Biotechnology annual review最新文献

Peroxidases have conquered a prominent position in biotechnology and associated research areas (enzymology, biochemistry, medicine, genetics, physiology, histo- and cytochemistry). They are one of the most extensively studied groups of enzymes and the literature is rich in research papers dating back from the 19th century. Nevertheless, peroxidases continue to be widely studied, with more than 2000 articles already published in 2002 (according to the Institute for Scientific Information). The importance of peroxidases is emphasised by their wide distribution among living organisms and by their multiple physiological roles. They have been divided into three superfamilies according to their source and mode of action: plant peroxidases, animal peroxidases and catalases. Among all peroxidases, horseradish peroxidase (HRP) has received a special attention and will be the focus of this review. A brief description of the three super-families is included in the first section of this review. In the second section, a comprehensive description of the present state of knowledge of the structure and catalytic action of HRP is presented. The physiological role of peroxidases in higher plants is described in the third section. And finally, the fourth section addresses the applications of peroxidases, especially HRP, in the environmental and health care sectors, and in the pharmaceutical, chemical and biotechnological industries.

Although postoperative chemotherapy in the treatment of cancer appears to have reached the limit of cytoreduction, this may be due to chemotherapeutic agents that are administered nonselectively rather than attainment of the true limit of cytoreduction. Molecular profiles of tumor cells may determine tumor response to chemotherapy, and therefore the selective use of chemotherapy based on prediction will ultimately provide a cure for breast cancer. In this paper, design strategies for clinical trials aimed at disclosing predictive markers are discussed.

Many biotechnology and pharmaceutical companies use clinical research organizations (CROs) to assist in the writing and preparation of clinical documents intended for submission to health authorities. Start-up companies often require the expertise of a CRO to prepare their first regulatory documents. Larger or more experienced companies often require CRO staff to assist at times of multiple simultaneous submissions. The timely production of high-quality new drug marketing applications requires close collaborations between the drug company and the CRO. The views of both CRO and industry in ensuring best practices are discussed.

The manufacturing of protein-based biopharmaceuticals is done in bacterial or mammalian cell cultures. While bacterial cultures are inexpensive, dependable, and approved by regulatory authorities, many complex proteins cannot be manufactured this way. Complex proteins must be manufactured in mammalian cell cultures to produce active products. Mammalian cell culture capacity is limited and has slowed the delivery of necessary biopharmaceutical products to patients. The nature of the production capacity problem and future outlook are critically examined.

As the population ages, a dramatic increase in the number of cases of cancer is expected and the need for supportive-care agents, those used to ameliorate some of the side effects of cancer or its treatment, becomes more urgent. At present, supportive-care products are available and new agents are being developed with novel mechanisms of action or modifications of existing agents that improve performance. Because of the urgent need for such products, efficient development is required to deliver useful products to patients as rapidly as possible. This chapter uses actual examples to illustrate the stages of drug development, phase I through phase 3.

Publication of clinical trial data is the final step in the scientific method and an important method by which pharmaceutical and biotechnology companies, i.e., drug sponsors, disseminate information about their products. Because of the nature of large, multicenter trials, multiple investigators from many institutions may be considered as authors of these papers. Controversy concerning the rights of academic institutions and the rights of drug sponsors has been widely debated. This chapter summarizes the controversy and the current policies.

The US Food and Drug Administration (FDA) requires reproducibility studies for premarket approval of in vitro diagnostic (IVD) tests. Results of reproducibility studies provide an estimate of the variability of the IVD test among study sites, reagent lots, site operators, within a single test run, and over multiple test days. In planning the study, discuss the product registration strategy, including the intended use of the product and desired label claims, and define the study team. Design the sample panel according to the limit of detection or quantitation of the test, dynamic range of the test, FDA guidelines, sample matrix, and genotype. Consider legal and ethical issues for obtaining the panel parent specimen, such as minimizing the privacy risk and keeping promises to donors. During the study, review data promptly to determine invalid runs, discover trends in the data that may require additional operator training, ensure correct completion of case report forms, and resolve queries quickly. At the end of the study, gather the study team to review and improve processes. Use the outcome to set expectations of other functional areas and to provide product feedback.

Endothelial cells play a pathological role in cancer and chronic inflammation and are therefore attractive targets for therapeutic intervention. This review focuses on endothelial cell specific drug targeting strategies for the treatment of these diseases. The cellular and molecular processes involved in the activation of endothelial cells in angiogenesis and inflammation will be reviewed. Various target epitopes expressed by activated endothelium suitable for targeting purposes, design and development of drug-carrier complexes, drugs of interest which might interfere with endothelial cell activation, as well as in vitro and in vivo experimental approaches to study (intra) cellular drug delivery will be discussed.

One of the challenges for the successful commercialization of therapeutic proteins is to maintain the safety and efficacy of the protein during the manufacturing process, storage, and administration. To achieve this, the purified form of the protein drug is usually "formulated" with carefully selected excipients. The operations that occur subsequent to protein purification, such as freezing of the purified protein bulk, thawing of the bulk, formulation (excipient addition), sterile filtration, filling, freeze-drying, and inspection are commonly referred as "formulation and fill-finish operations". This review is focused on the protein formulation and fill-finish operations, critical process parameters at each operation, and the process considerations required for maintaining safety and efficacy of the drug during manufacturing and storage. Since proteins have complex molecular structures that can influence the protein stability, the reader is first introduced to salient concepts related to protein structure. This is followed by a review of the possible protein-degradation mechanisms and how a variety of external factors can contribute to protein degradation during the in vitro processing of the protein drug. The reader is then introduced to each of the formulation and fill-finish operations mentioned above, the possible degradations during each unit-operation, and process considerations necessary to avoid those degradations.

The DNA chips are arrays of DNA probes immobilized on solid support for simultaneous identification of many target DNA sequences. DNA chips applied to diagnosis aims to detect genomic DNA or RNA after PCR amplification. This review provides an overview of DNA chip technology, focusing on diagnostic applications. A comparison between high density and low density microarrays is given showing that low density chips are more suitable for routine applications due to their simplicity, good reproducibility, easy data management and low cost.