Disease relevance of levamisole

• The cost of 5-FU/levamisole therapy for stage III colon cancer per year of life saved is less than $ 5,000, which represents a favorable cost-benefit relationship for a medical intervention [1].
• A randomized trial of levamisole versus placebo as adjuvant therapy in malignant melanoma [2].
• Use of levamisole in Hodgkin's disease [3].
• Toxic effects of levamisole alone were infrequent, usually consisting of mild nausea with occasional dermatitis or leukopenia, and those of levamisole plus fluorouracil were essentially the same as those of fluorouracil alone--i.e., nausea, vomiting, stomatitis, diarrhea, dermatitis, and leukopenia [4].
• Letter: Levamisole in sarcoidosis [5].
• These findings strongly suggest that levamisole decreases iRBC sequestration in falciparum malaria in vivo and should be considered as a potential adjunctive treatment for severe falciparum malaria [6].

Psychiatry related information on levamisole

• Enhanced host defense mechanisms with levamisole in suckling rats [7].

High impact information on levamisole

• Levamisole in Job's syndrome [8].
• Levamisole in insulin-dependent diabetes mellitus [9].
• Incubation in vitro of lymphocytes from patients with Hodgkin's disease with 40 mug per milliliter of levamisole resulted in a rise in the number of E-rosette-forming cells from 33.6 +/- 12.5 per cent (mean +/- S.D.) to 56.7 +/- 14.6 per cent [10].
• These results demonstrate a clear immunologic effect of levamisole in Hodgkin's disease and indicate that the low number of E-rosette-forming cells is not due to a real T-cell depletion [10].
• Levamisol in psoriatic arthritis [11].

Chemical compound and disease context of levamisole

• We analyzed tumor tissue from 460 patients with stage III and high-risk stage II colon cancer who had been treated with various combinations of adjuvant fluorouracil, leucovorin, and levamisole to determine the ability of these markers to predict survival [12].
• The effect of four immunomodulators (BCG, Corynebacterium parvum, pyran copolymer, and levamisole) on the cellular arm of antibody-dependent cellular cytotoxicity (ADCC) was investigated in mice with 51Cr-labeled chicken erythrocytes employed as targets [13].
• Three parameters of macrophage function: random migration, chemotaxis, and pinocytosis, were studied in the guinea pig after administration of Corynebacterium parvum, methanol-extraction residue of BCG, and levamisole (LMS), a synthetic anthelmintic [14].
• Chemotherapy of onchocerciasis: a controlled comparison of mebendazole, levamisole, and diethylcarbamazine [15].
• The antitumor efficacy of various immune stimulants [Corynebacterium parvum, Bordetella pertussis, and Bacillus Calmette-Guérin (BCG)] and levamisole alone or in conjunction with cyclophosphamide (CY) was studied in the CaD2 mammary adenocarcinoma system using schedules developed previously with C. parvum and CY [16].

Biological context of levamisole

• Acute effects of orally administered levamisole on random monocyte motility and chemotaxis in man [17].
• All these drugs, except levamisole, stimulated the effector cells of ADCC in the spleen, but the kinetics of their effect differed [13].
• Lymphocytes or macrophages from normal mice given levamisole had no effect on tumor cells in vitro, whereas lymphocytes incubated with levamisole in vitro enhanced tumor cell growth [18].
• However, no consistent pattern between cell-adhesion molecule expression, cell-cell adhesion, or levamisole concentration could be discerned [19].
• Levamisole effects on major histocompatibility complex and adhesion molecule expression and on myeloid cell adhesion to human colon tumor cell lines [19].

Anatomical context of levamisole

• When patients with the hyperimmunoglobulin E syndrome took levamisole by mouth, the abnormal chemotactic responses of their neutrophils were significantly improved towards normal [20].
• Effects of levamisole on normal and abnormal leukocyte locomotion [20].
• Random monocyte motility was significantly increased (P less than 0.025) in 13 of 17 patients receiving levamisole [17].
• Mechanism of synergy of levamisole and fluorouracil: induction of human leukocyte antigen class I in a colorectal cancer cell line [21].
• The stimulated tumor growth may have been mediated by a direct effect of levamisole on the lymphoma cells, through an effect on other cell types, or by both effects; these effects apparently outweighed potentially beneficial effects of levamisole on the immune system [22].

Associations of levamisole with other chemical compounds

• In vitro run-on transcription revealed that 5-FU caused a 20%-57% reduction in RNA synthesis, while levamisole caused a 30%-190% increase in RNA synthesis [21].
• Lymphocyte subsets in measles. Depressed helper/inducer subpopulation reversed by in vitro treatment with levamisole and ascorbic acid [23].
• The effect was then compared to that elicited by theophylline or levamisole, which both demonstrated thymosin-like action in vitro [24].
• To identify nAChR accessory proteins, which may regulate their expression or function, we performed tandem affinity purification of the levamisole-sensitive nAChR from Caenorhabditis elegans, mass spectrometry of associated components, and RNAi-based screening for effects on in vivo nicotine sensitivity [25].
• Experimental treatment consisted of one of three chemotherapy regimens: the low-dose leucovorin plus FU (Mayo Clinic; LDLV) regimen, the high-dose leucovorin plus FU (Roswell Park; HDLV) regimen, and the low-dose leucovorin plus levamisole plus FU (LDLV plus LEV) regimen, each administered for 30 to 32 weeks [26].

Gene context of levamisole

• We show that three of the eleven genes of the nematode Caenorhabditis elegans that mediate resistance to the nematocide levamisole and to other cholinergic agonists encode nicotinic acetylcholine receptor (nAChR) subunits. unc-38 encodes an alpha subunit while lev-1 and unc-29 encode non-alpha subunits [27].
• In the nematode Caenorhabditis elegans, a genetic screen for levamisole resistance has identified 12 genes, three of which (unc-38, unc-29, and lev-1) encode nicotinic acetylcholine receptor (nAChR) subunits [28].
• Genetic ablation of both the levamisole-sensitive receptor and acr-16 abolished all cholinergic synaptic currents at the NMJ and severely impaired C. elegans locomotion [29].
• In addition, since expression of functional unc-29 in muscle cells restored levamisole sensitivity under some but not all conditions, both neuronal and muscle cell UNC-29 receptors are likely to contribute to the regulation of egg-laying behavior [30].
• This study examined the effect of levamisole on PGE(2) production and COX-2 gene activation in immortalized human colon cells [31].

Analytical, diagnostic and therapeutic context of levamisole

• Letter: Immunotherapy with levamisole [32].
• Some aspects of host response to levamisole after chemotherapy in a murine leukemia [33].
• This effect correlated with the shortened survival time of BALB/c mice treated with levamisole prior to P1798 implantation compared to that of a control group not pretreated [22].
• These results indicated that increases in peripheral blood monocyte motility followed oral administration of levamisole [17].
• Administration of levamisole before tumor transplantation enhanced the early appearance of neoplasms but did not affect the overall incidence or course of tumor growth as compared with that observed in controls given saline injections or animals given levamisole with lethally X-irradiated tumor cells [18].

References