Elevated Syndecan-1 levels in the sera of patients with breast cancer correlate with tumor size.

BACKGROUND: Breast cancer is the leading type of cancer in Iranian women and affects them at least one decade younger than their counterparts in developed countries. Breast tumor progression and metastasis is accompanied by a decrease in the membranous expression of Syndecan-1 and an increase in its shedding. We measured the level of soluble Syndecan-1 in the sera of Iranian patients with breast cancer. METHODS: The study population included 61 chemotherapy-naïve breast cancer patients and 30 age/sex-matched healthy individuals. Blood was collected by venipuncture method and serum was separated, aliquoted and kept at -40 °C until used. A commercial ELISA was used to detect Syndecan-1 levels in the sera. RESULTS: Soluble Syndecan-1 levels were increased in the sera of patients with breast cancer compared to healthy controls (87.89 ± 89.29 vs. 47.57 ± 46.46 ng/ml, p = 0.005). There was a positive correlation between soluble Syndecan-1 levels and tumor size (p = 0.017). The serum level of Syndecan-1 in patients without calcification showed a trend of increase compared to that of patients with calcification (108.80 ± 101.76 vs. 59.82 ± 57.13 ng/ml). CONCLUSION: The positive correlation between soluble Syndecan-1 levels and tumor size in the present study highlights the importance of different varieties (cell-bound and soluble) of this molecule in the breast tumor progression and their significance as tumor biomarkers.

Circulating Levels of M30 and M65 Molecules in Transitional Cell Carcinoma of the Bladder and Their Relation to Tumor Progression.

BACKGROUND: Various markers are suggested for diagnosis and monitoring of transitional cell carcinoma of the bladder (TCC), including cytokeratins (CKs). OBJECTIVES: In the present study, the circulating CK18 (M65) and its caspase-cleaved form, ccCK18 (M30), have been investigated in a group of patients with TCC. PATIENTS AND METHODS: Serum samples were obtained from 60 patients before surgical resection, among which the samples of 26 patients after resection were also included. We measured the levels of soluble M30 and M65 molecules by enzyme-linked immunosorbent assay. The relation between these markers and patients' clinical characteristics was evaluated. RESULTS: M30 and M65 in total patient sera were 148 ± 16 U/L and 318 ± 34 U/L, respectively. A correlation existed between pre-operative M30 and M65 levels (P < 0.0001, Spearman r = 0.51). M65, but not M30, showed a significant relation to tumor stage and grade. The M65 quantity in patients with T3/T4 tumor stages (350 ± 42 U/L) was higher than that of patients with T1/T2 stages (293 ± 45U/L; P < 0.038). Patients with tumor grades III/IV also showed higher levels of M65 compared to patients with tumor grades I/II (P < 0.04). The M30:M65 ratio in all patients was 0.54 ± 0.04. There was a lower M30:M65 ratio in patients with T3/T4 stage tumors and those with tumor grades III/IV (P < 0.02). The M30 (133 ± 19 U/L) and M65 levels (240 ± 21 U/L) after surgery did not significantly differ compared to their pre-operative values. However, a correlation between the pre- and post-operative M30:M65 ratio in patients ≥ 70 years was seen (P = 0.009). CONCLUSIONS: These data suggested a relationship of both M65 and the M30:M65 ratio to tumor progression which might imply their importance in TCC monitoring.

Reduced serum levels of syndecan-1 in patients with tongue squamous cell carcinoma.

OBJECTIVES/HYPOTHESIS: To investigate soluble syndecan-1 (Sdc-1) in the sera of patients with tongue squamous cell carcinoma (SCC) and its correlation with the histopathological criteria of tumors. STUDY DESIGN: In a case-control study using a convenient method of sampling, 18 female and 25 male patients with confirmed diagnosis of tongue SCC, and 19 healthy females and 27 males were studied. METHODS: Soluble Sdc-1 was measured in the sera of 43 patients with tongue SCC and was compared with that of healthy age-/sex-matched controls using a commercial enzyme-linked immunosorbent assay. Clinical and pathological data, along with the demographic characteristics of the patients, were recorded at the time of sampling. RESULTS: The levels of soluble Sdc-1 were decreased in the sera of patients compared to controls (91.17 ± 88.60 vs. 158.17 ± 103.47 ng/mL, P = .002). Although patients who smoke tended to have higher grades (P = .043), there was no significant difference in the level of syndecan-1 between smokers and non-smokers. A significant difference between syndecan-1 in the sera of patients with tumors of different stages was observed (Kruskal-Wallis test P=0.039); however, scarcity of patients in stages I and III decreased the power of the comparison. CONCLUSIONS: Sdc-1 levels in the sera of patients do not correlate with the tumor progression in the tongue SCC. This is in contrast with the reported inverse correlation between the expression level of membranous Sdc-1 and the histological grade and size of head and neck tumors. Therefore, Sdc-1 shedding may not be a major mechanism in the progressive loss of its expression regarding tongue tumor. LEVEL OF EVIDENCE: NA Laryngoscope, 126:E191-E195, 2016.

