Stephen Grant, PhD - Nova Southeastern University - Associate Professor

Stephen Grant

PhD

Nova Southeastern University

Associate Professor

Fort Lauderdale, Florida | United States

Main Specialties: Public Health

Additional Specialties: Cancer, Genetics, Public Health

ORCID logohttps://orcid.org/0000-0002-9236-0913

Stephen Grant, PhD - Nova Southeastern University - Associate Professor

Stephen Grant

PhD

Introduction

Primary Affiliation: Nova Southeastern University - Fort Lauderdale, Florida , United States

Specialties:

Additional Specialties:

Research Interests:


View Stephen Grant’s Resume / CV

Metrics

Number of Publications

99

Publications

Number of Profile Views

376

Profile Views

Number of Article Reads

246

Reads

Number of Citations

370

Citations

Education

Jul 1992 - Jun 1993
University of California San Francisco
Clinical Fellowship
Aug 1985 - Oct 1988
Roswell Park Cancer Institute
Post-doctoral Fellowship
Sep 1976 - Apr 1979
University of Toronto
B.Sc. (Hons.)
Sep 1976 - Apr 1979
University of Toronto
B.Sc. (Hons.)

Experience

Oct 2011 - Oct 2013
Nova Southeastern University
Associate Professor
Oct 2011
Nova Southeastern University
Visiting Associate Professor
Aug 1994 - Dec 2000
University of Pittsburgh
Assistant Professor
Aug 1994 - Dec 2000
University of Pittsburgh
Assistant Professor
Apr 1992 - Jul 1994
University of California San Francisco
Research Scientist
Oct 1988 - May 1992
Lawrence Livermore National Laboratory
Senior Staff Scientist

Top co-authors

Jean J Latimer
Jean J Latimer

Nova Southeastern University AutoNation Cancer Institute

13
G Klopman
G Klopman

University of Pittsburgh

4
Wendy S Rubinstein
Wendy S Rubinstein

National Center for Biotechnology Information

3
Tiffany D Miles
Tiffany D Miles

University of Pittsburgh Cancer Institute

3
Victor G Vogel
Victor G Vogel

University of Pittsburgh School of Medicine

3
Phouthone Keohavong
Phouthone Keohavong

University of Pittsburgh

3
Liqiang Xi
Liqiang Xi

Laboratory of Pathology

3
Jennifer M Johnson
Jennifer M Johnson

University of Oklahoma Health Sciences Center

3
Crystal M Kelly
Crystal M Kelly

University of Pittsburgh School of Medicine

2

Publications

99Publications

246Reads

370PubMed Central Citations

Nucleotide excision repair is a predictor of early relapse in pediatric acute lymphoblastic leukemia.

BMC Med Genomics 2018 Oct 30;11(1):95. Epub 2018 Oct 30.

Department of Pharmaceutical Sciences, College of Pharmacy, 3200 S University Drive, Fort Lauderdale, FL, 33328, USA.

View Article
October 2018
2 Reads
2.873 Impact Factor

The arrow of carcinogenesis

Authors:
Stephen G Grant

J Mol Cancer 2017 Dec 15;1(1):1-6

Journal of Molecular Cancer

Many models of molecular carcinogenesis involve a multi-step progression through an accumulation of genetic and epigenetic events conferring various aspects of the transformed phenotype. Identification of tissue type- specific pathways involving distinctive genes has had some success, but it is becoming clear that such pathways may well be unique to each tumor. As an alternative, some researchers have targeted the mechanisms responsible for the accumulation of aberrant genes or gene expression, the “arrows” of transition between steps. The frequency of such genetic and epigenetic changes depends on both the lifelong exposure profile for an individual, as well as host factors, such as their innate rate of replication error and ability to remediate induced DNA damage. The totality of these effects can be evaluated functionally, however, using a number of approaches. Broadly defined, cumulative determinations of somatic mutational burden have been shown to predict subsequent cancer development, as well as demonstrating the development of genomic instability as a common characteristic of aging, that presages cancer incidence. Well-established and validated methodologies exist that can be applied to the monitoring of wellness in patients before cancer occurs.

View Article
December 2017
1 Read

Regulation and disregulation of mammalian nucleotide excision repair: a pathway to nongermline breast carcinogenesis.

Photochem Photobiol 2015 Mar-Apr;91(2):493-500. Epub 2014 Dec 19.

Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL.

View Article
September 2015
4 Reads
1 Citation
2.270 Impact Factor

Are Molecules Involved in Neuritogenesis and Axon Guidance Related to Autism Pathogenesis?

Neuromolecular Med 2015 Sep 20;17(3):297-304. Epub 2015 May 20.

Institute of Experimental Endocrinology, Slovak Academy of Sciences, Vlarska 3, Bratislava, Slovakia,

View Article
September 2015
8 Reads
11 Citations
3.680 Impact Factor

Pulsed-field gel electrophoresis analysis of multicellular DNA double-strand break damage and repair.

Methods Mol Biol 2014 ;1105:193-202

Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA.

View Article
November 2014
2 Reads

The blood-based glycophorin A (GPA) human in vivo somatic mutation assay.

Methods Mol Biol 2014 ;1105:223-44

Department of Pharmaceutical Sciences, Nova Southeastern University, Fort Lauderdale, FL, USA.

View Article
November 2014
2 Reads

Molecular analysis of mutations in the human HPRT gene.

