1.Effects of cancer stem cell surface marker CD44 in gastric cancer invasion and lymph node metastasis
Chinese Journal of Tissue Engineering Research 2015;(23):3669-3673
BACKGROUND:Tumor stem cels not only initiate tumorigenesis, but also are involved in the invasion and metastasis of tumor cels. For tumor stem cels, to identify the specific cel surface marker has become a research hotspot. OBJECTIVE:To explore the clinical significance of cancer stem cel surface marker CD44 in gastric cancer invasion and lymph node metastasis. METHODS: CD44 protein expression in specimens of gastric cancer tissue was detected by the immunohistochemical SABC method. The relationship between CD44 protein expression and biological characteristics and prognosis of gastric cancer was detected using Pearsonχ2 test and Cox regression analysis. RESULTS AND CONCLUSION:Among 100 cases of gastric carcinoma, 59 cases (59%) were positive for CD44 protein expression. CD44 protein expression in normal gastric mucosa at above 5 cm from the edge of primary gastric cancer was negative. CD44 protein was widely expressed in tissues of gastric cancer, mainly expressed in the cel membrane, and a smal amount of expression in the cytoplasm. CD44 protein expression in gastric cancer tissue was not correlated with sex of the patients or age (P > 0.05), but was associated with tumor staging and lymph duct tissue infiltration, histological grade, and tumor size (P < 0.05). Deep tumor invasion, high histological grade, big diameter of tumor, and lymph node metastasis could lead to high positive CD44 protein expression. Positive expression of CD44 is an independent prognostic factor affecting postoperative survival (P < 0.05). The results show that the cancer stem cel surface markers CD44 in gastric carcinoma tissues is strongly associated with invasion of gastric carcinoma and lymph node metastasis. High expression of CD44 presents poor prognosis.
2.Effect of C-fos antisense oligodeoxynucleotide-induced activation of Caspase 3 on inducing apoptosis of human hepatocellular carcinoma HepG2 cells
Yanming CHU ; Qiaoying XIE ; Wencheng LIU ; Kaishan TAO
Medical Journal of Chinese People's Liberation Army 1982;0(01):-
Objective Proliferation and apoptosis play a major role in the development of tumor cells,and the intranuclear transcriptional factor c-fos is significantly up-regulated in the primary hepatocellular carcinoma and involved in early carcinogenesis.The purpose of the present study is to investigate the apoptotic effect of c-fos antisense oligodeoxynucleotide(ASO) on human hepatocellular carcinoma HepG2 cells and the participation of Caspase3 in this process.Methods Cell culture,Hoechst 33258 staining,real-time PCR and Western blotting were used in present study.Cultured HepG2 cells were divided into 3 groups: 1) control group: cultured with 10?l saline;2) sense oligodeoxynucleotide(SO,used as a negative control) treated group: co-cultured with 10?l SO(5?g/?l);3) ASO treated group: co-cultured with ASO 10?l(5?g/?l).The subsequent experiments were performed 1h after cultivation for each group.Hoechst 33258 staining was performed to detect the apoptosis by observing the staining of nuclear chromatin.Real-time PCR and Western blotting were used respectively to detect the expression of Caspase 3 at mRNA and protein levels after different treatments.Results Hoechst 33258 staining revealed that the nuclei of HepG2 cells showed diffuse and adqulis fluorescence in control and SO-treated groups,while dense and dark fluorescence was observed in ASO-treated group,which indicated that c-fos ASO had significantly induced apoptosis of HepG2 cells.The expression of Caspase 3 in ASO group was enhanced both at mRNA and protein levels compared to that in control groups.Conclusions C-fos ASO significantly induces apoptosis in human hepatocellular carcinoma HepG2 cells,as shown by Hoechst 33258 staining and higher expression of Caspase 3 mRNA and protein.Moreover,Caspase 3 activation is involved and probably plays an important role in c-fos ASO-induced apoptosis of HepG2 cells.
