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Objective To explore the pattern of lymph node metastasis and provide guidance for the delineation of clinical target volume for patients diagnosed with hypopharyngeal squamous cell carcinoma (HSCC).Methods A total of 123 patients who were initially diagnosed with HSCC by electrolaryngoscope and computed tomography (CT) of the head and neck in Shandong Tumor Hospital between 2014 and 2017 were recruited in this study.The lymph node metastasis was evaluated based on the diagnostic criteria of CT scan.The lymphatic metastasis ratio (LMR) at each node level was calculated.Analysis of variance (ANOVA) andx2 test were used to analyze the relationship between LMR and primary tumors.Results Among 123 patients,primary tumors were originated from the pyriform sinus (PS) in 101 cases (82.1％),posterior pharyngeal wall (PPW) in 15 (12.2％) and postcricoid (PC) in 7 (5.7％),respectively.The overall LMR was calculated as 84.6％ (n=104),in detail,84.2％ for patients with primary tumors originating from PS,93.3％ for those from PPW and 71.4％ for patients from PC,respectively.For PSderived tumors,the ipsilateral neck LMR at the level Ⅰa,Ⅰb,Ⅱa,Ⅱb,Ⅲ,Ⅳ,Ⅴ,Ⅵa,Ⅵb,and Ⅶ was 0,3.0％,66.3％,42.6％,46.5％,10.9％,5.0％,2.0％,7.9％,and 11.9％,respectively,and 0,0,14.9％,5.0％,3.0％,2.0％,0,0,3.0％,and 2.0％ for the contralateral neck.For PPW tumors,the ipsilateral neck LMR at the level Ⅰa,Ⅰb,Ⅱa,Ⅱb,Ⅲ,Ⅳ,Ⅴ,Ⅵa,Ⅵb,and Ⅶ was 6.7％,6.7％,66.7％,46.7％,46.7％,20.0％,0,13.3％,33.3％,and 60.0％,respectively,and 6.7％,6.7％,33.3％,26.7％,20.0％,20.0％,0,0,13.3％,and 33.3％ for the contralateral neck.For PC tumors,the ipsilateral neck LMR at the level Ⅱa,Ⅱb,Ⅲ,Ⅳ,Ⅴ and Ⅵb was 71.4％,28.6％,14.3％,14.0％,14.0％,and 14.3％,respectively,and the LMR at the level Ⅱa was 14.3％ for the contralateral neck.No lymph node metastasis occurred in other lymph node levels.The mean levels of lymph node metastasis for the T1-T4 stage tumors were 2.4,1.9,2.2,3.3 with statistical significance (P =0.023),and 2.2,4.5 and 1.6 for patients with the tumors originated from PS,PPW and PC (P=0.000).The PPW invasion was significantly correlated with the level Ⅶ metastasis (P=0.000),and PC or esophageal invasion was intimately correlated with the level Ⅵ metastasis (P=0.002 and 0.001).Conclusions The most common lymphatic metastasis includes ipsilateral neck Ⅱa,Ⅲ,and Ⅱb,whereas the level Ⅰ and Ⅴ are rarely observed.For PPW-derived tumors,the LMR at the level Ⅶ is up to 60.0％.The incidence of PC or esophageal invasion enhances the risk of level Ⅵ lymph node metastasis.
