OBJECTIVE: To investigate the value of diffusion-weighted magnetic resonance imaging (DW-MRI) as a noninvasive tool to assess salivary gland function for follow-up of patients with radiation-induced xerostomia. MATERIALS AND METHODS: This study included 23 patients with nasopharyngeal carcinoma who had been treated with parotid-sparing radiotherapy (RT). Salivary function was assessed by DW-MRI pre-treatment and one week and one year post-RT, respectively. The maximum apparent diffusion coefficient (ADC) of parotid glands (pADCmax) and the time to peak ADC of parotid glands (pTmax) during stimulation were obtained. Multivariate analysis was used to analyze factors correlated with the severity of radiation-induced xerostomia. RESULTS: The ADCs of parotid and submandibular glands (1.26 ± 0.10 × 10−3 mm2/s and 1.32 ± 0.07 × 10−3 mm2/s pre-RT, respectively) both showed an increase in all patients at one week post-RT (1.75 ± 0.16 × 10−3 mm2/s, p < 0.001 and 1.70 ± 0.16 × 10−3 mm2/s, p < 0.001, respectively), followed by a decrease in parotid glands at one year post-RT(1.57 ± 0.15 × 10−3 mm2/s, p < 0.001) but not in submandibular glands (1.69 ± 0.18 × 10−3 mm2/s, p = 0.581). An improvement in xerostomia was found in 13 patients at one year post-RT. Multivariate analysis revealed 4 significant predictors for the improvement of xerostomia, including dose to parotid glands (p = 0.009, odds ratio [OR] = 0.639), the ADC of submandibular glands (p = 0.013, OR = 3.295), pADCmax (p = 0.024, OR = 0.474), and pTmax (p = 0.017, OR = 0.729) at one week post-RT. CONCLUSION: The ADC value is a sensitive indicator for salivary gland dysfunction. DW-MRI is potentially useful for noninvasively predicting the severity of radiation-induced xerostomia.
Diffusion ; Follow-Up Studies* ; Head and Neck Neoplasms ; Humans ; Magnetic Resonance Imaging* ; Multivariate Analysis ; Odds Ratio ; Parotid Gland ; Radiotherapy ; Salivary Glands* ; Submandibular Gland ; Xerostomia*

[Abstra ct] Objective To investigate the long-term efficacy and adverse effects of intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC).Methods A total of 869 patients with biopsy-proven NPC without distant metastasis who underwent the whole course of IMRT from 2009 to 2010 were enrolled.Of all the patients, 84.8%received cisplatin-based chemotherapy.The prescribed dose to the primary lesion in the nasopharynx was 66-70Gy in 30-32 fractions, and the dose to the positive lymph nodes in the neck was 66 Gy in 30-32 fractions.The Kaplan-Meier method was used to calculate survival rates, the log-rank test was used for difference analysis and univariate prognostic analysis , and the Cox proportional hazards model was used for multivariate prognostic analysis .Rseu lts The 5-year overall survival( OS ) , local recurrence-free survival, regional recurrence-free survival, distant metastasis-free survival, and disease-free survival ( DFS ) were 84.0%, 89.7%, 94.5%, 85.6%, and 76.3%, respectively.In the patients with locally advanced NPC,concurrent chemotherapy tended to reduce distant metastasis (83.6%vs.75.7%, P=0.050) and improve OS (82.6%vs.77.0 %, P=0.082).Induction chemotherapy tended to improve OS ( 80.7% vs.71.4%, P=0.057 ) , and the induction chemotherapy containing docetaxel or gemcitabine tended to improve OS (83.3%vs.72.2%, P=0.058).The patients who received a boost after the initial radiotherapy had a significantly lower DFS rate than those who did not (52.2%vs.71.1%, P=0.004).The concurrent chemotherapy increased the incidence rates of long-term xerostomia and trismus, while a high dose of cisplatin increased the incidence rates of xerostomia and hearing impairment.Conclusions IMRT for NPC provides satisfactory long-term efficacy.Concurrent chemotherapy combined with IMRT tends to reduce the incidence of distant metastasis, and other values need further investigation.The boost therapy after radiotherapy may be associated with poor prognosis.Chemotherapy increases the incidence of long-term toxicities.

