卵巢癌患者血浆溶血磷脂酸水平测定的临床意义
摘要
目的:通过测定卵巢癌,卵巢良性肿瘤,卵巢巧克力囊肿及正常健康妇女血浆中溶血磷脂酸(LPA)水平和血清cAl25水平,试图评估血浆LPA在卵巢癌诊断中的临床应用价值;进一步评估血浆LPA在早期卵巢癌诊断中的价值,以及作为术后患者病情监测指标的价值。
方法:收集2006年8月至2007年3月在广西医科大学第一附属医院妇科住院的卵巢癌患者28例,卵巢巧克力囊肿20例,卵巢良性肿瘤20例。另选择20例广西医科大学第一附属医院体检中心的健康女性作为正常对照组。除正常对照组外,其它病例均经手术后病理证实。抽取所有研究对象空腹静脉血,用生化法测定血浆溶血磷脂酸水平,进行LPA的提取、分离,高灵敏度显色液显色,636nm波长测定光吸收值,与标准值进行比较计算LPA的含量,正常参考值＜3.2umol/L。试剂由北京泰福仕科技开发公司生产。采用微粒子酶免分析法(MEIA)测定血清CA125。所有数据采用统计软件SPSS11.0进行统计分析。
结果:
1.卵巢癌组血浆LPA5.25±1.57umol/L,卵巢良性肿瘤组血浆LPA 1.74±0.71 umol/L,卵巢巧克力囊肿组血浆LPA 2.99±1.28umol/L,正常对照组血浆LPA1.85±0.35umol/L,卵巢癌组血浆LPA水平较卵巢良性肿瘤组、卵巢巧克力囊肿组、正常对照组明显升高,P值均＜0.05,差异有统计学意义。血浆LPA诊断卵巢癌的敏感性89.29%(25/28),特异性85%(51/60)。而血清CA125诊断卵巢癌的敏感性为75%(21/28),特异性为76.67%(46/60)。两者诊断卵巢癌的敏感性相比,血浆LPA的敏感性高于血清CA125(P＜0.05),而LPA诊断卵巢癌的特异性与CA125相比,差异无统计学意义(P＞0.05)。
2.卵巢癌组手术前后血浆LPA水平有明显变化。手术前血浆LPA水平5.25±1.57umol/L,术后一周再次测得血浆LPA为3.10±1.30 umol/L,两者相比较,P＜0.01,差异有统计学意义,术后血浆LPA明显下降。
3.血浆LPA水平与卵巢癌的病理类型和组织学分级无明显关系,而与临床分期有关。卵巢浆液性囊腺癌患者血浆LPA 5.35±1.53umol/L,粘液性囊腺癌患者血浆LPA5.81±1.22 umol/L,两者比较,P＞0.05,差异无统计学意义。组织学高分化组血浆LPA4.70±1.94 umol/L,中分化组血浆LPA5.01±1.04 umol/L,低分化组血浆LPA5.99±1.36 umol/L,两两比较,P均＞0.05,差异无统计学意义。卵巢癌早期(Ⅰ+Ⅱ)LPA水平为4.12±1.36umol/L,晚期(Ⅲ+Ⅳ)患者LPA水平为6.23±1.07 umol/L,两者比较,P＜0.01,差异有统计学意义。LPA诊断早期卵巢癌的敏感性为80%,而CA125诊断早期卵巢癌的敏感性为50%,差异有统计学意义(P＜0.05)。
结论:血浆LPA用于诊断卵巢癌具有高度敏感性和特异性,可用于鉴别卵巢良恶性肿瘤。尤其是对于早期卵巢癌,LPA也明显升高,其诊断的敏感性可达80%。同时对于手术后病人的病情监测可能有一定的临床价值。是一种方便、快捷、无创、经济的检测方法,值得临床推广。
Objective: By detecting LPA of plasma and CA125 of serum in the patients with ovarian cancer, ovarian benign tumor, chocolate cyst of ovary and the normal healthy woman, the significances of LPA in diagnosis in the patient with ovarian cancer; the diagnosis value of LPA in patient with the early-stage ovarian cancer and the value as the prognosis index for postoperative ovarian cancer are to be appraised.
Method: A test group consisted of 28 patients with ovarian cancer; 20 patient with ovarian chocolate cyst; 20 patient with benign ovarian tumor from the First Hospital of Guangxi Medical University during August 2006 to March 2007. And a control group 20 healthy women from medical examination center of Guangxi Medical University. The final diagnoses were confirmed by histopathology for all the patients apart from the healthy women. Biochemistry method was adopted to detect the LPA level in their plasma. Having been picked up, separated and digested, LPA from plasma was displayed by display fluid to measure the absorption of light in 636nm, with its values accounted. The reagents were produced by Beijing Taifushi Company. Serum CA125 was determined by MEIA. Using SPSS 11.0 statistical software for statistical analysis.
