Tinnitus characteristics in patients with hyperacusis and vertigo (including Ménière's disease) vs. hyperacusis alone.

INTRODUCTION AND OBJECTIVES: To compare clinical and psychoacoustic tinnitus characteristics in patients with the comorbidity of hyperacusis, hyperacusis and vertigo, and with Ménière's disease (MD). MATERIALS AND METHODS: Three hundred and twenty-nine tinnitus patients underwent audiological and otoneurological evaluation. Records of 94 individuals younger than 65 years, 40 women and 54 men (mean age 41.8, range 24-64 years), who complained of tinnitus and hyperacusis, were analyzed. One hundred and thirty-one ears with tinnitus were identified: 67 in the group of patients with tinnitus and hyperacusis (group 1; 41 patients); 28 in the group fulfilling criteria of MD diagnosis (group 2; 28); and 36 in the group with tinnitus, hyperacusis and typical symptoms of vertigo (group 3; 25). RESULTS AND CONCLUSIONS: Mean value of interaural difference in canal paresis in group 1 was 6.3%; in group 2: 23.7%; and in group 3: 25.9%; p<.001. Mean tinnitus pitch value was significantly lower in group 3 (1679Hz; SD=1139) and group 2 (2250Hz; SD=1162) compared to group 1 (4538Hz; SD=3123; p=.012). Values of tinnitus intensity and other characteristics did not significantly differ between the groups. Tinnitus and hyperacusis were most frequently preceded by acoustic trauma. Tinnitus coinciding with hyperacusis and vertigo was observed in patients after head trauma. Mean tinnitus pitch was lower in the groups of patients with hyperacusis and peripheral labyrinthine lesion than in tinnitus sufferers with hyperacusis alone. Tinnitus sufferers with low tinnitus pitch should undergo vestibular system evaluation. Hyperacusis and vertigo are likely comorbidities in tinnitus patients after head trauma. Hyperacusis may coincide in tinnitus patients after head trauma.

Expression of CTLA-4 and Foxp3 in peripheral blood T cells of patients with squamous cell laryngeal carcinoma.

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4, CD152) and Foxp3 (forkhead box P3) are receptors present on T cells which play a critical role in the down-regulation of antigen-activated immune responses. To evaluate the potential influences of CTLA-4 and Foxp3 on cancer invasiveness, a case-control study was conducted in 86 patients treated for squamous cell laryngeal carcinoma. The abundance of CTLA-4 and Foxp3 gene transcripts in the purified peripheral blood mononuclear cells (PBMCs) by quantitative real-time PCR (qRT-PCR) was determined. The analysis of proteins by Western blot was performed. The relationships between CTLA-4 and Foxp3 gene and protein expression as well as the aggressiveness of tumor determined on pT, type and depth of invasion were investigated. Our work revealed a significant dependence of mRNA CTLA-4 on tumor front grading (TFG) total score (p = 0.04) as well as CTLA-4 protein expression on pT (p = = 0.03) and type of invasion (p = 0.03). Advanced pT3-pT4 tumors with diffuse infiltration and > 14 TFG points were characterized by higher average values of CTLA-4 protein in PBMCs. Our data also demonstrated significant differences between Foxp3 protein levels in relation to pT (p = 0.04), depth of invasion (p = = 0.02) and type of invasion (p = 0.03). In tumors with the highest invasiveness identified by the pT3-pT4 status, deep invasion with involvement of cartilage and diffuse infiltration, the highest Foxp3 protein level was observed. In conclusion, these results suggest an impact of CTLA-4 and Foxp3 in determining proliferative and aggressive potential of laryngeal carcinoma, highlighting the significance of CTLA-4 and Foxp3 as potential predictive indicators.

Diagnostic impact of promoter methylation and E-cadherin gene and protein expression levels in laryngeal carcinoma.

AIM OF THE STUDY: Inactivation of the tumor suppressor E-cadherin (CDH1) and its decreased expression is an important occurrence during carcinogenesis. Nevertheless, the relationship of CDH1 expression and the promoter methylation with laryngeal cancer cell aggressiveness is still unclear. The purpose of this study was to elucidate the gene and protein E-cadherin expression and the DNA methylation levels and to describe the correlations with morphological features in squamous cell laryngeal cancer. MATERIAL AND METHODS: The authors studied E-cadherin and the DNA methylation level in 86 cases to gain a further understanding of the clinicopathologic significance of analyzed parameters. The pathological evaluation included pTNM classification and the tumor front grading (TFG) criteria. Quantitative analysis of the amplified product in real time (qRT-PCR) for estimation of CDH1 mRNA was used. The methylation status was investigated by using methyl-specific polymerase chain reaction (MSP). The level of CDH1 protein expression by Western blot was determined. RESULTS: Downregulation of E-cadherin was found to be related to promoter methylation (p < 0.001). In tumors with the highest invasiveness according to TFG criteria the lowest E-cadherin gene and protein level in the study group was observed (p = 0.046 and p = 0.0002, respectively). In SCLC with muscle and cartilage invasion and disperse infiltration the lowest CDH1 gene and protein expression was noted (p = 0.0003 and p = 0.003 for deep invasion, p = 0.033 and p = 0.003 for multifocal infiltration, respectively). CONCLUSIONS: The current findings suggest an association of E-cadherin tumor expression with progression of laryngeal cancer. CDH1 gene level may be an auxiliary molecular marker for advanced cases of laryngeal carcinoma; however, further studies are necessary.

