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Original Article

Application of Chemical Immunomodulators to the Treatment of Cancer and AIDS

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Pages 620-643 | Published online: 11 Jun 2009

References

  • Henkart PA, Yue CC, Yang JH. Cytolytic and biochemical properties of cytoplasmic granules of murine lymphokine activated killer cells. J Immunol 1986; 137: 2611–2617
  • Lin T, Chu TM. Enhancement of murine lymphokine-activated killer cell activity by retinoic acid. Cancer Res 1990; 50: 3013–3018
  • Traill KN, Huber LA, Wick G. Lipoprotein interactions with T cells: An update. Immunol Today 1990; 11: 411–417
  • Robb RJ, Munck A, Smith KA. T cell growth factor receptors. Quantitation, specificity, and biological relevance. J Exp Med 1981; 154: 1455–1465
  • Bowlin TL, Schroeder KK, Fanger BO. Swainsonine, an inhibitor of mannosidase II during glycoprotein processing, enhances concanavalin A-induced T cell proliferation and interleukin 2 receptor expression exclusively via the T cell receptor complex. Cell Immunol 1991; 137: 111–117
  • Di Virgilio F, Pizzo P, Zanovello P. Extracellular ATP as a possible mediator of cell-mediated cytotoxicity. Immunol Today 1990; 11: 274–277
  • Bize IB, Oberley LW, Morris HP. Superoxide dismutase and superoxide radical in Morris hepatomas. Cancer Res 1980; 40: 3686–3693
  • Hoffman B, Nishanian P, Baldwin RL. HIV inhibits the early steps of lymphocyte activation including initiation of inositol phospholipid metabolism. J Immunol 1990; 145: 3699–3705
  • Hrishikeshavan HJ, Ardalan B, Paget E. Inhibition of cyclic nucleotide phosphodiesterase by carbetimer in a human melanoma. Proc Am Assoc Cancer Res 1986; 27: 280, (abstract)
  • Breton P, Asseffa A, Grzegorzewski K. Swainsonine modulation of protein kinase C in murine peritoneal macrophages. Cancer Commun 1990; 2: 333–338
  • Watanabe H, Bannai S. Induction of cystine transport activity in mouse peritoneal macrophage. J Exp Med 1987; 165: 628–640
  • Koren HS, Anderson SJ, Fischer DG. Regulation of human natural killing. I. The role of monocytes, interferon, and prostaglandins. J Immunol 1981; 127: 2007–2013
  • Skinner M, Skinner S, Marbrook J. The effect of prostaglandins and indomethacin on cytotoxic T-lymphocytes and their precursors. Int J Immunopharmacol 1989; 11: 267–273
  • Elliott GR, Tak C, Pellens C. Indomethacin stimulation of macrophage cytostasis against MOP C315 tumor cells is inhibited by prostaglandin E2 and nordihydroguaiaretic acid, a lipoxygenase inhibitor. Cancer Immunol Immunother 1988; 27: 133–136
  • Muscoplat CC, Rakich PM, Thoen CO. Enhancement of lymphocyte blastogenic and delayed hypersensitivity skin responses by indomethacin. Infect Immun 1978; 20: 627–631
  • Manning LS, Bowman RV, Davis MR. Indomethacin augments lymphokine-activated killer cell generation by patients with malignant mesothelioma. Clin Immunol Immunopathol 1989; 53: 68–77
  • Braun DP, Harris ZL, Harris JE. Effect of interferon therapy on indomethacin-sensitive immunoregulation in the peripheral blood mononuclear cells of renal cell carcinoma patients. J Biol Response Mod 1983; 2: 251–262
  • Harris JE, Landay A, Kessler H. Abnormal indomethacin-sensitive suppressor cell function is associated with deficient lymphokine activated killer cell induction in patients infected with the human immunodeficiency disease virus. Proc Am Soc Clin Oncol 1987; 6: 3, (abstract)
  • Reddy BS, Maruyama H, Kelloff G. Dose-related inhibition of colon carcinogenesis by dietary piroxicam, a nonsteroidal antiinflammatory drug, during different stages of rat colon tumor development. Cancer Res 1987; 47: 5340–5346
  • Hial V, Horakova Z, Shaff RE. Alteration of tumor growth by aspirin and indomethacin: Studies with two transplantable tumors in mouse. Eur J Pharmacol 1976; 37: 367–376
  • Khoo N KS, Chan F PH, Saarloos MN. Immunotherapy of metastases with ibuprofen and IL-2. Proc Am Assoc Cancer Res 1990; 31: 275, (abstract)
  • Kim B, Warnaka P. Indomethacin-enhanced immunotherapy of pulmonary metastases using IL-2 and IFN-alpha. Surgery 1989; 106: 248–256
  • Furuta Y, Hall ER, Sanduja S. Prostaglandin production by murine tumors as a predictor for therapeutic response to indomethacin. Cancer Res 1988; 48: 3002–3007
  • Rosenberg L, Palmer JR, Zauber AG. A hypothesis: Nonsteroidal anti-inflammatory drugs reduce the incidence of largebowel cancer. J Natl Cancer Inst 1991; 83: 355–358
  • Kune GA, Kune S, Watson LF. Colorectal cancer risk, chronic illnesses, operations, and medications: Case control results from the Melbourne Colorectal Cancer Study. Cancer Res 1988; 48: 4399–4404
  • Thun MJ, Calle EE, Namboodiri MM. Risk factors for fatal colon cancer in a large prospective study. J Natl Cancer Inst 1992; 84: 1491–1500
  • Hirsch B, Johnson JT, Rabin BS. Immunostimulation of patients with head and neck cancer. Arch Otolaryngol 1983; 109: 298–301
  • Creagan ET, Buckner JC, Hahn RG. An evaluation of recombinant leukocyte A interferon with aspirin in patients with metastatic renal cell cancer. Cancer 1988; 61: 1787–1791
  • Creagan ET, Twito DI, Johansson SL. A randomized prospective assessment of recombinant leukocyte A human interferon with or without aspirin in advanced renal adenocarcinoma. J Clin Oncol 1991; 9: 2104–2109
  • Sosman JA, Kohler PC, Hank JA. Repetitive weekly cycles of interleukin-2. II. Clinical and immunologic effects of dose, schedule, and addition of indomethacin. J Natl Cancer Inst 1988; 80: 1451–1461
  • Miller RL, Steis RG, Clark JW. Randomized trial of recombinant [alpha]2b-interferon with or without indomethacin in patients with metastatic malignant melanoma. Cancer Res 1989; 49: 1871–1876
  • Mertens WC, Bramwell V HC, Lala PK. Do indomethacin and ranitidine contribute significantly to responses in advanced melanoma patients treated with high-dose interleukin 2. Proc Am Soc Clin Oncol 1991; 10: 209, (abstract)
  • Bramwell V HC, Mertens WC, Lala PK. Continuous oral indomethacin and ranitidine and continuous venous infusion interleukin-2 in advanced renal carcinoma. Proc Am Soc Clin Oncol 1991; 10: 171, (abstract)
  • Wang J, Walle A, Silver RT. The effect of indomethacin on patients with metastatic renal cell carcinoma receiving periodate-lymphokine activated killer cells and interleukin-2. Proc Am Soc Clin Oncol 1988; 7: 128, (abstract)
  • Morton DL, Hoon D, Nizze A. Active specific immuno-therapy with melanoma cell vaccine and immunomodulation in patients with metastatic melanoma. Proc Am Soc Clin Oncol 1991; 10: 295, (abstract)
  • Smith J, II, Urba W, Steis R. Phase II trial of interleukin-1 alpha in combination with indomethacin in melanoma patients. Proc Am Soc Clin Oncol 1991; 10: 293, (abstract)
  • Braun DP, Bonomi PD, Taylor SG, Harris JE. Modification of the effects of cytotoxic chemotherapy on the immune response of cancer patients with a nonsteroidal anti-inflammatory drug, piroxicam. A pilot study of the Eastern Cooperative Oncology Group. J Biol Response Mod 1987; 6: 331–345
