Targeting of cancer stem/progenitor cells plus stem cell-based therapies: the ultimate hope for treating and curing aggressive and recurrent cancers

The rapid progression from aggressive primary cancers into locally advanced and invasive and/or metastatic diseases remains a big obstacle for an early diagnosis and curative therapeutic intervention for cancer patients. The late-stage leukemias and disseminated and metastatic sarcomas, melanomas, brain tumors and epithelial cancers are the devastating diseases associated with a high rate of recurrence after treatment with the conventional clinical therapies including surgery, ionizing radiation, hormonal therapy and systemic chemotherapy, which generally lead to the death of patients. Therefore, the establishment of the molecular events underlying cancer initiation and progression into locally invasive and metastatic diseases is of major interest in basic cancer research as well as for the development of new effective clinical therapeutic options against the recurrent and lethal cancers. Recent advances have led to the identification of specific oncogenic products that are implicated in the malignant transformation of adult stem/progenitor cells into leukemic or tumorigenic and migrating cancer stem/progenitor cells during cancer progression. Of therapeutic interest, the molecular targeting of deregulated signaling elements in cancer stem/progenitor cells and their local microenvironment represents a new potential strategy for the development of more effective clinical treatments against aggressive cancers. Particularly, the combined use of chemotherapeutic drugs to eradicate cancer-initiating cells with hematopoietic stem cell or genetically-modified stem cell transplant is emerging as potential cancer treatments that hold great promise in the area of clinical cancer research. These targeting and stem cell-based therapies may offer the ultimate hope for treating and even curing the patients diagnosed with locally advanced cancers at high risk of recurrence, metastatic and/or relapsed cancers in the clinics.     

Molecular biological approaches for environmental medicine

A revolution in biology and medicine is taking place as a direct consequence of rapid developments in the field of molecular biology. The tremendous advances in our knowledge of basic molecular genetics and cell biology have opened the door for new methods of diagnosis, assessment of individual susceptibility to disease, and elucidation of the pathogenesis of disease. These advances will have a profound impact on the practice of occupational and environmental medicine. In this review, we intend to summarize the approaches we have applied in order to deal with the environmental problems we have faced.     

New approaches to neurorehabilitiation: the increasing evidence base

Recent advances in neuroscience have led to newer, more scientific approaches to rehabilitation for patients who have had a stroke or sustained a brain or spinal cord injury. Specifically, the pendulum in rehabilitation has swung away from a focus on compensatory techniques and toward impairment-mitigating therapies. In addition, there is a new push to base therapies on scientific evidence. This article explores these changes and the developments that led to them, including discoveries in basic science that have enhanced our understanding of neuroplasticity. It also describes new research directions in neurorehabilitation.     

Healthcare applications of knowledge discovery in databases

Many healthcare leaders find themselves overwhelmed with data, but lack the information they need to make informed decisions. Knowledge discovery in databases (KDD) can help organizations turn their data into information. KDD is the process of finding complex patterns and relationships in data. The tools and techniques of KDD have achieved impressive results in other industries, and healthcare needs to take advantage of advances in this exciting field. Recent advances in the KDD field have brought it from the realm of research institutions and large corporations to many smaller companies. Software and hardware advances enable small organizations to tap the power of KDD using desktop PCs. KDD has been used extensively for fraud detection and focused marketing. There is a wealth of data available within the healthcare industry that would benefit from the application of KDD tools and techniques. Providers and payers have a vast quantity of data (such as, charges and claims), but not effective way to analyze the data to accurately determine relationships and trends. Organizations that take advantage of KDD techniques will find that they offer valuable assistance in the quest to lower healthcare costs while improving healthcare quality.     

