Selectively sparing of the supraclavicular area during intensity-modulated radiotherapy in nasopharyngeal carcinoma: A double-center observation study.

BACKGROUND AND PURPOSE: This study was aimed at evaluating the feasibility of sparing the supraclavicular area, namely levels IVb and Vc, during intensity-modulated radiotherapy (IMRT) in nasopharyngeal carcinoma (NPC) patients with N1-2 disease[except N1 disease with purely restropharyngeal lymph nodes(RPN) involvement], and providing a basis for the revision of International Guideline for the delineation of the clinical target volume (CTV). PATIENTS AND MATERIALS: Patients with NPC (stage TanyN1-2M0) diagnosed pathologically in Fujian Cancer Hospital (Center 1, Only Lin SJ's attending group) from January 2014 to March 2018 and Jiangxi Cancer Hospital(Center 2) from January 2014 to December 2015 were included. According to our principle, the supraclavicular area (levels IVb and Vc) were excluded from the CTVnd. Survival outcomes focused on regional recurrence-free survival (RRFS) and recurrence rates of levels IVb and Vc were analysed. RESULTS: A total of 672 eligible patients were recruited (Center 1, n = 362; Center 2, n = 310). There was no significant difference in 5-year RRFS (97.33 % vs. 97.24 %, p = 0.980), overall survival (OS) (89.14 % vs. 88.56 %, p = 0.327), local recurrence-free survival (LRFS) (94.90 % vs. 95.30 %, p = 0.593) and distant metastasis-free survival (DMFS) (89.38 % vs. 86.60 %, p = 0.130) between Center 1 and Center 2. Twenty patients developed regional failure (median: 36 months), among them, only one case (0.15 %) was recorded as levels IVb and Vc recurrence. CONCLUSION: Omitting the supraclavicular area (levels IVb and Vc) during IMRT should be safe and feasible for N1-2 disease (except N1 disease with purely RPN involvement). Well-designed multicenter prospective trials should be conducted to confirm our findings.

A Novel Prognostic Model Predicts Outcomes in Non-Metastatic Nasopharyngeal Carcinoma Based on Inflammation, Nutrition, and Coagulation Signature.

Purpose: This study aimed to assess the prognostic and predictive value of a circulating hematological signature (CHS) and to develop a CHS-based nomogram for predicting prognosis and guiding individualized chemotherapy in non-metastatic nasopharyngeal carcinoma (NPC) patients. Patients and Methods: NPC patients were recruited between January 2014 and December 2017 at the Jiangxi Cancer Hospital. The CHS was constructed based on a series of hematological indicators. The nomogram was developed by CHS and clinical factors. Results: A total of 779 patients were included. Three biomarkers were selected by least absolute shrinkage and selection operator regression, including prognostic nutritional index, albumin-to-fibrinogen ratio, and prealbumin-to-fibrinogen ratio, were used to construct the CHS. The patients in the low-CHS group had better 5-year DMFS and OS than those in the high-CHS group in the training (DMFS: 85.0% vs 56.6%, p<0.001; OS: 90.3% vs 65.4%, p<0.001) and validation cohorts (DMFS: 92.3% vs 43.6%, p<0.001; OS: 92.1% vs 65.5%, p<0.001). The nomogram_CHS showed better performance than clinical stage in predicting distant metastasis (concordance index: 0.728 vs 0.646). In the low-TRS (total risk scores) group, the patients received RT alone, CCRT and IC plus CCRT had similar 5-year DMFS and OS (p>0.05). In the middle-TRS group, the patients received RT alone had worse 5-year DMFS (58.7% vs 80.8% vs 90.8%, p=0.002) and OS (75.0% vs 94.1% vs 95.0%, p=0.001) than those received CCRT or IC plus CCRT. In the high-TRS group, the patients received RT alone and CCRT had worse 5-year DMFS (18.6% vs 31.3% vs 81.5%, p<0.001) and OS (26.9% vs 53.2% vs 88.8%, p<0.001) than those received IC plus CCRT. Conclusion: The developed nomogram_CHS had satisfactory prognostic accuracy in NPC patients and may individualize risk estimation to facilitate the identification of suitable IC candidates.

Hsa_circ_0081069 facilitates tongue squamous cell carcinoma progression by modulating MAP2K4 expression via miR-634.

