Disease relevance of Tilorone hydrochloride

• Further observations on the inhibition of tumor growth by Corynebacterium parvum with cyclophosphamide. V. Comparison of the effects of tilorone hydrochloride, levamisole, methanol-soluble fraction of Mycobacterium butyricum, BCG, and a nonviable aqueous ether extract of Brucella abortus preparation in treatment of mice with tumors [1].
• Inhibition of deoxynucleotide-polymerizing enzyme activities of human leukemia lymphoblasts and simian sarcoma virus by tilorone and thirteen of its analogs [2].
• DFMO or tilorone administered alone showed 28 and 46% inhibition of tumor growth and 80 and 58% inhibition of metastases, respectively [3].
• In B16 melanoma, DFMO, tilorone, or poly(l) X poly(C), when administered alone, showed 85, 39, and 39% of inhibition of tumor growth, respectively [3].
• Necrosis of the spinal cord was produced by administering tilorone to rats before or during the incubation period of experimental allergic encephalomyelitis (EAE) [4].

High impact information on Tilorone hydrochloride

• The action of these compounds on murine leukemia virus was presumely different from that of tilorone [5].
• Drugs that did not activate macrophages, such as typhoid vaccine, tilorone, levamisole, WY-13876, and thymosin, were ineffective in prolonging the life of tumor-bearing mice [6].
• In vitro H-2Kb Ag-negative and -positive Hepa-1 cells are equally susceptible to tilorone-boosted NK cells, indicating that MHC class I Ag expression also does not affect in vitro NK susceptibility [7].
• Tilorone also depleted T lymphocytes, but light- and electron-microscopic examination revealed hyperplasia and vacuolation of the interdigitating cells that remained in the thymus-dependent areas, rather than shrinkage [8].
• Depletion of lymphoid tissues by tilorone. Ultrastructure and synergistic interaction with antilymphocyte serum [8].

Chemical compound and disease context of Tilorone hydrochloride

• Sixteen patients with amyotrophic lateral sclerosis (ALS) participated in a double-blind, placebo-controlled study using tilorone hydrochloride, a drug active against a variety of DNA and RNA viruses in animals [9].
• A mouse model of encephalitis caused by herpes simplex virus was used to compare the antiviral activity of tilorone hydrochloride with that of phosphonoacetic acid [10].
• Four microbial and two chemically defined immunomodulating agents namely viable BCG, killed Mycobacterium butyricum, killed Lactobacillus plantarum, zymosan, tilorone, and dimethyldioctadecylammonium bromide (DDA) were studied for their effects on macrophage functions in vitro and in vivo [11].
• Administration of 3,6-bis[2-(Dimethylamino)-ethoxy]-9H-xanthen-9-one dihydrochloride) Tilorone) or recombinant interleukin-2 (rIL-2) to mice with severe combined immunodeficiency (C.B.-17 scid/scid) resulted in an increase in YAC-1 lysis by their splenocytes as well as bone marrow cells [12].
• Polyriboinosinic-polyribocytidylic acid, statolon and tilorone arrested the growth of Ehrlich ascites tumour cells in vivo [13].

Biological context of Tilorone hydrochloride

• Effect of tilorone treatment on intracellular microbial infections in specific-pathogen-free mice [14].
• These kinetics correlated with the inhibition of in vivo lung colonization after tilorone analogue treatment [15].
• Thus, aniline hydroxylase activity, which develops very rapidly during the first 2 days postpartum, was depressed markedly by tilorone, ethylmorphine N-demethylase activity was depressed moderately, and benzo[a] pyrene hydroxylase, normally the slowest of the three monooxygenase activities to develop, was induced [16].
• Treatment of pregnant rats with tilorone on days 17-20 of gestation inhibited normal maternal weight gain and produced overt signs of toxicity.(ABSTRACT TRUNCATED AT 400 WORDS)[17]
• These findings suggest that tilorone hydrochloride has a specific effect on T-lymphocytes that accounts for its effect on cellular immunity, but that its antiviral activity is not primarily mediated by T-lymphocytes [18].

