Dose-response effects of TPI ASM8 in asthmatics after allergen.

Background: TPI ASM8 contains two modified antisense oligonucleotides (AON) targeting the beta subunit (β(c) ) of the IL-3, IL-5, GM-CSF receptors and the chemokine receptor CCR3. A previous study suggested that TPI ASM8 had broader effects than just inhibition of eosinophils in asthmatics.

Objective: We assessed whether TPI ASM8 caused a dose-dependent attenuation in the inflammatory and physiological changes after inhaled allergen challenge (AIC).

Safety, pharmacodynamics and pharmacokinetics of TPI 1020 in smokers with asthma.

Background: TPI 1020 is a novel compound with potential for anti-neutrophil effects. TPI 1020 exerts its effects by a dual mechanism of action involving corticosteroid activity and controlled donation of nitric oxide.

Objectives: We assessed the safety, pharmacodynamic and pharmacokinetic activity of ascending doses of TPI 1020 compared to budesonide in asthma.

Evaluation of cortisone-heparin and cortisone-maltose tetrapalmitate therapies against rodent tumors. II. Pathological studies.

Pathological studies were undertaken in three tumor-host models which were subjected to cortisone based treatments. The first model was Fisher 344 rats with established orthotopically implanted syngeneic bladder tumor. Cortisone-herapin and cortisone-maltose tetrapalmitate (MTP) treatments induced focal areas of tumor necrosis and necrobiosis, whereas cortisone alone caused necrobiosis.

Evaluation of cortisone-heparin and cortisone-maltose tetrapalmitate therapies against rodent tumors. I. Biological studies.

The antitumor activity of either cortisone-heparin or cortisone-maltose tetrapalmitate combination or both was tested against two animal tumor models. The first model was orthotopically implanted bladder tumor established in syngeneic Fisher 344 rats. Shrinkage and growth arrest of the tumors were induced by cortisone and amplified by its combination with either heparin or maltose tetrapalmitate (MTP).

Antitumor efficacies of maltose tetrapalmitate immunotherapy alone and in combinations with radiotherapy and with cyclophosphamide chemotherapy against dimethylhydrazine induced colon and anal cancers in CDI mice.

Treatment of human colonic cancer in early stages when the process is still limited to the colonic wall is primarily surgery. We wished to see if maltose tetrapalmitate (MTP) immunotherapy alone or in combination with radiotherapy (R) and cyclophosphamide (C) chemotherapy would be effective against primary colon cancer in a fashion similar to that reported by us for primary liver cancer (Anticancer Research 6: 245-250, 1986). One hundred female CD1 mice were subjected to dimethylhydrazine (DMH) treatment once a week for 26 weeks, a period one week before which, colon cancer was histologically documented in each animal of a group that was sacrificed.

Effects of single and combined maltose tetrapalmitate immunotherapy, cyclophosphamide chemotherapy and radiotherapy on ethyl carbamate accelerated primary lung cancer in A/J mice.

A/J mice were given ethyl carbamate to accelerate and to raise to 100 percent the incidence of lung tumours at 34 weeks (day 237) of age. The animals were then divided into groups which received the following treatments: group 1, no treatment; group 2, MTP alone; group 3, radiotherapy alone; group 4, cyclophosphamide alone; group 5, radiotherapy + MTP; group 6, MTP + cyclophosphamide; group 7, radiotherapy followed by cyclophosphamide and group 8, MTP and radiotherapy together followed by MTP and cyclophosphamide. Except for radiotherapy, which was given for 5 consecutive days, MTP and cyclophosphamide were continued till the death of the animals.

Combined radiotherapy, chemotherapy, and maltose tetrapalmitate immunotherapy in the treatment of 4'dimethylaminoazobenzene-induced liver cancer.

