Standardized fixation process is crucial to permit molecular analyses in formalin-fixed and paraffin-embedded melanoma samples.

Standardized fixation process is crucial to permit molecular analyses in formalin-fixed and paraffin-embedded melanoma samples.

Clin Chem Lab Med. 2016 Jun 11;

Authors: Uguen A, Guibourg B, Guéguen P

PMID: 27289004 [PubMed - as supplied by publisher]

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[Uveal and iridociliary melanomas in young patients : A retrospective analysis of 57 cases].

[Uveal and iridociliary melanomas in young patients : A retrospective analysis of 57 cases].

Ophthalmologe. 2016 Jun 10;

Authors: Heyer LJ, Metz C, Flühs D, Heyer CM, Bornfeld N

Abstract
BACKGROUND: Uveal melanomas (UM) are rare malignancies in young patients. It is unknown if UM in young patients significantly differs from those in older patients concerning tumor size and localization, metastasis and genetics. The aim of this study was to evaluate the clinical course and tumor characteristics in young patients with UM.
MATERIAL AND METHODS: All patients with UM below the age of 32 years who had been treated at our hospital were included in the study. Patient age and sex, duration of symptoms, visual impairment, tumor size and location, genetics, therapy, follow-up interventions and tumor-associated deaths were documented.
RESULTS: A total of 57 patients (67 % male, mean age 24.7 years) were included in the study with an average symptomatic course of 5 months. Of the patients 8 (14 %) had an initial visual acuity of ≥ 0.9, 16 (28 %) 0.5-0.8, 22 (39 %) 0.05-0.4 and 9 (16 %) < 0.05 (no data for 2 patients, 4 %). After therapy visual acuity was < 0.05 in 54 % and 53 % of the tumors were choroidal UM (70 % juxtapapillary/circumpapillary), whereas 47 % were ciliochoroidal (54 % with iridociliary involvement). The average tumor size was 12.7 ± 3.6 mm with an average prominence of 6.2 ± 3.2 mm. Genetic evaluation (n = 16) revealed disomy 3 in 64 % and 54 % of the patients received radiotherapy with local application of ruthenium 106. In 46 % of cases follow-up interventions were neccessary including 70 % due to radiogenic retinopathy.
CONCLUSION: In young patients UM did not show any preferred localization. The majority of genetically evaluated tumors revealed disomy 3 with no significant correlation to tumor location. Independent of tumor size, location and therapy, approximately half of the patients needed follow-up interventions, predominantly due to radiogenic retinopathy.

PMID: 27286673 [PubMed - as supplied by publisher]

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Neogenin defined as a GD3-associated molecule by enzyme-mediated activation of radical sources confers malignant properties via intra-cytoplasmic domain in melanoma cells.

Neogenin defined as a GD3-associated molecule by enzyme-mediated activation of radical sources confers malignant properties via intra-cytoplasmic domain in melanoma cells.

J Biol Chem. 2016 Jun 10;

Authors: Kaneko K, Ohkawa Y, Hashimoto N, Ohmi Y, Kotani N, Honke K, Ogawa M, Okajima T, Furukawa K, Furukawa K

Abstract
To investigate mechanisms for increased malignant properties in malignant melanomas by gangliosdide GD3, enzyme-mediated activation of radical sources and subsequent mass spectrometry were performed using an anti-GD3 antibody, and GD3-positive (GD3+) and GD3-negative (GD3-) melanoma cell lines. Neogenin defined as a GD3-neighbored molecule was largely localized in lipid/rafts in GD3+ cells. Silencing of neogenin resulted in the reduction of cell growth and invasion activity. Physical association between GD3 and neogenin was demonstrated by immunostaining of the immunoprecipitates with anti- neogenin antibody from GD3+ cell lysates. Intra-cytoplasmic domain of neogenin (Ne-ICD) was detected in GD3+ cells at higher levels than in GD3- cells when cells were treated by a proteasome inhibitor, but not when simultaneously treated with a γ-secretase inhibitor. Over-expression of Ne-ICD in GD3- cells resulted in the increased cell growth and invasion activity, suggesting that Ne-ICD plays a role as a transcriptional factor to drive malignant properties of melanomas after cleavage with γsecretase. γ-secretase was found in lipid/rafts in GD3+ cells. Accordingly, immunocytostaining revealed that GD3, neogenin and γ-secretase were co-localized at the leading edge of GD3+ cells. All these results suggested that GD3 recruits γ-secretase to lipid/rafts, allowing efficient cleavage of neogenin. ChIP-sequensing was performed to identify candidates of target genes of Ne-ICD. Some of them actually showed increased expression after expression of Ne-ICD, probably exerting malignant phenotypes of melanomas under GD3 expression.

PMID: 27288875 [PubMed - as supplied by publisher]

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Development and application of a rapid detection system for human papillomavirus and Herpes simplex virus -2 by loop-mediated isothermal amplification assay.

Development and application of a rapid detection system for human papillomavirus and Herpes simplex virus -2 by loop-mediated isothermal amplification assay.

Microb Pathog. 2016 Jun 8;

Authors: Yang JF, Zhao CZ, Lu KX

Abstract
Human papillomavirus (HPV) infection is an important factor that causes cervical cancer and non-melanoma skin cancer (NMSC), while HSV-2 plays an important role when HR-HPV triggers the cancer. Thus, a quick and convenient assay in the detection of HPV and HSV-2in the screening of HPV and HSV-2 infection is required. Two respective HPV and HSV-2 detection methods were established based on loop-mediated isothermal amplification (LAMP) assay. Specific outer primers, inner primers, and loop primers were designed according to the conserved domains of HPV and HSV-2 genomes, respectively, while degenerate primers were used for HPV assay. After optimizing the reaction conditions, the results were observed by LAMP Tubidimeter real-time LA-320. Standard plasmids HPV-L-P and HSV-2-L-P were cloned and used in sensitivity tests of HPV LAMP and HSV-2 LAMP, respectively. Fifty samples of actinic keratosis (AK), 20 samples of squamous cell carcinoma (SCC), 50 samples of basal cell carcinoma (BCC) and 20 samples of seborrheic keratosis (SK) were detected by HPV assay. Seventy three clinical samples of vaginitis, chronic cervicitis, cervical intraepithelial neoplasias and cervical cancer level positive were detected with HPV and HSV-2 assays. The reaction conditions of two assays were the same with a reaction temperature of 63 °C and a reaction time of 45 min. The sensitivity of HPV LAMP assay was 10 copies/μL, while that of the HSV-2 LAMP assay was 100 copies/μL. No cross-reactivity was observed. The HPV positive rates of AK, SCC, BCC and SK samples were 80% (40/50), 75% (15/20), 44% (22/50) and 21% (15/72), respectively. As an economic and quick diagnostic tool, LAMP assay is conducive to the extensive screening of HPV and HSV-2 and has huge potential to be promoted in resource-limited hospitals.

PMID: 27287497 [PubMed - as supplied by publisher]

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Identification of aryl hydrocarbon receptor signaling pathways altered in TCDD-treated red seabream embryos by transcriptome analysis.

Identification of aryl hydrocarbon receptor signaling pathways altered in TCDD-treated red seabream embryos by transcriptome analysis.

Aquat Toxicol. 2016 May 24;177:156-170

Authors: Iida M, Fujii S, Uchida M, Nakamura H, Kagami Y, Agusa T, Hirano M, Bak SM, Kim EY, Iwata H

Abstract
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces a broad spectrum of toxic effects including craniofacial malformation and neural damage in fish embryos. These effects are mainly mediated by the aryl hydrocarbon receptor (AHR). However, the mode of action between TCDD-induced AHR activation and adverse outcomes is not yet understood. To provide a comprehensive picture of the AHR signaling pathway in fish embryos exposed to TCDD, red seabream (Pagrus major) embryos were treated with graded concentrations of TCDD (0.3-37nM) in seawater, or with a mixture of TCDD and 500nM CH223191, an AHR-specific antagonist. The transcriptome of red seabream embryos was analyzed using a custom-made microarray with 6000 probes specifically prepared for this species. A Jonckheere-Terpstra test was performed to screen for genes that demonstrated altered mRNA expression levels following TCDD exposure. The signals of 1217 genes (as human homologs) were significantly altered in a TCDD concentration-dependent manner (q-value<0.2). Notably, the TCDD-induced alteration in mRNA expression was alleviated by co-exposure to CH223191, suggesting that the mRNA expression level of these genes was regulated by AHR. To identify TCDD-activated pathways, the microarray data were further subjected to gene set enrichment analysis (GSEA) and functional protein-protein interaction (PPI) network analysis. GSEA demonstrated that the effects of TCDD on sets of genes involved calcium, mitogen-activated protein kinase (MAPK), actin cytoskeleton, chemokine, T cell receptor, melanoma, vascular endothelial growth factor (VEGF), axon guidance, and renal cell carcinoma signaling pathways. These results suggest the hypotheses that TCDD induces immunosuppression via the calcium, MAPK, chemokine, and T cell receptor signaling pathways, neurotoxicity via VEGF signaling, and axon guidance alterations and teratogenicity via the dysregulation of the actin cytoskeleton and melanoma and renal cell carcinoma signaling pathways. Furthermore, the PPI network analysis indicated that the adverse outcome pathways of TCDD in the embryos might be propagated through several hub genes such as cell division control protein 42, phosphoinositide-3-kinase regulatory subunit 1, and guanine nucleotide-binding proteins. Understanding these pathways potentially allows for exploring the adverse outcome pathway of the effects of TCDD on the red seabream embryos.

PMID: 27288597 [PubMed - as supplied by publisher]

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Association between new-onset hypothyroidism and clinical response in patients treated with tyrosine kinase inhibitor therapy in phase I clinical trials.

Association between new-onset hypothyroidism and clinical response in patients treated with tyrosine kinase inhibitor therapy in phase I clinical trials.

