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H J Wallace

Publications and source records attributed to H J Wallace.

16 recordsLinked to original sources
PubMed1992

Potentiation of the activity of 1-beta-D-arabinofuranosylcytosine by the protein kinase C activator bryostatin 1 in HL-60 cells: association with enhanced fragmentation of mature DNA.

We have examined the interaction between 1-beta-D-arabinofuranosylcytosine (ara-C) and the macrocyclic lactone protein kinase C activator bryostatin 1 in the human promyelocytic leukemia cell line HL-60. Preexposure of cells to 10 nM bryostatin 1 for 24 h, followed by an additional 24-h incubation with 10 microM ara-C, resulted in greater than additive inhibitory effects toward clonogenic HL-60 cells. In a series of alkaline elution assays, cells preincubated with bryostatin 1 and prelabeled with [3H]thymidine exhibited a significant increase in DNA fragmentation following exposure to ara-C in comparison to cells exposed to ara-C alone. This increase in DNA damage was apparent at both neutral and alkaline pH and was not protein associated. In contrast, studies using cells pulse-labeled with [3H]thymidine immediately before analysis suggested that bryostatin 1 pretreatment did not increase the ability of ara-C to interfere with DNA replicative intermediates. Additional studies demonstrated that the increase in DNA fragmentation induced by bryostatin 1 and ara-C preceded both loss of cell membrane integrity (as determined by trypan blue exclusion) as well as depletion of intracellular ATP and NAD pools. Furthermore, the enhanced inhibitory effects of bryostatin 1 and ara-C toward clonogenic HL-60 cells did not appear to result from the induction of cellular differentiation. Finally, agarose gel electrophoresis of DNA obtained from cells exposed to both bryostatin 1 and ara-C revealed a pattern of integer multiples of 180- to 200-base pair fragments commonly associated with endonucleolytic cleavage; the extent of this fragmentation was considerably greater than that observed in cells exposed to ara-C alone. Taken together, these findings suggest that exposure of HL-60 cells to bryostatin 1 renders them more susceptible to ara-C-related DNA damage and that this phenomenon contributes to the cytotoxic effects of this drug combination. They also raise the possibility that bryostatin 1, perhaps through modulation of intracellular signaling events in leukemic cells, has the capacity to potentiate ara-C-related apoptosis or programmed cell death.

Adenosine Triphosphate↗
PubMed1992

Effects of bryostatin 1 and rGM-CSF on the metabolism of 1-beta-D-arabinofuranosylcytosine in human leukaemic myeloblasts.

The effects of the protein kinase C activator bryostatin 1, either with or without recombinant granulocyte-macrophage colony stimulating factor (rGM-CSF) were examined with respect to the in vitro metabolism of ara-C in leukaemic myeloblasts obtained from 10 patients with acute myelogenous leukaemia (AML). Coincubation of cells with 12.5 x 10(-9) M bryostatin 1 and 10(-5) M ara-C for 4 h resulted in a significant increase in ara-CTP formation (compared to controls) in 6/10 specimens (mean increase 106%; range 38-255%), and no change in the remainder. In contrast, coincubation of cells with 1.25 ng/ml rGM-CSF resulted in a significant increase in only one specimen, and decreases in two. Bryostatin 1 also significantly increased ara-C DNA incorporation in 6/9 evaluable samples, including two which did not display an increase in ara-CTP formation. Coincubation of cells with both bryostatin 1 and rGM-CSF did not lead to a further increase in ara-CTP formation or ara-C DNA incorporation compared to values obtained with either agent alone. Finally, exposure of blasts to bryostatin 1 for 24 h before ara-C led to an increase in ara-CTP formation in 3/8 additional specimens, and a decrease in one sample displaying evidence of bryostatin 1-induced macrophage differentiation. Incubation of cells with both rGM-CSF and bryostatin 1 for this period resulted in ara-CTP levels equivalent to those obtained with bryostatin 1 alone. These studies indicate that while bryostatin 1 exerts a heterogeneous effect on ara-C metabolism in leukaemic myeloblasts, it is capable of potentiating ara-C phosphorylation in a subset of patient samples, including some that do not exhibit an increase in response to rGM-CSF. They also raise the possibility that bryostatin 1-induced potentiation of ara-C metabolism in some leukaemic cells may contribute, at least in part, to the antileukaemic efficacy of this drug combination.

Antineoplastic Agents↗
PubMed1991

Metolazone pharmacokinetics and pharmacodynamics in renal transplantation.

Metolazone pharmacokinetics and pharmacodynamics were investigated in five renal transplant patients and five creatinine clearance matched controls. Whereas the time to peak metolazone excretion was similar in both groups (with the exception of one renal transplant patient who subsequently was found to have chronic rejection), the percent of the administered dose excreted over 48 h was significantly less in renal transplant patients (8% in renal transplant patients vs 24% in controls). Diminished bioavailability of metolazone or tubular secretion likely accounted for this disparity in metolazone excretion. Both groups developed diuretic tolerance as indicated by hysteresis in the dose response relationship. Cumulative sodium excretion over three successive 12-h time intervals did not differ between groups. Despite this comparable natriuresis, potassium excretion was significantly less in the renal transplant patients during the first day of the study. Accordingly, metolazone administration may provide a means to "unmask" subclinical, tubular secretory dysfunction in the transplanted kidney, as exemplified by defects in metolazone secretion and potassium excretion.

Adult↗
PubMed1978

Electrocardiographic changes following adriamycin treatment.

