The new ParaDIgm: IgM from bench to clinic

The inaugural IgM event entitled “The new ParaDIgm: IgM from bench to clinic” brought together the increasingly active and growing IgM antibody community to discuss recent advances and challenges facing the discovery and development of IgM antibody therapies and technologies. Researchers, clinicians and biomanufacturing experts delivered 21 talks on the basic science and isolation of IgM, upstream and downstream development, and formulation and clinical development of the molecules. Participants networked around topics aimed at exploring the full potential of IgM antibodies. The meeting was held at DECHEMA Gesellschaft für Chemische Technik und Biotechnologie e. V. (Society for Chemical Engineering and Biotechnology), a non-profit scientific and technical society based in Frankfurt am Main, Germany. The meeting was sponsored by Patrys, Laureate Biopharma, Bio-Rad Laboratories, BIA Separations, Percivia and the Bio Affinity Company (BAC). The second New ParaDIgm: IgM from bench to clinic meeting, will be held on April 23–24, 2013 in Frankfurt, Germany.     

Human genetics moves from clinic to bench - and back

A report on the European Society of Human Genetics Conference 2005, Prague, Czech Republic, 7-10 May 2005.     

From bench to the clinic: gamma-linolenic acid therapy of human gliomas

Malignant gliomas are among the most devastating of cancers and are a major cause of mortality in a young population with a median survival time of 9 months following cytoreductive surgery, radiotherapy and chemotherapy. Recent studies showed that polyunsaturated fatty acids especially gamma-linolenic acid (GLA) have selective tumoricidal action especially against malignant glioma cells both in vitro and in vivo. Limited open label clinical studies showed that intratumoral injection/infusion of GLA is safe and effective against malignant gliomas. In view of this, large-scale, double blind studies are needed to establish the usefulness of GLA in the treatment of malignant brain tumors.     

Wild type p53 reactivation: From lab bench to clinic

The p53 tumor suppressor is the most frequently inactivated gene in cancer. Several mouse models have demonstrated that the reconstitution of the p53 function suppresses the growth of established tumors. These facts, taken together, promote the idea of p53 reactivation as a strategy to combat cancer. This review will focus on recent advances in the development of small molecules which restore the function of wild type p53 by blocking its inhibitors Mdm2 and MdmX or their upstream regulators and discuss the impact of different p53 functions for tumor prevention and tumor eradication. Finally, the recent progress in p53 research will be analyzed concerning the role of p53 cofactors and cellular environment in the biological response upon p53 reactivation and how this can be applied in clinic.     

Regenerating cardiac cells: insights from the bench and the clinic

A major challenge in cardiovascular regenerative medicine is the development of novel therapeutic strategies to restore the function of cardiac muscle in the failing heart. The heart has historically been regarded as a terminally differentiated organ that does not have the potential to regenerate. This concept has been updated by the discovery of cardiac stem and progenitor cells that reside in the adult mammalian heart. Whereas diverse types of adult cardiac stem or progenitor cells have been described, we still do not know whether these cells share a common origin. A better understanding of the physiology of cardiac stem and progenitor cells should advance the successful use of regenerative medicine as a viable therapy for heart disease. In this review, we summarize current knowledge of the various adult cardiac stem and progenitor cell types that have been discovered. We also review clinical trials presently being undertaken with adult stem cells to repair the injured myocardium in patients with coronary artery disease.     

From bedside to bench to clinic trials: identifying new treatments for severe asthma

Asthmatics with a severe form of the disease are frequently refractory to standard medications such as inhaled corticosteroids, underlining the need for new treatments to prevent the occurrence of potentially life-threatening episodes. A major obstacle in the development of new treatments for severe asthma is the heterogeneous pathogenesis of the disease, which involves multiple mechanisms and cell types. Furthermore, new therapies might need to be targeted to subgroups of patients whose disease pathogenesis is mediated by a specific pathway. One approach to solving the challenge of developing new treatments for severe asthma is to use experimental mouse models of asthma to address clinically relevant questions regarding disease pathogenesis. The mechanistic insights gained from mouse studies can be translated back to the clinic as potential treatment approaches that require evaluation in clinical trials to validate their effectiveness and safety in human subjects. Here, we will review how mouse models have advanced our understanding of severe asthma pathogenesis. Mouse studies have helped us to uncover the underlying inflammatory mechanisms (mediated by multiple immune cell types that produce Th1, Th2 or Th17 cytokines) and non-inflammatory pathways, in addition to shedding light on asthma that is associated with obesity or steroid unresponsiveness. We propose that the strategy of using mouse models to address clinically relevant questions remains an attractive and productive research approach for identifying mechanistic pathways that can be developed into novel treatments for severe asthma.     

Methods for the identification of vascular markers in health and disease: From the bench to the clinic

Several diseases are characterized by changes in the molecular composition of vascular structures, thus offering the opportunity to use specific ligands (e.g., monoclonal antibodies) for imaging and therapy application. This novel pharmaceutical strategy, often referred to as “vascular targeting”, promises to facilitate the discovery and development of selective biopharmaceuticals for the management of angiogenesis-related diseases. This article reviews novel biomedical applications based on vascular targeting strategies, as well as methodologies which have been used for the discovery of vascular markers of pathology.     

