Effects of hepatocyte growth factor-transfected mesenchymal stem cell transplantation in canine injured vocal folds.

This study aimed to assess the efficacy of hepatocyte growth factor (HGF)-transfected adipose-derived mesenchymal stem cell (ADSC) transplantation in the injured vocal folds (VFs) of canines. A lentiviral vector encoding HGF was successfully produced via Gateway cloning, which was used to infect ADSCs. Four weeks after transoral laser microsurgery (type II) with CO2 laser, the beagles of each group were injected with HGF-transfected ADSCs or uninfected ADSCs into VFs. The results showed that the retention of HGF-transfected ADSCs in the VFs persisted about three months post-injection. The VFs in the HGF-transfected ADSCs group exhibited a closer-to-normal structure with less collagen deposition and higher amounts of hyaluronic acid (HA) in the third month. The short microvilli in the HGF-transfected ADSCs group showed a dense and uniform distribution. These results revealed that HGF-transfected ADSC is a potential treatment option for injured VFs.

Surgical and Functional Outcome After Endoscopic Resection Via Transthyrohyoid for Early Glottic Cancer.

Transthyrohyoid access to the larynx for endoscopic resection (TTER) for early-stage glottic cancer in patients with difficult laryngeal exposure (DLE) has recently been developed. However, little is known about the postoperative conditions of patients. Twelve early-stage glottic cancer patients with DLE who received TTER were retrospectively reviewed. Clinical information was collected during the perioperative period. Functional outcome was evaluated using Voice Handicap Index-10 (VHI-10) and Eating Assessment Tool-10 (EAT-10) preoperatively and 12 months after surgery. None of the patients experienced serious complications after TTER. The tracheotomy tube was removed in all patients. The 3-year local control rate was 91.6%. The VHI-10 score decreased from 18.92 to 11.75 (p < .001), and the EAT-10 scores of the 3 patients changed slightly. Thus, TTER may be a good option for early-stage glottic cancer patients with DLE.

LRP1B is a Potential Biomarker for Tumor Immunogenicity and Prognosis of HCC Patients Receiving ICI Treatment.

Background: New predictors of the efficacy of hepatocellular carcinoma (HCC) immunotherapy are needed. The ability of a single gene mutation to predict the therapeutic effect of immune checkpoint inhibitors (ICI) in HCC remains unknown. Methods: The most frequently mutated genes in HCC were analyzed using the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. Mutant genes that correlated with the tumor mutational burden (TMB) and prognosis were obtained. The mutation pattern and immunological function of one of the most frequently mutated genes, LRP1B, were determined. A pan-tumor analysis of LRP1B expression, association with cancer prognosis, and immunological role was also explored. A retrospective clinical study was conducted using 102 HCC patients who received ICI treatment to further verify whether gene mutations can predict the effectiveness of immunotherapy and prognosis of HCC. Results: LRP1B is among the most frequently mutated genes in HCC cohorts in TCGA and ICGC datasets. TCGA data showed that the LRP1B mutation activated immune signaling pathways and promoted mast cell activation. Patients with LRP1B mutations had significantly higher TMB than those with wild-type LRP1B. LRP1B expression correlated with the cancer-immunity cycle and immune cell infiltration. High LRP1B expression was also associated with poor survival among HCC patients. Results from the clinical study showed that HCC patients in the LRP1B mutation group had a poor response to ICI and worse prognosis than the wild-type group. The LRP1B mutation group had significantly higher TMB and mast cell infiltration in tumor tissues. Conclusion: This study is the first to report that a single gene LRP1B mutation is associated with a poor clinical response to ICI treatment and negative outcomes in HCC patients. HighLRP1B expression correlated with tumor immunity and HCC prognosis.

[Effect of Atractylodes macrocephala polysaccharide on proliferation and invasion of hepatocellular carcinoma cells in vitro].

OBJECTIVE: To investigate the inhibitory effect of polysaccharide of Atractylodes macrocephala (PAM) on the proliferation and invasion of hepatocellular carcinoma cells and the underlying mechanism. METHODS: Hepatocellular carcinoma HepG2 cells were treated with different concentrations of PAM, and their proliferation and invasive ability were examined using CCK-8 assay and Transwell assay. Immunofluorescence assay was performed to detect the expression level of ß-catenin, and real-time PCR and Western blotting were used to detect the mRNA and protein expressions of AKT, GSK-3ß and MMP-2 in the cells. The changes in the proliferation, invasiveness and the expressions of pGSK-3ß and MMP2 were examined in the cells following treatment with LiCl/PAM/LiCl plus PAM. RESULTS: PAM treatment significantly reduced the cell viability, the number of migration cells, and the expression levels of ß-catenin and MMP-2 (P < 0.05), and obviously inhibited the phosphorylation of AKT and GSK-3ß in the cells (P < 0.05) in a dose-dependent manner. The rescue experiment showed that LiCl reversed the inhibition of cell proliferation, invasiveness, and the Wnt/ß-catenin pathway induced by PAM. CONCLUSIONS: PAM can inhibit the proliferation and invasion of hepatocellular carcinoma cells in vitro possibly by inhibiting the Wnt/ß-catenin signaling pathway.

Expression and role of EGFR, cyclin D1 and KRAS in laryngocarcinoma tissues.