Methods Mol Biol 2014 ;1105:291-301

Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, 100 Technology Drive, Bridgeside Point, Pittsburgh, PA, 15219, USA,

View Article
November 2014
5 Reads

Molecular Toxicology Protocols, 2nd Edition

Keohavong, P., and Grant, S.G. (2014) Molecular Toxicology Protocols, 2nd Edition, Methods in Molecular Biology, Volume 1105, Humana Press, New York, New York, 646 pages.

View Article
January 2014
1 Read

WNT10B/β-catenin signalling induces HMGA2 and proliferation in metastatic triple-negative breast cancer.

EMBO Mol Med 2013 Feb 11;5(2):264-79. Epub 2013 Jan 11.

Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA.

View Article
February 2013
13 Reads
47 Citations
8.665 Impact Factor

Translating mutagenesis into carcinogenesis.

Authors:
Stephen G Grant

J Carcinogene Mutagene 2012;3(1):e106.

Journal of Carcinogenesis and Mutagenesis

The Journal of Carcinogenesis and Mutagenesis follows a now century-old tradition of publishing investigations into the genetic, i.e., mutational, basis of cancer. Insights from our field have been, and continue to be, critically important for human cancer treatment, detection and prevention. Genotoxicity provided the rationale for systemic cancer therapy, which is only, now after 70 years or so, giving way to new modalities. It is becoming standard practice to evaluate the genome and/or transcriptome of cancers in order to tailor targeted therapies using antibodies (and now, fusion antibodies), small molecule inhibitors, and, in the near future, microRNAs, both native and engineered. These methods usually target the altered or over-expressed products of activated oncogenes; normal cellular genes activated by site-specific mutation.

View Article
June 2012
1 Read

Identification of Hydroxysteroid (17β) dehydrogenase type 12 (HSD17B12) as a CD8+ T-cell-defined human tumor antigen of human carcinomas.

Cancer Immunol Immunother 2011 Jul 16;60(7):919-29. Epub 2011 Mar 16.

Division of Basic Research, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.

View Article
July 2011
6 Reads
6 Citations
3.941 Impact Factor

Nucleotide excision repair deficiency is intrinsic in sporadic stage I breast cancer.

Proc Natl Acad Sci U S A 2010 Dec 30;107(50):21725-30. Epub 2010 Nov 30.

Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA 15213-3180, USA.

View Article
December 2010
58 Reads
18 Citations
9.810 Impact Factor

Permanently blocked stem cells derived from breast cancer cell lines.

Stem Cells 2010 Jun;28(6):1008-18

Section of Hematology/Oncology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.

View Article
June 2010
9 Reads
15 Citations
6.523 Impact Factor

Tobacco smoke exposure and somatic mutation in newborns.

Authors:
Stephen G Grant

Open Pediatr Med J 2010 Jun 24;4:10-13.

Open Pediatric Medical Journal

Maternal exposure to tobacco smoke is known to have deleterious effects on the developing fetus, but it has only recently been shown that there may be life-long consequences due to genotoxic damage. Analysis of newborn cord bloods with the GPA somatic mutation assay demonstrates a significant effect of maternal active smoking and suggests that similar mutational induction occurs in mothers who experience only secondary exposure to environmental tobacco smoke (ETS). Moreover, in both cases, mutational induction occurs by the same molecular mechanism, likely chromosome missegregation, resulting in an effective loss of one parental chromosome 4 and duplication of the other. These data also suggest that quitting smoking during pregnancy without actively avoiding secondary ETS exposure is not effective at protecting the unborn child from the genotoxic effects of tobacco smoke.

View Article
June 2010
1 Read

Melatonin and breast cancer: cellular mechanisms, clinical studies and future perspectives.

Expert Rev Mol Med 2009 Feb 5;11:e5. Epub 2009 Feb 5.

University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15232, USA.

View Article
February 2009
6 Reads
27 Citations
5.152 Impact Factor

(Z)-1,1-Dichloro-2-(4-methoxyphenyl)-3-phenylcyclopropane induces concentration-dependent growth inhibition, apoptosis, and coordinates regulation of apoptotic genes in TRAMP cells.

Urol Oncol 2008 Jul-Aug;26(4):378-85. Epub 2007 Dec 21.

Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15260, USA.

View Article
September 2008
1 Read
2.770 Impact Factor

Cell-type-specific level of DNA nucleotide excision repair in primary human mammary and ovarian epithelial cell cultures.

Cell Tissue Res 2008 Sep 25;333(3):461-7. Epub 2008 Jun 25.

Center for Environmental Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, USA.

View Article
September 2008
10 Reads
4 Citations
3.565 Impact Factor

Elevated levels of somatic mutation in a manifesting BRCA1 mutation carrier.

Pathol Oncol Res 2007 25;13(4):276-83. Epub 2007 Dec 25.

Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, USA.

View Article
May 2008
7 Reads
2 Citations
1.810 Impact Factor

Association between biomarkers of environmental exposure and increased risk of breast cancer.

Nat Rev Cancer 2006 Aug;6(8)

University of Pittsburgh Cancer Institute, Center for Environmental Oncology, 5150 Centre Avenue, Suite 435, Pittsburgh, Pennsylvania, 15232, USA.

View Article
August 2006
11 Reads
37.400 Impact Factor

Prospective screening study of 0.5 Tesla dedicated magnetic resonance imaging for the detection of breast cancer in young, high-risk women.

