Retraction: a novel combination of Chinese medicines to treat advanced cancers and lymphomas tested in rats

<p>Abstract</p> <p/> <p>The author has withdrawn this article <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> from the public domain because they did not have permission to use the data that was presented within. In the light of this situation, BioMed Central regrets that this article is no longer available. The author apologises to all parties for the inconvenience.</p

Current Reflections on Collaborative and Engaged Research

The purpose of this article is to discuss the key elements of a meaningful research collaboration strategy between community-service organizations and academia. We discuss the challenges in developing an effective partnership, and we highlight current strategies for sustainable research partnerships between academia and community. To address the issue of effective partnership we include a case study to illustrate the connections among community-service organization contexts, by focusing on the research and capacity building infrastructure and specific forms of research education. Although the community-university relationship tends to push the work toward a consultant-driven model, this article emphasizes the need for a guiding framework to foster a more meaningful agenda for collaborative research in future

Liposomal irinotecan: formulation development and therapeutic assessment in murine xenograft models of colorectal cancer

ABSTRACT Purpose: The purpose is to demonstrate whether an appropriately designed liposomal formulation of irinotecan is effective in treating mice with liver-localized colorectal carcinomas. Experimental Design: Irinotecan was encapsulated in 1,2-distearoyl-sn-glycero-3-phosphocholine/cholesterol (55:45 molar ratio) liposomes using an ionophore (A23187)-generated transmembrane proton gradient. This formulation was evaluated in vivo by measuring plasma elimination of liposomal lipid and drug after i.v. administration. Therapeutic activity was determined in SCID/Rag-2M mice bearing s.c. LS180 tumors or orthotopic LS174T colorectal metastases. Results: Drug elimination from the plasma was significantly reduced when irinotecan was administered in the liposomal formulation. At 1 hour after i.v. administration, circulating levels of the liposomal drug were 100-fold greater than that of irinotecan given at the same dose. High-performance liquid chromatographic analysis of plasma samples indicated that liposomal irinotecan was protected from inactivating hydrolysis to the carboxylate form. This formulation exhibited substantially improved therapeutic effects. For the LS180 solid tumor model, it was shown that after a single injection of liposomal irinotecan at 50 mg/kg, the time to progress to a 400-mg tumor was 34 days (as compared with 22 days for animals treated with free drug at an equivalent dose). In the model of colorectal liver metastases (LS174T), a median survival time of 79 days was observed after treatment with liposomal irinotecan (50 mg/kg, given every 4 days for a total of three doses). Saline and free drug treated mice survived for 34 and 53 days, respectively. Conclusions: These results illustrate that liposomal encapsulation can substantially enhance the therapeutic activity of irinotecan and emphasize the potential for using liposomal irinotecan to treat liver metastases

Association between rheumatoid arthritis disease activity, progression of functional limitation and long-term risk of orthopaedic surgery : Combined analysis of two prospective cohorts supports EULAR treat to target DAS thresholds

Objectives: To examine the association between disease activity in early rheumatoid arthritis (RA), functional limitation and long-term orthopaedic episodes. Methods: Health Assessment Questionnaire (HAQ) disability scores were collected from two longitudinal early RA inception cohorts in routine care; Early Rheumatoid Arthritis Study and Early Rheumatoid Arthritis Network from 1986 to 2012. The incidence of major and intermediate orthopaedic surgical episodes over 25 years was collected from national data sets. Disease activity was categorised by mean disease activity score (DAS28) annually between years 1 and 5; remission (RDAS≤2.6), low (LDAS>2.6-3.2), low-moderate (LMDAS≥3.2-4.19), high-moderate (HMDAS 4.2-5.1) and high (HDAS>5.1). Results: Data from 2045 patients were analysed. Patients in RDAS showed no HAQ progression over 5 years, whereas there was a significant relationship between rising DAS28 category and HAQ at 1 year, and the rate of HAQ progression between years 1 and 5. During 27 986 person-years follow-up, 392 intermediate and 591 major surgeries were observed. Compared with the RDAS category, there was a significantly increased cumulative incidence of intermediate surgery in HDAS (OR 2.59 CI 1.49 to 4.52) and HMDAS (OR 1.8 CI 1.05 to 3.11) categories, and for major surgery in HDAS (OR 2.48 CI 1.5 to 4.11), HMDAS (OR 2.16 CI 1.32 to 3.52) and LMDAS (OR 2.07 CI 1.28 to 3.33) categories. There was no significant difference in HAQ progression or orthopaedic episodes between RDAS and LDAS categories. Conclusions: There is an association between disease activity and both poor function and long-term orthopaedic episodes. This illustrates the far from benign consequences of persistent moderate disease activity, and supports European League Against Rheumatism treat to target recommendations to secure low disease activity or remission in all patients.Peer reviewedFinal Published versio

