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Biomedical subjects

S Sica

Publications and source records attributed to S Sica.

At least 109 records · Page 6Linked to original sources
PubMed1995

Quercetin inhibits the growth of leukemic progenitors and induces the expression of transforming growth factor-beta 1 in these cells.

We previously showed that quercetin (3,3',4',5,7 pentahydroxyflavone) inhibits in a dose-dependent manner the growth of acute leukemias and is able to enhance the antiproliferative activity of cytosine arabinoside. We show here that quercetin inhibits the clonogenic activity of 20 of 22 acute leukemias (AL; 4 M1-AML, 3 M2-AML, 2 M3-AML, 3 M4-AML, 3 M5-AML, and 7 ALL). In the present report, we show that the induction of transforming growth factor-beta 1 (TGF-beta 1) in leukemic blasts is one of the growth-inhibitory mechanisms of quercetin in these cells. This observation was supported by the following data. (1) Quercetin-sensitive leukemic blasts, when treated with quercetin, secrete large amounts of TGF-beta 1 in the medium and show positivity for TGF-beta 1-immunoreactive material in the cytoplasm. (2) At a concentration of 8 mumol/L, antisense TGF-beta 1 oligonucleotides prevent the growth-inhibitory action of quercetin. (3) Anti-TGF-beta 1 neutralizing monoclonal antibodies can prevent almost completely the growth-inhibitory activity of quercetin. The analysis of quercetin-resistant cases confirmed as well the central role of TGF-beta 1 in the growth-inhibitory activity of quercetin. In conclusion, quercetin can act as a cytostatic agent for leukemic cells by modulating the production of TGF-beta 1.

Bone Marrow↗
PubMed1995

Microangiopathic hemolytic anemia and severe thrombocytopenia in Brucella infection.

A case of Brucella septicemia presenting at the onset as a severe microangiopathic hemolytic anemia with coexisting dramatic hemorrhagic syndrome (severe epistaxis, gross hematuria, and skin purpura) is reported. A hemogram showed severe thrombocytopenia, anemia, and leukopenia. Bone marrow morphology showed the typical features associated with Brucella infection: numerous histiocytes with signs of activation, multiple granulomata, giant cells, and hemophagocytosis. After appropriate antimicrobial therapy, the clinical and hematological status of the patient improved, and he is alive and well 1 year later with disappearance of all hematological abnormalities.

Adult↗
PubMed1995

Chemotherapy and recombinant human granulocyte colony-stimulating factor primed donor leukocyte infusion for treatment of relapse after allogeneic bone marrow transplantation.

Two patients affected by acute leukemia relapsed 10 and 12 months respectively after allogeneic bone marrow transplantation. They were treated with aggressive chemotherapy and then infused with HLA-identical donor leukocytes (DLI) collected after recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration. A total of 5.6 and 6.3 x 10(6)/kg CD34+ cells, 2.7 and 3.0 x 10(4)/kg CFU-GM, 4.7 and 4.4 x 10(8)/kg MNC, 4.6 and 3.9 x 10(9)/kg PMN respectively were infused. Both patients achieved complete remission (CR) and complete chimerism was re-established. One patient developed grade IV acute graft-versus-host disease of the liver requiring immunosuppression and he died in CR from disseminated aspergillosis, 7 months after chemotherapy; one patient is alive in relapse 12 months after treatment.

Acute Disease↗
PubMed1994

Autologous stem cell transplantation: release of early and late acting growth factors relates with hematopoietic ablation and recovery.

We have monitored the serum concentrations of hematopoietic growth factors (HGFs; ie, stem cell factor [SCF], leukemia inhibitory factor [LIF], interleukin-3 [IL-3], IL-6, IL-8, and granulocyte colony-stimulating factor [G-CSF]) in 15 lymphoma/leukemia and 6 ovarian cancer patients undergoing autologous bone marrow (BM) or peripheral blood (PB) stem cell transplantation (SCT). Thus, the analysis was performed during and after high-dose chemotherapy (from day -6 to day -1), at the time of SCT (day 0), and thereafter (through day +17). Despite the heterogeneity of these patients and their conditioning regimens, a consistent kinetic pattern was observed for all analyzed cytokines. Particularly, (1) SCF serum concentration did not significantly fluctuate. (2) High levels of LIF (approximately 250 to 450 pg/mL) before chemotherapy rapidly declined to markedly lower concentrations (approximately 10 ng/mL) starting from day -1 through day +17; (3) conversely, IL-3 level was low before treatment, sharply increased during chemotherapy, and rapidly returned to base-line level after SCT. Hypothetically, the sharp LIF decrease and IL-3 increase during chemotherapy may underlie the induction of stem cell cycling and differentiation caused by hematopoietic ablation. Furthermore, (4) IL-6 concentration was low before and immediately after chemotherapy, but increased starting from day +5, peaked at day +6 through 9 and then declined to baseline level from day +10 onward; (5) a strictly similar pattern was consistently observed for both G-CSF and IL-8 levels, in agreement with our previous studies. It is relevant that peak IL-6, G-CSF, and IL-8 concentrations were directly correlated to peak neutrophil numbers in the recovery phase, thus suggesting an important role for these cytokines in granulocyte rescue; in line with this interpretation, hematologic patients undergoing PBSCT (10 of 15) exhibited higher peaks of IL-6, G-CSF, and IL-8 and a more pronounced increase of neutrophil/platelet number than did hematologic cases undergoing BMSCT (5 of 15). Altogether, these studies indicate a coordinate pattern of cytokine release during hematopoietic ablation/recovery after chemotherapy and autologous SCT, the fluctuations of LIF and IL-3 levels during chemotherapy are seemingly related to stem cell recruitment, whereas the post-SCT increase of IL-6, G-CSF, and IL-8 may underlie the neutrophil recovery.

