Effect of intracoronary injection of mononuclear bone marrow stem cells on left ventricular function in patients with acute myocardial infarction.

To investigate the effect of intracoronary injection of autologous mononuclear bone marrow stem cells (BMSCs) in patients with ST-elevation myocardial infarction (STEMI) on left ventricular (LV) systolic and diastolic function using standard echocardiography and 2-dimensional systolic strain. A total of 60 patients with first anterior wall STEMI and LV ejection fraction of <40%, treated with successful primary percutaneous coronary intervention were randomly assigned to the treatment group (BMSC group) or the control group in a 2:1 ratio. Transcatheter intracoronary injection of BMSCs into the infarct-related artery was performed 7 days after STEMI.

The effects of intracoronary autologous mononuclear bone marrow cell transplantation on cardiac arrhythmia and heart rate variability.

Background: The results of stem cell therapy after myocardial infarction (MI) have been conflicting. The effects of this therapy on ventricular arrhythmias and autonomic control of heart rate have not yet been established.

Aim: To assess the effects of bone marrow cell (BMC) transplantation on the occurrence of arrhythmias and heart rate variability (HRV) parameters in short-term observation after ST-elevation myocardial infarction (STEMI).

Clofarabine as a novel nucleoside analogue approved to treat patients with haematological malignancies: mechanism of action and clinical activity.

Clofarabine is a second generation of purine nucleoside analogues designed to combine the most favorable pharmacokinetic properties of fludarabine and cladribine. Clofarabine acts by inhibiting DNA polymerases and ribonucleotide reductase as well as by inducing apoptosis in cycling and non-cycling cells. Phase I/II clinical studies revealed its efficacy in hematological malignancies, and in 2004 clofarabine was approved by the United States Food and Drug Administration for the treatment of pediatric relapsed or refractory acute lymphoblastic leukemia after at least two prior chemotherapy regimens.

Current status of older and new purine nucleoside analogues in the treatment of lymphoproliferative diseases.

For the past few years more and more new cytotoxic agents active in the treatment of hematological malignancies have been synthesized and become available for either in vitro studies or clinical trials. Among them the class of antineoplastic drugs belonging to the purine nucleoside analogues group (PNAs) plays an important role. Three of them: pentostatin (DCF), cladribine (2-CdA) and fludarabine (FA) were approved by Food and Drug Administration (FDA) for the treatment of hematological malignancies.

Impact of intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction on left ventricular perfusion and function: a 6-month follow-up gated 99mTc-MIBI single-photon emission computed tomography study.

Purpose: We investigated the impact of intracoronary injection of autologous mononuclear bone marrow cells (BMC) in patients with acute ST elevation myocardial infarction (STEMI) on left ventricular volumes, global and regional systolic function and myocardial perfusion.

Methods: The study included 39 patients with first anterior STEMI treated successfully with primary percutaneous coronary intervention. They were randomly assigned to the treatment group or the control group in a 2:1 ratio.

Novel purine nucleoside analogues for hematological malignancies.

Recently, the search for more effective and safer antineoplastic agents has led to synthesis and introduction into preclinical and clinical studies of a few new purine nucleoside analogues (PNA). Three of them: clofarabine (CAFdA), nelarabine, and forodesine (immucillin H, BCX-1777), despite belonging to the same group of drugs such as PNA, have shown some differences concerning their active forms, metabolic properties and mechanism of action. However, all these drugs have demonstrated promising activity in patients with relapsed and refractory acute lymphoblastic leukemia (ALL).

Older and new formulations of cladribine. Pharmacology and clinical efficacy in hematological malignancies.

The purine nucleoside analog (PNA)--cladribine (2-CdA, 2-chlorodeoxyadenosine) is a cytotoxic agent of high efficacy in lymphoid and myeloid malignancies. This drug was approved by the FDA for treatment of hairy cell leukemia and in some European countries for treatment of refractory/relapsed chronic lymphocytic leukemia. 2-CdA is usually administered as continuous or intermittent intravenous infusion.

Depsipeptide (FK228) as a novel histone deacetylase inhibitor: mechanism of action and anticancer activity.

Depsipeptide (FK228), a new histone deacetylase inhibitor, has been recently introduced into clinical trials. This agent shows interesting metabolic properties, novel mechanism of action, and is undergoing phase I-II clinical studies in hematopoietic malignancies and solid tumors. Mechanism of action, pharmacokinetics and anticancer activity of depsipeptide is the subject of this review.

Forodesine (BCX-1777, Immucillin H)--a new purine nucleoside analogue: mechanism of action and potential clinical application.

