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. 1985 Sep;52(3):293–302. doi: 10.1038/bjc.1985.193

The 1985 Walter Hubert lecture. Malignant cell differentiation as a potential therapeutic approach.

A C Sartorelli
PMCID: PMC1977206  PMID: 3899154

Abstract

Most drugs available for cancer chemotherapy exert their effects through cytodestruction. Although significant advances have been attained with these cytotoxic agents in several malignant diseases, response is often accompanied by significant morbidity and many common malignant tumours respond poorly to existing cytotoxic therapy. Development of chemotherapeutic agents with non-cytodestructive actions appears desirable. Considerable evidence exists which indicates that (a) the malignant state is not irreversible and represents a disease of altered maturation, and (b) some experimental tumour systems can be induced by chemical agents to differentiate to mature end-stage cells with no proliferative potential. Thus, it is conceivable that therapeutic agents can be developed which convert cancer cells to benign forms. To study the phenomenon of blocked maturation, squamous carcinoma SqCC/Y1 cells were employed in culture. Using this system it was possible to demonstrate that physiological levels of retinoic acid and epidermal growth factor were capable of preventing the differentiation of these malignant keratinocytes into a mature tissue-like structure. The terminal differentiation caused by certain antineoplastic agents was investigated in HL-60 promyelocytic leukaemia cells to provide information on the mechanism by which chemotherapeutic agents induce cells to by-pass a maturation block. The anthracyclines aclacinomycin A and marcellomycin were potent inhibitors of N-glycosidically linked glycoprotein biosynthesis and transferrin receptor activity, and active inducers of maturation; temporal studies suggested that the biochemical effects were associated with the differentiation process. 6-Thioguanine produced cytotoxicity in parental cells by forming analog nucleotide. In hypoxanthine-guanine phosphoribosyltransferase negative HL-60 cells the 6-thiopurine initiated maturation; this action was due to the free base (and possibly the deoxyribonucleoside), a finding which separated termination of proliferation due to cytotoxicity from that caused by maturation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abe E., Miyaura C., Sakagami H., Takeda M., Konno K., Yamazaki T., Yoshiki S., Suda T. Differentiation of mouse myeloid leukemia cells induced by 1 alpha,25-dihydroxyvitamin D3. Proc Natl Acad Sci U S A. 1981 Aug;78(8):4990–4994. doi: 10.1073/pnas.78.8.4990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BIEBER A. L., SARTORELLI A. C. THE METABOLISM OF THIOGUANINE IN PURINE ANALOG-RESISTANT CELLS. Cancer Res. 1964 Aug;24:1210–1215. [PubMed] [Google Scholar]
  3. BROCKMAN R. W. MECHANISMS OF RESISTANCE TO ANTICANCER AGENTS. Adv Cancer Res. 1963;7:129–234. doi: 10.1016/s0065-230x(08)60983-5. [DOI] [PubMed] [Google Scholar]
  4. Bodner A. J., Ting R. C., Gallo R. C. Induction of differentiation of human promyelocytic leukemia cells (HL-60) by nucleosides and methotrexate. J Natl Cancer Inst. 1981 Nov;67(5):1025–1030. [PubMed] [Google Scholar]
  5. Breitman T. R., Selonick S. E., Collins S. J. Induction of differentiation of the human promyelocytic leukemia cell line (HL-60) by retinoic acid. Proc Natl Acad Sci U S A. 1980 May;77(5):2936–2940. doi: 10.1073/pnas.77.5.2936. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brinster R. L. The effect of cells transferred into the mouse blastocyst on subsequent development. J Exp Med. 1974 Oct 1;140(4):1049–1056. doi: 10.1084/jem.140.4.1049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Carrico C. K., Sartorelli A. C. Effects of 6-thioguanine on RNA biosynthesis in regenerating rat liver. Cancer Res. 1977 Jun;37(6):1876–1882. [PubMed] [Google Scholar]
