Nicholas C. Popescu

Nicholas C. Popescu is a Cytogeneticist and cell Biologist, and conducts research on cancer molecular cytogenetics and molecular biology at the Center for Cancer Research, National Cancer Institute (NCI), USA. He began his scientific career in 1965 at the Oncological Institute in Bucharest, Romania, where he later became the Chief of the Laboratory of Biology. His pioneering studies in cytogenetics of experimentally induced cancer were among the first worldwide ones and marked the beginning of a new field in cancer genetics. After receiving his Ph.D. degree in genetics from the University of Bucharest, Romania, in 1971, he joined NCI. He is currently the Chief of the Molecular Cytogenetics Section, Laboratory of Experimental Carcinogenesis at NCI. With the advent of advances in genomic and molecular biology, Dr. Popescu developed and applied new cutting edge technologies in cancer genetics and made major contributions to the understanding of the role of genomic alterations in neoplasia and mapping and identification of a number of important cancer-related genes, some of which led to cancer molecular targeted therapy. His contribution to cancer research and basic genetics is reflected in publications of more than 250 original articles. He is a recipient of several national and international awards. Dr. Popescu has served on the Editorial Board of Cancer Genetics and Cytogenetics, Cytogenetics and Cell Genetics, Cytogenetics and Genome Research, International Journal of Oncology, Journal of Cellular and Molecular Medicine, and Molecular Medicine Reports. He is also a Member of the American Association for Cancer Research, a Founding Member of the International Cytogenetic and Genome Research Society, and an Honorary Member of the Romanian Academy of Medical Sciences.

Biography Updated on 26 June 2008

Personal Home Page

http://ccr.cancer.gov/staff/staff.asp?profileid=5836

Articles in Scholarly Journals [Incomplete List]

  1. The interferon-a responsive gene TMEM7 suppresses cell proliferation and is downregulated in human hepatocellular carcinoma
    Cancer Genetics and Cytogenetics, vol. 177, no. 1, pp. 6–15, 2007
  2. Inhibition of cell proliferation, induction of apoptosis, reactivation of DLC1, and modulation of other gene expression by dietary flavone in breast cancer cell lines
    Cancer Detection and Prevention, vol. 31, no. 2, pp. 110–118, 2007
  3. Morphological changes and nuclear translocation of DLC1 tumor suppressor protein precede apoptosis in human non-small cell lung carcinoma cells
    Experimental Cell Research, vol. 313, no. 18, pp. 3868–3880, 2007
  4. Deleted in liver cancer 3 (DLC-3), a novel Rho GTPase-activating protein, is downregulated in cancer and inhibits tumor cell growth
    Oncogene, vol. 26, no. 31, Article ID 1210244, 9 pages, 2007
  5. Oncogenic inhibition by a deleted in liver cancer gene requires cooperation between tensin binding and Rho-specific GTPase-activating protein activities
    Proceedings of the National Academy of Sciences, vol. 104, no. 21, pp. 9012–9017, 2007
  6. DLC-1:a Rho GTPase-activating protein and tumour suppressor
    Journal of Cellular and Molecular Medicine, vol. 11, no. 5, pp. 1185–1207, 2007
  7. Enrichment of a Population of Mammary Gland Cells that Form Mammospheres and Have In vivo Repopulating Activity
    Cancer Research, vol. 67, no. 17, pp. 8131–8138, 2007
  8. Nonclassic Functions of Human Topoisomerase I: Genome-Wide and Pharmacologic Analyses
    Cancer Research, vol. 67, no. 18, pp. 8752–8761, 2007
  9. Aberrant Methylation and Deacetylation of Deleted in Liver Cancer-1 Gene in Prostate Cancer: Potential Clinical Applications
    Clinical Cancer Research, vol. 12, no. 5, pp. 1412–1419, 2006
