Heme oxygenase-1 directly binds STAT3 to control the generation of pathogenic Th17 cells during neutrophilic airway inflammation

Abstract

Background

Specific JAK/STAT pathways play a critical role in the functional differentiation of distinct Th subsets. Previously, we showed that HO-1, a stress-inducible protein, inhibits Th17 cell differentiation and alleviates neutrophilic airway inflammation, but the responsible molecular basis remains unclear.

Methods

We employed Th17-skewing differentiation and NEA mouse models to study the role of HO-1 regulating IL-6-STAT3-RORγt/SOCS3 signaling pathway to control Th17 cell-mediated neutrophilic airway inflammation. The levels of cytokines and expressions of relative signaling molecular were measured by ELISA, western blot and qPCR, respectively. Frequency of CD4⁺IL-17A⁺, CD4⁺IL-6R⁺ and CD4⁺IL-23R⁺ cells was analyzed by FCM. The interaction between HO-1 and signaling pathway-related proteins was determined by Co-Immunoprecipitation and western blot.

Results

Here, we show that hemin-induced HO-1 over-expression is required to mediate this process. Specifically, HO-1 decreased STAT3 phosphorylation but not IL-6R/IL-23R expression or JAK1/JAK2 activation in CD4⁺ T cells. The effect was accompanied by co-inhibition of SOCS3, a negative feedback factor of STAT3 activation. HO-1 bound to three domains on STAT3, (DNA-binding, linker and transactivation domains) to directly regulate STAT3 activation. Conversely, either forced expression of a constitutively active STAT3 mutant or application of small interfering RNA (siRNA) for HO-1 reversed these effects.

Conclusions

Our data suggest that HO-1 exerts its inhibitory effect on Th17 cell differentiation by directly associating and blocking STAT3 phosphorylation. We speculate that hemin may be a potential therapeutic candidate for the treatment of other types of immune and pulmonary inflammatory-related diseases.

This article is protected by copyright. All rights reserved.

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Atypical presentation of sigmoid carcinoma

Abstract

Colorectal carcinoma is common worldwide and its metastasis represents the main cause of mortality related to the disease. Inguinal metastization of this tumor has been considered almost impossible, owing to colon anatomy and its cranial lymphatic drainage. We report the case of a 63-year-old man submitted to laparoscopical sigmoid colectomy, due a sigmoid adenocarcinoma. During follow-up, a right inguinal lymphadenopathy with 25 mm was detected. Fine needle aspiration biopsy revealed that it was a colon adenocarcinoma metastasis, and thus the patient underwent an inguinal lymphadenectomy. The histological study confirmed metastatic adenocarcinoma of the colon and the patient was submitted to 5-fluouracil and oxaliplatin chemotherapy. This case coursed with metastasis to the right inguinal region; although, the pathophysiological mechanism involved is difficult to understand. There are no solid data for the management of these patients. Inguinal lymphadenectomy and chemotherapy, proved to be effective.

http://ift.tt/2suOZKL

Ethmoid malformation associated with pediatric nasal polyposis and allergic fungal sinusitis

Abstract

A 17-year-old female with allergic fungal sinusitis and nasal polyposis presented with epistaxis in the emergency room. On examination, right-sided proptosis and irregular nasal obstruction were observed in the right nasal cavity. CT imaging revealed massive right-sided polyposis and significant ipsilateral malformation with boney architecture preservation of the ethmoidal labyrinth and lamina papyracea. The patient was treated surgically with symptomatic improvement. These findings indicate a unique malformation of the ethmoid while the patient was in development. To the authors' knowledge, this anatomical malformation has not been previously described in the literature. Physicians should implement diagnostic procedures early if nasal polyposis and allergic fungal sinusitis is suspected in pediatric patients, especially with periocular involvement, to mitigate the risk of boney malformations of the sinuses.

http://ift.tt/2suDCCg

Primary extrahepatic bile duct neuroendocrine tumor with obstructive jaundice masquerading as a Klatskin tumor

