Method for Inhibition of Photocarcinogenesis or Photoimmunosuppression Using Niacin

The invention is directed to novel methods for the suppression of photocarcinogenesis and photoimmunosuppression in mice. The novel methods comprises the step of administering to a subject a pharmaceutical composition comprising niacin and a pharmaceutical carrier

Reduction of Murine Cutaneous UVB-Induced Tumor-Infiltrating T Lymphocytes by Dietary Canthaxanthin

The effect of dietary canthaxanthin, retinyl palmitate, or their combination on the tumor-infiltrating T-lymphocyte response (T-TIL) in de novo murine ultraviolet type B irradiation-induced tumors was investigated to elucidate potential mechanisms of action of these compounds. We found that dietary canthaxanthin greatly reduced the number of tumor-infiltrating helper/inducer, suppressor/cytotoxic, and interleukin-2 receptor-positive T lymphocytes and also observed a concomitant statistically significant increase in tumour incidence in canthaxanthin-fed animals. The addition of retinyl palmitate to the canthaxanthin diet ameliorated this negative effect on TIL and the development of skin tumors. We conclude that dietary retinyl palmitate and canthaxanthin can modulate the host T-cell immune response within a growing tumor and may affect tumorigenicity

Analysis of western lowland gorilla (Gorilla gorilla gorilla) specific Alu repeats

Background: Research into great ape genomes has revealed widely divergent activity levels over time for Alu elements. However, the diversity of this mobile element family in the genome of the western lowland gorilla has previously been uncharacterized. Alu elements are primate-specific short interspersed elements that have been used as phylogenetic and population genetic markers for more than two decades. Alu elements are present at high copy number in the genomes of all primates surveyed thus far. The AluY subfamily and its derivatives have been recognized as the evolutionarily youngest Alu subfamily in the Old World primate lineage. Results: Here we use a combination of computational and wet-bench laboratory methods to assess and catalog AluY subfamily activity level and composition in the western lowland gorilla genome (gorGor3.1). A total of 1,075 independent AluY insertions were identified and computationally divided into 10 subfamilies, with the largest number of gorilla-specific elements assigned to the canonical AluY subfamily. Conclusions: The retrotransposition activity level appears to be significantly lower than that seen in the human and chimpanzee lineages, while higher than that seen in orangutan genomes, indicative of differential Alu amplification in the western lowland gorilla lineage as compared to other Homininae. © 2013 McLain et al.; licensee BioMed Central Ltd

Analysis of western lowland gorilla (Gorilla gorilla gorilla) specific Alu repeats

Abstract Background Research into great ape genomes has revealed widely divergent activity levels over time for Alu elements. However, the diversity of this mobile element family in the genome of the western lowland gorilla has previously been uncharacterized. Alu elements are primate-specific short interspersed elements that have been used as phylogenetic and population genetic markers for more than two decades. Alu elements are present at high copy number in the genomes of all primates surveyed thus far. The AluY subfamily and its derivatives have been recognized as the evolutionarily youngest Alu subfamily in the Old World primate lineage. Results Here we use a combination of computational and wet-bench laboratory methods to assess and catalog AluY subfamily activity level and composition in the western lowland gorilla genome (gorGor3.1). A total of 1,075 independent AluY insertions were identified and computationally divided into 10 subfamilies, with the largest number of gorilla-specific elements assigned to the canonical AluY subfamily. Conclusions The retrotransposition activity level appears to be significantly lower than that seen in the human and chimpanzee lineages, while higher than that seen in orangutan genomes, indicative of differential Alu amplification in the western lowland gorilla lineage as compared to other Homininae.http://deepblue.lib.umich.edu/bitstream/2027.42/112762/1/13100_2013_Article_86.pd