3.Influence of pregnant rats' prenatal chronic stress on hippocampal dendritic spines and the function of learning and memory in their offsprings
Xicheng TAO ; De WU ; Jiulai TANG ; Ziyun ZHOU ; Jing ZHU ; Wencheng XU
Chinese Journal of Applied Clinical Pediatrics 2015;30(12):909-912
Objective To study the influence of pregnant rats' prenatal chronic stress (PS) on learning and memory of their offspring rats and its possible molecular mechanisms.Methods Pregnant females were individually restrained for 45 min 3 times a day during pregnancy from day 14 to day 21.Control pregnant females were left undisturbed in their home cages.The rat offsprings were randomly assigned to PS group or control group.Males and females were kept for the study separately.The learning and memory of the developing rat offspring in the Morris water maze were examined.The basal levels of corticosterone (COR) and adreno-cortico-tropic-hormone (ACTH) were analyzed by using radioimmunoassay.The Golgi-Cox impregnation technique was used to compare density and morphology of the CA1 hippocampal dendritic spines.Results The escape latency (EL) to find the platform in the control group was significantly less than that in the PS group in female rat offspring (F =4.533,P < 0.05),and the difference was statistically significant on the 5th day (t =2.788,P < 0.01).EL to find the platform in the control group was significantly less than that in the PS group in male rat offspring (F =6.101,P <0.05),and the difference was statistically significant on the second day (t =3.051,P < 0.01).In the space exploration experiments of the water maze,the retention time observed for the control group and the PS group in the goal quadrant was similar(P > 0.05).The basal levels of the serum COR in the PS group were higher than those in the control group of female rat offspring(t =3.658,P < 0.01) and the basal levels of the serum ACTH in the PS group were higher than those in the control group of male rat offsprings(t =2.319,P < 0.05).A simplified pattern was observed in the CA1 hippocampal dendritic spines in the PS group,showing a less extent of dendritic arborization and the density was significantly lower than that in the control group(t =-3.072,P < 0.01).Conclusions Altered function of the hypothalamic-pituitary-adrenal axis in the offspring mediates the cognitive alterations observed following prenatal stress should to be associated with the lower density and simplified pattern of CA1 dendritic spines.
4.The study on the correlation between snoring and carotid artery plaques in the elderly population.
Zhangfeng WANG ; Tao YAO ; Liying WANG ; Wencheng YU
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2013;27(11):582-584
OBJECTIVE:
To explore the correlation between snoring and carotid artery plaques in the elderly population.
METHOD:
Sixty-seven patients with snoring and 61 healthy volunteers accepted questionnaire on sleep apnea were analyzed in the survey. Multivariate Logistic regression analysis was used to analyze the factors affecting carotid artery plaques.
RESULT:
Among the non-snorers (n = 61), mild snorer (n = 18), moderate snorers (n = 24) and severe snorers (n = 25) groups, the prevalence of carotid artery plaques in four groups were 19.7%, 44.4%, 62.5%, 84.0% respectively. There was statistically significant differences between groups. After multivariable adjustment, the moderate and severe snorers were still risk factors affecting carotid artery plaques, the OR (95% CI) values were 4.378 (1.181-16.225), and 19.572 (3.316-115.528) respectively.
CONCLUSION
The moderate and severe snoring in the elderly population were relevant to the increased prevalence of carotid artery plaques, and was a risk factor on carotid artery plaques.
