RNAs in tumour-derived extracellular vesicles and their significance in the tumour microenvironment.

Small extracellular vesicles (sEVs) secreted by various types of cells serve as crucial mediators of intercellular communication within the complex tumour microenvironment (TME). Tumour-derived small extracellular vesicles (TDEs) are massively produced and released by tumour cells, recapitulating the specificity of their cell of origin. TDEs encapsulate a variety of RNA species, especially messenger RNAs, microRNAs, long non-coding RNAs, and circular RNAs, which release to the TME plays multifaced roles in cancer progression through mediating cell proliferation, invasion, angiogenesis, and immune evasion. sEVs act as natural delivery vehicles of RNAs and can serve as useful targets for cancer therapy. This review article provides an overview of recent studies on TDEs and their RNA cargo, with emphasis on the role of these RNAs in carcinogenesis.

Quality of life in patients after vestibular schwannoma surgery.

AIM: To evaluate the most important factors of quality of life in patients after vestibular schwannoma surgery. MATERIALS AND METHODS: Patients with unilateral sporadic occurrence of vestibular schwannoma who underwent surgery via suboccipital-retrosigmoid approach were included in the prospective study (2018-2021). Patients after previous Leksell gamma knife irradiation (or other methods of stereotactic radiosurgery) were excluded. Quality of life was assessed using 10 validated questionnaires that were distributed preoperatively, 3 months and 1 year after the surgery. RESULTS: A total of 76 patients were included in the study, complete data were analysed in 43 of them (response rate 57%). Grade III and IV represented up to 70% of all tumors. Patients with larger tumors had a significantly higher risk of postoperative facial nerve paresis, liquorrhea and lower probability of hearing preservation. Patients with smaller tumors and those, who suffered from headaches before surgery had more frequent and severe headaches after surgery. Postoperative headaches were associated with higher incidence of anxiety and tinnitus. More frequent anxiety was also identified in patients with preoperative serviceable hearing who became deaf after surgery. Nevertheless, tinnitus and hearing impairment appeared to have less impact on overall quality of life compared to headaches and facial nerve function. CONCLUSION: According to our results, tumor size, postoperative function of the facial nerve and occurrence of postoperative headaches had the greatest influence on the overall postoperative quality of life in patients after vestibular schwannoma surgery.

Hemihypoglossal-facial nerve anastomosis: results and electromyographic characterization.

INTRODUCTION: The facial nerve surgery belongs to the basic procedures during lateral skull base approaches. Its damage has serious medical and psychological consequences, and therefore mastery of reconstruction and correction techniques should belong to the repertoire of skull base surgeons. The goal of this study was to demonstrate usefulness of electromyographic follow-up in facial nerve reconstruction. MATERIAL AND METHODS: A total of 16 patients underwent hemihypoglossal-facial anastomosis between 2005 and 2017. Most of the primary lesions came from vestibular schwannoma surgery. All patients were examined with electromyography and scored according to the House-Brackmann and IOWA grading scales. Function of the tongue has been evaluated. RESULTS: Ten patients achieved definitive House-Brackmann grade 3 score (62.5%). We did not observe any association with the patient's age, previous irradiation and the etiology of the damage. Electromyography showed pathological spontaneous activity after the first surgery. Incipient regeneration potentials were detected in 4-17 months (average 7.6) and reached maximum in 6.5-18 months (average 16). Electromyographic assessment of the effect of tongue movement showed better mimic voluntary activity by swallowing or by moving the tongue up. There was no relationship between the start of activity and the interval to achieving maximal activity. CONCLUSION: Hemihypoglossal-facial nerve anastomosis is a safe procedure and it is an optimal solution for cases lacking a proximal stump or in the case of reconstruction in the second stage. Electromyography can predict initial reinnervation activity after reconstructive procedures. During subsequent follow-up it can help to discover insufficiently recovering patients, however clinical characteristics are crucial.

