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PubMed2003

The contemporary drug development process: advances and challenges in preclinical and clinical development.

We are in a new era of drug discovery, in which it is feasible to develop therapeutic agents targeted at a particular protein or biological activity in a living cell. This has been made possible by major advances in our understanding of cell and molecular biology, epitomized by the 2001 Nobel prize award for Physiology or Medicine to Lee Hartwell, Tim Hunt and Paul Nurse, who were recognised for their work on key regulators of the cell cycle. Technological advances have also played a decisive role, leading to the sequencing of the human genome and increased throughput at many stages of the drug discovery and development process. For example, developments in high throughput screening, structural biology and microarray technology are increasing the speed of drug discovery. In this chapter we focus on the long, and often difficult, pathway which leads from identification of a hit in a screen to regulatory approval of a drug for disease treatment. The emphasis in this chapter is on the development of anticancer drugs, as this is our own area of expertise and also because cancer is a disease in which the cell cycle is already a major target for therapeutic intervention. However, many of the concepts, approaches and issues are generally common to other therapeutic areas.

Animals↗
PubMed2004

[Evaluation of a "stop smoking" contest in Japan].

BACKGROUND: In 1988, the Osaka Cancer Prevention and Detection Center developed a self-help smoking cessation program, the "stop smoking" contest, based on the Quit and Win strategy developed in the United States in the early 1980's. It consisted of a two-week preparation period, followed by a four-week complete abstinence period. Participants were asked to try to achieve their goals on their own, using self-help materials, mailed to all applicants. Successful participants--"contest winners"--were awarded prizes by lot. The purpose of the present study is to examine the applicability of the Quit and Win strategy in Japan, through evaluating the effectiveness of the program in general and identifying predictors of successful quitting. METHOD: We analyzed the results of three consecutive programs conducted in 1998, 1999, and 2000. The programs defined as "participants" all those who demonstrated that their intentions were sincere by signing on for the contest. Of the participants, those who reported complete abstinence for four weeks were defined as "winners." Finally, of the winners, those who reported successful abstinence during the following six- and twelve-month periods were defined as continuing winners. "Abstinent" status was confirmed through self-reporting letters signed by the subject and two witnesses. We hypothesized that successful quitting would be predicted by demographic and smoking-related variables. Predictors of successful quitting were analyzed statistically using logistic regression. RESULTS: Of 4,221 applicants, 2,550 (60%) smokers eventually joined the program as "participants." Forty-six percent of the participants reported complete tobacco abstinence during the four-week contest period. Twenty percent of the participants maintained abstinence during the following six months. Fifteen percent maintained abstinence for a full year. Significant predictors of tobacco abstinent for the four-week contest period were as follows; male, more advanced age, being married, lower nicotine dependence, greater readiness for quitting, higher confidence in quitting, and better health. Of these, sex and psychological characteristics for quitting such as readiness and confidence were the only factors significantly correlated with successful abstinence throughout the follow-up periods. Previous longer abstinence experiences and chronic disease did not predict four-week abstinence, though it was significantly correlated with abstinence maintenance during the follow-up periods. CONCLUSION: The present "stop smoking" contest, a "Quit and Win" type population-based, self-help smoking cessation program combined with incentives, could be successfully implemented in Japan. The success rate was essentially comparable to those of similar programs previously conducted in other countries, and other types of professional-assisted programs in Japan.

Adult↗
PubMed1989

[Endocrinology: lessons from the past, hopes for the future].

The social importance of endocrinology is apparent from an analysis of the prevalence of endocrinopathies in the CSSR. They affect (incl. diabetes and eufunctional goitre) some 10% of the population. The author submits a brief account of the development of knowledge of hormones and of Nobel prizes awarded for hormone research. On some examples he demonstrates the importance of endocrinology for other medical disciplines: the interrelationship of stress and infectious reactions via interleukin 1, the discovery of a series of new growth and immune factors; the participation TNF (cachectin, tumour necrosis factor) in pathological processes (tumours, atherosclerosis); vasoactive peptides EDRF (endothelium derived relaxation factor), endothelin (vasoconstriction), GM-CSF (granulocyte-macrophage colony stimulating factor) in treatment of radiation sickness and adjuvans in chemotherapy; interleukins. These new peptide hormones are words in the complex cellular signal alphabet the importance of which in the control of cellular activities we are beginning to understand.