  • Reddy MM, Manvar D, Ahuja KK. Augmentation of mitogen-induced proliferative responses by in vitro indomethacin in patients with acquired immune deficiency syndrome and AIDS-related complex. Int J Immunopharmacol 1985; 7: 917–921
  • Fessel WJ. Nonsteroidal anti-inflammatory drugs decrease CD4 and CD8 levels. J AIDS 1991; 4: 348–349, (abstract)
  • Santoro MG, Philpott GW, Jaffe BM. Inhibition of tumor growth in vivo and in vitro by prostaglandin E. Nature 1976; 263: 777–779
  • Marnett LJ. Aspirin and the potential role of prostaglandins in colon cancer. Cancer Res 1992; 52: 5575–5589
  • Plowman J, Narayanan VL, Dykes D. Flavone acetic acid: A novel agent with preclinical antitumor activity against colon adenocarcinoma 38 in mice. Cancer Treat Rep 1986; 70: 631–635
  • Corbett TH, Bissery MC, Wozniak A. Activity of flavone acetic acid (NSC 347512) against solid tumors of mice. Invest New Drugs 1986; 4: 207–220
  • Bissery M-C, Valeriote FA, Chabot GG. Flavone acetic acid (NSC 347512)-induced DNA damage in Glasgow osteogenic sarcoma in vivo. Cancer Res 1988; 48: 1279–1285
  • Zwi LJ, Baguley BC, Gavin JB. Blood flow failure as a major determinant in the antitumor action of flavone acetic acid. J Natl Cancer Inst 1989; 81: 1005–1013
  • Mahadevan V, Malik S TA, Meager A. Role of tumor necrosis factor in flavone acetic acid-induced tumor vasculature shutdown. Cancer Res 1990; 50: 5537–5542
  • Rubin J, Ames MM, Schutt AJ. Flavone-8-acetic acid inhibits ristocetin-induced platelet agglutination and prolongs bleeding time. Lancet 1987; 2: 1081–1082
  • Hornung RL, Back TC, Zaharko DS. Augmentation of natural killer activity, induction of IFN and development of tumor immunity during the successful treatment of established murine renal cancer using flavone acetic acid and IL-2. J Immunol 1988; 141: 3671–3679
  • Ching L-M, Baguley BC. Induction of natural killer cell activity by the antitumour compound flavone acetic acid (NSC 347512). Eur J Cancer Clin Oncol 1987; 23: 1047–1050
  • Wiltrout RH, Boyd MR, Back TC. Flavone-8-acetic acid augments systemic natural killer cell activity and synergizes with IL-2 for treatment of murine renal cancer. J Immunol 1988; 140: 3261–3265
  • Urba WJ, Longo DL, Lombardo FA. Enhancement of natural killer activity in human peripheral blood by flavone acetic acid. J Natl Cancer Inst 1988; 80: 521–525
  • Ghosh AK, Mellor M, Prendiville J. Recombinant interleukin-2 with flavone acetic acid in advanced malignant melanoma: Immunological studies. Br J Cancer 1990; 61: 471–474
  • Triozzi PL, Rinehart JJ, Malspeis L. Immunological effects of flavone acetic acid. Cancer Res 1991; 50: 6483–6485
  • Havlin KA., Kuhn JD, Craig JB. Phase I clinical and pharmacokinetic trial of flavone acetic acid. J Natl Cancer Inst 1991; 83: 124–128
  • Chabot GG, Branellec D, Sassi A. Tumour necrosis factor-alpha plasma levels after flavone acetic acid administration in man and mouse. Eur J Cancer 1993; 29A: 729–733
  • Grever MR., Leiby JM, Kraut EH. A phase I investigation of flavone acetic acid (NSC 347512). Proc Am Soc Clin Oncol 1988; 7: 62, (abstract)
  • Weiss RB, Greene RF, Knight RD. Phase I and clinical pharmacology study of intravenous flavone acetic acid (NSC 347512). Cancer Res 1988; 48: 5878–5882
  • Olver IN, Webster LK, Bishop JF. A phase I and pharmacokinetic study of 12-h infusion of flavone acetic acid. Cancer Chemother Pharmacol 1992; 29: 354–360
  • Kerr DJ., Kaye SB, Cassidy J. Phase J and pharmacokinetic study of flavone acetic acid. Cancer Res 1987; 47: 6776–6781
  • Pratt CB, Relling MV, Meyer WH. Phase I study of flavone acetic acid (NSC 347512, LM 975) in patients with pediatric malignant solid tumors. Am J Clin Oncol (CCT) 1991; 14: 483–486
  • Siegenthaler P, Kaye SB, Monfardini S. Phase II trial with flavone acetic acid (NSC 347512, LM 975) in patients with nonsmall cell lung cancer. Ann Oncol 1992; 3: 169–170
  • Kaye SB, Clavel M, Dodion P. Phase II trials with flavone acetic acid (NSC 347512, LM 975) in patients with advanced carcinoma of the breast, colon, head and neck, and melanoma. Invest New Drugs 1990; 8: S95–S99
  • Kerr DJ, Maughan T, Newlands E. Phase II trials of flavone acetic acid in advanced malignant melanoma and colorectal carcinoma. Br J Cancer 1989; 60: 104–106
  • Thatcher N, Dazzi H, Mellor M. Recombinant interleukin-2 with flavone acetic acid in advanced malignant melanoma: A phase II study. Br J Cancer 1990; 61: 618–621
  • Staubus AE., Grever MR, Malspeis L. Plasma protein binding of flavone acetic acid during continuous intravenous infusion to cancer patients. Proc Am Assoc Cancer Res 1988; 29: 188, (abstract)
  • Cummings J, Smyth JF, Double JA. Identification and characterization of the major human metabolites of flavone acetic acid. Proc Am Assoc Cancer Res 1988; 29: 486, (abstract)
  • Hoover HC, Jr., Jones D, Ketcham AS. The optimal level of anticoagulation for decreasing experimental metastases. Surgery 1976; 79: 625–630
  • Colucci M, Delaini F, Vitti G DB. Warfarin inhibits both procoagulant activity and metastatic capacity of Lewis lung carcinoma cells. Biochem Pharmacol 1983; 32: 1689–1691
  • Roncaglioni MC, Falanga A, Bolognese AP. Evidence of a warfarin-sensitive cancer procoagulant in V(2) carcinoma. Haematologica 1989; 74: 143–147
  • Hilgard P, Maat B. Mechanism of lung tumour colony reduction caused by coumarin anticoagulation. Eur J Cancer 1979; 15: 183–187
  • Van Buskirk JJ, Kirsch WM. Loss of hepatoma ribosomal RNA during warfarin therapy. Biochem Biophys Res Commun 1973; 52: 562–568
  • Chang JC, Hall TC. In vitro effect of sodium warfarin on DNA and RNA synthesis in mouse L1210 leukemic cells and Walker tumor cells. Oncology 1973; 28: 232–237
  • Zacharski LR. Mechanisms of inhibition of cancer dissemination by warfarin. Mechanisms of Cancer Metastasis, KV Honn, WE Powers, BF Sloane. Martinus Nijhoff, Boston 1986; 145–158
  • Maat B. Selective macrophage inhibition abolishes warfarin-induced reduction of metastases. Br J Cancer 1980; 41: 313–316
  • Piller NB. The ineffectiveness of coumarin treatment on thermal oedema of macrophage-free rats. Br J Exp Pathol 1976; 57: 170–178
  • Triozzi PL, Vicstein F, Ailabouni J. Effects of coumarins on interleukin-2 (IL-2) activity. Proc Am Assoc Cancer Res 1990; 31: 277, (abstract)
  • Feuer G, Kellen JA, Kovacs K. Suppression of 7,12-dimethylbenz(alpha) anthracene-induced breast carcinoma by coumarin in the rat. Oncology 1976; 33: 35–39
  • Marshall ME, Conley D, Hollingsworth P. Effects of coumarin (1,2-benzopyrone) on lymphocyte, natural killer cell, and monocyte functions in vitro. J Biol Response Mod 1989; 8: 70–85
  • Marshall ME, Riley LK, Rhoades J. Effects of coumarin (1,2-benzopyrone) and cimetidine on peripheral blood lymphocytes, natural killer cells, and monocytes in patients with advanced malignancies. J Biol Response Mod 1989; 8: 62–69
  • Zanker K, Blumel S.G., Lange J. Coumarin in melanoma patients: An experimental and clinical study. Future Trends Chemother 1985; 6: 473–480
