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- Associations between human papillomavirus and history of cancer among U.S. adults in the National Health and Nutrition Examination Survey (2003-2010). [JOURNAL ARTICLE]
- Br J Cancer 2014 Jul 24.
Background:Human papillomavirus (HPV) is an infectious agent that has been associated with human cancer. We have updated the U.S. population sero-prevalence using a large National Health and Nutrition Examination Survey (NHANES) sample of adults from 2003 to 2010, and have analysed the associations between HPV seropositivity and self-reported history of cancer.Methods:Four cross-sectional cycles (2003-2004, 2005-2006, 2007-2008, and 2009-2010) were used, for a total of 12 759 participants who had both cancer history and HPV serum information.Results:The sero-prevalences of HPV types 6, 11, 16, and 18 were 15.0%, 4.8%, 11.5%, and 4.1%, respectively. Females had significantly higher HPV prevalence than males (P<0.05) for all subtypes. Positive associations between HPV 16/18 seropositivity and lifetime history of any cancer (adjusted odds ratio-ORadj=1.68; 95% CI: 1.35, 2.01), history of any of eight selected cancers (ORadj=2.63; 95% CI: 1.78, 3.90), lung cancer (ORadj=5.14; 95% CI: 1.29, 20.44), and cervical cancer (ORadj=2.55; 95% CI: 1.63, 3.98) were observed.Conclusions:The finding of significant associations between HPV 16/18 seropositivity and lifetime history of cancer adds epidemiological evidence to the carcinogenicity potential of HPV 16 and 18 in other tissues. With increasing coverage of the HPV vaccine in the U.S., future NHANES data and sample collection may allow further detailed evaluation of the population impact of the HPV vaccination on cancer prevention.British Journal of Cancer advance online publication, 24 July 2014; doi:10.1038/bjc.2014.414 www.bjcancer.com.
- Phase I clinical trial of nintedanib plus paclitaxel in early HER-2-negative breast cancer (CNIO-BR-01-2010/GEICAM-2010-10 study). [JOURNAL ARTICLE]
- Br J Cancer 2014 Jul 24.
Introduction:Previous small-molecule antiangiogenics have compromised chemotherapy dose intensity in breast cancer. We present a phase I trial of a novel selective agent, nintedanib, plus standard chemotherapy in early breast cancer.Methods:Her-2-negative breast cancer patients with tumours larger than 2 cm were eligible for dose-escalation trial (classic 3+3 method).Results:The recommended phase II dose (RP2D) was 150 mg BID of nintedanib combined with standard dose of weekly paclitaxel followed by adriamycin plus cyclophosphamide. The dose-limiting toxicity was transaminase elevation. At the RP2D, the dose intensity was ∼100%. The pathologic complete response was 50%.Conclusions:The combination allows the delivery of full-dose intensity, while efficacy seems promising.British Journal of Cancer advance online publication, 24 July 2014; doi:10.1038/bjc.2014.397 www.bjcancer.com.
- The Frustrated Host Response to Legionella pneumophila Is Bypassed by MyD88-Dependent Translation of Pro-inflammatory Cytokines. [JOURNAL ARTICLE]
- PLoS Pathog 2014 Jul; 10(7):e1004229.
Many pathogens, particularly those that require their host for survival, have devised mechanisms to subvert the host immune response in order to survive and replicate intracellularly. Legionella pneumophila, the causative agent of Legionnaires' disease, promotes intracellular growth by translocating proteins into its host cytosol through its type IV protein secretion machinery. At least 5 of the bacterial translocated effectors interfere with the function of host cell elongation factors, blocking translation and causing the induction of a unique host cell transcriptional profile. In addition, L. pneumophila also interferes with translation initiation, by preventing cap-dependent translation in host cells. We demonstrate here that protein translation inhibition by L. pneumophila leads to a frustrated host MAP kinase response, where genes involved in the pathway are transcribed but fail to be translated due to the bacterium-induced protein synthesis inhibition. Surprisingly, few pro-inflammatory cytokines, such as IL-1α and IL-1β, bypass this inhibition and get synthesized in the presence of Legionella effectors. We show that the selective synthesis of these genes requires MyD88 signaling and takes place in both infected cells that harbor bacteria and neighboring bystander cells. Our findings offer a perspective of how host cells are able to cope with pathogen-encoded activities that disrupt normal cellular process and initiate a successful inflammatory response.