  10. POTE Paralogs Are Induced and Differentially Expressed in Many Cancers
    Cancer Research, vol. 66, no. 1, pp. 52–56, 2006
  11. Molecular Medicine, vol. 12, no. 1-3, p. 1, 2006
  12. The RhoGAP Protein DLC-1 Functions as a Metastasis Suppressor in Breast Cancer Cells
    Cancer Research, vol. 65, no. 14, pp. 6042–6053, 2005
  13. Assignment1 of murine placental cathepsin R to mouse chromosome bands 13B2–B3 by fluorescence in situ hybridization
    Cytogenetic and Genome Research, vol. 111, no. 1, pp. 96D–96D, 2005
  14. GTF2IRD1 in Craniofacial Development of Humans and Mice
    Science, vol. 310, no. 5751, pp. 1184–1187, 2005
  15. The Human AKNA Gene Expresses Multiple Transcripts and Protein Isoforms as a Result of Alternative Promoter Usage, Splicing, and Polyadenylation
    DNA and Cell Biology, vol. 24, no. 5, pp. 325–338, 2005
  16. DLC-1, a Rho GTPase-activating protein with tumor suppressor function, is essential for embryonic development
    FEBS Letters, vol. 579, no. 5, pp. 1191–1196, 2005
  17. Chromosomal aberrations in cell lines derived from thyroid tumors spontaneously developed in TRß mice
    Cancer Genetics and Cytogenetics, vol. 161, no. 2, pp. 104–109, 2005
  18. Rho GTPase activating protein cDNA on chromosome 13q12 is the deleted in liver cancer (DLC2) gene
    Biochemical and Biophysical Research Communications, vol. 315, no. 4, p. 781, 2004
  19. Senescing human cells and ageing mice accumulate DNA lesions with unrepairable double-strand breaks
    Nature Cell Biology, vol. 6, no. 2, Article ID ncb1095, 2 pages, 2004
  20. Fragile sites and cancer genes on the short arm of chromosome 8
    The Lancet Oncology, vol. 5, no. 2, pp. 77–77, 2004
  21. Thirteen-exon-motif signature for vertebrate nuclear and mitochondrial type IB topoisomerases
    Nucleic Acids Research, vol. 32, no. 7, pp. 2087–2092, 2004
  22. Aberrant Gene Expression in Human Non Small Cell Lung Carcinoma Cells Exposed to Demethylating Agent 5-Aza-2′-Deoxycytidine
    Neoplasia, vol. 6, no. 4, pp. 412–419, 2004
  23. WWOX, the common chromosomal fragile site, FRA16D, cancer gene
    Cytogenetic and Genome Research, vol. 100, no. 1-4, pp. 101–110, 2003
  24. High-penetrance mouse model of acute promyelocytic leukemia with very low levels of PML-RAR  expression
    Blood, vol. 102, no. 5, pp. 1857–1865, 2003
  25. Identification and characterization of a gene encoding a putative mouse Rho GTPase activating protein gene 8, Arhgap8
    Gene, vol. 303, pp. 55–61, 2003
  26. Genetic alterations in cancer as a result of breakage at fragile sites
    Cancer Letters, vol. 192, no. 1, pp. 1–17, 2003
  27. DLC-1 gene inhibits human breast cancer cell growth and in vivo tumorigenicity
    Oncogene, vol. 22, no. 3, Article ID 1206064, 5 pages, 2003
  28. Restoration of DLC-1 gene expression induces apoptosis and inhibits both cell growth and tumorigenicity in human hepatocellular carcinoma cells
    Oncogene, vol. 23, no. 6, Article ID 1207246, 5 pages, 2003
  29. DLC-1 operates as a tumor suppressor gene in human non-small cell lung carcinomas
    Oncogene, vol. 23, no. 7, Article ID 1207291, 6 pages, 2003
  30. Promoter hypermethylation of DLC-1, a candidate tumor suppressor gene, in several common human cancers
    Cancer Genetics and Cytogenetics, vol. 140, no. 2, pp. 113–117, 2003
  31. GCF2: expression and molecular analysis of repression
    Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression, vol. 1629, no. 1-3, pp. 15–25, 2003
  32. Gene structure, tissue expression, and linkage mapping of the mouse DLC-1 gene (Arhgap7)
    Gene, vol. 288, no. 1-2, pp. 119–127, 2002
  33. Chromosome and gene alterations in breast cancer as markers for diagnosis and prognosis as well as pathogenetic targets for therapy