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Objective To evaluate the treatment outcomes and toxicities of intensity-modulated radiation therapy (IMRT) combined with chemotherapy for children and adolescents with nasopharyngeal carcinoma.Methods Forty-three nasopharyngeal carcinoma patients less than 19 years old were recruited between April 2010 and April 2016.All patients were treated with IMRT (total dose 61.2-76 Gy) combined with cisplatin based chemotherapy.The Kaplan-Meier test was used to calculate overall survival (OS) and progression-free survival (PFS).The patient's clinical characteristics,side effects and longterm effects of treatment were retrospectively analyzed.Results Among 43 patients,there were 29 (67.4％) male and 14 (32.6％) female,and the median age was 14 years old (range,6-18 years).According to AJCC 7thstaging system,2 patients were in stage Ⅱ,26 in stage Ⅲ,7 in stage ⅣA and 8 in stage Ⅳ B.All patients were confirmed as non-keratinizing carcinoma.The positive rates of EB virus VCAIgA was 53.8％ (7/13),and Rta-IgG was 60.0％ (6/10) before treatment.The median radiation dose was 70 Gy (range,61.2-76 Gy) to the primary tumor.Thirty-three (76.7％) patients received neoadjuvant chemotherapy,with 20 (46.5％) and 36 (83.7％) patients treated by concurrent and adjuvant chemotherapy,respectively.With a median follow-up of 24 months (range,3-76 months),the 5-year OS and PFS ratios were 75.3％ and 64.7％,respectively.There were 5 patients (11.6％) occurred to bone metastasis within 2 years after treatment.Hypothyroidism was reported in 47.4％ (9/19) patients after IMRT.Conclusions Nasopharyngeal carcinoma in childhood and adolescence is mostly locally advanced diseases with poor differentiation.IMRT combined with chemotherapy produce a well treatment outcome with good tolerance in children and adolescents patients.The most common treatment failure bone metastasis.Radiation-induced hypothyroidism is common.
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Aims To observe the influences of met-formin ( MET ) on the expression of renal tissue ad-vanced glyclation end-products( AGEs) protein and its receptor mRNA ( RAGE mRNA ) in type 2 diabetes mellitus (T2DM) model rats, and to discuss the mech-anism of the MET in the treatment of diabetic nephrop-athy ( DN ) . Methods The rat model of T2 DM was established by fed with high-fat diet and intraperitoneal injection of low-dose of streptozotocin ( STZ ) . All rats were randomly divided into metformin group( MET,300 mg·kg-1 ·d-1 ) , glyburide group( GLY,5 mg·kg-1 ·d-1),T2DM model group(T2DM) and normal con-trol group ( NC ) . After 8 weeks ’ observation, blood glucose ( BG ) , glycated hemoglobin ( HbA1 c ) , blood urea nitrogen(BUN), urinary albumin,urinary AGEs and urine creatinine were detected. The expression of renal tissue AGEs was detected by immunohistochemis-try assay, and the expression of RAGE mRNA was measured by real-time PCR. Results The levels of BG, HbA1c , urinary albumin/urine creatinine ( UACR ) , glomerular basement membrane thickness ( GBMT ) in MET group and GLY group were signifi-cantly lower than those of T2DM group, while higher than those of NC group(P0. 05 ) . The urinary AGEs/urine creatinine( UGCR) , the expressions of re-nal tissue AGEs and RAGE mRNA in MET group and GLY group were significantly decreased compared with those of T2 DM group ( P < 0. 05 ) , but higher than those of NC group ( P <0. 05 ) . The UGCR, the ex-pressions of AGEs and RAGE mRNA in MET group were lower than those of GLY group(P<0. 05). Con-clusion MET can reduce the accumulation of AGEs in the renal tissue,and down-regulate the over-expres-sion of RAGE mRNA in T2DM rats.
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Purpose To study the effect and mechanism of miR-199a-5p on the invasion of breast cancer MDA-MB-231 cells. Meth-ods miR-199a-5p mimic was transfected into MDA-MB-231 cells. Influence of miR-199a-5p on the invasion of MDA-MB-231 cell was displayed by Transwell, the expression of epithelial-mesenchymal transition ( EMT) molecular markers ( E-cadherin, vimentin) regulated by miR-199a-5p was determined using immunofluorescence and Western blot. Western blot was employed to assess the levels of ERK5, pERK5, EGF and SP1 in MDA-MB-231 cells dealt with miR-199a-5p mimic and LNA-siRNA. Chromatin immunoprecipita-tion (CHIP) was applied for displaying the reaction of SP1 with ERK5 promoter. Results miR-199a-5p could inhibit the invasion of MDA-MB-231 cells, decrease the expression of vimentin and enhance E-cadherin. Meanwhile, miR-199a-5p decreased the expression of ERK5 and pERK5, the levels of EGF and SP1 were also downregulated. On the contrary, the levels of EGF, SP1, ERK5 and pERK5 were enhanced by employing LNA-siRNA targeting miR-199a-5p. SP1 could bind with ERK5 promoter. Conclusions miR-199a-5p could reduce the expression of ERK5 and pERK5 through regulating EGF and SP1, which functioning the inhibitory effect on invasion of MDA-MB-231 breast cancer cells.
