.
J Neurovirol. 2003 Apr;9(2):173-82. Review.
PMID: 12707848 [PubMed - indexed for MEDLINE]

242:  Inui A.
 Obesity--a chronic health problem in cloned mice?
Trends Pharmacol Sci. 2003 Feb;24(2):77-80. Review.
PMID: 12559771 [PubMed - indexed for MEDLINE]

243:  Deng M, Kishikawa H, Yanagimachi R, Kopf GS, Schultz RM, Williams CJ.
 Chromatin-mediated cortical granule redistribution is responsible for the
formation of the cortical granule-free domain in mouse eggs.
Dev Biol. 2003 May 1;257(1):166-76.
PMID: 12710965 [PubMed - indexed for MEDLINE]

244:  Hirata Y.
 Genetic abnormalities and oncogenesis.
Med Hypotheses. 1996 Jan;46(1):17-8.
PMID: 8746121 [PubMed - indexed for MEDLINE]

245:  Gardner RL.
 Experimental analysis of second cleavage in the mouse.
Hum Reprod. 2002 Dec;17(12):3178-89.
PMID: 12456621 [PubMed - indexed for MEDLINE]

246:  Liberski PP.
 [Ependymoblastoma]
Pol J Pathol. 2001;52(4 Suppl):135-7. Review. Polish. No abstract available.
PMID: 11987600 [PubMed - indexed for MEDLINE]

247:  Perez-Losada J, Balmain A.
 Stem-cell hierarchy in skin cancer.
Nat Rev Cancer. 2003 Jun;3(6):434-43. Review.
PMID: 12778133 [PubMed - indexed for MEDLINE]

248:  Schiffer D, Fabiani A, Monticone GF, Cognazzo A.
 On the nature of the lymphocyte-like cells of medulloblastoma.
Acta Neuropathol (Berl). 1966 Jun 1;6(3):290-7. No abstract available.
PMID: 5336256 [PubMed - indexed for MEDLINE]

249:  Vasil'ev IuM.
 [Neoplastic morphologic transformations and their normal analogs]
Vestn Ross Akad Med Nauk. 2001;(9):74-7. Review. Russian.
PMID: 11676262 [PubMed - indexed for MEDLINE]

250:  Bataller L, Dalmau J.
 Paraneoplastic neurologic syndromes.
Neurol Clin. 2003 Feb;21(1):221-47, ix. Review.
PMID: 12690651 [PubMed - indexed for MEDLINE]

251:  Velilla E, Escudero T, Munne S.
 Blastomere fixation techniques and risk of misdiagnosis for preimplantation
genetic diagnosis of aneuploidy.
Reprod Biomed Online. 2002 May-Jun;4(3):210-7.
PMID: 12709269 [PubMed - indexed for MEDLINE]

252:  Fathallah-Shaykh HM.
 Darts in the dark cure animal, but not human, brain tumors.
Arch Neurol. 2002 May;59(5):721-4. Review. No abstract available.
PMID: 12020251 [PubMed - indexed for MEDLINE]

253:  Thathiah A, Carson DD.
 Mucins and blastocyst attachment.
Rev Endocr Metab Disord. 2002 May;3(2):87-96. Review. No abstract available.
PMID: 12007285 [PubMed - indexed for MEDLINE]

254:  Gurdon JB.
 Nuclear reprogramming and the redirection of cell fate in Xenopus.
Oncol Res. 2003;13(6-10):301. No abstract available.
PMID: 12725517 [PubMed - indexed for MEDLINE]

255:  Kepes JJ.
 Gliosarcoma with areas of primitive neuroepithelial differentiation and
extracranial metastasis.
Clin Neuropathol. 2002 Jul-Aug;21(4):193-5; author reply 195-6. No abstract
available.
PMID: 12143929 [PubMed - indexed for MEDLINE]

256:  Marx JL.
 Three mice "cloned" in Switzerland.
Science. 1981 Jan 23;211(4480):375-6. No abstract available.
PMID: 7221545 [PubMed - indexed for MEDLINE]

257:  Park KY, Pfeifer K.
 Epigenetic interplay.
Nat Genet. 2003 Jun;34(2):126-8. No abstract available.
PMID: 12776111 [PubMed - indexed for MEDLINE]

258:  Ereskovsky AV.
 Polyaxial cleavage in sponges (Porifera): a new pattern of metazoan cleavage.
Dokl Biol Sci. 2002 Sep-Oct;386:472-4. No abstract available.
PMID: 12469417 [PubMed - indexed for MEDLINE]

259:  Hardarson T, Lofman C, Coull G, Sjogren A, Hamberger L, Edwards RG.
 Internalization of cellular fragments in a human embryo: time-lapse recordings.
Reprod Biomed Online. 2002 Jul-Aug;5(1):36-8.
PMID: 12470543 [PubMed - indexed for MEDLINE]

260:  DeWeese TL, Nelson WG.
 Inadequate "caretaker" gene function and human cancer development.
Methods Mol Biol. 2003;222:249-68. Review. No abstract available.
PMID: 12710692 [PubMed - indexed for MEDLINE]

261:  Cezar GG.
 Epigenetic reprogramming of cloned animals.
Cloning Stem Cells. 2003;5(3):165-80. No abstract available.
PMID: 14588135 [PubMed - in process]



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