Abstract

Neuroendocrine tumors (NETs) of the extrahepatic bile duct are extremely rare and reported infrequently in the literature. These tumors are difficult to diagnose preoperatively, and the prognosis is variable, often determined by extent of disease, tumor grade and resectability. This case report presents a 45-year-old male with history of biliary obstruction relieved by endobiliary stents with common hepatic duct stricture just above the cystic duct, thought to be a Klatskin's cholangiocarcinoma. Final pathological examination was consistent with primary extrahepatic NET.

http://ift.tt/2suDFhz

Laparoscopic harvest of the gastro-omental free flap for reconstruction after total pharyngolaryngectomy: Operative technique

Abstract

Circumferential defects following salvage pharyngolaryngectomy present significant challenges in reconstructive surgery. The gastro-omental free flap has been shown to reduce the incidence of major fistula and catastrophic complications. The current technique for harvest of the flap requires laparotomy, which is potentially associated with significant post-operative complications. Laparoscopic harvest of the gastro-omental free flap can negate some of the risks associated with open surgery. We describe here the operative technique for laparoscopic gastro-omental free flap harvest for use in reconstruction following total pharyngolaryngectomy. © 2017 Wiley Periodicals, Inc. Head Neck, 2017

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Prognostic value of lymphovascular invasion of the primary tumor in hypopharyngeal carcinoma after total laryngopharyngectomy

Abstract

Background

We aimed to determinate the prognostic value of lymphovascular invasion in the specimens resected during total laryngopharyngectomy for hypopharyngeal carcinoma.

Methods

Patients who underwent total laryngopharyngectomy at our institution between 2004 and 2014 were included in this study and retrospectively analyzed. We then discriminated for vascular invasion and lymphatic invasion of the primary tumor in all cases.

Results

We reviewed 135 records (120 men and 15 women; age range, 36–84 years). Tumors with lymphatic invasion tended to be associated with more metastatic lymph nodes and extracapsular spread (ECS) of metastatic lymph nodes. Tumors with vascular invasion tended to be associated with nonpyriform sinus locations. In a multivariate analysis, nonpyriform sinus locations, >3 metastatic lymph nodes, and vascular invasion remained significant prognostic factors for overall survival (OS); in recursive partitioning analysis, ECS and vascular invasion remained important categorical variables for OS.

Conclusion

Vascular invasion is a strong prognostic biomarker for advanced hypopharyngeal carcinoma. © 2017 Wiley Periodicals, Inc. Head Neck, 2017

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Multiple single nucleotide polymorphism analysis and association of specific genotypes in FHIT, SAMD4A, and ANKRD17 in Indian patients with oral cancer

Abstract

Background

Oral cancer has a high incidence primarily because of tobacco chewing habits. However, a small proportion of habitués develop oral cancer, implying a role for genomic variants in its susceptibility.

Methods

Thirteen single nucleotide polymorphisms (SNPs) in an Indian cohort comprising patients with oral cancer (n = 500) and healthy controls (n = 500) were genotyped using allelic discrimination real-time polymerase chain reaction (PCR).

Results

Prevalence of SNPs rs11130760, rs1957358, rs2306058, rs4883543, rs12637722, rs1457115, rs2353292, rs709821, rs2194861, rs4789378, rs3827538, rs2667552, and rs2886093 was determined in the Indian cohort. A significant association of rs11130760 GG (odds ratio [OR] 1.41; 95% confidence interval [CI] 1.08-1.84) and rs1957358 TT (OR 1.44; 95% CI 1.10-1.90) indicated increased risk; whereas rs1957358 TC (OR 0.67; 95% CI 0.53-0.87) and rs2306058 CT (OR 0.72; 95% CI 0.56-0.93) reflected decreased risk. The SNP rs11130760 wild-type (WT) allele G indicated an increased risk for oral cancer (OR 1.38; 95% CI 1.09-1.73), whereas SNP allele T indicated a decreased risk (OR 0.73; 95% CI 0.58-0.92) for oral cancer.