Result:
1. ovarian cancer group plasma LPA was 5.25±1.57umol/L, ovarian benign tumor group blood plasma LPA 1.74±0.71umol/L, the ovarian chocolate cyst group blood plasma LPA 2.99±1.28umol, normal control group blood plasma LPA 1.85±0.35umol. Comparing the plasma LPA level in ovarian cancer group with that of the ovary benign tumor group, the ovarian chocolate cyst group, the normal control group, plasma LPA levels of patients with ovarian cancer is significantly higher than those of benign ovarian tumor, ovarian chocolate cyst and healthy controls (P<0.05) . The sensitivity of LPA in diagnosis of ovarian cancer is 89.29% (25/28), the specificity is 85% (51/60). But the sensitivity of CA125 is 75% (21/28), the specificity is 76.67% (46/60).Comparing the sensitivity and specificity of LPA and CA125 in diagnosing ovarian cancer, the sensitivity of LPA is higher than that of CA125(P<0.05); But the specificity is not statistically significant(P>0.05).
2. The preoperative and postoperative plasma LPA levels in ovarian cancer group are obviously different. The plasma LPA level was 5.25±1.57umol/L in preoperative patients with ovarian cancer, the plasma LPA 3.10±1.30 umol/L a week after operation. Comparing the two groups, the difference has statistical significance(P<0.01), the postoperative levels of LPA obviously drops.
3. There is no significant relation between LPA value of ovarian cancer histopathologic types and histological grade, but there is correlation in the clinic stages. The LPA level in patients with ovarian serous cystadenocarcinoma was 5.35±1.53umol/L, the LPA level in patients with ovarian mucinous cystadenocarcinoma 5.81±1.22 umol/L, with the difference non-statistically significant(P>0.05). The LPA of well-differentiated group in histology was 4.70±1.94 umol/L, that of moderately differentiated group 5.01±1.04 umol/L, and that of poorly differentiated group 5.99±1.36 umol/L, with the difference non-statistically significant (P>0.05). The LPA level of early-stage ovarian cancer (I + II) was 4.12±1.36umol/L, and that of advanced stage (III + IV) patient 6.23±1.07 umol/L, with the difference having statistics significance(P<0.01). The sensitivity of LPA diagnosis was up to 80% in early-stage ovarian cancer,the sensitivity of CA125 diagnosis only 50%.The difference have statistics significance(P<0.05).
Conclusion: Plasma LPA has high sensitivity and specificity in diagnosing ovarian cancer. Detecting the level of plasma LPA in the patient with ovarian cancer is a simple, fast, convenient, high sensitive and specific method for diagnosing and monitoring of ovarian cancer. LPA obviously elevates, in particular, in early- stage ovarian cancer; its diagnosis sensitivity may reach 80%. Meanwhile, LPA is also a monitor index of postoperative ovarian cancer. The is a convenient, quick, non-invasive and economical detection method. It is worth the clinical promotion.
方法:收集2006年8月至2007年3月在广西医科大学第一附属医院妇科住院的卵巢癌患者28例,卵巢巧克力囊肿20例,卵巢良性肿瘤20例。另选择20例广西医科大学第一附属医院体检中心的健康女性作为正常对照组。除正常对照组外,其它病例均经手术后病理证实。抽取所有研究对象空腹静脉血,用生化法测定血浆溶血磷脂酸水平,进行LPA的提取、分离,高灵敏度显色液显色,636nm波长测定光吸收值,与标准值进行比较计算LPA的含量,正常参考值＜3.2umol/L。试剂由北京泰福仕科技开发公司生产。采用微粒子酶免分析法(MEIA)测定血清CA125。所有数据采用统计软件SPSS11.0进行统计分析。
结果:
1.卵巢癌组血浆LPA5.25±1.57umol/L,卵巢良性肿瘤组血浆LPA 1.74±0.71 umol/L,卵巢巧克力囊肿组血浆LPA 2.99±1.28umol/L,正常对照组血浆LPA1.85±0.35umol/L,卵巢癌组血浆LPA水平较卵巢良性肿瘤组、卵巢巧克力囊肿组、正常对照组明显升高,P值均＜0.05,差异有统计学意义。血浆LPA诊断卵巢癌的敏感性89.29%(25/28),特异性85%(51/60)。而血清CA125诊断卵巢癌的敏感性为75%(21/28),特异性为76.67%(46/60)。两者诊断卵巢癌的敏感性相比,血浆LPA的敏感性高于血清CA125(P＜0.05),而LPA诊断卵巢癌的特异性与CA125相比,差异无统计学意义(P＞0.05)。
2.卵巢癌组手术前后血浆LPA水平有明显变化。手术前血浆LPA水平5.25±1.57umol/L,术后一周再次测得血浆LPA为3.10±1.30 umol/L,两者相比较,P＜0.01,差异有统计学意义,术后血浆LPA明显下降。
3.血浆LPA水平与卵巢癌的病理类型和组织学分级无明显关系,而与临床分期有关。卵巢浆液性囊腺癌患者血浆LPA 5.35±1.53umol/L,粘液性囊腺癌患者血浆LPA5.81±1.22 umol/L,两者比较,P＞0.05,差异无统计学意义。组织学高分化组血浆LPA4.70±1.94 umol/L,中分化组血浆LPA5.01±1.04 umol/L,低分化组血浆LPA5.99±1.36 umol/L,两两比较,P均＞0.05,差异无统计学意义。卵巢癌早期(Ⅰ+Ⅱ)LPA水平为4.12±1.36umol/L,晚期(Ⅲ+Ⅳ)患者LPA水平为6.23±1.07 umol/L,两者比较,P＜0.01,差异有统计学意义。LPA诊断早期卵巢癌的敏感性为80%,而CA125诊断早期卵巢癌的敏感性为50%,差异有统计学意义(P＜0.05)。
结论:血浆LPA用于诊断卵巢癌具有高度敏感性和特异性,可用于鉴别卵巢良恶性肿瘤。尤其是对于早期卵巢癌,LPA也明显升高,其诊断的敏感性可达80%。同时对于手术后病人的病情监测可能有一定的临床价值。是一种方便、快捷、无创、经济的检测方法,值得临床推广。
Objective: By detecting LPA of plasma and CA125 of serum in the patients with ovarian cancer, ovarian benign tumor, chocolate cyst of ovary and the normal healthy woman, the significances of LPA in diagnosis in the patient with ovarian cancer; the diagnosis value of LPA in patient with the early-stage ovarian cancer and the value as the prognosis index for postoperative ovarian cancer are to be appraised.
