A randomized, controlled trial to investigate cognitive behavioral therapy in prevention and treatment of acute oral mucositis in patients with locoregional advanced nasopharyngeal carcinoma undergoing chemoradiotherapy.

Purpose: Oral mucositis is a common side effect of concurrent chemoradiotherapy (CCRT). This study aimed to determine whether cognitive behavioral therapy (CBT) could help prevent oral mucositis during chemoradiation therapy for locoregional advanced nasopharyngeal carcinoma (LA-NPC). Methods and materials: Between July 15, 2020, and January 31, 2022, a randomized controlled phase II trial was conducted. Eligible patients (N=282, 18-70 years old) with pathologically diagnosed LA-NPC were randomly assigned to receive CBT or treatment as usual (TAU) during CCRT (computer-block randomization, 1:1). The primary endpoints were the incidence and latency of oral mucositis. Results: The incidence of oral mucositis was significantly lower in the CBT group (84.8%; 95% confidence interval [CI], 78.7%-90.9%) than in the TAU group (98.6%; 95% CI, 96.6%-100%; P<0.001). The median latency period was 26 days and 15 days in the CBT and TAU groups, respectively (hazard ratio, 0.16; 95% CI, 0.12-0.22; P<0.001). CBT significantly reduced ≥ grade 3 oral mucositis (71.9% vs. 22.5%, P<0.001), dry mouth (10.8% vs. 3.7%, P=0.021), dysphagia (18% vs. 5.1%, P=0.001), and oral pain (10% vs. 3.6%, P=0.034) compared with TAU. Patients receiving CBT and TAU during CCRT had similar short-term response rates. Conclusions: CBT reduced the occurrence, latency, and severity of oral mucositis in patients with LA-NPC during CCRT.

Retraction notice to "Endogenous production of C-C motif chemokine ligand 2 by nasopharyngeal carcinoma cells drives radioresistance-associated metastasis" [Canc. Lett. 468 (2020) 27-40].

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Endogenous production of C-C motif chemokine ligand 2 by nasopharyngeal carcinoma cells drives radioresistance-associated metastasis.

Patients with recurrent nasopharyngeal carcinoma (NPC) have more co-existing distant metastasis than those of no-recurrence and are more likely to suffer distant metastasis after re-irradiation than patients with newly diagnosed NPC. However, the relationship between radioresistance and distant metastasis and the mechanisms involved in radioresistance-associated metastasis are still unclear. In this study, we proved that C-C motif chemokine ligand 2 (CCL2) expression was significantly elevated in HONE1-IR cells and recurrent NPC tumour. Inhibition of CCL2 enhanced sensitivity to radiotherapy in NPC cells. Moreover, autocrine CCL2 promoted NPC cell adaptive radioresistance, metastasis and epithelial-mesenchymal transition. Additionally, p53 activated CCL2 transcription. High CCL2 expression was highly associated with poorer locoregional recurrence free survival, progression free survival and overall survival in patients with newly diagnosed NPC. Notably, high CCL2 expression was an independent prognostic factor for distant metastasis free survival in recurrent NPC patients. Our results provide insights into the autocrine signalling mechanisms of CCL2 and suggest that inhibition of autocrine CCL2 may be a candidate treatment strategy for management of radioresistant NPC.

[Histological and histochemical studies on mouthpart of Whitmania pigra at different months age].