BMC Womens Health 2006 Jun 26;6:10. Epub 2006 Jun 26.

Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

View Article
June 2006
5 Reads
4 Citations
1.660 Impact Factor

DNA double strand break damage and repair assessed by pulsed-field gel electrophoresis

Joshi, N., and Grant, S.G. (2005) DNA double strand break damage and repair assessed by pulsed-field gel electrophoresis. In: Molecular Toxicology Protocols, (Keohavong, P., and Grant, S.G., eds.), Humana Press, Totowa, New Jersey. Methods in Molecular Biology 291: 121-129.

Methods in Molecular Biology

View Article
2005
1 Read

Qualitatively and quantitatively similar effects of active and passive maternal tobacco smoke exposure on in utero mutagenesis at the HPRT locus.

Authors:
Stephen G Grant

BMC Pediatr 2005 Jun 29;5:20. Epub 2005 Jun 29.

Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.

View Article
June 2005
4 Citations
1.920 Impact Factor

Haploinsufficiency for BRCA1 is associated with normal levels of DNA nucleotide excision repair in breast tissue and blood lymphocytes.

BMC Med Genet 2005 Jun 14;6:26. Epub 2005 Jun 14.

Department of Obstetrics, Gynecology and Reproductive Sciences, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

View Article
June 2005
8 Reads
9 Citations
2.083 Impact Factor

Use of the glycophorin A somatic mutation assay for rapid, unambiguous identification of Fanconi anemia homozygotes regardless of GPA genotype.

Am J Med Genet A 2005 May;135(1):59-65

Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, 3343 Forbes Avenue, Pittsburgh, PA 15213, USA.

View Article
May 2005
4 Reads
6 Citations
2.160 Impact Factor

HPRT gene alterations in umbilical cord blood T-lymphocytes in newborns of mothers exposed to tobacco smoke during pregnancy.

Mutat Res 2005 May;572(1-2):156-66

Department of Environmental and Occupational Health, University of Pittsburgh, 3343 Forbes Avenue, Pittsburgh, PA 15260, USA.

View Article
May 2005
3 Reads
5 Citations
3.680 Impact Factor

DNA double-strand break damage and repair assessed by pulsed-field gel electrophoresis.

Methods Mol Biol 2005 ;291:121-9

Department of Environmental and Occupational Health, University of Pittsburgh, PA, USA.

View Article
February 2005
2 Reads
6 Citations

The GPA in vivo somatic mutation assay.

Authors:
Stephen G Grant

Methods Mol Biol 2005 ;291:179-95

Department of Environmental and Occupational Health, University of Pittsburgh, PA, USA.

View Article
February 2005
2 Reads
2 Citations

Molecular analysis of mutations in the human HPRT gene.

Methods Mol Biol 2005 ;291:161-70

Department of Environmental and Occupational Health, University of Pittsburgh, PA, USA.

View Article
February 2005
3 Reads
1 Citation

Unusual pattern of bone marrow somatic mutation in pediatric patients referred for cytogenetic analysis.

Balkan J Med Genet 2005;8(1&2):45-51

Balkan Journal of Medical Genetics

Bone marrow somatic mutation frequency, as mea­sured by the glycophorin A (GPA) assay in circulating red blood cells, has been found to be increased in some hered­itable disease syndromes associated with constitutional malformation, mental retardation, cancer susceptibility and premature aging. Increased spontaneous GPA mutation frequency has been shown to be diagnostic for ataxia tel­angiectasia (AT) and Fanconi’s anemia (FA). We have applied the GPA assay to a 11 pediatric patients referred for cytogenetic analysis for a variety of reasons, including developmental delay and dysmorphology. There was no evidence of any cytogenetic abnormality in these patients, so we investigated the possible role of constitutive genom­ic instability expressed as a high frequency of bone mar­row somatic mutation. These patients had normal overall levels of GPA somatic mutation when compared to new­born and pediatric controls. When phenotypic subsets of mutants were considered, however, the patients had de­creased levels of simple allele loss mutation and increased levels of allele loss and duplication. Such a shift in types of mutation without an accompanying increase in overall mutation is difficult to understand, but may be related to inherent cytotoxic susceptibility and cellular inviability in this heterogeneous patient population.

View Article
January 2005
1 Read

Molecular Toxicology Protocols

Keohavong, P., and Grant, S.G. (2005) Molecular Toxicology Protocols, Methods in Molecular Biology, Volume 291, Humana Press, Totowa, New Jersey, 489 pages.

View Article
January 2005
1 Read

Comparison of established cell lines at different passages by karyotype and comparative genomic hybridization.

Biosci Rep 2004 Dec;24(6):631-9

Department of Pathology, West Virginia University, P. O. Box 9203, Morgantown, WV, 26506-9203, USA.

View Article
December 2004
2 Reads
22 Citations
2.640 Impact Factor

Unique tissue-specific level of DNA nucleotide excision repair in primary human mammary epithelial cultures.

Exp Cell Res 2003 Nov;291(1):111-21

Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA 15213, USA.

View Article
November 2003
5 Reads
10 Citations
3.250 Impact Factor

Molecular epidemiology of human cancer: biomarkers of genotoxic exposure and susceptibility.

Authors:
S G Grant

J Environ Pathol Toxicol Oncol 2001 ;20(4):245-61

Department of Environmental and Occupation Health, University of Pittsburgh, PA 15238, USA.