Recently a few new purine nucleoside analogues (PNA) have been synthesized and introduced into preclinical and clinical trials. The transition-state theory has led to the design of 9-deazanucleotide analogues that are purine nucleoside phosphorylase (PNP) inhibitors, termed immucillins. Among them the most promising results have been obtained with forodesine.

Purine nucleoside analogs as immunosuppressive and antineoplastic agents: mechanism of action and clinical activity.

The purine nucleoside analogs (PNA) form an important group of cytotoxic drugs active in the treatment of neoplastic and autoimmune diseases. Three of them, fludarabine (FA), cladribine (2-chlorodeoxyadenosine, 2-CdA) and pentostatin (2'-deoxycoformycin, DCF) have established clinical activity in hematological malignancies and have been approved by FDA. These drugs are also investigated in some autoimmune diosorders.

Pharmacological and clinical studies on purine nucleoside analogs--new anticancer agents.

More recently, three novel purine nucleoside analogs, including clofarabine, nelarabine and immucillin H, have been introduced into clinical trials. These agents have different metabolic properties, novel mechanism of action, and are undergoing phase I-II clinical studies for the treatment of hematopoietic malignancies. Pharmacology and anticancer activity of PNA are the subjects of this review.

Purine nucleoside analogues for the treatment of hematological malignancies: pharmacology and clinical applications.

The purine nucleoside analogues (PNAs), fludarabine (FA), 2-CdA (2-chlorodeoxyadenosine, 2-CdA) and pentostatin (2'-deoxycoformycin, DCF) represent a group of cytotoxic agents with high activity in lymphoid and myeloid malignancies. PNAs share similar chemical structure and mechanism of action. Several mechanisms could be responsible for their cytotoxicity both in proliferating and quiescent cells, such as inhibition of DNA synthesis, inhibition of DNA repair and accumulation of DNA strand breaks.

The influence of farnesyl protein transferase inhibitor R115777 (Zarnestra) alone and in combination with purine nucleoside analogs on acute myeloid leukemia progenitors in vitro.

R115777 (Tipifarnib, Zarnestra)-farnesyl transferase inhibitor belongs to the new class of signal transduction inhibitors which seems to be yielding results in the treatment of patients with solid tumors. Recently it has also been considered as a drug of promise in hematologic malignancies such as acute myeloid leukemia (AML), especially in older patients, in chronic myelogenous leukemia (CML) as well as myelodysplastic syndromes (MDS). The aim of our study was to evaluate the influence of R115777 used alone or with purine nucleoside analogs (PNA): cladribine (2-CdA) and fludarabine (F-ara-A) on leukemic progenitors [colony-forming unit-leukemia (CFU)-L] from AML patients.

Chronic myelomonocytic leukemia coexisting with B-cell chronic lymphocytic leukemia.

Coexistence of B-cell chronic lymphocytic leukemia (B-CLL) and chronic myelomonocytic leukemia (CMML) is an unusal event, and to our knowledge, only four such cases have been reported in the literature. We report a 68-year-old white woman in whom these two diseases were diagnosed concomitantly. The diagnosis was made on the basis of peripheral blood count, morphology and immunophenotyping, and bone marrow cytology and histology.

The influence of imatinib mesylate (STI571) used alone or in combination with purine nucleoside analogues on the normal and chronic myelogenous leukaemia progenitor cells in vitro.

Imatinib mesylate (STI571, Glivec), a signal transduction inhibitor used as a single agent demonstrates significant activity in patients with chronic myelogenous leukaemia (CML). Nevertheless, the interaction between STI571 and other antileukaemic drugs such as hydroxyurea, interferon alpha or cytarabine have also been investigated in order to further improve its effectiveness. In this study we have tried to answer the question if the combination of STI571 with purine nucleoside analogues (PNAs)- cladribine (2-CdA) and fludarabine (F-ara-A) intensifies the antiproliferative effect on granulocyte-macrophage progenitor cells (CFU-GM) from patients with CML as well as from normal persons.

Coexistence of chronic lymphocytic leukemia and essential thrombocythemia.

The association of chronic lymphocytic leukemia (CLL) with essential thrombocythemia (ET) is an extremely rare event and until now 3 patients with such coexistence have been reported in the literature. We report a 77-year-old white woman in whom these two disorders were diagnosed concomitantly on the basis of peripheral blood count and cytology, bone marrow cytology and histology, immunophenotyping, as well as exclusion criteria. The diagnosis of ET was also supported by spontaneous in-vitro erythroid colony growth and by evaluation of thrombopoietin (TPO) serum level.

Hodgkin's type of Richter's syndrome in familial chronic lymphocytic leukemia treated with cladribine and cyclophosphamide.