Two hundred and fifty-six patients with a wide variety of advanced neoplasms who were treated with adriamycin at Roswell Park Memorial Institute were studied for electrocardiographic changes. All the patients had pre- and posttreatment electrocardiograms (ECG's) and changes were found in 85 (33.2%). In the group of 1-8 patients with normal pretreatment ECG's, changes occurred in 51 (30.3%). In the group of 88 patients who had abnormal pretreatment ECG's, 34 (38.6%) developed further changes following treatment. Twenty-five patients received cytoxan concomitantly and ECG changes developed in 12 (48%); however, this and the above difference were not statistically significant. Frequency of ECG changes was higher and the extent of histologic abnormality in the myocardium was greater in those patients who received high doses of adriamycin. Arrythmias were rather benign and only a small number of patients required treatment. ECG changes following adriamycin treatment occurred more frequently than previously reported.

Arrhythmias, Cardiac↗
PubMed1977

Carcinoembryonic antigen in osteosarcoma.

Plasma carcinoembryonic antigen (CEA) assay was done in 30 patients with osteosarcoma. CEA was found positive (greater 2.5 ng/ml) in 17 of 21 patients who had active evidence of disease and negative (less than 2.5 ng/ml) in all 9 patients who were in complete remission resulting from previous amputation of chemotherapy. Serial CEA determinations demonstrated a fall to normal in 7 of 9 patients following successful surgery of chemotherapy and a ruse and fall (fluctuation) of levels in 8 patients who had tumor progression while on chemotherapy. Clinical recurrence of disease in two instances preceded or coincied with CEA elevation. The CEA assay in osteosarcoma although non-specific could be used as an inportant adjunct to experienced clinical judgment, periodic x-ray examination, and laboratory study to prognosticate the course of osteosarcoma during therapy. The interpretation of a rising or falling CEA titer alone, however, must be made with caution.

Adolescent↗
PubMed1977

Adriamycin-cyclophosphamide and adriamycin-cis-dichloro-diammineplatinum(II) combination chemotherapy in patients with advanced cancer.

Patients with a wide variety of previously treated, advanced solid tumors were assigned to receive either adriamycin-cis-dichlorodiammineplatinum(II) (cis-platinum) or adriamycin-cyclophosphamide as combination chemotherapy. Hematologic toxicity was prominent but short-lived in most patients; renal toxicity occurred in 14 of 23 patients receiving cis-platinum and frequently precluded further administration of that agent. Of the patients receiving adriamycin-cis-platinum, 37.5% had useful responses, with four of six patients with bronchogenic carcinomas showing partial regression of disease and two patients with embryonal cell carcinoma of the testes showing complete response. In the patients receiving adriamycin-cyclophosphamide, one complete response occurred in a patient with a malignant lymphoma, and the overall response rate was 18%. The combination of adriamycin-cis-platinum merits further study, especially in bronchogenic carcinoma.

Adolescent↗
PubMed1977

Clinical response and toxicity with cis-dichlorodiammineplatinum(II) in children.

cis-Dichlorodiammineplatinum(II) (DDP) was studied in 16 children with far-advanced malignancies. Three dosage schedules were tried: regimen A, 20 mg/m2/day x 5 days for 3-4 weeks (11 patients); regimen B, 50 mg/m2 once a week (four patients); and regimen C, 60 mg/m2/day x 2 days every 3-4 weeks (one patient). Four of 16 patients (25%) showed partial response, including one with osteogenic sarcoma, one with neuroblastoma, one with seminoma, and one with medullary carcinoma of the thyroid. Two patients showed clinical improvement. The major toxic manifestations included nausea and vomiting (16 of 16), renal toxicity (three of 16), transient pancytopenia (six of 12), and hearing loss (two of 16). It is apparent that DDP has activity in pediatric tumors; however, a more precise response rate must be delineated in a larger series of patients.

Adolescent↗
PubMed1975

Improvement in the results of treatment of osteogenic sarcoma.

Experience with 70 patients having osteogenic sarcomas treated between 1968 and 1973 demonstrated the importance of persistence in the management of the disease of these patients. Resection for pulmonary metastases in one or both lungs, often on more than one occasion, will salvage a number of these patients, thus improving the cure rate. Adriamycin has proved an effective palliative agent and a useful adjuvant to surgical therapy. Although the cure rate of tumors arising distal to the knee is much higher than that of more proximally situated tumors, resection of osteogenic sarcomas of the distal part of the femur does not require removal of the entire femur when care is taken to resect well above the site of the apparent tumor. Some osteogenic sarcomas are sensitive to adequate dosages of radiation therapy, but the exact role of this method is yet to be determined. No definite beneficial result could be attributed to any of a variety of modalities of immune stimulation therapy.

Adolescent↗
PubMedDate not supplied

Mutiple myeloma resistant to melphalan (NSC-8806) treated with cyclophosphamide (NSC-26271), prednisone (NSC-10023), and chloroquine (NSC-187208).

A prospective randomized study of the effects of two different therapeutic regimens was conducted in 41 patients with multiple myeloma resistant to therapy with melphalan. The results of treatment with cyclophosphamide plus prednisone were compared with those of cyclophosphamide, prednisone, and chloroquine. Chloroquine, which inhibits the repair process of DNA in animals, has reportedly produced responses to alkylating agents to which the animal had been resistant. No significant differences in response to the doses used with either regimen could be found. Toxocity consisted mainly of leukopenia and thrombocytopenia.

Antineoplastic Agents↗