1.Phase Ⅱ study of gemcitabine plus cisplatin chemotherapy combined with intensity modulated radiotherapy in locoregionally advanced nasopharyngeal carcinoma
Dan OU ; Xiayun HE ; Chaosu HU ; Hongmei YING ; Guopei ZHU
Chinese Journal of Radiation Oncology 2012;21(5):412-415
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.
2.Inhibition and mechanism of 15 (S)-hydroxyeicosate traenoic acid on proliferation of hypoxic retinal microvascular endothelial cells in vitro
Xiayun, HU ; Tao, HE ; Yiqiao, XING ; Qiong, WANG
Chinese Journal of Experimental Ophthalmology 2014;32(12):1067-1073
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.
3.Effects of preemptive analgesia with tramadol on stress reaction in patients with ovarian cancer after radical resection
Xiayun ZHOU ; Ruchun HU ; Yanqin CHEN ; Shizhong YANG
Chinese Journal of Primary Medicine and Pharmacy 2016;23(20):3121-3124,3125
Objective To study the effect of preemptive analgesia with tramadol on ovarian cancer patients with stress reaction.Methods 80 cases with ovarian cancer undergoing elective surgery under general anesthesia were divided into the observation group and the control group according to the computer randomly generated control table,40 cases in each group.Patients in the observation group with PECA were pumped into tramadol after anesthesia induction,while the control group was in the same conditions of pumping tramadol after operation.Patients were all treated with intravenous patient -controlled analgesia with sufentanil after waking up.The blood concentrations of cortisol (COR),adrenal cortical hormone (ACTH),angiotensin Ⅱ (AT Ⅱ)were determined by radioimmunoassay, and the blood concentrations C reactive protein (CRP)was determined by immune turbidity method.The adverse reactions and the VAS score of patients after 2h,6h,12h,24h,48h were recorded.Results The COR,ACTH,AT Ⅱ, CRP concentrations of the two groups had no significant differences (all P >0.05)before operation.After each time point,COR[(208.5 ±31.6)ng/mL vs (446.3 ±19.8)ng/mL],ACTH[(35.7 ±8.2)pg/mL vs (63.5 ±9.1)pg/mL],AT Ⅱ[(46.8 ±10.9)pg/mL vs (75.9 ±12.5)pg/mL],CRP[(3.9 ±0.7)mg/mL vs (40.5 ±2.9)mg/mL] concentrations were significantly higher than those of pre -operation (all P <0.05 );The concentration of COR [(446.3 ±19.8)ng/mL vs (570.8 ±67.2)ng/mL],ACTH (63.5 ±9.1)pg/mL vs (85.2 ±12.5)pg/mL),AT Ⅱ[(75.9 ±12.5)pg/mL vs (108.5 ±18.1)pg/mL]and CRP[(40.5 ±2.9)mg/mL vs (51.8 ±8.5)mg/mL]in the observation group was significantly lower than those in the control group (all P <0.05);After operation,the VAS scores of rest (2.4 ±0.7)and cough (3.4 ±1.0)in the observation group were significantly lower than those in the control group in 2h (t =5.812,P =0.017;t =14.606,P =0.044);At rest,the other time point of the two groups of VAS scores had no significant difference (P >0.05);At the time of coughing,the two groups were significantly differ-ent only at the 6h[(2.5 ±0.6)vs (3.1 ±0.8)]and 12h[(2.1 ±0.6)vs (2.9 ±0.4)]time point (t =13.406, P =0.012;t =12.625,P =0.025).Conclusion Preemptive analgesia with tramadol and sufentanil for postoperative analgesia can effectively reduce the radical resection of postoperative pain and the stress reaction after surgery.It is a safe and effective analgesic method.
4.Effect of heat preservation on the recovery of BIS and the concentration of propofol in the recovery of propofol in elderly patients
Xiaoguo LIU ; Guoyong XU ; Ruchun HU ; Xiayun ZHOU ; Yanqin CHEN
Chinese Journal of Biochemical Pharmaceutics 2017;37(5):362-364
Objective To analyze and discuss the effect of heat preservation on the recovery time of BIS and the concentration of propofol in the recovery period of the elderly patients with general anesthesia in order to provide guidance for clinical treatment.Methods78 elderly patients with general anesthesia were selected as the subjects, and the patients were divided into the control group and the study group with 39 cases in each group.The patients were divided into the control group and the study group.Control group, only to be liquid input and covered by drapes, research group take liquid input and peritoneal flushing fluid heating and heating blanket coverage of insulation measures, were recorded and compared between the two groups from anesthesia began to operation to complete the different time points of esophageal temperature and MAP, and to observe the recovery time of patients and effect compartment concentration differences.ResultsTwo groups at T0, T1 esophageal temperature no significant difference, study group t2-t6 esophageal temperatures were significantly higher than those of the control group (P<0.05), maps of the other two groups at different time points had no significant difference;when two groups of patients with propofol withdrawal BIS values had no significant difference (P<0.05), and in the time of discontinuation BIS is more than or equal to 80 recovery time and effect compartment concentration have significant difference (P<0.05).ConclusionThe surgical treatment of elderly patients with general anesthesia can help maintain the body temperature, shorten the recovery time of BIS and reduce the concentration of propofol in the recovery period.
