Periodontal tissue has a unique structure in that the human periodontal ligament (hPDL) lies between the hard tissues of cementum and alveolar bone. Although the role of cytokines in hPDL function is not clearly understood, we investigated the effect of mechanical stress as hydrostatic pressure (HP) on cytokine expression in hPDL cells.The hPDL cells were obtained from a healthy maxillary third molar. After the 3rd to 4th passage, the cells were exposed to HP ranging from 1 MPa to 6 MPa as previously described. The expression of cytokine mRNA was determined by RT-PCR and cytokines in the culture supernatants were assessed by enzyme-linked immunosorbent assay (ELISA).The exposure to 6 MPa of HP caused no morphological changes of hPDL cells, and did not affect cellular viability. No expression of IL-1β, IL-6, IL-8, TNF-α, RANK, RANKL or OPG mRNA was observed in the control cells under atmospheric pressure, whereas in hPDL cells treated with HP, enhancement of IL-6, IL-8, RANKL and OPG mRNA expression was observed between 10 and 60 minutes after the exposure to HP. After the exposure to HP, the production of IL-6 and TNF-α were induced significantly in hPDL cells, but IL-1β and IL-8 were not produced.These results suggest that hPDL cells may play a role in the production of cytokines in response to mechanical stress in vivo.

Objective: Elucidation of clonal origin of synchronous endometrial and ovarian cancers (SEOs). Methods: We reviewed 852 patients who diagnosed endometrial and/or ovarian cancer. Forty-five (5.3%) patients were diagnosed as SEOs. We evaluated blood and tissue samples from 17 patients. We analyzed the clonal origins of 41 samples from 17 patients by gene sequencing, mismatch microsatellite instability (MSI) polymerase chain reaction assay and immunohistochemical (IHC) staining of 4 repair genes. Results: Sixteen of 17 patients had at least 2 or more trunk mutations shared between endometrial and ovarian cancer suggesting the identical clonal origins. The shared trunk mutation are frequently found in endometrial cancer of the uterus, suggesting the uterine primary. Four out of 17 (24%) SEOs had mismatch repair (MMR) protein deficiency and MSI-high (MSI-H) states. One case was an endometrial carcinoma with local loss of MSH6 protein expression by IHC staining, and the result of MSI analysis using the whole formalin-fixed, paraffin-embedded specimen was microsatellite stable. In contrast, ovarian tissue was deficient MMR and MSI-H in the whole specimen. This indicated that MMR protein deficiency could occur during the progression of disease. Conclusion Most SEOs are likely to be a single tumor with metastasis instead of double primaries, and their origin could be endometrium. In addition, SEOs have a high frequency of MMR gene abnormalities. These findings not only can support the notion of uterine primary, but also can help to expect the benefit for patients with SEOs by immuno-oncology treatment.