Cancer-cell communication is an important and complex process, achieved through a diversity of mechanisms that allows tumor cells to mold and influence their environment. In recent years, evidence has accumulated indicating that cells communicate via the release and delivery of microRNAs (miRNAs) packed into tumor-released (TR) exosomes. Understanding the role and mode of action of miRNAs from TR exosomes is of paramount importance in the field of cancer biomarker discovery and for the development of new biomedical applications for cancer therapeutics. In this review, we focus on miRNAs secreted via TR exosomes, which by acting in a paracrine or endocrine manner, facilitate a diversity of signaling mechanisms between cancer cells. We address their contribution as signaling molecules, to the establishment, maintenance, and enhancement of the tumor microenvironment and the metastatic niche in cancer. Finally, we address the potential role of these molecules as biomarkers in cancer diagnosis and prognosis and their impact as a biomedical tool in cancer therapeutics.

/pdf/micrornas-transported-by-exosomes-in-body-fluids-as-3es4rl2q1y.pdf

MicroRNAs transported by exosomes in body fluids as mediators of intercellular communication in cancer

Polyphenol can improve osteoporosis and is closely associated with gut microbiota, while the mechanism and the relationship among polyphenol, osteoporosis, and gut microbiota colonization remain unclear. Here, an osteoporosis rat model established by ovariectomy was employed to investigate the improving mechanism of arecanut (Areca catechu L.) seed polyphenol (ACP) on osteoporosis by regulating gut microbiota. We analyzed the bone microstructure, Paneth cells, regulating microbial protein (lysozyme (LYZ)), proinflammatory cytokines, macrophage infiltration levels, and gut microbial communities in a rat. ACP improved the trabecular microstructure compared to OVX, including the increased trabecular number (Tb.N) (P < 0.01) and trabecular thickness (Tb.Th) (P < 0.001) and decreased trabecular separation (Tb.Sp) (P < 0.01). At the phylum level, Bacteroidetes was increased after ovariectomy (P < 0.001) and Firmicutes and Proteobacteria were increased in ACP (P < 0.001). Antiosteoporosis groups with lower LYZ and Paneth cells (P < 0.001) showed that the microbiota Alistipes, which have a negative effect on bone metabolism were decreased in ACP (P < 0.001). Altogether, these studies showed that the estrogen deficiency could induce the shedding of Paneth cells, which leads to the decrease of LYZ, while ACP could increase the LYZ expression by maintaining the population of Paneth cells in an estrogen-deficient host, which were implicated in gut microbiota regulation and improved osteoporosis by controlling the inflammatory reaction.

Arecanut (Areca catechu L.) Seed Polyphenol-Ameliorated Osteoporosis by Altering Gut Microbiome via LYZ and the Immune System in Estrogen-Deficient Rats.

One of the daunting challenges facing modern medicine lies in the understanding and treatment of tumor heterogeneity. Most tumors show intra-tumor heterogeneity at both genomic and proteomic levels, with marked impacts on the responses of therapeutic targets. Therapeutic target-related gene expression pathways are affected by hypoxia and cellular stress. However, the finding that targets such as eukaryotic initiation factor (eIF) 4E (and its phosphorylated form, p-eIF4E) are generally homogenously expressed throughout tumors, regardless of the presence of hypoxia or other cellular stress conditions, opens the exciting possibility that malignancies could be treated with therapies that combine targeting of eIF4E phosphorylation with immune checkpoint inhibitors or chemotherapy.

