Evaluation of BIRC6 Expression in Oral Squamous Cell Carcinoma, Epithelial Dysplasia, Lichen Planus with and without Dysplasia, and Hyperkeratosis.

BACKGROUND: BIRC6, regarded as the pivotal member of the inhibitor of the apoptosis (IAP) family, has been linked to the development of different types of cancer in humans. The objective of this study was to examine the expression of BIRC6 in various oral conditions, including OLP with dysplasia (OLPD), hyperkeratosis (HK), OLP, epithelial dysplasia (ED), and oral squamous cell carcinoma (OSCC), to investigate its potential involvement in the development of OSCC and the pathogenesis and malignant transformation of OLP, which is known as a precancerous condition. METHODS: In this retrospective cross-sectional study, 99 cases, consisting of 19 cases of OSCC, 21 cases of ED, 23 cases of OLP, 20 cases of OLPD, and 16 cases of HK as the control group, were investigated regarding BIRC6 expression by immunohistochemical staining. After that, the immunohistochemical expression of BIRC6 in the epithelial compartment was analyzed. Statistical analysis was performed to investigate the relationship between the expression of BIRC6 and clinicopathological variables. The statistical analysis of the data involved the use of one-way ANOVA, post hoc Tukey, Kruskal-Wallis, Chi-square, Spearman's correlation, and Mann-Whitney tests. The significance level was set at p < 0.05. RESULTS: Positive BIRC6 staining was found in 91.7% of the subjects of OLP, 88.1% of HK, 86.1% of ED, 93% of OLPD, and 94.7% of OSCC. OSCC showed the highest BIRC6 expression (p = 0.00). The average total staining score was remarkably greater in OSCC and dysplastic lesions compared with HK (p = 0.00, p = 0.00). CONCLUSIONS: While the current study suggested that BIRC6 may play a role in the tumorigenesis of OSCC, its role in the malignant transformation of OLP has yet to be definitively established.

Evaluation of Paxillin Expression in Epithelial Dysplasia, Oral Squamous Cell Carcinoma, Lichen Planus with and without Dysplasia, and Hyperkeratosis: A Retrospective Cross-Sectional Study.

BACKGROUND: Paxillin is a cytoskeletal protein involved in the pathogenesis of several types of cancers. However, the roles of paxillin in epithelial dysplasia (ED), oral squamous cell carcinoma (OSCC), oral lichen planus with dysplasia (OLPD), hyperkeratosis (HK), and oral lichen planus (OLP) have remained unnoticed in the literature. This study aimed to evaluate its attainable functions in the pathogenesis and malignant transformation of potentially malignant oral epithelium and benign lesions. METHODS: In this retrospective cross-sectional study, paxillin expression was investigated in 99 tissue samples, including 18 cases of OSCC, 21 ED, 23 OLP, 21 OLPD, and 16 cases of HK. The tissue sections also underwent immunohistochemical paxillin staining using 3,3-diaminobenzidine (DAB) chromogen. The intensity, location, and percentage of staining were examined across all groups. Data were analyzed using the Shapiro-Wilk test, ANOVA, Pearson chi-square, Kruskal-Wallis, and Dunn's post hoc test. RESULTS: The cytoplasmic percentage and intensity staining of Paxillin expression were evident in the central/suprabasal and basal/peripheral layers of all the obtained samples. The final staining score was significantly higher in OSCC and dysplasia compared to HK and OLP (p = 0.004). It was found that paxillin expression is associated with the grade of dysplastic samples (p < 0.001). CONCLUSION: The present study provides evidence that paxillin may be involved in the pathogenesis of OSCC and the development and progression of dysplastic tissue, since the paxillin expression was higher than that of HK and OLP.

Profile of Serum Heat Shock Protein-27 Level in Patients with Salivary Gland Tumor.