Attenuation of multi-targeted proliferation-linked signaling by 3,3'-diindolylmethane (DIM): from bench to clinic

Emerging evidence provide credible support in favor of the potential role of bioactive products derived from ingesting cruciferous vegetables such as broccoli, brussel sprouts, cauliflower and cabbage. Among many compounds, 3,3'-diindolylmethane (DIM) is generated in the acidic environment of the stomach following dimerization of indole-3-carbinol (I3C) monomers present in these classes of vegetables. Both I3C and DIM have been investigated for their use in preventing, inhibiting, and reversing the progression of cancer - as a chemopreventive agent. In this review, we summarize an updated, wide-ranging pleiotropic anti-tumor and biological effects elicited by DIM against tumor cells. It is unfeasible to point one single target as basis of cellular target of action of DIM. We emphasize key cellular and molecular events that are effectively modulated in the direction of inducing apoptosis and suppressing cell proliferation. Collectively, DIM orchestrates signaling through Ah receptor, NF-κB/Wnt/Akt/mTOR pathways impinging on cell cycle arrest, modulation of key cytochrome P450 enzymes, altering angiogenesis, invasion, metastasis and epigenetic behavior of cancer cells. The ability of DIM to selectively induce tumor cells to undergo apoptosis has been observed in preclinical models, and thus it has been speculated in improving the therapeutic efficacy of other anticancer agents that have diverse molecular targets. Consequently, DIM has moved through preclinical development into Phase I clinical trials, thereby suggesting that DIM could be a promising and novel agent either alone or as an adjunct to conventional therapeutics such as chemo-radio and targeted therapies. An important development has been the availability of DIM formulation with superior bioavailability for humans. Therefore, DIM appears to be a promising chemopreventive agent or chemo-radio-sensitizer for the prevention of tumor recurrence and/or for the treatment of human malignancies.     

Tissue engineering and cell based therapies,from the bench to the clinic: The potential to replace,repair and regenerate

The field of Regenerative Biology as it applies to Regenerative Medicine is an increasingly expanding area of research with hopes of providing therapeutic treatments for diseases and/or injuries that conventional medicines and even new biologic drug therapies cannot effectively treat. Extensive research in the area of Regenerative Medicine is focused on the development of cells, tissues and organs for the purpose of restoring function through transplantation. The general belief is that replacement, repair and restoration of function is best accomplished by cells, tissues or organs that can perform the appropriate physiologic/metabolic duties better than any mechanical device, recombinant protein therapeutic or chemical compound. Several strategies are currently being investigated and include, cell therapies derived from autologous primary cell isolates, cell therapies derived from established cell lines, cell therapies derived from a variety of stem cells, including bone marrow/mesenchymal stem cells, cord blood stem cells, embryonic stem cells, as well as cells tissues and organs from genetically modified animals. This mini-review is not meant to be exhaustive, but aims to highlight clinical applications for the four areas of research listed above and will address a few key advances and a few of the hurdles yet to be overcome as the technology and science improve the likelihood that Regenerative Medicine will become clinically routine.     

The transition from bench to bedside: lessons learned in the creation of a new T-cell product for the clinic

While the technology of translational research is sometimes considered a poor relation to 'basic science', it has become a central focus of work to turn exciting new concepts into practical therapies. Here we use the example of selective T-cell depletion of allografted lymphocytes to illustrate the problems of scale-up, reproducibility, sterility, safety and regulatory concerns encountered during the bench to bedside process.     

From bench to briefs

Patent law offers opportunities for those who wish to leave the lab but not science.     

Translating preclinical findings of (endothelial) progenitor cell mobilization into the clinic; from bedside to bench and back

It is generally accepted that angiogenesis plays a major role in tumor growth and numerous targeting agents directed against angiogenesis pathways have been developed and approved for clinical use. In the past years the concept of angiogenesis has developed into a multi-faceted process in which, besides local activation and division of endothelial cells, bone marrow derived progenitor cells (BMDPCs) contribute to neovascularization. A multitude of preclinical and clinical data indicates that the release of BMDPCs influences the response to certain anti-cancer modalities. In this review we provide an overview of all the preclinical and clinical studies contributing to this hypothesis and translate these findings to the clinic by pointing out the clinical implications these findings might have. The recent insight in the mechanism of a systemic host response, in response to various treatment modalities has shed new light on the mechanism of tumor regrowth, early recurrence and metastasis formation during or after treatment. This provides various new targets for therapy which can be used to improve conventional chemotherapy. Furthermore it provides a potential explanation why bevacizumab selectively enhances the effectiveness of only certain types of chemotherapy.     

Beyond the bench

Joshua Lederberg's latest honor, the Presidential Medal of Freedom Award, recognized not only his many scientific accomplishments but those that benefited society as well.     

泛素介导的蛋白质降解系统——从基础研究到临床应用

20世纪60～80年代,大多数生物科研人员都致力于核酸和遗传信息传递的研究。蛋白质降解被认为是非特异的过程,因此没有人感兴趣。泛素修饰的发现使蛋白质降解领域发生革命性的变化,人们逐渐认识到蛋白质降解是一个特异的受严格调控的过程。细胞内蛋白质降解事件的发生会调节许多生命过程,如细胞增殖、分化、衰老和死亡。细胞内蛋白质降解调控异常也会引发多种疾病,包括癌症和神经退行性疾病。人们对细胞内蛋白质降解的研究已经取得一定成果,但是还有很多问题没有解决,全面解读该过程还需要更多的努力和探索。     

Probiotics: from bench to market

"Probiotics: From Bench to Market" was a one-day conference convened by the New York Academy of Sciences on June 11, 2010, with the goal of stimulating discussion of the physiological effects of probiotics on the gastrointestinal, nervous, and immune systems. The program included speakers from academia, industry, and government to give conference participants a full understanding of the state of the field of probiotics. The overall goal of the program was to increase communication and collaboration among these groups to advance probiotic research and probiotic contributions to public health. The conference was divided into three sessions and included both oral and visual presentations as well as panel discussions.