/pdf/beyond-molecular-tumor-heterogeneity-protein-synthesis-takes-4o7dyr56vr.pdf

Beyond molecular tumor heterogeneity: protein synthesis takes control

Cytochrome b5 reductase 2 (CYB5R2), a member of the flavoprotein pyridine nucleotide cytochrome reductase family, is associated with a number of physiological reactions. However, its role in cancer, especially nasopharyngeal carcinoma (NPC), has not been addressed. Here, we investigate the transcript levels and promoter methylation status of CYB5R2 in NPC derived cell lines and tumor biopsies and experimentally address its role as a tumor suppressor gene. We find that CYB5R2 transcript levels are decreased in NPC cell lines and tumor biopsies. Promoter hypermethylation of CYB5R2 was detected in all six tested NPC cell lines and in 84% of primary NPC tumor biopsies but not in normal nasopharyngeal epithelium. Clinically, CYB5R2 methylation was associated with lymph node metastasis in NPC patients (P < 0.05). The endogenous expression of CYB5R2 could be restored in vitro by the methyltransferase inhibitor 5-aza-2'-deoxycytidine in NPC cell lines. Ectopic expression of CYB5R2 had an inhibitory effect on proliferation, clonogenicity and migration of NPC cells. Moreover, in vivo tests in nude mice indicated that ectopic expression of CYB5R2 reduces the tumorigenicity of CYB5R2-negative NPC cells. Collectively, these findings suggest that CYB5R2 may be a functional tumor suppressor gene, frequently inactivated by hypermethylation of its promoter in NPC. We report here the first instance of epigenetic downregulation in NPC tumor biopsies of a key enzyme, CYB5R2, which is responsible for the detoxification of environmental carcinogens. We propose the possibility of utilizing CYB5R2 promoter methylation as a diagnostic biomarker of NPC in the future.

/pdf/cytochrome-b5-reductase-2-is-a-novel-candidate-tumor-56ol6wdi0x.pdf

Cytochrome b5 reductase 2 is a novel candidate tumor suppressor gene frequently inactivated by promoter hypermethylation in human nasopharyngeal carcinoma.

Background: Deletion types of genetic variants of glutathione S-transferase (GST) M1 and T1, the GSTM1 null and GSTT1 null which are risk factors for certain cancers, have been ubiquitously found in human populations but their worldwide distribution pattern is unclear. Materials and Methods: To perform a meta-analysis, a systematic search for the literature on GSTM1 and GSTT1 null genotypes was done to identify 63 reports for 81 human populations. Relationships between the GSTM1 and GSTT1 null genotype frequencies and the absolute latitude of 81 populations were tested by Spearman’s rank correlation coefficient. Results: A significant positive correlation was detected between the GSTM1 null genotype frequency and the absolute latitude (r=0.28, p-value <0.05), whereas the GSTT1 null genotype frequency and absolute latitude showed a significant negative correlation (r= -0.41 p-value <0.01). There was no correlation between the frequencies of GSTM1 and GSTT1 null genotype in each population (r= -0.029, p-value=0.80). Conclusions: Latitudinal clines of the distribution of the GSTM1 and GSTT1 null genotypes may be attributed to the result of gene-environmental adaptation. No functional compensation between GSTM1 and GSTT1 was suggested by the lack of correlation between the null frequencies for GSTM1 and GSTT1.

http://koreascience.or.kr:80/article/JAKO201507964683352.pdf

Distributions of the GSTM1 and GSTT1 null genotypes worldwide are characterized by latitudinal clines.

MicroRNA-345-5p acts as an anti-inflammatory regulator in experimental allergic rhinitis via the TLR4/NF-κB pathway.

ObjectivesTo investigate the expression of eukaryotic initiation factor 4 E (eIF4E) in hypopharyngeal carcinoma compared with benign lesions, and the relationships between eIF4E expression and various clinicopathological parameters.MethodsExpression of eIF4E was analysed retrospectively in specimens from hypopharyngeal carcinomas and benign hypopharyngeal lesions using immunohistochemical staining and Western blotting. Tumours were classified using the tumour–node–metastasis staging system and the degree of histological differentiation was assessed.ResultsA total of 55 hypopharyngeal carcinoma and 20 benign specimens were analysed. All the hypopharyngeal carcinoma samples were positive for eIF4E expression on immunohistochemistry, whereas the benign lesions were negative or weakly positive. Semi-quantitative assessment (eIF4E score) showed that eIF4E expression was significatly higher in hypopharyngeal carcinoma than in benign lesions. On Western blotting, eIF4E expression assessed using integrated optica...