5.Construction and immunological analysis of a combined multi-epitope vaccine against EGFR/HER2.
Chunping HU ; Xueting CAI ; Wuguang LU ; Zhigang WANG ; Xiayun JI ; Peng CAO
Acta Pharmaceutica Sinica 2011;46(11):1326-31
A recombinant plasmid pET28a-HBcAg-delta n was constructed, in which three mimic B-epitopes of HER family were inserted into the truncated HBc vector. The fusion protein expressed was purified and used to immunize BALB/c mice to induce antibody against the epitopes. Three mimic epitope genes were inserted into the sequences of amino acid residues 78 and 79 of HBcAg by overlap PCR. The PCR product was then cloned into pET28a to construct recombinant expression plasmid which was transformed to E. coli BL21 (DE3) and induced by IPTG. After purification, the fused protein designed HBHE was used to immunize BALB/c mice to detect humoral immunoresponse. The recombinant plasmid was successfully constructed by DNA sequencing analysis. A fusion protein with correct molecular mass was expressed and confirmed by SDS-PAGE. High titre antibody was elicited in the mice immunized with HBHE by indirect ELISA and Western blotting. The HBc particle vector containing three B-epitopes of HER family had been successfully prepared, purified and high titre antibody against HBHE was detected. All these data are helpful in further research of the broad-spectrum anti-tumour effect of combine polypeptide epi-position vaccine of EGFR and HER2.
7.Comparing treatment outcomes of different chemotherapy sequences during radio-chemotherapy for stage N3 nasopharyngeal carcinoma
Tingting XU ; Chaosu HU ; Xiaoshen WANG ; Yongru WU ; Xiayun HE ; Hongmei YING
Chinese Journal of Radiation Oncology 2011;20(3):181-185
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.
8.Treatment results of nasopharyngeal carcinoma : a retrospective analysis of 1837 cases in a single institute
Yunsheng GAO ; Chaosu HU ; Hongmei YING ; Guopei ZHU ; Lin KONG ; Xiayun HE ; Tingting XU ; Xiaoshen WANG ; Jing YUAN ; Suqin WU ; Youwang ZHANG ; Taifu LIU
Chinese Journal of Radiation Oncology 2008;17(5):335-339
Objective To summarize our experience and treatment results of nasopharyngeal carcinoma treated in a single institution. Methods From Jan. 2000 to Dec.2003,1837 patients with histologically proven nasopharyngeal carcinoma(NPC) were retrospectively analyzed. The disease was staged according to the Fuzhou stage classification. 885 patients received cisplatin (DDP) based chemotherapy. All patients received radiotherapy to the nasopharynx and neck. The dose was 30.6-74.0 Gy, 1.8-2.0 Gy per fraction over 3.5-8.0 weeks to the primary site with 60Co γ rays or 6 MV X-rays. The dose to lymph nodes was 60-68 Gy. The residual disease was boosted by 192Ir afterloading brachytherapy,small external beam fields, conformal radiotherapy,or X-knife. Results The median follow-up time was 54(3-90) months. The 5-year overall survival(OS), disease-free survival (DFS), relapse-free survival (RFS) and distant metastasis free survival(DMSF) rates were 67.42% ,63.25% ,86.47% and 80.31% ,respectively. Clinical stage was the most significant prognostic factor,and OS was 88% ,74.8% ,65.9% ,52.4% and 20% for stage Ⅰ ,stage Ⅱ,stage Ⅲ,stage ⅣA and stage ⅣB,respectively. Gender,T,N and TNM stage were the significant prognostic factors of OS in multivariate analysis. Conclusions For NPC patients,the 5-year OS of 67.4% is achieved by conventional radiotherapy technique in our institution. Both univariate and multivariate analysis shows that gender and clinical stage are the significant prognostic factors of OS.
9.The role of Magnetic resonance sialography in evaluating radiation-induced xerostomia for patients with early stage nasopharyngeal carcinoma
Dan OU ; Yunyan ZHANG ; Xiayun HE ; Yajia GU ; Chaosu HU ; Hongmei YING ; Guopei ZHU ; Yongru WU ; Jian MAO ; Xigang SHEN ; Lei YUE
Chinese Journal of Radiation Oncology 2011;20(6):462-466
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.
10.Long-term efficacy and adverse effects of intensity-modulated radiotherapy for nasopharyngeal carcinoma
Xiaomin OU ; Qi SHI ; Xin ZHOU ; Youqi YANG ; Xing XING ; Tingting XU ; Chunying SHEN ; Xiaoshen WAGN ; Lin KONG ; Xiayun HE ; Hongmei YING ; Chaosu HU
Chinese Journal of Radiation Oncology 2016;25(4):304-309
[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.