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Publications in this journal

• Obesity and colorectal cancer

  Authors: Krasimira Aleksandrova Katharina Nimptsch Tobias Pischon

  Frontiers in bioscience (Elite edition).

  This review outlines the association of obesity with risk of colorectal cancer and the potential underlying mechanisms from an epidemiological perspective. Current research indicates that there is aThis review outlines the association of obesity with risk of colorectal cancer and the potential underlying mechanisms from an epidemiological perspective. Current research indicates that there is a moderate but consistently reported association between general obesity (as determined by BMI) and colorectal cancer incidence and mortality. The relative risk associated with obesity is higher for cancer of the colon than for cancer of the rectum and it is higher in men than in women. By contrast, abdominal adiposity (as determined by waist circumference or waistto- hip ratio) is similarly strongly associated with colon cancer in men and women, suggesting that abdominal adiposity is a more important risk factor for colon cancer than general adiposity, at least in women. Putative mechanisms that may account for the link between adiposity and colorectal cancer risk include hyperinsulinemia, insulin resistance, inflammation, altered immune response, oxidative stress, as well as disturbances in insulin-like growth factors, adipokines, and sex steroids. Understanding the link between obesity and colorectal cancer may pave the way for targeted prevention of colorectal cancer morbidity and mortality.

• Role of anti-EGFR target therapy in colorectal carcinoma.

  Authors: Aranda-Aguilar Enrique, Pulido-Cortijo Gema, Jimenez-Castro Jeronimo, Gomez-Espana Maria Auxiliadora

  Frontiers in bioscience (Elite edition). 4:12-22.

  The epidermal growth factor receptor (EGFR) has become an important target in cancer treatment. In consequence, drugs directed at this and other molecular targets are an increasingly important partThe epidermal growth factor receptor (EGFR) has become an important target in cancer treatment. In consequence, drugs directed at this and other molecular targets are an increasingly important part of the treatment of numerous tumours. Cetuximab and panitumumab, two monoclonal antibodies that target EGFR, have proved to be effective in metastatic colorectal cancer treatment. However, some patients do not respond to treatment with EGFR inhibitors and, for this reason, interest in the identification of patients most likely to benefit from treatment with these agents has grown considerably. K-Ras, a member of the RAS family of signalling proteins plays an important role in EGFR- mediated regulation of cellular proliferation and survival. Patients with wild-type K-Ras were found to have significantly greater overall survival, progression-free survival and/or response rate compared with patients harbouring K-Ras mutations.

• Purinergic signaling in giant cell formation.

  Authors: Irma Lemaire, Simonetta Falzoni, Elena Adinolfi

  Frontiers in bioscience (Elite edition). 4:41-55.

  Cell fusion into multinucleated giant cells (MGC) is an essential process that contributes to many important biological mechanisms in mammalians. In the bone and immune system, macrophages areCell fusion into multinucleated giant cells (MGC) is an essential process that contributes to many important biological mechanisms in mammalians. In the bone and immune system, macrophages are endowed with a remarkable potential for cell fusion events as evidenced by their propensity to fuse with other cells and between themselves during both normal processes and disease. Macrophage fusion is critical for the normal development of multinucleated osteoclasts, the cells responsible for bone resorption. Macrophages from various tissue compartments also undergo fusion into MGC, a hallmark of granulomatous inflammation. To date, the mechanisms underlying macrophage fusion remain poorly understood. Receptor-ligand interactions are thought to mediate this process and several lines of evidence implicate purinergic receptors in both osteoclast and MGC formation. Notably, the P2X7 receptor for extracellular ATP is expressed in osteoclasts and in many types of granulomas associated with infection, foreign body response and sterile inflammation. Through their ability to sense extracellular cues and ATP, a messenger of intercellular communication, purinergic receptors likely contribute to cell-cell interactions that result in macrophage fusion.

• Osteoarthritis: genetic factors, animal models, mechanisms, and therapies.

  Authors: Qin Bian, Yong-Jun Wang, Shu-Fen Liu, Yi-Ping Li

  Frontiers in bioscience (Elite edition). 4:74-100.

