PubMed Health⌕ Search

Biomedical subjects

F Valeriote

Publications and source records attributed to F Valeriote.

10 recordsLinked to original sources
PubMed1979

Application of flow cytometry and cell sorting to megakaryocytopoiesis.

We have employed flow cytometry (FCM) and cell sorting to quantitate and study megakaryocytes in mouse and rat femoral marrow following their 20- to 30-fold concentration by centrifugal elutriation (CE). This enrichment of megakaryocytes permitted the first determination of their DNA-related fluorescence by FCM analysis following DNA staining. Fluorescence distributions of CE-enriched cell fractions following supravital staining with Hoechst 33342 were similar to those following chromomycin A3 staining of ethanol-fixed cells. Microscopic examination of cells sorted onto glass slides on the basis of their DNA-related fluorescence following supravital staining together with specific acetylcholinesterase staining for megakaryocytes indicated that megakaryocytes generally increased in cell size with increasing DNA content. This technologic application represents a significant advance in the study of megakaryocytopoiesis, since the kinetics of either the normal or perturbed population can now be studied rapidly and quantitatively.

Animals↗
PubMed1979

Potentiation of anticancer agent cytotoxicity against sensitive and resistant AKR leukemia by amphotericin B1.

Amphotericin B was able to enhance the effects of actinomycin D (Act-D), adriamycin, and vincristine against AKR leukemia. AKR leukemia lines of increasing resistance to Act-D were obtained by passage in syngeneic mice treated with Act-D. The cells selected for Act-D resistance also eventually became cross-resistant to vincristine and Adriamycin, but resistance to these agents developed at a slower rate. Amphotericin B enhanced the effects of all these agents against the resistant cells, although the degree of enhancement varied among these antitumor agents and decreased as drug resistance increased in the late-passage leukemia lines.

Amphotericin B↗
PubMed1978

Growth and rejection of leukemia cells in individual mice after combined treatment with amphotericin B and 1,3-bis(2-chloroethyl)-1-nitrosourea.

We assayed the femoral marrows of individual AKR mice for leukemia colony-units (LCFU) after treatment with amphotericin B (AmB) and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or with BCNU alone. No differences between the groups were noted in the first 7 days after treatment. All the mice treated with BCNU alone were dead by day 8, and all the survivors among the animals receiving AmB and BCNU retained high levels of LCFU for 2 more days; these LCFU were subsequently rejected by the host. By day 12, LCFU were undetectable. Histologic examination of organs from the same mice on day 5 showed fewer leukemia cells in the mice treated with the combination of agents. In all treatment groups, mice dying of leukemia early (by day 9) had systemic leukemia and most had central nervous system (CNS) involvement. All animals dying between days 10 and 14 had CNS leukemia, but few had systemic leukemia; at later times, though few animals died, they invariably had CNS leukemia without systemic involvement.

Amphotericin B↗
PubMed1978

In vivo enhancement of 5-fluorouracil cytotoxicity to AKR leukemia cells by thymidine in mice.

The spleen colony assay was used to examine the effect of thymidine (dThd) on 5-fluorouracil (FUra) cytotoxicity in two transplantable leukemias, AKR (in AKR mice) and L1210 [in (BALB/c x DBA/2)F1 mice], in vivo. A large dose of dThd (10 mg/mouse) could not rescue these cell lines from FUra toxicity. Instead, when dThd was given within 1 hour before FUra, it enhanced FUra cytotoxicity by a factor between 100 and 1,000 in AKR leukemia. That dThd increased the cytotoxicity of FUra only by a factor of 3 in L1210 leukemia suggested a different mechanism of interaction of the two drugs in the two cell lines. Examination in hybrid mice capable of supporting the growth of both leukemias showed the enhancement to be tumor related rather than host related. We also demonstrated a dose-dependent effect of dThd injection 15 minutes before FUra in AKR leukemia. Concerning the kinetics of killing of AKR leukemia colony-forming units (LCFU) following the administration of dThd 15 minutes before FUra, LCFU survival continued to decrease for 24--36 hours following drug administration.

Animals↗
PubMed1977

Cellular quantitation of in vivo effects of 1-beta-D-arabinofuranosylcytosine on leukemia L1210.

We derived a cellular model for the use of the cytidine analogue 1-beta-D-arabinofuranosylcytosine (ara-C) against L1210 leukemia in vivo from dose- and time-survival studies. We employed a quantitative assay for leukemia colony-forming cells to construct dose- and time-survival curves for single, divided, and infused doses of ara-C. Time-survival curves for a large dose range of ara-C indicated not only cell killing but also progression delay effects in vivo. Divided dose studies showed the extent of cell killing (optimum effect) to be dependent upon both the dose and the interval of time between administration of the drugs. When the drug was given as an infusion, the extent of cell killing was as great as that produced by the best fractionation schedule, an effect which was verified in terms of therapeutic efficacy in leukemic mice.

