Seminal Plasma Enhances Cervical Adenocarcinoma Cell Proliferation and Tumour Growth In Vivo

Cervical cancer is one of the leading causes of cancer-related death in women in sub-Saharan Africa. Extensive evidence has shown that cervical cancer and its precursor lesions are caused by Human papillomavirus (HPV) infection. Although the vast majority of HPV infections are naturally resolved, failure to eradicate infected cells has been shown to promote viral persistence and tumorigenesis. Furthermore, following neoplastic transformation, exposure of cervical epithelial cells to inflammatory mediators either directly or via the systemic circulation may enhance progression of the disease. It is well recognised that seminal plasma contains an abundance of inflammatory mediators, which are identified as regulators of tumour growth. Here we investigated the role of seminal plasma in regulating neoplastic cervical epithelial cell growth and tumorigenesis. Using HeLa cervical adenocarcinoma cells, we found that seminal plasma (SP) induced the expression of the inflammatory enzymes, prostaglandin endoperoxide synthase (PTGS1 and PTGS2), cytokines interleukin (IL) -6, and -11 and vascular endothelial growth factor-A(VEGF-A). To investigate the role of SP on tumour cell growth in vivo, we xenografted HeLa cells subcutaneously into the dorsal flank of nude mice. Intra-peritoneal administration of SP rapidly and significantly enhanced the tumour growth rate and size of HeLa cell xenografts in nude mice. As observed in vitro, we found that SP induced expression of inflammatory PTGS enzymes, cytokines and VEGF-A in vivo. Furthermore we found that SP enhances blood vessel size in HeLa cell xenografts. Finally we show that SP-induced cytokine production, VEGF-A expression and cell proliferation are mediated via the induction of the inflammatory PTGS pathway

Comorbidity in patients with diabetes mellitus: impact on medical health care utilization

BACKGROUND: Comorbidity has been shown to intensify health care utilization and to increase medical care costs for patients with diabetes. However, most studies have been focused on one health care service, mainly hospital care, or limited their analyses to one additional comorbid disease, or the data were based on self-reported questionnaires instead of health care registration data. The purpose of this study is to estimate the effects a broad spectrum of of comorbidities on the type and volume of medical health care utilization of patients with diabetes. METHODS: By linking general practice and hospital based registrations in the Netherlands, data on comorbidity and health care utilization of patients with diabetes (n = 7,499) were obtained. Comorbidity was defined as diabetes-related comorbiiabetes-related comorbidity. Multilevel regression analyses were applied to estimate the effects of comorbidity on health care utilization. RESULTS: Our results show that both diabetes-related and non diabetes-related comorbidity increase the use of medical care substantially in patients with diabetes. Having both diabeterelated and non diabetes-related comorbidity incrases the demand for health care even more. Differences in health care utilization patterns were observed between the comorbidities. CONCLUSION: Non diabetes-related comorbidity increases the health care demand as much as diabetes-related comorbidity. Current single-disease approach of integrated diabetes care should be extended with additional care modules, which must be generic and include multiple diseases in order to meet the complex health care demands of patients with diabetes in the future

Staff understanding of recovery-orientated mental health practice: a systematic review and narrative synthesis

Background: Mental health policy is for staff to transform their practice towards a recovery orientation. Staff understanding of recovery-orientated practice will influence the implementation of this policy. The aim of this study was to conduct a systematic review and narrative synthesis of empirical studies identifying clinician and manager conceptualisations of recovery-orientated practice. Methods: A systematic review of empirical primary research was conducted. Data sources were online databases (n = 8), journal table of contents (n = 5), internet, expert consultation (n = 13), reference lists of included studies and references to included studies. Narrative synthesis was used to integrate the findings. Results: A total of 10,125 studies were screened, 245 full papers were retrieved, and 22 were included (participants, n = 1163). The following three conceptualisations of recovery-orientated practice were identified: clinical recovery, personal recovery and service-defined recovery. Service-defined recovery is a new conceptualisation which translates recovery into practice according to the goals and financial needs of the organisation. Conclusions: Organisational priorities influence staff understanding of recovery support. This influence is leading to the emergence of an additional meaning of recovery. The impact of service-led approaches to operationalising recovery-orientated practice has not been evaluated. Trial Registration: The protocol for the review was pre-registered (PROSPERO 2013: CRD42013005942)