  Osteoarthritis (OA) is the most common form of joint disease. OA frequently affects knees, hips, hands, and the spine. It is characterized by the progressive destruction of articular cartilage andOsteoarthritis (OA) is the most common form of joint disease. OA frequently affects knees, hips, hands, and the spine. It is characterized by the progressive destruction of articular cartilage and subchondral bone accompanied by low-grade inflammation that together result in pain and deformity. Recent studies have shed light on the nature of OA genetic susceptibility and confirmed a number of candidate genes involved in the destruction of the synovium, articular cartilage, and subchondral bone in OA pathogenesis. During the progression of OA, there are several cellular changes in joints, including an increase in the number of activated osteoclasts and macrophages and an infiltration of the synovium by activated T-cells and B-cells. Pro-inflammatory mediators (e.g. interleukin IL-1, IL-1beta, IL-6, IL-17, and IL-18, and Tumor necrosis actor-alpha), proteinases (e.g. matrix metalloproteinase 9 and cathepsin K), and regulators of cartilage and bone formation (e.g. BMPs) have been shown to have important roles in OA progression at the molecular level. Studies have suggested that OA shares several common characteristics with rheumatoid arthritis (RA). To systematically understand OA, this review summarizes OA disease genes, mouse models of human disease experimental mouse models, mechanisms of OA pathogenesis, and current OA therapies.

• Recent advances on tea polyphenols.

  Authors: Jyoti Kanwar, Mujtaba Taskeen, Imthiyaz Mohammad, Congde Huo, Tak Hang Chan, Qing Ping Dou

  Frontiers in bioscience (Elite edition). 4:111-31.

  Over the past decade many scientific and medical studies have focused on green tea for its long-purported health benefits. There is convincing evidence that tea is a cup of life. It has multipleOver the past decade many scientific and medical studies have focused on green tea for its long-purported health benefits. There is convincing evidence that tea is a cup of life. It has multiple preventive and therapeutic effects. This review thus focuses on the recent advances of tea polyphenols and their applications in the prevention and treatment of human cancers. Of the various polyphenols in tea, (-)-Epigallocatechin-3-gallate (EGCG) is the most abundant, and active compound studied in tea research. EGCG inhibits several molecular targets to inhibit cancer initiation and modulates several essential survival pathways to block cancer progression. Herein, we describe the various mechanisms of action of EGCG and also discuss previous and current ongoing clinical trials of EGCG and green tea polyphenols in different cancer types.

• Oxidative stress defense and repair systems of the ocular lens.

  Authors: Lisa Ann Brennan, Rebecca Susan McGreal, Marc Kantorow

  Frontiers in bioscience (Elite edition). 4:141-55.

  It is well accepted that reactive oxygen species (ROS) play a critical role in many biological processes including disease and longevity. Oxidation of proteins has been linked to many disease statesIt is well accepted that reactive oxygen species (ROS) play a critical role in many biological processes including disease and longevity. Oxidation of proteins has been linked to many disease states and even the aging process itself. This was first proposed as "The free radical theory of aging" in 1956 by Denham Harman which suggests that free radicals causes cumulative and irreversible damage to macromolecules, loss of cellular function and cell death over time directly impacting health and lifespan. Cellular damage from ROS exposure has been termed oxidative stress, which is an imbalance between cellular ROS production and the ability of the cell to regulate ROS levels and repair damage caused by ROS. This review focuses on the role of oxidative stress in the eye lens as a model for understanding the role of oxidative stress systems in age-related human disease.

• The nicotinic acetylcholine receptor: smoking and alzheimer's disease revisited.

  Authors: Mona Mehta, Abdu Adem, Maninder S Kahlon, Marwan N Sabbagh

  Frontiers in bioscience (Elite edition). 4:169-80.

  Epidemiological studies regarding Alzheimer's disease (AD) in smokers currently suggest inconsistent results. The clinicopathological findings also vary as to how AD pathology is affected by smokingEpidemiological studies regarding Alzheimer's disease (AD) in smokers currently suggest inconsistent results. The clinicopathological findings also vary as to how AD pathology is affected by smoking behavior. Even though clinicopathological, functional, and epidemiological studies in humans do not present a consistent picture, much of the in vitro data implies that nicotine has neuroprotective effects when used in neurodegenerative disorder models. Current studies of the effects of nicotine and nicotinic agonists on cognitive function in both the non-demented and those with AD are not convincing. More data is needed to determine whether repetitive activation of nAChR with intermittent or acute exposure to nicotine, acute activation of nAChR, or long-lasting inactivation of nAChR secondary to chronic nicotine exposure will have a therapeutic effect and/or explain the beneficial effects of those types of drugs. Other studies show multifaceted connections between nicotine, nicotinic agonists, smoking, and nAChRs implicated in AD etiology. Although many controversies still exist, ongoing studies are revealing how nicotinic receptor changes and functions may be significant to the neurochemical, pathological, and clinical changes that appear in AD.

