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Effect of Amiloride on Invasive Activity and uPA System of Lung Carcinoma Cell Line

Chinese Journal of Clinical Oncology.2010;37(5):241-245. doi:10.3969/j.issn.1000-8179.2010.05.001

Objective: To investigate the effect of amiloride on in vitro invasive activity and uPA (urokinase-type plasminogen activator)system of human highly metastatic lung carcinoma cell line PGCL3. Methods: At 6 hours after treatment with amiloride at the concentrations of 25μmol/L，50μmol/L and 100μmol/L for PGCL3 cells，Transwell Chamber assay was performed to detect the effect of amiloride on the invasive and migratory capacity of PGCL3 cells.Effect of amiloride on the activity of uPA and PAI-1(plasminogen activator inhibitor-1)secreted by PGCL3 cells were measured by chromogenic substrate assay after PGCL3 cells were incubated with amiloride for 24 hours.RT-PCR was used to analyze the effect of amilorede on mRNA levels of uPA，uPAR(urokinase-type plasminogen activator receptor)and PAI-1.The expression levels of uPA，ERK2(extracellular regulated protein kinases 2)and ras protein were assessed by Western blot. Results: The number of cells through membrane was significantly decreased in invasion and migration test in vitro.The inhibitory rates of invasion and migration after treatment with amiloride of 100μmol/L were 37.7%±4.1%and 64.9%±4.9%.respectively,with a significant difference from those in the control group(P<0.01).At 24 hours after amiloride treatment，the chromogenic substrate assay showed direct inhibition of the activity of uPA and PAI-1 secreted by PGCL3 cells.No effect on the expression of uPAR in mRNA level was observed,but the expression of PAI-1 in mRNA level was significantly inhibited.Amiloride of 100μmol/L dramatically inhibited the expression of uPA mRNA.The expression level of uPA protein was decreased with the increase of the concentration of amiloride,but no effect was observed on the expression of ERK2 and ras in protein level.Conclusion: Amiloride can inhibit the invasion and migration of PGCL3 cells,through inhibiting the expression and activity of uPA and PAI-1.Amiloride is a potential agent to inhibit cancer invasion and metastasis.

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Multivariate Analysis of the Survival of 109 Lung Adenocarcinoma Patients with Brain Metastases

Chunwa WU ; Kai LI

Chinese Journal of Clinical Oncology.2010;37(6):345-347. doi:10.3969/j.issn.1000-8179.2010.06.013

Objective: To investigate prognostic factors of survival of lung adenocarcinoma patients with brain metasta-ses.Methods: The clinical data of 109 lung adenocarcinoma patients with brain metastases were reviewed.Fifty-senven pa-tients survived more than 1 year, and 52 patients survived less than 1 year.The data were analyzed by SPSS 15.0 statisti-cal software.Results: Both the univariate analysis and multivariate analysis showed that patients' PS score, the interval be-tween diagnosis and brain metastasis, and multimodality treatment were independent prognostic factors for the survival of lung adenocarcinoma patients with brain metastases (P<0.05).Patients' gender, age, metastatic symptoms and extracrani-al metastases didn't significantly affect patient survival.Conclusion: Patients with PS score 0-1, the interval of more than 1 year between diagnosis and brain metastasis, and combined therapy have longer survival.The research provides an impor-tant guidance for the treatment of advanced lung adenocarcinoma patients with brain metastases.

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Clinical Characteristics of Cervical Cancer in Uygur Young Women in Xinjiang

Chonghua GE ; Yuhua PENG ; Yuping SUN ; Tingfang LI

Chinese Journal of Clinical Oncology.2010;37(6):342-344. doi:10.3969/j.issn.1000-8179.2010.06.012

Objective: To investigate the clinicopathologic characteristics and etiological factors of cervical cancer in young Uygur women in Xinjiang.Methods" We reviewed 350 cases of young Uygur females diagnosed with cervical cancer in our hospital during 1998-2007.The patients were divided into two groups according to their admission time (1998～2002 group and 2003～2007 group).Results: The incidence of cervical carcinoma among yong Uygur women was 12.9% in the 1998-2002 group and 10.3% in the 2003-2007 group.The first symptom was vaginal contactive bleeding.In both groups, most patients were peasants, but the percentages of highbrow was higher in the 2003-2007 group.Patients in the 2003～2007 group were of older age at first marriage and had lower rate of abortion.There was no significant difference in histological type between the two groups.However, patients in the 2003-2007 group presented with much earlier stage of cervical cancer and 56.9% of them were of stage Ⅱ disease, compared with 18.1% in the 1998-2002 group (P<0.05).Squamous cell carcinoma was the dominant histological type.Conclusion: The incidence of cervical carcinoma in young Uygur women tends to decrease due to screening and advocation of late marriage, less reproduction in remote rural areas of Xinjiang.

