HLA-DR expression in tumor epithelium is an independent prognostic indicator in esophageal adenocarcinoma patients

Abstract

Esophageal adenocarcinoma (EAC) is an aggressive cancer with poor prognosis, and incidence is increasing rapidly in the Western world. Measurement of immune markers has been shown to have prognostic significance in a growing number of cancers, but whether this is true for EAC has yet to be evaluated. This study aimed to characterize HLA-DR expression in the esophagus across the inflammation to cancer progression sequence and to assess the prognostic significance of HLA-DR expression in EAC. Tissue microarrays (TMA) were constructed from esophageal tissue taken from patients at different stages in the cancer progression sequence; normal, esophagitis, Barrett’s esophagus (BE), low- and high-grade dysplasia (LGD, HGD) and EAC. HLA-DR expression in tissue epithelium and stroma was assessed by immunohistochemistry. HLA-DR expression increased early in the inflammation to cancer progression sequence; with higher expression detected in esophagitis and BE compared to normal tissue. Patients with low (<50%) HLA-DR expression in the EAC tumor epithelium had significantly worse survival outcomes, compared to those with high expression, in both the tumor core (hazard ratio, HR = 2.178, p = 0.024, n = 70) and leading edge (HR = 2.86, p = 0.013, n = 41). Multivariate analysis demonstrated that low HLA-DR expression in leading edge tumor epithelium was an independent predictor of poor survival, associated with a 2.8-fold increase in disease-associated death (p = 0.023). This study shows that HLA-DR is an independent prognostic marker in EAC tumor epithelium. This may have implications for patient stratification strategies as well as EAC tumor immunology.

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The new issue is now available.The Journal of Physical Fitness and Sports Medicine

Vol.6 No.2

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The new issue is now available.Japanese Journal of Physical Fitness and Sports Medicine

Vol.66 No.2

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The rationale of indoleamine 2,3-dioxygenase inhibition for cancer therapy

Publication date: May 2017
Source:European Journal of Cancer, Volume 76
Author(s): Lieve Brochez, Ines Chevolet, Vibeke Kruse
Indoleamine 2,3-dioxygenase (IDO, also referred to as IDO1) has been demonstrated to be a normal endogenous mechanism of acquired peripheral immune tolerance in vivo.In the field of oncology, IDO expression and/or activity has been observed in several cancer types and has usually been associated with negative prognostic factors and worse outcome measures.This manuscript reviews current available data on the role of IDO in cancer and the current results obtained with IDO inhibition, both in animal models and in phase 1 and 2 clinical trials in humans. Preliminary results with IDO inhibitors, usually combined with other anti-cancer drugs, seem encouraging. Further studies are needed to clarify the conditions in which IDO inhibitors can be of value as an anti-cancer strategy. In addition, further research should address whether the expression of IDO in tissue or blood can be a marker to select patients who can benefit most from IDO inhibition.



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Biological mechanisms of immune escape and implications for immunotherapy in head and neck squamous cell carcinoma

Publication date: May 2017
Source:European Journal of Cancer, Volume 76
Author(s): Jennifer D. Moy, Jessica M. Moskovitz, Robert L. Ferris
Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with high morbidity and mortality. Despite advances in cytotoxic therapies and surgical techniques, overall survival (OS) has not improved over the past few decades. This emphasises the need for intense investigation into novel therapies with good tumour control and minimal toxicity. Cancer immunotherapy has led this endeavour, attempting to improve tumour recognition and expand immune responses against tumour cells. While various forms of HNSCC immunotherapy are in preclinical trials, the most promising direction thus far has been with monoclonal antibodies (mAbs), targeting growth factor and immune checkpoint receptors. Preclinical and early phase trials have shown unprecedented efficacy with minimal adverse effects. This article will review biological mechanisms of immune escape and implications for immunotherapy in HNSCC.



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Twin pregnancy complicated by esophageal atresia, duodenal atresia, gastric perforation, and hypoplastic left heart structures in one twin: a case report and review of the literature

The antenatal diagnosis of a combined esophageal atresia without tracheoesophageal fistula and duodenal atresia with or without gastric perforation is a rare occurrence. These diagnoses are difficult and can b...

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Impaired quality of life in patients with treated acromegaly despite long-term biochemically stable disease: results from a 5-year prospective study

Abstract

Objective

Patients with acromegaly demonstrate impaired quality of life (QoL), but data on long-term QoL changes in treated acromegaly are limited. This study evaluates and identifies factors that influence QoL in patients with long-term biochemical remission.

Design

The study consists of a cross-sectional arm comparing QoL between patients with treated and controlled acromegaly and healthy controls; and a longitudinal arm assessing QoL changes in patients with biochemically stable disease during 5.7±0.6yrs of follow-up.