Conclusion

Our study identified SNPs with susceptibility to oral cancer in high-risk populations.

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Functional outcomes of fasciocutaneous free flap and pectoralis major flap for salvage total laryngectomy

Abstract

Background

Pectoralis major muscle flaps (PMMFs) and fasciocutaneous free flaps (FFFs) are commonly used for reconstruction of the surgical defect after salvage total laryngectomy. This study compared swallowing function in patients who underwent reconstruction with either PMMF or FFF.

Methods

This study was based on a retrospective cohort of patients treated at the CHU de Québec between January 2000 and March 2015. Demographics, chemoradiation data, surgical protocol, pathologic results, complications, evolution, esophageal dilation, diet intake, and feeding tube dependence were documented.

Results

A total of 126 patients were analyzed (93 PMMFs and 33 FFFs). Of the patients who received PMMFs, 38.7% had a limited oral intake compared to 15.2% of patients who received FFFs (odds ratio [OR] 3.54; 95% confidence interval [CI] 1.25-9.99; P = .02). The need for esophageal dilation tended to be greater for PMMF patients (25% vs 9%; OR 3.38; 95% CI 0.94-12.13; P = .06). Complication rates were similar.

Conclusion

The FFF reconstruction led to better results in terms of swallowing function than PMMF reconstruction.

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AHNS Series – Do you know your guidelines? Lip cancer

Abstract

Background

Lip cancer is one of the most curable primary head and neck malignancies, as the prominent location typically lends to an early diagnosis. The incidence of lip cancer varies by sex, ethnicity, and region, but is estimated to be up to 2.5/100 000 in the United States (squamous cell carcinoma [SCC]).

Methods

This article will review the current literature and National Comprehensive Cancer Network practice guidelines in the treatment of lip cancer.

Results

Resection of lip cancer with negative margins remains the mainstay of therapy. Positive nodal disease should be treated with neck dissection and adjuvant radiotherapy.

Conclusion

Lip cancer remains highly curable when diagnosed at an early stage. A multidisciplinary approach is crucial to treating patients with advanced-stage lip cancer.

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Morphologic and topographic radiologic features of human papillomavirus–related and unrelated oropharyngeal carcinoma

Abstract

Background

The purpose of this study was to compare the clinicoradiologic characteristics of human papillomavirus (HPV)-related (HPV-positive) and HPV-unrelated (HPV-negative) oropharyngeal carcinoma (OPC).

Methods

Primary tumor and lymph node features of HPV-positive and HPV-negative OPCs from 2008 to 2013 were compared on pretreatment CT/MRI. Intrarater/interrater concordance was assessed. Multivariable analyses identified factors associated with HPV-positivity to be used in nomogram construction.

Results

Compared to HPV-negative (n = 194), HPV-positive (n = 488) tumors were more exophytic (73% vs 63%; p = .02) with well-defined border (58% vs 47%; p = .033) and smaller axial dimensions; lymph node involvement predominated (89% vs 69%; p < .001) with cystic appearance (45% vs 32%; p = .009) but similar topography. Intrarater/interrater concordance varied (fair to excellent). Nomograms combining clinical (age, sex, smoking pack-years, subsite, T/N classification) and/or radiologic (nonnecrotic tumor and cystic lymph node) features were used to weigh the likelihood of HPV-driven tumors (area under the curve [AUC] = 0.84).

Conclusion

HPV-positive OPC has different radiologic tumor (exophytic/well-defined border/smaller axial dimension) and lymph node (cystic) features but similar lymph node topography.

http://ift.tt/2qWpzn6

Issue Information

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Issue Information

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Long-term survival of a randomized phase III trial of head and neck cancer patients receiving concurrent chemoradiation therapy with or without low-level laser therapy (LLLT) to prevent oral mucositis

