OBJECTIVES: Transcription Factor 21 represses steroidogenic factor 1, a nuclear receptor required for gonadal development, sex determination and the regulation of adrenogonadal steroidogenesis. The aim of this study was to investigate whether silencing or overexpression of the gene Transcription Factor 21 could modulate the gene and protein expression of steroidogenic factor 1 in adrenocortical tumors. METHODS: We analyzed the gene expression of steroidogenic factor 1 using qPCR after silencing endogenous Transcription Factor 21 in pediatric adrenal adenoma-T7 cells through small interfering RNA. In addition, using overexpression of Transcription Factor 21 in human adrenocortical carcinoma cells, we analyzed the protein expression of steroidogenic factor 1 using Western blotting. RESULTS: Transcription Factor 21 knockdown increased the mRNA expression of steroidogenic factor 1 by 5.97-fold in pediatric adrenal adenoma-T7 cells. Additionally, Transcription Factor 21 overexpression inhibited the protein expression of steroidogenic factor 1 by 0.41-fold and 0.64-fold in two different adult adrenocortical carcinoma cell cultures, H295R and T36, respectively. CONCLUSIONS: Transcription Factor 21 is downregulated in adrenocortical carcinoma cells. Taken together, these findings support the hypothesis that Transcription Factor 21 is a regulator of steroidogenic factor 1 and is a tumor suppressor gene in pediatric and adult adrenocortical tumors.
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Πέμπτη 22 Ιουνίου 2017
New evidences on the regulation of SF-1 expression by POD1/TCF21 in adrenocortical tumor cells
Scholar : These new articles for Annals of GIS are available online
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Three-year pooled analysis of factors associated with clinical outcomes across dabrafenib and trametinib combination therapy phase 3 randomised trials
Source:European Journal of Cancer, Volume 82
Author(s): Dirk Schadendorf, Georgina V. Long, Daniil Stroiakovski, Boguslawa Karaszewska, Axel Hauschild, Evgeny Levchenko, Vanna Chiarion-Sileni, Jacob Schachter, Claus Garbe, Caroline Dutriaux, Helen Gogas, Mario Mandalà, John B.A.G. Haanen, Céleste Lebbé, Andrzej Mackiewicz, Piotr Rutkowski, Jean-Jacques Grob, Paul Nathan, Antoni Ribas, Michael A. Davies, Ying Zhang, Mathilde Kaper, Bijoyesh Mookerjee, Jeffrey J. Legos, Keith T. Flaherty, Caroline Robert
AimUnderstanding predictors of long-term benefit with currently available melanoma therapies is the key for optimising individualised treatments. A prior pooled analysis of dabrafenib plus trametinib (D + T)–randomised trials (median follow-up, 20.0 months) identified baseline lactate dehydrogenase (LDH) and number of organ sites with metastasis as predictive factors for progression-free (PFS) and overall (OS) survival. However, longer-term follow-up analyses are needed to confirm which patients treated with D + T can achieve maximum benefit.MethodsThree-year landmark data were retrospectively pooled for D + T patients in phase 3 trials (COMBI-d [NCT01584648]; COMBI-v [NCT01597908]). Univariate and multivariate analyses assessed prognostic values of predefined baseline factors; regression tree analysis determined hierarchy and interactions between variables.ResultsLong-term pooled outcomes were consistent with individual trial results (N = 563; 3-year PFS, 23%; 3-year OS, 44%). Baseline LDH level and number of organ sites remained strongly associated with and/or predictive of PFS and OS. In addition, baseline sum of lesion diameters (SLD) was identified as a predictor for progression. In the most favourable prognostic group (normal LDH, SLD <66 mm, <3 organ sites; n = 183/563 [33%]), 3-year PFS was 42%. Baseline number of organ sites was also predictive of outcomes in patients with PFS ≥ 6 months.ConclusionUsing the largest phase 3 data set available for BRAF/MEK inhibitor combination therapy in melanoma, these results demonstrate that durable responses lasting ≥3 years are possible in subsets of patients with BRAF-mutant melanoma receiving D + T. Although the best predictive model evolved with longer follow-up, factors predicting clinical outcomes with the combination remained consistent with previous analyses.
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Prognostic factors and outcomes in metastatic uveal melanoma treated with programmed cell death-1 or combined PD-1/cytotoxic T-lymphocyte antigen-4 inhibition
Source:European Journal of Cancer, Volume 82
Author(s): Markus V. Heppt, Lucie Heinzerling, Katharina C. Kähler, Andrea Forschner, Michael C. Kirchberger, Carmen Loquai, Markus Meissner, Friedegund Meier, Patrick Terheyden, Beatrice Schell, Rudolf Herbst, Daniela Göppner, Felix Kiecker, David Rafei-Shamsabadi, Sebastian Haferkamp, Margit A. Huber, Jochen Utikal, Mirjana Ziemer, Irmgard Bumeder, Christiane Pfeiffer, Susanne G. Schäd, Christoph Schmid-Tannwald, Julia K. Tietze, Thomas K. Eigentler, Carola Berking
BackgroundUveal melanoma (UM) is an ocular malignancy with high potential for metastatic spread. In contrast to cutaneous melanoma, immunotherapy has not yet shown convincing efficacy in patients with UM. Combined immune checkpoint blockade with checkpoint programmed cell death-1 (PD-1) and checkpoint cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibition has not been systematically assessed for UM to date.Patients and methodsPatients with metastatic UM treated with either PD-1 inhibitor monotherapy or combined PD-1 inhibitor and ipilimumab (an anti-CTLA-4 monoclonal antibody) were included from 20 German skin cancer centres. Records from 96 cases were analysed for treatment outcomes. Clinical and blood parameters associated with overall survival (OS) or treatment response were identified with multivariate Cox regression and binary logistic regression.ResultsEighty-six patients were treated with PD-1 inhibitors only (n = 54 for pembrolizumab, n = 32 for nivolumab) with a centrally confirmed response rate of 4.7%. Median OS was 14 months for pembrolizumab-treated and 10 months for nivolumab-treated patients (p = 0.765). Fifteen patients were treated with combined immune checkpoint blockade with partial response observed in two cases. Median OS was not reached in this group. Multivariate Cox regression identified Eastern Cooperative Oncology Group (ECOG) performance status (p = 0.002), elevated serum levels of lactate dehydrogenase (LDH) (p = 0.002) and C-reactive protein (CRP) (p = 0.001), and a relative eosinophil count (REC) <1.5% (p = 0.002) as independent risk factors for poor survival. Patients with elevated CRP and LDH and a REC <1.5% were at highest risk for disease progression and death (p = 0.001).ConclusionsBlood markers predict survival in metastatic UM treated with immune checkpoint blockade. Normal serum levels of LDH and CRP and a high REC may help identify patients with better prognosis.
