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Biomedical subjects

P Foa

Publications and source records attributed to P Foa.

At least 37 records · Page 2Linked to original sources
PubMed1989

Chronic myelogenous leukemia following radiation therapy for testicular seminoma.

A 43-year-old man was treated with orchiectomy and radiotherapy for testicular seminoma. Four years later, he developed a typical Philadelphia chromosome positive chronic granulocytic leukemia. Since the patient was not eligible for bone marrow transplantation, he was treated with busulfan. Long term follow-up of patients who received radiotherapy for testicular seminoma is warranted in order to detect possible secondary tumors.

Adult↗
PubMed1989

Suppressive biological activity of a synthetic pentapeptide on highly enriched human and murine marrow hematopoietic progenitors: synergism with recombinant human tumor necrosis factor-alpha and interferon-gamma.

The synthetic pentapeptide pGlu-Glu-Asp-Cys-Lys (SPI) was evaluated in vitro alone and in combination with recombinant human tumor necrosis factor-alpha (TNF-alpha) and/or interferon-gamma (IFN-gamma) for effects on colony formation by hematopoietic progenitor cells (HPC) present in low-density (LD), nonadherent low-density T-lymphocyte-depleted (NALT-), and highly enriched sorted progenitor cells from normal human bone marrow. Progenitor cells in NALT- fractions were further enriched by cell sorting using two-color fluorescence on a Coulter Epics 753 flow cytometry apparatus with My10 and HLA-DR monoclonal antibodies. The sorted My10 DR+ progenitor cell population had a cloning efficiency of up to 38% for granulocyte-macrophage colony-forming units (CFU-GM), erythroid burst-forming units (BFU-E), and multipotential colony-forming units (CFU-GEMM). SP1 inhibited, by up to 86%, each of the colony-forming cells in a dose-dependent fashion. The sensitivities of the different progenitor cells to inhibition by the pentapeptide were the same when My10 DR+ marrow cells were used, and the progenitor cells in the My10 DR+ fraction were more sensitive than the cells in the LD or NALT- fraction to inhibition by SP1. The suppressive activity of SP1 on purified HPC was confirmed when 10(-3) M SP1 completely inhibited colony and cluster formation from a population of mouse bone marrow cells in which one of two cells was a CFU-GM. The effects of SP1 were not absolutely cell-cycle-specific for human HPC, but the non-S-phase cells were less sensitive than the S-phase cells to the suppressive effects of SP1. SP1 synergized with TNF-alpha and/or IFN-gamma to inhibit proliferation of progenitor cells using both LD or My10 DR+ human marrow cells stimulated by recombinant human interleukin 3 (IL-3). These studies suggest that the suppressive effect of SP1 occurs in the absence of certain accessory cells (e.g., monocytes and T-lymphocytes), that this effect may be mediated directly at the level of the HPC, and that this pentapeptide can be considered a candidate modulatory molecule for HPC proliferation.

Animals↗
PubMed1987

Inhibitory activity of a synthetic pentapeptide on leukaemic myelopoiesis both in vitro and in vivo in rats.

The synthetic pentapeptide pGlu-Glu-Asp-Cys-Lys has recently been proposed as the active component of a granulocyte-derived inhibitor of normal haematopoiesis. We investigated its biological activity on leukaemic myelopoiesis both in vitro and in vivo in rats. Three different human permanent myeloid leukaemic cell lines (HL60, KG1, ML3) and a rat transplantable acute myeloid leukaemia (Shay leukaemia) were studied. Neither HL60 nor KG1 were sensitive to the peptide whereas a consistently reproducible inhibition of 3H-TdR uptake was observed in ML3 cells. This effect was not due to a unspecific toxic action on target cells and was spontaneously reversible. When injected i.p. twice daily at an appropriate concentration in rats bearing Shay leukaemia, the peptide caused a significant increase in survival. Our results therefore indicate that the synthetic pentapeptide studied inhibits not only normal but also leukaemic myelopoiesis.

Animals↗
PubMed1986

Inhibition of proliferation of human leukaemic cell populations by deferoxamine.

Deferoxamine is a hydroxylamine which binds ferric ions to form a highly stable complex. Since iron is thought to be required at a critical stage for cell proliferation, we investigated the effect of deferoxamine on the proliferative activity of human leukaemic cell populations in vitro by means of 3 permanent cell lines, HL60, U937 and 8402. We found deferoxamine to be a potent inhibitor of DNA synthesis and proliferation of leukaemic cells, acting by accumulating treated cells at the early S phase of the cell cycle. Suppression of leukaemic proliferation was obtained at deferoxamine concentrations in the range usually achieved in the treatment of patients for iron overload. Deferoxamine might therefore warrant further investigation as a potentially useful agent for leukaemia chemotherapy.

