Search PubMed⌕ Search

Biomedical subjects

M Aglietta

Publications and source records attributed to M Aglietta.

At least 127 records · Page 7Linked to original sources
PubMed1978

The relevance of cell kinetics for optimal scheduling of 1-beta-D-arabinofuranosyl cytosine and methotrexate in a slow growing acute myeloid leukemia (BNML).

1-beta-D-Arabinosyl cytosine and methotrexate were studied for their antitumor activity in acute myeloid leukemia of the BN rat (BNML), which is characterized by a slow growth rate due to the presence of a high proportion of nonproliferating cells. It was found that the two drugs showed the maximal cytotoxic action when given separately. The effect was highly dependent on the interval between the administration of each drug. The variation of the cell kinetic parameters produced by the recruitment into cycle of the resting population, as determined by labeling indices, correlates well with the antileukemic action of the drug combination.

Animals↗
PubMedDate not supplied

Atypical myeloproliferative disorder associated with a 21 trisomic clone.

The hematological and cytogenetical studies of a case of atypical myeloproliferative disorder are reported. The patient displayed moderate leukocytosis, anemia and thrombocytopenia. Reduced or absent growth of CFU-C was observed in the bone marrow and peripheral blood. The cytogenetical analysis revealed a trisomy 21 limited to the neoplastic clone. The overall results are discussed and compared with the rare cases of acquired trisomy 21 reported in the literature.

Aged↗
PubMedDate not supplied

Allogeneic hemopoietic stem cell transplantation in solid tumors.

The existence of a graft versus tumor (GVT) effect of donor-derived T cells after allogeneic hematopoietic stem cell transplantation is well established as a critical component for the success of the procedure in several hematologic malignancies. Although it has been suggested that a GVT effect might also be generated in patients affected by refractory solid tumors, the morbidity of conventional allogeneic hematopoietic stem cell transplantation has limited its investigation in these diseases. Recently introduced allogeneic nonmyeloablative regimens have greatly decreased morbidity and mortality related to transplants which retain a powerful GVT. On this basis, it has become possible to explore the existence of alloreactivity toward solid tumors. The present article reviews the early clinical results of this novel immunotherapeutic approach for solid tumors.

Carcinoma, Renal Cell↗
PubMedDate not supplied

Different growth factor requirements for the ex vivo amplification of transplantable human cord blood cells in a NOD/SCID mouse model.

The growth factor combination containing early acting cytokines FLT-3 ligand (FL), Stem Cell Factor (SCF) and thrombopoietin (TPO) is able to maintain, for an extended culture period, early stem cells, defined as long-term repopulating NOD/SCID mice (Scid Repopulating Cell-SRC) contained in cord blood (CB). In this culture system, the role of IL-6 and IL-3 has not been clearly established. Using a combination of FL+TPO+SCF with or without IL-6, we were able to form CB CD34+ cells for 30 weeks. The CB CD34+ cells cultured in this system engrafted NOD/SCID mice after 6 weeks of culture; the cells from primary recipients were also able to engraft secondary NOD/SCID mice. When CB CD34+ cells were cultured in the presence of IL-3 in the place of IL-6 we observed an even better expansion of cells and a similar clonogenic progenitor output in the first 8 weeks of culture. However, more primitive LTC-IC output increased up to week 6 with the growth factor combination containing IL-3 and then decreased and disappeared, while with the growth factor combination with or without IL-6 increased up to week 23. Cells cultured for 4 weeks with the 4-factor combination containing IL-3 engrafted NOD/SCID mice less efficiently. Repopulation of NOD/SCID mice was no longer observed when ex vivo expansion was performed for 6 weeks. This study provides some evidence that no differences could be detected in long-term maintenance and even expansion of human primitive cord blood cells cultured with FL+TPO+SCF in the presence or absence of IL-6. Under the culture conditions employed in this study, the presence of IL-3 reduced the repopulating potential of expanded CB CD34+ cells.

Animals↗
PubMedDate not supplied

Differential effect of transforming growth factor beta 1 on the proliferation of human lymphoid and myeloid leukemia cells.

BACKGROUND: Transforming Growth Factor beta (TGF beta) exerts different effects on the hemopoietic system which range from the growth stimulation of more mature myeloid progenitors to the growth inhibition of more immature and multilineage hemopoietic precursors. TGF beta is also an inhibitor of the proliferation and functional activities of normal T and B lymphocytes. The aim of this study was to evaluate its effect on the growth of a human leukemic cells of lymphoid and myeloid origin. METHODS: We tested its activity on the doubling time, the DNA synthesis rate and the clonal growth of a panel of lymphoid and myeloid leukemic cell lines. RESULTS: Among the myeloid cell lines, the proliferation in liquid cultures as well as the clonal growth of KG1, HL60 and U937 were suppressed by TGF beta 1 at doses ranging from 0.025 to 2.5 ng/ml; the degree of inhibition was, however, variable. BV 137, a Ph1-positive cell line derived from a very undifferentiated stem cell, was also highly responsive to TGF beta 1 inhibition. Among the six lymphoid neoplastic cell lines, only Nalm 6, a pre-B leukemic cell line, was consistently and reproducibly inhibited by the same doses of TGF beta 1. Conversely, two Burkitt lymphoma cell lines, Raji and Daudi, and three T-cell leukemias (Molt 4, Jurkat and PF 382) were insensitive to TGF beta inhibition.