It has been demonstrated that circular RNA (circRNA) is involved in the progression of tongue squamous cell carcinoma (TSCC). The aim of this study was to investigate the intrinsic mechanism of circ_0081069 in TSCC progression. The expression levels of circ_00081069, miR-634, and mitogen-activated protein kinase kinase 4 (MAP2K4) in TSCC tissues and cells were detected by quantitative real-time PCR (qRT-PCR). Cell counting kit 8 assay, Edu assay, and flow cytometry assay were used to detect cell proliferation and cell cycle distribution. Transwell assay was used to detect cell migration and invasion abilities. Western blot analysis was performed to detect the protein expression. Dual-luciferase reporter assay was used to detect the targeting relationships of circ_0081069, miR-634 and MAP2K4. Immunohistochemical staining was used to measure MAP2K4-positive cells in tissues. The effect of circ_0081069 silencing on tumor formation in TSCC in vivo was explored by xenograft tumor assay. Circ_0081069 was highly expressed in TSCC tissues and cells. Silencing of circ_0081069 inhibited cell proliferation, cell cycle progress, cell migration and invasion in vitro, as well as hindered tumor growth in vivo. Mechanistically, circ_0081069 targeted miR-634 to negatively regulate miR-634 expression, and inhibition of miR-634 was able to weaken the inhibitory effect of circ_0081069 knockdown on proliferation, migration, and invasion of TSCC cells. MiR-634 targeted MAP2K4 and negatively regulated MAP2K4 expression, and overexpression of miR-634 inhibited TSCC cell proliferation, migration, and invasion, while co-overexpression of MAP2K4 was able to reverse the effects of miR-634 in TSCC cells. Circ_0081069 is involved in the regulation of proliferation, cycle progress, migration, and invasion of TSCC cells through the miR-634/MAP2K4 axis and has the potential to serve as a diagnostic biomarker and therapeutic target.

Downregulation of circLPAR3 inhibits tumor progression and glycolysis by liberating miR-144-3p and upregulating LPCAT1 in oral squamous cell carcinoma.

Background: Increasing evidence demonstrated the important roles of circular RNAs (circRNAs) in human cancer progression, including oral squamous cell carcinoma (OSCC). The study intentions were to explore the role and molecular mechanism of hsa_circ_0004390 (circLPAR3) in OSCC progression. Methods: Expression of circLPAR3 in collected samples and cultured cell lines was detected with real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Loss-of-function experiments were performed to determine the effect of circLPAR3 silencing on OSCC cell proliferation, migration, invasion, apoptosis, angiopoiesis, and glycolysis. The sponge function of circLPAR3 was predicted by bioinformatics analysis and validated by the dual-luciferase reporter and RNA pull-down assays. In vivo experiments were conducted to validate the function of circLPAR3. Results: A marked increase in circLPAR3 expression was observed in OSCC samples and cell lines. Furthermore, circLPAR3 could distinguish OSCC samples from paired non-tumor samples, and patients with high circLPAR3 expression had a poor prognosis. Furthermore, circLPAR3 inhibition decreased OSCC growth in xenograft mouse models. Moreover, circLPAR3 silencing repressed cell proliferation, migration, invasion, angiopoiesis, glycolysis, and induced cell apoptosis in OSCC cells in vitro. Mechanically, circLPAR3 sponged miR-144-3p to prohibit the inhibiting effect of miR-144-3p on LPCAT1, thus promoting OSCC progression. Conclusion: CircLPAR3 exerted a tumor-promoting effect on OSCC growth through elevating LPCAT1 expression via functioning as a miR-144-3p sponge. This study supports the possible role of circLPAR3 in the diagnosis, prognosis, and treatment of OSCC.

Retrospective Analysis of a Modified Irrigation Method for Nasopharyngeal Carcinoma Patients With Post-Radiation Nasopharyngeal Necrosis.