Cell Division↗
PubMed1986

Cyclosporin A antileukemic activity: mode of action on target cells.

Cyclosporin A (CyA) is a potent immunosuppressive agent which has been reported to inhibit proliferation of human T leukemic lymphoblasts. We used the permanent cell line 8402 to perform a detailed investigation of the CyA mode of action on such cells. CyA treatment resulted in a dose-dependent inhibition of the 8402 cells growth rate which was paralleled by a decrease of tritiated thymidine uptake. These findings were the consequence of redistribution of treated cells in the cell cycle phase. By means of intracellular DNA content measurements made by flow cytometry, it was shown that the primary effect of CyA was accumulation of treated cells at the G1 phase of the cell cycle. At the doses used, CyA activity was not spontaneously reversible, resulting in death of treated cells which was apparent at about 72 h after exposure to the drug.

Cell Cycle↗
PubMed1985

Multimarker phenotypic characterization of adult and childhood acute lymphoblastic leukaemia: an Italian multicentre study.

A multicentre phenotypic study was carried out in Italy combining conventional immunological techniques with monoclonal antibody (MoAb) analysis in 190 cases of adult and childhood acute lymphoblastic leukaemia (ALL), in an attempt to define better the lineage relationship of the neoplastic cells. Of the 140 children evaluated, 79.3% expressed the common ALL (cALL) antigen (all analyses performed by MoAb), 11.4% were T-ALL and 9.3% were non-T, non-B, non-common ('null') ALL. The proportion of adult cALL cases was slightly lower (64% of the 50 cases studied) than that of childhood ALL, whilst the incidence of T-ALL was significantly higher in adults than in children (26% v. 11.4%, P less than 0.05). Because of the high proportion of cALL cases, the incidence of 'null' ALL in adult patients was similar (10%) to that of children, and lower than previously reported. The recognition of early pre-T-ALL cases (T1+, RFT2+, T10+, T6-, T11-, E-) contributed to the overall low proportion of 'null' ALL; prior to the use of MoAb, such cases would probably have been classified as undifferentiated acute leukaemia or 'null' ALL. The search for B-cell-related markers showed that the incidence of pre-B-ALL cases (cytoplasmic immunoglobulin positive cases) was similar in adults and in children (25.6% and 32%, respectively). Furthermore, the great majority of cases studied expressed the BA-1 antigen (92.8% of adults and 79% of children), whilst the BA-2 antigen was found in 53% of cases (tested only in children), confirming a hierarchy in the expression of B-cell related markers in cALL: BA-1, BA-2, CyIg. Several of the 'null' cases also expressed the BA-1 antigen on a variable proportion of cells, pointing to a possible B-cell origin of the blasts. This multicentre study shows that both in adult and in childhood ALL the combined use of conventional immunological markers and of a panel of MoAb allows identification of the cell lineage of the great majority of cases, thus reducing the number of 'null' ALL. Furthermore, these findings suggest that practically all cases of ALL belong either to the T or to the B cell compartment and that the neoplastic cells appear blocked at different levels along the lymphoid differentiation pathway.

Acute Disease↗
PubMed1982

Flow cytometric analysis of cellular DNA in human acute nonlymphatic leukemias and dysmyelopoietic syndromes.

The proliferation patterns of bone marrow cells from 16 cases of acute nonlymphatic leukemia (ANLL) and 13 of dysmyelopoietic syndromes were analyzed with DNA-flow cytometry. In order to reduce the contamination by nonproliferating peripheral blood cells, all aspirates were submitted to a density centrifugation step. DNA content measurements were performed with a PHYWEICP 22 flow system apparatus. The distribution of cells in te cell cycle phases was calculated by means of an automated fitting procedure. No significant difference between the cell cycle distribution in ANLL and dysmyelopoietic syndromes was detectable. No relationship was observed between the size of the S phase compartment and the percentage of blasts in the original samples. Aspirates from ANLL were also cultured in vitro in liquid phase on dialysis membranes. A clear relationship was observed between the size of the phase compartment and in vitro cell growth since, with the exception of one case, all samples with less than 11% cells in S phase failed to proliferate in vitro. The proliferation profile of ANLL cells after 10 days in culture was similar to that of the original samples.

Anemia, Aplastic↗
PubMed1982

Growth pattern of the human promyelocytic leukaemia cell line HL60.