Sensitivity to Cisplatin in Head and Neck Cancer Cells Is Significantly Affected by Patient-Derived Cancer-Associated Fibroblasts.

Cancer-associated fibroblasts (CAFs) are one of the most abundant and critical components of the tumor stroma. CAFs can impact many important steps of cancerogenesis and may also influence treatment resistance. Some of these effects need the direct contact of CAFs and cancer cells, while some involve paracrine signals. In this study, we investigated the ability of head and neck squamous cell carcinomas (HNSCC) patient-derived CAFs to promote or inhibit the colony-forming ability of HNSCC cells. The effect of cisplatin on this promoting or inhibiting influence was also studied. The subsequent analysis focused on changes in the expression of genes associated with cancer progression. We found that cisplatin response in model HNSCC cancer cells was modified by coculture with CAFs, was CAF-specific, and different patient-derived CAFs had a different "sensitizing ratio". Increased expression of VEGFA, PGE2S, COX2, EGFR, and NANOG in cancer cells was characteristic for the increase of resistance. On the other hand, CCL2 expression was associated with sensitizing effect. Significantly higher amounts of cisplatin were found in CAFs derived from patients who subsequently experienced a recurrence. In conclusion, our results showed that CAFs could promote and/or inhibit colony-forming capability and cisplatin resistance in HNSCC cells via paracrine effects and subsequent changes in gene expression of cancer-associated genes in cancer cells.

The evaluation of vestibular compensation by vestibular rehabilitation and prehabilitation in short-term postsurgical period in patients following surgical treatment of vestibular schwannoma.

PURPOSE: Vestibular schwannoma removal causes unilateral vestibular deafferentation, which results in dizziness and postural unsteadiness. Vertigo and balance problems together are among the most important aspects affecting quality of life. Intensive vestibular rehabilitation, which starts before surgery, with following postsurgical supervised rehabilitation, using visual biofeedback propose an instrument to accelerate a recovery process. Another option how to accelerate the vestibular compensation, is employment of presurgical gentamicin ablation together with vestibular rehabilitation (prehabilitation) of vestibular function. Purpose of present study was to examine the dynamics of vestibular compensation process using supervised intensive vestibular rehabilitation with visual biofeedback in the short-term postsurgical period. The second aim was to compare both studied groups mainly to evaluate if prehabilitation has potential to accelerate the compensation process in the early postoperative course. METHODS: The study included 52 patients who underwent the retrosigmoid vestibular schwannoma removal. They were divided into two groups. The first group was prehabilitated with intratympanic application of gentamicin before surgery to cause unilateral vestibular loss (14 patients), the second group (38 patients) was treated in standard protocol without prehabilitation. All patients underwent at home vestibular training before surgery to learn new movement patterns. Following the surgery supervised intensive vestibular rehabilitation including visual biofeedback was employed daily in both groups between the 5th and 14th postoperative day. Outcome measurements included an evaluation of subjective visual vertical (SVV), posturography and the Activities-Specific Balance Confidence Scale (ABC). ANOVA for repeated measurements was used for statistical analysis. RESULTS: We observed significant improvement in SVV (p < 0.05), posturography parameters (p < 0.05) and ABC scores (p < 0.05) with postoperative rehabilitation program following surgery in both groups. There was no statistically significant difference between group treated by prehabilitation and group without prehabilitation. CONCLUSIONS: Results of this study showed that intensive postsurgical rehabilitation represents key factor in compensation process following retrosigmoid vestibular schwannoma surgery. Prehabilitation did not speed up recovery process.

Baha implant as a hearing solution for single-sided deafness after retrosigmoid approach for the vestibular schwannoma: audiological results.

