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Objective: Adenoid cystic carcinoma (AdCC) and mucoepidermoid carcinoma (MEC) are the most frequent malignancies in the salivary glands. The purpose of this study was to explore the roles of sine oculis homeobox homolog 1 (SIX1), malic enzyme 2 (ME2), and AP‐2 complex subunit mu (AP2M1) in AdCC and MEC, as well as the potential relationship between SIX1, ME2, AP2M1, and proliferation marker cyclin D1. Material and methods: Immunohistochemistry was performed on human salivary gland tissue microarrays that contained 76 normal salivary glands (NSGs), 14 pleomorphic adenomas (PMAs), 81 AdCCs, and 52 MECs. Results: We observed that the expression levels of SIX1 and ME2 were significantly elevated in AdCC and MEC when compared with NSG and PMA. In addition, we detected that AP2M1 was overexpressed in AdCC and MEC when compared with NSG. We also found that SIX1 and AP2M1 were positively associated with cyclin D1. Conclusions: These results may prove that SIX1 and AP2M1 are involved in the proliferation of AdCC and MEC to cause tumor growth. [ABSTRACT FROM AUTHOR]

The current method for processing bud yellow tea usually results in astringent taste that is not sufficiently yellowing. Therefore, two factors in the production phase that affect tea quality were studied: number of times the tea leaves undergo the yellowing process and predrying of leaves to reduce their water content before a second yellowing process. We then evaluated the colour and nonvolatile compounds of the produced tea. Results revealed that gallated catechins and the polyphenol–amino acid ratio decreased significantly, and the colour of the tea changed from green to yellow after two yellowing processes. Predrying leaves to a lower water content resulted in the accumulation of free amino acids and soluble sugars, and an increase in the brightness and yellow colour of tea infusion. Bud yellow tea with the highest taste evaluation score and yellowness was obtained when the leave samples underwent two yellowing processes and the water content in the leaves was 40%. [ABSTRACT FROM AUTHOR]

BACKGROUND: Non‐volatile compounds play a key role in the quality and price of Keemun black tea (KBT). The non‐volatile compounds in KBT samples from different producing areas normally vary greatly. The development of rapid methods for tracing the geographical origin of KBT is useful. In this study, we develop models for the discrimination of KBT's geographical origin based on non‐volatile compounds. RESULTS: Seventy‐two KBT samples were collected from five towns in Anhui province to determine 13 KBT compounds by high‐performance liquid chromatography (HPLC). Analysis of variance showed that the content of 13 compounds in KBT indicated significant differences (P < 0.05) among five towns. Three multivariate statistical models including principal component analysis (PCA), soft independent modeling of class analogy (SIMCA), and linear discriminant analysis (LDA) were built to discriminate origin. Principal component analysis effectively extracted three principal components, namely theaflavins, galloylated catechins, and simple catechins. The high sensitivity (64.5%–99.2%) was achieved of SIMCA model. To establish the discriminant functions, six variables (gallic acid, (+)‐catechin, (−)‐epigallocatechin gallate, theaflavin‐3‐gallate, theaflavin‐3,3′‐di‐gallate, and total theaflavins) were chosen from 13 variables, and LDA was applied. This gave a satisfactory overall correct classification rate (94.4%) and cross‐validation rate (88.9%) for KBT samples. CONCLUSION: The results showed that HPLC analysis together with chemometrics is a reliable approach for tracing KBT and guaranteeing its authenticity. © 2019 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