In order to characterize the growth pattern of the human promyelocytic leukaemia cell line HL60, its kinetic parameters were studied. The doubling time was calculated from serial cell counts, the duration of the various cell cycle phases from the analysis of the labelled mitoses curve, and quiescent population from continuous labelling experiments. Proliferation in culture was exponential up to a saturation density of about 3.0 x 10(6) cells/ml, with a doubling time of 34.0 hr. The cell cycle duration was 24.3 +/- 4.1 hr (SD), and that of the cell cycle phases was: G1, 3.8 +/- 2.2 hr; S, 15.1 +/- 3 hr; and G2, 4 +/0 1.2 hr. The growth fraction was 0.85, and cell loss was restricted to the quiescent cells. The HL60 cell line, with fully characterized kinetics, provides a useful tool for the vitro study of substances which may affect human leukaemic myelopoietic proliferation.

Animals↗
PubMed1982

Effect of granulocytic chalone on the growth rate of continuous cell lines propagated in vitro: a new assay system.

The progress of research on granulocytic chalone has been hampered by a lack of reliable assay systems. This paper reports the use of continuous cell lines growing in liquid suspension culture as a new method for assessing the effect of granulocytic chalone on cell proliferation. Partially purified granulocytic chalone (PPGC) was added to cultures of a rat myeloid cell line (W25), a human myeloid cell line (HL60), a human B lymphocytic cell line (8392), and a human T lymphocytic cell line (8402). The growth rate of the target cell populations was directly assessed by serial cell counts. PPGC pretreatment resulted in a significant inhibition of cell proliferation of the 2 myeloid permanent cell lines, while the growth rate of the lymphocytic cell lines was not affected. Moreover, inhibition of cell proliferation was spontaneously reversed when PPGC treatment was discontinued. Since PPGC from ox leucocytes displayed an inhibitory effect on cell proliferation which was specific to the myeloid cells, spontaneously reversible and not species-specific, it appears to have all the essential properties of a granulocytic chalone.

Animals↗
PubMed1981

Detailed kinetic analysis of Shay chloroleukaemia cell population propagated in permanent suspension culture in vitro.

Detailed kinetic analysis of a growing cell population is difficult, even when assay conditions are nearly ideal. Therefore, it is usually essential to perform several types of experiments and analyse all the results in terms of a mathematical model, the use of which is not limited a priori by a specified application. In the present study we investigated cell population kinetics using rat chloroleukaemia cells propagated in suspension culture in vitro. The parameters were measured: doubling time of the population, fraction of labelled mitoses, changes in labelling index with time after pulse labelling, continuous labelling and stathmokinetic index. Analysis of the results was based on a computer program CECAM, which is a stochastic model capable of simulating essentially all types of kinetic experiments based on presently known assay techniques. The results showed that precise and reliable information on cell population kinetics could not be obtained from the analysis of any single type of experimental data. In particular, the technique of labelled mitoses underestimated the duration of the G1 phase, owing to subtle label-induced changes in population behaviour. These changes could not have been detected with any certainty without rigorous quantitative comparisons with other types of experimental data. As a whole, however, results obtained by the different techniques were in agreement and the kinetic behaviour of chloroleukaemia cells in vitro could be established in detail. In certain circumstances even minute changes in the kinetic parameters of the cells can modify population behaviour drastically. To study these cases adequately the experiments must be designed with utmost care, preferably with the aid of preceding simulations. This is because demonstration of small primary changes in population kinetics may be beyond the limit of detection of any single assay method.

Animals↗
PubMed1979

Granulocytic chalone is not a polyamine complex.

Recent studies have indicated that tissue extracts may contain sufficient amounts of free polyamines to account for the inhibitory effect of the extracts and hence mask any authentic chalone action. It has also been reported that bound polyamine may be the active moiety of some chalones. We show here that in our granulocytic and lymphocytic chalones polyamines, either free or bound, are not responsible for the inhibitory effects of the preparation.

Animals↗
PubMed1975

In vitro production of lymphocyte and granulocyte proliferation inhibitors (chalones?) from living cells.

Media conditioned with viable rat and calf spleen lymphocytes were seen to be able to inhibit 3H-thymidine uptake by rat thymocytes and the mitogenic response of human lymphocytes to PHA but not bone marrow cells proliferation. The inhibitor appeared to have a molecular weight greater than 50,000 daltons, as determined by Amicon Diaflo ultrafiltration. Media conditioned with rat granulocytes had a similar tissue specific but species non-specific inhibitory action. Also human leukemic cells appeared able to produce in vitro an inhibitor of cell proliferation when a certain degree of differentiation was present.

Animals↗