Skull base tumors and, in particular, vestibular schwannoma (VS) are among the etiological reasons for single-sided deafness (SSD). Patients with SSD have problems in understanding speech in a noisy environment and cannot localize the direction of sounds. For the majority, this is the handicap for which they try to find a solution. Apart from CROS hearing aids, Baha is one of the most frequently used systems for SSD compensation. 38 patients with single-sided deafness after retrosigmoid removal of a vestibular schwannoma underwent testing with a Baha softband from September 2010 to August 2014. Sixteen patients (42 %) finally decided to accept Baha implantation. Subjective experience with the Baha softband was evaluated by patients using the BBSS questionnaire immediately after testing. Objective evaluation of the effect was performed as a measurement of the sentence discrimination score in noise and side horizontal discrimination without a Baha and 6 weeks and 12 months after a sound processor fitting. There was a significant improvement in sentence discrimination in the 6 week (64.0 %) and 1 year (74.6 %) interval of follow-up in comparison with understanding without Baha (24.0 %, p = 0.001) in situations when sentences are coming from the side of the non-hearing ear and noise contralaterally with SNR -5 dB. Baha can significantly improve sentence discrimination in complex-listening situation in patients with SSD after the VS surgery.

Baha implant as a hearing solution for single-sided deafness after retrosigmoid approach for the vestibular schwannoma: surgical results.

Skull base tumors and, in particular, vestibular schwannoma (VS) are among the etiological reasons for single-sided deafness (SSD). Patients with SSD have problems in understanding speech in a noisy environment and cannot localize the direction of sounds. Baha is one of the most frequently used systems for SSD compensation. Out of 38 patients with SSD after retrosigmoid removal of VS who underwent testing with Baha softband, 16 were satisfied and were indicated for Baha implantation. Two surgical approaches have been used-the Nijmegen linear incision technique with subdermal thinning (Group I, implant BI300) and fast surgery technique without subdermal thinning (Group II, implant BIA400). The duration of the surgery, the implant stability measured by Ostell, and skin or soft tissue reactions in long range follow-up were evaluated and compared between Group I and II. There was a difference in duration of surgery, in Group II procedures averaged significantly faster (p > 0.001). In both groups, there was a similar trend of the gradual increase of implant stability. In the Group I and II, there was comparable rate of the skin or soft tissue reactions grade 0, I, II, or III. We have proved Baha to be a suitable possibility for SSD patients after the removal of VS, regardless of the approach. After the retrosigmoid approach to the VS, the key step of Baha implantation must be to reach intact healthy bone to avoid implantation into scar tissue.

[30 years of the cochlear implantations in the Czech Republic]. / 30 let kochleárních implantací v Ceské republice.

Cochlear implant is the unique sensory neuroprosthesis and still the only one used in clinical praxis. The function of the inner ear is replaced with direct electrical stimulation of the cochlear nerve. It is 30 years since the first cochlear implantation has been performed with the Czech single-channel cochlear neuroprosthesis. There are more than one thousand users of cochlear implants in the Czech Republic nowadays. Cochlear implants have become a standard of care of patients with severe hearing loss. It allows user inclusion to the society with only a minimum of obstacles.Key words: cochlear implant, history, neuroprosthesis, severe hearing loss.

Detection of Helicobacter pylori in oropharyngeal lymphatic tissue with real-time PCR and assessment of its carcinogenic potential.

Helicobacter pylori (HP) is considered a major gastric pathogen with oncogenic potential. The aim of this study was to determine whether HP is present in oropharyngeal lymphoid tissue and whether oropharyngeal HP strains carry virulence factor genes known to be involved in gastric carcinogenesis. The study included 104 subjects (41 patients with tonsillar carcinoma, 38 with chronic tonsillitis and 25 with obstructive sleep apnoea syndrome--OSAS). Detection of specific serum anti-HP antibodies was performed with an ELISA. The presence of HP in tissue was determined by culture and real-time PCR. Detection of virulence factors genes was also performed. Specific antibodies were found in 78.05% of tumour cases, 34.21% of chronic tonsillitis cases, and 72.0% of OSAS cases. The presence of HP in the tissue was detected in 73.91% of tonsillar tumours, 70.0% of tonsillitis cases, and 69.23% of OSAS specimens. The results of the virulence factor gene analysis showed the majority of the s1b (52.4%) and m2 (59.5%) alleles of vacA gene and limited abundance of cagA gene (12.5%). Results confirm that HP may colonise oropharyngeal lymphoid tissue. Oropharyngeal HP colonisation was frequently found in the oropharyngeal cancer group and in patients with benign oropharyngeal diseases. A virulence factor gene analysis showed differences from the predominant strains most commonly found in the stomach. The strains obtained from the oropharynx differed primarily by the lower abundance of the cagA gene and carried the less virulent vacA gene allele combination.