BACKGROUND Keemun black tea (KBT) is one of the most popular tea beverages in China as a result of its unique flavor and potential health benefits. The geographical origin of KBT influences its quality and price. The present study aimed to apply a head‐space solid phase microextraction approach and gas chromatography–mass spectrometry combined with chemometric analysis to profile the volatile compounds of KBT collected from five production areas. RESULTS: Thirty‐one peaks were detected in 61 KBT samples. Hierarchical cluster analysis, principal component analysis (PCA), k‐nearest neighbor (k‐NN) and stepwise linear discriminant analysis (SLDA) were employed to visualize the volatile fractions. The results of unsupervised statistical tools were compared using a test for similarities and distinctions, which showed that different sources may be associated. A satisfying combination of average recognition (91.7%) and cross‐validation prediction abilities (84.6%) was obtained for the PCA–k‐NN. Among all of the statistical tools, SLDA provided promising results, with 100% recognition and 96.4% prediction ability. CONCLUSION: The results obtained in the present study indicate that the volatile compounds can be used as indicators to identify the geographical origin of KBT. © 2019 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Background: This study aims to investigate the characteristic role of inhibitory receptor leukocyte‐associated immunoglobulin‐like receptor 1 (LAIR‐1) in oral squamous cell carcinoma (OSCC). Methods: The expressions of LAIR‐1 and other immune‐related molecules were detected in a human OSCC tissue microarray. LAIR‐1 expression difference among different clinicopathological parameters was analyzed. The correlations of LAIR‐1 with several immune‐related markers were assessed. Results: Compared with dysplasia and oral mucosa, the expression of LAIR‐1 was significantly upregulated in the stroma of OSCC, and its overexpression was correlated with advanced pathological grade. Overexpression of LAIR‐1 was significantly associated with tumor‐associated macrophage and myeloid‐derived suppressor cell markers (CD68, CD163; CD33, CD11b), indoleamine 2,3‐dioxygenase (IDO) and two immune checkpoints (B7‐H3 and VISTA). Conclusions: Overexpression of LAIR‐1 was associated with advanced pathological grade and correlated with immune suppressive features in OSCC. Further studies are required to identify the specific immunological role of LAIR‐1. [ABSTRACT FROM AUTHOR]

The adenosine‐induced immunosuppression hampers the immune response toward tumor cells and facilitates the tumor cells to evade immunosurveillance. CD73, an ecto‐5‐nucleotidase, is the ectoenzyme dephosphorylating extracellular AMP to adenosine. Here, using immunocompetent transgenic head and neck squamous cell carcinoma (HNSCC) mouse model, immune profiling showed high expression of CD73 on CD4+ and CD8+ T cells was associated with an “exhausted” phenotype. Further, treatment with anti‐CD73 monoclonal antibody (mAb) significantly blunted the tumor growth in the mouse model, and the blockade of CD73 reversed the “exhausted” phenotype of CD4+ and CD8+ T cells through downregulation of total expression of PD‐1 and CTLA‐4 on T cells. Whereas the population of CD4+CD73hi/CD8+CD73hi T cells expressed higher CTLA‐4 and PD‐1 as compared to untreated controls. In addition, the human tissue microarrays showed the expression of CD73 is upregulated on tumor infiltrating immune cells in patients with primary HNSCC. Moreover, CD73 expression is an independent prognostic factor for poor outcome in our cohort of HNSCC patients. Altogether, these findings highlight the immunoregulatory role of CD73 in the development of HNSCC and we propose that CD73 may prove to be a promising immunotherapeutic target for the treatment of HNSCC. [ABSTRACT FROM AUTHOR]

Abstract: A major challenge for traditional cancer therapy, including surgical resection, chemoradiotherapy, and immunotherapy, is how to induce tumor cell death and leverage the host immune system at the same time. Here, a myeloid‐derived suppressor cell (MDSC) membrane‐coated iron oxide magnetic nanoparticle (MNP@MDSC) to overcome this conundrum for cancer therapy is developed. In this study, MNP@MDSC demonstrates its superior performance in immune evasion, active tumor‐targeting, magnetic resonance imaging, and photothermal therapy (PTT)‐induced tumor killing. Compared with red blood cell membrane‐coated nanoparticles (MNPs@RBC) or naked MNPs, MNP@MDSCs are much more effective in active tumor‐targeting, a beneficial property afforded by coating MNP with membranes from naturally occurring MDSC, thus converting the MNP into “smart” agents that like to accumulate in tumors as the source MDSCs. Once targeted to the tumor microenvironment, MNPs@MDSC can act as a PTT agents for enhanced antitumor response by inducing immunogenic cell death, reprogramming the tumor infiltrating macrophages, and reducing the tumor's metabolic activity. These benefits, in combination with the excellent biocompatibility and pharmacological kinetics characteristics, make MNP@MDSC a promising, multimodal agent for cancer theranostics. [ABSTRACT FROM AUTHOR]