Therapeutic effects of radiotherapy (R), chemotherapy, and maltose tetrapalmitate (MTP) immunotherapy alone and in combinations were tried against 4' dimethylaminoazobenzene (DAB) induced primary liver cancer in Wistar rats in three separate protocols. Rats were fed a low protein synthetic diet containing 0.06% DAB for 90-120 days.

Effect of membrane fatty acid composition on radiosensitivity of V79 Chinese hamster cells.

Exponentially growing V79-379A Chinese hamster fibroblasts were transferred to low-lipid medium enriched with a single fatty acid of the C18 series. After 24 h at 37 degrees C, the fatty acid composition was determined by gas chromatography of the corresponding methyl esters for the total lipid extracts of the cells and for the nuclear membrane fraction. Radiation survival curves, based upon a clonogenic assay, were obtained by irradiation with low dose-rate 60Co gamma rays at either 4 degrees C or room temperature.

Combination of 60Co gamma-radiation, misonidazole, and maltose tetrapalmitate in the treatment of Dunning prostatic tumor in the rat.

Maltose tetrapalmitate (MTP), a synthetic nontoxic immunoadjuvant, the radiosensitizer misonidazole (MISO), and 60Co gamma-radiation, alone or in combination, were used in the management of Dunning prostatic tumor in the rat. Nine groups of 10 rats each were used to assess the efficacy of various therapeutic modalities. Tumor growth rates and animal survival times were determined for each group.

Systemic, bladder wall, and bladder tumor concentration of misonidazole following intravesical administration in the rat.

The hypoxic-cell radiosensitizer misonidazole was administered intravesically to normal and to bladder tumor-bearing female Fischer rats. Drug concentration was measured in the bladder wall, the tumor and in the serum using high pressure liquid chromatography at different times following administration. The data shows that misonidazole is readily adsorbed by the bladder wall and the tumor with tissue levels reaching up to 10 times those measured in the serum.

Dietary immunostimulation: interaction with BCG and LPS.

The action of BCG and LPS mR595 used in conjunction with a formula-defined diet is dependent on the administration timing and resembles that of interacting adjuvants affecting different elements of the immune system.

The role of diet on 5-fluorouracil toxicity.

In three experiments performed at two month intervals, rats eating a nutritionally adequate defined-formula diet (DFD) exhibit a remarkable similarity in the response to 5-FU as measured by survival time, leukopenia and weight loss. Conversely, the corresponding control groups eating the standard Purina rat food show a different degree of tolerance to 5-FU, which varies from a level similar to that of the DFD groups to twice that value. It is suggested that certain protective factors against 5-FU toxicity present in natural food are absent in formula diets produced on the basis of standard requirements for normal growth and nutrition.

Dietary enhancement of intestinal radioresistance during fractionated irradiation.

Rats fed laboratory chow or elemental diet 3 were given fractions of 240 rads of 60Co gamma-radiation abdominally (1200 rads/week) until all animals had died. Changes in appetite, body weight, and mortality were monitored as a function of the cumulative dose received. More radiation was needed in the diet-fed group to achieve both 0 and 100% mortality, a difference of 37% at the mean lethal dose level.

Enhanced 5-F.U. mortality in rats eating definded formula diets.

Rats eating nutritionally adequate defined-formula diets (D.F.D) before and following lethal i.

Immunostimulation by a formula-defined diet.

A formula-defined diet (diet 3, table 1) acted as an adjuvant as an adjuvant in the response of the immune system to SRBC in the rat. Similar minimum and maximum antibody levels were measured in both males and females. In the males, the maximum was reached with diet 3 alone while females required the complementary action of diet 3 and LPS mR 595.

Effects of feeding an elemental diet during abdominal irradiation.

Rats fed with normal laboratory feed or elemental diet 3200-BD (Mead Johnson) were administered fractions of 240 rd (-60Co gamma-radiation) abdominally. Consumption of food and its nutrition efficiency were the parameters studied. Anorexia occurred rapidly following only one fraction of 240 rd and was unaffected by the feeding of the diet.