View Article
January 2002
1 Read
3 Citations
0.880 Impact Factor

Rothmund-Thomson syndrome

Plon, S.E., and Grant, S.G. (2002) Rothmund-Thomson syndrome. In: NORD Guide to Rare Diseases, 3rd Edition, (Gruson, E., ed.), Lippincott, Williams and Wilkins, Philadelphia, pp. 135-136.

NORD Guide to Rare Diseases, 3rd Edition

View Article
January 2002
1 Read

A mathematical model of in vitro cancer cell growth and treatment with the antimitotic agent curacin A.

Math Biosci 2001 Mar;170(1):1-16

Department of Mathematics, Hampton University, VA 23668, USA.

View Article
March 2001
1 Read
7 Citations
1.303 Impact Factor

Physicochemical and graph theoretical descriptors in developmental toxicity SAR: a comparative study.

SAR QSAR Environ Res 2001 Feb;11(5-6):345-62

Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, 260 Kappa Drive, Pittsburgh, PA 15238 USA.

View Article
February 2001
1 Read

Mutational spectrum of N-hydroxy-N-acetyl-4- aminobiphenyl at exon 3 of the HPRT gene.

Biomarkers 2001;6(4):262-273.

Biomarkers

4-Aminobiphenyl is a human bladder carcinogen present in many environmental sources, including cigarette smoke. It can be metabolized in two steps to the mutagen N-hydroxy-N-acetyl-4-aminobiphenyl (N-OH-AABP). In this study the mutational spectrum of N-OH-AABP-exposed human lymphoblastoid cells (TK6) was deter- mined using HPRT as the target gene. Three large, HAT (hypoxanthine– aminopterin–thymidine)-cleaned TK6 cultures were independently treated with 20 m M N-OH-AABP for 24 h, allowed to recover for 4 days, then continuously exposed to 40 m M 6-thioguanine to select for induced mutants. Contemporary control cultures received vehicle in place of N-OH-AABP. N-OH-AABP treatment gave an 11-fold increase in mutation frequency. Mutations were delineated in exon 3 of the HPRT gene directly from genomic DNA extracted from both treated and untreated cells using the polymerase chain reaction, denaturing gradient gel electrophoresis (DGGE) and dideoxy sequencing. DGGE analysis showed N-OH-AABP increased both the number and type of mutations as compared with controls. The major background mutation was a G(197) to A transition. The major N-OH-AABP-induced changes were G(209-211) to T transversions (30 %), a seven-base repeat at position 185 (17%) and an A(215) to T transversion (2%). The shift in the control spectrum of a transition to that of transversions and insertions suggest that the electrophile N-OH-AABP forms bulky adducts at the same sites on exon 3 of HPRT as do many other bulky electrophiles, causes replication errors by similar mechanisms, but induces at least one potentially signature mutation.

View Article
January 2001
1 Read

Z-1,1-Dichloro-2,3-diphenylcyclopropanes block human prostate carcinoma cell proliferation, inhibit prostate-specific antigen expression, and initiate apoptosis.

Prostate 2000 Dec;45(4):277-88

Department of Environmental & Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15238, USA.

View Article
December 2000
2 Reads
1 Citation
3.565 Impact Factor

Analysis of genomic instability using multiple assays in a patient with Rothmund-Thomson syndrome.

Clin Genet 2000 Sep;58(3):209-15

Department of Environmental and Occupational Health, University of Pittsburgh, PA, USA.

View Article
September 2000
1 Read
7 Citations
3.931 Impact Factor

Genetic instability and hematologic disease risk in Werner syndrome patients and heterozygotes.

Cancer Res 2000 May;60(9):2492-6

Department of Pathology, University of Washington, Seattle 98195, USA.

View Article
May 2000
1 Read
17 Citations
9.330 Impact Factor

Modeling the mouse lymphoma forward mutational assay: the Gene-Tox program database.

Mutat Res 2000 Feb;465(1-2):201-29

Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15238, USA.

View Article
February 2000
4 Reads
1 Citation
3.680 Impact Factor

Impact of maternal lifestyle factors on newborn HPRT mutant frequencies and molecular spectrum--initial results from the Prenatal Exposures and Preeclampsia Prevention (PEPP) Study.

Mutat Res 1999 Dec;431(2):279-89

Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, PA 15238, USA.

View Article
December 1999
2 Reads
2 Citations
3.680 Impact Factor

Myeloperoxidase-catalyzed redox-cycling of phenol promotes lipid peroxidation and thiol oxidation in HL-60 cells.

Free Radic Biol Med 1999 Nov;27(9-10):1050-63

Department of Environmental & Occupational Health, University of Pittsburgh, PA 15238, USA.

View Article
November 1999
1 Read
3 Citations
5.740 Impact Factor

Diagnosis of ataxia telangiectasia with the glycophorin A somatic mutation assay.

Genet Test 1997-1998;1(4):261-7

Center for Environmental and Occupational Health and Toxicology, University of Pittsburgh, PA 15238, USA.

View Article
October 1999
2 Reads
4 Citations

Development, characterization and application of predictive-toxicology models.

SAR QSAR Environ Res 1999 ;10(2-3):277-98

Department of Environmental and Occupational Health, University of Pittsburgh, PA 15238, USA.

View Article
October 1999
1 Read
1 Citation

The utility of multiple random sampling in the development of SAR models.

AAAI Tech Rep 1999;SS-99-1:45-48.

