New single-chain (type 1) ribosome-inactivating proteins (RIPs) were isolated from the seeds of Basella rubra L. (two proteins) and from the leaves of Bougainvillea spectabilis Willd. (one protein). These RIPs inhibit protein synthesis both in a cell-free system, with an IC50 (concentration causing 50% inhibition) in the 10(-10) M range, and by various cell lines, with IC50S in the 10(-8)-10(-6) M range. All three RIPs released adenine not only from rat liver ribosomes but also from Escherichia coli rRNA, polyadenylic acid, herring sperm DNA, and artichoke mottled crinkle virus (AMCV) genomic RNA, thus being polynucleotide:adenosine glycosidases. The proteins from Basella rubra had toxicity to mice similar to that of most type 1 RIPs (Barbieri et al., 1993, Biochim Biophys Acta 1154: 237-282) with an LD50 (concentration that is 50% lethal) < or = 8 mg.kg-1 body weight, whilst the RIP from Bougainvillea spectabilis had an LD50 > 32 mg.kg-1. The N-terminal sequence of the two RIPs from Basella rubra had 80-93% identity, whereas it differed from the sequence of the RIP from Bougainvillea spectabilis. When tested with antibodies against various RIPs, the RIPs from Basella gave some cross-reactivity with sera against dianthin 32, and weak cross-reactivity with momordin I and momorcochin-S, whilst the RIP from Bougainvillea did not cross-react with any antiserum tested. An RIP from Basella rubra and one from Bougainvillea spectabilis were tested for antiviral activity, and both inhibited infection of Nicotiana benthamiana by AMCV.

Our study is the first demonstration in human tissue of increased secretion of PGI2 both in vitro and in vivo, after torasemide or furosemide administration. This phenomenon, which may explain in part the vasodilatory effects of these drugs, was more evident with torasemide and was reached at lower concentrations of the drug. Accordingly, we also found that furosemide but not torasemide stimulated the release of the PGI2 physiological antagonist thromboxane in CHF patients and healthy controls.

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Summary The present paper describes two immunoconjugates consisting of an anti-epidermal growth factor receptor (EGFR) monoclonal antibody (MAb), named Mint5, covalently linked to the type 1 ribosome-inactivating proteins (RlPs) ocymoidine (Ocy) and pyramidatine (Pyra) from Saponaria ocymoides and Vaccaria pyramidata respectively. Both antibody and toxins are shown to retain their respective biological properties upon chemical conjugation. The immunoconjugates exert specific inhibition of EGFR expressing target cell proliferation and protein synthesis in in vitro assays and also inhibit the growth of grafted human tumour cells in nude mice.Keywords: immunoconjugate; anti-epidermal growth factor receptor; ocymoidine; pyramidatineThe clinical use of immunotoxins for the treatment of cancer is currently under evaluation worldwide. The therapeutic potentiality of immunotoxins and preclinical and clinical results over the last 20 years have been reviewed recently (Thrush et al, 1996), indicating that, although immunotoxins seem promising for systemic therapy of haematological malignancies, a number of different problems still need to be solved, especially for the treatment of solid tumours. In particular, the refining of dose regimen and administration route, the combination with chemotherapy and the reduction of immunogenicity are the major goals of future research. In this paper, we describe the preparation of two new immunoconjugates made of an anti-epidermal growth factor receptor monoclonal antibody, named MintS, chemically linked to either ocymoidine or pyramidatine, toxins from Saponaria ocymoides and Vaccaria pyramidata respectively.The epidermal growth factor (EGF) and its receptor play a critical role in the growth and regulation of many normal and malignant cell types. EGFR overexpression is a common feature in most carcinomas and correlates with poor prognosis (Fox et al, 1994).The potential value of EGFR as a target for the diagnosis and therapy of human tumours has been recognized for several years, and the use of anti-EGFR monoclonal antibodies may provide therapeutic tools in the treatment of tumours overexpressing the receptor (Ennis et al, 1991).Moreover, immunoconjugates of EGFR-specific monoclonal antibodies to either gelonin (Ozawa et al, 1989) or ricin A chain (Masui et al, 1989) were shown to reduce the growth of human tumour cells transplanted into athymic mice.

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