Response of Transplanted AKR Leukemia to Combination Therapy With Amphotericin Band 1,3-Bis(2-chloroethyl)-1-nitrosourea: Dose and Schedule Dependency2

Medoff, Gerald; Valeriote, Fred; Ryan, Julia; Tolen, Sandra

doi:10.1093/jnci/58.4.949

Cited by 18 publications

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“…AraB has been variously reported to increase (5,15) and to decrease (4,5) cell numbers in vitro. In combination with some antitunmr agents, Arab exerted synergistic effects in curing a mouse leukemia (14). The differences in growth effects noted herein seemed to depend, at least in part, upon serum content of the medium, which may also refect differences in sterol content.…”

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confidence: 70%

Amphotericin B augments interleukin-6 production by human gingival fibroblasts In vitro

Lapp

1997

In Vitro Cell.Dev.Biol.-Animal

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Dear Editor:It has been suggested that gingival fibroblasts (GF) function as an accessory immune tissue in the oral cavity (1) because these cells respond to inflammatory stimuli such as lipopolysaccharide, interleukin-ll3 (IL-113), and tumor necrosis factor alpha (TNFa) by production of other proinflammatory mediators. During our studies to optimize the cell culture system used for research on IL-6 modulation by hormones in GF, other factors have been discovered to affect production of this cytokine. We report here that amphotericin B (AmB) at or above 2,5 pg/ml stimulates both cell growth and IL-6 release from GF in low-serum medium.Primary cultures of human GF were established from explants of normal tissue removed during periodontal surgery (12). These cells were maintained in Dulbecco's modified Eagle's medium (DMEM; GIBCOBRL, Grand Island, NY) containing 2% fetal bovine serum (FBS; Atlanta Biologicals, Atlanta, GA) and 8% NuSerum V (Collaborative Research Inc., Waltham, MA) with nonessential amino acids, penicillin (tO0 U/ml), and streptomycin (100 ~g/ml). For experiments, cells were detached with trypsin/EDTA. The plating medium (called 4% FBS +) was phenol red-free DMEM containing nonessential amino acids, 15 mM HEPES, 4% FBS, 1.5 X ReduSer II (Upstate Biological Inc., Lake Placid, NY) and a final concentration of 1.25 mg bovine serum albumin/ml, with antibiotics as just noted.For growth studies, a modification of the crystal violet assay of Keung et al. (9) was used to study proliferation. Ceils were plated into 4% FBS + at 3 to 9 × lO3/well in a 96-well plate and allowed to attach overnight. Plates were then washed with phenol red-free Hanks' balanced salt solution (HBSS), and various concentrations of AraB (Sigma Chenfical Co., St. Louis, MO) in fresh medium were added. After incubation for 48-72 h, the cells were fixed by the addition of 11% glutaraldehyde (10 ~tl/lO0 g1 medium). Plates were shaken for 20 min in a rotary shake~, then rinsed thoroughly and allowed to dry overnight. Cells were stained by the addition of 100 pl of 0.1% crystal violet (in 0.2 mM 2-[N-morpholino]-ethanesulfonic acid, pH 8.0) per well; after 20 min of shaking, plates were again rinsed and allowed to dry overnight. Dye was solubilized by the addition of 100 gl of 10% acetic acid/well. Plates were shaken for 10 min; then the optical densities were read in a microplate reader (Molecular Devices, Menlo Park, CA) at 562 nm. AmB, up to at least 2.5 ug/ml, stimulated cell growth in GF (Fig. 1). Cells from a single pool were allowed to attach in the absence of AmB, so the increased cell numbers were not due to effects on cellular attachment. Cells plated sparsely at 3 × 103 per well were more dramatically stimulated to grow by AmB doses, relative to the control. In this low-serum medium, doses of 1 and 2.5 ug/ml significantly increased cell numbers (P < 0.05), as measured by this crystal violet proliferation assay. These short-term stimulatory effects were not apparent in medium containing 10% FBS. Similar results were seen when ce...

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confidence: 70%

Amphotericin B augments interleukin-6 production by human gingival fibroblasts In vitro

Lapp

1997

In Vitro Cell.Dev.Biol.-Animal

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“…AmB is currently used as a primary therapeutic agent for the treatment of many systemic mycoses. Several lines of evidence suggest that the drug may considerably enhance host immune response (6,14,19) and may induce macrophage activation (11). Thus, AmB administration protects mice against bacterial (20) and helminthic (17) infections and leads to increased phagocytic and antibacterial activity of peritoneal macrophages in vitro (8,11).…”

Section: Resultsmentioning

confidence: 99%

“…Amphotericin B (AmB) is a polyene antifungal antibiotic that has immunoactive properties in mice (14). Since it stimulates both humoral (6) and cell-mediated (19) immunity and also enhances host resistance to Listeria monocytogenes (20) and Schistosoma mansoni (16) infections, it can be questioned whether at least part of the antifungal activity may be attributed to its immunoactive properties (12).…”

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confidence: 99%

Immunoadjuvant activity of amphotericin B as displayed in mice infected with Candida albicans