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Clinical Analysis of the Effect of Rituximab in Combination with CTOP Chemotherapy on B Cell Non-Hodgkin's Malignant Lymphoma

Xia HAN ; Huaqing WANG ; Xianming LIU ; Lihua QIU ; Huilai ZHANG ; Zhengzi QIAN ; Wei EI ; Xiuzhen CUI ; Xishan HAO

Chinese Journal of Clinical Oncology.2010;37(6):338-341. doi:10.3969/j.issn.1000-8179.2010.06.011

Objective: To evaluate the efficacy and toxicity of rituximab combined with cyclophosphamide, pirarubicin, vincristine, and prednisone (R-CTOP regimen) for B cell non-Hodgkin's lymphoma and to analyze the influential factors for patient response.Methods: The clinical data of patients with CD20 antigen treated with R-CTOP regimen were reviewed and the influence of sex, age, clinical stage, pathological type, and level of LDH and IPI on patient response was analyzed.Results: A total of 33 patients were evaluated for objective response.The complete response (CR) rate was 51.5%, the par-ticel response (PR) rate was 33.3%, and the overall response rate was 84.8%.For the 23 de novo patients, the CR rate was 56.5 %, the PR rate was 34.8%, and the OR rate was 91.3%.While in the 10 recurrent patients, the CR rate was 40%, the PR rate was 30%, and the OR rate was 70%.Sex, clinical stage, pathological type, and the level of LDH and IPI were not significantly related to clinical response.While patient age was related to clinical response.None of the patients died of therapy-related side effects.The most frequent adverse event was myelosuppression (Ⅲ-Ⅳ decrease of leukocyte account-ed for 32.1%).Cardiotoxicity and alopecia were mostly grade Ⅰ to grade Ⅱ.Other side effects can be tolerated after symp-tomatic treatment.Conclusion: R-CTOP regimen is a highly effective and well-toleraed therapy and should be the first choice in the treatment for B cell non-Hodgkin's lymphoma (NHL), especially for senior patients.

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Diagnostic Value of Serum Tumor Markers for Lung Cancer

Xiangmei FENG ; Guoqing WANG ; Ying CHEN ; Rong WANG ; Yajun GU ; Yunde LIU

Chinese Journal of Clinical Oncology.2010;37(6):331-334. doi:10.3969/j.issn.1000-8179.2010.06.009

Objective: To investigate the diagnostic value of serum SCC, NSE, CEA, and CYFRA21-1 for lung cancer patients.Methods" The levels of SCC, NSE, CEA, and CYFRA21-1 were detected by electrochemoluminescence immuno-assay in 132 lung cancer patients, 48 patients with benign lung diseases and 92 healthy people.Results: The levels of NSE, CEA, and CYFRA21-1 in patients with lung cancer were higher than those in patients with benign lung diseases and in.normal controls.The level of SCC in patients with lung cancer was higher than that in normal controls.The levels of CEA and CYFRA21-1 in patients with benign lung disease were higher than those in normal controls.Patients with adenocarci-noma had the highest level of GEA and patients with small cell lung cancer had the highest level of NSE.Patients with squamous cell carcinoma had the highest levels of SCC and CYFRA21-1.The sensitivity sequence of the tumor markers in lung cancer was: NSE>CEA>CYFRA21-1>SCC.CEA showed the highest sensitivity of about 58.8% in adenocarcinoma.CYFRA21-1 showed the highest sensitivity of about 71.4% in squamous cell carcinoma.NSE showed the highest sensitivi-ty of about 50% in small cell lung cancer.ROC curves showed that the under-curve area of NSE, CEA, and CYFRA21-1was 0.928±0.034, 0.957±0.026, and 0.964±0.023, respectively.The combination of NSE, CEA, and CYFRA21-1 presented with the highest sensitivity (75.6%) and good specificity (90.7%) for the diagnosis of lung cancer.The combination of SCC, NSE, and CEA detection presented with the highest sensitivity (73.5%) for the diagnosis of adenocarcinoma.The combina-tion of NSE, CEA, and CYFRA21-1 showed the highest sensitivity (87.5%) for the diagnosis of squamous call carcinoma.The combination of SCC, NSE, and CYFRA2.1-1 showed the highest sensitivity (75.0%) for the diagnosis of small cell lung cancer.Conclusion: The assay of SCC, NSE, CEA and CYFRA21-1 is useful for the diagnosis of lung cancer and the ex-pression of the four tumor markers is closely correlated with pathological types.The suitable combination of tumor markers is helpful for differential diagnosis of lung cencar.