Chemotherapy for lung cancer patients

The number of lung cancer-related deaths has increased since the 1960 and has become the leading cause of cancer-related death in Japan. It is anticipated that the number will double in the next 20 years. Chemotherapy is a hopeful systemic therapy because of distant metastases due to lung cancer. Platinum based doublets remain the standard of care for the first-line treatment of metastatic NSCLC. As salvage chemotherapy for patients, the effectiveness of docetaxel has been confirmed. The standard chemotherapy for extensive SCLC is the combination of cisplatin and irinotecan or etoposide. Recently, randomized trials have shown that platinum-based chemotherapy has the potential to improve survival among patients with completely resected NSCLC. Recent advances in molecular biology and genetics have created new molecular targeted therapies for lung cancer. New anti-cancer agents, including gefitinib, erlotinib, bevacizumab, pemetrexed and amrubicin, are being developed currently.     

Candidate sites of action for microdosimetry associated with exposure to extremely-low-frequency magnetic fields,electric fields and contact currents

Recent advances enable one to apply numerical techniques to anatomically-correct human models to compute current densities and electric fields in tissue due to exposure to electric fields, magnetic fields, or contact currents. These methods have proved to be informative in estimating exceedance of basic restrictions prescribed by exposure guideline organizations. To date, the analyses have been conducted with a resolution on the order of millimeters. However, these techniques have future roles to play at higher levels of resolution at those sites in target tissues suspected of transducing local electric fields into biological responses. Two specific cases in which high resolution "microdosimetry" would yield value involve (a) residential settings and childhood leukemia and (b) worker exposure and cardiovascular disease. Recent research suggests that residential contact currents on the order of microamperes can produce biologically significant dose (expressed as the local electric field) to the bone marrow of a child. Microdosimetry would focus on pluripotent progenitor cells resident in the marrow compartment, as well as anatomic features that distinguish a child's from an adult's marrow. Laboratory and epidemiologic research has suggested that magnetic field exposure may affect heart rate variability, a measure reflective of autonomic nervous system control of cardiac activity. Given the physical attributes of the central nervous system and the sites that could serve as substrates for field interactions, future microdosimetry addressing heart rate variability effects may be well-advised to focus on the electrically excitable dendritic arborizations of neurons. In both cases, microdosimetry will help shed light on primary interactions in tissue.     

Genetics and biological markers of risk for alcoholism

Substantial scientific evidence has accumulated that both genetic and environmental factors predispose the development of alcoholism in certain individuals. Evidence has accumulated to indicate that alcoholism is a heterogeneous entity arising from multiple etiologies. The demonstrated role of genetics in increasing the risk of alcoholism has promoted the search for biological markers that could objectively identify individuals who are genetically predisposed to alcoholism. Identifying such markers could allow for early diagnosis, focused prevention, and differential and type-specific treatment of alcoholism. Promising markers have been provided by research in electrophysiology, endocrinology, and biochemistry. Recent advances in molecular genetics are offering prospects for direct analysis of the human genome to determine elements that provide predisposition to, and protection from, alcoholism. Recent advances in research and new knowledge gained by the alcoholism treatment community and the lay public are helping to diminish the societal damage caused by alcohol abuse and alcoholism and to change prevailing attitudes about them.     

Principles of cost-effectiveness research

Recent advances in the theoretical concepts behind cost-effectiveness evaluation have led to a marked improvement of the techniques used in cost-effectiveness research. Any effective program will have not only dollar costs and dollar benefits but also nondollar costs and benefits. Cost studies evaluate the relative weights of these costs and benefits to determine whether the program's value is worth the expense. Key elements to consider include direct costs of the program, costs of future workup of treatment, costs of evaluating and treating complications resulting from the program, future medical costs averted, discounting of future costs and health effects, and a sensitivity analysis. Despite the recent theoretical advances, cost-effectiveness research raises multiple controversies, including some key ethical issues.     

Reproductive medicine. New procedures fool Mother Nature and evade ethical debate

Fetal tissue transplants that rely on abortions, and techniques used in prenatal diagnosis and artificial reproduction, have raised fervent and intractable opposition from the Roman Catholic Church and pro-life groups. Recent medical reports of advances in these areas have acknowledged the arguments offered by these organizations and, in turn, are offering some new ways for resolving the differences, as the following articles show.     

