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Background/aim: Bone resolution due to tumor invasion often occurs on the surface of the jaw and is important for clinical prognosis. Although cytokines, such as TNF-α are known to impair osteoblasts, the underlying mechanism remains unclear. Protein myristoylation, a post-translational modification, plays an important role in the development of immune responses and cancerization of cells. A clear understanding of the mechanisms underlying this involvement will provide insights into molecular-targeted therapies. N-myristoyltransferase1 (NMT1), a specific enzyme involved in myristoylation, is expressed in cancer cells and in other normal cells, suggesting that changes in myristoylation may result from the regulation of NMT1 in cancer cells., Materials and Methods: Using newly emerging state-of-the-art techniques such as the Click-it assay, RNA interference, mass spectrometry, immunoprecipitation, immunocytochemistry, and western blotting, the expression of myristoylated proteins and the role of TNF-α stimulation on NMT1 and Sorbs2 binding were evaluated in a murine osteoblastic cell line (MC3T3-E1)., Results: The expression of myristoylated proteins was detected; however, TNF-α stimulation resulted in their inhibition in MC3T3-E1 cells. The expression of NMT1 also increased. Immunoprecipitation and mass spectrometry identified Sorbs2 as a novel binding protein of NMT1, which upon TNF-α stimulation, inhibited myristoylation., Conclusion: The binding between NMT1 and Sorbs2 can regulate myristoylation, and NMT1 can be considered as a potential target molecule for tumor invasion., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: In this study, we investigated the diagnostic utility of submandibular gland (SMG) sonography and labial salivary gland (LSG) biopsy as a less invasive procedure for diagnosing IgG4-related dacryoadenitis and sialadenitis (IgG4-DS) Methods: Sixty-eight patients with suspected IgG4-DS by presenting swelling of elevated serum IgG (>1747 mg/dl) and/or swelling glands underwent SMG sonography, LSG biopsy and measurement for serum IgG4. SMG sonographic diagnosis was determined by the following characteristic changes; 'hypoechoic areas of a nodal pattern with high vascularity' and/or 'hypoechoic areas of a reticular pattern in the superficial part'. Results: Thirty-one patients were diagnosed with IgG4-DS, 5 with IgG4-RD unaccompanied by lacrimal and salivary gland lesions, 28 with Sjögren's syndrome, and 4 with malignant lymphoma. The sensitivity, specificity, and accuracy of SMG sonography and LSG biopsy were 100%, 83.8%, 91.2% and 64.5%, 73.8%, 75.0%, respectively. Moreover, those of SMG sonography and LSG biopsy combined with serum IgG4 concentration (>135 mg/dl) were 100%, 94.6%, 97.1% and 64.5%, 91.9%, 79.4%, respectively. Conclusion: LSG biopsy needs to be extremely careful to diagnose IgG4-DS because of its low sensitivity. SMG sonography is sufficient for the diagnosis of IgG4-DS, especially when combined with serologic analysis. Thus, SMG sonography could adapt to the diagnostic criteria of IgG4-DS as a non-invasive method.