http://ift.tt/2t0t5lx
A European randomised controlled trial of the addition of etoposide to standard vincristine and carboplatin induction as part of an 18-month treatment programme for childhood (≤16 years) low grade glioma – A final report
Source:European Journal of Cancer, Volume 81
Author(s): Astrid K. Gnekow, David A. Walker, Daniela Kandels, Susan Picton, Giorgio Perilongo, Jacques Grill, Tore Stokland, Per Eric Sandstrom, Monika Warmuth-Metz, Torsten Pietsch, Felice Giangaspero, René Schmidt, Andreas Faldum, Denise Kilmartin, Angela De Paoli, Gian Luca De Salvo
BackgroundThe use of chemotherapy to manage newly diagnosed low grade glioma (LGG) was first introduced in the 1980s. One randomised trial has studied two- versus four-drug regimens with a duration of 12 months of treatment after resection.MethodsWithin the European comprehensive treatment strategy for childhood LGG, the International Society of Paediatric Oncology–Low Grade Glioma (SIOP LGG) Committee launched a randomised trial involving 118 institutions and 11 countries to investigate the addition of etoposide (100 mg/m2, days 1, 2 & 3) to a four-course induction of vincristine (1.5 mg/m2 × 10 wkly) and carboplatin (550 mg/m2 q 3 weekly) as part of 18-month continuing treatment programme. Patients were recruited after imaging diagnosis, resection or biopsy with progressive disease/symptoms. Some 497 newly diagnosed patients (M/F 231/266; median age 4.26 years (interquartile range (IQR) 2.02–7.06)) were randomised to receive vincristine carboplatin (VC) (n = 249) or VC plus etoposide (VCE) during induction (n = 248), stratified by age and tumour site.FindingsNo differences between the two arms were found in term of survival and radiological response. Response and non-progression rates at 24 weeks for VC and VCE, were 46% versus 41%, and 93% versus 91% respectively; 5-year Progression-Free Survival (PFS) and Overall Survival (OS) were 46% (StDev 3.5) versus 45% (StDev 3.5) and 89% (StDev 2.1) versus 89% (StDev 2.1) respectively. Age and diencephalic syndrome are adverse clinical risk factors for PFS and OS. 5-year OS for patients in early progression at week 24 were 46% (StDev 13.8) and 49% (StDev 16.5) in the two arms, respectively.InterpretationThe addition of etoposide to VC did not improve PFS or OS. High non-progression rates at 24 weeks justify retaining VC as standard first-line therapy. Infants with diencephalic syndrome and early progression need new treatments to be tested. Future trials should use neurological/visual and toxicity outcomes and be designed to discriminate between the impact on disease outcomes of 'duration of therapy' and 'age at stopping therapy'.
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Scholar : These new articles for Acta Linguistica Hafniensia are available online
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Scholar : Annals of GIS, Volume 23, Issue 2, June 2017 is now available online on Taylor & Francis Online
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Scholar : These new articles for Critical Discourse Studies are available online
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Scholar : These new articles for Aphasiology are available online
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Scholar : These new articles for CoDesign are available online
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Obstructive Sleep Apnoea and Polycystic Ovary Syndrome; a comprehensive review of clinical interactions and underlying pathophysiology
Abstract
Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder in women of reproductive age. PCOS is associated with multiple co-morbidities including, obesity, insulin resistance and type 2 diabetes, as well as mood disorders and impaired quality of life (QoL). Obstructive sleep apnoea (OSA) is also a common medical condition that is often undiagnosed, particularly in women. OSA is associated with a similar spectrum of comorbidities to that observed in PCOS, including manifestations of the metabolic syndrome and impaired QoL, whilst obesity frequently constitutes a common denominator in the pathophysiology of both OSA and PCOS. Hence, it is not surprising that OSA and PCOS may co-exist in women of reproductive age, and the current clinical guidelines on the management of PCOS recommend screening for OSA symptoms in overweight/obese women with PCOS. In this review, we examine the relationship between OSA and PCOS and explore the potential underlying mechanisms that link these two conditions.
This article is protected by copyright. All rights reserved.
http://ift.tt/2sv1Iz7
Editorial Board
Source:Microbiological Research, Volume 202
http://ift.tt/2sVnYTb
Energy and exergy optimization of food waste pretreatment and incineration
Abstract
With the aim of upgrading current food waste (FW) management strategy, a novel FW hydrothermal pretreatment and air-drying incineration system is proposed and optimized from an energy and exergy perspective. Parameters considered include the extracted steam quality, the final moisture content of dehydrated FW, and the reactor thermal efficiency. Results show that optimal working condition can be obtained when the temperature and pressure of extracted steam are 159 °C and 0.17 MPa, the final moisture content of dehydrated FW is 10%, and the reactor thermal efficiency is 90%. Under such circumstance, the optimal steam energy and exergy increments reach 194.92 and 324.50 kJ/kg-FW, respectively. The novel system is then applied under the local conditions of Hangzhou, China. Results show that approximately 2.7 or 11.6% (from energy or exergy analysis perspective) of electricity can be additionally generated from 1 ton of MSW if the proposed novel FW system is implemented. Besides, comparisons between energy and exergy analysis are also discussed.
http://ift.tt/2rH6Kp4
Prognostic impact of vascular invasion in differentiated thyroid carcinoma: a systematic review and meta-analysis
Background
The role of vascular invasion (VI) as a prognostic marker in thyroid cancer is continuously debated among investigators. In this systematic review and meta-analysis, we aimed to investigate the association of VI with tumor recurrence and patient mortality in differentiated thyroid cancers (DTCs).
MethodsWe searched five electronic databases for cases of DTC matching our criteria. Data of tumor persistence, locoregional recurrence (LRR), distant recurrence (DR) and overall recurrence/persistence (RP) were extracted and pooled into odds ratios (OR) and corresponding 95% confidence intervals (CIs) using random effect model. Pooled hazard ratio (HR) for disease-specific survival (DSS) was calculated using random effect model weighted by inverse variance method. Publication bias was examined by using Egger's test and funnel plot.
ResultsFrom 1650 studies, we included 26 studies comprising 11 961 DTCs for meta-analyses. In DTC patients, we found significant associations of VI with tumor persistence (OR = 2.75; 95% CI = 1.46–5.18), LRR (OR = 4.44; 95% CI = 2.94–6.71), DR (OR = 5.08; 95% CI = 2.95–8.75), overall RP (OR = 3.53; 95% CI = 2.09–5.96) and worse DSS (HR = 2.47; 95% CI = 1.45–4.21). Our results also demonstrated that the presence of extensive VI is associated with a significantly higher risk for DR in follicular thyroid carcinomas as compared with focal VI.
ConclusionOur study demonstrated a significant impact of VI on tumor recurrence and patient survival in DTC patients. The presence and extent of VI should be considered an adverse prognostic factor in DTCs.
http://ift.tt/2rZw6Op
Cortisol-related metabolic alterations assessed by mass spectrometry assay in patients with Cushing's syndrome
Objective
Endogenous hypercortisolism is a chronic condition associated with severe metabolic disturbances and cardiovascular sequela. The aim of this study was to characterize metabolic alterations in patients with different degrees of hypercortisolism by mass-spectrometry-based targeted plasma metabolomic profiling and correlate the metabolomic profile with clinical and hormonal data.
DesignCross-sectional study.
MethodsSubjects (n = 149) were classified according to clinical and hormonal characteristics: Cushing's syndrome (n = 46), adrenocortical adenomas with autonomous cortisol secretion (n = 31) or without hypercortisolism (n = 27). Subjects with suspicion of hypercortisolism, but normal hormonal/imaging testing, served as controls (n = 42). Clinical and hormonal data were retrieved for all patients and targeted metabolomic profiling was performed.
