1.Correlation of EGFR gene mutation with its amplification and protein expression in non-small cell lung cancer
Shunping CHEN ; Haiyan SU ; Wenqiao WU ; Yinghao YU ; Wei LIU ; Hongwu SHEN
Chinese Journal of Clinical and Experimental Pathology 2015;(6):657-661,665
Purpose To investigate the corre1ation of the epiderma1 growth factor receptor( EGFR)gene mutation and amp1ification and protein expression with occurrence and deve1opment of non-sma11 ce11 1ung cancer( NSCLC),and to exp1ore the re1ationship be-tween the mutation and amp1ification of EGFR gene and other c1inica1 patho1ogica1 parameters. Methods qRT-PCR,FISH and immu-nohistochemistry were used to detect EGFR gene(exons 18,19,20 and 21)mutation,amp1ification and protein expression in paraf-fin-embedded tissues of NSCLC. Results EGFR gene(exons 18,19,20 and 21)mutation rate was 58. 18%(32/55)in NSCLC with qRT-PCR techno1ogy,in which the occurrence rate of exon 19 de1etions and exon 21 mutation of L858R was 87. 50%(28/32). EGFR gene mutation rate was significant1y different in gender,smoking history and patho1ogica1 type(P<0. 01),but no statistica1 sig-nificance in age,1ymph node metastasis and TNM staging(P>0. 05). EGFR gene amp1ification rate was 23. 64%(13/55)and its protein expression rate was 70. 91%(39/55). Both EGFR gene mutation and amp1ification was c1ose1y corre1ated(P<0. 05),but the two states of EGFR gene and its protein expression had no corre1ation(P>0. 05). Conclusion EGFR gene mutation with high pro-tein expression of NSCLC is common1y found in fema1e,no-smoking and adenocarinoma patients,who are main candidates of a tyrosine kinase inhibitor( TKI)screening. EGFR gene mutation and amp1ification is typica11y corre1ated,but their consequence is unknown, which needs to be further investigated. EGFR gene mutation and amp1ification is not consistent with protein expression,its under1ying machanism is to be determined.
2.Influences of gender, age, and body mass index on the arterial stiffness in hypertensive patients
Yinghao SHEN ; Junfeng ZHANG ; Jing ZHOU ; Xin RONG ; Hua GUO ; Qing GU ; Cailan ZHANG
Journal of Chinese Physician 2013;(4):465-468
Objective To investigate the influences of gender,age,and body mass index (BMI)on the arterial stiffness in hypertensive patients.Methods A total of 1026 hypertensive patients were enrolled in this study from 6 community health centers in Baoshan District and Shanghai Third People's Hospital.The Related medical histories and carotid-femoral(C-F) pulse wave velocity (PWV) were recorded and PWV were re-tested in 672 patients after 1 year's follow-up.The C-F PWV was analyzed from different group of Gender,age and BMI at baseline and after follow up.Results (1)C-F PWV of the male hypertensive patients were higher than that of female's and the corresponding figures were (13.63 ±3.07)m/s and (12.59±2.85)m/s(P <0.01).After one year's follow up,C-F PWV was increased in both male and female with corresponding figures of (14.11 ± 3.58) m/s and (13.51 ± 3.56) m/s (P < 0.05).(2) The C-F PWV was increased with age.The corresponding figures were [(11.11 ± 2.00) m/s for age group 30 ~ 50 years old,(12.73 ± 2.77) m/s for age group > 50 ~ 70 years old,and (14.74 ± 3.29) m/s for age group > 70 years old,all P <0.01].After one year's follow-up,C-F PWV of three age groups was increased and the corresponding figures were [(11.36±1.78)m/s(P >0.05),(13.39±3.33)m/s(P <0.01),and (15.68 ±3.94)m/s(P <0.05)].The increased range of C-F PWV (from high to low) was age group > 70,age group > 50 ~70 and age group 30 ~50.(3) C-F PWV of patients with BMI ≥ 24 kg/m2 was significantly lower than that of patients with BMI <24 kg/m2 and the corresponding figures were [(12.93 ±2.89)m/s and (13.39 ±3.18)m/s,P <0.05].After one year's follow up,C-F PWV was increased and the figures were [(13.54 ± 3.54) rn/s and (14.27±3.61) m/s,respectively(P <0.01)].Conclusions Except BMI,gender and age were the important influence factors on arterial stiffness.