Cancer Chemother Pharmacol. 2016 Jun 10;

Authors: Bilen MA, Patel A, Hess KR, Munoz J, Busaidy NL, Wheler JJ, Janku F, Falchook GS, Hong DS, Meric-Bernstam F, Habra MA, Naing A

Abstract
PURPOSE: Tyrosine kinase inhibitor (TKI)-induced thyroid dysfunction has been identified as an important but manageable adverse effect of targeted therapy. Several studies have suggested that patients who develop hypothyroidism respond better to TKIs, but this relationship is not well elucidated. We evaluated the relationship between new-onset hypothyroidism and clinical response in patients with advanced cancers treated with TKIs at our institution.
METHODS: We retrospectively reviewed records for patients from four clinical trials that included at least one TKI  therapy between January 2006 and December 2011. Patients with preexisting thyroid disease, including thyroid cancer, hypothyroidism, or hyperthyroidism, were excluded. Analysis of 197 patients was performed. Response was determined using RECIST 1.0. Clinical benefit was described as complete response, partial response, or stable disease greater than 4 months. Multivariable logistic regression analysis was performed to correlate patient characteristics with clinical response.
RESULTS: The median age for the 197 patients was 58 years (range, 13-85 years), and 56 % were female. Of the 197 patients, 52 (26 %) developed hypothyroidism after therapy. Clinical benefit rates were 50 % in patients with new-onset hypothyroidism versus 34 % in patients without hypothyroidism. In the univariate model, the odds ratio (OR) for new-onset hypothyroidism was 1.9 [95 % confidence interval (CI) (1.0, 3.6) and p = 0.05]. We grouped tumor types into six categories (breast, colorectal carcinoma, melanoma, non-small cell lung cancer, pancreas, and other). When adjusted for tumor type, age (>50 years) and sex, the OR was 2.9 [95 % CI (1.3, 6.5) and p = 0.012] for new-onset hypothyroidism.
CONCLUSION: New-onset hypothyroidism was associated with favorable clinical response in patients who received TKI treatment.

PMID: 27286994 [PubMed - as supplied by publisher]

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The use of multiplex PCR for the diagnosis of viral severe acute respiratory infection in children: a high rate of co-detection during the winter season.

The use of multiplex PCR for the diagnosis of viral severe acute respiratory infection in children: a high rate of co-detection during the winter season.

Eur J Clin Microbiol Infect Dis. 2016 Jun 10;

Authors: El Kholy AA, Mostafa NA, Ali AA, Soliman MM, El-Sherbini SA, Ismail RI, El Basha N, Magdy RI, El Rifai N, Hamed DH

Abstract
Respiratory tract infection is a major cause of hospitalization in children. Although most such infections are viral in origin, it is difficult to differentiate bacterial and viral infections, as the clinical symptoms are similar. Multiplex polymerase chain reaction (PCR) methods allow testing for multiple pathogens simultaneously and are, therefore, gaining interest. This prospective case-control study was conducted from October 2013 to February 2014. Nasopharyngeal (NP) and oropharyngeal (throat) swabs were obtained from children admitted with severe acute respiratory infection (SARI) at a tertiary hospital. A control group of 40 asymptomatic children was included. Testing for 16 viruses was done by real-time multiplex PCR. Multiplex PCR detected a viral pathogen in 159/177 (89.9 %) patients admitted with SARI. There was a high rate of co-infection (46.9 %). Dual detections were observed in 64 (36.2 %), triple detections in 17 (9.6 %), and quadruple detections in 2 (1.1 %) of 177 samples. Seventy-eight patients required intensive care unit (ICU) admission, of whom 28 (35.8 %) had co-infection with multiple viruses. AdV, HBoV, HRV, HEV, and HCoV-OC43 were also detected among asymptomatic children. This study confirms the high rate of detection of viral nucleic acids by multiplex PCR among hospitalized children admitted with SARI, as well as the high rate of co-detection of multiple viruses. AdV, HBoV, HRV, HEV, and HCoV-OC43 were also detected in asymptomatic children, resulting in challenges in clinical interpretation. Studies are required to provide quantitative conclusions that will facilitate clinical interpretation and application of the results in the clinical setting.

PMID: 27287764 [PubMed - as supplied by publisher]

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Healthcare use among preschool children attending GP-led urgent care centres: a descriptive, observational study.

Healthcare use among preschool children attending GP-led urgent care centres: a descriptive, observational study.

BMJ Open. 2016;6(6):e010672

Authors: Gnani S, Morton S, Ramzan F, Davison M, Ladbrooke T, Majeed A, Saxena S

Abstract
OBJECTIVE: Urgent care centres' (UCCs) hours were developed with the aim of reducing inappropriate emergency department (ED) attendances in England. We aimed to examine the presenting complaint and outcomes of care in 2 general practitioner (GP)-led UCCs with extended opening times.
DESIGN: Retrospective observational epidemiological study using routinely collected data.
SETTING: 2 GP-led UCCs in London, colocated with a hospital ED.
PARTICIPANTS: All children aged under 5 years, attending 2 GP-led UCCs over a 3-year period.
OUTCOMES: Outcomes of care for the children including: primary diagnosis; registration status with a GP; destination following review within the UCC; and any medication prescribed. Comparison between GP-led UCC visit rates and routine general practices was also made.
RESULTS: 3% (n=7747/282 947) of all attenders at the GP-led UCCs were children aged under 5 years. The most common reason for attendance was a respiratory illness (27%), followed by infectious illness (17%). 18% (n=1428) were either upper respiratory tract infections or viral infections. The majority (91%) of children attending were registered with a GP, and over two-thirds of attendances were 'out of hours'. Overall 79% were seen and discharged home. Preschool children were more likely to attend their GP (47.0 per 100) than a GP-led UCC (9.4 per 100; 95% CI 8.9 to 10.0).
CONCLUSIONS: Two-thirds of preschool children attending GP-led UCCs do so out of hours, despite the majority being registered with a GP. The case mix is comparable with those presenting to an ED setting, with the majority managed exclusively by the GPs in the UCC before discharge home. Further work is required to understand the benefits of a GP-led urgent system in influencing future use of services especially emergency care.

PMID: 27288373 [PubMed - as supplied by publisher]

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Prescribing antibiotics to 'at-risk' children with influenza-like illness in primary care: qualitative study.

Prescribing antibiotics to 'at-risk' children with influenza-like illness in primary care: qualitative study.

BMJ Open. 2016;6(6):e011497

Authors: Ashdown HF, Räisänen U, Wang K, Ziebland S, Harnden A, ARCHIE investigators*

Abstract
OBJECTIVES: National Institute for Health and Care Excellence guidelines recommend immediate antibiotic treatment of respiratory tract infections in 'at-risk' individuals with comorbidities. Observational evidence suggests that influenza particularly predisposes children to bacterial complications. This study investigates general practitioners' (GPs') accounts of factors influencing their decision-making about antibiotic prescribing in the management of at-risk children with influenza-like illness (ILI).
DESIGN: Qualitative interview study using a maximum variation sample with thematic analysis through constant comparison.
SETTING: Semistructured telephone interviews with UK GPs using a case vignette of a child with comorbidities presenting with ILI.
PARTICIPANTS: There were 41 GPs (41.5% men; 40 from England, 1 from Northern Ireland) with a range of characteristics including length of time in practice, paediatrics experience, practice setting and deprivation.
RESULTS: There was considerable uncertainty and variation in the way GPs responded to the case and difference of opinion about how long-term comorbidities should affect their antibiotic prescribing pattern. Factors influencing their decision included the child's case history and clinical examination; the GP's view of the parent's ability to self-manage; the GP's own confidence and experiences of managing sick children and assessment of individual versus abstract risk. GPs rarely mentioned potential influenza infection or asked about immunisation status. All said that they would want to see the child; views about delayed prescribing varied in relation to local health service provision including options for follow-up and paediatric services.
CONCLUSIONS: The study demonstrates diagnostic uncertainty and wide variation in GP decision-making about prescribing antibiotics to children with comorbidity. Future guidelines might encourage consideration of a specific diagnosis such as influenza, and risk assessment tools could be developed to allow clinicians to quantify the levels of risk associated with different types of comorbidity. However, the wide range of clinical and non-clinical factors involved in decision-making during these consultations should also be considered in future guidelines.

PMID: 27288385 [PubMed - as supplied by publisher]

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Inhibition of MNK pathways enhances cancer cell response to chemotherapy with temozolomide and targeted radionuclide therapy.

Inhibition of MNK pathways enhances cancer cell response to chemotherapy with temozolomide and targeted radionuclide therapy.

Cell Signal. 2016 Jun 8;

Authors: Grzmil M, Seebacher J, Hess D, Behe M, Schibli R, Moncayo G, Frank S, Hemmings BA

Abstract
Current standard-of-care treatment for malignant cancers includes radiotherapy and adjuvant chemotherapy. Here, we report increased MAP kinase-interacting kinase (MNK)-regulated phosphorylation of translation initiation factor 4E (eIF4E) in glioma cells upon temozolomide (TMZ) treatment and in medullary thyroid carcinoma (MTC) cells in response to targeted radionuclide therapy. Depletion of MNK activity by using two MNK inhibitors, CGP57380 or cercosporamide, as well as by MNK1-specific knockdown sensitized glioblastoma (GBM) cells and GBM-derived spheres to TMZ. Furthermore, CGP57380 treatment enhanced response of MTC cells to (177)Lu-labeled gastrin analogue. In order to understand how MNK signaling pathways support glioma survival we analyzed putative MNK substrates by quantitative phosphoproteomics in normal condition and in the presence of TMZ. We identified MNK inhibitor-sensitive phosphorylation sites on eIF4G1, mutations of which either influenced eIF4E phosphorylation or glioma cell response to TMZ, pointing to altered regulation of translation initiation as a resistance mechanism. Pharmacological inhibition of overexpressed MNK1 by CGP57380 reduced eIF4E phosphorylation and induced association of inactive MNK1 with eIF4G1. Taken together, our data show an activation of MNK-mediated survival mechanisms in response to either glioma chemotherapy or MTC targeted radiation and suggest that inhibition of MNK activity represents an attractive sensitizing strategy for cancer treatments.

PMID: 27289018 [PubMed - as supplied by publisher]

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Limited role for transforming growth factor-β pathway activation-mediated escape from VEGF inhibition in murine glioma models.

Limited role for transforming growth factor-β pathway activation-mediated escape from VEGF inhibition in murine glioma models.:

Limited role for transforming growth factor-β pathway activation-mediated escape from VEGF inhibition in murine glioma models.