Statement of the Problem: Heat shock protein 27 (HSP27) plays important roles in many cellular processes and has been implicated in different types of diseases such as cancers. Purpose: This study aimed to evaluate the serum level of HSP27 in patients with salivary gland tumors and to determine its possible correlation with the prognosis of the disease. Materials and Method: This cross-sectional study was performed on 60 patients with sali-vary gland tumor including 16 pleomorphic adenoma, 33 adenoid cystic carcinoma, 6 mu-coepidermoid carcinoma, 5 acinic cell carcinoma, and 28 healthy control subjects. The con-trol cases were healthy blood donors who matched the study group in age and sex. Serum samples were obtained from the clotted blood and HSP27concentrations were measured with sandwich enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed by using one-way ANOVA, post Hoc test, independent sample t-test, and ROC analysis. A p value of less than 0.05 was considered as significant. Results: The mean serum level of HSP27 was 3956.1±3830.1 (pg/ml) in patients with malig-nant salivary gland tumor, which was significantly higher than that in benign salivary gland tumor (752.2±485.6) and healthy controls (602.3±575.8) (p <0.001). However, there was no significant difference in the HSP27 serum levels between the patients with benign salivary gland tumors and healthy controls (p= 0.2). No association was detected between the mean serum levels of HSP27 and clinicopathologic factors such as age, sex, stage and nodal metas-tasis (p > 0.05), except for the tumor size (p= 0.04). Conclusion: The HSP27 concentration increased in patients with malignant salivary gland tumors. Moreover, the HSP27 level was correlated with tumor growth, invasiveness, and diagnosability. Yet, larger clinical studies are required to explore its prognostic value.

Oral Squamous Cell Carcinoma: The Role of BIRC6 Serum Level.

Background: Different factors are involved in the incidence, etiology, metastasis, diagnosis, and treatment of oral squamous cell carcinoma, including apoptosis inhibitor proteins. Baculoviral IAP repeat containing protein 6 (BIRC6) is one of the apoptosis inhibitor proteins contributing to cancer cells' survival in many cancer types with diagnostic and treatment importance. This study is aimed at assessing the serum level of BIRC6 in oral squamous cell carcinoma. Materials and Methods: In this retrospective cross-sectional study, 60 serum samples were collected from 45 male and 15 female patients with a mean age of 61 years as the case group and 28 serum samples of healthy people as a control group. The serum samples were analyzed using a commercial sandwich ELISA kit. Results: There were no significant differences between BIRC6 serum levels in patients and healthy subjects. Moreover, we did not observe any significant relationships between BIRC6 serum levels and the patients' demographic or clinical characteristics. Conclusions: There was no significant difference in serum BIRC6 levels in patients with oral squamous cell carcinoma and healthy individuals. Its use in determining the prognosis of squamous cell carcinoma or considering it a determinant marker in this type of cancer may not have a place. More in-depth studies for evaluating BIRC6 serum levels in oral squamous cell carcinoma patients are recommended for better insight into this protein's role in diagnosing, progression, and prognosis of the disease.

Combinatorial effects of telmisartan and docetaxel on cell viability and metastatic gene expression in human prostate and breast cancer cells.

The epithelial-to-mesenchymal transition (EMT) is a unique process resulting in enhanced cell motility, invasiveness, and metastasis in cancer. The EMT is regulated by several transcription factors, including Snail and Slug, which exert crucial roles during cancer progression. We have studied the effects of Docetaxel as the first-line chemotherapy agent for prostate cancer, and Telmisartan as an anti-hypertensive drug on the expression level of Snail and Slug. In addition, the effects of Docetaxel, Telmisartan and their combination on cancer cell proliferation were investigated. The PC3, DU145, MDA-MB468, and HEK cell lines were used for this study. Quantitative RT-PCR analysis and MTT assay were used to study the expression of Snail and Slug level and cell proliferative assay, respectively. We found that a combination of Docetaxel + Telmisartan effectively inhibits the cell proliferation in cancerous cells in comparison with each drug alone (P<0.05). Furthermore, in these cell lines, Docetaxel, Telmisartan and their combination significantly diminished the expression level of Snail and Slug genes compared to control cells (P<0.001), however, in the HEK cell line, this effect was seen only in the combination group. Our data imply that Telmisartan and its combination with Docetaxel exert strong inhibitory effects on the expression level of Snail and Slug genes. Also, these drugs and their combination could inhibit cancer cell proliferation. In conclusion, the combination of Telmisartan and Docetaxel has the potential to suppress the metastasis of prostate and breast cancer cells.