3.Expression of Dishevelled 2 gene and protein in clear-cell renal cell carcinoma tissues and its clinical significance
Yinhui YANG ; Jianguo HOU ; Chuanliang XV ; Li JIAO ; Jian SHEN ; Yinghao SUN
Cancer Research and Clinic 2011;23(6):364-367
Objective To explore the relationship of DVL2 expression and the development of (CCRCC) by comparing the changes of DVL2 mRNA and protein expression in CCRCC specimens and matched normal renal specimens and its clinical significance. Methods DVL2 mRNA expressions in 22 CCRCC tissues, the matched adjacent normal tissues, and 10 CCRCC tissues alone were examined by semiquantitative RT-PCR and fluorescence quantitative PCR (real-time RT-PCR). Meanwhile, the different expression of the CCRCC between TNM Stage Ⅲ + Ⅳ and Stage Ⅰ +Ⅱ was also examined. Furthermore,immunohistochemistry was employed to examine DVL2 protein expression in 22 CCRCC and the matched adjacent normal tissues, and the other 10 CCRCC tissuses without the matched tissues. Results The DVL2 mRNA expression levels in 17 CCRCC tissues were increased by semi-quantitative RT-PCR and by real time RT-PCR compared with that in corresponding adjacent normal tissues, with the difference being significantly different (t = 2.535, P =0.0197). The DVL2 expression of 8 in 13 Ⅲ + ⅣCCRCC was higher than Ⅰ +ⅡCCRCC. Immunohistochemical examination showed that the DVL2 protein was located in cytomembrane and cytoplasm. Moreover, the positive level of DVL2 protein in CCRCC tissues[81.8 % (18/22)]was significantly higher than those in the adjacent tissues. However the expression was not associated with patients' age, gender, TNM stages (Fisher exact frenquently, P >0.05). Conclusion The DVL2 expression in CCRCC is obviously higher than the corresponding normal tissues in the level of mRNA and protein. And the higher DVL2 expression might be closely associated with the development and progression of CCRCC in the level of mRNA, which may be a potential molecular marker of CCRCC development and metastasis mechanism.
4.Dianosis and treatment of hepatic metastasis from gastrointestinal stromal tumor
Yinghao SHEN ; Jia FAN ; Zhiquan WU ; Jian ZHOU ; Shuangjian QIU ; Yingyong HOU ; Yao YU ; Xiaowu HUANG
Chinese Journal of Digestive Surgery 2008;7(6):450-451
Objective To investigate the diagnosis and treatment of hepatic metastasis from gastrointestinal stromal turnor(GIST).Methods The clinical data of 16 patients with GIST who had been admitted to our hospitalfrom December 1993 to May 2007 were retrospectively analyzed.Results Of all patients,14 underwent radical resection and 2 underwent palliative operation.Two patients with palliative operation and 3 with radical resection were administered with imatinib postoperatively. All patients were followed up for 3-161 months,and GIST metastasis and invasion was observed in 8 of the 14 patients who received radical resection.Of the 7 patients with hepatic metastasis.3 were treated with hepatic artery chemoembolization,1 was administered with imatinib,2 received reoperation and 1 did not receive any treatment. Reoperation was carried out on 1 patient who had abdominal wall metastasis.The 1-and 3-year survival rates of the 16 patients were 92%and 74%,respectively.Conclusions The recurrence rate of GIST after hepatectomy is high.Complete surgical resection is the best curative treatment for hepatic metastasis from GIST and GIST recurrence.The combination of surgical resection and imatinib administration may help to improve the prognosis of patients with hepatic metastasis from GIST.
