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Σάββατο 2 Δεκεμβρίου 2017
Scholar : These new articles for Environmental Claims Journal are available online
Time and dose-related changes in lung perfusion after definitive radiotherapy for NSCLC
Source:Radiotherapy and Oncology
Author(s): Katherina P. Farr, Azza A. Khalil, Ditte S. Møller, Henrik Bluhme, Stine Kramer, Anni Morsing, Cai Grau
Background and purposeTo examine radiation-induced changes in regional lung perfusion per dose level in 58 non-small-cell lung cancer (NSCLC) patients treated with intensity-modulated radiotherapy (IMRT).Material and methodsNSCLC patients receiving chemo-radiotherapy (RT) of minimum 60 Gy were included prospectively in the study. Lung perfusion single-photon emission computed tomography (SPECT/CT) was performed before and serially after RT. Changes (relative to baseline, %) in regional lung perfusion were correlated with regional dose. Toxicity outcome was radiation pneumonitis (RP) CTC grades 2–5.ResultsPerfusion changes were associated with dose. Dose-dependent reduction in regional perfusion was observed at 3, 6 and 12 months of follow-up. Relative perfusion loss per dose bin was 4% at 1 month, 14% at 3 months, 13% at 6 months and 21% at 12 months after RT. In patients with RP, perfusion reduction was larger in high dose lung regions, compared to those without RP. Low dose regions, on the contrary, revealed perfusion gain in the patients with RP.ConclusionProgressive dose dependent perfusion loss is manifested on SPECT up to 12 months following IMRT. These findings suggest that the dynamic change in perfusion may have prognostic value in predicting radiation pneumonitis in NSCLC patients treated with IMRT.
http://ift.tt/2BDcV2Z
Patterns of locoregional failure in locally advanced non-small cell lung cancer treated with definitive conformal radiotherapy: Results from the Gating 2006 trial
Source:Radiotherapy and Oncology
Author(s): Emmanuel Jouglar, Vanina Isnardi, Dorothée Goulon, Céline Ségura-Ferlay, Myriam Ayadi, Claire Dupuy, Jean-Yves Douillard, Marc-André Mahé, Line Claude
PurposeTo determine the patterns of locoregional failure (LRF) in patients with locally advanced non-small cell lung cancer treated with definitive radiotherapy (RT).Patients and methodsOne hundred and fifty-four patients from the Gating 2006 prospective randomized trial were treated with conformal RT with or without respiratory motion management. For patients with a LRF as first event, treatment planning with simulation CT, pre-treatment 18FDG PET-CT and post-treatment images demonstrating recurrence were registered and analyzed. Measurable LRF was contoured (rGTV) and classified as in-field, marginal, or out-of-field.ResultsMedian follow-up was 27.8 months. Forty-eight patients presented with LRF. One-year and 2-year locoregional disease-free survival rates were 77% (95% CI 70–83) and 72% (95% CI 64–79) respectively. 79% of the patients with LRF as first event relapsed within the RT field (55% isolated), 30% had marginal LRF component. Isolated out-of-field failure occurred in only 3% of all patients. The regions of highest FDG-uptake on pre-treatment PET-CT were located within the recurrence in 91% of patients with in-field LRF.ConclusionIn-field failure was the most common pattern of failure. Escalated dose RT with high-dose fractions guided by PET parameters warrants further investigation.
http://ift.tt/2kkhMlD
Large-Scale Gradients in Human Cortical Organization
Publication date: Available online 1 December 2017
Source:Trends in Cognitive Sciences
Author(s): Julia M. Huntenburg, Pierre-Louis Bazin, Daniel S. Margulies
Recent advances in mapping cortical areas in the human brain provide a basis for investigating the significance of their spatial arrangement. Here we describe a dominant gradient in cortical features that spans between sensorimotor and transmodal areas. We propose that this gradient constitutes a core organizing axis of the human cerebral cortex, and describe an intrinsic coordinate system on its basis. Studying the cortex with respect to these intrinsic dimensions can inform our understanding of how the spectrum of cortical function emerges from structural constraints.
http://ift.tt/2zGkQLs
A real-time and registration-free framework for dynamic shape instantiation
Publication date: February 2018
Source:Medical Image Analysis, Volume 44
Author(s): Xiao-Yun Zhou, Guang-Zhong Yang, Su-Lin Lee
Real-time 3D navigation during minimally invasive procedures is an essential yet challenging task, especially when considerable tissue motion is involved. To balance image acquisition speed and resolution, only 2D images or low-resolution 3D volumes can be used clinically. In this paper, a real-time and registration-free framework for dynamic shape instantiation, generalizable to multiple anatomical applications, is proposed to instantiate high-resolution 3D shapes of an organ from a single 2D image intra-operatively. Firstly, an approximate optimal scan plane was determined by analyzing the pre-operative 3D statistical shape model (SSM) of the anatomy with sparse principal component analysis (SPCA) and considering practical constraints. Secondly, kernel partial least squares regression (KPLSR) was used to learn the relationship between the pre-operative 3D SSM and a synchronized 2D SSM constructed from 2D images obtained at the approximate optimal scan plane. Finally, the derived relationship was applied to the new intra-operative 2D image obtained at the same scan plane to predict the high-resolution 3D shape intra-operatively. A major feature of the proposed framework is that no extra registration between the pre-operative 3D SSM and the synchronized 2D SSM is required. Detailed validation was performed on studies including the liver and right ventricle (RV) of the heart. The derived results (mean accuracy of 2.19 mm on patients and computation speed of 1 ms) demonstrate its potential clinical value for real-time, high-resolution, dynamic and 3D interventional guidance.
Graphical abstract
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Learning Non-Linear Patch Embeddings with Neural Networks for Label Fusion
Publication date: Available online 2 December 2017
Source:Medical Image Analysis
Author(s): Gerard Sanroma, Oualid M. Benkarim, Gemma Piella, Oscar Camara, Guorong Wu, Dinggang Shen, Juan D. Gispert, José Luis Molinuevo, Miguel A. González Ballester
In brain structural segmentation, multi-atlas strategies are increasingly being used over single-atlas strategies because of their ability to fit a wider anatomical variability. Patch-based label fusion (PBLF) is a type of such multi-atlas approaches that labels each target point as a weighted combination of neighboring atlas labels, where atlas points with higher local similarity to the target contribute more strongly to label fusion. PBLF can be potentially improved by increasing the discriminative capabilities of the local image similarity measurements. We propose a framework to compute patch embeddings using neural networks so as to increase discriminative abilities of similarity-based weighted voting in PBLF. As particular cases, our framework includes embeddings with different complexities, namely, a simple scaling, an affine transformation, and non-linear transformations. We compare our method with state-of-the-art alternatives in whole hippocampus and hippocampal subfields segmentation experiments using publicly available datasets. Results show that even the simplest versions of our method outperform standard PBLF, thus evidencing the benefits of discriminative learning. More complex transformation models tended to achieve better results than simpler ones, obtaining a considerable increase in average Dice score compared to standard PBLF.
Graphical abstract
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GABAergic interneurons: the orchestra or the conductor in fear learning and memory?
Source:Brain Research Bulletin
Author(s): Elizabeth K. Lucas, Roger L. Clem
Fear conditioning is a form of associative learning that is fundamental to survival and involves potentiation of activity in excitatory projection neurons (PNs). Current models stipulate that the mechanisms underlying this process involve plasticity of PN synapses, which exhibit strengthening in response to fear conditioning. However, excitatory PNs are extensively modulated by a diverse array of GABAergic interneurons whose contributions to acquisition, storage, and expression of fear memory remain poorly understood. Here we review emerging evidence that genetically-defined interneurons play important subtype-specific roles in processing of fear-related stimuli and that these dynamics shape PN firing through both inhibition and disinhibition. Furthermore, interneurons exhibit structural, molecular, and electrophysiological evidence of fear learning-induced synaptic plasticity. These studies warrant discarding the notion of interneurons as passive bystanders in long-term memory.
http://ift.tt/2iCfIEX
Addiction: A Multi-determined Chronic Disease
Source:Brain Research Bulletin
Author(s): Patricia Sue Grigson
http://ift.tt/2ABpk9W
Comparative of transcranial magnetic stimulation and other treatments in experimental autoimmune encephalomyelitis
Source:Brain Research Bulletin
Author(s): Francisco J. Medina-Fernandez, Begoña M. Escribano, E. Luque, Javier Caballero-Villarraso, Jose L. Gomez-Chaparro, Montserrat Feijoo, Fe I. Garcia-Maceira, Alvaro Pacual-Leone, René Drucker-Colin, Isaac Tunez
The effects of transcranial magnetic stimulation (TMS), natalizumab (nata), dimethyl fumarate (DMF) and dexamethasone (DEX) on clinical score and oxidative stress produced by a single dose of myelin oligodendrocyte glycoprotein (MOG) in tail of Dark Agouti rats was studied. TMS (60Hz and 0.7 mT), nata (5mg/kg), DMF (15mg/kg) and DEX (300μg/kg) was applied for 21 after the administration of MOG (150μg). We estimated clinical score, as well as lipid peroxides, carbonylated proteins and reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio content in brain, spinal cord and blood. MOG triggered significant increase in clinical score and in the levels of lipid peroxides and carbonylated proteins levels, but reduced GSH/GSSG ratio in brain, spinal cord and blood. Both TMS and clinical treatments, although TMS more significantly, decreased the changes caused by MOG administration. These results support the antioxidant and neuroprotective action of TMS, as well as an activity higher than other clinical treatments.
http://ift.tt/2iBfvSx
Histopathological analysis of meningioma and its variants: A study of fifty cases
Indian Journal of Cancer 2017 54(1):313-315
BACKGROUND: The study was conducted to know the various histopathological variants of meningiomas, the age incidence and sex ratio. MATERIALS AND METHODS: A retrospective and prospective analysis of all the samples sent for histopathology for 2 years during June 2013–May 2015 was done to diagnose meningioma and its variants. Cases were analyzed in detail about the complete clinical history, exact location, and clinical and radiological diagnosis. The majority of the cases were clinically and radiologically diagnosed as meningioma. RESULTS: Of 50 cases which were diagnosed as meningiomas, 21 were meningothelial variant, 15 were psammomatous, 8 were fibroblastic, 4 were transitional, and 1 case each of anaplastic and atypical variant. The most common age group was between 41 and 50 years. The youngest age group was 16 years and oldest was 70. The male:female ratio was 1:1.5. CONCLUSION: The majority of the meningiomas have been observed between 41 and 50 years. Their proper recognition is therefore important to allow appropriate treatment. Histopathological study plays a major role by which we can diagnose the lesion. Meningiomas typically develop in middle-aged individuals and occur more frequently in women than men. These lesions may also occur in children.