[Analysis of HIF-1α and COX-2 expression in tumor stroma and correlation with the degree of neoplasm invasiveness in laryngeal cancer--preliminary study]. / Analiza ekspresji HIF-1α i COX-2 w utkaniu guza oraz korelacja ze stopniem inwazyjnosci zmian nowotworowych u chorych z rakiem krtani--badania wstepne.

INTRODUCTION: Despite extensive research in the field of molecular biology, immunology and histopathology, prognostically unambiguous morphological indicators of the invasiveness of tumor which allow the prediction of disease course in laryngeal cancer have not yet been identified. The aim of this study was to analyze gene and protein expression of HIF-1a and COX-2 in the tumor stroma and to find relationships between clinical and morphological features (pT, G, depth of tumor invasion, plasmalymphocytic infiltration) and certain markers in squamous cell laryngeal carcinoma. MATERIAL AND METHODS: We analyzed a group of 59 patients with verified squamous cell carcinoma of the larynx. The pathological evaluation was included pTNM classification criteria, depth of invasion according to tumor front grading and degree of morphological differentiation. Quantitative analysis of the amplified product in real time (real-time RT2-PCR) for estimation of mRNA HIF-1a and COX-2 expression in tumor cells were used. The level of HIF-1a and COX-2 protein expression by Western blot analysis was determined. RESULTS: In studied group of laryngeal cancers significant differences in expression of certain molecules analyzed in tumor tissue and noncancerous epithelium of the larynx have been shown. Increased expression of HIF-1a and COX-2 at both mRNA and protein level was indicator of greater aggressiveness of the tumor, evaluated on the basis of clinical and morphological features in laryngeal squamous cell carcinomas. Tumors with the most invasive growth (pT4 stage, low-differentiated tumors G3, neoplastic infiltration with invasion of cartilage of the larynx) had the highest expression of HIF-1a and COX-2 at the mRNA and protein level. CONCLUSIONS: The study pointed out the direction for further research to find unambiguous indicators for estimation of tumor invasiveness and the possibility of practical use of HIF-1a and COX-2 mRNA and protein level assessment as important methods for determining the advancement of clinical and morphological changes in laryngeal cancer, thereby selecting an appropriate model of treatment.

[Expression of Foxp3 and RORgamma t in peripheral blood mononuclear cells in patients with laryngeal carcinoma as indicators of tumor stage--preliminary study]. / Ocena ekspresji Foxp3 i RORgamma t w jednojadrzastych komórkach krwi obwodowej u chorych z rakiem krtani jako wskazników zaawansowania zmian nowotworowych--badania wstepne.

INTRODUCTION: The degree of activation of cells involved in cellular immune response against tumor antigens (cytotoxic lymphocytes Tc) as well as efficiency of the mechanisms which promote immunosuppression (Treg - regulatory cells CD4(+)CD25(+)Foxp3(+)) may determine the course of the neoplastic disease. The aim of this study was to assess the function of autologous peripheral blood mononuclear cells (PBMCs) involved in the immunological processes on the basis of expression of Foxp3 and RORgamma t molecules as well as analysis of the relationships with clinical and morphological features of the tumor (pT and pN stage, G feature, degree of invasiveness according to the TFG classification) in laryngeal carcinoma. MATERIAL AND METHODS: The analysis included a group of 59 patients with verified squamous cell carcinoma of the larynx. In the pathologic evaluation pTNM classification criteria, depth of invasion and degree of histological differentiation were used. Expression levels of mRNA for Foxp3 and RORgamma t in peripheral blood mononuclear cells by quantitative analysis of the amplified product in real time (real-time RT(2)-PCR) were evaluated. The level of Foxp3 and RORgamma t protein expression by Western blot analysis was determined. RESULTS: In squamous cell carcinomas of the larynx, with the highest tumor aggressiveness the significantly highest level of mRNA and protein expression for Foxp3 molecule were observed. The severity of Foxp3 expression at both gene and protein level were positively linearly correlated with the degree of local extent of the tumor (pT3-4), depth of invasion (invasion of cartilage) and the degree of histological differentiation (low-differentiated tumors G3). In the study group of laryngeal cancers significantly lower level of RORgamma t expression in carcinomas with less invasive changes (pT1-2, high-differentiated tumors G1, carcinomas with microinvasion without evidence of invasion beyond the lamina propria) was also noted. CONCLUSIONS: The study results indicate the important role of immune cell activity as indicators of advancement of clinical and morphological changes in squamous cell carcinoma of the larynx.