Neuro Oncol. 2016 Jun 10;

Authors: Mangani D, Weller M, Seyed Sadr E, Willscher E, Seystahl K, Reifenberger G, Tabatabai G, Binder H, Schneider H

Abstract
BACKGROUND: The vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-β pathways regulate key biological features of glioblastoma. Here we explore whether the TGF-β pathway, which promotes angiogenesis, invasiveness, and immunosuppression, acts as an escape pathway from VEGF inhibition.
METHODS: The role of the TGF-β pathway in escape from VEGF inhibition was assessed in vitro and in vivo and by gene expression profiling in syngeneic mouse glioma models.
RESULTS: We found that TGF-β is an upstream regulator of VEGF, whereas VEGF pathway activity does not alter the TGF-β pathway in vitro. In vivo, single-agent activity was observed for the VEGF antibody B20-4.1.1 in 3 and for the TGF-β receptor 1 antagonist LY2157299 in 2 of 4 models. Reduction of tumor volume and blood vessel density, but not induction of hypoxia, correlated with benefit from B20-4.1.1. Reduction of phosphorylated (p)SMAD2 by LY2157299 was seen in all models but did not predict survival. Resistance to B20 was associated with anti-angiogenesis escape pathway gene expression, whereas resistance to LY2157299 was associated with different immune response gene signatures in SMA-497 and GL-261 on transcriptomic profiling. The combination of B20 with LY2157299 was ineffective in SMA-497 but provided prolongation of survival in GL-261, associated with early suppression of pSMAD2 in tumor and host immune cells, prolonged suppression of angiogenesis, and delayed accumulation of tumor infiltrating microglia/macrophages.
CONCLUSIONS: Our study highlights the biological heterogeneity of murine glioma models and illustrates that cotargeting of the VEGF and TGF-β pathways might lead to improved tumor control only in subsets of glioblastoma.

PMID: 27286797 [PubMed - as supplied by publisher]

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Inhibition of MNK pathways enhances cancer cell response to chemotherapy with temozolomide and targeted radionuclide therapy.

Inhibition of MNK pathways enhances cancer cell response to chemotherapy with temozolomide and targeted radionuclide therapy.

Cell Signal. 2016 Jun 8;

Authors: Grzmil M, Seebacher J, Hess D, Behe M, Schibli R, Moncayo G, Frank S, Hemmings BA

Abstract
Current standard-of-care treatment for malignant cancers includes radiotherapy and adjuvant chemotherapy. Here, we report increased MAP kinase-interacting kinase (MNK)-regulated phosphorylation of translation initiation factor 4E (eIF4E) in glioma cells upon temozolomide (TMZ) treatment and in medullary thyroid carcinoma (MTC) cells in response to targeted radionuclide therapy. Depletion of MNK activity by using two MNK inhibitors, CGP57380 or cercosporamide, as well as by MNK1-specific knockdown sensitized glioblastoma (GBM) cells and GBM-derived spheres to TMZ. Furthermore, CGP57380 treatment enhanced response of MTC cells to (177)Lu-labeled gastrin analogue. In order to understand how MNK signaling pathways support glioma survival we analyzed putative MNK substrates by quantitative phosphoproteomics in normal condition and in the presence of TMZ. We identified MNK inhibitor-sensitive phosphorylation sites on eIF4G1, mutations of which either influenced eIF4E phosphorylation or glioma cell response to TMZ, pointing to altered regulation of translation initiation as a resistance mechanism. Pharmacological inhibition of overexpressed MNK1 by CGP57380 reduced eIF4E phosphorylation and induced association of inactive MNK1 with eIF4G1. Taken together, our data show an activation of MNK-mediated survival mechanisms in response to either glioma chemotherapy or MTC targeted radiation and suggest that inhibition of MNK activity represents an attractive sensitizing strategy for cancer treatments.

PMID: 27289018 [PubMed - as supplied by publisher]

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The impact of diabetes on dental implant failure: a systematic review and meta-analysis

Publication date: Available online 11 June 2016
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): V. Moraschini, E.S.P. Barboza
The aim of this study was to investigate the hypothesis that there is no difference in implant failure rate or marginal bone loss between type 1 or 2 diabetes subjects and non-diabetic subjects. An electronic search was conducted, without restrictions on date or language, in the PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science, and EMBASE databases, and in the grey literature, through August 2015. The eligibility criteria included prospective and retrospective cohort studies and randomized controlled trials. The initial search resulted in 1093 titles from PubMed/MEDLINE, 164 from the Cochrane Central Register of Controlled Trials, 134 from Web of Science, 228 from EMBASE, and four from the grey literature. Following the search and selection process, 14 studies published between 2000 and 2015 were included in this systematic review. According to the risk of bias analysis, all studies were classified as high quality. The results of this systematic review suggest that the number of implant failures does not differ between diabetic and non-diabetic subjects. Additionally, the results of the comparison between type 1 and 2 diabetes subjects showed no difference in the number of failures. With regard to marginal bone loss, there was a statistically significant difference favouring non-diabetic subjects.



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Thermal evaluation by infrared measurement of implant site preparation between single and gradual drilling in artificial bone blocks of different densities

Publication date: Available online 11 June 2016
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): S.C. Möhlhenrich, M. Abouridouane, N. Heussen, F. Hölzle, F. Klocke, A. Modabber
The aim of this study was to investigate the influence of bone density and drilling protocol on heat generation during implant bed preparation. Ten single and 10 gradual implant sites with diameters of 2.8, 3.5, and 4.2mm were prepared in four artificial bone blocks (density types I–IV; D1–D4). Drilling was done at constant speed (1500rpm) and with external irrigation (50ml/min); vertical speed was set at 2mm/s. An infrared camera was used for temperature measurements. Significantly higher temperatures for single drilling were found between 2.8-mm drills in D1 (P=0.0014) and D4 (P<0.0001) and between 3.5-mm drills in D3 (P=0.0087) and D4 (P<0.0001), as well as between 4.2-mm drills in D1 (P<0.0001) and D4 (P=0.0014). Low bone density led to a thermal decrease after single drilling and a thermal increase after gradual drilling. Burs with a large diameter always showed a higher temperature generation. In comparisons between 2.8- and 4.2-mm diameters for both single and gradual drills, significant differences (P<0.001) were noted for bone types II, III, and IV. Single drilling could generate more heat than traditional sequential drilling, and bone density, as well as drill diameter, influenced thermal increases. Particularly in lower-density bone, conventional sequential drilling seems to raise the temperature less.



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Oncogenic GNAQ Acts through a Single Node in Uveal Melanoma.

Oncogenic GNAQ Acts through a Single Node in Uveal Melanoma.

Cancer Discov. 2016 Jun 10;

Authors:

Abstract
GNAQ activates multiple oncogenic signaling pathways via ARF6 activation in uveal melanoma.

PMID: 27287290 [PubMed - as supplied by publisher]

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Next-generation sequencing identifies high frequency of mutations in potentially clinically actionable genes in sebaceous carcinoma.

Next-generation sequencing identifies high frequency of mutations in potentially clinically actionable genes in sebaceous carcinoma.

J Pathol. 2016 Jun 11;

Authors: Tetzlaff MT, Singh RR, Seviour EG, Curry JL, Hudgens CW, Bell D, Wimmer DA, Ning J, Czerniak BA, Zhang L, Davies MA, Prieto VG, Broaddus RR, Ram P, Luthra R, Esmaeli B

Abstract
Sebaceous carcinoma (SC) is a rare but aggressive malignancy with frequent recurrence and metastases. Surgery is the mainstay of therapy, but effective systemic therapies are lacking because the molecular alterations driving SC remain poorly understood. To identify these, we performed whole-exome next-generation sequencing of 409 cancer-associated genes on 27 SCs (18 primary/locally recurrent ocular, 5 paired metastatic ocular, and 4 primary extraocular) from 20 patients. In ocular SC, we identified 139 nonsynonymous somatic mutations (median/lesion, 3; range, 0-23). Twenty-five of 139 mutations (18%) occurred in potentially clinically actionable genes in 6 of 16 patients. The most common mutations were mutations in TP53 (n = 9), RB1 (n = 6), PIK3CA (n = 2), PTEN (n = 2), ERBB2 (n = 2), and NF1 (n = 2). TP53 and RB1 mutations were restricted to ocular SC and correlated with aberrant TP53 and RB protein expression. Systematic pathway analyses demonstrated convergence of these mutations to activation of the PI3K signalling cascade, and PI3K pathway activation was confirmed in tumours with PTEN and/or PIK3CA mutations. Considerable inter-tumoural heterogeneity was observed between paired primary and metastatic ocular SCs. In primary extraocular SC, we identified 77 nonsynonymous somatic mutations (median/lesion, 22.5; range, 3-29). This overall higher mutational load was attributed to a microsatellite instability phenotype in 3 of 4 patients and somatically acquired mutations in mismatch repair genes in 2 of 4 patients. Eighteen of 77 mutations (23%) were in potentially clinically actionable genes in 3 of 4 patients, including BTK, FGFR2, PDGFRB, HRAS, and NF1 mutations. Identification of potentially clinically actionable mutations in 9 of 20 SC patients (45%) underscores the importance of next-generation sequencing to expand the spectrum of genotype-matched targeted therapies. Frequent activation of PI3K signalling pathways provides a strong rationale for application of mTOR inhibitors in management of this disease.

PMID: 27287813 [PubMed - as supplied by publisher]

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Standardized fixation process is crucial to permit molecular analyses in formalin-fixed and paraffin-embedded melanoma samples.

Standardized fixation process is crucial to permit molecular analyses in formalin-fixed and paraffin-embedded melanoma samples.

Clin Chem Lab Med. 2016 Jun 11;

Authors: Uguen A, Guibourg B, Guéguen P

PMID: 27289004 [PubMed - as supplied by publisher]

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[Uveal and iridociliary melanomas in young patients : A retrospective analysis of 57 cases].

[Uveal and iridociliary melanomas in young patients : A retrospective analysis of 57 cases].

Ophthalmologe. 2016 Jun 10;

Authors: Heyer LJ, Metz C, Flühs D, Heyer CM, Bornfeld N

Abstract
BACKGROUND: Uveal melanomas (UM) are rare malignancies in young patients. It is unknown if UM in young patients significantly differs from those in older patients concerning tumor size and localization, metastasis and genetics. The aim of this study was to evaluate the clinical course and tumor characteristics in young patients with UM.
MATERIAL AND METHODS: All patients with UM below the age of 32 years who had been treated at our hospital were included in the study. Patient age and sex, duration of symptoms, visual impairment, tumor size and location, genetics, therapy, follow-up interventions and tumor-associated deaths were documented.
RESULTS: A total of 57 patients (67 % male, mean age 24.7 years) were included in the study with an average symptomatic course of 5 months. Of the patients 8 (14 %) had an initial visual acuity of ≥ 0.9, 16 (28 %) 0.5-0.8, 22 (39 %) 0.05-0.4 and 9 (16 %) < 0.05 (no data for 2 patients, 4 %). After therapy visual acuity was < 0.05 in 54 % and 53 % of the tumors were choroidal UM (70 % juxtapapillary/circumpapillary), whereas 47 % were ciliochoroidal (54 % with iridociliary involvement). The average tumor size was 12.7 ± 3.6 mm with an average prominence of 6.2 ± 3.2 mm. Genetic evaluation (n = 16) revealed disomy 3 in 64 % and 54 % of the patients received radiotherapy with local application of ruthenium 106. In 46 % of cases follow-up interventions were neccessary including 70 % due to radiogenic retinopathy.
CONCLUSION: In young patients UM did not show any preferred localization. The majority of genetically evaluated tumors revealed disomy 3 with no significant correlation to tumor location. Independent of tumor size, location and therapy, approximately half of the patients needed follow-up interventions, predominantly due to radiogenic retinopathy.