• Dietary patterns and prostatic diseases.

  Authors: Sebastiano Cimino, Vincenzo Favilla, Tommaso Castelli, Francesco Marchese, Giuseppe Sortino, Marco Russo, Giorgio Ivan Russo, Claudia Cali, Costanza Salamone, Massimo Madonia, Giuseppe Morgia

  Frontiers in bioscience (Elite edition). 4:195-204.

  Dietary patterns play a role on prostatic diseases in association with genetic, behavioral, occupational and environmental ones. Data from reviewed literature provide evidences of a possibleDietary patterns play a role on prostatic diseases in association with genetic, behavioral, occupational and environmental ones. Data from reviewed literature provide evidences of a possible relationship between dietary habits and the incidence of prostate disorders, even if it is not enough to justify a widespread adoption of new dietary habits. In this review the role of dietary patterns, including the use of supplements, in the prevention and treatment of the most frequent and known prostatic diseases, benign prostatic hyperplasia (BPH) and prostate cancer (PC) was analyzed. A limited number of well designed trials were identified in which diet and dietary supplement intervention appeared to slow disease progression. Although conclusive evidences are limited, the current data suggest that a diet low in total calories and fat, high in vegetables and fruits and that body weight control could be possibly effective in preventing prostatic diseases. On the other hand care must be taken to ensure that over-consumption of dietary supplements does not occur because it may be harmful.

• Chronic psychosocial stress exposes Alzheimer's disease phenotype in a novel at-risk model.

  Authors: Karim A Alkadhi

  Frontiers in bioscience (Elite edition). 4:214-29.

  Because of the extensive individual variations in the time of onset and severity of the prevalent sporadic form of Alzheimer's disease (AD), a patient-related external factor must be assumed to playBecause of the extensive individual variations in the time of onset and severity of the prevalent sporadic form of Alzheimer's disease (AD), a patient-related external factor must be assumed to play a significant role in the development of the disease. Since stress is increasingly recognized as an external factor in the development of AD, a number of labs, including this lab, have shown that chronic stress or corticosterone administration worsens the AD phenotype in both transgenic and non-transgenic models of the disease. Recently we develop a novel at-risk model that correlates with seemingly normal individuals who are predisposed to develop AD. This review is a summarized recount of the findings we have reported on the effect of chronic psychosocial stress in this at-risk model of AD. Behavioral (learning and memory tests), electrophysiological and molecular findings indicated that even mild chronic psychosocial stress clearly transforms this seemingly normal rat model to a full-fledge AD phenotype.

• Antibacterial agents from actinomycetes - a review.

  Authors: Girish Badrinath Mahajan, Lakshmi Balachandran

  Frontiers in bioscience (Elite edition). 4:240-53.

  The discovery of Penicillin in 1928 and that of Streptomycin in 1943, has been pivotal to the exploration of nature as a source of new lead molecules. Globally, the microbiologist today isThe discovery of Penicillin in 1928 and that of Streptomycin in 1943, has been pivotal to the exploration of nature as a source of new lead molecules. Globally, the microbiologist today is acknowledged as a crucial player in the drug discovery program. The microbial products, especially those from actinomycetes have been a phenomenal success for the past seven decades. Bioprospecting for new leads are often compounded by the recurrence of known antibiotics in newer microbial isolates. Despite all these deterrents, actinomycetes have proved to be a sustained mine of novel antibiotics, which selectively destroys the pathogens without affecting the host tissues. Each of these antibiotics is unique in their mode of action. Their versatility and immense economic value is something, which is extremely noteworthy. The anti-infective turn-over of over 79 billion US dollars in 2009, includes about 166 antibiotics and derivatives such as the Beta-lactam peptide antibiotics, the macrolide polyketide erythromycin, tetracyclines, aminoglycosides, daptomycin, tigecycline, most of which are produced by actinomycetes (1). Actinomycetes continue to play a highly significant role in drug discovery and development. Among the bioactive compounds that have been obtained so far from microbes, 45 % are produced by actinomycetes, 38 % by fungi and 17 % by unicellular eubacteria (2). Further many chemically synthesized drugs owe their origin to natural sources. In this review article, we highlight the recent antibiotics from actinomycetes with emphasis on their source, structures, activity, mechanism of action and current status.

