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Biomedical subjects

A Rojas

Publications and source records attributed to A Rojas.

At least 163 records · Page 9Linked to original sources
PubMed1985

Adrenal rest tumor of the liver causing Cushing's syndrome: treatment with ketoconazole preceding an apparent surgical cure.

Ketoconazole, an imidazole derivative known to inhibit cytochrome P450-dependent adrenal enzymes was given to a patient with a functioning adrenal rest tumor of the liver in preparation for surgery. The drug was administered in a stepwise manner for 42 days starting with 400 mg and reaching 1 g the last 4 weeks of the trial. Clear clinical improvement was evident early in the trial and was associated with evidence of amelioration of her hypercortisolism and striking changes in serum and urinary levels of steroid hormones and metabolites. Sex steroids in serum and urine fell dramatically from the first day to the end of the trial. Urinary 17-ketosteroid excretion fell from a basal average of 139 mg/24 h to near normal levels within a week of therapy; serum testosterone fell from a basal level of 2.4 to 0.18 ng/ml; serum 17 beta-estradiol fell likewise from 1096 to 150 pg/ml. In contrast, cortisol levels in serum and urine increased in the first 2 weeks of the trial and subsequently fell to values below the basal levels. Similarly, serum 17 alpha-OH-progesterone levels increased 63% above the basal levels by day 6 of the trial and declined afterwards. Nine months after successful tumor resection the patient is apparently cured as judged by steroid hormone levels and physical appearance. We conclude that ketoconazole was effective in blocking tumoral steroidogenesis which resulted in clinical benefit.

11-Hydroxycorticosteroids↗
PubMed1984

The influence of X ray dose levels on normal tissue radioprotection by WR-2721.

A variation in the degree of radioprotection by WR-2721 with X ray dose level is detectable in several normal tissue studies. A similar effect in tumors has been attributed to differential protection of oxic and hypoxic cells. For normal tissues it was previously postulated that it resulted from greater protection of 1 hit damage at low doses, with less protection of multihit damage. However, more extensive analysis of the normal tissue data, including both single dose and fractionated results show that it is not a universal effect in all normal tissues. It now seems more likely that varying PF values result from differential protection of cells at different oxygen tensions, even though the heterogeneity of oxygenation may not be detectable in the response to X rays alone.

Amifostine↗
PubMed1984

Glutathione depletion in tissues after administration of buthionine sulphoximine.

Buthionine sulphoximine (BSO) an inhibitor of glutathione (GSH) biosynthesis, was administered to mice in single and repeated doses of 0.5, 1 and 5 mmol kg-1 (i.p.). The resultant pattern of GSH depletion was studied in liver, kidney, skeletal muscle and three types of murine tumor. Liver and kidney exhibited a rapid depletion to GSH levels of ca. 20% of controls after single doses of 1-5 mmol kg-1 BSO. Muscle was depleted to a similar level, but at a slower rate after a single dose. All three tumors required repeated administration of BSO over several days to obtain a similar degree of depletion to that shown in the other tissues.

Animals↗
PubMed1984

Tumor sensitization and protection: influence of stromal injury on estimates of dose modification.

Tumor regrowth delay is an assay which reflects tumor cell kill but can be modified by growth rate changes resulting from damage to the stroma (tumor bed effects). If the stromal damage is modified by radiosensitizers and radioprotectors to a different degree from the tumor cells, the overall measurement of dose modifying factors may be influenced by the choice of a regrowth size for the growth delay analysis. We have studied the response of two mouse tumors; a fibrosarcoma which showed only a small TBE and a carcinoma which showed a very large TBE. Sensitizer enhancement ratios and protection factors have been obtained by assessing regrowth to a variety of endpoint sizes. The dose modifying effects on the stroma have then been determined by analyzing the regrowth rates of tumors after irradiation. The choice of endpoint size modified both the sensitizer enhancement ratio and the protection factor for both tumors. It appears that stromal damage may be the cause of the radioprotection observed in the carcinoma, whereas direct tumor cell radioprotection is indicated in the fibrosarcoma. Both direct tumor cell killing and cell death secondary to stromal damage will play an important role in determining the local control of irradiated tumors.

Amifostine↗
PubMed1984

Effects of radiomodifiers on high and low LET responses in vivo.

The radioprotector WR-2721 and the radiosensitizer misonidazole have been studied for their influence on the response of mouse skin and tumours when irradiated with either single or fractionated doses of 240 kV X-rays or 3 MeV neutrons. The modification of radiosensitivity to neutrons was significantly less than that for X-rays, both for tumours and skin. When the two drugs were given in combination before single neutron doses, competitive interaction was observed.

Animals↗
PubMed1984

Enhancement of misonidazole radiosensitization by buthionine sulphoximine.