Plectin as a prognostic marker in non-metastatic oral squamous cell carcinoma

Background: Oral squamous cell carcinoma (OSCC) is associated with a poor 5-year survival rate. In general, patients diagnosed with small tumors have a fairly good prognosis, but some small tumors have an aggressive behavior leading to early death. There are at present no reliable prognostic biomarkers for oral cancers. Thus, to optimize treatment for the individual patient, there is a need for biomarkers that can predict tumor behavior. Method: In the present study the potential prognostic value of plectin was evaluated by a tissue microarray (TMA) based immunohistochemical analysis of primary tumor tissue obtained from a North Norwegian cohort of 115 patients diagnosed with OSCC. The expression of plectin was compared with clinicopathological variables and 5 year survival. Results: The statistical analysis revealed that low expression of plectin in the tumor cells predicted a favorable outcome for patients with non-metastatic disease (p = 0.008). Furthermore, the expression of plectin was found to correlate (p = 0.01) with the expression of uPAR, which we have previously found to be a potential prognostic marker for T1N0 tumors. Conclusions: Our results indicate that low expression of plectin predicts a favorable outcome for patients with non-metastatic OSCC and the expression level of plectin may therefore be used in the treatment stratification for patients with early stage disease

Tofacitinib for the treatment of ankylosing spondylitis: a phase III, randomised, double-blind, placebo-controlled study

Objective To assess the efficacy/safety of tofacitinib in adult patients with active ankylosing spondylitis (AS).Methods This phase III, randomised, double-blind, placebo-controlled study enrolled patients aged >= 18 years diagnosed with active AS, meeting the modified New York criteria, with centrally read radiographs, and an inadequate response or intolerance to >= 2 non-steroidal anti-inflammatory drugs. Patients were randomised 1:1 to receive tofacitinib 5 mg two times per day or placebo for 16 weeks. After week 16, all patients received open-label tofacitinib until week 48. The primary and key secondary endpoints were Assessment of SpondyloArthritis international Society >= 20% improvement (ASAS20) and >= 40% improvement (ASAS40) responses, respectively, at week 16. Safety was assessed throughout.Results 269 patients were randomised and treated: tofacitinib, n=133; placebo, n=136. At week 16, the ASAS20 response rate was significantly (p tofacitinib, 2 (1.5%) patients had non-serious herpes zoster. There were no deaths, malignancies, major adverse cardiovascular events, thromboembolic events or opportunistic infections.Conclusions In adults with active AS, tofacitinib demonstrated significantly greater efficacy versus placebo. No new potential safety risks were identified.Pathophysiology and treatment of rheumatic disease

Biopolymers for Antitumor Implantable Drug Delivery Systems: Recent Advances and Future Outlook

In spite of remarkable improvements in cancer treatments and survivorship, cancer still remains as one of the major causes of death worldwide. Although current standards of care provide encouraging results, they still cause severe systemic toxicity and also fail in preventing recurrence of the disease. In order to address these issues, biomaterial-based implantable drug delivery systems (DDSs) have emerged as promising therapeutic platforms, which allow local administration of drugs directly to the tumor site. Owing to the unique properties of biopolymers, they have been used in a variety of ways to institute biodegradable implantable DDSs that exert precise spatiotemporal control over the release of therapeutic drug. Here, the most recent advances in biopolymer-based DDSs for suppressing tumor growth and preventing tumor recurrence are reviewed. Novel emerging biopolymers as well as cutting-edge polymeric microdevices deployed as implantable antitumor DDSs are discussed. Finally, a review of a new therapeutic modality within the field, which is based on implantable biopolymeric DDSs, is given