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Dual mutations and complex mutations in metastatic nonsmall cell lung cancer: A single-institution experience from South India
Indian Journal of Cancer 2017 54(1):228-230
Wide use and incorporation of newer diagnostic tools in the management of metastatic nonsmall cell lung cancer (NSCLC) has helped in achieving the goal of personalized treatment of this disease. With the wide use of polymerase chain reaction and fluorescence in situ hybridization increasing number of patients are being diagnosed with dual and complex mutations posing a new challenge in the management of patient with metastatic NSCLC. In this article, we would like to bring forth six such cases and the varied responses to the current available treatment in patients with complex and dual mutations. The appropriate management in these groups of patients is yet to be standardized.
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Is pulmonary metastasectomy beneficial in head and neck squamous cell carcinoma? A review of literature
Indian Journal of Cancer 2017 54(1):2-5
Metastatic head and neck squamous cell carcinoma (HNSCC) has traditionally carried a dismal prognosis; however with advances in care, it has been shown that pulmonary metastasectomy is a viable therapeutic option in selected patients, palliating symptoms and improving survival. With the increasing incidence of human papilloma virus-related HNSCC and better availability of minimal access surgery, there is a need to better understand the role of pulmonary metastasectomy in the treatment of HNSCC. This article summarizes the literature on indications, results, surgical options and approaches, clinical dilemmas, and controversies associated with pulmonary metastasectomy in HNSCC, to identify suitable candidates and optimize outcomes.
http://ift.tt/2jAHcqR
Testicular seminoma: Are clinical features and treatment outcomes any different in India?
Indian Journal of Cancer 2017 54(1):385-387
AIM: This study aims to identify clinical features, treatment outcomes, and prognostic factors for relapse and survival in patients with testicular seminoma. MATERIALS AND METHODS: Retrospective analysis of all patients with pure seminoma treated at our center during over a decade (January 2005–December 2014) was carried out. Patient demographics, tumor characteristics, and treatment details and pattern of recurrence were recorded in a structured format, and disease-free survival and overall survival were calculated. RESULTS: Sixty-three patients' case records were included in the analysis. Ten patients developed disease in the undescended testis. All patients underwent orchiectomy as the initial treatment procedure. Majority of the patients were Stage I (57.14%) followed by Stage II (39.6%). Among the patients with Stage I, 55.5% received adjuvant chemotherapy while 22.2% received adjuvant radiation and the rest opted for surveillance. The compliance for active surveillance was very poor. Among patients with Stage II disease, majority (80%) were treated with adjuvant chemotherapy and the rest with radiation. At a median follow-up of 49 months, there were four recurrences of which three were salvaged successfully, and one patient remained alive with disease. There were no disease-related deaths. CONCLUSIONS: Testicular seminoma remains to be relatively low and majority of them presented with Stage I disease and single agent carboplatin appeared to be the preferred adjuvant treatment. Advanced disease patients were treated with etoposide and cisplatin/bleomycin, etoposide and cisplatin chemotherapy and the clinical outcome is comparable with the Western literature.
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Comparison of conventional fractionation (five fractions per week) and altered fractionation (six fractions per week) in stage I and II squamous cell carcinoma of oropharynx: An institutional study
Indian Journal of Cancer 2017 54(1):6-10
BACKGROUND: The radiotherapy (RT) dose and fractionation schedule for head and neck cancers for locoregional control and acceptable organ toxicity are still debatable. Accelerated RT includes administration of six fractions per week with the same dose per fraction. AIM: Comparison of conventional versus accelerated RT in terms of locoregional control, and acute and late radiation toxicity in squamous cell carcinoma oropharynx (stage I and II). SETTINGS AND DESIGN: Prospective, double arm, phase 2, randomized study. MATERIALS AND METHODS: Sixty patients of squamous cell carcinoma oropharynx (stage I and II) were randomized in two arms (accelerated fractionation, arm 1 and conventional fractionation, arm 2). All patients received RT dose of 66 Gray (Gy) in 33 fractions (#). The patients in arm 1 received six fractions per week with 2 Gy/# (Monday–Saturday) and in arm 2, five fractions per week with 2 Gy/# (Monday–Friday). No chemotherapy was administered. During and after the treatment, locoregional control, and acute and late radiation toxicity were assessed. RESULTS: At 1-year follow-up, 76% patients in arm 1 and 64% patients in arm 2 had complete response. The recurrence rate at the end of 1 year in arm 1 was 12% and it was 20% in arm 2.The acute Grade 2 and 3 toxicities were higher in the accelerated arm and no significant difference in late toxicities was found. SPSS version 4.0 was used for statistical analysis. CONCLUSION: Accelerated fractionation provides better locoregional control with higher but acceptable acute and equal late radiation toxicity in squamous cell carcinoma oropharynx.
http://ift.tt/2i6IARK
Solitary pulmonary nodule evaluation in regions endemic for infectious diseases: Do regional variations impact the effectiveness of fluorodeoxyglucose positron emission tomography/computed tomography
Indian Journal of Cancer 2017 54(1):271-275
BACKGROUND: Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) has become a preferred imaging modality for the evaluation of solitary pulmonary nodule (SPN), particularly in the developed world. Since FDG can concentrate in infective/inflammatory lesions, the diagnostic utility of FDG-PET can be questioned, particularly in regions endemic for infectious decisions. AIM: To evaluate the accuracy of FDG-PET/CT in evaluation of SPNs in a population endemic for infectious disease and to assess if regional variations have an impact on its effectiveness. MATERIALS AND METHODS: All patients who underwent an FDG/PET-CT with a clinico-radiological diagnosis of SPN categorized as indeterminate were included. Based on a maximum standardized uptake values (SUVmax) cut-off of 2.5, lesions were classified as benign (<2.5) or malignant (>2.5) and compared with gold standard histopathology. The diagnostic accuracy of PET-CT to detect malignancy was calculated. On the basis of final histopathology, lesions were grouped as (a) malignant nodules (b) infective/granulomatous nodules with a specific diagnosis and (c) nonspecific inflammatory nodules. The SUVmaxbetween these groups was compared using nonparametric statistical tests. RESULTS: A total of 191 patients (129 males, 62 females) with a median age of 64 years (range: 36–83) were included. Totally, 144 nodules (75.3%) were malignant and 47 were benign (24.7%). Adenocarcinoma (n = 84) was the most common malignancy. Tuberculosis (n = 16) and nonspecific infections (n = 24) were the two most common benign pathologies. There was a significant overlap in the metabolic uptake of malignant (median SUVmax-11.2, range: 3.3–34.6) and tuberculous nodules (median SUVmax-10.3, range: 2.7–22.5) with no statistically difference between their SUVmaxvalues (P = 0.43). The false-positive rate was 65.2% and the false-negative rate was 5.5%. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FDG-PET/CT for detecting malignancy were 94.4%, 34.7%, 81.9%, 66.6%, and 79.5%, respectively. CONCLUSIONS: Though FDG-PET scans show a very high sensitivity for malignant nodules, it has a high false-positive rate and reduced specificity when characterizing SPNs in an infectious endemic region. Physicians must be aware of this limitation in the workup of lung nodules, and regional variations must be considered before further management decisions are taken.
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Oral health-related quality of life in patients treated for oral malignancy at Kanchipuram district, India: A cross-sectional study
Indian Journal of Cancer 2017 54(1):11-15
BACKGROUND: The modern-day onco-surgical therapy is now concerned on the overall Quality of Life after treatment of the patient. There is need to evaluate final outcome following the different combination of treatment modalities available to make better therapeutic treatment decisions. AIM: The aim of this study was to assess Oral health related quality of life (OHRQoL) in patients with oral malignancies who had undergone various treatments. SETTINGS AND DESIGN: A Cross sectional study was conducted among 90 patients between October 2016 to January 2017 in private hospitals, kanchipuram, India. MATERIALS AND METHODS: Participants were grouped based on the treatment they had undergone into Group I - Surgery alone, Group II - Surgery and Radiotherapy, Group III- Surgery, chemotherapy and radiotherapy and assessed for OHRQoL using the shorter version of Oral health impact profile -14 (OHIP-14) questionnaire. STATISTICAL ANALYSIS: Descriptive analysis of socio demographic variables and OHIP 14 was performed using Chi-square test and one way ANOVA. RESULTS: Among the 90 participants, 43.3% belonged to upper lower class and 38.3% to lower class. Buccal mucosa (58.9%) was found to be the most frequent site. Among the clinical staging, Stage II (33.33%) oral cancer was more prevalent. No statistically significant differences in the OHIP mean score for Groups, I, II, III. Among the domains functional limitation was significantly different in the three groups. CONCLUSION: Patients with oral malignancies who had been treated surgically alone had better Quality of life when compared to the combined treatment modalities.