OBJECTIVETo investigate the effects of rs10916581, a common single nucleotide polymorphism (SNP) located in the promoter region of pre-miR-320b-2, on coronary heart disease (CHD) risk and circulating microRNA-320b (miR-320b) level. To explore potential factors influencing circulating miR-320b level.

METHODSRs10916581 was genotyped in a case-control study with 1 507 CHD cases and 1 379 age- and sex-frequency-matched controls. The cases were consecutively recruited from 3 hospitals (Tongji Hospital, Union Hospital, and Wugang Hospital) in Wuhan city (Hubei, China) between May 2004 and October 2009 and all the controls resided in Wuhan communities. A subgroup of 174 CHD cases and 181 non-diabetes controls without acute infection were randomly selected and their circulating miR-320b levels were detected using quantitative reverse transcriptase polymerase chain reaction assays. The association of rs10916581 with CHD susceptibility was analyzed with multivariable logistic regression model. Generalized linear regression model was used to explore the associations of rs10916581 and some other factors with circulating miR-320b level.

RESULTSIn single-factor logistic regression analysis, no association was found between rs10916581 and CHD risk. After adjustment for age, sex, BMI, smoking status, hypertension, diabetes, total triglyceride, total cholesterol/high density lipoprotein (TC/HDL-C), the result did not materially alter(compared with CC genotype, the OR (95%CI) of CHR in the subjects carried CT, TT, CT+TT genotypes were 0.94 (0.76-1.15), 0.99 (0.74-1.33) and 0.95 (0.78-1.16) ). No significant interactions were observed between the conventional risk factors of CHD (age, gender, smoking status, BMI, hypertension, diabetes, CHD family history) and rs10916581 on CHD risk (P > 0.05). Rs10916581 showed no significant association with circulating miR-320b level in cases, controls or total population (β(95%CI) was -0.028 (-0.495-0.440), 0.250 (-0.226-0.727) and 0.134 (-0.218-0.486) respectively, P > 0.05). However, circulating miR-320b level was negatively associated with BMI (β (95%CI) was -0.140 (-0.261--0.020), P = 0.022) while positively associated with TC/HDL(β (95%CI) was 0.620 (0.261-0.979), P = 0.001) in cases, and in total population, its circulating level tended to be lower in diabetes or hypertension patients (β(95%CI) was -1.025 (-1.696--0.354) and -0.594 (-1.138--0.049) respectively, P = 0.003, 0.033 respectively) and was positively associated with TC/HDL-C (β(95%CI) was 0.108 (0.027-0.190), P = 0.009).

CONCLUSIONThe common SNP (rs10916581) in the promoter region of pre-miR-320b-2 might have little contribution to the CHD predisposition in Chinese Han population, and it might not affect circulating miR-320b level. Conventional CHD risk factors (BMI, TC/HDL-C, hypertension and diabetes) might have effects on its circulating level.

Aged ; Case-Control Studies ; China ; ethnology ; Coronary Disease ; genetics ; Diabetes Mellitus ; Genotype ; Humans ; Hypertension ; Logistic Models ; MicroRNAs ; adverse effects ; blood ; genetics ; Polymorphism, Single Nucleotide ; genetics ; Promoter Regions, Genetic ; Risk Factors ; Triglycerides

Anaplastic thyroid cancer (ATC) is the most aggressive thyroid tumor, with lower morbidity and higher mortality rates. Radical surgery could improve local control and survival rates. Conformal radiotherapy is superior to conventional radiotherapy, which could improve the patients’ quality of life. There are a few chemotherapeutic drugs against ATC, and the outcome of chemotherapy alone is modest. Concurrent chemoradiotherapy can prolong the survival. Targeted therapy brings new hope for refractory patients. Many cancer centers are exploring surgery, radiotherapy, chemotherapy, targeted therapy and other biological treatment of comprehensive application, in order to enhance the curative effect. This article reviewed the foregoing treatments for ATC.