Method: A test group consisted of 28 patients with ovarian cancer; 20 patient with ovarian chocolate cyst; 20 patient with benign ovarian tumor from the First Hospital of Guangxi Medical University during August 2006 to March 2007. And a control group 20 healthy women from medical examination center of Guangxi Medical University. The final diagnoses were confirmed by histopathology for all the patients apart from the healthy women. Biochemistry method was adopted to detect the LPA level in their plasma. Having been picked up, separated and digested, LPA from plasma was displayed by display fluid to measure the absorption of light in 636nm, with its values accounted. The reagents were produced by Beijing Taifushi Company. Serum CA125 was determined by MEIA. Using SPSS 11.0 statistical software for statistical analysis.
Result:
1. ovarian cancer group plasma LPA was 5.25±1.57umol/L, ovarian benign tumor group blood plasma LPA 1.74±0.71umol/L, the ovarian chocolate cyst group blood plasma LPA 2.99±1.28umol, normal control group blood plasma LPA 1.85±0.35umol. Comparing the plasma LPA level in ovarian cancer group with that of the ovary benign tumor group, the ovarian chocolate cyst group, the normal control group, plasma LPA levels of patients with ovarian cancer is significantly higher than those of benign ovarian tumor, ovarian chocolate cyst and healthy controls (P<0.05) . The sensitivity of LPA in diagnosis of ovarian cancer is 89.29% (25/28), the specificity is 85% (51/60). But the sensitivity of CA125 is 75% (21/28), the specificity is 76.67% (46/60).Comparing the sensitivity and specificity of LPA and CA125 in diagnosing ovarian cancer, the sensitivity of LPA is higher than that of CA125(P<0.05); But the specificity is not statistically significant(P>0.05).
2. The preoperative and postoperative plasma LPA levels in ovarian cancer group are obviously different. The plasma LPA level was 5.25±1.57umol/L in preoperative patients with ovarian cancer, the plasma LPA 3.10±1.30 umol/L a week after operation. Comparing the two groups, the difference has statistical significance(P<0.01), the postoperative levels of LPA obviously drops.
3. There is no significant relation between LPA value of ovarian cancer histopathologic types and histological grade, but there is correlation in the clinic stages. The LPA level in patients with ovarian serous cystadenocarcinoma was 5.35±1.53umol/L, the LPA level in patients with ovarian mucinous cystadenocarcinoma 5.81±1.22 umol/L, with the difference non-statistically significant(P>0.05). The LPA of well-differentiated group in histology was 4.70±1.94 umol/L, that of moderately differentiated group 5.01±1.04 umol/L, and that of poorly differentiated group 5.99±1.36 umol/L, with the difference non-statistically significant (P>0.05). The LPA level of early-stage ovarian cancer (I + II) was 4.12±1.36umol/L, and that of advanced stage (III + IV) patient 6.23±1.07 umol/L, with the difference having statistics significance(P<0.01). The sensitivity of LPA diagnosis was up to 80% in early-stage ovarian cancer,the sensitivity of CA125 diagnosis only 50%.The difference have statistics significance(P<0.05).
Conclusion: Plasma LPA has high sensitivity and specificity in diagnosing ovarian cancer. Detecting the level of plasma LPA in the patient with ovarian cancer is a simple, fast, convenient, high sensitive and specific method for diagnosing and monitoring of ovarian cancer. LPA obviously elevates, in particular, in early- stage ovarian cancer; its diagnosis sensitivity may reach 80%. Meanwhile, LPA is also a monitor index of postoperative ovarian cancer. The is a convenient, quick, non-invasive and economical detection method. It is worth the clinical promotion.
引文
1.连丽娟,刘彤华,刘炽明等.林巧稚妇科肿瘤学,第三版,人民卫生出版社,1999,403-405。
2.Jemal A,Siegel R,Ward E,et al.Cancer statistics.CA Cancer [J]Clin,2006;56(2):106-130.
3.Xu Y,Gaudette DC,Boynton JD,et al.Charactrization of an ovarian cancer activing factor(OCAF)in ascites from ovarian cancer patients.[J].Clin cancer Res,1995,1(10):1223-1232.
4.Xu Y,Shen Z,Wiper DW,et al.Lysophosphatidic acid as a potential biomarker for ovarian and other gynecologic cancers [J].Am Med Assoc,1998;280(8):719-723.
5.Valet P,Pages C,Jeanneton O,et al.Alpha2-adrenergic receptor-mediated release of Lysophosphatidic acid by adipocytes[J].Clin Invest,1998,101:1431-1438.
6.Pages C,Simon M,Valet P,et al.Lysophosphatidic acid synthesis and release[J].Prostaglandins,2001,64:1-10.