Patients

58 patients and 116 matched controls were recruited for the cross-sectional arm; 28 patients completed the longitudinal arm.

Measurements

Three generic questionnaires [Psychological General Well-Being Schedule (PGWBS), 36-item Short-Form (SF-36), EuroQoL (EQ-5D)] and the disease-specific acromegaly QoL questionnaire (AcroQoL) were applied.

Results

QoL assessment was performed 11.6±8.2yrs following diagnosis and treatment of acromegaly. Patients with treated acromegaly had lower QoL scores compared with controls in all questionnaires with the exception of the PGWBS “Anxiety” subscale. The AcroQoL “Appearance” subscale and the “physical function” subscales of the remaining questionnaires were the most underscored domains. No difference in the total and subscale scores of all questionnaires was observed between baseline and follow-up, with the exception of the SF-36 “Physical Function”, where a decline was found (58.5±24.7% vs. 43.1±31.1%; p=0.002). However, after adjusting for covariates, no significant change in any of the QoL scores was seen. Duration of IGF-1/GH control was positively correlated with QoL scores in most questionnaires at baseline, whereas use of GH lowering therapy at the time of QoL assessment was a negative predictive factor of QoL.

Conclusions

Patients with biochemically controlled acromegaly demonstrate impaired QoL, which persists despite long-term disease control. This primarily consists of impaired physical function and secondly of impaired psycho-social well-being. Duration of biochemical disease control and current use of GH lowering therapy were the predominant factors determining patients’ QoL.

This article is protected by copyright. All rights reserved.

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The effects of DASH diet on weight loss, anti-Müllerian hormone and metabolic profiles in women with polycystic ovary syndrome: a randomized clinical trial

Summary

Objective

This study was designed to evaluate the effects of the Dietary Approaches to Stop Hypertension (DASH diet) on weight loss, anti-Müllerian hormone (AMH) and metabolic profiles in women with polycystic ovary syndrome (PCOS).

Design, Patients and Measurements

A randomized controlled clinical trial was conducted among 60 overweight or obese patients with PCOS. Patients were randomly assigned to receive either low-calorie DASH (N=30) or control diet (N=30) for 12 weeks. The DASH and control diets were consisted of 52-55% carbohydrates, 16-18% proteins and 30% total fats; however, the DASH diet was designed to be rich in fruits, vegetables, whole grains, low-fat dairy products, cholesterol and refined grains. Both diets were equicaloric.

Results

Adherence to the DASH diet, compared to the control diet, resulted in a significant decrease in BMI (-1.6±0.5 vs. -1.2±0.7 kg/m², P=0.02). Significant decreases in AMH (-1.1±3.1 vs. +0.3±0.7 ng/mL, P=0.01), insulin (-25.2±51.0 vs. -1.2±28.8 pmol/L, P=0.02), homeostasis model of assessment-estimated insulin resistance (-0.9±2.0 vs. -0.1±1.0, P=0.02), free androgen index (FAI) (-0.03±0.09 vs. +0.06±0.21, P=0.02) and malondialdehyde (MDA) levels (-0.5±0.4 vs. +0.2±0.3 μmol/L, P<0.001), and significant increases in quantitative insulin sensitivity check index (+0.01±0.03 vs. -0.004±0.01, P=0.02), sex hormone-binding globulin (SHBG) (+3.7±8.5 vs. -1.5±7.2 nmol/L, P=0.01) and nitric oxide (NO) (+9.0±4.9 vs. +0.6±2.3 μmol/L, P<0.001) were also seen in the DASH group compared with the control group .

Conclusions

Adherence to the DASH diet for 12 weeks among PCOS women had beneficial effects on BMI, AMH, insulin metabolism, SHBG, FAI, NO and MDA levels.

This article is protected by copyright. All rights reserved.

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RT @ecancer_espanol : Comienza nuestro día del Congreso https://t.co/ws2OfqSKs4 https://t.co/C13HoDPUvc

RT @ecancer_espanol : Comienza nuestro día del Congreso https://t.co/ws2OfqSKs4 https://t.co/C13HoDPUvc

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RT @ecancer_espanol : Dr Carlos Castro hablando sobre tratamientos en de seno https://t.co/ws2OfqSKs4 https://t.co/xstoQvX4Uv

RT @ecancer_espanol : Dr Carlos Castro hablando sobre tratamientos en de seno https://t.co/ws2OfqSKs4 https://t.co/xstoQvX4Uv

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RT @ecancer_espanol : Comienza nuestro taller en radioterapia https://t.co/ws2OfqSKs4 https://t.co/4EINTKfOI4