Aged
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Carotid Stenosis
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epidemiology
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Female
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Humans
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Logistic Models
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Male
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Prevalence
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Risk Factors
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Snoring
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epidemiology
5.Analysis of recurrent and prognosis factors of primary retroperitoneal liposarcoma
Daling ZHANG ; Yafei DING ; Xinquan ZHANG ; Huhuang ZOU ; Tao WANG ; Jun WANG ; Wencheng YAO ; Zhankui JIA ; Xiaowei DANG ; Jinjian YANG
Chinese Journal of Urology 2021;42(2):137-143
Objective:To investigate the factors related to recurrence and prognosis of retroperitoneal liposarcoma.Method:The clinical data of patients with primary retroperitoneal liposarcoma who underwent surgical treatment in the First Affiliated Hospital of Zhengzhou University from June 2011 to January 2020 were analyzed retrospectively. There were 42 males and 47 females and patients’median age was 53 (26-78). Sixty-five cases were treated by operation in our hospital, and 24 cases were primarily treated by the operation in another hospital. The clinical manifestations of the initial diagnosis included retroperitoneal mass in 41 cases, abdominal distension in 12 cases, abdominal pain in 10 cases, fever in 11 cases, nausea, vomiting and poor appetite in 8 cases, frequent urination and dysuria in 6 cases, and bilateral lower limb edema in 1 case. Preoperative CT imaging showed that the tumor body was located in the retroperitoneal kidney area in 58 cases, while in the retroperitoneal space or the pelvic extraperitoneal space in 31 cases. There were 55 single cases and 34 multiple cases. The median tumor length was 20(3-52) cm. Among the primarily treated 65 patients, 47(72.3%) were considered as primary retroperitoneal liposarcoma by preoperative imaging examination. Among the 89 patients treated by surgery, 78 underwent endoscopic surgery, among which 21 underwent laparoscopic surgery, 38 cases of retroperitoneal laparoscopic surgery, 19 cases of Da Vinci robot-assisted laparoscopic surgery. Open operation was performed in 11 cases. There were 87 patients undergoing radical resection and 2 patients undergoing palliative resection. Forty-two patients underwent intraoperative combined resection of the adjacent organs. The recurrence and survival status of patients were followed up.Results:All the 89 patients underwent the operation successfully, with the median operative blood loss of 200 (10-2000) ml. There were 23 cases being diagnosed of well differentiated liposarcoma, 40 cases of dedifferentiated, 20 cases of myxoid/round, 5 cases of myxoid liposarcoma, and 1 cases of mixed type. Pathologically, there 42 cases with low grade histology and 47 cases with high grade histology. In this study, 89 patients were followed up for 3 to 108 months, and the median follow-up time was 28 months. The 5-year recurrence free survival rate, disease-free survival rate and overall survival rate of the patients were 16.7%, 16.1% and 52.6%, respectively. There were 57 patients presenting local recurrence, 1 patient of lung metastasis, and 1 patient of liver metastasis, and the median disease-free survival time was 24 months. There were 42 patients died of the disease, with a median survival time of 64 months. Univariate analysis showed that intraoperative blood loss( P<0.01), whether multiple cases( P<0.01), pathologic types( P<0.01), and histological grades ( P<0.01) were related to disease-free survival.The intraoperative blood loss( P<0.01), multiple cases( P<0.05), pathologic types ( P<0.05), and recurrence ( P<0.01)were related with overall survival. Gender, age, tumor size, tumor location, whether primary surgery, radical resection or combined resection of adjacent organ had no effect on the prognosis of patients ( P>0.05). Cox regression model multivariate analysis revealed that surgical bleeding ( RR=2.360, 95% CI 1.313-4.241, P=0.004), multiple tumor ( RR=1.899, 95% CI 1.068-3.375, P=0.029), and pathological type ( RR=4.976, 95% CI 1.622-15.264, P=0.005) were independent factors affecting disease-free survival. The recurrence was an independent factor affecting the overall survival of patients ( RR=31.495, 95% CI 1.062-933.684, P=0.046). Conclusions:Retroperitoneal liposarcoma is a rare disease with high recurrence rate. The intraoperative blood loss, whether multiplicity and pathological type are independent factors affecting the disease-free survival, and recurrence is independent factors affecting the overall survival.