Comparing Castability of Nickel-Chromium, Cobalt-Chromium, and Non-Precious Gold Color Alloys, Using two Different Casting Techniques.

Statement of the Problem: The castability of nonprecious gold color alloy using torch/ centrifugal and induction/vacuum-pressure casting techniques has not been studied yet. Purpose: This study was conducted to compare the castability of nickel chromium, cobalt-chromium and nonprecious gold color alloy using torch/centrifugal and induction/ vacuum-pressure casting techniques. Materials and Method: In this in vitro study, a total number of 54 identical acrylic wax meshes were prepared and divided into 6 different groups of 9 each. Group 1: nickel-chromium alloy, which was casted with induction technique. Group 2: nickel-chromium alloy was casted with centrifugal technique. Group 3: cobalt-chromium alloy was casted with induction technique. Group 4: cobalt-chromium alloy was casted with centrifugal technique. Group 5: nonprecious gold color alloy was casted with induction technique. Group 6: nonprecious gold color alloy was casted with centrifugal technique. Then castability of specimens was measured using modified Whitlock's method. The results were analyzed using two way ANOVA and post hoc tests. Results: ANOVA test revealed no statistically significant difference between different alloys with a p Value of 0.313. Moreover, it represented no significant differences within the groups regarding alloy types and casting techniques with a p Value of 0.511 and 0.682, respectively. Conclusion: No significant difference was found in the castability value of nickel-chromium, cobalt-chromium, and nonprecious gold color alloys. In addition, the castability value of three alloys tested in this study was not different by using torch/centrifugal or induction/vacuum-pressure casting machines.

Effect of folic acid and vitamin E on promoter DNA methylation and expression of TGF-ß1, ESR-1 and CDH-1 in the uterus of STZ-induced diabetic rats.

The present study is the first attempt made to investigate the effects of diabetes on expression and promoter DNA methylation of TGF-ß1, ESR-1, and CDH-1 genes and also the effects of folic acid (FA) and vitamin E (Vit E) supplementations on improving diabetes mellitus. STZ-induced diabetic rats were treated with Vit E (200 mg/kg/day) and FA (25 mg/kg/day) for 8 weeks and expression and DNA methylation of TGF-ß1, ESR-1, and CDH-1 genes in uterus were analysed. Data indicated that diabetes increases the expression of TGFß-1 and ESR-1 and decreases CDH-1 expression and TGFß-1 promoter methylation in the uterus of rats. Vit E and FA improved the negative effects of diabetes by decreasing the expression of TGFß-1 and ESR-1 and increasing that of CDH-1 in diabetic rats. In conclusion, these findings emphasise that Vit E and FA supplementations could improve negative effects caused by diabetes on uterus function and fertility in diabetic rats.

Combination Effect of Caffeine and Caffeic Acid Treatment on the Oxidant Status of Ectopic Endometrial Cells Separated from Patients with Endometriosis.