RT @ecancer_espanol : Comienza nuestro taller en radioterapia https://t.co/ws2OfqSKs4 https://t.co/4EINTKfOI4

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RT @ecancer_espanol : Equipo de ecancer con ponentes internacionales https://t.co/ws2OfqSKs4 https://t.co/gj8WhMpWNu

RT @ecancer_espanol : Equipo de ecancer con ponentes internacionales https://t.co/ws2OfqSKs4 https://t.co/gj8WhMpWNu

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RT @ecancer_espanol : Dr Jose Valerio - manejó quirúrgico en metástasis de columna vertebral https://t.co/xP1BPTu18p https://t.co/vNN7ucqa42

RT @ecancer_espanol : Dr Jose Valerio - manejó quirúrgico en metástasis de columna vertebral https://t.co/xP1BPTu18p https://t.co/vNN7ucqa42

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Employment status and occupational level of adult survivors of childhood cancer in Great Britain: the British Childhood Cancer Survivor Study

Abstract

The British Childhood Cancer Survivor Study (BCCSS) provides the first detailed investigation of employment and occupation to be undertaken in a large population-based cohort. Previous studies have been limited by design issues such as using small numbers of survivors with specific diagnoses, and involved limited assessment of employment status and occupational level.

The BCCSS includes 17,981 5-year survivors of childhood cancer. Employment status and occupational level were ascertained by questionnaire from eligible survivors (n = 14,836). Multivariate logistic regression was used to explore factors associated with employment and occupation, and to compare survivors to their demographic peers in the general population.

Employment status was available for 10,257 survivors. Gender, current age, cancer type, radiotherapy, age at diagnosis and epilepsy were consistently associated with being: employed; unable to work; in managerial or non-manual occupations. Overall, survivors were less likely to be working than expected (OR (99% CI): 0.89 (0.81-0.98)), and this deficit was greatest for irradiated CNS neoplasm survivors (0.34 (0.28-0.41)). Compared to the general population, survivors were five-fold more likely to be unable to work due to illness/disability; the excess was fifteen-fold among CNS neoplasm survivors treated with radiotherapy. Overall survivors were less likely to be in managerial occupations than expected (0.85 (0.77-0.94)). However, bone sarcoma survivors were more likely to be in these occupations than expected (1.37 (1.01-1.85)) and also similarly for non-manual occupations (1.90 (1.37-2.62)). Survivors of retinoblastoma (1.55 (1.20-2.01)) and ‘other' neoplasm group (1.62 (1.30-2.03)) were also more likely to be in non-manual occupations than expected. This article is protected by copyright. All rights reserved.

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Sensitivity and specificity of antibodies against HPV16 E6 and other early proteins for the detection of HPV16-driven oropharyngeal squamous cell carcinoma

Abstract

To determine the sensitivity and specificity of HPV16 serology as diagnostic marker for HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), 214 HNSCC patients from Germany and Italy with fresh-frozen tumor tissues and sera collected before treatment were included in this study. 120 cancer cases were from the oropharynx and 94 were from head and neck cancer regions outside the oropharynx (45 oral cavity, 12 hypopharynx and 35 larynx). Serum antibodies to early (E1, E2, E6 and E7) and late (L1) HPV16 proteins were analyzed by multiplex serology and were compared to tumor HPV RNA status as the gold standard. A tumor was defined as HPV-driven in the presence of HPV16 DNA and HPV16 transformation-specific RNA transcript patterns (E6*I, E1^E4 and E1C). Of 120 OPSCC, 66 (55%) were HPV16-driven. HPV16 E6 seropositivity was the best predictor of HPV16-driven OPSCC (diagnostic accuracy 97% [95%CI 92-99%], Cohen's kappa 0.93 [95%CI 0.8-1.0]). Of the 66 HPV-driven OPSCC, 63 were HPV16 E6 seropositive, compared to only one (1.8%) among the 54 non-HPV-driven OPSCC, resulting in a sensitivity of 96% (95%CI 88-98) and a specificity of 98% (95%CI 90-100). Of 94 HNSCC outside the oropharynx, 6 (6%) were HPV16-driven. In these patients, HPV16 E6 seropositivity had lower sensitivity (50%, 95%CI 19-81), but was highly specific (100%, 95%CI 96-100). In conclusion, HPV16 E6 seropositivity appears to be a highly reliable diagnostic marker for HPV16-driven OPSCC with very high sensitivity and specificity, but might be less sensitive for HPV16-driven HNSCC outside the oropharynx. This article is protected by copyright. All rights reserved.

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Risks of dioxins resulting from high exposure via breast-feeding?