Background Retninal neovascular diseases caused by hypoxia has become a major blinding disease,which is lack of effective chemical treatment currently,it's important to study the molecuar mechanism of the disease,so as to guide the clinical medication.Objective This study was to explore the effect of 15 (S)-hydroxyeicosate traenoic acid (15-HETE) on the proliferation of hypoxic retinal microvascular endothelial cells (RMVECs) and its probable mechanism.Methods RMVECs were isolated from C57BL/6J mice and incubated and then identified with anti-Ⅷ factor antibody by immunochemistry and immunofluorescence.The cells were divided into the normoxia group and the hypoxia group.The hypoxia cell models were established by treated with 125 μmol/L CoCl2.The cells were cultured with serum-free DMEM containing endothelial cell growth supplement (ECGS)and high glucose for 48 hours,and then different concentrations of 15-HETE (0.0,0.1,1.0,5.0 μmol/L) were added in the medium for 48 hours respectively to subgroup the groups.The proliferation of the cells (absorbance,A) was detected using MTT.The relative expression levels of protein and mRNA of hypoxia inducible factor-1α (HIF-1α),bcl-2 and caspase-3 were assayed by reverse transcription PCR (RT-RCR)and Western blot.Results The cells showed the positive response for anti-Ⅷ factor antibody with the positive rate of (94.38 ±4.25)％.No significant difference was found in the cell proliferation of various groups under the normoxia condition (F =0.283,P =0.837),but under the hypoxia condition,the proliferation values were significantly different among various groups (F =702.582,P＜0.001).The cell proliferation value in the 1.0 μmol/L 15-HETE group and 5.0 μmol/L 15-HETE group was lower than that of the simple hypoxia group respectively(both at P＜0.05).The inhibitory rates in the 0.1,1.0,5.0 μ mol/L 15-HETE groups were (1.09±0.31) ％,(21.09± 3.53) ％ and (49.86 ±4.15) ％,showing a dosedependent manner.No significant difference was seen in the expression levels of bcl-2,caspase-3 and HIF-1α mRNA in various groups under the normoxia conditions.However,compared with the simple normoxia group,the relative expressions of bcl-2 mRNA and HIF-1α mRNA in the cells were increased by 1.53 folds and 1.7 folds in the simple hypoxia group respectively,and caspasse-3 mRNA expression decreased by 70％ (all at P ＜ 0.05).Under the normoxia condition,the expression of bcl-2 and pro-caspase-3 protein in the cells were not significantly different among the various groups (P＞0.05),however,the expressions of bcl-2 and pro-caspase-3 proteins were elevated by 1.6 folds and 1.9 folds in the hypoxia group in compared with the normoxia group (P＜0.05).Compared with the simple hypoxia group,the expressions of bcl-2 and pro-caspase-3 were lowed by 40.4％ and 42.5％ in the 5.0 μmol/L 15-HETE group (P＜0.05).Conclusions 15-HETE inhibits the proliferation of RMVECs and therefore suppresses neovascularization by down-regulating the expressions of HIF-1α and bcl-2 and the activation of caspase-3 in a dose-dependent manner.

Objective To compare the efficacy after conventional radiotherapy and late course accelerated fractionation radiotherapy for nasopharyngeal carcinoma (NPC).Methods A total of 200 NPC patients were enrolled and randomly assigned to conventional radiotherapy (CF) group with 99 cases or late course accelerated fractionation radiotherapy (LCAF) group with 101 cases,who received irradiation to 60Co γ or 6 MV X-rays.In the CF group,the total dose of nasopharynx was 70 Gy/35 fractions at 2 Gy daily.In the LCAF group,for the first two-thirds of the treatment,two daily fractions of 1.2 Gy were given to the primary lesion and the total dose was 48 Gy/40 fractions.For the last one third of the treatment,the dose per fraction was increased to 1.5 Gy and the total dose was 30 Gy/20 fractions.Results There were 25,16,25 in CF group and 16,13,18 patients in LCAF group who had recurrence of nasophaynx,cervical lymph nodes,and distant metastasis,respectively.The 5-year nasopharyngeal control and overall survival rates was 75.9％ and 87.6％ in CFgroup (x2 =4.066,P＜0.05),58.0％ and 74.1％(x2 =5.076,P ＜ 0.05) in LCAF group,respectively.Cervical lymph nodes local rates and distant metastasesfree rates at 5 years were 8 1.5％ and 90.0％ in CF group (P ＞ 0.05),74.1％ and 83.3％ (P ＞ 0.05) in LCAF group,respectively.Conclusions Compared with CF,LCAF can improve nasopharyngeal control and overall survival rates,but there are no significant difference in the recurrence rates of cervical lymph nodes and distant metastasis.