Anatomical context of Tilorone hydrochloride

• Ultrastructural and histochemical studies of the renal lesion produced by tilorone and one of its analogs revealed striking accumulation of vacuoles and/or acid-phosphatase-positive lemellar bodies retricted to glomeruli, ascending limb of Henle's loop, and distal convoluted tubules [19].
• The large size and large number of nuclear bodies produced by tilorone should facilitate studies of this poorly understood nuclear organelle [20].
• Nuclear bodies produced in astrocytes by tilorone [20].
• Large, eosinophilic, nonglycogenic nuclear inclusions were produced in the central nervous system by the drug tilorone [20].
• The combination of ALS and a tilorone analog that was capable of depleting lymph node but not spleen, gave a synergistic effect only in lymph node and not in spleen [8].

Associations of Tilorone hydrochloride with other chemical compounds

• RNA blotting analysis demonstrates that interferon-alpha (IFN-alpha) and its inducers, i.e. poly(I).poly(C), bacterial lipopolysaccharide (LPS) and tilorone (2,7-bis-[2-(diethylamino)ethoxy]fluoren-9-one), increase the expression of XD mRNA in liver [21].
• No increase in survival rate was obtained by use of phosphonoacetic acid and tilorone hydrochloride in combination [10].
• Neither ABPP nor tilorone induced TNF or IL-6 [22].
• Pregnant rats received either tilorone or poly IC and saline, PB, MC or PCN, and microsomes from their livers and those of their fetuses were examined for cytochrome P-450 content, aminopyrine (AP) N-demethylase activity and benzo[a]pyrene (BP) hydroxylase activity [17].
• The antitumor potential against LLC has been evaluated in comparison with standard synthetic immunomodulators such as pyran copolymer (MVE-2), isoprinosine, levamisole, and tilorone while manipulating the immune systems by immunosuppressive agents, cyclophosphamide (CY) and 2-chloroadenosine [23].

Gene context of Tilorone hydrochloride

• NK cells mediate increase of phagocytic activity but not of proinflammatory cytokine (interleukin-6 [IL-6], tumor necrosis factor alpha, and IL-12) production elicited in splenic macrophages by tilorone treatment of mice during acute systemic candidiasis [24].
• Mice reconstituted with AKR bone marrow were deficient both in interferon production using tilorone and Newcastle disease virus as inducers, and at the level of natural killer cells responding to exogenously administered interferon [25].
• Tilorone treatment reduced the granulomatous response within the Salmonella-infected liver, suggesting that the drug interferes with the mobilization of the mononuclear defenses within the normal host [26].
• In passive EAE, the most significant increase occurred only in the lower spinal cord for cathepsins A and C, and fourthly, in monocytic EAE induced by tilorone, there was an exceptionally large, 3-fold increase in cathepsin C in lower cord as compared to a 1.5-2 fold increase for other cathepsins [27].
• Tilorone (2,7-bis[(diethylamino)ethoxy]fluoren-9-one) can enhance the humoral immune response of mice to SRBC although Tilorone has no effect on functional activity of splenic B cells in the absence of immunogen [28].

Analytical, diagnostic and therapeutic context of Tilorone hydrochloride

• On the basis of neurologic examination, pulmonary function studies, quantitative muscle examination, speech recording, and periodic filming of functional muscle strength, it was concluded that at a dose of 1 gm per week, tilorone did not alter the course of ALS [9].
• Skin and heart allograft prolongation in tilorone-treated rats [29].
• The present study determines the amounts and patterns of glycosaminoglycans stored in cultured corneal fibroblasts after treatment with tilorone and three related compounds [30].
• The magnitude of the synergy was similar to that produced by adrenalectomy, but the effect of tilorone was not mediated by the adrenal glands [31].
• Adjuvant arthritis is inhibited by the interferon-inducing anti-viral agents statolon, pyran copolymer and tilorone, and by the passive transfer of interferon [32].

References