PMID: 27286673 [PubMed - as supplied by publisher]

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Neogenin defined as a GD3-associated molecule by enzyme-mediated activation of radical sources confers malignant properties via intra-cytoplasmic domain in melanoma cells.

Neogenin defined as a GD3-associated molecule by enzyme-mediated activation of radical sources confers malignant properties via intra-cytoplasmic domain in melanoma cells.

J Biol Chem. 2016 Jun 10;

Authors: Kaneko K, Ohkawa Y, Hashimoto N, Ohmi Y, Kotani N, Honke K, Ogawa M, Okajima T, Furukawa K, Furukawa K

Abstract
To investigate mechanisms for increased malignant properties in malignant melanomas by gangliosdide GD3, enzyme-mediated activation of radical sources and subsequent mass spectrometry were performed using an anti-GD3 antibody, and GD3-positive (GD3+) and GD3-negative (GD3-) melanoma cell lines. Neogenin defined as a GD3-neighbored molecule was largely localized in lipid/rafts in GD3+ cells. Silencing of neogenin resulted in the reduction of cell growth and invasion activity. Physical association between GD3 and neogenin was demonstrated by immunostaining of the immunoprecipitates with anti- neogenin antibody from GD3+ cell lysates. Intra-cytoplasmic domain of neogenin (Ne-ICD) was detected in GD3+ cells at higher levels than in GD3- cells when cells were treated by a proteasome inhibitor, but not when simultaneously treated with a γ-secretase inhibitor. Over-expression of Ne-ICD in GD3- cells resulted in the increased cell growth and invasion activity, suggesting that Ne-ICD plays a role as a transcriptional factor to drive malignant properties of melanomas after cleavage with γsecretase. γ-secretase was found in lipid/rafts in GD3+ cells. Accordingly, immunocytostaining revealed that GD3, neogenin and γ-secretase were co-localized at the leading edge of GD3+ cells. All these results suggested that GD3 recruits γ-secretase to lipid/rafts, allowing efficient cleavage of neogenin. ChIP-sequensing was performed to identify candidates of target genes of Ne-ICD. Some of them actually showed increased expression after expression of Ne-ICD, probably exerting malignant phenotypes of melanomas under GD3 expression.

PMID: 27288875 [PubMed - as supplied by publisher]

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Development and application of a rapid detection system for human papillomavirus and Herpes simplex virus -2 by loop-mediated isothermal amplification assay.

Development and application of a rapid detection system for human papillomavirus and Herpes simplex virus -2 by loop-mediated isothermal amplification assay.

Microb Pathog. 2016 Jun 8;

Authors: Yang JF, Zhao CZ, Lu KX

Abstract
Human papillomavirus (HPV) infection is an important factor that causes cervical cancer and non-melanoma skin cancer (NMSC), while HSV-2 plays an important role when HR-HPV triggers the cancer. Thus, a quick and convenient assay in the detection of HPV and HSV-2in the screening of HPV and HSV-2 infection is required. Two respective HPV and HSV-2 detection methods were established based on loop-mediated isothermal amplification (LAMP) assay. Specific outer primers, inner primers, and loop primers were designed according to the conserved domains of HPV and HSV-2 genomes, respectively, while degenerate primers were used for HPV assay. After optimizing the reaction conditions, the results were observed by LAMP Tubidimeter real-time LA-320. Standard plasmids HPV-L-P and HSV-2-L-P were cloned and used in sensitivity tests of HPV LAMP and HSV-2 LAMP, respectively. Fifty samples of actinic keratosis (AK), 20 samples of squamous cell carcinoma (SCC), 50 samples of basal cell carcinoma (BCC) and 20 samples of seborrheic keratosis (SK) were detected by HPV assay. Seventy three clinical samples of vaginitis, chronic cervicitis, cervical intraepithelial neoplasias and cervical cancer level positive were detected with HPV and HSV-2 assays. The reaction conditions of two assays were the same with a reaction temperature of 63 °C and a reaction time of 45 min. The sensitivity of HPV LAMP assay was 10 copies/μL, while that of the HSV-2 LAMP assay was 100 copies/μL. No cross-reactivity was observed. The HPV positive rates of AK, SCC, BCC and SK samples were 80% (40/50), 75% (15/20), 44% (22/50) and 21% (15/72), respectively. As an economic and quick diagnostic tool, LAMP assay is conducive to the extensive screening of HPV and HSV-2 and has huge potential to be promoted in resource-limited hospitals.

PMID: 27287497 [PubMed - as supplied by publisher]

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Identification of aryl hydrocarbon receptor signaling pathways altered in TCDD-treated red seabream embryos by transcriptome analysis.

Identification of aryl hydrocarbon receptor signaling pathways altered in TCDD-treated red seabream embryos by transcriptome analysis.

Aquat Toxicol. 2016 May 24;177:156-170

Authors: Iida M, Fujii S, Uchida M, Nakamura H, Kagami Y, Agusa T, Hirano M, Bak SM, Kim EY, Iwata H

Abstract
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces a broad spectrum of toxic effects including craniofacial malformation and neural damage in fish embryos. These effects are mainly mediated by the aryl hydrocarbon receptor (AHR). However, the mode of action between TCDD-induced AHR activation and adverse outcomes is not yet understood. To provide a comprehensive picture of the AHR signaling pathway in fish embryos exposed to TCDD, red seabream (Pagrus major) embryos were treated with graded concentrations of TCDD (0.3-37nM) in seawater, or with a mixture of TCDD and 500nM CH223191, an AHR-specific antagonist. The transcriptome of red seabream embryos was analyzed using a custom-made microarray with 6000 probes specifically prepared for this species. A Jonckheere-Terpstra test was performed to screen for genes that demonstrated altered mRNA expression levels following TCDD exposure. The signals of 1217 genes (as human homologs) were significantly altered in a TCDD concentration-dependent manner (q-value<0.2). Notably, the TCDD-induced alteration in mRNA expression was alleviated by co-exposure to CH223191, suggesting that the mRNA expression level of these genes was regulated by AHR. To identify TCDD-activated pathways, the microarray data were further subjected to gene set enrichment analysis (GSEA) and functional protein-protein interaction (PPI) network analysis. GSEA demonstrated that the effects of TCDD on sets of genes involved calcium, mitogen-activated protein kinase (MAPK), actin cytoskeleton, chemokine, T cell receptor, melanoma, vascular endothelial growth factor (VEGF), axon guidance, and renal cell carcinoma signaling pathways. These results suggest the hypotheses that TCDD induces immunosuppression via the calcium, MAPK, chemokine, and T cell receptor signaling pathways, neurotoxicity via VEGF signaling, and axon guidance alterations and teratogenicity via the dysregulation of the actin cytoskeleton and melanoma and renal cell carcinoma signaling pathways. Furthermore, the PPI network analysis indicated that the adverse outcome pathways of TCDD in the embryos might be propagated through several hub genes such as cell division control protein 42, phosphoinositide-3-kinase regulatory subunit 1, and guanine nucleotide-binding proteins. Understanding these pathways potentially allows for exploring the adverse outcome pathway of the effects of TCDD on the red seabream embryos.

PMID: 27288597 [PubMed - as supplied by publisher]

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Association between new-onset hypothyroidism and clinical response in patients treated with tyrosine kinase inhibitor therapy in phase I clinical trials.

Association between new-onset hypothyroidism and clinical response in patients treated with tyrosine kinase inhibitor therapy in phase I clinical trials.

Cancer Chemother Pharmacol. 2016 Jun 10;

Authors: Bilen MA, Patel A, Hess KR, Munoz J, Busaidy NL, Wheler JJ, Janku F, Falchook GS, Hong DS, Meric-Bernstam F, Habra MA, Naing A

Abstract
PURPOSE: Tyrosine kinase inhibitor (TKI)-induced thyroid dysfunction has been identified as an important but manageable adverse effect of targeted therapy. Several studies have suggested that patients who develop hypothyroidism respond better to TKIs, but this relationship is not well elucidated. We evaluated the relationship between new-onset hypothyroidism and clinical response in patients with advanced cancers treated with TKIs at our institution.
METHODS: We retrospectively reviewed records for patients from four clinical trials that included at least one TKI  therapy between January 2006 and December 2011. Patients with preexisting thyroid disease, including thyroid cancer, hypothyroidism, or hyperthyroidism, were excluded. Analysis of 197 patients was performed. Response was determined using RECIST 1.0. Clinical benefit was described as complete response, partial response, or stable disease greater than 4 months. Multivariable logistic regression analysis was performed to correlate patient characteristics with clinical response.
RESULTS: The median age for the 197 patients was 58 years (range, 13-85 years), and 56 % were female. Of the 197 patients, 52 (26 %) developed hypothyroidism after therapy. Clinical benefit rates were 50 % in patients with new-onset hypothyroidism versus 34 % in patients without hypothyroidism. In the univariate model, the odds ratio (OR) for new-onset hypothyroidism was 1.9 [95 % confidence interval (CI) (1.0, 3.6) and p = 0.05]. We grouped tumor types into six categories (breast, colorectal carcinoma, melanoma, non-small cell lung cancer, pancreas, and other). When adjusted for tumor type, age (>50 years) and sex, the OR was 2.9 [95 % CI (1.3, 6.5) and p = 0.012] for new-onset hypothyroidism.
CONCLUSION: New-onset hypothyroidism was associated with favorable clinical response in patients who received TKI treatment.

PMID: 27286994 [PubMed - as supplied by publisher]

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[Integrating patient education in your oncology practice].

[Integrating patient education in your oncology practice].:

[Integrating patient education in your oncology practice].