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A prospective randomized trial comparing capecitabine-based chemoradiotherapy with 5-FU-based chemoradiotherapy in neoadjuvant setting in locally advanced carcinoma rectum
Indian Journal of Cancer 2017 54(1):347-351
INTRODUCTION: Fluorouracil (FU)based chemoradiotherapy is regarded as a standard perioperative treatment in locally advanced rectal cancer. Capecitabine is an oral fluoropyrimidine that generates 5FU preferentially at the tumor site by exploiting the higher activity of the enzyme thymidine phosphorylase in tumor tissue compared with healthy tissue. As an oral agent, capecitabine can be administered in the outpatient setting, potentially providing FU exposure similar to a lowdose continuous infusion of 5FU. AIMS AND OBJECTIVES: To compare capecitabine with 5FU, with regard to efficacy and toxicity when used in neoadjuvant setting along with radiotherapy for locally advanced carcinoma rectum. MATERIALS AND METHODS: Thirty patients were enrolled, 14 in 5FU and 16 in capecitabine arm. All patients were planned for 45 Gy/25#/5 weeks pelvic radiotherapy followed by a boost of 5.4 Gy/3#/3 days. 5FU was prescribed at a dose of 500 mg/m2 #1–#5 and #21–#25 of RT and capecitabine was given at 1650 mg/m2 on RT days throughout the course of radiotherapy. A magnetic resonance imaging/computerized tomography scan was done at the start of treatment and 1 month after completion of treatment, followed by surgery. Toxicity was assessed weekly during treatment and on the first followup. RESULTS: Response rates and toxicity profile of capecitabinebased cathode ray tube (CRT) was similar to 5FUbased CRT with nonsignificant P values. CONCLUSION: Capecitabine may be used as an alternative in patients who do not tolerate 5FU.
http://ift.tt/2jDs105
Impact of induction chemotherapy to concurrent chemoirradiation over radiotherapy alone in advanced oral cavity
Indian Journal of Cancer 2017 54(1):16-19
BACKGROUND: Oral and oropharyngeal carcinomas representing about 90% of all oral malignancies are the sixth most common cancers worldwide. Basic modalities of cancer treatment are surgery, radiotherapy, and chemotherapy (CT) either alone or in combination. For squamous cell carcinoma (SCC) patients, induction CT followed by radiotherapy and concurrent CT are effective methods for improving response rates. MATERIALS AND METHODS: Fifty patients with advance stage oral cavity cancer with performance status >60% on Karnofsky performance scale and having no prior exposure to CT, radiotherapy, and surgery were included in the study. CT including bleomycin, methotrexate, and cisplatin was given on day 1 and repeated at an interval of 21 days. After the completion of three cycles, two groups (n = 25 each) were formed. One group was treated with radiotherapy alone and other group of patients treated with radiotherapy and concurrent cisplatin infusion. The patient toxicities and response were evaluated. RESULTS: After completion of induction CT, both the groups responded with almost similar result. Nausea, vomiting, mucositis, and skin reactions during radiotherapy were observed in both groups but comparatively higher in Group "B." In Group B, 84% (vs. 60% in Group A) of patients showed complete response (CR) after completion of treatment, and out of 13 patients who responded partially to induction CT, 9 patients showed CR after concurrent chemoradiotherapy. CONCLUSION: This study showed the superiority of induction followed by concurrent chemoradiotherapy over induction plus radiotherapy alone in the treatment of advanced oral cavity neck SCC.
http://ift.tt/2i6lJWw
Anaplastic lymphoma kinase immunohistochemistry in lung adenocarcinomas: Evaluation of performance of standard manual method using D5F3 antibody
Indian Journal of Cancer 2017 54(1):209-213
OBJECTIVE: Immunohistochemistry (IHC) with anaplastic lymphoma kinase (ALK) antibodies is considered as an economical screening method in lung adenocarcinomas. Automated Ventana D5F3-IHC is approved by US Food and Drug Administration for targeted therapy; however, the automated IHC apparatus are not widely used in most laboratories. We evaluated the performance of ALK IHC using the manual semiquantitative method to assess the concordance with Ventana ALK IHC assay. MATERIALS AND METHODS: We tested 156 cases of primary lung adenocarcinomas for ALK protein expression by D5F3-IHC. The intensity of cytoplasmic staining was classified as 0 or 1+/2+/3+ (weak/medium/strong). Binary score of positive and negative was used for Ventana assay. A comparison analysis and clinicopathological features were recorded. RESULTS: ALK IHC was positive in 25 (16.02%) cases, of which 18 were men and mostly nonsmokers. The mean age for all patients was 55 years, and for ALK IHC-positive cases was 48 years. Nine of 25 (36%) ALK IHC-positive cases showed signet ring cell and mucinous morphology. On comparison, all, but one, cases positive by manual method showed positive results by automated assay. IHC negative cases by manual method were negative by Ventana assay. CONCLUSION: Manual IHC is equally effective in the detection of ALK-rearranged cases as automated methods. It can be easily integrated as a screening method into routine practice thus reducing the cost of automated systems. However, equivocal cases should be tested by approved methods.
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Comparison of paclitaxel-cetuximab chemotherapy versus metronomic chemotherapy consisting of methotrexate and celecoxib as palliative chemotherapy in head and neck cancers
Indian Journal of Cancer 2017 54(1):20-24
BACKGROUND: The present match pair analysis was planned to compare the efficacy of cetuximab-paclitaxel-based chemotherapy versus metronomic therapy. MATERIALS AND METHODS: Sixty patients with metastatic/recurrent head and neck squamous cell cancer treated with weekly paclitaxel (80 mg/m2) and cetuximab were matched with sixty patients treated with oral metronomic chemotherapy consisting of methotrexate and celecoxib. The progression-free survival (PFS) and overall survival (OS) between the cohorts were compared using log-rank test. Cox proportional regression model was used to identify independent factors affecting PFS and OS. RESULTS: The median OS was 191 days (95% confidence interval [CI]: 122.2–259.8 days) in metronomic cohort and 256 days (95% CI 177.0–334.9 days) in cetuximab cohort (hazard ratio: 0.58, 95% CI: 0.35–0.95, P = 0.031). On Cox proportional hazard model, Eastern Cooperative Oncology Group Performance Status (0–1 vs. 2) and therapy (cetuximab versus metronomic) had a statistically significant impact on OS. CONCLUSION: Cetuximab-based chemotherapy leads to a significant improvement in OS in the match pair analysis in comparison to metronomic chemotherapy.
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Chemosuppressive effect of plumbagin on human non-small lung cancer cell xenotransplanted zebrafish
Indian Journal of Cancer 2017 54(1):253-256
BACKGROUND: Plumbagin (5-hydroxy-2-methyl-1,4-napthoquinone) derived from Plumbago species is a potential anti-tumour agent. Plumbagin has been tested for anti-cancer activity in vitro and in vivo using mice model. AIM: To study the tumour suppressing efficacy of plumbagin using zebrafish model. MATERIALS AND METHODS: Human Non-small lung cancer cell line were cultured in vitro and transplanted in to zebrafish. The development of tumour was confirmed by performing histology. The tumour was then allowed to progress in vivo and the fishes were administered with plumbagin orally for three continuous days. The tumour suppression capacity was monitored subsequently using transcriptosome analysis. STATISTICAL METHODS: The pixel integrated density obtained was converted into relative gene expression using IBM SPSS. RESULTS: The administration of plumbagin had an ability to suppress tumour and the size of the tumour were relatively lesser when compared with the control sample; it has also increased p53 gene expression. CONCLUSION: The study helps to conclude that plumbagin is an effective anti-tumour agent against human cancer cells based on the study in vivo in zebrafish.
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Retrospective analysis of palliative metronomic chemotherapy in head and neck cancer
Indian Journal of Cancer 2017 54(1):25-29
BACKGROUND: Metronomic chemotherapy has shown promising results in selected patients of head and neck cancer in a small randomized study. This retrospective analysis was done to see whether the efficacy of metronomic chemotherapy in an unselected cohort of head and neck cancer patients is similar to that reported in the randomized study and the influence of the site and subsite of head and neck cancer on survival. MATERIALS AND METHODS: This was a retrospective analysis of head and neck cancer patients who received palliative metronomic chemotherapy between January 2013 and February 2015. The data of these patients were collected from our palliative chemotherapy database maintained in medical oncology outpatient department. The overall survival (OS) was calculated in days from the date of start of chemotherapy to the date of death. Patients who had not expired at last follow-up were censored during estimation of OS by Kaplan–Meier method. Factors affecting OS were identified by COX regression analysis. RESULTS: Over the stipulated time period, 340 patients received palliative metronomic chemotherapy. The median age of these patients was 48 years (22–90 years). The sites of tumor origin were oral cavity in 281 patients (82.6%), oropharynx in 33 patients (9.7%), larynx in seven patients (2.1%), hypopharynx in 12 patients (3.5%), and maxilla in seven patients (2.1%). Previous treatment was received by 286 patients (84.1%). The median time to failure was 3.5 months (interquartile range 2.0–6.0 months). The overall median survival was 155 days (95% confidence interval 140.2–169.8 days). Failure within 6 months of previous treatment was the most important factor influencing OS. There was a trend toward lower OS in patients with oral cancers (139 days vs. 210 days). Among the various oral cancer subsites, oral tongue primary had a lower OS. CONCLUSION: Oral metronomic chemotherapy has promising results when used in a selected cohort of patients but has dismal results in patients who failed within 6 months of previous treatment.
http://ift.tt/2i6juSW
The single-incision versus multiple-incision video-assisted thoracoscopic surgery in the treatment of lung cancer: A systematic review and meta-analysis
Indian Journal of Cancer 2017 54(1):291-300
OBJECTIVE: We conducted this meta-analysis to compare the clinical outcomes of single-incision and multiple-incision video-assisted thoracoscopic surgery (VATS) lobectomy for lung cancer patients. METHODS: A literature search was conducted of the Cochrane Controlled Trials Register Databases, Medline, EMBASE, Web of Science databases, and Chinese Biomedical Literature Database. Eleven studies that compared single-incision VATS with multiple-incision VATS in the treatment of lung cancer were analyzed. Statistical analysis was carried out using RevMan 5.1 software. RESULTS: Eleven trials totaling 1273 patients were included. There were statistically significant differences in the duration of chest tube (standardized mean difference [SMD] = −0.42; 95% confidence interval [CI] [−0.78, −0.07], P < 0.02), hospital stays after surgery (SMD = −0.28; 95% CI [−0.41, −0.15], P < 0.0001), hospital stays after surgery in the subgroup analysis of lobectomy (SMD = −0.28; 95% CI [−0.42, −0.14], P < 0.0001), length of wound (P < 0.05), and pain visual analog scale (VAS) in the postoperative 1 day (SMD = −1.19; 95% CI [−1.94, −0.44], P = 0.002) between single-incision VATS group and multiple-incision VATS group. Compared with patients receiving multiple-incision VATS group, there were no statistically significant differences between the two groups with regard to the operative time (OT), blood loss (BL), rate of conversion to thoracotomy, and complication. CONCLUSION: Compared with multiple-incision VATS on the condition of same lymph nodes retrieved number, single-incision VATS reduced the length of wound, shortened the duration of chest tube, cut down the hospital stays after surgery, alleviated the pain VAS in the postoperative 1 day, did not significantly increase the OT and the BL in operation, and did not increase the rate of conversion to thoracotomy and complication.
