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M D Simone

Publications and source records attributed to M D Simone.

13 recordsLinked to original sources
PubMed2000

Patients treated with antitumor drugs displaying neurological deficits are characterized by a low circulating level of nerve growth factor.

The aim of our study was to explore whether nerve growth factor (NGF) plays any role in the development of peripheral neuropathy induced by anticancer treatment. We measured the circulating NGF levels in 23 cancer patients before and after chemotherapy. We evaluated whether the development of peripheral neurotoxicity was associated with changes in basal NGF concentrations in patients studied with a comprehensive neurological and neurophysiological examination. The results of these studies showed that the circulating levels of NGF, which are about 20 pg/ml in plasma of controls, decrease during chemotherapy and in some cases completely disappeared after prolonged treatment with antitumor agents. The decrease in NGF levels seems to be correlated with the severity of neurotoxicity. These results clearly suggest that NGF might become a useful agent to prevent neuropathies induced by antineoplastic drugs and restore peripheral nerve dysfunction induced by these pharmacological compounds.

Aged↗
PubMed1999

Nerve growth factor: a survey of activity on immune and hematopoietic cells.

Nerve growth factor (NGF) is a well characterized molecule required for the survival and differentiation of a variety of cell types both in the peripheral and central nervous system. Numerous studies published in recent years have demonstrated that NGF affects different functional activities of mature immune and hematopoietic cells. Other studies have revealed that hematopoietic progenitor cells from bone marrow, umbilical cord blood and peripheral blood are receptive to the action of NGF and that bone marrow stromal cells produce/respond to NGF during different steps of normal hematopoiesis. Elevated levels of NGF have been found in a number of inflammatory diseases, including those of autoimmune nature and in myeloproliferative pathologies. This review presents these data and discusses the hypothesis of a possible functional role of NGF in immune and hematopoietic disorders.

Animals↗
PubMed1997

Minimally differentiated acute myeloid leukemia (AML-M0): comparison of 25 cases with other French-American-British subtypes.

We compared the immunophenotypic and karyotypic features of 25 cases of minimally differentiated acute myeloid leukemia (AML-M0) with those of 247 cases comprising all AML French-American-British (FAB) classification. Myeloperoxidase (MPO) was detectable with a specific monoclonal antibody in all cases of AML-M0, whereas CD13 and CD33 were both negative in 4 of the 25 cases. Thus, anti-MPO reliably detects minimal myeloid differentiation in AML-M0. CD34 and terminal deoxynucleotidyl transferase (TdT) were more frequently expressed in AML-M0 (96% and 68% of the cases, respectively) than in the other FAB subsets (P < .001 for both). By contrast, GP-170 and CD7 were less frequently expressed in AML-M0 than in FAB classes such as M1, M4, and M5 (P = .02 and .003, respectively). A total of 80% of AML-M0 cases carried lymphoid markers (including TdT), and 48% showed a coordinate positivity for two or more of them. CD2, CD5, CD10, and CD19 were expressed in a similar fashion among the different FAB groups, whereas CD4 expression was significantly more frequent in AML-M0, AML-M4, and AML-M5 (P = .014). AML-M0 was characterized by a more frequent occurrence of complex karyotypes. In addition, approximately 20% of cases had TdT positivity, complex karyotypes, and anomalies of chromosome 5 and/or 7, a pattern not observed in the other FAB subsets. Finally, 80% of anomalies of chromosome 5 and/or 7 in AML-M0 were comprised within complex karyotypes, whereas only 13% of the remaining FAB cases carried this feature. In summary, AML-M0 frequently expresses immunophenotypic and karyotypic aspects that are likely to identify a "stem cell" pattern.

Adolescent↗
PubMed1997

P-glycoprotein expression in de novo acute myeloid leukemia.

