RESUMO
BACKGROUND: Patients with recurrent or locally advanced head and neck squamous cell carcinoma (HNSCC) typically have limited treatment options and poor prognosis. AIM: To evaluate the efficacy and safety of two drugs with potent radio-sensitization properties including gemcitabine and nedaplatin as concurrent chemoradiotherapy regimens in treating HNSCC. METHODS: This single-arm prospective study enrolled patients with HNSCC to receive gemcitabine on days 1 and 8 and nedaplatin on days 1 to 3 for 21 days. Intensity-modulated radiation therapy with a conventional fraction was delivered 5 days per week. Objective response rate (ORR), disease control rate, and toxicity were observed as primary endpoints. Overall survival (OS) and progression free survival were recorded and analyzed as secondary endpoints. RESULTS: A total of 24 patients with HNSCC were enrolled. During the median 22.4-mo follow-up, both ORR and disease control rate were 100%. The one-year OS was 75%, and one-year progression-free survival (PFS) was 66.7% (median PFS was 15.1 mo). Recurrent HNSCC patients had a poorer prognosis than the treatment-naïve patients, and patients who achieved complete response had better survival than those in the PR group (all P < 0.05). The most common grade 1-4 (100%) or grade 3-4 toxicities (75%) were hematological, and the most common grade 3-4 non-hematological toxicity was mucositis in 17 (71%) patients. CONCLUSION: Gemcitabine plus nedaplatin with concurrent chemoradiotherapy is a therapeutic option for HNSCC with predictable tolerability. Considering the high adverse event rate, the optimized dose and schedule must be further explored.
RESUMO
Bisphenol A (BPA) is a well-known endocrine disruptor compound reported to have prostate toxicity. This study aimed to assess the effect of BPA on the proliferation of dorsolateral prostate (DLP) and the expression of epithelial-mesenchymal transition (EMT)-related genes in aged rats. Male aged SD rats were treated with BPA (10.0, 30.0, and 90.0 µg/kg i.g., daily) or vehicle (i.g., daily) for 3 months. Treatment with BPA resulted in increased the expression of PCNA, DLP weight and DLP epithelial height compared with the control group (P < 0.01); such effects were more obvious at higher BPA doses. 90 µg/kg BPA significantly increased the estrogen to androgen ratio (P < 0.05). The EMT chip showed the BPA induced upregulation of vimentin, Snail, Twist1, and transforming growth factor beta 1, as well as the downregulation of E-cadherin in the DLP. Immunohistochemical data showed that the expression of vimentin, estrogen receptor subtypes, and androgen receptor increased and the expression of E-cadherin decreased in 30 and 90 µg/kg BPA groups. It was concluded that environmental exposure to low doses of BPA might promote the proliferation of DLP in aged rats by increasing the estrogen to androgen ratio and inducing EMT.
