This is an RSS newsfeed from BioMed Central It is intended to be used with an RSS reader. For more information about RSS newsfeeds from BioMed Central, visit http://www.biomedcentral.com/info/about/rss/ http://www.translational-medicine.commostviewed/ Most viewed articles in last 30 days from Journal of Translational Medicine (ISSN 1479-5876) published by BioMed Central Background: Nitric oxide-releasing nonsteroidal antiinflammatory drugs (NO-NSAIDs) are reported to be safer than NSAIDs because of their lower gastric toxicity. We compared the effect of a novel NO-releasing derivate, NCX 4040, with that of aspirin and its denitrated analog, NCX 4042, in in vitro and in vivo human colon cancer models and investigated the mechanisms of action underlying its antitumor activity. Methods: In vitro cytotoxicity was evaluated on a panel of colon cancer lines (LoVo, LoVo Dx, WiDr and LRWZ) by sulforhodamine B assay. Cell cycle perturbations and apoptosis were evaluated by flow cytometry. Protein expression was detected by Western blot. In the in vivo experiments, tumor-bearing mice were treated with NCX 4040, five times a week, for six consecutive weeks. Results: In the in vitro studies, aspirin and NCX 4042 did not induce an effect on any of the cell lines, whereas NCX 4040 produced a marked cytostatic dose-related effect, indicating a pivotal role of the -NO2 group. Furthermore, in LoVo and LRWZ cell lines, we observed caspase-9 and -3-mediated apoptosis, whereas no apoptotic effect was observed after drug exposure in WiDr or LoVo Dx cell lines. In in vivo studies, both NCX 4040 and its parental compound were administered per os. NCX 4040 induced a 40% reduction in tumor weight. Conversely, aspirin did not influence tumor growth at all. Conclusions: NCX 4040, but not its parental compound, aspirin, showed an in vitro and in vivo antiproliferative activity, indicating its potential usefulness to treat colon cancer. http://www.translational-medicine.com/content/3/1/7 Anna Tesei, Paola Ulivi, Francesco Fabbri, Marco Rosetti, Carlo Leonetti, Marco Scarsella, Gabriella Zupi, Dino Amadori, Manlio Bolla and Wainer Zoli Journal of Translational Medicine 2005, 3:7 Number of accesses: 704 2005-02-03 doi:10.1186/1479-5876-3-7 Journal of Translational Medicine 1479-5876 3 7 2005-02-03 Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions whose incidence is reaching epidemic proportions, afflicting approximately 1 in 166 children. Autistic disorder, or autism is the most common form of ASD. Although several neurophysiological alterations have been associated with autism, immune abnormalities and neural hypoperfusion appear to be broadly consistent. These appear to be causative since correlation of altered inflammatory responses, and hypoperfusion with symptology is reported. Mesenchymal stem cells (MSC) are in late phases of clinical development for treatment of graft versus host disease and Crohn's Disease, two conditions of immune dysregulation. Cord blood CD34+ cells are known to be potent angiogenic stimulators, having demonstrated positive effects in not only peripheral ischemia, but also in models of cerebral ischemia. Additionally, anecdotal clinical cases have reported responses in autistic children receiving cord blood CD34+ cells. We propose the combined use of MSC and cord blood CD34+cells may be useful in the treatment of autism. http://www.translational-medicine.com/content/5/1/30 Thomas E Ichim, Fabio Solano, Eduardo Glenn, Frank Morales, Leonard Smith, George Zabrecky and Neil H Riordan Journal of Translational Medicine 2007, 5:30 Number of accesses: 666 2007-06-27 doi:10.1186/1479-5876-5-30 Journal of Translational Medicine 1479-5876 5 30 2007-06-27 Background: The golden retriever muscular dystrophy (GRMD) dogs represent the best available animal model for therapeutic trials aiming at the future treatment of human Duchenne muscular dystrophy (DMD). We have obtained a rare litter of six GRMD dogs (3 males and 3 females) born from an affected male and a carrier female which were submitted to a therapeutic trial with adult human stem cells to investigate their capacity to engraft into dogs muscles by local as compared to systemic injection without any immunosuppression. Methods: Human Immature Dental Pulp Stem Cells (hIDPSC) were transplanted into 4 littermate dogs aged 28 to 40 days by either arterial