Disease relevance of Novantron

• Combination of a long-acting delivery system for luteinizing hormone-releasing hormone agonist with Novantrone chemotherapy: increased efficacy in the rat prostate cancer model [1].
• Eight of the 14 patients had relapsed or had refractory non-Hodgkin's lymphoma (NHL) and received rhGM-CSF after intensive chemotherapy with novantrone (NO) and high-dose Ara-C (AC) (NOAC) as salvage regimen [2].
• PURPOSE: To determine if inhibition of stem-cell activity induced by granulocyte-macrophage colony-stimulating factor ([GM-CSF]; Sargramostim; Immunex Corporation, Seattle, WA) withdrawal or priming protects hematopoietic stem cells from the cytotoxic effects of adjuvant chemotherapy for early-stage breast cancer [3].
• PURPOSE: To determine the toxicity, maximum-tolerated dose (MTD), and pharmacokinetics of recombinant human CD40 ligand (rhuCD40L) (Avrend; Immunex Corp, Seattle, WA), suggested in preclinical studies to mediate cytotoxicity against CD40-expressing tumors and immune stimulation [4].
• In this phase II multicenter trial, the efficacy and safety of mitoxantrone (Novantrone; Lederle Laboratories, Wayne, NJ) were evaluated in the treatment of 206 patients with relapsed non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) previously treated with other agents [5].

High impact information on Novantron

• Lymphokine racketeers? Cistron alleges foul play over IL-1, but Immunex sees it differently [6].
• Testes and ventral prostate weights were significantly diminished by the administration of microcapsules of [D-Trp6]LH-RH alone or in combination with Novantrone [1].
• PURPOSE: To determine the biologic effect of granulocyte-macrophage colony-stimulating factor (sangramostim, GM-CSF; Immunex Corporation, Seattle, WA) as measured by prostate-specific antigen (PSA) kinetics in patients with serologic progression of prostate cancer after definitive local therapy [7].
• The release of L1 occurs in mouse and human cells and is blocked by the metalloproteinase inhibitor TAPI (Immunex compound 3) [8].
• The protease inhibitors, TNFalpha protease inhibitor 1 and Immunex compound 2, could inhibit the production of leptin binding protein, indicating that the enzyme responsible for leptin binding protein cleavage belongs to the metalloprotease family [9].

Chemical compound and disease context of Novantron

• MN (N = Novantrone) COP-B therapy on high and intermediate grade non-Hodgkin's lymphoma: an alternative to MA (A = adriamycin) COP-B [10]?
• From February, 1987 to August, 1988, fifty-one patients with high and intermediate grade non-Hodgkin's lymphoma (NHL) entered a chemotherapy program MNCOP-B (M = Methotrexate, N = Novantrone, C = Cytoxan, O = Oncovin, P = 6 methyl-prednisolone, B = Bleomycin) [10].
• Prednisone, oral etoposide, and novantrone for treatment of non-Hodgkin's lymphoma: a preliminary report [11].
• Fludarabine, ara-C, novantrone and dexamethasone (FAND) in previously treated chronic lymphocytic leukemia patients [12].
• As valid therapeutic alternatives to adriamycin, with a more favourable safety profile, epirubicin (E) and novantrone (N) were compared in combination with fluorouracil (F) and cyclophosphamide (C) in a prospective randomized clinical trial as first-line treatment for metastatic breast cancer (mbc) [13].

Biological context of Novantron

• Half of the studied AML cases were completely resistant to Novantrone-induced apoptosis with no correlation between sensitivity to Novantrone and bcl-2 expression [14].
• Novantrone alone, at a concentration of 20-30 ng/ml, given to cultures for 1 h, inhibits cell growth by about 50% and causes cells to accumulate in S and G2 phase and to enter a higher DNA ploidy level [15].
• Effects on blood coagulation of adjuvant CNF (cyclophosphamide, novantrone, 5-fluorouracil) chemotherapy in stage II breast cancer patients [16].
• Knock-in and knock-out. Transgenes, Development and Disease: A Keystone Symposium sponsored by Genentech and Immunex, Tamarron, CO, USA, January 12-18, 1991 [17].
• Four years later, researchers at the biotechnology company Immunex (now part of Amgen) reported the cloning and characterization of the human TWEAK receptor [18].