• Bladder tumors and aromatic amines - historical milestones from Ludwig Rehn to Wilhelm Hueper.

  Authors: Holger Georg Dietrich, Klaus Golka

  Frontiers in bioscience (Elite edition). 4:279-88.

  We know today that environmental factors must be regarded as a significant cause of the urinary bladder carcinoma. In Germany, the urinary bladder carcinoma is the second most common urological tumorWe know today that environmental factors must be regarded as a significant cause of the urinary bladder carcinoma. In Germany, the urinary bladder carcinoma is the second most common urological tumor among men and the most common among women and more than 100 occupational bladder cases are recognized and compensated per year. Scientific studies of this problem reach back to the 18th century. However it was only in 1895 that the surgeon Ludwig Rehn firstly described 3 cases of occupational bladder tumors in at most 45 fuchsine workers in Frankfurt / M. This extremely significant discovery was followed by a description of a large number of cases of urinary bladder tumors among workers in the paint industry. Nevertheless, it was impossible to induce bladder cancer in animals by aromatic amines for many years. In the 1930s, the pathologist Wilhelm C. Hueper was the first to induce bladder cancer in animal experiments, applying beta-naphthylamine to dogs. Based on these experiments and corroborated by epidemiologic studies, beta-naphthylamine was banned in Germany and many countries from the 1950s on. This review will highlight work and life of these two pioneering medical researchers.

• Coronary artery ectasia: current concepts and interventions.

  Authors: Ahmed S Aboeata, Siva P Sontineni, Venkata M Alla, Dennis J Esterbrooks

  Frontiers in bioscience (Elite edition). 4:300-10.

  Coronary artery ectasia (CAE) is a well-recognized angiographic finding, characterized by abnormal dilatation of the coronary arteries. We reviewed the current concepts of the condition includingCoronary artery ectasia (CAE) is a well-recognized angiographic finding, characterized by abnormal dilatation of the coronary arteries. We reviewed the current concepts of the condition including etiology, pathogenesis, flow alterations, clinical implications, prognosis and treatment. CAE is often viewed as a variant of obstructive coronary atherosclerosis. Exaggerated positive vascular remodeling due to inflammation, and chronic overstimulation of the endothelium by nitric oxide are potential causative mechanisms. The condition is associated with cardiovascular risk factors such as smoking and hypertension, while it appears to be inversely associated with age and diabetes mellitus. Patients with CAE typically present with angina, and are at risk for myocardial infarctions and sudden cardiac death due to slow flow, coronary vasospasm, dissection, and/or intracoronary thrombosis. CAE may be a diffuse disease associated with dilatation in other parts of the vasculature. As the incidence of this not so benign condition is expected to rise, the optimal treatment options remain undefined. Medical therapy with anticoagulants, nitrates and calcium channel blockers has been proposed and seems rational; however prospective studies with proof of efficacy are needed.

• Development and deployment of antigen arrays for investigation of B-cell fine specificity in autoimmune disease.

  Authors: Jeremy Sokolove, Tamsin M Lindstrom, William H Robinson

  Frontiers in bioscience (Elite edition). 4:320-30.

  Recent developments in proteomic technologies have enabled the high-throughput, multiplex measurement of large panels of antibodies in biological fluids of patients with immune-driven diseases.Recent developments in proteomic technologies have enabled the high-throughput, multiplex measurement of large panels of antibodies in biological fluids of patients with immune-driven diseases. Antigen microarrays are increasingly being used to delineate the natural history of autoantibody formation and epitope spread, and thus gain insight into the pathogenesis of autoimmune diseases, as well as into host immunity and its shortcomings. Characterization of autoimmunity that precedes the onset of clinically apparent disease has the potential to guide disease prevention using either conventional immunosupression or novel, antigen-specific tolerizing therapies. In addition, autoantibody profiling has the potential to identify molecular subtypes of a disease, which could allow for prediction of disease outcomes such as severity, tissue damage, and response to therapy.

• Trophinin in cell adhesion and signal transduction.