or muscular injections. Two non-injected dogs were kept as controls. Clinical translation effects were analyzed since immune reactions by blood exams and physical scores capacity of each dog. Samples from biopsies were checked by immunohistochemistry (dystrophin markers) and FISH for human probes. Results and Discussion: We analyzed the cells' ability in respect to migrate, engraftment, and myogenic potential, and the expression of human dystrophin in affected muscles. Additionally, the efficiency of single and consecutive early transplantation was compared. Chimeric muscle fibers were detected by immunofluorescence and fluorescent in situ hybridisation (FISH) using human antibodies and X and Y DNA probes. No signs of immune rejection were observed and these results suggested that hIDPSC cell transplantation may be done without immunosuppression. We showed that hIDPSC presented significant engraftment in GRMD dog muscles, although human dystrophin expression was modest and limited to several muscle fibers. Better clinical condition was also observed in the dog, which received monthly arterial injections and is still clinically stable at 25 months of age. Conclusions: Our data suggested that systemic multiple deliveries seemed more effective than local injections. These findings open important avenues for further researches. http://www.translational-medicine.com/content/6/1/35 Irina Kerkis, Carlos E Ambrosio, Alexandre Kerkis, Daniele S Martins, Eder Zucconi, Simone AS Fonseca, Rosa M Cabral, Carlos MC Maranduba, Thais P Gaiad, Adriana C Morini, Natassia M Vieira, Marina P Brolio, Osvaldo A Sant'Anna, Maria A Miglino and Mayana Zatz Journal of Translational Medicine 2008, 6:35 Number of accesses: 664 2008-07-03 doi:10.1186/1479-5876-6-35 Journal of Translational Medicine 1479-5876 6 35 2008-07-03 "Translational medicine" as a fashionable term is being increasingly used to describe the wish of biomedical researchers to ultimately help patients. Despite increased efforts and investments into R&D, the output of novel medicines has been declining dramatically over the past years. Improvement of translation is thought to become a remedy as one of the reasons for this widening gap between input and output is the difficult transition between preclinical ("basic") and clinical stages in the R&D process. Animal experiments, test tube analyses and early human trials do simply not reflect the patient situation well enough to reliably predict efficacy and safety of a novel compound or device. This goal, however, can only be achieved if the translational processes are scientifically backed up by robust methods some of which still need to be developed. This mainly relates to biomarker development and predictivity assessment, biostatistical methods, smart and accelerated early human study designs and decision algorithms among other features. It is therefore claimed that a new science needs to be developed called 'translational science in medicine'. http://www.translational-medicine.com/content/6/1/31 Martin Wehling Journal of Translational Medicine 2008, 6:31 Number of accesses: 614 2008-06-17 doi:10.1186/1479-5876-6-31 Journal of Translational Medicine 1479-5876 6 31 2008-06-17 Angiogenesis is a critical component of the proliferative endometrial phase of the menstrual cycle. Thus, we hypothesized that a stem cell-like population exist and can be isolated from menstrual blood. Mononuclear cells collected from the menstrual blood contained a subpopulation of adherent cells which could be maintained in tissue culture for >68 doublings and retained expression of the markers CD9, CD29, CD41a, CD44, CD59, CD73, CD90 and CD105, without karyotypic abnormalities. Proliferative rate of the cells was significantly higher than control umbilical cord derived mesenchymal stem cells, with doubling occurring every 19.4 hours. These cells, which we termed "Endometrial Regenerative Cells" (ERC) were capable of differentiating into 9 lineages: cardiomyocytic, respiratory epithelial, neurocytic, myocytic, endothelial, pancreatic, hepatic, adipocytic, and osteogenic. Additionally, ERC produced MMP3, MMP10, GM-CSF, angiopoietin-2 and PDGF-BB at 10–100,000 fold higher levels than two control cord blood derived mesenchymal stem cell lines. Given the ease of extraction and pluripotency of this cell population, we propose ERC as a novel