Bistoni¹,

Vecchiarelli²,

Mazzolla³

et al. 1985

Antimicrob Agents Chemother

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Mice receiving a single intraperitoneal injection of amphotericin B showed increased resistance to subsequent challenge with either Candida albicans or Staphylococcus aureus. This enhancement of resistance was obvious in terms of both survival criteria and clearance of the intravenously injected organism from different organs. The protective effect of amphotericin B was conditioned by dose, time of drug administration, and size of yeast or bacterial inoculum and was reversed by cyclophosphamide. Effector cells from mice treated with amphotericin B displayed enhanced fungicidal activity in vitro as measured in a short-term 51Cr release assay. Macrophages from intact animals exposed in vitro to amphotericin B also acquired strong candidacidal reactivity.Amphotericin B (AmB) is a polyene antifungal antibiotic that has immunoactive properties in mice (14). Since it stimulates both humoral (6) and cell-mediated (19) immunity and also enhances host resistance to Listeria monocytogenes (20) and Schistosoma mansoni (16) infections, it can be questioned whether at least part of the antifungal activity may be attributed to its immunoactive properties (12).In an approach to this problem, and following a line of research in our laboratory on modulation of resistance to Candida albicans infection by chemotherapeutic agents in mice (2, 4), we investigated the impact of AmB treatment on host resistance to the yeast as measured under both in vivo and in vitro conditions. The animals were studied in vivo for their ability to resist infection at different times after AmB exposure, and an array of in vitro tests were devoted to clarification of the mechanisms underlying changes in susceptibility.We found that a single dose of AmB was followed by a long-lasting augmentation of resistance which was mirrored by modifications in in vitro functions. harvested by low-speed centrifugation (1,000 x g), washed twice in saline, and diluted to the desired density. In the in vivo studies, C. albicans was injected intravenously via the tail vein in a volume of 0.5 ml per mouse.(ii) Staphylococcus aureus. A coagulase-positive S. aureus strain (Cowan, NCTC, Colindale) was grown at 37°C on Mannitol salt agar (BBL). After the 24-h culture, microorganisms were harvested by low-speed centrifugation, washed twice in saline, and diluted to the desired density of CFU per milliliter. Each experimental group consisted of at least 10 mice.AmB assay. Levels of AmB in pooled serum obtained from 10 mice 3 to 90 h after injection of AmB (10 mg/kg) were determined by an agar well diffusion method (18).Briefly, a quantity of C. albicans from a 24-h culture sufficient to produce 105 CFU/ml of Sabouraud glucose medium was added to molten agar (48°C) containing 20 U of penicillin and 20 ,ug of streptomycin per ml (GIBCO Laboratories, Grand Island, N.Y.).The C. albicans-containing agar was distributed in 25-ml volumes into plastic dishes (100 by 15 mm). A 5-mm-diameter cylinder punch was used to cut wells into seeded agar so that there were nine evenly distributed ...

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“…It is possible that two horizontally oriented AmB molecules and one dipalmitoyl phosphatidylcholine (DPPC) molecule in the vertical position form a stable complex that affects the thermodynamic properties of phospholipid membrane ( Minones et al, 2004 ). At the same time, in recent years, some studies have found that AmB has the potential to induce immunogenic cell death and that induction is relative to the effect of AmB on the cell membrane ( Medoff et al, 1974 ; Stein et al, 1982 ). With the gradual discovery of more functions of AmB, it is increasingly urgent to investigate the interaction mechanism between AmB and phospholipids in cell membranes.…”

Section: Introductionmentioning

confidence: 99%

Effect of high sodium ion level on the interaction of AmB with a cholesterol-rich phospholipid monolayer

Wang,

Qiang,

et al. 2024

Front. Mol. Biosci.

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Invasive fungal infections are a primary reason for high mortality in immunocompromised people, especially in critically ill patients, such as intensive care unit (ICU) patients, advanced cancer patients, or severe burn patients. Hypernatremia also can increase mortality in severely ill patients. Amphotericin B (AmB) is the gold standard for treating infections, but in severely ill patients, AmB can cause hematotoxicity when administered intravenously due to its interaction with cholesterol on red blood cell membranes. This results in limited doses of AmB and affects the treatment of infections. The proportion of cholesterol molecules in membrane lipids in red blood cells is as high as 50 mol%, and the sodium ions can influence the interaction between AmB and lipids on the membrane. Therefore, in the complex clinical situation of a severely ill patient with a fungal infection and hypernatremia, the interaction between amphotericin B and the red blood cell membranes is worth studying in depth. In this work, the interaction between AmB and the dipalmitoyl phosphatidylcholine (DPPC)/cholesterol mixed monolayer in the presence of high sodium ion levels was studied when the proportion of cholesterol was 50%. The results show that the effect of AmB on reducing the monolayer’s area at a high level of sodium ions is slightly stronger at 30 mN/m. The effect of AmB on reducing the elastic modulus of the DPPC/Chol monolayer is significantly weakened by a high sodium ion level, compared with the level of sodium ions at normal physiological concentration. The higher the sodium ion concentration, the weaker the intermolecular force of the DPPC/Chol/AmB mixed monolayers. The scanning electron microscope (SEM) and atomic force microscopy (AFM) observations suggest that at a high sodium ion level, the presence of AmB significantly reduces the surface roughness of the DPPC/Chol monolayer. AmB may bind to cholesterol molecules, and it isolates cholesterol from the monolayer, resulting in a reduced height of the cholesterol-rich monolayer and an increasingly dispersed monolayer region. The results are beneficial to understanding the mechanism of impact of a high sodium ion level on the relationship between AmB and red blood cell membranes rich in cholesterol and are valuable for understanding the hemolytic toxicity of AmB to red blood cells at a high sodium ion level.

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Response of Transplanted AKR Leukemia to Combination Therapy With Amphotericin Band 1,3-Bis(2-chloroethyl)-1-nitrosourea: Dose and Schedule Dependency2

Cited by 18 publications

References 0 publications

Amphotericin B augments interleukin-6 production by human gingival fibroblasts In vitro

Amphotericin B augments interleukin-6 production by human gingival fibroblasts In vitro

Immunoadjuvant activity of amphotericin B as displayed in mice infected with Candida albicans

Effect of high sodium ion level on the interaction of AmB with a cholesterol-rich phospholipid monolayer

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