Can gas replace protein function? CO abrogates the oxidative toxicity of myoglobin.

Outside their cellular environments, hemoglobin (Hb) and myoglobin (Mb) are known to wreak oxidative damage. Using haptoglobin (Hp) and hemopexin (Hx) the body defends itself against cell-free Hb, yet mechanisms of protection against oxidative harm from Mb are unclear. Mb may be implicated in oxidative damage both within the myocyte and in circulation following rhabdomyolysis.

Carbon monoxide induced erythroid differentiation of K562 cells mimics the central macrophage milieu in erythroblastic islands.

Growing evidence supports the role of erythroblastic islands (EI) as microenvironmental niches within bone marrow (BM), where cell-cell attachments are suggested as crucial for erythroid maturation. The inducible form of the enzyme heme oxygenase, HO-1, which conducts heme degradation, is absent in erythroblasts where hemoglobin (Hb) is synthesized. Yet, the central macrophage, which retains high HO-1 activity, might be suitable to take over degradation of extra, harmful, Hb heme.

Carbon monoxide promotes respiratory hemoproteins iron reduction using peroxides as electron donors.

The physiological role of the respiratory hemoproteins (RH), hemoglobin and myoglobin, is to deliver O(2) via its binding to their ferrous (Fe(II)) heme-iron. Under variety of pathological conditions RH proteins leak to blood plasma and oxidized to ferric (Fe(III), met) forms becoming the source of oxidative vascular damage. However, recent studies have indicated that both metRH and peroxides induce Heme Oxygenase (HO) enzyme producing carbon monoxide (CO).

Precise quantification of haemoglobin in erythroid precursors and plasma.

Introduction: Haemoglobin (Hb) quantification in whole blood is possible by various spectrophotometric methods. However, determination of low-level Hb in erythroid precursors or haemolytic plasma is inaccurate because of contribution from light scatter and/or nonhaemoglobin components with overlapping absorbance. Therefore, this study developed a sole method allowing accurate spectrophotometric quantification of Hb at a low concentration range.

Salvage chemotherapy with dexamethasone, etoposide, ifosfamide and cisplatin (DVIP) for relapsing and refractory non-Hodgkin's lymphoma.

Background: There is currently no standard salvage chemotherapy for the 40-50% of patients with non-Hodgkin's lymphoma who fail first-line treatment.

Objectives: To review the experience of a major tertiary medical center with DVIP (dexamethasone, etoposide, ifosfamide and cisplatin) salvage therapy for primary refractory/relapsing NHL.

Methods: We reviewed the records of all patients with NHL who received DVIP salvage therapy during the period 1993 to 2005.

Pivanex, a histone deacetylase inhibitor, induces changes in BCR-ABL expression and when combined with STI571, acts synergistically in a chronic myelocytic leukemia cell line.

Chronic myelogenous leukemia (CML) is associated with the high TK activity chimeric protein BCR-ABL, known to contribute to cell tumorogenicity, resistance to apoptosis and differentiation. STI571, the TK inhibitor, is the current treatment for CML. One possible approach to overcome STI571 resistance appearing in some cases, involves the combination of histone deacetylase inhibitors (HDI) and STI571.

Collagen binding induces changes in its platelet integrin receptor alpha2beta1.

Integrins can signal upon binding of their ligand, presumably because of conformational changes induced by ligand-binding. It has been postulated that ligand binding causes changes in the affinity of the integrin to its ligand. In order to test for ligand-induced change in the affinity of platelet alpha2beta1 to collagen, labelled viable platelets were passaged through a column of fibrillar collagen and stringent lysis conditions were used to remove all low-affinity receptors.

Antiphospholipid antibodies may be a new prognostic parameter in aggressive non-Hodgkin's lymphoma.

Objectives: Patients with malignancies have an increased prevalence of antiphospholipid antibodies (APA). The aim of this study was to determine the prevalence of IgG, IgM, and IgA anticardiolipin antibodies (aCL) and anti-beta-2 glycoprotein I antibodies (anti-beta2-GPI) in patients with non-Hodgkin's lymphoma (NHL), and to investigate their clinical and prognostic significance.

Methods: The study group included 86 patients with NHL.

Vascular damage by unstable hemoglobins: the role of heme-depleted globin.