PURPOSE: Post-radiation nasopharyngeal necrosis (PRNN) is one of the most serious late effects of nasopharyngeal carcinoma (NPC) after radiotherapy. Standard conservative treatments are not always effective, and this study sought to investigate the feasibility of modified nasopharyngeal irrigation in the treatment of PRNN. METHODS: Between September 2011 and September 2018, 113 NPC patients with pathologically or radiologically diagnosed PRNN were analyzed retrospectively. All patients received the traditional conservative treatments of debridement of the necrotic tissues guided by an endoscope and systematic antibiotic therapy partly guided by culture results. The patients were divided into two groups according to the irrigation method used: traditional and modified groups. Modified irrigation used an irrigation device made by our hospital, guided by endoscopy, while the patients in the traditional irrigation group used a nasopharyngeal irrigation pot to wash the nasopharynx by themselves each day. RESULTS: Survival was affected by ICA (internal carotid artery) exposure, necrosis grade, and re-irradiation, but only ICA exposure and re-irradiation were found to be independent prognostic factors. The modified irrigation had a significantly more positive effect on the recovery rates of patients with mild- and moderate-grade PRNN than did traditional irrigation. The 2-year overall survival (OS) of the 113 patients was 68.4%. The modified irrigation was associated with better OS in the mild- and moderate-grade groups, in the one-course radiotherapy group, and in the low-risk group (according to the 2017 system). CONCLUSIONS: More intense modified irrigation under the physicians control may be an effective treatment for PRNN, especially mild- and moderate-grade, one-course radiotherapy, or low-risk PRNN.

A randomized, double-blind, placebo-controlled trial of probiotics to reduce the severity of oral mucositis induced by chemoradiotherapy for patients with nasopharyngeal carcinoma.

BACKGROUND: The objective of this study was to evaluate the effect of a probiotic combination on the severity of oral mucositis (OM), which is a common, unpreventable complication induced by radiochemotherapy in patients with nasopharyngeal carcinoma who undergo concurrent radiochemotherapy (CCRT). METHODS: Eligible patients (n = 99) with locally advanced nasopharyngeal carcinoma who were undergoing CCRT were randomly assigned (2:1) to receive a probiotic combination or placebo during radiochemotherapy, and the incidence of severe OM (grade 3 or higher) was the primary endpoint. RESULTS: Patients taking the probiotic combination showed a significant reduction in the severity of OM. The incidences of grade 0, 1, 2, and 3 OM in the placebo group and the probiotic combination group were 0% and 12.07%, 0% and 55.17%, 54.29% and 17.24%, and 45.71% and 15.52%, respectively. Furthermore, CCRT greatly lowered the number of immune cells, whereas the probiotic combination markedly lowered the reduction rates of CD4+ T cells (76.59% vs 52.85%; P < .05), CD8+ T cells (62.94% vs 29.76%; P < .05), and CD3+ T cells (69.72% vs 45.49%; P < .05) in an A-CCRT-P (after treatment with radiotherapy plus chemotherapy plus the probiotic combination) group. High-throughput sequencing results indicated that CCRT had obviously disturbed the intestinal diversity of patients in an A-CCRT (after treatment with radiotherapy plus chemotherapy plus a placebo) group, whereas the probiotic combination distinctly restored the microbial diversity in the A-CCRT-P group toward that of healthy people and a B-CCRT-P (before the treatment of radiotherapy plus chemotherapy plus the probiotic combination) group. CONCLUSIONS: A probiotic combination significantly enhances the immune response of patients and reduces the severity of OM through modification of gut microbiota.

Risk factors and distribution features of level IB lymph nodes metastasis in nasopharyngeal carcinoma.

OBJECTIVE: The objective of this study is to investigate the risk factors and distribution features for level IB metastasis in nasopharyngeal carcinoma (NPC) and provide clinical evidence for defining the indications and clinical target volume (CTV) of prophylactic level IB irradiation. METHODS: We retrospectively analyzed 798 patients with newly-diagnosed, non-metastatic and histologically confirmed NPC underwent intensity-modulated radiation therapy (IMRT). Two sides of neck in each patient have been analyzed separately. The correlations of level IB metastasis and the clinical risk factors were analyzed with Chi-square test and logistic regression model. The risk score model (RSM) of level IB metastasis was calculated by totaling up the scores of each independent variable. We divided level IB into three areas, including anterolateral space of submandibular glands, medial space of the submandibular glands and submandibular glands. RESULTS: Maximal axial diameter (MAD) of level IIA nodes >20mm or extra capsular spread (ES) of level IIA nodes, anterior half of nasal cavity involvement and submandibular gland involvement/compression were independently significantly risk factors for level IB lymph nodes (LNs) metastasis at diagnosis. Two groups based on RSM were obtained: low risk (total score=0-2.5); high risk (4-8.5). The incidence of IB LNs metastasis at diagnosis of the two groups were 0.9% and 6.3%, respectively (P<0.001). The cervical lymph nodes of level IB were distributed in the anterolateral space of submandibular glands. There was no positive/negative LNs inside or medial space of the submandibular glands. CONCLUSION: Level IB LNs metastasis is associated with MAD of level IIA nodes >20mm or ES of level IIA nodes, anterior half of nasal cavity involvement and submandibular gland involvement/compression in NPC patients. Omission of level IB irradiation may be feasible for patients with low-risk IB LNs metastasis at diagnosis. The submandibular gland should not be included in level IB.