In vitro inhibitory effects of thymol and carvacrol on dendritic cell activation and function.

CONTEXT: Thyme has been used in traditional medicine for medicinal purposes since ancient times. OBJECTIVE: The objective of this study was to investigate the effects of thymol and carvacrol as two major constituents of thyme on dendritic cells (DCs) maturation and T cell activation. MATERIALS AND METHODS: Splenic DCs were treated with non-cytotoxic concentrations of the components and then analyzed for MHC II, CD86, and CD40 expression by flow cytometry. The effects of compounds on mitogenic, as well as allogenic T cell responses in mixed lymphocyte culture (MLR) and the release of cytokines were investigated. RESULTS: At 0.1 µg/ml, reduced mean fluorescent intensity (MFI) of CD86 for thymol (80.3 ± 0.2% of untreated control) and CD40 for carvacrol (79.5 ± 0.14%) was observed (p < 0.001). Decreased mitogenic T cell proliferation by thymol [proliferation index (PI) from 0.93 ± 0.11 at 1 µg/ml to 0.42 ± 0.16 at 100 µg/ml (p < 0.01)] and carvacrol [PI from 1.08 ± 0.3 at 1 µg/ml to 0.28 ± 0.1 at 100 µg/ml (p < 0.001)] was seen. Ten micrograms/ml thymol (PI, 0.85 ± 0.04) and carvacrol (PI, 0.89 ± 0.03) inhibited allogenic T cell response (p < 0.05). Decreased IFN-γ level in MLR supernatant from 1441 ± 27.7 pg/ml in untreated cells to 944 ± 32.1 at 10 µg/ml of thymol and of carvacrol (886 ± 31.7 pg/ml) (p < 0.01) was found. IL-4 levels were decreased in the presence of both compounds (p < 0.01). CONCLUSION: These data showed the suppressive effects of thymol and carvacrol on DCs maturation and function, as well as T cell responses.

IL-17A Levels in the Sera of Patients with Gastric Cancer Show Limited Elevation.

BACKGROUND: Inflammation plays a major role in the development and progression of gastric and other gastrointestinal tumors. The IL-17 family of cytokines has been under investigation as targets of immunotherapy. MATERIALS AND METHODS: We investigated the levels of IL-17A inflammatory cytokine in the sera of 57 patients with gastric cancer (GC) and 90 healthy age/sex matched controls using ELISA methods. RESULTS: In only 5 (8.8%) of the patients' sera was IL-17A detectable. No IL-17A was apparent in the sera of healthy controls. The maximum concentration of IL-17A in patients was 7.004 pg/ml. Vascular and lymphatic invasions were only seen in one of the 5 positive cases. Although all of them were in the age group >60 years, no correlation was seen between age and IL-17A level. These results are somewhat different from our findings for colorectal cancer (CRC) in the same population. CONCLUSIONS: It is possible that the inflammopathology of CRC and GC are rather different, at least in Fars, a southern province of Iran.

Investigating the Association of IL-17A and IL-17F with Susceptibility to Pre-eclampsia in Iranian Women.