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Sister Mary Joseph's nodule: Two rare cases of inoperable gallbladder cancer
Indian Journal of Cancer 2017 54(1):29-30
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Pattern of distant metastasis in molecular subtypes of carcinoma breast: An institutional study
Indian Journal of Cancer 2017 54(1):327-332
BACKGROUND: Molecular subtypes of carcinoma breast show a particular pattern of distant metastasis, the knowledge of which can help to diagnose and intervene early in the course of the disease. AIM: The aim of this study was to investigate and establish an association between the molecular subtypes of carcinoma breast and the pattern of distant metastasis. SETTINGS AND DESIGN: Single arm, retrospective study. MATERIALS AND METHODS: Totally 400 patients of carcinoma breast (Stage I and II) were selected who were treated between January 2010 and December 2013. All these patients were treated with the standard treatment protocol for breast cancer. The estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 (HER-2) Neu status, and Ki-67 were done, and patients were classified into luminal A/B, HER-2 enriched, luminal/HER-2, and triple-negative subtypes. All patients were followed up until December 2015, and the pattern of local failure as well as distant metastasis was correlated with the molecular subtypes. RESULTS: A total of 143 patients developed distant metastasis and local recurrence. Bone was the most common site of metastasis overall. It was the most common type of metastasis in luminal A/B (53.3%) and luminal-HER (57.1%). Brain metastasis was most common in HER-2-enriched subtype (30.3%), whereas liver was the most common site of metastasis in HER-2-enriched subtype (45.45%). The incidence of brain metastasis was comparatively lower in luminal A/B subtype. Local recurrence was most common in HER-2-enriched subtype. The results were statistically significant for lung metastasis and local recurrence (with P = 0.004 and 0.047, respectively). CONCLUSION: A strong association exists between the molecular subtypes and the site of distant metastasis in breast cancer which can be used for greater vigilance to detect site-specific distant metastasis beforehand.
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An audit and analysis of different causes of defaults in patients receiving radiation for head and neck cancers: A tertiary regional cancer center experience
Indian Journal of Cancer 2017 54(1):31-34
CONTEXT: Strict adherence and timely completion of the external beam radiation therapy (EBRT) schedule is an important prognostic factor in the survival of head and neck cancer patients. However, many patients are unable to complete the radiation treatment due to various reasons resulting in a poor outcome. AIMS: This study aims to study the pattern and various possible causes of defaults for possible intervention. SETTINGS AND DESIGN: A retrospective epidemiological analysis. SUBJECTS AND METHODS: Patients receiving EBRT for head and neck cancers with curative intent from January 2015 to December 2015 but did not complete the prescribed treatment were included. Unplanned treatment breaks in the treatment was not taken into consideration. STATISTICAL ANALYSIS USED: SPSS version 21. RESULTS: Out of 458, 92 (20.08%) patients did not complete the EBRT (P = 0.06). Fifty-six out of total 92 patients (60.9%) who defaulted stopped taking treatment within halfway of the treatment (15 fraction) and 12 out of total 92 patients (13%) just at the 22nd/23rd fraction. Defaulter rates in patients from different places are in the range of 12.8% to 33.0% but was statistically not significant (P = 0.224). There was no particular age (P = 0.966), disease site (P = 0.354) preponderance among defaulters. Use of concurrent chemo-radiation in radical or adjuvant settings was also not related to defaults (P = 0.406). CONCLUSIONS: Radiation-induced acute toxicity, socioeconomic status and distance plays minimal role as a cause of patients who stop taking EBRT. There is no particular relation between age, disease site, treatment received before radiotherapy, intent of treatment, and concurrent chemoradiation-induced acute reactions with defaults among patients. Loss of income and work in the poor population during the treatment may be an important possible cause of defaults.
http://ift.tt/2i7BkFc
Survival and prognostic factors for glioblastoma multiforme: Retrospective single-institutional study
Indian Journal of Cancer 2017 54(1):362-367
INTRODUCTION: Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults. The standard management has been maximum surgical resection followed by adjuvant radiotherapy with concurrent chemotherapy followed by adjuvant chemotherapy. Although the survival rate of patients with GBM has improved with recent advancements in treatment, the prognosis remains generally poor. The median survival rates are in the range of 9–12 months and 2-year survival rates are in the range of 8%–12%. MATERIALS AND METHODS: A single-institution retrospective review of 61 patients of GBM from 2012 to 2014. Data regarding patient factors, disease factors, and treatment factors were collected and survival has been calculated. RESULTS: A total of 61 patients with GBM were analyzed. GBM is commonly seen in sixth decade of life. Male to female ratio is 2.6:1. The right side of the brain is commonly involved with right frontal lobe being the most common site. The median follow-up was 4.6 months. The median survival of our patients was 8 months. The 1-year and 2-year survival rates were 20% and 3.27%, respectively.CONCLUSIONS: The overall survival and prognosis in patients with GBM remains poor despite of constant research and studies. Concurrent chemoradiotherapy followed by adjuvant chemotherapy with temozolomide should be used after maximal resection to improve the survival.
http://ift.tt/2iaNq0x
Induction chemotherapy in locally advanced T4b oral cavity squamous cell cancers: A regional cancer center experience
Indian Journal of Cancer 2017 54(1):35-38
OBJECTIVES: The present study aimed to investigate the efficacy, toxicity, and impact of induction chemotherapy (IC) in locally advanced T4b oral cavity squamous cell cancers (OSCCs). MATERIALS AND METHODS: Patients diagnosed with locally advanced T4b OSCC from January 2013 to October 2016 at our center, who received 2–3 cycles of IC and then assessed for resectability, were reviewed retrospectively. Patients' profile, response, and toxicity of IC, resectability status, and overall survival (OS) were evaluated. Statistical analyses were performed by SPSS software version 17. RESULTS: A total of 116 patients received IC, and out of them 90 (77.6%) were males. Median age at diagnosis was 43 years (range 31–62 years). Nearly 103 (88.8%) of our patients received doublet chemotherapy and the rest of the patients received triplet regimen. Majority of the patients had buccal mucosa cancers (71.6%), followed by gingivobuccal complex (21.6%) and oral tongue (6.9%) primaries. After IC, partial response was achieved in 20 (17.3%) patients, stable disease in 68 (58.6%) patients, and disease progression was noted in 28 (24.1%) patients. Post-IC, resectability was achieved in 22 (19%) of 116 patients, but 6 of them did not undergo surgery due to logistic and personal reasons. The median OS of patients who underwent surgery followed by adjuvant local therapy (n = 16) was 19.7 months (95% confidence interval [CI]: 16.0–22.8 months) and for those treated with nonsurgical local therapy (n = 100) was 7.1 months (95% CI: 5.8–8.2 months) (log-rank P = 0.000). CONCLUSIONS: IC had a manageable toxicity profile and achieved resectability in 19% of our patients with T4b OSCC. Patients underwent resection had a significantly better median OS than those who received nonsurgical local treatment.
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Clinical profile and outcomes of patients with Stage IV adenocarcinoma of lung: A tertiary cancer center experience
Indian Journal of Cancer 2017 54(1):197-202
BACKGROUND: There is limited Indian data on clinical profile and treatment outcomes for patients with Stage IV adenocarcinoma of lung. AIM: We aimed to prospectively study the clinical profile and treatment outcomes for patients with Stage IV adenocarcinoma of lung at a tertiary cancer center. MATERIALS AND METHODS: One hundred and ninetyfour patients with Stage IV adenocarcinoma of lung were prospectively analyzed for demographic and molecular profile (epidermal growth factor receptor [EGFR] and echinodermal microtubuleassociated proteinlike 4anaplastic lymphoma kinase [EML4ALK] mutations). Patients with EGFR and EML4ALK mutations were treated with tyrosine kinase inhibitors. Patients without these mutations were treated with standard chemotherapy regimens. Maintenance chemotherapy was offered to patients as per standard guidelines. Clinical outcomes measured were response rate (RR), progressionfree survival (PFS), and overall survival (OS). RESULTS: Median age of patients was 56 years (range, 26–82) with a male:female ratio of 2.3:1. EGFR and ALK mutation testing was feasible in 169 (87.1%) and 164 (84.5%), respectively, and detected in 37.9% and 5.5% patients, respectively. Overall RR, PFS and OS of whole cohort were 44.3%, 6.9, and 15.5 months, respectively. PFS and OS of mutated group (EGFR, EML4ALK) were longer than nonmutated group (10.5 vs. 5.4 months, P < 0.0001 and 21.5 vs. 11 months, P = 0.0001, respectively). PFS and OS of patients who received pemetrexed maintenance were longer than those who did not receive maintenance (8.5 vs. 6.5 months, P = 0.1613 and 18.5 vs. 12.5 months, P = 0.0219, respectively). CONCLUSIONS: Mutation testing at diagnosis is feasible in the vast majority of patients with Stage IV adenocarcinoma of the lung. Patients with EGFR or EML4ALK mutation and those who received pemetrexed maintenance had better clinical outcomes.