7.Moolenaar WH.Lysophosphatidic acid,a multifunctional phospholipids messenger.[J]Biol Chem 1995;270(22):12949-12952.
8.Shen Z,Belinson J,Morton RE,et al.Phorbol 12-myristate 13-acetate stimulates lysophosphatidic acid secretion from ovarian cancer and cervical cancer cell but not from breast or leukemia cells.[J].Gynecol Oncol,1998;71(3):364-368.
9.Ren Juan,Xiao Yi-jin,Singh Lisam Shanjukumar,et al.Lysophosphatidic acid is constitutively produced by human peritoneal mesothelial cells and enhances adhesion, migration, and invasion of ovarian cancer cells [J]. Cancer Research , 2006 ,66:3006-3014.
10. Moolenaar WH. Bioactive Lysophospholipids and their G Protein-Coupled receptors[J]. Exp Cell Res, 1999; 253(1) :230-238.
11. Takuwa Y, Okamoto H, Takuwa N, et al. Subtype-specific, differential activities of the Edg family receptors for sphingosine-I-phosphate, a novel lysophospholipid mediator[J]. Mol Cell Endocrinol, 2001,177:3-11.
12. Goetzl EJ, An S. Diversity of cellular receptors and functions for the lysophospholipid growth factors lysophosphatidic acid and sphingosine 1-phosphate. FASEB [J]. 1998; 12(15): 1589-1598.
13. Contos JJ, Ishii I, Chun J. Lysophosphatidic acid receptors. [J].Mol Pharmacol, 2000, 58(6): 1188-1196.
14. Eder AM , Sasagawa T, Mao M, et al. Constituctive and lysophophatidic acid(LPA)-induced LPA production: role of phospholipase D and phospholipase A2. [J].Clin Cancer Res, 2000,6:2482-2491.
15. Sawada K, Morishige KI, Tahara M, et al. Alendronate inhibits lysophosphatidic acid-induced migration of human ovarian cancer cells by attenuating the activation of Rho. [J]. Cancer Res, 2002,62(21) :6015-6020.
16. Tanyi Janos L, Morris AJ, Wolf JK, et al. The human lipid phosphate phosphatase-3 decreases the growth, survival, and tumorigenesis of ovarian cancer cells: validation of the lysophosphatidic acid signaling cascade as a target for therapy in ovarian cancer. [J]Cancer Res, 2003, 63(5): 1073-1082.
17. Hu Yu-Long, Tee Meng-Kian, Goetzl Edward J. et al. Lysophosphatidic acid induction of vascular endothelial growth factor expression in human ovarian cancer cells. [J]. The National Cancer Institute, 2001; 93(10):762-768.
18. Hu Yu-Long, Albanese Chris, Pestell Richard G. et al .Dual mechanisms for lysophosphatidic acid stimulation of human ovarian carcinoma cells. [J] . the National Cancer Institute, 2003; 95(10): 733-740.
19. Takuji Fujita, Shingo Miyamoto, Ichiro Onoyama, et al. Expression of lysophosphatidic acid receptors and vascular endothelial growth factor mediating lysophosphatidic acid in the development of human ovarian cancer. Cancer Letters,2003,192:161-169.
20. So John, Wang Feng-qiang, Navari Jason, et al, LPA-induced epithelial ovarian cancer (EOC) in vitro invasion and migration are mediated by VEGF receptor-2(VEGF-R2). [J]. Gynecol Oncol. 2005; 97(3): 870-878.
21. Barbara Schmalfeldt, Dieter Prechtel, Kathrin Harting. et al. Increased expression of matrix metalloproteinases(MMP)-2, MMP-9, and the urokinase-type plasminogen activator is associated with progression from benign to advanced ovarian cancer. [J]. Clinical Cancer Research, 2001, 7(8): 2396-2404.
22. Konecny Gottfried, Untch Michael, Pihan Astrid. et al. Association of urokinase-type plasminogen activator and its inhibitor with disease progression and prognosis in ovarian cancer.[J].Clinical Cancer Research,2001,7(6):1743-1749.
23.Li Hong-bin,Ye Xiao-qin,Mahanivong Chitladda.et al.Signaling mechanisms responsible for LPA-induced urokinase plasminogen activator expression in ovarian cancer cells.[J].Biol.Chem,2005,280(11):10564-10571.
24.Fishman DA,Liu YY,Ellerbroek SM,et al.Lysophosphatidic acid promotes matrix metalloproteinase(MMP)activation and MMP-dependent invasion in ovarian cancer cells[J].Cancer Res,2001,61:3194-3199.
25.Sawada K,Morishige K,Tahara M,et al.Lysophosphatidic acid induces focal adhesion assembly through Rho/Rho-associated kinase pathway in human ovarian cancer cells[J].Gynecol Oncol,2002,87:252-259.
26.Fang XJ,Schummer M,Mao M,et al.Lysophosphatidic acid is a bioactive mediator in ovarian cancer[J].Biochem Biophys Acta,2002,1582:257-264.
27.王辉,吴小华,史丽,溶血磷脂酸诱导人卵巢上皮癌裸鼠腹腔移植瘤的生长研究,南方医科大学学报,2007,2:228-231。
28.Xu Jun,Lai Yun-Ju,Lin Weei-Chin,et al,TRIP6 enhances lysophosphatidic acid-induced cell migration by interacting with the lysophosphatidic acid 2 receptor.[J].Biol.Chem,2004,279(11):10459-10468.
