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Biomedical subjects

V Rizzoli

Publications and source records attributed to V Rizzoli.

At least 91 records · Page 5Linked to original sources
PubMed1990

Fructose-1,6-diphosphate as an in vitro and in vivo anti-alcohol agent in the rat.

Fructose-1, 6-diphosphate (FDP) decreases the effect of ethanol on Ca++ entry and inhibits the ethanol-stimulated phosphate efflux in rat heart slices. FDP also inhibits the ethanol-stimulated [36Cl-]-uptake by rat brain microvesicles and affects the isolated GABA-receptor in a way opposite to that of ethanol. The in vivo effects of FDP include a dose-dependent decrease in ethanol-induced gastric ulcers and a decrease in the serum transaminase levels raised by chronic ethanol administration. Other central actions of ethanol such as diuresis, narcosis, dependence and withdrawal symptoms are also counteracted by FDP.

Animals↗
PubMed1990

Hematopoietic growth factors: in vitro and in vivo studies in bone marrow transplantation.

The results of in vivo studies conducted with colony-stimulating factors (CSFs) in autologous bone marrow transplantation (ABMT) are summarized. Our own data obtained from in vitro models dealing with the use and possible applications of CSFs in ABMT are reported. In particular, we show data concerning: 1) the use of interleukin 3, granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 1 to expand hematopoietic progenitor cell growth in the early phase of ABMT; 2) in vitro marrow purging with Mafosfamide and GM-CSF in chronic myelogenous leukemia; and 3) growth requirements of MY10-derived leukemic colony-forming units. The use of CSFs, alone or in combination, may provide us with new strategic approaches for the treatment of acute and chronic leukemias. CSFs in combination with chemotherapeutic agents are very promising agents for purging marrow prior to ABMT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Phase II cooperative study with a new alkylating drug, PTT-119, in the treatment of non-Hodgkin's lymphomas.

In a phase II cooperative study involving eleven Italian haematological units, the efficacy and toxicity of a new alkylating compound, PTT-119, was evaluated in 53 patients with non-Hodgkin's lymphoma (NHL). Forty-five of the patients had been previously treated with various regimens of chemotherapy, the remaining eight were at the onset of the disease. PTT-119 was scheduled at 3.0 mg/kg every three weeks for a minimum of three administrations. Seven patients achieved a complete remission (CR), 19 a partial remission (PR); the overall response rate was 49%. The median duration of response was 6 months. Most frequent adverse effects were alopecia, nausea and vomiting and phlebitis due to the drug infusion. Myelosuppression was severe only in patients with bone marrow involvement or who were heavily pretreated. No liver, cardiac or renal toxicity was recorded. These data indicate that PTT-119 is an effective drug in the treatment of NHL; the matter of its non-cross-resistance with other alkylating compounds warrants further studies.

Adult↗
PubMed1990

Growth of CD34+ acute myeloblastic leukemia colony-forming cells in response to recombinant hematopoietic growth factors.

In order to minimize the interactions of clonogenic cells with accessory cells and characterize the direct effect of recombinant hematopoietic growth factors (HGF) on acute myelogenous leukemia colony-forming cells (AML-CFU), the response of CD34+ AML-CFU to individual or combined recombinant HGF, i.e., interleukin-1 (IL-1), interleukin-3 (IL-3), interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and macrophage colony-stimulating factor (M-CSF), was studied in 10 patients and compared with the growth response obtained from unfractionated marrow cells. IL-3 and GM-CSF had a similar stimulating activity on AML-CFU growth. G-CSF resulted the most efficient stimulus for colony formation and was additive or synergistic with IL-3 and GM-CSF, M-CSF, used alone, had a negligible stimulating activity. When CD34+ cells were used, IL-1 by itself had a low stimulating activity and displayed little or no synergy with IL-3, GM-CSF, and G-CSF. On the contrary, when unfractionated cells were used, IL-1 was very effective in inducing AML-CFU formation and was markedly synergistic with IL-3 and GM-CSF. These results show that IL-1-induced leukemic colony formation is prevalently mediated by accessory cells. IL-6 supported AML-CFU growth in seven of 10 cases, thus showing a direct effect on CD34+ leukemic cells, and enhanced the growth of IL-3-(+47 to +167%) and GM-CSF-dependent (+60 to +110%) AML-CFU. Recloning studies of single colonies demonstrated that primary CD34+ AML-CFU, stimulated by IL-3 and GM-CSF, generated secondary and tertiary colonies, whereas primary AML-CFU stimulated by G-CSF and IL-6 failed to give rise to secondary colonies, thus indicating a complete suppression of self-renewal. Sequential recloning of colonies grown in the presence of IL-3 + IL-6 demonstrated that addition of IL-6 and IL-3-containing plates resulted in a nearly complete suppression of self-renewal. In conclusion, these results demonstrate the heterogeneity of the CD34+ leukemic cell fraction and indicate the existence of complex regulatory events at the level of CD34+ leukemic cells. Data obtained from recloning experiments are of therapeutic interest in view of the clinical application of HGFs in the treatment of myeloid leukemias.