Polygenic risk scores have high diagnostic capacity in ankylosing spondylitis

We would like to thank all participating subjects with AS and healthy individuals who provided the DNA and clinical information necessary for this study. The TASC study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) grants P01-052915, R01-AR046208. Funding was also received from the University of Texas Health Science Center at Houston CTSA grant UL1RR02418, Cedars-Sinai GCRC grant MO1-RR00425, Intramural Research Program, NIAMS/NIH, and Rebecca Cooper Foundation (Australia). This study was funded, in part, by Arthritis Research UK (Grants 19536 and 18797), by the Wellcome Trust (grant number 076113), and by the Oxford Comprehensive Biomedical Research Centre ankylosing spondylitis chronic disease cohort (Theme Code: A91202). JZB was funded by a grant from the Zhejiang Provincial Natural Science Foundation of China (LD18H120001LD). The New Zealand data was derived from participants in the Spondyloarthritis Genetics and the Environment Study (SAGE) and was funded by The Health Research Council, New Zealand. HX was funded by the National Natural Science Foundation of China (Grant 81430031) and China Ministry of Science and Technology (973 Program of China 2014CB541800). We acknowledge the Understanding Society: The UK Household Longitudinal Study. This is led by the Institute for Social and Economic Research at the University of Essex and funded by the Economic and Social Research Council. The survey was conducted by NatCen and the genome-wide scan data were analysed and deposited by the Wellcome Trust Sanger Institute. Information on how to access the data can be found on the Understanding Society website https: www.understandingsociety.ac.uk/. French sample collection was performed by the Groupe Française d’Etude Génétique des Spondylarthrites, coordinated by Professor Maxime Breban and funded by the Agence Nationale de Recherche GEMISA grant reference ANR-10-MIDI-0002. We acknowledge and thank the TCRI AS Group for their support in recruiting patients for the study (see below). The authors acknowledge the sharing of data and samples by the BSRBR-AS Register in Aberdeen. Chief Investigator, Prof Gary Macfarlane and Dr. Gareth Jones, Deputy Chief Investigator created the BSRBR-AS study which was commissioned by the British Society for Rheumatology, funded in part by Abbvie, Pfizer and UCB. We are grateful to every patient, past and present staff of the BSRBR-AS register team and to all clinical staff who recruited patients, followed them up and entered data – details here: https://www.abdn.ac.uk/iahs/research/epidemiology/spondyloarthritis.php#panel1011. The QIMR control samples were from parents of adolescent twins collected in the context of the Brisbane Longitudinal Twin Study 1992–2016, support by grants from NHMRC (NGM) and ARC (MJW). We thank Anjali Henders, Lisa Bowdler, Tabatha Goncales for biobank collection and Kerrie McAloney and Scott Gordon for curating samples for this study. MAB is funded by a National Health and Medical Research Council (Australia) Senior Principal Research Fellowship (1024879), and support for this study was received from a National Health and Medical Research Council (Australia) program grant (566938) and project grant (569829), and from the Australian Cancer Research Foundation and Rebecca Cooper Medical Research Foundation. We are also very grateful for the invaluable support received from the National Ankylosing Spondylitis Society (UK) and Spondyloarthritis Association of America in case recruitment. Additional financial and technical support for patient recruitment was provided by the National Institute for Health Research Oxford Musculoskeletal Biomedical Research Unit and NIHR Thames Valley Comprehensive Local Research and an unrestricted educational grant from Abbott Laboratories. This research was funded/supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London and/or the NIHR Clinical Research Facility. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.Peer reviewedPublisher PD

Prediction of outcome in individuals with diabetic foot ulcers: focus on the differences between individuals with and without peripheral arterial disease. The EURODIALE Study

Aims/hypothesis Outcome data on individuals with diabetic foot ulcers are scarce, especially in those with peripheral arterial disease (PAD). We therefore examined the clinical characteristics that best predict poor outcome in a large population of diabetic foot ulcer patients and examined whether such predictors differ between patients with and without PAD. Methods Analyses were conducted within the EURODIALE Study, a prospective cohort study of 1,088 diabetic foot ulcer patients across 14 centres in Europe. Multiple logistic regression modelling was used to identify independent predictors of outcome (i.e. non-healing of the foot ulcer). Results After 1 year of follow-up, 23% of the patients had not healed. Independent baseline predictors of non-healing in the whole study population were older age, male sex, heart failure, the inability to stand or walk without help, end-stage renal disease, larger ulcer size, peripheral neuropathy and PAD. When analyses were performed according to PAD status, infection emerged as a specific predictor of non-healing in PAD patients only. Conclusions/Interpretation Predictors of healing differ between patients with and without PAD, suggesting that diabetic foot ulcers with or without concomitant PAD should be defined as two separate disease states. The observed negative impact of infection on healing that was confined to patients with PAD needs further investigation