5.Effects of fast-track surgery on postoperative rehabilitation of patients with liver cancer
Jie HU ; Zongjun LI ; Jia FAN ; Yang XU ; Jian ZHOU ; Yinghao SHEN ; Yongsheng XIAO ; Zheng WANG
Chinese Journal of Digestive Surgery 2009;8(4):281-283
Objective To investigate the effects of fast-track surgery on postoperative rehabilitation of patients with liver cancer. Methods Forty-one patients with liver cancer who had been admitted to Zhongshan Hospital of Fudan University from 9 to 30 in July 2008 were randomly divided into fast-track surgery group (n =20) and routine treatment group (n =21) according to the random number table. Patients in fast-track surgery group were preoperatively educated in order to lessen their anxiety. Bowel preparation was not applied before operation, and they were orally administered with 1000 ml of enteral nutrition emulsion (1300 kcal), then they were fasted for 4 hours before operation. Urethral catheter and gastric tube were removed after operation. They were orally administered with 1000 ml of enteral nutrition emulsion on postoperative day 2, and were encouraged to partake in off-bed activity shortly after the operation. The off-bed time, anus exhaust time, postoperative complica-tions, hospitalization time, expense, nutritional and metabolic indexes on postoperative day 1, 3 and 5, hepatic and renal function, immune and stress indexes between the 2 groups were compared by t test and chi-square test. Results There were significant differences in off-bed time, anus exhaust time, patients' weight, expense, total bilirubin level on postoperative day 1, 3 and 5, and level of serum TNF-α on postoperative day 3 between the 2 groups (t =7.065, 5.483, 3.754, 2.291,2.289, 3.218, 3.192, 2.434, 2.089, P <0.05). Conclusions Fast-track surgery can accelerate the postoperative rehabilitation of patients with liver cancer.
6.Apoptotic effect of 4,5,6,7-tetrabromobenzotriazole on human cervical cancer HeLa cells and its mechanism
Xueyuan JIANG ; Xianji PIAO ; Chang LIU ; Yinghua LUO ; Hunan SUN ; Yinghao HAN ; Guinan SHEN ; Yanqing ZANG ; Chenghao JIN
Journal of Jilin University(Medicine Edition) 2017;43(3):561-565
Objective:To investigate the promotive effect of 4,5,6,7-tetrabromobenzotriazole (TBB) on the apoptosis of the human cervical cancer HeLa cells,and to clarify its effect mechanism in related signaling pathways.Methods:The human cervical cancer HeLa cells at logarithmic growth phase were divided into control group(without TBB) and experiment group(with TBB).MTT assay was used to detect the survival rate of the HeLa cells;the morphology of HeLa cells was observed under inverted microscope;Annexin Ⅴ-FITC/PI double staining and flow cytometry(FCM) were used to determine the apoptotic rates of the HeLa cells;the expression levels of apoptosis-related proteins p-Akt,Akt,Bcl-2,Bax,cleaved-caspase-3,and Pro-caspase-3 were detected by Western blotting method.Results:The MTT results showed that the survival rates of the HeLa cells in experiment group were significantly decreased(P<0.01) in a dose-dependent manner compared with control group.The apoptotic morphology of the HeLa cells in experiment group were found as cell shrinkage and karyopyknosis under inverted microscope.The Annexin Ⅴ-FITC/PI double staining and FCM results showed that the apoptotic rates of the HeLa cells in experiment group (3,6,12 and 24 h) were higher than that in control group (P<0.05 or P<0.01).The Western blotting results showed that compared with control group,the expression levels of the anti-apoptotic proteins p-Akt and Bcl-2 in HeLa cells in experiment group were decreased obviously,whereas the expression levels of the pro-apoptotic proteins Bax and cleaved-caspase-3 were increased and the expression levels of Pro-caspase-3 were decreased.Conclusion:TBB may promote the apoptosis of human cervical cancer HeLa cells by inhibiting the Akt signaling pathway.
