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Although effective, immune checkpoint blockade induces response in only a subset of cancer patients. There is an urgent need to discover new immune checkpoint targets. Recently, it was found that a class of sialic acid–binding immunoglobulin‐like lectins (Siglecs) expressed on the surface of T cells in cancer patients inhibit T cell activation through their intracellular immunosuppressive motifs by recognizing sialic acid–carrying glycans, sialoglycans. However, ligands of Siglecs remain elusive. Here, we report sialylated IgG (SIA‐IgG), a ligand to Siglec‐7, that is highly expressed in epithelial cancer cells. SIA‐IgG binds Siglec‐7 directly and inhibits TCR signals. Blocking of either SIA‐IgG or Siglec‐7 elicited potent antitumor immunity in T cells. Our study suggests that blocking of Siglec‐7/SIA‐IgG offers an opportunity to enhance immune function while simultaneously sensitizing cancer cells to immune attack. [ABSTRACT FROM AUTHOR]

Background and Purpose: Cancer cachexia is a common cause of death among cancer patients with no currently effective treatment available. In animal models, aberrant activation of STAT3 in skeletal muscle contributes to muscle wasting. However, clinically the factors regulating STAT3 activation and the molecular mechanisms involved remain incompletely understood.Experimental Approach: The expression of HSP90 and the activation of STAT3 were detected in muscle from the patients with cancer cachexia or the tumour-bearing cachectic mice. HSP90 inhibitors, including 17DMAG (alvespimycin) and PU-H71, were administered to cachexic mice and cachexia parameters, weight loss, food intake, survival rate, body composition, serum metabolites, muscle wasting pathology and catabolic activation were analysed. The co-culture of C2C12 myotube cells with C26 conditioned media was performed to investigate the pathological mechanism involved in catabolic muscle wasting. The roles of HSP90, STAT3 and FOXO1 in myotube atrophy were explored via overexpression or knockdown.Results: An enhanced interaction between activated STAT3 and HSP90 in the skeletal muscle of cancer cachexia patients, is a crucial for the development of cachectic muscle wasting. HSP90 inhibitors 17DMAG and PU-H71 alleviated the muscle wasting in C26 and models or the myotube atrophy of C2C12 cells induced by C26 conditional medium. Prolonged STAT3 activation transactivated FOXO1 by binding directly to its promoter and triggered the muscle wasting in a FOXO1-dependent manner in muscle cells.Conclusion and Implications: The HSP90/STAT3/FOXO1 axis plays a critical role in cachectic muscle wasting, which might be a potential therapeutic target for the treatment of cancer cachexia. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) remains a worldwide healthcare concern, and the exploration of the host‐pathogen interaction is essential to develop therapeutic modalities and strategies to control Mycobacterium tuberculosis (M.tb). In this study, RNA sequencing (transcriptome sequencing) was employed to investigate the global transcriptome changes in the macrophages during the different strains of M.tb infection. THP‐1 cells derived from macrophages were exposed to the virulent M.tb strain H37Rv (Rv) or the avirulent M.tb strain H37Ra (Ra), and the M.tb BCG vaccine strain was used as a control. The cDNA libraries were prepared from M.tb‐infected macrophages and then sequenced. To assess the transcriptional differences between the expressed genes, the bioinformatics analysis was performed using a standard pipeline of quality control, reference mapping, differential expression analysis, protein‐protein interaction (PPI) networks, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Q‐PCR and Western blot assays were also performed to validate the data. Our findings indicated that, when compared to BCG or M.tb H37Ra infection, the transcriptome analysis identified 66 differentially expressed genes in the M.tb H37Rv‐infected macrophages, out of which 36 genes were up‐regulated, and 30 genes were down‐regulated. The up‐regulated genes were associated with immune response regulation, chemokine secretion, and leucocyte chemotaxis. In contrast, the down‐regulated genes were associated with amino acid biosynthetic and energy metabolism, connective tissue development and extracellular matrix organization. The Q‐PCR and Western blot assays confirmed increased expression of pro‐inflammatory factors, altered energy metabolic processes, enhanced activation of pro‐inflammatory signalling pathways and increased pyroptosis in H37Rv‐infected macrophage. Overall, our RNA sequencing‐based transcriptome study successfully identified a comprehensive, in‐depth gene expression/regulation profile in M.tb‐infected macrophages. The results demonstrated that virulent M.tb strain H37Rv infection triggers a more severe inflammatory immune response associated with increased tissue damage, which helps in understanding the host‐pathogen interaction dynamics and pathogenesis features in different strains of M.tb infection. [ABSTRACT FROM AUTHOR]

With a great interest, we read the recent paper by Freire and colleagues, entitled 'The expression landscape of cachexia-inducing factors in human cancers'.1 The authors concluded that a panel of cachexia induced secreted factors (CIFs) initially used for screening of pancreatic cachectic patients2 was correlated with the cachexia prevalence and predicted patient survival in multiple types of cancers. The number of CIFs in the DEGs of each cancer was counted and used to index the weight loss and prevalence of cachexia in that cancer. The number of CIFs, range from 9 to 14 ( I Table i 1), reorganized the order of cancer landscape, which showed no correlation of the CIFs with average weight loss or prevalence of cachexia in these cancers ( I Figure i 1). [Extracted from the article]

Background: Radiation to the head and neck is a well‐established risk factor for the development of carotid artery stenosis. Our objective was to identify the prevalence, incidence, and degree of carotid stenosis in patients with a history of head and neck irradiation. Methods: This study was performed according to the PRISMA guidelines. A random effects model meta‐analysis was conducted. Results: Nineteen studies comprising 1479 patients were included. The prevalence of carotid stenosis >50%, >70%, and carotid occlusion was 25% (95% CI: 19%‐32%), 12% (95% CI: 7%‐17%), and 4% (95% CI: 2%‐8%), respectively. The cumulative 12‐month incidence of carotid stenosis >50% was 4% (95% CI: 2%‐5%), the 24‐month was 12% (95% CI: 9%‐15%), and the 36‐month was 21% (95% CI: 9%‐36%). Conclusions: The yearly incidence of carotid stenosis >50% increased every year during the first 3 years following radiotherapy. We propose routine yearly Doppler ultrasound screening beginning 1 year after head and neck radiotherapy. [ABSTRACT FROM AUTHOR]

This study presents a pricing model for power exchange options, in which the possibility of default by the risky counterparty as well as the arrival of important business information are taken into consideration. The idiosyncratic and common jump components induced by the arrival of business information are subsumed into all asset price processes whose dynamics are correlated with each other. Employing the measure-change technique, we obtain a pricing formula for the values of power exchange options with counterparty risk. At last, based on the derived formula, we numerically analyze the impacts of counterparty risk and jump risk on option prices. © 2016 Wiley Periodicals, Inc. Jrl Fut Mark 37:499-521, 2017 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis Delayed lower cranial neuropathy is a rare complication following primary radiotherapy for head and neck cancer, and has been most associated with nasopharyngeal carcinoma with minimal data regarding this outcome in the treatment of the oropharynx. No reports, to the authors' knowledge, have described this complication following intensity modulated radiation therapy (IMRT) for oropharyngeal primaries. Once encountered, this adverse outcome can have serious impacts on speech and swallowing. We present here our institution's experience with delayed cranial neuropathies following primary radiation therapy for oropharyngeal squamous cell carcinoma, as well as document the only reported case following IMRT. [ABSTRACT FROM AUTHOR]