Presence of different genotypes of Helicobacter pylori in patients with chronic tonsillitis and sleep apnoea syndrome.

Helicobacter pylori, a well-known gastric pathogen, has been detected in the oral cavity and oropharynx in tonsillar tissue. In our study, the presence of H. pylori in the tonsillar tissue of patients with chronic tonsillitis and sleep apnoea syndrome (SAS) was investigated. The aim was to detect and genotype H. pylori for a collection of data supporting the possible role of H. pylori in the aetiology of chronic tonsillitis and SAS. Helicobacter pylori was detected by real-time polymerase chain reaction (rt-PCR). 89 patients, 60 with a diagnosis of chronic tonsillitis and 29 with SAS, were tested. In the chronic tonsillitis group, Helicobacter was detected in 48 (80 %) specimens, cagA gene was detected in 12 samples (25 %) and 12 samples were negative. In SAS group, Helicobacter was found in 24 samples (82.76 %), cagA gene was detected in 5 (20.83 %) and 5 samples (17.24 %) were negative. Helicobacter pylori-specific immunoglobulins were tested by ELISA in the serum of 57 patients only with 41 (71.93 %) showing positive. Our results on H. pylori DNA detection and H. pylori seropositivity show 26.32 % discrepancy, slightly in favour of rt-PCR (15.79 % compared to 10.53 %). The H. pylori presence in tonsillar tissue does not depend on the type of oropharyngeal disease (p = 0.756). This study shows that oropharynx constitutes an extragastric reservoir of H. pylori infection which could serve as an aetiopathogenetic factor for chronic tonsillitis and tonsillar hyperplasia by SAS. No conclusion has yet been drawn about the mechanism of the process.

Upregulation of IL-6, IL-8 and CXCL-1 production in dermal fibroblasts by normal/malignant epithelial cells in vitro: Immunohistochemical and transcriptomic analyses.

BACKGROUND INFORMATION: Considering an analogy between wound healing and tumour progression, we studied chemokine and cytokine transcription and expression in normal fibroblasts by co-culture and in situ. RESULTS: Whole-genome transcriptome profiling revealed strong upregulation for the interleukin (IL)-6, IL-8 and the chemokine CXCL-1 in in vitro co-cultures of normal fibroblasts with either normal or malignant epithelial cells compared to fibroblast cultures. The same ILs/chemokines were distinctly upregulated in clinical samples of squamous cell carcinoma when compared with paired normal mucosae. Analysis of culture supernatants showed that during the course of co-culture of the fibroblasts with the epithelial cells, IL-6, IL-8 and CXCL-1 were secreted to the culture medium. Experiments with addition of any of the proteins to the culture medium supported the notion that these ILs/chemokines strongly contributed to maintenance of a low-differentiation phenotype of epithelial cells, evaluated by the detection of keratin-8. Simultaneous addition of all factors increased the extent of the effect. These studies were extended by experiments with epithelial cells, either cultured in medium conditioned by preceding use for malignant keratinocytes without and in the presence of normal or cancer-associated fibroblasts or medium containing antibodies against IL-6, IL-8 and CXCL-1. CONCLUSIONS: Our results indicate an analogy between wound healing and tumour growth, support the importance of epithelial-mesenchymal interaction in this model system and establish a potential bio-inspired anticancer therapy.