Adult↗
PubMed1990

Pharmacological-mediated purging with mafosfamide in acute and chronic myeloid leukemias. The Italian Study Group.

The success of autologous bone marrow transplantation (ABMT) in acute leukemia (AL) in complete remission (CR) is limited by the high relapse rate. It is generally accepted that minimal residual disease (MRD) plays a major role in determining the relapse of disease. In our study we investigated in adult acute leukemia and in chronic myelogenous leukemia (CML), the efficacy of ex vivo marrow purging with mafosfamide (an in vitro derivative of cyclophosphamide). We also describe an improved purging approach ("programmed method") based on the evaluation of sensitivity to the drug measured in each individual patient prior to ABMT. The analysis of clinical data in terms of disease-free survival (DFS) shows that the "programmed method" gives significantly better results than those obtained using the standard dose of mafosfamide (80% DFS in 18 AL patients vs. 44% in 33 ANLL patients and 33% in 56 ALL patients). The evaluation of the CR to purging interval in ALL and ANLL shows that a period of greater than 6 months is necessary to obtain longer DFS. Considering pre-transplant regimens, busulfan-cyclophosphamide is more effective in ANLL, and cyclophosphamide-fractionated total body irradiation is the best treatment for ALL. The studies using mafosfamide marrow purging in CML demonstrate that the drug is able to achieve a decrease of the Ph1+ marker. Three patients who showed conversion of this cytogenetic marker have been autografted with interesting clinical results.

Adult↗
PubMed1989

Some effects of fructose-1,6-diphosphate on rat myocardial tissue related to a membrane-stabilizing action.

This study aims at elucidating the mechanism of action of extracellular fructose-1,6-diphosphate (FDP). FDP is able to inhibit Ca++ entry into the myocardial tissue with an IC50 value of 11.5 mM and in addition, it is bound by rat heart slices, the binding being activated by Zn and conditions of chemical hypoxia induced by KCN and iodoacetate. The overall effect of extracellular FDP includes an increase of frequency and amplitude of contraction of perfused heart at concentration below 1 mM, and, in general, a stimulation of the oxygen consumption of the tissue. The antihaemolytic effect of FDP suggests its action as a membrane stabilizer. The effects of extracellular FDP on the myocardial cell can be interpreted both on the basis of a limited permeability of the cell membrane to it and as a purely extracellular effect transduced through the cell membrane with a final response consisting of an increase in the intracellular FDP.

Animals↗
PubMed1987

The effect of colony stimulating factor-1 in vivo.

The present studies were undertaken to determine whether colony stimulating factor-1 (CSF-1) stimulates hemopoietic cell proliferation and differentiation in vivo. Groups of mice were injected with 25,000 units of pure, endotoxin-free L-cell CSF every 6 hours for intervals up to 8 days. Virtually no changes were detected in blood neutrophils or monocytes. No consistent increases in marrow granulopoiesis were noted. Variable but inconsistent changes in marrow and splenic progenitor cells were noted. Serum CSF was elevated 2 hours after injection but returned to baseline values within 4-6 hours. These studies indicate essentially no effect from exogenous administration of purified CSF; however, higher doses of this factor will be required in further studies.

Animals↗
PubMed1986

Normal blast colony formation: an in vitro tool for monitoring human bone marrow 'purging'.

A major problem in autologous bone marrow transplantation is that it is impossible to evaluate in vitro the effect of drug treatment on haematopoiesis. However, Gordon and colleagues have recently established a colony forming assay which detects very immature blast progenitor cells. This method can be used to measure the myelotoxicity of drugs used for removing malignant cells from bone marrow ('purging') before autografting and we have analysed the action of mafosfamide on normal blast colony formation. Treatment in vitro with mafosfamide did not impair the formation of blast colonies containing very primitive cells (type I) but suppressed the formation of the colonies of more mature cells (types II and III) which grow under the same culture conditions. The surviving type I blast colony-forming cells were capable of self-renewal and differentiation. In contrast granulocyte-macrophage colony-forming units (GM-CFU) were totally destroyed by treatment with mafosfamide.

Bone Marrow↗
PubMed1985

High-dose methotrexate-leucovorin rescue therapy: selected application in non-Hodgkin's lymphoma.