Detection of the multidrug resistance P-glycoprotein (PGP) phenotype was performed at the time of diagnosis in 223 patients with acute myeloid leukemia (AML) by flow cytometry using C219 Monoclonal Antibody (MoAb). On the other hand, JSB1 MoAb was tested in 173 of these samples. At onset, PGP was detected in 57.4% of cases with C219 and 75.9% of cases with JSB1. There was no correlation between PGP expression and sex, age, marrow blast percentage or extramedullary disease. On the contrary, strict correlations were noted either between C219 negativity and FAB M3 subtype or between C219 positivity and FAB M5 group (P = 0.003). Significant correlation was found between PGP phenotype and CD7, as 143 of 223 samples had similar patterns of staining with C219 (P < 0.0001). Finally, there was a close relationship between C219 and JSB1 positivity: all the C219+ cases were positive for JSB1 (P < 0.0001). Concerning the karyotype, most patients with monosomy or del (7) were MDR positive; on the other hand, most patients with t(8;21) or t(15;17) were MDR negative. Rh123 accumulation studies showed a significant decrease of mean fluorescence intensities both in C219 and in JSB1 positive cases in comparison with PGP negative ones (P < 0.001). A significant decrease of remission induction rates (CR) was highlighted both between C219+ and C219- and between JSB1+ and JSB1- cases (32.1% v 62.1% and 32.6% v 73.8%, respectively, with P < 0.0001). The overall survival and the remission duration (CCR) were significantly shorter both in C219+ and in JSB1+ patients with no relationship to age. Furthermore, a higher rate of early relapses was noted among MDR+ when compared with MDR- patients both for C219+ and JSB1+ cases. The combination (C219- JSB1+) identified a subset of patients with an intermediate prognosis. On multivariate analysis, C219 and JSB1 were confirmed to be independent prognostic factors for achievement of CR, overall survival and CCR. In conclusion, the assessment of MDR phenotype by flow cytometry is a crucial prognostic factor of treatment outcome in AML.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Minimally differentiated acute myeloid leukemia (AML-M0): a distinct clinico-biologic entity with poor prognosis.

FAB proposals for the diagnosis of AML-M0 represent the formal recognition of a distinct entity which has been described over the past few years by several authors and called minimally differentiated acute myeloid leukemia. By definition, AML-M0 includes acute leukemias which do not fit morphological and cytochemical criteria for the diagnosis of AML, and for which myeloid lineage assignment can be made by immunological assay showing positivity for MPO, CD13, and CD33 and negativity for lymphoid markers. Involvement of an early myeloid progenitor in the leukemic process is a possible theory hypothesized to explain the existence of such a form. Validity of this assumption has been based on the observation that AML-M0 frequently bears "stem cell" markers such as CD34, HLA-DR, Tdt, CD7, and promiscuous IgH/TCR gene rearrangements, which are thought to occur in uncommitted cells. Finally, AML-M0 very frequently carries cytogenetic abnormalities common to MDS or secondary AML, such as -5/5q- or -7/7q- deletions and or complex karyotype. In our experience, AML-M0 is also very often associated with the MDR phenotype, which in turn has been found strictly linked to "stem cell" features, especially in MDS. These biological aspects, altogether, translate into a very unfavorable prognosis, confirming even from a clinical point of view that AML-M0 is a distinct entity. In conclusion, "stem cell" markers, MDR phenotype, complex chromosome lesions, frequent occurrence in elderly patients, and intrinsic chemoresistance characterize AML-M0 and indicate the need for tailored treatments, possibly involving the use of MDR modulators and/or differentiating agents.

Humans↗
PubMed1995

Contribution of immunophenotypic and genotypic analyses to the diagnosis of acute leukemia.

Diagnostic accuracy in acute leukemia (AL) can be improved if traditional morphology and cytochemistry are supplemented with immunophenotypic and genotypic analyses. This multiparameter approach is of crucial importance for the management of patients, as it enables the identification of leukemic syndromes with distinct biological features and response to treatment. Immunophenotyping using monoclonal antibodies has been universally accepted as a useful adjunct to morphological criteria. This technique is particularly valuable in diagnosing and subclassifying acute lymphoblastic leukemia and is also essential in certain types of acute myeloid leukemia (AML), such as AML with minimal differentiation or acute megakaryoblastic leukemia. Cytogenetic findings can be quite helpful in establishing the correct diagnosis and can add information of prognostic significance. A number of specific chromosomal abnormalities have been recognized that are very closely, and sometimes uniquely, associated with morphologically and clinically distinct subsets of leukemia. An even more basic understanding of normal and malignant hematopoietic cells has begun to evolve as molecular biology begins to unravel gene misprogramming by Southern and Northern blot analysis, the polymerase chain reaction, and fluorescence in situ hybridization. With the extensive use of these techniques it has become apparent that a proportion of leukemias exhibit the biologically relevant molecular defect in the absence of a karyotypic equivalent. On the other hand, apparently uniform chromosomal abnormalities such as the t(1;19) (q23;p13), t(9;22) (q33;q11), t(8;14) (q24;q32), or t(15;17) (q21;q21) may differ at the molecular level. Data collected from these modern technologies have introduced a greater complexity, which needs to be taken into consideration to improve both the diagnostic precision and the reproducibility of current classifications.