Impact of video-endoscopy on the results of retrosigmoid-transmeatal microsurgery of vestibular schwannoma: prospective study.

Endoscopy-assisted microsurgery represents modern trend of treatment of the cerebellopontine angle (CPA) pathologies including vestibular schwannoma (VS). Endoscopes are used in adjunct to microscope to achieve better functional results with less morbidity. Angled optics, magnification and illumination enable superior view in the operative field. Consecutive 89 patients with untreated unilateral sporadic vestibular schwannoma undergoing tumor resection via a retrosigmoid approach during 2008-2010 were prospectively analysed. Endoscopy-assisted microsurgical (EA-MS) removal was performed in 39 cases (Grade 1: 2, Grade 2: 5, Grade 3: 9, Grade 4: 22, Grade 5: 1) and microsurgical (MS) removal was performed in 50 cases (Grade 1: 1, Grade 2: 3, Grade 3: 9, Grade 4: 34, Grade 5: 3). Minimally invasive approach with craniotomy ≤ 2.5 cm was employed for small tumors (Grade 1 and 2) in the EA-MS group. Endoscopic technique was used for monitoring of neuro-vascular anatomy in CPA, during dissection of the meatal portion of tumors, assessment of radicality and for identification of potential pathways for CSF leak formation. All cases in MS group were deemed as radically removed. In the EA-MS group, residual tumor tissue in the fundus of internal auditory canal not observable with microscope was identified with endoscope in four cases. Such cases were radicalized. Tumor recurrence was not observed during the follow-up in EA-MS group. There is a suspicious intrameatal tumor recurrence on the repeated MRI scan in one patient in the MS group. Neither mortality nor infection was observed. The most common complication was pseudomeningocele (EA-MS 20 cases; MS 23). It was managed with aspiration with or without tissue-gluing in all cases without the need for any surgical revision. Adjunctive use of endoscope in the EA-MS group identified potential pathways for CSF leak formation, which was not observable with the microscope in five patients. Improved cochlear nerve (EA-MS: 22, MS: 14; p = 0.012), brainstem auditory evoked potentials (EA-MS: 3 of 8, MS: 0 of 4) and hearing (EA-MS: 14 of 36, MS: 4 of 45; p = 0.001) preservation were observed in EA-MS group. Despite the trend for better useful hearing (Gardner-Robertson class 1 and 2) preservation (EA-MS: 8 of 26, MS: 1 of 16) there were no significant differences in the postoperative hearing handicap inventory in both groups. There were no differences in the postoperative tinnitus in both groups. Better facial nerve preservation (EA-MS: 39, MS: 44; p = 0.027) and excellent-very good (House-Brackmann 1 or 2) facial nerve function (EA-MS: 31, MS: 29; p = 0.035) were observed in EA-MS group. Postoperative compensation of vestibular lesion, symptoms typical for VS, patients assessed by dizziness handicap inventory, facial disability index were comparable in both studied groups. Adjunctive use of endoscope during the VS surgery due to its magnification and illumination enable superior view in the operative field. It is valuable for assessment of radicality of resection in the region of internal auditory meatus. Improved information about critical structures and tumor itself helps the surgeon to preserve facial nerve and in selected cases also hearing. These techniques can help to decrease incidence of postoperative complications.

Which Epidemiological Characteristics Drive Decision Making in the Management of Patients with Vestibular Schwannoma?

