Search PubMed⌕ Search

Biomedical subjects

J Laszlo

Publications and source records attributed to J Laszlo.

142 records · Page 8Linked to original sources
PubMed1966

Actinomycin D: inhibition of respiration and glycolysis.

Actinomycin D inhibited respiration and anaerobic glycolysis of human leukemic leukocytes and lowered the adenosine triphosphate content of the cells. Inhibitory effects on respiration and on RNA synthesis could not be dissociated from one another over a wide range of drug concentrations. Actinomycin D also impaired protein synthesis, probably by decreasing the availability of adenosine triphosphate and by inhibiting messenger RNA.

Adenosine Triphosphate↗
PubMedDate not supplied

Antiemetic effect of intramuscular levonantradol in patients receiving anticancer chemotherapy.

Positive results of investigations of the antiemetic activity of delta-9-tetrahydrocannabinol (THC) in patients receiving cancer chemotherapy have led to the development of levonantradol, a synthetic derivative of THC. We assessed both the antiemetic activity and toxicity of intramuscular levonantradol in patients receiving cancer chemotherapy who were refractory to conventional antiemetic therapy. An open dose-finding study was conducted using initial doses of 0.5 mg. Doses were escalated by 0.5 mg when an incomplete response with no toxicity was observed. Of the 28 patients initially treated, 25/28 (89 per cent) achieved a complete or partial antiemetic response at doses ranging from 0.5 to 1.5 mg. There was no difference in response rate with respect to age or patient size. Of the 31 patients evaluable for toxicity, six reported none. Dysphoria, the dose-limiting toxicity, occurred in five patients (16 per cent) at 1.0 to 1.5-mg doses. The most commonly reported side effects were somnolence (48 per cent) and dry mouth (32 per cent). We conclude that intramuscular levonantradol is an effective antiemetic at doses as low as 0.5 mg.

Adolescent↗
PubMedDate not supplied

Levonantradol for chemotherapy-induced emesis: phase I-II oral administration.

Thirty five patients were enrolled into a Phase I-II study of oral levonantradol being tested as an antiemetic for chemotherapy patients who were refractory to the aggressive use of standard antiemetic agents. Sixty-nine total courses were given. Dysphoric reactions (fear, anxiety, hallucinations) were the most serious side effects, and were most prevalent at the highest dose tested (2.0 mg q4h). Somnolence, a "high" feeling, hypotension were also noted. Antiemetic responses were seen at 0.5, 1.0, 1.5 and 2.0 mg dose levels: the two intermediate doses gave responses comparable to those previously reported for oral THC. It is suggested that a combination of oral and parenteral levonantradol may prove to be a very effective program to relieve the otherwise disabling problems of persistent nausea and vomiting.

Administration, Oral↗
PubMedDate not supplied

The role of interferon in cancer therapy: a current perspective.

Recombinant interferon alpha has now been established as having a distinct if narrow role when used as a single agent in cancer therapy. The responses to single-agent therapy can be grouped as shown in Table 7. Interferon is likely to be the treatment of choice for hairy cell leukemia and possibly also for symptomatic nodular lymphoma. Interferon is very useful in treating papillomas and condylomas, and its role as a local agent will probably expand. The list of responding cancers for alpha interferon or other subtypes as a single agent is unlikely to expand greatly over the next few years. Nevertheless, in both melanoma and renal carcinoma, meaningful responses do occur. It is important to be aware of the possibility of both delayed and increasing extent of response with duration of treatment; adequate trials of interferon may therefore require longer periods of treatment than does conventional chemotherapy. Furthermore, because prior failure to respond to chemotherapy does not predict response to interferon, its use as a second-line agent should also be considered. The future of such biological agents, however, clearly lies in combination with other agents as the "fourth arm" of cancer therapy. The challenge is to define what the role of that fourth arm will be. There seems to be a clear choice with the interferons. They can be used at pharmacological doses, in which case their antiproliferative effect is likely to be due to induction of certain enzymes that result in a cytostatic effect in susceptible cancers, of which there are a limited but therapeutically important number. Alternatively, the interferons can be used at physiological doses, which are more likely to cause immunological and cell membrane effects such as NK-cell stimulation, as well as Fc-receptor and tumor-antigen expression. Thus, combination with cytotoxic agents may well require high doses, whereas combination with other biological agents, such as monoclonal antibodies or LAK cells, may be most effective at much lower doses. Over the next few years it will be important to establish the optimal biological doses of the interferons, so that we can maximize their usefulness in therapy and avoid the trap of thinking of them as purely cytotoxic agents.

Humans↗
PubMedDate not supplied

Suppression of natural killer cell activity by hydrocortisone.

The in vitro effect of physiological levels of hydrocortisone (HC) on NK activity of human lymphocytes was investigated. Lymphocytes incubated with HC 20-80 micrograms/dl (200-800 ng/ml) prior to NK assay showed depressed NK activity similar to that previously reported at higher doses. The responsiveness of NK cells to augmentation by alpha and gamma interferon was also appreciably depressed by HC. Inhibition of cytotoxicity was not due to a toxic effect of the drug since the viability of the effector cells after incubation was comparable to control cells. Indomethacin was able to partially reverse hydrocortisone suppression in 7 out of 12 experiments. Results of these in vitro studies demonstrate that hydrocortisone, when used at the levels found in humans treated with interferon, could have significant immunomodulatory effects that would be expected to alter the immunostimulation induced by the interferons.

Cytotoxicity Tests, Immunologic↗
PubMedDate not supplied

Phase II study of human lymphoblastoid interferon in patients with advanced renal carcinoma.

Twenty-two patients with measurable metastatic renal carcinoma were treated with human alpha lymphoblastoid interferon (Wellferon) (3 million units/m2 of body surface area) im three times a week for 6 weeks; 21 were evaluable for response and toxicity. One patient had a partial regression of disease lasting 39 weeks and another had a minor response. Six patients had partial or minor response in one area but no change in the disease elsewhere (mixed response); they were classified as having stable disease. An additional seven patients had no change in measurable disease and in six the disease progressed. The tumor regressions by metastatic site were four of 14 patients, pulmonary; three of four, soft tissue; one of nine, bone (? soft tissue); none of three, mediastinal; none of four, renal; none of five, liver; and none of ten, other abdominal sites of tumor. The side effects were fever (101 degrees F-103 degrees F), chills, malaise, anorexia, minor (10%-20%) decrease in performance status, and weight loss. We concluded that interferon had some activity against metastatic renal carcinoma, although clinically useful responses were quite infrequent. While lung metastases appeared to be more responsive than those at other sites, careful examination of the data suggests that this simply reflects differences in the bulk of the metastatic disease. Smaller metastases appear more likely to respond than bulky metastases.

Adult↗