Immune evasion is a hallmark feature of cancer, and it plays an important role in tumour initiation and progression. In addition, tumour immune evasion severely hampers the desired antitumour effect in multiple cancers. In this study, we aimed to investigate the role of the Notch pathway in immune evasion in the head and neck squamous cell carcinoma (HNSCC) microenvironment. We first demonstrated that Notch1 signaling was activated in a Tgfbr1/ Pten-knockout HNSCC mouse model. Notch signaling inhibition using a γ-secretase inhibitor (GSI-IX, DAPT) decreased tumour burden in the mouse model after prophylactic treatment. In addition, flow cytometry analysis indicated that Notch signaling inhibition reduced the sub-population of myeloid-derived suppressor cells (MDSCs), tumour-associated macrophages (TAMs) and regulatory T cells (Tregs), as well as immune checkpoint molecules (PD1, CTLA4, TIM3 and LAG3), in the circulation and in the tumour. Immunohistochemistry (IHC) of human HNSCC tissues demonstrated that elevation of the Notch1 downstream target HES1 was correlated with MDSC, TAM and Treg markers and with immune checkpoint molecules. These results suggest that modulating the Notch signaling pathway may decrease MDSCs, TAMs, Tregs and immune checkpoint molecules in HNSCC. [ABSTRACT FROM AUTHOR]

Immature myeloid cells including myeloid-derived suppressor cells (MDSCs) and tumour-associated macrophages (TAMs) promote tumour growth and metastasis by facilitating tumour transformation and angiogenesis, as well as by suppressing antitumour effector immune responses. Therefore, strategies designed to reduce MDSCs and TAMs accumulation and their activities are potentially valuable therapeutic goals. In this study, we show that negative immune checkpoint molecule B7-H3 is significantly overexpressed in human head and neck squamous cell carcinoma (HNSCC) specimen as compared with normal oral mucosa. Using immunocompetent transgenic HNSCC models, we observed that targeting inhibition of B7-H3 reduced tumour size. Flow cytometry analysis revealed that targeting inhibition of B7-H3 increases antitumour immune response by decreasing immunosuppressive cells and promoting cytotoxic T cell activation in both tumour microenvironment and macroenvironment. Our study provides direct in vivo evidence for a rationale for B7-H3 blockade as a future therapeutic strategy to treat patients with HNSCC. [ABSTRACT FROM AUTHOR]

Nanoparticles possess the potential to revolutionize cancer diagnosis and therapy. The ideal theranostic nanoplatform should own long system circulation and active cancer targeting. Additionally, it should be nontoxic and invisible to the immune system. Here, the authors fabricate an all-in-one nanoplatform possessed with these properties for personalized cancer theranostics. Platelet-derived vesicles (PLT-vesicles) along with their membrane proteins are collected from mice blood and then coated onto Fe3O4 magnetic nanoparticles (MNs). The resulting core-shell PLT-MNs, which inherit the long circulation and cancer targeting capabilities from the PLT membrane shell and the magnetic and optical absorption properties from the MN core, are finally injected back into the donor mice for enhanced tumor magnetic resonance imaging (MRI) and photothermal therapy (PTT). Meanwhile, it is found that the PTT treatment impels PLT-MNs targeting to the PTT sites (i.e., tumor sites), and exactly, in turn, the enhanced targeting of PLT-MNs to tumor sites can improve the PTT effects. In addition, since the PLT membrane coating is obtained from the mice and finally injected into the same mice, PLT-MNs exhibit stellar immune compatibility. The work presented here provides a new angle on the design of biomimetic nanoparticles for personalized diagnosis and therapy of various diseases. [ABSTRACT FROM AUTHOR]

SRC family kinases (SFKs), a group of nonreceptor tyrosine kinases, modulate multiple cellular functions, such as cell proliferation, differentiation and metabolism. SFKs display aberrant activity in progressive stages of human cancers. However, the precise role of SFKs in the head and neck squamous cell carcinoma (HNSCC) signaling network is far from clear. In this study, we found that the inhibition of SFKs activity by dasatinib effectively reduced the tumor size and population of MDSCs in the HNSCC mouse model. Molecular analysis indicates that phosphorylation of LYN, rather than SRC, was inhibited by dasatinib treatment. Next, we analyzed LYN expression by immunostaining and found that it was overexpressed in the human HNSCC specimens. Moreover, LYN expression in stromal cells positively correlated with myeloid-derived suppressor cells (MDSCs) makers CD11b and CD33 in human HNSCC. The dual positive expression of LYN in epithelial and stromal cells (EPI+ SRT+) was associated with unfavorable overall survival of HNSCC patients. These findings indicate that SFKs may be a potential target for an effective immunotherapy of HNSCC by decreasing MDSCs and moreover, LYN will have an impact on such therapeutic strategy. [ABSTRACT FROM AUTHOR]