29.L i L,Wang L,Zhang W,et al.Correlation of serum VEGF levels with clinical stage,therapy efficacy,tumor metastasis and patient survival in ovarian cancer[J].Anticancer Res,2004,24:197321979.
30.Sutphen Rebecca,Xu Yan,Wilbanks George D.,et al.Lysophospholipids are potential biomarkers of ovarian cancer.[J].Cancer Epidemiology Biomarkers & Prevention,2004,13(7):1185-1191.
31.段满乐,武凡。磷脂酶A2和溶血磷脂酸在卵巢癌诊断中的价值,中华检验医学杂志,2005,6:622-624。
1. Moolenaar WH. Lysophosphatidic acid a multifunction Phospholipid messenger. [J]. Biol Chem, 1995; 270 (22) :12949-2952.
2. Xu Y, Xiao YJ, Baudhuin LM, et al. The role and clinical applications of bioactive lysolipids in ovarian cancer. [J]. Soc Gynecol Investig, 2001, 8(1): 1-13.
3. Moolenaar WH. Bioactive Lysophospholipids and their G Protein-Coupled receptors. [J]. Exp Cell Res, 1999; 253(1): 230-238.
4. Goetzl EJ, An S. Diversity of cellular receptors and functions for the lysophospholipid growth factors lysophosphatidic acid and sphingosine 1-phosphate. FASEB J. 1998; 12(15):1589-1598.
5. Xu Y, Shen Z, Wiper DW, et al. Lysophosphatidic acid as a potential biomarker for ovarian and other gynecologic cancers .[J]. Am Med Assoc, 1998;280(8):719-723.
6. Shen Z, Belinson J, Morton RE, et al. Phorbol 12-myristate 13-acetate stimulus lysophosphatidic acid secretion from ovarian cancer and cervical cancer cell but not from breast or leukemia cells . J. Gynecol Oncol, 1998; 71(3): 364-368.
7. Ren Juan, Xiao Yi-jin, Singh Lisam Shanjukumar. et al. Lysophosphatidic acid is constitutively produced by human peritoneal mesothelial cells and enhances adhesion, migration, and invasion of ovarian cancer cells. J. Cancer Research ,2006 ,66:3006-3014.
8. Hu Yu-Long, Tee Meng-Kian, Goetzl Edward J. et al. Lysophosphatidic acid induction of vascular endothelial growth factor expression in human ovarian cancer cells. [J]. The National Cancer Institute, 2001; 93(10):762-768.
9. Hu Yu-Long, Albanese Chris,Pestell Richard G. et al .Dual mechanisms for lysophosphatidic acid stimulation of human ovarian carcinoma cells. [J] .the National Cancer Institute, 2003; 95(10): 733-740.
10. Takuji Fujita, Shingo Miyamoto, Ichiro Onoyama, et al. Expression of lysophosphatidic acid receptors and vascular endothelial growth factor mediating lysophosphatidic acid in the development of human ovarian cancer. Cancer Letters, 2003,192:161-169.
11. So. John, Wang Feng-qiang, Navari Jason, et al, LPA-induced epithelial ovarian cancer (EOC) in vitro invasion and migration are mediated by VEGF receptor-2(VEGF-R2). [J]. Gynecol Oncol. 2005; 97(3): 870-878.
12. Xu Jun, Lai Yun-Ju, Lin Weei-Chin. et al, TRIP6 enhances lysophosphatidic acid-induced cell migration by interacting with the lysophosphatidic acid 2 receptor. [J]. Biol. Chem, 2004, 279(11): 10459-10468.
13. Fishman DA, Liu YY, Ellerbroek SM, et al. Lysophosphatidic acid promotes matrix metalloproteinase(MMP) activation and MMP-dependent invasion in ovarian cancer cells[J]. Cancer Res, 2001,61:3194-3199.
14.Barbara Schmalfeldt,Dieter Prechtel,Kathrin Harting.et al.Increased expression of matrix metalloproteinases(MMP)-2,MMP-9,and the urokinase-type plasminogen activator is associated with progression from benign to advanced ovarian cancer.J.Clinical Cancer Research,2001,7(8):2396-2404.
15.Gottfried Konecny,Michael Untch,Astrid Pihan.et al.Association of urokinase-type plasminogen activator and its inhibitor with disease progression and prognosis in ovarian cancer.[J].Clinical Cancer Research,2001,7(6):1743-1749.
16.Li Hong-bin,Ye Xiao-qin,Mahanivong Chitladda.et al.Signaling mechanisms responsible for LPA-induced urokinase plasminogen activator expression in ovarian cancer cells.[J].Biol.Chem,2005,280(11):10564-10571.
17.Sawada K,Morishige K,rahara M,et al.Lysophosphatidic acid induces focal adhesion assembly through Rho/Rho-associated kinase pathway in human ovarian cancer cells[J].Gynecol Oncol,2002,87:252-259.
18.Fang XJ,Schummer M,Mao M,et al.Lysophosphatidic acid is a bioactive mediator in ovarian cancer[J].Biochem Biophys Acta,2002,1582:257-264.
19.王辉,吴小华,史丽,溶血磷脂酸诱导人卵巢上皮癌裸鼠腹腔移植瘤的生长研究,南方医科大学学报,2007,2:228-231.