Second malignancies are frequent complications in patients with chronic lymphocytic leukemia (CLL). Hodgkin's disease (HD) has been observed in approximately 0.5% of the patients with CLL and is known as Hodgkin's type Richter's syndrome (H-RS).

The effect of cyclosporin A used alone and in combination with either 2-chlorodeoxyadenosine or fludarabine on normal and chronic myelogenous leukemia progenitors in vitro.

We evaluated the influence of cyclosporin A (CsA) used alone or together with the new purine nucleoside analogues (PNAs) 2-chlorodeoxyadenosine (2-CdA) and fludarabine (F-ara-A) on the colony growth of normal and chronic myelogenous leukemia (CML) granulocyte-macrophage progenitor cells (CFU-GM) in cultures in vitro. The assay was based on the Iscove's method in our modification. Specimens of bone marrow were collected from 15 patients with CML in the chronic phase and from 10 hematologically normal patients.

Influence of gemcitabine (2',2'-difluoro-deoxycytidine) and 2-chlorodeoxyadenosine on growth of normal and leukemic cells in vitro.

The aim of the study was to investigate the influence of gemcitabine (2',2'-difluorodeoxycytidine, dFdC) used alone and in combination with 2-chlorodeoxyadenosine (2-CdA) on the colony growth of normal granulocyte-macrophage progenitor cells (CFU-GM) from 15 hematologically healthy donors as well as on CFU-GM from 15 chronic myelogenous leukemia (CML) patients in semisolid cultures in vitro. dFdC and 2-CdA were used either separately or in the following combinations of concentrations: (1) 0.25 nM of dFdC and 2.

Influence of granulocyte-macrophage colony stimulating factor on pituitary-adrenal axis (PAA) in rats in vivo.

We have studied the in vivo influence of granulocyte-macrophage colony stimulating factor (GM-CSF) on blood plasma concentration of adrenocorticotropic hormone (ACTH) and corticosterone in Wistar rats. The administration of 10 micrograms/kg b.w.

The influence of amifostine used alone or in combination with 2-chlorodeoxyadenosine on normal and chronic myelogenous leukemia granulocyte-macrophage progenitor cells in vitro.

We evaluated the influence of amifostine used alone or in combination with 2-chlorodeoxyadenosine (2-CdA) on the colony growth of normal and chronic myeloid leukemia (CML) granulocyte-macrophage progenitor cells (CFU-GM) in semisolid culture in vitro. Amifostine at a concentration of 1 mg/ml was either added directly to the culture medium of normal and CML CFU-GM, or mononuclear cells (MNCs) were first preincubated with amifostine at the same concentration, washed in Iscove's modified Dulbecco minimum essential medium (IDMEM) and then added to the culture medium. Amifostine used alone inhibited the growth of CML CFU-GM colonies to a higher degree than those of normal CFU-GM, but the differences were not statistically significant.

The interaction of gemcitabine and cytarabine on murine leukemias L1210 or P388 and on human normal and leukemic cell growth in vitro.

Background And Objective: Gemcitabine (dFdC) is a new nucleoside antimetabolite of deoxycytidine that resembles cytarabine (Ara-C) in both its structure and metabolism. Little is known about dFdC efficacy in hematologic malignancies, either as a single drug or in combination with other drugs. In this study we have tried to determine whether the cytotoxic effect of Ara-C can be increased by using it in combined therapy with dFdC.

Serum levels of IL-6 type cytokines and soluble IL-6 receptors in active B-cell chronic lymphocytic leukemia and in cladribine induced remission.

We have investigated the serum concentrations of interleukin-6 (IL-6) and two IL-6 family cytokines-oncostatin M (OSM) and leukemia inhibitory factor (LIF)-in 63 patients with B-cell chronic lymphocytic leukemia (B-CLL) and 17 healthy controls using the enzyme-linked immunosorbent assay (ELISA) method. Simultaneously, we measured the serum levels of the soluble forms of two subunits of the IL-6 receptor complex-ligand binding glycoprotein 80 (sIL-6R) and glycoprotein 130 (sgp130). The cytokines and receptors were evaluated in 25 untreated patients and 38 patients treated with cladribine (2-CdA), as well as in 17 healthy controls.

Pituitary-adrenocortical responses to the chronic administration of granulocyte colony-stimulating factor in rats.

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor, but it may play a role in the regulation of the neuroendocrine system activity. Only few data are available about its possible influence on the pituitary gland. We have recently reported an acute stimulatory effect of G-CSF (and of GM-CSF) on adrenocorticotropic hormone (ACTH) secretion in rats in vivo.