- Regional anaesthesia in paediatrics: marching forward. [JOURNAL ARTICLE]
- Curr Opin Anaesthesiol 2014 Jul 23.
This review highlights new data and current trends of well tolerated and effective paediatric regional anaesthesia. Historically, the practice of paediatric regional anaesthesia was based largely on information from adult studies, but recent literature contains information on paediatric specific risks and benefits of old and new techniques as well as the impact of new ideas and technologies.Excellent pain relief with regional anaesthesia is well demonstrated in children. Several databases of paediatric regional anaesthesia (over 46 000 regional anaesthetics) demonstrate overall safety and lack of major complications. Detailed analysis demonstrates additional safety and decreased failure rates of peripheral compared with neuraxial nerve blocks. Ultrasound technology confers additional safety and efficacy benefits.Increasingly, data support the safety and efficacy of novel peripheral nerve blocks, transversus abdominis plane and ultrasound-guided paravertebral, and the use of perineural catheters for both inpatients and outpatients. Regional anaesthesia as a sole agent for surgical anaesthesia and the use of regional anaesthesia for pain in nonsurgical pain patients remains underutilized.Paediatric specific data for regional anaesthesia are available to help guide optimal pain management. The paediatric regional anaesthesia literature lags behind literature available for adult populations and increased studies are needed for additional information for informed decision-making.
- Evaluation of 89Zr-Pertuzumab in breast cancer xenografts. [JOURNAL ARTICLE]
- Mol Pharm 2014 Jul 24.
Pertuzumab is a monoclonal antibody that binds to HER2 and is used in combination with another HER2-specific monoclonal antibody, Trastuzumab, for the treatment of HER2+ metastatic breast cancer. Pertuzumab binds to an HER2 binding site distinct from that of Trastuzumab, and its affinity is enhanced when Trastuzumab is present. We aim to exploit this enhanced affinity of Pertuzumab for its HER2 binding epitope and adapt this antibody as a PET imaging agent by radiolabeling with 89Zr to increase the sensitivity of HER2 detection in vivo. Here, we investigate the biodistribution of 89Zr-Pertuzumab in HER2-expressing BT-474 and HER2-nonexpressing MDA-MB-231 xenografts to quantitatively assess HER2 expression in vivo. In vitro cell binding studies were performed resulting in retained immunoreactivity and specificity for HER2-expressing cells. In vivo evaluation of 89Zr-Pertuzumab was conducted in severely combined immunodeficient mice, subcutaneously inoculated with BT-474 and MDA-MB-231 cells. 89Zr-Pertuzumab was systemically administered and imaged at 7 days post-injection (p.i.) followed by terminal biodistribution studies. Higher tumor uptake was observed in BT-474 compared to MDA-MB-231 xenografts with 47.5 ± 32.9 and 9.5 ± 1.7 %ID/g, respectively at 7 d p.i (P = 0.0009) and blocking studies with excess unlabeled Pertuzumab showed a 5-fold decrease in BT-474 tumor uptake (P = 0.0006), confirming the in vivo specificity of this radiotracer. Importantly, we observed that the tumor accumulation of 89Zr-Pertuzumab was increased in the presence of unlabeled Trastuzumab, at 173 ± 74.5 %ID/g (P = 0.01). Biodistribution studies correlate with PET imaging quantification using max SUV (r = 0.98, P = 0.01). Collectively, these results illustrate that 89Zr-Pertuzumab as a PET imaging agent may be beneficial for the quantitative and noninvasive assessment of HER2 expression in vivo especially for patients undergoing Trastuzumab therapy.
- Science to Practice: Can Intravoxel Incoherent Motion Diffusion-weighted MR Imaging Be Used to Assess Tumor Response to Antivascular Drugs? [JOURNAL ARTICLE]
- Radiology 2014 Aug; 272(2):307-308.
Summary In the study by Joo et al ( 1 ), perfusion-sensitive parameters derived from diffusion-weighted (DW) magnetic resonance (MR) imaging using intravoxel incoherent motion (IVIM) analysis were significantly decreased 4 hours after administration of a vascular disrupting agent (VDA) (CKD-516), in keeping with drug-induced vascular collapse. A larger decrease in the perfusion-sensitive IVIM parameters was correlated with smaller tumor size increase 7 days after treatment.