  • Thornes D, Daly L, Lynch G. Prevention of early recurrence of high risk malignant melanoma by coumarin. Eur J Surg Oncol 1989; 15: 431–435
  • Mohler JL, Gomella LG., Crawford ED. Phase II evaluation of coumarin (1,2-benzopyrone) in metastatic prostatic carcinoma. Prostate 1992; 20: 123–131
  • Zacharski LR, Henderson WG, Rickles FR. Effect of warfarin anticoagulation on survival in carcinoma of the lung, colon, head and neck, and prostate. Final report of VA Cooperative Study #75. Cancer 1984; 53: 2046–2052
  • Chahinian AP, Propert KJ, Ware JH. A randomized trial of anticoagulation with warfarin and of alternating chemotherapy in extensive small-cell lung cancer by the Cancer and Leukemia Group B. J Clin Oncol 1989; 7: 993–1002
  • Mauer LH, Herndon JE, Hollis DR. A randomized trial of chemotherapy and radiation therapy with or without warfarin for limited disease small cell lung cancer. Proc Am Soc Clin Oncol 1993; 12: 335, (abstract)
  • Bourinbaiar AS, Tan X, Nagorny R. Effect of the oral anticoagulant, warfarin, on HIV-1 replication and spread. AIDS 1993; 7: 129–130
  • Obiri NI, Dupere SL, Pruett SB. Levamisole meets sulfhydryl requirements of CTLL-2 cells and mediates enhanced proliferative response to mitogen stimulation without increasing interleukin-2 production. J Biol Response Mod 1990; 9: 288–299
  • Pabst HF, Crawford J. L-Tetramisole: Enhancement of human lymphocyte response to antigen. Clin Exp Immunol 1975; 21: 468–473
  • Obiri N, Pruett S., Dupere S. Enhanced cellular responsiveness to interleukin-2 mediated by levamisole. Proc Am Assoc Cancer Res 1989; 30: 381, (abstract)
  • Schmidt ME, Douglas SD. Effects of levamisole on human monocyte function and immunoprotein receptors. Clin Immunol Immunopathol 1976; 6: 299–305
  • Chattopadhyay U, Bhattacharyya S, Chakrabarty NG. Tumor associated macrophage mediated lysis of autologous tumor cells. Neoplasma 1986; 33: 157–165
  • Kalafut F, Kusenda J, Novotna L. Restoration of immune response by levamisole in B-77 virus induced tumor-bearing rats. Neoplasma 1988; 35: 369–378
  • Morimoto C, Abe T, Homma M. Restoration of T-cell function in aged mice with long-term administration of levamisole. Clin Immunol Immunopathol 1979; 12: 316–322
  • Stevenson HC, Green I, Hamilton JM. Levamisole: Known effects on the immune system, clinical results, and future applications to the treatment of cancer. J Clin Oncol 1991; 9: 2052–2066
  • Pavlovsky S, Muriel FS, Garay G. Chemoimmunotherapy with levamisole in acute lymphoblastic leukemia. Cancer 1981; 48: 1500–1507
  • Lewinski UH, Mavligit GM., Hersh EM. Cellular immune modulation after a single high dose of levamisole in patients with carcinoma. Cancer 1980; 46: 2185–2194
  • Joensuu E, Nordman E, Toivanen A. Long-term effect of levamisole on the immune functions in melanoma patients. Strahlenther Onkol 1986; 162: 753–756
  • Tempero M, Haga Y, Sivinski C. Absence of biologic effects with levamisole treatment. Proc Am Soc Clin Oncol 1990; 9: 121, (abstract)
  • Janik J, Kopp WC, Smith JW, II. Dose-related immunologic effects of levamisole in patients with cancer. J Clin Oncol 1993; 11: 125–135
  • Danish Breast Cancer Cooperative Group. Increased breast cancer recurrence rate after adjuvant therapy with levamisole. Lancet 1980; 2: 824–827
  • Anthony HM, Mearns AJ, Mason MK. Levamisole and surgery in bronchial carcinoma patients. Increase in deaths from cardiovascular failure. Thorax 1979; 34: 4–12
  • Laurie JA, Moertel CG, Fleming TR. Surgical adjuvant therapy of large-bowel carcinoma: An evaluation of levamisole and the combination of levamisole and fluorouracil. J Clin Oncol 1989; 7: 1447–1456
  • Moertel CG, Fleming TR, MacDonald JS. Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med 1990; 322: 352–358
  • Quirt IC, Shelley WE, Pater JL. Improved survival in patients with poor-prognosis malignant melanoma treated with adjuvant levamisole: A phase III study by the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 1991; 9: 729–735
  • Spitler LE. A randomized trial of levamisole versus placebo as adjuvant therapy in malignant melanoma. J Clin Oncol 1991; 9: 736–740
  • Loutfi A, Shakr A, Jerry LM. Double blind randomized prospective trial of levamisole/placebo in stage 1 cutaneous malignant melanoma. Clin Invest Med 1987; 10: 325–328
  • Lejeune FJ, Macher E, Kleeberg U. An assessment of DTIC versus levamisole or placebo in the treatment of high risk stage I patients after surgical removal of a primary melanoma of the skin. A phase III adjuvant study. EORTC protocol 18761. Eur J Cancer Clin Oncol 1988; 24: S81–S90, (Suppl 2)
  • Surapaneni N, Raghunathan R, Beall GN. Levamisole, immunostimulation and the acquired immunodeficiency syndrome. Ann Inter Med 1985; 102: 137, (letter)
  • Garzon MC, Mubita M, Kachinka L. Levamisole treatment in HIV-infected Zambian children. Lancet 1992; 340: 1099–1100, (letter)
  • Mossalayi MD, Dalloul AH, Bertho JM. Induction of T lymphocyte-related functions by imuthiol through down regulation of prostaglandin secretion by monocytes/macrophages. Fifth Int Conf on AIDS, MontrealCanada, 1989, 398, (abstract)
  • Renoux G, Renoux M, Lebranchu Y. Immunopharmacology of DTC in mice and men. Immunomodulating Drugs and Modifiers of the Biological Response, B Serrou, U Rosenfeld. Elsevier Biomedical Press, New York 1982; 113–132
  • Cohen JD, Robins HI. Cytotoxicity of diethyldithiocarbamate in human versus rodent cell lines. Invest New Drugs 1990; 8: 137–142
  • Lin PS, Kwock L, Goodchild NT. Copper chelator enhancement of bleomycin cytoxicity. Cancer 1980; 46: 2360–2364
  • Perchellet JP, Abney NL., Thomas RM. Inhibition of multistage tumor promotion in mouse skin by diethyldithiocarbamate. Cancer Res 1987; 47: 6302–6309
  • Pompidou A, Delsaux MC., Telvi L. Isoprinosine and imuthiol, two potentially active compounds in patients with AIDS-related complex symptoms. Cancer Res 1985; 45: 4671s–4673s, (Suppl)
  • Escaich S, Ritter J, Retornaz G. Comparison of the effects of therapy with suramin 3′azidothymidine and diethyldithiocarbamate on HIV replication. Fourth Int Conf on AIDS. 3156, StockholmSweden, June 12–16, 1988, 258, (abstract)
  • Hersh EM, Funk CY, Ryschon KL. Effective therapy of the LP-BM5 murine retrovirus-induced lymphoproliferative immunodeficiency disease with diethyldithiocarbamate. AIDS Res Hum Retroviruses 1991; 7: 553–561
  • Paredes J, Hong WK, Felder TB. Prospective randomized trial of high-dose cisplatin and fluorouracil infusion with or without sodium diethyldithiocarbamate in recurrent and/or metastatic squamous cell carcinoma of the head and neck. J Clin Oncol 1988; 6: 955–962
  • Lang JM, Oberling F., Aleksijevic A. Immunomodulation with diethyldithiocarbamate in patients with LAV/HTLV-III-related illness. Cancer Immunol Immunother 1986; CII: 22–23; A42, (Suppl) (abstract)
  • Kaplan CS, Petersen E, Yocum A.D. A randomized, controlled dose response study of intravenous sodium diethyldithio-carbamate in patients with advanced human immunodeficiency virus infection. Life Sci 1989; 45: 3–9