  Authors: Michiko N Fukuda, Kazuhiro Sugihara

  Frontiers in bioscience (Elite edition). 4:342-50.

  The process of human embryo implantation is mediated not only by evolutionarily conserved mechanisms but by activities unique to humans. Among the latter, evidence suggests that the cell adhesionThe process of human embryo implantation is mediated not only by evolutionarily conserved mechanisms but by activities unique to humans. Among the latter, evidence suggests that the cell adhesion molecule trophinin plays a unique role in human embryo implantation. Here, we describe characteristics of trophinin protein and of the trophinin-associated proteins bystin and tastin. We then describe trophinin-mediated signal transduction in trophectoderm cells during human embryo implantation and events related to human sperm tail motility. We also report dual roles for trophinin in human cancers in terms of promoting malignancy in some tumor types and suppressing it in others.

• Tissue factor in health and disease.

  Authors: Julie C Williams, Nigel Mackman

  Frontiers in bioscience (Elite edition). 4:358-72.

  Tissue Factor (TF) is a crucial initiator of the extrinsic coagulation cascade. TF is expressed on cells which are normally sequestered from blood. However, upon injury TF is exposed to the bloodTissue Factor (TF) is a crucial initiator of the extrinsic coagulation cascade. TF is expressed on cells which are normally sequestered from blood. However, upon injury TF is exposed to the blood resulting in activation of the coagulation cascade. TF dependent generation of coagulation proteases also initiates intracellular signaling through protease activated receptors. Pathologic TF expression is found in patients with a number of different diseases. This review will describe the roles of TF in health and disease as well as discuss approaches to reduce pathologic TF expression.

• Posttranslational modifications of tissue factor.

  Authors: Saulius Butenas, Jolanta Amblo-Krudysz, Kenneth G Mann

  Frontiers in bioscience (Elite edition). 4:381-91.

  Tissue factor (TF), a membrane protein, is an initiator of blood coagulation in vivo. In this review we discuss how posttranslational modifications affect activity and other properties of TF.Tissue factor (TF), a membrane protein, is an initiator of blood coagulation in vivo. In this review we discuss how posttranslational modifications affect activity and other properties of TF. Glycosylation of the extracellular domain and the composition of carbohydrates at three glycosylation sites have an influence on TF activity in the extrinsic FXase by increasing the rate of FX proteolysis. No influence of TF glycosylation on the activity of the FVIIa/TF complex towards small synthetic substrates was observed, suggesting that glycosylation has no effect on TF interaction with FVIIa. There are no published data suggesting a direct influence of phosphorylation or palmitoylation in the cytoplasmic domain on TF procoagulant activity. There has been a debate in the recent literature related to the role and formation of the Cys¹⁸⁶-Cys²⁰⁹ disulfide bond. Published opinions from various laboratories range from this bond being essential for the expression of cell TF activity to having no role in it. Overall, it is clear that some modifications of TF have an effect on TF procoagulant activity, signaling functions and trafficking. The influences of other modifications are debatable.

• Microdialysis: improving local chemotherapy in cancer using a mathematical model.

  Authors: Filipe Correia Martins, Jose Luis Santos, Carlos Freire de Oliveira

  Frontiers in bioscience (Elite edition). 4:401-9.

  Although intratumoral chemotherapy administration has been evaluated in the past, its results have not been frequently comparable to those from systemic administration. We recently describedAlthough intratumoral chemotherapy administration has been evaluated in the past, its results have not been frequently comparable to those from systemic administration. We recently described microdialysis as a method for local chemotherapy administration with increasing effectiveness while reducing systemic toxicity. We present a mathematical model which supports the successful application of this procedure in optimizing the administered drug in different cases, using informatics tools and considering several parameters. We also review and discuss important aspects of cancer biology that should be taken into consideration in cancer chemotherapy, such as tumor heterogeneity, drug resistance and metastasis, and how this technique may be used to overcome any set-backs presented by these.

• New strategies in cancer chemoprevention by phytochemicals.

  Authors: Madhulika Singh, Payal Singh, Yogeshwer Shukla

  Frontiers in bioscience (Elite edition). 4:426-52.