Mouthpart developmental histology of Whitmania pigra at different month of age were studied by paraffin section, HE staining combined alcian blue and periodic acid schifts reaction procedure (AB-PAS). The following results was obtained: Change ranges: oral width 0.6 mm (1-3 month), 1.2 mm (34 month); oral diameter 0.3 mm (1-3 month); 1.2 mm (34 month), the oral size reached maximum during 4-6 months and unchanged thereafter. Oral lip had a thin protective film located in the front of the mouthpart. The W. pigra possessed three jaws in oral cavity, the big one was in dorsum, the other two separated on both side of abdomen respectively. Jaws and muscular pharynx were interrelated closely. The jaws were composed by cuticle, epithelial layer, muscularis and jaw cavity from outside to inside. In the front of jaws had mastoid abdomen with function of secreting acidophilic granule from 2 month age. Oral cavity was composed by mucosa, submucosa and muscularis inside and outside. Oral cavity was rich of peristomial nerves. And pharynx was composed of mucosa, muscularis, adventitia from inside to outside. The folds height and width become heighten and thicken. Mucosa epithelium from complex flat epithelium changed into columnar epithelium, muscularis gradually developed into thickened along with growing. Muscular thickness reached maximum at 4 months. Mucous cells of W. pigra were classified into I-IV types based on different staining and two mainly morphological shapes (Tubular, Pear-shaped). Jaws, oral cavity, pharynx by AB-PAS staining showed little changes at different month of age. Mucous cells were few at 1 month age, and type II cells were increased rapidly in 2-3 month age in oral lip. Oral cavity contains more mucous gland cells type I. Under the muscularis there were connective tissues which distributed a few of mucous cells type II.

Down-regulation of Sp1 suppresses cell proliferation, clonogenicity and the expressions of stem cell markers in nasopharyngeal carcinoma.

BACKGROUND: Transcription factor Sp1 is multifaceted, with the ability to function as an oncogene or a tumor suppressor, depending on the cellular context. We previously reported that Sp1 is required for the transcriptional activation of the key oncogenes in nasopharyngeal carcinoma (NPC), including B-lymphoma mouse Moloney leukemia virus insertion region 1 (Bmi1) and centromere protein H (CENPH), but the role of Sp1 and its underlying mechanisms in NPC remained largely unexplored. The objective of this study was to investigate the cellular function of Sp1 and to verify the clinical significance of Sp1 as a potential therapeutic target in NPC. METHODS: The levels of Sp1 in the normal primary nasopharyngeal epithelial cells (NPECs) and NPC cell lines were analyzed by Quantitative Real-time RT-PCR (qRT-PCR) and Western blot. The location and expression of Sp1 in the NPC tissues were detected by immunohistochemistry staining (IHC). The effect of Sp1 knockdown on the cell proliferation, clonogenicity, anchorage-independent growth and the stem-cell like phenotype in NPC cells were evaluated by MTT, flow cytometry, clonogenicity analysis and sphere formation assay. RESULTS: The mRNA and protein levels of Sp1 were elevated in NPC cell lines than in the normal primary NPECs. Higher expression of Sp1 was found in NPC tissues with advanced clinical stage (P=0.00036). Either inhibition of Sp1 activity by mithramycin A, the FDA-approved chemotherapeutic anticancer drug or Sp1 silencing by two distinct siRNA against Sp1 suppressed the growth of NPC cells. Mechanism analysis revealed that Sp1 silencing may suppress cell proliferation, clonogenicity, anchorage-independent growth and the stem-cell like phenotype through inducing the expression of p27 and p21, and impairing the expressions of the critical stem cell transcription factors (SCTFs), including Bmi1, c-Myc and KLF4 in NPC cells. CONCLUSIONS: Sp1 was enriched in advanced NPC tissues and silencing of Sp1 significantly inhibited cell proliferation, clonogenicity, anchorage-independent growth and the stem-cell like phenotype of NPC cells, suggesting Sp1 may serve as an appealing drug target for NPC.

Paired study of 172 cases of nasopharyngeal carcinoma with or without dermatomyositis.