alternative to current stem cells sources. http://www.translational-medicine.com/content/5/1/57 Xiaolong Meng, Thomas E Ichim, Jie Zhong, Andrea Rogers, Zhenglian Yin, James Jackson, Hao Wang, Wei Ge, Vladimir Bogin, Kyle W Chan, Bernard Thébaud and Neil H Riordan Journal of Translational Medicine 2007, 5:57 Number of accesses: 572 2007-11-15 doi:10.1186/1479-5876-5-57 Journal of Translational Medicine 1479-5876 5 57 2007-11-15 Background: The pathogenesis of nasopharyngeal carcinoma (NPC) is a complicated process involving genetic predisposition, Epstein-Bar Virus infection, and genetic alterations. Although some oncogenes and tumor suppressor genes have been previously reported in NPC, a complete understanding of the pathogenesis of NPC in the context of global gene expression, transcriptional pathways and biomarker assessment remains to be elucidated. Methods: Total RNA from 32 pathologically-confirmed cases of poorly-differentiated NPC was divided into pools inclusive of four consecutive specimens and each pool (T1 to T8) was co-hybridized with pooled RNA from 24 normal non-cancerous nasopharyngeal tissues (NP) to a human 8K cDNA array platform. The reliability of microarray data was validated for selected genes by semi-quantitative RT-PCR and immunohistochemistry. Results: Stringent statistical filtering parameters identified 435 genes to be up-regulated and 257 genes to be down-regulated in NPC compared to NP. Seven up-regulated genes including CYC1, MIF, LAMB3, TUBB2, UBE2C and TRAP1 had been previously proposed as candidate common cancer biomarkers based on a previous extensive comparison among various cancers and normal tissues which did not, however, include NPC or NP. In addition, nine known oncogenes and tumor suppressor genes, MIF, BIRC5, PTTG1, ATM, FOXO1A, TGFBR2, PRKAR1A, KLF5 and PDCD4 were identified through the microarray literature-based annotation search engine MILANO, suggesting these genes may be specifically involved in the promotion of the malignant conversion of nasopharyngeal epithelium. Finally, we found that these differentially expressed genes were involved in apoptosis, MAPK, VEGF and B cell receptor signaling pathways and other functions associated with cell growth, signal transduction and immune system activation. Conclusion: This study identified potential candidate biomarkers, oncogenes/tumor suppressor genes involved in several pathways relevant to the oncogenesis of NPC. This information may facilitate the determination of diagnostic and therapeutic targets for NPC as well as provide insights about the molecular pathogenesis of NPC. http://www.translational-medicine.com/content/6/1/32 Weiyi Fang, Xin Li, Qingping Jiang, Zhen Liu, Huiling Yang, Shuang Wang, Siming Xie, Qiuzhen Liu, Tengfei Liu, Jing Huang, Weibing Xie, Zuguo Li, Yingdong Zhao, Ena Wang, Francesco M Marincola and Kaitai Yao Journal of Translational Medicine 2008, 6:32 Number of accesses: 543 2008-06-20 doi:10.1186/1479-5876-6-32 Journal of Translational Medicine 1479-5876 6 32 2008-06-20 We have known for some time that the epidemiology of human stroke is sexually dimorphic until late in life, well beyond the years of reproductive senescence and menopause. Now, a new concept is emerging: the mechanisms and outcome of cerebral ischemic injury are influenced strongly by biological sex as well as the availability of sex steroids to the brain. The principal mammalian estrogen (17 β estradiol or E2) is neuroprotective in many types of brain injury and has been the major focus of investigation over the past several decades. However, it is becoming increasingly clear that although hormones are a major contributor to sex-specific outcomes, they do not fully account for sex-specific responses to cerebral ischemia. The purpose of this review is to highlight recent studies in cell culture and animal models that suggest that genetic sex determines experimental stroke outcome and that divergent cell death pathways are activated after an ischemic insult. These sex differences need to be identified if we are to develop efficacious neuroprotective agents for use in stroke patients. http://www.translational-medicine.com/content/6/1/33 Jesse T Lang and Louise D McCullough Journal of Translational Medicine 2008, 6:33 Number of accesses: 436 2008-06-23 doi:10.1186/1479-5876-6-33 Journal of Translational Medicine 1479-5876 