Small interfering RNA (siRNA)-based gene silencing strategy has high potential on suppressing specific molecular targets, involved in cancer progression. However, the lack of an effective nanocarrier system that safely delivers siRNA to its target still limits the clinical applications of siRNA. This study aimed to develop albumin-sericin nanoparticles (Alb-Ser NPs) as a novel siRNA delivery system for laryngeal cancer treatment. Nanoparticle formulations composed of albumin and sericin at different ratios (1:1, 2:1, 1:2 w/w) were synthesized by desolvation method. The nanoparticles were modified with poly-L-lysine (PLL) for siRNA binding and decorated with hyaluronic acid (HA) to target laryngeal cancer cell line, Hep-2. HA/PLL/Alb-Ser NPs were individually loaded with siRNAs for casein kinase 2 (CK2), Absent, Small, or Homeotic-Like (ASH2L), and Cyclin D1 genes, which are overexpressed in Hep-2 cells. Downregulation of genes was confirmed by real-time PCR (RT-PCR). Size, morphological, and thermogravimetric characterizations revealed that Alb-Ser NPs having 2:1 (w/w) ratio are the most optimized formulation. Between 36.8 and 61.3% of siRNA entrapment efficiencies were achieved. HA/PLL-siRNA/Alb-Ser (2:1) NPs-mediated gene silencing resulted in a significant inhibition of cell growth and induction of apoptosis in cells. Our findings showed that HA/PLL/Alb-Ser (2:1) NPs were promising as a siRNA carrier.
7 October 2014 in European Archives of Oto-Rhino-Laryngology
Objective: To reveal the incidence and predictive parameters of occult cervical lymph node metastasis (LNM) in patients with cN0 laryngeal squamous cell cancer (LSCC) who underwent surgery as definitive treatment. Methods: Patients with cN0 laryngeal cancer who had undergone elective neck dissection together with partial or total laryngectomy between January 2006 and November 2020 were retrospectively analyzed. Clinical and histopathologic predictors of occult metastasis were also analyzed. Follow-up data were used to obtain recurrence and survival analysis. Results: A total of 86 patients with a mean age of 62.5 years were included in the study. Occult LNM was detected in 15 (17.4%) patients. Tumor grade, pT stage, thyroid cartilage invasion, and extralaryngeal extension were found to predict occult neck metastasis in univariate analysis. The mean follow-up time was 60.7 months and in the survival/recurrence analysis, pT stage, tumor location, tumor grade, presence of occult metastasis, pre-epiglottic space involvement. and extralaryngeal extension were found to predict poorer outcome. Conclusion: Overall occult LNM is low (17.4%) in N0 laryngeal cancer, but the presence of LNM is a poor prognostic factor. Correct determination of the neck status and proper treatment is crucial. The incidence of LNM is very low in T1–T2 stages and well-differentiated tumors. The “wait and see” strategy may be applied in T1–T2 cases as well as selected T3 cases with well-differentiated tumors.
19 April 2016 in European Archives of Oto-Rhino-Laryngology