AAAI Technical Report

We propose an approach that incorporates into the model-building process resampling of the parent chemical database to form N random databases, from which N independent random models are generated. The multiple random sampling allows us to treat the parent database as an empirical chemical population distribution. This approach helps to overcome to some degree the representation bias in the parent database. Model building researchers will recognize the similarity of this approach to the bootstrap. In fact, it is the bootstrap methodology but applied not only to estimate the distribution of the prediction accuracy/error, but also to evaluate the consistency of random models developed from a given database. The idea for employing the bootstrap approach for this purpose was presented by Efron and Gong in a demonstration that dealt with a similar prediction problem, a situation which they deemed to be "hopelessly beyond traditional theoretical solutions"

View Article
March 1999
1 Read

Induction of human breast cancer cell apoptosis from G2/M preceded by stimulation into the cell cycle by Z-1,1-dichloro-2,3-diphenylcyclopropane.

Biochem Pharmacol 1999 Jan;57(1):97-110

Department of Environmental & Occupational Health, The Magee-Womens Research Institute, University of Pittsburgh, PA 15238, USA.

View Article
January 1999
2 Reads
1 Citation
5.010 Impact Factor

Antiandrogenic properties of the microtubule-perturbing agent Z-1,1-dichloro-2,3-diphenylcyclopropane

Proceedings of the American Association for Cancer Research Annual Meeting

View Article
January 1999
1 Read

Increased sensitivity of the antiestrogen-resistant MCF7/LY2 human breast carcinoma cell line to apoptosis induced by the novel microtubule-stabilizing agent (+)-discodermolide.

Breast J 1998 Nov;4(6):409-419

The Breast Journal

(+)-Discodermolide is a sponge-derived natural product with the most potent microtubule stabilizing activity yet discovered. Its actions parallel that of the promising anti-breast cancer agent paclitaxel, despite the lack of any apparent similarities in the drugs’ structures. To complement our previous studies on human breast cancer cells, we compared the effects of the tow drugs against the estrogen receptor positive, but tamoxifen-resistant MCF-7/LY2 line. Grpwth inhibition, cell, and nuclear morphological, electrophoretic, and flow cytometric analyses were performed. (+)-Discoderolide potently inhibited the growth of the cells (e.g., 48-hours IC50 of 1.5 nM) at concentrations similar to those observed with paclitaxel, and somewhat lower than the values observed previously with estrogen responsive MCF-7 and estrogen nonresponsive MDA-MB231 cells. (+)-Discodermolide-treated MCF-7/LY2 cells had condensed and highly fragmented nuclei, as well as micronuclei, suggesting mitotic block and the induction of apoptosis. Flow cytometric comparison of cells treated with either drug at 10 nM showed both caused accumulation into the G2/M portion of the cell cycle as well as induction of a pronounced hypodiploid cell population, with )+)-discodermolide yielding a greater effect. The timing and type of high molecular weight DNA fragmentation induced by the two agents was fully consistent with the induction of apoptosis, again with (+)-discodermolide showing an advantage over paclitaxel in this regard. More extensive DNA fragmentation was noted in MCF-7/LY2 than has been observed in MCF-7 and MDA-MB231 cells. These in vitro results, coupled with those obtained previously , suggest that (+)-discodermolide might have promise as a new chemotherapeutic agent against breast cancers. In addition, its novel and synthetically approachable structure make (+)-discodermolide a promising lead compound for design and discovery of new microtubule stabilizing agents as alternatives to taxoids.

View Article
November 1998
2 Reads

Human in vivo somatic mutation measured at two loci: individuals with stably elevated background erythrocyte glycophorin A (gpa) variant frequencies exhibit normal T-lymphocyte hprt mutant frequencies.

Mutat Res 1998 Feb;397(2):119-36

Center for Environmental and Occupational Health and Toxicology, Graduate School of Public Health, University of Pittsburgh, PA, USA.

View Article
February 1998
4 Reads
3 Citations
3.680 Impact Factor

Induction of forward mutations at the thymidine kinase locus of mouse lymphoma cells: evidence for electrophilic and non-electrophilic mechanisms.

Mutat Res 1998 Feb;397(2):313-35

Department of Environmental and Occupational Health, University of Pittsburgh, PA 15238, USA.

View Article
February 1998
1 Read
3.680 Impact Factor

The potent microtubule-stabilizing agent (+)-discodermolide induces apoptosis in human breast carcinoma cells--preliminary comparisons to paclitaxel.

Anticancer Drugs 1998 Jan;9(1):67-76

Department of Environmental & Occupational Health, University of Pittsburgh, PA 15238, USA.

View Article
January 1998
1 Read
1.891 Impact Factor

Radiobiological evaluation of immigrants from the vicinity of Chernobyl.

Int J Radiat Biol 1997 Dec;72(6):703-13

Occupational Medicine Department, DynCorp of Colorado Inc., Rocky Flats, Golden 80402-0464, USA.

View Article
December 1997
2 Reads
3 Citations
1.840 Impact Factor

SfaNI polymorphism distinguishes the alleles of the glycophorin A locus that determine the MN blood group.

Acta Haematol 1997 ;98(1):51-3

Biomedical Sciences Division, Lawrence Livermore National Laboratory, Calif, USA.

View Article
July 1997
2 Reads
0.994 Impact Factor

Glycophorin A as a biological dosimeter for radiation dose to the bone marrow from iodine-131.

