Aberrations in Wnt signaling pathway are related to the pathogenesis of head and neck carcinomas and their activation frequently results from epigenetic alterations. This study aimed to assess the ...frequency of the methylation of DAB2, which acts as a negative regulator of Wnt signaling, and correlate it with clinicopathological features in a group of oral cancer patients.
Forty nine patients with primary oral squamous cell carcinoma were enrolled in the study. DNA samples were isolated from surgical sections using phenol-chloroform extraction. Methylation-specific PCR was used to detect gene promoter methylation.
The analysis of the occurrence of DAB2 promoter methylation in primary oral carcinomas indicated that the gene is methylated in 70% of cases. However, no correlation was found between its methylation and TNM staging or overall survival.
Our findings corroborate that DAB2 is a frequent target of epigenetic silencing in oral carcinomas and may be potentially used for tumor detection.
Objectives
Aberrations in Wnt and Shh signaling pathways are related to the pathogenesis of head and neck carcinomas, and their activation frequently results from epigenetic alterations. This study ...aimed to assess the frequency of methylation of negative regulators of Wnt signaling:
CXXC4
,
DACT2
,
HDPR1
, and
FBXW11
and Shh signaling:
HHIP
,
PTCH1
,
SUFU
,
ZIC1
, and
ZIC4
and correlate it with clinicopathological features in this group of patients.
Materials and methods
Methylation-specific PCR was used to detect gene promoter methylation, and real-time PCR was used to assess gene expression level.
Results
The analysis of the occurrence of gene promoter methylation in head and neck carcinoma cell lines indicated that
CXXC4
,
DACT2
,
HHIP
,
ZIC1
, and
ZIC4
are methylated in these tumors. These genes were further analyzed in tumor sections from oral and laryngeal cancer patients. Gene methylation rate was higher in laryngeal tumors. The methylation index in tumor samples correlated with the overall survival in a subgroup of oral cancer patients who died of the disease. Moreover,
ZIC4
methylation correlated with lymph node involvement in oral cancer patients.
Conclusions
Our findings corroborate that the activation of Wnt signaling in head and neck squamous cell carcinoma (HNSCC) is related to epigenetic silencing of its negative regulators. Moreover, the results indicate that the same mechanism of activation may operate in the case of Shh signaling.
Clinical relevance
The methylation of
ZIC4
may be considered a new prognostic marker in oral cavity and oropharyngeal tumors. Further investigations should determine the diagnostic significance of methylation of
ZIC4
,
HHIP
, and
DACT2
in head and neck carcinomas.
The deregulation of Wnt signaling has recently emerged as one of the drivers of head and neck cancers. This is frequently related to the methylation of several antagonists of this pathway. This study ...aimed at the assessment of the profile of methylation of Wnt pathway antagonists and the determination of the prognostic value of the methylation of selected genes in oral carcinomas. The methylation of
DACH1
,
DKK1
,
LKB1
,
PPP2R2B
,
RUNX3
,
SFRP2
, and
WIF-1
was analyzed in 16 oral squamous cell carcinoma cell lines using the methylation-specific polymerase chain reaction. The methylation of selected genes was further analyzed in tumor sections from 43 primary oral carcinoma patients. The analysis of oral carcinoma cell lines showed very frequent methylation of
SFRP2
and
WIF-1
and also a less frequent methylation of
DACH1
and
DKK1
. On the other hand,
RUNX3
was methylated only in one cell line, while
LKB1
and
PPP2R2B
were not methylated in any of the cell lines
.
The biallelic methylation of
DKK1
correlated with the low level of expression of this gene. Further evaluation of the methylation of
DACH1
,
DKK1
, and
WIF1
in a clinical patient group confirmed the frequent methylation of
WIF1
and intermediate or low frequency of methylation of
DACH1
or
DKK1
, respectively. Importantly, the methylation of
WIF-1
correlated with shorter survival in oral cancer patients. Overall, the methylation of the antagonists of Wnt pathway is frequently detected in oral squamous cell carcinomas. The methylation of
WIF1
may be considered a prognostic marker in oral cancers.
Unilateral sinus disease (USD) occurs in 23 % of all cases. It is believed that it is mainly associated with cancer development. Retrospective data from large rhinological centers show that the most ...common USD is chronic rhinosinusitis (CRS), followed by mycosis, inverted papilloma and finally cancer, but only in a small percent of cases.
