Court decisions in criminal proceedings for dental malpractice in Taiwan.

BACKGROUND/PURPOSE: Malpractice claims place heavy economic and emotional burdens on both dentists and patients. Recently, medical malpractice lawsuits are decreasing in prevalence but increasing in severity. The percentage of dental malpractice payments is also growing among the health profession. The present study aimed to explore criminal convictions in dental malpractice litigation and to analyze the factors affecting the judgment in dental disputes in Taiwan. METHODS: The keywords "dentist," "professional negligence," "medical malpractice," and "professional liability" were used to search Taiwan's Law and Regulations Retrieving System for criminal dental malpractice cases in all district courts from January 1, 2000 to June 30, 2021. The eligible judgments were summarized and analyzed. RESULTS: Overall, 425 cases were identified, with 28 dental disputes included in the final analysis. The dentists lost in 10 cases (35.7%). The average claim time was 36.75 ± 16.34 months. Taipei and Taichung dealt with more lawsuit cases (n = 8). Local clinics were the most common institution of the defendants (75%) and had the highest number of convictions (n = 9). Implant dentistry was the most common specialty involved. Expert testimony of the Medical Review Committee (MRC) had a high K coefficient of agreement with court judgments regarding professional negligence (p < 0.001). CONCLUSION: The overall criminal conviction rate was 35.7%. Implant therapy and local clinics had the highest rate of lawsuits and a considerably higher conviction rate. All guilty dentists were fined or given probation. The court judgments were highly consistent with the expert testimony of the MRC.

HDAC2 promotes cell migration/invasion abilities through HIF-1α stabilization in human oral squamous cell carcinoma.

BACKGROUND: Histone deacetylase 2 (HDAC2) expressions in oral squamous cell carcinoma (OSCC) had been implicated in advanced stage and poor prognosis. It suggests a possible link between the migration/invasion potential of oral cancer cells and the prevalent expression of HDAC2. METHODS: Five head and neck cancer (HNC) cell lines, including Ca9-22, Cal-27, HSC-3, SAS, and TW2.6, were used. Cells stably overexpressing HDAC2 and shRNA against HDAC2 were established to investigate migration/invasion ability in vitro and tumorigenesis and progression in vivo. RESULTS: We found that alterations in the HDAC2 level in OSCC cell lines modulated their invasive ability with a positive correlation. Animal model also showed that knockdown of HDAC2 expression in SAS cells, originally containing high endogenous HDAC2 expression, resulted in decrease in tumor initiation and progression. Using high-throughput transcriptome analysis, numerous genes involved in HIF-1α-associated pathways were found. At the mechanism levels, using agents to block de novo protein synthesis or prevent protein degradation by ubiquitination, we found the stability of hypoxia inducible factor 1α (HIF-1α) protein was maintained in OSCC cells with HDAC2 overexpression. In addition, co-immunoprecipitation assay also revealed that HDAC2-mediated HIF-1α protein stability is because of direct interaction of HIF-1α with von Hippel-Lindau (VHL) protein. CONCLUSIONS: Our work demonstrates that HDAC2 maintains HIF-1α stability, probably at the level of protein modification, which in turn leads to the increase in cell invasion/migration ability in oral cancer progression. These findings implicate the potential of HDAC inhibitors for oral cancer therapy.

Polyethylenimine-mediated PUMA gene delivery to orthotopic oral cancer: suppression of tumor growth through apoptosis induction in situ and prolonged survival.

BACKGROUND: PUMA (a p53 up-regulated modulator of apoptosis) is induced by p53 tumor suppressor and other apoptotic stimuli. It was found to be a principal mediator of cell death in response to diverse apoptotic signals, implicating PUMA as a likely tumor suppressor. METHODS: In this study, we examined the efficacy of targeted PUMA gene therapy in human oral cancer (SAS) cells using polyethylenimine (PEI)-mediated transfection for gene delivery. RESULTS: Exogenous expression of PUMA in SAS cells resulted in apoptosis with cytochrome c release, activation of caspase-3 and -9, and cleavage of PARP. Gene delivery of PEI/PUMA in SAS xenografts induced apoptosis and resulted in significant reductions (∼60%) of tumor growth in vivo. Furthermore, we have shown that PEI-mediated PUMA gene therapy prolonged survival of animals with orthotopic SAS oral cancers. CONCLUSIONS: Taken together, these results indicated that PUMA gene therapy via PEI delivery could be a promising method for the treatment of oral squamous cell carcinoma.