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The Association of Thrombocytosis with the Prognosis of Patients with Gastric Cancer

Hua LIU ; Dingzhi HUANG ; Xiang LI ; Hongli LI ; Biyun QIAN ; Ting DENG ; Likun ZHOU ; Yi BA

Chinese Journal of Clinical Oncology.2010;37(6):327-330. doi:10.3969/j.issn.1000-8179.2010.06.008

Objective: To analyze the association of thrombocytosis with the prognosis of patients with gastric cancer.Methods: The clinical materials of 782 patients with gastric cancer who underwent initial surgery in our hospital between January 1995 and December 1999 were retrospectively analyzed.Kaplan- Meier and Log-Rank test were used to analyze the data.Prognostic factors were analyzed by multivariate Cox proportional hazards model.Results: Thrombocytosis oc-curred in 11.4% (87/782) patients.The platelet level was not significantly different among patients of different gender, tumor stage, and histological differentiation (P>0.05).However, a significant difference was observed in the platelet level among patients with different age and surgical approach (P<0.05).The 1-, 3-, and 5-year survival rates were 75.0%, 40.1% and 28.9% in patients without thrombocytosis and 52.8%, 16.9%, and 13.5% in patients with thrombocytosis (P=0.002).Univari-ate analysis showed that histological differentiation, pathological stage, surgical approach and thrombocytosis significantly affected the survival of patients.While age and gender had no significant impact on patient survival.Multivariate analysis showed that pathological stage, surgical approach, and thrombocytosis were independent prognostic factors for gastric can-cer.The relative risk of death of patients with thrombocytosis was elevated by 1.454 times (RR=1.454, 95% CI: 1.135～1.861, P=0.005).Conclusion: Thrombocytosis is an independent prognostic indicator for the survival of initially treated pa-tients with gastric cancer.

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Effect of Argon-Helium Cryosurgery on Regulatory T Lymphocytes in the Peripheral Blood of Patients with Advanced Renal Carcinoma

Changfu LIU ; Zhi GUO ; Wenge XING ; Fang LIU ; Tongguo SI ; Haipeng YU

Chinese Journal of Clinical Oncology.2010;37(6):317-319. doi:10.3969/j.issn.1000-8179.2010.06.005

Objective: To analyze the effect of Argon-Helium cryosurgery (AHCS) on CD4+ CD25+ regulatory T cells (Treg) and its implication in patients with advanced renal carcinoma.Methods:,Peripheral venous blood samples were ob-tained from 32 patients with advanced renal cell carcinoma before and after AHCS.The proportions of Treg cells and T lym-phocyte subsets (CD3+ T, CD4+ T, CD8+ T, CD4+ T/CD8+ T, and NK cells) in the peripheral blood were measured by flow cytometry.Enhanced CT or enhanced MRI was used to observe the necrosis of tumor at 1 month after AHCS.The areas with no imaging enhancement in tumor were regarded as tumor necrosis.The necrosis rate was measured by Cavalieri method and the tumor burden was evaluated.Results: At 3 months after AHCS, the percentages of Treg cells were gradual-ly decreased from 4.18%±1.58% to 1.96%±0.54%, with a significant difference (P=0.001).At 3 months after AHCS, the pro-portions of CD3+ T, CD4+ T, NK and CD4+ T/CD8+ T were gradually increased from 19.26%±7.52%, 43.54%±12.99%, 1.15%±0.57%, and 17.49%±8.36% to 30.83%±5.69%, 49.58±10.76%, 1.84%±0.12%, and 27.63%±8.20%, with a statistical significance (P=0.000, P=0.003, P=0.02, and P=0.001).The proportion of CD8 + T was decreased from 40.86%±8.89% to the lowest ratio (26.74%±4.29%) at 3 months after AHCS, with a significant difference (P=0.000).At 3～6 months after cryo-therapy, there was only a slight change in the proportions of CD3 + T, CD4 + T, CD4 + T/CD8 + T, NK, CD8 + T, and Treg cells, with no significant difference (P>0.05).Correlation analysis showed that the decrease in tumor burden was positively correlated with the decrease of the proportion of Treg cells (r=0.793, P<0.01).Conclusion: After AHCS, the distribution of T-lymphocyte subsets can be improved and the anti-tumor immune response was strengthened.The percentage of Treg cells is correlated with tumor burden.

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Chuanyuan LIU ; Sen ZHANG ; Feng GAO ; Jungang LIU ; Shen HUANG

Chinese Journal of Clinical Oncology.2010;37(6):313-316. doi:10.3969/j.issn.1000-8179.2010.06.004