Radiat Res 1997 Jun;147(6):747-52

Department of Laboratory Medicine, School of Medicine, University of California San Francisco 94143-0808, USA.

View Article
June 1997
1 Read
2.911 Impact Factor

Structural and mechanistic bases for the induction of mitotic chromosomal loss and duplication ('malsegregation') in the yeast Saccharomyces cerevisiae: relevance to human carcinogenesis and developmental toxicology.

Mutat Res 1997 Mar;374(2):209-31

Department of Environmental and Occupational Health, University of Pittsburgh, PA 15238, USA.

View Article
March 1997
3 Reads
1 Citation
3.680 Impact Factor

Glycophorin A somatic cell mutation frequencies in Finnish reinforced plastics workers exposed to styrene.

Cancer Epidemiol Biomarkers Prev 1996 Oct;5(10):801-10

Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh Cancer Institute, Pennsylvania 15238, USA.

View Article
October 1996
5 Reads
2 Citations
4.125 Impact Factor

Sensitivity of somatic mutations in human umbilical cord blood to maternal environments.

Environ Mol Mutagen 1995 ;26(3):203-12

Children's Hospital, Division of Genetic Services, Denver, CO 80218, USA.

View Article
December 1995
1 Read
4 Citations
2.630 Impact Factor

Molecular characterization of glycophorin A transcripts in human erythroid cells using RT-PCR, allele-specific restriction, and sequencing.

Vox Sang 1995 ;68(2):121-9

Biotechnology and Biomedical Research Division, Lawrence Livermore National Laboratory, Calif., USA.

View Article
June 1995
1 Read
2 Citations
2.800 Impact Factor

Elevated frequency of glycophorin A mutations in erythrocytes from Chernobyl accident victims.

Radiat Res 1995 Feb;141(2):129-35

Department of Laboratory Medicine, University of California, San Francisco 94143-0808.

View Article
February 1995
1 Read
4 Citations
2.911 Impact Factor

Use of allele-specific glycophorin A antibodies to enumerate fetal erythroid cells in maternal circulation.

Ann N Y Acad Sci 1994 Sep;731:128-32

Department of Environmental and Occupational Health, University of Pittsburgh, Pennsylvania 15238.

View Article
September 1994
1 Read
4.313 Impact Factor

Bone marrow somatic mutation after genotoxic cancer therapy.

Lancet 1994 Jun;343(8911):1507-8

View Article
June 1994
1 Read
45.220 Impact Factor

Analysis of somatic cell mutations at the glycophorin A locus in atomic bomb survivors: a comparative study of assay methods.

Radiat Res 1993 Oct;136(1):111-7

Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, Livermore, California 94550.

View Article
October 1993
1 Read
2 Citations
2.911 Impact Factor

In vivo somatic mutation and segregation at the human glycophorin A (GPA) locus: phenotypic variation encompassing both gene-specific and chromosomal mechanisms.

Mutat Res 1993 Jul;288(1):163-72

Department of Radiology, University of California, San Francisco 94143.

View Article
July 1993
1 Read
5 Citations
3.680 Impact Factor

Use of the glycophorin A human mutation assay to study workers exposed to styrene.

Environ Health Perspect 1993 Mar;99:297-301

Department of Environmental Health Sciences, University of California, Berkeley 94720.

View Article
March 1993
1 Read
1 Citation
7.980 Impact Factor

Use of hematopoietic cells and markers for the detection and quantitation of human in vivo somatic mutation

Grant, S.G., and Jensen, R.H. (1993) Use of hematopoietic cells and markers for the detection and quantitation of human in vivo somatic mutation. In: Immunobiology of Transfusion Medicine, (Garratty, G., ed.), Marcel Dekker, New York, pp. 299-323.

Immunobiology of Transfusion Medicine

View Article
January 1993
1 Read

MUTATION, SEGREGATION, AND CHILDHOOD-CANCER

Late Effects of Treatment For Childhood Cancer

View Article
1992
1 Read

Somatic cell genotoxicity at the glycophorin A locus in humans.

Prog Clin Biol Res 1991 ;372:329-39

Biomedical Sciences Division, Lawrence Livermore National Laboratory, Livermore, CA 94550.

View Article
January 1992
1 Read
3 Citations

Mutation, segregation, and childhood cancer.

Authors:
S G Grant

Curr Clin Oncol 1992;2:121-32.

Current Clinical Oncology

It is becoming clear that most, if not all, cancer has a genetic basis. Moreover, our current understanding of tumorigenesis indicates that somatic events, either classical mutations or segregationlike mechanisms that result in reduction of mutant cancer-predisposing genes to homozygosity, are necessary for the development of cancer. Two types of cellular cancer genes have been identified: the proto-oncogenes and the tumor suppressor genes. The first, and in some cases only, step necessary for tumor progression resulting from either of the classes of oncogenes is mutation. The specific types of mutation necessary are very different between the two classes of oncogene, however. To be involved in tumorigenesis, positive-acting proto-oncogenes must first be activated by a somatic event that leads to unregulated hyperactivity of the gene product. In contrast, the first step towards tumorigenesis involving tumor suppressor genes requires a somatic or germline mutation to inactivity, followed by a somatic reduction to homozygosity of the mutant allele.

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January 1992
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Methods for the detection of mutational and segregational events: relevance to the monitoring of survivors of childhood cancer.