20.L i L,Wang L,Zhang W,et al.Correlation of serum VEGF levels with clinical stage,therapy efficacy,tumor metastasis and patient survival in ovarian cancer[J].Anticancer Res,2004, 24: 197321979.
21. Konecny Gottfried, Untch Michael, Pihan Astrid. et al. Association of urokinase-type plasminogen activator and its inhibitor with disease progression and prognosis in ovarian cancer. [J]. Clinical Cancer Research, 2001, 7(6): 1743-1749.
22. Hannun YA. Apoptosis and dilemma of cancer chemotherapy. [J]. Blood, 1997, 89(6): 1845-1853.
23. Meng Yu-ru, Kang Shijun, So John, et al. Translocation of Fas by LPA prevents ovarian cancer cells from anti-Fas-induced apoptosis. [J]. Gynecologic Oncology, 2005, 96(2):462-469.
24. Meng Yu-ru, Graves Laura, Do Thuy-Vy. et al. Upregulation of FasL by LPA on ovarian cancer cell surface leads to apoptosis of activated lymphocytes. [J]. Gynecologic Oncology, 2004, 95(3): 488-495.
25. Meng Yu-ru, Kang Shi-jun, Fishman David A. et al. Lysophosphatidic acid stimulates fas ligand microvesicle release from ovarian cancer cells. [J]. Cancer Immunology, Immunotherapy, 2005, 54(8): 807-814.
26. Kang Y-C, Kim K-M, Lee K-S, et al. Serum bioactive lysophospholipids prevent TRAIP-induced apoptosis via P13K/AKT-dependent cFLIP expression and Bad phosphorylation. [J]. Cell Death and Differentiation, 2004, 11(12):1287-1298.
27. Xu Y, Gaudette DC, Boynton JD, et al. Charactrization of an ovarian cancer activing factor(OCAF) in ascites from ovarian cancer patients. [J].Clin cancer Res, 1995,1 (10) :1223-1232.
28. Sutphen Rebecca, Xu Yan, Wilbanks George D. et al. Lysophospholipids are potential biomarkers of ovarian cancer.[J].Cancer Epidemiology Biomarkers & Prevention,2004,13(7):1185-1191.
2.Jemal A,Siegel R,Ward E,et al.Cancer statistics.CA Cancer [J]Clin,2006;56(2):106-130.
3.Xu Y,Gaudette DC,Boynton JD,et al.Charactrization of an ovarian cancer activing factor(OCAF)in ascites from ovarian cancer patients.[J].Clin cancer Res,1995,1(10):1223-1232.
4.Xu Y,Shen Z,Wiper DW,et al.Lysophosphatidic acid as a potential biomarker for ovarian and other gynecologic cancers [J].Am Med Assoc,1998;280(8):719-723.
5.Valet P,Pages C,Jeanneton O,et al.Alpha2-adrenergic receptor-mediated release of Lysophosphatidic acid by adipocytes[J].Clin Invest,1998,101:1431-1438.
6.Pages C,Simon M,Valet P,et al.Lysophosphatidic acid synthesis and release[J].Prostaglandins,2001,64:1-10.
7.Moolenaar WH.Lysophosphatidic acid,a multifunctional phospholipids messenger.[J]Biol Chem 1995;270(22):12949-12952.
8.Shen Z,Belinson J,Morton RE,et al.Phorbol 12-myristate 13-acetate stimulates lysophosphatidic acid secretion from ovarian cancer and cervical cancer cell but not from breast or leukemia cells.[J].Gynecol Oncol,1998;71(3):364-368.
9.Ren Juan,Xiao Yi-jin,Singh Lisam Shanjukumar,et al.Lysophosphatidic acid is constitutively produced by human peritoneal mesothelial cells and enhances adhesion, migration, and invasion of ovarian cancer cells [J]. Cancer Research , 2006 ,66:3006-3014.
10. Moolenaar WH. Bioactive Lysophospholipids and their G Protein-Coupled receptors[J]. Exp Cell Res, 1999; 253(1) :230-238.
11. Takuwa Y, Okamoto H, Takuwa N, et al. Subtype-specific, differential activities of the Edg family receptors for sphingosine-I-phosphate, a novel lysophospholipid mediator[J]. Mol Cell Endocrinol, 2001,177:3-11.
12. Goetzl EJ, An S. Diversity of cellular receptors and functions for the lysophospholipid growth factors lysophosphatidic acid and sphingosine 1-phosphate. FASEB [J]. 1998; 12(15): 1589-1598.
13. Contos JJ, Ishii I, Chun J. Lysophosphatidic acid receptors. [J].Mol Pharmacol, 2000, 58(6): 1188-1196.
14. Eder AM , Sasagawa T, Mao M, et al. Constituctive and lysophophatidic acid(LPA)-induced LPA production: role of phospholipase D and phospholipase A2. [J].Clin Cancer Res, 2000,6:2482-2491.
15. Sawada K, Morishige KI, Tahara M, et al. Alendronate inhibits lysophosphatidic acid-induced migration of human ovarian cancer cells by attenuating the activation of Rho. [J]. Cancer Res, 2002,62(21) :6015-6020.