Acute Disease↗
PubMed1995

CD7 expression in acute myeloid leukemia.

The clinical significance of the expression of CD7 antigen on the blasts of 207 consecutive patients with de novo acute myeloid leukemia (AML) was evaluated. For this purpose, fifty-three CD7+ patients (23 females and 30 males; mean age 52 years) were analyzed and classified into the following subtypes according to French-American-British (FAB) classification: 7 M0, 13 M1, 9 M2, 1 M3, 9 M4, 14 M5. Immunophenotypic studies were carried out by flow cytometry and blast cells were selected on the basis of forward light scatter gating and pan-myeloid marker, either CD13 or CD33. All the CD7+ patients were negative for surface CD3 and T-cell-receptor (TCR) molecules. We found no correlation between CD7 expression and sex, age, hepatosplenomegaly and/or central nervous system involvement. The immaturity of CD7+ leukemic cells was supported by the high expression of CD34 (P = 0.001). CD7 positivity was significantly associated with a white blood cell count (WBC) greater than 100 x 10(9)/L (P = 0.003). P-Glycoprotein (P-170) expression was also evaluated in 135 patients by a flow-cytometric assay: there was a close relationship between CD7 and P-170 positivity (P < 0.001). For remission induction, all patients received therapeutic regimens routinely used for AML. The complete remission (CR) rate was significantly lower in CD7+ cases (32% vs 74%, P = 0.001). The overall survival and disease free survival rate of CD7+ AML was lower than those of CD7- patients (P < 0.001 and = 0.002, respectively). CD7+ AML with coexpression of CD14 had a particularly unfavourable response and prognosis in comparison with CD7+ patients without CD14.(ABSTRACT TRUNCATED AT 250 WORDS)

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Minimally differentiated acute myeloid leukaemia (AML-M0): cytochemical, immunophenotypic and cytogenetic analysis of 19 cases.

We describe our experience in the identification of 19 cases of AML-M0 categorized among 200 consecutive AML cases. Leukaemic cells from our cases were morphologically marked by agranular basophilic cytoplasm, finely dispersed chromatin and prominent nucleoli. In two cases heavily vacuolated and monocytoid-shaped blasts were also observed. Cytochemistry (MPO, SBB, alpha ANAE, alpha NBE, NASDCAE, AP, PAS) was negative in 14 cases, five cases expressing a very faint cytoplasmic positivity for alpha NBE (not exceeding 30% of the blasts) and alpha ANAE (not exceeding 41%) which was sodium fluoride resistant. In these five cases other monocytic markers (e.g. CD14) were not in favour of myelomonocytic differentiation. All the cases were anti-MPO positive at frequency > 10%. Phenotypic analysis also revealed myeloid features with all the patients having at least one myeloid antigen (CD13, CD33, CD15), Tdt was expressed in nine cases and CD7 in six cases. All cases but one were positive for CD34. Cytogenetic analysis, performed in 16 cases, showed no adequate growth in two cases and no consistent abnormality in four; among the remaining 10 cases no consistent abnormality was observed, the most common finding was trisomy 8 (two cases) and 4 (two cases) and aberrations of chromosomes 2, 3, 5, 7, 9, 12 and 21. No cases of (t9;22), Ph chromosome were observed. Interestingly three out of five patients with faint alpha NBE/alpha ANAE positivity relapsed as typical M4 (one case) or M5a (two cases).