Curr Clin Oncol 1992;2:133-150

Current Clinical Oncology

In the last decade, the new techniques of molecular genetics have gone far towards elucidating the relationship between mutagenesis and cancer. It is now generally accepted that most, if not all, cancer has a genetic basis, and that the progressive steps in multistage carcinogenesis represent genetic mutations and/or a relatively new class of events involving not only classical mutation, but also chromosome recombination and missegregation events and epigenetic mechanisms. This class of somatic mechanisms is collectively known as segregation, although “reduction to homozygosity,” “loss of heterozygosity,” and simple “allele loss” have also been used. Childhood cancer, due to their early onset, represent a class of tumors that not only may have the simplest etiology, but may also result from hereditary predisposition to neoplasia.

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January 1992
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Biodosimetry of ionizing radiation in humans using the glycophorin A genotoxicity assay

Jensen, R.H., Langlois, R.G., Grant, S.G., and Bigbee, W.L. (1992) Biodosimetry of ionizing radiation in humans using the glycophorin A genotoxicity assay. In: Radiation Research: A Twentieth-Century Perspective, Volume II: Congress Proceedings, (Dewey, W.C., Edington, M., Fry, R.J.M., Hall, E.J.

Radiation Research: A Twentieth-Century Perspective, Volume II: Congress Proceedings

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January 1992
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Allele loss at the human GPA locus: a model for recessive oncogenesis with potential clinical application.

Clin Biotechnol 1993 Fall;3(3):177-185.

Clinical Biotechnology

We have derived an in vivo assay, based on loss of heterozygosity at the human glycophorin A locus, to identify and quantitate variant erythrocytes arising by the same mechanisms of mutation and segregation that are responsible for recessive oncogenesis. With the current assay, which involves immunolabeling of whole blood with fluorescence–conjugated allele-specific monoclonal antibodies followed by flow cytometric analysis, two classes of variants are distinguishable: simple allele loss variants, and variants arising by loss of one allele and duplication of the remaining homologue. This assay has important clinical implications as a biodosimeter to measure exposure to genotoxic agents; it may also provide a means of estimating cancer risk, especially the risk of recurrence after childhood cancer.

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September 1991
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Laser-based flow cytometric analysis of genotoxicity of humans exposed to ionizing radiation during the Chernobyl accident.

SPIE Proc 1991;1403:372-380.

SPIE Proceedings

An analytical technique has been developed that allows laser-based flow cytometric measurement of the frequency of red blood cells that have lost allele-specific expression of a cell surface antigen due to genetic toxicity in bone marrow precursor cells. Previous studies demonstrated a correlation of such effects with the exposure of each individual to mutagenic phenomena, such as ionizing radiation, and the effects can persist for the lifetime of each individual. During the emergency response to the nuclear power plant accidert at Chemobyl, Ukraine, USSR, a number of people were exposed to whole body doses of ioniing radiation. Some of these individuals were tested with this laser-based assay and found to express a dose-dependent increase in the frequency of variant red blood cells that appears to be a persistent biological effect. This effect is similar to that which was previously observed in individuals who were exposed to ionizing radiation at Hiroshima in 1945 because of the A-bomb explosion. All data indicate that this assay might well be used as a biodosimeter to estimate radiation dose and also as an element to be used for estimating the risk of each individual to develop cancer due to radiation exposure.

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May 1991
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Detailed genetic mapping of the A-raf proto-oncogene on the mouse X chromosome.

Oncogene 1991 Mar;6(3):397-402

Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York 14263.

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March 1991
1 Read
8.460 Impact Factor

Characterization of a murine cDNA encoding a member of the carboxylesterase multigene family.

Genomics 1991 Feb;9(2):344-54

Institute for Developmental Research, Children's Hospital Medical Center, Cincinnati, Ohio 45229.

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February 1991
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11 Citations
2.284 Impact Factor

Localization of the mouse Mcf-2 (Dbl) protooncogene within a conserved linkage group on the mouse X chromosome.

Cytogenet Cell Genet 1990 ;54(3-4):175-81

Department of Molecular and Cellular Biology, Roswell Park Memorial Institute, New York State Department of Health, Buffalo 14263.

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February 1991
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Characterization of the cDNA coding for mouse prothrombin and localization of the gene on mouse chromosome 2.

DNA Cell Biol 1990 Sep;9(7):487-98

Children's Hospital Research Foundation, Cincinnati, OH.

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September 1990
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8 Citations
2.060 Impact Factor

Efficient linkage of 10 loci in the proximal region of the mouse X chromosome.

Genomics 1990 May;7(1):19-30

Department of Molecular and Cellular Biology, Roswell Park Memorial Institute, Buffalo, New York 14263.

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May 1990
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1 Citation
2.284 Impact Factor

Localization of the rhodopsin gene to the distal half of mouse chromosome 6.

Genomics 1990 Apr;6(4):635-44

Department of Molecular and Cellular Biology, Roswell Park Memorial Institute, Buffalo, New York 14263.

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April 1990
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2.284 Impact Factor

cis-acting determinants of basal and lipid-regulated apolipoprotein A-IV expression in mice.

J Biol Chem 1989 Nov;264(32):19009-16

Department of Human Genetics, Roswell Park Memorial Institute, Buffalo, New York 14263.

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November 1989
2 Reads
6 Citations
4.573 Impact Factor

Gene inactivation as a mechanism for the expression of recessive phenotypes.

Am J Hum Genet 1989 Oct;45(4):619-34

Genetics Department and Research Institute, Hospital for Sick Children, Toronto.