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Determinants for Effective ALECSAT Immunotherapy Treatment on Autologous Patient-Derived Glioblastoma Stem Cells
Publication date: January 2018
Source:Neoplasia, Volume 20, Issue 1
Author(s): Anna Wenger, Katja Werlenius, Alexander Hallner, Fredrik Bergh Thorén, Dan Farahmand, Magnus Tisell, Anja Smits, Bertil Rydenhag, Asgeir S. Jakola, Helena Carén
AbstractGlioblastoma (GBM) is the most aggressive primary brain tumor with a median survival of less than 15 months, emphasizing the need for better treatments. Immunotherapy as a treatment for improving or aiding the patient's own immune defense to target the tumor has been suggested for GBM. A randomized clinical trial of adoptive cell transfer using ALECSAT (Autologous Lymphoid Effector Cells Specific Against Tumor Cells) is currently ongoing in Sweden. Here we performed a paired pre-clinical study to investigate the composition and in vitro effect of ALECSAT and identify determinants for the effect using autologous GBM-derived cancer stem cells (CSC), immunocytochemistry and flow cytometry. We show a clear dose-response relationship of ALECSAT on CSC, suggesting that the number of infused cells is of importance. In addition, the in vitro effect of ALECSAT on CSC correlated significantly to the blood count of T helper (Th) cells in the patient indicating a potential benefit of collecting cells for ALECSAT preparation at an even earlier stage when patients generally have a better blood count. The factors identified in this study will be important to consider in the design of future immunotherapy trials to achieve prolonged survival.
http://ift.tt/2kcx0sy
Rapamycin Synergizes with Cisplatin in Antiendometrial Cancer Activation by Improving IL-27–Stimulated Cytotoxicity of NK Cells
Publication date: January 2018
Source:Neoplasia, Volume 20, Issue 1
Author(s): Wen-Jie Zhou, Kai-Kai Chang, Ke Wu, Hui-Li Yang, Jie Mei, Feng Xie, Da-Jin Li, Ming-Qing Li
Natural killer (NK) cell function is critical for controlling initial tumor growth and determining chemosensitivity of the tumor. A synergistic relationship between rapamycin and cisplatin in uterine endometrial cancer (UEC) in vitro has been reported, but the mechanism and the combined therapeutic strategy for endometrial cancer (EC) are still unknown. We found a positive correlation between the level of IL-27 and the differentiated stage of UEC. The increase of IL-27 in uterine endometrial cancer cell (UECC) lines (Ishikawa, RL95-2 and KLE) led to a high cytotoxic activity of NK cells to UECC in the co-culture system. Exposure with rapamycin enhanced the cytotoxicity of NK cells by upregulating the expression of IL-27 in UECC and IL-27 receptors (IL-27Rs: WSX-1 and gp130) on NK cells and further restricted the growth of UEC in Ishikawa-xenografted nude mice. In addition, treatment with rapamycin resulted in an increased autophagy level of UECC, and IL-27 enhanced this ability of rapamycin. Cisplatin-mediated NK cells' cytotoxic activity and anti-UEC activation were independent of IL-27; however, the combination of rapamycin and cisplatin led to a higher cytotoxic activity of NK cells, smaller UEC volume and longer survival rate in vivo. These results suggest that rapamycin and cisplatin synergistically activate the cytotoxicity of NK cells and inhibit the progression of UEC in both an IL-27–dependent and –independent manner. This provides a scientific basis for potential rapamycin-cisplatin combined therapeutic strategies targeted to UEC, especially for the patients with low differentiated stage or abnormally low level of IL-27.
http://ift.tt/2Bz46qN
The effects of repetitive transcranial magnetic stimulation on eating behaviors and body weight in obesity: A randomized controlled study
Source:Brain Stimulation
Author(s): Se-Hong Kim, Ju-hye Chung, Tae-Hong Kim, Seong Hoon Lim, Youngkook Kim, Yun-Ah Lee, Sang-Wook Song
BackgroundAlthough some studies have reported significant reductions in food cravings following repetitive transcranial magnetic stimulation (rTMS), none have examined changes in body weight.ObjectiveWe conducted 2-week randomized, sham-controlled, single-blind, parallel-group trial to examine the effect of rTMS on body weight in obese patients.MethodsSixty obese patients (body mass index [BMI] ≥25 kg/m2) aged between 18 and 65 years were recruited. A total of 4 sessions of rTMS targeting the left dorsolateral prefrontal cortex (DLPFC) was provided over a period of 2 weeks, with a follow-up assessment conducted two weeks after treatment had finished. The primary outcome measure was weight change in kilograms from baseline to 4 weeks. Secondary endpoints included changes in anthropometric measures, cardiovascular risk factors, food intake, and appetite.ResultsOf the 60 volunteers, 57 completed the 4-week follow-up (29 in the TMS group and 28 in the sham treatment group). Participants in the rTMS group showed significantly greater weight loss from baseline following the 4 session of rTMS (p = 0.002). Consistent with weight loss, there was a significant reduction in BMI, fat mass and VAT at week 4 in the rTMS group compared with the control group (p < 0.05). After the 4 sessions of rTMS, the TMS group consumed fewer total kilocalories per day than the control group (p < 0.01).ConclusionsrTMS delivered to the left DLPFC was effective in decreasing food intake and facilitating weight loss in obese patients. The results of this study suggest that rTMS could be an effective treatment option for obesity.
http://ift.tt/2izZZGC
Παρασκευή 1 Δεκεμβρίου 2017
Recovering Wood and McCarthy’s ERP-prototypes by means of ERP-specific procrustes-rotation
Source:Journal of Neuroscience Methods, Volume 295
Author(s): André Beauducel
BackgroundThe misallocation of treatment-variance on the wrong component has been discussed in the context of temporal principal component analysis of event-related potentials. There is, until now, no rotation-method that can perfectly recover Wood and McCarthy's prototypes without making use of additional information on treatment-effects.New methodIn order to close this gap, two new methods: for component rotation were proposed. After Varimax-prerotation, the first method identifies very small slopes of successive loadings. The corresponding loadings are set to zero in a target-matrix for event-related orthogonal partial Procrustes- (EPP-) rotation. The second method generates Gaussian normal distributions around the peaks of the Varimax-loadings and performs orthogonal Procrustes-rotation towards these Gaussian distributions. Oblique versions of this Gaussian event-related Procrustes- (GEP) rotation and of EPP-rotation are based on Promax-rotation.ResultsA simulation study revealed that the new orthogonal rotations recover Wood and McCarthy's prototypes and eliminate misallocation of treatment-variance. In an additional simulation study with a more pronounced overlap of the prototypes GEP Promax-rotation reduced the variance misallocation slightly more than EPP Promax-rotation.Comparison with Existing Method(s): Varimax- and conventional Promax-rotations resulted in substantial misallocations of variance in simulation studies when components had temporal overlap. A substantially reduced misallocation of variance occurred with the EPP-, EPP Promax-, GEP-, and GEP Promax-rotations.ConclusionsMisallocation of variance can be minimized by means of the new rotation methods: Making use of information on the temporal order of the loadings may allow for improvements of the rotation of temporal PCA components.
http://ift.tt/2zWGpvw
The effect of monitor raster latency on VEPs, ERPs and Brain–Computer Interface performance
Source:Journal of Neuroscience Methods, Volume 295
Author(s): Sebastian Nagel, Werner Dreher, Wolfgang Rosenstiel, Martin Spüler
BackgroundVisual neuroscience experiments and Brain–Computer Interface (BCI) control often require strict timings in a millisecond scale. As most experiments are performed using a personal computer (PC), the latencies that are introduced by the setup should be taken into account and be corrected. As a standard computer monitor uses a rastering to update each line of the image sequentially, this causes a monitor raster latency which depends on the position, on the monitor and the refresh rate.New methodWe technically measured the raster latencies of different monitors and present the effects on visual evoked potentials (VEPs) and error-related potentials (ERPs). Additionally we present a method for correcting the monitor raster latency and analyzed the performance difference of a code-modulated VEP BCI speller by correcting the latency.Comparison with existing methodsThere are currently no other methods validating the effects of monitor raster latency on VEPs and ERPs.ResultsThe timings of VEPs and ERPs are directly affected by the raster latency. Furthermore, correcting the raster latency resulted in a significant reduction of the target prediction error from 7.98% to 4.61% and also in a more reliable classification of targets by significantly increasing the distance between the most probable and the second most probable target by 18.23%.ConclusionsThe monitor raster latency affects the timings of VEPs and ERPs, and correcting resulted in a significant error reduction of 42.23%. It is recommend to correct the raster latency for an increased BCI performance and methodical correctness.
http://ift.tt/2AP60GI
EJC's biennial report on metastatic soft tissue sarcoma: State of the art and future perspectives
Source:European Journal of Cancer, Volume 88
Author(s): Melissa Vos, Stefan Sleijfer
In the last decade the limited treatment options for patients with metastatic soft tissue sarcoma have expanded considerably. With the addition of olaratumab to first-line treatment with doxorubicin, the introduction of several new agents in second-line treatment and beyond and other promising agents in the pipeline, perspectives of patients with metastatic soft tissue sarcoma are improving. Due to increasing insight into the biology of the different soft tissue sarcoma subtypes, choice of treatment has become much more histology-driven, although more prognostic and predictive factors are needed to further personalise therapy. This report summarises the current state of the art and discusses the promising developments in the treatment of patients with metastatic soft tissue sarcoma.
http://ift.tt/2i9qpLe
The association between irisin and muscle metabolism in different thyroid disorders
Summary
Background
Irisin is a new adipo-myokine, encoded by the FNDC5 gene. Currently, there is a discussion regarding the relation between thyroid function and irisin concentration. This prospective study assesses the influence of thyrometabolic changes on serum irisin concentration in association with altered muscle metabolism. This is performed on a large cohort of patients affected by severe hypo- or hyperthyroidism, as well as by the expression of the FNDC5 gene in thyroid tissue affected by different pathologies.
