Overexpression of Laminin 5γ2 Chain Correlates with Tumor Cell Proliferation, Invasion, and Poor Prognosis in Laryngeal Squamous Cell Carcinoma.

Objective: Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor. Laminin 5γ2 chain (LAMC2) was reported to be associated with tumorigenesis. This study explored the role of LAMC2 on LSCC progression by regulating the integrinß1/FAK/Src/AKT pathway. Methods: The level of LAMC2 in 46 LSCC patients was detected by qRT-PCR and western blot. Then the relationship between LAMC2 expression and LSCC malignancy as well as prognosis was analyzed, and the effect of LAMC2 expression on LSCC patient survival was also analyzed using the Kaplan-Meier survival curves. Afterwards, the LSCC cells were transfected with LAMC2 overexpression and knockdown vectors, the effect of LAMC2 on LSCC cell viability, proliferation ability, cell cycle, cell migration, and invasion were detected by CCK-8, colony formation, flow cytometry, wound healing, and Transwell assays. The expression of EMT-related biomarkers and integrin ß1/FAK/Src/AKT signaling-related proteins was detected by western blot. Moreover, the effect of LAMC2 on LSCC tumor growth was evaluated by in vivo xenograft experiments and western blot. Results: LAMC2 was expressed at high level in LSCC tissues and associated with poor prognosis. LAMC2 overexpression increased TU177 cell viability, proliferation ability, promoted cell cycle, cell migration, and invasion capacity. The expression of N-cadherin, vimentin, and integrinß1/FAK/Src/AKT related proteins was increased, while the expression of E-cadherin protein was decreased. When the LAMC2 knockdown in AMC-HN-8 cells had opposite effects. Furthermore, shLAMC2 decreased tumor volume and the expression of LAMC2, Ki-67 and integrinß1, but increased the expression of E-cadherin in LSCC tumor-bearing mice. Conclusion: The findings suggested that LAMC2 was overexpressed in LSCC and correlated with poor prognosis. LAMC2 knockdown inhibited LSCC progression by regulating the integrinß1/FAK/Src/AKT signaling pathway. Therefore, LAMC2 could be a target for LSCC therapy.

KRT17 Accelerates Cell Proliferative and Invasive Potential of Laryngeal Squamous Cell Carcinoma (LSCC) through Regulating AKT/mTOR and Wnt/ß-Catenin Pathways.

Background: Laryngeal squamous cell carcinoma (LSCC) is a prevalent malignant tumor of the head and neck with a dismal prognosis. Keratin17 (KRT17) has been proven to serve as an oncogene in various cancers, but it has never been explored in LSCC. We proposed to assess the impact and possible mechanisms of KRT17 in the development of LSCC. Methods: Quantitative reverse transcription-PCR (qRT-PCR) was utilized to examine the mRNA levels. The Kaplan-Meier method was used to calculate the relationship between KRT17 expression and survival curves in LSCC patients. Cell counting kit-8 (CCK-8), colony formation, and flow cytometry assays were utilized to estimate LSCC cell proliferation. The migration and invasion abilities of LSCC cells were ascertained by wound-healing and transwell assays. Immunohistochemical and western blot assays were utilized to appraise protein levels. The xenograft tumor model was used to determine the effect of KRT17 on tumor growth. Results: In the present study, KRT17 was extremely high in LSCC tissues and cells and correlated with a poor prognosis. Inhibition of KRT17 weakens cell proliferative, migratory, and invasive abilities in LSCC and contributes to cell cycle arrest. Besides, we approved that knockdown of KRT17 extraordinarily restrained the xenograft tumor growth in vivo. We preliminarily investigated the role of KRT17 on the AKT/mTOR and Wnt/ß-catenin signaling axes and found that these signaling pathways were largely blocked by KRT17 deletion. Conclusion: Collectively, we uncovered that exhaustion of KRT17 suppresses LSCC progression through coordinating AKT/mTOR and Wnt/ß-catenin signaling axes, illustrating KRT17 as a promising biomarker for making strides in LSCC treatment.

Postauricular injection of methylprednisolone sodium succinate as a salvage treatment for refractory sudden sensorineural hearing loss.

BACKGROUND: Postauricular steroid administration has been popular for treating sudden sensorineural hearing loss. However, there are few reports on its use in patients with refractory sudden sensorineural hearing loss (RSSNHL). AIMS: The objective of this study was to investigate the therapeutic efficacy of postauricular steroid injection as a salvage treatment for RSSNHL patients. METHODS: This retrospective study enrolled 63 RSSNHL patients between January 2016 and January 2019. Thirty-three patients of them who have been divided into the treatment group received postauricular methylprednisolone sodium succinate injection. The remaining 30 patients who formed the control group did not receive any steroid as a salvage therapy. Improvements in hearing were evaluated between pre-salvage therapy and 3 months follow-up after salvage therapy. RESULTS: The median hearing gain in PTA was 9.88 dB HL (quartile range 7.58, 18.65) in the treatment group and 0.90 dB HL (quartile range 0.00, 4.90) in the control group (P<0.01). According to the criteria of Furuhashi, the total percentage for effective prognosis was 48.48% (16/33) in the treatment group and 10.00% (3/30) in the control group (P<0.01). The time interval from onset to study entry was significantly and independently associated with the prognosis for RSSNHL patients (P< 0.01). CONCLUSIONS: The present findings suggest that postauricular corticosteroid administration as a salvage treatment demonstrated better results than no treatment for RSSNHL patients. The time interval from onset to study entry was mainly the prognostic factor for RSSNHL patients. It is therefore considered that postauricular corticosteroid administration may be used as a salvage therapy for RSSNHL patients.

Positive therapy of andrographolide in vocal fold leukoplakia.

PURPOSE: Vocal fold leukoplakia is a premalignant precursor of squamous cell carcinoma. Although many efforts have been contributed to therapy of this disease, none exhibits a satisfactory result. The aims of this study were to investigate the effectiveness and feasibility of andrographolide therapy in vocal fold leukoplakia and to explore the preliminary mechanism underlying. MATERIALS AND METHODS: Forty-one eligible patients were enrolled in the study. The patients were treated for 10-minute exposures of 5 ml (25mg/ml) andrographolide injection aerosols twice a day, and 2 weeks was considered as one treatment course. Electronic laryngoscope was used to observe the condition of vocal fold leukoplakia during the treatment. Every patient received one or two treatment courses, and the follow-up was carried out for 12 months. Toxic reactions of treatments were evaluated on the basis of the standards of the United States MD Anderson Cancer Center. Moreover, laryngeal carcinoma cell line Hep2 was applied to explore the mechanism of effect of andrographolide. Anti-proliferative effect on Hep2, cell nuclear morphology, express of mitogen-activated protein kinases (MAPK) and pro-apoptotic protein were detected after andrographolide treatment. RESULTS: We found that andrographolide exhibited significant curative effects on treatments, which were accompanied by thinning of the lesion of leukoplakia, reduction in the whitish surface area, and return of pink or red epithelium. A complete response up to 85% was observed, and no toxic side effect events occurred during the study. No patient with a complete response had a recurrence in the follow-up. Moreover, cellular experiments in Hep2 indicated that andrographolide activated MAPK pathway and caspase cascade, and finally induced apoptosis in laryngeal carcinoma cell. CONCLUSIONS: The advantages of andrographolide are connected with minimally invasive and localized character of the treatment and no damage of collagenous tissue structures, which are more convenient and less painful for patients. These results suggest that andrographolide treatment is a viable strategy for curing vocal fold leukoplakia.