  8. Cline P. R., Rice R. H. Modulation of involucrin and envelope competence in human keratinocytes by hydrocortisone, retinyl acetate, and growth arrest. Cancer Res. 1983 Jul;43(7):3203–3207. [PubMed] [Google Scholar]
  9. Collins S. J., Bodner A., Ting R., Gallo R. C. Induction of morphological and functional differentiation of human promyelocytic leukemia cells (HL-60) by componuds which induce differentiation of murine leukemia cells. Int J Cancer. 1980 Feb 15;25(2):213–218. doi: 10.1002/ijc.2910250208. [DOI] [PubMed] [Google Scholar]
  10. Cossu G., Kuo A. L., Pessano S., Warren L., Cooper R. A. Decreased synthesis of high-molecular-weight glycopeptides in human promyelocytic leukemic cells (HL-60) during phorbol ester-induced macrophage differentiation. Cancer Res. 1982 Feb;42(2):484–489. [PubMed] [Google Scholar]
  11. Creek K. E., Morré D. J., Silverman-Jones C. S., Shidoji Y., De Luca L. M. Mannosyl carrier functions of retinyl phosphate and dolichyl phosphate in rat liver endoplasmic reticulum. Biochem J. 1983 Feb 15;210(2):541–547. doi: 10.1042/bj2100541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Crooke S. T., Duvernay V. H., Galvan L., Prestayko A. W. Structure-activity relationships of anthracyclines relative to effects on macromolecular syntheses. Mol Pharmacol. 1978 Mar;14(2):290–298. [PubMed] [Google Scholar]
  13. DeCosse J. J., Gossens C. L., Kuzma J. F., Unsworth B. R. Breast cancer: induction of differentiation by embryonic tissue. Science. 1973 Sep 14;181(4104):1057–1058. doi: 10.1126/science.181.4104.1057. [DOI] [PubMed] [Google Scholar]
  14. DuVernay V. H., Essery J. M., Doyle T. W., Bradner W. T., Crooke S. T. The antitumor effects of anthracyclines. The importance of the carbomethoxy-group at position-10 of marcellomycin and rudolfomycin. Mol Pharmacol. 1979 Mar;15(2):341–356. [PubMed] [Google Scholar]
  15. DuVernay V. H., Jr, Pachter J. A., Crooke S. T. Deoxyribonucleic acid binding studies on several new anthracycline antitumor antibiotics. Sequence preference and structure--activity relationships of marcellomycin and its analogues as compared to adriamycin. Biochemistry. 1979 Sep 4;18(18):4024–4030. doi: 10.1021/bi00585a028. [DOI] [PubMed] [Google Scholar]
  16. Ebert P. S., Wars I., Buell D. N. Erythroid differentiation in cultured Friend leukemia cells treated with metabolic inhibitors. Cancer Res. 1976 May;36(5):1809–1813. [PubMed] [Google Scholar]
  17. Falcone G., Tatò F., Alemà S. Distinctive effects of the viral oncogenes myc, erb, fps, and src on the differentiation program of quail myogenic cells. Proc Natl Acad Sci U S A. 1985 Jan;82(2):426–430. doi: 10.1073/pnas.82.2.426. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Felsted R. L., Gupta S. K., Glover C. J., Fischkoff S. A., Gallagher R. E. Cell surface membrane protein changes during the differentiation of cultured human promyelocytic leukemia HL-60 cells. Cancer Res. 1983 Jun;43(6):2754–2761. [PubMed] [Google Scholar]
  19. Fibach E., Gambari R., Shaw P. A., Maniatis G., Reuben R. C., Sassa S., Rifkind R. A., Marks P. A. Tumor promoter-mediated inhibition of cell differentiation: suppression of the expression of erythroid functions in murine erythroleukemia cells. Proc Natl Acad Sci U S A. 1979 Apr;76(4):1906–1910. doi: 10.1073/pnas.76.4.1906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Friend C., Scher W., Holland J. G., Sato T. Hemoglobin synthesis in murine virus-induced leukemic cells in vitro: stimulation of erythroid differentiation by dimethyl sulfoxide. Proc Natl Acad Sci U S A. 1971 Feb;68(2):378–382. doi: 10.1073/pnas.68.2.378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Fuchs E., Green H. Regulation of terminal differentiation of cultured human keratinocytes by vitamin A. Cell. 1981 Sep;25(3):617–625. doi: 10.1016/0092-8674(81)90169-0. [DOI] [PubMed] [Google Scholar]
