BACKGROUND:The authors studied the efficacy of neoadjuvant chemotherapy, consisting of a taxane, cisplatin, and 5-fluorouracil (5-FU) (the TPF regimen) followed by concurrent chemoradiation, in 2 separately designed and synchronously executed phase 2 trials for stage III and IVA=IVB nasopharyngeal cancer (NPC
Cetuximab plus IMRT with or without chemotherapy for locoregionally advanced NPC is effective and tolerated. Further investigations are warranted.
Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors with poor prognosis and recurrence in South China. The hard eradication of NPC in clinic is predominantly due to cancer stem cells (CSCs). Increasing evidence revealed that the aberrant activation of Wnt/β-catenin was positively correlated with the produce of CSCs. To further investigate the effect of β-catenin on CSCs and tumorigenesis in NPC, a CNE2 cell line ( pLKO.1-sh-β-catenin-CNE2) with stably suppressed expression of β-catenin was used in this study. The expressions of biomarkers in CSCs including c-myc, Nanog, Oct3/4, Sox2, EpCAM as well as adhesion-related proteins like E-cadherin and vimentin were analyzed by western blot analysis and immunofluorescent staining. The proliferation and migration abilities were investigated by MTT assay and Transwell assay, respectively. Cell cycle was analyzed by flow cytometry. Finally, xenograft was performed to determine the effect of β-catenin on oncogenesis in vivo. Results showed that the expressions of c-myc, Nanog, Oct3/4, Sox2, and EpCAM were all decreased in pLKO.1-sh-β-catenin-CNE2 cells. It was also found that vimentin was downregulated, while E-cadherin was upregulated. Results of MTT and Transwell assays suggested that the proliferation and migration abilities were impaired by silencing of β-catenin, and more cells were arrested in G1 phase when compared with the control. In vivo study indicated that the tumor growth was markedly suppressed in experimental group. Based on current findings, β-catenin may function as an essential protein for the maintenance of migration and proliferation abilities of NPC cells, and a complicated network consisting of c-myc, Nanog, Oct3/4, Sox2, EpCAM, E-cadherin, vimentin, and β-catenin may be involved in the inherent regulation mechanisms.
Background: Localized-type tenosynovial giant cell tumor (TGCT) is a rare, neoplastic disease with only limited data supporting treatment protocols. We describe treatment protocols and evaluate their oncological outcome, complications, and functional results in a large multicenter cohort of patients. A secondary study aim was to identify factors associated with local recurrence after surgical treatment.Methods: Patients with histologically proven localized TGCT of a large joint were included if they had been treated between 1990 and 2017 in 1 of 31 tertiary sarcoma centers. Of 941 patients with localized TGCT, 62% were female. The median age at initial treatment was 39 years, and the median duration of follow-up was 34 months. Sixty-seven percent of the tumors affected the knee, and the primary treatment at the tertiary center was 1-stage open resection in 73% of the patients. Proposed factors for predicting a first local recurrence after treatment in the tertiary center were tested in a univariate analysis, and those that demonstrated significance were subsequently included in a multivariate analysis. Results:The localized TGCT recurred in 12% of all cases, with local-recurrence-free rates at 3, 5, and 10 years of 88%, 83%, and 79%, respectively. The strongest factor for predicting recurrent disease was a prior recurrence (p < 0.001). Surgical treatment decreased pain and swelling in 71% and 85% of the patients, respectively, and such treatment was associated with complications in 4% of the patients. Univariate and multivariate analyses of the patients who had not continued *In addition to the listed authors, members of the Tenosynovial Giant Cell Tumors (TGCT) Study Group include M.
Purpose Nasopharyngeal carcinoma (NPC) is a malignant tumor that commonly occurs in southern China and Southeast Asia. Radiation therapy is the main treatment for patients with NPC, and the radioresistance of NPC is an unresolved clinical problem. This study focuses on the mechanism of NPC radioresistance and explores therapeutic targets and research directions for increasing the radiosensitivity of radioresistant cells. Methods We used a gradient dose model to establish radioresistant strains of 6-10B and CNE-2 human NPC cells. Plate colony formation assays were used to verify the radioresistance of the cells. We evaluated the expression of epidermal growth factor receptor (EGFR), lysosome-associated transmembrane protein 4β (LAPTM4B), Beclin1 and the autophagy-related proteins p62, LC3I, and LC3II by Western blot and observed GFP-LC3 puncta by confocal microscopy. The interaction between proteins was verified by immunofluorescence and coimmunoprecipitation analyses. Flow cytometry was performed to detect differences related to the apoptosis of radioresistant strains. Results The EGFR and LAPTM4B expression levels and autophagic flux were higher in radioresistant cells than in nonradioresistant cells, suggesting that EGFR and LAPTM4B are associated with autophagy levels. We observed that EGFR and LAPTM4B interact and stabilize each other in endosomes by confocal microscopy. LAPTM4B knockdown decreased the survival fraction of radioresistant cells and increased apoptosis after exposure to radiation. Coimmunoprecipitation experiments demonstrated that LAPTM4B interacts with Beclin1, which in turn promotes the initiation of autophagy. Conclusion This study illustrates a relationship among EGFR, LAPTM4B and autophagy in radioresistant NPC cell lines. LAPTM4B interacts with EGFR and Beclin 1, which promotes autophagy. LAPTM4B knockdown decreases radioresistance by inhibiting autophagy. This study proposes a possible mechanism for NPC radioresistance and provides a new research direction and theoretical basis for addressing the radioresistance of NPC.
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