Publication date: August 2017
Source:Oral Oncology, Volume 71
Author(s): Héliton S. Antunes, Daniel Herchenhorn, Isabele A. Small, Carlos M.M. Araújo, Celia Maria Pais Viégas, Gabriela de Assis Ramos, Fernando L. Dias, Carlos G. Ferreira
BackgroundThe impact of low-level laser therapy (LLLT) to prevent oral mucositis in patients treated with exclusive chemoradiation therapy remains unknown. This study evaluated the overall, disease-free and progression-free survival of these patients. Methods: Overall, disease-free and progression-free survival of 94 patients diagnosed with oropharynx, nasopharynx, and hypopharynx cancer, who participated on a phase III study, was evaluated from 2007 to 2015. The patients were subjected to conventional radiotherapy plus cisplatin every 3weeks. LLLT was applied with an InGaAlP diode (660nm–100mW–1J–4J/cm²).ResultsWith a median follow-up of 41.3months (range 0.7–101.9), patients receiving LLLT had a statistically significant better complete response to treatment than those in the placebo group (LG=89.1%; PG=67.4%; p=0.013). Patients subjected to LLLT also displayed increase in progression-free survival than those in the placebo group (61.7% vs. 40.4%; p=0.030; HR:1:93; CI 95%: 1.07–3.5) and had a tendency for better overall survival (57.4% vs. 40.4%; p=0.90; HR:1.64; CI 95%: 0.92–2.91).ConclusionThis is the first study to suggest that LLLT may improve survival of head and neck cancer patients treated with chemoradiotherapy. Further studies, with a larger sample, are necessary to confirm our findings.



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Prognostic role of tumor infiltrating lymphocytes in EBV positive and EBV negative nasopharyngeal carcinoma

Publication date: August 2017
Source:Oral Oncology, Volume 71
Author(s): Marc L. Ooft, Jolique A. van Ipenburg, Weibel W. Braunius, Charlotte I. Zuur, Senada Koljenović, Stefan M. Willems
ObjectivesTumor infiltrating lymphocytes (TILs) correlate with both better and worse prognosis in solid tumors. As therapeutic modalities for nasopharyngeal carcinoma (NPC) are limited, immunotherapy could be a potential alternative. Up till now there is limited prognostic data on the role of TILs in NPC, so we assessed the prognostic role of TILs in Epstein-Barr-virus (EBV) positive and negative NPC.MethodsTissue of 92 NPCs was assessed for CD3, CD4, CD8, PD1 and PDL1 expression in the tumor's micro-environment. Correlations between clinicopathological characteristics was assessed using the Pearson X² test, Fisher's exact test and ANOVA. Survival was analyzed with the Kaplan-Meier method and Cox regression. Differences in CD3, CD4, CD8, PD1, PDL1 counts/(co)expression between EBV positive and negative NPCs were evaluated using the Mann-Whitney U test. Two-tailed P values below 0.05 were considered statistically significant.ResultsEBV positive NPC contains significantly more CD3, CD4 and CD8 TILs than EBV negative NPC. In the whole NPC group, increased CD8 count is associated with better overall survival (OS) (HR 0.219 (95%CI 0.075–0.640)), but also in cases with PDL1 co-expression (HR 0.073 (95%CI 0.010–0.556)). In EBV positive NPC co-expression of CD8 and PDL1 showed better disease free survival (HR 0.407 (95%CI 0.195–0.850)) and OS (HR 0.170 (95%CI 0.037–0.787)).ConclusionsAlthough TILs are significantly different between EBV positive and negative NPCs, it is especially composition of the infiltrate which determines prognosis. Effects of PD1 and CD8 need more study, because these findings show much potential in using immunotherapeutic modalities in NPC treatment.



