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Biomedical subjects

D Russo

Publications and source records attributed to D Russo.

At least 37 records · Page 2Linked to original sources
PubMed1996

Screening for multidrug resistance in leukemia: cell reactivity to MRK-16 correlates with anthracycline retention and sensitivity of leukemic cells.

The biologic and clinical importance of the multidrug resistance (MDR) that is related with the overexpression of the P170 glycoprotein (Pgp) is widely recognized. However, a major issue that has not yet been solved is the definition of the degree of Pgp expression which is associated with a significant decrease of the sensitivity of the cells to chemotherapy. For this reason we studied the leukemic cells from 83 cases of acute leukemia. Leukemic cells were fixed in PLP and treated with saponine. Pgp expression was assayed by flow cytometry, using the anti Pgp monoclonal antibody MRK-16. Results were expressed both as the number of positive cells and by the intensity of the reaction as defined by the mean fluorescence index (MFI), i.e. the ratio between the mean fluorescence intensity of the MRK-16 incubated cells and of the IgG2a incubated cells. Thus, Pgp expression was compared with the results of two in vitro tests of cell sensitivity to anthracyclines, daunorubicin (DNR) cell retention and DNR cytotoxicity. We found that it was not the number of MRK-16 positive cells, but the degree of the reaction with MRK-16 (MFI) that significantly related to the anthracycline toxicity tests. Therefore, we propose that for clinical purposes a quick and cheap determination of Pgp-related MDR in leukemic cells may be obtained by measuring the MFI with MRK-16 in a standard flow cytometry assay and that the assay may indeed be sufficient to estimate Pgp expression as well as the influence of Pgp on cell sensitivity to anthracyclines.

Anthracyclines↗
PubMed1995

Activating mutations of the TSH receptor in differentiated thyroid carcinomas.

A series of 14 thyroid carcinomas, characterized for their basal adenyl cyclase activity (ACA), was examined for the presence of activating point mutations in the TSH receptor (TSHR) gene. Sequencing of the carboxyl-part of this gene revealed the presence of a somatic and heterozygotic point mutation in codon 623 in three out of six tumors showing a constitutively enhanced ACA and a poor response to TSH stimulation. The mutation determines the substitution of a serine for an alanine in the third intracellular loop of the receptor, in a region critical for signal transduction. One tumor bearing a TSHR mutation presented also a N-ras point mutation. Both mutations were detected also in a lung metastasis of this tumor. Our data represent the first report of alterations in the TSHR gene in thyroid malign neoplasia. TSHR mutations may indeed participate, as well as the G alpha s protein (gsp oncogene), in the oncogenesis of some differentiated thyroid carcinomas presenting increased basal levels of cAMP and a poor response to TSH.

Adenocarcinoma, Follicular↗
PubMed1995

Solitary plasmacytoma of bone and extramedullary plasmacytoma: two different entities?

BACKGROUND: The objective of this study was to evaluate the similarities between solitary plasmacytoma of bone (SPB) and extramedullary plasmacytoma (EP). PATIENTS AND METHODS: The clinical features, treatment and survival of 54 patients with localized plasmacytoma (LP) 1990 were carefully reviewed. Follow-up was expected to continue until June 1993. RESULTS: Thirty-two patients were classified as having SPB and 22 EP. Most of the patients were males. particularly those in the SPB group. Their median age at diagnosis was 54 years and no significant difference between the two groups was observed. SPB occurred most frequently in the vertebral column (42%) and EP in the upper respiratory tract (73%). Fifteen patients with SPB and 2 with EP had paraproteinemia at diagnosis, multiple myeloma (MM) became evident in 75% of the patients with persistent paraprotein after therapy, and in only 22% of those in whom it disappeared. Four patients in the SPB group had immunoparesis, and 3 developed MM. Disease progression toward MM was significantly different (p=0.003) in the two groups, while overall survival differences were not significant (p=0.07) unless unrelated causes were excluded (p=0.02). Adjuvant chemotherapy did not seem to limit diffusion of the disease. CONCLUSIONS: Although EP and SPB are both localized forms of plasma cell dyscrasias, SPB seems to have a greater tendency to progression MM. It appears, however, that the apparent stronger propensity of SPB to progress is actually due to the great number of cases that at diagnosis conceal an occult MM.

Adult↗
PubMed1995

Molecular analysis of PML-RAR alpha fusion mRNA detected by reverse transcription-polymerase chain reaction assay in long-term disease-free acute promyelocytic leukaemia patients.