The study compared the damage inflicted to endothelial cells (ECs) by intact hemoglobin (Hb) and isolated chains. To compare optional in vivo contact of acellular Hb with the endothelium, oxy-forms of Hb and its isolated alpha- and beta-chains existing in the thalassemias were added to primary confluent cultures of bovine aorta EC. Cell damage was followed by morphological changes or leakage of lactic dehydrogenase and pre-inserted 51Cr from the cells, followed for 27 h.

Jasmonates: novel anticancer agents acting directly and selectively on human cancer cell mitochondria.

We reported previously that jasmonates can kill human cancer cells. Many chemotherapeutic drugs induce mitochondrial membrane permeability transition, membrane depolarization, osmotic swelling, and release of cytochrome c, involving the opening of the permeability transition pore complex (PTPC). Because jasmonates exert their cytotoxic effects independent of transcription, translation, and p53 expression, we hypothesized that these compounds may act directly on mitochondria.

Serum CA 125 levels in patients with chronic lymphocytic leukemia.

Cancer antigen 125 (CA 125) is a glycoprotein expressed in normal tissues originally derived from celomic epithelia and its serum level is elevated in various benign and malignant conditions that involve stimulation of these tissues. Elevated levels have been reported in 40-43% of patients with non-Hodgkin's lymphoma (NHL) at diagnosis and were associated with parameters known to be associated with advanced and disseminated disease, and with event-free and overall survival. No difference in CA 125 level was found between indolent and aggressive lymphomas, and four of six patients with small lymphocytic lymphoma had elevated CA 125 levels.

Expression of adhesion molecules on leukemic B cells from chronic lymphocytic leukemia patients with predominantly splenic manifestations.

Background: The highly tissue-specific trafficking of normal and malignant lymphocytes to particular organs is mediated by adhesion molecules, or "homing receptors." Among our patients with B cell chronic lymphocytic leukemia 15% demonstrate predominantly splenic manifestations and are classified as stage II(S).

Objective: To investigate whether expression of cell surface adhesion molecules can distinguish stage II(S) patients from stage 0 or stage 0 and I CLL patients.

Serum CA 125 as a prognostic factor in non-Hodgkin's lymphoma.

Cancer antigen 125 (CA 125) is a glycoprotein expressed in normal tissues originally derived from coelomic epithelia such as peritoneum, pleura, pericardium, fallopian tubes and endometrium. Serum CA 125 levels are elevated in various benign and malignant conditions that involve stimulation of these tissues. Although elevated levels have been reported in patients with non-Hodgkin's lymphoma (NHL), its role as a prognostic factor remained uncertain.

All three receptors for vascular endothelial growth factor (VEGF) are expressed on B-chronic lymphocytic leukemia (CLL) cells.

B-chronic lymphocytic leukemia (B-CLL) cells have a long survival owing to an alteration in the normal pathways of apoptosis. CLL cells have been found to produce and secrete vascular endothelial growth factor (VEGF). In addition to its major role in angiogenesis, VEGF affects cell survival by interfering with apoptosis.

Human T lymphotropic virus type 1 in a seronegative B chronic lymphocytic leukemia patient.

Human T lymphotropic virus type 1 (HTLV-1) is the etiological agent of adult T cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. HTLV-1 infection in patients with B cell-type chronic lymphocytic leukemia (B-CLL) is rare and has been reported only in areas in which HTLV-1 is endemic. In the present study, we detected HTLV-1 proviral DNA by polymerase chain reaction, using tax primers, in peripheral blood lymphocytes from a B-CLL patient, an immigrant to Israel, where HTLV-1 infection is not endemic.

Detection of methylated ABL1 promoter in philadelphia-negative myeloproliferative disorders.

Aberrant methylation of tumor-suppressor gene promoter regions may play a causal role in the pre-neoplastic stage of cancer progression. In chronic myeloid leukemia, changes in the methylation status of the CpG-rich islands at several sites in the proximal ABL1 promoter (Pa) on the Philadelphia (Ph)-chromosome have been observed. It remains unclear if the Pa methylation precedes the translocation event (t9;22) that generates the Ph-chromosome or if Pa methylation is a stochastic event in a progenitor cell which will later acquire other mutations, namely t9;22.

Expression of basic fibroblast growth factor is associated with poor outcome in non-Hodgkin's lymphoma.

