ABSTRACT
Objective: To evaluate the value of the age-adjusted Charlson comorbidity Index (ACCI) in predicting the prognosis and guiding the clinical treatment of laryngeal squamous cell carcinoma (LSCC) in patients over 60 years old. Methods: Retrospective analysis of 249 cases of LSCC in Shanxi Provincial Cancer Hospital and First Hospital of Shanxi Medical University from 2008 to 2015 was performed. There were 234 males and 15 females, aged from 60 to 88 years. The clinical characteristics, treatment information and follow-up data were collected. ACCI was used to score the comorbidities of the patients. Receiver operating characteristic (ROC) curve was drawn and the patients were divided into high ACCI group and low ACCI group according to the cut-off value of ACCI. Prognostic factors were analyzed. Kaplan-Meier method was used for survival analysis, rank sum test was used for comparison between groups, χ2 test was used for enumeration data. Results: Overall survival (OS) was 54.6%, progression-free survival (PFS) was 59.4%, and cancer-specific survival (CSS) was 58.6%. Both the median survival time and PFS time were 60 months. The best cutoff point of the ACCI group was 5. Cox multivariate analysis showed that ACCI was an independent risk factor for OS, PFS and CSS (OR=1.553, 1.499 and 1.534,respectively, all P<0.05). In the high ACCI group, OS (χ2=4.120 and 4.115,P<0.05) and CSS (χ2=4.510 and 5.009,P<0.05) of patients treated with surgery plus radiotherapy and patients with radiotherapy alone were better than those of patients with surgery alone (P<0.05). But in the low ACCI group, there was no significant difference in prognosis among the three treatment regimens (P>0.05). Conclusion: High ACCI offors important prognostic information for LSCC in patients over 60 years old, and can guide clinical treatment options.
Subject(s)
Female , Humans , Male , Middle Aged , Age Factors , Comorbidity , Head and Neck Neoplasms , Prognosis , Retrospective Studies , Squamous Cell Carcinoma of Head and NeckABSTRACT
@#【Objective】 To use next generation sequencing （NGS） for examing 295 gene mutations in Chinese mucosal melanoma，and explore the mutation landscape of Chinese mucosal melanoma for potential therapeutic targets. 【Methods】The specimens were from 25 mucosal melanoma patients from September 2017 to September 2018 in Biotherapy Center，Sun Yat-sen University Cancer Center. Mutations of 295 genes were detected by NGS sequencing in the Department of Molecular Diagnostics in our hospital. 【Results】 The mutation frequency of major driver genes of melanoma was：BRAF 20%（5/25），KIT 20%（5/25），NRAS 12%（3/25），and NF1 8%（2/25），respectively. The most common mutation was an increase copy number in MYC（9/25，36%），followed by an increase in KDR copy number，24%（6/25）. DNA damage repair，cell cycle，PI3K-mTOR，growth factor receptor，MAPK，immune response and WNT/NOTCH related pathways were widely mutated. Mutation rates were 76%（19/25），72%（18/25），56%（14/25），60%（15/25），36%（9/25），28%（7/25），and 24%（6/25），respectively. Multiple therapeutic targets were observed，such as ATM，ATRX，EMSY， FANCI，RAD52，MET，PDGFRA，KDR，FLT4，ALK，ERBB3 and ROS1.【Conclusion】Gene mutations in Chinese mucosal melanoma were different from that of Chinese cutaneous melanoma and that of Caucasians. NGS could provide potential therapeutic targets for the treatment of Chinese mucosal melanoma.
ABSTRACT
@#【Objective】The aim of this study was to investigate the effect and mechanism of cabozantinib combined with anti-PD-L1 antibody on the growth of subcutaneous transplanted malignant melanoma in mice.【Methods】Established mouse subcutaneous xenograft model using mouse melanoma cell line B16- F10，and then randomly divided into five groups：saline control group，vehicle control group，anti PD- L1 antibody group，cabozantinib group，cabozantinib in combined with anti- PD- L1 antibody group （combination group）. Tumor growth was observed and tumor volume was measured every 2 days. The research endpoint was defined as when the tumor volume reached 2 000 mm3 or the difference between the groups was statistically significant. Then the mice were sacrificed and tissue samples were taken at the endpoint of the study. Infiltrating immune cells including CD4 + ，CD8 + T lymphocytes and myelogenous suppressor cells （MDSC）were detected by flow cytometry. In addition，B16-F10 cells cultured in vitro were treated with different drugs， the apoptosis was detected by flow cytometry ，and the protein expressions of AKT ，p-AKT ，mTOR and p-mTOR were detected by western blot assay.【Results】B16- F10 melanoma xenograft model showed that anti- PD- L1 antibody group had no obvious antitumor effect ，while both cabozantinib group and combination group produced significant antitumor effect，and the combination group had more obvious antitumor effect compared to cabozantinib group（P=0.001 5）. B16- F10 cells were treated with different drugs in vitro，and the apoptosis rate of the combination group was significantly higher than that of cabozantinib group at 24 h and 48 h，respectively（24 h:P=0.003 5；48 h:P=0.002 9）. Western blot assay showed that the combination group and cabozantinib group had no significant effect on the protein expression of AKT and mTOR，but both could reduce their phosphorylation levels，and the combination group was more remarkable. 【Conclusion】Cabozantinib in combined with anti-PD-L1 antibody had synergistic anti-tumor effect，which might be achieved by promoting B16-F10 cells apoptosis and inhibiting of AKT/mTOR pathway.