ObjectiveTo evaluate the function of the salivary glands with gustatory stimulation by using MR DWI.MethodsA prospective study was conducted in 30 patients with nasopharyngeal carcinoma who had normal salivary function.A DWI sequence was performed on the salivary glands at resting state,and continually repeated on the parotid immediately after oral ascorbic acid stimulation over a period of 21 minutes (once every 18 seconds).The multiple b-values (0,400,600,800,1000 s/mm2) were used.ADC maps were evaluated with a manually placed region of interest including the entire salivary gland.The ADC of each gland was obtained by taking the mean of values on three contiguous sections containing the largest areas of the gland.The paired two-tailed Student t test was used to compare the ADC values of the parotid and the submandibular glands at rest,and of the parotid before and after stimulation.ResultsThe mean ADC value at rest was significantly lower in the parotid [ (1.23 ±0.12) × 10-3 mm2/s] than in the submandibular glands [(1.34 ± 0.07 ) × 10 -3 mm2/s,t =4.545,P ＜ 0.01 ].After acid stimulation,the ADC value increased from the baseline to (1.41 ±0.19) × 10-3 mm2/s firstly and then fluctuated at the following time,with a peak value of ( 1.49 ± 0.20 )× 10 -3 mm2/s and the average value of ( 1.36 ±0.17) × 10-3 mm2/s.The average value was significantly different from the baseline value (t =15.127,t =11.905,P ＜ 0.01 ).The minimum value [ ( 1.24 ± 0.14) × 10-3 mm2/s] was not significantly different compared to the baseline value (t =1.329,P ＞ 0.05 ).ConclusionMR DW1 can noninvasively evaluate the physiologic changes of salivary glands before and after acid stimulation.

ObjectiveTo evaluate the efficacy and toxicity of gemcitabine plus cisplatin (GP)chemotherapy combined with intensity-modulated radiation therapy (IMRT)in locoregionally advanced nasopharyngeal carcinoma (NPC).Methods71 patients (Stage Ⅲ:41,Stage ⅣA:30) with locoregionally advanced NPC were entered this study.Neoadjuvant chemotherapy was consisted of cisplatin 25 mg/m2 intravenously on d1-3 and gemcitabine 1000 mg/m2 in 30 minutes intravenous infusion on days 1 and 8,every 3 weeks for 2 cycles.Adjuvant chemotherapy consisted of 2 cycles of the same GP regimen was given at 28 days after the end of radiotherapy.The prescription doses was 66.0-70.4 Gy to the gross tumor volume,66 Gy to positive neck nodes,60 Gy to the high-risk clinical target volume,54 Gy to the low-risk clinical target volume.ResultsThe overall response rate to neoadjuvant chemotherapy was 91.2％,acute toxicity was mainly grade 1-2 myleosuppression.All patients completed IMRT.The median follow-up duration was 38 months.The 3-year nasopharyngeal local control,regional control,distant metastasis-free survival rate and overall survival rate were 93％,99％,91％,90％,respectively.Severe late toxicities included grade 3 trismus in 1 patient,grade 3 hearing impairment in 2 patients and cranial nerve palsy in 2 patients,respectively.No grade 4 late toxicities were observed.Conclusions The combination of GP chemotherapy and IMRT for locoregionally advanced nasopharyngeal carcinoma is well-tolerated,convenient,effective,and warrants further studies of more proper cycles of GP regimen.

