Disease relevance of NSC-3088

• BACKGROUND: To determine whether chlorambucil treatment benefits patients with indolent chronic lymphocytic leukemia (CLL), we conducted two randomized trials in 1535 patients with previously untreated stage A CLL [1].
• Although immediate complications were minimal, the potential for long-term toxicity still requires careful selection of patients who receive chlorambucil [2].
• Chlorambucil treatment of frequently relapsing nephrotic syndrome [3].
• A randomized trial of methylprednisolone and chlorambucil in idiopathic membranous nephropathy [4].
• Increased incidence of acute leukemia in polycythemia vera associated with chlorambucil therapy [5].

Psychiatry related information on NSC-3088

• The present study describes the effects of chlorambucil treatment at various gestational ages on neonatal renal function to determine if critical periods other than day 11 exist for inducing functional developmental toxicity of the kidneys [6].

High impact information on NSC-3088

• Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia [7].
• Although chlorambucil slowed disease progression, there was no effect on overall survival [1].
• Methylprednisolone plus chlorambucil as compared with methylprednisolone alone for the treatment of idiopathic membranous nephropathy. The Italian Idiopathic Membranous Nephropathy Treatment Study Group [8].
• Eighty-one patients with proteinuria (greater than or equal to 3.5 g per day) and biopsy-proved membranous nephropathy were randomly assigned to receive either supportive therapy alone or a six-month course of corticosteroids alternated with chlorambucil (0.2 mg per kilogram of body weight per day) every other month [4].
• Side effects were minimal in all treated patients except two, who were dropped from the study because of peptic ulcer and gastric intolerance to chlorambucil [9].

Chemical compound and disease context of NSC-3088

• The concept of attaching cytotoxic drugs, such as the alkylating agent chlorambucil (CBL), to "tumor-specific" antibodies for the treatment of cancer is attractive, inasmuch as the specificity of CBL could be increased and its systemic toxicity reduced [10].
• Prednisolone and chlorambucil treatment in idiopathic membranous nephropathy with deteriorating renal function [11].
• Ninety-eight patients with advanced ovarian cancer took part in a prospective, randomised trial comparing low-dose cisplatin and chlorambucil with low-dose cisplatin, chlorambucil, and doxorubicin [12].
• INTERVENTION: Five patients received cyclophosphamide (dose range, 1.25 to 2.2 mg/kg body weight) and one patient received chlorambucil (0.1 mg/kg) [13].
• Cladribine with prednisone versus chlorambucil with prednisone as first-line therapy in chronic lymphocytic leukemia: report of a prospective, randomized, multicenter trial [14].

Biological context of NSC-3088

• Chlorambucil-induced chromosome damage to human lymphocytes [15].
• The high frequency of deletions and translocations among the mutations induced in post-spermatogonial stages by chlorambucil, combined with its overall high efficiency in inducing mutations in these stages, should make chlorambucil mutagenesis useful for generating experimentally valuable germ-line deletions throughout the mouse genome [16].
• Thus far, all but one of the tested mutations induced by chlorambucil in post-stem-cell stages have been proved deletions or other structural changes by genetic, cytogenetic, and/or molecular criteria [17].
• Chlorambucil-induced mutations in mice recovered in homozygotes [18].
• Intact plasma depleted of albumin by chromatography on Cibacron blue-Sepharose or plasma from a subject with analbuminemia failed either to activate AKT or to protect CLL cells from chlorambucil-induced apoptosis [19].

Anatomical context of NSC-3088

• Eleven had benign lymphocytic angiitis and granulomatosis, in the past included in the above categories and characterized by nodular collections of mature lymphocytes and plasma cells, with predominantly pulmonary involvement and consistent responsiveness to chlorambucil [20].
• Genetic and molecular analysis of chlorambucil-induced germ-line mutations in the mouse [16].
• We have estimated that the proportion of gametes carrying a recessive visible mutation may be as high as 25% after a dose of 10 mg of chlorambucil per kg to early spermatids [18].
• Chemosensitivity of lymphocytes from patients with B-cell chronic lymphocytic leukemia to chlorambucil, fludarabine, and camptothecin analogs [21].
• Chlorambucil (CLB) contributes to the decrease in GSH in B-CLL lymphocytes; after incubation with the drug, lower levels of GSH were found than in the normal B or T lymphocytes, B-CLL T cells, or T-CLL (CD4 or CD8) cells [22].

Associations of NSC-3088 with other chemical compounds

• The median duration of remission and the median progression-free survival in the fludarabine group were 25 months and 20 months, respectively, whereas both values were 14 months in the chlorambucil group (P<0.001 for both comparisons) [7].
• Human carcinoma cells that maintained high levels of metallothionein because of chronic exposure to heavy metals were resistant to cis-diamminedichloroplatinum(II), melphalan, and chlorambucil [23].
• One case was uninterpretable because of concomitant administration of high doses of prednisone and chlorambucil and brief treatment with TF [24].
• Methotrexate and chlorambucil, each covalently linked to either abrus agglutinin, abrin, ricinus agglutinin, ricin, or concanavalin A, were prepared [25].
• Chlorambucil induced intracellular Ca+2 influx, pointing to the involvement of two signaling pathways that might explain its synergy with theophylline through their effects on oncogenes [26].

Gene context of NSC-3088

• However, when the BL-bcl-2 cells were treated with CMB together with ligation of CD40, apoptosis was reduced further to only 17% at 96 h [27].
• Cells overexpressing GSTM1 displayed a 3- to 4-fold increase in resistance to anticancer drugs vincristine (VCR) and chlorambucil (CHB) in proliferation, cytotoxic, and clonogenic survival assays [28].
• Increased mdr1/P-glycoprotein mRNA levels were also found in relapsed state acute myelogenous leukaemias (AML), and in chronic lymphocytic leukaemias (CLL) treated with chlorambucil and/or prednisone for several years [29].
• MRP2 was able to support GSTA1-1-mediated resistance to chlorambucil (CHB) cytotoxicity in HepG2 cells [30].
• The aim of this study was to evaluate the prognostic impact of CD38 expression by peripheral blood lymphocytes on progression-free survival after first-line therapy with high-dose chlorambucil in 53 previously untreated patients affected by typical CD5+ CD23+ B-CLL [31].

Analytical, diagnostic and therapeutic context of NSC-3088

• However, the risk of acute leukemia in patients given chlorambucil was 2.3 times that in patients given radioactive phosphorus and 13 times that in patients treated with phlebotomy alone [5].
• Group A (n = 53) was scheduled to have a second-look laparotomy, followed by cyclical oral chlorambucil [32].
• Association of acute leukaemia with chlorambucil after renal transplantation [33].
• Two patients with progressive hairy cell leukemia following splenectomy were treated with low-dose daily chlorambucil [34].
• A Burkitt lymphoma (BL) cell line transfected with either human bcl-2 (BL-bcl-2) or control plasmid (BL-Sv2) was used to examine the effects of Bcl-2 overexpression on the cellular response and long-term survival after treatment with the DNA-alkylating drug chlorambucil (CMB) in the presence or absence of CD40 ligation and IL-4 [27].

References