Gene/protein expression of CAPN1/2-CAST system members is associated with ERK1/2 kinases activity as well as progression and clinical outcome in human laryngeal cancer.

Recent evidence indicates the involvement of calpains (CAPNs), a family of cysteine proteases, in cancer development and progression, as well as the insufficient response to cancer therapies. The contribution of CAPNs and regulatory calpastatin (CAST) and ERK1/2 kinases to aggressiveness, disease course, and outcome in laryngeal cancer remains elusive. This study was aimed to evaluate the CAPN1/2-CAST-ERK1/2 enzyme system mRNA/protein level and to investigate whether they can promote the dynamic of tumor growth and prognosis. The mRNA expression of marker genes was determined in 106 laryngeal cancer (SCLC) cases and 73 non-cancerous adjacent mucosa (NCLM) controls using quantitative real-time PCR. The level of corresponding proteins was analyzed by Western Blot. SLUG expression, as indicator of pathological advancement was determined using IHC staining. Significant increases of CAPN1/2-CAST-ERK1/2 levels of mRNA/protein were noted in SCLC compared to NCLM (p < 0.05). As a result, a higher level of CAPN1 and ERK1 genes was related to larger tumor size, more aggressive and deeper growth according to TFG scale and SLUG level (p < 0.05). There were also relationships of CAPN1/2 and ERK1 with incidences of local/nodal recurrences (p < 0.05). An inverse association for CAPN1/2, CAST, and ERK1/2 transcripts was determined with regard to overall survival (p < 0.05). In addition, a higher CAPN1 and phospho-ERK1 protein level was related to higher grade and stage (p < 0.05) and was found to promote worse prognosis. This is the first study to show that activity of CAPN1/2- CAST-ERK1/2 axis may be an indicator of tumor phenotype and unfavorable outcome in SCLC.

Comparative evaluation of the diagnostic value of the VHIT and Dix-Hallpike test in patients with balance system disorders in out-patient healthcare practice and expertise preparation.

INTRODUCTION: The aim of the paper was the comparative analysis of the diagnostic value of the Video Head Impulse Testing (VHIT) Ulmer I and Dix-Hallpike Test in patients with balance system disorders in out-patient practice and expertise preparation. MATERIAL AND METHODS: The examination was performed in 63 patients aged 20-79, including 28 women aged 20-72 and 35 men aged 23-79, divided into two groups: Group I (study group) - 33 patients with mixed cause vertigo (on the basis of the Fitzgerald-Hallpike caloric test during the VNG examination), and Group II (reference group) - 30 healthy patients. After the ENT interview and physical examination, exclusion of pathological lesions in the external acoustic meatus and middle ear, each patient was subjected to a Fitzgerald-Hallpike caloric test during VNG examination, as well as a VHIT test and Dix-Hallpike test, with the evaluation of eyeball reaction during head rotation. RESULTS: In the group of patients with mixed-cause vertigo (Group I), the Fitzgerald-Hallpike caloric test showed unilateral labyrinth deficiencies in 90.9% of the patients (with the average value of 41.8%) and relative directional preponderance with the average value of 19.0%, while in 9.1% of the patients, the detected values of labyrinth excitability were normal. In the examination of patients with vertigo, benign paroxysmal positional vertigo was diagnosed in 9.1% of cases. This diagnosis was based on the positive response to the Dix-Hallpike manoeuvre and indicative of damage to the posterior semicircular canal in the VHIT test (without signs of deficiency in the VNG examination). CONCLUSION: The VHIT test and Dix-Hallpike test enable quick and precise detection of benign paroxysmal positional vertigo in out-patient practice and expertise preparation.