Cancer drugs. Weighing the risks and benefits.
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Few deliberations have greater bearing on human health than when the Food and Drug Administration weighs the risks and benefits of drugs designed to treat life-threatening diseases, such as cancer. (+info)
The embryonic stem cell test for the early selection of pharmaceutical compounds.
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Potential teratogenicity is a major consideration in the development of pharmaceutical substances. Currently its assessment involves large numbers of animal tests at high cost. This study assessed the feasibility of using the embryonic stem cell test (EST), validated by ECVAM in 1999, as a tool for the prediction of embryonic toxicity of pharmaceutical substances early in their development programmes. ESTs were carried out on 6 chemicals with well established toxicity characteristics established from literature and from the ECVAM study, and then on 10 Roche internal pharmaceutical substances already tested in vivo. The model correctly classified 81% of the substances. Further experiments are necessary to increase the database of the assay. (+info)
Neuronal cell culture from human embryonic stem cells as in vitro model for neuroprotection.
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In the context of efficacy testing of pharmacological compounds in animal models, replacement of some of these models with a relevant human in vitro system appears attractive, in particular with regard to large scale screening. Here, we show results from initial phases of a project, which attempts to explore the outstanding potential of human embryonic stem cell (hESC)-based in vitro models with special regard to neuronal stress as a potential replacement of animal models for human neurodegenerative diseases. We show the functionality of neurons derived from hESC precursors by calcium imaging, mitochondrial potential measurements and Western blots and moreover demonstrate that this model reproduces crucial mechanistic aspects observed during ischemia and excitotoxicity that are thought to be at the core of some neurodegenerative diseases. Also, the broader possibilities for refining surrogate molecular information emerging from the detailed analysis of this model are discussed. (+info)
Oral, direct factor Xa inhibitors in development for the prevention and treatment of thromboembolic diseases.
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Anticoagulants are recommended for the prevention and treatment of a wide variety of thromboembolic events. Although existing anticoagulants are effective, their use is limited by parenteral administration or the requirement for frequent monitoring and subsequent dose adjustment. Therefore, there is an urgent need for novel, oral agents with a predictable anticoagulant action. Because of its key position in the coagulation cascade and its limited roles outside of coagulation, Factor Xa has emerged as an attractive target for novel anticoagulants. As a result, the past decade has witnessed an explosion of research into small-molecule, oral, direct Factor Xa inhibitors, and several are now in clinical development. Rivaroxaban, LY517717, YM150, apixaban, PRT054021, and DU-176b, among others, have shown considerable promise; rivaroxaban is currently furthest ahead in its developmental program, having entered phase III in 3 indications. It is hoped that, before long, these anticoagulants will allow us to enter an era of convenient, oral anticoagulation, without the need for regular monitoring or dose adjustment. (+info)
Respiratory controversies in the critical care setting. When caring for critically ill patients, do clinicians have a responsibility to be innovative and try unproven approaches when accepted approaches are failing?
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As the first paper in this Journal Conference on intensive care unit controversies, the editors wished us to set the tone for the debate by discussing the ethics of medical "adventurism" in the intensive care unit. More life-or-death decisions are made in the intensive care unit than elsewhere in the hospital, and the critical care specialist often sees himself or herself as a warrior in a battle with death. This adrenaline-charged calling attracts highly intelligent, hard-working, and compassionate caregivers, as well as fiercely independent clinicians. The result of this is that critical care specialists passionately debate about the meaning and application of published "evidence" and this leads to thoughtful debate, as exemplified by the papers in this and the next issue of Respiratory Care, as well as thoughtless and often dangerous disregard for evidence-based medicine. Physicians are morally obligated to provide the best and most appropriate care possible for their patients, but when accepted approaches are failing and a critically ill patient is getting worse, the critical care physician must make a decision regarding innovative therapy, based on the patient's prognosis, the available evidence, the resources on hand, the expertise of the physicians, and the values of the patient and the physician. This decision may lead, at times, to trying unproven and innovative strategies to achieve a clinical goal. In such cases, it is to be hoped that this can be done in such a way that data are formally and prospectively collected to increase our knowledge. (+info)
Role of functional magnetic resonance imaging in drug discovery.
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In this review, we survey the state of the field of functional magnetic resonance imaging (fMRI) as it relates to drug discovery and drug development. We highlight the advantages and limitations of fMRI for this purpose and suggest ways to improve the use of fMRI for developing new therapeutics, with emphasis on treatments for anxiety disorders. Fundamentally, pharmacological studies with standard psychiatric treatments using standardized behavioral probes during fMRI will need to be carried out to determine characteristic brain signatures that could be used to predict whether novel compounds are likely to have specific therapeutic effects. (+info)
Age disparity between a cancer population and participants in clinical trials submitted as a new drug application of anticancer drugs in Japan.
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BACKGROUND: Underrepresentation of older patients in cancer clinical trials has been reported previously. METHODS: To evaluate disparities in age between actual cancer patients and those enrolled in clinical trials, the authors examined all the review reports of the Pharmaceuticals and Medical Devices Agency, Tokyo, Japan, and summaries of data submitted by applicants for the approval of new cancer drugs and that of a partial change in approved cancer drugs. RESULTS: Information regarding 68 clinical trials was available on the Internet. The median age of trial participants ranged from 33 years to 73 years and was older than 65 years in 13 trials, whereas the estimated median age of patients with all cancers was 69 years, and 64% of these individuals were age > or =65 years. The median age of trial participants was found to be lower than that of the patient population in 60 trials. The median difference in age between the 2 groups was 7 years (range, -16 to +33). With regard to molecular-targeting agents (16 trials) and hormonal agents (10 trials), trial participants were younger than the patient population in 25 of the 26 trials, with a median difference of 6 years (range, -9.5 to +20). The difference was larger for molecular-targeting agents (median, 9.5 years; range, birth-20 years) compared with hormonal agents (median, 2 years; range, -9.5 to +15). CONCLUSIONS: The results of the current study show that participants in cancer clinical trials are younger than the actual Japanese cancer patient population. (+info)
Inhibition of chemically induced carcinogenesis by drugs used in homeopathic medicine.
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Homeopathy is considered as one modality for cancer therapy. However, there are only very few clinical reports on the activity of the drugs, as well as in experimental animals. Presently we have evaluated the inhibitory effects of potentized homeopathic preparations against N'-nitrosodiethylamine (NDEA) induced hepatocellular carcinoma in rats as well as 3-methylcholanthrene-induced sarcomas in mice. We have used Ruta, Hydrastis, Lycopodium and Thuja, which are commonly employed in homeopathy for treating cancer. Administration of NDEA in rats resulted in tumor induction in the liver and elevated marker enzymes such as gamma-glutamyl transpeptidase, glutamate pyruvate transaminase, glutamate oxaloacetate transaminase and alkaline phosphatase in the serum and in liver. Concomitant administration of homeopathic drugs retarded the tumor growth and significantly reduced the elevated marker enzymes level as revealed by morphological, biochemical and histopathological evaluation. Out of the four drugs studied, Ruta 200c showed maximum inhibition of liver tumor development. Ruta 200c and phosphorus 1M were found to reduce the incidence of 3-methylcholanthrene-induced sarcomas and also increase the life span of mice harboring the tumours. These studies demonstrate that homeopathic drugs, at ultra low doses, may be able to decrease tumor induction by carcinogen administration. At present we do not know the mechanisms of action of these drugs useful against carcinogenesis. (+info)