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D Ferrero

Publications and source records attributed to D Ferrero.

At least 73 records · Page 4Linked to original sources

Induction of differentiation of human myeloid leukemias: surface changes probed with monoclonal antibodies.

The surface changes occurring in three acute myeloid leukemia cell lines (HL60, ML3, and KG1) induced to differentiate by a variety of agents (dimethylsulfoxide, retinoic acid, 12-O-tetradecanoylphorbol-13-acetate, and factors present in lymphocyte conditioned medium) were probed using monoclonal antibodies that are differentiation stage- and lineage-specific. In all cases, the differentiated phenotype was defective and varied with the inducing agent and the cell line used. HL60 proved to be the most sensitive to the effect of the inducers. Retinoic acid was better than DMSO, and TPA was better than the medium factors in the ability to induce granulocytic and monocytic differentiation, respectively, in HL60 cells. These findings indicate that the differentiation block in acute myeloid leukemias is heterogeneous and that each cell line has different phenotypic characteristics that are responsible for the extent of differentiation obtained with a given inducer. These results also suggest that the extent of the differentiation response in vitro may be improved by the use of more suitable inducers for each specific leukemic line.

Antibodies, Monoclonal↗

Human granulocyte surface molecules identified by murine monoclonal antibodies.

We have investigated the nature of the antigens recognized by four classes of mouse anti-human monoclonal antibodies that characteristically reacted with neutrophilic granulocytes and their precursor cells, but not with monocytes or other normal hemopoietic cells. The antigenic targets of the majority (9/12) of the independently isolated monoclonal antibodies were present on two surface glycoproteins (Mr 145,000 and 105,000) and glycolipids. This antigen(s) was also detected on granulocyte precursor cells, including the bone marrow granulocyte/monocyte progenitor cells (CFU-GM). The same antigen(s) detected by these monoclonal antibodies was also present in non-hemopoietic cell lines (colon carcinoma and neuroblastoma). Three other antigens, defined by monoclonal antibodies AHN-8, L12.2, and L13.1 and present on granulocytes and their mid-late precursor cells, could not be identified as proteins but were detected in a protein-free glycolipid extract of these cells. The diversity of the antigens was confirmed by cross-competition experiments and by the identification of their different patterns of reactivity with cell lines and bone marrow cells.

Animals↗

Induction of differentiation of human myeloid leukemias by phorbol diesters: phenotypic changes and mode of action.

Treatment with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) of acute myeloblastic leukemia cells halts proliferation and induces expression of monocyte/macrophage markers. Surface characteristics of leukemic HL60 cells, as defined using a panel of monoclonal antibodies, were found to be similar to those of normal human promyelocytes. TPA treatment, however, induced a phenotype that, unlike normal monocytes, contained several myeloid-specific markers and lacked several monocyte-specific markers. TPA treatment of HL60 cells causes the rapid disappearance of the transferrin receptor from the cell surface. Because transferrin is essential for HL60 cell proliferation in culture, the disappearance of this receptor is followed by an irreversible accumulation of the cells in the G1 phase of the cell cycle. The TPA-induced arrest of cell proliferation suggests the potential of this agent in experimentally treating myeloblastic leukemias.

Animals↗

Induction of differentiation of HL-60 cells by dimethyl sulfoxide: evidence for a stochastic model not linked to the cell division cycle.

Induction of differentiation of human promyelocytic leukemia cell line HL-60 by dimethyl sulfoxide (Me2SO) was analyzed to determine the relationship between exposure time of the inducer and cell cycle. A minimum incubation time of 12 hr with Me2SO was required in order to induce differentiation in a small but significant proportion of cells. These expressed differentiation markers (morphology, phagocytosis, and nitroblue tetrazolium reduction) up to 12 hr after Me2SO was removed from the medium. For periods beyond 12 hr and as long as 120 hr of contact of HL-60 cells with the inducing agent, a linear rise in the percentage of differentiated cells was observed. The sensitivity to Me2SO of HL-60 cells synchronized by double thymidine block was examined and was found to be similar to that of nonsynchronized cells. The effect of Me2SO was not altered when incubated with cells at different phases of the cell cycle. Finally, even nonproliferating cells were sensitive to the inducing effect of Me2SO. The data are consistent with a stochastic model of induction to differentiation without having any linkage to the cell cycle.

Cell Cycle↗

Terminal differentiation of the human promyelocytic leukemia cell line, HL-60, in the absence of cell proliferation.

Induction of differentiation of the human promyelocytic leukemia cell line, HL-60, by dimethyl sulfoxide was analyzed for a requirement for cell replication. The ability of HL-60 cells to undergo terminal granulocytic differentiation as judged by nitroblue tetrazolium reduction, phagocytosis, and morphological criteria was not impaired by a total block in cellular proliferation. Retinoic acid, actinomycin D, and butyric acid also induced differentiation of HL-60 cells in the absence of cell growth. These results and the earlier demonstration that phorbol ester-induced macrophage differentiation of HL-60 occurred independently of DNA synthesis indicate that in these leukemic cells there is a dissociation of proliferation and maturation. The ability of retinoic acid to enhance differentiation of HL-60 cells was not altered in the presence of various growth-inhibiting concentrations of two clinically useful chemotherapeutic agents: hydroxyurea and 1-beta-D-arabinofuranosylcytosine. These results suggest that combination therapy in a program aimed at both inhibiting proliferation and inducing differentiation of leukemia cells could be beneficial.

Cell Cycle↗

[Primary carcinoma of the gallbladder. Clinico-statistical findings in 24 cases].