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Exogenous H2S prevents high glucose-induced damage to osteoblasts through regulation of KATP channels

Publication date: Available online 18 March 2017
Source:Biochimie
Author(s): Yuanyuan Liu, Jianyong Liu, Xin Li, Fantao Wang, Xin Xu, Chunling Wang
Association between diabetes and osteoporosis has been extensively investigated. However, whether the effects of H2S on osteoblast function under high glucose (HG) condition relate to ATP-sensitive potassium (KATP) channels is unclear. To investigate the effects of H2S on the proliferation, apoptosis, and mineralization of osteoblasts under HG condition, and to observe whether H2S exert this effect through the KATP channels. Primary osteoblasts (POBs) were obtained from the calvaria of Sprague-Dawley rats. Cells were pre-treated with 400 μmol/L NaHS (a H2S donor), and/or 0.1 mmol/L non-selective KATP channel opener pinacidil (Pia), and/or KATP channel inhibitor glibenclamide (Gli). They then were cultured in DMEM with 26.5 mmol/L (HG) or 5.5 mmol/L (control) glucose. Cell proliferation, apoptosis, and mineralization were determined. In addition, expression of KATP SUR1 was also determined. NaHS pretreatment significantly inhibited the HG down-regulation of KATP SUR1 expression in POBs. NaHS also significantly prevented osteoblast injury induced by HG, through decreasing the rate of cell proliferation and increasing the number of apoptotic cells, which was similar with the effects of Pia. In addition, NaHS significantly deterred the HG-induced POB mineralization inhibition. H2S prevents the HG-induced osteoblast damage through regulation of KATP channels.



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A Case-control Study of the Association between Ulcerative Colitis and Hyperthyroidism in an Asian Population

Summary

Objective

Ulcerative colitis (UC) is a chronic relapsing inflammatory disease with significant clinical diversity. However, the etiology, pathogenesis, and optimal treatment of UC remain unclear. The purpose of this case-control study was to investigate the association between previously diagnosed hyperthyroidism and UC using a large population-based dataset in Taiwan.

Methods

The data for this population-based case-control study were retrieved from the Taiwan Longitudinal Health Insurance Database 2005. We included 2709 patients with UC as cases and 8127 sex- and age-matched patients without UC as controls. A conditional logistic regression analysis was conducted to compute the odds ratio (OR) and corresponding 95% confidence interval (CI) for the association between UC and prior hyperthyroidism.

Results

We found that, in total, 327 of the 10,836 sampled patients (3.02%) had previously been diagnosed with hyperthyroidism. There was a higher proportion of prior hyperthyroidism among cases than controls (4.10% vs. 2.66%, p<0.001). A conditional logistic regression showed that the OR of prior hyperthyroidism was 1.57 (95% CI=1.24~1.98) compared to controls. Similarly, after adjusting for monthly income, geographic location, and urbanization level, cases were still more likely to have previously been diagnosed with hyperthyroidism than controls (OR=1.61, 95% CI=1.27~2.05). Furthermore, we analyzed the ORs of prior hyperthyroidism between cases and controls according to age group. We found that of the youngest group of sampled patients (18~39 years), cases had the greatest adjusted OR for having previously been diagnosed with hyperthyroidism than controls (OR=1.98, 95% CI=1.04~3.79).

Conclusions

This study demonstrated an association between UC and hyperthyroidism.

This article is protected by copyright. All rights reserved.

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Understand the variety of treatment options which exist for chemoprevention in high risk groups for #breastcancer… https://t.co/TyLmK7bQhK

Understand the variety of treatment options which exist for chemoprevention in high risk groups for #breastcancer… https://t.co/TyLmK7bQhK

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Construction of an agroinfectious clone of bean rugose mosaic virus using Gibson Assembly

Abstract

Construction of agroinfectious viral clones usually requires many steps of cloning and sub-cloning and also a binary vector, which makes the process laborious, time-consuming, and frequently susceptible to some degree of plasmid instability. Nowadays, novel methods have been applied to the assembly of infectious viral clones, and here we have applied isothermal, single-step Gibson Assembly (GA) to construct an agroinfectious clone of Bean rugose mosaic virus (BRMV) using a small binary vector. The procedure has drastically reduced the cloning steps, and BRMV could be recovered from agroinfiltrated common bean twenty days after inoculation, indicating that the infectious clone could spread in the plant tissues and efficiently generate a systemic infection. The virus was also recovered from leaves of common bean and soybean cultivars mechanically inoculated with infectious clone two weeks after inoculation, confirming the efficiency of GA cloning procedure to produce the first BRMV agroinfectious clone to bean and soybean.

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