ResultsPatients with hypercortisolism showed lower levels of short-/medium-chain acylcarnitines and branched-chain and aromatic amino acids, but higher polyamines levels, in comparison to controls. These alterations were confirmed after excluding diabetic patients. Regression models showed significant correlation between cortisol after dexamethasone suppression test (DST) and 31 metabolites, independently of confounding/contributing factors. Among those, histidine and spermidine were also significantly associated with catabolic signs and symptoms of hypercortisolism. According to an discriminant analysis, the panel of metabolites was able to correctly classify subjects into the main diagnostic categories and to distinguish between subjects with/without altered post-DST cortisol and with/without diabetes in >80% of the cases.
ConclusionsMetabolomic profiling revealed alterations of intermediate metabolism independently associated with the severity of hypercortisolism, consistent with disturbed protein synthesis/catabolism and incomplete β-oxidation, providing evidence for the occurrence of metabolic inflexibility in hypercortisolism.
http://ift.tt/2sFSP3O
Genetic defects in pediatric-onset adrenal insufficiency in Japan
Context
Most patients with pediatric-onset primary adrenal insufficiency (PAI), such as 21-hydroxylase deficiency, can be diagnosed by measuring the urine or serum levels of steroid metabolites. However, the etiology is often difficult to determine in a subset of patients lacking characteristic biochemical findings.
ObjectiveTo assess the frequency of genetic defects in Japanese children with biochemically uncharacterized PAI and characterize the phenotypes of mutation-carrying patients.
MethodsWe enrolled 63 Japanese children (59 families) with biochemically uncharacterized PAI, and sequenced 12 PAI-associated genes. The pathogenicities of rare variants were assessed based on in silico analyses and structural modeling. We calculated the proportion of mutation-carrying patients according to demographic characteristics.
ResultsWe identified genetic defects in 50 (85%) families: STAR in 19, NR0B1 in 18, SAMD9 in seven, AAAS in two, NNT in two, MC2R in one and CDKN1C in one. NR0B1 defects were identified in 78% of the male patients that received both glucocorticoid and mineralocorticoid replacement therapy and had normal male external genitalia. STAR defects were identified in 67% of female and 9% of male patients. Seven of the 19 patients with STAR defects developed PAI at age two or older, out of whom, five did not have mineralocorticoid deficiency.
ConclusionsMolecular testing elucidated the etiologies of most biochemically uncharacterized PAI patients. Genetic defects such as NR0B1 defects are presumed based on phenotypes, while others with broad phenotypic variability, such as STAR defects, are difficult to diagnose. Molecular testing is a rational approach to diagnosis in biochemically uncharacterized PAI patients.
http://ift.tt/2rW47Uz
Muscle strength in patients with acromegaly at diagnosis and during long-term follow-up
Objective
Patients with acromegaly have decreased body fat (BF) and increased extracellular water (ECW) and muscle mass. Although there is a lack of systematic studies on muscle function, it is believed that patients with acromegaly may suffer from proximal muscle weakness despite their increased muscle mass. We studied body composition and muscle function in untreated acromegaly and after biochemical remission.
DesignProspective observational study.
MethodsPatients with acromegaly underwent measurements of muscle strength (dynamometers) and body composition (four-compartment model) at diagnosis (n = 48), 1 year after surgery (n = 29) and after long-term follow-up (median 11 years) (n = 24). Results were compared to healthy subjects.
ResultsUntreated patients had increased body cell mass (113 ± 9% of predicted) and ECW (110 ± 20%) and decreased BF (67 ± 7.6%). At one-year follow-up, serum concentration of IGF-I was reduced and body composition had normalized. At baseline, isometric muscle strength in knee flexors and extensors was normal and concentric strength was modestly increased whereas grip strength and endurance was reduced. After one year, muscle strength was normal in both patients with still active disease and patients in remission. At long-term follow-up, all patients were in remission. Most muscle function tests remained normal, but isometric flexion and the fatigue index were increased to 153 ± 42% and 139 ± 28% of predicted values, respectively.
ConclusionsPatients with untreated acromegaly had increased body cell mass and normal or modestly increased proximal muscle strength, whereas their grip strength was reduced. After biochemical improvement and remission, body composition was normalized, hand grip strength was increased, whereas proximal muscle fatigue increased.
http://ift.tt/2sFTpP9
Improving risk estimates for metabolically healthy obesity and mortality using a refined healthy reference group
Objective
We aimed to re-examine mortality risk estimates for metabolically healthy obesity by using a 'stable' healthy non-obese referent group.
DesignProspective cohort study.
MethodsParticipants were 5427 men and women (aged 65.9 ± 9.4 years, 45.9% men) from the English Longitudinal Study of Ageing. Obesity was defined as body mass index ≥30 kg/m2 (vs non-obese as below this threshold). Based on blood pressure, HDL cholesterol, triglycerides, glycated hemoglobin and C-reactive protein, participants were classified as 'healthy' (0 or 1 metabolic abnormality) or 'unhealthy' (≥2 metabolic abnormalities).
ResultsTotally, 671 deaths were observed over an average follow-up of 8 years. When defining the referent group based on 1 clinical assessment, the unhealthy non-obese (hazard ratio (HR) = 1.22; 95% CI: 1.01, 1.45) and unhealthy obese (HR = 1.29; CI: 1.05, 1.60) were at greater risk of all-cause mortality compared to the healthy non-obese, yet no excess risk was seen in the healthy obese (HR = 1.14; CI: 0.83, 1.52). When we re-defined the referent group based on 2 clinical assessments, effect estimates were accentuated and healthy obesity was at increased risk of mortality (HR = 2.67; CI: 1.64, 4.34).
ConclusionAn unstable healthy referent group may make 'healthy obesity' appear less harmful by obscuring the benefits of remaining never obese without metabolic dysfunction.
http://ift.tt/2rVHY8U
Long-acting PEGylated recombinant human growth hormone (Jintrolong) for children with growth hormone deficiency: phase II and phase III multicenter, randomized studies
Objective
We assessed the efficacy and safety of a weekly pegylated human growth hormone (PEG-rhGH) (Jintrolong) vs daily rhGH for children with growth hormone deficiency (GHD).
DesignPhase II and III, multicenter, open-label, randomized controlled trials.
Methods108 and 343 children with treatment-naive GHD from 6 hospitals in China were enrolled in the phase II and III studies respectively. Patients in the phase II study were randomized 1:1:1 to weekly Jintrolong (0.1 mg/kg/week PEG-rhGH complex), weekly Jintrolong (0.2 mg/kg/week PEG-rhGH complex) or daily rhGH (0.25 mg/kg/week) for 25 weeks. Patients in the phase III study were randomized in a 2:1 ratio to weekly Jintrolong (0.2 mg/kg/week) or daily rhGH (0.25 mg/kg/week) for 25 weeks. The primary endpoint for both studies was height velocity (HV) increase at the end of treatment. Other growth-related parameters, safety and compliance were also monitored.
ResultsThe phase II study established the preliminary efficacy, safety and recommended dose of Jintrolong PEG-rhGH. In the phase III study, we demonstrated significantly greater HV increases in patients receiving Jintrolong treatment (from 2.26 ± 0.87 cm/year to 13.41 ± 3.72 cm/year) vs daily rhGH (from 2.25 ± 0.82 cm/year to 12.55 ± 2.99 cm/year) at the end of treatment (P < 0.05). Additionally, significantly greater improvement in the height standard deviation scores was associated with Jintrolong throughout the treatment (P < 0.05). Adverse event rates and treatment compliance were comparable between the two groups.
