VAT? A Look Inside Canada\u27s Experience with the Goods and Services Tax

Consumption taxes have been and continue to be utilized as a staple revenue producer within systems of taxation. The value-added tax (VAT) is one form of consumption tax that has grown in popularity among nations over the last several decades. In fact, after the passage of a goods and services tax (one type of VAT) in Australia in 2000, the United States now stands alone as the only remaining OECD nation, among its 30 members, without some form of a value-added tax on consumption. As the massive topic of tax reform continually appears at the forefront of the political landscape, having potentially far-reaching effects of a political, social and economic nature, this comment seeks to provide insight into one country\u27s recent experience with a value-added tax. Section II of this paper includes a brief history of the value-added tax, an explanation of the basic structure of a VAT and its foundational principles, distinguished from alternative forms of taxation and concludes with a list of generally accepted economic effects resulting from the institution of a value-added tax. Section III delves into Canada\u27s value-added tax, the Goods and Services Tax (GST), exploring the origins of GST, public opinion surrounding GST and its subsequent passage, purposes for its adoption, implementation, administration and enforcement, and a detailed look into the structure of the tax itself. Section IV investigates whether the economic effects from the Canadian GST have emulated those understood by the tax community to result from instituting a VAT and what Canada has done to address the effects brought about by the GST. Section V provides an overall conclusion about Canada\u27s experience with the GST, what lessons, both good and bad, can be extrapolated and whether the Canadian experience encourages or cautions nations exploring the possibility of instituting a VAT

Secreted and tumour targeted human carboxylesterase for activation of irinotecan

Irinotecan (CPT-11) is an anticancer agent for the treatment of colon cancer. CPT-11 can be considered as a prodrug, since it needs to be activated into the toxic drug SN-38 by the enzyme carboxylesterase. An approach to achieve tumour specific activation of CPT-11 is to transduce the cDNA encoding carboxylesterase into tumour cells. A secreted form of carboxylesterase may diffuse through a tumour mass and may activate CPT-11 extracellularly. This could enhance the antitumour efficacy by exerting a bystander effect on untransduced cells. In addition a secreted tumour-targeted form of carboxylesterase should prevent leakage of the enzyme from the site of the tumour into the circulation. We have constructed a secreted form of human liver carboxylesterase-2 by deletion of the cellular retention signal and by cloning the cDNA downstream of an Ig kappa leader sequence. The protein was secreted by transfected cells and showed both enzyme activity and efficient CPT-11 activation. To obtain a secreted, tumour-targeted form of carboxylesterase-2 the cDNA encoding the human scFv antibody C28 directed against the epithelial cell adhesion molecule EpCAM, was inserted between the leader sequence and carboxylesterase-2. This fusion protein showed CPT-11 activation and specific binding to EpCAM expressing cells. Importantly, in combination with CPT-11 both recombinant carboxylesterase proteins exerted strong antiproliferative effects on human colon cancer cells. They are, therefore, promising new tools for gene directed enzyme prodrug therapy approaches for the treatment of colon carcinoma with CPT-11