  22. Gallagher R. E., Ferrari A. C., Zulich A. W., Yen R. W., Testa J. R. Cytotoxic and cytodifferentiative components of 6-thioguanine resistance in HL-60 cells containing acquired double minute chromosomes. Cancer Res. 1984 Jun;44(6):2642–2653. [PubMed] [Google Scholar]
  23. Garrett C., Kredich N. M. Induction of hemoglobin synthesis by xylosyladenine in murine erythroleukemia cells. Metabolism of xylosyladenine and effects on transmethylation. J Biol Chem. 1981 Dec 25;256(24):12705–12709. [PubMed] [Google Scholar]
  24. Gootwine E., Webb C. G., Sachs L. Participation of myeloid leukaemic cells injected into embryos in haematopoietic differentiation in adult mice. Nature. 1982 Sep 2;299(5878):63–65. doi: 10.1038/299063a0. [DOI] [PubMed] [Google Scholar]
  25. Green H., Watt F. M. Regulation by vitamin A of envelope cross-linking in cultured keratinocytes derived from different human epithelia. Mol Cell Biol. 1982 Sep;2(9):1115–1117. doi: 10.1128/mcb.2.9.1115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Gusella J. F., Housman D. Induction of erythroid differentiation in vitro by purines and purine analogues. Cell. 1976 Jun;8(2):263–269. doi: 10.1016/0092-8674(76)90010-6. [DOI] [PubMed] [Google Scholar]
  27. Gusella J., Geller R., Clarke B., Weeks V., Housman D. Commitment to erythroid differentiation by friend erythroleukemia cells: a stochastic analysis. Cell. 1976 Oct;9(2):221–229. doi: 10.1016/0092-8674(76)90113-6. [DOI] [PubMed] [Google Scholar]
  28. HAMPTON A. REACTIONS OF RIBONUCLEOTIDE DERIVATIVES OF PURINE ANALOGUES AT THE CATALYTIC SITE OF INOSINE 5'-PHOSPHATE DEHYDROGENASE. J Biol Chem. 1963 Sep;238:3068–3074. [PubMed] [Google Scholar]
  29. Heifetz A., Keenan R. W., Elbein A. D. Mechanism of action of tunicamycin on the UDP-GlcNAc:dolichyl-phosphate Glc-NAc-1-phosphate transferase. Biochemistry. 1979 May 29;18(11):2186–2192. doi: 10.1021/bi00578a008. [DOI] [PubMed] [Google Scholar]
  30. Hill D. L., Bennett L. L., Jr Purification and properties of 5-phosphoribosyl pyrophosphate amidotransferase from adenocarcinoma 755 cells. Biochemistry. 1969 Jan;8(1):122–130. doi: 10.1021/bi00829a017. [DOI] [PubMed] [Google Scholar]
  31. Huberman E., Callaham M. F. Induction of terminal differentiation in human promyelocytic leukemia cells by tumor-promoting agents. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1293–1297. doi: 10.1073/pnas.76.3.1293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Ishiguro K., Sartorelli A. C. Enhancement of the differentiation-inducing properties of 6-thioguanine by hypoxanthine and its nucleosides in HL-60 promyelocytic leukemia cells. Cancer Res. 1985 Jan;45(1):91–95. [PubMed] [Google Scholar]
  33. Ishiguro K., Schwartz E. L., Sartorelli A. C. Characterization of the metabolic forms of 6-thioguanine responsible for cytotoxicity and induction of differentiation of HL-60 acute promyelocytic leukemia cells. J Cell Physiol. 1984 Nov;121(2):383–390. doi: 10.1002/jcp.1041210216. [DOI] [PubMed] [Google Scholar]
  34. Keoffler H. P., Yen J., Carlson J. The study of human myeloid differentiation using bromodeoxyuridine (BrdU). J Cell Physiol. 1983 Jul;116(1):111–117. doi: 10.1002/jcp.1041160117. [DOI] [PubMed] [Google Scholar]