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A network meta-analysis of the sequencing and types of systemic therapies with definitive radiotherapy in locally advanced squamous cell carcinoma of the head and neck (LASCCHN)☆

Publication date: August 2017
Source:Oral Oncology, Volume 71
Author(s): Katarzyna J. Jerzak, Keemo Delos Santos, Ronak Saluja, Kelly Lien, Justin Lee, Kelvin K.W. Chan
ObjectivesThe current standard therapy for locally advanced squamous cell carcinoma of the head and neck (LASCCHN) is platinum-based chemotherapy plus concurrent radiotherapy (CRT), but several systemic therapies have been evaluated. We performed a Bayesian network meta-analysis (NMA) with random effects to enable direct and indirect comparisons of all existing treatment modalities for LASCCHN simultaneously.Material and methodsA systematic review was conducted using MEDLINE, EMBASE, ASCO abstracts, ASTRO abstracts and the Cochrane Central of Registered Trials using Cochrane methodology to identify randomized controlled trials (RCTs) up to June 2016. Only abstracts that involved the same definitive radiotherapy in the arms for the RCT were included.ResultsSixty-five RCTs involving 13,574 patients and 16 different treatment strategies were identified. Chemotherapy plus concurrent radiation (CRT) was superior to RT with a HR of 0.74 (95%CR 0.69–0.79) for OS in the NMA. Only 3 trials compared RT alone to concurrent therapy with an EGFR antibody (ERT), demonstrating a superior OS (HR 0.75, 95% CR 0.60–0.94), but this difference was not statistically significant when interpreted in a NMA (HR 0.84, 95%CR 0.65–1.08). ERT was not superior to CRT (HR 1.19, 95%CR 0.93–1.54), and the addition of neo-adjuvant taxane-based chemotherapy to CRT was not beneficial (HR 0.86, 95% CR 0.70–1.07).ConclusionThe addition of either adjuvant or neoadjuvant chemotherapy to the CRT backbone does not confer an OS benefit in the treatment of LASCCHN. Similarly, ERT does not confer an OS benefit for patients who are eligible for CRT.



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Unusual presentation of right coronary artery fistula

Ahmed MSEK Abdelaty<br />May 12, 2017; 2017:bcr-2017-220424-bcr-2017-220424<br />other

http://ift.tt/2qUPzPE

Anisakiasis: a growing cause of abdominal pain!

Joana Carmo<br />May 11, 2017; 2017:bcr2016218857-bcr2016218857<br />case-report

http://ift.tt/2rq2UDj

Long-term stabilisation of myeloma with curcumin

Abbas Zaidi<br />Apr 16, 2017; 2017:bcr2016218148-bcr2016218148<br />case-report

http://ift.tt/2qUKQ0z

Kinesiology taping as an adjunct for pain management in cancer?

Gourav Banerjee<br />Jul 14, 2016; 2016:bcr2016216439-bcr2016216439<br />case-report

http://ift.tt/2rTkCAo

Locally advanced adenocarcinoma of the rectum presenting with necrotising fasciitis of the perineum: successful management with early aggressive surgery and multimodal therapy

Luís Ferreira
Dec 16, 2015; 2015:bcr2015213245-bcr2015213245
case-report

http://ift.tt/2st1hmS

Surviving stroke in an Ebola Treatment Centre

Paul Dhillon<br />Oct 29, 2015; 2015:bcr2015211062-bcr2015211062<br />case-report

http://ift.tt/2rTbImx

Open removal of a retained retrohepatic inferior vena cava filter with a residual primary neuroectodermal renal tumoral thrombus

Carlos A Hinojosa<br />Oct 29, 2015; 2015:bcr2015212190-bcr2015212190<br />case-report

http://ift.tt/2ssvWAF

Freeman-Sheldon syndrome in a 29-year-old woman presenting with rare and previously undescribed features

Robert L Chamberlain<br />Oct 22, 2015; 2015:bcr2015212607-bcr2015212607<br />case-report

http://ift.tt/2rTkAbK

Serotonin syndrome in a breast-fed neonate

Rachel Morris<br />May 6, 2015; 2015:bcr2015209418-bcr2015209418<br />case-report

http://ift.tt/2sspiKL

Takotsubo cardiomyopathy case series: typical, atypical and recurrence

Jakub Lagan<br />Mar 5, 2015; 2015:bcr2014208741-bcr2014208741<br />case-report

http://ift.tt/2rTx6Io

Three-dimensional spectral domain optical coherence tomography in vitreomacular traction