6.Transperitoneal robot-assisted nephroureterectomy with a single body position and original ports: a simplified surgical technique for upper urinary tract urothelial carcinoma
Zhankui JIA ; Tao WANG ; Huiwu XING ; Yafei DING ; Jun WANG ; Wencheng YAO ; Songchao LI ; Jinjian YANG
Chinese Journal of Urology 2020;41(7):503-506
Objective:To investigate the efficacy and safety of transperitoneal robot-assisted nephroureterectomy (RANU) with a single body position and original ports for upper urinary tract urothelial carcinoma(UTUC).Methods:Clinical data of 21 patients from March 2018 to November 2019 in the First Affiliated Hospital of Zhengzhou University was retrospectively analyzed, including 14 males and 7 females. The age was (63.8±11.4) years and the BMI was (23.6±2.5) kg/m 2.Of the 21 localized UTUC patients, 8 pelvic tumors, 3 middle ureter tumors, 10 lower ureter tumors; 11 on the left, 10 on the right; 20 of 21 tumors (95.2%) were high risk. Surgery was done by the same urologist. Under general anesthesia, the patients were in 75 ° healthy side lying position and overall 15 ° head down and foot high position. Improved layout of ports: camera port C was located at two fingers lateral to the umbilicus, 2 cm below the umbilicus; robotic arm port 1 and 2 were respectively located at pararestus line, close to costal margin and 2 cm below the midpoint between C and the affected iliac crest. Assistant port 1 and 2 were respectively located at 2 cm above the umbilicus and 4 cm below the umbilicus. The right cases need an additional assistant port under the xiphoid to provoke the liver. Hem-o-lok cliped the ureter distal to the tumor and the affected kidney was radically removed. Under the principle of tumor free, the ureter and the surrounding bladder wall within 1 cm were excised and the bladder was sutured. Lymphadenectomy was performed when the kidney and ureter were dissociated. Results:All 21 procedures were successful without open surgery or position change and intraoperative complications. No patients required a blood transfusion. The operation time was (205.2±57.3) min. The median intraoperative blood loss was 50 ml (20-120 ml). The median drainage tube indwelling time was 4d(3-7 d) and the median urinary catheter indwelling time was 7 d(5-8 d), the median postoperative hospital stay was 7 d(6-12 d).7 cases(33.3%)of Clavien-Dindo grade Ⅰ complications after surgery and they all relieved after giving symptomatic treatment. All postoperative pathology showed UTUC and negative resection margins. The median follow-up time was 12 months (4-22 months), 1 patient died of an accident 7 months after surgery and 3 patients had recurrence at 6, 8, and 10 months after surgery, survival at the last follow-up after treatment.Conclusions:The transperitoneal RANU with a single body position and original ports is safe and effective. The operation time is saved, the incidence of intraoperative and postoperative complications is low, the postoperative patients recover quickly.Short-term follow-up results prompt low recurrence rate and good tumor control effect.
7.Study on safety of adjuvant radiotherapy concurrent with weekly chemotherapy for stage ⅡB?ⅣA esophageal carcinoma after radical resection
Wenjie NI ; Shufei YU ; Jinsong YANG ; Wencheng ZHANG ; Zongmei ZHOU ; Hongxing ZHANG ; Dongfu CHEN ; Qinfu FENG ; Jima LYU ; Jun LIANG ; Xiaozhen WANG ; Xin WANG ; Lei DENG ; Wenqing WANG ; Tao ZHANG ; Nan BI ; Zefen XIAO
Chinese Journal of Oncology 2019;41(6):415-420
Objective To evaluate the tolerability and short?term efficacy of chemo?radiotherapy in 125 patients with stageⅡB?ⅣA esophageal carcinoma after radical resection. Methods We retrospectively evaluated the rate of completion, toxicity and survival of patients undergoing adjuvant concurrent chemo?radiotherapy after radical resection of esophageal carcinoma from January 2004 to December 2014 in our institution. The survival rate was determined by the Kaplan?Meier method and analyzed using the log?rank test. Multivariate prognostic analysis was performed using the Cox proportional hazard model. Results 122 patients received more than 50 Gy dose (97.6%). A total of 52 patients received more than 5 weeks chemo? radiotherapy (41.6%), while 73 patients underwent only 1?4 weeks (58.4%). The median following up was 48.4 months. 8 patients lost follow up ( 6.4%). The 1?year and 3?year overall survival rate were 91.6%and 57.0%, respectively, with a median survival time of 64.4 months. The 1?year and 3?year disease free survival rate were 73.2% and 54.3%, respectively, with a median disease free survival time of 59.1 months. The most common acute complications associated with chemo?radiotherapy were myelosuppression, radiation esophagitis and radiation dermatitis, the majority of which were Grade 1?2. Of the 125 patients, there were 59 cases of recurrence, including 23 cases with local regional recurrence, 26 cases with hematogenous metastasis, and 8 cases with mixed recurrence. Univariate analysis showed that the numbers of concurrent chemotherapy was associated with the overall survival (P=0.006). But receiving more than 5 weeks was not the prognostic factor compared to 1 to 4 weeks chemotherapy (P=0.231). Multivariate analysis showed that only the numbers of concurrent chemotherapy was an independent prognostic factor ( P = 0.010 ). Conclusions Postoperative radiotherapy concurrent with weekly chemotherapy could improve the overall survival and decrease the recurrence for stage ⅡB?ⅣA esophageal carcinoma after radical resection. However, the completion rate of chemotherapy was low, so it was necessary to explore reasonable regimens to improve the completion rate and carry out prospective randomized controlled trial.
