Advanced Stages Of Clinical Testing Research Articles

New anticoagulants: beyond heparin, low-molecular-weight heparin and warfarin.

The limitations of traditional anticoagulants, heparin and warfarin, have prompted the development of new anticoagulant drugs for prevention and treatment of both venous and arterial thromboembolism. After a brief review of thrombogenesis and its regulation, this paper focuses on new anticoagulant agents in more advanced stages of clinical testing.

Blood substitutes

Risk of disease transmission and limitations in the ability to transfuse in the prehospital or combat setting have stimulated research in the field of oxygen therapeutics. Several products have completed safety trials and are presently undergoing investigation for their efficacy. In the near future, the clinician will likely employ these products in the management of a variety of patient populations. Though similar in their oxygen carrying capacity, each agent possesses distinct physiologic effects. Understanding of the benefits and shortcomings of the various compounds is essential in order to optimally utilize them in various clinical settings. This review provides an overview of recent developments in the field of oxygen therapeutics and highlights results of clinical trials. Modified hemoglobin solutions of human or bovine origin and perfluorochemical-based emulsions are in advanced stages of clinical testing. Bovine hemoglobin-based solutions have been associated with vascular reactivity, methemoglobin formation and development of antibodies. Larger safety trials are necessary before they can find widespread use. Polymerized human hemoglobin solutions have a favorable safety profile in early trials and have been effective as a resuscitation fluid in circumstances when red cells may be unavailable. Unfortunately, outdated human blood, the substrate for this product, is itself in short supply. Perfluorocarbons similarly reduce the need for allogeneic transfusion, but the need for high-inspired oxygen levels currently limits use. Recombinant, polymer-encapsulated and additional forms of chemically modified hemoglobins are being developed and are undergoing testing in animal models Oxygen carriers offer a viable alternative to allogeneic transfusion. All oxygen therapeutic agents are not clinically equivalent. Optimal utilization requires a thorough understanding of the therapeutic potentials and adverse effects of the solution being considered for use.

An Update on New Anticoagulants

A variety of new anticoagulants for the prevention and treatment of venous and arterial thromboembolism are under development. Designed to overcome the limitations of heparin and vitamin K antagonists, these new agents are at various stages of clinical testing. This paper reviews venous and arterial thrombogenesis, discusses the regulation of coagulation, identifies the molecular targets for new anticoagulants, describes new anticoagulants in more advanced stages of clinical testing, and provides perspective on how these agents will impact on practice.

Emerging Anticoagulant Drugs

The limitations of traditional anticoagulants, heparin and warfarin, have prompted the development of new anticoagulant drugs for prevention and treatment of both venous and arterial thromboembolism. After a brief review of thrombogenesis and its regulation, this study focuses on new anticoagulant agents in more advanced stages of clinical testing.

New anticoagulants.

The limitations of heparin and warfarin have prompted the search for new anticoagulants for the prevention and treatment of venous and arterial thromboembolism. Although many such agents are in development, only a few have reached phase II or higher levels of clinical testing. This article reviews venous and arterial thrombogenesis, discusses the regulation of coagulation, identifies the molecular targets for new anticoagulants currently under development, describes the agents in more advanced stages of clinical testing, and provides clinical perspective on the opportunities for new anticoagulant drugs.

An update on epidermal growth factor receptor inhibitors.

The epidermal growth factor receptor (EGFR) is part of a family of plasma membrane receptor tyrosine kinases that control many important cellular functions, from cell growth and proliferation to cell death. Dysregulation of the EGFR signal transduction pathway has been implicated in tumorigenesis and cancer progression, making it a clinically relevant target for novel anticancer treatments. This paper reviews recent progress in the development of cancer therapies that are directed toward particular aspects of the extracellular and intracellular domains of EGFR. Promising new compounds in the advanced stages of clinical testing are emphasized.

Monoclonal antibody therapy for lymphoma: an update.

The purpose of this article is to review the historical development and recent advances in the application of monoclonal antibodies for the treatment of lymphoma. The history of clinical applications of monoclonal antibodies has been intertwined with that of lymphomas. The first report of a complete remission in 1981 described a patient with follicular lymphoma who was treated with a murine anti-idiotype antibody. Later that decade there appeared additional encouraging reports of radiolabeled monoclonal antibodies, immunotoxins, and other antibodies with antitumor effects against lymphoma and chronic lymphocytic leukemia. Monoclonal antibodies as a treatment of malignancy became reality in late 1997 when the US Food and Drug Administration approved the anti-CD20 chimeric monoclonal antibody rituximab for the treatment of B-cell lymphoma. Since that time an anti-CD25 monoclonal antibody (dacliximab) and an anti-CD25 immunotoxin fusion product (denileukin diftitox) have become clinically available. Several radio- labeled antibodies, including the murine anti-CD20 products (131)I-tositumomab and (90)Y-ibritumomab tiuxetan, are in advanced stages of clinical testing as are other unlabeled monoclonal antibodies with antilymphoma activity. Other antilymphoma immunotoxins that react with CD25, CD19, and CD22 also have shown promise. The therapeutic arsenal against lymphoma has been significantly changed by the addition of these antibody products that are active as single agents, and are synergistic, additive, or both with other antilymphoma treatments.

3″-Azido-3′-Deoxythymidine and 2′,3′-Dideoxycytidine Do Not Inhibit Gene-Specific DNA Repair in Hamster Cells

3″-Azido-3′-deoxythymidine (AZT) was the first approved drug for the treatment of the AIDS; however, despite its usefulness, AZT often produces side effects that require cessation of therapy. 2′,3′-Dideoxycytidine (ddC) is a related anti-retroviral agent in advanced stages of clinical testing. A previous report demonstrated that AZT decreased the repair of UV-induced DNA strand breaks in mammalian cells after ultraviolet (UV) irradiation. We studied the effect of AZT and ddC on DNA repair from the hamster DHFR gene of the major UV-induced DNA lesion, cyclobutane pyrimidine dimers (CPDs). We conclude that neither AZT nor ddC inhibited DNA replication or the gene-specific repair of CPDs in the hamster DHFR gene after 8 or 24 hrs of repair incubation at concentrations of 25μM and 10μM, respectively.

Liposomes as carriers of cancer chemotherapy. Current status and future prospects.

Chemotherapy is a modality of cancer therapy that needs much improvement. Development of a new chemical entity is very costly and time consuming, but improvements in delivery of existing agents may yield more rapid clinical results. Liposomes and other lipid-based drug delivery systems have the advantage, in this context, of utilising no new chemical entities. In terms of mechanism of action, tumour targeting has been the focus of much work in liposomal drug delivery. The recent development of liposomes with longer circulation times has led to improved tumour targeting in animal studies. Other mechanisms of action, such as release from drug depot formulations, heat-triggered local drug release, and transfection of genetic materials, may prove to be useful in humans. Liposomal formulations of more than a dozen antineoplastic agents have shown promise in vitro and in animal models. Somewhat mundane, but nevertheless crucial, issues of medical rationale and formulation engineering, and commercial considerations, have slowed testing in patients with cancer. However, 3 antineoplastic agents, doxorubicin, daunorubicin and cytarabine, are in advanced stages of clinical testing in humans. One or more of these should prove to be a medically useful and commercially viable product within the next few years.