Background/aim: Adenoid cystic carcinoma (AdCC) is a rare cancer of the salivary gland with high risk of recurrence and metastasis. Wnt signalling is critical for determining tumor grade in AdCC, as it regulates invasion and migration. β-catenin dephosphorylation plays an important role in the Wnt pathway, but its underlying molecular mechanism remains unclear., Materials and Methods: Because the regulatory subunits of protein phosphatase 2A (PP2A) drive Wnt signalling via target molecules, including β-catenin, we used qRT-PCR and immunoblot analysis to investigate the expression of these subunits in an AdCC cell line (ACCS) and a more aggressive subline (ACCS-M)., Results: PR55β was highly expressed in ACCS-M, suggesting its functional importance. In addition, PR55β expression was associated with tumor grade, with ACCS-M exhibiting higher PR55β levels. More importantly, knockdown of PR55β in ACCS-M cells significantly reduced invasiveness and metastatic ability. Furthermore, dephosphorylation and total levels of β-catenin were dependent on PR55β in ACCS-M. Finally, we confirmed a correlation between PR55β staining intensity and histopathological type in human AdCC tissues., Conclusion: Our study provides new insight into the interaction between PR55β and β-catenin and suggests that PR55β may be a target for the clinical treatment of AdCC., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: This study was undertaken to determine whether induction of systemic inflammation accelerates the development of Sjögren's syndrome (SS) in genetically susceptible mice., Methods: Female (NZB x NZW)F1 mice were treated with either Freund's incomplete adjuvant (IFA) or phosphate buffered saline (PBS) at monthly intervals. Salivary gland function was monitored by measuring pilocarpine-induced saliva volume. Mice were killed at different time points and examined for sialadenitis and salivary gland-infiltrating cells. Sera were analyzed for autoantibodies to salivary gland antigens, nuclear antigens, and Ro60., Results: While IFA-treated mice had significantly decreased salivary secretion 7 weeks after the initial treatment, salivary secretion did not decrease in PBS-treated controls until 17 weeks. At 7 weeks, the severity of sialadenitis and the number of T and B cells infiltrating the salivary glands did not differ between the 2 groups. However, at this time point IFA-treated mice showed significantly higher frequencies of CD11clow, B220+, Ly6C+, mouse PDCA-1+ dendritic cells (DCs) in the salivary glands. While levels of autoantibodies did not differ between the 2 groups at early time points, by late time points IFA-treated mice had higher levels. The gland dysfunction observed in IFA-treated mice at earlier time points did not correlate with the severity of sialadenitis or levels of autoantibodies. Instead, it was associated with increased frequency of plasmacytoid DCs in the gland., Conclusion: Our data suggest that generalized inflammatory stimuli can accelerate the development of SS-like disease in (NZB x NZW)F1 mice, and that gland dysfunction in SS can develop prior to the generation of a robust adaptive autoimmune response.

We recently described that the SART-1(690-698) peptide could induce HLA-A24-restricted cytotoxic T lymphocytes (CTLs), which recognize the SART-1(259) (+) tumor cells from peripheral blood mononuclear cells (PBMCs) of HLA-A24(+) cancer patients. In our study, in 5 of 14 HLA-A24(+) patients with oral squamous cell carcinomas (SCCs), CTLs could be induced with the SART-1(690-698) peptide from the PBMCs. In 2 of the patients from whom the highest CTL activities were induced, the T-cell receptor (TCR) Vbeta repertoire expressed by the SART-1(690-698)-specific CTLs was found to be restricted and multiple Vbeta families were predominantly expressed in each patient. Although the predominant Vbeta families were different between the 2 patients, Vbeta7 was highly and commonly predominant. The same predominant Vbeta families were also detected in the tumor-infiltrating lymphocytes (TILs) from each patient, and each Vbeta family contained one or more unique T-cell clonotypes. The unique T-cell clonotypes were found to be common between the TILs and SART-1(690-698)-specific CTLs from each patient, and especially 2 T-cell clonotypes with Vbeta7 were identical even in the 2 patients. One of the 2 T-cell clonotypes with Vbeta7 was detected in the TILs from 11 of 14 HLA-A24(+) patients and another was found in those from 8 of HLA-A24(+) patients, while none of 10 HLA-A24(-) patients demonstrated both T-cell clonotypes. These results strongly suggest that the T-cell clonotypes with Vbeta7 are major TCR Vbeta genes expressed by SART-1(690-698)-specific CTLs. Furthermore, autologous tumor cells from one of the HLA-A24(+) patients stimulated the PBMCs and regional lymph node cells (LNCs) to expand the same T-cell clonotypes as those in the SART-1(690-698)-specific CTLs. These results strongly suggest that the SART-1(690-698)-specific CTLs clearly accumulate in vivo, especially in the TILs, as a consequence of in situ antigenic stimulation by autologous tumor cells. The identification of the unique TCR Vbeta genes used by SART-1(259)-specific CTLs should help to improve the diagnosis of the specific immune response in patients with SART-1(259) (+) cancers, especially during anticancer immunotherapy., (Copyright 2003 Wiley-Liss, Inc.)