Methotrexate with leucovorin rescue (HDMTX-LV rescue), has been used to treat solid tumors and non-Hodgkin's lymphomas (NHL). We studied the use of HDMTX-LV rescue in patients with widespread NHL with histologic diagnosis of diffuse poorly differentiated lymphocytic and diffuse histiocytic including involvement of the central nervous system (CNS) and/or bone marrow. The prognosis with conventional chemotherapy is extremely poor. Three patients have bone marrow involvement, 2 patients CNS, and 2 both. These patients were unresponsive to conventional chemotherapy and had a rapid progression of their disease. Therapy with HDMTX-LV rescue induced responses in 5 patients: 2 patients achieved a complete remission and three a partial remission. Regression of CNS involvement was observed in 3 patients; bone marrow toxicity was not observed. Only 1 patient failed to respond. These data suggest that HDMTX-LV rescue may be useful as primary therapy in lymphoma patients with CNS and/or bone marrow involvement.

Adult↗
PubMed1985

In vitro restoration of polyclonal hematopoiesis in a chronic myelogenous leukemia after in vitro treatment with 4-hydroperoxycyclophosphamide.

Bone marrow cells of a 45-year-old female with Philadelphia chromosome (Ph1)-positive, early-phase chronic myelogenous leukemia (CML), who was heterozygous for the glucose-6-phosphate dehydrogenase (G6PD) locus, were pretreated in vitro with 4-hydroperoxycyclophosphamide (4-HC) and tested for G6PD activity in several colony formation assays and for karyotypic abnormalities. All cells within the mixed (CFU-GEMM), the erythroid burst (BFU-E), and the granulocyte-macrophage (CFU-GM) colonies expressed type A and type B G6PD activity and a normal karyotype, whereas untreated cells expressed type A G6PD and the Ph1 chromosome. This reversal of G6PD activity type and the disappearance of the Ph1 chromosome in colonies grown from 4-HC-treated cells indicate that this cytotoxic agent spares a residual normal stem cell population in bone marrow cells of early-phase CML patients. This finding, in turn, suggests a therapeutic approach in CML based on in vitro chemotherapy of autologous bone marrow grafts.

Bone Marrow Cells↗
PubMed1983

Ontogeny of granulocyte-macrophage progenitor cells in the human fetus.

The CFU-Gm content of liver, spleen and bone marrow of human fetuses was determined from the 8th to 28th week of gestational age. The study of progenitor cells from 43 fetal livers revealed that the CFU-Gm increased from 8 to 12 weeks, was relatively stable through 16 weeks and thereafter declined by 22 to 24 weeks. The total number of liver CFU-Gm rose from 10(4) to greater than 10(6) CFU-Gm by the 16th week of gestation and declined to approximately 4 X 10(5) progenitor cells by 22 to 24 weeks. Peak values of bone marrow CFU-Gm were noted at 10 to 14 weeks of gestation. Generally, the numbers of these progenitor cells declined by 16 to 18 weeks; however, several high values were obtained at later times. Splenic CFU-Gm were relatively constant in number between 12 and 28 weeks of gestation with no correlation with fetal age. Thus, these studies indicate that certain fetal tissues contain substantial numbers of hemopoietic progenitor cells. Based on the quantity of CFU-Gm obtained, it appears feasible to use fetal liver cells as a source of progenitor cells for transplantation.

Bone Marrow↗
PubMed1983

Inhibition of murine CFU-C by vindesine: restoration of colony growth by colony stimulating factor.

Vindesine (VDS) is a new vinca-alkaloid related to vinblastine and vincristine that blocks production of the microtubules in the mitotic phase of the cell cycle. Studies were undertaken to investigate the inhibitory effect of VDS on normal murine bone marrow cell proliferation and the possible interactions between this compound and L-cell derived colony stimulating factor (CSF). One X 10(7) murine bone marrow cells were exposed to various concentrations of VDS, ranging from 0.1 to 1.5 micrograms/ml for 1 h at 37 degrees C. Following this period, the cells were plated in agar in the presence of 100 units of CSF. A dose-dependent inhibition of colony formation was noted with increasing doses of the drugs. To determine whether an increased dose of CSF could overcome the inhibitory effect of VDS, further studies compared colony growth in response to 100 and 200 units of CSF. Virtually no inhibition of colony growth was detected in VDS-treated cells exposed to this higher dose of CSF while a dose-dependent reduction in CFU-C was noted with 100 units of CSF. Preincubation of cells with VDS and CSF prevented the inhibition that occurred with VDS alone. The addition of anti-CSF serum during the preincubation phase abolished the protective effect of CSF. The studies show that short-term exposure of marrow cells to VDS causes a dose-dependent inhibition of in vitro colony formation; this inhibition is prevented by increasing doses of CSF in agar culture or by simultaneous preincubation with CSF. The CSF action appears specific as its protective effect is neutralized by antibody to CSF, suggesting a potential role for CSF in preventing the antimitotic activity of VDS.

Animals↗