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October 1989
2 Reads
3 Citations
10.931 Impact Factor

Comparison of the physical and recombination maps of the mouse X chromosome.

Genomics 1989 Aug;5(2):177-84

Department of Pathology, University of Washington, Seattle 98195.

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August 1989
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2 Citations
2.284 Impact Factor

Mechanisms of X-chromosome regulation.

Annu Rev Genet 1988 ;22:199-233

Department of Molecular and Cellular Biology, Roswell Park Memorial Institute, Buffalo, New York 14263.

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May 1989
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47 Citations
15.724 Impact Factor

Differential activation of the hprt gene on the inactive X chromosome in primary and transformed Chinese hamster cells.

Mol Cell Biol 1989 Apr;9(4):1635-41

Genetics Department, Hospital for Sick Children, Toronto, Ontario, Canada.

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April 1989
1 Read
1 Citation
4.780 Impact Factor

Activation of the hprt gene on the inactive X chromosome in transformed diploid female Chinese hamster cells.

J Cell Sci 1989 Apr;92 ( Pt 4):723-32

Genetics Department and Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.

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April 1989
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5.432 Impact Factor

Multilocus molecular mapping of the mouse X chromosome.

Genomics 1988 Oct;3(3):187-94

Roswell Park Memorial Institute, Molecular and Cellular Biology Department, Buffalo, New York 14263.

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October 1988
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8 Citations
2.284 Impact Factor

X-chromosome gene order in different Mus species crosses.

Curr Top Microbiol Immunol 1988 ;137:18-24

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October 1988
2 Reads
4.100 Impact Factor

X-chromosome linked mutations affecting mosaic expression of the mouse X chromosome.

Curr Top Microbiol Immunol 1988 ;137:183-90

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October 1988
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1 Citation
4.100 Impact Factor

Golden: a novel coat color mutant in the wild mouse Mus caroli.

J Hered 1988 May-Jun;79(3):151-4

Department of Molecular and Cellular Biology, Roswell Park Memorial Institute, Buffalo, New York 14263.

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August 1988
1 Read
2.090 Impact Factor

Identification of an X-linked member of the Odc gene family in the mouse.

Nucleic Acids Res 1988 Feb;16(4):1642

Department of Molecular and Cellular Biology, Roswell Park Memorial Institute, Buffalo, NY 14263.

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February 1988
1 Read
1 Citation
9.112 Impact Factor

Regional localization of the murine Duchenne muscular dystrophy gene on the mouse X chromosome.

Somat Cell Mol Genet 1987 Nov;13(6):671-8

Institute for Molecular Genetics, Baylor College of Medicine, Houston, Texas 77030.

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November 1987
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4 Citations

Segregation-like events in Chinese hamster cells

Worton, R.G., and Grant, S.G. (1985) Segregation-like events in Chinese hamster cells. In: Molecular Cell Genetics, (Gottesman, M.M., ed.), John Wiley and Sons, New York, pp. 831-867.

Molecular Cell Genetics

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January 1985

Gene inactivation and reactivation at the emt locus in Chinese hamster cells.

Prog Cancer Res Ther 1984;30:265-72.

Progress in Cancer Research and Therapy

The ability to detect gene inactivation and reactivation in animal cells is severely hampered by the presence of two copies of autosomal genes in diploid cells. In heterozygotes (m/+) carrying a recessive mutant allele (m) and a wild-type allele (+) it is possible to specifically monitor the activity of the single wild-type allele; however, studies of gene expression require that cells with an inactive + gene remain viable. Heterozygous cells meeting this condition are difficult to obtain. We have created a series of somatic cell hybrids of Chinese hamster ovary (CHO) cells that fulfill these conditions. The hybrids are heterozygous at the emt locus and were created by fusing emetine-resistant cells carrying a single recessive emtr allele with wild-type CHO carrying a single dominant emt+ allele. The emtr/emt+ hybrids have a wild-type phenotype (sensitive to emetine), but “segregants” that reexpress the Emtr phenotype occur at high frequency. Some of these are due to loss of the chromosome carrying the emt+ gene but a few appear to be due to loss of expression of the emt+ gene. Two criteria suggest that these are the result of gene inactivation. First, transfer of the chromosome carrying the putative null emt (emt null) allele into a cell where it should be expressed fails to reveal any gene expression. Second, treatment of the putative inactivants with 5-azacytidine results in reexpression of the emt+ gene in 15 to 20% of cells. This suggests the possibility that the original gene inactivation event involves DNA methylation or perhaps some other mechanism sensitive to reversal by this cytidine analog.

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January 1984

Top co-authors

Jean J Latimer
Jean J Latimer

Nova Southeastern University AutoNation Cancer Institute

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G Klopman
G Klopman

University of Pittsburgh

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Wendy S Rubinstein
Wendy S Rubinstein

National Center for Biotechnology Information

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Tiffany D Miles
Tiffany D Miles

University of Pittsburgh Cancer Institute

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Victor G Vogel
Victor G Vogel

University of Pittsburgh School of Medicine

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Phouthone Keohavong
Phouthone Keohavong

University of Pittsburgh

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Liqiang Xi
Liqiang Xi

Laboratory of Pathology

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Jennifer M Johnson
Jennifer M Johnson

University of Oklahoma Health Sciences Center

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Crystal M Kelly
Crystal M Kelly

University of Pittsburgh School of Medicine

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