Essential roles of caspases and their upstream regulators in rotenone-induced apoptosis.

In the present study, we examined whether caspases and their upstream regulators are involved in rotenone-induced cytotoxicity. Rotenone significantly inhibited the proliferation of oral cancer cell lines in a dose-dependent manner compared to normal oral mucosal fibroblasts. Flow cytometric analysis of DNA content showed that rotenone treatment induced apoptosis following G2/M arrest. Western blotting showed activation of both the caspase-8 and caspase-9 pathways, which differed from previous studies conducted in other cell types. Furthermore, p53 protein and its downstream pro-apoptotic target, Bax, were induced in SAS cells after treatment with rotenone. Rotenone-induced apoptosis was inhibited by antioxidants (glutathione, N-acetylcysteine, and tiron). In conclusion, our results demonstrate significant involvement of caspases and their upstream regulators in rotenone-induced cytotoxicity.

Immunohistochemical analysis of Th1/Th2 cytokine profiles and androgen receptor expression in the pathogenesis of nifedipine-induced gingival overgrowth.

BACKGROUND: Numerous studies have demonstrated that gingival overgrowth may be associated with androgen and cytokine expression in tissues. OBJECTIVES: The aim of this study was to compare the expression of androgen receptor-presenting cells (AR+ cells) and Th1/Th2 cytokine [Th1: interleukin (IL)-2, interferon-gamma (IFN-gamma); Th2: IL-4, IL-10, IL-13] expression cells in tissue sections of patients with gingival overgrowth. MATERIALS AND METHODS: Tissue samples were collected from patients with healthy periodontium (H group), adult periodontitis (P group), surgically extracted teeth (S group), and nifedipine-induced gingival overgrowth (NIGO group). The clinical periodontal parameters of pocket depth (PD), bleeding on probing (BOP), and plaque control record (PCR) were measured around selected sample teeth. Gingival biopsies were further processed by immunohistochemical staining method. The expressions of cells positive for AR, IL-2, IFN-gamma, IL-4, IL-10, and IL-13 were counted by predetermined semiquantitative methods. RESULTS: Our results indicated that AR, IL-2, IFN-gamma, IL-4, IL-10, and IL-13 were intensively expressed in the nuclei of inflammatory cells and fibroblasts of gingival connective tissue. Stronger expressions of AR, IL-2, and IFN-gamma were found in the NIGO group. The AR+ cells/0.01 mm2 in gingival fibroblasts were significantly higher in the NIGO group (80.2 +/- 10.7) than those of the periodontitis group (52.5 +/- 11.8) and control group (37.4 +/- 11.3) (P < 0.05). The cytokine expression of the NIGO group showed a trend towards Th1-type expression (IL-2; P = 0.0001). In the surgically extracted tooth group, a stronger expression of Th2-type cytokine (IL-4, Il-10, IL-13; P < 0.05) was found in inflammatory cells. In a comparison of the IL-2/IL-4-labeled cell ratio of the four groups, a descending sequence was discovered as NIGO group (0.92 +/- 0.97) > H group (0.81 +/- 0.61) > P group (0.77 +/- 0.82) > S group (0.58 +/- 1.77). CONCLUSIONS: Our data support the following: (i) taking nifedipine may elevate the expression of AR in susceptible oral tissue, e.g. gingiva; (ii) the cytokine profile of T-cells in NIGO tissue indicates a trend preferentially towards Th1 activity; and (iii) elevation of AR expression cells and prominent Th1 cytokine-labeled cells are two significant factors in the pathogenesis of NIGO.