BACKGROUND: Pre-eclampsia (PE) is one of the most important and life-threatening pregnancy disorders that affect at least 3-5% of all pregnancies. Imbalance in helper T cell functions may play a role in predisposing to PE or severity of the disease. Elevated frequencies of Th17 cells in the peripheral blood of PE patients have been reported. Several single nucleotide polymorphisms (SNP) within IL-17 gene have been identified that may affect the IL-17 production. OBJECTIVES: To investigate the association between IL-17A (-197A/G) and IL-17F (+7488T/C) gene polymorphisms and susceptibility to PE in a group of Iranian women. Moreover, to study any correlation of the polymorphisms data with the level of IL-17, at mRNA level in the paternal and maternal parts of the placentas and also at protein level in the peripheral and placental blood samples. METHODS: A group of 261 PE patients and 278 age-matched healthy women with at least two previous normal pregnancies formed the cases and controls of this study. IL-17A (-197A/G) and IL-17F (+7488T/C) polymorphisms were genotyped using PCR-RFLP method. The protein level of IL-17A was assessed in the sera of 40 PE and 40 healthy women using ELISA method and mRNA expression was also measured in placental samples of 19 PE and 19 control women using Q-PCR technique. RESULTS: Statistical analysis indicated that there were no differences in genotype, allele or haplotype frequencies regarding the studied SNPs between cases and controls. The level of IL-17A was elevated in the placental blood and the fetal tissue at protein and mRNA levels (p< 0.009 and p<0.000, respectively) in PE as compared with the healthy women. CONCLUSIONS: The effect of IL-17 cytokine in pre-eclampsia is not due to the studied cytokine polymorphisms but local production of IL-17 might have an effect on the predisposition to the disease.

The frequency of follicle stimulating hormone receptor gene polymorphisms in Iranian infertile men with azoospermia.

BACKGROUND: Azoospermia is the medical condition of a man not having any measurable level of sperm in his semen. Follicle stimulating hormone (FSH) is a member of the glycoprotein hormone family that plays an important role in human reproduction because of its essential role in normal spermatogenesis. Various Single Nucleotide Polymorphisms (SNPs) have been reported within FSH receptor (FSHR) gene that may affect the receptor function. OBJECTIVE: The present study aimed to investigate the correlation between two FSHR SNPs at positions A919G, A2039G, and susceptibility to azoospermia in a group of Iranian azoospermic men. The association between FSH levels within the sera and A919G and A2039G alleles and genotypes were also investigated. MATERIALS AND METHODS: This case control study was performed on 212 men with azoospermia (126 non-obstructive and 86 obstructive) and 200 healthy Iranian men. Two FSHR gene SNPs were genotyped using PCR-RFLP method. The relationship between FSH levels within the sera and A919G and A2039G alleles and genotypes were also investigated. RESULTS: Statistical analysis indicated that at A919G position, AA genotype and A allele were more frequent in obstructive azoospermia cases compared to non-obstructive or normal men (p=0.001). Regarding A2039G polymorphisms, no significant difference was observed between both azoospermia groups and the controls. The mean level of serum FSH was higher in the non-obstructive men compared to the obstructive patients (23.8 versus 13.8, respectively, p= 0.04). CONCLUSION: The results of the present study indicated that the genetic polymorphisms in the FSHR gene might increase the susceptibility to azoospermia in Iranian men.

Apoptosis in transitional cell carcinoma of bladder and its relation to proliferation and expression of p53 and bcl-2.

Transitional cell carcinoma of bladder (TCC) is a relatively common cancer among men. Tumor progression is associated with expression or modulation of several gene products that control apoptosis and proliferation. Apoptosis is a negative growth regulatory mechanism in tumors. The aim of this study is to examine apoptosis and related regulatory molecular markers in a group of patients with TCC. Paraffinembedded tissues from 49 patients with TCC were examined for the expression of bcl-2, p53 and Ki-67 by immunohistochemistry. Apoptosis was detected by TUNEL method. Correlation between apoptotic index (AI), proliferation index (PI) and bcl-2 and p53 expression with each other and with pathological grade was determined. Apoptosis was observed in 28.1% of TCC cases. The mean AI of all cases was 13.7+/-24. No correlation was found between apoptosis and differentiation status of carcinoma. Bcl-2 expression was weakly detected in only one sample. P53 expression was detected in 26 of cases with mean staining index of 102+/-96. A significant correlation between p53 and Ki-67 staining indices was observed (r=0.521, p=0.001). Both p53 and Ki-67 expression showed a good association with the pathological grade (p=0.0001 and p=0.004, respectively). None of the markers showed significant correlation with AI and no correlation was found between the ratio of AI to PI and other parameters either. In conclusion, the frequency of apoptosis in TCC of bladder appears not to be associated with tumor grade, and with bcl-2, p53 and Ki-67 expression.