    American Journal of Medical Genetics, vol. 115, no. 3, pp. 142–149, 2002
  34. A Polymorphism in the Human UGRP1 Gene Promoter That Regulates Transcription Is Associated with an Increased Risk of Asthma
    The American Journal of Human Genetics, vol. 70, no. 3, pp. 718–725, 2002
  35. Chromosome-mediated alterations of the MYC gene in human cancer
    Journal of Cellular and Molecular Medicine, vol. 6, no. 2, pp. 151–159, 2002
  36. Reassignment1 of Mycs gene to mouse chromosome XA1.2–2 by radiation hybrid mapping and fluorescence in situ hybridization
    Cytogenetic and Genome Research, vol. 97, no. 1-2, pp. 140G–0, 2002
  37. Cloning, expression, and chromosomal localization of the mouse gene (Scgb3a1, alias Ugrp2) that encodes a member of the novel uteroglobin-related protein gene family
    Cytogenetic and Genome Research, vol. 97, no. 1-2, pp. 120–127, 2002
  38. Telomerase contributes to tumorigenesis by a telomere length-independent mechanism
    Proceedings of the National Academy of Sciences, vol. 99, no. 20, pp. 12606–12611, 2002
  39. POTE, a highly homologous gene family located on numerous chromosomes and expressed in prostate, ovary, testis, placenta, and prostate cancer
    Proceedings of the National Academy of Sciences, vol. 99, no. 26, pp. 16975–16980, 2002
  40. Human mitochondrial topoisomerase I
    Proceedings of the National Academy of Sciences, vol. 98, no. 19, pp. 10608–10613, 2001
  41. Nature Medicine, vol. 7, no. 8, pp. 961–966, 2001
  42. claudin-18, a Novel Downstream Target Gene for the T/EBP/NKX2.1 Homeodomain Transcription Factor, Encodes Lung- and Stomach-Specific Isoforms through Alternative Splicing
    Molecular and Cellular Biology, vol. 21, no. 21, pp. 7380–7390, 2001
  43. Thirteen UDPglucuronosyltransferase genes are encoded at the human UGT1 gene complex locus
    Pharmacogenetics, vol. 11, no. 4, pp. 357–368, 2001
  44. Human breast cancer cells generated by oncogenic transformation of primary mammary epithelial cells
    Genes & Development, vol. 15, no. 1, pp. 50–65, 2001
  45. UGRP1, a Uteroglobin/Clara Cell Secretory Protein-Related Protein, Is a Novel Lung-Enriched Downstream Target Gene for the T/EBP/NKX2.1 Homeodomain Transcription Factor
    Molecular Endocrinology, vol. 15, no. 11, pp. 2021–2036, 2001
  46. Integration of a c-myc Transgene Results in Disruption of the Mouse Gtf2ird1 Gene, the Homologue of the Human GTF2IRD1 Gene Hemizygously Deleted in Williams–Beuren Syndrome
    Genomics, vol. 73, no. 1, pp. 20–27, 2001
  47. Characterization of a familial RCC-associated t(2;3)(q33;q21) chromosome translocation
    Journal of Human Genetics, vol. 46, no. 12, pp. 685–693, 2001
  48. Identification of rat mammary tumor-1 gene (RMT-1), which is highly expressed in rat mammary tumors
    Cancer Letters, vol. 174, no. 1, pp. 45–55, 2001
  49. Nature Medicine, vol. 7, no. 11, pp. 1255–1255, 2001
  50. Novel genomic imbalances and chromosome translocations involving c-myc gene in Burkitt’s lymphoma
    Leukemia, vol. 15, no. 10, Article ID 2402281, 6 pages, 2001
  51. Deletion 5p11 accompanied by multiple numerical changes in testicular lymphoma
    Cancer Genetics and Cytogenetics, vol. 131, no. 1, pp. 79–81, 2001
  52. Identification of a YAC from 16q24 carrying a senescence gene for breast cancer cells
    Oncogene, vol. 19, no. 2, pp. 217–222, 2000
  53. Vitamin E reduces chromosomal damage and inhibits hepatic tumor formation in a transgenic mouse model
    Proceedings of the National Academy of Sciences, vol. 97, no. 5, pp. 2196–2201, 2000
  54. Comprehensive genetic analysis of cancer cells
    Journal of Cellular and Molecular Medicine, vol. 4, no. 3, pp. 151–163, 2000