7.Submucosa dilation assisted laser resection of bladder tumor for the treatment of solitary non-muscle invasive bladder cancer: initial experience
Zhensheng ZHANG ; Chuanliang XU ; Yinghao SUN ; Bo YANG ; Yang WANG ; Dan SHEN ; Chengyao WU ; Weidong XU ; Qinsong ZENG ; Liang TANG
Chinese Journal of Urology 2011;32(11):771-774
ObjectiveTo evaluate the safety and efficacy of submucosa dilation assisted laser resection of bladder tumor for the treatment of solitary non-muscle invasive bladder cancer. MethodsA total of 12 patients with solitary non-muscle invasive bladder tumor were treated with the procedure of submucosa dilation assisted laser resection under total intravenous anesthesia or epidural anesthesia.lntravesical instillation chemotherapy was performed according to CUA 2007 guidelines.Patients were followed up for 4 - 36 months after the operation. ResultsThe diameter range of the tumors was 0.5 - 2.3 cm with the clinical stage Ta - T1 and low pathology grade.Submucosa dilation assisted laser resection of bladder tumor was successfully performed on all patients.The average operation time was 25 min (range,20 -45 min ),and the catheter time was 3 d ( range,1 -4 d).The mean volume of bleeding was less than 5 ml,no patient required blood transfusion.No complications such as obturator nerve reflex,bladder perforation and over-hydration occurred.No recurrence occurred during the follow-up. ConclusionsSubmucosa dilation assisted laser resection of bladder tumor could be an effective,safe,and excellent alternative procedure for the treatment of solitary non-muscle invasive bladder cancer,with few complications and a low recurrence rate.More studies and long-term follow-up should be warranted to ultimately evaluate this procedure.
8.Hypertension intervention program organized by tertiary hospitals with community health centers
Jing ZHOU ; Junfeng ZHANG ; Yinghao SHEN ; Jincheng HUANG ; Haihong TANG ; Meijuan YUAN ; Ping WANG ; Jiewen XIAO ; Deying ZHANG
Chinese Journal of General Practitioners 2012;11(9):689-691
Five hundred and nineteen patients with essential hypertension from 6 community health centers in Baoshan Distract of Shanghai were enrolled in the program,all patients received direct or indirect comprehensive interventions.These interventions were conducted by doctors from tertiary hospitals and community health serwice centers.Among these hyperpietic,462 patients were followed-up for 1 year.After interventions,the awareness rate of hypertension was significantly increased,unhealthy life styles were changed; blood pressure control rate and risk factors control rate were also increased; carotid-femoral artery pulse wave velocity and carotid-radial artery pulse wave velocity were decreased (P < 0.01 or P < 0.05).The results indicate that comprehensive interventions organized by tertiary hospitals with community health centers are effectivc in managcmcnt of hypcrtension.