ConclusionJintrolong PEG-rhGH at a dose of 0.2 mg/kg/week for 25 weeks is effective and safe for GHD treatment and is non-inferior to daily rhGH.
http://ift.tt/2sFug7u
Hypoinsulinaemic, hypoketotic hypoglycaemia due to mosaic genetic activation of PI3-kinase
Objective
Genetic activation of the insulin signal-transducing kinase AKT2 causes syndromic hypoketotic hypoglycaemia without elevated insulin. Mosaic activating mutations in class 1A phospatidylinositol-3-kinase (PI3K), upstream from AKT2 in insulin signalling, are known to cause segmental overgrowth, but the metabolic consequences have not been systematically reported. We assess the metabolic phenotype of 22 patients with mosaic activating mutations affecting PI3K, thereby providing new insight into the metabolic function of this complex node in insulin signal transduction.
MethodsThree patients with megalencephaly, diffuse asymmetric overgrowth, hypoketotic, hypoinsulinaemic hypoglycaemia and no AKT2 mutation underwent further genetic, clinical and metabolic investigation. Signalling in dermal fibroblasts from one patient and efficacy of the mTOR inhibitor Sirolimus on pathway activation were examined. Finally, the metabolic profile of a cohort of 19 further patients with mosaic activating mutations in PI3K was assessed.
ResultsIn the first three patients, mosaic mutations in PIK3CA (p.Gly118Asp or p.Glu726Lys) or PIK3R2 (p.Gly373Arg) were found. In different tissue samples available from one patient, the PIK3CA p.Glu726Lys mutation was present at burdens from 24% to 42%, with the highest level in the liver. Dermal fibroblasts showed increased basal AKT phosphorylation which was potently suppressed by Sirolimus. Nineteen further patients with mosaic mutations in PIK3CA had neither clinical nor biochemical evidence of hypoglycaemia.
ConclusionsMosaic mutations activating class 1A PI3K cause severe non-ketotic hypoglycaemia in a subset of patients, with the metabolic phenotype presumably related to the extent of mosaicism within the liver. mTOR or PI3K inhibitors offer the prospect for future therapy.
http://ift.tt/2rW1su1
Study of PET Imaging With 18F-TFB in Patients With Thyroid Cancer
Interventions: Procedure: PET Imaging; Other: 18F-tetrafluoroborate (18F-TFB)
Sponsor: Memorial Sloan Kettering Cancer Center
Recruiting - verified June 2017
http://ift.tt/2sYnvjY
Epacadostat and Pembrolizumab in Treating Patients With Metastatic or Unresectable Gastroesophageal Junction or Gastric Cancer
Interventions: Drug: Epacadostat; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab
Sponsor: Pamela L. Kunz
Not yet recruiting - verified June 2017
http://ift.tt/2tyhDLd
Phase I Study of Oral STAT3 Inhibitor, C188-9, in Patients With Advanced Cancers
Intervention: Drug: C188-9
Sponsors: StemMed, Ltd., USA; M.D. Anderson Cancer Center
Not yet recruiting - verified June 2017
http://ift.tt/2sYSIn0
Removal of the emerging contaminant bisphenol A by an ureasil–PEO hybrid membrane: experimental study and molecular dynamic simulation
Abstract
This work reports the use of a cross-linked ureasil–PEO hybrid matrix (designated PEO800) as an efficient adsorbent to retain the emerging contaminant bisphenol A (BPA) from an aqueous medium. The in-deep experimental and theoretical results provide information about the interactions between PEO800 and BPA. The in situ UV-vis spectroscopy data and the pseudo-first order, pseudo-second order, Elovich, and Morris–Webber intraparticle diffusion models allowed us to propose a three-step mechanism for the adsorption of BPA onto PEO800. The results indicate that the pseudo-first-order kinetic model effectively describes the adsorption of BPA onto PEO800. Differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy confirmed the interaction of PEO800 with BPA, showing an alteration in the chemical environment of the polymer ether oxygen atoms present in the hybrid matrix. The molecular dynamic simulation provides further evidence that the BPA molecules interact preferentially with PEO. The amount of desorbed BPA depended on the pH and solvent used in the assays. This work provides new opportunities for using the hydrophilic ureasil–PEO matrix which has demonstrated its abilities in being a fast and easy alternative to successfully removing organic contaminants from aqueous mediums and therefore having potential applications in water remediation.
http://ift.tt/2rZwY5N
Primary Tumor Sidedness and Screening, Colonoscopy, and Surveillance
http://ift.tt/2rGOuwb
HPV Testing for Women With Atypical Cytology
http://ift.tt/2sZixDc
End-of-Life Care and Costs for Older Patients With Malignant Brain Tumors
http://ift.tt/2rGTdxG
Primary Tumor Sidedness and Screening, Colonoscopy, and Surveillance—Reply
http://ift.tt/2sZrOLs
Breast Cancer Screening in Younger Women Undergoing Breast Conservation Therapy
http://ift.tt/2rGkSza
HPV Triage of Women With Atypical Squamous Cells of Uncertain Significance
http://ift.tt/2sZH8Ys
Crosstalk between M2 macrophages and glioma stem cells
Abstract
Purpose
Given its extremely poor prognosis, there is a pressing need for an improved understanding of the biology of glioblastoma multiforme (GBM), including the roles of tumor subpopulations that may contribute to their growth rate and therapy resistance. The most malignant phenotypes of GBM have been ascribed to the presence of subpopulations of cancer stem cells (CSCs), which are resistant to chemotherapeutic drugs and ionizing radiation and which promote invasiveness and metastasis. The mechanisms by which the CSC state is obtained and by which it promotes tumor maintenance are only beginning to emerge. We hypothesize that M2 polarized macrophages may affect CSC phenotypes via cell-cell communication.
Methods
We investigated the interplay between glioma CSCs and macrophages via co-culture. The invasiveness of CSCs in the absence and presence of macrophages was assessed using collagen degradation and Transwell migration assays. The role of STAT3 as a CSC phenotypic mediator was assessed using siRNA-mediated gene silencing.
Results
We found that the levels of a M2 macrophage-specific secreted cytokine, TGF-β1, were elevated in the presence of CSCs, regardless of whether the cells were plated as contacting or non-contacting co-cultures. In addition, we found that the co-culture resulted in enhanced expression of M2 markers in macrophages that were previously polarized to the M1 phenotype. siRNA-mediated STAT3 silencing was found to reduce the chemo-responsiveness and migratory abilities of the CSCs. Combination treatment of STAT3 siRNA and DNA alkylating agents was found to further abrogate CSC functions.