The incidence of sporadic vestibular schwannoma has significantly increased over the past few decades. However, there is no method currently available to accurately predict the risk of subsequent tumor growth. The difference in the management of five patient groups has been evaluated: wait and scan, conversion to microsurgery, conversion to stereoradiotherapy, sterioradiotherapy, and microsurgery. In total, 463 patients with vestibular schwannoma have been consulted in our department from 2010 through 2016. Of the 250 patients initially indicated for observation, 32.4% were later indicated for active treatment. Younger patients were more frequently indicated for surgery (mean age 48 years) compared to older patients, who were more often indicated for stereoradiotherapy (mean age 62 years). Tumor growth was observed more often in patients under 60 years of age and in patients with tumors greater than 10 mm. In elderly patients, including those with larger tumors, a conservative approach is the optimal solution. If tumor growth occurs in the wait-and-scan strategy, it is still possible to continue with a conservative approach in some situations. The duration of follow-up scans is still a matter of debate, as tumors can begin to grow after 5 years from the initial diagnosis.

Hearing After Vestibular Schwannoma Surgery: Is It Preserved Forever?

INTRODUCTION: Currently, it is possible to preserve the auditory nerve in a large number of cases, but the preservation of the hearing itself is unpredictable. Apart from wait and scan strategy and stereoradiotherapy, hearing after vestibular schwannoma surgery is considered to remain stable even in long-term follow-up. MATERIALS AND METHODS: Twenty-eight patients had preserved hearing after retrosigmoid suboccipital microsurgery of the vestibular schwannoma between 2008 and 2014. A standard audiological protocol was performed together with an magnetic resonance imaging evaluation of the fluid content of the inner ear. RESULTS: The mean difference in pure-tone average between the direct and final postsurgical examination was 12.758 dB ( p = 2.5E - 06). The word recognition score deteriorated by 17.45% ( p = 0.03516). The mean American Academy of Otolaryngology-Head and Neck Surgery score on the second examination was 2.5, and that on the second examination was 3.111 ( p = 0.00483). There was no significant deterioration in the healthy ear.The signal intensity ratio in the basal turn of the cochlea increased by an average of 0.13 points ( p < 0.05).Patients with persistent tumor or nodular enhancement in the internal acoustic meatus deteriorated significantly in hearing according to the American Academy of Otolaryngology-Head and Neck Surgery scale compared with patients without any finding in the meatus ( p = 0.01299). CONCLUSIONS: There is a discrete but gradual deterioration of the hearing in the postoperative period. Hearing impairment is more pronounced in patients with a nodular process in the internal acoustic meatus, regardless of whether it is growth active. After surgery, the pathological content of the inner ear normalizes (evaluated on T2 magnetic resonance imaging sequences).

High incidence of occult familial SDHD cases amongst Czech patients with head and neck paragangliomas.

Introduction: Head and neck paragangliomas (HNPGLs) are rare neuroendocrine tumors, which are mostly benign in nature. Amongst all genes, Succinate Dehydrogenase Subunit D (SDHD) is the most commonly mutated in familial HNPGLs. In about 30% of HNPGLs, germline mutations in SDHD can also occur in the absence of positive family history, thus giving rise to "occult familial" cases. Our aim was to evaluate the pattern of SDHD germline mutations in Czech patients with HNPGLs. Materials and methods: We analyzed a total of 105 patients with HNPGLs from the Otorhinolaryngology departments of 2 tertiary centers between 2006 - 2021. All underwent complex diagnostic work-up and were also consented for genetic analysis. Results: Eighty patients aged 13-76 years were included; around 60% with multiple PGLs were males. Carotid body tumor was the most frequently diagnosed tumor. Germline SDHD mutation was found in only 12% of the Czech patients; approximately 78% of those harboring the mutation had negative family history. The mutation traits had higher affiliation for multiple tumors with nearly 70% patients of ≤ 40 years of age. Conclusion: An SDHD mutation variant was shared amongst unrelated patients but no founder-effect was established. Our findings confirmed that the pattern of SDHD mutation distribution amongst HNPGLs in Czech Republic differs from most studies worldwide.

Efficacy and Safety of Intranasal Betahistine in the Treatment of Surgery-Induced Acute Vestibular Syndrome: A Double-Blind, Randomized, Placebo-Controlled Phase 2 Study.

