Periodontitis is a chronic inflammatory disease that leads to destruction of tooth supporting tissues. Porphyromonas gingivalis (P. gingivalis), especially its lipopolysaccharides (LPS), is one of major pathogens that cause periodontitis. Bee venom (BV) has been widely used as a traditional medicine for various diseases. Previous studies have demonstrated the anti-inflammatory, anti-bacterial effects of BV. However, a direct role and cellular mechanism of BV on periodontitis-like human keratinocytes have not been explored. Therefore, we investigated the anti-inflammatory mechanism of BV against P. gingivalis LPS (PgLPS)-induced HaCaT human keratinocyte cell line. The anti-inflammatory effect of BV was demonstrated by various molecular biological methods. The results showed that PgLPS increased the expression of Toll-like receptor (TLR)-4 and pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, and interferon (IFN)-γ. In addition, PgLPS induced activation of the signaling pathways of inflammatory cytokines-related transcription factors, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activator protein 1 (AP-1). BV effectively inhibited those pro-inflammatory cytokines through suppression of NF-κB and AP-1 signaling pathways. These results suggest that administration of BV attenuates PgLPS-induced inflammatory responses. Furthermore, BV may be a useful treatment to anti-inflammatory therapy for periodontitis.

Endometrial stromal tumor (EST) is an uncommon and unusual mesenchymal tumor of the uterus characterized by multicolored histopathological, immunohistochemical, and molecular features. The morphology of ESTs is similar to normal endometrial stromal cells during the proliferative phase of the menstrual cycle. ESTs were first classified into benign and malignant based on the number of mitotic cells. However, recently WHO has divided ESTs into four categories: endometrial stromal nodules (ESN), undifferentiated uterine sarcoma (UUS), low-grade endometrial stromal sarcoma (LG-ESS), and high-grade endometrial stromal sarcoma (HG-ESS). HG-ESS is the most malignant of these categories, with poor clinical outcomes compared to other types. With advances in molecular biology, ESTs have been further classified with morphological identification. ESTs, including HG-ESS, is a relatively rare type of cancer, and the therapeutics are not being developed compared to other cancers. However, considering the tumor microenvironment of usual stromal cancers, the advance of immunotherapy shows auspicious outcomes reported in many different stromal tumors and non-identified uterine cancers. These studies show the high possibility of successful immunotherapy in HG-ESS patients in the future. In this review, we are discussing the background of ESTs and the BCOR and the development of HG-ESS by mutations of BCOR or other related genes. Among the gene mutations of HG-ESSs, BCOR shows the most common mutations in different ways. In current tumor therapies, immunotherapy is one of the most effective therapeutic approaches. In order to connect immunotherapy with HG-ESS, the understanding of tumor microenvironment (TME) is required. The TME of HG-ESS shows the mixture of tumor cells, vessels, immune cells and non-malignant stromal cells. Macrophages, neutrophils, dendritic cells and natural killer cells lose their expected functions, but rather show pro-tumoral functions by the matricellular proteins, extracellular matrix and other complicated environment in TME. In order to overcome the current therapeutic limitations of HG-ESS, immunotherapies should be considered in addition to the current surgical strategies. Checkpoint inhibitors, cytokine-based immunotherapies, immune cell therapies are good candidates to be considered as they show promising results in other stromal cancers and uterine cancers, while less studied because of the rarity of ESTs. Based on the advance of knowledge of immune therapies in HG-ESS, the new strategies can also be applied to the current therapies and also in other ESTs.

Secretory carcinoma of the salivary gland (SC) is a newly introduced rare salivary gland tumor that shares histological, immunohistochemical, and genetic characteristics with secretory carcinoma of the breast. Here, we report the cytologic features of two cases of SC confirmed by surgical resection. In these two cases, SC was incidentally detected in a 64-year-old female and a 56-yearold male. Fine needle aspiration cytology revealed nests of tumor cells with a papillary or glandular structure floating in mucinous secretions. The tumor cells demonstrated uniform, round, smooth nuclear contours and distinct nucleoli. Multiple characteristic cytoplasmic vacuoles were revealed. Singly scattered tumor cells frequently showed variable sized cytoplasmic vacuoles. The cytopathologic diagnosis of SC should be considered when characteristic cytological findings are revealed. Further immunohistochemistry and gene analyses are helpful to diagnose SC.

Background: Mesenchymal epidermal transition (MET) and receptor originating from nantes (RON) are transmembrane tyrosine kinase receptors. Both are members of a proto-oncogene family and thus play a role in the pathogenesis of various cancers and acquired resistance to kinase inhibitors in lung cancer. Aims: The aim of this study was to investigate the immunohistochemical expression of c-MET and RON in lung adenocarcinoma and its clinicopathologic correlation. Settings and Design: Retrospective study. Materials and Methods: The immunohistochemical c-MET and RON expression in specimens obtained from lung adenocarcinoma (n = 175) and associated clinicopathologic parameters were evaluated. Statistical Analysis Used: The correlation between c-MET and RON expression was analyzed by Chi-square test. A Cox proportional hazards model and Kaplan-Meier curve analysis were used to evaluate the risk factors and prognosis. Results: High expression of the c-MET protein showed a strong correlation with that of RON (P = 0.013, kappa = 0.183). Five-year survival and recurrence-free 5-year survival were not associated with high expression of c-MET or RON. High c-MET expression was significantly associated with age older than 60 years (P = 0.000), tumor differentiation (P = 0.009), lymphovascular invasion (P = 0.016), and pleural invasion (P = 0.005). High RON expression was associated with a solid growth pattern (P = 0.001) and pleural invasion (P = 0.002). Conclusions: The results point to the potential of immunohistochemical expression of c-MET and RON as useful prognostic markers of unfavorable histopathologic features in lung adenocarcinoma.