Bull Cancer. 2016 Jun 7;

Authors: Thariat J, Creisson A, Chamignon B, Dejode M, Gastineau M, Hébert C, Boissin F, Topfer C, Gilbert E, Grondin B, Guennoc H, Mari V, Buzzo S, Saja D, Duboue N, Boulahssass R, Tosi A, Verne S, Ducray J, Benard-Thiery I, Ferrero JM

Abstract
BACKGROUND: Patient education is the process by which health professionals impart information to patients and their caregivers that will alter their health behaviors; improve their health status to better manage their lives with a chronic disease. Patient education implies a profound paradigm shift in the conception of care among health professionals, and should result in structural care changes. Patient education has been promoted by the French Health system for 30years, including in the 2009 HPST law and Cancer Plan 2014-2019. A patient education program was designed in our hospital for breast cancer patients.
MATERIAL AND METHODS: A multidisciplinary and transversal team of health professionals and resource patients was trained before grant application for funding of the program by the regional health care agency. Management of the project required that a functional unit be built for recording of all patient education related activities. A customized patient education program process was built under the leadership of a coordinator and several patient education project managers during bimonthly meetings, using an accurate timeline and a communication strategy to ensure full institutional support and team engagement.
RESULTS: The grant was prepared in four months and the program started within the next four months with the aim to include 120 patients during year 1. The program includes a diagnosis of patient abilities and well-being resources, followed by collective and individual workshops undertaken in 4months for each patient.
DISCUSSION: Patient education is positively evaluated by all participants and may contribute to better health care management in the long term but the financial and human resources allocated to such programs currently underestimate the needs. Sustainability of patient education programs requires that specific tools and more commitment be developed to support health care professionals and to promote patient coping and empowerment in the long term.

PMID: 27286758 [PubMed - as supplied by publisher]

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Effect of genetic factors on the development of atopy and reactivity to specific allergens

Publication date: Available online 11 June 2016
Source:Annals of Allergy, Asthma & Immunology
Author(s): Linnea Skov, Howraman Meteran, Vibeke Backer, Simon Francis Thomsen




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Th9 cells elicit eosinophil-independent bronchial hyperresponsiveness in mice

Publication date: Available online 11 June 2016
Source:Allergology International
Author(s): Mayumi Saeki, Osamu Kaminum, Tomoe Nishimura, Noriko Kitamura, Akio Mori, Takachika Hiroi
BackgroundAirway accumulation of eosinophils and bronchial hyperresponsiveness (BHR) are prominent features of bronchial asthma, though the contribution of eosinophils to the development of BHR is controversial. Similar to Th2 cell-mediated pathology, Th9 cells, characterized by IL-9-producing activity, have been demonstrated to induce airway eosinophilia and BHR. In this study, we investigated the role of eosinophils in Th9-mediated BHR by employing Th9 cell-transferred murine airway inflammation model.MethodsOvalbumin (OVA)-specific Th2 and Th9 cells were differentiated from CD4⁺ T cells of DO11.10/RAG-2^−/− mice in vitro and cytokine-producing activity of those cells was examined. BALB/c mice were adoptively transferred with Th2 or Th9 cells and challenged with OVA. Then, the number of inflammatory cells in bronchoalveolar lavage fluid and bronchial responsiveness to inhaled methacholine were determined.ResultsBoth in Th2 and Th9 cell-transferred mice, substantial accumulation of eosinophils in the lungs and BHR were induced by challenge with specific antigen. Nevertheless, an essential and dispensable role of eosinophils in Th2- and Th9-mediated BHR, respectively, was demonstrated by employing eosinophil-deficient mice. The neutralization of IL-9 as well as deficiency of IL-10 in the donor cells did not affect Th9-mediated BHR.ConclusionsIn contrast to Th2-mediated and eosinophil-dependent BHR, Th9 could induce BHR independently from eosinophils and its characteristic cytokines, IL-9 and IL-10.



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Poorly controlled asthma and strongyloidiasis in a nonendemic area of the United States

Publication date: Available online 11 June 2016
Source:Annals of Allergy, Asthma & Immunology
Author(s): Santiago Alvarez Arango, Vineet Reddy, David L. Rosenstreich, Sunit P. Jariwala




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Cross sectional questionnaire-based internet study: Self-perception and clinical course of drug allergy in Greece

Publication date: Available online 11 June 2016
Source:Allergology International
Author(s): Michael P. Makris, Theodoros N. Sergentanis, Xenophon Aggelides, Stamatios Tzanninis, Efthimia Polyzou, Dimitrios Rigopoulos, Theodora Psaltopoulou
BackgroundData on self perception of drug allergy in the general population are lacking. Epidemiological studies focus either on specific populations or document adverse drug reactions in general. Our objective was to document self-reported drug allergy in Greece, through a simple, informative internet-based questionnaire.MethodsA questionnaire on drug allergy was accessible online for a 3-month period. Participants voluntarily answered 28 questions referring to: suspected drug, clinical manifestations, concomitant factors, received treatment, reaction's re-occurrence.ResultsA total of 2528 questionnaires were included in study analysis. Beta-lactams and non-steroidal anti-inflammatory drugs were the most prevalent culprit agents (53% and 27.5% respectively) while half of the participants acknowledged skin manifestations as the most common symptoms. One out of three reported subsequent exposure to the drug presumed to be responsible for the reaction and 74.5% of those stated a new reaction upon re-exposure. Only 26.7% underwent allergological evaluation. Reactions manifested with respiratory or cardiovascular symptoms, parenteral administration of the culprit drug and personal history of allergy to agents of >1 different pharmacological categories were associated with increased risk of hospitalization.ConclusionsAllergic reactions to drugs are adverse events difficult to define and diagnose. A remarkable proportion of presumed as hypersensitivity reactions are not referred to allergists; therefore these patients may be either re-exposed to potentially noxious drugs, or needlessly avoid whole classes of drugs as b-lactams for more costly or less appropriate treatments. Internet-based questionnaires may contribute to awareness programs concerning drug allergy and help improve proper referral.



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A case of selective IgG subclass deficiency with STAT3 mutation

Publication date: Available online 11 June 2016
Source:Allergology International
Author(s): Hidenori Ohnishi, Norio Kawamoto, Hideo Kaneko, Kimiko Kasahara, Osamu Ohara, Zenichiro Kato, Toshiyuki Fukao




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[Integrating patient education in your oncology practice].

[Integrating patient education in your oncology practice].

Bull Cancer. 2016 Jun 7;

Authors: Thariat J, Creisson A, Chamignon B, Dejode M, Gastineau M, Hébert C, Boissin F, Topfer C, Gilbert E, Grondin B, Guennoc H, Mari V, Buzzo S, Saja D, Duboue N, Boulahssass R, Tosi A, Verne S, Ducray J, Benard-Thiery I, Ferrero JM

Abstract
BACKGROUND: Patient education is the process by which health professionals impart information to patients and their caregivers that will alter their health behaviors; improve their health status to better manage their lives with a chronic disease. Patient education implies a profound paradigm shift in the conception of care among health professionals, and should result in structural care changes. Patient education has been promoted by the French Health system for 30years, including in the 2009 HPST law and Cancer Plan 2014-2019. A patient education program was designed in our hospital for breast cancer patients.
MATERIAL AND METHODS: A multidisciplinary and transversal team of health professionals and resource patients was trained before grant application for funding of the program by the regional health care agency. Management of the project required that a functional unit be built for recording of all patient education related activities. A customized patient education program process was built under the leadership of a coordinator and several patient education project managers during bimonthly meetings, using an accurate timeline and a communication strategy to ensure full institutional support and team engagement.
RESULTS: The grant was prepared in four months and the program started within the next four months with the aim to include 120 patients during year 1. The program includes a diagnosis of patient abilities and well-being resources, followed by collective and individual workshops undertaken in 4months for each patient.
DISCUSSION: Patient education is positively evaluated by all participants and may contribute to better health care management in the long term but the financial and human resources allocated to such programs currently underestimate the needs. Sustainability of patient education programs requires that specific tools and more commitment be developed to support health care professionals and to promote patient coping and empowerment in the long term.

PMID: 27286758 [PubMed - as supplied by publisher]

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Effect of genetic factors on the development of atopy and reactivity to specific allergens

Publication date: Available online 11 June 2016
Source:Annals of Allergy, Asthma & Immunology
Author(s): Linnea Skov, Howraman Meteran, Vibeke Backer, Simon Francis Thomsen




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Poorly controlled asthma and strongyloidiasis in a nonendemic area of the United States

Publication date: Available online 11 June 2016
Source:Annals of Allergy, Asthma & Immunology
Author(s): Santiago Alvarez Arango, Vineet Reddy, David L. Rosenstreich, Sunit P. Jariwala




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Th9 cells elicit eosinophil-independent bronchial hyperresponsiveness in mice

Publication date: Available online 11 June 2016
Source:Allergology International
Author(s): Mayumi Saeki, Osamu Kaminum, Tomoe Nishimura, Noriko Kitamura, Akio Mori, Takachika Hiroi
BackgroundAirway accumulation of eosinophils and bronchial hyperresponsiveness (BHR) are prominent features of bronchial asthma, though the contribution of eosinophils to the development of BHR is controversial. Similar to Th2 cell-mediated pathology, Th9 cells, characterized by IL-9-producing activity, have been demonstrated to induce airway eosinophilia and BHR. In this study, we investigated the role of eosinophils in Th9-mediated BHR by employing Th9 cell-transferred murine airway inflammation model.MethodsOvalbumin (OVA)-specific Th2 and Th9 cells were differentiated from CD4⁺ T cells of DO11.10/RAG-2^−/− mice in vitro and cytokine-producing activity of those cells was examined. BALB/c mice were adoptively transferred with Th2 or Th9 cells and challenged with OVA. Then, the number of inflammatory cells in bronchoalveolar lavage fluid and bronchial responsiveness to inhaled methacholine were determined.ResultsBoth in Th2 and Th9 cell-transferred mice, substantial accumulation of eosinophils in the lungs and BHR were induced by challenge with specific antigen. Nevertheless, an essential and dispensable role of eosinophils in Th2- and Th9-mediated BHR, respectively, was demonstrated by employing eosinophil-deficient mice. The neutralization of IL-9 as well as deficiency of IL-10 in the donor cells did not affect Th9-mediated BHR.ConclusionsIn contrast to Th2-mediated and eosinophil-dependent BHR, Th9 could induce BHR independently from eosinophils and its characteristic cytokines, IL-9 and IL-10.