BACKGROUND: Endometriosis is a common gynecological disease in which oxidative stress is a potential factor. Caffeine and caffeic acid are present in various foods and beverages with anti-oxidant, anti-inflammatory, and anti-carcinogenic properties. In this study, we aimed to investigate the ameliorative effects of caffeine, caffeic acid, and caffeine+caffeic acid treatments on oxidative stress in ectopic endometrial cells taken from patients and eutopic ones from women without endometriosis. METHODS: In this experimental study, eutopic and ectopic endometrial cells were obtained from biopsies of women free of disease (n=10) and patients with endometriosis (n=10) who referred to Shiraz reference hospitals (2017-2018). Both eutopic and ectopic endometrial cells were divided into four groups: Treated with caffeine, with caffeic acid, with caffeine+caffeic acid, and the control. Also, antioxidant enzyme activities and the levels of glutathione (GSH) and malondialdehyde (MDA) were determined in each group. The data were analyzed using independent sample t test and one-way ANOVA followed by Tukey post-hoc test. RESULTS: Caffeic acid, but not caffeine treatment demonstrated a decrease in MDA level (P<0.001) as well as an increase in GSH level (P<0.001) and antioxidant enzyme activities in ectopic endometrial cells. Also, the treatment of the cells with caffeine+caffeic acid caused similar effects as those ectopic cells treated with caffeic acid. CONCLUSION: According to the findings of the present study, caffeic acid reduced oxidative stress which may alleviate the complications associated with endometriosis. However, more investigations are needed for evaluating the efficiency and safety of caffeic acid.

Nicotine-Induced Oxidative Stress in Human Primary Endometrial Cells.

Nicotine is a major component of tobacco plants and is responsible for the development of reproductive problems in smokers. Nicotine has been recognized to result in oxidative stress by inducing the generation of reactive oxygen species (ROS) in some parts of female reproductive system, but the effect of nicotine on endometrium that plays an important role in reproductive biology stays unexplored. The aim of this work was to clarify the direct effects of nicotine administration on the antioxidant defense system and lipid peroxidation in human endometrial cells. Human endometrial stromal primary cells were treated with nicotine (0, 10-11, 10-8, and 10-6 M) for 24 hours. On nicotine administration, the endometrial cells were associated with a decrease in antioxidant defense markers such as Glutathione (GSH) level, glutathione peroxidase (GPx), glutathione reductase (GR), and catalase (CAT) enzymes activity and higher levels of malondialdehyde (MDA) in a dose-dependent manner when compared to the control. We concluded that nicotine as a pro-oxidant affects the oxidative state of the endometrial cells.

Evaluation of Glypican-3 expression in benign and malignant salivary gland tumors.

INTRODUCTION: Glypican-3 (GPC3) is involved in regulation of cell proliferation and morphogenesis. It is abundant in embryonic tissue, but limited in most adult tissues. GPC3 deletion or mutation can disturb the balance between cell apoptosis and proliferation, which may result in tumorigenesis. This study aimed to investigate the GPC3 expression in salivary gland tumors (SGTs) and the adjacent non-neoplastic tissues. METHODS: This study reviewed 50 samples of salivary tumors from the archive of Khalili Hospital, Shiraz, Iran, including 17 cases of pleomorphic adenoma (PA), 16 cases of mucoepidermoid carcinoma (MEC), and 17 cases of adenoid cystic carcinoma (ACC); as well as a control group of 23 cases of normal salivary gland tissues. GPC3 expression was investigated through immunohistochemistry. RESULTS: GPC3 expression was significantly higher in malignant tumors (MEC and ACC) than in PA, and higher in PA than in the normal salivary glands (P < 0.001). The expression intensity was moderate to strong in malignant tumors and weak to moderate in benign tumors. No strong positivity was observed in normal salivary gland tissues (P < 0.001). Nor was any association detected between the GPC3 expression and intensity with the clinicopathologic parameters. CONCLUSION: Although GPC3 overexpression was observed at the protein level in SGTs, and its expression was not related with the clinicopathologic factors, the potential use of GPC3 for diagnostic, therapeutic, and prognostic purposes requires further investigations.

Investigation of IL-33 serum levels in patients with benign and malignant salivary gland tumors.