Functional imaging in stroke

Recent advances in magnetic resonance techniques make it possible to image physiological parameters such as molecular diffusion, tissue perfusion and cortical activation. These techniques greatly contribute to the early detection and to the understanding of the pathophysiological evolution and recovery from ischaemic stroke.     

Myostatin: a therapeutic target for skeletal muscle wasting

PURPOSE OF REVIEW: This review discusses recent developments in myostatin research, focusing on the basic actions of myostatin on skeletal muscle, the identification of key regulatory elements of the myostatin pathway, and the promise of myostatin as a therapeutic target in muscle-related disorders. RECENT FINDINGS: In addition to a well-characterized role in muscle development, recent research advances have solidified the importance of myostatin in adult muscle, although questions remain. A number of possible regulatory proteins for myostatin have been identified, showing a complex picture of myostatin regulation that requires clarification. The identification of an antimyostatin monoclonal antibody (JA16) shows the promise of myostatin as a target for muscle-wasting disorders; the antibody has already been shown to increase muscle mass in healthy older mice and muscle function in postnatal mdx mice. SUMMARY: Since its discovery in 1997, myostatin has quickly been established as a key regulator of skeletal muscle mass. Recent developments strengthen the idea that myostatin will be an important therapeutic target for muscle-wasting-related disorders, and as more details of myostatin regulation and its mechanisms of action are clarified, myostatin will continue to dominate the skeletal muscle development and muscle-wasting literature.     

Early imaging of the infarct

Radionuclide techniques for the detection of acutely infarcted myocardium have been available for several years, but they are rarely used. Recent advances, such as the introduction of single-photon emission computed tomography and the introduction of novel radiopharmaceuticals, have suggested new clinical and research applications for them.     

Radiological investigation of impotence

Recent advances in the understanding of the causes of impotence have led to the recognition of various treatable physical causes. Some of these causes are related to vascular abnormalities which have necessitated the development of new imaging techniques. These now allow more precise diagnosis and the development of more appropriate surgical and radiological treatment.     

Experimental and clinical applications of molecular cell biology in nutrition and metabolism.

Rapid advances in molecular biology have yielded important new techniques for understanding the cellular mechanisms of normal homeostasis and disease. In particular, molecular laboratory methodologies have become important investigative tools for nutritional studies. Detection techniques for specific DNAs, RNAs, and proteins allow direct examination of cellular regulation of protein expression in health and illness. Construction of transgeneic models by recent techniques of inserting foreign genes into experimental animals has provided novel models for studies of cellular metabolism. In addition, molecular biology has had impact on clinical nutrition and therapy. Molecular techniques not only allow for early diagnosis of many inborn genetic errors of metabolism, recombinant technology has also provided for large-scale production of proteins and hormones of potential therapeutic value. The possibility for direct gene therapies is also nearing reality. Hence, understanding the language of molecular biology and the recent developments in this field is not only of research interest, but is also of clinical relevance.     

A methodological overview on molecular preimplantation genetic diagnosis and screening: a genomic future?

The genetic diagnosis and screening of preimplantation embryos generated by assisted reproduction technology has been consolidated in the prenatal care framework. The rapid evolution of DNA technologies is tending to molecular approaches. Our intention is to present a detailed methodological view, showing different diagnostic strategies based on molecular techniques that are currently applied in preimplantation genetic diagnosis. The amount of DNA from one single, or a few cells, obtained by embryo biopsy is a limiting factor for the molecular analysis. In this sense, genetic laboratories have developed molecular protocols considering this restrictive condition. Nevertheless, the development of whole-genome amplification methods has allowed preimplantation genetic diagnosis for two or more indications simultaneously, like the selection of histocompatible embryos plus detection of monogenic diseases or aneuploidies. Moreover, molecular techniques have permitted preimplantation genetic screening to progress, by implementing microarray-based comparative genome hybridization. Finally, a future view of the embryo-genetics field based on molecular advances is proposed. The normalization, cost-effectiveness analysis, and new technological tools are the next topics for preimplantation genetic diagnosis and screening. Concomitantly, these additions to assisted reproduction technologies could have a positive effect on the schedules of preimplantation studies.     