Objective To investigate the value of magnetic resonance sialography (MRS) as a noninvasive tool in evaluating major salivary gland function before and after radiotherapy (RT) for nasopharyngeal carcinoma patients.Methods From August 2009 to June 2010,patients with stage Ⅰ and Ⅱa (AJCC/UICC 2002) nasopharyngeal carcinoma were enrolled.All the patients were treated with intensity modulated radiation therapy alone.MRS with salivary stimulation was performed in patients before and after RT on a 3.0T MR scanner.An MRS categorical scoring system was used to compare the visibility of ducts pre-RT and post-RT.The relationship between MRS score and EORTC Core QOL and EORTC Head and Neck QOL was analyzed.Spearman rank correlation test was performed to analyze the non-stimulated and stimulated MRS findings and the clinical severity of xerostomia.Results All 10 enrolled patients completed planned treatment.The mean dose of the parotid glands and submandibular glands were (37.99 + 3.70) Gy and (55.65 + 2.99) Gy,respectively.Good-quality MRS images were obtained.The visibility scores of both the parotid and submandibular ducts were increased after secretion stimulation.Irradiation decreased the visualization of the salivary ducts and attenuated the response to secretion stimulation.There were specific correlations between post-RT secretion response of the parotid gland and EORTC QLQ scales ( global QOL scale in QLQ-C30 ( rs =0.636,P =0.048 ) and xerostomia scale in QLQ H&N35 ( rs =- 0.694,P =0.026) ).Conclusions MRS can be used as a non-invasive way to evaluated of the functional changes of major salivary glands before and after RT and as a promising approach for investigating radiation-induced xerostomia.

Objective Nasopharyngeal carcinoma patients with stage N3 disease are prone to develop distant metastasis even treated with standard concurrent chemoradiotherapy(CRT).The aim of this study is to compare the ettlcacy of difierent chemotherapy sequences in these patients.Methotis All patients with histologically proven,carcinoma of the nasopharynx treated between July 1999 and November 2003 were restaged according to the AJCC 2002 stage classification system.A total of 114 patients had AJCC N3 diseases were analyzed retrospectively.Patients were treated by conventional RT technique using 6 MV photons or 60 Coγ-ray with 1.8-2.0 Gy per fraction,5 fractions a week,to a planned dose of 70 Gy.The prophylactic irradiation dose of the neck wss 54-60 Gy.Any positive lymph node was boosted to a total dose of 60-68 Gy.All patients received cisplatin-based chemotherapy of difierent sequences but 9 patients RT alone.CRT regimen was delivered in 37 patients,neoadjuvant chemotherapy(NACT)+CRT regimen in 53 patients and CRT+adjuvant chemotherapy(AC)regimen in 15 patients.Results The prophylactic irradiation dose of the neck wss 54-60 Gy.Any positive lymph node was boosted to a total dose of 60-68 Gy.All patients received cisplatin-based chemotherapy of difierent sequences but 9 patients received RT alone.CRT regimen was delivered in 37 patients,neoadjuvant chemotherapy(NACT)+CRT regimen in 53 patients and CRT+adjuvant chemotherapy(AC)regimen in 15 patients.Results The median follow up time was 54 months(3-117months).The 5-year overall survival rate was 59.1%in whole groups,and with 17%,51%,68%and 71%in RT,CRT,NACT+CRT and CRT+AC group,respectively(X2=15.44,P=0.001).The 5-year relapse-free survival rates were 83%,77%,88%and 93%in RT,CRT,NACT+CRT and CRT+AC group,respectively(X2=2.34,P=0.505).The 5-year metastasis-free survival rates were 17%,54%,72%and 80%in RT,CRT,NACT+CRT and CRT+AC group,respectively(X2=19.28,P=0.000).Conclusions The NACT+CRT and CRT+AC regimens were more effective than CRT alone for N3 disease in the current study.Large prospective,randomized clinieal studies are warranted.