Acute Disease↗
PubMedDate not supplied

Nerve growth factor: a neurotrophin with activity on cells of the immune system.

Numerous studies published in the last two decades provide evidence that nerve growth factor (NGF), a polypeptide originally discovered because of its neurotrophic activity, acts on a variety of cells of the immune system, including mast cells, eosinophils, and B and T lymphocytes. NGF has been shown to increase during inflammatory responses, autoimmune disorders, parasitic infections, and allergic diseases. Moreover, stress, which is characterized also by activation of a variety of immune cells, causes a significant increase in basal plasma NGF levels. Recently published studies reveal that hematopoietic progenitor cells seem to be able to produce and/or respond to NGF. We report these data and discuss the hypothesis of the possible implication of NGF on the functional activities of immune cells.

Animals↗
PubMedDate not supplied

Soluble factors levels in the initial staging of high-grade non-Hodgkin's lymphomas.

Plasma levels of several soluble factors were assayed in 31 untreated patients with high-grade non-Hodgkin's lymphomas (NHL). The results showed statistically significant higher average levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-2 receptor (IL-2r) and transferrin receptor (TF-r) in NHL patients compared to controls (p = 0.045, p = 0.047, p = 0.020, p = 0.026 and p = 0.033 respectively). IL-2, IL-2r and TF-r levels were found more elevated in Stages III/IV than in Stages I/II (p = 0.031, p = 0.016 and p = 0.048 respectively), whereas IL-6 concentrations were higher in patients presenting B symptoms (p = 0.011). Significant correlations were found between the erythrocyte sedimentation rate (ESR) and IL-6 (r = 0.681), and between beta 2 microglobulin (B2-m) and IL-2r (r = 0.622).

Adult↗
PubMedDate not supplied

Triple immunofluorescence evaluation of CD15, CD34 and class II expression by flow cytometry in normal and leukemic bone marrows.

BACKGROUND: The CD15/CD34 phenotype has been reported as aberrant and exploited for monitoring minimal residual disease in acute myeloid leukemia (AML) patients. Moreover, CD15/CD34 has been described as a rare phenotype in normal bone marrow (NBM) (< 0.10%). We used a triple immunofluorescence assay to investigate the expression of CD15, CD34 and class II antigens in normal (NMB) and leukemic (LBM) bone marrows. METHODS: A FACScan for quantitative fluorescence and the PAINT-A-GATE program for multiparametric analysis were utilized. Fifteen normal bone marrow and fifteen leukemic bone marrow samples were studied with a triple immunofluorescence assay. A FACSorter was used for sorting. RESULTS: Eleven out of 15 normal marrows contained less than 0.67% (range 0.01-0.66) cells which coexpressed CD15, CD34 and class II antigens. Three normal marrows contained more than 0.67% but less than 1.84% (range 1.05-1.83) triple stained cells. The entire group of leukemic marrows coexpressed triple stained cells with a frequency higher than 1% (range 1.1-48.6); furthermore, 10 samples contained the same population at frequencies higher than 10%. The difference between normal and leukemic marrows was statistically significant (p = < 0.001). Triple positive cells (TPc) from NBM were sorted for morphology, which proved to be consistent with myeloid progenitor features (early myeloblasts). This confirms that CD15+ CD34+ Class II+ precursors are commonly expressed in NMB, although at low frequency. Interestingly, 12 (80%) AMLs out of 15 were diagnosed as M1 (5) or M2 (7), while the remaining were M4 (2) and M5a (1). Additionally, all M2 cases were positive at percentages higher than 10%. Apparently CD15, CD34, class II expression correlates mainly with granulocyte differentiation. Two complete remission (CR) LBM, positive at onset for the triple combination, were regularly monitored. In one case the TPc percentage always remained near the normal values found in NBM (0.72%), and this patient is still in CR. In the other, overt relapse was preceded by a progressive increase in the TPc percentage. CONCLUSIONS: Although the presence in NBM of CD15+ CD34+ and class II+ precursors hinders minimal residual disease detection, we conclude that this unusual combination may distinguish a leukemic population and may allow monitoring of "early relapse".

Acute Disease↗