Agricultural Approaches to Improving Phytonutrient Content in Plants: An Overview

Recent advances in plant molecular biology, functional genomics, and biochemistry have opened up a number of new avenues of research that will enable plant biologists to characterize, increase and modify plant content of a wide range of essential minerals and vitamins, as well as a number of secondary plant compounds that appear to play a role in improving human health and nutrition. In this review, several examples of exciting new research applying plant genomic and molecular genetic approaches to the improvement of phytonutrient content and composition in plants are presented. Research focusing on the elucidation of many of these complex biosynthetic and transport pathways in plants will require considerable resources in terms of funding, time, and personnel. As plant biologists move into interdisciplinary collaborations with nutritionists and food scientists, attention must be paid to a more complete identification and characterization of specific bioactive phytonutrients. Also, a more detailed assessment of the health-promoting properties of these compounds is needed, particularly for many of the secondary plant compounds for which clear epidemiologic and clinical data are still lacking. Finally, in order for significant progress to be made in modifying the nutrient composition of crops, a major investment must be made by funding agencies.     

Recent advances in molecular diagnostic techniques for human lymphatic filariasis and their use in epidemiological research

Diagnosis of lymphatic filariasis for epidemiological studies is an area of science that has been greatly modernized over the last two decades. Recent developments and the introduction of new technologies have led to the replacement of traditional diagnostic methods that were insensitive, tedious and often impractical with molecular biology techniques that have considerable potential for field use. This paper reviews some of these major new techniques and the applications of molecular diagnosis in the field of lymphatic filariasis.     

Immunology in the medical practice. XXXIII. Hereditary immune deficiencies: from genotype to phenotype

The advances of molecular biological techniques of the last decade have made possible identification of a rapidly increasing number of congenital (or primary) immune deficiencies at the genetic level. As soon as an immune deficiency is becoming a likely conclusion from a series of diagnostic laboratory tests, these recent developments in molecular techniques allow us in principle to make a conclusive diagnosis on the basis of a well-defined genetic defect. The hereditary immune deficiencies can be divided in 4 groups according to the functional immune aberration: antigen recognition, communication between immune cells, adhesion and directional motility, and killing as an effector mechanism.     

特发性智能迟缓病因研究的进展

近年来分子、细胞遗传学的发展,各先进技术如CT、MRI、PET等的开展,临床上对以往不明原因的智能迟缓的病因研究有了可喜的进展。本文阐述了特发性智能迟缓病因一染色体异常、中枢神经系统畸形,多种先天性异常及其它有关因素四个方面的进展情况,有助于临床医生对特发性智能迟缓儿童的评价。     

Diagnosis of hepatitis C in clinical practice: review of the literature]

The objective of this study was to review the literature concerning laboratory tests to detect hepatitis C virus infection, which have been available since 1989. The diagnosis of hepatitis C is mainly based on serological techniques and on molecular techniques. Serological techniques to detect hepatitis C virus antibodies are the method of choice to identify past or present infection. There are two types of serological assays: highly sensitive enzyme-linked immunosorbent screening assays; and more specific immunoblot techniques, which are used as supplemental or confirmatory tests. With respect to molecular diagnostic techniques, there are several types of assays. One such assay detects viral RNA. It is useful for diagnosis in such situations as the early stages of infection, with immunosuppressed patients, and with persons who have a low probability of infection. Molecular assays are also recommended before treatment with interferon and ribavirin, in order to monitor response to treatment. Other assays allow determination of viral load by either target amplification (as in polymerase chain reaction) or signal amplification (as in branched-DNA). Determining the hepatitis C virus genotype is possible using either molecular techniques or serotyping. Determining viral load and genotype is useful for planning the duration of interferon and ribavirin treatment. There have been major advances in the diagnosis of hepatitis C in the past decade Improvements in the sensitivity and specificity of antibody tests have provided faster, less expensive diagnoses. However, more accurate assays are still needed for such groups as immunosuppressed persons and acute hepatitis patients.