  Fruits, vegetables, spices, herbs and/or beverages are typical foods containing various phytochemicals that have been used for prevention and treatment of a variety of human ailments since timeFruits, vegetables, spices, herbs and/or beverages are typical foods containing various phytochemicals that have been used for prevention and treatment of a variety of human ailments since time immemorial. Nowadays, a large number of individuals are motivating towards the use of phytochemicals inorder to prevent or treat chronic diseases. Recent research efforts have been greatly emphasized on the recognition of naturally occurring plant derived substances that are capable of inhibiting, retarding or reversing the development of cancer. Several epidemiological annotations and a number of laboratory studies have indicated cancer chemopreventive and anti-carcinogenic potential of plant derived agents that have been traditionally used for treatment of varied human disorders in different parts of the globe. Molecular mechanisms which are involved for eliciting the effects of phytochemicals in cancerous cells are noticed in a range of experimental systems. This has opened up new avenue for researchers working in the field of chemoprevention and merits further scrutiny to establish the role of phytochemicals in prevention of fatal human diseases like cancer.

• Extended hepatic resection in advanced hepatoblastoma.

  Authors: Joerg Fuchs, Guido Seitz, Rupert Handgretinger, Steven W Warmann

  Frontiers in bioscience (Elite edition). 4:462-9.

  Complete surgical resection of the primary tumor is one of the most important prognostic factors for hepatoblastoma (HB). This goal can mean a relevant challenge in some cases of advanced HB,Complete surgical resection of the primary tumor is one of the most important prognostic factors for hepatoblastoma (HB). This goal can mean a relevant challenge in some cases of advanced HB, especially since an anatomical resection should be realised. Over recent years several surgical techniques for advanced liver resections in children have been developed and refined. In this article the authors summarize their own experience with advanced liver resections for HB and give an overview over indications and specifications for the different approaches.

• Activation of Wnt and Myc signaling in hepatoblastoma.

  Authors: Stefano Cairo, Carolina Armengol, Marie Annick Buendia

  Frontiers in bioscience (Elite edition). 4:480-6.

  Hepatoblastoma (HB) is the most common type of pediatric liver cancer. This tumor is thought to derive from hepatic progenitor cells that are arrested at various stages of liver development, asHepatoblastoma (HB) is the most common type of pediatric liver cancer. This tumor is thought to derive from hepatic progenitor cells that are arrested at various stages of liver development, as illustrated by a variety of histologic subtypes. Recent genomic studies have led to better understand the molecular pathogenesis of HB, to point out the crucial roles of the Wnt Myc signaling pathways in malignant transformation of liver progenitor cells. Molecular classification of HB based on genome-wide studies, as well as identification of reliable diagnostic prognostic markers, open the way to the development of new personalized targeted therapies for the management of aggressive lethal childhood tumors.

• Treatment of hepatoblastoma in the German cooperative pediatric liver tumor studies.

  Authors: Beate Haeberle, Dietrich von Schweinitz

  Frontiers in bioscience (Elite edition). 4:493-8.

  Treatment with neoadjuvant and adjuvant chemotherapy together with tumor resection changed treatment strategies in hepatoblastoma and led to prospective cooperative studies. The treatment strategiesTreatment with neoadjuvant and adjuvant chemotherapy together with tumor resection changed treatment strategies in hepatoblastoma and led to prospective cooperative studies. The treatment strategies and results of three German liver tumor studies HB89, HB94 and HB99 are reviewed. Here we provide an overview of the treatment of this tumor in the years 1989 to 2008 in Germany. The treatment protocols, aim of studies and results are outlined. The overall-survival (OS), response to chemotherapy and toxicity are followed over this period of different treatment. The overall-survival improved over the last years with 75 % in HB89, 77 % in HB94 and 89 % HB99. Patients with potentially resectable tumors have a good prognosis although the treatment was reduced over the last years. Patients with non resectable tumors or lung metastases have also a better but still bad prognosis. The intensified treatment for these patients in Germany in the last years showed comparable results to international studies but no advantage.

• Hair dye use and risk of human cancer.

  Authors: Yawei Zhang, Christopher Kim, Tongzhang Zheng

  Frontiers in bioscience (Elite edition). 4:516-28.