Animals↗
PubMed1977

Response of transplanted AKR leukemia to combination therapy with amphotericin B and 1,3-bis(2-chloroethyl)-1-nitrosourea: dose and schedule dependency.

A number of different amphotericin B (AmB)-1,3-bis(2 chloroethyl)-1-nitrosourea (BCNU) treatment regimens were evaluated with our model of transplantable AKR leukemia. We found that dose levels and treatment schedules were critical in determining the number of survivors. A 4-day treatment regimen of 0.5 mg AmB/mouse on days 1, 2, 3, and 4 and 0.2 mg BCNU/mouse on day 4 was found to be the most effective and has been chosen as our standard regimen. The efficacy of the treatment regimen depended on the presence of a large tumor burden, and the response was abolished when the mice were preirradiated or treated with the immunosuppressive agent, cyclophosphamide. These results, as well as others which we discuss, supported our notion that AmB affected host immune response to the tumor.

Amphotericin B↗
PubMed1977

Biological characterization of a prolonged antileukemic effect of 5-azacytidine.

A prolonged cytotoxic effect of 5-azacytidine (aza-CR) on leukemic colony-forming units (LCFU) was observed in mice with transplanted L1210 leukemia. LCFU showed rapid reaccumulation in the marrow 12 hr after injection of 0.1 mg of aza-CR per mouse. However, after 0.5 mg of aza-CR, repopulation was delayed for at least 6 days. Experiments were performed to determine the mechanism of this prolonged antileukemic effect. Suspensions of leukemic marrow prepared from mice treated 4 days previously with 0.5 mg of aza-CR were exposed to [3H]thymidine in vitro in order to kill cells in S phase. Suspensions exhibited a 40% reduction in LCFU, indicating the prolonged effect was not due to cell cycle progression delay. Mice given whole-body irradiation prior to receiving L1210 demonstrated the same delayed repopulation following the high dose of aza-CR as nonirradiated mice, suggesting that the effect was likely not due to an immune reaction. aza-CR, when given to normal mice as long as 2 days prior to leukemic transplantation, was able to prolong the survival of leukemic mice, but not when given at longer intervals. Administration of aza-CR to mice 1 day or 1 hr prior to leukemic transplantation resulted in decreased LCFU survival as well as delayed repopulation of LCFU; the rate of repopulation was not changed. This indicated a prolonged residual activity of the drug, but not sufficient to explain the total in vivo suppression. In contrast, administration of aza-CR to leukemic mice suppressed repopulation of a subsequent leukemic transplant for 4 days, even when the cells were given 2 days after the aza-CR. Cytidine was partially able to reverse the delayed repopulation of LCFU when given 1 day after aza-CR, but it was unable to reverse the phenomenon 2 days after aza-CR. Therefore, a high dose of aza-CR produces a prolonged antileukemic effect which is probably mediated by continued availability of an aza-CR metabolite. Since this effect is more pronounced in leukemic mice than in nonleukemic mice, the pharmacokinetics of high doses of aza-CR probably differ in normal and leukemic mice.

Animals↗
PubMed1975

Kinetics of both leukemic and normal cell population reduction following 5-azacytidine.

The cytotoxic effect of 5-azacytidine (AzaCR) on normal hematopoietic colony-forming units (NCFU) and L1210 leukemic colony-forming units (LCFU) in the femoral marrow of BALB/c x DBA/2 F1 mice was studied using the spleen colony assay. Dose-survival curves for LCFU and NCFU were biphasic. Repopulation of LCFU was rapid at a low dose of AzaCR (0.1 mg/mouse) but was delayed for greater than 6 days at higher doses (0.25 mg/mouse and above). Of the agents tested in this system, only AzaCR exhibited these properties. Survival of mice with L1210 leukemia following AzaCR administration was prolonged beyond that predicted by the degree of LCFU reduction alone, and reflected the delay in LCFU repopulation. In contrast, repopulation of NCFU in normal mice was not delayed at a high dose of AzaCR (0.5 mg/mouse). AzaCR produced a nine-fold greater reduction of NCFU in leukemic mice than in normal mice, measured 5 days after AzaCR injection. While divided doses of AzaCR produced LCFU cytotoxicity equivalent to a single dose, 24-hr infusions of high doses were inferior to single infections.

Animals↗