The analysis of USD in the group of patients who underwent FESS at the secondary referral center.
The retrospective study of patients treated for USD in the Department of Otolaryngology in the Provincial Hospital in Poznan between June 2014 and June 2016. The analysis includes age, sex, the localization of lesions, histopathological and microbiological results, an extension of the surgery and treatment results.
Over the analyzed period of time, 415 FESS for chronic sinusitis were performed. In this group, 83 patients underwent surgery for USD. There were 35 women and 48 men.CRS was found in 48 cases, mycosis in nine cases, 12 patients were operated for non-malignant tumors, such as inverted papilloma (9), osteoma (2) and fibrosis tumor(1); seven patients had a choanal polyp and two of them had a foreign body in maxillary sinus - a tooth root lying loose. Four patients were diagnosed with a hypoplastic maxillary sinus and one patient suffered from frontal sinus pyocele. One side endoscopic opening of all sinuses was performed in the group with CRS, endoscopic medial maxillectomy was conducted in patients with inverted papilloma, and an isolated opening of the affected sinus was performed in the cases with mycosis.
USD must be always suspected of malignant degeneration until proven otherwise. Endoscopic sinus surgery with the use of angled scope allows for the removal of even very extensive lesions. In our opinion, the extent of operation is determined by the nature of pathology. While extensive surgery is recommended in patients with inverted papilloma, a limited procedure should be performed in those with isolated mycosis.
Oral and oropharyngeal cancers are characterized by relatively low 5- year survival rates due to many factors, including local recurrence. The identification of new molecular markers may serve for ...the estimation of prognosis and thus augment treatment decisions and affect therapy outcome. The aim of this study was to describe the morphological characteristics and the DNA methylation status of the CDKN2A,CDH1, ATM, FHIT and RAR- genes in the central and peripheral part of the tumor and the surgical margin and evaluate their prognostic significance. 53 patients with oral and oropharyngeal cancer were enrolled to the prospective study, and had been primarily treated surgically. Correlations between morphological data, hypermethylation status and clinicopathological data, as well as prognosis, were assessed. Nuclei polymorphism highly correlated with T stage (
p
< 0.0001), N stage (
p
< 0.046), and metastases to the lymph nodes pN (
p
< 0.004 ). Also, the number of cells in irregular mitosis correlated with T stage (
p
< 0.004), and highly with pN (
p
< 0.009). The significance of CDKN2A hypermethylation as a good prognostic factor was also established in the Kaplan-Meir test. The ultrastructural analysis showed that none of the examined tumors had homogenous texture and that resection margin specimens clean in HE stained tissue samples frequently contained single tumor cells or few cells in groups surrounded by connective tissue. This indicates the superiority of electron microscopy over standard histopathological analysis. Thus, a combination of such morphological examination with epigenetic parameters described herein could result in the discovery of promising new prognostic markers of the disease.
Stapes surgery is performed using both conventional techniques and a variety of laser systems. The Er-Yag laser is a type of pulsation laser deemed by many to be the safest for ear surgery. The aim ...of this study was to assess the long-term effects of using the Er-Yag laser in stapes surgery and its impact on inner ear function. The study was conducted on 95 ears (48 right and 47 left) that had undergone Er-Yag laser-assisted stapedotomy. The follow-up time was at least 3 years. Pure tone audiometry was performed on all patients. The frequency ranged from 125 to 8,000 Hz. Air conduction and bone conduction were both assessed. Moreover, all patients had their stapedius reflex assessed and were given a Rinne test. The results were evaluated according to the Committee on Hearing and Equilibrium guidelines and then statistically analyzed using the Wilcoxon sequence pair test with a
p
value of <0.05. A decrease in the hearing threshold of 0.5, 1, and 3 kHz, for both bone and air conduction was observed for all patients (
p
< 0.0001). The Wilcoxon sequence pair test revealed a statistically significant correlation between the pre- and postoperative treatment mean air-bone gap values (
p
< 0.0001). No facial nerve paralysis was observed. No Er-Yag laser side effects were observed on inner ear function. The patients also had lower hearing thresholds. These observations demonstrate the usefulness of Er-Yag lasers in stapes surgery.