T-cell immunoglobulin mucin 3 ( TIM3) contributes to immune suppression during progression of many cancers, but the precise role of TIM3 in head and neck squamous cell carcinoma ( HNSCC) is not clearly understood. In this study, we report that TIM3 expression was significantly up-regulated in patients with HNSCC and associated with lymph node metastasis. Additionally, TIM3 expression was increased in patients with recurrent HNSCC and patients with preradiotherapy or prechemotherapy. We also characterized CD8+ T cells and CD11b+ CD33+ myeloid-derived suppressor cells ( MDSCs) in human HNSCC, and found that their expression was positively correlated with TIM3 expression. To determine the underlying mechanism of TIM3 in immune response during HNSCC progression, we utilized the Tgfbr1/Pten 2c KO HNSCC mouse model with TIM3 overexpression. Treatment with anti- TIM3 monoclonal antibody effectively suppressed tumor growth through restoring effector T-cell function by targeting CD4+ TIM3+ cells and CD8+ TIM3+ cells and decreasing MDSCs. Our findings demonstrate TIM3 expression in patients with HNSCC and suggest anti- TIM3 immunotherapy as a novel therapeutic approach for effective treatment of HNSCC. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective The specific purposes of this study were (1) to undertake a thorough systematic review and meta-analysis based only on randomized clinical trials (RCTs) to compare the rates of survival and complications of short implants to those of long implants; (2) to compare the surgical time and cost of short implants to those of long implants. Methods RCTs were identified from the major electronic databases (MEDLINE, Embase and Cochrane Library) using the keywords 'dental implant,' 'short implant' and 'atrophic maxilla,' and a quantitative meta-analysis was conducted. The survival rate of implants and complications were the primary outcome measures, and other parameters assessed included costs and surgical time. Results Seven RCTs that met the inclusion criteria included 554 implants (265 implants in the short implant group). There was no significant difference in survival rate between two groups (RR: 1.00; 95% CI: [0.97, 1.03]; p = .96; seven trials, 554 participants). Compared with long implant group, the short implant group had a lower complications and the effect measure was significant (RR: 0.58; 95% CI: [0.37, 0.90]; p = .02; seven trials, 554 participants). Conclusion This systematic review showed that no difference between the survival rates of short implants (5-8 mm) and long implants (>8 mm); complications in short implants are lower than that in long implants. However, further studies are required to substantiate our findings. [ABSTRACT FROM AUTHOR]

Cell membrane–based nanosystems with desirable characteristics have been studied extensively for many therapeutic applications. However, current research has focused on single cell membrane, and multifunctional fused membrane materials from different membrane types are still rare. Herein, a platelet–cancer stem cell (CSC) hybrid membrane‐coated iron oxide magnetic nanoparticle (MN) {[CSC‐P]MN} is presented for the first time for the enhanced photothermal therapy of head and neck squamous cell carcinoma (HNSCC). Inherited from the original source cells, the platelet membrane shows immune evading ability due to the surface marker comprising a number of "don't eat me" signals, and the CSC membrane has homotypic targeting capabilities due to the specific surface adhesion molecules. The [CSC‐P]MNs possess superior characteristics for immune evasion, active cancer targeting, magnetic resonance imaging, and photothermal therapy. Compared with single cell membrane–coated MNs, [CSC‐P]MNs exhibit prolonged circulation times and enhanced targeting abilities. Moreover, the [CSC‐P]MNs exhibit a superior photothermal ability that provides excellent HNSCC tumor growth inhibition, particularly in an immunocompetent Tgfbr1/Pten conditional double knockout HNSCC mouse model that contains a more complex tumor microenvironment that is similar to the human HNSCC microenvironment. Collectively, this biomimetic multimembrane‐coated nanoplatform may provide enhanced antitumor efficacy in the complex tumor microenvironment. A natural cancer stem cell‐platelet hybrid mimic membrane is collected from tumor‐bearing mice and further used for magnetic nanoparticle coating. The obtained biomimetic nanoparticles are then injected into the same mice for magnetic resonance imaging and photothermal therapy. The work presents a novel design strategy for personalized cancer theranostics. [ABSTRACT FROM AUTHOR]

An all‐in‐one nanoplatform based on platelet membrane‐coated Fe3O4 magnetic nanoparticles (PLT‐MNs) for enhanced tumor magnetic resonance imaging (MRI) and photothermal therapy (PTT) is presented by Wei Liu, Zhi‐Jun Sun, and co‐workers in article number 1604774. The approach represents a new angle on the design of biomimetic nanoparticles for personalized diagnosis and therapy of various diseases. [ABSTRACT FROM AUTHOR]