Conclusions
Our data indicate that the co-culture of CSCs and macrophages results in bi-directional signaling that alters the phenotypes of both cell types. These results provide an explanation for recently observed effects of macrophages on GBM tumor cell growth, motility and therapeutic resistance, and suggest potential therapeutic strategies to disrupt the CSC phenotype by impairing its communication with macrophages.
http://ift.tt/2txIqav
Effect of oxidative stress from nanoscale TiO 2 particles on a Physarum polycephalum macroplasmodium under dark conditions
Abstract
Information regarding the effect of nanoscale titanium dioxide particles (nTiO2) on the environment under dark conditions is scarce, and the effect of nTiO2 on fungi is largely unknown. Due to its huge size and high sensitivity to external stimuli, the slime mold fungi cell, Physarum polycephalum macroplasmodium, was utilized as a novel subject for the toxicity investigations in the present study, and oxidative stress from nTiO2 on the macroplasmodium was assessed under dark conditions. Short exposure (2–3 h) caused an intracellular reactive oxygen species (ROS) imbalance, and an anti-oxidative mechanism was activated from intermediate doses of nTiO2 (5–18 mg/mL). At long exposure times (~3 days), relatively low doses of nTiO2 (≤9 mg/mL) stimulated the growth of macroplasmodium and oxidative stress without DNA damage, whereas higher doses of nTiO2 (≥15 mg/mL) led to growth inhibition, significant DNA oxidative damage, and activation of the DNA single-strand repairing system. Although DNA oxidative damage was decreased to the same level as the control group by the supplementation of the anti-oxidant vitamin C, growth of the macroplasmodium failed to be completely restored. We inferred that nTiO2 induced a complicated toxicity effect on P. polycephalum in addition to DNA oxidative damage. Taken as a whole, the present study implied the probability of using P. polycephalum macroplasmodium for toxicity studies at the single-cell level, indicating that nTiO2 could induce oxidative stress or damage in P. polycephalum even under dark conditions and suggesting that the release of nTiO2 could lead to a growth imbalance of slime molds in the environment.
http://ift.tt/2rZKdTI
A New Perspective on Isotretinoin Treatment of Hidradenitis Suppurativa: A Retrospective Chart Review of Patient Outcomes
Dermatology
http://ift.tt/2rGtsh2
Impact and prognostic value of 18F-fluorodeoxyglucose positron emission tomography-computed tomography scan in the evaluation of residual head and neck cancer: Single-center experience from Pakistan
South Asian Journal of Cancer 2017 6(2):81-83
Background: Overview of clinical impact of positron emission tomography-computed tomography (PET-CT) scans in patients with head and neck carcinomas at our center. Methods: Retrospective review of posttreatment 18F-fluorodeoxyglucose (18F-FDG) PET-CT scans in patients with head and neck carcinomas with risk of residual disease. Clinical outcome served as the reference standard. Results: This study included 93 patients (65.6% males, mean age: 48.8 years ± 17.2 standard deviation) with squamous cell carcinoma as most frequent histopathology (91.4%). PET-CT scans were performed on average 6 months posttreatment. Diagnostic accuracy, positive predictive value, and negative predictive value of PET-CT for disease were found to be 88%, 88%, and 92%, respectively. A median follow-up of 24 months was available for 91 patients. Kaplan–Meier curves showed significantly higher disease-free survival with negative PET-CT as compared to positive PET-CT (P = 0.01) and maximum standardized uptake values of <5.0 (P = 0.01). Conclusion: FDG PET-CT has diagnostic and prognostic implications in treated patient of head and neck cancers.
http://ift.tt/2tRZ44j
Outcome of HER2 Testing by FISH applying ASCO/CAP 2007 and 2013 guideline in IHC equivocal group of breast cancer: Experience at tertiary cancer care centre
South Asian Journal of Cancer 2017 6(2):45-46
Background and Objectives: HER2 testing guideline of ASCO/CAP for interpretation and reporting has recently been revised. The study is aimed to measure the impact of 2013 CAP guideline on equivocal HER2 test outcome (immunohistochemistry [IHC] 2+) when tested by fluorescent in situ hybridization (FISH). The study also aims at finding the frequency of polysomy and monosomy of chromosome 17. Materials and Methods: Specimens were collected in Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India. IHC was performed in every case, and FISH was performed in IHC2+ cases. Results: In final analysis includes 557 subjects on the basis of CAP guideline 2007 and CAP guideline 2013. One hundred ninety-two subjects (34.4%) were HER2 amplified according to CAP scoring 2007, and 246 subjects (44%) according to 2013 CAP scoring. Conclusions: FISH results were evaluated (IHC2 + interpreted according to CAP 2007 guideline) with both 2007 and 2013 ASCO/CAP scoring criteria, we identified significantly more HER2 positive cases as compared to cases evaluated using the 2007 criteria (P < 0.05). We also found that in breast carcinoma, HER2 status in the presence of polysomy 17 may vary with the scoring criteria used. Evaluation of FISH result using 2013 ASCO/CAP criteria means that more patients with breast cancer may be appropriate for targeted treatment with trastuzumab, potentially improving their outcome.
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In the era of next generation sequencing, is the cytogenetic analysis still important in polycythemia vera?
South Asian Journal of Cancer 2017 6(2):46-50
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Scoring criteria for the evaluation of micronuclei in oral exfoliated cells
South Asian Journal of Cancer 2017 6(2):89-89
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Efficacy and safety of short course adjuvant trastuzumab combination chemotherapy in breast cancer
South Asian Journal of Cancer 2017 6(2):47-50
Background: The adjuvant short course 9-week trastuzumab combination therapy for human epidermal receptor 2 positive breast cancer patients may often be considered as a cost-effective and safe option and has important implications for the Indian subcontinent as well as other developing countries. However, such regimens of shorter duration trastuzumab therapy like FinHer, offered in view of economic constraints, may not be able to achieve globally comparable cure rates in early breast cancer especially with high-risk women with more than 3 lymph node positive. Methods and Material: Outcome of 21 patients with HER2 positive breast cancer was treated with short course trastuzumab combination chemotherapy in the adjuvant setting was studied. Results: Out of 21 patients 15 are alive and disease free with a follow up of up to 73 months (median follow up 42 months).
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Presentation of mucinous adenocarcinoma of renal pelvis masquerading as gross hydronephrosis: A histopathological surprise
South Asian Journal of Cancer 2017 6(2):78-84
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Breast cancer in young women: A retrospective study from tertiary care center of north India
South Asian Journal of Cancer 2017 6(2):51-53
Aim: Breast cancer is the most common cause of cancer in women worldwide. They have more aggressive clinical behaviour with poor outcomes in younger patients. The aim of this study was to evaluate the impact of age on prognosis of breast cancer in women above and under 40 years of age. Material and Methods: Medical record of 415 patients with invasive breast cancer were analysed from January 2011 to December 2014 in our department.The last was done in December 2015.All cases diagnosed with breast cancer stages I to IV were evaluated, and grouped on the basis of age [less than 40 and above 40 years].Baseline categorical variables were analysed using the Chi-square test or Fisher's exact test. Non categorical variable were analysed using t-test. Result: A total of 372 patients were reviewed because 42 patients defaulted. The median age at the time of diagnosis was 44.6 years (range 23 to 90 years).Metastasis to distant organs were more in women with age <40. Tumour relapse occurred in 131 cases, among which 84 cases died, 35 patients (26.31%) in less than 40 group vs.49 patients (20.50%) in above 40 groups. The estimated median OS in the two groups are 32 and 41 months respectively. Conclusion: The biological behaviour of breast cancer in younger age group has been shown to be associated with aggressive nature and has a worse clinical outcome as compared to that in older group.