  55. Acquired, nonrandom chromosomal abnormalities associated with the development of acute promyelocytic leukemia in transgenic mice
    Proceedings of the National Academy of Sciences, vol. 97, no. 24, pp. 13306–13311, 2000
  56. Defects in transforming growth factor-beta signaling cooperate with a Ras oncogene to cause rapid aneuploidy and malignant transformation of mouse keratinocytes
    Proceedings of the National Academy of Sciences, vol. 96, no. 26, pp. 14949–14954, 1999
  57. Recurrent alterations of the short arm of chromosome 3 define a tumor suppressor region in rat mammary tumor cells
    Carcinogenesis, vol. 20, no. 10, pp. 2033–2036, 1999
  58. Flavone acetic acid induces a G2/M cell cycle arrest in mammary carcinoma cells
    British Journal of Cancer, vol. 80, no. 12, pp. 1905–1911, 1999
  59. Nonrandom Breakpoints of Unbalanced Chromosome Translocations in Human Hepatocellular Carcinoma Cell Lines
    Cancer Genetics and Cytogenetics, vol. 111, no. 1, pp. 37–44, 1999
  60. Palmitoyl-protein thioesterase gene expression in the developing mouse brain and retina: Implications for early loss of vision in infantile neuronal ceroid lipofuscinosis
    Gene, vol. 231, no. 1-2, pp. 203–211, 1999
  61. Sister Chromatid Exchange Formation in Mammalian Cells Is Modulated by Deoxyribonucleotide Pool Imbalance
    Somatic Cell and Molecular Genetics, vol. 25, no. 2, pp. 101–108, 1999
  62. Human FRAG1 Encodes a Novel Membrane-Spanning Protein That Localizes to Chromosome 11p15.5, a Region of Frequent Loss of Heterozygosity in Cancer
    Genomics, vol. 62, no. 1, pp. 59–66, 1999
  63. Novel recurrent genetic imbalances in human hepatocellular carcinoma cell lines identified by comparative genomic hybridization
    Hepatology, vol. 29, no. 4, pp. 1208–1214, 1999
  64. Localization of the Human Stat6 Gene to Chromosome 12q13.3–q14.1, a Region Implicated in Multiple Solid Tumors
    Genomics, vol. 52, no. 2, pp. 192–200, 1998
  65. BID, a Proapoptotic BCL-2 Family Member, Is Localized to Mouse Chromosome 6 and Human Chromosome 22q11
    Genomics, vol. 53, no. 2, pp. 235–238, 1998
  66. Identification of Mammaglobin B, a Novel Member of the Uteroglobin Gene Family
    Genomics, vol. 54, no. 1, pp. 70–78, 1998
  67. In silico- initiated cloning and molecular characterization of a novel human member of the L1 gene family of neural cell adhesion molecules
    Human Genetics, vol. 103, no. 3, pp. 355–364, 1998
  68. Natural melatonin 'knockdown' in C57BL/6J mice: rare mechanism truncates serotonin N-acetyltransferase
    Molecular Brain Research, vol. 63, no. 1, pp. 189–197, 1998
  69. A Chromosome 4 Satellite I DNA Isolated from SV40-Transformed Human Cells
    DNA Research, vol. 5, no. 5, pp. 271–276, 1998
  70. Cloning, Mapping, Expression, Function, and Mutation Analyses of the Human Ortholog of the Hamster Putative Tumor Suppressor Gene doc-1
    Journal of Biological Chemistry, vol. 273, no. 12, pp. 6704–6709, 1998
  71. GFRalpha 3 is an orphan member of the GDNF/neurturin/persephin receptor family
    Proceedings of the National Academy of Sciences, vol. 95, no. 10, pp. 5801–5806, 1998
  72. Molecular Cloning, Chromosomal Localization, and Expression of Murine Dipeptidyl Peptidase I
    Journal of Biological Chemistry, vol. 272, no. 16, pp. 10695–10703, 1997
  73. Mechanism of Homophilic Binding Mediated by Ninjurin, a Novel Widely Expressed Adhesion Molecule
    Journal of Biological Chemistry, vol. 272, no. 34, pp. 21373–21380, 1997
  74. Purification and molecular cloning of a secreted, Frizzled-related antagonist of Wnt action
    Proceedings of the National Academy of Sciences, vol. 94, no. 13, pp. 6770–6775, 1997