  35. Kim K. H., Schwartz F., Fuchs E. Differences in keratin synthesis between normal epithelial cells and squamous cell carcinomas are mediated by vitamin A. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4280–4284. doi: 10.1073/pnas.81.14.4280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Kwan S. W., Kwan S. P., Mandel H. G. The incorporation of 6-thioguanine into RNA fractions and its effect on RNA and protein biosynthesis in mouse sarcoma 180 ascites cells. Cancer Res. 1973 May;33(5):950–955. [PubMed] [Google Scholar]
  37. LEPAGE G. A., HOWARD N. Chemotherapy studies of mammary tumors of C3H mice. Cancer Res. 1963 May;23:622–627. [PubMed] [Google Scholar]
  38. LEPAGE G. A. Incorporation of 6-thioguanine into nucleic acids. Cancer Res. 1960 Apr;20:403–408. [PubMed] [Google Scholar]
  39. LEPAGE G. A., JONES M. Further studies on the mechanism of action of 6-thioguanine. Cancer Res. 1961 Dec;21:1590–1594. [PubMed] [Google Scholar]
  40. Lazo J. S., Hwang K. M., Sartorelli A. C. Inhibition of L-fucose incorporation into glycoprotein of Sarcoma 180 ascites cells by 6-thioguanine. Cancer Res. 1977 Dec;37(12):4250–4255. [PubMed] [Google Scholar]
  41. Lazo J. S., Shansky C. W., Sartorelli A. C. Reduction in cell surface concanavalin A binding and mannose incorporation into glycoproteins of sarcoma 180 by 6-thioguanine. Biochem Pharmacol. 1979 Mar 1;28(5):583–588. doi: 10.1016/0006-2952(79)90139-4. [DOI] [PubMed] [Google Scholar]
  42. Lotem J., Sachs L. Different blocks in the differentiation of myeloid leukemic cells. Proc Natl Acad Sci U S A. 1974 Sep;71(9):3507–3511. doi: 10.1073/pnas.71.9.3507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Lotem J., Sachs L. Induction of specific changes in the surface membrane of myeloid leukemic cells by steroid hormones. Int J Cancer. 1975 May 15;15(5):731–740. doi: 10.1002/ijc.2910150504. [DOI] [PubMed] [Google Scholar]
  44. Lotem J., Sachs L. Regulation of normal differentiation in mouse and human myeloid leukemic cells by phorbol esters and the mechanism of tumor promotion. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5158–5162. doi: 10.1073/pnas.76.10.5158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Lucas D. L., Robins R. K., Knight R. D., Wright D. G. Induced maturation of the human promyelocytic leukemia cell line, HL-60, by 2-beta-D-ribofuranosylselenazole-4-carboxamide. Biochem Biophys Res Commun. 1983 Sep 30;115(3):971–980. doi: 10.1016/s0006-291x(83)80030-8. [DOI] [PubMed] [Google Scholar]
  46. Lucas D. L., Webster H. K., Wright D. G. Purine metabolism in myeloid precursor cells during maturation. Studies with the HL-60 cell line. J Clin Invest. 1983 Dec;72(6):1889–1900. doi: 10.1172/JCI111152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. MCCOLLISTER R. J., GILBERT W. R., Jr, ASHTON D. M., WYNGAARDEN J. B. PSEUDOFEEDBACK INHIBITION OF PURINE SYNTHESIS BY 6-MERCAPTOPURINE RIBONUCLEOTIDE AND OTHER PURINE ANALOGUES. J Biol Chem. 1964 May;239:1560–1563. [PubMed] [Google Scholar]
  48. Metcalf D., Moore M. A., Warner N. L. Colony formation in vitro by myelomonocytic leukemic cells. J Natl Cancer Inst. 1969 Oct;43(4):983–1001. [PubMed] [Google Scholar]
  49. Miech R. P., Parks R. E., Jr, Anderson J. H., Jr, Sartorelli A. C. An hypothesis on the mechanism of action of 6-thioguanine. Biochem Pharmacol. 1967 Nov;16(11):2222–2227. doi: 10.1016/0006-2952(67)90022-6. [DOI] [PubMed] [Google Scholar]
  50. Miech R. P., York R., Parks R. E., Jr Adenosine triphosphate-guanosine 5'-phosphate phosphotransferase. II. Inhibition by 6-thioguanosine 5'-phosphate of the enzyme isolated from hog brain and sarcoma 180 ascites cells. Mol Pharmacol. 1969 Jan;5(1):30–37. [PubMed] [Google Scholar]
  51. Morin M. J., Sartorelli A. C. Inhibition of glycoprotein biosynthesis by the inducers of HL-60 cell differentiation, aclacinomycin A and marcellomycin. Cancer Res. 1984 Jul;44(7):2807–2812. [PubMed] [Google Scholar]