  • Lang JM, Trepo Kirstetter C.M. Randomized, doubleblind, placebo-controlled trial of ditiocarb sodium (“imuthiol”) in human immunodeficiency virus infection. Lancet 1988; 2: 702–706
  • Pameix P., Salmi LR, Dabis F. Effectiveness of ditiocarb sodium in HIV-infected patients: A long term comparative study. Seventh Int Conf on AIDS, Florence, Italy, June 16–21, 1991. 2: 222, (abstract)
  • Reisinger EC, Kem P, Ernst M. Inhibition of HIV progression by dithiocarb. Lancet 1990; 335: 679–682
  • Hersh EM, Brewton G., Abrams D. Ditiocarb sodium (diethyldithiocarbamate) therapy in patients with symptomatic HIV infection and AIDS. JAMA 1991; 265: 1538–1544
  • The HIV87 Study Group. Multicenter, randomized, placebocontrolled study of ditiocarb (imuthiol) in human immunodeficiency virus-infected asymptomatic and minimally symptomatic patients. AIDS Res Hum Retroviruses 1993; 9: 83–89
  • Damle N, Gupta K.S. OKT(8)+ T cells mediate histamineinduced suppressor T cell function. IRCS J Med Sci 1981; 9: 911–912
  • Griswold DE, Alessi S., Badger AM. Inhibition of T suppressor cell expression by histamine type 2 (H2) receptor antagonists. J Immunol 1984; 132: 3054–3057
  • Osband ME, Shen Y-J, Shlesinger M. Successful tumour immunotherapy with cimetidine in mice. Lancet 1981; 1: 636–638
  • Gifford R RM, Ferguson RM, Voss BV. Cimetidine reduction of tumour formation in mice. Lancet 1981; 1: 638–640
  • Gifford R RM, Sr, Hatfield SM, Schmidtke JR. Cimetidine-induced augmentation of human lymphocyte blastogenesis by mitogen, bacterial antigen, and alloantigen. Transplantation 1980; 29: 143–148
  • Gifford R RM, Voss BV, Schmidtke JR. Histamine type-2 receptor antagonist immune modulation I. Increased cell-mediated cytotoxicity in normal and in down-regulated systems. Surgery 1988; 103: 184–192
  • Gifford R RM, Tilberg AF. Histamine type-2 receptor antagonist immune modulation. II. Cimetidine and ranitidine increase interleukin-2 production. Surgery 1987; 102: 242–247
  • Charpentier B, Ph Lang, Martin B. Cimetidine does not stimulate human T lymphocyte functions in vitro. Biomedicine 1982; 36: 250–254
  • Haines RL, Barna BP. Studies of cimetidine in immunologic function and tumor growth. Fed Proc 1980; 39(Part I)475, (abstract)
  • Kikuchi Y, Oomori K, Kizawa I. Augmented natural killer activity in ovarian cancer patients treated with cimetidine. Eur J Cancer Clin Oncol 1986; 22: 1037–1043
  • Allen JI, Syropoulos HJ, Grant B. Cimetidine modulates natural killer cell function of patients with chronic lymphocytic leukemia. J Lab Clin Med 1987; 109: 396–401
  • Aweeka F, Amend W, Garavoy M. The effects of H-2 antagonists on immunological function. Clin Pharmacol Ther 1988; 43: 128, (abstract)
  • Kikuchi Y, Kizawa I, Oomori K. Effects of cimetidine on interleukin-2 production by peripheral blood lymphocytes in advanced ovarian carcinoma. Eur J Cancer Clin Oncol 1988; 24: 1185–1190
  • Nielsen HJ., Pedersen BK, Moesgaard F. Effect of ranitidine on postoperative suppression of natural killer cell activity and delayed hypersensitivity. Acta Chir Scand 1989; 155: 377–382
  • McGregor C GA, Ogg LJ, Smith IS. Immunological and other laboratory studies of patients receiving short-term cimetidine therapy. Lancet 1977; 1: 122–123
  • Morton R, Creagan Chang E.M. New approaches to the therapy of disseminated malignant melanoma. Proc Am Soc Clin Oncol 1986; 5: 129, (abstract)
  • Mandanas R, Schultz S, Scullin D. Phase II trial of cimetidine in metastatic melanoma. Am J Clin Oncol (CCT) 1991; 14: 397–399
  • Hutchins LF, Cash DK, Lang NP. Coumarin and cimetidine as active agents in melanoma and renal cell carcinoma. Clin Res 1984; 32: 873A, (abstract)
  • Marshall ME, Butler K, Cantrell J. Treatment of advanced malignant melanoma with coumarin and cimetidine: A pilot study. Cancer Chemother Pharmacol 1989; 24: 65–66
  • Nolte H, Pedersen L, Mouridsen HT. Combined treatment of advanced malignant melanoma with coumarin and cimetidine. Anticancer Res 1987; 7: 449–450
  • Hill NO, Pardue A, Khan A. Interferon and cimetidine for malignant melanoma. N Engl J Med 1983; 308: 286, (letter)
  • Flodgren P, Borgstrom S, Jonsson PE. Metastatic malignant melanoma: Regression induced by combined treatment with interferon [HulFN-alpha(Le)] and cimetidine. Int J Cancer 1983; 32: 657–665
  • Abdi EA, McPherson TA, Tan YH. Combination of fibroblast interferon, carboxamide, and cimetidine for advanced malignant melanoma. J Biol Response Mod 1986; 5: 423–428
  • Inhorn L, Williams SD, Nattam S. High-dose cimetidine for the treatment of metastatic renal cell carcinoma. Am J Clin Oncol (CCT) 1992; 15: 157–159
  • Osband ME, Lavin PT, Babayan RK. Effect of autolymphocyte therapy on survival and quality of life in patients with metastatic renal-cell carcinoma. Lancet 1990; 335: 994–998
  • Marshall ME, Mendelsohn L, Butler K. Treatment of metastatic renal cell carcinoma with coumarin (1,2-benzopyrone) and cimetidine: A pilot study. J Clin Oncol 1987; 5: 862–866
  • Dexeus FH, Logothetis CJ, Sella A. Phase II study of coumarin and cimetidine in patients with metastatic renal cell carcinoma. J Clin Oncol 1990; 8: 325–330
  • Venook AP, Davenport Y, Tseng A, Jr. Activity of coumarin and cimetidine in metastatic renal cell carcinoma. J Clin Oncol 1989; 7: 402–404, (letter)
  • Herrmann R, Manegold C, Maurer B. Phase II trial of coumarin and cimetidine in advanced melastatic renal cell carcinoma. Anns Oncology 1990; 1: 445–446
  • Marshall ME, Butler K, Fried A. Phase 1 evaluation of coumarin (1,2-benzopyrone) and cimetidine in patients with advanced malignancies. Mol Biother 1991; 3: 170–178
  • Mamus SW, Mladenovic J, Hordinsky MK. Cimetidine-induced remission of mycosis fungoides. Lancet 1984; 2: 409, (letter)
  • Tonnesen H, Bulow S, Fischerman K. Effect of cimetidine on survival after gastric cancer. Lancet 1988; 2: 990–992
  • Marshall ME, Mendelsohn L, Butler K. Treatment of nonsmall cell lung cancer with coumarin and cimetidine. Cancer Treat Rep 1987; 71: 91–92
  • Marshall ME, Butler K, Hermansen D. Treatment of hormone refractory stage D carcinoma of prostate with coumarin (1,2- benzopyrene) and cimetidine: A pilot study. Prostate 1990; 17: 95–99
  • Ahuja K, Manvar D, Reddy M. Cimetidine as an immunomodulating agent in the A.I.D. syndrome. J Allergy Clin Immunol 1983; 71: 132, (abstract)
  • Brockmeyer NH, Kreuzfelder E, Mertins L. Immunomodulatory properties of cimetidine in ARC patients. Clin Immunol Immunopathol 1988; 48: 50–60
  • Smith TJ, Kaplowitiz LG. Pilot study of cimetidine in the treatment of Kaposi's sarcoma in patients with acquired immunodeficiency syndrome. J Natl Cancer Inst 1991; 83: 139–141
  • Chihara G, Hamuro J, Maeda YY. Antitumor and metastasis-inhibitory activities of lentinan as an immunomodulator. Cancer Detect Prev Suppl 1987; 1: 423–443
  • Peter G, Karoly V, Imre B. Effects of lentinan on cytotoxic functions of human lymphocytes. Immunopharmacol Immunotoxicol 1988; 10: 157–163