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Cross sectional questionnaire-based internet study: Self-perception and clinical course of drug allergy in Greece

Publication date: Available online 11 June 2016
Source:Allergology International
Author(s): Michael P. Makris, Theodoros N. Sergentanis, Xenophon Aggelides, Stamatios Tzanninis, Efthimia Polyzou, Dimitrios Rigopoulos, Theodora Psaltopoulou
BackgroundData on self perception of drug allergy in the general population are lacking. Epidemiological studies focus either on specific populations or document adverse drug reactions in general. Our objective was to document self-reported drug allergy in Greece, through a simple, informative internet-based questionnaire.MethodsA questionnaire on drug allergy was accessible online for a 3-month period. Participants voluntarily answered 28 questions referring to: suspected drug, clinical manifestations, concomitant factors, received treatment, reaction's re-occurrence.ResultsA total of 2528 questionnaires were included in study analysis. Beta-lactams and non-steroidal anti-inflammatory drugs were the most prevalent culprit agents (53% and 27.5% respectively) while half of the participants acknowledged skin manifestations as the most common symptoms. One out of three reported subsequent exposure to the drug presumed to be responsible for the reaction and 74.5% of those stated a new reaction upon re-exposure. Only 26.7% underwent allergological evaluation. Reactions manifested with respiratory or cardiovascular symptoms, parenteral administration of the culprit drug and personal history of allergy to agents of >1 different pharmacological categories were associated with increased risk of hospitalization.ConclusionsAllergic reactions to drugs are adverse events difficult to define and diagnose. A remarkable proportion of presumed as hypersensitivity reactions are not referred to allergists; therefore these patients may be either re-exposed to potentially noxious drugs, or needlessly avoid whole classes of drugs as b-lactams for more costly or less appropriate treatments. Internet-based questionnaires may contribute to awareness programs concerning drug allergy and help improve proper referral.



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A case of selective IgG subclass deficiency with STAT3 mutation

Publication date: Available online 11 June 2016
Source:Allergology International
Author(s): Hidenori Ohnishi, Norio Kawamoto, Hideo Kaneko, Kimiko Kasahara, Osamu Ohara, Zenichiro Kato, Toshiyuki Fukao




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Anatomy and relations of the infraspinatus and the teres minor muscles: a fresh cadaver dissection study.

Anatomy and relations of the infraspinatus and the teres minor muscles: a fresh cadaver dissection study.

Surg Radiol Anat. 2016 Jun 10;

Authors: Bacle G, Gregoire JM, Patat F, Clavert P, de Pinieux G, Laulan J, Lakhal W, Favard L

Abstract
PURPOSE: Despite their functional importance, the infraspinatus (ISP) and teres minor (TM) muscles have been little investigated. This study aimed to describe the macroscopic morphology, innervation, and inter-relations of the ISP and TM muscles.
METHODS: Forty fresh cadaver dissections and histologic analysis were performed. Three groups of specimens were distinguished according to the rotator cuff tendon status: (1) intact rotator cuff; (2) supraspinatus tendon tears with intact ISP tendon; and (3) both supraspinatus and ISP tendons torn. Muscle fiber organization and muscle and tendon length were recorded. ISP and TM innervation and fiber structure were studied.
RESULTS: ISP muscles were composed of three groups of fiber organized in two planes: two superficial groups, with mean pennation angles of, respectively, 27° ± 4° and 23° ± 3° with respect to the axis of the central tendon of the underlying group. TMs were thick fusiform muscles showing a parallel organization; 26 specimens (67 %) had aponeuroses isolating the TM, with a mean length of 5.2 ± 2.7 cm. Rotator cuff lesions were associated with relatively greater ISP tendon than muscle length. Innervation of the ISP muscle comprised 2-4 main branches from the suprascapular nerve and that of the TM 1 branch from the axillary nerve.
CONCLUSION: ISP muscle body morphology derives from three groups of fibers in two planes. The TM has a parallel organization. Several nerve branches innervate the ISP muscle, whereas only one supplies the TM. The limits between the two muscles bodies consist of an aponeurotic fascia in two-thirds of cases.

PMID: 27286948 [PubMed - as supplied by publisher]

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Interventions for Menière's disease: protocol for an umbrella systematic review and a network meta-analysis.

Interventions for Menière's disease: protocol for an umbrella systematic review and a network meta-analysis.

BMJ Open. 2016;6(6):e010269

Authors: van Esch BF, van der Zaag-Loonen HJ, Bruintjes TD, van Benthem PP

Abstract
INTRODUCTION: The large number of treatment modalities for patients diagnosed with Menière's disease (MD) complicates the selection of the best available treatment as the comparative efficacy of these interventions is not clear. We aim to identify the treatment or treatments with the highest efficacy of current pharmacological and non-pharmacological treatments for MD.
METHODS AND ANALYSIS: We will identify all available systematic reviews on the treatment of MD. An online database search will be conducted in association with the UK Cochrane Centre, particularly the Ear, Nose and Throat Group. We will screen the systematic reviews for eligible randomised controlled trials (RCTs) to execute a network meta-analysis. In addition, online databases will be checked for eligible RCTs on treatments that were published after the latest systematic search was conducted. The characteristics of each RCT will be summarised, including the general design, the participants, the interventions, the outcome measurements, the duration of therapy and adverse events. The risk of bias will be assessed by means of the Cochrane Collaboration's risk of bias tool. The included studies will be assessed for methodological and statistical heterogeneity; the latter will be quantified by means of the I(2) statistic. The primary outcome will be the efficacy of treatment in terms of control of vertigo attacks. Secondary outcome measures will be the loss or improvement of hearing, severity of vertigo attacks and tinnitus, perception of aural fullness, quality of life, and the incidence of adverse events and complications.
ETHICS AND DISSEMINATION: Formal ethical approval is not required as primary data will not be collected. The review will be disseminated in peer-reviewed publications and conference presentations.
PROSPERO REGISTRATION NUMBER: CRD42015024243.

PMID: 27288370 [PubMed - as supplied by publisher]

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Glioma-mediated microglial activation promotes glioma proliferation and migration: roles of Na+/H+ exchanger isoform 1.

Glioma-mediated microglial activation promotes glioma proliferation and migration: roles of Na+/H+ exchanger isoform 1.

Carcinogenesis. 2016 Jun 9;

Authors: Zhu W, Carney KE, Pigott VM, Falgoust LM, Clark PA, Kuo JS, Sun D

Abstract
Microglia play important roles in extracellular matrix remodeling, tumor invasion, angiogenesis, and suppression of adaptive immunity in glioma. Na(+)/H(+) exchanger isoform 1 (NHE1) regulates microglial activation and migration. However, little is known about the roles of NHE1 in intratumoral microglial activation and microglia-glioma interactions. Our study revealed up-regulation of NHE1 protein expression in both glioma cells and tumor-associated Iba1(+) microglia in glioma xenografts and GBM microarrays. Moreover, we observed positive correlation of NHE1 expression with Iba1 intensity in microglia/macrophages. Glioma cells, via conditioned medium or non-contact glioma-microglia co-cultures, concurrently upregulated microglial expression of NHE1 protein and other microglial activation markers (iNOS, arginase-1, TGF-ß, IL-6, IL-10 and the matrix metalloproteinases MT1-MMP and MMP9). Interestingly, glioma-stimulated microglia reciprocally enhanced glioma proliferation and migration. Most importantly, inhibition of microglial NHE1 activity via siRNA knockdown or the potent NHE1-specific inhibitor HOE642 significantly attenuated microglial activation and abolished microglia-stimulated glioma migration and proliferation. Taken together, our findings provide the first evidence that NHE1 function plays an important role in glioma-microglia interactions, enhancing glioma proliferation and invasion by stimulating microglial release of soluble factors. NHE1 upregulation is a novel marker of the glioma-associated microglial activation phenotype. Inhibition of NHE1 represents a novel glioma therapeutic strategy by targeting tumor-induced microglial activation.

PMID: 27287871 [PubMed - as supplied by publisher]

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The value of intraoperative and early postoperative MRI in low-grade glioma surgery A retrospective study.

The value of intraoperative and early postoperative MRI in low-grade glioma surgery A retrospective study.

World Neurosurg. 2016 Jun 8;

Authors: Pala A, Brand C, Kapapa T, Hlavac M, König R, Schmitz B, Wirtz CR, Coburger J

Abstract
Presence of residual tumor is crucial in decision making in low grade gliomas (LGGs), since patients with residual tumor and age over 40 are considered for adjuvant treatment. There are hints, that early postoperative FLAIR and T2 (within 48 hours) may overestimate residual tumor volume in LGG. Intraoperative MRI (iMRI) without subsequent resection or ultra-early postoperative MRI may assess the amount of residual tumor more adequately. To evaluate the utility of postoperative imaging in LGG we volumetrically analyzed intraoperative, early and late (3-4 months after surgery) postoperative MRI in LGG.
PATIENTS AND METHODS: A total of 33 patients with LGG were assessed retrospectively. Residual tumor was defined as signal enhanced tissue in T2 and FLAIR. Volumetric assessment was performed using intraoperative, early and late postoperative T2/Flair using Brainlab-iPlan 3.0. Wilcoxon and Chi-Square tests were used for statistical analysis.
RESULTS: A significant difference of FLAIR/T2 abnormalities was found in intraoperative and early postoperative MRI (FLAIR mean volume=5.433cm(3),T2 mean volume=3.374 cm(3) vs. FLAIR mean volume=14.090 cm(3), p=0.002,T2 mean volume=7.597 cm(3),p=0.006). There was no significant difference between intraoperative and late postoperative FLAIR/T2 abnormalities (late postoperative FLAIR/T2 mean volume=5.560 cm(3) and 2.370 cm(3), p=0.520, p=0,398) whereas a significant difference was detected between early and late postoperative images (FLAIR, p<0.0001,T2, p<0.00001).
CONCLUSION: Intraoperative MRI without further resection or ultra-early postoperative MRI seems to reflect the actual volume of residual tumor in LGG more precisely compared to early postoperative MRI and therefore seems to be more useful regarding decisions for adjuvant therapy.

PMID: 27288582 [PubMed - as supplied by publisher]

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Epithelial Anion Transport as Modulator of Chemokine Signaling

The pivotal role of epithelial cells is to secrete and absorb ions and water in order to allow the formation of a luminal fluid compartment that is fundamental for the epithelial function as a barrier against environmental factors. Importantly, epithelial cells also take part in the innate immune system. As a first line of defense they detect pathogens and react by secreting and responding to chemokines and cytokines, thus aggravating immune responses or resolving inflammatory states. Loss of epithelial anion transport is well documented in a variety of diseases including cystic fibrosis, chronic obstructive pulmonary disease, asthma, pancreatitis, and cholestatic liver disease. Here we review the effect of aberrant anion secretion with focus on the release of inflammatory mediators by epithelial cells and discuss putative mechanisms linking these transport defects to the augmented epithelial release of chemokines and cytokines. These mechanisms may contribute to the excessive and persistent inflammation in many respiratory and gastrointestinal diseases.