By use of RT-PCR of PML/RAR alpha, we evaluated bone marrow aspirates in 10 patients with APL in long-term disease-free status after induction chemotherapy and consolidation (median 54 months: range 33-101 months from complete remission). All patients were in clinical and cytogenetic remission at the time of molecular evaluation (range 32-96 months from CR). All patients but one were found to be RT-PCR negative at the molecular level for the expression of PML-RAR alpha transcript, confirming that the majority of the patients with long-term survival of APL are characterized by the eradication of the neoplastic clone.

Bone Marrow↗
PubMed1995

Genetic alterations in thyroid hyperfunctioning adenomas.

Thirty-seven thyroid autonomously hyperfunctioning adenomas were screened for mutations in the TSH receptor (TSHR), G alpha s (gsp), and ras genes. Polymerase chain reaction-amplified fragments of the TSHR C-terminal part (exon 10), the G alpha s (exons 8 and 9), and the three ras genes were obtained from the genomic DNA extracted from 37 tumors and their adjacent normal tissues and were studied by direct nucleotide sequencing and hybridization with synthetic probes. A point mutation in the third intracellular loop (codon 623) of the TSHR was found in 3 of 37 adenomas studied. This mutation codes for a change (Ala to Ser) in the TSHR structure and is somatic and heterozygotic. Constitutive activation of the TSHR was demonstrated by an increase in basal cAMP levels after transfection of Chinese hamster ovary cells with a mutated Ser623-TSHR complementary DNA. Nine gsp[00ae]MDRV[00af]- and one ras-activating mutations were also detected. No simultaneous alteration of the studied genes was present. Thus, in hyperfunctioning thyroid adenomas, our data suggest that a mutational activation of the TSHR and gsp genes may play a tumorigenic role through constitutive activation of the cAMP pathway.

Adenoma↗
PubMed1995

Early effects of contrast media on renal hemodynamics and tubular function in chronic renal failure.

The pathophysiology and prevention of contrast media (CM)-induced nephropathy in chronic renal failure (CRF) are still ill defined. GFR, RPF, endothelin-1 (ET-1) levels, urinary sodium concentration, and fractional excretion of sodium were measured in CRF patients undergoing water diuresis in basal conditions and 20 to 120 min after an iv bolus of either the high-osmolar CM diatrizoate (D) or the low-osmolar CM iopamidol (I). The two CM induced an immediate and progressive decline of both GFR and RPF in the absence of hypovolemia, more pronounced in D (-36% at 120 min) than after I (-19% at 120 min; P < 0.05 versus D). Both CM determined a marked and steady increase of the fractional excretion of sodium. The natriuresis could not be totally ascribed to a CM-induced osmotic diuresis as because the urinary sodium concentration markedly increased. In two further groups of patients receiving D, we studied the effects of pretreatment with a single dose of either captopril or nifedipine. Both drugs, although not preventing the increase of natriuresis, partially antagonized D-induced renal hypoperfusion: GFR and RPF were equally reduced by 20% in D/captopril and D/nifedipine (P < 0.05 versus D). In unpretreated patients receiving either D or I, plasma ET-1 did not change but urinary levels increased; these changes were, however, dissociated from those observed in renal hemodynamics. Both plasma and urinary levels of ET-1 did not vary in pretreated groups. The 72-h follow-up evidenced a significant reduction of renal function only in the unpretreated D group. Therefore, the main findings after CM administration in CRF patients are: (1) an immediate GFR decline proportional to the osmolarity of CM and secondary to the renal hypoperfusion that is neither caused by hypovolemia nor mediated by ET-1, (2) an early tubular dysfunction at the level of the proximal nephron, and (3) a protective effect of single-dose pretreatment with either captopril or nifedipine on D-induced acute and short-term GFR changes.

Contrast Media↗
PubMed1995

Does the type of BCR/ABL junction predict the survival of patients with Ph1-positive chronic myeloid leukemia?

The prognostic value of the site of DNA rearrangement within the M-BCR on chromosome 22 or of the type of transcript has been debated in the last years. The majority of the studies do not support the hypothesis of a predictive value of such molecular parameters. Results coming from a multicentric, prospective trial, based on alpha-IFN therapy, seem to indicate a better karyotypic response in 3' rearranged patients. The possibility of evoking a cytotoxic immune response directed towards peptides originating from each of the different BCR/ABL junctions constitute an important challenge for the future.

Fusion Proteins, bcr-abl↗
PubMed1995

P170 glycoprotein expression and impaired anthracycline retention in chronic myeloid leukaemia.