  • Hamuro J, Wagner H, Rollinghoff M. Beta (1–3)-glucans as a probe for T cell specific immune adjuvants. II. Enhanced in vitro generation of cytotoxic T lymphocytes. Cell Immunol 1978; 38: 328–335
  • Dennert G, Tuckor D. Antitumor polysaccharide lentinan: A T cell adjuvant. J Natl Cancer Inst 1973; 51: 1727–1729
  • Suzuki M, Higuchi S, Taki Y. Induction of endogenous lymphokine-activated killer activity by combined administration of lentinan and interleukin-2. Int J Immunopharmacol 1990; 12: 613–623
  • Yamasaki K, Sone S, Yamashita T. Synergistic induction of lymphokine (IL-2)-activated killer activity by IL-2 and the polysaccharide lentinan, and therapy of spontaneous pulmonary metastases. Cancer Immunol Immunother 1989; 29: 87–92
  • Shimizu Y, Chen J-T, Hirai Y. Augmentative effect of lentinan on immune responses of pelvic lymph node lymphocytes in patients with uterine cervical cancer. Acta Obstet Gynaecol Jpn 1988; 40: 1557–1558
  • Arinaga S, Karimine N, Takamuku K. Enhanced induction of lymphokine-activated killer activity after lentinan administration in patients with gastric carcinoma. Int J Immunopharmacol 1992; 14: 535–539
  • Arinaga S, Karimine N, Takamuki K. Enhanced production of interleukin-1 and tumor necrosis factor by peripheral monocytes after lentinan administration in patients with gastric carcinoma. Int J Immunopharmacol 1992; 14: 43–47
  • Okuyama K, Isono K, Juan I-K. Evaluation of treatment for gastric cancer with liver metastases. Cancer 1985; 55: 2498–2505
  • Oka M, Yoshino S, Hazama S. Immunological analysis and clinical effects of intraabdominal and intrapleural injection of lentinan for malignant ascites and pleural effusion. Biotherapy 1992; 5: 107–112
  • Taguchi T, Kaneko Y. Lentinan: An overview of experimental and clinical studies of its action against cancer. Host Defense Mechanisms Against Cancer, I Urushizaki, T Aoki, E Tsubura. Excerpta Medica, Amsterdam 1986; 221–228
  • Abrams D, Greco M, Wong R. Results of a phase I/II placebo-controlled dose finding pilot study of lentinan in patients with HIV infection. Sixth Int Conf on AIDS, San Francisco, 1990. 3: 207, (abstract)
  • Teodorcyk-Injeyan JA, Makowka L, Falk RE. Mechanisms of altered in vitro antibody response in the rat by a small synthetic polymer. Scand J Immunol 1982; 15: 9–16
  • Rotstein LE, Makowka L, Falk RE. Selective immune stimulation during induction of allograft tolerance in the rat by radical immunosuppression. Transplantation 1980; 30: 417–420
  • Remington JS, Merigan TC. Synthetic polyanions protect mice against intracellular bacterial infection. Nature 1970; 226: 361–363
  • Pearson JW, Chirigos MA, Chaparas SD. Combined drug and immunostimulation therapy against a syngeneic murine leukemia. J Natl Cancer Inst 1974; 52: 463–468
  • Pavlidis NA, Schultz RM, Chirigos MA. Effect of maleic anhydride-divinyl ether copolymers on experimental M109 metastases and macrophage tumoricidal function. Cancer Treat Rep 1978; 62: 1817–1822
  • Merigan TC. Induction of circulating interferon by synthetic anionic polymers of known composition. Nature 1967; 214: 416–417
  • Dean JH, Padarathsingh ML, Keys L. Response of murine leukemia to combined BCNU-maleic anhydride-vinyl ether (MVE) adjuvant therapy and correlation with macrophage activation by MVE in the in vitro growth inhibition assay. Cancer Treat Rep 1978; 62: 1807–1816
  • Tagliabue A, Mantovani A, Polentarutti N. Effect of immunomodulators on effector cells involved in antibodydependent cellular cytotoxicity: Brief communication. J Natl Cancer Inst 1977; 59: 1019–1022
  • Morahan PS, Barnes DW, Munson AE. Relationship of molecular weight to antiviral and antitumor activities and toxic effects of maleic anhydride-divinyl ether (MVE) polyanions. Cancer Treat Rep 1978; 62: 1797–1805
  • Breslow DS, El Edwards, Newburg NR. Divinyl ether-maleic anhydride (Pyran) copolymer used to demonstrate the effect of molecular weight on biological activity. Nature 1973; 246: 160–162
  • Rinehart JJ, Young DC, Neidhart JA. Evaluation of the immunological and toxicological properties of MVE-2 in phase I trials. Cancer Res 1983; 43: 2358–2362
  • Rios A, Rosenblum M, Powell M. Phase I study of MVE-2 therapy in human cancer. Cancer Treat Rep 1983; 67: 239–243
  • Hainsworth JD, Forbes JT, Grosh WW. Phase I study of MVE-2 evaluating toxicity and biologic response modification capability. Cancer Immunol Immunother 1986; 22: 68–71
  • Rinehart J, LaForge J, Gochnour D. Phase II trial of MVE-II in metastatic malignant melanoma. Cancer Immunol Immunother 1987; 24: 244–246
  • Saito T, Ruffmann R, Welker RD. Development of hyporesponsiveness of natural killer cell to augmentation of activity after multiple treatments of biological response modifiers. Cancer Immunol Immnother 1985; 19: 130–135
  • Fields JE, Asculai SS, Johnson JH. Carboxyimamidate, a low-molecular-weight polyelectrolyte with antitumor properties and low toxicity. J Med Chem 1982; 25: 1060–1064
  • Kisner DL, Mehta P, Paget E. Anti-tumor activity of N-137 (carbethimer) in a human tumor cloning system. Proc Am Soc Clin Oncol 1983; 2: 26, (abstract)
  • Ardalan B, Paget GE. Mechanism of action of a new antitumor agent, carbetimer. Cancer Res 1986; 46: 5473–5476
  • Teodorcyk-Injeyan JA, Filion L, Falk R. Mechanism of enhanced humoral response in rodents by a synthetic polymer. J Immunopharmacol 1983; 5: 147–172
  • Ardalan B, Hussein AM, Shanahan WR, Jr. Carbetimer: A reevaluation of a drug with a novel mechanism of action. Cancer Treat Rev 1991; 18: 73–83
  • Hanauske A-R, Melink TJ, Harman GS. Phase I clinical trial of carbetimer. Cancer Res 1988; 48: 5353–5357
  • Grunberg SM, Ehler E, Francis RB, Jr. Phase I trial of a 5-day course of carbetimer. Invest New Drugs 1990; 8: S41–S49
  • Dodion P, De Valeriola D, Body JJ. Phase I clinical trial with carbetimer. Eur J Cancer Clin Oncol 1989; 25: 279–286
  • Ardalan B, Hussein A, Shanahan W. Phase I continuous intravenous infusion of carbetimer in refractory malignancies. Proc Am Assoc Cancer Res 1989; 30: 283, (abstract)
  • Audeh MW, Jacobs CD, Davis TE. A phase II trial of carbetimer for the treatment of colorectal cancer. Am J Clin Oncol (CCT) 1990; 13: 324–326
  • Keaton M, Brown T, Craig J. Phase II study of carbetimer in non-small cell lung cancer. Invest New Drugs 1990; 8: 385–386
  • Campoli-Richards DM, Sorkin EM, Heel RC. Inosine Pranobex: A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy. Drugs 1986; 32: 383–424
  • Tsang K-Y, Fundenberg HH, Gnagy MJ. Restoration of immune responses of aging hamsters by treatment with isoprinosine. J Clin Invest 1983; 71: 1750–1755
  • Fischback M, Talal N. Ability of isoprinosine to restore interleukin-2 production and T cell proliferation in autoimmune mice. Clin Exp Immunol 1985; 61: 242–247
  • Tsang K-Y, Gnagy MJ, Phillips CB. In vitro effects of isoprinosine on the immune responses of cancer patients. Proc 13th Int Cancer Congress, Seattle, WA, 1982, 32, (abstract)