8.Study on safety of adjuvant radiotherapy concurrent with weekly chemotherapy for stage ⅡB?ⅣA esophageal carcinoma after radical resection
Wenjie NI ; Shufei YU ; Jinsong YANG ; Wencheng ZHANG ; Zongmei ZHOU ; Hongxing ZHANG ; Dongfu CHEN ; Qinfu FENG ; Jima LYU ; Jun LIANG ; Xiaozhen WANG ; Xin WANG ; Lei DENG ; Wenqing WANG ; Tao ZHANG ; Nan BI ; Zefen XIAO
Chinese Journal of Oncology 2019;41(6):415-420
Objective To evaluate the tolerability and short?term efficacy of chemo?radiotherapy in 125 patients with stageⅡB?ⅣA esophageal carcinoma after radical resection. Methods We retrospectively evaluated the rate of completion, toxicity and survival of patients undergoing adjuvant concurrent chemo?radiotherapy after radical resection of esophageal carcinoma from January 2004 to December 2014 in our institution. The survival rate was determined by the Kaplan?Meier method and analyzed using the log?rank test. Multivariate prognostic analysis was performed using the Cox proportional hazard model. Results 122 patients received more than 50 Gy dose (97.6%). A total of 52 patients received more than 5 weeks chemo? radiotherapy (41.6%), while 73 patients underwent only 1?4 weeks (58.4%). The median following up was 48.4 months. 8 patients lost follow up ( 6.4%). The 1?year and 3?year overall survival rate were 91.6%and 57.0%, respectively, with a median survival time of 64.4 months. The 1?year and 3?year disease free survival rate were 73.2% and 54.3%, respectively, with a median disease free survival time of 59.1 months. The most common acute complications associated with chemo?radiotherapy were myelosuppression, radiation esophagitis and radiation dermatitis, the majority of which were Grade 1?2. Of the 125 patients, there were 59 cases of recurrence, including 23 cases with local regional recurrence, 26 cases with hematogenous metastasis, and 8 cases with mixed recurrence. Univariate analysis showed that the numbers of concurrent chemotherapy was associated with the overall survival (P=0.006). But receiving more than 5 weeks was not the prognostic factor compared to 1 to 4 weeks chemotherapy (P=0.231). Multivariate analysis showed that only the numbers of concurrent chemotherapy was an independent prognostic factor ( P = 0.010 ). Conclusions Postoperative radiotherapy concurrent with weekly chemotherapy could improve the overall survival and decrease the recurrence for stage ⅡB?ⅣA esophageal carcinoma after radical resection. However, the completion rate of chemotherapy was low, so it was necessary to explore reasonable regimens to improve the completion rate and carry out prospective randomized controlled trial.