Chronic myeloid leukaemia (CML) is a well known model of a disease refractory to chemotherapy, including anthracyclines and other drugs that are believed to be pumped out of the cells by a 170 Kd transmembrane glycoprotein (P170). In 35 cases of Ph+ CML we investigated the reactivity of leukaemic cells to a P170-directed monoclonal antibody (MRK-16), by means of flow cytometry. P170 overexpression was found in 4/14 (29%) chronic phase CML cases and in 16/23 (70%) accelerated and blastic phase CML cases (P = 0.01). The same cells were assayed for their ability to retain Daunorubicin and Idarubicin after 2-hours in vitro incubation with 1000 ng/ml of either drug. It was found that anthracycline cell concentration was negatively related with the degree of the reactivity to MRK-16. In accelerated and blastic phase, CML cells simultaneously expressed P170 and the stem cell related marker, CD34. These data confirm that Ph+ leukaemic cells overexpress P170, show that P170 overexpression is functionally relevant, and suggest that P170-related multidrug resistance may be an important factor for chemotherapy failure in Ph+ CML.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

MDR-related P170-glycoprotein modulates cytotoxic activity of homoharringtonine.

Homoharringtonine (HHT) is a new drug with antileukemic activity which is currently tested for treatment of acute and chronic leukemias, either alone or in combination with other agents. Since HHT showed a low efficacy in refractory and relapsed acute leukemia and in the blastic phase of chronic myeloid leukemia (CML) which are frequently characterized by an overexpresion of the multidrug resistance (MDR)-related P170-glycoprotein, we postulated a relationship between the poor antileukemic effect of HHT in these leukemias and the expression of P170-glycoprotein. For this reason, sensitive (LOVO109 and CEM) and MDR (LOVO DX and CEM VLB) cell lines were exposed to HHT with or without some MDR modifiers, namely, Cyclosporine A (CyA), the Cyclosporine derivative SDZ PSC 833 (PSC), and the D-isomer of Verapamil (DVRP). It was found that MDR cells were about 15 times more resistant to HHT than non-MDR cells, and that resistance to HHT was significantly decreased by all the MDR modifiers that were tested. This in vitro study showed that HHT belongs to the category of MDR-related drugs, like anthracyclines, vinca alkaloids, epipodophylline derivatives, and taxol.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

The role of granulocyte colony-stimulating factor (filgrastim) in maintaining dose intensity during conventional-dose chemotherapy with ABVD in Hodgkin's disease.

BACKGROUND: The aim of the study was to evaluate the role and potential benefit of granulocyte colony-stimulating factor (G-CSF, Filgrastim), administered following cytotoxic chemotherapy with the ABVD regimen in Hodgkin's disease, in maintaining cycle schedule and dose intensity and in decreasing neutropenia and number of infections. PATIENTS AND METHODS: Twenty-two patients affected by high-risk Hodgkin's disease (14 localized and 8 diffuse), aged 15 to 69 years (median, 34), were given ABVD chemotherapy for a total of 6 courses (for the purpose of this study, each single course of chemotherapy was considered as two 15-day periods). No patient was given G-CSF after the first cycle. After each cycle, G-CSF was administered only for: 1)absolute neutrophil count < 1 x 10(9)/L between cycles; 2) delay in cycle schedule due to an absolute neutrophil count < 1 x 10(9)/L on the planned day of treatment; or 3) fever or a documented infection, regardless the absolute neutrophil count. Once administered, G-CSF was maintained in the subsequent cycles. RESULTS: Seventeen of 22 patients (77%) required the administration of G-CSF (5 micrograms/kg b.w.; a median of 5 doses/cycle); most of them (13/17) before the 5th dose of chemotherapy. The main reason for introducing G-CSF into therapy was neutropenia during the interval between courses (n = 4) or on the planned day of treatment (n = 11). Comparing 112 courses where G-CSF was not administered with 124 where it was, in the latter group we observed: 1) a significantly lower (P = 0.0002) incidence of cycle delays (0 vs 13), with a median delay of 7 days (5 to 11). The main reason for cycle delay was neutropenia (n = 13); 2) a greater dose intensity delivered to the patients while on G-CSF (100% vs 95.2 +/- 8.8%; P = 0.0001); 3) an absolute neutrophil count significantly higher at day 8 (P < 0.0001) and day 15 (P < 0.0001); 4) a significantly lower (P = 0.0003) incidence of neutropenia (2 vs. 17). No difference in the incidence of infections was observed between the two groups of cycles (P = 0.5889), but the duration and severity of the same were greater during chemotherapy without G-CSF, requiring antibiotic therapy and causing cycle delay. CONCLUSIONS: In conclusion, our data suggest the use of Filgrastim in Hodgkin's disease also during conventional-dose chemotherapy with ABVD. It is not required from the first dose of therapy, but as soon as neutropenia appears between cycles or on the planned day of treatment. Then, its use allows maintenance of the chemotherapy schedule and dose intensity. It also decreases frequency, duration and severity of neutropenia and its sequelae.