9.Clinical efficacy of combination therapy with lenvatinib and programmed death-1 antibodies in unresectable or advanced hepatocellular carcinoma
Bin XU ; Xiaodong ZHU ; Cheng HUANG ; Yinghao SHEN ; Jinjin ZHU ; Meiling LI ; Jie LIU ; Jian ZHOU ; Jia FAN ; Huichuan SUN
Chinese Journal of Digestive Surgery 2021;20(2):197-204
Objective:To investigate the clinical efficacy of the combination therapy of lenvatinib and programmed death-1 (PD-1) antibodies in unresectable or advanced hepatocellular carcinoma (HCC).Methods:The retrospective and descriptive study was conducted. The clinico-pathological data of 59 patients with unresectable or advanced HCC who were admitted to Zhongshan Hospital of Fudan University from September 2018 to January 2020 were collected. There were 54 males and 5 females, aged from 25 to 73 years, with a median age of 52 years. All 59 patients underwent combination therapy with lenvatinib and PD-1 antibodies including 43 cases undergoing first-line therapy and 16 cases who cannot tolerate first-line therapy or with tumor progressed after first-line therapy undergoing second-line therapy. Observation indicators: (1) clinical efficacy; (2) adverse drug reactions and treatment; (3) follow-up and survival. Follow-up was performed using outpatient examination or telephone interview to detect tumor diameter of the target lesion, overall survival and progression free survival of patients up to December 2020. Measurement data with skewed distribution were expressed as M ( P25,P75) or M (range). Count data were represented as absolute numbers and (or) percentages. The Kaplan-Meier method was used to calculate the median duration of response (DoR), median overall survival time, median progression free survival time, survival rates and draw survival curves. Results:(1) Clinical efficacy: the objective response rate (ORR), complete response rate (CR), partial response rate (PR), stable disease rate (SD), progression disease rate (PD), time to response (TTR) and median DoR of 59 HCC patients were 37.3%(22/59), 11.9%(7/59), 25.4%(15/59), 37.3%(22/59), 25.4%(15/59), 2.6 months(2.1 months, 4.0 months), 6.3 months[95% confidence interval ( CI) as 2.2 to 10.5 months], respectively. The ORR, CR, PR, SD, PD and TTR of 43 HCC patients undergoing first-line therapy were 41.9%(18/43), 16.3%(7/43), 25.6%(11/43), 37.2%(16/43),20.9%(9/43), 2.2 months(2.0 months, 3.5 months), respectively. The median DoR of 43 patients undergoing first-line therapy was not reached. The ORR, CR, PR, SD, PD, TTR and median DoR of 16 HCC patients undergoing second-line therapy were 4/16, 0, 4/16, 6/16, 6/16, 3.8 months (3.6 months, 4.1 months), 4.2 months(95% CI as 2.0 to 6.3 months), respectively. Six of 59 HCC patients underwent R 0 resection due to tumor converting to resectable HCC with the conversion and resection rate of 10.2%(6/59). Among the 6 patients, 5 cases undergoing first-line treatment had the conversion and resection rates of 11.6% (5/43) and 1 case undergoing second-line treatment had the conversion and resection rates of 1/16, respectively. (2) Adverse drug reactions and treatment: 25 of 59 HCC patients underwent 3 to 4 grade adverse drug reactions with the incidence of 42.4%(25/59). Among the 25 patients, 10 cases including 5 cases undergoing first-line therapy and 5 cases undergoing second-line therapy had the level of gamma glutamyltransferase >5×upper limit of normal (ULN), 9 cases including 4 cases undergoing first-line therapy and 5 cases undergoing second-line therapy had the level of aspartate aminotransferase >5×ULN, 5 cases including 4 cases undergoing first-line therapy and 1 case undergoing second-line therapy occurred gastrointestinal hemorrhage, 4 cases undergoing first-line therapy had the level of white blood cell count <2.0×10 9/L, 4 cases including 1 case undergoing first-line therapy and 3 cases under-going second-line therapy had the level of total bilirubin >3×ULN, 3 cases undergoing first-line therapy had the level of neutrophil count <1.0×10 9/L, 3 cases including 2 cases undergoing first-line therapy and 1 case undergoing second-line therapy occurred ascites, 2 cases including 1 case undergoing first-line therapy and 1 case undergoing second-line therapy had the level of platelet count <50.0×10 9/L, 2 cases undergoing first-line therapy