PGF2α-F-prostanoid receptor signalling via ADAMTS1 modulates epithelial cell invasion and endothelial cell function in endometrial cancer

<p>Abstract</p> <p>Background</p> <p>An increase in cancer cell invasion and microvascular density is associated with a poorer prognosis for patients with endometrial cancer. In endometrial adenocarcinoma F-prostanoid (FP) receptor expression is elevated, along with its ligand prostaglandin (PG)F_2α, where it regulates expression and secretion of a host of growth factors and chemokines involved in tumorigenesis. This study investigates the expression, regulation and role of a disintegrin and metalloproteinase with thrombospondin repeat 1 (ADAMTS1) in endometrial adenocarcinoma cells by PGF_2αvia the FP receptor.</p> <p>Methods</p> <p>Human endometrium and adenocarcinoma tissues were obtained in accordance with Lothian Research Ethics Committee guidance with informed patient consent. Expression of ADAMTS1 mRNA and protein in tissues was determined by quantitative RT-PCR analysis and immunohistochemistry. Signal transduction pathways regulating ADAMTS1 expression in Ishikawa cells stably expressing the FP receptor to levels seen in endometrial cancer (FPS cells) were determined by quantitative RT-PCR analysis. In vitro invasion and proliferation assays were performed with FPS cells and human umbilical vein endothelial cells (HUVECs) using conditioned medium (CM) from PGF_2α-treated FPS cells from which ADAMTS1 was immunoneutralised and/or recombinant ADAMTS1. The role of endothelial ADAMTS1 in endothelial cell proliferation was confirmed with RNA interference. The data in this study were analysed by T-test or ANOVA.</p> <p>Results</p> <p>ADAMTS1 mRNA and protein expression is elevated in endometrial adenocarcinoma tissues compared with normal proliferative phase endometrium and is localised to the glandular and vascular cells. Using FPS cells, we show that PGF2α-FP signalling upregulates ADAMTS1 expression via a calmodulin-NFAT-dependent pathway and this promotes epithelial cell invasion through ECM and inhibits endothelial cell proliferation. Furthermore, we show that CM from FPS cells regulates endothelial cell ADAMTS1 expression in a rapid biphasic manner. Using RNA interference we show that endothelial cell ADAMTS1 also negatively regulates cellular proliferation.</p> <p>Conclusions</p> <p>These data demonstrate elevated ADAMTS1 expression in endometrial adenocarcinoma. Furthermore we have highlighted a mechanism whereby FP receptor signalling regulates epithelial cell invasion and endothelial cell function via the PGF_2α-FP receptor mediated induction of ADAMTS1.</p

Synergism between particle-based multiplexing and microfluidics technologies may bring diagnostics closer to the patient

In the field of medical diagnostics there is a growing need for inexpensive, accurate, and quick high-throughput assays. On the one hand, recent progress in microfluidics technologies is expected to strongly support the development of miniaturized analytical devices, which will speed up (bio)analytical assays. On the other hand, a higher throughput can be obtained by the simultaneous screening of one sample for multiple targets (multiplexing) by means of encoded particle-based assays. Multiplexing at the macro level is now common in research labs and is expected to become part of clinical diagnostics. This review aims to debate on the “added value” we can expect from (bio)analysis with particles in microfluidic devices. Technologies to (a) decode, (b) analyze, and (c) manipulate the particles are described. Special emphasis is placed on the challenges of integrating currently existing detection platforms for encoded microparticles into microdevices and on promising microtechnologies that could be used to down-scale the detection units in order to obtain compact miniaturized particle-based multiplexing platforms