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ABSTRACT: Endometriosis is a common gynecological disease. This study aimed to screen proteins that were expressed differently in patients with endometriosis versus normal controls using proteomic techniques, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS).
Protein chip SELDI-TOF-MS combines the advantages of microarray and mass spectrometry, and can screen latent markers in sera of patients with endometriosis. Serum samples from patients and normal volunteers were analyzed by SELDI-TOF-MS.
After comparing the serum protein spectra of 36 patients with 24 normal controls, 24 differently expressed potential biomarkers (P < 0.01) were identified. Using Biomarker Pattern software, we established a tree model of the 60 serum protein spectra. When using the three biomarkers to classify the samples, the sensitivity for diagnosing endometriosis was 91.7%, specificity was 95.8%, and coincidence rate was 93.3%. Then we used serum samples from 12 patients and 8 normal controls to validate the tree model and report the sensitivity for diagnosing endometriosis was 91.7%, specificity was 75%, and coincidence rate was 85%.
SELDI-TOF-MS may be a useful tool in high-risk population screening for endometriosis. The identification and application of the biomarkers need to further study.
Chinese medical journal 02/2009; 122(4):373-6. · 0.86 Impact Factor
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Li Dong,
Xiao-Hong Chang,
Xue Ye,
Li-Rong Zhu,
Yang Zhao,
Li Tian,
Hong-Yan Cheng,
Xiao-Ping Li, Hong Zhang,
Qin-Ping Liao,
Tian-Yun Fu,
Ye-Xia Cheng,
Heng Cui
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ABSTRACT: To evaluate the value of human epididymis secretory protein 4 (HE4) and CA(125) in the diagnosis of ovarian malignancy.
HE4 and CA(125) in the serum specimens of malignant ovarian tumor group (30 cases), benign ovarian diseases (110 cases; 45 benign ovarian tumor, 57 endometriotic diseases and 8 pelvic inflammation were included) and healthy women group (137 cases) were assayed double blindly. The levels and the diagnosis efficiency of the HE4 and CA(125) were analyzed.
(1) The median levels of HE4 and CA(125) were significantly higher in malignant ovarian tumor group (244 pmol/L and 601 kU/L respectively) than those of the benign ovarian diseases group (32 pmol/L and 22 kU/L respectively) and healthy women group (32 pmol/L and 11 kU/L respectively) (P = 0.000 - 0.029). The median levels of CA(125) were also higher in endometriotic diseases and pelvic inflammation groups (53 and 41 kU/L respectively) than those of benign ovarian tumor group and healthy women group (12 and 11 kU/L respectively; P = 0.000 - 0.031). (2) The positive rate of HE4 was lower than that of CA(125) in malignant ovarian tumor group (P = 0.036). HE4 was negative in benign diseases and healthy women groups. But the positive rates of CA(125) were 56.1% and 5/8 respectively in endometriotic diseases and pelvic inflammation groups and there were significant differences compared with HE4 (P = 0.000). (3) The HE4 assay had advantage over the CA(125) assay in receiver operating characteristic-area under the curve (ROC-AUC) and sensitivity with a specificity of 100% when ovarian malignancy was compared with controls having benign diseases and healthy women, benign tumor or benign diseases groups respectively. The CA(125) assay had advantage over the HE4 assay in ROC-AUC and sensitivity with the same specificity when ovarian cancers were compared with controls having healthy women group. (4) Combined assay of HE4 and CA(125) was better than CA(125) alone when ovarian malignancy was compared with controls having any group. (5) Combined assay was better than HE4 alone in ROC-AUC and sensitivity with the same specificity when ovarian cancers were compared with controls having benign diseases and healthy women or healthy women groups. And combined assay was lower in the ROC-AUC and the sensitivity with specificity of 100% than HE4 when ovarian cancers were compared with controls having benign tumors or benign diseases groups respectively. (6) The diagnosis efficiency of the HE4 assay at the level 86 pmol/L determined in ROC curve with controls having benign diseases and healthy women group and at the 95% reference level 50 pmol/L of healthy women or 150 pmol/L recommended by the kit respectively was compared. The sensitivity of 50 pmol/L was 73% higher than 150 pmol/L and 86 pmol/L, while the specificity and positive predictive value were lower (P = 0.002, P = 0.000). The specificity, accuracy and positive predictive value of HE4 assay at the set point of 150 pmol/L and 86 pmol/L were 100%, 96% and 96%. The set point of 86 pmol/L had advantage over 150 pmol/L at the sensitivity of diagnosis, 70% and 63% respectively. But the positive predictive value was 95% lower than 150 pmol/L, being 100%. There was no significant difference (P = 0.883, P = 0.883).
The specificity of HE4 assay is higher than CA(125) assay in the diagnosis of ovarian cancer and HE4 combined with CA(125) assay can improve the diagnoses. The set point of 150 pmol/L is advantageous for the accurate diagnosis, while the set point of 86 pmol/L is advantageous for the screening of malignant ovarian cancer.
Zhonghua fu chan ke za zhi 01/2009; 43(12):931-6.