16. Tanyi Janos L, Morris AJ, Wolf JK, et al. The human lipid phosphate phosphatase-3 decreases the growth, survival, and tumorigenesis of ovarian cancer cells: validation of the lysophosphatidic acid signaling cascade as a target for therapy in ovarian cancer. [J]Cancer Res, 2003, 63(5): 1073-1082.
17. Hu Yu-Long, Tee Meng-Kian, Goetzl Edward J. et al. Lysophosphatidic acid induction of vascular endothelial growth factor expression in human ovarian cancer cells. [J]. The National Cancer Institute, 2001; 93(10):762-768.
18. Hu Yu-Long, Albanese Chris, Pestell Richard G. et al .Dual mechanisms for lysophosphatidic acid stimulation of human ovarian carcinoma cells. [J] . the National Cancer Institute, 2003; 95(10): 733-740.
19. Takuji Fujita, Shingo Miyamoto, Ichiro Onoyama, et al. Expression of lysophosphatidic acid receptors and vascular endothelial growth factor mediating lysophosphatidic acid in the development of human ovarian cancer. Cancer Letters,2003,192:161-169.
20. So John, Wang Feng-qiang, Navari Jason, et al, LPA-induced epithelial ovarian cancer (EOC) in vitro invasion and migration are mediated by VEGF receptor-2(VEGF-R2). [J]. Gynecol Oncol. 2005; 97(3): 870-878.
21. Barbara Schmalfeldt, Dieter Prechtel, Kathrin Harting. et al. Increased expression of matrix metalloproteinases(MMP)-2, MMP-9, and the urokinase-type plasminogen activator is associated with progression from benign to advanced ovarian cancer. [J]. Clinical Cancer Research, 2001, 7(8): 2396-2404.
22. Konecny Gottfried, Untch Michael, Pihan Astrid. et al. Association of urokinase-type plasminogen activator and its inhibitor with disease progression and prognosis in ovarian cancer.[J].Clinical Cancer Research,2001,7(6):1743-1749.
23.Li Hong-bin,Ye Xiao-qin,Mahanivong Chitladda.et al.Signaling mechanisms responsible for LPA-induced urokinase plasminogen activator expression in ovarian cancer cells.[J].Biol.Chem,2005,280(11):10564-10571.
24.Fishman DA,Liu YY,Ellerbroek SM,et al.Lysophosphatidic acid promotes matrix metalloproteinase(MMP)activation and MMP-dependent invasion in ovarian cancer cells[J].Cancer Res,2001,61:3194-3199.
25.Sawada K,Morishige K,Tahara M,et al.Lysophosphatidic acid induces focal adhesion assembly through Rho/Rho-associated kinase pathway in human ovarian cancer cells[J].Gynecol Oncol,2002,87:252-259.
26.Fang XJ,Schummer M,Mao M,et al.Lysophosphatidic acid is a bioactive mediator in ovarian cancer[J].Biochem Biophys Acta,2002,1582:257-264.
27.王辉,吴小华,史丽,溶血磷脂酸诱导人卵巢上皮癌裸鼠腹腔移植瘤的生长研究,南方医科大学学报,2007,2:228-231。
28.Xu Jun,Lai Yun-Ju,Lin Weei-Chin,et al,TRIP6 enhances lysophosphatidic acid-induced cell migration by interacting with the lysophosphatidic acid 2 receptor.[J].Biol.Chem,2004,279(11):10459-10468.
29.L i L,Wang L,Zhang W,et al.Correlation of serum VEGF levels with clinical stage,therapy efficacy,tumor metastasis and patient survival in ovarian cancer[J].Anticancer Res,2004,24:197321979.
30.Sutphen Rebecca,Xu Yan,Wilbanks George D.,et al.Lysophospholipids are potential biomarkers of ovarian cancer.[J].Cancer Epidemiology Biomarkers & Prevention,2004,13(7):1185-1191.
31.段满乐,武凡。磷脂酶A2和溶血磷脂酸在卵巢癌诊断中的价值,中华检验医学杂志,2005,6:622-624。
1. Moolenaar WH. Lysophosphatidic acid a multifunction Phospholipid messenger. [J]. Biol Chem, 1995; 270 (22) :12949-2952.
2. Xu Y, Xiao YJ, Baudhuin LM, et al. The role and clinical applications of bioactive lysolipids in ovarian cancer. [J]. Soc Gynecol Investig, 2001, 8(1): 1-13.
3. Moolenaar WH. Bioactive Lysophospholipids and their G Protein-Coupled receptors. [J]. Exp Cell Res, 1999; 253(1): 230-238.
4. Goetzl EJ, An S. Diversity of cellular receptors and functions for the lysophospholipid growth factors lysophosphatidic acid and sphingosine 1-phosphate. FASEB J. 1998; 12(15):1589-1598.
5. Xu Y, Shen Z, Wiper DW, et al. Lysophosphatidic acid as a potential biomarker for ovarian and other gynecologic cancers .[J]. Am Med Assoc, 1998;280(8):719-723.
6. Shen Z, Belinson J, Morton RE, et al. Phorbol 12-myristate 13-acetate stimulus lysophosphatidic acid secretion from ovarian cancer and cervical cancer cell but not from breast or leukemia cells . J. Gynecol Oncol, 1998; 71(3): 364-368.
7. Ren Juan, Xiao Yi-jin, Singh Lisam Shanjukumar. et al. Lysophosphatidic acid is constitutively produced by human peritoneal mesothelial cells and enhances adhesion, migration, and invasion of ovarian cancer cells. J. Cancer Research ,2006 ,66:3006-3014.