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Pretransplant Immune- and Apoptosis-Related Gene Expression Is Associated with Kidney Allograft Function

Renal transplant candidates present immune dysregulation, caused by chronic uremia. The aim of the study was to investigate whether pretransplant peripheral blood gene expression of immune factors affects clinical outcome of renal allograft recipients. Methods. In a prospective study, we analyzed pretransplant peripheral blood gene expression in87 renal transplant candidates with real-time PCR on custom-designed low density arrays (TaqMan). Results. Immediate posttransplant graft function (14-day GFR) was influenced negatively by TGFB1 () and positively by IL-2 gene expression (). Pretransplant blood mRNA expression of apoptosis-related genes (CASP3, FAS, and IL-18) and Th1-derived cytokine gene IFNG correlated positively with short- (6-month GFR CASP3: , FAS: , and IFNG: ) and long-term graft function (24-month GFR CASP3: , FAS: , IL-18: , and IFNG: ). Conclusion. Lowered pretransplant Th1-derived cytokine and apoptosis-related gene expressions were a hallmark of subsequent worse kidney function but not of acute rejection rate. The pretransplant IFNG and CASP3 and FAS and IL-18 genes' expression in the recipients' peripheral blood is the possible candidate for novel biomarker of short- and long-term allograft function.

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Germline CDKN2A Mutation Status and Survival in Familial Melanoma Cases.

Germline CDKN2A Mutation Status and Survival in Familial Melanoma Cases.:

Germline CDKN2A Mutation Status and Survival in Familial Melanoma Cases.

J Natl Cancer Inst. 2016 Nov;108(11)

Authors: Helgadottir H, Höiom V, Tuominen R, Nielsen K, Jönsson G, Olsson H, Hansson J

Abstract
BACKGROUND: Germline mutations in CDKN2A have been associated with increased risk of melanoma and tobacco-related cancers in respiratory and upper digestive tissues. In CDKN2A wild-type (wt) melanoma families, other known high-risk, melanoma-predisposing mutations are rare, and no increased risk has been observed for nonskin cancers in this group. This study is the first to compare survival in germline CDKN2A mutated (mut) and nonmutated melanoma cases.
METHODS: Melanoma-prone families participating in this study were identified through a nationwide predictive program starting in 1987. Information on cancer diagnoses (types, stages, and dates) and deaths (causes and dates) were obtained through the Swedish Cancer Registry and Cause of Death Registry. Kaplan Meier and Cox proportional hazards regression models were used to assess survival in CDKN2A(mut) (n = 96) and CDKN2A(wt) (n = 377) familial melanoma cases and in matched sporadic melanoma cases (n = 1042). All statistical tests were two-sided.
RESULTS: When comparing CDKN2A(mut) and CDKN2A(wt) melanoma cases, after adjusting for age, sex, and T classification, CDKN2A(mut) had worse survival than melanoma (hazard ratio [HR] = 2.50, 95% confidence interval [CI] = 1.49 to 4.21) and than nonmelanoma cancers (HR = 7.77, 95% CI = 3.65 to 16.51). Compared with matched sporadic cases, CDKN2A(mut) cases had statistically significantly worse survival from both melanoma and nonmelanoma cancers while no differences in survival were seen in CDKN2A(wt) compared with sporadic cases.
CONCLUSIONS: CDKN2A(mut) cases had statistically significantly worse survival than nonmelanoma cancers and, intriguingly, also from melanoma, compared with melanoma cases with no CDKN2A mutations. Further studies are required to elucidate possible mechanisms behind increased carcinogen susceptibility and the more aggressive melanoma phenotype in CDKN2A mutation carriers.

PMID: 27287845 [PubMed - as supplied by publisher]

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Fwd: Journal of Dermatology and Venereology, Year 2016, Issue 01 -New Issue Alert.

Fwd: Journal of Dermatology and Venereology, Year 2016, Issue 01 -New Issue Alert.:

From: order@email.oriprobe.com
Date: June 12, 2016 at 08:10AM

New Issue TOC AlertDear Valued Customer,

We are pleased to deliver your requested table of contents alert for Journal of Dermatology and Venereology. Year 2016 Issue 01 is now available on CAOD.

In this issue:

Curative effect of spleen aminopeptide oral lyophilized powder combined with recombinant human interferon α-2b ointment on verruca plana and its influence on t-lymphocyte subsets, IL-2, IL-4, INF-γ in adolescent patients (脾氨肽联合干扰素α-2b治疗青少年扁平疣临床研究及对淋巴细胞亚群、IL-2、IL-4、INF-γ的影响)QING Ping-ping, ,LIU Run-qiu, ,LV Dong
…… page:1-4Retrospective clinical analysis of the genotypes distribution of HPV infection (HPV感染基因型分布的回顾性分析)LI Ling-jia, ,ZHANG Sheng, ,GU Hua, ,ZHANG Jie
…… page:5-8Analysis of clinical and serological results in 90 cases of early syphilis (90例早期梅毒患者治疗前后的临床及血清学结果分析)YUAN Li-li, ,YUAN Hao-chen
…… page:8-10The therapeutic effects of pyrithione zinc aerosol combined with calcipotriol betamethasone ointment on plaque psoriasis patients with topical sequential therapy (吡硫翁锌气雾剂联合钙泊三醇倍他米松软膏序贯治疗斑块型银屑病的观察)HAO Wei-li, ,CAO Bing-qing, ,ZHANG Heng-po
…… page:10-12The study of onychomadesis cases in Deqing county of Yunnan province (云南德钦9名藏族患儿甲损害病例调查分析)ZHEN Bo-wen, ,QU Hong-ye
…… page:12-15quan shen ying yong tang pi zhi ji su de bu liang fan ying ji fang zhi dui ce (全身应用糖皮质激素的不良反应及防治对策)GU Youshou
…… page:16-18wai yong tang pi zhi ji su de shi ying zheng yu fu zuo yong (外用糖皮质激素的适应症与副作用)LIU Huai, ,LIU Jingzuo
…… page:19-20Research progress of electro-optical device for hair removal and rare complications (光电设备脱毛的研究进展及罕见并发症)CHEN Yuan, ,YANG Zhi
…… page:21-23Research progresses of paracrine effects of keratinocyte on keloid (角质形成细胞旁分泌作用在瘢痕疙瘩形成中的研究进展)ZHOU Nian, ,TANG Yang
…… page:23-26The research progress of callicarpa nudiflora hook.et Arn in dermatology department (裸花紫珠片在皮肤科中应用研究进展)LI Feng, ,LI Wen-shuang, ,HUANG Yun-li
…… page:26-30Progresses on the treatments of acne (痤疮的治疗进展)JIANG Hong-jing, ,TU Yin, ,HE Li
…… page:30-32Experimental study on the effect of traditional Chinese medicine plant polysaccharide on malignant melanoma (中药植物多糖对恶性黑素瘤作用的实验研究进展)MA Wen-yu, ,WU Deng-ting
…… page:33-3550 sui yi shang ren qun hiv liu xing te zheng yu xiang guan wei xian yin su de xi tong xing fen xi (50岁以上人群HIV流行特征与相关危险因素的系统性分析)GAO Liangmin, ,FU Jincui, ,LI Shifu, ,LI Shaosheng, ,CHEN Liang, ,ZHANG Jun, ,LIU Xiaochun, ,CHEN Lianqiu, ,JING Jun
…… page:36-42yu xi shi (2006-2013) nian 14 sui ren qun hiv gan ran bing li fen xi (玉溪市(2006-2013)年≤14岁人群HIV感染病例分析)ZI Ruhe, ,YANG Xinyan, ,SHI Jiayou, ,LIU Liqun, ,FU Jincui, ,DUAN Zuozuo, ,CHEN Yiyun, ,YANG Zhiying, ,LI Shifu
…… page:42-44yun nan meng zi 1996 nian 2014 nian ai zi bing liu xing te zheng fen xi (云南蒙自1996年～2014年艾滋病流行特征分析)WANG Shuxiu, ,JING Zhengchao
…… page:44-46yuan yang xian 50 sui ji yi shang hiv/aids huan zhe te dian ji si wang nian xian fen xi (元阳县50岁及以上HIV/AIDS患者特点及死亡年限分析)BAI Xihai, ,MA Yong, ,LIU Hongyan, ,LUO Qiongying, ,ZHENG Li, ,LI Qionghua, ,guo , ,LIU Huai, ,LI Hong
…… page:46-48lin cang shi 2010-2013 nian ai zi bing zi yuan zi xun jian ce qiu xun zhe qing kuang fen xi (临沧市2010-2013年艾滋病自愿咨询检测求询者情况分析)YANG Cuiyun, ,GUO Qing, ,ZHU Qiongmei, ,CUI Xiuhong, ,YUAN Qinghua
…… page:48-51aids/hiv huan zhe zhi liao yi cong xing diao cha (AIDS/HIV患者治疗依从性调查)ZHANG Lijuan
…… page:51-52yun nan sheng 2010-2014 nian mei du liu xing xing shi fen xi (云南省2010-2014年梅毒流行形势分析)ZHANG Zuoyue, ,GUO Yan, ,FANG Qingyan, ,YANG Zhifang, ,ZHANG Xiu, ,CUI Wenqing, ,SU Xingfang, ,HU Zuo, ,LUO Hongbing
…… page:52-542010-2014 nian wu lu mu qi shi mei du bao gao zhun que xing diao cha fen xi (2010-2014年乌鲁木齐市梅毒报告准确性调查分析)GAO Xuelian, ,MA Yan, ,YANG Jiandong
…… page:54-56yao an xian 2005-2014 nian mei du liu xing bing xue fen xi (姚安县2005-2014年梅毒流行病学分析)YANG Lifen, ,WANG Lin, ,ZHU Qiang
…… page:57tan tao lin chuang yi xue yan jiu sheng de ke yan neng li pei yang (探讨临床医学研究生的科研能力培养)XU Dan, ,WU Wenjuan, ,SUN Dongjie, ,TU Ying, ,YANG Zhi, ,LIU Tongyun, ,GU Hua, ,NONG Xiang, ,HE Li
…… page:58-59luo hua zi zhu pian lian he ke zuo yin tong ning jiao zhi liao zuo chuang 76 li liao xiao guan cha (裸花紫珠片联合克痤隐酮凝胶治疗痤疮76例疗效观察)ZHANG Ying, ,ZHANG Yao, ,LI Yaoxing
…… page:59-60zi ni yin xie bing 1 hao fang zhi liao ji xing dian di zhuang yin xie bing lin chuang yan jiu (自拟银屑病1号方治疗急性点滴状银屑病临床研究)YUE Xiang, ,ZOU Yong
…… page:60-61duo dian qu cai zi ti zuo pi xia mai zhi zhi liao duo fa xing bian ping zuo liao xiao guan cha (多点取材自体疣皮下埋植治疗多发性扁平疣疗效观察)LIANG Zuohui, ,ZHANG Ying
…… page:61-62hua zuo zuo ban jiao nang lian he qing zuo ru gao zhi liao huang he ban liao xiao guan cha (化瘀祛斑胶囊联合氢醌乳膏治疗黄褐斑疗效观察)HAN Zuomei, ,LI Yuxiao, ,GUO Xiaoguang, ,ZHAO Binchao, ,WANG Lijie, ,LU Jie
…… page:62-64huo zhen jia hong lan guang zhi liao zuo chuang 60 li liao xiao guan cha (火针加红蓝光治疗痤疮60例疗效观察)SHEN Bin
…… page:64-65sapho zong he zheng 2 li (SAPHO综合征2例)GU Jingxin
…… page:66-67han leng xing duo xing hong ban 1 li (寒冷性多形红斑1例)YANG Xujuan, ,NONG Xiang, ,HU Zuoxia, ,LIU Tongyun
…… page:67-68fu zi tong huan ban bo bing 1 li bao gao (父子同患斑驳病1例报告)WANG Qizuo, ,SUN Dongjie
…… page:68-69man xing zuo ma zhen 395 li guo min yuan jian ce jie guo fen xi (慢性荨麻疹395例过敏原检测结果分析)HU Hu
…… page:70chang xiao kang jun cai liao lian he bing suan bei ta mi song ru gao zhi liao ji xing ya ji xing shi zhen de liao xiao guan cha (长效抗菌材料联合丙酸倍他米松乳膏治疗急性亚急性湿疹的疗效观察)ZHONG Xiaona
…… page:71chang xiao kang jun cai liao fu zhu zhi liao shou zu kou bing 60 li liao xiao guan cha (长效抗菌材料辅助治疗手足口病60例疗效观察)SU Shunqin, ,LI Wencang
…… page:72-73jian pi bu shen zuo feng tang pei he xi yao zhi liao ban tu 60 li liao xiao guan cha (健脾补肾祛风汤配合西药治疗斑秃60例疗效观察)LI Xuelin, ,WANG Hongbing
…… page:73-741li ji xing bian tao ti yan you fa fan fa xing nong zuo xing yin xie bing de hu li (1例急性扁桃体炎诱发泛发性脓疱型银屑病的护理)LEI Lei, ,LIU Jiecheng
…… page:75yan xu xing hu li zai ti gao er ke fu wu man yi du de ying yong ti hui (延续性护理在提高儿科服务满意度的应用体会)WANG Yunqiao, ,WU Xinhong, ,HUANG Zuo
…… page:75-77kun ming di qu pu tong ren qun ma feng bing jian kang jiao yu xiao guo ping gu (昆明地区普通人群麻风病健康教育效果评估)LI Na, ,TU Ying, ,LI Qiongyan, ,NENG Yajie
…… page:77-78