6 33 2008-06-23 Background: Quantification of T-cell receptor (TCR) chain families can be utilized for detection of clonal T-cell populations. Besides southern blotting and antibody-based approaches, quantitative real time PCR (qRT PCR) has been more widely applied in this context during the last years. Here, the heterogeneity of sequences within single families is the most challenging problem for exact quantification.MethodVβ-families were quantified using a universal reverse primer and family-specific forward primers with TaqMan technology on a light cycler instrument. Relative concentrations were calculated considering slopes and crossing points of each PCR reaction. Total expression of α/β TCR was assessed by quantification of the constant α-chain as a further control. Results: The method was tested by serial dilutions of clonal T-cells in mononuclear cells from healthy volunteers. Calculated percentages were in good correspondence with qRT PCR results demonstrating high reliability. Duplicates showed excellent technical reproducibility. We analyzed blood samples of 20 healthy volunteers for determination of mean and standard deviation for each family. The method was applied both to tissue and blood samples from patients with carcinomas and hematological disorders. Conclusion: We introduce a versatile method for the relative quantification of Vβ-families by real time PCR. The experimental strategy described allows the identification of alterations in the Vβ-family repertoire. http://www.translational-medicine.com/content/6/1/34 Sebastian Ochsenreither, Alberto Fusi, Antonia Busse, Dirk Nagorsen, David Schrama, Jürgen Becker, Eckhard Thiel and Ulrich Keilholz Journal of Translational Medicine 2008, 6:34 Number of accesses: 426 2008-07-01 doi:10.1186/1479-5876-6-34 Journal of Translational Medicine 1479-5876 6 34 2008-07-01 Research has found that certain bacteria are associated with human cancers. Their role, however, is still unclear. Convincing evidence links some species to carcinogenesis while others appear promising in the diagnosis, prevention or treatment of cancers. The complex relationship between bacteria and humans is demonstrated by Helicobacter pylori and Salmonella typhi infections. Research has shown that H. pylori can cause gastric cancer or MALT lymphoma in some individuals. In contrast, exposure to H. pylori appears to reduce the risk of esophageal cancer in others. Salmonella typhi infection has been associated with the development of gallbladder cancer; however S. typhi is a promising carrier of therapeutic agents for melanoma, colon and bladder cancers. Thus bacterial species and their roles in particular cancers appear to differ among different individuals. Many species, however, share an important characteristic: highly site-specific colonization. This critical factor may lead to the development of non-invasive diagnostic tests, innovative treatments and cancer vaccines. http://www.translational-medicine.com/content/4/1/14 DL Mager Journal of Translational Medicine 2006, 4:14 Number of accesses: 392 2006-03-28 doi:10.1186/1479-5876-4-14 Journal of Translational Medicine 1479-5876 4 14 2006-03-28 When we launched the Journal of Translational Medicine a few months ago, we were interested primarily in exploring scientific consideration of this discipline. However, as editors of JTM, we have been contacted almost daily to discuss the problems faced by scientists and clinicians around the world who are challenging the traditional boundaries of science and medicine. Through these conversations, we have learned that translational medicine is in fact "lost in translation," inspiring much angst, many promises and some Federal appropriations. However, little has been done to substantively promote this important field. Authoritative reviews on the subject are available to the interested reader 1234567. In this article, we will address JTM's "constituency" to report what we've learned about the obstacles to translational medicine from the myriad of phone conversations and e-mail interactions. http://www.translational-medicine.com/content/2/1/14 Stacey P Mankoff, Christian Brander, Soldano Ferrone and Francesco M Marincola Journal of Translational Medicine 2004, 2:14 Number of accesses: 338 2004-05-18 doi:10.1186/1479-5876-2-14 Journal of Translational Medicine 1479-5876 2 14 2004-05-18