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Xiao-Ping Li,
Heng Cui,
Jing-Wei Zhou,
Li-Hui Wei,
Jian-Liu Wang,
Yan Zhao,
Yue Wang,
Shi-Jun Wang,
Hong-Lan Zhu,
Li Dong, Hong Zhang
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ABSTRACT: To evaluate the efficacy and tolerability of the combination of oxaliplatin, ifosfamide and epirubicin (IAP) in treatment of recurrent or platinum-resistant ovarian cancer patients.
A total of 25 patients received the combined chemotherapy of ifosfamide (3 - 4 g/m(2)), epirubicin (50 - 60 mg/m(2)) and oxaliplatin (130 mg/m(2)). The cycles were repeated every 21 days. The efficacy and toxicity were evaluated in 21 patients who received more than 2 cycles of IAP chemotherapy.
The overall response rate was 71%, with a complete response in 10 (48%), partial response in 5 (24%), stable disease in one (5%), and disease progression in 5 (24%). The median progression-free and overall survival time were 11 (1 to 33) months and 31 (1 to 71) months. While overall response rate was 60% in 10 patients with primary platinum resistant, and 88% in 8 patients with secondary platinum-resistant. Grade III - IV myelosuppression rate was 30%. The most common non-hematologic toxicity was perineurotoxicity (38%).
The combination of oxaliplatin, ifosfamide and epirubicin appears to be effective for recurrent or platinum-resistant ovarian cancer patients as salvage chemotherapy and the toxicity is also tolerable. However, it needs to be evaluated by multiple clinical trials.
Zhonghua fu chan ke za zhi 11/2008; 43(10):724-7.
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Wenlan Yang,
Jie Feng,
Xiaohong Chang,
Tianyun Fu,
Xue Ye, Hong Zhang,
Xiaoping Li,
Hongwu Wen,
Limin Feng,
Chunrong Tong,
Heng Cui
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ABSTRACT: 6B11 anti-idiotype minibody, a fusion protein, has been shown to mimic ovarian carcinoma associated antigen OC166-9. This study was designed to determine whether 6B11 anti-idiotype minibody-pulsed dendritic cells (DCs) can induce cytotoxic T cells against ovarian cancer cells.
Monocytes were isolated from peripheral blood mononuclear cells collected from patients with epithelial ovarian carcinoma (n=10). The monocytes-derived immature DCs were stimulated by cytokines, and mature DCs were pulsed with 6B11 anti-idiotype-minibody or murine F(ab)'2 fragments. The proliferation of autologous T cells induced by DCs was determined by 3H-thymidine uptake. The cytotoxicity of DC-activated T cells against autologous carcinoma cells was determined by 51Cr-release assay.
Purified T cells demonstrated strong proliferation following incubation with 6B11 anti-idiotype minibody-pulsed DCs in 4 of 10 patients. The specific cytotoxicity of purified T cells against autologous carcinoma cells was induced after stimulation with 6B11 anti-idiotype minibody-pulsed DCs in 5 of 10 patients with cytotoxic effects ranging from 25 to 95%. In contrast, isotype murine F(ab)'2 fragments-pulsed DCs did not induce T cell proliferation and cytotoxicity against the targets. Additionally, the cytotoxic effect was partially inhibited by anti-MHC class-I antibody indicating that the cytotoxic effects are antigen-specific.
6B11 anti-idiotype-antibody-pulsed DCs can induce T cell proliferation and T cell-mediated cytotoxicity against autologous ovarian tumor cells in vitro. The cytotoxic effects of T cells against autologous tumor cells are antigen-specific. These data implicate the rationale for the use of 6B11 anti-idiotype minibody as immunotherapy against ovarian carcinoma.
Gynecologic Oncology 05/2007; 105(1):238-43. · 3.89 Impact Factor
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ABSTRACT: To use proteomic techniques, including two-dimensional electrophoresis (2-DE), Western blot, and mass spectrometry, to screen and identify proteins that were expressed differently in patients with endometriosis versus normal controls.
First, we aimed to find a difference in the way serum and eutopic endometrial proteins were expressed in women with and without endometriosis. Second, we were interested in searching for endometriotic proteins, which were specifically recognized by sera from patients with endometriosis.
Collaborative investigation in an academic research environment.
Consenting women of reproductive age taking no medications and with laparoscopically proven endometriosis.
Surgical excision of eutopic and ectopic endometrial biopsy and phlebotomization of patients with endometriosis and controls.
Protein expression.
Thirteen protein spots from serum correlated with 11 known proteins and 11 protein spots from endometrium correlated with 11 known proteins were found differently expressed between women with and without endometriosis. Some proteins may be cytoskeletons, and some may be involved in the regulation of cell cycle, signal transduction, or immunological function. Three proteins, which were identified as vimentin, beta-actin, and ATP synthase beta subunit, hybridized significantly differently between endometriosis sera and normal sera.
The data help to establish a human endometriosis proteome database and broaden our understanding of the pathogenesis of endometriosis. Further study of the proteins identified herein will assist in the eventual development of new diagnoses and treatments for endometriosis.