https://journals.sagepub.com/doi/pdf/10.1177/0300060514527912

Expression of eukaryotic initiation factor 4 E in hypopharyngeal carcinoma

Objectives: To investigate the expression of eukaryotic initiation factor 4E (eIF4E) in hypopharyngeal carcinoma compared with benign lesions, and the relationships between eIF4E expression and various clinicopathological parameters. Methods: Expression of eIF4E was analysed retrospectively in specimens from hypopharyngeal carcinomas and benign hypopharyngeal lesions using immunohistochemical staining and Western blotting. Tumours wereclassified using the tumour–node–metastasis staging system and the degree of histological differentiation was assessed. Results: A total of 55 hypopharyngeal carcinoma and 20 benign specimens were analysed. All the hypopharyngeal carcinoma samples were positive for eIF4E expression on immunohistochemistry, whereas the benign lesions were negative or weakly positive. Semi-quantitative assessment (eIF4E score) showed that eIF4E expression was significatly higher in hypopharyngeal carcinoma than in benign lesions. On Western blotting, eIF4E expression assessed using integrated optical density (IOD) was significantly higher in hypopharyngeal carcinoma than in benign lesions. The eIF4E score and IOD value were significantly associated with tumour stage, lymphatic metastasis and degree of differentiation. The IOD value was significantly higher in recurrent compared with initial cases. Conclusions: eIF4E may play an important role in the development and metastasis of hypopharyngeal carcinoma;its expression may be helpful in establishing the diagnosis, stage and prognosis of this tumour type.

https://imr.sagepub.com/content/42/4/976.full.pdf

Expression of eukaryotic initiation factor 4E in hypopharyngeal carcinoma

Objective
To investigate the clinical features, diagnosis and surgical intervention for orbital complications of acute rhinosinusitis in adults. 


Methods
Four adults patients with orbital complications of acute rhinosinusitis were restrospectively reviewed. After conservative managements failed, these patients were treated by transnasal endoscopic sinus surgery or combined with eyebrow incision. 


Results
There were 2 cases with orbital abscess, 2 cases with subperiosteal abscess. Among them, 2 patients suffered from diabetes. After operation, constitutional symptoms and ocular symptoms disappeared in all 4 patients. CT was rechecked during the postoperative follow-up. The imaging showed that the orbital and nasal lesions were obviously relieved or disappeared. 


Conclusions
The orbital complications of acute rhinosinusitis in adults are clinically rare. The patients are usually with lowered immunity or with underlying conditions, such as diabetes. On the basis of controlling basic diseases, the treatment outcome of orbital complications of acute rhinosinusitis in adults is affirmative by surgery and conservative managements.


Key words: 
Sinusitis ;  Orbital diseases ;  Adult;  Acute disease

Clinical analysis of orbital complications of acute rhinosinusitis in adults

Aim: The study was performed to assess the potential role of GSTM1, GSTT1 and GSTP1 polymorphisms in the risk of nasopharyngeal cancer in Chinese population. Method: We collected 182 cases undergoing pathologic examination and 366 controls from the affiliated hospital of Medical College of Qingdao University from April 2006 to July 2010. Genotyping was based upon duplex polymerase-chain-reactions with the PCRCTPP method. Results: More smokers were found in NPC patients than controls, and a higher IgA/VCA+ . Individuals carrying null GSTM1 and GSTT1 had 1.76 and 2.01 fold risk of NPC when compared with non-null genotypes, respectively. A non-significant increase risk of NPC was found in individuals with 1b/1b genotype when compared with 1a/1a genotype (OR=1.32, 95%CI=0.60-2.94). When compared with non-null GSTM1 and GSTT1 genotypes, the combination of null/null GSTM1 and GSTT1 genotypes showed moderate increased risk of NPC (OR=3.03, 95% CI=1.74-5.08). Conclusion: Our study provides evidence that genetic deletion of GSTM1 and GSTT1 may contribute to increased susceptibility to NPC in Chinese population, while GSTP1 may not. Our findings provide information relevant to the prevention of NPC.

Polymorphisms in GSTM1, GSTTI and GSTP1 and nasopharyngeal cancer in the east of China: a case-control study.

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