Forum (Genoa, Italy)最新文献

The requirements of gene therapy for cancer are distinct from those of gene therapy for hereditary monogenic diseases. In cancer the aim is to kill, not cure tumour cells. Also issues such as duration of gene expression and immunogenicity of vector systems are of less relevance than efficiency of delivery to all tumour cells. In this light, we discuss the vector systems currently available and the methods to target transgenes to tumour cells. In view of the current limitations in both vector systems and targeting of tumours, we discuss the strategies that may be applied to increase the effectiveness of inefficient delivery, such as immune activation, bystander cytotoxicity and replication-competent viruses.

Following the approval on May 1998 of the European Union Common position no. 19/98 regarding the legal protection of biotechnological inventions, the debate on bioethical aspects of biotechnologies is increased. The European Union document clearly protects the patentability of inventions (that concerns more than a particular plant or animal variety or a single procedure if they are of industrial interest), but not the finding or discovery of that is in the nature, e.g. a gene. Some safeguards (the dignity and integrity of the person and of the human embryo, the plant diversity, etc.) and exclusions from patentability (plant and animal varieties, processes for the production of plants or animals, the human body at any stage of growth, cloning of human beings, modifications of germ line, use of human embryos for industrial or commercial purposes as well as the inventions whose publication or exploitation would offend against public policy or morality, according to the Article 53a of the European Patenting Convention) are also indicated. Ethical issues discussed include the nature of human life and its protection, the safeguard of plant-animal biological diversity, the safeguard of human dignity and nature, whereas on several aspects (e. g. limits of the use of genetic material, xenotransplantation, etc.) the Parliament Assembly of the Council of Europe has requested a discussion or a moratorium (April, 1999). In this case an evaluation on the basis of the ethical beneficial principles should be performed and society should decide whether to master technologies and emulate the positive action of the hero Theseus against the Labyrinth-Minotaur syndrome or to renounce or "misuse" technologies like Daedalus and Icarus, who met a tragic end.

This paper examines ethical issues associated with two recent major developments in biotechnology: 1. The question of whether it is ethically acceptable to patent living organisms and genes and 2. Ethical issues related to the ability to predict or prognosticate disease susceptibility using increasingly refined genetic markers. In both instances, a pragmatic consequentialist approach is proposed which encourages biotechnology development while adhering to ethical standards. The paper concludes by encouraging public education about modern genetics in order to avoid inappropriate public fear and concern.

Anticancer drug discovery has changed fundamentally owing to recent progress in basic research. Historically, the discovery of potential new drugs for the treatment of cancer has largely relied on large-scale random screening. Although several useful agents have become available, sometimes after the development of chemical analogues of the original OhitO, this approach has generally been disappointing in terms of the efficacy/toxicity balance. To date, a range of cancer-specific molecular and biological drug targets are available providing opportunities for the design and discovery of specific anti-cancer agents with better tumour selectivity, and therefore less toxicity, than conventional agents. Among the many innovative approaches currently explored in pre-clinical and clinical research and development programs are inhibition of angiogenesis and metastasis, tumour vaccines/immunotherapy and gene therapy approaches. Several promising drug development projects are currently underway in these areas. The advent of innovative anticancer agents also has important consequences for the organisation of new drug development. Traditional drug development methodologies are often not appropriate for agents having completely new modes of action. The design of new drug development templates for such agents therefore has high priority in anti-cancer drug development organisations.

This meeting has suggested many conclusions and opens many problems for the application of the biotechnologies. Patents are a useful legal instrument developed to protect intellectual property rights, thus allowing Society to promote and support the innovation and development of useful inventions.

The last fifteen years have witnessed impressive changes in our approach to patients with different haematological malignancies. These have largely stemmed from the continuous development of biotechnologies and from their progressive implementation in the clinical setting. In this brief review, we will highlight some of the areas (diagnosis, follow-up and treatment) in which biotechnologies have had an objective impact and will also underline how a close biologico-clinical integration, unparalleled in all other fields of oncology, is today mandatory for an up-to-date management of haematological malignancies.

Accumulating experimental evidence demonstrates that tumour growth and lethality are dependent on angiogenesis. When angiogenesis is inhibited by administering molecules which specifically suppress the growth of vascular endothelial cells, tumours in animals can be limited to a dormant microscopic size where they are essentially harmless. The most recent evidence that vascular endothelial cells exert potent growth control over tumour cells comes from the following studies, i. administration of an angiogenesis inhibitor specific for proliferating vascular endothelium in the tumour bed; ii. optimisation of the dose and schedule of conventional cytotoxic chemotherapy for the vascular endothelium; iii. targeting of low dose cytotoxic chemotherapy only to the vascular endothelium in the tumour bed; or iv. sensitisation of vascular endothelium in the tumour bed to radiotherapy by co-administration of an angiogenesis inhibitor. In the future, anti-angiogenic therapy may be added to conventional chemotherapy, radiotherapy, immunotherapy or other novel modalities such as gene therapy. Also, angiogenesis inhibitors may be administered together for increased efficacy. The overall goal of anti-angiogenic therapy is to reduce toxicity, reduce the risk of drug resistance and to increase anti-cancer efficacy.

Systems analysis has been applied to hepatology with the aim of providing a reasonable organisation of domain knowledge and supporting the improvement of clinical performance. To this extent liver structures and functions have been classified and defined, clinical parameters have been carefully selected and suitably associated to describe individual liver functions, and methodological criteria for clinical evaluation have been assessed. Three major outcomes of such an approach, respectively concerning the development of a shareable clinical database, the application of a suitable methodology for clinical reasoning, and the computer-based support to medical decision-making, have been discussed.

Human thyroid tumours represent an example of the interplay of genetic and non genetic carcinogenesis. Recently, genetic abnormalities in the elements of the Thyrotropin receptor (TSH-R) dependent cAMP regulatory cascade have been found to be involved both in benign and malignant thyroid tumours. The presence of activating mutations has been demonstrated in the TSH-R gene as well as in the Gs alpha protein gene in thyroid toxic adenoma resulting in the constitutive activation of the cAMP pathway and it has been hypothesised that these genetic alterations may play a causative role in the disease. However, recent observations suggest more caution in accepting such a hypothesis. The presence of activating TSH-R mutations has also been demonstrated in differentiated thyroid carcinomas. At present, the percentage of such a modification is low, unless referred to selected series of tumours. Activating mutations of the TSH-R gene have been detected in a group of differentiated carcinomas with high basal adenylyl cyclase activity, and in a few cases of hyperfunctioning thyroid carcinoma. However, the role of the TSH-R-related cAMP pathway alterations in thyroid transformation remains to be elucidated. In this review, the role of TSH-R gene alterations in benign and malignant thyroid neoplasia is examined.