8. Hu Yu-Long, Tee Meng-Kian, Goetzl Edward J. et al. Lysophosphatidic acid induction of vascular endothelial growth factor expression in human ovarian cancer cells. [J]. The National Cancer Institute, 2001; 93(10):762-768.
9. Hu Yu-Long, Albanese Chris,Pestell Richard G. et al .Dual mechanisms for lysophosphatidic acid stimulation of human ovarian carcinoma cells. [J] .the National Cancer Institute, 2003; 95(10): 733-740.
10. Takuji Fujita, Shingo Miyamoto, Ichiro Onoyama, et al. Expression of lysophosphatidic acid receptors and vascular endothelial growth factor mediating lysophosphatidic acid in the development of human ovarian cancer. Cancer Letters, 2003,192:161-169.
11. So. John, Wang Feng-qiang, Navari Jason, et al, LPA-induced epithelial ovarian cancer (EOC) in vitro invasion and migration are mediated by VEGF receptor-2(VEGF-R2). [J]. Gynecol Oncol. 2005; 97(3): 870-878.
12. Xu Jun, Lai Yun-Ju, Lin Weei-Chin. et al, TRIP6 enhances lysophosphatidic acid-induced cell migration by interacting with the lysophosphatidic acid 2 receptor. [J]. Biol. Chem, 2004, 279(11): 10459-10468.
13. Fishman DA, Liu YY, Ellerbroek SM, et al. Lysophosphatidic acid promotes matrix metalloproteinase(MMP) activation and MMP-dependent invasion in ovarian cancer cells[J]. Cancer Res, 2001,61:3194-3199.
14.Barbara Schmalfeldt,Dieter Prechtel,Kathrin Harting.et al.Increased expression of matrix metalloproteinases(MMP)-2,MMP-9,and the urokinase-type plasminogen activator is associated with progression from benign to advanced ovarian cancer.J.Clinical Cancer Research,2001,7(8):2396-2404.
15.Gottfried Konecny,Michael Untch,Astrid Pihan.et al.Association of urokinase-type plasminogen activator and its inhibitor with disease progression and prognosis in ovarian cancer.[J].Clinical Cancer Research,2001,7(6):1743-1749.
16.Li Hong-bin,Ye Xiao-qin,Mahanivong Chitladda.et al.Signaling mechanisms responsible for LPA-induced urokinase plasminogen activator expression in ovarian cancer cells.[J].Biol.Chem,2005,280(11):10564-10571.
17.Sawada K,Morishige K,rahara M,et al.Lysophosphatidic acid induces focal adhesion assembly through Rho/Rho-associated kinase pathway in human ovarian cancer cells[J].Gynecol Oncol,2002,87:252-259.
18.Fang XJ,Schummer M,Mao M,et al.Lysophosphatidic acid is a bioactive mediator in ovarian cancer[J].Biochem Biophys Acta,2002,1582:257-264.
19.王辉,吴小华,史丽,溶血磷脂酸诱导人卵巢上皮癌裸鼠腹腔移植瘤的生长研究,南方医科大学学报,2007,2:228-231.
20.L i L,Wang L,Zhang W,et al.Correlation of serum VEGF levels with clinical stage,therapy efficacy,tumor metastasis and patient survival in ovarian cancer[J].Anticancer Res,2004, 24: 197321979.
21. Konecny Gottfried, Untch Michael, Pihan Astrid. et al. Association of urokinase-type plasminogen activator and its inhibitor with disease progression and prognosis in ovarian cancer. [J]. Clinical Cancer Research, 2001, 7(6): 1743-1749.
22. Hannun YA. Apoptosis and dilemma of cancer chemotherapy. [J]. Blood, 1997, 89(6): 1845-1853.
23. Meng Yu-ru, Kang Shijun, So John, et al. Translocation of Fas by LPA prevents ovarian cancer cells from anti-Fas-induced apoptosis. [J]. Gynecologic Oncology, 2005, 96(2):462-469.
24. Meng Yu-ru, Graves Laura, Do Thuy-Vy. et al. Upregulation of FasL by LPA on ovarian cancer cell surface leads to apoptosis of activated lymphocytes. [J]. Gynecologic Oncology, 2004, 95(3): 488-495.
25. Meng Yu-ru, Kang Shi-jun, Fishman David A. et al. Lysophosphatidic acid stimulates fas ligand microvesicle release from ovarian cancer cells. [J]. Cancer Immunology, Immunotherapy, 2005, 54(8): 807-814.
26. Kang Y-C, Kim K-M, Lee K-S, et al. Serum bioactive lysophospholipids prevent TRAIP-induced apoptosis via P13K/AKT-dependent cFLIP expression and Bad phosphorylation. [J]. Cell Death and Differentiation, 2004, 11(12):1287-1298.
27. Xu Y, Gaudette DC, Boynton JD, et al. Charactrization of an ovarian cancer activing factor(OCAF) in ascites from ovarian cancer patients. [J].Clin cancer Res, 1995,1 (10) :1223-1232.
28. Sutphen Rebecca, Xu Yan, Wilbanks George D. et al. Lysophospholipids are potential biomarkers of ovarian cancer.[J].Cancer Epidemiology Biomarkers & Prevention,2004,13(7):1185-1191.
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