had the level of alanine aminotransferase >5×ULN, 2 cases undergoing first-line therapy occurred hyponatremia, 2 cases including 1 case undergoing first-line therapy and 1 case undergoing second-line therapy occurred pulmonary infection, 2 cases including 1 case undergoing first-line therapy and 1 case undergoing second-line therapy occurred type 1 diabetes, 1 case undergoing first-line therapy occurred hypokalemia, 1 case undergoing first-line therapy occurred myocarditis, 1 case undergoing first-line therapy occurred hypophysistis, 1 case undergoing first-line therapy occurred bullous dermatitis, 1 case undergoing first-line therapy occurred hypertension. Three of 59 HCC patients underwent 5 grade adverse drug reactions ,with the incidence of 5.1%(3/59), including 1 case undergoing first-line therapy with immune hepatitis, 1 case undergoing second-line therapy with immune pneumonia and 1 case undergoing second-line therapy with immune enteritis. Some of patients underwent multiple adverse drug reactions at the same time. Twenty five patients undergoing 3 to 4 grade adverse drug reactions were relieved with the treatment of drug reduction, drug withdrawal, symptomatic treatment or hormone therapy. Three patients undergoing 5 grade adverse drug reactions died after being treated with high-dose hormone shock and hepatoprotective treatment. (3) Follow-up and survival: all 59 patients were followed up for 1.5 to 25.2 months, with a median follow-up time of 13.3 months. Of them, patients undergoing first-line therapy were followed up for 1.9 to 25.2 months, with a median follow-up time of 13.5 months. During follow-up,20 cases undergoing first-line therapy died with the fatality rate of 46.5%(20/43). Patients undergoing second-line therapy were followed up for 1.5 to 24.4 months, with a median follow-up time of 10.8 months. During follow-up, 10 cases undergoing second-line therapy died with the fatality rate of 10/16. Up to the latest follow-up, the tumor diameter of the target lesion in all 59 patients, in patients undergoing first-line therapy and in patients undergoing second-line therapy was 75 mm(38 mm, 125 mm), 74 mm(36 mm, 116 mm), 84 mm(48 mm,150 mm), respectively. The ratio of tumor diameter of the target lesion at latest follow-up to tumor diameter of the target lesion at baseline were -9.05%(-27.3%, 19.7%), -16.1%(-28.8%, 13.6%), 13.2%(-24.7%, 23.5%) for all 59 patients, patients undergoing first-line therapy and patients undergoing second-line therapy, respectively. The median overall survival time and median progression free survival time of patients undergoing first-line therapy and patients undergoing second-line therapy were 17.1 months(95% CI as 11.0 to 23.2 months), 10.8 months(95% CI as 5.0 to 16.6 months) and 10.8 months(95% CI as 9.2 to 12.4 months), 3.0 months(95% CI as 1.6 to 4.4 months), respectively. Conclusion:For unresectable or advanced HCC, combination therapy with lenvatinib and PD-1 antibodies can obtain effective antitumor activity and less incidence of adverse drug reactions.
10.Focal nodular hyperplasia of the liver: a report of 60 cases
Yinghao SHEN ; Jia FAN ; Zhiquan WU ; Zengchen MA ; Xinda ZHOU ; Jian ZHOU ; Shuangjian QIU ; Lunxiu QIN ; Qinghai YE ; Huichuan SUN ; Xiaowu HUANG ; Zhaoyou TANG
Chinese Journal of General Surgery 2001;0(07):-
Objective To evaluate the diagnosis and treatment of focal nodular!hyperplasia of the liver (FNH). Methods Retrospective analysis was made on 60 FNH cases in terms of clinical findings, images, pathologic examination and surgical treatment. Results Of the 60 FNH patients in our hospital from 1993 to 2003, 41 were male and 19 female. The average age was 37 year′s old. Fifty-five cases had single focus, the other five were of multiple lesion, with tumor diameter 10cm in one. Correct preoperative diagnosis was made in 33 cases (55%). The correct diagnostic rate of BUS, CT and MRI was 33.3%, 58.3% and 72.0%, respectively. All 60 cases underwent operation with an uneventful recovery and without recurrence at follow-up. ConclusionsCT and MRI are mandatory for the diagnosis of FNH. Definite preoperative diagnosis is usually difficult even in cases of typical type of FNH. Surgical resection is the treatment of choice when a patient becomes symptomatic or when malignancy could not be excluded.