Epidermal growth factor receptor (EGFR), cyclin D1 and KRAS proto-oncogene, GTPase (KRAS) genes serve roles in the occurrence and development of tumors. The aim of the current study was to investigate the expression levels of EGFR, cyclin D1 and KRAS in laryngocarcinoma tissues and their association with clinical features. In addition, correlation between the expression levels of EGFR, cyclin D1 and KRAS was analyzed in laryngocarcinoma tissues. The expression levels of EGFR, cyclin D1 and KRAS in 46 patients with laryngocarcinoma and 20 patients with vocal cord polyps as the control group were determined using Super Vision immunohistochemical staining assay kits. The differences in clinical and pathological parameters between groups were statistically analyzed using SPSS software version 16.0. The expression rates of EGFR, cyclin D1 and KRAS were 71.7, 52.2 and 39.1%, respectively in laryngocarcinoma tissues, and 10.0, 5.0 and 10.0%, respectively in vocal cord polyps. There was a positive correlation between the expression levels of EGFR, cyclin D1 and KRAS. The expression of these genes was also closely associated with the clinical stage, treatment response and prognosis of patients with laryngocarcinoma. Multivariate analysis of prognosis using the Cox regression model indicated that EGFR expression in laryngocarcinoma tissues and the clinical stage of patients with laryngocarcinoma were closely associated with patient prognosis. The results of the current study indicated that EGFR, cyclin D1 and KRAS were synergistically involved in the occurrence and development of laryngocarcinoma, directly affecting the prognosis of patients. Additionally, high expression of EGFR, cyclin D1 and KRAS facilitated the invasion and metastasis of laryngocarcinoma cells. The expression of EGFR in laryngocarcinoma tissues and clinical stage were two independent risk factors affecting the prognosis of patients.

Interactions between dendritic cells and T lymphocytes in pathogenesis of nasal polyps.

The aim of the present study was to investigate the functional status of dendritic cells (DCs) in nasal polyps (NP) and their interactions with T lymphocytes. The interactions between DC and T lymphocytes in the pathogenesis of NP was also studied. The expression of cluster of differentiation (CD)1a and CD83 in NP was detected using immunohistochemistry and the ratio of CD83 DC/CD1a+DC was counted. The distribution of DCs in NP and normal inferior turbinate mucosa (nITM) was evaluated using double immunostaining (CD1a/CD40) and low illumination fluorescence microscopy. The number of CD1a+ cells, CD83+ cells and CD1a/CD40-dual positive cells in was significantly higher in NP tissues compared with nITM. Furthermore, the density of DCs observed in NP was significantly greater than that observed in nITM. The ratio of CD83 DC/CD1a+DC in NP was significantly higher compared with in nITM tissues. The results of the present study revealed significant infiltration of DCs in NP, with the majority being mature DCs. DCs are able to interact with T cells via the CD40/CD40L costimulatory factor, thus serving an important role in the development and progression of NP.

Increased serum amyloid A in nasal polyps is associated with systemic corticosteroid insensitivity in patients with chronic rhinosinusitis with nasal polyps: a pilot study.

BACKGROUND: Serum amyloid A (SAA) was involved in the pathogenesis of glucocorticoid resistance in lung diseases. However, their association with systemic corticosteroid insensitivity in chronic rhinosinusitis with nasal polyps (CRSwNP) patients remains to be assessed. METHODS: This study enrolled 32 CRSwNP patients to evaluate the association between SAA expression in NP and corticosteroid insensitivity, and the value of polyp SAA level for predicting the response to oral corticosteroids in CRSwNP patients. All patients were given a course of oral prednisone (30 mg daily for 2 weeks) and subdivided into glucocorticoid(GC)-sensitive and -insensitive subgroup according to the change in polyp size scores. The polyp specimens were obtained before and after corticosteroid treatment. SAA levels in polyp tissues were evaluated by enzyme-linked immunosorbent assay and quantitative reverse transcription polymerase chain reaction. Regression analysis was performed to analyze the association between SAA protein levels and corticosteroid insensitivity. RESULTS: 13/32 (40.62%) CRSwNP patients were insensitive to the oral corticosteroid therapy. SAA mRNA and protein levels were significantly increased in GC-insensitive NP compared to those in GC-sensitive NP. Tissue SAA protein levels were positively correlated with tissue neutrophil numbers. Regression analysis revealed tissue SAA levels were significantly correlated with corticosteroid insensitivity (P < 0.01). ROC curves indicated that the area under the curve was 0.87. When the polyp SAA protein level was 122.2 ng/ml or higher, the sensitivity and specificity were 76.92 and 73.68%, respectively. CONCLUSIONS: Our findings suggest that increased SAA in NP is associated with reduced response to oral corticosteroids in CRSwNP. SAA levels in NP may have potential value in predicting corticosteroid insensitivity in CRSwNP patients.

Expression and distribution of dendritic cells in nasal polyps.

The aim of the present study was to investigate the expression, distribution and function of dendritic cells (DCs) and to study their role in nasal polyps. The study involved 55 participants, 45 of whom had nasal polyps and were the study group and 10 who had normal inferior turbinates and were the control group. Immunohistochemical staining was used to visualize the expression and distribution of the S-100 protein. A double immunostaining method was used to visualize the CD1a and CD40 expression and the images were analyzed with Axioplan 2 microscopy. The expression level of the S-100 protein in the nasal polyps was higher than that in the normal inferior turbinates with a significant difference (P<0.01). The distribution area, number and density of the double stained cells in the nasal polyps were all greater than in the normal inferior turbinates (P<0.01). The S-100 protein and double stained cells were mainly located in the lamina propria below the mucous membrane. The present study demonstrates that DCs are involved in the pathogenesis of nasal polyps and the presence of CD40-positive DCs suggests that this was related to the reciprocal interaction between the DCs and T lymphocytes.