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Background and purpose:Nir1 is a transmembrane receptor for chemokine (C-C motif) ligand 18. CCL18 speciifcally binds to Nir1 at the cellular membrane of breast cancer cells to exert its invasion and metastasis. However, the speciifc mechanism of Nir1 is not clear in glioma. This study probed the effect and mechanism of Nir1 in the invasion of glioma cells.Methods:Western blot was used to detect the expression of Nir1 in glioma cells. siRNA plasmid was used to transfect U251 cells. Western blot was used to analyze the expression of Nir1 and protein phosphorylation of Akt in the cells transfected by Nir1 plasmid.In vitro Matrigel invasion assay was used to detect the invasive ability in the cells that were transfected. F-actin polymerization assay was used to detect F-actin recognition ability in cells.Results:The expression of Nir1 was higher in all glioma cells. After transfection, the invasion of siNir1/U251 was obviously decreased than the SCR/U251, F-actin content was reduced compared to the control group. Akt phosphorylation experiment result showed that the protein phosphorylation of Akt was enhanced in control group cells CCL18 following stimulation. However, the existence of CCL18 would affect the phosphorylation of Akt in siNir1/U251.Conclusion:Nir1 is high expression in glioma cells, and Nir1 binding to chemokine CCL18 promotes glioma cells invasion and metastasis through regulation the phosphorylation of Akt and F-actin polymerization .
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Purpose To investigate the expressions of PKCζ, MMP-2, and MMP-9 in breast cancer and the relationship with the inva-sion and metastasis of breast cancer. Methods The expression of PKCζ, MMP-2 and MMP-9 in 100 cases with breast cancer was as-sessed with immunohistochemistry PV 9000 method. PKCζ-siRNA was transfected into MDA-MB-231 cell lines, called siPKCζ/MDA-MB-231. While siRNA construct containing a scrambled sequence was transfected into MDA-MB-231 cells to generate control cells, which were designated as Scr/MDA231 cells. Western blotting was used to measure the expression of PKCζ in transfected cells, and the Transwell invasion assay was used to detect the invasion ability in vitro. The content of MMP-2, MMP-9 were measured by ELISA. Results The expression rates of PKCζ, MMP-2 and MMP-9 in breast cancer tissues were 62.5%, 37.5% and 32.5%, and there were significant differences among them (P0.05). The expres-sion of PKCζ, MMP-2 and MMP-9 were lower in siPKCζ/ MDA-MB-231 group than those in scr/ MDA-MB-231 group, and the in vitro invasion ability was significantly decreased (P<0.05). Conclusions PKCζ can promote the invasion and metastasis of breast canc-er, and correlated with the expression of MMP-2, MMP-9(P<0.05).
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Objective To compare the severity of sensorineural hearing impairment resulted from radiotherapy (RT) and radiochemotberapy (CRT) in patients with nasopharyngeal carcinoma (NPC). Methods Between March 2002 and May 2007, 100 initially diagnosed NPC patients in Shandong Tumor Hospital and Qi Lu Hospital were randomized to RT group and CRT group. All patients underwent intensity modulated radiation therapy. In CRT group, concurrent and adjuvant CDDP were administered (CDDP 25 mg/m2/d for 3 days to 4 cycles). Pure tone auditory threshold examination was performed 1 week ,6 months, 1 year and 2 years after the completion of radiotherapy. Statistical analyses were performed using Mann-Whit-ney U test,chi-square test and Fisber's exact probability test. Results The high-frequency threshold was significantly increased in CRT group comparing with RT group at 1- and 2-year after the treatment. In RT group, the hearing threshold was impaired immediately after the treatment, partially recovered within the first year but impaired again after 2 years. In CRT group, hearing threshold was impaired at the same time and kept getting worse until 1 year after radiotherapy, which could not be recovered. Conclusions Patients with NPC treated with radiotherapy and concurrent/adjuvant chemotherapy have more severe sensorineural hearing impairment comparing with those with radiotherapy alone, especially to the high frequency sound in the speech range. Inner ear tissue tolerance should be redefined for patients receiving radiochemotherapy.