The influence of glutathione (GSH) depletion on the radiation response and on the radiosensitizing efficiency of misonidazole (miso) has been studied in two types of mouse tumour and in mouse skin. Buthionine sulphoximine (BSO) has been administered in a variety of regimes, leading to a maximal depletion of GSH to 37% of control values in one tumour (CA MT) and 61% in the other (SA FA). Pretreatment with BSO did not alter the radiosensitivity of either tumour when treated with X-rays. It had a slight effect on the sensitizing efficiency of miso, corresponding to a factor less than three, which was detectable only at the highest X-ray doses used. No enhancement of miso efficiency was seen with 5 daily fractions. Prolonged administration of BSO resulted in a slight radiosensitization of mouse skin. When combined with miso the effect was very small and was only detectable at high X-ray doses. BSO however produced a marked enhancement of the acute toxicity of miso, as judged by lethality after large single doses.

Animals↗
PubMed1983

Radioprotection of two mouse tumors by WR-2721 in single and fractionated treatments.

The radioprotective effect of WR-2721 has been studied in two murine tumors using single doses or five daily fractions. Single dose irradiations of the SA FA resulted in a highly variable radio-protective response. In one experiment large protection factors (1.2-2.5) were obtained, with the greatest protection at low X ray doses. In later experiments with the same tumor, there was little or no radioprotection. The Ca MT was significantly protected against single dose irradiation with both 250 mg/kg and 400 mg/kg of the drug. In a five fraction schedule the extent of radioprotection for CA MT was greater than with single X ray doses for the same drug dose per fraction. Tumor protection factors from the present work and from the literature are compared with published protection factors for normal tissues. Significant tumor radioprotection is seen in most studies. The data indicate more variability in the extent of tumor protection for a given drug dose than is seen in normal tissues. Tumor protection is often greatest at low X ray doses which may be a result of preferential protection of the better-oxygenated tumor cells.

Amifostine↗
PubMed1983

Interaction of misonidazole and WR-2721--II. Modification of tumour radiosensitization.

Two types of mouse tumour have been used to study the radiomodifying actions of Misonidazole (MISO) and WR-2721 when used alone and in combination with each other. Single dose studies were performed in both of the tumours and fractionated studies were performed on the anaplastic carcinoma, CA MT. Radioprotection with WR-2721 was seen in both tumours, being most marked at low X-ray doses. The protection was more obvious and the sensitization by MISO less in the fractionated experiment. The combination of MISO and WR-2721 gave an intermediate response compared with either drug used alone, resulting in some sensitization with single doses and an overall protection with repeated small doses. An interactive toxicity of the 2 drugs was also observed, suggesting an additive effect when assessed in terms of lethality. These studies indicate that the effects of both MISO and WR-2721 are dependent upon the oxygen status of the cells in the tumour, and that MISO can act in an oxygen-mimetic manner to modify the radioprotection observed with WR-2721.

Amifostine↗
PubMed1982

Interaction of radiosensitizers and WR-2721. I. Modification of skin radioprotection.

We have studied the radiomodifying action in mouse skin of WR-2721 and misonidazole (MISO) when used alone or in combination. The radioprotection with WR-2721 was drug-dose dependent and highly influenced by the O2 concentration at the time of irradiation. Significant sensitizaton was observed with MISO, especially in air-breathing mice. The combination of WR-2721 and MISO produced a radiation response intermediate between the resistant and sensitive responses to either drug alone. The precise degree of sensitivity was dependent on the relative doses of protector and sensitizer. We have also studied the interaction of both drugs in terms of drug-induced lethality, which showed a clear toxic interaction. The WR-2721 LD50 was reduced by a factor of 1.4 with only 200 mg/kg of MISO. We conclude that the combination of WR-2721 and MISO shows an interaction in terms of drug toxicity and radiation response, such that the radioprotection of skin is reduced or even abolished with low doses of MISO.

Amifostine↗
PubMed1982

Radioprotection of mouse skin by WR-2721 in single and fractionated treatments.

The radioprotective action of WR-2721 on mouse skin has been studied using single doses, two and five fractions. Significant radioprotection was observed with 200-500 mg/kg, in animals breathing air or oxygen at the time of irradiation. The degree of radioprotection increased with increasing dose, and was significantly greater in air than in oxygen, especially at low drug doses. Cumulative drug toxicity limited the fractionated treatments to lower drug doses, but the protection observed was similar to that seen with single doses at the same drug levels. The protection factors observed are lower than many published values for skin, and we conclude that a single protection factor cannot yet be stated for any dose of WR-2721. Local tissue oxygenation may account for some of the discrepancies in different studies.

Amifostine↗
PubMed1976

Cell-mediated immune response in head and neck cancer patients.

The immune reactivity of 100 head and neck cancer patients was studied by means of DNCB, candidine, blastic transformation with PHA, and lymphocyte counts. DNCB reactivity was strong in only 21% of the population and was found impaired in patients with advanced primitive tumors, with more than one primitive tumor, and in patients after radiation. Candidine reactivity was impaired in bigger primitive tumors, positive nodes, and advanced stages, as well as in postradiation patients. Blastic transformation was significantly worse in patients over 70 years and tended to be lower in patients with more than one primitive tumor. Good blastic transformation was also lowered in postradiation patients.

Aged↗