Objective: To investigate the clinical and pathological factors related to metachronous liver metastases in patients with Dukes'C colorectal cancer.Methods: A total of 170 patients with Dukes'C colorectal cancer treated with radical surgery in our hospital between January 2003 and December 2006 were reviewed.Factors including sex, age, tumor size (cm), depth of invasion, histological type, and serum CEA level were analyzed.Univariate and multivariate analyses were used to evaluate the factors concerned by Binary logistic regression (SPSS 13.0 for windows).Results: Of the 170 cases, 36 cases had metachronous liver metastases and 26 of them (72.2%) were found with metachronous liver metastases with-in two years after surgery.Thirty-two cases (88.9%) were identified with metachronous liver metastases within three years after surgery.Univariate analysis showed that depth of invasion, histological type and serum CEA level were predictors that could affect metachronous liver metastases.Depth of invasion and serum CEA level were independent risk factors for meta-chronous liver metastases of colorectal cancer.Multivariate analysis revealed that histological type was independent favor-able factor for metachronous liver metastases of colorectal cancer.Conclusion: Depth of invasion, histological type and se-rum CEA level were independent factors related to metachronous liver metastases of colorectal cancer.It is necessary to closely follow up Dukes'C colorectal cancer patients for two or three years after surgery in order to detect metachronous liv-er metastases early, especially for patients with higher preoperative serum CEA level or with tumor invasion to serosa.

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Expression of Bcl-x and Its Clinical Significance in Endometrial Cancer

Yanhui ZHAO ; Xiaoxin MA ; Hong GAO ; Ling HUANG ; Yingnan JIN

Chinese Journal of Clinical Oncology.2010;37(6):309-312. doi:10.3969/j.issn.1000-8179.2010.06.003

Objective: To investigate the roles of Bcl-xl and Bcl-xs in the development and progression of endometrial carcinoma, and to explore their correlation.Methods: The expression of Bcl-xl and Bcl-xs in 32 cases of endometrial carci-noma, 12 cases of endometrial atypical hyperplasia, 6 cases of endometrial simple hyperplasia and 10 cases of normal en-dometrial tissues were examined by RT-PCR and Western-blot.Results: The expression of Bcl-xl mRNA and protein was significantly higher in endometrial cancer tissues than in normal endometrial tissues (P<0.05), and was statistically associat-ed with the pathological stage of endometrial carcinoma.(F=5.33, P=0.02).The expression of Bcl-xs mRNA and protein in atypical endometrial hyperplasia and endometrial carcinoma tissues were significantlly lower than that in normal endometri-al tissues (P<0.05), which was also associated with clinical stage and lymph node metastasis of endometrial carcinoma (P<0.05).The expression of Bcl-xl was negatively correlated with the expression of Bcl-xs in different endometrial tissues (r=-0.76).Conclusion: The abnormal expression of Bcl-xs and Bcl-xl was a factor for the pathogenesis and development of endometrial carcinoma.The negative correlation between Bcl-xl and Bcl-xs in different endometrial tissues as well as their relative expression ratio may have certain impact on the genesis of endornetrial cancer.

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The Expression of Twist, E-cadherin and β-catenin in Hepatocellular Carcinoma and Its Correlation with Recurrence, Metastasis and Prognosis

Na CHE ; Xiulan ZHAO ; Qiang GO ; Tao SUN ; Xinghui WANG ; Shiwu ZHANG ; Nan ZHAO ; Jing DO ; Baocun SUN

Chinese Journal of Clinical Oncology.2010;37(6):305-308. doi:10.3969/j.issn.1000-8179.2010.06.002

Objective: To investigate the effect of Twist, β-catenin and E-cadherin on the recurrence and metastasis of hepatocellular carcinoma (HCC) and its correlation with clinical prognosis.Methods; Immunohistochemical staining (SP) was conducted to detect the expression of Twist, β-catenin and E-cadherin in 97 hepatocellular carcinoma patients (49 with recurrence and metastasis and 48 without recurrence and metastasis).Results: The recurrence and metastasis of HCC were correlated with clinical stage (P=0.000), but were not correlated with sex or age (P=0.424, P=0.738).The abnormal expression of Twist and β-catenin in the recurrence and metastasis group was higher than that in the group without recur-rence or metastasis (,0=-0.000, P=0.000).The positive ratio of E-cadherin in the recurrence and metastasis group was lower than that in the group without recurrence or metastasis (P=0.027).The mean survival was 28.880±3.285 months in patients with positive expression of Twist and 31.477±3.359 months in patients with positive expression of β-catenin.The median survival time of them was 26 and 28 months, respctively.The mean survival was 44.603±3.521 months in patients without Twist expression and 42.009±3.720 months in patients without β-catenin expression.The median survival time of them was 49 and 45 months, respectively.The survival of patients with positive expression of Twist and β-catenin was shorter than that in patients without expression of Twist and β-catenin (P=0.002, P=0.029).The mean survival time and median survival time of patients with Twist and β-catenin expression were 44.514±3.447 months and 49 months, respectively, significantly higher than those in patients without Twist and β-catenin expression (P=0.002), which were 29.110±3.581 months and 25 months, respectively.Conclusion: The overexpression of Twist and β-catenin as well as decreased expression of E-cad-herin may play critical roles in the recurrence and metastasis of HCC and indicate poor prognosis.

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