Cell Differentiation↗
PubMedDate not supplied

Oncology in the nineties: from genes to therapy.

Thanks to the impressive development and application of new sophisticated technologies, the last decade has offered remarkable advances in our understanding of the molecular and biological features of human neoplastic cells. DNA analysis in particular has contributed to the unravelling of some of the possible events which give rise to a transformed cell and which enable it to proliferate indiscriminately and to infiltrate. Cloning techniques which have allowed researchers to obtain and utilize purified molecules represent another milestone. This has opened the era of cytokines and growth factors, both in terms of their possible role in the establishment and/or progression of neoplastic conditions (autocrine/paracrine models) and of their use in clinical practice. Thus, growth factors such as granulocyte-macrophage colony stimulating factors (GM-CSF) and interleukin 3 (IL-3) are currently being employed in the management of cancer patients, mainly to support normal hemopoiesis. Conversely, recombinant interleukin 2 (IL-2) through its unique capacity to generate previously unrecognized cytotoxic activity, lymphokine active killer (LAK), has brought about new and more specific immunotherapeutic strategy. Further therapeutic possibilities will arise from the clinical use of monoclonal antibodies. Finally, the development of genetic engineering has opened the way to the early and revolutionary clinical exploitation of gene therapy; the possibility of utilizing in vivo anti-sense oligonucleotides in an attempt to block the action of specific genes is also being contemplated.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Transformation, Neoplastic↗
PubMedDate not supplied

Modulation by retinoic acid of the growth of bone marrow cell progenitors from patients with myelodysplastic syndrome.

The in vitro effect of increasing concentrations of retinoic acid on the growth of day 7 and day 14 CFU-GM and of pre-CFU-GM from patients with myelodysplastic syndromes has been studied. Unlike in normal cells, where retinoic acid enhances the in vitro growth of myeloid progenitors, there was an overall inhibition of bone marrow progenitors from patients with myelodysplastic syndromes at concentrations of 10(-7) to 10(-6) M retinoic acid, with the exception of day 14 CFU-GM whose growth may be enhanced by 10(-7) M retinoic acid.

Bone Marrow↗
PubMedDate not supplied

Expression of the hybrid P210 bcr/abl protein in Philadelphia chromosome positive B-lymphoid cell lines.

An altered c-abl protein (P210) bearing increased tyrosine kinase activity represents the product of the hybrid bcr/c-abl gene arising as a consequence of the Philadelphia (Ph1) chromosome translocation, the consistent cytogenetic abnormality of chronic myelogenous leukemia (CML). Although the chronic phase of this disease is substantially characterized by a marked proliferation of myeloid cells, the Ph1 translocation occurs in an early multipotent stem cell, giving rise to both myeloid and lymphoid cell lineages. Here we show that P210 bcr/abl protein expression varies greatly in different Ph1 chromosome positive B-lymphoid cell lines obtained from Epstein-Barr virus-transformed lymphocytes of a CML patient in the chronic phase. In addition Ph1 positive and Ph1 negative lymphoid cell lines obtained from the same patient were tested for a number of biological properties including the immunophenotype, the capacity to grow in soft agar and possible tumorigenicity in nude mice. No differences were found.

Animals↗
PubMedDate not supplied

Diagnostic paracentesis. A two-step approach.

Diagnostic paracentesis is usually considered the first test to be performed in the assessment of the ascitic patient and a large number of investigations on ascitic fluid have been proposed. To assess the value of a simplified procedure, serum to ascites albumin gradient and ascitic white blood cell counts were employed as a first step. One hundred and fifty-three paired serum and ascitic fluid samples were analysed and allowed patients to be divided into three groups: 1) serum to ascites albumin gradient > = 11 g/L and white blood cells < 0.5 x 10(9)/L predicted cirrhosis (or liver carcinoma) without peritonitis with 83% efficacy, 96% positive predictive value and 65% negative predictive value; 2) serum to ascites albumin gradient > = 11 g/L and white blood cells > = 0.5 x 10(9)/L predicted cirrhosis (or liver carcinoma) with peritonitis with 86% efficacy, 45% positive predictive value and 99% negative predictive value; 3) serum to ascites albumin gradient < 11 g/L predicted the other diagnoses with 92% efficacy, 77% positive predictive value and 95% negative predictive value. As serum to ascites albumin gradient > = 11 g/L and white blood cells < 0.5 x 10(9)/L predicted cirrhosis (or liver carcinoma) without peritonitis in 96% of the cases and excluded peritonitis in 99% of the cases, further fluid ascitic analyses could be considered as a second step only in patients with serum to ascites albumin gradient < 11 g/L and/or white blood cells > = 0.5 x 10(9)/L. In a group of ascitic patients where the prevailing diagnosis is cirrhosis (or liver carcinoma) without peritonitis, this simplified approach could provide a favourable cost/benefit ratio.

Aged↗