CONCLUSION: The prognosis and late adverse effects of radiotherapy (RT) in the patients with nasopharyngeal carcinoma (NPC) with or without dermatomyositis (DM) were similar, although the NPC patients with DM had higher Epstein-Barr virus (EBV) VCA-IgA titers and more severe acute side effects. Gender, TNM stage, and chemotherapy were independent prognostic factors of overall survival for NPC with DM. Glucocorticoid treatment did not affect the survival of NPC patients with DM. OBJECTIVES: We evaluated the clinical characteristics, prognosis, and differences in the toxicity of RT in patients with NPC with or without DM. METHODS: A paired study of 172 NPC cases with DM (DM group) or without DM (control group) from Sun Yat-sen University Cancer Center was conducted. RESULTS: The DM group had higher EBV VCA-IgA titers than the control group (p = 0.017) and more acute adverse effects of RT (p < 0.001). No significant differences in the overall survival or late adverse effects were found between the two groups. Gender, TNM stage, and chemotherapy were independent prognostic factors for the overall survival in the DM group. No significant differences in the overall survival were found between the patients in the DM group who were taking glucocorticoids and those who were not.

Prognostic value and differences of the sixth and seventh editions of the UICC/AJCC staging systems in nasopharyngeal carcinoma.

BACKGROUND: The aim of this study was to identify the prognostic value and differences between the 6th and 7th International Union Against Cancer/American Joint Committee on Cancer staging systems in nasopharyngeal carcinoma. METHODS: The magnetic resonance imaging scans and medical records of 903 patients with histologically diagnosed non-disseminated nasopharyngeal carcinoma were reviewed retrospectively. Moreover, the extent of nasopharyngeal carcinoma was restaged according to the 6th and 7th editions of the staging systems. RESULTS: Among the 903 patients, the 5-year survival rates were as follows: overall survival (OS), 81 %; local relapse-free survival (LRFS), 90 %; distant metastasis-free survival, 86 %; and disease-free survival, 77 %. Using the 7th edition of the staging system, significant differences in OS between categories T1 and T3, categories T1 and T4, categories T2 and T3, and categories T2 and T4 were achieved (P < 0.001 for all models). However, LRFS differed only between categories T1 and T3 and categories T1 and T4 (P = 0.008 and P = 0.003). No statistically significant differences in LRFS were observed among the different groups of anatomic masticator space invasion (P = 0.781, P = 0.457 and P = 0.696). Significant differences in DMFS were achieved, except between categories N3a and N3b (P = 0.826). The T category and N category were independent prognostic factors for the major endpoints in the Cox multivariate regression analysis (P < 0.005). CONCLUSION: The revisions of the 7th edition of the staging system are acceptable with regard to the distribution of patient classifications and the separation of survival curves. Moreover, this study will help to develop a better classification system and to better identify the appropriate treatment regimens in nasopharyngeal carcinoma.

Prognostic value of pretreatment and recovery duration of cranial nerve palsy in nasopharyngeal carcinoma.

BACKGROUND: The purpose of this study was to evaluate the prognostic value of cranial nerve (CN) palsy in nasopharyngeal carcinoma (NPC) patients. METHODS: A retrospective analysis was performed on CN involvement using medical records of 178 consecutive patients with histologically diagnosed, non-disseminated NPC. RESULTS: In 178 NPC patients with CN palsy, the 5-year survival rates were as follows: overall survival (OS), 61.0%; disease-specific survival (DSS), 69.6%; local relapse-free survival (LRFS), 75.2%; distant metastasis-free survival (DMFS), 73.4%; and disease-free survival (DFS), 55.3%. Significant differences were observed in the 5-year OS rates between patients with single and multiple CN palsy (69.8% vs. 54.3%; P=0.033) and the OS rates between patients with different pretreatment durations (68.7% vs. 43.3%, P=0.007). However, no significant differences were observed in OS, DSS, LRFS and DFS rates between patients with upper and lower CN palsy (P=0.581, P=0.792, P=0.729 and P=0.212, respectively). The results showed that recovery duration was an independent prognostic factor for OS (HR=2.485; P<0.001), DSS (HR=2.065; P=0.016), LRFS (HR=3.051; P=0.001) and DFS (HR=2.440; P<0.001). CONCLUSIONS: Recovery duration is an independent prognostic factor for NPC patients with CN palsy and is related to recurrence, which leads to poor survival. Recovery duration requires close surveillance and different treatment regimens.