  75. Fluorescence in situ hybridization analysis of keratinocyte growth factor gene amplification and dispersion in evolution of great apes and humans
    Proceedings of the National Academy of Sciences, vol. 94, no. 21, pp. 11461–11465, 1997
  76. Molecular cytogenetic characterization of cancer cell alterations
    Cancer Genetics and Cytogenetics, vol. 93, no. 1, pp. 10–21, 1997
  77. TrnR2, a Novel Receptor That Mediates Neurturin and GDNF Signaling through Ret
    Neuron, vol. 18, no. 5, pp. 793–802, 1997
  78. Neurturin, a Novel Neurotrophic Factor, Is Localized to Mouse Chromosome 17 and Human Chromosome 19p13.3
    Genomics, vol. 44, no. 1, pp. 137–140, 1997
  79. Mapping of the galectin-3 gene (LGALS3) to human Chromosome 14 at region 14q21–22
    Mammalian Genome, vol. 8, no. 9, pp. 706–707, 1997
  80. Papillomaviruses and potential copathogens
    Toxicology Letters, vol. 88, no. 1-3, pp. 1–7, 1996
  81. Deletion and Translocation Involving Chromosome 3(p14) in Two Tumorigenic Kaposi's Sarcoma Cell Lines
    Journal of the National Cancer Institute, vol. 88, no. 7, pp. 450–455, 1996
  82. Human Macrophage Metalloelastase
    Journal of Biological Chemistry, vol. 270, no. 24, pp. 14568–14575, 1995
  83. Molecular cytogenetics of human papillomavirus-negative cervical carcinoma cell lines
    Cancer Genetics and Cytogenetics, vol. 82, no. 1, pp. 1–8, 1995
  84. Structural organization of the human sorbitol dehydrogenase gene (SORD)
    Genomics, vol. 26, no. 1, pp. 55–62, 1995
  85. Acquisition of multiple copies of a mutant topoisomerase IIa allele by chromosome 17 aneuploidy is associated with etoposide resistance in human melanoma cell lines
    Somatic Cell and Molecular Genetics, vol. 21, no. 6, pp. 451–471, 1995
  86. Refined localization of the erbB-3 proto-oncogene by direct visualization of FISH signals on LUT-inverted and contrast-enhanced digital images of DAPI-banded chromosomes
    Cancer Genetics and Cytogenetics, vol. 80, no. 2, pp. 100–102, 1995
  87. CDKN2 in HPV-positive and HPV-negative cervical-carcinoma cell lines
    International Journal of Cancer, vol. 63, no. 2, pp. 226–230, 1995
  88. Integration site of human papillomavirus type-18 DNA in chromosome band 8q22.1 of C4-1 cervical carcinoma: DNase I hypersensitivity and methylation of cellular flanking sequences
    Genes, Chromosomes and Cancer, vol. 9, no. 1, pp. 28–32, 1994
  89. Putative “MDR enhancer” is located on human chromosome 20 and not linked to theMDRI gene on chromosome 7
    Genes, Chromosomes and Cancer, vol. 10, no. 4, pp. 267–274, 1994
  90. An improved procedure for chromosome preparations from solid tumors
    Cancer Genetics and Cytogenetics, vol. 72, no. 2, p. 161, 1994
  91. Multistage carcinogenesis utilizing human genital cells and human papillomaviruses
    Toxicology Letters, vol. 72, no. 1-3, pp. 7–11, 1994
  92. Mapping of a Rat Multidrug Resistance Gene by Fluorescence in Situ Hybridization
    Genomics, vol. 15, no. 1, pp. 182–184, 1993
  93. A Burkitt Lymphoma Cell Line with Integrated Epstein-Barr Virus at a Stable Chromosome Modification Site
    Virology, vol. 195, no. 1, pp. 248–251, 1993
  94. Cytogenetics of cervical neoplasia
    Cancer Genetics and Cytogenetics, vol. 60, no. 2, pp. 214–215, 1992
  95. HSV-2-induced tumorigenicity in HPV16-immortalized human genital keratinocytes
    Virology, vol. 177, no. 2, pp. 777–779, 1990
  96. Chromosomal localization of the gene for a human cytosolic thyroid hormone binding protein homologous to the subunit of pyruvate kinase, subtype M2
    Somatic Cell and Molecular Genetics, vol. 16, no. 6, pp. 593–598, 1990
  97. A Cluster of Hematopoietic Serine Protease Genes is Found on the Same Chromosomal Band as the Human  /  T-Cell Receptor Locus