Methods
The study group comprised 119 patients with newly diagnosed severe hyperthyroidism or hypothyroidism, and a control group of 45 healthy subjects. Body composition, serum irisin concentrations, and thyroid-related hormones, creatine kinase, dystrophin and titin concentrations were evaluated. FNDC5 expression was also analyzed in tissue samples from 80 patients with non-toxic multinodular goiter, toxic goiter, Graves' disease and papillary thyroid cancer.
Results
Irisin concentration was lower in patients with prolonged hypothyroidism. There was a tendency toward lower dystrophin and titin concentrations in patients with hypothyroidism and hyperthyroidism. Restoration of euthyroidism in patients with hypothyroidism resulted in a decreased muscle mass with an increase in irisin concentrations, while the hyperthyroid group showed an increase in fat mass. Statistically significant overexpression of FNDC5 gene was found in patients with toxic goiter as compared to Graves' disease, papillary thyroid cancer and controls.
Conclusions
The presented data support the theory that irisin concentration changes are associated with prolonged hypothyroidism and might primarily constitute the result of prolonged myopathy. These changes are most likely not related to the expression of the FNDC5 gene in the thyroid gland.
This article is protected by copyright. All rights reserved.
http://ift.tt/2BD1rfJ
Characteristics of polycyclic aromatic hydrocarbons in PM 2.5 emitted from different cooking activities in China
Abstract
Nineteen polycyclic aromatic hydrocarbons (PAHs) in PM2.5 emitted from five different cooking activities were characterized, and their influencing factors were determined. The total quantified particle-bounded PAH concentrations (ΣPAHs) in the airs from the cooking activities were 4.2–36.5-fold higher than those in corresponding backgrounds. The highest ΣPAHs were seen in cafeteria frying (783 ± 499 ng/m3), followed by meat roasting (420 ± 191 ng/m3), fish roasting (210 ± 105 ng/m3), snack-street boiling (202 ± 230 ng/m3), and cafeteria boiling (150 ± 65 ng/m3). The main influencing factors on the PAH emissions were cooking methods, fat contents in raw materials, and oil consumptions. Four- to six-ringed PAHs had the highest contributions to the ΣPAHs (avg. 87.5%). Diagnostic ratios of individual PAH were similar between the two charbroiling and other three conventional Chinese cooking methods, respectively, demonstrating the dominance of cooking methods in the PAH emissions. Remarkably high benzo(b)fluoranthene/benzo(k)fluoranthene (BbF/BkF) ratio (8.31) was seen in the snack-street boiling, attributed to the coal combustion as cooking fuel. Both fluoranthene/(fluoranthene + pyrene) [FLT/(FLT + PYR)] and benzo(a)anthracene/(benzo(a)anthracene + chrysene) [BaA/(BaA + CHR)] ratios were higher for the oil-based cooking than those from the water-based ones. In addition, two ratios of indeno(1,2,3-cd)pyrene/(indeno(1,2,3-cd)pyrene + benzo(g,h,i)perylene) [IPY/(IPY + BPE)] and benzo(a)pyrene/(benzo(a)pyrene + benzo(g,h,i)perylene) [BaP/(BaP + BPE)] were higher for two charbroiling than the three conventional Chinese cooking methods. The characterization work in this study is particularly important since cooking is a potential contributor of atmospheric PAHs in urban China. Carcinogenic potencies of PAHs were assessed by comparison with the air quality guideline and health risk estimation. The BaP and BaP equivalent were higher for the oil-based than the water-based cooking activities.
http://ift.tt/2AAGTa6
Prolonged use of alendronate alters the biology of cranial repair in estrogen-deficient rats’ associated simultaneous immunohistochemical expression of TGF-β1+, α-ER+, and BMPR1B-
Abstract
Objectives
TGF-β1 is a cytokine that may induce both osteoneogenesis through Runx-2 or fibrosis via the transcription of α-smooth muscle actin (α-SMA). Because it has been previously known that alendronate increases the level of TGF-β1 and that under the usual condition of bone metabolism the estrogen may prevent the fibrotic effect of TGF-β1, the aim of this study was to evaluate if alendronate alters the cellular differentiation process post calvarial surgery in estrogen-deficient specimens.
Materials and methods
A transosseous defect that was 5 mm in diameter was created on the calvarium of each of 32 female rats with previous ovarian-salpingo-oophorectomy. All defects were treated with autografts, and 16 rats received the administration of 1 mg/kg of alendronate three times a week until euthanasia on the 15th and 60th day post surgery. Histomorphometric and immunohistochemical analyses of the expression of TGF-β1, estrogen receptor alpha nuclear (α-ER), α-SMA, BMPR1B, and Runx-2 were performed, and ELISA was used to measure the level of estrogen.
Results
All animals demonstrated low levels of estrogen post ovarian-salpingo-oophorectomy. The histological results demonstrated larger bone matrix deposition in specimens treated with alendronate on the 15th day post surgery. The result was associated with a higher co-expression of TGF-β1, BMPR1B, and Runx-2 when compared with the control group. In addition, on the 60th day post surgery, the increase of bone matrix deposition from 15th to 60th day was discrete in specimens treated with alendronate compared with the control group. This result coincided with the intense simultaneous expression of TGF-β1, α-ER, and α-SMA, whereas the expression of BMPR1B and Runx-2 decreased.
Conclusion
The prolonged administration of alendronate altered the cranial repair in ovarian-salpingo-oophorectomized specimens due to the simultaneous occurrence of low estrogen and the presence of TGF-β1+/α-ER+ inducing the presence of α-SMA+, whereas BMPR1B and Runx-2 were suppressed.
Clinical relevance
The prolonged administration of alendronate alters osteoneogenesis and induces an unusual microenvironment in the bone that seems to imitate the physiological tissue damage that culminates in the loss of the functional layer of endometrium.
http://ift.tt/2j9kMhf
The influence of early life stress on the integration of emotion and working memory
Source:Behavioural Brain Research, Volume 339
Author(s): Sophie Metz, Sabine Aust, Yan Fan, Luisa Bönke, Zjala Harki, Matti Gärtner, Malek Bajbouj, Simone Grimm
IntroductionEarly life stress (ELS) impacts emotional and cognitive competences. We aimed to investigate whether the effects of ELS on working memory (WM) performance depend on the valence of the stimuli.MethodsBetween January and October 2015, we recruited (N=31) healthy subjects with (N=15) and without (N=16) ELS experiences. Participants performed a WM-task with emotional stimuli.ResultsResults show a trend towards decreased WM accuracy in subjects with ELS experiences (p=.06) with increased WM accuracy (p=.08) and an altered pattern of BOLD responses in the left posterior cingulate cortex (PCC)/precuneus (p<.001) and the rostral anterior cingulate cortex (rACC) (p<.01) in response to negative stimuli.LimitationsThe small sample size and potential confounding factors should be considered when interpreting the results.ConclusionOur data suggests that negative valence influences cognitive performance and brain activity in subjects with ELS experiences.
http://ift.tt/2j7dc6r
Cognitive, neurohistological and mortality outcomes following the four-vessel occlusion/internal carotid artery model of chronic cerebral hypoperfusion: The impact of diabetes and aging
Publication date: 26 February 2018
Source:Behavioural Brain Research, Volume 339
Author(s): Amanda Nunes Santiago, Emilene Dias Fiuza Ferreira, Rúbia Maris Weffort de Oliveira, Humberto Milani
Chronic cerebral hypoperfusion (CCH) may be involved in the etiology of aging-related dementias, and several risk factors contribute to their development and/or aggravation. We previously reported on the development of the 4-VO/ICA model of CCH, and the impact of hypertension on the cognitive and histological outcomes of CCH. Here, we advanced those studies by investigating how 4-VO/ICA alone or in combination with diabetes affects survival, body weight and cognitive performance in both young and middle-aged rats. Subsequently, middle-aged rats were examined for the impact of diabetes on CCH-induced neurodegeneration, white matter damage, and glial cells response. Diabetes alone reduced body weight and increased mortality rate slightly in young rats; these effects were striking, however, in the older animals. After CCH alone, neither body weight nor mortality rate changed significantly in both age groups. However, when CCH was combined with diabetes, mortality rate increased significantly in both aged groups. Young rats were cognitively asymptomatic to CCH, but they became 'mildly' impaired after CCH combined with diabetes. In middle-aged rats, CCH severely impaired memory, which was significantly worsened by diabetes. Moreover, diabetes aggravated neurodegeneration in the hippocampus and white matter injury in the corpus callosum and it promoted glial activation in the hippocampus and white matter of CCH middle-aged rats. These data suggest that diabetes interacts synergistically with age and reduces the capacity of the brain to adequately respond to CCH and highlight the importance of associating risk factors in the preclinical investigation of age-related cerebrovascular diseases physiopathology and potential therapies.