  • De Simone C, De Marco F, Arancia G. Influence of methisoprinol (isoprinosine) on HIV-infected human lymphocytes: In vitro immunological, virological, and ultrastructural studies. J Clin Lab Anal 1989; 3: 26–33
  • Tsang P, Bekesi JG. Normalization of immunoregulatory T-helper T-suppressor sublineages and cell-mediated immunity by isoprinosine in vitro in the early stages of AIDS. Cancer Detect Prev Suppl 1987; 1: 611–618
  • Tsang KY, Fudenberg HH, Galbraith G MP. Partial restoration of impaired interleukin-2 production and Tac antigen (putative interleukin-2 receptor) expression in patients with acquired immune deficiency syndrome by isoprinosine treatment in vitro. J Clin Invest 1985; 75: 1538–1544
  • Teglbjaerg L LS, Kroon S, Sandstrom E. Effect of isoprinosine on HIV antigenemia. AIDS 1992; 6: 199–201
  • Fridman H, Calle R, Morin A. Double-blind study of isoprinosine influence on immune parameters in solid tumor-bearing patients treated with radiotherapy. Int J Immunopharmacol 1980; 2: 194, (abstract)
  • Colozza M, Tonato M, Belsanti V. 5-Fluorouracil and isoprinosine in the treatment of advanced colorectal cancer. Cancer 1988; 62: 1049–1052
  • Banzet P, Jacquillat CI, Khayat D. Preliminary results of a nonspecific immunotherapy using a new isoprinosine schedule for adjuvant treatment of low risk malignant melanoma. Proc Am Soc Clin Oncol 1991; 10: 297, (abstract)
  • Martinez J, Miller L, Allen R. A randomized trial of isoprinosine as surgical adjuvant therapy of melanoma: Final report. Proc Am Assoc Cancer Res 1990; 31: 203, (abstract)
  • De Simone C, Albertini F, Almaviva M. Clinical and immunological assessment in HIV + subjects receiving inosinepranobex. A randomized, multicentric study. Med Oncol Tumor Pharmacother 1989; 6: 63–67
  • Wallace JI, Bekesi JG. A double-blind clinical trial of the effects of inosine pranobex in immunodepressed patients with prolonged generalized lymphadenopathy. Clin Immunol Immunopathol 1986; 39: 179–186
  • Glasky AJ, Gordon JF. Isoprinosine (Inosine Pranobex BAN, INPX) in the treatment of AIDS and other acquired immunodeficiencies of clinical importance. Cancer Detect Prev Suppl 1987; 1: 597–609
  • Pedersen C, Sandstrom E, Petersen CS. The efficacy of inosine pranobex in preventing the acquired immunodeficiency syndrome in patients with human immunodeficiency virus infection. N Engl J Med 1990; 322: 1757–1763
  • Thorsen S, Pederson C, Sandstrom E. One-year follow-up on the safety and efficacy of isoprinosine for human immunodeficiency virus infection. J Intern Med 1992; 231: 607–615
  • Loveless MO, Robins DS. US/UK Isoprinosine Clinical Investigators Group USA: The effect of isoprinosine in HIV seropositive patients with low risk for developing AIDS. 5th Int Conf AIDS Montreal, QuebecCanada, June 4–9, 1989, 399, (abstract)
  • Richard KA, Mortensen RF, Tracey DE. Cytokines involved in the augmentation of murine natural killer cell activity by pyrimidinones in vivo. J Biol Response Mod 1987; 6: 647–663
  • Scheringa M, Ijzermans J NM, Jeekel J. The antiproliferative effect of the interferon-inducer bropirimine is partly medialed by TNF. Proc Am Assoc Cancer Res 1990; 31: 297, (abstract)
  • Eggermont A MM, Sugarbaker PH, Marquet RL. In vivo generation of lymphokine activated killer cell activity by ABPP and interleukin-2 and their antitumor effects against immunogenic and nonimmunogenic tumors in murine tumor models. Cancer Immunol Immunother 1988; 26: 23–30
  • Shaw DR, Tilden AB, Kirchler TJ. Demonstration of immune modulation during phase II trials of oral bropirimine. Proc Am Assoc Cancer Res 1989; 30: 381, (abstract)
  • Borden EC, Sidky YA, Erturk E. Protection from carcinogen-induced murine bladder carcinoma by interferons and oral interferon-inducing pyrimidinone, bropirimine. Cancer Res 1990; 50: 1071–1074
  • Sidky YA, Borden EC, Wierenga W. Inhibitory effects of interferon-inducing pyrimidinones on the growth of transplantable mouse bladder tumors. Cancer Res 1986; 46: 3798–3802
  • Li LH, Johnson MA, Moeller RB. Chemoimmunotherapy of B16 melanoma and P388 leukemia with cyclophosphamide and pyrimidinones. Cancer Res 1984; 44: 2841–2847
  • Sarosdy MF, Lamm DL, Williams RD. Phase I trial of oral bropirimine in superficial bladder cancer. J Ural 1992; 147: 3133
  • Chachoua A, Hochster H, Green M. Phase II trial of bropirimine in patients with AIDS related Kaposi's sarcoma. Proc Am Soc Clin Oncol 1988; 7: 6, (abstract)
  • Shapiro PE, Edelson RL. Effects of retinoids on the immune system. Retinoids: New Trends in Research and Therapy, JH Saurat. Karger, Basel 1984; 225–235
  • Dennert G. Immunostimulation by retinoic acid. Retinoids, Differentiation and Disease, J Nugent, S Clark. Pitman, London 1985; 117–126
  • Micksche M, Colot M, Uchida A. Immunomodulation in cancer patients by synthetic biological response modifiers. Cancer Treat Symp 1985; 1: 27–35
  • Micksche M, Cerni C, Kokron O. Stimulation of immune response in lung cancer patients by vitamin A therapy. Oncology 1977; 34: 234–238
  • Lotan R, Nicolson GL. Inhibitory effects of retinoic acid or retinyl acetate on the growth of untransformed, transformed and tumor cells in vitro. J Natl Cancer Inst 1977; 59: 1717–1722
  • Moon RC, Grubbs CJ, Sporn MB. Inhibition of 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis by retinyl acetate. Cancer Res 1976; 36: 2626–2630
  • Eccles SA, Barnett SC, Alexander P. Inhibition of growth and spontaneous metastasis of syngeneic transplantable tumors by an aromatic retinoic acid analogue. 1. Relationship between tumour immunogenicity and responsiveness. Cancer Immunol Immunother 1985; 19: 109–114
  • Wuarin L, Verity MA, Sidell N. Effects of interferon-gamma and its interaction with retinoic acid on human neuroblastoma differentiation. Int J Cancer 1991; 48: 136–141
  • Hemmi H, Breitman TR. Combinations of recombinant human interferons and retinoic acid synergistically induce differentiation of the human promyelocytic leukemia cell line HL-60. Blood 1987; 69: 501–507
  • Marth Daxenbichler C, Dapunt O. Synergistic antiproliferative effect of human recombinant interferons and retinoic acid in cultured breast cancer cells. J Natl Cancer Inst 1986; 77: 1197–1202
  • Hong WK, Endicott J, Itri LM. 13-cis-Retinoic acid in the treatment of oral leukoplakia. N Engl J Med 1986; 315: 1501–1505
  • Lippman SM, Kessler JF, Meyskens FL, Jr. Retinoids as preventive and therapeutic anticancer agents (Part II). Cancer Treat Rep 1987; 71: 493–515
  • Benner SE, Lippman SM, Earley C. Long term follow-up: 13-cis-Retinoic acid prevention of second primary tumors following squamous cell carcinoma of the head and neck. Proc Am Soc Clin Oncol 1993; 12: 279, (abstract)
  • Huang M, Hu-Chen Y, Shu-Rong C. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood 1988; 72: 567–572
  • Castaigne S, Chomienne C, Daniel MT. All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. I. Clinical results. Blood 1990; 76: 1704–1709
  • Warrell RP, Jr, Frankel SR, Miller WH, Jr. Differentiation therapy of acute promyelocytic leukemia with tretinoin (alltrans-retinoic acid). N Engl J Med 1991; 324: 1385–1393