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Folfox encephalopathy: A rare case series
South Asian Journal of Cancer 2017 6(2):86-87
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The impact of irradiation dose on the computed tomography radiographic response of metastatic nodes and clinical outcomes in cervix cancer in a low-resource settingLetter to the Editor
South Asian Journal of Cancer 2017 6(2):54-58
Introduction: The aim of this study is to investigate the relationship between the radiation dose to pelvic and para-aortic lymph nodes, nodal response, and clinical outcomes in a resource-poor setting based on computed tomography (CT) nodal size alone. Materials and Methods: This retrospective study from 2009 to 2015 included 46 cervical cancer patients with 133 metastatic pelvic and para-aortic lymph nodes definitively treated with chemoradiation and brachytherapy in a public hospital with limited access to positron emission tomography (PET) scans. Hence, short axis of the lymph node on CT scan was used as a measure of metastatic nodal disease, before and following radiation therapy. Inclusion criteria required the pelvic and para-aortic nodes to have the shortest axis diameter on CT scan of ≥8 mm and ≥10 mm, respectively. Based on PET resolution, a node that decreased to half of its inclusion cutoff size was considered to have a complete response (CR). Relevant clinical outcomes were documented and correlated with nodal features, nodal radiation doses, and treatment characteristics. Results: After controlling for other predictive factors, increased nodal dose was associated with increased probability of CR per study definition (P = 0.005). However, there was no statistically significant association between dose and pelvic/para-aortic, distant and total recurrence (TR), and any recurrence at any location (P = 0.263, 0.785, 1.00, respectively). Patients who had no CR nodes had shorter pelvic/para-aortic recurrence-free survival (PPRFS) and TR-free survival (TRFS) than patients who had at least one CR node (P = 0.027 and 0.046, respectively). Patients with no CR nodes also had shorter PPRFS than patients who had all nodes completely respond (P < 0.05). Conclusions: Using CT-based measures, we found that increased nodal dose is associated with an increased probability of CR (as defined) and nodal CR is associated with increased PPRFS and TRFS. We were unable to determine the cutoff dose required for a CR.
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Estimation of cancer risk due to exposure to lead contamination in Joss paper
South Asian Journal of Cancer 2017 6(2):90-91
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Epithelioid angiosarcoma: 10 years postrenal transplant
South Asian Journal of Cancer 2017 6(2):58-63
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Megakaryocytic morphology in Janus kinase 2 V617F positive myeloproliferative neoplasm
South Asian Journal of Cancer 2017 6(2):75-78
Context: Alterations in megakaryocyte morphology are the hallmark of myeloproliferative neoplasms (MPNs). These neoplasm are also associated with Janus kinase 2 (JAK2) V617F mutation in nearly 95% patients with polycythemia vera (PV), 40% patients of essential thrombocythemia (ET) and 50% patients of myelofibrosis (MF). The utility of megakaryocyte morphology in these disorders in correlation with JAK2 V617F remains unresolved. Aims: The aim of the study was to assess the morphology of megakaryocytes in bone marrow aspirates (BMAs) and bone marrow biopsies of patients of BCR-ABL negative MPNs with JAK2 V617F mutation. Settings and Design: This study was a retrospective and prospective, hospital-based study undertaken for a period ranging from January 2011 to April 2015. Subjects and Methods: Assessment of morphological features of megakaryocytes in 15 BMAs and their respective biopsies which included seven cases of PV, three cases of ET, and five cases of MF with JAK2 V617F mutation. Statistical Analysis Used: Chi-square test and Fisher exact test were used to compare the different features of megakaryocytes. Software version SPSS 13.0 was used. Results: Megakaryocytes in ET were found to have characteristically large size with staghorn multinucleated nuclei and exhibiting large amount of cytoplasm. MF showed dense clustering of megakaryocytes with staghorn nucleus along with sinusoidal dilatation and intrasinusoidal hematopoiesis. PV showed loose and dense clustering of megakaryocytes with a predominance of cloud-like nuclei. Few of the megakaryocytic morphologic features showed overlap between MF and PV and between ET and early MF. Conclusions: Megakaryocytic morphology can aid in the accurate diagnosis of the different subcategories of MPNs. This would help in categorization of clinically suspicious patients of JAK2 V617F negative patients.
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18F-fluorodeoxyglucose positron emission tomography-computed tomography scan after gastric endoscopy in those who present with non-specific symptoms, is it necessary or not?
South Asian Journal of Cancer 2017 6(2):59-63
Background and Aims: Retrospectively analyze the sensitivity of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) in the diagnosis of gastric malignancy compared with gastric endoscopy in persons with nonspecific symptoms and evaluate the necessity of 18F-FDG PET-CT scan before surgery. Materials and Methods: A total of 53 patients with gastric malignancy proven by surgery and pathology were enrolled in the study. All the patients underwent gastric endoscopy and PET-CT scan before surgery. And the PET-CT images were interpreted by the observers who were blinded to the results of the gastric endoscopy. The sensitivity of gastric endoscopy, 18F-FDG PET-CT, and serum tumor markers in the diagnosis of gastric malignancy were calculated ultimately. Results: Of 53 gastric malignancy patients, five cases were proven to be false-negative detected by gastric endoscopy, and the sensitivity of which was 90.57%. The sensitivity of PET scan alone was 86.79%, which was observed no significant difference to that of gastric endoscopy diagnosis, P = 0.54. While all of the patients had been detected positive on PET-CT images, the sensitivity of which was significantly higher than that of the gastric endoscopy diagnosis or that of the serum tumor markers, P < 0.001. And the FDG uptake was positively correlated with the depth of the cancer invasion into the gastric wall (P < 0.0001) and the degree of lymph nodes infiltration (P = 0.02). It also various from different differentiation degree significantly, P = 0.04. Conclusions: 18F-fluorodeoxyglucose PET-CT could detect gastric carcinoma in persons with nonspecific symptoms which showed negative in gastric endoscopy. And it is necessary to be aware of the possibility of gastric malignancy when the result of PET-CT scan is positive.
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An observational study on safety and efficacy of povidone-iodine for pleurodesis in cancer patients
South Asian Journal of Cancer 2017 6(2):79-80
Introduction: Pleurodesis is a time-honored procedure for malignant effusion as one of the palliative procedures to treat recurrent effusions. Various agents have been used in the past such as tetracycline, talc, bleomycin, and povidone-iodine. This paper aims at evaluating safety and efficacy of povidone-iodine for the procedure. Materials and Methods: One hundred and four patients underwent of pleurodesis with povidone-iodine done at our center for malignant effusion between June 2008 and August 2015. The safety and efficacy of the procedure was analyzed. Results: One hundred and four patients of malignant effusion with mean age of 53 years and a mean follow-up of 7.8 months were evaluated. A total of 79% patients did not show any reaccumulation of fluid in their follow-up. There was no periprocedural mortality. Eight patients had severe pain; eleven patients had fever, while one patient had arrhythmia.Conclusion: Povidone-iodine is a simple, cheap, and effective method of pleurodesis with no major complication and a high success rate.