BACKGROUND: Interleukin-33 (IL-33) has been recently discovered as an influential factor in the process of tumor immunity, and is presented in cancer pathogenesis. OBJECTIVE: This study aimed to determine the serum levels of IL-33 in patients with benign and malignant Salivary gland tumors (SGTs). METHODS: This descriptive cross-sectional study was performed on 47 samples of malignant SGTs including 18 mucoepidermoid carcinoma (MEC), 8 adenoid cystic carcinoma (ADCC), 21 malignant mixed tumor (MMT), and 14 benign pleomorphic adenoma (PA). A control group was considered consisting of 28 healthy subjects. The serum level of IL-33 was measured by using sandwich ELISA method. The data were statistically analyzed through Kruskal-Wallis and Mann-Whitney tests. RESULTS: The median concentration of IL-33 was 6.91 in malignant, 5.14 in benign, and 5.01 in healthy cases, with a statistically significant difference (P= 0.001). The median serum levels of IL-33 increased significantly in ADCC (7.15), MEC (7.03), and MMT (6.91) compared with the control group (5.01) (P< 0.05). The mean rank of MEC was significantly higher than PA (P= 0.01). IL-33 concentration was positively and significantly correlated with the tumor stage (P= 0.02) and tumor size (P= 0.03). CONCLUSIONS: IL-33 could be suggested as a novel biomarker to distinguish different types of SGTs.

Evaluation of Midkine Expression in Dentigerous Cysts, Odontogenic Keratocysts and Different Types of Ameloblastoma.

OBJECTIVE: Midkine is a heparin-binding growth factor whose expression is increased in most tumors, namely ameloblastomas. This study aimed to compare Midkine expression in different odontogenic lesions. MATERIAL AND METHOD: This analytical cross-sectional study was performed on 52 definitely diagnosed odontogenic lesions including 15 dentigerous cysts, 13 odontogenic keratocysts, and 17 unicystic and 5 multicystic ameloblastomas archived from 1997 to 2015. Midkine expression was examined in tissue samples through immunohistochemistry. The nonparametric Kruskal-Wallis and Mann-Whitney tests were run as appropriate (P < 0.05). RESULTS: The frequency of Midkine expression was < 20% in 7.7%, 20-50% in 25%, and > 50 % in 67.3% of the samples, indicating significant differences among the groups (P = 0.002). Moreover, the expression intensity was strong in 63.5%, moderate in 23.1%, and weak in 13.5% of odontogenic lesion samples (P = 0.071). The total staining score was weak in 3.8%, moderate in 48.1%, and strong in 48.1% of the cells, displaying significant differences between the study groups in this regard (P = 0.043). CONCLUSION: Midkine can be considered as both a differentiating factor and a molecular-targeted therapy in odontogenic lesions. Yet, further studies are required to approve the role of this cytokine in different biological and pathological stages of the tumors.

Combination of vitamin E and folic acid ameliorate oxidative stress and apoptosis in diabetic rat uterus.

This study was designed to assess oxidative damage and cell apoptosis in the uterus of rats with streptozotocin (STZ)-induced diabetes. The role of vitamin E (VE) and/or folic acid (FA) in the protection from such damage was also evaluated. The treatments were performed for 4 weeks on six groups of rats: 1) normal control 2) diabetic control 3) diabetic rats receiving olive oil as a vehicle (without VE) 4) diabetic rats treated with VE (200 mg/kg) in olive oil 5) diabetic rats treated with FA (25 mg/kg) and 6) diabetic rats treated with VE+FA (200 and 25 mg/kg, respectively). We measured the malondialdehyde level (MDA), glutathione content (GSH) and the activity of GSH peroxidase (GPx), GSH reductase (GR) and catalase. Changes in caspase-3 activity were quantified in uterine tissue to assess the rate of apoptosis. In the rat uterine tissues, MDA content and caspase-3 activity were significantly elevated, while GPx, GR and CAT activities and the GSH level were significantly decreased in the diabetic control compared with those in normal rats (p<0.05). The combination of the vitamins (VE+FA) restored uterine GSH content and enzymatic activities of GPx, GR and CAT and reduced the MDA level (p<0.05). A prominent reduction in apoptosis of uterine cells was detected in diabetic rats treated with two vitamins (p<0.05). Overall, VE alone, not FA, produced results similar to those of the VE+FA combination. Thus, in the uterine tissue of diabetic rats, diabetes complications (that are caused by oxidative damage and apoptosis induction) can be prevented by the systemic administration of VE and FA.