Endocrine System Diseases↗
PubMed1997

[Nobel Prize of Medicine 1997 awarded for prion theory].

The Nobel Prize 1997 for Medicine and Physiology was awarded to S.B. Prusiner, who proposed the prion hypothesis. Prions are small 'proteinaceous infectious particles' that lack nucleic acids and hence genetic information. Prions are normal host encoded proteins but with an abnormal tertiary structure, which makes them extremely resistant to chemical and physical inactivation that would modify nucleic acids. They 'replicate' by forcing their conformation upon the normal prion proteins. Recently it was demonstrated that the prion disease, bovine spongiform encephalopathy (BSE) can be transmitted to man in whom it causes a new variant of Creutzfeldt-Jakob disease.

Animals↗
PubMed1993

Excellent population research prize to be awarded.

In order to promote the development of population science in China, mobilize the initiativeness of demographers and more effectively serve the purpose of controlling population growth and improving the quality of human resources, the Population Association of China has sponsored an Excellent Population Research Award to encourage the demographers with outstanding achievements within the term (January 1991-June 30, 1993) of the Association. All the research staff and family planning workers with the membership of the Population Association of China as well as research institutes with notable achievements are eligible to the application for the award. The research achievements include monographs (or teaching materials), papers, survey reports, translated works, dictionaries or reference books, and softwares. For each category, 2 classes of prizes have been set, and winners are to be awarded with diplomas and money. The evaluation work will be started in September and October and concluded by the end of November 1993.

Asia↗
PubMed1991

The question of nepotism in the award of Nobel prizes: a critique of the view of Hans Krebs.

While reviewing his development as a scientist, in 1967, Hans Krebs traced his scientific geneology to the von Baeyer 'family'. Almost every other member of this scientific family became a Nobel laureate. Krebs was of the opinion that there was no nepotism in the selection of the Nobel awards. This paper presents evidence, based on the recently released census of Nobel nominees and nominators for the chemistry prize between 1901 and 1937, that the von Baeyer 'family' of scientists had in fact practised a sort of 'nomination-nepotism'.

Chemistry↗
PubMed1997

NOVEL Award 1996: 2nd prize Tenodeses do not fully restore ankle joint loading characteristics: a biomechanical in vitro investigation in the hind foot.

OBJECTIVE: In order to understand the biomechanical consequences of ligament injuries and surgical reconstruction procedures, their effects on intra-articular loading in the ankle joint complex and Chopart joint line and on the plantar pressure patterns were investigated in vitro. METHODS: Twelve fresh-frozen lower leg specimens were freed of soft tissue down to the malleoli and prepared for accessing the talocrural, subtalar, talonavicular and calcaneocuboid joints. The specimens were fixed in a loading simulator and axially loaded with 600 N in six experimental conditions: intact; after cutting the anterior talofibular ligament; after additionally cutting the calcaneofibular ligament; after performing three common types of tenodeses, the Evans, Watson-Jones and Chrisman-Snook procedures. The intra-articular loading characteristics were determined with pressure sensitive film. Plantar loading patterns were measured with a capacitive EMED pressure distribution platform. RESULTS: Average intra-articular pressures were increased and were related either to decreased contact areas or to increased contact forces found in all joints after ligament resections and tenodeses. Plantar loading was increased under the medial aspect of the foot and decreased under the midfoot region. CONCLUSIONS: The results indicate that ankle ligament injuries, as well as surgical reconstructions by tenodeses, affect joint loading characteristics and may exacerbate joint degeneration. RELEVANCE: Excessive laxity of the ankle joint is considered a pre-arthrotic condition and is treated with various surgical procedures. Some of these procedures that utilize the tendon of the peroneus brevis have been shown to change joint kinematics. The aim was to evaluate joint loading characteristics and the potential danger of developing arthritis as a consequence of various tenodeses techniques. For this purpose, in vitro investigations are needed to directly determine intra-articular pressure measurements.

Journal Article↗