Wound healing is a dynamic process that involves highly coordinated cellular events, including proliferation and migration. Oral gingival fibroblasts serve a central role in maintaining oral mucosa ...homeostasis, and their functions include the coordination of physiological tissue repair. Recently, surface pre‑reacted glass‑ionomer (S‑PRG) fillers have been widely applied in the field of dental materials for the prevention of dental caries, due to an excellent ability to release fluoride (F). In addition to F, S‑PRG fillers are known to release several types of ions, including aluminum (Al), boron (B), sodium (Na), silicon (Si) and strontium (Sr). However, the influence of these ions on gingival fibroblasts remains unknown. The aim of the present study was to examine the effect of various concentrations of an S‑PRG filler eluate on the growth and migration of gingival fibroblasts. The human gingival fibroblast cell line HGF‑1 was treated with various dilutions of an eluent solution of S‑PRG, which contained 32.0 ppm Al, 1,488.6 ppm B, 505.0 ppm Na, 12.9 ppm Si, 156.5 ppm Sr and 136.5 ppm F. Treatment with eluate at a dilution of 1:10,000 was observed to significantly promote the migration of HGF‑1 cells. In addition, the current study evaluated the mechanism underlying the mediated cell migration by the S‑PRG solution and revealed that it activated the phosphorylation of extracellular signal‑regulated kinase 1/2 (ERK1/2), but not of p38. Furthermore, treatment with a MEK inhibitor blocked the cell migration induced by the solution. Taken together, these results suggest that S‑PRG fillers can stimulate HGF‑1 cell migration via the ERK1/2 signaling pathway, indicating that a dental material containing this type of filler is useful for oral mucosa homeostasis and wound healing.
Development and nurturing of oral functions IWATA, Kokoro; IWAMOTO, Tsutomu
The Journal Of The Japan Health Care Dental Association,
2022/12/20, Letnik:
23, Številka:
1
Journal Article
Odprti dostop
The oral cavity plays a role as a feeding organ for food and water intake, an articulatory organ for speech, and a respiratory tract for emergency breathing. In addition, the morphology of the oral ...cavity, including the alignment of teeth and jaw shape, is an esthetic component of the face, and its problems are linked to functional problems such as mastication and speech, and the psychological impact of such disharmony is significant. Childhood is a period of dynamic change in oral morphology, as represented by the replacement of deciduous teeth with permanent teeth, and a period in which these functions are acquired in parallel. The development of morphology and function is always linked, and children's internal psychological factors also have a great impact on them. In particular, the psychological aspect of children is greatly influenced by their nurturing environment.For the healthy development of the oral cavity, it is extremely important to achieve a good balance between morphology, function, and psychology, and we need to provide support from multiple perspectives, not just one. On the other hand, systemic factors also play a major role in the development of oral morphology and function.This article is to summarize general oral development and the systemic factors that influence the development, and concludes with an overview of support for the development of oral function.
We aimed to confirm the efficacy and safety of the oral histone deacetylase inhibitor entinostat in Japanese patients with hormone receptor-positive advanced/recurrent breast cancer and to explore ...potential biomarkers.
This phase II, double-blind, randomized, placebo-controlled trial (ClinicalTrials.gov; NCT03291886) was conducted at 28 Japanese sites (September 2017-July 2020; interim analysis cutoff: April 2019). Patients with progression/relapse following non-steroidal aromatase inhibitors were randomized 1:1 to entinostat (5 mg/week) or placebo, plus exemestane (25 mg/day). Primary endpoint was progression-free survival; secondary endpoints included overall survival and safety. Exploratory biomarker outcomes included lysine acetylation, immune cell profiles, estrogen receptor 1 mutations and plasma chemokines.
Of 133 randomized patients, 131 (65 entinostat, 66 placebo) who received study drug were analyzed. Median (95% confidence interval) progression-free survival was 5.8 (3.2-7.8) months for entinostat and 3.3 (3.1-5.8) months for placebo (hazard ratio 95% confidence interval: 0.75 0.50 - 1.14; P = 0.189). Median overall survival was not reached in either group. Entinostat tended to prolong progression-free survival in patients aged ≥65 years, not endocrine resistant, or with estrogen receptor 1 Y537S mutation. Candidate biomarkers of efficacy (progression-free survival) included lysine acetylation in CD3+ cells, plasma interferon gamma-induced protein 10, dendritic cell CD86 expression, and CD4+ cell expression of human leukocyte antigen-DR and inducible T-cell co-stimulator. Safety was similar to non-Japanese populations; however, seven entinostat-treated patients (10.8%) had reversible lung injury.
In Japanese patients, the safety of entinostat plus exemestane was acceptable and progression-free survival was prolonged, although not significantly. Exploratory analyses identified potential biomarkers, including lysine acetylation, of efficacy.
Adjuvant trastuzumab monotherapy has not been compared with trastuzumab + chemotherapy. We investigated the relative value of trastuzumab monotherapy for older patients with breast cancer.
This study ...was an open-label, randomized controlled study with a treatment selection design in which a noninferiority criterion was predefined. Patients aged 70-80 years with surgically treated human epidermal growth factor receptor 2-positive invasive breast cancer received trastuzumab monotherapy or trastuzumab + chemotherapy. The primary end point was disease-free survival (DFS) with assessment of prespecified hazard ratio (HR), relapse-free survival (RFS), adverse events (AEs), health-related quality of life (HRQoL), and restricted mean survival time (RMST).
The study involved 275 patients (mean age, 73.5 years) who were followed up for a mean of 4.1 years (range, 0.3-8.0 years). The percentages of patients by cancer stage were as follows: I (pT > 0.5 cm), 43.6%; IIA, 41.7%; IIB, 13.5%; and IIIA, 1.1%. Three-year DFS was 89.5% with trastuzumab monotherapy versus 93.8% with trastuzumab + chemotherapy (HR, 1.36; 95% CI, 0.72 to 2.58;
= .51). At 3 years, RMST differed by -0.39 months between arms (95% CI, -1.71 to 0.93;
= .56). Three-year RFS was 92.4% with trastuzumab monotherapy versus 95.3% with trastuzumab + chemotherapy (HR, 1.33; 95% CI, 0.63 to 2.79;
= .53). Common AEs were anorexia (7.4%
44.3%;
< .0001) and alopecia (2.2%
71.7%;
< .0001), and grade 3/4 nonhematologic AEs occurred in 11.9% versus 29.8% (
= .0003) for trastuzumab monotherapy versus trastuzumab + chemotherapy, respectively. Clinically meaningful HRQoL deterioration rate showed significant differences at 2 months (31% for trastuzumab monotherapy
48% for trastuzumab + chemotherapy;
= .016) and at 1 year (19%
38%;
= .009).
The primary objective of noninferiority for trastuzumab monotherapy was not met. However, the observed loss of survival without chemotherapy was < 1 month at 3 years. Therefore, and in light of the lower toxicity and more favorable HRQoL profile, trastuzumab monotherapy can be considered an adjuvant therapy option for selected older patients.
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