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Background/purpose: Oral squamous cell carcinoma (OSCC) is a common cancer worldwide, and its metastasis is difficult to predict and prevent. Inhibin beta B (INHBB) protein has been linked to cancer prognosis and epithelial-mesenchymal transition (EMT). However, previous study about INHBB expression focused on patients in a single region while the risk factors vary among regions. This study aimed to provide a broader perspective on INHBB expression in OSCC. Materials and methods: Tissue micro-arrays comprising 118 specimens were subjected to immunohistochemistry, and all slides were quantified using StrataQuest software. Results: The ratio of INHBB-positive cells to total cells was significantly higher in OSCC samples than in normal samples, and the intensity of INHBB expression was significantly greater in the late-stage OSCC. After classifying specimens into high and low INHBB expression groups, a significant association with clinical staging was found. Though a previous study suggested that menin regulates INHBB, menin expression was not detected in specimens. Conclusion: The ratio of INHBB-positive cells in OSCC may be druggable for targeting tumor cells or assisting in diagnosis, and the intensity of INHBB expression may provide prognostic information for predicting potential metastasis. Moreover, the regulatory mechanism of INHBB in OSCC remains unclear and requires further investigation.
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BACKGROUND/PURPOSE: Culture environments play a critical role in stem cell expansion. This study aimed to evaluate the effects of 2,3,5,4'-tetrahydroxystilbene-2-O-b-D-glucoside (THSG) on the proliferation and differentiation of human dental pulp stem cells (DPSCs) in 2-dimensional (2D) and 3-dimensional (3D) culture systems. MATERIALS AND METHODS: Human DPSCs were seeded in T25 flasks for 2D cultivation. For the 3D culture system, DPSCs were mixed with microcarriers and cultured in spinner flasks. Cells in both culture systems were treated with THSG, and cell proliferation was determined using a cell counter and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. In THSG-treated DPSCs, the genes associated with proliferation, adipogenesis, neurogenesis, osteogenesis, pluripotency, oncogenesis, and apoptosis were analyzed using real-time polymerase chain reactions. RESULTS: The spinner flask time-dependently improved cell numbers, cell viability, and expansion rates in THSG-treated DPSCs. In both the T25 and spinner flasks, the messenger RNA (mRNA) levels of proliferation, osteogenesis, and pluripotent-related genes had a significant maximum expression with 10 µM THSG treatment. However, 0.1 µM of THSG may be the most suitable condition for triggering neurogenesis and adipogenesis gene expression when DPSCs were cultured in spinner flasks. Furthermore, the number of oncogenes and apoptotic genes decreased considerably in the presence of THSG in both the T25 and spinner flasks. CONCLUSION: The spinner flask bioreactor combined with THSG may upregulate proliferation and lineage-specific differentiation in DPSCs. Thus, the combination can be used to mass-produce and cultivate human DPSCs for regenerative dentistry.
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BACKGROUND/PURPOSE: Dental pulp stem cells (DPSCs) contribute to the regeneration of various tissues and have superior proliferation, immune privilege, and anti-inflammation properties to other mesenchymal stem cells. 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside (THSG) not only enhances the aforementioned properties of DPSCs but also promotes self-renewal and reprogramming-like ability. However, whether THSG enhances the aforementioned properties and abilities through direct or indirect interaction mechanisms remains unclear. To address this knowledge gap, we examined the effects of THSG-stimulated DPSC-derived conditioned medium (THSG-CM) on the activity and anti-inflammation properties of cells. MATERIALS AND METHODS: DPSCs were treated with various concentrations of THSG to produce THSG-CM, which was then collected, analyzed, and lyophilized. A cytokine profiling antibody assay was used to compare protein components between THSG-treated and nontreated CM. Human skin fibroblasts (HSFs) and human gingival fibroblasts (HGFs) were used to investigate the effect of THSG-CM on cell proliferation, anti-inflammation, and wound healing abilities; for this investigation, MTS assay, quantitative real-time PCR analysis, and 2-well silicone inserts wound model were conducted. RESULTS: We observed that THSG enhanced the secretion of growth- and immune-associated proteins in THSG-CM and increased the proliferation of HSFs and HGFs. Furthermore, THSG-CM significantly attenuated lipopolysaccharide-stimulated mRNA levels of cytokines in both cells and improved wound healing abilities. CONCLUSION: We conclude that THSG-CM had more beneficial effects on cell activity and anti-inflammation in the HSFs and HGFs than DPSC-derived CM. DPSC-derived CM can be developed into a cell-free regenerative strategy in the future, and its therapeutic efficacy may be improved by THSG-CM.
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BACKGROUND/PURPOSE: Dysregulation of cell cycle checkpoint control may lead to the independence of growth regulating signals. Checkpoint protein such as the PD-1/PD-L1 immune checkpoint involving tumor cells and host immune defense lymphocytes is a well-studied therapeutic target in oncology. Acting at a cell surface receptor on plasma membrane integrin αvß3, thyroxine stimulates intracellular accumulation of PD-L1 in cancer cells. Although resveratrol also binds to integrin αvß3, it reduces PD-L1 expression. MATERIALS AND METHODS: In current studies, we investigated the roles of resveratrol and thyroxine in regulating expression of proliferation-related genes and checkpoint genes, PD-L1, BTLA in two oral cancer cell lines. RESULTS: Thyroxine suppressed the expression of pro-apoptotic BAD but induced proliferative CCND1 expression in SSC-25â¯cells and OEC-M1 cells. It activated expression of PD-L1 and BTLA in both cell lines. On the other hand, resveratrol suppressed the expression of all. Alternatively, it activated BAD expression. Thus thyroxine induces checkpoint gene expression which may promote proliferation in cancer cells. Alternatively, resveratrol reverses the stimulatory effects of thyroid hormone to induce anti-proliferation. CONCLUSION: These findings provide new insights into the antagonizing effect of resveratrol on the thyroxine-induced expression of checkpoint genes and proliferative genes in oral cancers.