OBJECTIVE: To evaluate the safety and efficacy of AM-125 nasal spray (intranasal betahistine) in the treatment of surgery-induced acute vestibular syndrome (AVS). STUDY DESIGN: Prospective, double-blind, randomized, placebo-controlled exploratory phase 2 study with dose escalation (part A) followed by parallel dose testing (part B); open-label oral treatment for reference. SETTING: Twelve European study sites (tertiary referral centers). PATIENTS: One hundred and twenty-four patients 18 to 70 years old undergoing surgery for vestibular schwannoma resection, labyrinthectomy or vestibular neurectomy with confirmed bilateral vestibular function presurgery and acute peripheral vertigo postsurgery. INTERVENTIONS: AM-125 (1, 10, or 20 mg) or placebo or betahistine 16 mg p.o. t.i.d. for 4 weeks, starting 3 days postsurgery; standardized vestibular rehabilitation. MAIN OUTCOME MEASURES: Tandem Romberg test (TRT) for primary efficacy, standing on foam, tandem gait, subjective visual vertical and spontaneous nystagmus for secondary efficacy, Vestibular Rehabilitation Benefit Questionnaire (VRBQ) for exploratory efficacy; nasal symptoms and adverse events for safety. RESULTS: At treatment period end, mean TRT improvement was 10.9 seconds for the 20-mg group versus 7.4 seconds for the placebo group (mixed model repeated measures, 90% confidence interval = 0.2 to 6.7 s; p = 0.08). This was corroborated by nominally higher frequency of complete spontaneous nystagmus resolution (34.5% vs. 20.0% of patients) and improvement in the VRBQ; the other secondary endpoints showed no treatment effect. The study drug was well tolerated and safe. CONCLUSIONS: Intranasal betahistine may help accelerate vestibular compensation and alleviate signs and symptoms of vestibular dysfunction in surgery-induced AVS. Further evaluation in a confirmatory manner appears warranted.

Smooth muscle actin-expressing stromal fibroblasts in head and neck squamous cell carcinoma: increased expression of galectin-1 and induction of poor prognosis factors.

Tumor stroma is an active part influencing the biological properties of malignancies via molecular cross-talk. Cancer-associated fibroblasts play a significant role in this interaction. These cells frequently express smooth muscle actin and can be classified as myofibroblasts. The adhesion/growth-regulatory lectin galectin-1 is an effector for their generation. In our study, we set the presence of smooth muscle actin-positive cancer-associated fibroblasts in relation to this endogenous lectin and an in vivo competitor (galectin-3). In squamous cell carcinomas of head and neck, upregulation of galectin-1 presence was highly significantly correlated to presence of smooth muscle actin-positive cancer-associated fibroblasts in the tumor (p = 4 × 10(-8)). To pinpoint further correlations on the molecular level, we applied microarray analyses to the transcription profiles of the corresponding tumors. Significant correlations of several transcripts were detected with the protein level of galectin-1 in the cancer-associated fibroblasts. These activated genes (MAP3K2, TRIM23, PTPLAD1, FUSIP1, SLC25A40 and SPIN1) are related to known squamous-cell-carcinoma poor-prognosis factors, NF-κB upregulation and splicing downregulation. These results provide new insights into the significance of presence of myofibroblasts in squamous cell carcinoma.

Hearing improvement after vestibular schwannoma surgery in the era of the hearing preservation rule - case report and literature review.

