B. Grassi

Reversing of chlorambucil resistance by ethacrynic acid in a B-CLL patient

Summary We evaluated the reversing activity of ethacrynic acid in a B‐CLL patient resistant to chlorambucil. The glutathione S‐transferase (GST) activity, measured in peripheral blood lymphocytes, resulted extremely elevated. Etha crynic acid, at pharmacological concentrations, partially reversed chlorambucil resistance and this result appeared related to the increased GST levels.

Evaluation of resistance index of several anticancer agents on parental and resistant P-388 cell lines

Multidrug resistance is frequently detected in haematological malignancies and in acute leukaemias with a poor prognosis. In the last few years, several reports seem to suggest that the new anthracycline derivative idarubicin and the anthraquinone mitoxantrone have some advantages in the management of untreated or relapsed acute leukaemias compared with older anthracyclines. This could be due to a different interaction of these drugs with multidrug resistance. To evaluate this possibility, we compared the activity of doxorubicin (DOXO), epirubicin (EPI), idarubicin (IDA) and mitoxantrone (MITO) on a murine, multidrug resistant, leukaemic cell line (P-388/Dx) cultured in vitro. ID50 of IDA and MITO was in the ng range whereas that of DOXO and EPI was in the microgram(s) range. Moreover, IDA has a resistance index of 50 whereas DOXO has one of 250. Verapamil is able to almost completely abolish the resistance to IDA. Efflux experiments confirm that verapamil increases IDA intracellular concentration. IDA and MITO appear to be less involved in multidrug resistance than older anthracyclines.

Serum Cholesterol and Triglycerides in Hematological Malignancies

Serum levels of total cholesterol and triglycerides were studied in 202 patients affected by various hematological malignancies at the time of diagnosis. A hypocholesterolemia was found in 44% of patients affected by lymphoproliferative diseases and acute lymphoblastic leukemia, with an evident correlation with the clinical stage (5.7% of patients in nonadvanced stages, 67.8% in advanced stages). In acute and chronic myeloproliferative diseases, the overall incidence of hypocholesterolemia was 71%. In particular, a greater incidence of low cholesterol values was found in chronic myeloid leukemia and in idiopathic myelofibrosis than in polycythemia vera. No significant correlation was found in this group of diseases between the values of cholesterol and the main hematological parameters studied (WBC, number of circulating blasts, degree of splenomegaly, levels of hemoglobin, hematocrit). The incidence of significant alterations of triglycerides appeared negligible. It is thus possible to affirm that hypocholesterolemia constitutes an interesting biological aspect in hematological malignancies, and that total cholesterol could represent a parameter, even though secondary, in the follow-up of hematological neoplastic pathologies.

Severe Pancytopenia due to Copper Deficiency

A patient with copper deficiency and renal failure was suffering from pancytopenia. Marrow examination showed cytoplasmic and nuclear vacuolizations of the erythroid and myeloid series. These abnormal

Idarubicin is active on MDR cells : evaluation of DNA synthesis inhibition on P388 cell lines

SummaryMultidrug resistance is frequently found in patients affected by hematological malignancies and has been related to a poor prognosis of acute leukemia. In the present paper we report results concerning the activity of idarubicin, an anthracycline derivative, on the leukemic P388 and P388 doxorubicin-resistant cell lines. The results clearly show that idarubicin inhibits DNA synthesis in the resistant cell line more actively than doxorubicin.

1,25-Dihydroxycholecalciferol inhibits the cochemotactic activity of Gc (vitamin D binding protein).

The identification of Gc (vitamin D binding protein) with the anionic polypeptide cochemotaxin has recently been reported. In this paper we investigate its dose dependent cochemotactic activity and report the inhibition of Gc enhanced Chemotaxis by vitamin D3. These results further support the role of immunomodulating hormone played by vitamin D.

Third Generation Chemotherapy with P-VABEC for Aggressive Non-Hodgkin's Lymphomas of the Elderly

Between July 1990 and March 1992, 23 elderly patients with intermediate or high-grade non-Hodgkins lymphomas (NHL) received a combination chemotherapy (P-VABEC: Etoposide, Adriamycin and Cyclophosphamide on days 1, 15, 29, 43, Vincristine and Bleomycin on days 8, 22, 36, 50 and Prednisolone on weeks 1-9). The regimen was administered on an outpatient basis. The median age of the patients was 67 years (range 60-78); 15 were previously untreated, 8 were on second line therapy; 6 patients (44%) had stage IV disease, 19 (83%) B symptoms, 15 (65%) had bulky disease, and (26%) bone marrow involvement. The complete remission (CR) rate was 57%, and the partial remission (PR) rate 43%, with an overall response rate of (100%). No difference in response rate was observed between previously untreated patients and patients treated with P-VABEC as second-line therapy while hematological and clinical toxicity were very mild.

GST-7T and P-170 co-expression in multiple myeloma

Summary. Bone marrow samples from 40 patients affected by multiple myeloma either treated or untreated were examined for expression of glutathione‐S‐transferase n (GST‐TT), P‐glycoprotein and the protein product of ras oncogenes family, p‐21, on plasma cells, by immuno‐cytochemical detection. 72% of evaluated samples were positive for P‐170 and 82% for GST‐7T without any correlation with clinical or prognostic parameters. A significant relationship between GST‐7T expression and P‐l 70 positivity was found and co‐expression was observed in 91% of evaluated samples.

Effects of lithium carbonate on leukocyte functions in chronic benign neutropenia.

The effects of lithium carbonate on leukocyte functions in a case of chronic benign neutropenia are presented. Lithium was able to induce leukocytosis and to bring about increases in chemotaxis, marrow granulocyte reserve test and phagocytosis. After lithium interruption, leukocyte functions returned to initial values. Some hypotheses are advanced to account for lithium action.

Low-Frequency Electromagnetic Fields Do Not Affect Cell Growth, Erythroid Differentiation, and Virus Production in Variant Lines of Untreated and Dimethyl Sulfoxide-Treated Friend Erythroleukemia Cells

We compared the effects of exposing to low-frequency (50 Hz) sinusoidal electromagnetic fields (EMF) (magnetic field amplitude of 200 μT) four variant Friend erythroleukemia (FL) cell lines with regard to their capacity to proliferate, synthesize hemoglobin (Hb), and produce virus proteins, before and after treatment with dimethyl sulfoxide (DMSO). Our results confirm previous data indicating that: (1) clonal FL cells are variable in their growth, differentiation, and viral properties; (2) erythroid differentiation and virus production are under separate control; (3) cell replication is apparently necessary for virus production. When FL cells were exposed to EMF, no significant difference was observed in cell counts, induction of Hb synthesis, or virus production and release, comparing untreated and EMF-treated cell cultures.