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Verrucous carcinoma of foot at an unusual site: Lessons to be learnt
South Asian Journal of Cancer 2017 6(2):63-78
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Carotid blowout syndrome: An oncological emergency less discussed
South Asian Journal of Cancer 2017 6(2):85-86
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Phase IIb trial comparing two concurrent cisplatin schedules in locally advanced head and neck cancer
South Asian Journal of Cancer 2017 6(2):64-68
Background: Concurrent chemoradiation with 3 weekly cisplatin (100 mg/m2) is the standard of care for locally advanced head and neck cancer. However, this regimen has been shown to be associated with lesser compliance and higher toxicities. Hence, there is a need to explore alternative concurrent cisplatin regimens. Objectives: The objective of this study was to compare the efficacy and toxicities of 3 weekly cisplatin (100 mg/m2) with weekly cisplatin (40 mg/m2) concurrently with radiation in patients with locally advanced head and neck cancer. Patients and Methods: This phase IIb trial randomized 56 patients with Stage III and IV squamous cell carcinoma of oropharynx, hypopharynx, and larynx to Arm A or Arm B. Arm A received cisplatin 100 mg/m2 3 weekly and Arm B received cisplatin 40 mg/m2 weekly concurrently with radiation. The primary end point was disease-free survival (DFS) and secondary end points were overall survival (OS) and acute toxicity. DFS and OS were estimated using Kaplan–Meier method, and log-rank test was used to assess the difference in these distributions with respect to treatment. Results: The 2-year DFS in Arm A and Arm B was 64.5% and 52.8%, respectively (P = 0.67). The OS at 2 years was 71% and 61.1% in Arm A and Arm B, respectively (P = 0.61). There were no significant differences in acute hematological, renal, or mucosal toxicities between the two arms. Conclusion: This study showed a nonsignificant improvement in DFS and OS in the 3 weekly cisplatin arm over the weekly arm with comparable toxicities. The trial is registered with Clinical Trial Registry of India (CTRI registration number: CTRI/2013/05/003703, URL-http://ctri.nic.in).
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Long-term survival following repeat liver resections in metastatic ovarian granulosa cell tumor: Case report with review of the literature
South Asian Journal of Cancer 2017 6(2):87-88
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Plasmablastic lymphoma in immunocompetent and in immunocompromised patients: Experience at a regional cancer centre in India
South Asian Journal of Cancer 2017 6(2):69-71
Introduction: Plasmablastic lymphoma (PBL) is a rare lymphoma associated with immunosuppression. It is strongly associated with immunosuppression (human immunodeficiency virus [HIV]) and often occurs within the oral cavity. PBL is also seen in patients receiving immunosuppressive therapy; however, despite its predisposition for the immunocompromised patients, PBL has been diagnosed in immunocompetent patients. Aim: This study aims to prognostic factors and outcome of PBL in immunocompromised and in immunocompetent patients. Materials and Methods: We conducted a retrospective study at our institute from the year 2008 to 2015. Results: A total of 13 patients (8 males and 5 females) with PBL were identified. Eight patients (61.5%) had extraoral PBL (median age 30.2 years) and 5 patients (38.5%) had oral PBL (median age 44 years). Most common extraoral site was gastrointestinal tract. Eight (61.5%) out of 13 patients were HIV positive. More than 50% of patients had Ann Arbor Stage III or IV. All the cases were CD20 negative and CD138 positive. Seven out of 13 patients had Ki-67 more than 80%. Nine patients received cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy. Three patients were on best supportive care due to poor performance status (PS). One patient received intensive chemotherapy with CODOX-M/IVAC. The median overall survival was 9 months in HIV-positive patients and 6 months in HIV-negative patients. The prognosis was worse in patients with Ki-67 of >80%. Statistical Analysis: Survival curves were generated using the Kaplan–Meier method and analyzed using log-rank test and Fisher's t-test. Conclusion: The present study confirms that PBL in both HIV-positive and in HIV-negative patients has an overall unfavorable outcome. The most important prognostic factors are stage, ki-67, and the Eastern Cooperative Oncology Group PS of the patient at the time of presentation.
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Complete response with crizotinib in two children with chemotherapy resistant neuroblastoma
South Asian Journal of Cancer 2017 6(2):89-90
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Evaluation of the in vivo cosmetic efficacy of the MFIII blue cell serum gel. One- and two-month test results
Summary
Introduction
Skin is changing over time showing signs of aging: dryness, increase in visual and tactile roughness, decrease in collagen content and stiffness, and eventually formation of deep and surface wrinkles, and fine lines.
Methods
Eight-week open experimental study was conducted to test efficacy of MFIII Blue Cell Serum Gel. Main criteria to determine product efficacy by following skin biophysical techniques were as follows: skin moisturization, firmness, epidermal and dermal density, skin surface properties and sebum level, reduction in fine lines and wrinkles. Secondary criteria were as follows: participant's opinion during study and product tolerance evaluation. Days 29 and 57 assessments included visual evaluation, skin biophysical techniques, and compliance check. The self-assessment questionnaires completed.
Results
After week 8, obtained results showed very good hydration effect of test product, despite the fact being serum gel. Moisturizing increased continuously during study period. Important increases on skin firmness were observed which are in line with typical anti-aging claims. Dermal density steady improvement noted especially after 4th week of study, and effect on deep skin layers was due to increase in collagen content and stiffness. Sebum regulation process was evidenced. Further significant roughness reduction in skin surface showed decrease or disappearance of fine lines and wrinkles. Products were well tolerated with no adverse events. Most of participants noticed visible improvement and increase in facial radiance, skin smoothness, and overall skin improvement.
Conclusion
Twice daily application of MFIII Blue Cell Serum Gel led to significant improvement in skin hydration, firmness, dermal density, sebum regulation, roughness reduction, decrease or disappearance of fine lines and wrinkles.
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Metastasis of breast cancer cells to the bone, lung, and lymph nodes promotes resistance to ionizing radiation
Abstract
Background
Metastasis represents the leading cause of breast cancer deaths, necessitating strategies for its treatment. Although radiotherapy is employed for both primary and metastatic breast cancers, the difference in their ionizing radiation response remains incompletely understood. This study is the first to compare the radioresponse of a breast cancer cell line with its metastatic variants and report that such metastatic variants are more radioresistant.
Materials and methods
A luciferase expressing cell line was established from human basal-like breast adenocarcinoma MDA-MB-231 and underwent in vivo selections, whereby a cycle of inoculations into the left cardiac ventricle or the mammary fat pad of athymic nude mice, isolation of metastases to the bone, lung and lymph nodes visualized with bioluminescence imaging, and expansion of obtained cells was repeated twice or three times. The established metastatic cell lines were assessed for cell proliferation, wound healing, invasion, clonogenic survival, and apoptosis.
Results
The established metastatic cell lines possessed an increased proliferative potential in vivo and were more chemotactic, invasive, and resistant to X‑ray-induced clonogenic inactivation and apoptosis in vitro.
Conclusion
Breast cancer metastasis to the bone, lung, and lymph nodes promotes radioresistance.
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The JAK/STAT3 axis: A comprehensive drug target for solid malignancies
Source:Seminars in Cancer Biology
Author(s): Jennifer Huynh, Nima Etemadi, Frédéric Hollande, Matthias Ernst, Michael Buchert
Intercellular communication between tumor cells, immune cells and the stroma characterises the tumor microenvironment, which is instrumental for establishing the ecological niche that fosters tumor growth and metastasis. While tumor cell intrinsic STAT3 signaling provides a crucial axis to support cell proliferation and survival, it also regulates many activities of the non-transformed cells that collectively make up the tumor microenvironment. Accordingly, excessive activation of STAT3 is a hallmark of many malignancies, and often occurs in response to cytokines of the IL-6 and IL-10 families. However, tumor extrinsic STAT3 signaling also regulates the effector function of tumor-associated immune and stromal cells, which support the growth of tumors by suppressing the host's anti-tumor immune response. Given that STAT3 mediates tumorigenic effects in many cell types, the molecular players of STAT3 signaling and its upstream JAK kinases provide viable therapeutic targets for the treatment of cancer. Here we provide an update on novel insights into the role of STAT3 in immune suppression and describe current therapeutic strategies that target the JAK/STAT3 signaling axis for the treatment of malignancies.