Sandeep Saxena<br />Jun 17, 2014; 2014:bcr2013202065-bcr2013202065<br />case-report

http://ift.tt/2ssv5zM

Primary gut aspergillosis in a patient with acute myeloid leukaemia: the importance of early suspicion and definitive treatment

Elizabeth Li<br />Mar 18, 2014; 2014:bcr2013202316-bcr2013202316<br />case-report

http://ift.tt/2rTdFze

Two rare manifestations of Q fever: splenic and hepatic abscesses and cerebral venous thrombosis, with literature review ma non troppo

Manuel Mendes Gomes<br />Feb 5, 2014; 2014:bcr2013202843-bcr2013202843<br />case-report

http://ift.tt/2ssHdRi

Lemierre syndrome: more than just a sore throat

Christine Azzopardi<br />Nov 28, 2013; 2013:bcr2013201868-bcr2013201868<br />case-report

http://ift.tt/2rTlaGl

Postcaesarean open-heart surgery for Streptococcus sanguinis infective endocarditis

Kiattisak Kongwattanakul<br />Nov 14, 2013; 2013:bcr2013010103-bcr2013010103<br />case-report

http://ift.tt/2sskepz

Partial priapism

Peter Hoyerup<br />Aug 9, 2013; 2013:bcr2013200031-bcr2013200031<br />case-report

http://ift.tt/2rTbf3U

Complication of etanercept treatment for rheumatoid arthritis - purulent pericarditis caused by a commensal organism

Gemma K Taylor<br />May 8, 2012; 2012:bcr0120125644-bcr0120125644<br />case-report

http://ift.tt/2ssGYWu

Pluripotent stem cell models of Blau syndrome reveal an IFN-γ–dependent inflammatory response in macrophages

Publication date: Available online 3 June 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Sanami Takada, Naotomo Kambe, Yuri Kawasaki, Akira Niwa, Fumiko Honda-Ozaki, Kazuki Kobayashi, Mitsujiro Osawa, Ayako Nagahashi, Katsunori Semi, Akitsu Hotta, Isao Asaka, Yasuhiro Yamada, Ryuta Nishikomori, Toshio Heike, Hiroyuki Matsue, Tatsutoshi Nakahata, Megumu K. Saito
BackgroundBlau syndrome, or early-onset sarcoidosis, is a juvenile-onset systemic granulomatosis associated with a mutation in nucleotide-binding oligomerization domain 2 (NOD2). The underlying mechanisms of Blau syndrome leading to autoinflammation are still unclear, and there is currently no effective specific treatment for Blau syndrome.ObjectivesTo elucidate the mechanisms of autoinflammation in patients with Blau syndrome, we sought to clarify the relation between disease-associated mutant NOD2 and the inflammatory response in human samples.MethodsBlau syndrome–specific induced pluripotent stem cell (iPSC) lines were established. The disease-associated NOD2 mutation of iPSCs was corrected by using a CRISPR-Cas9 system to precisely evaluate the in vitro phenotype of iPSC-derived cells. We also introduced the same NOD2 mutation into a control iPSC line. These isogenic iPSCs were then differentiated into monocytic cell lineages, and the statuses of nuclear factor κB pathway and proinflammatory cytokine secretion were investigated.ResultsIFN-γ acted as a priming signal through upregulation of NOD2. In iPSC-derived macrophages with mutant NOD2, IFN-γ treatment induced ligand-independent nuclear factor κB activation and proinflammatory cytokine production. RNA sequencing analysis revealed distinct transcriptional profiles of mutant macrophages both before and after IFN-γ treatment. Patient-derived macrophages demonstrated a similar IFN-γ–dependent inflammatory response.ConclusionsOur data support the significance of ligand-independent autoinflammation in the pathophysiology of Blau syndrome. Our comprehensive isogenic disease-specific iPSC panel provides a useful platform for probing therapeutic and diagnostic clues for the treatment of patients with Blau syndrome.

Graphical abstract

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