Protein a treatment of cancer: Activation of a serum component with trans‐species anti‐B16 melanoma activity

Cooper, Penny; Masinello, Gillian R.

doi:10.1002/ijc.2910320614

Cited by 15 publications

(3 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When it was identified as the active principle of inulin preparations (8) it was developed as a specific reagent for in vivo activation ofthe APC. Since APC activators had an antitumour action on the B16 melanoma in mice (9,10), a similar antitumour activity for g-IN in this system was predicted and found (11). In addition, there was a strong correlation among some 20 substances between ability to activate the APC and antitumour and adjuvant activities (12).…”

Section: Introductionsupporting

confidence: 59%

The adjuvanticity of gamma inulin

Cooper

Steele

1988

Immunol Cell Biol

View full text Add to dashboard Cite

Gamma-inulin (g-IN) is a polymorph identified as the active component of inulin preparations that specifically activates the alternative pathway of complement (APC). The APC is central to many leucocyte functions, including B cell activation. We show here that g-IN, when formulated as a pure, endotoxin-free, fine suspension insoluble at 37 degrees C and given at 50-100 micrograms per mouse, is a potent adjuvant for both humoral and cell-mediated responses to a variety of antigens. g-IN increased secondary IgG responses five- to 28-fold (P less than 0.001), using as antigen phosphorylcholine coupled to keyhole limpet haemocyanin; subclasses IgG 2a, 2b, and 3 were boosted several hundred-fold, IgG 1 10-fold. IgM and IgA were increased four- to six-fold. Delayed hypersensitivity, by footpad swelling after secondary challenge with sheep red blood cells (SRBC), was increased more than two-fold (P less than 0.001) if g-IN was included with the primary SRBC, equivalent to increasing primary doses 10-fold. g-IN was equally active if given 5 days before the primary SRBC. Thus it is an immune stimulant rather than a depot or vehicle for antigen. Mice primed subcutaneously with 30-300 HA units of H2N2 influenza virus (strain A/JAP) and challenged intranasally with a lethal dose of H1N1 virus (strain A/WSN) all died, but if g-IN was given with the primary antigen 50% of the mice survived (P less than 0.001), a deduced but not proven boost to cytotoxic T cell-mediated immunity. Unpublished work has shown that g-IN has no adverse effects at adjuvant-active doses.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

Section: Introductionsupporting

confidence: 59%

The adjuvanticity of gamma inulin

Cooper

Steele

1988

Immunol Cell Biol

View full text Add to dashboard Cite

show abstract

“…Micro-particulate inulin (MPI) was originally developed (Cooper and Carter 1986a) as an anti-cancer therapeutic based on the premise that in vivo alternative pathway complement activation may have anti-tumor effects (Cooper and Masinello 1983;Cooper and Sim 1984;Cooper 1985). The first therapeutic isoform (gamma inulin (GI)) was followed by the more active delta inulin (DI), which is the clinically preferred option .…”

Section: Introductionmentioning

confidence: 99%

The polysaccharide inulin is characterized by an extensive series of periodic isoforms with varying biological actions

2013

View full text Add to dashboard Cite

In studying the molecular basis for the potent immune activity of previously described gamma and delta inulin particles and to assist in production of inulin adjuvants under Good Manufacturing Practice, we identified five new inulin isoforms, bringing the total to seven plus the amorphous form. These isoforms comprise the step-wise inulin developmental series amorphous → alpha-1 (AI-1) → alpha-2 (AI-2) → gamma (GI) → delta (DI) → zeta (ZI) → epsilon (EI) → omega (OI) in which each higher isoform can be made either by precipitating dissolved inulin or by direct conversion from its precursor, both cases using regularly increasing temperatures. At higher temperatures, the shorter inulin polymer chains are released from the particle and so the key difference between isoforms is that each higher isoform comprises longer polymer chains than its precursor. An increasing trend of degree of polymerization is confirmed by end-group analysis using 1 H nuclear magnetic resonance spectroscopy. Inulin isoforms were characterized by the critical temperatures of abrupt phase-shifts (solubilizations or precipitations) in water suspensions. Such (aqueous) "melting" or "freezing" points are diagnostic and occur in strikingly periodic steps reflecting quantal increases in noncovalent bonding strength and increments in average polymer lengths. The (dry) melting points as measured by modulated differential scanning calorimetry similarly increase in regular steps. We conclude that the isoforms differ in repeated increments of a precisely repeating structural element. Each isoform has a different spectrum of biological activities and we show the higher inulin isoforms to be more potent alternative complement pathway activators.

show abstract

“…Among the techniques used for inulin analysis, HPAEC-PAD is the most powerful tool as its resolution power enables one to separate each DP and its isomers (distinction between F n and GF n-1 ). [41,42] With the above-described method, glucose, fructose, and sucrose, eluted before inulin and each subsequent peak in a chromatogram, represents a chain with one additional fructose. Identification of individual peaks was carried out by spiking with standards.…”

Section: Resultsmentioning

confidence: 99%

Chain length distribution of inulin from dahlia tubers as influenced by the extraction method

Kriukova

Jakubiak-Augustyn

Ilyinska

et al. 2017

International Journal of Food Properties

View full text Add to dashboard Cite

A variety of fructans occurs in plants, having various configuration and chain lengths from 3 up to a few hundred fructose units. The structurally simplest fructan is a linear inulin, where the fructose units are linked by β-2,1 bonds, present mostly in Asteraceae and Cichorioideae (e.g. dahlia). The pharmacological effects of fructans depend mainly on the degree of polymerization (DP). Hence, a controlled DP distribution profile is essential for the expected spectrum of pharmacological activities. The aim of this study was to purify fructans from dahlia (Dahlia x hortensis Guill. cv.'Ken's Flame') tubers with different inulin chain lengths profile. We developed the selective preparative approach, followed by qualitative and quantitative analyses by pulsed amperometry-high performance anion-exchange chromatography. The fructans were obtained by the extraction of dahlia tubers with water, concentrated under vacuum, subsequent precipitation of carbohydrate fraction by ethanol, followed by purification using four different combinations of absorbents such as Dowex ® ion-exchange resin, aluminium oxide, calcium carbonate, and activated carbon. The highest content of short-chain inulin (38%) was in the crude fraction and after the separation on Al 2 O 3 and CaCO 3 . All methods selectively enriched inulin in the middle-length chains. The highest concentration of high-quality longchain inulin (16%) was obtained by consecutive washing through CaCO 3 , Al 2 O 3 , Dowex, and charcoal. This complex was also the most balanced in terms of the proportion among short-, medium-, and long-chain inulin (33%, 43%, and 16%, respectively). ARTICLE HISTORY

show abstract

Protein a treatment of cancer: Activation of a serum component with trans‐species anti‐B16 melanoma activity

Cited by 15 publications

References 25 publications

The adjuvanticity of gamma inulin

The adjuvanticity of gamma inulin

The polysaccharide inulin is characterized by an extensive series of periodic isoforms with varying biological actions

Chain length distribution of inulin from dahlia tubers as influenced by the extraction method

Contact Info

Product

Resources

About