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Temperature that can promote Zika virus infection: A summary from Thai cases
Annals of Tropical Medicine and Public Health 2017 10(2):479-479
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Walking severe thrombocytopenia dengue patient: How about its rate?
Annals of Tropical Medicine and Public Health 2017 10(2):466-466
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Uniting the efforts of stakeholders to end tuberculosis globally by 2030
Annals of Tropical Medicine and Public Health 2017 10(2):297-298
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Zika virus infection: Factor contributing to emergence and pathogenesis
Annals of Tropical Medicine and Public Health 2017 10(2):458-459
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Accelerating progress to achieve the sustainable development goal target 3.3 worldwide
Annals of Tropical Medicine and Public Health 2017 10(2):299-300
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Lymphadenopathy is not common among Thai patients with Zika virus infection
Annals of Tropical Medicine and Public Health 2017 10(2):473-473
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Improving urban health standards: Promotion of equity and development of healthier cities for sustainable development
Annals of Tropical Medicine and Public Health 2017 10(2):301-302
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Is there any role of Porphyromonas endodontalis for dental implant failure or not?
Annals of Tropical Medicine and Public Health 2017 10(2):486-486
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Terminating the status of public health emergency of international concern for ebola outbreak in West Africa: What does it mean? What next?
Annals of Tropical Medicine and Public Health 2017 10(2):303-304
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“Have you ever seen mosquito in the airplane?”: Risk implication
Annals of Tropical Medicine and Public Health 2017 10(2):462-463
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Moving ahead from leprosy elimination to leprosy-free world by 2020
Annals of Tropical Medicine and Public Health 2017 10(2):305-306
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Health implications of some precepts from Buddhist eight precepts: A religious public health concept
Annals of Tropical Medicine and Public Health 2017 10(2):469-470
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The public health concern of mental illnesses: Strengthening of the mental health sector
Annals of Tropical Medicine and Public Health 2017 10(2):307-308
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World Health Organization advocates for a two-point strategy to achieve eradication of Yaws from the endemic nations
Annals of Tropical Medicine and Public Health 2017 10(2):475-476
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Addressing the public health concern of depression and anxiety disorders: Financial perspective
Annals of Tropical Medicine and Public Health 2017 10(2):309-310
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Hemorrhagic presentation and platelet count in dengue patients
Annals of Tropical Medicine and Public Health 2017 10(2):483-483
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Advocating for the implementation of the updated guidelines for the management of Hepatitis C infection universally
Annals of Tropical Medicine and Public Health 2017 10(2):311-312
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Advocating for the community empowerment and family support to improve the quality of care to schizophrenia patients
Annals of Tropical Medicine and Public Health 2017 10(2):490-491
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Radiation exposure in pediatric imaging: Justification, optimization, and risk communication
Annals of Tropical Medicine and Public Health 2017 10(2):313-314
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Committing suicide by physicians: A summary from Thai situation
Annals of Tropical Medicine and Public Health 2017 10(2):460-461
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Health risks of environmental exposure to metals and herbicides in the Pardo River, Brazil
Abstract
Mixture of metals and herbicides in rivers may pose relevant risks for the health of surrounding communities. Humans may be exposed to river pollution through intake of contaminated water and fish, as well as irrigated agricultural products. The aim of this study was to assess the human health risks of environmental exposure to metals and herbicides through water and fish intake in the Pardo River. Metals (Al, As, Be, Cd, Cr, Cu, Pb, Mn, Hg, Ni, Tl, Sn, V, and Zn) were analyzed in river water and in edible fish. Herbicides (ametryn, atrazine, diuron, hexazinone, simazine, and tebuthiuron) were analyzed in river water. Seasonal variances were also studied. Aluminum, Cd, Cu, Mn, Pb, and Zn levels in river water were higher than the USEPA benchmarks. Non-carcinogenic risks due to pollutants mixture exposure were above the limit, and carcinogenic risks of As exposure were >10−6 in the sampling points during the rainy season. Metal levels in fish were lower than the Brazilian legislation and do not pose a threat to public health. Herbicides were detected in four sampling points, with atrazine concentrations (range 0.16–0.32 μg/L) below the Brazilian standard (2.0 μg/L), but above the European Union standard (0.1 μg/L). Considering the water supply needs of cities located in the Pardo River Basin and the persistence of metals and herbicides, the present study indicated that there was a seasonal influence on non-carcinogenic and carcinogenic risks to human health, especially in the rainy season. Studies for water treatment plants implantation should consider the risks of exposure to persistent substances, in order to protect the population.
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Highly efficient biosorptive removal of lead from industrial effluent
Abstract
This study has been focused on the efficient removal of Pb (II) from contaminated waters by biosorption using plant derived material. Accordingly an indigenous shrub, Tinospora cordifolia has been identified as the most suitable biosorbent. The plant biomass was subjected to optimization of various parameters such as the pH, equilibrium time, dosage, concentration, temperature and the applicable adsorption models. The optimum pH identified was 4.0 with a contact time of 60 min at room temperature (27 ± 2 °C). The experimental data fitted well to adsorption isotherms and the uptake capacity of Pb (II) was found to be 20.83 and 63.77 mg/g in batch mode and column mode, respectively. The high correlation factors obtained for Langmuir and Freundlich models indicated that both models were obeyed by the system. Kinetic study for adsorption of Pb (II) follow only pseudo second order rate of reaction. The accumulation of lead in biomass was confirmed by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) analysis. The FTIR analysis indicated the involvement of hydroxyl (−OH), alkenes (=CH) and carbonyl group (C = O) chelates in metal binding. The SEM and EDX analysis showed the structural changes and the filling of voids in the biomass thus, it indicated the metal-binding mechanism. In elution studies, the 0.1 M Na2CO3 was found to be the best with about 71% elution of the adsorbed metal. The biomass was then used for the removal of Pb (II) in synthetic and real wastewater samples from a lead-acid battery industry. It is also noteworthy that even at a very high concentration of 450 mg/L, the biomass was showing about 92% removal. The result is to establish the efficacy of T. cordifolia as a very good bioadsorbent for the Pb (II) removal from contaminated water.
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The role of solubility on the rejection of trace organics by nanofiltration membrane: exemplified with disinfection by-products
Abstract
Interactions of trace organic compounds (TOrCs) with polymeric nanofiltration (NF) membrane can affect their rejection. It is desirable to investigate whether solubility which depends on the free energy of interaction between these solutes and water correlates with rejection/adsorption and the potential to be incorporated in the partitioning terms of current NF model. A total of ten neutral disinfection by-products (DBPs) were selected as the model compounds for TOrCs to comprehensively investigate the role of solubility on rejection and adsorption. Pearson correlation analysis indicated that the correlation between MW and rejection ratio was highly significant (r = 0.778, p = 0.008) and that between solubility and rejection ratio was moderately significant (r = −0.636, p = 0.48) in a cross-flow system. By fitting Freundlich equation from adsorption isotherm experiment, the adsorption affinity (K f) of DBPs was roughly correlated with their solubility with regard to the comparison of n value with 1. α was then introduced as a parameter of solute-membrane interaction from the perspective of partitioning term in the hydrodynamic model. Exponential relationship can be observed between the solubility and α, demonstrating the possibility of incorporating solubility into the partitioning terms in NF model to accurately predict the rejection of DBPs.
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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...