OBJECTIVES: Hearing preservation after vestibular schwannoma (VS) surgery remains a surgical challenge. In some patients with preserved inner ear function, hearing improvement is achievable. As it is currently impossible to determine which patients will present this outcome, predictions must rely on previously published reports. Our case report describes a patient who experienced hearing improvement from an unuseful level to a useful one after vestibular schwannoma surgery. METHODS: Surgery was performed via suboccipital retrosigmoid approach. The patient underwent a basic audiovestibular protocol before and after the surgery - pure tone and speech audiometry, otoacoustic emissions, auditory brainstem responses, electronystagmography - together with a detailed questionnaire study. Usefulness of hearing was evaluated using the AAO-HNS guidelines, supplemented by a frequency of 4 kHz. RESULTS: Hearing was preserved and even improved from an unuseful level to a useful one. Based on the available literature, the most informative predictive factors for such a result seem to be: sudden sensorineural hearing loss prior to surgery, elicitable otoacoustic emissions and the origin from the superior vestibular nerve. CONCLUSION: There are a limited number of studies on this topic and it is still impossible to regularly improve hearing in properly selected patients. Furthermore, the importance of postoperative hearing quality compared to other symptoms and complications remains debatable.

Tumor Biology and Microenvironment of Vestibular Schwannoma-Relation to Tumor Growth and Hearing Loss.

Vestibular schwannoma is the most common benign neoplasm of the cerebellopontine angle. It arises from Schwann cells of the vestibular nerve. The first symptoms of vestibular schwannoma include hearing loss, tinnitus, and vestibular symptoms. In the event of further growth, cerebellar and brainstem symptoms, along with palsy of the adjacent cranial nerves, may be present. Although hearing impairment is present in 95% of patients diagnosed with vestibular schwannoma, most tumors do not progress in size or have low growth rates. However, the clinical picture has unpredictable dynamics, and there are currently no reliable predictors of the tumor's behavior. The etiology of the hearing loss in patients with vestibular schwannoma is unclear. Given the presence of hearing loss in patients with non-growing tumors, a purely mechanistic approach is insufficient. A possible explanation for this may be that the function of the auditory system may be affected by the paracrine activity of the tumor. Moreover, initiation of the development and growth progression of vestibular schwannomas is not yet clearly understood. Biallelic loss of the NF2 gene does not explain the occurrence in all patients; therefore, detection of gene expression abnormalities in cases of progressive growth is required. As in other areas of cancer research, the tumor microenvironment is coming to the forefront, also in vestibular schwannomas. In the paradigm of the tumor microenvironment, the stroma of the tumor actively influences the tumor's behavior. However, research in the area of vestibular schwannomas is at an early stage. Thus, knowledge of the molecular mechanisms of tumorigenesis and interactions between cells present within the tumor is crucial for the diagnosis, prediction of tumor behavior, and targeted therapeutic interventions. In this review, we provide an overview of the current knowledge in the field of molecular biology and tumor microenvironment of vestibular schwannomas, as well as their relationship to tumor growth and hearing loss.

mRNA Subtype of Cancer-Associated Fibroblasts Significantly Affects Key Characteristics of Head and Neck Cancer Cells.

Head and neck squamous cell carcinomas (HNSCC) belong among severe and highly complex malignant diseases showing a high level of heterogeneity and consequently also a variance in therapeutic response, regardless of clinical stage. Our study implies that the progression of HNSCC may be supported by cancer-associated fibroblasts (CAFs) in the tumour microenvironment (TME) and the heterogeneity of this disease may lie in the level of cooperation between CAFs and epithelial cancer cells, as communication between CAFs and epithelial cancer cells seems to be a key factor for the sustained growth of the tumour mass. In this study, we investigated how CAFs derived from tumours of different mRNA subtypes influence the proliferation of cancer cells and their metabolic and biomechanical reprogramming. We also investigated the clinicopathological significance of the expression of these metabolism-related genes in tissue samples of HNSCC patients to identify a possible gene signature typical for HNSCC progression. We found that the right kind of cooperation between cancer cells and CAFs is needed for tumour growth and progression, and only specific mRNA subtypes can support the growth of primary cancer cells or metastases. Specifically, during coculture, cancer cell colony supporting effect and effect of CAFs on cell stiffness of cancer cells are driven by the mRNA subtype of the tumour from which the CAFs are derived. The degree of colony-forming support is reflected in cancer cell glycolysis levels and lactate shuttle-related transporters.