Graphical abstract
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Factors Correlating With Microsurgical Performance: A Clinical and Experimental Study
Publication date: Available online 1 December 2017
Source:Journal of Surgical Education
Author(s): Mark V. Schaverien, Jun Liu, Charles E. Butler, Jesse C. Selber
BackgroundMicrosurgery is one the most complex surgical skills to master. The factors correlating with microsurgical performance, however, are poorly understood. Understanding these factors will aid in the training and assessment of microsurgeons.MethodsA total of 29 microsurgery fellows enrolled in a dedicated 1-year microsurgery fellowship were included in the study. For the clinical evaluations, microsurgical anastomosis performance was evaluated during multiple procedures in the operating room at the start, midpoint, and end of the fellowship by all departmental faculty using a validated microsurgical assessment tool. For the laboratory evaluations, blinded video recordings of each fellow performing an arterial femoral anastomosis in a live rat model at the start and end of the fellowship were evaluated using 3 validated microsurgical global ratings scale tools. Correlations between performance and the factors assessed by the tools were evaluated.ResultsIn the clinical study there were a total of 474 anastomosis evaluations; clinical performance correlated best with speed, instrument handling, and motion. In the laboratory study 58 evaluations were conducted, and performance tracked most closely with instrument handling, flow of operation, and operative steps, as well as correlating significantly inversely with time taken. The most common errors committed were unequal stitch bites, wrong grasp/damage tissue, and loose knot.ConclusionsSpeed, both subjective and objective, instrument handling, operative flow, and motion, were relevant to performance of a microsurgical anastomosis. A prospective trial is now necessary to determine whether these factors should be considered in definitions of competency in microsurgery training pathways.
http://ift.tt/2Ajegh0
Radiation therapy improves disease-specific survival in women with Stage II endometrioid endometrial cancer—Brachytherapy may be sufficient
Source:Brachytherapy
Author(s): Chika R. Nwachukwu, Rie Von-Eyben, Elizabeth A. Kidd
PurposeTo evaluate disease-specific survival (DSS) outcomes in Stage II endometrioid endometrial cancer (EC) patients based on pathology and treatment information including adjuvant radiotherapy and lymph node assessment.Methods and MaterialsUsing the Surveillance, Epidemiology, and End Results database, 2877 patients with Stage II EC diagnosed between 2004 and 2012 treated with radiation were identified. DSS was determined for different modalities of radiation. Kaplan–Meier estimates of survival and Cox regression modeling were used to explore the risk associated with various factors on DSS.ResultsThe 4-year DSS for the study population was 90%. Radiation was associated with improved 4-year DSS when compared to no radiotherapy (p = 0.03). Patients with Grade 2 and 3 tumors had improved 4-year DSS with radiation (94% vs. 90%, p = 0.02 and 81% vs. 73%, p = 0.15), respectively, but no differences in DSS when vaginal brachytherapy alone was compared with external beam alone or both. Patients with Grade 2 (p = 0.002) and Grade 3 (p < 0.001) tumors without a lymph node dissection (LND) had worse DSS compared to patients with any LND. Patients with Grade 3 tumors without an LND who received radiation showed improved DSS (p = 0.008). Multivariable analysis revealed that age >60 years (p < 0.001), Grade 3 (p < 0.001), no radiotherapy (p = 0.05), and no LNDs (p < 0.001) were significant prognostic factors for worse DSS.ConclusionsAdjuvant radiation, whether delivered by brachytherapy or external beam radiation, is associated with improved DSS in Stage II EC patients with high-grade tumors, therefore brachytherapy may be sufficient.
http://ift.tt/2zWREEc
Initial clinical assessment of “center-specific” automated treatment plans for low-dose-rate prostate brachytherapy
Source:Brachytherapy
Author(s): Mustafa Ege Babadagli, John Doucette, Nawaid Usmani, John Amanie, Albert Murtha, Don Yee, Mohammad Jamaluddin, Ron S. Sloboda
PurposeTo report results of an initial pilot study assessing iodine-125 prostate implant treatment plans created automatically by a new seed-placement method.Methods and MaterialsA novel mixed-integer linear programming method incorporating spatial constraints on seed locations in addition to standard dose–volume constraints was used to place seeds. The approach, described in detail elsewhere, was used to create treatment plans fully automatically on a retrospective basis for 20 patients having a wide range of prostate sizes and shapes. Corresponding manual plans used for patient treatment at a single institution were combined with the automated plans, and all 40 plans were anonymized, randomized, and independently evaluated by five clinicians using a common scoring tool. Numerical and clinical features of the plans were extracted for comparison purposes.ResultsA full 51% of the automated plans were deemed clinically acceptable without any modification by the five practitioners collectively versus 90% of the manual plans. Automated plan seed distributions were for the most part not substantially different from those for the manual plans. Two observed shortcomings of the automated plans were seed strands not intersecting the prostate and strands extending into the bladder. Both are amenable to remediation by adjusting existing spatial constraints.ConclusionsAfter spatial and dose–volume constraints are set, the mixed-integer linear programming method is capable of creating prostate implant treatment plans fully automatically, with clinical acceptability sufficient to warrant further investigation. These plans, intended to be reviewed and refined as necessary by an expert planner, have the potential to both save planner time and enhance treatment plan consistency.
http://ift.tt/2ANqtvv
Improved rectal dosimetry with the use of SpaceOAR during high-dose-rate brachytherapy
Source:Brachytherapy
Author(s): Susan Y. Wu, Lauren Boreta, Ashley Wu, Joey P. Cheung, J. Adam M. Cunha, Katsuto Shinohara, Albert J. Chang
PurposeHydrogel spacers have been suggested to limit rectal radiation dose with improvements in clinical outcomes in patients undergoing external beam radiation treatment for prostate cancer. No studies to date have assessed the utility and dosimetric effect of SpaceOAR (Augmenix, Inc, Waltham, MA), the only Food and Drug Administration–approved hydrogel rectal spacer, for high-dose-rate (HDR) brachytherapy.MethodsEighteen consecutive patients scheduled for HDR brachytherapy in the treatment of prostate cancer underwent transperineal ultrasound-guided placement of 10 cc of SpaceOAR hydrogel following catheter implantation. Treatment plans were generated using an inverse planning simulated annealing algorithm. Rectal dosimetry for these 18 patients was compared with the 36 preceding patients treated with HDR brachytherapy without SpaceOAR.ResultsFifty-four plans were analyzed. There was no difference in age, pretreatment prostate-specific antigen, Gleason score, clinical stage, prostate volume, or contoured rectal volume between those who received SpaceOAR and those who did not. Patients who received SpaceOAR hydrogel had significantly lower dose to the rectum as measured by percent of contoured organ at risk (median, V80 < 0.005% vs. 0.010%, p = 0.003; V75 < 0.005% vs. 0.14%, p < 0.0005; V70 0.09% vs. 0.88%, p < 0.0005; V60 = 1.16% vs. 3.08%, p < 0.0005); similar results were seen for rectal volume in cubic centimeters. One patient who received SpaceOAR developed a perineal abscess 1 month after treatment.ConclusionsTransperineal insertion of SpaceOAR hydrogel at the time of HDR brachytherapy is feasible and decreases rectal radiation dose. Further investigation is needed to assess the clinical impact of this dosimetric improvement and potential toxicity reduction.
http://ift.tt/2zXmQTW
Pulmonary papillary adenocarcinoma with Aspergillus versicolor infection in a dog
Publication date: March 2018
Source:Medical Mycology Case Reports, Volume 19
Author(s): Rathiymaler Maniam, Gayathri Thevi Selvarajah, Mazlina Mazlan, Leslie Thian Lung Than
Papillary adenocarcinoma of the lungs is the most common primary lung adenocarcinoma, with the feature of papillary-like structure formation by cells. A dog was presented with the primary complaint of vomiting, hyporexia and increased respiratory effort. Thoracic radiography revealed increased soft tissue radiopacity of the right cranial lung lobe suggestive of possible consolidation or collapsed lung lobe, with generalised miliary nodular pattern throughout the other lung fields. The dog was euthanized humanely and necropsy was performed. Histopathology confirmed the diagnosis of primary pulmonary lung neoplasm (papillary adenocarcinoma) with Aspergillus versicolor infection identified through fungal culture and PCR. There have been several reports on humans and dogs with fungal infections that often mimic or coexist with pulmonary neoplasm. This is the first documented report of A. versicolor isolated from a lung neoplasm in a dog in Malaysia.
http://ift.tt/2BssSZ0
Hypercoagulability and Vascular Disease
Source:Hematology/Oncology Clinics of North America
Author(s): Ali T. Taher, Maria Domenica Cappellini, Rayan Bou-Fakhredin, Daniel Coriu, Khaled M. Musallam
Teaser
The presence of a high incidence of thrombotic events, mainly in nontransfusion-dependent β-thalassemia syndromes, has led to the identification of a hypercoagulable state in thalassemia patients. This article highlights the mechanisms leading to hypercoagulability in thalassemia. It also discusses the clinical experience and available evidence on prevention and management approaches.http://ift.tt/2ApMu0t
Accreditation of service hospitals: Time to move towards state of readiness
Source:Medical Journal Armed Forces India
Author(s): K.M. Adhikari, Deepak Joshi, Rakesh Gupta
http://ift.tt/2iECIDb
Sclerosing stromal cell tumor of ovary
Source:Medical Journal Armed Forces India
Author(s): Shazia Khan, Virendra Singh, I.D. Khan, Sujatha Panda
http://ift.tt/2AD4zuo
Th1 epitope peptides induce protective immunity against Rickettsia rickettsii infection in C3H/HeN mice
Source:Vaccine, Volume 35, Issue 51
Author(s): Pengcheng Wang, Xiaolu Xiong, Jun Jiao, Xiaomei Yang, Yongqiang Jiang, Bohai Wen, Wenping Gong
Rickettsia rickettsii is the causative pathogen of Rocky Mountain spotted fever (RMSF). Adr2, YbgF and OmpB are protective antigens of R. rickettsii. In this study, 90 candidate peptides were selected from these antigens based on their high-affinity binding capacity for the MHC class II molecule H2 I-A or H2 I-E using bioinformatic methods. Six peptides were determined using ELISPOT assay to be immunodominant based on the IFN-γ recall responses of CD4+ T cells from mice immunized with R. rickettsii. Six nucleotide sequences encoding the immunodominant peptides were linked in series and inserted into a plasmid for expression in Escherichia coli cells, resulting in a new, recombinant polypeptide termed GWP. After immunization and challenge, the rickettsial load or histopathological lesions in the organs of mice immunized with GWP or pooled peptides was significantly lower than that in organs of mice immunized with PBS or the individual peptide OmpB399. An in vitro neutralization test revealed that sera from mice immunized with GWP, OmpB399, or pooled peptides reduced R. rickettsii adherence to, and invasion of, vascular endothelial cells. Furthermore, significantly higher levels of IgG, IgG1, or IgG2a were detected in sera from mice immunized with GWP or pooled peptides, and significantly higher levels of IFN-γ or TNF-α secreted by CD4+ T cells from R. rickettsii-infected mice were detected after immunization with GWP. Altogether, our results indicated that polypeptides, especially GWP, could induce a Th1-type immune response against R. rickettsii infection, which might contribute to the rational design of peptide-based vaccines for RMSF.
