Case Report: A Rare Case of Nasal Forehead Mass in Kimura's Disease.

Background: Kimura's disease is a rheumatic immune disease and head and neck lymph nodes are often involved. A mass occurring in the nasal forehead is rare. Good prognosis after surgical resection by glucocorticoid therapy is more rare. Case Summary: We report the rare case of a nasal forehead mass in a 45-year-old male patient with Kimura's disease. The patient underwent resection of the mass in October 2018 in a local hospital and the postoperative pathology was unclear. He then underwent a second resection in our department in December 2019 mainly because growth of the mass was affecting his appearance. Postoperative pathology confirmed that the patient had Kimura's disease, and he accepted systemic treatment with prednisone. We followed the patient for 10 months after surgery. He is now recovering well and continues to be closely monitored during follow-up. Conclusion: It is rare that the painless mass in the nasal forehead is diagnosed as a Kimura's disease.After completely resection of the mass and systemic treatment with prednisone, the patient had a good outcome. We provide experience for the treatment of Kimura's disease in nasal forehead.

The environmental hormone nonylphenol interferes with the therapeutic effects of G protein-coupled estrogen receptor specific agonist G-1 on murine allergic rhinitis.

The G protein-coupled estrogen receptor (GPER) specific agonist G-1 has therapeutic effects in patients with allergic diseases, but any role for G-1 as a therapy for inflammation associated with allergic rhinitis (AR) remains unclear. The structure of the environmental hormone nonylphenol (NP) is very similar to that of estrogen; it binds to the estrogen receptor to produce estrogen-like effects and thus may also bind to the membrane GPER. We explored whether NP administration would reduce the effects of G-1 on AR, the interactions between the two materials, and their mechanisms of action using a murine model of AR. Mice were randomly assigned into control, AR, G-1, and G-1 + NP groups (n = 10/group). AR nasal symptoms were scored. Eosinophils in nasal mucosa were counted after staining with hematoxylin and eosin. Serum ovalbumin (OVA)-specific IgE was determined by ELISA. The proportions of splenic Th1, Th2, and Treg cells were determined by flow cytometry. The expression of transcription factors unique to Th1, Th2, Treg cells and cytokine levels in nasal mucosa were evaluated by real-time PCR and cytometric bead arrays. AR nasal symptoms, including sneezing, nasal scratching, eosinophil infiltration of nasal mucosa, and serum IgE, were reduced in G-1 group. After injection, Th2 cells proportions, Th2-immune response-related cytokines (IL-4, IL-5, and IL-13), and a Th2 cell-specific transcription factor (GATA-3) were significantly decreased in G-1 group. Treg immune response was enhanced (as reflected by Treg cell, IL-10, and Foxp3 levels). The levels of all of these were significantly increased after adding NP, and the Treg immune response was significantly decreased. These results indicate that G-1 attenuated the nasal symptoms, serum OVA-specific IgE, and Th2 cell immune response, whereas it enhanced Treg immune response, in mice with AR. Adding NP weakened these therapeutic effects.

Osthole induces cell cycle arrest and apoptosis in head and neck squamous cell carcinoma by suppressing the PI3K/AKT signaling pathway.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the most common lethal tumors with a high recurrence rate and low survival rate. Therefore, an urgent need exists for novel and effective treatment strategies for HNSCC patients. METHODS: Osthole, a natural ingredient extracted from Cnidium monnieri (L.) 'Cusson', has multiple pharmacological effects including antineoplastic activity. Regrettably, the antineoplastic effect of osthole in HNSCC cells remains undefined. We utilize in vitro assays to assess the anti-proliferative effects of osthole in HNSCC cells and tumorigenesis assays using FaDu cells in murine HNSCC models to assess in vivo function. Moreover, the possible molecular mechanisms of Osthole on HNSCC cells was also investigated. RESULTS: Our findings show that the anti-proliferation effect of osthole might function through induction of cell cycle arrest (G2/M phase) and apoptosis in HNSCC. Osthole could also down-regulating the protein level of cell cycle and apoptosis related proteins, such as Bcl-2, PARP1, Survivin, CyclinB1 and Cdc2, while up-regulating expression of Cleaved Caspase3/9, Cleaved PARP1 and Bax. Similarly, osthole suppressed the in vivo growth of FaDu cells in a subcutaneous tumor model. In terms of mechanism, our data show that osthole can suppress the PI3K/AKT pathway. CONCLUSIONS: In the current study, our in vitro and in vivo assay showed the suppressive effect of Osthole on HNSCC cells through induce cell cycle arrest (G2/M phase) and apoptosis. Moreover, the action mechanisms of Osthole on proliferation related signaling pathways was disclosed. Our present study suggests that osthole might be used as an effective therapeutic agent for patients with HNSCC.

T-Helper Type 9 Cells Play a Central Role in the Pathogenesis of Respiratory Epithelial Adenomatoid Hamartoma.