It is now clear that angiogenesis and angiogenesis factors are important in the pathogenesis of haematological malignancies. High pretreatment levels of serum basic fibroblast growth factor have been shown to be associated with poor prognosis in patients with non-Hodgkin's lymphoma. The aim of this study was to evaluate whether non-Hodgkin's lymphoma cells express basic fibroblast growth factor and/or its receptor (fibroblast growth factor receptor-1) and whether basic fibroblast growth factor expression correlates with basic fibroblast growth factor serum levels, intratumoral microvessel density, and patient outcome.

Lack of HER-2/neu expression in Hodgkin and non-Hodgkin lymphoma.

Objective: Overexpression of HER-2/neu oncoprotein, a tyrosine kinase receptor, occurs in a variety of human cancers and has been shown to play a critical role in their development. This overexpression is usually associated with poor clinical outcome. The significance of HER-2/neu in lymphomas is unknown.

Clinical severe hepatic venoocclusive disease during induction treatment of acute monoblastic leukemia managed with defibrotide.

Hepatic venoocclusive disease (VOD) is the most common complication of cytoreductive therapy used for stem cell transplantation, but it is rarely encountered during induction treatment of acute leukemia. We describe a patient in whom severe clinical VOD developed shortly after induction treatment for acute monoblastic leukemia. Administration of intravenous defibrotide for 19 days induced complete resolution of the VOD.

Doxorubicin and a butyric acid derivative effectively reduce levels of BCL-2 protein in the cells of chronic lymphocytic leukemia patient.

B-chronic lymphocytic leukemia (B-CLL) is a disease caused primarily by defects in the apoptosis mechanism. AN-9, a butyric acid (BA) derivative, is a potent differentiating and an anti-cancer drug that induces apoptosis in HL-60 cells. Herein we show the affect of AN-9, alone and in combination with doxorubicin, on cell cultures from B-CLL patients.

Bcl-2 expression correlates positively with serum basic fibroblast growth factor (bFGF) and negatively with cellular vascular endothelial growth factor (VEGF) in patients with chronic lymphocytic leukaemia.

A large proportion of B-chronic lymphocytic leukaemia (B-CLL) cells express the anti-apoptotic protein Bcl-2. Basic fibroblast growth factor (bFGF) has been shown to upregulate the expression of Bcl-2 in B-CLL cell lines. Vascular endothelial growth factor (VEGF) has been shown to enhance the survival of endothelial cells by upregulating the expression of Bcl-2.

Uptake of pivaloyloxymethyl butyrate into leukemic cells and its intracellular esterase-catalyzed hydrolysis.

Unlabelled: Pivaloyloxymethyl butyrate (AN-9), a butyric acid (BA) prodrug, exhibited low toxicity and significant anticancer activity in vitro and in vivo. The purpose of this study was to elucidate the basis for AN-9 increased anticancer activity compared to BA, by studying the uptake of BA and AN-9 into the cells.

Methods: The uptake rate and level of [14C]-AN-9 and [14C]-BA, labeled on the carboxylic moiety of BA, into HL-60 and MEL leukemic cell lines was measured.

Microvessel density in chemosensitive and chemoresistant diffuse large B-cell lymphomas.

Preliminary reports involving a number of different kinds of tumors have indicated that microvessel quantification may be useful in predicting disease outcome. The aim of this study was to examine the relationship between microvessel density (MVD) as a parameter of tumor angiogenesis and the response to chemotherapy in diffuse large B-cell (DLBC) lymphomas. A total of 36 DLBC lymphoma patients were evaluated, 23 of them with a chemosensitive; responsive disease (median survival 8y) and 13 with a chemoresistant, refractory disease (median survival 8 months).

Expression of bcl-2 and bax in cells isolated from B-chronic lymphocytic leukemia patients at different stages of the disease.

B-Chronic lymphocytic leukemia (B-CLL) is an example of a human malignancy caused by alterations in the pathways of programmed cell death. In this disease the anti-apoptotic protein, bcl-2, is overexpressed and may lead to the prolonged survival of a malignant CLL clone. In the present study we examined the expression of bcl-2 and bax, which has an antagonistic role against the function of bcl-2, in cells from CLL patients at different stages of the disease, by immunoblot analysis.