In vivo inhibition of angiogenesis by sulphamoylated derivatives of 2-methoxyoestradiol

Drugs that inhibit growth of tumours and their blood supply could have considerable therapeutic potential. 2-Methoxyoestradiol-3,17-O,O-bis-sulphamate (2-MeOE2bisMATE) has been shown to inhibit the proliferation of MCF-7 (ER+) breast cancer cells and angiogenesis in vitro. 2-MeOE2bisMATE and its analogue, 17-Cym-2-MeOE2MATE, were investigated for their ability to inhibit in vivo angiogenesis and tumour growth. The mouse Matrigel plug assay for angiogenesis was used to investigate the effect of compounds on neovascularisation and was quantified using a FITC-dextran injection technique. Nude mice bearing tumours derived from MCF-7 cells were used to assess efficacy on tumour growth. Tumour sections were stained for VEGFR-2 and Ki67 to assess tumour angiogenesis and cell proliferation respectively. Matrigel plugs supplemented with basic fibroblast growth factor resulted in increased neovascularisation over 7 days. Oral administration of 2-MeOE2bisMATE for 7 days at 10 or 50 mg kg(−1) significantly reduced neovascularisation to or below control levels respectively. 17-Cym-2-MeOE2MATE at 20 mg kg(−1) was equally effective. 2-MeOE2bisMATE, dosed daily for 21 days, caused a 52% reduction in tumour growth at 5 mg kg(−1) and 38% regression at 20 mg kg(−1). 17-Cym-2-MeOE2MATE (20 mg kg(−1)) reduced tumour growth by 92%. Immunohistochemistry revealed a reduction in angiogenesis and proliferation. Matrigel plug and tumour imaging after FITC-dextran injection indicated that 2-MeOE2bisMATE caused a marked disruption of vasculature. These sulphamoylated oestrogen derivatives have been shown to be potent inhibitors of angiogenesis in vivo. This, together with their ability to inhibit tumour growth, indicates the potential of this new class of drugs for further development for cancer therapy

Prostigmata (Acari: Trombidiformes) as Biological Control Agents

Prostigmata is the larger of the two suborders of the order Trombidiformes within the superorder Acariformes. This suborder constitutes a large assemblage of morphologically, biologically and ecologically diverse groups consisting of 36 superfamilies, some of which consist largely of predatory or parasitic species. In relation to the groups treated in this chapter, most studies concerning the potential as natural enemies of pest organisms refer to the Bdelloidea, Pyemotoidea and Tarsonemoidea. However, these studies are usually limited, conducted by a reduced number of specialists, usually from restricted geographic areas. They involve mainly laboratory trials, with rare consistent attempts toward the expansion of the work to conditions more similar to the habitats in which those natural enemies are expected to be used. Considering the behavior and biological characteristics of the different groups discussed in this chapter, several species have shown good potential for practical use. It seems that the main obstacle to the expansion of the efforts dedicated to the discovery of promising prostigmatid natural enemies is the lack of trained personnel to conduct the research work. New stimulus to the study of biodiversity in some countries might lead to the conduction of solid and comprehensive projects to determine species with good qualities in biological control.Departamento de Zoologia, Universidade Estadual Paulista (UNESP)Universidade Estadual de Roraima (UERR)Departamento de Entomologia e Acarologia, Escola Superior de Agricultura “Luiz de Queiroz” (ESALQ), Universidade de São Paulo (USP)Departamento de Zoologia, Universidade Estadual Paulista (UNESP