  52. Murate T., Kaneda T., Rifkind R. A., Marks P. A. Inducer-mediated commitment of murine erythroleukemia cells to terminal cell division: the expression of commitment. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3394–3398. doi: 10.1073/pnas.81.11.3394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Nakai Y., LePage G. A. Characterization of the kinase(s) involved in the phosphorylation of - and -2'-deoxythioguanosine. Cancer Res. 1972 Nov;32(11):2445–2451. [PubMed] [Google Scholar]
  54. Nakayasu M., Terada M., Tamura G., Sugimura T. Induction of differentiation of human and murine myeloid leukemia cells in culture by tunicamycin. Proc Natl Acad Sci U S A. 1980 Jan;77(1):409–413. doi: 10.1073/pnas.77.1.409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Omary M. B., Trowbridge I. S. Biosynthesis of the human transferrin receptor in cultured cells. J Biol Chem. 1981 Dec 25;256(24):12888–12892. [PubMed] [Google Scholar]
  56. Osborne H. B., Bakke A. C., Yu J. Effect of dexamethasone on hexamethylene bisacetamide-induced Friend cell erythrodifferentiation. Cancer Res. 1982 Feb;42(2):513–518. [PubMed] [Google Scholar]
  57. Painter R. B. Inhibition of DNA replicon initiation by 4-nitroquinoline 1-oxide, adriamycin, and ethyleneimine. Cancer Res. 1978 Dec;38(12):4445–4449. [PubMed] [Google Scholar]
  58. Papac R. J., Brown A. E., Schwartz E. L., Sartorelli A. C. Differentiation of human promyelocytic leukemia cells in vitro by 6-thioguanine. Cancer Lett. 1980 Jul;10(1):33–38. doi: 10.1016/0304-3835(80)90062-2. [DOI] [PubMed] [Google Scholar]
  59. Paran M., Sachs L., Barak Y., Resnitzky P. In vitro induction of granulocyte differentiation in hematopoietic cells from leukemic and non-leukemic patients. Proc Natl Acad Sci U S A. 1970 Nov;67(3):1542–1549. doi: 10.1073/pnas.67.3.1542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Parkinson E. K., Grabham P., Emmerson A. A subpopulation of cultured human keratinocytes which is resistant to the induction of terminal differentiation-related changes by phorbol, 12-myristate, 13-acetate: evidence for an increase in the resistant population following transformation. Carcinogenesis. 1983;4(7):857–861. doi: 10.1093/carcin/4.7.857. [DOI] [PubMed] [Google Scholar]
  61. Pierce G. B., Nakane P. K., Martinez-Hernandez A., Ward J. M. Ultrastructural comparison of differentiation of stem cells of murine adenocarcinomas of colon and breast with their normal counterparts. J Natl Cancer Inst. 1977 May;58(5):1329–1345. doi: 10.1093/jnci/58.5.1329. [DOI] [PubMed] [Google Scholar]
  62. Pierce G. B., Wallace C. Differentiation of malignant to benign cells. Cancer Res. 1971 Feb;31(2):127–134. [PubMed] [Google Scholar]
  63. Plagemann P. G., Marz R., Wohlhueter R. M., Graff J. C., Zylka J. M. Facilitated transport of 6-mercaptopurine and 6-thioguanine and non-mediated permeation of 8-azaguanine in Novikoff rat hepatoma cells and relationship to intracellular phosphoribosylation. Biochim Biophys Acta. 1981 Sep 21;647(1):49–62. doi: 10.1016/0005-2736(81)90294-7. [DOI] [PubMed] [Google Scholar]
  64. Prasad K. N. Therapeutic potentials of differentiating agents in neuroblastomas. Prog Clin Biol Res. 1983;132C:75–89. [PubMed] [Google Scholar]
  65. Prescott D. M. The cell cycle and the control of cellular reproduction. Adv Genet. 1976;18:99–177. doi: 10.1016/s0065-2660(08)60438-1. [DOI] [PubMed] [Google Scholar]
  66. Reiss M., Pitman S. W., Sartorelli A. C. Modulation of the terminal differentiation of human squamous carcinoma cells in vitro by all-trans-retinoic acid. J Natl Cancer Inst. 1985 May;74(5):1015–1023. [PubMed] [Google Scholar]