Adolescent↗
PubMed1994

Sequential peripheral blood progenitor cell transplantation after mobilization with salvage chemotherapy and G-CSF in patients with resistant lymphoma.

We enrolled 18 patients affected by refractory or relapsed lymphoma (HD, NHL) in a two-step protocol that included salvage chemotherapy with mitoxantrone, carboplatinum, methylprednisolone, and cytosine arabinoside (MiCMA) plus G-CSF (5 micrograms/kg/day), peripheral blood progenitor cell (PBPC) collection, and subsequent transplantation after BUCY2 regimen. After MiCMA chemotherapy, four patients (22%) achieved complete response, eight patients (44%) obtained a partial response, and six showed progression of disease (PD). Fourteen out of 18 patients (78%) were considered eligible for PBPC transplantation. Three patients with complete response refused PBPCT; they are currently in continuous complete remission (CCR) at 15, 13, and 15 months, respectively. One patient has been recently transplanted but is too early to be evaluated. Ten patients so far completed the study, eight of whom are currently alive in CR, with a median follow-up of 7.5 months (range 2-13). Hematologic reconstitution was very rapid with a median time to achieve WBC > 1 x 10(9)/L, PMN > 0.5 x 10(9)/L, platelets > 50 x 10(9)/L and > 100 x 10(9)/L of 13 (range 9-15), 12 (range 9-14), 10 (range 0-22), and 14 (range 5-49) days, respectively. Our protocol is highly effective as a salvage treatment, while permitting PBPC collection after G-CSF administration. Hemopoietic reconstitution after transplantation of PBPCs collected with this procedure is complete, rapid, and sustained.

Adolescent↗
PubMed1994

Acute parotitis during induction therapy including L-asparaginase in acute lymphoblastic leukemia.

In a patient affected by acute lymphoblastic leukemia (ALL) and subjected to therapy with Erwinia L-asparaginase, acute parotitis was observed. Microbiological studies excluded any infectious etiology. Regression of parotitis was spontaneous. This complication has not been previously reported and could be due to the same mechanism of pancreatic injury. The occurrence of acute parotitis needs to be promptly recognized in order to avoid the continuation of L-asparaginase.

Acute Disease↗
PubMed1994

Aggressive chemotherapy for acute leukemia relapsed after transplantation.

Bone marrow transplantation procedure has emerged as an effective treatment for hematological malignancies. However, recurrence of leukemia is still the major cause of treatment failure. Subsequent treatment in this category of patients, generally considered incurable, has not been yet standardized. At our institution, 13 patients, 7 with acute non lymphoid leukemia (ANLL) and 6 with acute lymphoid leukemia (ALL), were treated at relapse after bone marrow transplantation either autologous or allogeneic (AuBMT 8, ABMT 4) performed in complete remission (CR). The interval between BMT and relapse was less than 9 months in 6 patients (2 ABMT and 4 AuBMT) and more than 9 months in 7 patients. Early relapsed patients showed no response to treatment and died at a median of 5.5 months (range 1-13) after relapse. Late relapse after BMT was characterized by a high percentage of response (5 CR and 1 PR), particularly after intensive chemotherapy and by a longer survival (median 14 months; range 2-36). Chemotherapy after transplantation should be carefully evaluated in patients relapsed after BMT in order to select a population that can achieve long term disease free survival.

Adolescent↗
PubMed1994

Characterization of peripheral blood CD34+ progenitor cells mobilized with chemotherapy and granulocyte colony-stimulating factor.