9.Prognostic analysis of definitive three-dimensional radiotherapy for non-surgically resectable esophageal squamous cell carcinoma:a multi-center retrospective study ( 3JECROG R-01)
Xin WANG ; Lan WANG ; Junqiang CHEN ; Wencheng ZHANG ; Xiaomin WANG ; Xiaolin GE ; Wenbin SHEN ; Miaomiao HU ; Qianqian YUAN ; Yonggang XU ; Chongli HAO ; Zhiguo ZHOU ; Shuai QIE ; Na LU ; Qingsong PANG ; Yidian ZHAO ; Xinchen SUN ; Kaixian ZHANG ; Gaofeng LI ; Ling LI ; Xueying QIAO ; Miaoling LIU ; Yadi WANG ; Lei DENG ; Wenqing WANG ; Nan BI ; Tao ZHANG ; Wei DENG ; Chen LI ; Wenjie NI ; Xiao CHANG ; Weiming HAN ; Zongmei ZHOU ; Jun LIANG ; Qinfu FENG ; Lvhua WANG ; Dongfu CHEN ; Jima LY ; Shuchai ZHU ; Chun HAN ; Zefen XIAO
Chinese Journal of Radiation Oncology 2018;27(11):959-964
Objective To evaluate the survival and prognostic factors of esophageal cancer treated with definitive ( chemo ) radiotherapy by applying novel radiation techniques including three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT). Methods Clinical data of 2762 patients with non-operated esophageal squamous cell carcinoma who underwent definitive ( chemo ) radiotherapy from 2002 to 2016 in 10 hospitals were retrospectively analyzed.The prognostic factors were also identified and analyzed. Results The median follow-up time was 60. 8 months. The 1-, 2-, 3-and 5-year overall survival (OS) of all patients was 71. 4%,48. 9%,39. 3%,and 30. 9%,respectively.The 1-,2-,3-and 5-year progression-free survival (PFS) was 59.5%,41.5%,35.2%,and 30%,respectively.The median survival was 23 months.The median time to progression was 17. 2 months.Multivariate analysis demonstrated that age, primary tumor location, clinical stage, tumor target volume, EQD2 and treatment mode were the independent prognostic factors for OS.Primary tumor location,clinical stage,tumor target volume and EQD2 were the independent prognostic factors for PFS. Conclusions In this first large-scale multi-center retrospective analysis of definitive ( chemo) radiotherapy for esophageal squamous cell carcinoma in China, the 5-year OS of patients with esophageal squamous cell carcinoma is significantly improved by 3DCRT, IMRT combined with chemotherapy drugs. However, the findings remain to be validated by prospective clinical trials with high-level medical evidence.
10.Characteristics and Clinical Implication of UGT1A1 Heterozygous Mutation in Tumor.
Qian LI ; Tao SUN ; Hua ZHANG ; Wei LIU ; Yu XIAO ; Hongqi SUN ; Wencheng YIN ; Yanhong YAO ; Yangchun GU ; Yan'e LIU ; Fumei YI ; Qiqi WANG ; Jinyu YU ; Baoshan CAO ; Li LIANG
Chinese Journal of Lung Cancer 2022;25(3):137-146
BACKGROUND:
The literature recommends that reduced dosage of CPT-11 should be applied in patients with UGT1A1 homozygous mutations, but the impact of UGT1A1 heterozygous mutations on the adverse reactions of CPT-11 is still not fully clear.
METHODS:
A total of 107 patients with UGT1A1 heterozygous mutation or wild-type, who were treated with CPT-11 from January 2018 to September 2021 in Peking University Third Hospital, were retrospectively enrolled. The adverse reaction spectra of patients with UGT1A1*6 and UGT1A1*28 mutations were analyzed. Adverse reactions were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 5.0. The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The genotypes of UGT1A1*6 and UGT1A1*28 were detected by digital fluorescence molecular hybridization.
RESULTS:
There were 43 patients with UGT1A1*6 heterozygous mutation, 26 patients with UGT1A1*28 heterozygous mutation, 8 patients with UGT1A1*6 and UGT1A1*28 double heterozygous mutations, 61 patients with heterozygous mutation at any gene locus of UGT1A1*6 and UGT1A1*28. Logistic regression analysis showed that the presence or absence of vomiting (P=0.013) and mucositis (P=0.005) was significantly correlated with heterozygous mutation of UGT1A1*28, and the severity of vomiting (P<0.001) and neutropenia (P=0.021) were significantly correlated with heterozygous mutation of UGT1A1*6. In colorectal cancer, UGT1A1*6 was significantly correlated to diarrhea (P=0.005), and the other adverse reactions spectrum was similar to that of the whole patient cohort, and efficacy and prognosis were similar between patients with different genotypes and patients treated with reduced CPT-11 dosage or not.
CONCLUSIONS
In clinical use, heterozygous mutations of UGT1A1*6 and UGT1A1*28 are related to the risk and severity of vomiting, diarrhea, neutropenia and mucositis in patients with Pan-tumor and colorectal cancer post CPT-11 therpy. In colorectal cancer, UGT1A1*6 is significantly related to diarrhea post CPT-11 use, efficacy and prognosis is not affected by various genotypes or CPT-11 dosage reduction.
Camptothecin/therapeutic use*
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Glucuronosyltransferase/genetics*
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Humans
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Lung Neoplasms/drug therapy*
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Mutation
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Polymorphism, Genetic
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Retrospective Studies