    Proceedings of the National Academy of Sciences, vol. 87, no. 3, pp. 960–963, 1990
  98. Preferential sites for viral integration on mammalian genome
    Cancer Genetics and Cytogenetics, vol. 42, no. 2, pp. 157–171, 1989
  99. Two type II keratin genes are localized on human chromosome 12
    Human Genetics, vol. 82, no. 2, pp. 109–112, 1989
  100. Chromosomal localization of DBL oncogene sequences*1, *2
    Genomics, vol. 5, no. 3, pp. 546–553, 1989
  101. Localization of the human erbB-2 gene on normal and rearranged chromosomes 17 to bands q12?21.32*1
    Genomics, vol. 4, no. 3, pp. 362–366, 1989
  102. Chromosomal localization of three humanras genes by in situ molecular hybridization
    Somatic Cell and Molecular Genetics, vol. 11, no. 2, pp. 149–155, 1985
  103. Isolation and Chromosomal Localization of the Human fgr Protooncogene, a Distinct Member of the Tyrosine Kinase Gene Family
    Proceedings of the National Academy of Sciences, vol. 82, no. 19, pp. 6595–6599, 1985
  104. Human and rodent transformed cells are more sensitive to in vitro induction of SCE by N-methyl-N?-nitro-N-nitrosoguanidine (MNNG) than normal cells
    Human Genetics, vol. 63, no. 1, pp. 53–57, 1983
  105. 12-O-tetradecanoyl-phorbol-13-acetate and its relationship to SCE induction in syrian and chinese hamster cells
    Environmental Mutagenesis, vol. 4, no. 1, pp. 73–81, 1982
  106. Cytologic detection of virus-specific DNA by in situ hybridization in syrian hamster embryo cells transformed by viral or combined chemical and viral treatment
    Cancer Genetics and Cytogenetics, vol. 7, no. 3, pp. 197–207, 1982
  107. Relationship of carcinogen-induced sister-chromatid exchange (SCE) and neoplastic cell transformation
    Mutation Research/Environmental Mutagenesis and Related Subjects, vol. 85, no. 6, p. 439, 1981
  108. Relationship of carcinogen-induced sister chromatid exchange and neoplastic cell transformation
    International Journal of Cancer, vol. 28, no. 1, pp. 71–76, 1981
  109. Induction by inorganic metal salts of sister chromatid exchanges and chromosome aberrations in human and syrian hamster cell strains
    Environmental Mutagenesis, vol. 3, no. 6, pp. 597–606, 1981
  110. Reduced N-methyl-N?-nitro-N-nitrosoguanidine sister chromatid exchange induction in chinese hamster V79 cells pre-exposed to 5-bromodeoxyuridine
    Chromosoma, vol. 76, no. 3, pp. 329–338, 1980
  111. Antipain Inhibits N-methyl-N'-nitro-N-nitrosoguanidine-induced Transformation and Increases Chromosomal Aberrations
    Proceedings of the National Academy of Sciences, vol. 77, no. 11, pp. 6649–6653, 1980
  112. Enhancement of N-methyl-N'-nitro-N-nitrosoguanidine Transformation of Syrian Hamster Cells by a Phorbol Diester is Independent of Sister Chromatid Exchanges and Chromosome Aberrations
    Proceedings of the National Academy of Sciences, vol. 77, no. 12, pp. 7282–7286, 1980
  113. cis-platinum(II) diamine dichloride causes mutation, transformation, and sister-chromatid exchanges in cultured mammalian cells
    Mutation Research/Genetic Toxicology, vol. 66, no. 3, pp. 267–275, 1979
  114. The relevance of caffeine post-treatment to SCE incidence induced in Chinese hamster cells
    Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, vol. 60, no. 3, pp. 313–320, 1979
  115. Banding pattern analysis of initial structural chromosome alterations induced by N-methyl-N'-nitro-N-nitrosoguanidine in Syrian hamster cells
    Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, vol. 44, no. 3, pp. 359–368, 1977
  116. Vulnerability of specific rat chromosomes toin vitro chemically induced damage
    International Journal of Cancer, vol. 19, no. 3, pp. 419–433, 1977