http://ift.tt/2ANqQGD
An in vitro cell-based potency assay for pharmaceutical type A botulinum antitoxins
Source:Vaccine, Volume 35, Issue 52
Author(s): Amram Torgeman, Eran Diamant, Lilach Levin, Alon Ben David, Eyal Epstein, Meni Girshengorn, Ohad Mazor, Ronit Rosenfeld, Ran Zichel
Botulism therapy relies on passive immunization with antitoxin. The mouse neutralization test is the only pharmacopeia assay to measure the potency of antitoxin preparations. Herein, we present an in vitro cell-based assay for the measurement of pharmaceutical type A antitoxin potency. Accuracy, reproducibility and compatibility with the mouse bioassay were demonstrated using different batches of standard antitoxin and toxin preparations. The established assay may substantially reduce the use of laboratory animals in the process of pharmaceutical antitoxin production.
http://ift.tt/2zUGUpJ
Selection of vaccine strains for serotype O foot-and-mouth disease viruses (2007–2012) circulating in Southeast Asia, East Asia and Far East
Source:Vaccine, Volume 35, Issue 51
Author(s): Mana Mahapatra, Sasmita Upadhyaya, Sharie Aviso, Aravindh Babu, Geoff Hutchings, Satya Parida
Foot-and-mouth disease (FMD) is endemic in Southeast Asia (SEA) and East Asia with circulation of multiple serotypes and multiple genotypes within each serotype of the virus. Although countries like Japan and South Korea in the Far East were free of FMD, in 2010 FMD serotype O (O/Mya-98) outbreaks were recorded and since then South Korea has experienced several FMD outbreaks despite regular vaccination. In this study a total of 85 serotype O FMD viruses (FMDV) isolated from 2007 to 2012 from SEA, East Asia and Far East were characterized by virus neutralisation tests using antisera to four existing (O/HKN/6/83, O/IND/R2/75, O/SKR/2010 and O/PanAsia-2) and one putative (O/MYA/2009) vaccine strains, and by full capsid sequencing. Serological studies revealed broad cross-reactivity with the vaccine strains; O/PanAsia-2 exhibited a good match with 95.3%, O/HKN/6/83 with 91.8%, O/IND/R2/75 with 80%, and the putative strain O/MYA/2009 with 89.4% isolates employed in this study. Similarly O/PanAsia-2 and O/IND/R2/75 vaccines showed a good match with all eight viruses belonging to O-Ind-2001d sublineage whereas the vaccines of O/Mya-98 lineage, O/MYA/2009 and O/SKR/2010 exhibited the lowest match indicating their unsuitability to protect infections from O-Ind-2001d viruses. A Bayesian analysis of the capsid sequence data indicated these circulating viruses (n = 85) to be of either SEA or Middle East-South Asian (ME-SA) topotype. The ME-SA topotype viruses were mainly detected in Lao PDR, Vietnam, Myanmar and Thailand reflecting the trade links with the Indian subcontinent, and also within the SEA countries. Implications of these results in the context of FMD control in SEA and East Asian countries are discussed.
http://ift.tt/2AOv54M
Differences between vaccinated and unvaccinated women explain increase in non-vaccine-type human papillomavirus in unvaccinated women after vaccine introduction
Source:Vaccine, Volume 35, Issue 52
Author(s): Lili Ding, Lea E. Widdice, Jessica A. Kahn
The aim of this study was to determine whether an observed increase in non-vaccine-type human papillomavirus (HPV) in unvaccinated women during the first eight years after vaccine introduction may be explained by differences in demographics or sexual behaviors, instead of type replacement. We analyzed data from three cross-sectional surveillance studies of 13–26 year-old women (total N = 1180). For women recruited from a health department clinic, older age (OR = 1.4, 95% CI: 1.2–1.6) and consistent condom use with main partner in the past 3 months (OR = 11.6, 95% CI: 3.4–40) were associated with being unvaccinated. For women recruited from a teen health center African American race (OR = 0.2, 95% CI: 0.07–0.7) and having Medicaid health insurance (OR = 0.3, 95% CI: 0.1–0.7) were inversely associated with being unvaccinated. The observed increase in non-vaccine-type HPV prevalence in unvaccinated women may be explained by differences between unvaccinated and vaccinated women.
http://ift.tt/2zY3NZu
Conflicting results in article describing “HPV-vaccination and risk of chronic fatigue syndrome/myalgic encephalomyelitis”
Source:Vaccine, Volume 35, Issue 51
Author(s): L. Andersson
http://ift.tt/2AODvsJ
Herpes zoster vaccine live: A 10 year review of post-marketing safety experience
Source:Vaccine, Volume 35, Issue 52
Author(s): English D. Willis, Meredith Woodward, Elizabeth Brown, Zoran Popmihajlov, Patricia Saddier, Paula W. Annunziato, Neal A. Halsey, Anne A. Gershon
BackgroundZoster vaccine is a single dose live, attenuated vaccine (ZVL) indicated for individuals ≥50 years-old for the prevention of herpes zoster (HZ). Safety data from clinical trials and post-licensure studies provided reassurance that ZVL is generally safe and well tolerated. The objective of this review was to provide worldwide post-marketing safety information following 10 years of use and >34 million doses distributed.MethodsAll post-marketing adverse experience (AE) reports received worldwide between 02-May-2006 and 01-May-2016 from healthcare professionals following vaccination with ZVL and submitted to the MSD AE global safety database, were analyzed.ResultsA total of 23,556 AE reports, 93% non-serious, were reported. Local injection site reactions (ISRs), with a median time-to-onset of 2 days, were the most frequently reported AEs followed by HZ. The majority of HZ reports were reported within 2 weeks of vaccination and considered, based on time-to-onset, pathogenesis of HZ, and data from clinical trials, to be caused by wild-type varicella-zoster virus (VZV). HZ confirmed by PCR analysis to be VZV Oka/Merck vaccine-strain was identified in an immunocompetent individual 8 months postvaccination and in 4 immunocompromised individuals. Disseminated HZ was reported very rarely (<1%) with 38% occurring in immunocompromised individuals. All reports of disseminated HZ confirmed by PCR as VZV Oka/Merck vaccine-strain were in individuals with immunosuppressive conditions and/or therapy at the time of vaccination.ConclusionsThe safety profile of ZVL, following 10 years of post-marketing use, was favorable and consistent with that observed in clinical trials and post-licensure studies.
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In vivo electroporation enhances vaccine-mediated therapeutic control of human papilloma virus-associated tumors by the activation of multifunctional and effector memory CD8+ T cells
Source:Vaccine, Volume 35, Issue 52
Author(s): Natiely S. Sales, Jamile R. Silva, Luana R.M.M. Aps, Mariângela O. Silva, Bruna F.M.M. Porchia, Luís Carlos S. Ferreira, Mariana O. Diniz
In vivo electroporation (EP) has reignited the clinical interest on DNA vaccines as immunotherapeutic approaches to control different types of cancer. EP has been associated with increased immune response potency, but its capacity in influencing immunomodulation remains unclear. Here we evaluated the impact of in vivo EP on the induction of cellular immune responses and therapeutic effects of a DNA vaccine targeting human papillomavirus-induced tumors. Our results demonstrate that association of EP with the conventional intramuscular administration route promoted a more efficient activation of multifunctional and effector memory CD8+ T cells with enhanced cytotoxic activity. Furthermore, EP increased tumor infiltration of CD8+ T cells and avoided tumor recurrences. Finally, our results demonstrated that EP promotes local migration of antigen presenting cells that enhances with vaccine co-delivery. Altogether the present evidences shed further light on the in vivo electroporation action and its impact on the immunogenicity of DNA vaccines.
http://ift.tt/2ANeSwB
Editorial Board/Aims and Scope
Source:Vaccine, Volume 35, Issue 52
http://ift.tt/2zUGDTJ
Lambda display phage as a mucosal vaccine delivery vehicle for peptide antigens
Source:Vaccine, Volume 35, Issue 52
Author(s): Patricia González Cano, Lakshman N.A. Gamage, Kristen Marciniuk, Connie Hayes, Scott Napper, Sidney Hayes, Philip J. Griebel
Bacteriophage are structurally stable in the gastro-intestinal tract and have favorable traits of safety, stability, ease of production, and immunogenicity. These attributes make them potential candidates as oral vaccine delivery vehicles but little is known about their capacity to induce mucosal immune responses in the small intestine. Whole body imaging of mice confirmed lambda bacteriophage (LP) were distributed throughout the gastro-intestinal tract 24 h after oral delivery. In newborn calves, targeted delivery of LP within the small intestine confirmed LP were immunogenic in a dose-dependent manner and were taken up by Peyer's patches. LP-specific IgA responses were induced within both Peyer's patches and draining mesenteric lymph nodes. A lambda display phage (LDP) was constructed to present three immunogenic disease specific epitopes (DSE) from cervid prion protein (amino acids 130–140 [YML]; 163–170 [YRR]; and 171–178[YRR]) fused to phage capsid head protein D (LDP-DSE). Targeted delivery of purified LDP-DSE to intestinal segments induced IgA responses to all three peptide epitopes. Further, delivery of bacteria expressing soluble D-DSE also induced epitope-specific IgA responses in the targeted Peyer's patches. These are the first studies to report use of LDP to induce epitope-specific IgA responses in the small intestine andconfirm Peyer's patchesfunction as a site for LP uptake. Furthermore, IgA responses to peptide epitopes on LDP were observed in the absence of a mucosal adjuvant. These observations confirm LDP have the capacity to function as a mucosal delivery vehicle with protein D as an effective carrier for peptide epitopes.
http://ift.tt/2ANOVNq
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Ειδοποίηση Μελετητή:[ ωτα ] [HTML] Gender, identity and material: Film screening C Brand - 2017 ftypM4V *M4V M4A mp42isom*a┌moovlmvhd...
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Publication date: September 2017 Source: Free Radical Biology and Medicine, Volume 110 Author(s): Lucía Fernández-del-Río, Anish Nag, Elen...