The etiology and pathogenesis of respiratory epithelial adenomatoid hamartoma (REAH) remain poorly understood, although some reports have suggested that REAH features an inflammatory process. T-helper type 9 (Th9) cells are a newly identified subset of CD4 T-helper cells characterized by the expression of high levels of interleukin (IL)-9, which may promote inflammation. As REAH may involve an inflammatory process, we evaluated whether IL-9 and/or Th9 cells were present in REAH and compared the levels thereof to those of normal nasal mucosa. Eleven patients with REAH and 5 exhibiting cerebrospinal fluid leakage were included in the study. Flow cytometry was used to measure Th9 cell numbers, a cytometric bead assay was applied to measure IL-9 levels, and real-time polymerase chain reaction was used to quantify the levels of mRNA encoding IL-9. Th9 cells, IL-9 mRNA, and IL-9 were detected in all REAH and control samples. The proportion of Th9 cells in the patients with REAH was significantly greater than that in the controls. The expression levels of IL-9-encoding mRNA and IL-9 protein were significantly higher in the patients with REAH than in the controls. The Th9 cell subset was expanded, the synthesis of IL-9-encoding mRNA was upregulated, and IL-9 secretion was increased in REAH tissue, suggesting that Th9 cells play a central role in the pathogenesis of the disease.

Clinical significance of epigenetic silencing and re-expression of O6-methylguanine-DNA methyltransferase using epigenetic agents in laryngeal carcinoma.

The aim of the present study was to investigate the association between O6-methylguanine-DNA methyltransferase (MGMT) gene expression levels, and DNA methylation status and histone modifications in laryngeal squamous cell carcinoma (LSCC). Chromatin immunoprecipitation, methylation-specific polymerase chain reaction (PCR), and reverse transcription-quantitative PCR were performed to analyze histone modifications, DNA methylation status and mRNA expression levels in the promoter region of the MGMT gene in laryngeal carcinoma HEp-2 cells, as well as in 50 paired healthy and LSCC tissue samples. The present study demonstrated that treatment of HEp-2 cells with 5-aza-2'-deoxycytidine (Aza), a DNA methyltransferase inhibitor, significantly upregulated MGMT mRNA expression levels, reduced MGMT DNA methylation, reduced MGMT histone H3 lysine 9 (H3K9) di-methylation, and increased MGMT histone H3 lysine 4 di-methylation without a significant change in H3K9 acetylation. Trichostatin A (TSA), a histone deacetylase inhibitor, marginally upregulated MGMT mRNA expression levels without affecting the DNA methylation status, or H3K9 or H3K4 di-methylation, however, TSA treatment caused a significant increase in H3K9 acetylation. Furthermore, Aza and TSA combination treatment produced a synergistic effect. In the LSCC samples, the rate of DNA methylation in the MGMT gene was 54%, compared with 24% in the healthy control group (P<0.05). Therefore, data from the present study indicates that MGMT may serve as a novel therapeutic target in the treatment of LSCC.

[Beta-catenin and cyclin D1 mRNA levels in newly diagnosed patients with acute myeloid leukemia and their significance].

This study was aimed to quantitatively detect the levels of beta-catenin and cyclin D1 mRNA in various subgroups of acute myeloid leukemia (AML) and to analyze their potential relationship, so as to provide theoretical basis for exploring the role of Wnt/beta-catenin pathway in the pathogenesis of AML. Real time fluorescent quantitative RT-PCR was used to detect the relative expression levels of beta-catenin and cyclin D1 mRNA, to analyze changes of the two gene expressions and their relationship. The results showed that the beta-catenin mRNA expression level in BMMNC of AML patients was significantly higher than that in benign blood disease patients (p < 0.05), but no statistical difference was found among the various subgroups of AML (p > 0.05). In AML there was overexpression of cyclin D1 mRNA, and its expression level was significantly higher than that in benign blood disease group (p < 0.05), but there was no statistical difference among the subtypes of AML. The expression levels of beta-catenin and cyclin D1 were correlated each other in AML-M(1), M(2) and M(4) (r values were 0.822, 0.627, 0.712 respectively; p values were 0.001, 0.020, 0.002 respectively). It is concluded that the over-expressions of beta-catenin and cyclin D1 exit in AML patients, and the significant correlation appears in part of the subgroups, which means that the Wnt/beta-catenin pathway is aberrantly activated in AML, probably activating the downstream target gene cyclin D1 and participating in the regulation of cell cycle disturbance and abnormal proliferation of leukemic cells.

[Wnt/beta-catenin signal pathway and malignant hematological disease -- review].

Wnt/beta-catenin is the most important and more understanding pathway in Wnt pathways, which is closely related to pathogenesis and development of many solid tumors. Recently, researches discovered that Wnt/beta-catenin signal pathway may be involved in malignant hematopoiesis, and abnormally activated in many hematological-malignancies. This article reviews the newest studies on relationship between Wnt/beta-catenin signal pathway and hematological malignancies (multiple myeloma, chronic myeloid leukemia, chronic lymphocytic leukemia, acute leukemia and so on) in order to reveal the related pathogenesis of hematological malignancies and provide new opinions for target therapy of these diseases.