Adolescent↗
PubMed1994

Granulocyte-macrophage colony-stimulating factor in combination with pentavalent antimony for the treatment of visceral Leishmaniasis.

The efficacy of GM-CSF was investigated in 20 neutropenic patients (< 1500 neutrophils/microliters) with acute visceral leishmaniasis due to Leishmania chagasi. Patients were randomized to receive either GM-CSF, 5 micrograms/kg daily (intravenously or subcutaneously), or placebo for ten days, in combination with pentavalent antimony, 10-20 mg/kg daily for 20 days. Neutrophil counts were significantly greater on days 5 and 10 of treatment in the GM-CSF group compared with the placebo group (p < 0.02). Eosinophil and monocyte counts were also significantly increased in the GM-CSF group at day 10 (p < or = 0.03). Interestingly, at day 30, platelet counts were significantly increased in the GM-CSF group on days 5 and 10 (p = 0.04 and 0.02, respectively). Patients in the GM-CSF group experienced fewer secondary bacterial or viral infections than placebo patients. Infections occurred in only three patients given GM-CSF compared with eight patients given placebo (p < 0.04). All patients had complete resolution of disease symptoms at three months. Few adverse events were recorded. GM-CSF given subcutaneously at a dose of 5 micrograms/kg daily for ten days was well tolerated, reversed neutropenia rapidly and reduced the number of secondary infections in patients with leishmaniasis.

Adolescent↗
PubMed1994

Different molecular mechanisms are involved in the multihormonal control of glucose transport in FRTL5 rat thyroid cells.

We investigated the molecular mechanisms by which TSH, insulin and IGF-1 modulate the glucose transport system in FRTL5 cells. We found that TSH, insulin and IGF-1 increased the glucose transporter Glut-1 specific mRNA levels 6, 8 and 5 fold over control, respectively. The effect on Glut-1 mRNA was evident after 2 hours, followed by an increased Glut-1 protein expression in whole cells, as judged by western blot analysis, after 5 hours of stimulation with all the hormones studied. In contrast, plasma membrane Glut-1 increased (300-400% over control) after 2 hours of stimulation with TSH (10 mU/ml), dibutyryl-cAMP (1mM), IGF-1 (10 ng/ml) and insulin (10 nM). These data indicate that the glucose transport system is under multihormonal control in FRTL5 cells. Two different mechanisms are involved in TSH, IGF-1 and insulin stimulation of the glucose transport: a) neosynthesis of Glut-1 by activation of gene expression; b) recruitment of carriers from the intracellular pool to the plasma membrane.

Animals↗
PubMed1994

Recombinant human granulocyte-macrophage colony-stimulating factor reverses neutropenia and reduces secondary infections in visceral leishmaniasis.

Twenty-four patients with acute visceral leishmaniasis and leukopenia (< 1500 neutrophils/mm3) due to Leishmania chagasi were studied, 4 in an open-label pilot study and 20 in a double-blind, placebo-controlled trial. Patients received granulocyte-macrophage colony-stimulating factor (GM-CSF), 5 micrograms/kg daily, or placebo for 10 days, plus 10-20 mg/kg pentavalent antimony daily for 20 days. In GM-CSF recipients, neutrophil counts increased threefold and fourfold over baseline at 5 and 10 days, respectively, and were significantly higher than those in placebo recipients (P < .02). Eosinophil and monocyte counts were significantly increase in GM-CSF recipients at 10 days (P < or = .03). Secondary infections occurred in 3 GM-CSF and in 8 placebo recipients (P = .04). All patients had complete resolution of their leishmaniasis at 3 months. Few adverse events were recorded. GM-CSF, 5 micrograms/kg daily for 10 days, was safe, rapidly reversed neutropenia, and reduced the number of secondary infections in patients with leishmaniasis.

Adolescent↗
PubMed1994

Role of loop diuretics in chronic renal failure.

The natriuretic effects of furosemide and the long-acting loop diuretic torasemide have been compared in patients with chronic renal failure with and without nephrotic syndrome. In patients with chronic renal failure without nephrotic syndrome, furosemide and torasemide exerted similar natriuretic activity. In patients with chronic renal failure complicated by nephrotic syndrome, torasemide showed a greater natriuretic potency and a longer duration of action than furosemide.

Administration, Oral↗