  • Lippman SM, Kavanagh JJ, Paredes-Espinoza M. 13-cis-Retinoic acid plus interferon alpha-2a: Highly active systemic therapy for squamous cell carcinoma of the cervix. J Natl Cancer Inst 1992; 84: 241–245
  • Lippman SM, Parkinson DR, Itri LM. 13-cis-Retinoic acid and interferon alpha-2a: Effective combination therapy for advanced squamous cell carcinoma of the skin. J Natl Cancer Inst 1992; 84: 235–241
  • Von Roenn J, Von Gaten C, Mullane M. All-transretinoic acid in the treatment of AIDS-related Kaposi's sarcoma. Proc Am Soc Clin Oncol 1993; 12: 51, (abstract)
  • Marcus PI, Sekellick MJ. Defective interfering particles with covalently linked [±] RNA induce interferon. Nature 1977; 266: 815–819
  • Lampkin BC, Levine AS, Levy H. Phase II trial of poly (I,C)-LC, an interferon inducer, in the treatment of children with acute leukemia and neuroblastoma: A report from the Children's Cancer Study Group. J Biol Response Mod 1985; 4: 531–537
  • Durie B GM, Levy HB, Voakes J. Poly (I,C)-LC as an interferon inducer in refractory multiple myeloma. J Biol Response Mod 1985; 4: 518–524
  • Krown SE, Kerr D, Stewart WE, II. Phase I trials of poly (I,C) complexes in advanced cancer. J Biol Response Mod 1985; 4: 640–649
  • Stevenson HC, Abrams PG, Schoenberger CS. A phase I evaluation of poly (I,C)-LC in cancer patients. J Biol Response Mod 1985; 4: 650–655
  • Hawkins MJ, Levin M, Borden EC. An Eastern Cooperative Oncology Group phase I-II pilot study of polyriboinosinicpolyribocytidylic acid poly-L-lysine complex in patients with metastatic melanoma. J Biol Response Mod 1985; 4: 664–668
  • Ewel CH, Urba WJ, Kopp WC. Polyinosinic-polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose in combination with interleukin-2 in patients with cancer: Clinical and immunological effects. Cancer Res 1992; 52: 3005–3010
  • Smalley RV, Oldham RK. Chemical inducers of lymphokines. Principles of Cancer Biotherapy, RK Oldham. Raven Press, New York 1987; 223–245
  • Hovanessian AG, Youn JK, Buffet-Janvrese C. Enhancement of natural killer cell activity and 2–5A synthetase in operabie breast cancer patients treated with polyadenylic; polyuridylic acid. Cancer 1985; 55: 357–362
  • Lacour J, Spira A, Petit J-Y. Adjuvant treatment with polyadenylic-polyuridylic acid (poly A-poly U) in operable breast cancer. Lancet 1980; 2: 161–164
  • Youn JK, Kim BS, Min JS. Adjuvant treatment of operable stomach cancer with polyadenylic-polyuridylic acid in addition to chemotherapeutic agents: A preliminary report. Int J Immunopharmacol 1990; 12: 289–295
  • Lacour J, Laplanche A, Malafosse M. Polyadenylicpolyuridylic acid as an adjuvant in resectable colorectal carcinoma: A 6 1/2 year follow-up analysis of a multicentric double blind randomized trial. Eur J Surg Oncol 1992; 18: 599–604
  • Carter WA, Hubbell HR, Krueger LJ. Comparative studies of ampligen (mismatched double-stranded RNA) and interferons. J Biol Response Mod 1985; 4: 613–620
  • Carter WA, Strayer DR, Hubbell HR. Preclinical studies with ampligen (mismatched double-stranded RNA). J Biol Response Mod 1985; 4: 495–502
  • Hubbell HR, Kvalnes-Krick K, Carter WA. Antiproliferative and immunomodulatory actions of beta interferon and double-stranded RNA, individually and in combination, on human bladder tumor xenografts in nude mice. Cancer Res 1985; 45: 2481–2486
  • Brodsky I, Strayer DR, Krueger LJ. Clinical studies with ampligen (mismatched double-stranded RNA). J Biol Response Mod 1985; 4: 669–675
  • Strayer DR, Carter WA, Crilley P. Antitumor activity of mismatched double-stranded RNA in phase I-II studies. Proc Am Soc Clin Oncol 1989; 8: 185, (abstract)
  • Strayer DR, Hubbell HR, Carter WA. A phase I-II study of ampligen treatment of metastatic renal cell carcinoma: Comparison of treatment with low dose vs high dose. Proc Am Soc Clin Oncol 1992; 11: 210, (abstract)
  • Montefiori DC, Mitchell WM. Antiviral activity of mismatched double-stranded RNA against human immunodeficiency virus in vitro. Proc Natl Acad Sci USA 1987; 84: 2985–2989
  • Mitchell WM, Montefiori DC, Robinson WE, Jr. Mismatched double-stranded RNA (ampligen) reduces concentrations of zidovudine (azidothymidine) required for in vitro inhibition of human immunodeficiency virus. Lancet 1987; 1: 890–892
  • Carter WA, Brodsky I, Pellegrino MG. Clinical, immunological and virological effects of ampligen, a mismatched double-stranded RNA, in patients with AIDS or AIDS-related complex. Lancet 1987; 1: 1286–1292
  • Armstrong JA, McMahon D, Huang X-L. A phase I study of ampligen in human immunodeficiency virus-infected subjects. J Infect Dis 1992; 166: 717–722
  • Strayer DR, Brodsky I, Pequignot E. Improvement in T4 level and decrease in opportunistic infections and lymphomas in ARC/PRE-ARC patients receiving ampligen compared to placebo. Sixth Int Conf On AIDS, San Francisco, June 20–24, 1990. 3: 208, (abstract)
  • Mastrangelo MJ, Berd D, Maguire H. The immunoaugmenting effects of cancer chemotherapeutic agents. Semin Oncol 1986; 13: 186–194
  • Braun DP, Harris JE. Modulation of the immune response by chemotherapy. Pharmacol Ther 1981; 14: 89–122
  • Kleinerman ES, Zwelling LA, Muchmore AV. Enhancement of naturally occurring human spontaneous monocyte-mediated cytotoxicity by cis-diamminedichloroplatinum (II). Cancer Res 1980; 40: 3099–3102
  • Sodhi A, Pai K. Increased production of interleukin-1 and tumor necrosis factor by human monocytes treated in vitro with cisplatin or other biological response modifiers. Immun Lett 1992; 34: 183–188
  • Ehrke MJ, Maccubbin D, Ryoyama K. Correlation between adriamycin-induced augmentation of interleukin-2 production and of cell mediated cytotoxicity in mice. Cancer Res 1986; 46: 54–60
  • Dray S, Bocian RC, Ben Efraim S. Mechanisms of melphalan-mediated modulation of antitumor immune potential of tumor-bearer lymphoid cells. Cancer Treat Symp 1985; 1: 3–10
  • Abdul Hamied TA, Turk JL. Enhancement of interleukin-2 release in rats by treatment with bleomycin and Adriamycin in vivo. Cancer Immunol Immunother 1987; 25: 245–249
  • Bogoan C, Ding A. Taxol, a microtubule-stabilizing antineoplastic agent, induces expression of tumor necrosis factor alpha and interleukin-I in macrophages. J Leukoc Biol 1992; 52: 119–121
  • Glaser M. Regulation of specific cell-mediated cytotoxic response against SV 40-induced tumor associated antigens by depletion of suppressor T cells with cyclophosphamide in mice. J Exp Med 1979; 149: 774–779
  • Graziano F, Haley C, Gundersen L. IgE antibody production in guinea pigs treated with cyclophosphamide. J Immunol 1981; 127: 1067–1070
  • Askenase PW, Hayden BJ, Gershon RK. Augmentation of delayed-type hypersensitivity by doses of cyclophosphamide which do not affect antibody responses. J Exp Med 1975; 141: 697–702
  • Braun DP, Harris JE. Effects of cytotoxic chemotherapy on immune function in cancer patients. Cancer Treat Symp 1985; 1: 19–26