Gene content evolution in the arthropods

Arthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from and recorded in adaptive changes in the genome. Dissection of the genomic record of sequence change enables broad questions regarding genome evolution to be addressed, even across hyper-diverse taxa within arthropods. Using 76 whole genome sequences representing 21 orders spanning more than 500 million years of arthropod evolution, we document changes in gene and protein domain content and provide temporal and phylogenetic context for interpreting these innovations. We identify many novel gene families that arose early in the evolution of arthropods and during the diversification of insects into modern orders. We reveal unexpected variation in patterns of DNA methylation across arthropods and examples of gene family and protein domain evolution coincident with the appearance of notable phenotypic and physiological adaptations such as flight, metamorphosis, sociality, and chemoperception. These analyses demonstrate how large-scale comparative genomics can provide broad new insights into the genotype to phenotype map and generate testable hypotheses about the evolution of animal diversity

Brown marmorated stink bug, Halyomorpha halys (Stål), genome: putative underpinnings of polyphagy, insecticide resistance potential and biology of a top worldwide pest

Background Halyomorpha halys (Stål), the brown marmorated stink bug, is a highly invasive insect species due in part to its exceptionally high levels of polyphagy. This species is also a nuisance due to overwintering in human-made structures. It has caused significant agricultural losses in recent years along the Atlantic seaboard of North America and in continental Europe. Genomic resources will assist with determining the molecular basis for this species’ feeding and habitat traits, defining potential targets for pest management strategies. Results Analysis of the 1.15-Gb draft genome assembly has identified a wide variety of genetic elements underpinning the biological characteristics of this formidable pest species, encompassing the roles of sensory functions, digestion, immunity, detoxification and development, all of which likely support H. halys’ capacity for invasiveness. Many of the genes identified herein have potential for biomolecular pesticide applications. Conclusions Availability of the H. halys genome sequence will be useful for the development of environmentally friendly biomolecular pesticides to be applied in concert with more traditional, synthetic chemical-based controls

Rapid Changes in the Light/Dark Cycle Disrupt Memory of Conditioned Fear in Mice

Background: Circadian rhythms govern many aspects of physiology and behavior including cognitive processes. Components of neural circuits involved in learning and memory, e.g., the amygdala and the hippocampus, exhibit circadian rhythms in gene expression and signaling pathways. The functional significance of these rhythms is still not understood. In the present study, we sought to determine the impact of transiently disrupting the circadian system by shifting the light/ dark (LD) cycle. Such ‘‘jet lag’ ’ treatments alter daily rhythms of gene expression that underlie circadian oscillations as well as disrupt the synchrony between the multiple oscillators found within the body. Methodology/Principal Findings: We subjected adult male C57Bl/6 mice to a contextual fear conditioning protocol either before or after acute phase shifts of the LD cycle. As part of this study, we examined the impact of phase advances and phase delays, and the effects of different magnitudes of phase shifts. Under all conditions tested, we found that recall of fear conditioned behavior was specifically affected by the jet lag. We found that phase shifts potentiated the stress-evoked corticosterone response without altering baseline levels of this hormone. The jet lag treatment did not result in overall sleep deprivation, but altered the temporal distribution of sleep. Finally, we found that prior experience of jet lag helps to compensate for the reduced recall due to acute phase shifts. Conclusions/Significance: Acute changes to the LD cycle affect the recall of fear-conditioned behavior. This suggests that

Antisense oligonucleotides as therapeutics for the treatment of aggressive breast cancer

There are many drugs currently available for the treatment of aggressive breast cancer. These include anthracyclines, taxanes, alkylating agents, anti-metabolites, plant alkaloids, nucleoside analogues and anti-hormonal agents. Unfortunately, even armed with this impressive arsenal, there has been little ground gained in terms of disease free years or reduced mortality for what is an essentially incurable disease in the metastatic state. Clearly, we need to improve upon the therapies available for these patients. A key step toward this goal is the development of reproducible and relevant models in which newly developed drugs may be tested. This thesis outlines the characterisation of what is anticipated to be a powerful human xenograft model of aggressive breast cancer, that of the MDA435/LCC6 cell line. This cell line may be grown easily in vitro, as well as an ascitic or as a solid tumour in mice. In order to have a major impact in the field of breast cancer treatment, it will not suffice to develop yet another cytotoxic agent. Instead, we must turn to the newer technologies, including gene targeted therapies, which target the molecular root of the disease. This work includes the use of both free antisense oligonucleotides (ODN), as well as those formulated within a lipid carrier. These encapsulated ODN are retained in the circulation for a longer period of time, are less susceptible to the actions of nucleases, and due to pharmacokinetic and pharmacodistribution properties of the liposomal carrier, result in enhanced tumour cell uptake of the ODN. Finally, ODN, both free and liposome encapsulated, were administered to tumour bearing female SCID/Rag2m mice, either singly or in combination with a commonly used anticancer agent (doxorubicin). It is shown that ODN are capable of mediating the specific down-regulation of the target protein as well as impacting the rate of tumour growth. It is the intention of the author to demonstrate the necessity for not only good models and newly developed and specifically targeted therapeutic agents, but that we must also consider the use of combination strategies in the treatment of aggressive breast cancer such that current mortality statistics may be improved.Medicine, Faculty ofPathology and Laboratory Medicine, Department ofGraduat