Twenty-four cases of primary carcinoma of the gallbladder (1.3% of gallbladder operations) collected over a period of 8 years are compared with those reported in the literature. This form has a very poor prognosis due to delays in diagnosis, early regional extension, and often insufficient surgical management. Women over 60 are the main victims. Abdominal pain is nearly always present, with icterus in 50% of cases. In 5/24 cases, the diagnosis was based on histological examination of the surgical specimen in the absence of clinical signs preceding the operation. It is felt that prophylactic cholecystectomy is desirable in cases of symptomatic or asymptomatic lithiatic cholecystopathy, especially in subjects most at risk. Suitable treatment of curable forms requires cholecystectomy combined with cuneiform hepatic resection and regional lymphadenectomy.

Age Factors↗

A novel human lymphokine that inhibits haematopoietic progenitor cell proliferation.

T lymphocytes in culture synthesize and secrete a variety of factors that activate and guide the differentiation, replication and maturation of haematopoietic cells in vitro. Malignant T-cell lines as well as T-cell hybridomas producing several of these factors have been established. We report here a factor produced by a human cell line that exerts a potent inhibitory effect on the growth of bone marrow progenitor cells. The properties of this factor, which we have termed colony-inhibiting lymphokine ( CIL ), differ from other inhibitors of haematopoietic progenitor cell proliferation, but resemble those of a T-cell-derived factor causally linked with some cases of severe aplastic anaemia in humans. Sensitivity of cells to this factor appears to correlate positively with expression of HLA-DR surface antigens.

Bone Marrow↗

MACOP-B treatment for intermediate and high-grade non-Hodgkin's lymphomas at diagnosis and in relapse.

Between October, 1984 and October, 1987 a study program was carried out to evaluate the efficacy of MACOP-B in the advanced stages of intermediate/high-grade malignancy non-Hodgkin's lymphomas (NHL). Thirty patients were treated at diagnosis: 14 with D-E-F histology (median age = 56.5 years) and 16 with G-H histology (median age = 46.5). Complete remission (CR) rate was 42.8% for the D-E-F subgroup and 81.2% for the G-H subgroup. Bone marrow involvement was the major adverse factor for CR achievement in patients with intermediate-grade NHL. Overall, disease stage, bulky presentation and the presence of systemic symptoms did not significantly affect response to therapy. Survival curves predict 73% of patients alive at 45 months (median follow-up = 30 mo.). No significant differences were seen between D-E-F (64%; median follow-up = 36 mo.) and the G-H patients (81%; median follow-up = 27 mo.). The disease-free survival curve for all patients in CR reached a plateau phase at 78% (median follow-up = 30 mo). MACOP-B was much less effective when employed in 10 patients at relapse; only 2 out of these 10 reached a durable CR, which persisted 51 and 27 mo. after MACOP-B. The remaining 8 patients had a partial response, followed closely by disease progression: 7 died, whereas 1 patient is still alive after salvage therapy with bone marrow transplant. Thus, MACOP-B proved to be effective in patients at diagnosis with G-H histology.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Variability of the response to recombinant human erythropoietin in patients undergoing hemodialysis treatment].

The paper assesses the existence of possible interference between dialysis and the response to human recombinant erythropoietin administered i.v. in a group of patients undergoing regular dialysis. The results obtained show that the time taken to reach the set hemoglobin target (Hb 10 g%) was shorter in hemodiafiltered (HDF) patients compared to those receiving bicarbonate dialysis (BD). A plausible explantation may be the different depurative characteristics and the greater degree of biocompatibility of alternative dialysis which is able to achieve a more rapid cellular response to pharmacological stimulation.

Adult↗

Angiocentric lymphoma: a case report.

A group of rare lymphoproliferative disorders, now called angioimmunoproliferative lesions, are histologically characterized by mononuclear cells surrounding and infiltrating vessel walls. This process results in angiodestruction and originates necrosis. Angiocentric lymphoma, a neoplasia generally deriving from the T cell lineage, is the most aggressive form of these entities characterized by prevalent extranodal involvement. A case of primary angiocentric lymphoma with lymph-nodel and systemic presentation and rapidly fatal outcome is described.

Aged↗

Conditions influencing the expansion of the circulating hemopoietic progenitor cell compartment.

Eighteen patients (6 breast cancer, 10 non-Hodgkin's lymphoma, 2 Hodgkin's disease) were treated with high-dose cyclophosphamide (7 gr/mq), while 12 (2 breast cancer, 5 non-Hodgkin's lymphoma, 5 multiple myeloma) were additionally treated with rhGM-CSF for 14 days after cyclophosphamide. During recovery, increased peak values of circulating CFU-GM were observed in 23 out of 30 patients (13 patients after cyclophosphamide, median: 5,000 CFU-GM/ml; 10 patients after cyclophosphamide + rhGM-CSF, median: 20,150 CFU-GM/ml); five of these "high releaser patients" were in 1st relapse after MACOP-B. Seven patients showed low release of CFU-GM; they had either a history of multiple exposures to chemoradiotherapeutic treatments or bone marrow replacement by neoplastic cells or both. Four out of 23 patients with high CFU-GM release were subsequently studied after administration of high-dose etoposide (2 gr/mq): increased levels of circulating progenitors were seen again, although peak values were reduced when compared to post-cyclophosphamide period. Three patients with low release and bone marrow involvement had a clear increase of circulating CFU-GM after etoposide. The results show the influence of high-dose chemotherapy, rhGM-CSF, type of previous treatment and bone marrow involvement on the degree of circulating CFU-GM release.

Antineoplastic Agents↗