Peripheral blood (PB) mononuclear cells mobilized with chemotherapy and granulocyte colony-stimulating factor (G-CSF) were enriched in CD34+ cells; aliquots were seeded in long-term cultures (LTC) on bone marrow (BM)-derived stromal layers and in liquid cultures containing various growth factors. The final recovery of PB CD34+ cells was similar to normal BM controls, and no difference was found in the expression of CD33 and CD13 antigens; a lower number of CD34+/HLA-DR- cells was found in PB with respect to BM samples (p < 0.001). PB cells sustained hematopoiesis in LTC at least as long as BM cells. At week 3 and 4, PB total mononuclear cell (MC) and CD34(+)-selected cell cultures showed a higher nonadherent cell recovery compared to the respective BM controls (p = 0.05 and p < 0.01). The liquid culture of PB CD34+ cells in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and stem cell factor (SCF) resulted in a marked and long-lasting increase of colony-forming units-granulocyte/macrophage (CFU-GM). Taken together, our data suggest that chemotherapy and G-CSF-primed cells contain a considerable number of both committed and early precursors, accounting for the rapid hematopoietic recovery observed after their reinfusion following myeloablative chemotherapy.

Antigens, CD↗
PubMed1993

Trisomy 4 in acute myeloblastic and acute lymphoblastic leukemia.

We report three cases of trisomy 4 in acute leukemia. This alteration was detected as the sole cytogenetic abnormality in a case of FAB M4 leukemia; it occurred in association with 5q deletion in a case of M1, and concomitant with Ph chromosome and trisomy 17 in a case of L2 leukemia. The latter case represents the fourth report of trisomy 4 in acute lymphoblastic leukemia.

Adult↗
PubMed1993

Five-year experience in PBSC collection: results of the Catholic University of Rome.

Several authors have reported a faster immunological and hemopoietic post-transplant reconstitution using autologous peripheral blood stem cell (PBSC) than using autologous bone marrow stem cells. A large number of PBSC can be collected by leukapheresis during the hematological recovery after induction or salvage chemotherapy. In our experience we demonstrated that several separators, even if they have different results in mononuclear cell (MNC) yields, red blood cell and platelet contaminations, are able to collect PBSC for autotransplantation in patients with several malignant diseases and different status of disease. Eighty three patients were submitted to 590 leukapheresis procedures using 4 different blood cell separators: the results showed that all employed protocols are efficient in the collection of peripheral MNC even if after the widespread use of granulocytecolony stimulating factor (G-CSF) in the harvesting phase, the blood cell separator efficiency in terms of MNC is reduced. The use of GCSF in combination with other growth factors, during chemotherapy mobilization could simplify, in the future, this therapeutical program even if improvements in the efficiency of PBSC collection protocols are required.

Adolescent↗
PubMed1993

Recovery from diabetes insipidus associated with AML after a BMT conditioning regimen including busulfan.

We describe a patient who, at the onset of acute myelomonocytic leukemia, presented with marked polyuria, polydipsia and laboratory findings consistent with diabetes insipidus (DI). He was treated with vasopressin (DDAVP) with a good response and concurrently induced with daunorubicin and conventional doses of cytosine arabinoside. CR was achieved. The vasopressin requirement decreased progressively, but the patient remained DDAVP-dependent after consolidation treatment. He underwent allogeneic BMT, conditioned with busulfan and cyclophosphamide. By day 15 after BMT vasopressin was no longer required and at a follow-up of 9 months the patient has no evidence of DI. In the absence of specific findings, we think it possible that he had leukemic microinfiltration of the hypothalamic-pituitary area. The drugs used for conditioning may have eradicated CNS disease.

Adult↗
PubMed1992

Aggressive chemotherapy for acute leukemia relapsed after bone marrow transplantation: a second chance?

Eight patients, 5 with acute non lymphoid leukemia and 3 with lymphoid leukemia, were treated at relapse after bone marrow transplantation (BMT; 4 autologous BMT and 4 allogeneic BMT). Of these, 2 relapsed within 3 months after BMT (2 allogeneic BMT) and 6 (2 allogeneic and 4 autologous BMT) after more than 9 months after BMT. The 2 patients relapsing early showed no response to treatment and died. Five out of 6 patients relapsing late achieved complete remission (4 of them with intensive chemotherapy). Four patients are currently alive. Aggressive combination chemotherapy can produce long-term survival in selected patients relapsed after BMT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Apparent isolated skin relapse in acute monocytic leukemia. A case report.

A case of acute monocytic leukemia with an apparent isolated skin relapse is reported. The cutaneous involvement was associated with a morphological bone marrow remission but a cytogenetic relapse was present. Regression of the skin lesions was obtained with a protocol including daunoblastine, aracytin and thioguanine, but the patient relapsed and died a few months later without achieving another remission. The relation between cutaneous and medullary disease is discussed.

Adult↗