  Over 50% of the adult population will use hair dyes at some point in their lifetimes. Hair dyes consist of various chemicals and the composition of these chemicals vary by hair dye types. ChemicalsOver 50% of the adult population will use hair dyes at some point in their lifetimes. Hair dyes consist of various chemicals and the composition of these chemicals vary by hair dye types. Chemicals p-phenylenediamine and aminophenyl have been suggested as possible carcinogens or mutagens in experimental studies. The scientific community has been interested in this potential public health impact and the results of published epidemiological studies are summarized here. The current evidence provides limited evidences on the association between personal hair dye use and human cancer risk, except for the possibility of hematopoietic cancers and to a lesser extent, bladder cancer. Risk appears to be affected by time period of use and by specific genetic polymorphisms. Future studies should investigate potential gene and environment interaction to assess possible genetic susceptibility. Several methodological issues should also be considered in future studies including completed hair dye use information such as on timing, duration, frequency and type of hair dye product use.

• Dietary supplements and natural products in breast cancer trials.

  Authors: Karl Kado, Andrew Forsyth, Priyesh Ramesh Patel, Janice Ann Schwartz

  Frontiers in bioscience (Elite edition). 4:546-67.

  The association between breast cancer and modifiable health behaviors is well supported. At least one-half of all cancers are suggested to have a dietary component. It is not surprising thereforeThe association between breast cancer and modifiable health behaviors is well supported. At least one-half of all cancers are suggested to have a dietary component. It is not surprising therefore that many of the dietary agents and natural health products that have attracted the attentions of scientists and practitioners are now moving into clinical trials. In this report, we review 65 clinical intervention trials evaluating over 30 dietary supplements and natural health products for use in breast cancer. The products being tested in these trials fall broadly into the following categories: (i) vitamins, minerals, cofactors; (ii) herbal extracts; (iii) amino acids; (iv) fatty acids; (v) animal products; (vi) probiotics; (vii) phytochemicals; and (viii) combination formulations. Trial outcome measures include risk modification, efficacy testing (with dietary supplements alone or dietary supplement-anticancer drug combinations), toxicity reduction, biomarker identification, symptom management, and quality of life parameters. The wide range of interests in natural product testing at the clinical trial level supports the potential utility of these agents in the breast cancer prevention, treatment, and management regimens of the future.

• Transcriptional regulation of CFTR gene expression.

  Authors: Austin E Gillen, Ann Harris

  Frontiers in bioscience (Elite edition). 4:587-92.

  Cystic Fibrosis results from mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The gene was identified in 1989, but more than 20 years later, the regulatory mechanismsCystic Fibrosis results from mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The gene was identified in 1989, but more than 20 years later, the regulatory mechanisms controlling its complex expression are still not fully understood. Though the promoter binds transcription factors and drives some aspects of CFTR gene expression, it cannot alone account for tissue specific control. This implicates other distal cis-acting elements in cell-type-specific regulation of CFTR expression. Several of these elements, including intronic enhancers and flanking insulators, were identified within or near the CFTR locus. Here we summarize the known regulatory mechanisms controlling CFTR transcription, including those acting through elements in the promoter and others elsewhere in the locus. A special focus will be elements that contribute to tissue specific regulation of expression.

• Neuroprotective role of estrogens: relationship with insulin/IGF-1 signaling.

  Authors: Ana Alonso, Celestino Gonzalez

  Frontiers in bioscience (Elite edition). 4:607-19.

  Postmenopausal women have an elevated risk of developing a neurodegenerative disease. These clinical observation supported by basic research, suggest that estrogens are neuroprotective. InsulinPostmenopausal women have an elevated risk of developing a neurodegenerative disease. These clinical observation supported by basic research, suggest that estrogens are neuroprotective. Insulin resistance represents an independent factor in the etiology of age-associated disease and metabolic syndrome should be considered as a contributing factor to the higher post-menopausal vulnerability to neurological disorders. Elucidating the relationship between insulin resistance associated with aging in females, and the cross-talk between estradiol, insulin, and insulin-like growth factor (IGF-1) signaling pathways, will lead to a more complete understanding of the mechanism underlying estradiol-mediated neuroprotection. In past decades, estrogen replacement therapy (ERT) was commonly used as a palliative therapy during menopause, but the mid-term and long-term effects of estrogen as possible promoters of breast cancer and the increased risk of coronary illness or stroke, has limited current usage. A deeper understanding of the molecular mechanisms common to all forms of neurodegenerative diseases may hasten the development of protective strategies against chronic age-related deterioration and acute illness, ultimately providing a better quality of life for the elderly.

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