25-Hydroxyvitamin D3 attenuates experimental periodontitis through downregulation of TLR4 and JAK1/STAT3 signaling in diabetic mice.

Vitamin D has been known to be closely associated with diabetes and periodontitis while the underlying mechanism has yet to be clarified. The present study aimed to discover the effect of 25-hydroxyvitamin D3 (25-OHD3) on glycemic control and periodontal health in mice with periodontitis superimposed on experimental diabetes (known as diabetic periodontitis). We showed that 25-OHD3 intraperitoneal injection attenuated diabetic periodontitis by reducing serum fasting blood glucose, glycosylated hemoglobin and TNF-α levels, which led to decreased alveolar bone loss. Immunohistochemical staining and western blot analysis of gingival epithelia revealed that vitamin D receptor (VDR) expression was enhanced upon 25-OHD3 treatment, while toll-like receptor 4 (TLR4) expression was reduced. The expressions of Janus family kinase (JAK) 1 and signal transducer and activator of transcription (STAT) 3 as well as their phosphorylation were inhibited in gingival epithelia of diabetic periodontitis mice, whereas the expression and phosphorylation of STAT1 remained unchanged. These results suggest that 25-OHD3 could improve diabetic periodontitis through downregulation of TLR4 and JAK1/STAT3 signaling in the gingival epithelium. Our study extends the previous findings on the regulation of diabetes with periodontitis, and may also provide a potential therapy for the patients with this disease.

25-hydroxyvitamin D3 ameliorates periodontitis by modulating the expression of inflammation-associated factors in diabetic mice.

Periodontitis is a complication of diabetes mellitus, and the two diseases are highly associated with the dysfunction of inflammatory mediators. 25-hydroxyvitamin D(3) (25(OH)D(3)) plays a pivotal role in inflammatory modulation, but little is known about its effects on the progression of diabetic periodontitis and the underlying mechanism. In this paper, we showed that 25(OH)D(3) ameliorated experimental periodontitis in diabetic mice. The intraperitoneal administration of 25(OH)D(3) to streptozotocin-induced diabetic mice reduced fasting glucose and serum TNF-α levels, leading to decreased alveolar bone loss. Western blot analyses of gingival epithelia showed that vitamin D receptor (VDR) and protein tyrosine phosphatase N2 (PTPN2) were upregulated, while the expression of NF-κB and the phosphorylation of Janus family kinase 1 (JAK1) were attenuated upon 25(OH)D(3) treatment. These data may provide an explanation for the therapeutic benefits and anti-inflammatory effects of 25(OH)D(3). Our findings should have important implications for the clinical therapy of diabetic periodontitis.

Effect of Galla chinensis on the remineralization of two bovine root lesions morphous in vitro.

The present study aims to evaluate the effect of Galla chinensis compounds on the remineralization of two artificial root lesions morphous in vitro. Sixty bovine dentine blocks were divided into two groups and individually treated with two levels of demineralization solutions to form erosive and subsurface artificial carious lesions in vitro. Each group was then divided into three subgroups, each of which were treated with a remineralization solution (positive control), deionized water (negative control), or 4 000 mg⋅L(-1) aqueous solutions of Galla chinensis extract. The dentine blocks were then subjected to a pH-cycling regime for 7 days. During the first 4 days, the daily cycle included 21-h deal and 3-h demineralization applications. The dentine blocks were dealt with the entire day during the remaining 3 days. Two specimens from each of the treatment groups were selected and observed under a polarized light microscope. Data collected using a laser scanning confocal microscope were computerized and analyzed. Galla chinensis extract clearly enhanced the remineralization of both erosive lesion and subsurface lesion patterns in the specimens (P<0.05). The level of remineralization of the erosive lesion by Galla chinensis extract was lower than that of the subsurface lesion (P<0.05). In addition, the remineralization of the subsurface lesion by Galla chinensis extract was higher than that of the remineralization solution (P<0.05). No significant difference between the remineralization of erosive lesions by Galla chinensis extract and the remineralization solution was observed (P>0.05). So Galla chinensis extract has the potential to improve the remineralization of artificial root lesions under dynamic pH-cyclic conditions, indicating its potential use as a natural remineralization medicine.