Fertility and sterility 09/2006; 86(2):274-82. · 3.97 Impact Factor
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ABSTRACT: To purify MAb183B2 corresponding antigen of ovarian carcinomas and study its physical and chemical characteristics.
The strongest positive samples reacted with MAb183B2 were screened from ovarian cancer ascites with indirect enzyme linked immunosorbent assay (ELISA). Then the antigen was purified from ascitic fluid by affinity chromatography with MAb183B2. Nature of the purified antigen was examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blot and its reactivity was determined after treatment with NaIO4, trypsin, pronase, neuraminidase, deglycolipid mixture and heating. Two dimensional electrophoresis combined with western blot was then used to isolate and identify the antigen from ovarian cancer cell line SKOV3.
The reactivity of the antigen after treated by NaIO4, neuraminidase and deglycolipid mixture was still positive, while it was negative after treated by trypsin, pronase and heating. The antigen proved to be composed of two different subunits of 56,000 and 25,000 by SDS-PAGE, and MAb183B2 could blot the 56,000 band by western blot. The antigen from the SKOV3 cell line displayed microheterogeneity appearing as three spots over a pI range 5.3 approximately 5.8 at 56,000.
The epitope of 183B2-antigen is at its peptide core. The antigen belongs to the Ig super family and might be a new ovarian carcinoma associated antigen.
Zhonghua fu chan ke za zhi 10/2005; 40(9):614-8.
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ABSTRACT: To find out markers of endometriosis.
The two dimensional gel images of proteins extracted from eutopic endometrium from endometriosis patients and controls were analyzed by software Phoretix 2D,and the proteins expressed differently were identified primarily by query of data base. The proteins extracted from ectopic endometrium of ovarian endometriosis were transferred from two dimensional gel onto nitrocellulose membranes, followed by incubation with sera from women with and without endometriosis. Analyzed by MALDI-TOF-MS, the proteins hybridized differently were identified through their Peptide Mass Footprints.
Having compared the reproducible two dimensional gel images of proteins from eutopic endometrium of women with and without endometriosis,we obtained 11 proteins expressed differently. Through Western Blot technique,we found three proteins hybridized differently which were identified as vimentin, beta-actin and ATP synthase beta subunit respectively.
The protein expression spectra of eutopic endometrium from patients with endometriosis are significantly different from those of the controls, and the anti-endometrial autoantibodies against vimentin, beta-actin and ATP synthase beta subunit may be induced.
Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 09/2005; 37(4):366-70.
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Wen-Lan Yang,
Heng Cui,
Jie Feng,
Xiao-Hong Chang,
Tian-Yun Fu,
Xue Ye, Hong Zhang,
Xiao-Ping Li,
Hong-Wu Wen,
Li-Min Feng,
Chun-Rong Tong
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ABSTRACT: Immunotherapy of sensitizing dendritic cells (DCs) with antigen,protein,and frozen cancer cell has been widely used in treating various cancers. The 6B11 anti-idiotype-antibody,a fusion protein prepared by our research center,can mimic ovarian cancer-associated antigen OC166-9. This study was to induce T cell cytotoxicity against autologous tumor cells of patients with ovarian cancer by 6B11 anti-idiotype-antibody.
Peripheral blood samples were collected from 10 patients with epithelial ovarian cancer,Monocytes were isolated and cultured to obtain DCs. Immature DCs were stimulated with 6B11 anti-idiotype-antibody (MINI-DC group); unpulsed DCs (unpulsed-DC group),mouse F(ab) '2 fragments pulsed DCs [F(ab)'2-DC group],and T cells alone (T group) were served as controls. Mature DCs were harvested. (3)H-thymidine ((3)H-TdR) incorporation approach was used to measure effect of DCs on stimulating auto-T cell proliferation. Cytotoxicity of DC-activated T cells against auto-tumor cells was measured with (51)Cr 6-h release test,tumor cell lines,SKOV3,HLE,and K562, were used as controls.
In 4 cases,cpm value of (3)H-TdR incorporation,as symbol of auto-T cell proliferation, in MINI-DC group was significantly higher than those in control groups. In 5 cases,specific cytotoxicity effect of T cells on auto-tumor cells was observed in MINI-DC group at effect-target ratio of 20:1,the toxicity effect of T cells in MINI-DC group was 25%-100%,significantly higher than those in F(ab)'2-DC group (18%-40%), unpulsed-DC group (13%-43%),and T group (9%-58%). In 4 cases,the toxicity effect of T cells in MINI-DC group, at effect-target ratio of 20:1,on auto-tumor cells was 25%-100%, higher than those on SKOV3 cells (5%-51%),HLE cells (2%-38%),and K562 cells (2%-25%). Moreover,the toxicity effect of T cells in MINI-DC group on auto-tumor cells can be partially blocked by anti-MHC-I antibody,which indicated that the toxicity was antigen-specific.
DCs loaded with 6B11 anti-idiotype antibody that mimic ovarian cancer antigen can induce antigen specific T cell cytotoxicity against auto-ovarian tumor cells in vitro.
Ai zheng = Aizheng = Chinese journal of cancer 12/2004; 23(12):1639-45.