- An outbreak of food-borne salmonellosis linked to a bread takeaway shop in Ben Tre City, Vietnam. [JOURNAL ARTICLE]
- Int J Infect Dis 2014 Jul 21.
To identify the vehicle, source, and causative agent of a community-wide food-borne outbreak of gastroenteritis [Au?1].We conducted a case-control study. Cases were city residents diagnosed with gastroenteritis and hospitalized in Ben Tre City from 22 to 25 May 2013; 41 cases were selected randomly from a list of hospitalized patients. Controls were age- and gender-matched healthy neighbours of cases. Participants were interviewed using a standard questionnaire. Samples from patients and food were tested at reference laboratories. We used conditional logistic regression to calculate matched odds ratios (mORs) for the association of gastroenteritis with food items consumed.Of the 41 cases enrolled in the study, 61% were males and the median age was 33 years; cases resided in 12 wards of the City. Of 13 food items consumed by the cases, only stuffed bread was significantly associated with gastroenteritis (mOR 21.3, 95% confidence interval 6.3-71.8). Among the 29 cases who ate stuffed bread, the median time to illness onset was 9h. Patient stool samples and bread samples were positive for Salmonella species.Stuffed bread was the likely vehicle of the outbreak. The laboratory testing capacity for serotypes of Salmonella should be strengthened in Vietnam. Food-handler training in basic food safety measures should be improved.
- Topical and Systemic Antimicrobial Therapy for Venous Leg Ulcers. [JOURNAL ARTICLE]
- JAMA 2014 Jun 25; 311(24):2534-2535.
Is treatment with topical or systemic antimicrobial agents associated with better venous leg ulcer healing compared with usual care (dressings and bandages without antimicrobials) or an alternative topical or systemic antimicrobial agent?Available evidence, from underpowered pooled data, neither supports nor refutes an association of systemic antibiotic therapy with improved venous leg ulcer healing. Among topical antimicrobials, cadexomer iodine may be associated with better healing compared with usual care.
- Comparison of the effects of CORM-2, CORM-3 and CORM-A1 on coagulation in human plasma. [JOURNAL ARTICLE]
- Blood Coagul Fibrinolysis 2014 Jul 23.
Carbon monoxide derived from the catalytic action of heme oxygenase-1 or carbon monoxide-releasing molecules (CORMs) has been found to potentially be an anticoagulant or procoagulant agent. Of interest, two water-soluble CORMs, CORM-3 and CORM-A1, recently became commercially available. Thus, the purpose of the present study was to assess and compare the effects of the previously well studied CORM-2 to the effects of CORM-3 and CORM-A1 on coagulation in citrated human plasma with thrombelastography. Plasma exposed to CORMs was incubated at 37°C for at least one carbon monoxide release half-time, and then tissue factor-activated coagulation was commenced with calcium addition. CORM-2 and CORM-3 enhanced the velocity of clot formation and thrombus strength in a similar manner, whereas CORM-A1 did not affect coagulation. However, CORM-A1 did diminish tissue-type plasminogen activator initiated fibrinolysis. The similarity in effect on coagulation by CORM-2 and CORM-3 was likely secondary to the relatively inert effect of their ruthenium-containing carrier molecule, whereas the boron-containing CORM-A1 may have had no effect secondary to boron binding to fibrinogen, preventing carbon monoxide-mediated changes in fibrinogen protein structure via attached heme group(s). Future investigations with CORMs should have special attention to confounding effects of the carrier molecule.
- The New Epidemiology of Primary Biliary Cirrhosis. [JOURNAL ARTICLE]
- Semin Liver Dis 2014 Aug; 34(3):318-328.
Primary biliary cirrhosis (PBC) is an autoimmune cholestatic liver disease. Susceptibility to PBC probably arises from a combination of genetic and environmental factors. The prevalence of PBC varies both on an international and a regional level. This can be explained, in part, by differences in clinical practice and case-finding activity. It is likely, however, that substantive geographical differences exist both in terms of genetic susceptibility and environmental factors that potentially trigger the disease in genetically susceptible individuals. The study of the epidemiology of PBC has strongly supported the concept of an environmental triggering factor, but as yet no specific agent has been identified. Ongoing work to discover the environmental agent, as well as the mechanism that causes the disease will answer key questions as to the epidemiology of this complex autoimmune disease as well as providing useful information for other autoimmune conditions.