  67. Reuben R. C., Rifkind R. A., Marks P. A. Chemically induced murine erythroleukemic differentiation. Biochim Biophys Acta. 1980 Sep 22;605(3):325–346. doi: 10.1016/0304-419x(80)90015-3. [DOI] [PubMed] [Google Scholar]
  68. Rheinwald J. G., Beckett M. A. Defective terminal differentiation in culture as a consistent and selectable character of malignant human keratinocytes. Cell. 1980 Nov;22(2 Pt 2):629–632. doi: 10.1016/0092-8674(80)90373-6. [DOI] [PubMed] [Google Scholar]
  69. Rice R. H., Cline P. R., Coe E. L. Mutually antagonistic effects of hydrocortisone and retinyl acetate on envelope competence in cultured malignant human keratinocytes. J Invest Dermatol. 1983 Jul;81(1 Suppl):176s–178s. doi: 10.1111/1523-1747.ep12541067. [DOI] [PubMed] [Google Scholar]
  70. SARTORELLI A. C., LEPAGE G. A., MOORE E. C. Metabolic effects of 6-thioguanine. I. Studies on thioguanine-resistant and-sensitive Ehrlich ascites cells. Cancer Res. 1958 Nov;18(10):1232–1239. [PubMed] [Google Scholar]
  71. Sakurai M., Sampi K., Hozumi M. Possible differentiation of human acute myeloblastic leukemia cells by daily and intermittent administration of aclacinomycin-A. Leuk Res. 1983;7(2):139–143. doi: 10.1016/0145-2126(83)90004-8. [DOI] [PubMed] [Google Scholar]
  72. Scher W., Friend C. Breakage of DNA and alterations in folded genomes by inducers of differentiation in Friend erythroleukemic cells. Cancer Res. 1978 Mar;38(3):841–849. [PubMed] [Google Scholar]
  73. Schubert D., Humphreys S., Jacob F., de Vitry F. Induced differentiation of a neuroblastoma. Dev Biol. 1971 Aug;25(4):514–546. doi: 10.1016/0012-1606(71)90004-2. [DOI] [PubMed] [Google Scholar]
  74. Schulman H. M., Wilczynska A., Ponka P. Transferrin and iron uptake by human lymphoblastoid and K-562 cells. Biochem Biophys Res Commun. 1981 Jun;100(4):1523–1530. doi: 10.1016/0006-291x(81)90691-4. [DOI] [PubMed] [Google Scholar]
  75. Schwartz E. L., Brown B. J., Nierenburg M., Marsh J. C., Sartorelli A. C. Evaluation of some anthracycline antibiotics in an in vivo model for studying drug-induced human leukemia cell differentiation. Cancer Res. 1983 Jun;43(6):2725–2730. [PubMed] [Google Scholar]
  76. Schwartz E. L., Ishiguro K., Sartorelli A. C. Induction of leukemia cell differentiation by chemotherapeutic agents. Adv Enzyme Regul. 1983;21:3–20. doi: 10.1016/0065-2571(83)90005-5. [DOI] [PubMed] [Google Scholar]
  77. Schwartz E. L., Sartorelli A. C. Structure-activity relationships for the induction of differentiation of HL-60 human acute promyelocytic leukemia cells by anthracyclines. Cancer Res. 1982 Jul;42(7):2651–2655. [PubMed] [Google Scholar]
  78. Skubitz K. M., August J. T. Analysis of cell-surface protein changes accompanying differentiation of HL-60 cells. Arch Biochem Biophys. 1983 Oct 1;226(1):1–9. doi: 10.1016/0003-9861(83)90265-5. [DOI] [PubMed] [Google Scholar]
  79. Studzinski G. P., Ellem K. A. Differences between diploid and heteroploid cultured mammalian cells in their response to puromycin aminonucleoside. Cancer Res. 1968 Sep;28(9):1773–1782. [PubMed] [Google Scholar]
  80. Sun T. T., Green H. Differentiation of the epidermal keratinocyte in cell culture: formation of the cornified envelope. Cell. 1976 Dec;9(4 Pt 1):511–521. doi: 10.1016/0092-8674(76)90033-7. [DOI] [PubMed] [Google Scholar]
  81. Taetle R., Honeysett J. M., Trowbridge I. Effects of anti-transferrin receptor antibodies on growth of normal and malignant myeloid cells. Int J Cancer. 1983 Sep 15;32(3):343–349. doi: 10.1002/ijc.2910320314. [DOI] [PubMed] [Google Scholar]
  82. Taetle R., Rhyner K., Castagnola J., To D., Mendelsohn J. Role of transferrin, Fe, and transferrin receptors in myeloid leukemia cell growth. Studies with an antitransferrin receptor monoclonal antibody. J Clin Invest. 1985 Mar;75(3):1061–1067. doi: 10.1172/JCI111768. [DOI] [PMC free article] [PubMed] [Google Scholar]
