Intratumoral gene therapy versus intravenous gene therapy for distant metastasis control with 2-diethylaminoethyl-dextran methyl methacrylate copolymer non-viral vector-p53.

Lung cancer still remains to be challenged by novel treatment modalities. Novel locally targeted routes of administration are a methodology to enhance treatment and reduce side effects. Intratumoral gene therapy is a method for local treatment and could be used either in early-stage lung cancer before surgery or at advanced stages as palliative care. Novel non-viral vectors are also in demand for efficient gene transfection to target local cancer tissue and at the same time protect the normal tissue. In the current study, C57BL/6 mice were divided into three groups: (a) control, (b) intravenous and (c) intatumoral gene therapy. The novel 2-Diethylaminoethyl-Dextran Methyl Methacrylate Copolymer Non-Viral Vector (Ryujyu Science Corporation) was conjugated with plasmid pSicop53 from the company Addgene for the first time. The aim of the study was to evaluate the safety and efficacy of targeted gene therapy in a Lewis lung cancer model. Indeed, although the pharmacokinetics of the different administration modalities differs, the intratumoral administration presented increased survival and decreased distant metastasis. Intratumoral gene therapy could be considered as an efficient local therapy for lung cancer.

Effect of adjuvants on antibody responses of sheep immunised with recombinant pili from Dichelobacter nodosus.

OBJECTIVE: To compare the effects of two oil emulsion adjuvants (incomplete Freunds adjuvant and a proprietary oil adjuvant), DEAE-dextran, L-tyrosine particles and Quil A on the humoral immune responses of sheep immunised with recombinant pili of Dichelobacter Nodosus (strain A). PROCEDURE: Antibody titres were studied for up to 32 weeks and were measured by bacterial agglutination and ELISA. The relative avidity of antibodies for pili was determined and the incidence and severity of adverse reactions at the site of injection of vaccines were recorded. RESULTS: The oil emulsion adjuvants and Quil A were more effective than either DEAE-dextran or L-tyrosine at stimulating antibodies in sheep. The incidence and severity of adverse reactions was lower in sheep which received vaccines containing either Quil A or DEAE-dextran than in sheep which received vaccines containing oil emulsion adjuvants. L-tyrosine had no adverse effects. CONCLUSION: Quil A was as effective as oil adjuvants at stimulating high levels of antibodies against recombinant pili in sheep and had the significant advantage of being less irritant after subcutaneous injection.

Evidence of a lack of enteric side-effects induced by DEAE-dextran in man.

The breakdown of the carbohydrates by the colonic bacterial flora can cause intestinal symptoms, such as meteorism, abdominal pain and diarrhoea. The ability of human bacterial flora to break down the DEAE-dextran, a new lipid lowering resin, similar to cholestyramine, was investigated in man. Colonic bacterial flora did not appear to break down DEAE-dextran, as assessed by hydrogen respiratory excretion measured in healthy volunteers. Furthermore, the blood levels of vitamin A, E and D (as 25-OH and 1,25-OH derivatives) were measured in patients treated with the DEAE-dextran in order to study the interference of DEAE-dextran on the absorption of liposoluble vitamins. With the exception of slightly depressed vitamin A levels in 3 patients out of 16, the blood values of the vitamins A, E and D were within the normal ranges, indicating that DEAE-dextran does not interfere with liposoluble vitamin absorption by the gut.

Clinical pharmacology of DEAE-dextran for long-term administration (one year).

Twenty-eight patients with hyperlipoproteinaemia types II and IV according to Fredrickson were treated for one year with diethylaminoethyl-dextran (DEAE-D). The drug, used at a daily oral dosage of 2 to 3 g, proved very effective in reducing both blood cholesterol and triglycerids (mean reduction was 24 percent and 31 percent respectively). The drug also proved itself to be remarkably free from side-effects, as assessed both by a comprehensive check of biochemical parameters as well as by the patients themselves. The results obtained confirm the hypolipaemic effectiveness of DEAE-Dextran, due to an increased elimination of bile acids and fatty acids by the G.I. route.

Life span, leukaemia and amyloid incidences of untreated and polycation-treated AKR mice.

AKR mice, which have a short mean survival time and usually die with leukaemia, were studied from one month of age for correlation between these two parameters. For untreated animals we found the same mean survival time whether or not leukaemia occurred. By treating sucklings with the polycations diethylaminoethyl-dextran or hexadimethrine bromide the leukaemia incidence was significantly reduced. However, the mean survival time was unchanged, and remained the same in leukaemic and non-leukaemic animals. It is therefore suggested that the early death of AKR mice results from an ageing process and does not require leukaemia for implementation. Our prophylactic polycation treatment was furthermore found to induce spleen amyloid in some but not all of the mice that remained non-leukaemic.

[Comparison of a bivalent anti-foot-and-mouth disease vaccine with oil adjuvant to a vaccine with DEAE-dextran adjuvant in swine]. / Comparaison d'un vaccin antiaphteux bivalent avec adjuvant huileux à un vaccin avec adjuvant DEAE-dextran chez les porcs.

The report compares the compatibility, efficacity and serology response of two bivalent anti-foot-and-mouth disease vaccines (OC). One is oil-adjuvanted and the other based on diethyl-amino-ethyl-dextran (DEAE-Dextran). After vaccination no general clinical or local reactions are normally observed. Tissular reactions at the inoculation site are more severe with the oil-adjuvanted vaccine than with the DEAE-Dextran vaccine. Meat inspection, about three months after injection of the vaccine, showed the lesions to be in regression and negligible. The control of activity has been performed by the virulence test. For the oil-adjuvanted vaccine, protection against O1-Lausanne, 5, 21 and 90 days after vaccination is 90%, 80-100% and 55% respectively. For the DEAE-Dextran vaccine, these levels of protection are 80% after 5 days and 20-70% after 21 days. The percentage of swine protected against C-Noville 35 days after vaccination is 100% for the oil-adjuvanted vaccine and 70% for the DEAE-Dextran vaccine. The evolution of the amount of serum antibodies was followed for three months by the method of seroneutralization on cell cultures.