Laminins are a family of glycoproteins that consist of one heavy α chain and two light β and γ chains. The laminin molecule is a major component of the basement membrane and plays an important roles ...in cell differentiation, adhesion, and migration. It has been reported that laminin is strongly expressed at the invasive front of the tumor and plays an important role in forming the metastases. The aim of the study was to assess the importance of laminin expression in a group of patients with laryngeal carcinoma and neck metastases. The study was carried out on 70 patients with squamous cell carcinoma of the larynx treated at the ENT Department University of Medical Sciences in Poznań. The clinical data consisted of sex, age, stage of the tumor, and histological and immunohistochemical studies. The average time of the follow-up was 3 years. The immunohistochemical study was performed using formalin-fixed and paraffin-embedded tissue sections. Monoclonal mouse anti-human laminin (DAKO, code no. MO638) antibodies were used for immunohistochemistry. To evaluate the laminin staining, a four-point grading system were used: score 0, continuous; score 1, loss of staining <10%; score 2, loss of staining <50%; score 3, loss of staining >50%. The correlation between staining intensity of the laminin and the presence of neck metastases (classified as N-positive “N+” and N-negative “N−”neck) was calculated. All parameters underwent statistical analysis. The patients with advanced clinical disease dominated in our material. Most of the tumors were classified as T3 and T4. A total of 36 patients had metastases to the regional lymph nodes. Positive laminin staining was observed in 62 cases. There was no correlation between laminin staining and occurrence of neck metastases in our studied group (30 N+ and 32 N−). The gravity level in Wilcoxon test was at
P
< 0.000001 and in Spearman rank order correlation was statistically not significant (
P
> 0.09).
The aim of the study was to compare 2 laser systems, Er-Yag and CO2, in stapes surgery.
The study design was retrospective.
The study was conducted at an academic tertiary referral center.
There were ...88 women and 34 man in the analyzed group. The study was carried out on 142 ears: 52 on the right ear, 50 on the left ear, and 20 bilateral. Forty-seven ears underwent a CO2 laser-assisted stapedotomy, and 95 underwent Er-Yag-assisted stapedotomy; 23 left and 24 right ears were operated on using the CO2 laser. The Er-Yag laser was used in 48 right and 47 left ears. The follow-up time was at least 1 year.
When the postoperative air-bone gap was compared with the preoperative air-bone gap for the 2 laser systems using the Student t test, as well as the Mann-Whitney U test, no statistical differences were found between the 2 groups, that is, with the use of Er-Yag and CO2 lasers. Also, no statistically significant differences were measured over all frequencies by the Student t test between preoperative and postoperative bone conduction in each group.
To sum up, our observations have proven the usefulness of 2 laser systems: CO2 and Er-Yag lasers in stapes surgery. In both groups, a decrease in the hearing threshold was obtained.
Chronic sinusitis is one of the most common presenting complaints of all doctor visits in the United States and Europe, with more than 13% of people affected in any given year. This disease has a ...wide range of impact on communities. Patients with recurrent or chronic sinusitis report a deteriorative sense of general health and vitality, when compared to general population. In our Department we perform about 600 functional endoscopic sinus surgeries (FESS) per year. Chronic rhinosinusitis represents a spectrum of inflammatory and infectious processes concurrently affecting the nose and paranasal sinuses. Among chronic paranasal sinusitis one must single out paranasal sinusitis with and without polyps. In the paranasal sinusitis patomechanism the blockage of natural ostium plays one of the most important roles. The closure of sinus proper ventilation passages leads to the triggering of many pathological occurrences within mucous membrane of this region. The treatment of paranasal sinusitis is diversified and involves a surgical procedure as well as anti-inflammatory and antiallergic drugs (medications) and mucolytics. Its purpose is to clear the nose through the elimination of bacterial infection, liquidating and removal of lying discharge and the restoration of the proper muco-ciliary transportation, and through this the improvement of local condition and faster recovery. In this work the usage of carboxycysteine to treat paranasal sinus conditions has been presented.
It was established, that HPV virus (Human Papilloma Virus) is responsible for tumor induction in some anatomical regions of head and neck, mainly in palatine tonsils. The characteristics of ...HPV-related tumors as well as the course of the disease are definitely different compared to tobacco-smoking related tumors; patients HPV-positve have better prognosis - less patients develops recurrences and dies from the disease. There is no full compliance about patients' characteristics, although most indications concern "young adults" with their intensive sexual life. Because the course of HPV-related tumors is milder, there is a need to distinguish the cause of disease to carry on the therapy adjusted to the causative factor. This approach might help to select HPV-negative patients with severe course of disease to apply more aggressive chemotherapy.
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