  83. Takenaga K., Hozumi M., Sakagami Y. Effects of retinoids on induction of differentiation of cultured mouse myeloid leukemia cells. Cancer Res. 1980 Mar;40(3):914–919. [PubMed] [Google Scholar]
  84. Tei I., Makino Y., Sakagami H., Kanamaru I., Konno K. Decrease of transferrin receptor during mouse myeloid leukemia (M1) cell differentiation. Biochem Biophys Res Commun. 1982 Aug 31;107(4):1419–1424. doi: 10.1016/s0006-291x(82)80157-5. [DOI] [PubMed] [Google Scholar]
  85. Terada M., Epner E., Nudel U., Salmon J., Fibach E., Rifkind R. A., Marks P. A. Induction of murine erythroleukemia differentiation by actinomycin D. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2795–2799. doi: 10.1073/pnas.75.6.2795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  86. Testa U., Thomopoulos P., Vinci G., Titeux M., Bettaieb A., Vainchenker W., Rochant H. Transferrin binding to K562 cell line. Effect of heme and sodium butyrate induction. Exp Cell Res. 1982 Aug;140(2):251–260. doi: 10.1016/0014-4827(82)90112-4. [DOI] [PubMed] [Google Scholar]
  87. Trowbridge I. S., Lesley J., Schulte R. Murine cell surface transferrin receptor: studies with an anti-receptor monoclonal antibody. J Cell Physiol. 1982 Sep;112(3):403–410. doi: 10.1002/jcp.1041120314. [DOI] [PubMed] [Google Scholar]
  88. Trowbridge I. S., Lopez F. Monoclonal antibody to transferrin receptor blocks transferrin binding and inhibits human tumor cell growth in vitro. Proc Natl Acad Sci U S A. 1982 Feb;79(4):1175–1179. doi: 10.1073/pnas.79.4.1175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  89. Wille J. J., Jr, Pittelkow M. R., Shipley G. D., Scott R. E. Integrated control of growth and differentiation of normal human prokeratinocytes cultured in serum-free medium: clonal analyses, growth kinetics, and cell cycle studies. J Cell Physiol. 1984 Oct;121(1):31–44. doi: 10.1002/jcp.1041210106. [DOI] [PubMed] [Google Scholar]
  90. Wotring L. L., Roti Roti J. L. Thioguanine-induced S and G2 blocks and their significance to the mechanism of cytotoxicity. Cancer Res. 1980 May;40(5):1458–1462. [PubMed] [Google Scholar]
  91. Yamada K., Nakamura T., Tsuruo T., Kitahara T., Maekawa T., Uzaka Y., Kurita S., Masaoka T., Takaku F., Hirota Y. A phase II study of aclacinomycin A in acute leukemia in adults. Cancer Treat Rev. 1980 Dec;7(4):177–182. doi: 10.1016/s0305-7372(80)80033-8. [DOI] [PubMed] [Google Scholar]
  92. Yeh C. J., Papamichael M., Faulk W. P. Loss of transferrin receptors following induced differentiation of HL-60 promyelocytic leukemia cells. Exp Cell Res. 1982 Apr;138(2):429–433. doi: 10.1016/0014-4827(82)90192-6. [DOI] [PubMed] [Google Scholar]
  93. Yen A. Control of HL-60 myeloid differentiation. Evidence of uncoupled growth and differentiation control, S-phase specificity, and two-step regulation. Exp Cell Res. 1985 Jan;156(1):198–212. doi: 10.1016/0014-4827(85)90274-5. [DOI] [PubMed] [Google Scholar]
  94. Yen A., Reece S. L., Albright K. L. Dependence of HL-60 myeloid cell differentiation on continuous and split retinoic acid exposures: precommitment memory associated with altered nuclear structure. J Cell Physiol. 1984 Mar;118(3):277–286. doi: 10.1002/jcp.1041180310. [DOI] [PubMed] [Google Scholar]
  95. Young R. C., Ozols R. F., Myers C. E. The anthracycline antineoplastic drugs. N Engl J Med. 1981 Jul 16;305(3):139–153. doi: 10.1056/NEJM198107163050305. [DOI] [PubMed] [Google Scholar]
  96. Yuspa S. H., Morgan D. L. Mouse skin cells resistant to terminal differentiation associated with initiation of carcinogenesis. Nature. 1981 Sep 3;293(5827):72–74. doi: 10.1038/293072a0. [DOI] [PubMed] [Google Scholar]

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