Anatomical context of Novantron

• In male germ cells, the clinical preparation Novantrone, the dihydrochloride salt of mitoxantrone, did not induce sex-linked recessive lethal mutations in feeding and injection experiments with adult flies, although statistically the results were inconclusive rather than truly negative [19].
• However, in the present study we observe that 5 mM caffeine reverses the cell kinetic and cytotoxic effects of the intercalating drug Novantrone (mitoxantrone) on L1210, HL-60 and CHO cells [15].
• The patient was treated with two courses of fludarabine 30 mg/m2 (days 1-5) + Ara-C 2 g/m2 (days 1-5) + novantrone 5 mg/m2 (days 1-3) and G-CSF from day 0 to neutrophil recovery [20].
• Modified glutathione S-transferase (GST) activity was detected in MCF-7 cell lines selected in vitro for modest levels of resistance (2.6- to 13.7-fold) not only to Adriamycin but also to Novantrone, vincristine (VCR), and etoposide (VP-16) [21].
• The B cell grows up. B-lymphocyte Development: a UCLA Symposium sponsored by Immunex and Ortho, Park City, UT, USA, March 31-April 6, 1990 [22].

Associations of Novantron with other chemical compounds

• Twenty patients, age 68 to 86 years, each received 250 microg/m2 of GM-CSF (Sargramostatin; Immunex, Seattle, WA, USA) subcutaneously (s.c.) or intravenously (i.v.) for 3 days followed by GM-CSF at the same dose and cytarabine 100 mg/m2 i.v. for 3 days [23].
• Notably, PMA and NEM also promoted shedding of GHBP into the conditioned medium of the cells, as determined by a chromatographic [125I]human GH binding assay; this GHBP shedding was also inhibited by Immunex Compound 3 [24].
• Four successive protocols evolved, each with three phases induction chemotherapy (adriamycin or novantrone, cyclophosphamide) (three cycles), radiotherapy then chemotherapy (cyclophosphamide, methotrexate, 5-fluorouracil) of progressively shorter duration [25].
• A mouse monoclonal antibody (NO-1) with specificity for the anti-cancer drug mitozantrone (MZ) (Novantrone) was produced by immunization of a BALB/c mouse with mitozantrone-keyhole limpet haemocyanin (MZ-KLH) conjugate [26].
• Clinical analysis for the anti-neoplastic agent 1,4-dihydroxy-5,8-bis((2-[(2-hydroxyethyl)amino]ethyl)-amino)9,10-anthracenedio ne dihydrochloride (NSC 301739) in plasma. Application of temperature control to provide selectivity in paired-ion high-performance liquid chromatography [27].

Gene context of Novantron

• The effect of etanercept, a soluble p75 tumor necrosis factor (TNF) receptor:Fc fusion protein (Enbrel; Immunex, Seattle, WA) on plasma cytokines was evaluated in 11 HIV-infected subjects receiving highly active antiretroviral therapy (HAART) for 28 weeks with or without subcutaneous or intravenous recombinant human interleukin 2 (rhIL-2) [28].
• Etanercept (Enbrel, Immunex Corporation, Seattle, Washington, USA) is a new biological disease-modifying antirheumatic drug (DMARD) for the treatment of active rheumatoid arthritis (RA) [29].
• Pretreatment of rats with the immunex monomeric soluble P75 receptor binding protein for TNF-alpha (TNFsr, 0.5 mg/kg, iv) 15 min prior to LPS administration decreased circulating TNF-alpha from 92,137 +/- 12,456 U/ml to undetectable levels as determined by the L929 bioassay [30].
• The most advanced in terms of clinical development is etanercept (Enbrel, Immunex), a fusion protein between soluble TNF receptor Type II and the Fc region of human IgG1 [31].
• To better define the importance of the GS in predicting treatment results in a group of patients treated with uniform therapy, we performed GS prior to treatment in 46 patients with pathologically or clinically staged I-III Hodgkin's disease who received three cycles of NOVP (Novantrone, vincristine, vinblastine, prednisone) followed by XRT [32].

Analytical, diagnostic and therapeutic context of Novantron

• Tumor weights were much less in the groups treated with either microcapsules (3.28 +/- 0.69 g) or Novantrone (19.53 +/- 3.3 g) alone [1].
• When the therapy was started 45 days after transplantation and continued for 70 days, tumor volume in the presence of the microcapsules (966 +/- 219 mm3) or Novantrone (3606 +/- 785 mm3) given alone was significantly decreased compared to controls (14,476 +/- 3045 mm3) [1].
• Mitoxantrone (Novantrone) as single agent and in combination chemotherapy in the treatment of advanced breast cancer [33].
• The simultaneous isolation and determination of mitoxantrone (Novantrone) and its two known metabolites (the mono- and dicarboxylic metabolites) were carried out using a high-performance liquid chromatographic (HPLC) system equipped with an automatic pre-column-switching system that permits drug analysis by direct injection of biological samples [34].
• METHODS: MEDLINE (1966-present) and the Cochrane Central Register of Controlled Trials (1994-present) were searched for relevant randomized, blinded, controlled clinical trials using the terms mitoxantrone, Novantrone, and multiple sclerosis [35].

References