While significant progress has been made in understanding the induction of tumor vasculature by secreted angiogenic factors, little is known regarding contact-dependent signals that promote tumor angiogenesis. Here, we report that the Notch ligand Jagged1 induced by growth factors via mitogen-activating protein kinase (MAPK) in head and neck squamous cell carcinoma (HNSCC) cells triggered Notch activation in neighboring endothelial cells (ECs) and promoted capillary-like sprout formation. Jagged1-expressing HNSCC cells significantly enhanced neovascularization and tumor growth in vivo. Moreover, the level of Jagged1 was significantly correlated with tumor blood vessel content and associated with HNSCC development. Our results elucidate a novel mechanism by which the direct interplay between tumor cells and ECs promotes angiogenesis through MAPK and Notch signaling pathways.

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Objectives To evaluate the effect of stem cells  from  exfoliated  deciduous  teeth on the hyposalivation caused by Sjögren syndrome (SS) and investigate the mechanism. Methods Stem cells were injected into the tail veins of non‐obese diabetic mice, the animal model of SS. The saliva flow was measured after pilocarpine intraperitoneal injection. Apoptosis and autophagy were evaluated by TUNEL and Western blot. Lymphocyte proportions were detected by flow cytometer. Results Fluid secretion was decreased in 21‐week‐old mice. Stem cell treatment increased fluid secretion, alleviated inflammation in the submandibular glands and reduced inflammatory cytokine levels in the serum, submandibular glands and saliva. Stem cells decreased the apoptotic cell number and the expressions of ATG5 and Beclin‐1 in the submandibular glands. Stem cells have no effect on other organs. Furthermore, the infused stem cells migrated to the spleen and liver, not the submandibular gland. Stem cells directed T cells towards Treg cells and suppressed Th1 and Tfh cells in spleen lymphocytes. Conclusion Stem cells  from  exfoliated  deciduous  teeth alleviate the hyposalivation caused by SS via decreasing the inflammatory cytokines, regulating the inflammatory microenvironment and decreasing the apoptosis and autophagy. The stem cells regulated in T‐cell differentiation are involved in the immunomodulatory effects.

Lung metastasis is a major factor affecting long-term survival in adenoid cystic carcinoma patients. Here, we showed that the long noncoding RNA (lncRNA) MRPL23 antisense RNA 1 (MRPL23-AS1) was highly expressed and correlated with lung metastasis and overall survival in salivary adenoid cystic carcinoma (SACC) patients. MRPL23-AS1 positively regulated epithelial-mesenchymal transition by forming a RNA-protein complex with enhancer of zeste homolog 2 (EZH2).MRPL23-AS1 increased the binding of EZH2 and H3K27me3 on the E-cadherin promoter region. Moreover, MRPL23-AS1 levels were higher in exosomes isolated from the blood plasma of SACC patients, and exosomal MRPL23-AS1 affected pulmonary microvascular endothelial cells in an 'exosomecrine' manner.MRPL23-AS1-enriched exosomes increased microvascular permeability and facilitated the metastasis of SACC in vivo. Collectively, these findings highlight a molecular mechanism of lung metastasis in SACC. MRPL23-AS1 may represent a biomarker and target for clinical intervention to control this intractable disease.

Oral squamous cell carcinoma (OSCC) is predominantly a disease of middle-aged men with long-term exposure to tobacco and alcohol. An increasing trend has been reported at a younger age worldwide. Clinical records of 100 patients under the age of 45 years treated specifically for oral cavity SCC in our hospital during a 10-year period were retrospectively analyzed to calculate the survival rates. An obvious male predominance coincided with smoking trend among Chinese young individuals and female patients were more likely to have no traditional risk factors such as smoking or drinking. The 5-year overall survival rate and disease-free survival rate were 61.0% and 75.5%, respectively, consistent with other published series over the decade showing a relatively better survival among the young. No significant differences clearly correlated with outcome when comparing non-smokers non-drinkers to ever-smokers and ever drinkers (P>0.05). Overall survival rate and disease free survival rate was found to be significantly higher in patients with early-stage disease than with advanced stage disease (P=0.001, P=0.009 respectively). The strong influence of clinical stage on prognosis emphasizes the importance of early diagnosis and treatment of oral malignancies for this unique clinical subgroup.