  • Schwartz A, Askenase PW, Gershon RK. Regulation of delayed type hypersensitivity reactions by cyclophosphamide-sensitive T cells. J Immunol 1978; 121: 1573–1577
  • Mokyr MB, Dray S. Some advantages of curing mice bearing a large subcutaneous MOPC-315 tumor with a low dose rather than a high dose of cyclophosphamide. Cancer Res 1983; 43: 3112–3119
  • Wadler S, Schwartz EL. Antineoplastic activity of the combination of interferon and cytotoxic agents against experimental and human malignancies: A review. Cancer Res 1990; 50: 3473–3486
  • Mitchell MS. Combining chemotherapy with biological response modifiers in treatment of cancer. J Natl Cancer Inst 1988; 80: 1445–1450
  • Mithcell MS, Kempf RA, Harel W. Effectiveness and tolerability of low-dose cyclophosphamide and low-dose intravenous interleukin-2 in disseminated melanoma. J Clin Oncol 1988; 6: 409–424
  • Oratz R, Dungan M, Rosen DF, Harris MN, Speyer JL, Hochster H, Weissman J, Henn M, Bystryn J-C. Lack of effect of cyclophosphamide on the immunology of a melanoma antigen vaccine. Cancer Res 1991; 51: 3643–3647
  • Stalhandske T, Eriksoo E, Sandberg B-M. A novel quinolinecarboxamide with interesting immunomodulatory activity. Int J Immunopharmacol 1982; 4: 336, (abstract)
  • Kalland T, Alm G, Stalhandske T. Augmentation of mouse natural killer activity by LS 2616, a new immunomodulator. J Immunol 1985; 134: 3956–3960
  • Kalland T. Regulation of natural killer progenitors: Studies with a novel immunomodulator with distinct effects at the precursor level. J Immunol 1990; 144: 4472–4476
  • Ilback N-G, Fohlman J, Slorach S. Effects of the immunomodulator LS 2616 on lymphocytes subpopulations in murine coxsackievirus B3 myocarditis. J Immunol 1989; 142: 3225–3228
  • Larsson E-L. Mechanism of action of the new immunomodulator LS 2616 on T cell responses. Int J Immunopharmacol 1987; 9: 425–431
  • Kalland T. Effects of the immunomodulator LS 2616 on growth and metastasis of the murine B16-F10 melanoma. Cancer Res 1986; 46: 3018–3022
  • Stalhandske T, Jansson A-H, Karlstrom R. Restoration of suppressed immune response with the immune modulator quinoline-3-carboxamide (LS 2616) during experimental trypanosomas infection. Int J Immunopharmacol 1985; 7: 391, (abstract)
  • Bengtsson M, Simonsson B, Carlsson K. Stimulation of NK cell, T cell, and monocyte functions by the novel immunomodulator linomide after autologous bone marrow transplantation. Transplant 1992; 53: 882–888
  • Sredni B, Caspi RR, Klein A. A new immunomodulating compound (AS-101) with potential therapeutic application. Nature 1987; 330: 173–176
  • Kalechman Y, Albeck M, Oron M. Radioprotective effects of the immunomodulator AS101. J Immunol 1990; 145: 1512–1517
  • Sredni B, Kalechman Y, Shalit F. Synergism between AS101 and PMA in lymphocyte production. Immunology 1990; 69: 110–116
  • Sredni B, Kalechman Y, Albeck M. Cytokine secretion effected by synergism of the immunomodulator AS 101 and the protein kinase C inducer bryostatin. Immunology 1990; 70: 473–477
  • Vonsover A, Loya S, Sredni B. Inhibition of the reverse transcriptase activity and replication of human immunodeficiency virus type 1 by AS 101 in vitro. AIDS Res Hum Retroviruses 1992; 8: 613–623
  • Kalechman Y, Barkai IS, Albeck M. Use and mechanism of action of AS 101 in protecting bone marrow colony forming units-granulocyte-macrophage following purging with ASTA-Z 7557. Cancer Res 1991; 51: 5614–5620
  • Kalechman Y, Albeck M, Oron M. Protective and restorative role of AS101 in combination with chemotherapy. Cancer Res 1991; 51: 1499–1503
  • Shani A, Tichler T, Catane R. Immunologic effects of AS 101 in the treatment of cancer patients. Natl Immun Cell Growth Regul 1990; 9: 182–190
  • Laporte JP, Gonzales C, Lebas J. A new immunomodulating compound (AS 101) in the treatment of AIDS. 5th International Conference on AIDS, MontrealCanada, 1989, 399, (abstract)
  • Ruiz-Palacois GM, Ponce de Leon A, Alacon-Segovia D. Tolerance and clinical response to AS101, a new immunomodulator in AIDS patients. IV International Conference on AIDS, StockholmSweden, 1988, 229
  • Falloon J, Ogata-Arakaki D, Baseler M. Therapy of HIV infection with AS-101 and zidovudine. 6th Int Conf AIDS, San Francisco, June 23–24, 1990. 3: 209, (abstract)
  • Mohla S, White S, Grzegorzewski K. Inhibition of growth of subcutaneous xenografts and metastasis of human breast carcinoma by swainsonine: Modulation of tumor cell HLA class 1 antigens and host immune effector mechanisms. Anticancer Res 1990; 10: 1515–1522
  • Dennis JW, Koch K, Beckner D. Inhibition of human HT29 colon carcinoma growth in vitro and in vivo by swainsonine and human interferon-alpha 2. J Natl Cancer Inst 1989; 81: 1028–1033
  • Dennis JW, Koch K, Yousefi S. Growth inhibition of human melanoma tumor xenografts in athymic nude mice by swainsonine. Cancer Res 1990; 50: 1867–1872
  • Newton SA, White SL, Humphries MJ. Swainsonine inhibition of spontaneous metastasis. J Natl Cancer Inst 1989; 81: 1024–1028
  • Das PC, Breton P, Grzegorzewski K. Induction of tumoricidal activity in murine alveolar macrophages by swainsonine is modulated by protein kinase C. Proc Am Assoc Cancer Res 1992; 33: 333, (abstract)
  • Yagita M, Noda I, Maehara M. The presence of concanavalin-A like molecules on natural-killer sensitive target cells: Their possible role in swainsonine-augmented human NK cytotoxicity. Int J Cancer 1992; 52: 664–672
  • Humphries MJ, Matsumoto K, White SL. Augmentation of murine natural killer cell activity by swainsonine, a new antimetastatic immunomodulator. Cancer Res 1988; 48: 1410–1415
  • Yagita M, Saksela E. Swainsonine, an inhibitor of glycoprotein processing, enhances cytotoxicity of large granular lymphocytes. Scand J Immunol 1990; 31: 275–282
  • Grzegorzewski K, Newton SA, Akiyama SK. Induction of macrophage tumoricidal activity, major histocompatibility complex class II antigen (lak) expression, and interleukin-1 production by swainsonine. Cancer Commun 1989; 1: 373–379
  • Bowlin TL, McKown BJ, Kang MS. Potentiation of human lymphokine-activated killer cell activity by swainsonine, an inhibitor of glycoprotein processing. Cancer Res 1989; 49: 4109–4113
  • Humphries MJ, Matsumoto K, White SL. An assessment of the effects of swainsonine on survival of mice injected with B16-F10 melanoma cells. Clin Exp Metastatis 1990; 8: 89–102
  • Seftor RE, Seftor EA, Grimes WJ. Human melanoma cell invasion is inhibited in vitro by swainsonine and deoxymannojirimycin with a concomitant decrease in collagenase IV expression. Melanoma Res 1991; 1: 43–54
  • Pulverer G, Beuth J, Ko HL. Glycoprotein modifications of sarcoma L-1 tumor cells by tunicamycin, swainsonine, bromoconduritol or 1-desoxynojirimycin treatment inhibits their metastatic lung colonization in Balb/c-mice. J Cancer Res Clin Oncol 1988; 114: 217–220
  • Goss P, Baker M, Baptist J. Phase I clinical trial of swainsonine in patients with advanced malignancies. Proc Am Soc Clin Oncol 1993; 12: 146, (abstract)

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