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Anatomy and relations of the infraspinatus and the teres minor muscles: a fresh cadaver dissection study.

Anatomy and relations of the infraspinatus and the teres minor muscles: a fresh cadaver dissection study.

Surg Radiol Anat. 2016 Jun 10;

Authors: Bacle G, Gregoire JM, Patat F, Clavert P, de Pinieux G, Laulan J, Lakhal W, Favard L

Abstract
PURPOSE: Despite their functional importance, the infraspinatus (ISP) and teres minor (TM) muscles have been little investigated. This study aimed to describe the macroscopic morphology, innervation, and inter-relations of the ISP and TM muscles.
METHODS: Forty fresh cadaver dissections and histologic analysis were performed. Three groups of specimens were distinguished according to the rotator cuff tendon status: (1) intact rotator cuff; (2) supraspinatus tendon tears with intact ISP tendon; and (3) both supraspinatus and ISP tendons torn. Muscle fiber organization and muscle and tendon length were recorded. ISP and TM innervation and fiber structure were studied.
RESULTS: ISP muscles were composed of three groups of fiber organized in two planes: two superficial groups, with mean pennation angles of, respectively, 27° ± 4° and 23° ± 3° with respect to the axis of the central tendon of the underlying group. TMs were thick fusiform muscles showing a parallel organization; 26 specimens (67 %) had aponeuroses isolating the TM, with a mean length of 5.2 ± 2.7 cm. Rotator cuff lesions were associated with relatively greater ISP tendon than muscle length. Innervation of the ISP muscle comprised 2-4 main branches from the suprascapular nerve and that of the TM 1 branch from the axillary nerve.
CONCLUSION: ISP muscle body morphology derives from three groups of fibers in two planes. The TM has a parallel organization. Several nerve branches innervate the ISP muscle, whereas only one supplies the TM. The limits between the two muscles bodies consist of an aponeurotic fascia in two-thirds of cases.

PMID: 27286948 [PubMed - as supplied by publisher]

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Interventions for Menière's disease: protocol for an umbrella systematic review and a network meta-analysis.

Interventions for Menière's disease: protocol for an umbrella systematic review and a network meta-analysis.

BMJ Open. 2016;6(6):e010269

Authors: van Esch BF, van der Zaag-Loonen HJ, Bruintjes TD, van Benthem PP

Abstract
INTRODUCTION: The large number of treatment modalities for patients diagnosed with Menière's disease (MD) complicates the selection of the best available treatment as the comparative efficacy of these interventions is not clear. We aim to identify the treatment or treatments with the highest efficacy of current pharmacological and non-pharmacological treatments for MD.
METHODS AND ANALYSIS: We will identify all available systematic reviews on the treatment of MD. An online database search will be conducted in association with the UK Cochrane Centre, particularly the Ear, Nose and Throat Group. We will screen the systematic reviews for eligible randomised controlled trials (RCTs) to execute a network meta-analysis. In addition, online databases will be checked for eligible RCTs on treatments that were published after the latest systematic search was conducted. The characteristics of each RCT will be summarised, including the general design, the participants, the interventions, the outcome measurements, the duration of therapy and adverse events. The risk of bias will be assessed by means of the Cochrane Collaboration's risk of bias tool. The included studies will be assessed for methodological and statistical heterogeneity; the latter will be quantified by means of the I(2) statistic. The primary outcome will be the efficacy of treatment in terms of control of vertigo attacks. Secondary outcome measures will be the loss or improvement of hearing, severity of vertigo attacks and tinnitus, perception of aural fullness, quality of life, and the incidence of adverse events and complications.
ETHICS AND DISSEMINATION: Formal ethical approval is not required as primary data will not be collected. The review will be disseminated in peer-reviewed publications and conference presentations.
PROSPERO REGISTRATION NUMBER: CRD42015024243.

PMID: 27288370 [PubMed - as supplied by publisher]

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Glioma-mediated microglial activation promotes glioma proliferation and migration: roles of Na+/H+ exchanger isoform 1.

Glioma-mediated microglial activation promotes glioma proliferation and migration: roles of Na+/H+ exchanger isoform 1.

Carcinogenesis. 2016 Jun 9;

Authors: Zhu W, Carney KE, Pigott VM, Falgoust LM, Clark PA, Kuo JS, Sun D

Abstract
Microglia play important roles in extracellular matrix remodeling, tumor invasion, angiogenesis, and suppression of adaptive immunity in glioma. Na(+)/H(+) exchanger isoform 1 (NHE1) regulates microglial activation and migration. However, little is known about the roles of NHE1 in intratumoral microglial activation and microglia-glioma interactions. Our study revealed up-regulation of NHE1 protein expression in both glioma cells and tumor-associated Iba1(+) microglia in glioma xenografts and GBM microarrays. Moreover, we observed positive correlation of NHE1 expression with Iba1 intensity in microglia/macrophages. Glioma cells, via conditioned medium or non-contact glioma-microglia co-cultures, concurrently upregulated microglial expression of NHE1 protein and other microglial activation markers (iNOS, arginase-1, TGF-ß, IL-6, IL-10 and the matrix metalloproteinases MT1-MMP and MMP9). Interestingly, glioma-stimulated microglia reciprocally enhanced glioma proliferation and migration. Most importantly, inhibition of microglial NHE1 activity via siRNA knockdown or the potent NHE1-specific inhibitor HOE642 significantly attenuated microglial activation and abolished microglia-stimulated glioma migration and proliferation. Taken together, our findings provide the first evidence that NHE1 function plays an important role in glioma-microglia interactions, enhancing glioma proliferation and invasion by stimulating microglial release of soluble factors. NHE1 upregulation is a novel marker of the glioma-associated microglial activation phenotype. Inhibition of NHE1 represents a novel glioma therapeutic strategy by targeting tumor-induced microglial activation.

PMID: 27287871 [PubMed - as supplied by publisher]

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The value of intraoperative and early postoperative MRI in low-grade glioma surgery A retrospective study.

The value of intraoperative and early postoperative MRI in low-grade glioma surgery A retrospective study.

World Neurosurg. 2016 Jun 8;

Authors: Pala A, Brand C, Kapapa T, Hlavac M, König R, Schmitz B, Wirtz CR, Coburger J

Abstract
Presence of residual tumor is crucial in decision making in low grade gliomas (LGGs), since patients with residual tumor and age over 40 are considered for adjuvant treatment. There are hints, that early postoperative FLAIR and T2 (within 48 hours) may overestimate residual tumor volume in LGG. Intraoperative MRI (iMRI) without subsequent resection or ultra-early postoperative MRI may assess the amount of residual tumor more adequately. To evaluate the utility of postoperative imaging in LGG we volumetrically analyzed intraoperative, early and late (3-4 months after surgery) postoperative MRI in LGG.
PATIENTS AND METHODS: A total of 33 patients with LGG were assessed retrospectively. Residual tumor was defined as signal enhanced tissue in T2 and FLAIR. Volumetric assessment was performed using intraoperative, early and late postoperative T2/Flair using Brainlab-iPlan 3.0. Wilcoxon and Chi-Square tests were used for statistical analysis.
RESULTS: A significant difference of FLAIR/T2 abnormalities was found in intraoperative and early postoperative MRI (FLAIR mean volume=5.433cm(3),T2 mean volume=3.374 cm(3) vs. FLAIR mean volume=14.090 cm(3), p=0.002,T2 mean volume=7.597 cm(3),p=0.006). There was no significant difference between intraoperative and late postoperative FLAIR/T2 abnormalities (late postoperative FLAIR/T2 mean volume=5.560 cm(3) and 2.370 cm(3), p=0.520, p=0,398) whereas a significant difference was detected between early and late postoperative images (FLAIR, p<0.0001,T2, p<0.00001).
CONCLUSION: Intraoperative MRI without further resection or ultra-early postoperative MRI seems to reflect the actual volume of residual tumor in LGG more precisely compared to early postoperative MRI and therefore seems to be more useful regarding decisions for adjuvant therapy.

PMID: 27288582 [PubMed - as supplied by publisher]

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